Primitive Neuroectodermal Tumors (PNETs) of the Female Genital Tract (FGT): A Morphologic, Immunohistochemical, and Molecular Study of 18 Cases
S Kojiro, A Quer, M Snuderl, D Daya, T Hayashi, L Bosincu, F Ogawa, Q Vu, AE Rosenberg, AJ Iafrate, E Oliva. Massachusetts General Hospital, Boston, MA; McMaster Hospital, Hamilton, ON, Canada; Saitama International Medical Center, Hidaka, Saitama, Japan; Universita di Sassari, Sassari, Italy; Prefectural Miyazaki Hospital, Miyazaki, Japan
Background: PNETs of FGT are very rare, ovary and uterus being the most common locations. Although these tumors have been traditionally classified as primitive neuroectodermal tumors and in the ovary frequently resemble neoplasms of the central nervous system (CNS), in other locations, distinction between CNS-PNET and peripheral Ewing/PNET is frequently difficult.
Design: The clinicopathologic features of eighteen PNETs involving ovary (9), uterus (8), and vulva (1) were studied. Immunohistochemistry for Fli-1, CD99, Synaptophysin, Chromogranin, CD56, Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), Neurofilament (NF), S-100, Vimentin, and Cytokeratin (CK) was performed. A break-apart probe was used to evaluate any rearrangement of the EWSR1 gene by fluoresence in situ hybridization (FISH).
Results: Patients ranged in age from 14 to 66 (mean 37) years. Six patients had stage I tumors, while 1, 9, and 2 had stage II, III and IV tumors. Twelve neoplasms morphologically resembled CNS PNETs with variable degrees of neuronal differentiation, 3 of them also showing focal ependymal differentiation; one had classical features of medulloepithelioma and another showed features of mixed PNET and glioblastoma. In four cases, the morphologic features of CNS PNET were not recognized. Associated tumors included mature cystic teratoma (5), endometrioid endometrial carcinoma (2) and carcinosarcoma (1). Fli-1 was positive in 16/18 tumors (9 strong/diffuse), CD99 in 10/18 (5 strong/diffuse), Synaptophysin in 10/18, Chromogranin in 1/18, CD56 in 14/18, GFAP in 4/18, NSE in 8/18, S-100 in 8/18, Vimentin in 18/18, and CK in 4/18. Only 2/18 tumors showed EWSR1 gene rearrangement by FISH, both lacking morphological features of CNS PNETs.
Conclusions: Most PNETs of the FGT resemble histologically their CNS counterparts. Immunohistochemistry is not helpful in distinguishing peripheral from CNS PNET, particularly, Fli-1 and CD99 as they are expressed in both subsets. Tumors lacking any degree of CNS differentiation should undergo molecular testing as may represent peripheral PNET/Ewing. This distinction may be important for therapeutic and prognostic purposes.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 163, Wednesday Morning