Genetic analysis and clinicopathological features of ALK‐rearranged renal cell carcinoma in a large series of resected Chinese renal cell carcinoma patients and literature review

Abstract

ALK-rearranged RCC is a rare subtype of adult RCC and is associated with distinct histological features and a poor prognosis. Identification of ALK-rearranged RCC has important clinical significance, because patients might benefit from ALK inhibitor therapy as used in lung adenocarcinoma.

New and emerging renal entities: a perspective post‐WHO 2016 classification

“…In a recent prospective study of RCCs in paediatric and young adult patients, 3.8% were found to be ALK ‐rearranged . To our knowledge, since the first report in 2011, a total of 22 cases of ALK rearrangement‐associated RCC have been reported . The majority of patients were male (male/female ratio of 1.4:1), and they demonstrated a wide age range.…”

“…In contrast to RMC, the VCL – ALK ‐rearranged RCCs showed preserved INI‐1 protein expression and a low Ki67 index. The heterogeneous group of non‐ VCL /non‐ TPM3 – ALK ‐rearranged RCCs had variable morphologies, often showing a combination of patterns, including papillary (or pseudopapillary), cribriform, solid, trabecular, and tubular or tubulocystic (Figure B–D) . Abundant background mucin and intracytoplasmic mucin have been documented in several non‐ VCL – ALK ‐rearranged RCCs (Figure E).…”

“…Owing to the rarity and diversity of ALK rearrangement‐associated RCC, the clinical behaviour and histopathological characteristics of this tumour are not completely established. ALK rearrangement was found in <1% of adult RCCs and in ~2% of papillary RCCs, in large institutional series, based on retrospective TMA screening . In a recent prospective study of RCCs in paediatric and young adult patients, 3.8% were found to be ALK ‐rearranged .…”

“…One ALK rearrangement‐associated RCC without VCL – ALK fusion ( ALK partner unknown) was discovered concomitantly with Hodgkin lymphoma in a 19‐year‐old patient . Eight cases were documented in Asian patients: five were Japanese, one was Korean, and two were Chinese . The great majority of patients were either stage pT1a or pT1b.…”

“…Melanocytic markers such as melan‐A, S100, HMB45, and cathepsin‐K are consistently negative . Immunoreactivity for TFE3, but without genuine TFE3 rearrangement as determined with FISH, has been reported almost exclusively in paediatric cases and in only one adult ALK ‐rearrangement‐associated RCC with TPM3 – ALK fusion . Reactivity for TFE3 may signify amplification of MiTF signals by a mechanism other than translocation.…”