Year : 2019 | Volume
: 3 | Issue : 3 | Page : 102--104
Smallcell ovarian carcinoma of the hypercalcemic type: Report of three cases and literature review
Khedija Meddeb, Wafa Sbika, Amina Mokrani, Essia Mezni, Yosra Yahyaoui, Feriel Letaif, Azza Gabsi, Mghirbi Fahmi, Mouna Ayadi, Nesrine Chraiet, Henda Rais, Amel Mezlini
Department of Medical Oncology, Salah Azaiez Institute, University of Tunis EL Manar, Tunis, Tunisia
Dr. Wafa Sbika
Department of Medical Oncology, Salah Azaiez Institute, University of Tunis EL Manar, Tunis
The small-cell carcinoma of hypercalcemic type (SCOCHT) of the ovary is a rare and highly aggressive tumor. Due to the rarity of the disease, there is no consensus on its optimal therapy, and the treatment options are usually combines surgery, chemotherapy, and radiotherapy. Herein, we report the clinical presentation, management, and outcome of three cases of SCCOHT treated at Salah Azaiez Institution in Tunisia. The literature on this rare disease is also reviewed.
|How to cite this article:|
Meddeb K, Sbika W, Mokrani A, Mezni E, Yahyaoui Y, Letaif F, Gabsi A, Fahmi M, Ayadi M, Chraiet N, Rais H, Mezlini A. Smallcell ovarian carcinoma of the hypercalcemic type: Report of three cases and literature review.Libyan J Med Sci 2019;3:102-104
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Meddeb K, Sbika W, Mokrani A, Mezni E, Yahyaoui Y, Letaif F, Gabsi A, Fahmi M, Ayadi M, Chraiet N, Rais H, Mezlini A. Smallcell ovarian carcinoma of the hypercalcemic type: Report of three cases and literature review. Libyan J Med Sci [serial online] 2019 [cited 2023 Mar 30 ];3:102-104
Available from: https://www.ljmsonline.com/text.asp?2019/3/3/102/269223
Small-cell ovarian carcinoma of the hypercalcemic type (SCCOHT) is a very rare and highly aggressive tumor. Usually, it occurs in young women and it is characterized by a deleterious germline or somatic mutations in SMARCA4. There is no consensus on the optimal treatment given the rarity of these tumors. The majority of recommended treatment are derived from case reports and small case series. Herein, we report three cases of this rare entity from our clinical practice and discuss through the existing literature its differential diagnosis and management.
Between 2013 and 2015, three cases of SCCOHT were diagnosed and treated at Salah Azaiez Institution in Tunis, Tunisia. A PUBMED research from January 1996 to January 2016 using the keywords “Small-cell ovarian cancer” and “Hypercalcemic type” found 25 case reports with available data.
Case report 1
A 16-year-old female patient presented with a 1-month history of painful abdominal distension. Physical examination revealed a large pelvic mass of 15 cm. Ultrasound computed tomography (CT) found a 20 cm intraperitoneal heterogeneous mass with medium peritoneal effusion. Alpha-fetoprotein and human chorionic gonadotropin serum level were normal. Lactate dehydrogenase was elevated to 931 UI/l (normal value: 140–280 UI/l). The serum calcium was normal. At laparotomy, she was found to have a friable tumor of 30 cm at the expense of the right ovary. A debulking surgery with a right oophorectomy and appendectomy was performed. Histological examination showed an undifferentiated tumor proliferation with round cells and spindle cell components. The appendicular meso was infiltrated. The tumor stained positive for angiotensin-converting enzyme and epithelial membrane antigen (EMA) in tubular structures and negative for alpha-fetoprotein, human placenta-like alkaline phosphatase, and progesterone and estrogen receptor. The diagnosis of Stage IIC Sertoli -Leydig tumor was made. One month postoperative CT showed a pelvic mass of 10 cm × 7.5 cm. It was associated with peritoneal carcinosis and hepatic metastasis. Considering this unusual presentation, revision of the pathology yielded a diagnosis of ovarian small-cell carcinoma of hypercalcemic type.
The patient underwent three courses of cisplatin/ Adriamycin/ Etoposide/ cyclophosphamide (PAVEP) regimen chemotherapy. Assessment after three cycles of chemotherapy showed a partial response. The patient had progressive disease 1 month after completing six cycles of chemotherapy. She died of the disease 1 month later.
Case report 2
A 21-year-old female presented with abdominal distension, weight loss, and anorexia. She complained of the right iliac fossa pain. Ultrasonography showed a voluminous heterogeneous mass with mixed echogenicity arising from the uterus. It was associated with a right urinary distal distension and fluid effusion. Serum CA125 level was high (45.48 UI/) (normal value 35 UI/l). The serum calcium level was elevated at 2.64 mmol/l (normal level: 2.22–2.52 mmol/l). Pelvic MRI found an 18 cm × 16.5 cm × 11.5 cm right ovarian cystic solid mass infiltrating the right anterior abdominal wall. Gastroscopy and colonoscopy examinations were normal.
