Renal angiomyoadenomatous tumor: morphologic, immunohistochemical, and molecular genetic study of a distinct entity

Michal, Michael; Hes, Ondřej; Němcová, Jana; Šíma, Radek; Kuroda, Naoto; Bulimbašić, Stela; Franco, Mônica Regina; Sakaida, Noriko; Daniš, Dušan; Kazakov, Dmitry V.; Ohe, Chisato; Hora, Milan

doi:10.1007/s00428-008-0697-3

Cited by 90 publications

(82 citation statements)

References 22 publications

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“…Often the epithelium demonstrated a tufted growth into the lumen of the glands with an ill-defined apical cytoplasmic border, similar to the 'blister-like' appearance described by Michal et al 3 Surrounding the epithelial elements, a layer of capillaries was often prominent, imparting a dualcell layer pattern resembling a basal cell or myoepithelial cell layer. The endothelial nature of these cells was supported by immunohistochemistry for CD34, with some areas showing an interrupted or discontinuous capillary network surrounding the glands.…”

Section: Discussionsupporting

confidence: 59%

“…[1][2][3][4] However, the relationship of these tumors to other renal epithelial neoplasms, particularly clear cell renal cell carcinoma 4 and clear cell papillary renal cell carcinoma, 5-11 is incompletely understood. 13 To shed light on these relationships, in this study we assessed clinicopathological, immunohistochemical, and molecular features of renal epithelial neoplasms with a prominent stromal smooth muscle component.…”

Section: Discussionmentioning

confidence: 99%

“…Cytological features were assessed, including nuclear grade, 14 presence of ill-defined apical cytoplasm, 3 and cytoplasmic staining characteristics. Other features studied included the light microscopic appearance of the stromal component (smooth muscle-like, hyalinized, or edematous, with or without hemangioma-like areas), ossification, and other forms of calcification.…”

Section: Pathology and Light Microscopymentioning

confidence: 99%

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Renal cell carcinoma with angioleiomyoma-like stroma: clinicopathological, immunohistochemical, and molecular features supporting classification as a distinct entity

et al. 2015

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Rare renal epithelial neoplasms have been recognized to have an angioleiomyoma or leiomyoma-like proliferation of stromal smooth muscle; however, the nature of these tumors and their relationships to other renal cell carcinomas are poorly understood. We analyzed 23 such tumors for their clinicopathological, immunohistochemical, and cytogenetic features using fluorescence in situ hybridization. Twelve showed a homogeneous combination of features and were reclassified as renal cell carcinoma with angioleiomyoma-like stroma. These were composed of neoplastic glandular structures lined by cells with mixed clear, pale, and eosinophilic cytoplasm forming occasional papillary tufts. The stroma resembled smooth muscle and often extended away from the epithelial component, entrapping perinephric fat or non-neoplastic renal elements. Immunohistochemistry showed the epithelium to have reactivity for: carbonic anhydrase IX, CD10, vimentin, cytokeratin 7, cytokeratin 34bE12, and PAX8 but not a-methylacyl-coA-racemase. The stroma labeled for smooth muscle (smooth muscle actin 3 þ , desmin 1 þ , caldesmon 3 þ ) but not epithelial antigens. Neither component showed substantial reactivity for HMB45, melan-A, cathepsin K, or TFE3 protein. An interrupted, conspicuous layer of CD34-positive endothelial cells rimmed the epithelium, imparting a two-cell layer pattern resembling myoepithelial or basal cells. Chromosome 3p deletion and trisomy 7 and 17 were uniformly absent. Follow-up was available for three patients, none of whom experienced malignant behavior. Eleven tumors were excluded from this category and considered to be clear cell renal cell carcinoma with a reactive proliferation of smooth muscle (n ¼ 4) or tangential sectioning of the pseudocapsule (n ¼ 2), renal cell carcinoma unclassified (n ¼ 4), or clear cell papillary renal cell carcinoma (n ¼ 1). In summary, renal cell carcinoma with angioleiomyoma-like stroma is a distinct neoplasm with characteristic morphological, immunohistochemical, and molecular features, unrelated to clear cell renal cell carcinoma. The immunoprofile overlaps partly with that of clear cell papillary renal cell carcinoma, though morphology and reactivity for CD10 are points of contrast.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Pathology and Light Microscopymentioning

confidence: 99%

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Renal cell carcinoma with angioleiomyoma-like stroma: clinicopathological, immunohistochemical, and molecular features supporting classification as a distinct entity

et al. 2015

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“…22 Michal et al 23 similarly reported the 'renal angiomyoadenomatous tumor,' which has subsequently been studied by other authors. [24][25][26][27][28][29] Although a link to clear cell papillary renal cell carcinoma has been proposed, 29 the relationship of these entities remains uncertain. 4,24 At least some of these lesions have demonstrated abnormalities of chromosomes 3 and the VHL gene, in addition to chromosomes 1, 11, and 16.…”

