rare tumors

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Synonyms include epidermoid carcinoma of the scrotum, chimney sweepers cancer, mule- spinners cancer and epithelioma of the scro- tum. It is customary to ...
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rare tumors ISSN 2036-3605 ı eISSN 2036-3613 ı www.pagepress.org/rt Editor-in-Chief: Robert C. Miller, USA Volume 1, 2009

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RARE TUMORS ISSN 2036-3605 - eISSN 2036-3613

Editor-in-Chief Robert C. Miller, Rochester, MN, USA

Editorial Staff Nicole Pezzolo, Managing Editor Cristiana Poggi, Production Editor Anne Freckleton, Copy Editor Jeanette Mitchell, Copy Editor Filippo Lossani, Technical Support

Editorial Board Prakash Adhikari, Department of ENT and Head and Neck Surgery, GMS Memorial Academy of ENT and Head and Neck Studies, TU Teaching Hospital, Kathmandu, Nepal Rafael Álvarez-González, Graduate School of Biomedical Sciences, University of North Texas, Healt Science Center at Forth Worth, Forth Worth, Texas, USA Armando Bartolazzi, Cellular and Molecular Tumor Pathology Laboratory, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden Archit Bhatt, Department of Neurology and Ophtalmology, Clinical Center East Lansing, East Lansing, Michigan, USA Kevin Camphausen, Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA Joseph R. Carver, Abramson Cancer Center, University of Pennsylvania, Pennsylvania, USA William Cho, Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Domenico Coppola, Anatomic Pathology and Neuroendocrine Cancer Research Divisions, Moffit Cancer Center and Research Institute, Tampa, Florida, USA Undurti N. Fams Das, UND Life Sciences, Shaker Heights, Ohio, USA Ozsahin E. Mahmut, Department of Radiooncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland Jimmy Thomas Efird, Centre of Health Vulnerable Populations, University of Carolina, Greensboro, Carolina, USA Amany Elwakkad, National Research Center, Cairo, Egypt Gulgun Engin, Department of Radiology, Faculty of Medicine, Istanbul University, Istanbul, Turkey Guy Eslick, Harvard School of Public Health, MA, USA Patricia D. Evilliers, Department of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, USA Luis E. Fayad, Department of Lymphoma & Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas, USA Faris Farassati, Department of Medicine, University of Kansas School of Medicine, Kansas City, Kansas, USA Ali Gholamrezanezhad, Research Institute for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Samy Lewiz Habib, Department of Medicine, Division of Nephrology, University of Texas Health Science Center, San Antonio, Texas, USA Paul H. Hartel, Broaddus Hospital of Davis Health System, Elkins, West Virginia, USA Ghulam Sarwar Hashmi, Department of Oral and Maxillofacial Surgery, Z.A. Dental College, Medical Colony, A.M.U. Aligarh, India Joseph Herman, Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore Maryland USA Kanya Honoki, Department of Orthopedic Surgery, Nara Medical University, Nara, Japan Charles Hsu, Division of Plastic and Reconstructive Surgery, Stanford University Medical Center, Palo Alto, CA, USA Sergio Huerta, Dallas VA Medical Center Surgical Services, Dallas, Texas, USA Abdul Hussain, Minimal Access Unit, General Surgery Department, Princess Royal University Hospital, London, UK Rafael Jimenez, Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA Bleddyn Jones, Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK Honoki Kanya, Department of Orthopedic Surgery, Nara Medical University, Nara, Japan Babak Kateb, Intraoperative Surgical Planning Society, Los Angeles, CA, USA Sunali Khanna, Department of Oral Medicine & Radiology, Nair Hospital Dental College, Mumbai, India Boris Kirshtein, Department of Surgery, Soroka University Medical Center, Beer

Sheva, Israel Antoniades Konstantinos, School of Dentistry, Aristotle University of Thessaloniki, Thessaloniki, Greece Masafumi Koshiyama, Department of Ob/Gy at Otsu Red Cross Hospital, Otsu, Japan Sunil Krishnan, Radiation Oncology, Gastrointestinal Translational Research, M.D. Anderson Cancer Center, Houston, TX, USA Calin Lazar, Department of Plastic and Reconstructive Surgery, Rouen University Hospital, Rouen, France Wei Li, Institute of Biomedical Engineering, School of Control Science and Engineering, Shandong University, Shandong, China Simon Lo, Department of Radiation Medicine, The Ohio State University Arthur G. James Cancer Hospital, Columbus, OH, USA Lorenzo Lo Muzio, Surgical Sciences Department, Faculty of Medicine, University of Foggia, Foggia, Italy Paulette M. Fauceglia, Roswell Park Cancer Institute, Buffalo, New York, USA Sridhar Mani, Departments of Medicine and Molecular Genetics, Division of Oncology, Albert Einstein School of Medicine, New York, USA Hiroyuki Matsubayashi, Shizuoka Cancer Center, Shizuoka-ken, Japan Toshihiro Matsuo, Department of Artificial Joints and Biomaterial, Hiroshima University, Hiroshima, Japan Axel Merseburger, Department of Urology, Eberhard-Karls-University, Tübingen, Germany Oliver Micke, Department of Radiotherapy and Radiation Oncology, Franziskus Hospital, Bielefeld, Germany Rene Mirimanoff, Service de Radio-Oncologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland Luca Morelli, Operative Unit of Patological Anatomy and Cytological Diagnostics, P.O. S. Chiara, Hospital of Trento, Trento, Italy Charbel D. Moussallem, Orthpedic Surgery, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon Hidenari Nagai, Division of Gastroenterology and Hepatology, Toho University Medical Center, Omori Hospital, Tokyo, Japan Tan Dat Ngyuen, Department of Radiation Oncology, Institut Jean-Godinot, Reims, France Athanasios Papatsoris, University of Athens, Athens, Greece Nicholas A. Pavlidis, Department of Medical Oncology, School of Medicine, University of Ioannina, Ioannina, Greece Yi Chu Pei, Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan Shahid Pervez, Department of Pathology and Microbiology, Agakhan University Hospital, Karachi, Pakistan Camillo Porta, IRCCS San Matteo University Hospital Foundation, Pavia, Italy Fernando Quevedo, Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA Malcolm Schinstine, Division of Pathology, Hilo Medical Center Laboratories, Hilo, Hawaii, USA Andrzej Semczuk, Lublin Medical University, Lublin, P oland Khan Shah Alam, Department of Orthopaedics, All India Institute of Medical Sciences Ansari Nagar, New Delhi, India Mark G. Shrime, Department of Otolaryngology/Head and Neck Surgery, Boston University Medical Center, Boston, Massachusetts, USA Vernon Keith Sondak, Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA Giuseppe Spriano, Department of Otolaryngology/Head and Neck Surgery, National Cancer Institute Regina Elena, Rome, Italy Keith Stubbs, University of Western Australia, Perth, Australia Fabio Tavora, Department of Genitourinary Pathology, Armed Forces Institute of Pathology, Washington, DC, USA Juliette Thariat, Department of Radiation Oncology, Anti Cancer Center AntoineLacassagne, University Nice Sophia-Antipolis, Nice, France Takeshi Tomonaga, Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba Japan Mark Gerard Trombetta, Department of Radiation Oncology, West Penn Allegheny Health System Allegheny General Hospital, PA, USA Lyuba Varticovski, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA Salvador Villa I Freixa, Department of Radiation Oncology, Hospital Universitari Germans Trías, Badalona, Catalunya, Spain Takuya Watanabe, Department of Internal Medicine and Gastroenterology, Medical Hospital, The Nippon Dental University of Life Dentistry at Nigata, Nigata, Japan Shigeru Yamada, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan Leandra Náira Zambelli Ramalho, Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirdo Preto, SP, Brazil

RARE TUMORS 2009; Volume 1 Metastatic pleomorphic sarcoma to left atrium Ammar H. Hawasli, Rachael Cayce, Trung Luong, Evelyn Taiwo, Michael N. Feliciano, Sharon C. Reimold, John M. DiMaio, Barbara B. Haley..........................................................................................................................................................................................................................................................1 Squamous cell carcinoma of the scrotum in a Nigerian: case report Jerome E. Azike, N.O. Chukwujama, T.C. Oguike...................................................................................................................................................................................................4 Extraosseous osteosarcoma in Ibadan: case series over a 20-year period Temitope O. Alonge, Henry A. Obamuyide, Gabriel Olabiyi Ogun......................................................................................................................................................................6 A multimodal approach to the treatment of bilateral choroidal metastases from thyroid carcinoma Maria Grazia Fabrini, Federica Genovesi-Ebert, Franco Perrone, Mario De Liguoro, Clara Giovannetti, Fausto Bogazzi, Stanislao Rizzo, Enio Martino, Luca Cionini.......................................................................................................................................................................................................................................9 Pleomorphic sarcoma metastatic to the duodenum? Fabio R. Tavora, Allen P. Burke ...............................................................................................................................................................................................................................12 Complete small bowel obstruction caused by metastasis from primary nasopharyngeal carcinoma Chi Pan Lau, Edwin Pun Hui, Anthony Tak-Cheung Chan .................................................................................................................................................................................16 Diagnosis of vulvar lesions by non-invasive optical analysis: a pilot study Anne-Therese Vlastos, Igor Charvet, Ilaria Dellacasa, Federica Capanna, Marie-Françoise Pelte, Philippe Thueler, Michel Saint-Ghislain, Christian Depeursinge, Paolo Meda.............................................................................................................................................................................18 Congenital giant melanocytic nevi Ghulam S. Hashmi, Syed S. Ahmed, Shahla Khan ................................................................................................................................................................................................23 Intramedullary capillary hemangioma of the thoracic spine: case report and review of the literature Rahul Kasukurthi, Wilson Z. Ray, Spiros L. Blackburn, Eriks A. Lusis, Paul Santiago..................................................................................................................................26 A case report of surgical debulking for a huge mass of elephantiasis neuromatosa Manabu Hoshi, Makoto Ieguchi, Susumu Taguchi, Shinya Yamasaki.............................................................................................................................................................29 Value of centrifugated liquid-based cytology by Papanicolaou and May-Grünwald in oral epithelial cells Hussain Gadelkarim Ahmed, Ali Mahmmoud Edris, Eneel Ahmed Mohmed, Mohammed Omer M. Hussein ..........................................................................................31 Retroperitoneal lipoma arising from the urinary bladder Shingo Ukita, Masafumi Koshiyama, Megumi Ohnaka, Naoyuki Miyagawa, Yukio Yamanishi, Fumitomo Nishimura, Michikazu Nagura, Tomoko Kim, Masaya Hirose, Tomoyuki Shirase, Hisato Kobayashi, Hiroshi Ozasa ..............................................................................................34 Primary breast lymphomas Olivier Julen, Ilaria Dellacasa, Marie-Françoise Pelte, Bettina Borish, Christine Bouchardy, Federica Capanna, Georges Vlastos, Jean-Bernard Dubuisson, Anne-Thérèse Vlastos..................................................................................................................................................................................................36 Neuroblastoma occurring in a 38-year old Nigerian man: a rare finding Martin A. Nzegwu, Aloy Aghaji................................................................................................................................................................................................................................42 Primary lymphoepithelial carcinoma of the parotid gland in a North African woman Soumaya Ben Abdelkrim, Amel Trabelsi, Faten Hammedi, Monia Omezzine, Soumaya Rammeh, Atef Ben Abdelkader, Badreddine Sriha .......................................................................................................................................................................................................................................................44 A review of the history, epidemiology and treatment of squamous cell carcinoma of the scrotum Jerome E. Azike ..........................................................................................................................................................................................................................................................47 Assessment of cytological atypia, AgNOR and nuclear area in epithelial cells of normal oral mucosa exposed to toombak and smoking Hussain Gadelkarim Ahmed, Abd-Elraheem Ali Babiker ...................................................................................................................................................................................50 Desmoplastic small round cell tumor: impact of 18F-FDG PET induced treatment strategy in a patient with long-term outcome Dorra Ben-Sellem, Kun-Lun Liu, Sébastien Cimarelli, André Constantinesco, Alessio Imperiale ..............................................................................................................53 [Rare Tumors 2009; volume 1]

