Ovarian dysgerminoma with normal serum tumour ...

[Downloaded free from http://www.cancerjournal.net on Sunday, February 28, 2016, IP: 5.110.27.53]

E-JCRT Correspondence

Ovarian dysgerminoma with normal serum tumour markers presenting in a child with precocious puberty ABSTRACT A 7‑year‑old female child was presented to the emergency room with acute abdominal pain and vaginal bleeding. Her assessment revealed a firm large lower abdominal mass with evidence of precocious puberty with bilaterally symmetrically enlarged breast (Tanner stage B4‑P1‑A1). Abdominal imaging showed a well‑defined soft midline pelvi‑abdominal single mass measuring 7.0 × 12.6 × 11.7 cms with no ascites. Serum tumour markers including lactate dehydrogenase (LDH), beta‑subunit of human chorionic gonadotropin (B‑hCG) and luteinizing hormone/follicular stimulating hormone (LH/FSH) were all normal. At operation, there was a huge abdominal tumour weighing 558 grams, localized to the right ovary sparing the left ovary, uterus, lymph nodes and other abdominal organs. Unilateral right salpingo‑oophorectomy was performed. Histopathologic examination revealed ovarian dysgerminoma with intact capsule; FIGO Ia. Immunohistochemical stainings were positive for placental alkaline phosphatase (PALP), CD 117(c‑kit) and calretinin focally but was negative for cancer antigen‑125 (CA‑125), B‑hCG, S‑100, carcinoembryonic antigen (CEA), and leukocyte common antigen (LCA). Being fitting in the low risk classification, the wait and see protocol was selected with strict follow‑up with pediatric oncologist and pediatric surgeon. Along the duration of 2 years follow up, there was no more vaginal bleeding with dramatic reduction of the breast size and no recurrence. KEY WORDS: Immunohistochemistry, ovarian dysgerminoma, pediatrics, precocious puberty, tumour markers

INTRODUCTION Germinomas include the malignant germ cell tumours of childhood that are usually found in the ovaries (dysgerminoma), in the pineal region, and in the mediastinum.[1] In females, dysgerminoma is the most common malignant germ cell tumour of the ovary and represents only 2% of all ovarian cancers.[1] This diagnosis is even more uncommon in the pediatric age group with incidence of 1/80000.[2] Elevation of serum lactate‑dehydrogenase (LDH), cancer‑antigen‑125 (CA‑125), beta‑subunit‑human‑chorionic-gonadotrophin (B‑hCG), S‑100‑protein, neurone‑specific‑enolase (NSE), and placental‑alkaline‑phosphatase (PALP) are the frequent findings in patients with germinomas.[1] We present a pediatric patient with an ovarian dysgerminoma who have a unique finding of normal serum tumour markers levels, and a very odd presentation of precocious puberty. CASE REPORT A 7‑year‑old female child presented with severe recurrent attacks of acute abdominal pain and massive vaginal bleeding. Examination revealed firm large mobile lower abdominal mass, 13 × 12 cm2,

with associated evidence of precocious puberty with bilaterally symmetrically enlarged breast (Tanner stage B4 P1 A1), [Figure 1]. Otherwise, body system review was normal including perineum and per rectal (P/R) examination. Abdominal ultrasonography and computed tomography showed a well‑defined soft midline pelvi‑abdominal single mass, 7.0 × 12.6 × 11.7 cm3, with remarkable increased surrounding vascularity and low resistance internal vascularity. The mass appeared inseparable from the right ovary with non‑visualization of the right ovary. It was extending anteriorly to the anterior abdominal wall, posteriorly to the para‑vertebral muscles with compression of both ureters, and inferiorly to the urinary bladder with displacement of intestinal loops on both sides [Figure 2]. The uterus appeared separable from the mass but was seen abnormally bulky for the age of the patient, with endometrial thickness 6‑7 mm, with internal echogenic mass, possibly bleeding. Pelvi‑calyceal system was mildly dilated on both sides with mildly dilated proximal right ureter. No ascites was detected. The study was otherwise normal with no definite evidence of direct invasion or lymph node enlargement.

Naglaa M. Kamal, Ubaidullah Khan1, Shazia Mirza1, Kais Mazoun1, Farahat M. Mirza1, Majd Jundi2 Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt, and Consultant Pediatrician, Alhada Armed Forces Hospital, Taif, Saudi Arabia, Departments of 1Surgery, and 2 Histopathology, Alhada Armed Forces Hospital, Taif, Saudi Arabia For correspondence: Naglaa M. Kamal, Department of Pediatric, Faculty of Medicine, Cairo University, Cairo, Egypt. E‑mail: nagla. kamal@kasralainy. edu.eg

Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.137920 PMID: *** Quick Response Code:


