Ten additional adrenocortical oncocytic tumors are presented: 2 benign oncocytomas, 4 borderline oncocytomas of uncertain malignant potential, and 4 oncocytic carcinomas. Histologically all tumors were entirely or predominantly composed of oncocytes. Immunohistochemically all tumors were immunoreactive for mitochondrial antigen mES-13. Electron microscopy was performed in 8 cases and was confirmatory of the oncocytic cell change. The morphologic parameters of the Weiss system, considered to be predictive of the biologic behavior of conventional (nononcocytic) adrenocortical tumors, are reviewed in the context of their possible application to the oncocytic tumor variant. Proposed major criteria (high mitotic rate, atypical mitoses, venous invasion) and minor criteria (large size and huge weight, necrosis, capsular invasion, sinusoidal invasion) in distinguishing malignant tumors are discussed, and definitional criteria (predominantly cells with eosinophilic and granular cytoplasm, high nuclear grade, diffuse architectural pattern) in common with all types of oncocytic tumors are outlined. The authors' proposed working rules for diagnostic categorization of oncocytic adrenocortical tumors are defined, with the presence of 1 major criterion indicating malignancy, 1 to 4 minor criteria indicating uncertain malignant potential (borderline), and the absence of all major and minor criteria indicative of benignancy. Using these criteria, the diagnosis of malignancy was straightforward in 3 of the 4 cases designated as oncocytic carcinoma (presence of at least 2 major criteria and all the minor criteria), while in 1 case the original diagnosis of benign oncocytoma was reversed to malignant following critical review of the original pathologic material after local tumor recurrence. Tumor recurrence occurred in 2 carcinomas at 8 and 20 months, respectively, and was followed in 1 case by the patient's death. The third patient expired at 6 months from unrelated causes, and the fourth patient is free of disease at the relatively short follow-up interval of 6 months. Regarding the 4 patients with borderline tumors, all are alive with no evidence of disease, with follow-up ranging from 10 to 61 months (mean 38.7 months). The 2 benign tumors have a follow-up of 25 and 30 months, respectively. Diagnostic difficulties are delineated and a complete review of the literature on this topic has also been performed.

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The plasmacytoid variant of urothelial carcinoma is rare, of which less than 40 cases have been reported in the English language literature. Herein we report the largest series to date of 17 cases of urothelial carcinoma with plasmacytoid features and report the associated clinicopathologic findings. The architectural pattern of the tumor varied from cells arranged in cords and single cells (35%), small nests (17%), solid sheetlike growth (29%), and diffuse discohesive patternless architecture (23%). The plasmacytoid component varied from 15% to 100% of the specimen analyzed; in 12 cases the plasmacytoid component composed greater than 50% of the tumor. The individual tumor cells had striking morphologic overlap with plasma cells with an eccentrically placed nucleus and abundant amphophilic to eosinophilic cytoplasm. The nuclei were of low to intermediate nuclear grade with minimal nuclear pleomorphism. Thirteen of 17 cases (76%) were associated with conventional high-grade invasive urothelial carcinoma and 9 cases showed very focal intracytoplasmic vacuoles mimicking signet ring cells. One case also showed sarcomatoid dedifferentiation. The tumor cells were positive for cytokeratin 7 (94%) and cytokeratin 20 (31%); CD138 was positive in 94% of cases. All cases were invasive -- 7 into at least the lamina propria, 7 into at least the muscularis propria, and 3 into perivesical fat. Follow-up information was available in 16 cases (range: 2 wk to 43 mo; mean 10 mo; median 5.5 mo). Eleven patients died of disease and 5 patients were alive with disease. Plasmacytoid variant of urothelial carcinoma is an aggressive subtype associated with poor prognosis. In limited samples, it may be misdiagnosed as chronic cystitis or plasmacytoma, a pitfall further compounded by CD138 expression. Distinction from metastatic carcinoma from other primary sites such as stomach and breast is critical due to differing therapeutic implications.

