Abstract
Purpose
Ovarian small cell carcinoma of the hypercalcaemic type is a very rare and highly aggressive malignant disease, mainly affecting young women. Due to the rarity of this tumour entity, prospective randomised trials are unlikely to be conducted, and the only retrospective analysis based on a large case series is from 1994. Since diagnostic and treatment modalities may have changed, we initiated this analysis.
Methods
The aim of our study was to review and analyse cases published since 1975 to validate former findings and to gather more information about therapy options, diagnostic and prognostic factors. A systematic literature search of the PubMed/Medline database was performed assessing all articles until September 2010. All retrieved articles were evaluated and cross-checked for references on the topic. In total, 135 cases were included, selected from 62 case reports and smaller case studies.
Results
Small cell carcinoma mostly affects women with a mean age of 23.4 years. They present with unspecific symptoms like abdominal pain or palpable mass, sometimes accompanied by an elevated calcium or CA-125 serum concentration. The tumour appears nearly almost unilaterally, mostly affecting the right ovary. Tumour stage is a clearly prognostic factor. Adjuvant chemotherapy consisting of etoposide, cisplatinum/carboplatinum or vinca alkaloids has shown improved survival, whereas radiotherapy has not.
Conclusions
In spite of limitations this analysis provides new insights especially with respect to therapeutic aspects. This review underlines the importance of case reports in rare tumour entities in order to answer open questions.
Similar content being viewed by others
References
Dickersin GR, Kline IW, Scully RE (1982) Small cell carcinoma of the ovary with hypercalcemia: a report of eleven cases. Cancer 49:188–197
Cannon PM, Smart CR, Wilson ML, Edwards CB (1975) Hypercalcemia with ovarian granulosa cell carcinoma. Rocky Mt Med J 72:72–74
Young RH, Oliva E, Scully RE (1994) Small cell carcinoma of the ovary, hypercalcemic type. A clinicopathological analysis of 150 cases. Am J Surg Pathol 18:1102–1116
Dickersin GR, Scully RE (1998) Ovarian small cell tumors: an electron microscopic review. Ultrastruct Pathol 22:199–226
Ulbright TM, Roth LM, Stehman FB, Talerman A, Senekjian EK (1987) Poorly differentiated (small cell) carcinoma of the ovary in young women: evidence supporting a germ cell origin. Hum Pathol 18:175–184
Eichhorn JH, Bell DA, Young RH et al (1992) DNA content and proliferative activity in ovarian small cell carcinomas of the hypercalcemic type. Implications for diagnosis, prognosis, and histogenesis. Am J Clin Pathol 98:579–586
Roth LMTA, Dietel M, Senzaki H (2003) Miscellaneous tumours and tumour-like conditions of the ovary. In: Tavassoli FA, Devilee P (eds) World Health Organization classification of tumours, pathology and genetics. tumours of the breast and female genital organs. IARC Press, Lyon, pp 182–190
Abeler V, Kjorstad KE, Nesland JM (1988) Small cell carcinoma of the ovary. A report of six cases. Int J Gynecol Pathol 7:315–329
Baeyens L, Amat S, Vanden Houte K, Vanhoutte P, L’Hermite M (2008) Small cell carcinoma of the ovary successfully treated with radiotherapy only after surgery: case report. Eur J Gynaecol Oncol 29:535–537