Section: Discussionmentioning

confidence: 99%

Clear cell papillary renal cell carcinoma: differential diagnosis and extended immunohistochemical profile

et al. 2013

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Clear cell papillary renal cell carcinoma is a recently recognized renal neoplasm, composed of cells with clear cytoplasm lining cystic, tubular, and papillary structures. These tumors have immunohistochemical and genetic profiles distinct from clear cell renal cell carcinoma and papillary renal cell carcinoma. We studied morphologic and immunohistochemical features (cytokeratin 7 (CK7), carbonic anhydrase IX (CAIX), CD10, alpha-methylacylCoA racemase, smooth muscle actin, desmin, estrogen and progesterone receptors) in 55 tumors from 34 patients, 8 of whom had end-stage renal disease. These tumors comprised 3% of all adult renal cell carcinoma resections over a period of 3 years. The patients' ages ranged from 33 to 87 years (mean 61). Multiple tumors (2-8) were present in 9 patients. Other renal tumors were present concurrently in four patients and subsequently in two patients, including: oncocytoma, clear cell renal cell carcinoma, and multilocular cystic renal cell carcinoma. Sizes ranged from 0.2 to 7.5 (mean 2.0) cm; 87% were Fuhrman grade 2, and 96% were stage pT1a. Papillary architecture was usually limited to focal branching papillae (51% of 55 tumors) or small, blunt papillae (35%). Large areas of extensively branched papillae were present in only 14% of tumors. Almost all tumors (98%) included cysts, and 18 tumors were extensively (Z90%) cystic. Immunoprofile showed CK7 þ , AMACR À , CD10 À , CAIX þ in the tubular and papillary components of all tumors; however, CD10 labeled the apical cell membrane of cyst epithelium in 59%. The stroma was focally actin positive (94%), with infrequent desmin expression (13%). Estrogen receptor and progesterone receptor were negative. During a median follow-up period of 56 months, no patient developed local recurrence, distant or lymph-node metastasis, or cancer death. Branched tubules, small papillae, and the immunohistochemical and molecular profiles aid in distinguishing these tumors from clear cell renal cell carcinoma and multilocular cystic renal cell carcinoma.

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“…One such subtype is clear-cell papillary renal cell carcinoma, a typically low-grade renal epithelial neoplasm with morpho-logical features mimicking both clear-cell renal cell carcinoma and papillary renal cell carcinoma that also occasionally exhibits prominent smooth muscle metaplasia within the intratumoral stroma. We, and others, believe that a variety of other recently described entities, including renal angiomyoadenomatous tumor, 2 clear-cell tubulopapillary renal cell carcinoma, 3 renal cell carcinoma with prominent leiomyomatous proliferation 4 and clearcell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivity 5 are either closely related, if not the same, tumors as clear-cell papillary renal cell carcinoma described in the literature with alternative nomenclature. 3,[5][6][7][8] Our contention is further supported by presentations at the most recent annual meeting of United States and Canadian Association of Pathologists (USCAP, 2011) regarding clear-cell papillary renal cell carcinoma and renal angiomyoadenomatous tumor.…”

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confidence: 86%

Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins

et al. 2011

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Over the past few years several investigators have independently described unique low-grade renal epithelial neoplasms with clear cytoplasm, focal to diffuse papillary architecture, and occasional leiomyomatous stromal metaplasia that are not currently recognized in the World Health Organization classification of renal tumors. These tumors have been referred to by a variety of names including clear-cell papillary renal cell carcinoma and recently ''clear-cell tubulopapillary renal cell carcinoma''. On the basis of the available data, such tumors are positive for cytokeratin 7 (CK7) and carbonic anhydrase IX (CA9), while being negative for CD10, a-methylacyl-CoA racemase (AMACR), and TFE3. These tumors reportedly lack trisomies of chromosomes 7 and 17, deletions of 3p25, von Hippel-Lindau (VHL) gene mutations, and VHL promoter hypermethylation. Herein, we report on nine cases of this tumor emphasizing detailed studies of the VHL gene and hypoxiainducible factor (HIF) pathway. Molecular studies performed included VHL mutational analysis, copy number changes assessed using single-nucleotide polymorphism arrays, and qRT-PCR for VHL mRNA expression. Immunohistochemical stains for markers of HIF pathway activation (HIF-1a, CA9, and glucose transporter-1 (GLUT-1)) as well as other relevant markers (CK7, CD10, AMACR, and TFE3) were performed. None of our tumors harbored VHL gene mutations, losses of chromosomal region 3p25, or trisomies of chromosomes 7 or 17. VHL mRNA was overexpressed in our tumors relative to normal renal tissue and clear-cell renal cell carcinoma. All cases showed strong co-expression of CK7, HIF-1a, GLUT-1, and CA9. No expression of TFE3, CD10, or AMACR was seen. The morphological, immunophenotypic, and molecular features of these unique low-grade tumors are sufficiently distinct to allow separation from other renal cell carcinoma subtypes. The coexpression of CA9, HIF-1a, and GLUT-1 in the absence of VHL gene alterations in clear-cell papillary renal cell carcinoma suggests activation of the HIF pathway by non-VHL-dependent mechanisms.

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Renal angiomyoadenomatous tumor: morphologic, immunohistochemical, and molecular genetic study of a distinct entity

Cited by 90 publications

References 22 publications

Renal cell carcinoma with angioleiomyoma-like stroma: clinicopathological, immunohistochemical, and molecular features supporting classification as a distinct entity

Renal cell carcinoma with angioleiomyoma-like stroma: clinicopathological, immunohistochemical, and molecular features supporting classification as a distinct entity

Clear cell papillary renal cell carcinoma: differential diagnosis and extended immunohistochemical profile

Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel–Lindau gene and hypoxia-inducible factor pathway-related proteins

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