Concurrent angiomyolipoma and renal cell neoplasia: a study of 36 cases. (9/183)

Little is known about the association of angiomyolipoma and adult renal-cell neoplasia. We studied the clinicopathologic features of 36 patients with concurrent angiomyolipoma and renal-cell neoplasia from the consultation and surgical pathology files of nine institutions. HMB-45 immunoreactivity was analyzed in both neoplasms. Twenty-five sporadic cases of patients with angiomyolipoma and renal-cell neoplasia and 11 cases of patients with tuberous sclerosis, as defined by Gomez' criteria, had mean ages of 59 and 53 years, respectively, and female-male ratios of 2:1 and 5:1, respectively. The mean size of the angiomyolipomas was 1 cm in the sporadic cases and 3 cm in those patients with tuberous sclerosis (medians: 0.5 and 3 cm, respectively, P =.002). The mean sizes of the renal-cell neoplasms were 5 cm in sporadic cases and 6 cm in patients with tuberous sclerosis (medians: 4 and 5 cm, respectively; P =.88). In both clinical settings, angiomyolipoma was more commonly the incidental tumor. Clear-cell (conventional) renal-cell carcinoma was the most common renal-cell neoplasm in both groups of patients, accounting for approximately two thirds of the tumors. In patients with tuberous sclerosis, 27% of renal-cell neoplasms were oncocytomas, compared with 8% in sporadic cases (P =.15). Papillary neoplasia, chromophobe, and collecting-duct renal-cell carcinoma were found only in sporadic cases. All of the 22 renal-cell neoplasms studied were negative for HMB-45, whereas all 25 angiomyolipomas studied were positive.  (+info)

Oncocytic biliary cystadenocarcinoma is a form of intraductal oncocytic papillary neoplasm of the liver. (10/183)

Biliary cystadenocarcinoma with oncocytic differentiation was first reported in 1992. This is a report of a second case. The patient (a 71-year-old man) was admitted to our hospital complaining of abdominal fullness. Multicystic lesions were identified in the left hepatic lobe radiologically. The patient died of peritoneal dissemination of carcinoma 20 months later. At autopsy, the tumor of the left hepatic lobe was found to be composed of adjoining multiple cystic lesions and a solid lesion with infiltration of the hepatic hilus and peritoneal dissemination. Histologically, the multicystic lesions were covered by papillary neoplastic epithelial cells with an eosinophilic granular cytoplasm resembling that of oncocytes and a fine fibrovascular core. The cyst wall was fibrous, but there was no mesenchymal stroma. In the solid lesion and infiltrated areas, acidophilic and granular carcinoma cells formed small glandular or solid cord patterns with much mucin secretion (mucinous carcinoma). Immunohistochemically, carcinoma cells of both components were found to contain many mitochondria and showed the phenotypes of hepatocytes and cholangiocytes. Interestingly, the intrahepatic biliary tree also was invaded by carcinoma cells. This may be a case of intraductal oncocytic papillary neoplasm of the left hepatic lobe followed by secondary cystic dilatation of the affected bile duct.  (+info)

Clinical significance of molecular expression profiles of Hurthle cell tumors of the thyroid gland analyzed via tissue microarrays. (11/183)