Epithelioid hemangioendothelioma of the temporal artery presenting as temporal arteritis: case report and literature review Dina El Demellawy, Ahmed Nasr, Salem Alowami ..............................................................................................................................................................................................56 Retrorectal epidermoid cyst with unusually elevated serum SCC level, initially diagnosed as an ovarian tumor Masaru Hayashi, Shigeki Tomita, Takahiro Fujimori, Hitoshi Nagata, Keiichi Kubota, Akiko Shoda, Kazumi Tada, Nobuaki Kosaka, Ichio Fukasawa, Noriyuki Inaba ...........................................................................................................................................................................................................................59 Metastatic rectal cancer to the breast Hsiao C. Li, Prapti Patel, Payal Kapur, Sergio Huerta .........................................................................................................................................................................................63 Plexiform neurofibroma in the hepatic hilum associated with neurofibromatosis type 1: a case report Sojun Hoshimoto, Zenichi Morise, Chinatsu Takeura, Masahiro Ikeda, Tadashi Kagawa, Yoshinao Tanahashi, Yasuhiro Okabe, Yoshikazu Mizoguchi, Atsushi Sugioka .................................................................................................................................................................................................................66 Cystadenofibroma of the rete ovarii: a case report with review of literature Manisha Ram, Abdel Abdulla, Khalil Razvi, Ivilina Pandeva, Awatif Al-Nafussi..........................................................................................................................................69 Angiomyomatous hamartoma: a rare case report with review of the literature Manisha Ram, Nazar Alsanjari, Naseem Ansari...................................................................................................................................................................................................75 Malignant neuroectodermal tumor with melanocytic and rhabdomyoblastic differentiation Munir R. Tanas and Brian P. Rubin ........................................................................................................................................................................................................................79 Malignant Triton tumor in the retroperitoneal space associated with neurofibromatosis type 1: a case study Sojun Hoshimoto, Zenichi Morise, Chinatsu Takeura, Masahiro Ikeda,Tadashi Kagawa, Yoshinao Tanahashi, Yasuhiro Okabe, Yoshikazu Mizoguchi, Atsushi Sugioka ................................................................................................................................................................................................................82 A case of primary renal angiosarcoma Kazuhiko Yoshida, Fumio Ito, Hayakazu Nakazawa, Yoshiko Maeda, Hikaru Tomoe, Motohiko Aiba..................................................................................................85 A legacy of tinnitus: multiple head and neck paragangliomas Tricia M.M. Tan, Emma C.I. Hatfield, Rajesh V. Thakker, Eamonn R. Maher, Karim Meeran, Niamh M. Martin, Jeremy J. Turner......................................................88 Soft tissue mixed tumor of the hand Hiroshi Shimosawa, Michiro Susa, Takayuki Honma, Eiichi Hiraishi, Hiroshi Sakihara .........................................................................................................................90 Primary sarcoma of the liver and transplantation: a case study and literature review Benjamin Bismuth, Hélène Castel, Emmanuel Boleslawski, David Buob, Marc Lambert, Nicole Declerck,Valérie Canva, Eli-Serge Zafrani, Philippe Mathurin, François-René Pruvot, Sébastien Dharancy ......................................................................................................................................93 Pitfalls in neuroendocrine tumor diagnosis Emilio Bajetta, Marco Platania ..............................................................................................................................................................................................................................96 Hepatic angiosarcoma five years following spontaneous intraperitoneal bleed of a hepatic mass Jessica L. Cioffi-Pretti, Alexandra N. Kalof, George Ebert, Laurence E. McCahill .........................................................................................................................................98 Colonic cancer in adolescents. A report of three cases M.A.C. Odike, A.E. Dongo, E.F. Alufohai, A.I. Odike............................................................................................................................................................................................102 Tumors and tumor-like lesions of the heart valves Shi-Min Yuan, Hua Jing, Jacob Lavee ..................................................................................................................................................................................................................105 Treatment outcome of maxillary sinus cancer Hye Sung Won, Sang Hoon Chun, Bum-soo Kim, So Ryoung Chung, Ie Ryung Yoo, Chan-Kwon Jung, Yeon-Sil Kim, Dong-il Sun, Min Sik Kim, Jin-Hyoung Kang ......................................................................................................................................................................................................110 Invasive neuroendocrine tumor of the kidney: a case report Ephrem O. Olweny, Michael H. Hsieh, Jill C. Buckley, Jack W. McAninch.....................................................................................................................................................115 Bilateral angiosarcoma of the breast in a fourteen-year-old child Albertus N. van Geel, Michael A. den Bakker......................................................................................................................................................................................................117 Primary extrauterine endometrial stromal sarcoma: response to hormone therapy Gunjal Garg, Awoniyi O. Awonuga, Eugene P. Toy .............................................................................................................................................................................................119

[Rare Tumors 2009; volume 1]

The managament of rare nasal mass-nasal dermoid sinus cysts: open rhinoplasty Emel Cadalli Tatar, Ömer Tarik Selçuk, Güleser Saylam, Ali Özdek, Hakan Korkmaz ..............................................................................................................................121 Lipid-rich histology in a basal-type immuno-profile breast carcinoma: a clinicopathological histochemical and immunohistochemical analysis of a case Serena Russo, Diana Coppola, Paola Vinaccia, Antonella Siciliano, Francesca Baldassarre, Giovanni Battista, Giuseppe Pisani.................................................124 Synchronous malignant B-cell lymphoma and gastric tubular adenocarcinoma associated with paraneoplastic cutaneous vasculitis: hypereosinophilic syndrome with mixed cryoglobulinemia is an important sign of paraneoplastic syndrome Kazuhisa Nozawa, Hiroshi Kaneko, Tomoyasu Itoh, Yoko Katsura, Masaaki Noguchi, Fujihiko Suzuki, Yoshinari Takasaki, Hideoki Ogawa, Kenji Takamori, Iwao Sekigawa.............................................................................................................................................................................................128 Hemangiopericytomas of the spine: case report and review of the literature Chad D. Cole Meic H. Schmidt...............................................................................................................................................................................................................................132 Cervical intramedullary schwannoma: a case report and review of the literature Jardel Mendonça Nicácio, José Carlos Rodrigues Jr, Marcos Henrique Lima Galles, Igor Vilela Faquini, Clemente Augusto de Brito Pereira, Mario Ganau.............................................................................................................................................................................................137 Primary mediastinal giant cell tumor Judd Goldberg, Shameen Azizad, Jela Bandovic, Arfa Khan............................................................................................................................................................................141 Benign multicystic mesothelioma: a case report of three sisters Eve M. Bernstein, Alison Tate, Dan Arin Silasi, Thomas Rutherford...............................................................................................................................................................143 Congenital infantile digital fibromatosis: a case report and review of the literature Valérie Failla, Odile Wauters, Nazli Nikkels-Tassoudji, Alain Carlier, Josette André, Arjen F. Nikkels....................................................................................................146 Giant mesenteric cystic lymphangioma presenting with abdominal pain and masquerading as a gynecologic malignancy John Maa, Christianne Wa, Adnan Jaigirdir, Soo-Jin Cho, Carlos U. Corvera ..............................................................................................................................................148 Malignant peritoneal mesothelioma. Is there a new treatment? Kakil Ibrahim Rasul, David J. Kerr .......................................................................................................................................................................................................................150 Intracystic papillary carcinoma of the breast in a 21-year old premenopausal Nigerian woman: a case report Ivy N. Umanah, Akpan S. Okpongette ..................................................................................................................................................................................................................155 Diagnostic confusion resulting from CD56 expression by cutaneous myeloid sarcoma Thanh Ho, Franklin Sedarat, Nagesh Rao, Sheeja T. Pullarkat........................................................................................................................................................................156 The epidemiology of malignant giant cell tumors of bone: an analysis of data from the Surveillance, Epidemiology and End Results Program (1975-2004) Jennifer L. Beebe-Dimmer, Karynsa Cetin, Jon P. Fryzek, Scott M. Schuetze, Kendra Schwartz ...............................................................................................................159 Temsirolimus in the treatment of renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion proteins: a case report and review of literature Jigarkumar Parikh, Teresa Coleman....................................................................................................................................................................................................................164 Metastasizing pleomorphic adenoma presenting as an asymptomatic kidney tumor twenty-nine years after parotidectomy – urological viewpoint and overview of the literature to date Jan Ebbing, Carolin Blind, Harald Stein, Kurt Miller, Christoph Loddenkemper ........................................................................................................................................167 A case of primary mucosa-associated lymphoid tissue lymphoma of the prostate Noriko Koga, Masanori Noguchi, Fukuko Moriya, Kouichi Ohshima, Nobuyuki Yoshitake, Kei Matsuoka, Jan Ebbing, Carolin Blind, Harald Stein, Kurt Miller, Christoph Loddenkemper.........................................................................................................................................................................................169 Re: Koga et al. A case of primary mucosa-associated lymphoid tissue lymphoma of the prostate Damien C. Weber......................................................................................................................................................................................................................................................171 A clinical and molecular project on gonadoblastoma needs international collaboration Nicolas Kalfa, Olivier Maillet, Charles Sultan....................................................................................................................................................................................................172 Primary NK/T cell lymphoma nasal type of the stomach with skin involvement: a case report Sebastian Kobold, Hartmut Merz, Markus Tiemann, Carolina Mahuad, Carsten Bokemeyer, Irmtraut Koop, Walter Fiedler............................................................173

[Rare Tumors 2009; volume 1]

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[Rare Tumors 2009; volume 1]

Rare Tumors 2009; volume 1:e1

Metastatic pleomorphic sarcoma to left atrium Ammar H. Hawasli,1 Rachael Cayce,2 Trung Luong,2 Evelyn Taiwo,1 Michael N. Feliciano3, Sharon C. Reimold,2,4 John M. DiMaio,5 Barbara B. Haley1,2 Departments of 1Hematology-Oncology, 2 Internal Medicine, 3Pathology, 4 Cardiology, and 5Cardiothoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA

Abstract Although several thousand patients are diagnosed with sarcoma annually in the United States, metastases to the heart are very uncommon. In this case report, an overall low frequency cancer presents masquerading with common cardiac symptomology. This case illustrates the importance for detailed diagnostic cardiac evaluations and heightened suspicion by physicians to consider metastatic disease to the heart in cancer patients with cardiovascular complications. Also discussed is a review of surgical and chemotherapeutic options for this problem.

strength, focal tenderness over the sacrum, pitting edema in the lower extremities and a murmur of mitral regurgitation with basilar crackles and dullness. Computed tomography (CT) showed a wedge-shaped splenic infarct and magnetic resonance imaging (MRI) of the spine demonstrated osseous metastatic disease involving the vertebral bodies, with epidural and neuroforaminal tumor extension in the sacrum. A TTE was performed in anticipation of chemotherapy with adriamycin and revealed a large vegetation attached to the anterior leaflet of the mitral valve with prolapse into the left atrium and ventricle (Figure 1A, arrow) and hypoechoic regions within the cardiac tissue (Figure 1A, arrowhead). The patient was taken to the operating room to remove the vegetation, biopsy the hypoechoic mass and replace the mitral valve. A 9 cm vegetation was excised from the anterior mitral valve leaflet (Figure 1B, left and middle). Intraoperatively, the patient was noted to have diffuse disease throughout the atrial septum and mitral valve (Figure 1B, right) and the procedure was terminated. Post-operative cardiac MRI showed a lobulated cardiac mass infiltrating the atrial septum, the posterior aortic wall and the posterior aspect of the anterior mitral valve annulus. In the axial plane, the mass measured at least 5.3 x 2.2 cm and extended to the superior portion of the left atrium near the entry of the right superior pulmonary vein

Correspondence: Dr. Barbara B. Haley, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA E-mail: [email protected] Key words: sarcoma, cardiac metastases, tumor, cancer. Received for publication: 1 May 2009. Accepted for publication: 5 May 2009. Acknowledgement: we would like to thank Dr. John Bagwell and Leah Gaither for their assistance. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0) ©Copyright A.H. Hawasli et al., 2009 Rare Tumors 2009; 1:e1 doi:10.4081/rt.2009.e1

(Figure 1C; mass indicated with arrowheads). Histology of the atrial mass revealed a highgrade pleomorphic sarcoma, metastatic to heart. Low power frozen sections of the atrial wall showed hypercellularity (Figure 2A). Medium and high power frozen (Figure 2B and C) and permanent (Figure 2D) sections showed tumor giant cells (indicated with arrowheads) among spindled and epithelioid

Introduction A 53-year-old Caucasian gentleman presented with progressive lower back pain, urinary and bowel incontinence, and lower extremity swelling over a one month period. He had been diagnosed six months prior at an outside institution with a high-grade pleomorphic sarcoma with focal myxoid and epithelioid elements of the duodenum. Small bowel resection was performed because of bowel obstruction. Perioperatively, the patient suffered a myocardial infarction (MI) due to focal narrowing of the left anterior descending artery and a drugeluting stent was placed during cardiac catheterization. Post-operative transthoracic echocardiogram (TTE) was interpreted as mild mitral valve thickening, with flail chordae tendineae and an estimated ejection fraction of 35-40%. After discharge, the patient was lost to follow-up.

Case report On presentation to our facility, physical examination revealed normal lower extremity

Figure 1. Echocardiography (A) performed before excision of vegitation (B) and postoperative cardiac MRI (C).

[Rare Tumors 2009; 1:e1]

[page 1]

Case Report tumor cells. The atrial mass was immunohistochemically positive for vimentin, confirming mesenchymal differentiation (Figure 2E). Immunohistochemical stains for other markers, including CD117, AE1/AE3, desmin, myogenin, caldesmon, S100, HMB-34, calretinin, CD31 and CD34 were negative (Figure 2F). A diagnosis of metastatic cardiac sarcoma was established and treatment with gemcitabine and docetaxel was initiated. Adriamycin-based therapy was not considered secondary to the patient’s reduced cardiac function (37% ejection fraction). Five weeks after initiating chemotherapy, the patient was admitted for worsening lower extremity edema but denied shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, chest pains, palpitations, weight gain, or symptoms of transient ischemic attacks. Electrocardiogram revealed atrial flutter at 119 beats per minute with 2:1 block and the old anterolateral infarct. The patient declined cardioconversion and was treated with amiodarone. At the time of preparation of this report, the patient was tolerating palliative gemcitabine and docetaxel chemotherapy.

