Intraglomerular microlesions in renal angiomyolipoma

doi:10.1053/hupa.2000.16533

Human Pathology

Volume 31, Issue 10, October 2000, Pages 1325-1328

https://doi.org/10.1053/hupa.2000.16533 Get rights and content

Abstract

A unique case of bilateral multiple intrarenal angiomyolipomas in a 21-year-old woman with tuberous sclerosis is reported. The microscopic examination showed peculiar intraglomerular microlesions, epithelioid areas, microscopic foci of renal cell carcinoma and renal cysts, and the classical features of angiomyolipoma lesion. HMB-45 positivity was detected within some nodules and epithelioid areas. Intraglomerular microlesions were composed of adipose and smooth-muscle cells within the glomerular capillary tuft. These lesions, which were continuous with the capillary tuft, did not show any attachment to the Bowman's capsule. These findings suggest that these are not a consequence of an infiltration from the outside but were originated from inside the glomerulus. The simultaneous presence of multiple angiomyolipoma nodules either inside or outside the glomeruli, multifocality and bilaterality of these lesions, together with the HMB-45 positivity and the finding of scattered epithelioid areas supports the theory that there is a progenitor cell giving origin to all these lesions, the cell which has been named as perivascular epithe lioid cell by most authors. HUM PATHOL 31:1325-1328.

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Cited by (16)

Stimulator of interferon genes (STING) immunohistochemical expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney
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Citation Excerpt :
Both inherited and most sporadic angiomyolipomas demonstrate loss of heterozygosity and mutation of chromosome 16p (TSC2).15,16 Intraglomerular PEC lesions have been reported in patients with tuberous sclerosis and in the TSC2/PKD1 contiguous gene syndrome.17,18 Also, AMLEC has been found in patients with and without tuberous sclerosis.19
Angiomyolipoma is the prototype of renal perivascular epithelioid cell (PEC) lesions whose pathogenesis is determined by mutations affecting TSC genes, with eventual deregulation of the mTOR pathway. It is well known that mTOR complex protein is involved in autophagy, and recently the role of STING in this process has been demonstrated. Based on this background, we sought to investigate STING immunohistochemical expression in a series of PEC lesions of the kidney. Fifty classic angiomyolipomas, 14 epithelioid angiomyolipomas/pure epithelioid PEComas, two angiomyolipomas with epithelial cysts (AMLEC), and two intraglomerular PEC lesions were collected. Immunostaining for STING was carried out in all cases and FISH analysis using dual colour break apart TFE3 and TFEB probes was performed in all pure epithelioid PEComas and AMLEC. Control cases including 20 normal adult kidneys, five fetal kidneys, and 30 MiT family translocation renal cell carcinomas (the main differential diagnosis with epithelioid angiomyolipoma/pure epithelioid PEComa) were also immunohistochemically stained with STING. Strong and diffuse cytoplasmic expression of STING was observed in 100% of classic angiomyolipomas, AMLEC, and intraglomerular lesions, and in 79% (11/14) of epithelioid angiomyolipomas/pure epithelioid PEComas. TFE3 gene rearrangement was demonstrated in two epithelioid angiomyolipomas/pure epithelioid PEComas, both completely negative for STING. None of the MiT family translocation renal cell carcinomas expressed STING. In conclusion, we demonstrate the expression of STING in almost all PEC lesions of the kidney. This result provides novel insights into the possible role of autophagy in PEC lesions of the kidney. Moreover, this finding may be useful for diagnostic purposes, particularly in distinguishing epithelioid angiomyolipoma/pure epithelioid PEComa from MiT family translocation renal cell carcinoma and detecting intraglomerular PEC lesions.
Angiomyolipoma of the kidney: from simple hamartoma to complex tumour
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Citation Excerpt :
When there are extremely numerous merging lesions occupying a large amount of the renal parenchyma, the macroscopic appearance may resemble an infiltrative mass. Intraglomerular lesions, first described by Ferez in 1930 as epithelial and fatty inclusions in the glomerulus, consist of minute nodules composed of epithelioid smooth muscle cells occasionally intermixed with a few adipocytes within the glomerular capillary tuft30,31 (Fig. 5). They have been reported sporadically or in patients with tuberous sclerosis and in the TSC2/PKD1 contiguous gene syndrome, a disease with a deletion disrupting both TSC2 and PKD1 (autosomal dominant polycystic disease gene).32
Angiomyolipoma is the most common mesenchymal tumour of the kidney, even if for a long time it has been viewed as a hamartoma rather than a neoplasm. It belongs to a family of neoplasms, named PEComa, characterised by the constant presence of perivascular epithelioid cells that co-express smooth muscle and melanogenesis markers. Angiomyolipoma can occur in patients with tuberous sclerosis, a hereditary syndrome due to the alteration of TSC1 or TSC2 genes, or sporadically. Angiomyolipoma and its variants are indolent tumours; however, some epithelioid angiomyolipomas/pure epithelioid PEComas are aggressive, and criteria for malignancy have been proposed to identify those cases. Although typical angiomyolipoma is a straightforward diagnosis, pathologists should be aware of the wide morphological spectrum of its variants which could be tricky in routine clinical practice and could require immunohistochemical analysis for resolution. The differential diagnosis may range from an inflammatory process (for instance xanthogranulomatous pyelonephritis) to the most common renal cancers and sarcomas. The immunoexpression of melanogenesis markers (HMB45 and Melan-A) and cathepsin K is extremely helpful in the majority of cases. Recently, a subset of epithelioid angiomyolipoma/pure epithelioid PEComa harbouring TFE3 gene fusions has been described, raising questions about its relationship with the family of perivascular epithelioid cell tumour. The activation of the mTOR pathway due to genetic alterations of tuberous sclerosis complex in TSC1 or TSC2 genes in angiomyolipoma has also been reported as well as the subsequent therapeutic implications.
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Case StudiesIntraglomerular microlesions in renal angiomyolipoma

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Case Studies
Intraglomerular microlesions in renal angiomyolipoma