Ovarian Sarcoma a Diagnostic Dilemma- A Case Report.

An 8-year-old girl presented with rapidly progressive abdominal distension of 4 weeks duration. Child was cachexic with a large palpable hard mass occupying the whole of the abdomen. Blood evaluation suggested hemoglobin – 10.2 g/dl, leukocyte counts – 14060/μl, alpha-fetoprotein (AFP) – 302 ng/ml, β-HCG – 4.6 mIU/ml, and LDH – 2197U/l (high tumor burden). Magnetic resonance imaging of the abdomen and pelvis showed solid mass lesion measuring 18.2 cm × 16.9 cm × 8.1 cm in the abdomen and pelvis with bilateral hydroureteronephrosis and nonvisualization of ovaries. Gonadal germ cell tumor was the first working diagnosis in view of if raised AFP. Tru-cut biopsy showed spindle-shaped cells along with some round cells with hyperchromatic nucleus. Reporting was inconclusive, but immunohistochemistry (IHC) suggested high-grade sarcoma, as it was strongly positive for vimentin and was negative for myoglobin, myo D, desmin, and AFP. Positron emission tomography and bone marrow biopsy showed absent metastasis. Neoadjuvant chemotherapy was initiated with vincristine, actinomycin D, and cyclophosphamide regimen. Child tolerated chemotherapy, with a reduction in tumor mass as seen in follow-up computerized tomography [ Figure 1 ]. Repeat serum AFP values were in normal limits. Following three cycles of neoadjuvant chemotherapy, the child underwent laparotomy and excision of tumor, which showed a large encapsulated mass measuring 14 cm × 13 cm, adherent to a small part of proximal transverse colon, falciform ligament, appendix, and right fallopian tube. The left ovary was not visualized separately and the right ovary appeared flattened due to the pressure effect. Complete tumor resection was possible with omentectomy and left salpingo-oophorectomy [ Figure 2 ]. Final histopathology examination showed necrosis of most of the tumor mass with small ovarian tissue noted in the microscopy. The IHC was positive for vimentin and was negative for calretinin and CD-117 and AFP. It was reported as primary ovarian sarcoma. Child has received postoperative radiotherapy image-guided radiotherapy. The patient has completed 42 weeks of adjuvant chemotherapy and has completed 1 year of follow-up since then. Image of tumor after neoadjuvant chemotherapy Excised tumor specimen

Abdominal soft-tissue sarcoma (STS) is a common mesenchymal tumor of childhood. However, ovarian sarcoma is a rare entity. Ovarian sarcoma could be associated with other gonadal neoplasia such as teratoma, Sertoli–Leydig cell tumors, and malignant mixed mesenchymal tumors. Mature teratoma is also known to get transformed into other malignancies, mostly in the postpubertal age group. Metastasis to the ovary is also not uncommon in alveolar rhabdomyosarcoma (RMS), primary lesion being situated elsewhere. Hence, a complete evaluation of the patient to search for any distant primary as well as evaluation of the entire surgical specimen, is necessary to rule out the above conditions.[ 1 ]

Primary sarcomas of the ovaries are reported in the literature. However, the number of cases reported in the pediatric age group is scarce to suggest any protocol for this tumor management. We could find 12 cases of pediatric (6 years to 16 years of age) RMS arising from the ovary in the literature. Guerard in 1983 suggested hypothesis of the development of ovarian sarcoma in his review. Often RMS develops in the region where there is no striated muscle, this could be due to the totipotent undifferentiated mesenchyme that has an ability to either produce skeletal muscle or a neoplasia in case of the altered signal. In the case of the ovary, it would probably arise from the stromal fibroblasts of primitive mesenchyme located in the genital ridge. It is also suspected that the tumor cells may also originate from the stromal fibroblast of ovarian endometriosis. The source of this endometriosis tissue would be the fibroblasts of the endometrial stoma. This does not explain the disease process in prepubertal girls.[ 4 ] His article included a total of three pediatric patients. Description used in the histopathological reporting was not on par with present-day understanding. Two of the three articles were from non-English literature, hence not included in our review. Nielson provided us with the data of three children among 13 patients in his study which suggest high overall mortality that was attributed to a lack of chemotherapy.[ 2 ] Cribbs et al. added two more cases of metastatic ovarian sarcomas. One other patient in the review was found to have ovarian pathology after the pathological autopsy where the patient was initially treated for leukemia.[ 1 ] One of the patients had DICER 1 syndrome, which has predisposition for various malignancies, where the patient had multiple neoplasia in the form of ovarian RMS, cystic nephroma, hepatic focal nodular hypoplasia, and fibroadenoma breast. No locoregional recurrence or distant disease was noted in 16-year follow-up.[ 3 ] Common symptoms among the patients were abdominal pain, abdominal distension, cachexia, and bone pain. Urinary and bowel disturbances were also noted in few. Among the 13 patients, five patients have died (two due to sepsis and rest three with the disease), six patients were in the follow-up, and one had lost the follow-up. Most of the follow-ups were for less than 16 months, two patients had event-free follow-ups of 45 months and 16 years. Five patients were noted to have bilateral tumors and all of them were alveolar variety except one where the variety was not mentioned but the description suggested embryonal type. Five patients had embryonal RMS, five had alveolar variety, one patient had spindle cell type, and histology was not mentioned in two patients. All the tumors except one were very large at presentation. The information about staging was not uniform in the available literature. We could infer from the available data that six of them had Stage 4 disease. Among the Stage 4 disease, three had bilateral alveolar tumor, and one each had unilateral alveolar RMS, spindle variety, and embryonal RMS. Non-RMS STS is distinct from the RMS, which constitutes 7% of STS. Although its surgical management is similar to RMS, the prognosis is not dependent on histology, site, age, or gender; instead is determined by the size at initial presentation, positive margin, and the presence of metastasis.[ 5 ] The postpubertal teratoma is also known to transform into malignancy of other cell lines such as adenocarcinoma, squamous cell carcinoma, and RMS in 0.2%–1.4% of cases.[ 6 7 ] Surgery is the main modality of treatment, along with chemotherapy and radiotherapy in necessary patients. Initially, we had a dilemma due to the discrepancy between serum AFP and IHC in the initial biopsy. Based on the IHC, nonrhabdomyomatous tumor of retroperitoneal tumor was suspected. Histopathology of the excised specimen showed complete necrosis of the tumor; hence, we could not get the exact tissue diagnosis. We consider our tumor as a primary ovarian RMS since initial Tru-cut biopsy showed spindle cells with no teratoma component; the tumor also responded well to preoperative chemotherapy of the RMS regimen, and non-rhabdomayomatous STS is not reported in the ovarian tumor of the pediatric age group. This signifies the need for adequate biopsy for the STS and utilization of immunohistochemistry. Other differential diagnoses of ovarian mass with round cell tumor are desmoplastic small round cell tumor (desmin positive), lymphoma (CD45/LCA positive), PNET (CD99 positive), small-cell carcinoma of hypercalcemic type, small-cell neuroendocrine carcinoma (synaptophysin/chromogranin positive). Such tumors arising from the fallopian tube also cannot be entirely ruled out.[ 8 9 ] At present, the overall outcome of the disease is dismal. Increased available data and clinical trials may help in improvising the treatment option for this rare tumor. The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Nil. There are no conflicts of interest.