Barondeau J, Rodgers M, Braun L, Azarow K, Forouhar M, Faucette K (2010) Small cell ovarian carcinoma: a rare, aggressive tumor masquerading as constipation in a teenager with a fatal outcome. J Pediatr Hematol Oncol 32:e139–e141
Benrubi GI, Pitel P, Lammert N (1993) Small cell carcinoma of the ovary with hypercalcemia responsive to sequencing chemotherapy. South Med J 86:247–248
Bertoni F, Ferramosca B, Bacchini P (1983) Small cell ovarian carcinoma with hypercalcemia: the role of the parathyroid hormone. G Clin Med 64:564–570
Bourgain A, Acker O, Lambaudie E et al (2005) Small cell carcinoma of the ovary of the hypercalcaemic type revealed by a severe acute pancreatitis: about one case. Gynecol Obstet Fertil 33:35–38
Buono JP, Dechelotte P, Glowaczower E et al (1995) Ploidy analysis in a case of ovarian small cell carcinoma with hypercalcemia. Ann Pathol 15:134–137
Chakraborty J, Biswas S, Sanyal S, Mukherjee C, Chaudhuri MK (2007) Small cell carcinoma of ovary: a rare pathology. Indian J Pathol Microbiol 50:322–324
Chan LC, Cheung A, Cheng D (1994) Small cell carcinoma of the ovary associated with ins(10;5)(p13;q31q13). Cancer Genet Cytogenet 77:89–90
Chen F, Koenig C, Heller DS (2006) A 26-year-old woman with right ovarian mass. Small cell carcinoma of ovary, hypercalcemic type. Arch Pathol Lab Med 130:e56–e58
Chen L, Dinh TA, Haque A (2005) Small cell carcinoma of the ovary with hypercalcemia and ectopic parathyroid hormone production. Arch Pathol Lab Med 129:531–533
Christin A, Lhomme C, Valteau-Couanet D, Dubrel M, Hartmann O (2008) Successful treatment for advanced small cell carcinoma of the ovary. Pediatr Blood Cancer 50:1276–1277
Dharan M (1993) Intraoperative cytology of small cell carcinoma of the ovary with hypercalcemia. A case report. Acta Cytol 37:61–66
Di Vagno G, Melilli GA, Cormio G et al (2000) Large-cell variant of small cell carcinoma of the ovary with hypercalcaemia. Arch Gynecol Obstet 264:157–158
Distelmaier F, Calaminus G, Harms D et al (2006) Ovarian small cell carcinoma of the hypercalcemic type in children and adolescents: a prognostically unfavorable but curable disease. Cancer 107:2298–2306
Donato G, Conforti F, Zuccala V et al (2008) Large cell variant ovarian small cell carcinoma: case report. Ultrastruct Pathol 32(5):206–210
Dykgraaf RH, de Jong D, van Veen M, Ewing-Graham PC, Helmerhorst TJ, van der Burg ME (2009) 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 19:348–353
Ferrera PC, Whitman MC (2000) Ovarian small cell carcinoma: a rare neoplasm in a 15-year-old female. Pediatr Emerg Care 16:170–172
Fignon A, Fetissof F, Calais G et al (1993) Small cell carcinoma of the ovary. A clinical and anatomo-pathologic entity. J Gynecol Obstet Biol Reprod (Paris) 22:372–378
Florell SR, Bruggers CS, Matlak M, Young RH, Lowichik A (1999) Ovarian small cell carcinoma of the hypercalcemic type in a 14 month old: the youngest reported case. Med Pediatr Oncol 32:304–307
Forster C, Ostertag H, Schmitt J, Roessner A (1997) Small cell carcinoma of the ovary, hypercalcemic type. A case report with immunohistochemical, ultrastructural and cytophotometric analysis and review of the literature. Gen Diagn Pathol 142:365–370
Fukunaga M, Endo Y, Nomura K, Ushigome S (1997) Small cell carcinoma of the ovary: a case report of large cell variant. Pathol Int 47:250–255
Hamilton S, Beattie GJ, Williams AR (2004) Small cell carcinoma of the ovary: a report of three cases and review of the literature. J Obstet Gynaecol 24:169–172