Discussion Soft-tissue sarcomas are a diverse mix of cancers with an incidence of 10,390 new cases diagnosed annually in the United States.1 Despite aggressive treatment with surgery, radiation and chemotherapy, outcomes remain suboptimal as 3,680 (35%) soft-tissue sarcoma patients die annually.1 Death secondary to metastases is common and sites of metastases vary depending on the type of soft-tissue sarcoma with most types showing a predilection for the lungs. Metastatic involvement of the heart by soft-tissue sarcoma has been reported in the literature but most cases of cardiac involvement occur in the setting of widespread metastases.2 Our patient is among the first reported cases of an epithelioid high-grade pleomorphic sarcoma metastatic to the heart in absence of known widespread metastases. Familiarity with the unique characteristics of the soft-tissue sarcomas will enable a physician to identify expected patterns of metastatic spread. One should be suspicious of cardiac metastases in a soft-tissue sarcoma patient who suddenly develops unexplained congestive heart failure, new cardiac murmurs, arrhythmias or embolic phenomena. For such patients, metastatic cardiac disease should be included in the differential diagnosis and further evaluation with electrocardiograms, echocardiograms, and cardiac MRI should be made. Accurate imaging of cardiac cancer is very important in the multimodal medical and surgical management of metastatic cardiac [page 2]

Figure 2. Histology of atrial mass.

sarcoma.3 In this patient, cardiac metastasis was only incidentally discovered during prechemotherapy cardiac evaluation. However, several aspects of this patient’s clinical course suggested the presence of this diagnosis. The patient’s initial myocardial infarction prompted cardiac catheterization, which showed luminal narrowing assumed to be secondary to atherosclerotic disease. Yet, on repeat studies, the patient had no evidence of significant atherosclerotic disease. The patient’s infarct likely resulted from an embolic event originating from the large mitral valve vegetation or from extrinsic compression of the artery by tumor. The splenic lesions noted on CT scans likely represent distant emboli with infarction. Finally, review of the outside hospital TTE abnormalities noted after the patient’s perioperative MI indicated that he had cardiac metastases at initial presentation. A high degree of suspicion for cardiac involvement by sarcoma may have hastened a correct diagnosis.

Conclusions Management of metastatic sarcoma to the heart remains a difficult task. Some reports discuss surgical resection of cardiac metastatic lesions with variable success,4,5 while others report the use of cardiac transplantation.6 In this case, surgical excision was attempted, but the extensive infiltrating nature of the tumor prohibited complete debridement leaving systemic therapy as the only viable option. There are several generally accepted systemic therapies for metastatic sarcoma with most regimens including doxorubicin as a single agent7 or in combination with other drugs. The most widely employed combination chemotherapy regimens are doxorubicin/dacarbazine,8,9 doxorubicin/ifoxfamide/mesna10,11 mesna/doxorubicin/ifosfamide/dacarbazine,12 ifosfamide/epi [Rare Tumors 2009; 1:e1]

rubicin/mesna,13 and gemcitabine/docetaxel.14-16 However, the use of doxorubicin was felt to be contraindicated due to the depressed cardiac function in this patient. If a sarcoma expresses CD117, imatinib would be a viable treatment option due to the drug’s oral administration, favorable toxicity profile, and anti-tumor activity on some subsets of sarcoma, particularly gastrointestinal stromal tumors.17-19 Expression of this marker is felt to be favorable due to this relationship. Thus far, reports do not associate imatinib with induction of cardiac failure.20 Unfortunately our patient’s cardiac tumor did not express CD117 and the drug was not a treatment option. Since metastatic sarcoma to the heart is a rare occurrence, no prospective or randomized trials exist to help guide treatment. In fact, there are no data to show whether systemic treatment of unresectable cardiac sarcomas significantly improves duration or quality of life. In the setting of congestive or restrictive heart failure, many of the first-line chemotherapy options are not feasible for fear of therapy worsening cardiac function. In our case, gemcitabine/docetaxel chemotherapy was felt to be an active regimen with controllable toxicity and without potential devastating cardiac side effects. Tolerance to the treatment regimen thus far has been acceptable and the patient is continuing this chemotherapy.

References 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58: 71-96. 2. Catton C. The management of malignant cardiac tumors: clinical considerations. Semin Diagn Pathol 2008;25:69-75. 3. Yuan SM, Shinfeld A, Lavee J, et al. Imaging morphology of cardiac tumours. Card-

Case Report iol J 2009;16:26-35. 4. Harting MT, Messner GN, Gregoric ID, Frazier OH. Sarcoma metastatic to the right ventricle: surgical intervention followed by prolonged survival. Tex Heart Inst J 2004;31:93-5. 5. Kono T, Amano J, Sakaguchi M, Kitahara H. Successful resection of cardiac metastatic liposarcoma extending into the SVC, right atrium, and right ventricle. J Card Surg 2005;20:364-5. 6. Goldstein DJ, Oz MC, Rose EA, et al. Experience with heart transplantation for cardiac tumors. J Heart Lung Transplant 1995;14:382-6. 7. Tierney J Fea. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 1997;350:1647-54. 8. Antman K, Crowley J, Balcerzak SP, et al. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol 1993;11:1276-85. 9. Zalupski M, Metch B, Balcerzak S, et al. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas:

10.

11.

12.

13.

14.

15.

a Southwest Oncology Group study. J Natl Cancer Inst 1991;83:926-32. Edmonson JH, Ryan LM, Blum RH, et al. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol 1993;11:1269-75. Grobmyer SR, Maki RG, Demetri GD, et al. Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol 2004;15:1667-72. Elias A, Ryan L, Sulkes A, et al. Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol 1989;7:1208-16. Frustaci S, Gherlinzoni F, De Paoli A, et al. Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial. J Clin Oncol 2001;19: 1238-47. Hensley ML, Maki R, Venkatraman E, et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol 2002;20: 2824-31. Leu KM, Ostruszka LJ, Shewach D, et al. Laboratory and clinical evidence of synergis-

[Rare Tumors 2009; 1:e1]

16.

17.

18.

19.

20.

tic cytotoxicity of sequential treatment with gemcitabine followed by docetaxel in the treatment of sarcoma. J Clin Oncol 2004;22: 1706-12. Maki RG. Gemcitabine and docetaxel in metastatic sarcoma: past, present, and future. Oncologist 2007;12:999-1006. Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004;364: 1127-34. Blanke CD, Demetri GD, von Mehren M, et al. Long-term results from a randomized phase II trial of standard- versus higherdose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol 2008;26:620-5. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347:472-80. Verweij J, Casali PG, Kotasek D, et al. Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISGAGITG study 62005. Eur J Cancer 2007;43: 974-8.

[page 3]

Rare Tumors 2009; volume 1:e2

Squamous cell carcinoma of the scrotum in a Nigerian: case report Jerome E. Azike,1,2 N.O. Chukwujama,1,2 T.C. Oguike1,2 1

Department of Surgery, College of Medicine and Health Sciences, Imo State University, Orlu, Imo State, Nigeria; 2 Imo State University Teaching Hospital, Orlu, Imo State, Nigeria

Abstract Squamous cell carcinoma of the scrotum is rare and to the best of our knowledge has never been reported from Nigeria. We report on a case thought to be occupation-related in a 42-year old Nigerian taxi driver who had previously been an automobile mechanic and later a long-haul truck driver. He presented with a stage D disease and only palliation was feasible.

Case report A 42-year old taxi driver who had been a car mechanic for four years 25 years earlier presented in 2007 with a ten-year history of a small pruritic painless nodule on his ventral scrotal surface which had ulcerated but failed to heal. He infrequently washed his work-outfit while an auto-mechanic and admitted to its frequent soiling, sometimes up to his underwear, with used engine oil while at work. He took a bath at the close of work each day; however, his personal hygiene outside the workplace was good. On examination he was pale, had a foulsmelling, grotesque, fungating, ulcero-proliferative mass with rolled edges which involved the whole scrotum and proximal third of the penile shaft, extending 5 cm to the right thigh antero-medially and 3 cm of the anal verge. The scrotum was fixed to the pubis. There were bilateral inguinal lymphadenopathy involving both the vertical and horizontal chains. He looked otherwise well nourished and was ambulant. He was also rather depressed emotionally. Ultrasonography revealed a hepatomegaly and para-aortic lymphadenopathy, the largest 2.8 cm in diameter. His general condition was optimized and biopsy confirmed the diagnosis. He had palliative scrotectomy with bilateral orchidectomy and subsequently cisplatinumbased combination chemotherapy, after he had been counseled and informed consent [page 4]

obtained. Histopathological review showed scrotal squamous cell carcinoma with testicular involvement (Figure 1). He succumbed to the disease after seven months.

Correspondence: Jerome E. Azike, MBBS, FWACS, Department of Surgery, College of Medicine & Health Sciences, Imo State University, Orlu, Nigeria. E-mail: [email protected]

Discussion

Key words: cancer of the scrotum, occupational cancer, automobile mechanic, used engine oil.

The scrotum is a seven-layer pouch which invests the testes, testicular adnexae, and distal spermatic cord. The scrotal lymphatics drain into the corresponding superficial inguinal nodes. Anastomoses exist between the lymphatics of the contralateral network across the median raphe. Tumors have been reported that arise out of virtually any of the components of the scrotal wall.1 Squamous cell carcinoma of the scrotum is now exceedingly rare. It was the first malignancy linked to occupational exposure.1-2 Previously, it most commonly resulted from exposure to environmental carcinogens such as chimney soot, tars, paraffin, and some petroleum products. Currently most cases result from poor hygiene and chronic inflammation.3 Used engine oils have elevated polycyclic aromatic hydrocarbons which tend to be greater for petrol engines than for diesel engines. Prolonged and repeated contact with such oils can cause skin and scrotal cancer. Car mechanics are at potential risk from used engine oil.4 Best occupational health practices are invaluable at the workplace for those at risk to

Received for publication: 2 May 2009. Accepted for publication: 8 May 2009. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0) ©Copyright J.E. Azike et al., 2009 Rare Tumors 2009; 1:e2 doi:10.4081/rt.2009.e2

minimize exposure. Prognosis correlates with extent of nodal involvement with virtually no survivors if iliac nodes are involved.3,5 Ability to achieve a negative margin at the time of initial surgery is an important prognostic factor as adjunctive therapy such as radiotherapy or chemotherapy or both has not proven useful.1 In conclusion, the index patient presented very late when even surgery, chemotherapy and radiotherapy could not possibly offer any meaningful improvement in terms of outcome. We believe this case will raise the awareness in our environment of the existence of this disease and improve the index of suspicion among practicing surgeons and oncologists.

Figure 1. a, b, c, d. Histology of the various sections of the tumor; (a) Normal skin and contiguous areas the well differentiated squamous cell carcinoma invading the surrounding deeper tissue; (b) High magnification of the malignant squamous cells; (c) Remnants of the testicular tubules being invaded by the tumor; (d) The malignant squamous cells invading the deeper testes.

[Rare Tumors 2009; 1:e2]

Case Report

References 1. Rowland RG, Herman JR. Tumors and Infectious Diseases of the Testis, Epididymis, and Scrotum. In Gillenwater JY, Grayhack JT, Howards SS and Mitchell

ME, eds. Adult and Pediatric Urology, Philadelphia: Lippincott, Williams and Wilkins; 2002. 2. Waldron HA. A brief history of scrotal cancer. Br J Ind Med 1983;40:390-401. 3. Presti JC Jr. Genital Tumors. In Tanagho EA, McAnich JW, editors. Smith’s General Urology. New York: Mc Graw Hill 2008:375-87.

[Rare Tumors 2009; 1:e2]

4. Wyre Borough Council, Lancashire U.K., Health and Safety Factsheet – No. 12 (internet), 2002. Available from: http:// www.wyrebc.gov.uk (Cited 5th July, 2008) 5. Ray B, Whitmore WF Jr. Experience with Carcinoma of the Scrotum. J Urol 1977; 117:741-5.

[page 5]

Rare Tumors 2009; volume 1:e3

Extraosseous osteosarcoma in Ibadan: case series over a 20-year period Temitope O. Alonge,1 Henry A. Obamuyide,2 Gabriel Olabiyi Ogun3 1

Consultant Orthopedic Surgeon/Senior Lecturer, Department of Orthopedics and Trauma, University College Hospital, and College of Medicine, University of Ibadan, Ibadan, Nigeria; 2 Resident in Surgery, Department of Surgery, University College Hospital, Ibadan, Nigeria; 3 Consultant Pathologist/Lecturer, Department of Pathology, College of Medicine, and University College Hospital, Ibadan, Nigeria

Abstract Extraosseous osteosarcoma (EOO) is a rare form of sarcoma. There have been few reports of cases and outcome from an African population. Out of 112 cases of sarcomas seen at the UCH, Ibadan between 1986-2005, 5 were EOO. All presented late on account of initial excision without histology and outcomes were poor. EOO occurs in the black population of SubSaharan Africa. The outlook for these patients is still bleak.

