Small cell carcinoma of the ovary hypercalcemic type (SCCOHT): report of three cases and literature review

Background: Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), is a rare ovarian tumor with hypercalcaemia mainly affecting young females, but its histogenesis remains largely unknown, which makes it a challenge for effective diagnosis and treatment. This report describes three cases of SCCOHT in young women aging between 23 and 31 years. Material and Methods: All three patients with SCCOHT were subjected to sex hormone and normal blood calcium test, B-ultrasound, and microscopic examination for diagnosis. Expression of low molecular weight Cytokeratin, Vimentin, INI1, WT1, and SMARCA4 were determined by immunohisto-chemistry. Morphological features of cancer cells were observed using electron microscopy, and gene mutation was analyzed by DNA sequencing. Results: All three SCCOHT patients were diagnosed by pathology examination, B-ultrasound, and increased blood calcium level, and underwent surgical resection followed by chemotherapy. Immunohistochemistry showed positive expression of WT-1, CK, INI1, Vimentin, EMA, CD10, and CD56 in tumor tissues of all three cases, but no expression of a-Inhibin, Bcl6, PLAP, Alk, SALL4, SMARCA4, OCT3/4, SF1, Calretinin, MPO, CD20, AFP, CD5, hCG-β, BCL2, ER, and S100. No mutations in FOXL2 gene were detected in these three SCCOHT cases. Two patients died within one year after surgery, and one was lost to follow-up. Conclusion: Three cases of young female SCCOHT patients were reported in this report, featured with poor prognosis even after surgery and chemotherapy.

SCCOHT; Small cell carcinoma of the ovary; Hypercalcaemia; INI1; SMARCA4.

[1] Korivi B.R., Javadi S., Faria S., Sagebiel T., Garg N., Patnana M., et al.: “Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Clinical and Imaging Review”. Curr. Probl. Diagn. Radiol., 2018, 47, 333.

[2] Witkowski L., Goudie C., Foulkes W.D., McCluggage W.G.: “SmallCell Carcinoma of the Ovary of Hypercalcemic Type (Malignant Rhabdoid Tumor of the Ovary): A Review with Recent Developments on Pathogenesis”. Surg. Pathol. Clin., 2016, 9, 215.

[3] Foulkes W.D., Clarke B.A., Hasselblatt M., Majewski J., Albrecht S., McCluggage, W.G.: “No small surprise - small cell carcinoma of the ovary, hypercalcaemic type, is a malignant rhabdoid tumour”. J. Pathol., 2014, 233, 209.

[4] Young R.H., Oliva, E., Scully, R.E.: “Small cell carcinoma of the ovary, hypercalcemic type. A clinicopathological analysis of 150 cases”. Am. J. Surg. Pathol.,1994, 18, 1102.

[5] Rouzbahman M., Clarke B.: “Neuroendocrine tumors of the gynecologic tract: Select topics”. Semin. Diagn. Pathol., 2013, 30, 224.

[6] Bourdeaut F., Lequin D., Brugières L., Reynaud S., Dufour C., Doz F., et al.: “Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor”. Clin. Cancer Res., 2011, 17, 31.

[7] Foulkes W.D., Clarke B.A., Hasselblatt M., Majewski J., Albrecht S., McCluggage,. W.G.: “No small surprise-small cell carcinoma of the ovary, hypercalcaemic type, is a malignant rhabdoid tumour”. J. Pathol., 2014, 233, 209.

[8] Witkowski L., Carrot-Zhang J., Albrecht S., Fahiminiya S., Hamel N., Tomiak E.: “Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type.” Nat Genet, 2014, 46, 438-443.

[9] Boussios S., Moschetta M., Zarkavelis G., Papadaki A., Kefas A., Tatsi K.: “Ovarian sex-cord stromal tumours and small cell tumours: Pathological, genetic and management aspects”. Crit. Rev. Oncol. Hematol., 2017, 120, 43.

[10] Ghazi A., Ayaz A., Hamid T., Farooq M.U., Islam N.: “Small cell carcinoma of the ovary hypercalcemic type (SCCOHT): A rare case after in vitro fertilization (IVF)”. Pak. J. Med. Sci., 2017, 33, 241.

[11] Young R.H., Goodman A., Penson R.T., Russell A.H., Uppot R.N., Tambouret R.H.: “Case records of the Massachusetts General Hospital. Case 8-2010. A 22-year-old woman with hypercalcemia and a pelvic mass”. N. Engl. J. Med., 2010, 362, 1031.

[12] Dykgraaf R.H., de Jong D., van Veen M., Ewing-Graham P.C., Helmerhorst T.J., van der Burg M.E.: “Clinical management of ovarian small-cell carcinoma of the hypercalcemic type: a proposal for conservative surgery in an advanced stage of disease”. Int. J. Gynecol. Cancer, 2009, 19, 348.

[13] Biegel J.A., Zhou J.Y., Rorke L.B., Stenstrom C., Wainwright L.M., Fogelgren B.: “Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors”. Cancer Res., 1999, 59, 74.

[14] Conlon N., Silva A., Guerra E., Jelinic P., Schlappe B.A., Olvera N., et al.: “Loss of SMARCA4 Expression Is Both Sensitive and Specific for the Diagnosis of Small Cell Carcinoma of Ovary, Hypercalcemic Type”. Am. J. Surg. Pathol., 2016, 40, 395.

[15] Karanian-Philippe M., Velasco V., Longy M., Floquet A., Arnould L., Coindre J.M., et al.: “SMARCA4 (BRG1) loss of expression is a useful marker for the diagnosis of ovarian small cell carcinoma of the hypercalcemic type (ovarian rhabdoid tumor): a comprehensive analysis of 116 rare gynecologic tumors, 9 soft tissue tumors, and 9 melanomas”. Am. J. Surg. Pathol., 2015, 39, 1197.

[16] Jamshidi F., Nielsen T.O., Huntsman D.G.: “Cancer genomics: why rare is valuable”. J. Mol. Med. (Berl.), 2015, 93, 369.

[17] McCluggage W.G., Oliva E., Connolly L.E., McBride H.A., Young R.H.: “An immunohistochemical analysis of ovarian small cell carcinoma of hypercalcemic type”. Int. J. Gynecol. Pathol., 2004, 23, 330.

[18] Hildebrandt R.H., Rouse R.V., Longacre T.A.: “Value of inhibin in the identification of granulosa cell tumors of the ovary”. Hum. Pathol., 1997, 28, 1387.

[19] Bús D., Buzogány M., Nagy G., Vajda G.: “Rare virilizing granulosa cell tumor in an adolescent”. Mol. Clin. Oncol., 2017, 6, 88.

[20] Harrison M.L., Hoskins P., du Bois A., Quinn M., Rustin G.J., Ledermann J.A., et al.: “Small cell of the ovary, hypercalcemic type -- analysis of combined experience and recommendation for management. A GCIG study”. Gynecol. Oncol., 2006, 100, 233.

[21] Callegaro-Filho D., Gershenson D.M., Nick A.M., Munsell M.F., Ramirez P.T., Eifel P.J., et al.: “Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT): A review of 47 patients”. Gynecol. Oncol., 2015, 140, 53.