Ependymomas of the central nervous system and adult extra-axial ependymomas are morphologically and immunohistochemically distinct--a comparative study with assessment of ovarian carcinomas for expression of glial fibrillary acidic protein.

Extra-axial ependymomas are very rare but have been reported in the ovary, broad ligament, sacrococcygeal region, lung, and mediastinum. The histogenesis is obscure, and a thorough immunohistochemical analysis is lacking. We reviewed the morphologic and immunohistochemical features of 5 extra-axial ependymomas occurring in adults, 1 arising in an infantile sacrococcygeal teratoma, and a control group of 10 central nervous system (CNS) ependymomas in adults. All cases were evaluated for expression of epithelial membrane antigen, estrogen receptor (ER), progesterone receptor (PR), WT1, CD99, CK18, AE1:3, CAM 5.2, 34betaE12, CK7, CK20, synaptophysin, chromogranin, and glial fibrillary acidic protein (GFAP) using formalin-fixed, paraffin-embedded tissue. One hundred twelve ovarian carcinomas in 3 tissue microarrays were also studied with GFAP. The adult extra-axial cases demonstrated more architectural variability than the CNS cases. We observed that both the CNS and adult extra-axial ependymomas expressed GFAP diffusely, whereas only 9 stage III, high-grade ovarian serous papillary carcinomas stained with GFAP (2 strongly and diffusely and 7 exhibiting focally weak expression). There were significant immunophenotypic differences between adult extra-axial and CNS ependymomas, with extra-axial cases preferentially expressing 34betaE12 (60% vs. 0%), CK18 (100% vs. 20%), CAM 5.2 (60% vs. 10%), CK7 (80% vs. 10%), ER (100% vs. 10%), and PR (80% vs. 20%). Two spinal cord ependymomas expressed CK18, 1 expressed CK7, and 1 expressed CAM 5.2. CNS ependymomas more frequently expressed CD99 (100% vs. 20%). The following stains were not differentially expressed: epithelial membrane antigen (expressed in 2 of 15 cases, including both extra-axial and CNS ependymomas), synaptophysin (1/15), chromogranin (0/15), WT1 (8/15), AE1:3 (10/15), and CK20 (0/15). The ependymal elements of the sacrococcygeal tumor failed to express 34betaE12, CK18, CAM 5.2, and CK7, like most CNS ependymomas. The morphologic and immunophenotypic differences between extra-axial and CNS ependymomas suggest that they derive from distinct precursors and/or differentiate along distinct pathways. The differential diagnosis of extra-axial ependymomas is extensive, and GFAP expression in primary ovarian serous carcinomas, although rare, could theoretically contribute to diagnostic difficulties. ER and PR expression in extra-axial ependymomas may provide targets for hormonal therapy.

Teratocarcinosarcoma of the nasal cavity and paranasal sinuses: report of 3 cases with assessment for chromosome 12p status.

Sinonasal teratocarcinosarcoma (SNTCS) is a rare malignant neoplasm with 63 reported cases to date. Patients are exclusively adults, with a mean age of 60 years and marked male predominance. Histologically, these tumors are characterized by the presence of admixed epithelial and mesenchymal components. The histogenesis of SNTCS remains uncertain and genetic studies have not been reported to date. Two SNTCSs from the archives of Memorial Sloan-Kettering Cancer Center and one submitted from St Luke's-Roosevelt Hospital Center were evaluated by fluorescent in situ hybridization for amplification of chromosome12p, an event usually associated with the genesis of bona fide germ cell neoplasms (including mediastinal and testicular teratomas). Microscopic examination revealed admixed epithelial and mesenchymal elements in all 3 cases; benign squamous and glandular epithelium and neuroepithelial tissue were identified, the squamous epithelium demonstrating "fetal-like" cytoplasmic clearing. Mesenchymal proliferations were recognized ranging from well-differentiated smooth muscle to high-grade sarcoma. A malignant germ cell component was not identified in any of the cases. Fluorescent in situ hybridization evaluation demonstrated only 2 copies of chromosome 12 per case. Although the histogenesis of SNTCS remains uncertain, we have found an absence of 12p amplification in 3 cases. Our findings suggest that 12p amplification, if it occurs at all in this setting, is exceptional and that SNTCS is a somatic-type neoplasm exhibiting divergent differentiation rather than a germ cell tumor.

Hu Immunolabeling as a Marker of Neural and Neuroendocrine Differentiation in Normal and Neoplastic Human Tissues: Assessment Using a Recombinant Anti-Hu Fab Fragment.

The recombinant antibody fragment Fab GLN 495 recognizes an epitope shared by members of the neuron-associated Hu protein family (including HuC, HuD, and HelNl). This novel reagent labels the nuclei of neurons throughout the peripheral and central neuraxes and has been shown to recognize pulmonary small cell carcinomas and central nervous system (CNS) tumors of mature neuronal phenotype or neuronogenic differentiating capacity. Using this Fab fragment, we have undertaken a systematic survey of normal human tissues and an assessment of 554 non-CNS tumor samples for immunohistochemical evidence of Hu expression. Adrenomedullary cells, pancreatic islet cells, paraganglial chief cells, isolated adenohypophyseal cells, and spermatogonia were the only nonneuronal normal tissue elements to bind Fab GLN 495. In addition to labeling all 10 small cell carcinomas studied (six of which were extrapulmonary in origin), this recombinant anti-Hu Fab proved immunoreactive with neuroblastomas (four/four), esthesioneuroblastomas (one/one), typical (three/four) and atypical (one/four) pulmonary carcinoids, pancreatic islet cell tumors (two/six), large-cell neuroendocrine carcinoma of lung (one/four), Merkel cell tumors (two/three), medullary carcinomas of the thyroid (four/six), pheochromocytomas (two/four) and paragangliomas (four/four). Nonneural/neuroendocrine tumor labeling was restricted to the neuronal and immature neuroepithelial components of teratomas, to extraskeletal myxoid chondrosarcomas (three/four) and to small subsets of cells within examples of renal rhabdoid tumor (one/four), desmoplastic small cell tumor (one/four), alveolar rhabdomyosarcoma (two/four), Ewing sarcoma/PNET (two/nine), and Wilms tumor (one/four). Immunoreactivity was principally nuclear, with variable cytoplasmic labeling. Our findings support the largely restricted expression of Hu by neural/neuroendocrine neoplasms, suggest a potential role for Fab GLN 495 in the identification of small cell carcinomas irrespective of primary site, and support a recent proposal that at least some extraskeletal myxoid "chondrosarcomas" actually represent neuroendocrine tumors of soft parts. Int J Surg Pathol 8(2):109-117, 2000