Kamal, et al.: Ovarian dysgerminoma with precocious puberty

Serum levels of various tumour markers such as LDH, alpha‑feto‑protein (AFP), Beta‑hCG, FSH/LH, and estradiol were surprisingly normal. Karyotyping revealed a normal female; 46XX. Surgery was performed via a pfannestiel incision. The main tumour arose from the right ovary [Figure 2], sparing the left ovary, the uterus, the abdominal lymph nodes and other abdominal organs [Figure 2]. Unilateral right simple salpingo‑oophorectomy was performed. On pathological examination, the cut surface of the tumour was solid, tan, and lobulated with intact capsule. On histopathology [Figure 3], there were large aggregates and cords of uniform cells surrounded by strands of connective tissue containing variable amount lymphoid cells. The tumour cells were large oval or rounded with little clear cytoplasm and large rounded centrally located vesicular nuclei with fine chromatin and eosinophilic nucleoli. Mitotic figures were abundant with the presence of atypical forms. Lymphovesicular invasion was present. These histopathologic findings confirmed the diagnosis of ovarian dysgerminoma. The right fallopian tube was normal by histopathological assessment. The tumour cells exhibited highly positive immunohistochemical staining [Figure 3], for PALP (rabbit‑polyclonal‑anti‑PALP‑antibody, Nichirei, Japan), focal reactivity to calretinin, CD 117 (c kit), and LMW‑cytokeratin focally with negative staining for CA‑125 (mouse‑monoclonal‑anti–CA‑125‑antibody, Immunotech, France), B‑hCG (mouse‑monoclonal‑antibody‑anti–B‑hCG, Nichirei, Japan), S‑100 (rabbit‑polyclonal‑anti–S‑100‑antibody, Zymed), alpha fetoprotein (AFP), CD‑30, HMW‑cytokeratin, carcino‑embryonic antigen (CEA), and leukocyte common antigen (LCA).

which was considered low risk and candidate for the wait and see strategy by most of the oncology groups. Pediatric oncology consultation with conjoint pediatric surgeon and parental opinion agreed for not starting postoperative chemo‑ or radiotherapy management and planned for strict follow‑up. After about 2 years of follow up, the breast size decreased dramatically to normal with cessation of bleeding and no evidence of recurrence. DISCUSSION Ovarian tumours are rare in the pediatric age group, but represent nearly 50% of all ovarian masses; 90% are benign[3] and germ cell tumours represent the most frequent histological type in this population (60‑70%), with teratoma as the main form.[4] Dysgerminomas are rare but are among the most frequent malignant germ cell tumours in girls.[5] The incidence in the pediatric population is not well known and only rare case reports are found in the pediatric literature.[5] Most patients with dysgerminomas, present with either non‑specific symptoms,[6] or most commonly with abdominal pain and pelvic/abdominal mass.[7] Similarly, the reported patient presented with abdominal pain and pelvi‑abdominal mass but with a very rare association which is vaginal bleeding with precocious puberty which occurs mostly in non‑malignant tumours like juvenile‑granulosa‑cell tumours not dysgerminaomas. Ovarian dysgerminoma with precocious puberty presentation is very unlikely.[8] In that respect, we greatly matched with Song and co‑workers,[8] who reported ovarian dysgerminoma in a 6‑year‑old female with precocious puberty but with high serum tumour markers unlike to us. Ovarian dysgerminoma is usually hormonally inert, but when it contains syncytiotrophoblastic

The tumour was fitting with the stage Ia of the International Federation of Gynecology and Obstetrics classification (FIGO Ia)

a

b

Figure 1: Evidence of precocious puberty with bilaterally symmetrically enlarged breasts

c

Figure 2: (a) Pre-operative abdominal CT scan pictures, showing huge solid pelvi-abdominal mass (b) Intra-operative picture showing the Rt ovary involved with a huge solid capsulated mass. Rt Fallopian tube appears normal (c) Intra-operative picture showing normal Lt ovary, Fallopian tube and uterus



their results using the MAIKEI protocols.[11] They settled a protocol in which the indication for primary tumour resection and a supplementary radiotherapy, or, in selected cases, primary chemotherapy and delayed tumour resection after the spreading, has been graded.[11] The described patient fits into FIGO Ia which is candidate for surgical excision and the wait and see strategy. Higher FIGO scores must receive chemotherapy.[10] a

b

c

d

Although dysgerminoma is bilateral in 10-15% of cases,[3] we performed simple right salpingo‑oophorectomy without taking biopsy from the other unaffected ovary. The issue of taking biopsy is still controversial. We agree with those who recommend leaving the normal contra‑lateral ovary undisturbed aiming to preserve fertility.[12] We believe that the strict frequent follow‑up can allow early detection of an occult dysgerminoma in the remaining ovary which can be promptly treated while still in early stage. Previous reports described that the median follow‑up was 127 months‑15.9 years and the 10‑year survival rate was 81.8‑82.9%.[13]