Introduction Extraosseous osteosarcoma (EOO) is a malignant mesenchymal neoplasm that produces osteoid, bone or chondroid material and is located in the soft tissue without attachment to the skeleton as determined by imaging modalities or inspection during surgical operative procedure.1 EOO is a rare type of tumor making up only 1% of all soft tissue sarcomas2,3 and 4% of all osteosarcomas.4 Wilson reported the first case of EOO in 19415 and since then fewer than 300 cases have been reported in the English Language literature.6 The tumor is most common in middle-aged and elderly patients. A previous study showed that EOO is a doxorubicin-resistant lesion with a poor prognosis and a form of soft tissue sarcoma that should be viewed by clinicians as clinically and therapeutically distinct from osseous osteosarcoma.6 The single most important criteria for diagnosis of this tumor is the presence of neoplastic osteoid and bone; sometimes with neoplastic cartilage.1,5 The histological variants of EOO include osteoblastic, chondroblastic, fibroblas[page 6]

tic, osteoclastic or giant cell type, telangiectatic, small cell or well differentiated forms. The immunohistochemical profile includes the expression of osteocalcin and osteonectin which are specific for osseous osteosarcomas, but a study by Fanburg-Smith et al.7 showed that osteocalcin is highly sensitive for EOO neoplastic cells.1 Closely related differentials include calcified hematoma, myositis ossificans, synovial sarcoma, epithelial sarcoma, liposarcoma or malignant fibrous histiocytoma.

Methods All sarcomas recorded at our institution between January 1986 and December 2005 were compared and extraosseous variety identified. Their charts were selected and reviewed for relevant data. Out of 112 cases of osteosarcoma recorded in our hospital between January 1986 and December 2005, 5 cases were extraosseous. This series presents the 5 cases of EOO recorded at our institution during the 20-year period from 1986-2005 and this includes one patient reported previously by Ogundiran et al.8

Case Series Case #1 A 16-year-old male student who presented with a 4-year history of progressive left ankle swelling and pain. He had excision of a mass in his left ankle at a private facility without histological evaluation a year prior to presentation at the University College Hospital (UCH), Ibadan. On presentation at the UCH, examination revealed a 10x7 cm mass over the left lateral malleolus that was tender, differentially warm, with both cystic and solid areas. No significant popliteal or inguinal lymphadenopathy was noted. Laboratory studies were essentially normal. He had a local excision of the mass and the operative finding was a 10x7 cm multiloculated brownish soft tissue mass over the left lateral malleolus covered with a fibrous capsule with a pedicle arising from the ankle joint. There was associated erosion of the adjoining bone and the histology report revealed soft tissue osteosarcoma. He was lost to follow-up but represented two years later with recurrence.

Case #2 A 70-year-old man who presented with a 1-year history of a painful scalp swelling associated with bleeding. A similar swelling had recently grown on the right temporal region prior to presentation at the UCH. Incisional [Rare Tumors 2009; 1:e3]

Correspondence: Temitope O. Alonge, Consultant Orthopedic Surgeon/Senior Lecturer, Department of Orthopedics and Trauma, University College Hospital and College of Medicine, University of Ibadan, Ibadan, Nigeria E-mail: [email protected] Key words: extraosseous osteogenic sarcomas, Sub-Saharan Africa, histology. Received for publication: 3 May 2009. Accepted for publication: 5 May 2009. Contributions: TOA conceived, designed, supervised and helped to draft the manuscript and approved the final version; HAO participated in the design, gathered the data, drafted the manuscript and approved the final copy; GOO reviewed the manuscript for critical content and approved the final copy. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0) ©Copyright T.O. Alonge et al., 2009 Rare Tumors 2009; 1:e3 doi:10.4081/rt.2009.e3

biopsy and histology of the initial mass at the source of referral revealed an extraskeletal osteosarcoma. Examination revealed a 15x7 cm left frontoparietal mass with overlying scar. He also had a smaller temporal mass. Both were tender and hemorrhagic. Skull X-ray showed an extensive soft tissue swelling extending from the left frontal to the left parietal region. There was an associated increase in the density of the underlying subcutaneous tissue but no calcifications. Routine laboratory studies were within normal limits. He had radiotherapy but later represented with facial recurrence after two months.

Case #3 A 21-year-old man with a 1-year history of a painful left upper back swelling and 4 month history of progressive weakness of both legs which progressed to paraplegia. He had a biopsy of the mass at a private facility five months before presentation at the UCH but no histological evaluation of the mass was carried out. Examination at the UCH revealed a left periscapular fluctuant mass with overlying hypertrophic scar which was also attached to underlying structures. He also had a T5 paraplegia. Chest X-ray showed a left paravertebral soft tissue mass lesion with evidence of destruction of the 5th rib and left sided pulmonary effusion. Urinary Bence Jones protein was negative, the full blood count was normal but the ESR was elevated. Two pleural aspirates were hemorrhagic and CT myelography showed an isolated left sided isodense lesion

Case Report in the spinal cord with extensive erosion of the ribs as well as infiltration into the left pleural cavity. Incisional biopsy of the left chest wall lesion revealed osteogenic sarcoma. Chemotherapy was to be administered but the patient could not afford it and he was subsequently lost to follow-up.

Case #4 A 20-year-old man who presented with an 11-month history of progressive soft tissue swelling of the right thigh associated with pain. The soft tissue mass was excised initially at a private facility but no histological evaluation of the specimen was carried out. Examination at the UCH revealed a massively swollen right thigh with multiple areas of ulceration. Biopsy and histology at the UCH revealed extraosseous osteogenic sarcoma. The patient was given a hemostatic dose of radiotherapy but was subsequently lost to follow-up.

Case #5 A 40-year-old housewife who presented with a 20-month history of painful left breast lump which had been excised previously at another hospital without histological evaluation, but recurred eight months before presentation at UCH. Examination revealed a globular left breast mass which was warm, multinodular, fixed to the pectoralis fascia and which measured 20x18 cm. There was associated ipsilateral axillary lymph node enlargement. Other systems were essentially normal. A clinical diagnosis of locally advanced cancer of the left breast was made. A core needle biopsy revealed an osteogenic sarcoma which was confirmed by the histology of the mastectomy specimen. She was scheduled for postoperative radiotherapy but defaulted and died six months post-mastectomy.

Discussion The exact cause of EOO is unknown and it is presumed to be mainly an idiopathic condition. Unlike osseous osteosarcoma (OOO), it has not been documented in siblings or in association with hereditary retinoblastoma but risk factors associated with the development of this tumor include previous exposure to radiation, such as X-rays and radioactive thorium dioxide (Thorothrast).9 Other associated factors suggested in literature in the development of EOO include trauma, the assessment and evaluation of which is difficult and controversial.10 Some cases have been associated with intramuscular injection11 while some EOO have been reported to follow myositis ossificans.12,13

A common mode of presentation is as a swelling of insidious onset with associated pain in one-third of patients but often the tumor grows to a large size before the patient seeks medical advice.14 It may ulcerate with growth, but that usually occurs after biopsy or attempts at excision and the tumor usually occurs in middle-aged and elderly patients.15 The anatomic location of EOO is usually the muscles of the thigh, which are the most commonly affected; the large muscles around the pelvic and shoulder girdles and the retroperitoneum, though rare locations like the thyroid gland, penis, mediastinum and the kidney are occasionally encountered.1,12,15,17,18 At the Memorial Sloan-Kettering cancer center, a review of 48 cases of EOO during 1950-1983 showed a median age at diagnosis of 51 years (range, 6-80 years).14 The most common primary sites were the thighs and buttocks (54.2%) with preponderance in patients aged 50 years and above and slightly more common in males (58%) than in females.12 In the report by Chung and Enzinger, EOO occurs principally as a soft tissue mass involving an extremity with a predilection for the thighs (lower extremity 46.6%; upper extremity 20.5%) and the retroperitoneum in 17%. In most cases, the tumor was deep seated and firmly attached to the fascia, but occasionally they are freely movable and confined to the subcutis or dermis. The duration of symptoms prior to presentation ranges from two weeks to 25 years (median six months). Prior trauma to the site was observed in 12.5% and irradiation to the affected site in 5.7% of cases.12 Although osseous osteosarcoma (OOO) occurs predominantly in the first two decades of life, EOO are rarely encountered under 40 years of age.15 However, in this case series, 3 of the 5 patients were aged 21 years and under in keeping with other cases which have been documented in the pediatric age group.16 Imaging modalities by either plain conventional radiograph, CT scan or MRI of the soft tissue is essential to rule out any continuity of tumor with bone. If adjacent bone shows radiological changes of involvement by the tumors, it is most likely to be originating from the bone rather than from the soft tissue. A soft tissue mass with spotty to massive calcification without adjacent bone involvement is one of the classic radiographic appearances of this tumor.15 EOO is a difficult disease to treat and the optimum therapy has not been fully determined due to the relative rarity of these tumors. Advances in the care of these patients will require disease-specific clinical trials.6 A wide local excision, with at least 5cm margin of normal tissues should be the treatment of choice.15 The local recurrence-free survival rate observed in a recent study6 suggests that patients with extremity EOO can be treated with limb salvage operative procedures. [Rare Tumors 2009; 1:e3]

However, if these are not possible due to the anatomic location of the tumor, amputation is recommended.19 In a review of 48 cases of EOO and 39 trials of chemotherapeutic agents reported by Sordillo et al. they showed that no patient had a major response.14 The average 5-year survival rate in 5 previous studies ranges from 1525%2,9 and the response to multimodality therapy is not as good as for OOO.14 Tumor size (50 mitotic figures/10 high power fields) and extensive geographic tumor necrosis (Figure 3). The cells were arranged in cohesive sheets, focally forming anastomosing vascular channels with prominent hob-nailing and scattered intracytoplasmic lumina. The tumor infiltrated the surrounding hepatic parenchyma with entrapment of benign bile ducts and hepatocytes. Lymphovascular invasion was not identified. Positive immunohistochemical stains included: CD31, CD34, Podoplanin (D2-40), EMA, and Factor VIII Ag, while Keratin CAM 5.2, Keratin MAK 6, Keratin AE1-AE3, and HepPar1 were negative. The immunohistochemical findings support vascular differentiation with high-grade morphology, extensive necrosis, and epithelioid morphology characteristic of an epithelioid angiosarcoma.

Acute abdominal bleeds occur spontaneously or following percutaneous biopsy in 15-27% of cases, and thus hepatic angiosarcoma should be considered in the differential workup of a patient with spontaneous hemoperitoneum. Associated laboratory findings tend to be nonspecific, although more than half of the patients have unexplained thrombocytopenia and elevated alkaline phosphatase levels. The remaining liver function tests are normal and tumor markers are negative. To date, there has not been any association with known viral markers identified.3 Radiographically, hepatic angiosarcomas have a varying appearance. There may be one dominant focus or multiple masses that correlate with the gross appearance. Metastases are

common at the time of presentation, with the most usual metastatic sites being the lung and spleen. Unenhanced CT images of these masses are observed to be hypodense when compared to normal hepatic parenchyma, while lesions observed with contrast-enhanced CT may be either hypo- or hyperdense, depending on the presence of hemorrhage within the tumor. Optimal imaging techniques for the diagnosis of hepatic angiosarcoma include unenhanced, multiple-phase enhanced, and delayed CT or MR imaging to adequately capture all phases of the tumor and eliminate potentially benign mimickers.4 Pathologically, hepatic angiosarcomas of the deep soft tissue and in visceral locations generally are high-grade malignant neoplasms

A

Discussion Angiosarcomas are rare, malignant vascular tumors that may occur in any area of the body, but are most common in the region of the head and neck. Sarcomas of the soft tissues constitute less than 1% of all cancers, with angiosarcomas compromising approximately 2% of soft tissue sarcomas. Predisposing factors include a prior history of radiation therapy, chronic lymphedema, exposure to Thorotrast (thorium dioxide, a radiologic contrast medium), use of anabolic steroids or synthetic estrogens, insecticide exposure, and long-term exposure to vinyl chloride. Typically angiosarcomas are high-grade, aggressive tumors that tend to recur and metastasize despite treatment. Current therapies include surgical resection, with radiation therapy and/or adjuvant chemotherapy depending on the anatomic location and size. Overall prognosis is poor for soft tissue angiosarcomas, with a five-year survival reported in the range of 10-35%.1 Hepatic angiosarcoma is very rare, constituting 2% of all primary hepatic cancers. The average incidence of hepatic angiosarcoma is estimated to be 25 cases per year in the United States. There is a male to female predominance of 3:1 with the majority of patients diagnosed in their sixth decade of life. Approximately 60% of patients have evidence of metastatic disease at the time of diagnosis.2 Clinical presentation is nonspecific typically, with presenting symptoms including abdominal pain, weakness, fatigue, and weight loss; while physical examination findings may include hepatomegaly, ascites, and jaundice.

B

C

Figure 1. CT images showing regression rather than progression of the liver lesion, (A) initial presentation in 2003, (B) diminished to 3.0 cm in 2007, and (C) progression in 2008.

