Cell Carcinoma Of Hypercalcemic Type Research Articles

Use of monoclonal antibody against human inhibin as a marker for sex cord-stromal tumors of the ovary.

Inhibin is a glycoprotein hormone produced by normal ovarian granulosa cells and testicular sertoli cells. In the ovary, it inhibits the secretion of follicle-stimulating hormone. Patients with granulosa cell tumors (GCT) have elevated serum levels of inhibin and this finding has been used to detect recurrent tumor. This study attempts to determine whether inhibin antibody (IAB) can preferentially mark GCT and Sertoli-cell or Sertoli-Leydig cell tumors (SCT) in paraffin-embedded tissues and facilitate distinction of GCT from small cell carcinoma of hypercalcemic type (SCC), SCT from Sertoliform endometrioid carcinoma (SEC), and primitive gonadal-stromal tumors from a variety of poorly differentiated neoplasms. Applying microwave-enhanced immunohistochemistry, a total of 126 paraffin-embedded and microwave-enhanced archival ovarian tumors and tissues were studied by using monoclonal IAB. The tumors included 32 adult GCT, 7 juvenile GCT, 4 metastatic GCT, 8 SCT, 7 SCC, 6 primitive gonadal stromal tumors (PGST), 5 fibrothecomas, 6 lipid cell tumors (LCT), 5 extrauterine endometrial stromal sarcomas (ESS), 5 hemangiopericytomas (HPC), 1 metastatic malignant melanoma, 1 metastatic malignant lymphoma, and 27 epithelial tumors including 8 SEC, 5 mucinous tumors, and 4 Brenner tumors. Seven pregnancy luteomas (nodular theca lutein hyperplasia of pregnancy), 3 corpora lutea and 2 ovarian follicles were also studied. The intensity of immunostaining was scored from one to three and the percentage of the immunoreactive tumor cells was determined and expressed in 10% increments. Among 32 adult GCT, 31 (97%) tumors reacted positively with IAB. The percent of positive cells ranged from 30% to 100% (average 80%). Similarly, all four metastatic GCT, 7 juvenile GCT and 4 of 5 fibrothecomas were immunoreactive with monoclonal IAB. Seven of 8 (88%) SCT, 5 of 6 (83%) PGST, all 6 LCT, 7 pregnancy luteomas, 3 corpora lutea and the 2 ovarian follicles were also positive with IAB. The most intense positivity was observed in luteinized stromal cells regardless of tumor type. No immunoreactivity was observed in any of the 7 SCC, 5 ESS, 5 HPC, 1 metastatic malignant melanoma, 1 metastatic malignant lymphoma and the epithelial component of all 27 epithelial tumors including 8 SEC. Among the mucinous tumors of the ovary, however, 3 tumors with luteinized stromal cells showed immunoreactivity in these cells, but no positivity was seen in the mucinous epithelium. We conclude that IAB is an excellent marker for sex cord differentiation in ovarian tumors. It can be used effectively in the diagnosis of GCT and its distinction from epithelial neoplasms particularly SCC. The IAB may also be helpful in differentiating LCT from epithelial malignancies. However, it cannot be used to distinguish GCT from SCT.

Dysgerminoma of the Ovary Associated with Hypercalcemia

A 19-year-old female presented with a 3-week history of abdominal swelling, polydipsia, and polyuria. Ultrasound examination disclosed a right adnexal mass. Preoperative workup showed that the serum calcium level was elevated to 12.2 mg/dl. Laporotomy disclosed a right ovarian tumor and a right salpingo-oophorectomy was performed. The serum calcium level fell to within the normal range postoperatively. The ovarian tumor was a typical dysgerminoma on both gross and microscopic examination. The majority of ovarian tumors associated with paraneoplastic hypercalcemia in young females are small cell carcinomas of hypercalcemic type. It is important, however, for pathologists to be aware that the dysgerminoma is the second most common ovarian neoplasm associated with hypercalcemia in this age group, as diagnostic confusion between these two tumors may rarely occur on microscopic examination. The literature on ovarian tumors associated with hypercalcemia is briefly reviewed.

Small Cell Carcinoma of Hypercalcemic Type

The small cell carcinoma of the ovary that is associated with paraendocrine hypercalcemia in two thirds of cases is characterized typically by poorly differentiated small cells with scanty cytoplasm, although larger cells with abundant cytoplasm are frequently observed as well, usually as a minor component of the tumor. The tumor almost always occurs in women in the second to fourth decade, usually presenting at a stage higher than stage 1A. It must be distinguished from other primary and metastatic small cell carcinomas that may involve the ovary. The tumor differs in its histologic, electron microscopic, immunohistochemical, and flow cytometric features from the pulmonary type of small cell carcinoma that may metastasize to the ovary from the lung and other organs or rarely may be primary in the ovary. The cell lineage of the small cell carcinoma remains a mystery. The tumor is highly malignant, with only a 30% survival rate in Stage 1A cases. It may be responsive to radiation therapy and combination chemotherapy, but long-term survival is rare once the tumor has spread beyond the ovary.