We assessed the usefulness of a mouse monoclonal antibody (13B10) against human herpesvirus 8 (HHV-8) latent nuclear antigen-1 (LNA-1) in diagnosis of Kaposi sarcoma (KS) and for distinguishing it from various mimickers by studying 50 cases of KS and 53 mimickers (angiosarcoma, 15; kaposiform hemangioendothelioma, 6; spindle cell hemangioma, 3; reactive angioendotheliomatosis, 3; bacillary angiomatosis, 4; acroangiomatous dematitis, 2; microvenular hemangioma, 2; hobnail hemangioma, 2; pyogenic granuloma, 5; dermatofibroma, 8; arteriovenous hemangioma, 1; verrucous hemangioma, 1; nonspecific vascular proliferation, 1) from patients with or without acquired HIV infection. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections. All 50 cases of KS were positive for HHV-8 LNA-1, with immunolocalization in the nuclei of the spindle cells and cells lining the primitive and thin-walled vascular channels, whereas all 53 mimickers (including 4 lesions from HIV-positive patients) tested negative. The results idicate that positive immunostaining for HHV-8 LNA- 1 exhibits high sensitivity and specificity for the diagnosis of KS and is, thus, useful for distinguishing it from the mimickers.

We assessed the usefulness of a mouse monoclonal antibody (13B10) against human herpesvirus 8 (HHV-8) latent nuclear antigen-1 (LNA-1) in diagnosis of Kaposi sarcoma (KS) and for distinguishing it from various mimickers by studying 50 cases of KS and 53 mimickers (angiosarcoma, 15; kaposiform hemangioendothelioma, 6; spindle cell hemangioma, 3; reactive angioendotheliomatosis, 3; bacillary angiomatosis, 4; acroangiomatous dematitis, 2; microvenular hemangioma, 2; hobnail hemangioma, 2; pyogenic granuloma, 5; dermatofibroma, 8; arteriovenous hemangioma, 1; verrucous hemangioma, 1; nonspecific vascular proliferation, 1) from patients with or without acquired HIV infection. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections. All 50 cases of KS were positive for HHV-8 LNA-1, with immunolocalization in the nuclei of the spindle cells and cells lining the primitive and thin-walled vascular channels, whereas all 53 mimickers (including 4 lesions from HIV-positive patients) tested negative. The results idicate that positive immunostaining for HHV-8 LNA- 1 exhibits high sensitivity and specificity for the diagnosis of KS and is, thus, useful for distinguishing it from the mimickers.

We investigated the metabolic and genetic basis of diabetes in the Cohen Diabetic rat, a model of diet-induced diabetes, as a means to identify the molecular mechanisms involved. By altering individual components in the diabetogenic diet, we established that the dietary susceptibility that leads to the development of diabetes in this model is directly related to the high casein and low copper content in chow. The development of diabetes is accompanied by depletion of the acini from the exocrine pancreas and replacement with fat cells, while the appearance of the islets of Langerhans remains intact. With reversion back from diabetogenic to regular diet, the diabetic phenotype disappears but the histological changes in the exocrine pancreas prevail. Using positional cloning, we detected a major quantitative trait locus (QTL) on rat chromosome 4 with a chromosomal span of 4.9 cM, and two additional loci on chromosomes 7 and X. A screen for genes within that QTL in the rat and in the syntenic regions in mouse and man revealed only 23 candidate genes. Notable among these genes is Ica1, which has been causally associated with diabetes and bovine casein. We conclude that the development of diabetes in our model is dependent upon high casein and low copper in diet, that it is accompanied by histomorphological changes in the exocrine but not endocrine pancreas, that it is reversible, and that it is associated with a major QTL on chromosome 4 in which we detected Ica1, a high priority candidate gene.

Extraneuraxial hemangioblastoma occurs in nervous paraneuraxial structures, somatic tissues, and visceral organs, as part of von Hippel-Lindau disease (VHLD) or in sporadic cases. The VHL gene plausibly plays a key role in the initiation and tumorigenesis of both central nervous system and extraneuraxial hemangioblastoma, therefore, the underlying molecular and genetic mechanisms of the tumor growth are initially reviewed. The clinical criteria for the diagnosis of VHLD are summarized, with emphasis on the distinction of sporadic hemangioblastoma from the form fruste of VHLD (eg, hemangioblastoma-only VHLD). The world literature on the topic of extraneuraxial hemangioblastomas has been comprehensively reviewed with ∼200 cases reported to date: up to 140 paraneuraxial, mostly of proximal spinal nerve roots, and 65 peripheral, 15 of soft tissue, 6 peripheral nerve, 5 bone, and 39 of internal viscera, including 26 renal and 13 nonrenal. A handful of possible yet uncertain cases from older literature are not included in this review. The clinicopathologic features of extraneuraxial hemangioblastoma are selectively presented by anatomic site of origin, and the differential diagnosis is emphasized in these subsets. Reference is made also to 10 of the authors' personal cases of extraneuraxial hemangioblastomas, which include 4 paraneuraxial and 6 peripheral (2 soft tissue hemangioblastoma and 4 renal).

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