[Rare Tumors 2009; 1:e33]

[page 99]

Article that have an epithelioid to spindled appearance. As in the current case, angiosarcomas of the liver are characterized by nests and solid sheets of malignant cells of high nuclear grade that form irregular vascular channels and exhibit invasion of the adjacent liver parenchyma. Tumor necrosis is a common finding. Grossly, the tumor may appear with one of four different growth patterns: multiple nodules, a single dominant mass, mixed patterns of a dominant mass with smaller nodules, or an infiltrating micronodular tumor.2 For the past 40 years, a link has been established between hepatic angiosarcoma and environmental toxins, including Thorotrast, vinyl chloride, arsenic, radiation, and exogenous estrogens or anabolic steroids. However, in nearly 75% of cases, no causative agent is identified. In all cases of environmental exposure, a prolonged latency period has been established of 20-30 years on average, yet the gross and microscopic pathology of idiopathic angiosarcomas and those caused by environmental toxins remain identical.5 Treatment for hepatic angiosarcoma is delayed often owing to the nonspecific symptoms with which the tumor typically presents. The average time until diagnosis is six months from the initial presentation to a health care professional; however, many patients do not seek medical attention for several months following the onset of symptoms. Thus, a large tumor size and the presence of metastases are common on diagnosis. Median survival time following diagnosis is six months, with near 100% mortality by one year. Improved prognosis has been observed with a single tumor mass, a smaller tumor size, lack of metastases, a low-grade lesion, and negative surgical resection margins; however, owing to the infrequent nature of the tumor, this still has to be quantified.2 Given the poor prognosis for patients diagnosed with hepatic angiosarcoma, surgical resection is the only definitive treatment; however, this is not possible in many cases either because of multifocal disease or the extent of the liver involvement.6 Adjuvant treatment remains undefined owing to the rarity of the tumor. Chemotherapy has not been well studied except on a case report basis, and in general angiosarcomas are resistant to radiation therapy. Liver transplantation has been attempted, but the tumor recurrence rate remains high (64%) and longterm survival has not been observed (average survival time, 23 mth).7 If definitive resection can be achieved prior to microscopic spread of the disease, long-term survival is possible. This has been reported in three adult cases that were without evidence of recurrence at 64 months, 38 months, and 10 years.3 Although our patient’s tumor was amenable to resection, the associated hepatic fibrosis documented by previous core biopsies and the [page 100]

Figure 2. Gross liver resection specimen.

Figure 3. Hepatic mass and adjacent liver parenchyma with associated capsular disruption and inflammatory reaction (H&E stain, 40x magnification).

clinical diagnosis of portal hypertension portends a worse prognosis. Pathologic examination results including high-grade nuclear features with epithelioid morphology are additional unfavorable findings. Paradoxically, the radiographic finding of a tumor mass that had been present for the previous five years in our patient would suggest a less aggressive clinical course of the disease. In hindsight, this patient’s splenomegaly appears to be a result of periportal fibrosis and the splenomegaly and thrombocytopenia were long standing. These clinical findings have been reported previously as precursors to the development of angiosarcoma in other patients. An analysis of patients with significant polyvinyl chloride exposure by Lee et al. (1996)8 described a patient with a history of splenomegaly and thrombocytopenia, who later presented with esophageal varices and presinusoidal hypertension via a screening program. Ultimately a core needle biopsy lead to the diagnosis of presinusoidal hepatic fibrosis. The patient later sustained a fatal gastrointestinal hemorrhage, and at autopsy was found [Rare Tumors 2009; 1:e33]

to have primary hepatic angiosarcoma.8 In the case of our patient, liver biopsies of the uninvolved liver in 2003 failed to demonstrate characteristic periportal fibrosis, but this was identified on repeat liver biopsies in 2007, after the patient developed esophageal varices. We are unaware of any previous reports suggesting such a prolonged natural history of a hepatic angiosarcoma. This case may represent the possibility of malignant transformation of a lower grade vascular neoplasm, such as hepatic epithelioid hemangioendothelioma, to a more aggressive angiosarcoma. While angiosarcoma may present with spontaneous and often catastrophic intraperitoneal bleeding, this patient’s spontaneous intraperitoneal bleed was five years prior to eventual resection of the tumor. The patient had well-documented radiographic gradual reduction in size of the lesion over four and a half years, before its rapid enlargement just prior to excision; a very unusual progression in the natural history of a high-grade angiosarcoma, thus raising the possibility of malignant transformation of a benign precursor.

Article

References 1. Mark RJ, Poen JC, Tran LM, et al. Angiosarcoma. A report of 67 patients and a review of the literature. Cancer 1996; 77:2400-6. 2. Mani H and Van Thiel DH. Mesenchymal tumors of the liver. Clin Liver Dis 2001;5: 219-57, viii. 3. Molina E and Hernandez A. Clinical mani-

festations of primary hepatic angiosarcoma. Dig Dis Sci 2003;48:677-82. 4. Koyama T, Fletcher JG, Johnson CD, et al. Primary hepatic angiosarcoma: findings at CT and MR imaging. Radiology 2002;222: 667-73. 5. Louagie YA, Gianello P, Kestens PJ, et al. Vinylchloride induced hepatic angiosarcoma. Br J Surg 1984;71:322-3. 6. Ozden I, Bilge O, Erkan M, et al. Five years and 4 months of recurrence-free survival

[Rare Tumors 2009; 1:e33]

in hepatic angiosarcoma. J Hepatobiliary Pancreat Surg 2003;10:250-2. 7. Maluf D, Cotterell A, Clark B, et al. Hepatic angiosarcoma and liver transplantation: case report and literature review. Transplant Proc 2005;37:2195-9. 8. Lee FI, Smith PM, Bennett B, et al. Occupationally related angiosarcoma of the liver in the United Kingdom 19721994. Gut 1996;39:312-8.

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Rare Tumors 2009; volume 1:e34

Colonic cancer in adolescents. A report of three cases M.A.C. Odike,1 A.E. Dongo,2 E.F. Alufohai,2 A.I. Odike3 1

2

Departments of Pathology, Surgery and Pediatrics, Ambrose Alli University, Ekpoma, Edo State, Nigeria

genetic predisposition, including hereditary polyposis and non-polyposis syndromes.4,7,11 Three cases of colonic cancer amongst Nigerian adolescents aged 17 and 19 years are presented. These are uncommon findings, and hence should be of interest to clinicians to increase their index of suspicion as early cases are potentially curable.

Case #1

Abstract Colorectal cancer is a common malignant neoplasm in adults, with a peak incidence of 60-79 years. About 1 million cases of the disease and half a million deaths associated with it are reported world-wide each year. Colorectal cancer, however, is very uncommon in children and adolescents. This is a presentation of 3 cases of colon cancer in Nigerians aged 17 and 19 years. Two of them were adenocarcinoma and the other leiomyosarcoma. The pathogenesis and aspects of management are discussed.

Introduction Colon cancers are the second most common cancer in both men and women in America.1,2 World-wide they are the third major cause of cancer for men and the fourth most common cause of cancer for women.2,3 They are the second most common causes of cancer-related deaths in developed countries and the most common gastro-intestinal carcinoma.4-6 The incidence is highest in the westernized countries of North America, Northern Europe, Australia, and New Zealand. Intermediate rates are found in Southern Europe, and low rates in Africa.2,4 Reports have shown that close to 1 million new cases of colo-rectal cancer and nearly half a million deaths associated with colorectal cancer are reported world-wide each year.4,7 About 98% of them are primary adenocarcinomas.4,8,9 The remaining 2% are made up of carcinoid, mesenchymal and lymphoid tumors. These figures have decreased in the West due to increased rate of screening and polyp removal.10 The peak incidence for colorectal carcinoma is put at between ages 60 and 79 years, with fewer than 20% occurring before the age of 50 years.8 According to another author, 90% of patients are older than 50 years; with highest incidence rates in individuals aged 70 to 85 years.4 Very occasionally, it may affect much younger adults from the age of 20 years.6 The risk factors for development of colo-rectal cancer include age, a diet rich in fat and cholesterol, inflammatory bowel disease, and [page 102]

OS, a 19-year old male student presented to the surgical out-patient (SOP) department of the Irrua Specialist Teaching Hospital (ISTH) with complaints of passage of bloody and watery stools, abdominal pain, lower abdominal distension and vomiting of between one week and three months duration. The abdominal pain was intermittent and colicky. He reported mild weight loss. There was no family history of similar illness. Physical examination showed a mildly dehydrated young man with tense and distended abdomen, visible peristaltic waves, and hyperactive bowel sounds. He was admitted, and after one week the abdominal distension worsened and he developed constipation. Digital rectal examination and proctoscopy showed an empty rectum with a circumferential and fungating irregular, firm mass about 5 cm from the anal verge. An impression of intestinal obstruction secondary to rectal tumor was made, and incisional biopsy taken for histology. The histopathology diagnosis was adenocarcinoma. The patient was offered a dysfunctioning (loop) sigmoid colostomy after decompression of the dilated sigmoid colon. He was commenced on 5flurouracil (5FU) and adriamycin following confirmation of mesenteric lymph node involvement in the colostomy biopsy specimen. He received 5 courses of chemotherapy and was referred to another center for radiotherapy. The patients has responded well to this.

Case #2 EB was a 17-year old student. She presented to the SOP of ISTH, six weeks after appendicectomy in a private hospital, with colicky abdominal pain, vomiting, weakness, and discharge from the appendicectomy scar of about two weeks duration. Family and social history was not significant. Physical examination revealed a fixed and firm, non-fluctuant mass of about 10x11 cm in the right iliac fossa region of the abdomen. Abdominal ultrasound found a large intra-abdominal mass, and suggested retained foreign body, to rule out infected appendix stump. At exploratory laparotomy, an infected appendicectomy wound and a firm to hard cecal pole mass were observed. The mass measured about 15x12 cm and was associated with about 20 mls of abscess. Right hemi-colectomy was done and histopathology examination requested. The request was never received by the laboratory. The patient recov[Rare Tumors 2009; 1:e34]

Correspondence: M.A.C. Odike, Ambrose Alli University, Ekpoma, Edo State, Nigeria. E-mail: [email protected] Key words: colon cancer, adolescents. Received for publication: 21 June 2009. Revision received: 17 July 2009. Accepted for publication: 30 July 2009. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright M.A.C. Odike et al., 2009 Rare Tumors 2009; 1:e34 doi:10.4081/rt.2009.e34

ered and was discharged home. Two months post-operation, she developed a nodule on the anterior abdominal wall over the laparotomy scar. This was thought to be a pyogenic granuloma. A repeat abdominal ultrasound reported an anterior abdominal wall mass and enlarged inguinal lymph nodes, and made an impression of rhabdomyosarcoma. The lump was excised and sent for histopathology examination, together with the hemi-colectomy specimen. Both of them showed similar histologic features composed of malignant glands and cells within fibro-cellular stroma. A diagnosis of colonic adenocarcinoma with metastasis to the anterior abdominal wall was made. The patient was commenced on 5-FU and referred for radiotherapy, after receiving 5 courses of chemotherapy. She died about two and a half years after diagnosis

Case #3 A 19-year old male, PO, presented to the emergency room of Joe Alufohai Medical Center, Sabongida-Ora on 26/10/07 with a twoweek history of abdominal pain and vomiting. On examination he was found to be in painful distress and to have moderate rebound tenderness and guarding. This was worse over the right lower quadrant of the abdomen. A diagnosis of acute appendicitis was made and the patient taken in for emergency appendicectomy. Findings at surgery included a dilated, longish and coiled appendix; dilated terminal ileum; and an atrophic cecum with a localized firm mass. In view of these findings, an additional intra-operative impression of congenital hypertrophy of the ileo-cecal valve was considered and a limited right hemi-colectomy performed. The specimen was sent for histology. The patient did well and was discharged to the out-patient clinic two weeks after surgery. The histopathology diagnosis was leiomyosarcoma, together with acute appendicitis. The patient has yet to honor his out-patient appointment, six months after discharge.

