Tumori, 97: e27-e30, 2011
Primary adrenal gland carcinosarcoma associated with metastatic rectal cancer: a hitherto unreported collision tumor Federica Bertolini1, Giulio Rossi2, Federica Fiocchi3, Marco Giacometti4, Annalisa Fontana1, Maria Chiara Gibertini3, Luca Roncucci5, Gabriele Luppi1, Pietro Torricelli3, Aldo Rossi4, and Pier Franco Conte1 1Department
of Oncology, 2Pathology Section, 3Radiology Institute, 4Department of General Surgery, and 5Department of Internal Medicine, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
ABSTRACT
In this report we describe the case of a young woman with familial adenomatous polyposis who developed metastatic rectal cancer during pregnancy. At diagnosis, we decided to perform a transabdominal laparoscopic adrenalectomy, because of the high risk of bowel obstruction, and to define the origin of the adrenal gland lesion, suspected to be primary on the basis of imaging results. The histological specimen showed a collision tumor between an adrenal metastasis of a rectal tumor and a primary adrenal gland carcinosarcoma. The peculiarity of the case is due not only to its clinical presentation during pregnancy, but also to the presence of this uncommon adrenal collision tumor. A particular challenge for the clinician is to define the priority between these two tumors: the presence of two distinct and colliding aggressive neoplasms poses a problem in the choice of the best therapeutic approach, also given the impossibility to biopsy all metastatic sites. However, we decided to treat the patient as having a metastatic rectal cancer, because we had a solid histological confirmation of metastases.
Introduction Familial adenomatous polyposis (FAP) is the most frequent among the gastrointestinal polyposis syndromes. It is a genetic disease inherited as an autosomal dominant trait. The gene most frequently responsible for the disease is the adenomatous polyposis coli gene (APC). The main clinical features of FAP are the presence of at least 100 adenomas scattered in the various tracts of the large bowel, together with several extracolonic manifestations such as polyps or adenomas in other organs (including adrenal glands), desmoid tumors, dental abnormalities, osteomas and congenital hypertrophy of the retinal pigmented epithelium1. Extraintestinal tumors can be found in the majority of APC mutation carriers if the affected patients are examined carefully. FAP leads to development of colorectal carcinoma in almost 100% of cases. Whereas adrenal adenomas are frequently occurring extraintestinal manifestations of FAP (around 50 cases since the last century, the majority of which asymptomatic), adrenal carcinomas are very rare and fewer than 10 cases have been described2,3. Collision tumors are unusual entities consisting of 2 distinct tumor types. They include benign or malignant primary tumors with a coexistent metastatic neoplasm in the same site, lymph node metastases from 2 different malignant tumors, or even tumors with divergent differentiation such as lymphoma, carcinoma or sarcoma in the same site or organ. In the adrenal gland, collision tumors are exceedingly rare with the exception of adrenocortical adenoma colliding with metastatic tumors. The few cases described so far in the adrenal gland were adrenocortical adenomas with metastases from lung, sigmoid or breast carcinomas, melanoma and leiomyosarcoma4.
Key words: familial adenomatous polyposis, collision tumor, primary adrenal gland carcinosarcoma. Grants for the research: none. Conflict of interest: none. Correspondence to: Federica Bertolini, Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy. Tel +39-059-4223252; fax +39-059-4224429; e-mail
[email protected] Received September 20, 2010; accepted January 21, 2011.
e28
F BERTOLINI, G ROSSI, F FIOCCHI ET AL
Adrenocortical carcinomas mixed with a sarcoma (carcinosarcoma) or sarcoma-like component (sarcomatoid carcinoma) are exceptionally rare and have never been described in association with FAP. Only 6 cases have been detailed in the literature, 3 including osteosarcoma, chondrosarcoma or rhabdomyosarcoma components, and 3 with a malignant spindle cell carcinomatous component. These uncommon histological types are poorly differentiated and extremely aggressive forms of carcinoma, with locoregional recurrence and metastases rapidly arising from the sarcomatous or sarcomatoid component, and death occurring in a few months5. The present report describes a patient with FAP who developed a metastatic cancer during pregnancy and focuses on the clinical management of colliding aggressive neoplasms.