Hurthle cell tumors are rare thyroid neoplasms for which disease biology is poorly understood and diagnosis of carcinoma can be challenging. The aim of the study was to characterize molecular expression profiles of Hurthle cell tumors and to determine the clinical significance of identified phenotypes. Paraffin-embedded tissue cores of normal thyroid (n = 18), and histopathologically well-defined Hurthle cell adenomas (n = 27), Hurthle cell tumors of unknown malignant behavior (n = 7), and minimally (n = 14) and widely (n = 21) invasive Hurthle cell carcinomas were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, and Ki-67 were detected by immunohistochemistry and correlated with clinicopathological data and patient outcome using standard statistical methodology. Median follow-up time was 8 years. High Ki-67 proliferative index was evident only in the clinically aggressive widely invasive Hurthle cell carcinomas and was associated with significantly reduced relapse-free (P = 0.001) and disease-specific (P < 0.001) survival. The molecular phenotype of Hurthle cell tumors, independent of histopathological subtype diagnosis, was characterized by p53(-), mdm-2(+), p21(+/-), cyclin D1(-), and Bcl-2(+/-). Normal thyroid tissue demonstrated a p53(-), mdm-2(-), p21(-), cyclin D1(-), and Bcl-2(+) phenotype. The Bcl-2(+) phenotype was associated with improved relapse-free survival (P = 0.04) and disease-specific survival (P = 0.01) in widely invasive carcinomas and the Ki-67(+)/Bcl-2(-) phenotype was associated with the diagnosis of widely invasive Hurthle cell carcinoma (P < 0.001). This study demonstrates that tissue microarray-based profiling allows identification of molecular markers that are associated with patient prognosis. High Ki-67 proliferative index was associated with adverse outcome in Hurthle cell neoplasms. Together with down-regulation of Bcl-2, high Ki-67 proliferative index may be useful for diagnosing widely invasive Hurthle cell carcinomas. Molecular alterations in the p53 pathway play a role in Hurthle cell tumorigenesis, but other unidentified molecular changes seem to be required to induce the malignant phenotype.  (+info)

Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hurthle cell tumors. (12/183)

In an attempt to progress in the understanding of the relationship of mitochondrial DNA (mtDNA) alterations and thyroid tumorigenesis, we studied the mtDNA in 79 benign and malignant tumors (43 Hurthle and 36 non-Hurthle cell neoplasms) and respective normal parenchyma. The mtDNA common deletion (CD) was evaluated by semiquantitative polymerase chain reaction. Somatic point mutations and sequence variants of mtDNA were searched for in 66 tumors (59 patients) and adjacent parenchyma by direct sequencing of 70% of the mitochondrial genome (including all of the 13 OXPHOS system genes). We detected 57 somatic mutations, mostly transitions, in 34 tumors and 253 sequence variants in 59 patients. Follicular and papillary carcinomas carried a significantly higher prevalence of non-silent point mutations of complex I genes than adenomas. We also detected a significantly higher prevalence of complex I and complex IV sequence variants in the normal parenchyma adjacent to the malignant tumors. Every Hurthle cell tumor displayed a relatively high percentage (up to 16%) of mtDNA CD independently of the lesion's histotype. The percentage of deleted mtDNA molecules was significantly higher in tumors with D-loop mutations than in mtDNA stable tumors. Sequence variants of the ATPase 6 gene, one of the complex V genes thought to play a role in mtDNA maintenance and integrity in yeast, were significantly more prevalent in patients with Hurthle cell tumors than in patients with non-Hurthle cell neoplasms. We conclude that mtDNA variants and mtDNA somatic mutations of complex I and complex IV genes seem to be involved in thyroid tumorigenesis. Germline polymorphisms of the ATPase 6 gene are associated with the occurrence of mtDNA CD, the hallmark of Hurthle cell tumors.  (+info)

Oncocytoma of the caruncle. (13/183)

A rare case of oncocytoma of the caruncle in a 75-year-old female is reported. Clinical differential diagnosis and histopathologic features are discussed.  (+info)

Cytokeratins 7 and 20 immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas. (14/183)

