Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney

Abstract

The perivascular epithelioid cell (PEC) is a unique cell type coexpressing contractile proteins (mainly a-smooth muscle actin), melanocytic markers, including microphthalmia-associated transcription factor (MITF), and estrogen and progesterone receptors. It is constantly present in a group of tumors called PEComas. Renal PEComas include the common angiomyolipoma as well as less common lesions such as microscopic angiomyolipoma, intraglomerular lesions, angiomyolipoma with epithelial cysts, epithelioid angiomyolipoma, oncocytoma-like angiomyolipoma and lymphangioleiomyomatosis of the renal sinus. It has been demonstrated that most of these lesions are determined by mutations affecting genes of the tuberous sclerosis complex, tuberous sclerosis 1 (TSC1) and tuberous sclerosis 2 (TSC2), with eventual deregulation of the RHEB/MTOR/RPS6KB2 pathway, and it has been observed that some PEComas regressed during sirolimus therapy, an MTOR inhibitor. Recently, overexpression of MITF has been related to the expression of the papainlike cysteine protease cathepsin K in osteoclasts where it has inhibited MTOR. The aim of this study is to evaluate cathepsin K immunohistochemically in the entire spectrum of PEComa lesions in the kidney. The study population consisted of 84 renal PEComa lesions, including 5 composed predominantly of fat (lipoma-like angiomyolipoma), 15 almost exclusively composed of spindle-shaped smooth muscle cells (leiomyoma-like angiomyolipoma) and 31 common angiomyolipomas composed of a mixture of fat, spindle and epithelioid smooth muscle cells, and abnormal thick-walled blood vessels, 15 microscopic angiomyolipomas, 5 intraglomerular lesions, 2 oncocytoma-like angiomyolipomas, 8 epithelioid angiomyolipomas, 2 angiomyolipomas with epithelial cysts and 1 example of lymphangioleiomyomatosis of the renal sinus. In all of the renal PEComas, cathepsin K was found to be constantly and strongly expressed and seems to be a more powerful marker than other commonly used markers for their identification, especially to confirm the diagnosis on needle biopsies. Modern Pathology (2012) 25, 100-111; doi:10.1038/modpathol.2011.136; published online 26 August 2011Keywords: angiomyolipoma; cathepsin K; epithelioid angiomyolipoma; PEC; PEComa; tuberous sclerosisThe perivascular epithelioid cell (PEC) is a unique cell type coexpressing contractile proteins (mainly a-smooth muscle actin (a-SMA)), melanocytic markers, including microphthalmia-associated transcription factor (MITF), and estrogen and progesterone receptors. The PEC is constantly present in a group of tumors called PEComas including angiomyolipoma, clear-cell 'sugar' tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor of the falciform ligament and ligamentum teres, and rare clear-cell tumors of other anatomical sites. PEComas of the kidney include the common angiomyolipoma, microscopic angiomyolipoma, intraglomerular lesions, angiomyolipoma with epithelial cysts, epithelioid angiomyolipoma (pure epithelioid PEComa),

Aggressive and nonaggressive translocation t(6;11) renal cell carcinoma: comparative study of 6 cases and review of the literature

“…"+" = weak positivity; "++" = moderate positivity; "+++" = strong positivity; "−" = negative. these neoplasms; however, there are many false-positive/negative staining as a result of fixation, autolysis, and other steps related to the tissue processing [5,20]. Furthermore, CD117 was found to be another potential distinguishing marker between the t(6;11) TRCC and Xp11.2 TRCC.…”

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

“…A prominent smooth muscle-like component was uniformly present as the basis for inclusion in this study; however, other areas of the stroma were edematous or hyalinized. Arguing against the possibility of a 'collision' between angiomyolipoma and renal cell carcinoma, 2 the stroma lacked labeling for HMB45, melan-A, and cathepsin K. 32 The epithelial component of the renal cell carcinomas with angioleiomyoma-like stroma was composed of glandular elements lined by cells with variably clear to eosinophilic or flocculent cyto- Figure 5 Tumors excluded from the category of renal cell carcinoma with angioleiomyoma-like stroma: Two tumors had a prominent component of smooth muscle-like stroma containing numerous blood vessels in only one of the tumor sections (a), whereas the remainder of the tumor had a typical morphological appearance (b) and immunohistochemical profile of clear cell renal cell carcinoma. This was interpreted as tangential sectioning of the tumor pseudocapsule in one tissue block.…”

Giant Perivascular Epithelioid Cell Tumor of the Orbit: A Clinicopathological Analysis and Review of the Literature

“…Tyrosinase is yet another melanocytic marker that PEComas may express [7]. In renal PEComas, cathepsin K has been reported to be constantly and strongly expressed much more than other commonly used markers for their identification, although only one of the orbital PEComas in the literature was reported to have a positive result for this marker [10, 17]. …”