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Angiomyolipomas (AMLs) are polymorphic renal tumors that are composed of mature tissues and frequently associated with tuberous sclerosis; AMLs have long been considered hamartomatous in nature. We report the routine histologic and immunohistochemical features and DNA content analysis of two fatal cases of renal giant multicentric AML with distant organ involvement, and we contrast the findings with those of four similarly studied cases of classic solitary AML. Severe nuclear pleomorphism, significant mitotic activity, and necrosis, which are all characteristics of multicentric AML, were not seen in the cases of classic AML. Quantitation of DNA by image analysis of Feulgen-stained slides from paraffin-embedded blocks revealed an aneuploid pattern in the two cases of multicentric AML and an aneuploid pattern in one of the four cases of classic AML. Tumors in the liver, spleen, and lungs in one of the cases of multicentric AML were diploid. Immunohistochemical analysis revealed positive staining reaction of vascular and adipose tissue components with HMB-45 antibody in three of the six cases of AML. We conclude that AMLs may occur in a sarcomatous, infiltrating multicentric form involving multiple organs, that aneuploidy may be seen in lesions of both the multicentric AML and classic AML variants, that AMLs may feature DNA ploidy heterogeneity in multiple-organ sites, that HMB-45 immunoreactivity may be encountered in AMLs without evidence of nevomelanocytic differentiation, and that continued study of AMLs is needed to clarify further the histogenesis, lineage, clonality, and malignant potential of these tumors.

Context.--Accurate classification of follicular-patterned thyroid lesions is not always an easy task on routine surgical hematoxylin-eosin-stained or cytologic fine-needle aspiration specimens. The diagnostic challenges are partially due to differential diagnostic criteria that are often subtle and subjective. In the past decades, tremendous advances have been made in molecular gene profiling of tumors and diagnostic immunohistochemistry, aiding in diagnostic accuracy and proper patient management. Objective.--To evaluate the diagnostic utility of the most commonly studied immunomarkers in the field of thyroid pathology by review of the literature, using the database of indexed articles in PubMed (US National Library of Medicine) from 1976-2013. Data Sources.--Literature review, authors' research data, and personal practice experience. Conclusions.--The appropriate use of immunohistochemistry by applying a panel of immunomarkers and using a standardized technical and interpretational method may complement the morphologic assessment and aid in the accurate classification of difficult thyroid lesions. (Arch Pathol Lab Med. 2015; 139:67-82; doi: 10.5858/arpa.2014-0056-RA), In 2013, the American Cancer Society estimated that 60 220 new cases of thyroid carcinoma would be diagnosed in the United States, and 1850 persons would die of the disease. [...]

Context.--Invasion and the depth of invasion affect significantly the prognosis in urothelial carcinomas. The histopathologic evaluation of invasion may be problematic in some cases. Application of new immunohistochemical markers may facilitate the assessment of invasion. Fascin, one of these markers, is an actin-bundling protein involved in tumor cell migration. Fascin expression is increased in various carcinomas. Prior to this research, to our knowledge, only one study exists regarding fascin expression in urothelial carcinomas. Objective.--To characterize the expression of fascin in additional cases of urothelial carcinoma and to verify statistically a relationship between fascin overexpression and invasiveness in these tumors. Design.--We examined fascin immunoreactivity in 116 specimens of urothelial carcinomas obtained from 116 patients including 96 men and 20 women. Fifty-eight cases were ranked as low-grade carcinomas, pTa stage, and 58 cases were ranked as high-grade carcinomas--11 were ranked as stage pTa, 21 were ranked as pT1, and 26 were ranked as pT2 carcinomas. Fascin immunoreactivity was assessed semiquantitatively in tumor cells. In each case, we ascribed 3 immunoreactivity scores, one for extent, one for intensity, and a combined immunoreactivity score. Results.--The combined immunoreactivity score was significantly higher in invasive carcinomas. In addition, strong staining was observed exclusively in invasive carcinomas. None of the pTa tumors demonstrated intense staining, including those ranked at the higher grade. Conclusions.--Our results point to an association between fascin immunostaining and urothelial carcinoma invasiveness and suggest that fascin overexpression may be a marker of aggressive urothelial carcinomas., Fascin is a 55-kDa globular protein that belongs to a unique family of actin-bundling proteins. Three forms of fascin exist in vertebrates: fascin 1, which is expressed by mesenchymal tissues [...]