Exploratory laparotomy found a bulky solido-cystic mass of 10 cm with exophytic vegetations and several infracentimetric nodules on the pelvic peritoneum and the posterior face of the uterus. The contralateral ovary was normal. The patient underwent a right oophorectomy and peritoneal lavage. Definitive histology revealed a malignant proliferation of spans and cellular masses poorly defined within a fibrous or focally myxoid stroma. It was associated with a small-cell component. Foci of necrosis are present as well as numerous tumor emboli. Immunohistochemistry showed positive staining for cytokeratin, EMA, synaptophysin, and chromogranin. Inhibin was negative. The diagnosis of OSCCHT was made. The postoperative CT scan revealed a tumor progression with large spreading of pelvic nodules, muscular metastasis in the abdominal wall, and hepatic metastasis. The patient received four cycles of chemotherapy based on PAVEP regimen with evidence of pelvic lymph nodes, hepatic, and pulmonary progression. Second-line chemotherapy including docetaxel and gemcitabin was decided. This patient was lost to follow-up, and we do not have any information about the response.
Case report 3
A 10-year-old girl presented with a 4-week history of the right iliac fossa pain. Physical examination showed a palpable mass in the pelvis. The ultrasonographic scan showed a pelvic mass of 5.7 cm × 5.5 cm associated with intraperitoneal fluid in the pouch of Douglas. The tumor was highly vascularized on Doppler. An exploratory laparotomy was performed. Torsion of the right ovary with a solid mass of 7 cm was found. The patient underwent a right oophorectomy. The histopathological examination concluded to a small-cell tumor of the ovary of hypercalcemic type. There was no evidence of distant metastases at CT scan.
She received adjuvant chemotherapy in the form of four cycles of bleomycin/etoposide/cisplatinum (BEP) including bleomycin at a dose of 30 UI × 3 per cycle, etoposide at a dose of 100 mg/m2 × 5 per cycle, and cisplatin at a dose of 20 mg/m2 × 5 per cycles. The evaluation after chemotherapy showed a complete clinical and radiologic remission.
The SCCOHT is a rare tumor, described in 1979 by Scully. There are about 300 cases described in the literature seen mainly in young women. Young et al. reported the largest series of OSCCHT, which includes 150 patients. The median age at diagnosis is 24 years. Our patients were younger at diagnosis (21, 16, and 10 years old). No specific symptoms exist for OSCCHT. Abdominal pain and distension with or without a palpable pelvic mass are the most frequent presenting symptom. Tumor markers are noninformative in SCCOHT. In two-thirds of cases, this tumor is associated with hypercalcemia. The physiopathology of hypercalcemia is unclear. In some cases, it may be due to the secretion of parathyroid hormone (PTH) by tumor (PTH-related protein). In our cases, only one patient had a high level of serum calcium. Fifty percent of tumors were Stage I FIGO classification and 45% are diagnosed at FIGO Stage III. A bilateral tumor with an average size of 15 cm (range, 6–26) was found mostly. In our cases, there was no bilateral mass, and the size of the mass were, respectively, 20, 18, and 7 cm.
The histological diagnosis is hard because of similarities with other ovarian tumors. The differential diagnosis included the tumor granulosa cell type, the juvenile cell tumor of the adult-type granulosa, lymphoma, small-cell lung carcinoma, and metastases of melanoma. In 50% of cases, the main contingent of large cells and form a histological variant of small-cell carcinoma can be found. Some unusual findings have been described, such as mucinous glands, mucinous signet-ring cells, spindle cell sarcomatoid change, and rhabdoid cytomorphology. Moreover, the absence of a specific immunohistochemical profile of this tumor is an independent entity. It can express EMA, cytokeratin, vimentin, neuron-specific enolase, CD10, WT1, and p53.
There is no consensus for the treatment of OSCCHT because of its rarity. Surgery is the first step to do for the diagnosis and to treat the patients. Although at the early stage of the disease, we recommend radical surgery (hysterectomy and bilateral oophorectomy. Fertility-sparing surgery could be seen in the early stages for these young patients. For patients with advanced SCCOHT, an aggressive approach is applied. Adjuvant chemotherapy improves the survival in FIGO Stage IA compared with those who underwent surgery. Several protocols have been used. The best result was obtained with PAVEP and BEP. Protocols, including cyclophosphamid, doxorubicin with or without cisplatin, or paclitaxel in combination with cisplatin with the advanced disease by analogy to other epithelial tumors of the ovary, were with no efficacy.
Most patients with better outcomes had received adjuvant radiotherapy (abdominal, pelvic, or para-aortic) or concurrent with chemotherapy. In the study of Harrison et al., five of seven patients received chemotherapy had better survival. The good prognostic factors reported by Young et al. are the localized stage of tumor, size <10 cm, and the patient age >30 years. Tumors without a large contingent of cells are also associated with significantly better survival. In the series of Young, a better survival (1–13 years) for Stage IA and for patients who had undergone radical surgery was reported.
In conclusion, we presented three cases of SCCOHT with poor prognostic factors. A multimodality approach is the standard of care in SCCOHT. Despite the rarity of this tumor, the treatment must be done in expert center and discussed in multidisciplinary meeting board to provide the best outcomes.
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Conflicts of interest
There are no conflicts of interest.
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