e

f

Figure 3: Histological findings of the tumour (Dysgerminoma): (a) Aggregates of tumour cells surrounded by delicate strands of connective tissue (b) Slight variation in the size of tumour cells, mitoses is present (c) Large cells with vesicular nuclei and centrally located nucleoli (d) Lympho-vascular invasion (e) Immunohistochemical staining showing strong reactivity for PLAP (IHC) (f) Immunohistochemical staining showing strong reactivity for CD117 (c-kit)

giant cells or undergoes malignant transformation, the level of estradiol might be elevated.[8] Elevation of serum LDH, CA‑125, B‑hCG, PALP, and NSE are frequent findings in patients with germinomas.[1] However, our patient was unique in having negative results for all serum tumour markers, an observation, that is very unlikely to find. In dysgerminomas, diagnosis is usually confirmed by positive immunohistochemical staining for LDH, CA‑125, B‑hCG, PALP, NSE, cytokeratin 18, and S‑100 protein.[1] About 5% of dysgerminomas are found in girls with chromosomal abnormalities such as 46XY (testicular‑feminization or Sweyer‑syndrome) or 45X/46XY mosaic. Therefore, in cases of pre‑pubertal pelvic masses, karyotyping should be carried out. Karyotyping was done in our patient and revealed a normal female, 46XX. Accurate surgical staging is essential to properly ascertain the correct risk‑based treatment.[9] The FIGO classification is the most accepted.[10] The German children cancer registry has been registering their patients since 1980s and Gobel et al. published

In conclusion, dysgerminoma can have different presentations including precocious puberty and normal serum tumour markers. Histopathology and immune‑histochemical staining are the gold standard. The aim of management is almost always to preserve fertility in these young females. REFERENCES 1. Tatekawa Y, Kemmotsu H, Mouri T, Joe K, Ohkawa H. A case of pediatric ovarian dysgerminoma associated with high serum levels and positive immunohistochemical staining of neuron‑specific enolase. J Pediatr Surg 2004;39:1437‑9. 2. Gocht A, Löhler J, Sçheidel P, Stegner HE, Saeger W. Gliomatosis peritonei combined with mature ovarian teratoma: Immunohistochemical observations. Pathol Res Pract 1995;191:1029‑35. 3. von Allmen D. Malignant lesions of the ovary in childhood. Semin Pediatr Surg 2005;14:100‑5. 4. Capito C, Arnaud A, Hameury F, Fremond B, Lardy H, Leclair MD, et al. Dysgerminoma and gonadal dysgenesis: The need for a new diagnosis tree for suspected ovarian tumours. J Pediatr Urol 2011;7:367‑72. 5. Biswajit D, Patil CN, Sagar TG. Clinical presentation and outcome of pediatric ovarian germ cell tumour: A study of 40 patients. J Pediatr Hematol Oncol 2010;32:e54‑6. 6. Major T, Borsos A, Lampé L, Juhász B. Ovarian malignancies in childhood and adolescence. Eur J Obstet Gynecol Reprod Biol 1995;63:65‑8. 7. Al Jama FE, Al Ghamdi AA, Gasim T, Al Dakhiel SA, Rahman J, Rahman MS. Ovarian tumours in children and adolescents‑a clinical study of 52 patients in a university hospital. J Pediatr Adolesc Gynecol 2011;24:25‑8. 8. Song ES, Lee JP, Han JH, Kim HY, Mun SH, Ryu HS, et al. Dysgerminoma of the ovary with precocious puberty: A case report. Gynecol Endocrinol 2007;23:34‑7. 9. Rescorla FJ. Pediatric germ cell tumours. Semin Pediatr Surg 2012;21:51‑60. 10. Benedet JL, Bender H, Jones H 3rd, Ngan HY, Pecorelli S. FIGO Staging classification and clinical practice guidelines of gynecologic cancers. FIGO committee on gynecologic oncology. Int J gynecol obstet 2000;70:209‑62.



11. Göbel U, Bamberg M, Calaminus G, Jürgens H, Pelzer V, Simon WE, et al. Dysgerminomas. Clinical aspects, therapy and prognosis with reference to the cooperative therapy study MAIKEI 83/86 for non‑testicular germ cell tumours of the society of pediatric oncology [Article in German]. Geburtshilfe Frauenheilkd 1989;49:737‑42. 12. Brewer M, Gershenson DM, Herzog CE, Mitchell MF, Silva EG, Wharton JT. Outcome and reproductive function after chemotherapy for ovarian dysgerminoma. J Clin Oncol 1999;17:2670‑5. 13. Buskirk SJ, Schray MF, Podratz KC, Lee RA, Stanhope CR, Gaffey TA,

et al. Ovarian dysgerminoma: A retrospective analysis of results of treatment, sites of treatment failure, and radiosensitivity. Mayo Clin Proc 1987;62:1149‑57. Cite this article as: Kamal NM, Khan U, Mirza S, Mazoun K, Mirza FM, Jundi M. Ovarian dysgerminoma with normal serum tumour markers presenting in a child with precocious puberty. J Can Res Ther 2015;11:661. Source of Support: Nil, Conflict of Interest: None declared.