Diapositiva 1

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OVARIAN NON-SMALL CELL UNDIFFERENTIATED CARCINOMA OF NEUROENDOCRINE TYPE M Mora*, E Fulcheri*, ML Carcangiu**.

*Department of Surgical and Morphological Sciences, Anatomic Pathology Division, University of Genova, Italy.

**Department of Pathology, Istituto Nazionale Tumori, Milan, Italy.

Introduction Neuroendocrine carcinomas of the ovary include small cell carcinoma of pulmonary type, small cell carcinoma of hypercalcemic type and non-small cell undifferentiated carcinoma of neuroendocrine type (NSCNEC) which is often associated to epithelial-stromal tumours [1-2-3] .

A large variety of primary ovarian epithelial-stromal tumours may express neuroendocrine trabecular and insular growth pattern [2] .

differentiation, with neuroendocrine cells arranged singularly or in solid areas with

Methods /1 Pelvic mass in a 41 year-old woman with no significant past medical history.

Pelvic ultrasound cystic appearance of 41 x 40 mm and a second one of solid appearance.

showed two masses in right ovary, one of Laboratory test 125, no hypercalcemia or paraneoplastic syndromes were observed.

showed normal levels for serum CEA and CA-

Methods /2 Right salpingo-oophorectomy for introperative consultation.

was performed and the ovary sent After the diagnosis of carcinoma was given, patient underwent: • hysterectomy with left salpingo-oophorectomy, • omentectomy, • pelvic lymph node dissection, • multiple biopsies of abdominal side wall and peritoneal ligaments.

Results Microscopic investigation revealed that the tumour was composed of a G2 endometroid carcinoma commisted to a solid tumour with neuroendocrine features , consisting of cells of medium to large size with scanty cytoplasm and nuclei with evenly distributed chromatin and occasional large nucleoli.

These latter were arranged in solid sheet, island or nest, with little or no intervening stroma; in other areas they were disposed in single-elements ribbons surrounding endometrioid glands without infiltrating them. No high cytologic atypia and mitotic activity were demonstrated.

E&E, 20x

E&E, 20x

E&E, 40x

Results Immunohistochemical staining showed: positivity of the neuroendocrine component for: • Chromogranin A • NSE • Synaptophysin positivity of the endometrioid component for: • CEA (focally) • CA-125 • EMA • ER and PGR receptors

Chromogranin A, 20x

Synaptophysin, 20x

Conclusion We concluded that the lesion was a primary ovarian cell carcinoma of neuroendocrine type (NSCNEC) associated to an endometroid carcinoma .

non-small Tumour stage was pT1c/G2/N0/Mx.

Conclusion At present in the literature there are 27 previous cases of NSCNEC, 26 of which associated to epithelial-stromal tumours:

Authors

Collins RJ, 1991 [4] Khurana KK, 1994 [5] Jones K, 1996 [6] Eichhorn JH, 1996 [7] Chen KTK, 2000 [8]

NEC non-small cell NEC non-small cell NEC non-small cell NE tumors non-small cell NEC non-small cell

Behnam K, 2004 [9] Hirasawa T, 2004 [10]

NEC non-small cell NEC non-small cell

Ohira S, 2004 [11] Ahmed Z, 2005 [12] Duk Choi, 2007 [13] Veras E, 2007 [14]

NEC non-small cell NEC non-small cell NEC non-small cell NEC non-small cell n. of cases

1 1 1 5 2

Association with:

borderline mucinous tumour with focal cancerization borderline mucinous tumour with focal cancerization mucinous cystadenoma borderline mucinous tumour with focal cancerization (n. 2) mucinous carcinoma (n. 2) endometrioid carcinoma G1 (n. 1) mucinous carcinoma in situ (n. 1) mucinous carcinoma in situ with focal stromal invasion(n. 1) 1 2 1 1 1 11 No surface epithelial tumoral components.

mucinous carcinoma (n. 1) mucinous cystadenoma (n. 1) endometrioid carcinoma G1 mucinous cystadenoma serous carcinoma mucinous carcinoma (n. 1) LMP mucinous with foci of cancerization (n. 2) LMP mucinous (n. 1) endometrioid carcinoma (n. 2) mucinous carcinoma + endometrioid carcinoma (n. 1) Carcinoma NAS (n. 2) dermoid cyst (n. 1) benign cyst NAS (n. 1)

Conclusion NSCNEC can be misdiagnosed as metastasis of large cell endocrine carcinoma of unknown origin but clinical findings help the pathologist to the correct diagnosis and the association with a epithelial-stromal neoplasia is a clue to the primary nature of the neoplasm.

References 1] Eichhorn JH, Young RH. Neuroendocrine tumours of the genital tract. Am J Clin Pathol; 2001; 115(Suppl. 1):S94-112 .

2] Scully RE et al. Tumors of the ovary, maldeveloped gonads, fallopian tube and broad ligament, chapter 17. Whashington D.C.: Ed.

Armed Forces Institute of Pathology 1996.

3] WHO Classification of Tumours. Pathology&Genetics. Tumours of the Breast and Female Genital Organs. IARCPress, Lyon 2003.

4] Collins R, Cheung A, Ngan H, et al. Primary mixed neuroendocrine and mucinous carcinoma of the ovary. Arch Gynecol Obstet.

1991;248:139–143.

5] Khurana K, Tornos C, Silva E. Ovarian neuroendocrine carcinoma associated with a mucinous neoplasm. Arch Pathol Lab Med.

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6] Jones K, Diaz J, Donner L. Neuroendocrine carcinoma arising in an ovarian mucinous cystadenoma. Int J Gynecol Pathol.

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7] Eichhorn J, Lawrence W, Young R, et al. Ovarian neuroendocrine carcinomas of non-small-cell type associated with surface epithelial adenocarcinomas—A study of .ve cases and review of the literature. Int J Gynecol Pathol. 1996;15:303–314.

8] Chen KT. Composite large-cell neuroendocrine carcinoma and surface epithelial-stromal neoplasm of the ovary. Int J Surg Pathol.

2000;8:169–174.

9] Behnam K, Kabus D, Behnam M. Primary ovarian undi.erentiated non-small cell carcinoma, neuroendocrine type. Gynecol Oncol.

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10] Hirasawa T. Ovarian neuroendocrine carcinoma associated with mucinous carcinoma and teratoma. Nippon Rinsho 2004;62:973– 8.

11] Ohira S, Itoh K, Shiozawa T, Horiuchi A, Ono K, Takeuchi H, et al. Ovarian non-small cell neuroendocrine carcinoma with paraneoplastic parathyroid hormone-related hypercalcemia. Int J Gynecol Pathol 2004;23:393–7.

12] Ahmed Z, Aftab K, Kayani N.Ovarian Primary Neuroendocrine Carcinoma of Non-Small Cell type: report of an extremely rare Neoplasm. J Pak Med Assoc. 2005;55:82–84.

13] Duk Choi Y, Shin Lee J, Choi C, Soo Park C, Hee Nam J. Ovarian neuroendocrine carcinoma, non-small cell type, associated with serous carcinoma. Gynecologic Oncology 2007;104: 747–752.

14] Veras E, Deavers MT, Silva EWG, Malpica A. Ovarian Nonsmall Cell Neuroendocrine Carcinoma A Clinicopathologic and Immunohistochemical Study of 11 Cases. Am J Surg Pathol 2007;31:774–782).