* Context.--Thyroid lesions with nodular architecture and follicular pattern of growth often pose difficulties in accurate diagnosis during the assessment of cytologic and histologic specimens. The diagnosis of follicular neoplasm on cytology or of follicular tumor of uncertain malignant potential on histology is likely to cause confusion among clinicians and delay effective management of these lesions. Occasionally, thyroid tumors represent unusual or metastatic lesions and their accurate diagnosis requires immunohistochemical confirmation. Objective.--To review the literature on the applications of immunohistochemistry in the differential diagnosis of thyroid tumors. Data Sources.--Relevant articles indexed in PubMed (National Library of Medicine) between 1976 and 2006. Conclusions.--Our review supports the use of ancillary techniques involving a panel of antibodies suitable for immunohistochemistry and molecular analysis in the assessment of thyroid nodules. These tools can improve diagnostic accuracy when combined with standard morphologic criteria., Thyroid cancer is the most common endocrine malignancy, and more than 95% of thyroid carcinomas originate from follicular epithelial cells. (1) The incidence of thyroid carcinomas derived from follicular cells [...]

* Background.--Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor. Objective.--To further characterize the immunopheno. typic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell). Design.--Formalin.fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases. Results.--All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF35), and calponin. Overall, HMB-45, HMB-50, and NKI/ C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB.45, HMB-50, and NKI/C3. Muscle-specific actin (HHF.35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin. Conclusion.--In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues. (Arch Pathol Lab Med. 2001 ;125:751-758), Renal angiomyolipoma is an unusual, generally benign tumor that has been associated with tuberous sclerosis and is characterized by a histologic triad of tortuous, thick-walled blood vessels, phenotypic smooth muscle [...]

Context.--We have observed intraluminal crystalloid morphology in seminal vesicles that is superficially similar to that seen in prostate neoplasia, but found little information on such morphology in the literature. Design.--Two hundred fifty-three prostate specimens (163 needle biopsies, 75 radical prostatectomies with prostate carcinoma, 11 prostates from autopsy, and 4 cystoprostatectomies without prostate carcinoma) were examined for seminal vesicle secretions, which were categorized as (a) dense platelike inspissated, (b) fluidlike, (c) crystalloid morphology, and (d) absent. Histochemical stains (periodic acid-Schiff with and without diastase, Alcian blue at pH 2.5, and mucicarmine) were performed to characterize the nature of secretions. Results.--Proteinaceous secretions were identified in 82% of seminal vesicles examined. Of these, 61% had predominantly dense, platelike, inspissated secretions, 15% had predominantly fluidlike secretions, and 24% had predominantly crystalloid morphology. Although in some cases the crystalloid morphology resembled that of prostatic intraluminal crystalloids, the seminal vesicle crystalloids differed in that they were invariably multiple, had curved edges, and had varied forms (elliptical, cylindrical, rodlike, and rectangular). Seventy-one percent of seminal vesicle crystalloids were associated with dense, platelike, inspissated secretions and appeared to be created by fracturing within platelike secretions. There was no relationship between seminal vesicle crystalloid morphology and associated malignancy in the prostate gland, as it was seen in 24% of cases with prostate carcinoma and 25% of cases without prostate carcinoma (P = 1.0000). Fluidlike secretions were positive for Alcian blue (pH 2.5) and mucicarmine, whereas dense platelike secretions and crystalloid morphology were negative for Alcian blue (pH 2.5) and mucicarmine. Conclusions.--Seminal vesicle secretions are fairly common and, when fluidlike, are composed of acid mucopolysaccharides. Inspissation of secretions appears to be associated with loss of acidity, presumably resulting in dense platelike secretions and crystallization. Awareness of both the crystalloid morphology in seminal vesicle tissue and the distinguishing features from prostatic crystalloids may be important while interpreting prostate needle biopsies in which seminal vesicle epithelium may be confused for prostate carcinoma because of a small acinar morphology with accompanying cytologic atypia and crystalloid morphology. (Arch Pathol Lab Med. 2001;125:141-145), Particular Emphasis on Their Crystalloid Morphology In recent years, there has been a tremendous increase in the number of prostate needle biopsies, resulting in increased detection of prostate cancer and [...]