Harrison ML, Hoskins P, du Bois A et al (2006) Small cell of the ovary, hypercalcemic type—analysis of combined experience and recommendation for management. A GCIG study. Gynecol Oncol 100:233–238
Holtz G, Johnson TR Jr, Schrock ME (1979) Paraneoplastic hypercalcemia in ovarian tumors. Obstet Gynecol 54:483–487
Idei Y, Kitazawa S, Fujimori T et al (1996) Ovarian small cell carcinoma with K-ras mutation: a case report with genetic analysis. Hum Pathol 27(1):77–79
Inadome Y, Shibata T, Suzuki K, Tsugata M, Shimabukuro K, Noguchi M (2009) Hypercalcemic-type ovarian small cell carcinoma with unique CD34 expression. Pathol Int 59:766–768
Isonishi S, Nishii H, Saitou M et al (2008) Small cell carcinoma of the ovary: clinical and biological study. Int J Clin Oncol 13:161–165
Kanwar VS, Heath J, Krasner CN, Pearce JM (2008) Advanced small cell carcinoma of the ovary in a seventeen-year-old female, successfully treated with surgery and multi-agent chemotherapy. Pediatr Blood Cancer 50:1060–1062
Kedzia H (1994) Small cell carcinoma of the ovary. Ginekol Pol 65:146–152
Lamovec J, Bracko M, Cerar O (1995) Familial occurrence of small-cell carcinoma of the ovary. Arch Pathol Lab Med 119:523–527
Lifschitz-Mercer B, David R, Dharan M, Czernobilsky B (1992) Small cell carcinoma of the ovary: an immunohistochemical and ultrastructural study with a review of the literature. Virchows Arch A Pathol Anat Histopathol 421:263–270
Longy M, Toulouse C, Mage P, Chauvergne J, Trojani M (1996) Familial cluster of ovarian small cell carcinoma: a new mendelian entity? J Med Genet 33:333–335
Malfetano JH, Degnan E, Florentin R (1990) Para-endocrine hypercalcemia and ovarian small cell carcinoma. N Y State J Med 90:206–207
Martinez-Borges AR, Petty JK, Hurt G, Stribling JT, Press JZ, Castellino SM (2009) Familial small cell carcinoma of the ovary. Pediatr Blood Cancer 53:1334–1336
McCormick TC, Muffly T, Lu G, Shoup B (2009) Aggressive small cell carcinoma of the ovary, hypercalcemic type with hypercalcemia in pregnancy, treated with conservative surgery and chemotherapy. Int J Gynecol Cancer 19:1339–1341
Meganck G, Moerman P, De Schrijver D, Berteloot P, Vergote I (1998) A non-diploid, small cell carcinoma of the ovary of the hypercalcemic type. Int J Gynecol Cancer 8:430–433
Niimi S, Kiyokawa T, Takakura S, Ochiai K, Tanaka T (2006) Recurrent small cell carcinoma of the ovary treated with docetaxel: A case report. Int J Gynecol Cancer 16:1944–1946
Patsner B, Piver MS, Lele SB, Tsukada Y, Bielat K, Castillo NB (1985) Small cell carcinoma of the ovary: a rapidly lethal tumor occurring in the young. Gynecol Oncol 22:233–239
Peccatori F, Bonazzi C, Lucchini V, Bratina G, Mangioni C (1993) Primary ovarian small cell carcinoma: four more cases. Gynecol Oncol 49:95–99
Powell JL, McAfee RD, McCoy RC, Shiro BS (1998) Uterine and ovarian conservation in advanced small cell carcinoma of the ovary. Obstet Gynecol 91:846–848
Pruett KM, Gordon AN, Estrada R, Lynch GR (1988) Small-cell carcinoma of the ovary: an aggressive epithelial cancer occurring in young patients. Gynecol Oncol 29:365–369
Rana S, Warren BK, Yamada SD (2004) Stage IIIC small cell carcinoma of the ovary: survival with conservative surgery and chemotherapy. Obstet Gynecol 103:1120–1123
Rasmussen KL, Jensen ML, Nielsen KM, Velander G (1991) Small cell carcinoma of the ovary diagnosed in early pregnancy. Acta Obstet Gynecol Scand 70:377–379