Case Report

Discussion Almost all bowel cancers arise in the colorectum, since the small intestine is strikingly free from cancer risk.6 Colon cancer is a silent killer, often causing no recognizable symptoms until it is too late.3 Most of them occur sporadically in the absence of well-defined familial syndromes. Regardless of the inciting event, a well-described set of genetic alterations occurs that ultimately leads to colorectal malignancy.8 Fitzgibbons et al. described a genetic factor found in young patients belonging to Scandinavian families with the Lynch syndrome.12 The vast majority of colorectal cancers are adenocarcinomas, which arise from pre-existing adenomatous polyps.6 This adenoma-carcinoma sequence is a well-characterized clinical and histopathologic series of events with which discrete molecular genetic alterations have been associated.7 However, about 30% of colorectal carcinomas arise from flat lesions without evidence of adenomatous precursors.6 These suggest that some dysplastic lesions can degenerate into malignancy without passing through a polypoid stage.8 This particularly occurs with cancers of the proximal colon and rectum.6 Two of the cases being reported were in the proximal colon; the third was in the rectum. Sebbag et al. did not consider heredity to be involved in the pathogenesis of colon cancer.13 More recently though a known genetic link was described in first degree biological family members of persons with colon cancer.3 They have 3 times greater risk of developing colon cancer than the general population. However, 80% of colon cancers strike people without genetic connection to the disease.3 No family history of similar illness was obtained from any of the index patients. Vogelstein and colleagues identified a number of very important genetic alterations that contribute, through their multiplicity over the years, to the eventual development of colorectal cancer.14,15 These are grouped into two pathogenetically distinct pathways that are believed to be responsible for the development of colon cancer.16 Both pathways involve the stepwise accumulation of multiple mutations. The first pathway (APC/β-caterin pathway) is characterized by chromosomal instability that results in accumulation of mutations in a series of oncogenes and tumor suppressor genes. These include mutations of the adenomatous polyposis coli (APC) gene and K-RAS gene, and loss of SMAD4 (formerly called DPC4 – deleted in pancreatic cancer – gene) and p53 genes.7,8 The morphologic evolution of the lesion is through a localized colon epithelial proliferation to formation of small adenoma that progressively enlarge, become more dysplastic, and ultimately develop into invasive cancer

(the adenoma-carcinoma sequence). The second pathway (microsatellite instability pathway) is characterized by inheritance of a mutation in one of several genes involved in DNA mismatch repair, which are MSH2, MLH1, MSH6, PMS1 and PMS2. It is involved in 1015% of sporadic cases of colon cancer and in the hereditary non-polyposis colonic cancer (HNPCC or Lynch) syndrome.6-8 Inheritance in this type of cancer is autosomal dominant. Affected patients also carry an increased risk of cancers of the stomach, ovaries, breast and uterus. The colon cancers in this syndrome tend to develop as flat lesions rather than as polyps. Cancers arising through this pathway occur at a younger age, usually before 45 years.6 Unlike in the adenoma-carcinoma sequence, this pathway does not produce identifiable morphologic correlates. These pathogenic pathways, which involve stepwise accumulation of mutations, explain why colorectal cancer is a disease of adults. It is rare in patients under 40 years of age, and even rarer in younger age groups.17 Of the 1,250 cases seen by Sebbag et al. over a 25-year period, only 3 (0.24%) were under 19 years.13 It is said that when colorectal cancer is found in a young person, pre-existing ulcerative colitis or one of the polyposis syndromes must be suspected.8 None of our cases had any of these. Environmental factors, especially dietary practices, have been implicated in the observed striking geographic contrasts in incidence. People who eat high calorie, high fat (Western) diets are at higher risk than people who eat balanced low fat, high fiber (Eastern) diets.3,18 This is partly because fiber increases the bulk and the transit time of stool. This does not allow enough time for both bacterial breakdown of bile salts into carcinogenic lithocholic and deoxycholic acids, and their contact with colonic mucosa.2 It had been mentioned that low fecal pH had a role to play in the genesis of colon cancer. Also the role of obesity in colorectal cancer has been discussed.20 There is a well-known link between obesity and a Western diet. Japanese and Polish families who migrated from their low risk areas to the US acquired, over the course of 20 years, the rate prevailing in their new environment.6 They had adopted the dietary practices of their hosts.8 Dietary factors account for 90% of the risks for bowel cancer.21 A Western-type dieting has become very common with us in Africa, even without migrating. This may account for why the incidence in black Africans is increasing, especially in the major urban cities.2 Its introduction to our children very early in life may be an important influence when combined with other environmental/racial/social factors peculiar to us, which have not been studied. After all, black Americans are said to be more prone to developing colon cancer than their white counterparts.22 Apart from this, a possi[Rare Tumors 2009; 1:e34]

ble increased risk among lower socioeconomic groups especially in the third world has been suggested.23,24 This is related to poor nutrition or chronic gastro-intestinal infections, such as amoebiasis and schistosomiasis, which are thought to be associated with an increased incidence of malignancy. All three cases being presented belonged to the lower socioeconomic group. None of them was immunosuppressed. Their exposure to chronic gastrointestinal infestations was not determined. Colon cancers progress slowly and may be asymptomatic for as many as five years or until a much later phase.9 However, patients usually have occult blood losses from their tumor.4 It is likely that the index tumors started while the patients were still in the pediatric age group. Most studies suggest a delay in diagnosis with an associated deleterious effect on outcome. This is because many of the clinical features are similar to those found in common childhood problems such as intussusception, appendicitis, gastro-enteritis and simple constipation.23 Two of the presented cases were initially thought to be appendicitis. This is understandable considering the rarity of colon cancer in children/adolescents. Treatment must be aggressive and include a combination of surgery and adjuvant chemotherapy. The surgical resection must be as radical as feasible for growth.13 Both systemic and loco-regional chemotherapy, such as intrahepatic, intra-arterial for liver metastasis, have a role.7 Where technically feasible, resection of metastatic deposits in the lungs or liver is advisable.25,26 The chemotherapeutic agents in use include 5-FU, irinotecan, leucovorin, and the more recent anti-vascular endothelial growth factor, bevacizumab.7 Radiotherapy finds use in cases of rectal cancer to reduce the risk of local recurrence. When tumors are detected early, 90% of patients survive at least five years after diagnosis and treatment.27 This is not the case for adolescents where it carries an extremely poor prognosis, owing to late diagnosis and aggressive tumor biology.23

Conclusions Colorectal cancer remains a leading cause of death from cancer in adults, especially in the Western world. It is a very rare disease in children and adolescents. Even so, colon cancer in the young is of great concern, especially since screening strategies are focused on older patients.17 Progress has been made in understanding the molecular basis of its predisposition and progression. Efforts are being made on to develop better treatment and preventive approaches, and better screening strategies. Such screening strategies must incorporate [page 103]

Case Report children and adolescents since they are not immune to colorectal cancers, as demonstrated by this report. As Sebbag et al. put it, the distribution pattern of colorectal carcinoma appears to have changed.13 There is no point waiting until older age to check for risks.

9. 10. 11.

References 12. 1. Mansell DE. Colon Polyps & Colon cancer. http://www.personalweb.sunset.net. 2. Archampong EQ, Tandoh JFK, Nwako FA, et al. Malignant tumours of the colon and rectum. In: Badoe EA, Archampong EQ and Rocha-Afodu JT (eds). Principles and Practice of Surgery including Pathology in the Tropics. 3rd ed. Ghana Publishing Corporation, Accra 2000; pp 670-82. 3. Colon cancer – A Pain in The Butt. http://www.coloncancer-info.com 4. Hassan I. Colon adenocarcinoma. http://www.emedicine.com/radio/topic182. htm. 5. Torpy JM, Lynm C,Glass RM. Colon cancer screening. JAMA 2006;295:1208. 6. Rhodes J. Bowel cancer. http://www.netdoctor.co.uk/cancer/index.shtml. 7. Wafik SE. Colon Cancer, Adenocarcinoma. http://www.emedicine.com/med/topic413.h tm. 8. Liu C, Crawford JM. Tumors of the Colon and Rectum. In: Kumar V, Abbas AK and

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Fausto N (eds). Robbins and Cotran Pathologic Basis of Disease. 7th ed. Elsevier Saunders, Philadelphia 2004; 85768. National Cancer Institute. http://www.cancer.gov. Johnson RW. Colorectal cancer. http://www.rwjuh.edu/health_information. Desai PB. Carcinoma of the colon. http://www.indiansurgeons.com. Fitzgibbons R Jr, Lynch HT, Stanslav GV. Recognition and treatment of patients with hereditary non-polyposis colon cancer (Lynch syndrome I and II) Ann Surg 1987;206:289-95. Sebbag G, Lantsberg L, Arish A, Levi I, Hoda J. Colon carcinoma in the adolescent. Pediatr Surg Int 1997;12:446-8. Kinzler KW, Vogelstein B. Lessons from hereditary colo-rectal cancer. Cell 1996;87: 159. Glinghammar B, Rafter J. Carcinogenesis in the colon: interaction between luminal factors and genetic factors. Eur J Cancer Prev 1999;8:S87-94. Jass JR. Pathogenesis of colo-rectal cancer. Surg Clin N Am 2002;82:891. Domergue J, Ismail M, Astre C, et al. Colorectal carcinoma in patients younger than 40 years of age: Montpellier Cancer Institute experience with 78 patients. Cancer 1988;61:835-40. Kim Y. AGA technical review: Impact of dietary fiber on colon cancer occurrence. Gastroenterology 2000; 118:1235-57.

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19. Walker AR, Walker BF, Walker AJ. Fecal pH, dietary fiber intake and proneness to colon cancer in four South African population. Br J Cancer 1986;53:4895-8. 20. Siegel RL, Jemal A, Ward EM. Increase in incidence of colorectal cancer among young men and women in the United States. Cancer Epidemiol Biomarkers Prev 2009;18:1695. 21. Hill MJ. Mechanisms of diet and colon carcinogenesis. Eur J Cancer Prev 1999;8:958. 22. O'Keefe SJ, Chung D, Mahmoud N, et al. Why do African Americans get more colon cancer than Native Africans? J Nutr 2007;137:175-82. 23. Shankar A, Whelan J, Renaut AJ, Taylor I. Colo-rectal cancer in adolescents. Ann R Coll Engl 1999;81:100-4. 24. Ming-Chai C. Colorectal cancer and schistosomiasis. Lancet 1981;2:971-3. 25. Wilking N, Petrelli NJ, Herrera L, et al. Surgical resection of pulmonary metastasis from colorectal adenocarcinoma. Dis Colon Rectum 1985; 28:562-4. 26. Scheele J, Gall FP, Wopfner F, et al. Surgical treatment of liver metastasis of colorectal cancers. Fortschr Med 1985;103: 577-83. 27. Treatment for colon cancer. http://www. coloncancer-info.com/treatmentforcoloncancer.html

Rare Tumors 2009; volume 1:e35

Tumors and tumor-like lesions of the heart valves Shi-Min Yuan,1,2 Hua Jing,2 Jacob Lavee1 1

Department of Cardiac and Thoracic Surgery, The Chaim Sheba Medical Center, Tel Hashomer Israel; 2Department of Cardiothoracic Surgery, Jinling Hospital, School of Clinical Medicine, Nanjing University, Nanjing, Jiangsu Province, People’s Republic of China

Abstract Valvular tumors and tumor-like lesions may have similar morphological and clinical characteristics, and may place the patients at a high risk of stroke in different ways. From January 2004 to June 2008, 11 patients underwent surgery for a suspected valvular tumor. Valvular tumor and tumor-like lesions accounted for 0.32% of adult cardiac operations. Five (45.5%) valvular lesions were papillary fibroelastomas, one (9.1%) was myxoma, 2 (18.2%) were organized thrombi, and 3 (27.3%) were calcification lesions. There was a total of 5 (45.5%) atrioventricular valve lesions, 4 arising from the atrial side of the leaflets, and one from the ventricular side. All 5 (45.5%) semilunar valvular lesions were from the aortic valve. One (9.1%) lesion originated from the chorda tendinea of the mitral valve. All leaflet lesions were resected by a simple shave technique, and all the patients recovered favorably. Valvular tumor and tumor-like lesions are rare. Pre-operative differential diagnoses among these valvular lesions pose important clinical implications for appropriate treatment for the underlying diseases. Prompt therapeutic measures in view of the underlying diseases of the valvular lesions are essential to prevent potential embolic events.

Patients and Methods The records from January 2004 to June 2008 for tumors and tumor-like lesions involving the heart valves were reviewed. The lesions mainly included valvular papillary fibroelastoma, valvular myxoma, valvular thrombus and valvular calcification. The diagnoses of the tumors and tumor-like lesions were made by echocardiography before operation and confirmed by surgery and histopathology. Vegetations of the heart valves subjected to infective endocarditis were easily distinguished from the tumors and tumor-like lesions, and were, therefore, excluded from this study. Size of the valvular lesions was expressed as mean ± SD.

Results

Correspondence: Hua Jing, Department of Cardiothoracic Surgery, Jinling Hospital, School of Clinical Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, People’s Republic of China. E-mail: [email protected] Jacob Lavee, Department of Cardiac and Thoracic Surgery, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel. E-mail: [email protected] Key words: cardiac myxoma, cardiac papillary fibroelastoma, differential diagnosis, heart valve, intracardiac thrombus, surgical resection. Received for publication: 20 August 2009. Accepted for publication: 24 August 2009. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright S-M Yuan et al., 2009 Rare Tumors 2009; 1:e35 doi:10.4081/rt.2009.e35

Clinical presentation From January 2004 to June 2008, 11 patients underwent surgery in this institute for a suspected valvular tumor, covering 32% of 3,412 adult cardiac surgical patients in the same period. Patients’ clinical characteristics were listed in Table 1. There were 7 males and

4 females, aged 50.91±15.21 (31-78) years. All patients had a good left ventricular function with an ejection fraction of 61.82±5.13 (5575) percent. One patient (9.1%) was asymptomatic, 5 (45.5%) manifested shortness of breath, fatigue and weakness, 2 (18.2%) pre-

Figure 1. Case #5. Aortic valvular papillary fibroelastoma. (A) Long-axis view, and (B) short axis view of transesophageal echocardiography showed a dense, lobulated, highly mobile mass (arrow) extending 1.2 cm attached to the noncoronary cusp.

Introduction Cardiac valve tumors are rare. Fibroelastoma is the most common valvular tumor, followed by myxoma. Atypical valvular lesions, such as organized thrombus,1 valvular calcification2 and valvular abscess3 may develop symptoms and present morphological features similar to those of the valvular tumors. We report on 11 patients who underwent a valvular lesion resection in this institute, and discuss the clinical implications.

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[page 105]

Article sented with vertigo or dizziness, 2 (18.2%) had chest pain, one (9.1%) had lumbago. The symptomatic patients had a disease course of 3.11±7.36 (0.25-24) months. The 2 patients who had valvular thrombus were associated with cardiac or non-cardiac diseases. One had a history of cheek squamous cell carcinoma, and polycythemia vera associated with severe aortic valve stenosis and coronary artery disease, and the other had a history of peripheral embolic events, carotid artery stenting for carotid artery stenosis, patent foramen ovale and coronary artery disease.