Case report In April 2009 a 23-year-old woman with a history of FAP was found to have a fixed mass in the rectum during a clinical examination for a pregnancy. Her mother died of colon cancer at age 40 and her sister underwent a subtotal colectomy with ileorectal anastomosis for widespread colorectal polyposis at age 23. The patient and her sister harbored a 3926-3930 del5 mutation in exon 15 of the APC gene. She presented to her oncologist with fatigue and loss of appetite. Subsequent diagnostic procedures included a colonoscopy with biopsy, chest and abdominal computed tomography (CT), lower abdomen magnetic resonance imaging (MRI), and rectal endoscopic ultrasonography. CT showed a large inhomogeneous mass with circumferential and transmural extension of the rectum. The mass had a caudocranial extension of 14 cm and was inseparable from the cervix and vaginal pouch. Enlarged lymph nodes (up to 2 cm) were identified in the pericolic fat tissue. In addition, pre-contrast CT scan (Figure 1A) showed a voluminous, apparently capsulated, solid
A
B
mass with gross calcification in the left adrenal region. The mass presented peripheral arterial inhomogeneous contrast enhancement (Figure 1B) that increased in the venous phase (Figure 1C) with a central colliquativenecrotic component. The imaging results were consistent with a metastasis from rectal cancer or a primary adrenal neoplasm. Pelvis MRI identified external muscle involvement and sacral bone metastasis. Radiocholesterol scintigraphy and noriodocholesterol scintigraphy were not performed because of the presence of concomitant rectal carcinoma that had to be removed. Moreover, the risk of rupture and hemorrhage of the adrenal mass prompted a decision of surgical resection. Clinical and radiological assessment plus rectal biopsy showing an infiltrating adenocarcinoma led to a diagnosis of stenotic locally advanced rectal adenocarcinoma with pulmonary, hepatic, adrenal, nodal and bone metastases (cT4N1M1; TNM stage IV). At diagnosis, the performance status defined by the Eastern Cooperative Oncology Group (ECOG) score was 2. KRAS mutational status determined on the primary tumor biopsy specimen showed a point mutation in exon 2 (G12A). Routine blood tests revealed chronic hypochromic anemia (hemoglobin 7.1 g/dL) and increased values of CEA and CA 19.9 (63.7 ng/mL and 118.8 U/mL, respectively). The patient did not present any signs of corticosteroid hypersecretion. Because of the high risk of bowel obstruction and to define the origin of the adrenal gland lesion (which was suspected to be a primary adrenal neoplasm on imaging), we decided to perform a left iliac colostomy and a transabdominal laparoscopic adrenalectomy. Gross pathological examination of the surgical specimen revealed a 14-cm lesion with an irregular grey surface and a central cavity containing mucinous material (Figure 2). Histopathological examination surprisingly showed the presence of a malignant tumor with 2 distinct components (Figure 3A). Up to 80% of the specimen consisted of a primary adrenal carcinosarcoma in-
C
Figure 1 - CT image of the left adrenal region. A) Pre-contrast graphic scan shows gross and diffuse calcification of the lesion in the left adrenal region. The left adrenal gland is not recognizable. Dynamic imaging during contrast medium administration (B, arterial phase; C, equilibrium phase) shows that the lesion is hypervascular in the periphery with almost no enhancement in the central zone due to a colliquativenecrotic component.
UNREPORTED CASE OF COLLISION TUMOR
Figure 2 - Surgical specimen.
e29
cluding poorly differentiated carcinoma (Figure 3B, on the left) that was positive for inhibin A and calretinin (Figure 3C) and negative for cytokeratins. Part of the carcinosarcoma showed osteosarcomatous differentiation (Figure 3D). The remaining malignancy consisted of metastatic rectal cancer (Figure 3B, on the right), which was positive for CDX-2. The adrenal carcinoma had a score of 7 according to the prognostic scoring system by Weiss et al.6 The patient started systemic chemotherapy for the metastatic rectal cancer consisting of oxaliplatin 85 mg/m2 day 1, folinic acid 100 mg/m2 days 1 and 2, and a 5-fluorouracil bolus of 400 mg/m2 days 1 and 2; continuous infusion 600 mg/m2 days 1 and 2 every 2 weeks (FOLFOX4) in combination with bevacizumab (5 mg/kg every 2 weeks) and zoledronic acid (4 mg every 4 weeks) for the multiple but asymptomatic bone metastases. After 6 cycles hemoglobin levels increased to 12 g/dL and CEA and
A
B
C
D
Figure 3 - The adrenal gland tumor consisted of a poorly differentiated primary carcinosarcoma (asterisks) colliding with metastatic rectal adenocarcinoma (arrows). The carcinosarcoma was characterized by poorly differentiated carcinoma expressing calretinin (C, immunohistochemistry) with areas of osteosarcoma (D).
