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Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a newly proposed clinicopathologic entity; a few cases of LCNEC have been reported in other sites, such as the uterine cervix and the thymus. In the salivary glands, LCNEC is extremely rare and is not recognized as a specific entity in the World Health Organization classification. We retrospectively reviewed from our files 1675 cases of surgically resected primary parotid gland tumors and found 2 cases of LCNEC that fulfilled the criteria of pulmonary LCNEC. These cases occurred in 72-and 73-year-old men who had short histories of enlarging parotid gland tumors. The tumors were composed of large cells that exhibited organoid, solid, trabecular, and rosette-like growth patterns with a high mitotic rate and a conspicuous tendency for necrosis. The tumor cells were polygonal and characterized by a moderate nuclear:cytoplasmic ratio, coarse chromatin, and conspicuous nucleoli. Immunohistochemical examination revealed that the tumor cells were positive for six general neuroendocrine markers, cytokeratin, p53, bcl-2, epidermal growth factor receptor, and cyclin D1. Markedly reduced expressions of p21 Waf1 and p27 Kip1 were also noticed. The Ki-67 labeling index was more than 50% in both cases. One case showed loss of heterozygosity at TP53 accompanied by a p53 gene point mutation. Loss of heterozygosity at chromosome 9p21 was detected in both cases; one was accompanied by a p16 gene silent point mutation.Both patients died of the disease, with recurrence 5 months and 4 years after surgery, respectively. These findings indicate that LCNEC is a rare but distinct salivary gland tumor with highly aggressive biologic behavior. Multiple alterations of cell cycle regulators and tumor suppressor genes may play an important role in presenting the biologic characteristics of this rare parotid gland tumor.KEY WORDS: bcl-2, Cyclin D1, K-ras, Large-cell neuroendocrine carcinoma, p16, p27 Kip1

Background. Although there have been a few reports dealing with the sarcomatous changes of intrahepatic cholangiocarcinoma, its clinicopathologic features as well as immunohistochemical nature remain obscure. Methods. Among 155 cases of intrahepatic cholangiocarcinoma, 7 cases of sarcomatous cholangiocarcinoma were chosen. Immunohistochemical studies using the avidin‐biotin‐peroxidase complex method were performed on these cases. Results. The tumor showed both mucin‐producing adenocarcinoma areas and sarcomatous areas, the latter being predominant in three cases and focal in the other four. All the sarcomatous areas consisted of atypical spindle cells arranged in sheets or bundles. Pleomorphic giant cells were observed in some sarcomatous components in five cases. Immunohistochemical staining for keratin and epithelial membrane antigen revealed apparent positivity in the sarcomatous components of five cases. The patients with these tumors showed aggressive intrahepatic spreading and widespread metastasis of the sarcomatous cells, and demonstrated poorer prognosis than those with ordinary cholangiocarcinoma, with one exception, a patient who remained disease‐free for 3 years after surgery. Conclusions. These findings favor the possible epithelial origin of sarcomatous cells. Radical operation would be necessary for patients with this special type of cholangiocarcinoma.

UCLS of the salivary gland is an extremely rare tumor in Japanese patients characterized by consistent association with EBV. Distinction between BLEL and UCLS is possible by examining for evidence of EBV infection, expression of p53, and cell proliferative activity.

Our cases confirmed the possibility of malignant transformation of the epithelial component in WT to MEC.

Two women, aged 82 and 58 years old, cases 1 and 2, respectively, with the non-tubular and matrix-producing variant of malignant adenomyoepithelioma (MAM) of the breast are described. The tumors were 20 and 35 mm in diameter, respectively, and had cut surfaces with a tan-white-colored appearance and vague lobulation. Although both tumors showed marked central necrosis and a high level of mitoses, the tumor cells had relatively monomorphous nuclei and exhibited only mild atypia. The invasive component was predominantly trabecular and lobular, and the intraductal component demonstrated a focal-comedo pattern. The cytoplasm of the tumor cells was rather scanty, vacuolar or pale with ill-defined borders. The tumor in case 2 contained intermingled spindle-shaped cells. The stroma of both tumors resembled that of pleomorphic adenoma, containing a myxoid and chondroid matrix and, in case 2, cartilage and mature bone. Immunohistochemical and ultrastructural analyses of both tumors revealed dual cytological differentiation, predominantly of myoepithelial cells with secretory epithelial cells intermingled haphazardly. Although these tumors resembled metaplastic carcinomas, particularly matrix-producing carcinomas, they showed marked myoepithelial differentiation without overt tubular differentiation, a pattern quite different from matrix-producing carcinomas and from the adenomyoepitheliomas reported so far. MAM of the breast, non-tubular and matrix-producing variant, resembles epithelioid myoepithelial carcinoma of the salivary gland and has not been reported previously in the English literature.

Medulloblastomas are highly malignant and poorly understood childhood neoplasms. To determine if neurotrophins might influence the phenotypic properties of medulloblastoma in a paracrine or autocrine manner, 51 pediatric brain tumors including 20 biopsy specimens of these primitive neuroectodermal tumors (PNETs) and 31 other pediatric brain tumors were studied. Immunohistochemistry was used with antibodies to nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3, their cognate high affinity receptors as well as to neuronal and glial markers. TrkA, TrkB, and TrkC were observed in 5 (25%), 8 (40%), and 17 (85%), respectively, of these medulloblastomas while NGF, BDNF, and NT-3 were observed in 6 (30%), 8 (40%), and 3 (15%), respectively, and antibodies to neurofilament (NF) and glial fibrillary acidic proteins (GFAP) stained 16 (80%) and 11 (55%), respectively. TrkA and NGF were not observed in the same biopsy samples, while TrkB and BDNF were co-distributed in 6 of the cases, all of which expressed NF proteins. TrkC and NT-3 were co-distributed in 3 of the medulloblastomas, and these areas overlapped with NF protein-positive tumor cells in all 3 cases. In contrast to medulloblastomas, TrkA and NGF co-distributed in other pediatric brain tumors, and both Trk receptors and their neurotrophins co-distributed with GFAP-positive tumor cells in 13 (42%) of the non-PNET pediatric brain tumors. The absence of medulloblastomas that contain NGF and TrkA is consistent with in vitro data demonstrating that NGF-mediated TrkA signaling induces apoptosis. Finally, this study also suggests that BDNF and NT-3 may act in a paracrine or autocrine manner through TrkB and TrkC receptors, respectively, to induce neuronal differentiation in medulloblastomas.