Kidney cancer. Principles and practice. Second edition. Primo N. Lara, Jr. Eric Jonasch (Editors). Springer International Publishing (2015)
Early in the 1990s, Zbar et al. discovered multiple families affected by papillary renal cell carcinoma (pRCC) with a very high penetrance [16, 17]. Interestingly, the affected individuals displayed no loss of chromosome 3p, which lead the researchers to suspect a separate heritable RCC syndrome, hereditary papillary RCC (HPRC). This second hereditary RCC syndrome was later linked to 7q31 and found to be caused by a genetic mutation in the MET proto-oncogene . MET encodes for a crucial tyrosine kinase receptor binding the hepatocyte growth factor (HGF), and the mutant variant demonstrates a high degree of phosphorylation corresponding to elevated enzymatic activity . Activated MET signaling is believed insufficient in tumorigenesis alone, but nonrandom duplication of copies of the affected gene is commonly detected in HPRC perhaps contributing to carcinogenesis .
Unlike VHL, HPRC presents only with kidney tumors without any extrarenal manifestations. Without a set of distinguishing features, diagnosis can be difficult and may rely on a meticulous documentation of familial pedigree. The penetrance for this disorder is considerable. Moreover, the risk of RCC only increases with age, upward to 67% by age 60 [21, 22]. Generally speaking, the disease is detected after the age of 30, but subtypes with earlier onset have been described . HPRC presents with papillary type 1 , and it is not uncommon for there to be several thousand small papillary foci to be present in the renal parenchyma of affected individuals .
Fig. 8.2. Radical nephrectomy specimen of a 15 cm left renal mass. The tumor was believed localized to the lower pole of the kidney, but on final pathology, the tumor infiltrated throughout in all regions of the kidney
Fig. 8.3. 5x magnification of a cutaneous shave biopsy of a cutaneous leiomyoma in a patient with HLRCC. The underlying dermis contains interlacing smooth muscle bundles and fascicles
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