e30
CA 19.9 decreased substantially. ECOG performance status was 0. No skeletal-related events were recorded. Restaging chest-abdomen CT in July 2009 showed a reduction of all measurable lesions, especially in the lung, liver, abdominal lymph nodes and rectum. No signs of relapse were present in the left adrenal region. The response was maintained on the follow-up chestabdomen CT scan of September 2009. The patient continued systemic treatment (bevacizumab alone as maintenance therapy after 12 cycles of chemotherapy + bevacizumab), with a good toxicity profile and marked clinical benefit. After 3 administrations of bevacizumab monotherapy her clinical condition worsened (ECOG = 3). The chest-abdomen CT scan of January 2010 documented progression of lung, liver and rectal lesions. She started second-line treatment with FOLFIRI (CPT11 180 mg/m2 day 1, folinic acid 100 mg/m2 days 1 and 2 and a 5-fluorouracil bolus of 400 mg/m2 days 1 and 2; continuous infusion 600 mg/m2 days 1 and 2 every 2 weeks) in association with zoledronic acid. After the first 6 cycles relevant clinical benefit was observed (ECOG = 0). In May 2010 she developed seizures and ataxia and the clinical condition worsened. CT and MRI of the brain revealed a solitary cerebellar metastasis of 2 cm. She underwent whole brain irradiation (3 Gy daily up to 30 Gy) and started third-line treatment with capecitabine monotherapy 1000 mg/m2/bid 14 days every 21 days (1 cycle). On 28 June 2010 the patient died suddenly at home.
Discussion To the best of our knowledge, collision tumors comprising adrenal gland carcinosarcoma and metastatic rectal cancer have never been reported. Moreover, rectal or colon cancer during pregnancy is a very rare event, almost always related to inherited familial polyposis7. In our case the presence of 2 distinct and colliding aggressive neoplasms posed a problem in the choice of the best therapeutic approach, also given the impossibility to biopsy all the metastatic sites. Radiocholesterol scintigraphy can have an important role in diagnosing adrenocortical carcinomas, but in the present case the poor differentiation of the mass did not lead to tracer uptake. Moreover, this technique is used to identify nonviewable lesions but this was not the case and the risk of hemorrhage of the adrenal lesion prompted surgical resection8,9.
F BERTOLINI, G ROSSI, F FIOCCHI ET AL
We decided to treat the patient as having a metastatic rectal cancer because we had histological proof that distant metastasis from rectal cancer had developed in the adrenal gland. This is why we decided not to treat the patient with mitotane. Moreover, on the first radiological tumor assessment all metastatic lesions responded to first-line treatment for rectal cancer. This is one of the major issues concerning the peculiarity and the difficulty of the patient’s clinical management. In conclusion, a hitherto unreported adrenal gland collision tumor between a primary carcinosarcoma and a metastatic rectal adenocarcinoma occurring in a young pregnant woman affected by FAP syndrome has been described. From an academic viewpoint, this case adds a new histological combination to the category of collision tumors of the adrenal gland; at the same time, it poses several important implications regarding the therapeutic approach to patients with double synchronous aggressive malignancies.
References 1. Rozen P, Macrae F: Familial adenomatous polyposis. The practical applications of clinical and molecular screening. Fam Cancer, 5: 227-235, 2006. 2. Thorin-Savourè A, Tissier Rible F, Guignat L, Pellerin A, Bertagna X, Bertherat J, Lefebvre H: Collision/composite tumors of the adrenal gland: a pitfall of scintigraphy imaging and hormone assays in the detection of adrenal metastasis. J Clin Endocrinol Metab, 90: 4924-4929, 2005. 3. Groen EJ, Roos A, Muntinghe FL, Enting RH, de Vries J, Kleibeuker JH, Witjes MJ, Links TP, van Beek AP: Extra-intestinal manifestations of familial adenomatous polyposis. Ann Surg Oncol, 15: 2439-2450, 2008. 4. Traill Z, Tuson J, Woodham C: Adrenal carcinoma in a patient with Gardner's syndrome: imaging findings. AJR Am J Roentgenol, 165: 1460-1461, 1995. 5. Sturm N, Moulai N, Laverrière MH, Chabre O, Descotes JL, Brambilla E: Primary adrenocortical sarcomatoid carcinoma: case report and review of literature. Virchows Arch, 452: 215-219, 2008. 6. Weiss LM, Medeiros LJ, Vickery AL Jr: Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol, 13: 202-206, 1989. 7. Lolis ED, Likoudis P, Voiniadis P, Hassiakos D, Samanides L: Synchronous rectal and colon cancer caused by familial polyposis coli during pregnancy. J Obstet Gynaecol Res, 33: 199-202, 2007. 8. Barzon L, Zucchetta P, Boscaro M, Marzola MC, Bui F, Fallo F: Scintigraphic patterns of adrenocortical carcinoma: morpho-functional correlates. Eur J Endocrinol, 145: 743-748, 2001. 9. Dominguez-Gadea L, Diez L, Bas C, Crespo A: Differential diagnosis of solid adrenal masses using adrenocortical scintigraphy. Clin Radiol, 49: 796-799, 1994.