Diagnosis Diagnoses were made by echocardiography pre-operatively in all cases, and none of them were noted incidentally by surgical investigation. There was a total of 10 (90.9%) left-sided lesions, and one (9.1%) right-sided lesion. Echocardiographic appearances of these lesions were round, soft, lobulated and highly mobile in 4 papillary fibroelastomas (Figure 1) and one myxoma, round and dense in one papillary fibroelastoma, thick, dense and less mobile in both thrombi (Figure 2), and thick, dense and non-mobile in 3 calcification lesions

(Figure 3). All 6 tumors (54.5%), including 5 papillary fibroelastomas and one myxoma were pedicled by a short stalk, and both patients with a valvular thrombus (18.2%), and 3 patients with a valvular calcification (27.3%) were sessile. Trivial mitral valve regurgitation was noted in 2 of the 4 patients with mitral valve lesions: one was mitral papillary fibroelastoma and the other was mitral thrombus. Mild aortic regurgitation was associated with both aortic valvular papillary fibroelastomas. Mild tricuspid regurgitation was present in the patient with tricuspid valve myxoma. The 3

Table 1. Patients’ clinical characteristics and valvular mass. Case Sex Age Diagnosis

Associated

Presentation

Location

Appearance

Associated disease

1

F

34

Papillary fibroelastoma

No

Weak, fatigue 1 month

Atrial side of posterior mitral leaflet

Lobulated, round

No

2

F

65

Papillary fibroelastoma

No

Fatigue 2 weeks

Vessel side, right. cusp of aortic valve

Lobulated, round

No

3

M

33

Papillary fibroelastoma

No

Vertigo, taxia Diplopia one week

Vessel side, non-coronary cusp of aortic valve

Dense, round

No

5

M

31

Papillary fibroelastoma

No

Chest pain 3 weeks

Vessel side, non-coronary cusp of aortic valve

Lobulated, round

No

6

M

43

Myxoma

No

Asymptomatic

Atrial side of septal tricuspid leaflet

Lobulated, round

No

7

M

78

Thrombus

Coronary artery disease, aortic valve stenosis, polycythemia vera, atrial fibrillation

Dizziness 10 days

Ventricular side of posterior mitral leaflet

Thick, dense

Coronary artery disease, aortic valve stenosis, polycythemia vera, atrial fibrillation

8

M

53

Thrombus

Coronary artery disease, patent foramen ovale, peripheral embolic events, carotid artery stenosis

Lumbago 2 weeks

Atrial side of the posterior mitral leaflet

Thick, dense

Coronary artery disease, paten foramen ovale, peripheral embolic events, carotid artery stenosis

9

F

45

Calcification

Aortic valve regurgitation, oral and vaginal candidosis

Shortness of breath and

Edge of the left cusp of weakness 1 year aortic valve

Dense, thick, non-mobile

Aortic valve regurgitation, oral and vaginal candidosis

10

M

64

Calcification

Aortic valve regurgitation, mitral valve regurgitation, hypertension, peripheral vascular disease

Shortness of breath and weakness 2 months

Atrial side of anterior mitral leaflet

Dense, thick, non-mobile

Aortic valve regurgitation, mitral valve regurgitation, hypertension, peripheral vascular disease

11

M

53

Calcification

Mitral valve regurgitation, hypothyroidism

Shortness of breath 3 weeks

Vascular side of the right coronary cusp of the aortic valve

Dense, thick, non-mobile

Mitral valve regurgitation, hypothyroidism

[page 106]

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Article patients with valvular calcification presented dominantly with severe valvular dysfunction, with either mitral or aortic regurgitation, which required valve replacement.

Figure 2. Case #7. Mitral valve thrombus. Fourchamber view of transthoracic echocardiography showed a thick, dense, less mobile mass (arrow) attached to the ventricular side of the anterior mitral leaflet.

Surgery Eight patients (80%) underwent conventional cardiopulmonary bypass with cardioplegic arrest. One patient with mitral fibroelastoma and the patient with tricuspid valve myxoma (20%) were operated on via port access under femoral cardiopulmonary bypass, with the former having cardioplegic arrest, and the latter, a beating heart. All leaflet lesions were resected by a simple shave technique as described by Gowda et al.,4 followed by leaflet plication with direct suture. None had impairment of the valvular leaflet function. The patient with fibroelastoma of the mitral chord had trivial mitral regurgitation after tumor resection which was repaired successfully by implanting two artificial chordea. Simultaneous coronary artery bypass, aortic valve replacement, and closure of foramen ovale were carried out. The cardiopulmonary bypass time and cross-clamp time were 68.36±29.57 (38-113) and 48.9±24.29 (21-98) min, respectively. There was a total of 5 (45.5%) atrioventricular valve lesions, with 4 arising from the atrial side of the leaflets, and one from the ventricular side. Five (45.5%) semilunar valvular lesions were all from the aortic valve. Three aortic papillary fibroelastomas and one aortic valve calcification lesion were from the vascular side of the leaflets, and another aortic calcification lesion was from the edge of the left cusp. Besides, one (9.1%) lesion originated from the chorda tendinea of the mitral valve. A solitary lesion was presented in 10 (90.9%) patients and multiple lesions in one (9.1%), and originated from the midportion of the valve leaflet away from the margin or the annulus of the leaflet in 9 (81.8%), from the edge of the leaflet in one (9.1%), and from the chorda tendinea in one (9.1%). Five (45.5%) of

Figure 3. Case #11. Mitral valve calcification. Longaxis view of transthoracic echocardiography showed a thick, dense, nonmobile mass (arrow) attached to the vascular side of the right coronary cusp of the aortic valve.

these valvular masses were papillary fibroelastomas, one (9.1%) was myxoma, 2 (18.2%) were organized thrombi, and 3 (27.3%) were calcification lesions. Five (45.5%) lesions were located in the mitral valve leaflets. Of them, 2 were papillary fibroelastomas, 2 were thrombi, and one was calcification. Three of them were on the atrial side of the posterior leaflets, one was on the ventricular side of the anterior leaflet, and one attached to the mitral chorda tendinea. There were 5 (45.5%) aortic valvular lesions, arising from the left, right and non-

coronary cusps in 2, 1, and 2 patients, respectively. Three of them were papillary fibroelastomas, and 2 were calcification lesions. One (9.1%) originated from the atrial aspect of the septal leaflet of the tricuspid valve, which was proved to be a myxoma. Similar to pre-operative echocardiographic findings, gross appearances of these lesions at surgery were round, soft, lobulated and frondlike in all valvular tumors except in one aortic valvular papillary fibroelastoma which were round and dense. Both thrombi from the mitral

Table 2. Surgery and size of the tumor. Case

Surgery

1 2 3 4 5 6 7 8 9 10 11

Valvular tumor resection (port access) Valvular tumor resection Valvular tumor resection, artificial chorda Valvular tumor resection Valvular tumor resection Valvular tumor resection (port access) Valvular tumor resection, coronary artery bypass, aortic valve replacement Valvular tumor resection, coronary artery bypass, closure of foreman ovale Aortic valve replacement Aortic valve replacement, resection of small mass from anterior mitral leaflet Valvular mass resection, mitral valve repair

Size (cm)

z-score of the size

1x0.5x0.5 0.5 0.7 0.5 1.2 1.5 1.8x0.7 1.4x1.1x0.8 0.4 0.4 Multiple 0.3-1.0

0.102 -0.918 -0.510 -0.918 0.510 1.327 1.735 0.918 -1.222 -1.222 -1.444~0.111

[Rare Tumors 2009; 1:e35]

[page 107]

Article leaflet were dense and lumpy. Three calcification lesions were dense and thick. These lesions measured 0.95±0.49 (0.4-1.8) cm, while 4 papillary fibroelastomas were ≤1cm, and one papillary fibroelastoma was larger than 1cm. Estimation of the z-scores of the dimensions of these lesions also showed the papillary fibroelastoma or the calcification lesions were smaller than the myxoma and thrombi (Table 2). All the patients recovered favorably. Their hospital stay was 5±1.73 (3-8) days after surgery. All patients were doing well without recurrence on a regular post-operative follow-up.

Discussion Valvular tumors are rare. Yater was the first to describe valvular tumors in 1931.5 They area characterized by a smaller size, greater mobility, and more significant tendency to embolize by way of tumor fragments or thrombus formed around the tumor than the intramural tumors.6,7 In the past, most valvular tumors were located incidentally by autopsy. Nowadays, the development of non-invasive diagnostic tools, such as echocardiography, computed tomography and magnetic resonance imaging, has greatly contributed to the prompt evaluation of valvular tumors.7 The majority of valvular tumors are papillary fibroelastomas, with aortic valve being the most commonly affected valve (52%), followed by the mitral valve (16%).7,8 Cardiac papillary fibroelastomas although rare, constitute the second cause of benign cardiac tumors. They predominantly affect cardiac valves and account for most cases of valvular tumor. Its true incidence is unknown.9 Papillary fibroelastomas are usually smaller than 1cm, attached to the valve by a short stalk, thereby having greater freedom and mobility, which might explain the frequent occurrence of embolic events.7 Papillary fibroelastomas can be reliably diagnosed by echocardiography.10 Myxomas are the most common primary cardiac tumors with a growing predilection on the intraatrial septum of the left atrium.11 Valvular myxomas are exceedingly rare accounting for 8.8% of cardiac myxomas.12 They are gelatinous, lobulated tumors, often solitary with a short stalk.11 Echocardiography is very helpful in the evaluation of a suspected valvular myxoma in determining the location, size, attachment, and influence on valve function.10 Myxoma differs histologically from the cardiac papillary fibroelastoma by the presence of polygonal myxoma cells and blood vessels in the papillae, while the cardiac papillary fibroelastoma is of avascular structure in the papillae.7 Surgical excision of the myxoma should be performed after the diagnosis without delay. The pedicle or broad

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base of the tumor along with adjacent endocardium should be removed. Cardiac thrombi are more common than tumors, and timely diagnosis and treatment are mandatory. Atrial fibrillation,13 mitral valve dysfunction,14 patent foramen ovale,15 carotid artery stenosis,16 polycythemia vera, and a history of peripheral arterial thrombosis17 have been identified as predisposing risk factors for intracardiac thrombus formation. Valvular thrombus is also mobile and small extending about 1 cm in size. Most thrombi are sessile without a stalk. However, there have been a few reported cases in which valvular thrombi were pedicled by a stalk1,18 and were larger than 2 cm.1 From the present study, we observed that the dimensions of the valvular masses formed a sequence of thrombus > myxoma > papillary fibroelastoma > calcification, which might be indicative of differential diagnoses between each other. Equivocal findings by an echocardiography might be ascertained by magnetic resonance imaging which demonstrates increased signal intensity on T1-weighted, and uniform reduced signal intensity on T2-weighted images.19 Valvular calcification or abscess is usually associated with severe valve dysfunction and is easily distinguished from valvular tumors by echocardiography. However, in atypical cases, these lesions might be tumor-like and make diagnoses difficult. One important feature of mitral annular calcification is a heterogeneous echo signal combining a calcified region and soft tissue, which may extend to the anterior mitral leaflet.20 In extreme cases of mitral valve abscesses, definite diagnoses can only be obtained during surgery.3 In summary, valvular tumors and tumor-like lesions are rare. They may have similar morphological and clinical characteristics, such as round appearance, small size, high mobility with movement of the valves, predisposition for embolic events, and amenable to surgical resection. All these small lesions have little influence on related leaflet function. The tumors differ from the thrombus by a round, friable, and pedicled mass compared with the thick, dense, and sessile lesion of the latter. Degree of mobility of the valvular masses on echocardiography might be helpful in differentiating tumors from tumor-like lesions. Patients with a valvular tumor are usually younger than those with a tumor-like lesion. Valvular tumors and tumor-like lesions place the patients at a high risk of stroke in different ways. Valvular tumor and tumor-like lesions accounted for 0.34% of adult cardiac operations. Pre-operative differential diagnoses among these valvular lesions pose important clinical implications for appropriate treatment for the underlying diseases. Prompt surgical resection is necessary to prevent potential embolic events. Port access is a practical approach for some valvular lesions in selected patients.