Reckova M, Mego M, Rejlekova K, Sycova-Mila Z, Obertova Z, Mardiak J (2010) Small-cell carcinoma of the ovary with breast metastases: a case report. Klin Onkol 23:43–45
Reed WC (1995) Small cell carcinoma of the ovary with hypercalcemia: report of a case of survival without recurrence 5 years after surgery and chemotherapy. Gynecol Oncol 56:452–455
Saika N, Malhotra P, Khandelwal N, Joshi K (2005) Small cell carcinoma of the ovary presenting as bone marrow metastasis: a rare presenting feauture. Indian J Pathol Microbiol 48:402–404
Schleef J, Wagner A, Kleta R et al (1999) Small-cell carcinoma of the ovary of the hypercalcemic type in an 8-year-old girl. Pediatr Surg Int 15:431–434
Schweiger LM, Hsiang HY (2002) Pathological case of the month. Acute symptomatic hypercalcemia associated with ovarian small cell carcinoma. Arch Pediatr Adolesc Med 156:83–84
Selvaggi SM (1994) Small-cell carcinoma of the ovary in peritoneal fluid. Diagn Cytopathol 11:266–270
Senekjian EK, Weiser PA, Talerman A, Herbst AL (1989) Vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide in the treatment of small cell carcinoma of the ovary. Cancer 64:1183–1187
Sholler GL, Luks F, Mangray S, Meech SJ (2005) Advanced small cell carcinoma of the ovary in a pediatric patient with long-term survival and review of the literature. J Pediatr Hematol Oncol 27:169–172
Taraszewski R, Rosman PM, Knight CA, Cloney DJ (1991) Small cell carcinoma of the ovary. Gynecol Oncol 41:149–151
Tewari K, Brewer C, Cappuccini F, Macri C, Rogers LW, Berman ML (1997) Advanced-stage small cell carcinoma of the ovary in pregnancy: long-term survival after surgical debulking and multiagent chemotherapy. Gynecol Oncol 66:531–534
Walt H, Hornung R, Fink D et al (2001) Hypercalcemic-type of small cell carcinoma of the ovary: characterization of a new tumor line. Anticancer Res 21:3253–3259
Wynn D, Everett GD, Boothby RA (2004) Small cell carcinoma of the ovary with hypercalcemia causes severe pancreatitis and altered mental status. Gynecol Oncol 95:716–718
Young RH, Goodman A, Penson RT, Russell AH, Uppot RN, Tambouret RH (2010) 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 362:1031–1040
Morris CR, Sands MT, Smith LH (2010) Ovarian cancer: predictors of early-stage diagnosis. Cancer Causes Control 21:1203–1211
Markmann S, Gerber B, Briese V (2007) Prognostic value of Ca 125 levels during primary therapy. Anticancer Res 27:1837–1839
Wakabayashi MT, Lin PS, Hakim AA (2008) The role of cytoreductive/debulking surgery in ovarian cancer. J Natl Compr Canc Netw 6:803–810
Pautier P, Ribrag V, Duvillard P et al (2007) Results of a prospective dose-intensive regimen in 27 patients with small cell carcinoma of the ovary of the hypercalcemic type. Ann Oncol 18:1985–1989
Hornung R, Fink D, Dobler-Girdziunaite D, Stallmach T, Haller U, Walt H (1999) Photodynamic therapy for the hypercalcemic type of the small cell carcinoma of the ovary in a mouse xenograft model. Gynecol Oncol 75:447–452
Acknowledgments
The authors thank Dr. Igor Hrgovic for his support during the study.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Estel, R., Hackethal, A., Kalder, M. et al. Small cell carcinoma of the ovary of the hypercalcaemic type: an analysis of clinical and prognostic aspects of a rare disease on the basis of cases published in the literature. Arch Gynecol Obstet 284, 1277–1282 (2011). https://doi.org/10.1007/s00404-011-1846-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00404-011-1846-5