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Answer added in Cytopathology11 Do any informed guidelines exist for a morphological evaluation of circulating, epithelial, tumor cells? If so, what are they based on?By Christer Ericsson · Karolinska InstituteBorislav Alexiev · University of Maryland, BaltimoreThere are no established criteria for morphological evaluation of circulating epithelial tumor cells - most likely because the clinical significance o... [more]There are no established criteria for morphological evaluation of circulating epithelial tumor cells - most likely because the clinical significance of this finding remains unknown (controversial data in the literature). Keep in mind that circulation of tumor cells does not necessarily lead to a metastatic disease. In addition to the well-known morphological criteria of malignancy (high n/c ratio, pleomorphism, anisonucleosis, etc), epithelial (carcinoma) cells have a more or less characteristic immunocytochemical profile. For instance, pulmonary adenocarcinoma express pancytokeratins (AE1/3 and Cam5.2), TTF-1, napsin-A, and CK7, while renal cell carcinoma are positive for PAX-8, RCC (clear cell and papillary subtypes), vimentin, AMACR (papillary), CK7 (papillary).Following
Publications (34) View all
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Article: 5α-reductase type 3 expression in human benign and malignant tissues: a comparative analysis during prostate cancer progression.
Alejandro Godoy, Elzbieta Kawinski, Yun Li, Daizo Oka, Borislav Alexiev, Faris Azzouni, Mark A Titus, James L Mohler[show abstract] [hide abstract]
ABSTRACT: A third isozyme of human 5α-steroid reductase, 5α-reductase-3, was identified in prostate tissue at the mRNA level. However, the levels of 5α-reductase-3 protein expression and its cellular localization in human tissues remain unknown. A specific monoclonal antibody was developed, validated, and used to characterize for the first time the expression of 5α-reductase-3 protein in 18 benign and 26 malignant human tissue types using immunostaining analyses. In benign tissues, 5α-reductase-3 immunostaining was high in conventional androgen-regulated human tissues, such as skeletal muscle and prostate. However, high levels of expression also were observed in non-conventional androgen-regulated tissues, which suggest either multiples target tissues for androgens or different functions of 5α-reductase-3 among human tissues. In malignant tissues, 5α-reductase-3 immunostaining was ubiquitous but particularly over-expressed in some cancers compared to their benign counterparts, which suggests a potential role for 5α-reductase-3 as a biomarker of malignancy. In benign prostate, 5α-reductase-3 immunostaining was localized to basal epithelial cells, with no immunostaining observed in secretory/luminal epithelial cells. In high-grade prostatic intraepithelial neoplasia (HGPIN), 5α-reductase-3 immunostaining was localized in both basal epithelial cells and neoplastic epithelial cells characteristic of HGPIN. In androgen-stimulated and castration-recurrent prostate cancer (CaP), 5α-reductase-3 immunostaining was present in most epithelial cells and at similar levels, and at levels higher than observed in benign prostate. Analyses of expression and functionality of 5α-reductase-3 in human tissues may prove useful for development of treatment for benign prostatic enlargement and prevention and treatment of CaP.The Prostate 07/2011; 71(10):1033-46. · 3.48 Impact Factor -
Article: Nephrogenic adenoma of the urinary tract: a review.
Borislav A Alexiev, Charles M LeVea[show abstract] [hide abstract]
ABSTRACT: Nephrogenic adenoma (NA) is an uncommon and intriguing lesion in the urinary tract. The pathogenesis of NA is not entirely clear. NA was considered to be a metaplastic process of the urothelium in response to chronic irritation of the urinary tract. However, recent evidence has shown that NA is not a metaplastic lesion but rather a proliferation of exfoliated and implanted renal epithelial cells in the urinary tract. Histologically, NAs exhibit, singly or in combination, tubules, small papillae, and microcystic structures lined by cells with little cytological atypia and focal hobnail changes. Solid formations and compressed spindled cells within a fibromyxoid background are rarely observed. Differential diagnosis includes, but is not limited to, malignant neoplasms occurring at the same sites, in particular urothelial carcinoma with deceptively bland morphology (with small tubules, microcystic and nested variants), prostatic adenocarcinoma, and clear cell adenocarcinoma. Immunohistochemical studies with antibodies targeting members of the paired box gene family (PAX2 and/or PAX8) in NAs may be helpful in the differential diagnosis of urothelial lesions and prostatic adenocarcinoma. NAs are most likely to be confused with clear cell adenocarcinoma, especially in small biopsy specimens. This is confounded by both lesions being frequently positive for PAX2, PAX8, and CK7 and not infrequently positive for p504S (α-methylacyl-CoA-racemase, AMACR) by immunohistochemistry. Recognition of its characteristic morphological patterns and awareness of its unusual architectural and cytological features are important in making the diagnosis of NA and distinguishing this lesion from its mimickers.International Journal of Surgical Pathology 03/2012; 20(2):123-31. · 1.00 Impact Factor -
Article: Renal-cell carcinomas in end-stage kidneys: a clinicopathological study with emphasis on clear-cell papillary renal-cell carcinoma and acquired cystic kidney disease-associated carcinoma.