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References 1. Mottram PM, Gelman JS. Mitral valve thrombus mimicking a primary tumor in the antiphospholipid syndrome. J Am Soc Echocardiogr 2002;15:746-8. 2. Kato M, Nakatani S, Okazaki H, et al. Unusual appearance of mitral annular calcification mimicking intracardiac tumor prompting early surgery. Cardiology 2006; 106:164-6. 3. Sowa S, Kleinrok A, Gburek T, Zaremba-Flis E. Abscess of the mitral annulus mimicking left atrial tumour -- case report. Kardiol Pol 2007;65:571-4. 4. Gowda RM, Khan IA, Nair CK, et al. Cardiac papillary fibroelastoma: a comprehensive analysis of 725 cases. Am Heart J 2003; 146:404-10. 5. Available at: http://www.utmem.edu/cardiology/ppt/Sea%20anemone.ppt#279,10,Histori cal Reference. Accessed on 3 September 2009. 6. Jaleski TC. Myxoma of the heart valves: report of a case. Am J Pathol 1934;10:399405. 7. Edwards FH, Hale D, Cohen A, et al. Primary cardiac valve tumors. Ann Thorac Surg 1991;52:1127-31. 8. Ngaage DL, Mullany CJ, Daly RC, et al. Surgical treatment of cardiac papillary fibroelastoma: a single center experience with eighty-eight patients. Ann Thorac Surg 2005;80:1712-8. 9. Kanarek SE, Wright P, Liu J, et al. Multiple fibroelastomas: a case report and review of the literature. J Am Soc Echocardiogr 2003; 16:373-6. 10. Wintersperger BJ, Becker CR, Gulbins H, et al. Tumors of the cardiac valves: imaging findings in magnetic resonance imaging, electron beam computed tomography, and echocardiography. Eur Radiol 2000; 10:4439. 11. Bjessmo S, Ivert T. Cardiac myxoma: 40 years' experience in 63 patients. Ann Thorac Surg 1997;63:697-700. 12. Wold LE, Lie JT. Cardiac myxomas: a clinicopathologic profile. Am J Pathol 1980; 101: 219-40. 13. Ramos AI, Magalhães HM, Maldonado M. Incidence of intracardiac thrombus and thromboembolism in the first three months after bioprosthetic valve implantation. Arq Bras Cardiol 2004;83:46-52 14. Stein JH, Soble JS. Thrombus associated with mitral valve calcification. A possible mechanism for embolic stroke. Stroke 1995;26:1697-9. 15. Krumsdorf U, Ostermayer S, Billinger K, et al. Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale closure devices in

Article 1,000 consecutive patients. J Am Coll Cardiol 2004;43:302-9. 16. Wein TH, Bornstein NM. Stroke prevention: cardiac and carotid-related stroke. Neurol Clin 2000;18:321-41. 17. Brenner B, Blumenfeld Z, Markiewicz W, Reisner SA. Cardiac involvement in patients with primary antiphospholipid syndrome. J

Am Coll Cardiol 1991;18:931-6. 18. Hashimoto Y, Furumi K, Tanaka M, et al. Mitral valve thrombus attached to the intact mitral valve associated with distal embolism. Jpn Circ J 1999;63:394-6. 19. Vaz D, Teague SD, Mahenthiran J. Cardiac tumor versus thrombus differentiation: role of cardiac magnetic resonance imaging.

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Cardiol Rev Available at: http://www.cardiologyreviewonline.com/issues/articles/200712_01.asp. Accessed on 3 September 2008. 20. Kato M, Nakatani S, Okazaki H, et al. Unusual appearance of mitral annular calcification mimicking intracardiac tumor prompting early surgery. Cardiology 2006;106:164-6.

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Rare Tumors 2009; volume 1:e36

Treatment outcome of maxillary sinus cancer Hye Sung Won,1,7 Sang Hoon Chun,1,7 Bum-soo Kim,1,2 So Ryoung Chung,1,2 Ie Ryung Yoo,1,3 Chan-Kwon Jung,1,4 Yeon-Sil Kim,1,5 Dong-il Sun,1,6 Min Sik Kim,1,6 Jin-Hyoung Kang,1,7 1

Head and Neck Cancer Interdisciplinary Team, Departments of 2Diagnostic Radiology, 3Nuclear Medicine, 4Hospital Pathology, 5Radiation Oncology, 6 Otorhinolaryngology, 7Medical Oncology, The Catholic University of Korea, College of Medicine, Seoul, Korea

Abstract The standard treatment in the early stage of maxillary sinus cancer is surgical resection followed by postoperative radiation therapy. However, for locally advanced maxillary sinus cancer, a multimodality treatment approach is strongly recommended to improve the survival rate and quality of life of the patient. We determined the treatment outcomes of induction chemotherapy, concurrent chemoradiation therapy, and surgical resection for locally advanced maxillary sinus cancer. Forty-four patients with locally advanced maxillary sinus cancer, who had been treated between January 1990 and April 2008 at Kangnam St. Mary's Hospital, were retrospectively analyzed. The objective response rates were 70%, 53%, and 57% in the intra-arterial induction chemotherapy, intravenous induction chemotherapy, and concurrent chemoradiation therapy groups, respectively. The orbital preservation rates were 83%, 100%, and 75% in the intra-arterial induction chemotherapy, intravenous induction chemotherapy, and surgical resection groups, respectively. In seven of nine patients in whom the orbit could be preserved after induction chemotherapy, the primary tumors were removed completely. However, although the orbits were preserved in three patients who underwent surgical resection as a primary treatment, all three cases were confirmed to be incomplete resections. We found that active induction chemotherapy for locally advanced cancer of the maxillary sinus increased the possibility of complete resection with orbital preservation as well as tumor down-staging.

3% of head and neck cancers and 0.5% of all malignant diseases. The annual incidence of maxillary sinus cancer is 0.5-1.0 case per 100,000 of the population.1 Squamous cell carcinoma is the most common histologic type, accounting for approximately 70-80% of the cancers. The other histologic types of maxillary sinus cancer include adenoid cystic carcinomas, adenocarcinomas, mucoepidermoid carcinomas, sarcomas, and lymphomas. Smoking and histories of chronic sinusitis are the most common risk factors for maxillary sinus cancer. In addition, occupational exposure to chemical substances, such as formaldehyde, chromium, nickel, and air pollution is associated with an increased risk for malignant tumors of the maxillary sinus.2 Most patients with maxillary sinus cancer have no symptoms in the early stage and, therefore, many of these patients are diagnosed in the advanced stage of the disease. The complexity of the anatomy and the proximity of the eyes, brain, and cranial nerves render complete surgical resection difficult, which leads to local recurrence, a major cause of treatment failure.3 The other issues pertaining to maxillary sinus cancer include the functional aspects of eyesight and the cosmetic aspects of facial contours, which make patients avoid surgical resection. The standard treatment for maxillary sinus cancer has been surgical resection with or without orbital exenteration, followed by postoperative radiation therapy. However, in the advanced stages, tumor control and survival rate are still considered to be unsatisfactory, with a local control rate of 50-60% and a fiveyear disease-specific survival rate of 30-50%.3,4 Since the late 1970s, multimodality treatments have been investigated for the treatment of locally advanced maxillary sinus cancer, with the purpose of improvement in tumor control rate and reduction of functional impairment. Notably, induction chemotherapy (ICT) and concurrent chemoradiation therapy (CCRT) are the most common multimodality treatments for stages III and IV locally advanced maxillary sinus cancer. We investigated the treatment outcomes including orbital preservation, complete resection, pathologic downstaging, and relapse patterns in patients with locally advanced maxillary sinus cancer who underwent ICT, CCRT, and surgical resection.

Materials and Methods Patients

Introduction Malignant tumors of the maxillary sinus are rare neoplasms that account for approximately [page 110]

Seventy-five patients who had been diagnosed with maxillary sinus cancer at Kangnam St. Mary's Hospital between 1 January 1990 and 30 April 2008 were reviewed. Among these patients, 10 received only palliative care owing [Rare Tumors 2009; 1:e36]

Correspondence: Jin-Hyoung Kang, Division of Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, Korea. E-mail: [email protected] Key words: maxillary sinus cancer, induction chemotherapy, intra-arterial chemotherapy, organ preservation. Conflict of interest: the authors report no conflicts of interest. Received for publication: 11 August 2009 Revision received: 16 September 2009. Accepted for publication: 17 September 2009. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright H.S. Won et al., 2009 Rare Tumors 2009; 1:e36 doi:10.4081/rt.2009.e36

to poor performance status, and seven patients with a history of prior surgery or chemotherapy were excluded. In addition, fourteen patients with malignant lymphomas or soft tissue sarcomas were excluded. Finally, 44 patients were analyzed and reviewed on the basis of their medical records, pathology slides and interpretation reports, and imaging studies. The following data were collected: age, gender, performance status, histopathologic diagnosis, tumor staging, orbital invasion, treatment modalities, recurrences, and survival rates. A detailed assessment of the tumor extent was performed in all patients, based on CT scans and/or MRI including the maxillary sinus and skull base. The orbital invasion was determined on these findings: contact of the mass with the lamina papyracea, erosion or destruction of the medial and/or inferior orbital wall, and invasion of the periorbital soft tissue including the optic nerves and extraocular muscles. Tumor staging was done using the 2006 edition of the American Joint Committee on Cancer (AJCC) classification, and retrospective restaging was done in previously diagnosed patients. The performance status was evaluated according to Eastern Cooperative Oncology Group (ECOG) criteria.

Chemotherapy One of four different treatment modalities, including intra-arterial (IA)-ICT, intravenous (IV)-ICT, CCRT, and surgical resection, was selected as a primary treatment based on the TNM stage, performance status, age, and comorbidity. ICT was administered through the IA or IV route. Superselective IA infusion of chemotherapeutic drugs was attempted via a

Article series of processes. The contrast-enhanced tumor mass and tumor feeding vessels were confirmed via diagnostic angiographic procedures of the internal and external carotid arteries by means of transfemoral access. The internal maxillary artery was superselected with a microcatheter, and then the chemotherapeutic drug was administered via a microcatheter into the tumor-supplying artery. The transfemoral catheter was removed on completion of the infusion. Cisplatin (100 mg/m2) was administered via a microcatheter into the internal maxillary artery over two hours on day 1, and then 5-FU (1000 mg/m2/day) was continuously infused from day 1 to day 5 over 120 hours through the IV route. A standard hydration and mannitol diuresis regimen were applied. The entire procedure was repeated 23 times every 3-4 weeks. The IV-ICT was performed 2-3 times every four weeks as well. Cisplatin (100 mg/m2) was administered intravenously over two hours on day 1, and 5-FU (1000 mg/m2/day) was infused continuously from day 1 to day 5 over 120 hours through the IV route. All patients who received ICT were re-evaluated for tumor response with CT and/or MRI at least 4-6 weeks after the completion of ICT. The decision to perform surgery after ICT was based on the tumor response. The chemotherapeutic agent used in the CCRT group was cisplatin. During radiation therapy, cisplatin (30 mg/m2) was administered by a weekly schedule on days 1, 8, 15, 22, 29, 36, 43, and 50, or cisplatin (100 mg/m2) was administered every 3 weeks on days 1, 22, and 43. All patients treated with CCRT were reevaluated for tumor response, and then the next treatment modality, surgical resection or salvage chemotherapy, was determined. The periodic follow-up was done at least 6-8 weeks after the completion of radiation therapy.

Surgical resection and radiation therapy In most cases, a total maxillectomy with orbital preservation was carried out. However, if the tumor mass extended to the lamina papyracea and invaded the orbit and muscles, an orbital exenteration with a total maxillectomy should be performed. The patients with metastatic cervical lymphadenopathy underwent a modified radical neck dissection. Three-dimensional conformal radiation therapy (3DCRT) was applied as an external radiation therapy technique. The total dose of 55-60 Gy with 1.8-2.0 Gy daily fractions five times per week was given to the clinical target volume (CTV) in postoperative adjuvant radiation therapy. In the case of CCRT, the total dose of 70-75 Gy in 35-40 fractions was given with a shrinking-field technique; 50 Gy was given to the CTV with daily fractions of 1.8 Gy five times per week, and followed by 20-25 Gy to the gross tumor volume (GTV).

Evaluation of treatment outcomes The primary end point of our study was the response rate of the primary treatment modalities (IA-ICT, IV-ICT, and CCRT). For the evaluation of tumor response, a physical examination, nasal endoscopy, and CT or MRI were performed. Tumor response was assessed according to the RECIST criteria (version 1.0). An objective tumor response was defined as more than partial response (PR). When recurrence or distant metastasis was suspected, PET-CT and other imaging studies of suspicious lesions were performed and, if needed, confirmed by biopsy. The secondary end points were the complete resection and orbital preservation rates in patients who underwent surgical resection after ICT and surgical resection as a primary treatment. Complete resection was defined as where there were no microscopic residual tumor cells on the resection margin, and incomplete resection was defined as where there were residual tumors on the resection margin, identified by gross and/or microscopic examination. Orbital preservation was defined as when a case underwent total maxillectomy without orbital exenteration, among the patients with the evidence of orbital invasion on physical examinations and/or imaging studies at the time of diagnosis. The tertiary end points were overall survival, recurrence rate, and the toxicity profile. Overall survival was defined as from the date

Table 1. Patient characteristics. Patient characteristics (n=44) Gender (male/ female) Median age (years, range) ECOG performance 0/1/2 Histologic type Squamous cell carcinoma Adenoid cystic carcinoma Adenocarcinoma Myoepithelial carcinoma Undifferentiated carcinoma TNM stage II/III/IVa/IVb Tstage T2/T3/T4a/T4b Nstage N0/N1/N2 Orbit invasion yes/ no Treatment modalities † IA-ICT/‡IV-ICT § CCRT/Surgical resection

of diagnosis to the date of death or date of last follow-up. The adverse events occurring during ICT and CCRT were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC, version 2.0).

Statistical analysis For categorical outcomes, between-group comparisons were done using either the Fisher’s exact test or a Chi-square test. The overall survival curve was estimated using the Kaplan-Meier method, and the log-rank test was applied to assess statistical significance. All statistical analyses were performed using the SPSS program (version 13.0) and a p value of