Chromophobe renal cell carcinomas and renal oncocytomas share morphologic similarities and may present a diagnostic challenge on routine hematoxylin-eosin staining. Currently recommended additional studies of Hale's colloidal iron staining and electron microscopy are often difficult to interpret and technically challenging and may not be readily available. Previous studies have reported conflicting results with regard to the cytokeratin 7 staining pattern in chromophobe renal cell carcinomas and renal oncocytomas. Cytokeratin 20 expression in chromophobe renal cell carcinomas has not previously been studied. Formalin-fixed paraffin-embedded tissue of 11 chromophobe renal cell carcinomas and 21 renal oncocytomas were retrieved from the archived files (1984-2000) of four teaching hospitals. Of the 11 chromophobe renal cell carcinomas, eight stained positive (73%) for cytokeratin 7, one stained focally positive (9%), and two cases (18%) were completely negative. Cytokeratin 7 staining of the 21 oncocytomas revealed 4 positive (19%), 7 focally positive (33%), and 10 negative cases (48%). Cytokeratin 20 was uniformly negative on all 11 cases of chromophobe renal cell carcinomas and all 21 cases of oncocytomas. Cytokeratin 7 does not appear to show the consistent immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas, as has been previously suggested. Cytokeratin 20 immunostaining in chromophobe renal cell carcinomas and renal oncocytomas is uniformly negative. Despite the technical and interpretive challenges of Hale's colloidal iron, it is still the most useful stain in differentiating chromophobe renal cell carcinomas from renal oncocytomas.  (+info)

Interpretation of RET immunostaining in follicular lesions of the thyroid. (15/183)

We applied monoclonal antibodies against RET and cytokeratin 19 (CK19) to the following tumor sections: classic papillary carcinoma (PC), 16; Hurthle-type PC (HPC), 1; sclerosing PC with nodular fasciitis-like stroma (SPC), 1; PC, follicular variant (FVPC), 12; follicular adenoma (FA), 9; Hurthle cell adenoma (HA), 4; Hurthle cell carcinoma (HC), 3; and follicular carcinoma (FC), 7. CK19+ tumors included 16 PCs, 1HPC, 1SPC, 11 FVPCs, 7 FAs, 4 FCs, and 1HC. RET+ tumors included 4 HAs, 3 HCs, 1HPC, 12 PCs, 7 FVPCs, and 2 FAs. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a RET transcript in 6 Hurthle cell lesions. RET immunoreactivity is less sensitive and specific for PC than CK19. CK19 is useful for identifying PC, although only lesions with diffuse, intense staining should be considered positive. The detection of RET protein by immunohistochemical analysis was corroborated by the presence of the RET transcript by RT-PCR. Further study is warranted to determine whether this represents activation by gene fusion or some other mechanism in this subset of thyroid neoplasms.  (+info)

Oncocytic adrenocortical carcinoma: a morphologic, immunohistochemical and ultrastructural study of four cases. (16/183)

We present the clinical, histologic, immunohistochemical, and ultrastructural findings of four cases of non-functioning oncocytic adrenocortical carcinomas. The patients' ages ranged from 39 to 71 years. There was no sex predilection. Large yellow-tan tumors (8.5 to 17.0 cm), well demarcated from the adjacent kidney, were seen with a thin rim of normal adrenal gland along one edge. One tumor invaded the inferior vena cava and extended up to the level of the right atrium, and another metastasized to bone. The other two tumors had similar morphologic features and therefore were considered carcinomas. Histologic sections of all four cases showed a diffuse proliferation of polygonal neoplastic cells with large nuclei containing prominent nucleoli and abundant granular and eosinophilic cytoplasm. Occasional mononuclear and binucleated giant cells were noted in one case. There were rare mitotic figures (less than one per 10 high power fields). All tumors were immunoreactive for cytokeratins (AE1/AE3 and CAM5.2). Inhibin was focally expressed by one tumor and its bone metastasis. Ultrastructurally, the cytoplasm of the neoplastic cells was packed with innumerable mitochondria. Cytologic atypia or mitotic rate cannot reliably predict the biologic behavior of oncocytic adrenocortical neoplasms. Large tumor size (4/4), extracapsular extension (3/4), blood vessel invasion (2/4), necrosis (4/4), and metastasis (1/4) are features of malignancy for oncocytic adrenocortical carcinomas. The treatment of these tumors is complete surgical excision.  (+info)