Ramneesh Bhatnagar, Borislav A Alexiev[show abstract] [hide abstract]
ABSTRACT: Clear-cell papillary renal-cell carcinoma (CCPC) and acquired cystic kidney disease-associated carcinoma (ACDAC) are neoplasms with distinct morphological characteristics that behave less aggressively than conventional renal-cell carcinomas. End-stage kidney specimens from 61 patients (47 males and 14 females) with 109 renal-cell carcinomas were selected. Papillary renal-cell carcinoma was the most common malignancy (61/109, 56%), followed by CCPC (20/109, 18%). The CCPC showed a papillary or tubular/solid architecture, clear cytoplasm, low nuclear grade, and a distinct immunohistochemical profile (RCC-, vimentin+, CK7+, p504S-). ACDAC displayed a variety of architectural patterns, eosinophilic cytoplasm, high nuclear grade, intratumoral calcium oxalate deposits, and an immunohistochemical profile similar to type 2 papillary renal-cell carcinoma (RCC+, vimentin+, CK7-/+, p504S+). Less than 5% (3/69) of pathologically staged renal-cell carcinomas in end-stage kidneys presented with lymphogenous and/or hematogenous metastases.International Journal of Surgical Pathology 07/2011; 20(1):19-28. · 1.00 Impact Factor -
Article: Adenomatoid tumor of the testis with intratesticular growth: a case report and review of the literature.
[show abstract] [hide abstract]
ABSTRACT: Adenomatoid tumor of the male genitourinary tract is a rare benign neoplasm thought to be of mesothelial origin. In exceptional cases, these lesions may involve the testicular parenchyma, of which there are only 9 published cases in the literature. The authors describe a rare case of a testicular tumor in a 41-year-old male with normal tumor markers. Histopathology and immunohistochemical studies revealed an adenomatoid tumor with intratesticular growth. No involvement of the epididymis or testicular membranes was identified. The morphological clues leading to the correct diagnosis of adenomatoid tumor and the possible histogenesis and differential diagnosis are discussed.International Journal of Surgical Pathology 03/2011; 19(6):838-42. · 1.00 Impact Factor -
Article: Localization of p53 and proliferating cell nuclear antigen in fine-needle aspirates of benign and primary malignant tumors of the human breast: an immunocytochemical study using supersensitive monoclonal antibodies and the biotin-streptavidin-amplified method.
B A Alexiev[show abstract] [hide abstract]
ABSTRACT: p53 and proliferating cell nuclear antigen (PCNA) status was determined in fine-needle aspirates (FNAs) and methacarn-fixed paraffin-embedded tissue sections of six fibroadenomas and 50 primary breast carcinomas using supersensitive monoclonal antibodies and the biotin-streptavidin-amplified method. Nuclear accumulation of p53 was identified in 28% of carcinomas, while a heterogeneous immunostaining for PCNA was seen in all benign and malignant tumors examined. p53 expression in relation to nuclear plemorphism and lymph-node status showed weak correlation only as to nuclear grade (r = 0.28; P < 0.01). No direct or inverse correlation was found to exist between PCNA score and the evaluated prognostic parameters. In conclusion, although the identification of p53 in FNAs of breast tumors may assist in the diagnosis of malignancy, its application in the laboratory practice of cytopathology appears to be limited, since only 28% of primary breast carcinomas accumulate p53. Moreover, PCNA immunocytochemistry can be used as an alternative to traditional methods of evaluating the proliferative rate of tumors in FNAs.Diagnostic Cytopathology 12/1996; 15(4):277-81. · 1.16 Impact Factor