VCL-ALK renal cell carcinoma in adult patient without sickle cell trait

Anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC) is a provisional renal cell carcinoma subtype with a growing list of published fusion partners. VCL-ALK gene fusion represents an uncommon fusion partner (only 6 reported cases), almost always associated with sickle cell trait and typically in a pediatric population. Herein, we report only the second case of VCL-ALK gene fusion ALK-RCC from a 31-year-old female without associated sickle cell trait, and also only the third reported case occurring in an adult patient. The tumor (measuring 8.5 cm and confined to the kidney) demonstrated mostly solid growth, pleomorphic nuclei, variably rhabdoid to vacuolated cytoplasm, and showed diffuse strong immunoreactivity for both PAX8 and ALK stains. Gene panel sequencing confirmed VCL-ALK gene fusion in the tumor. This study expands the clinical framework for diagnostic consideration of this rare tumor with potential targeted pharmacotherapy. READ ARTICLE

Human Pathology: Case Reports DOI:10.1016/j.ehpc.2021.200528

Authors: Ankur R. Sangoi, Simon Y. Kimm, EmilyChan

Case StudyKirk SmithSeptember 1, 2021Kidney, Renal cell carcinoma, ALK, VCL, Sickle cell

Anaplastic lymphoma kinase (ALK) rearrangement in adult renal cell carcinoma with lung metastasis: a case report and literature review

Renal cell carcinoma (RCC) with anaplastic lymphoma kinase (ALK) rearrangement is rare, and the genetic profiles of the tumor have not been elucidated. Here, we report a case with recurrent papillary RCC and lung metastasis after nephrectomy for nearly 7 years. The patient first received sunitinib, whereas the drug toxicity was intolerable. Combined Immunohistology (IHC) and fluorescence in situ hybridization (FISH) revealed the patient has an ALK rearrangement, and the patient then was treated with crizotinib. The patient had good tolerance, and a partial response in the target lesions was achieved. In order to further understand the benefit of crizotinib in ALK-rearranged RCC, the patient was detected with whole exome sequencing (WES) to study her genetic profiles. Compared those of RCC cases without ALK rearrangement (nALK-RCC), the patient and nine RCC cases with ALK rearrangement (ALK-RCC) revealed unique genetic characteristics: 1) The common mutations that occurred in RCC were n..... READ ARTICLE

Translational Andrology and Urology DOI: 10.21037/tau-20-1343

Authors: Zhou S, Sun G, Wang J, Zhang H.

ALK rearrangement in TFE3-positive renal cell carcinoma: Alternative diagnostic option to exclude Xp112 translocation carcinoma

Anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC) is a rare subtype of RCC with gene fusion involving ALK at 2p23. It was first included in the renal tumor classification system by WorldHealth organization (WHO) as a distinct emerging/provisional renal entity in 2016. To date, only a few cases of ALK-RCC have been reported. Here, we report an exceptional case of ALK-RCC in a 15-year-old girl and review the literature. The patient presented with gross hematuria and a tumor measured 7 cm × 6 cm was found in the left kidney by imaging examination. Then a laparoscopic radical nephrectomy combined with local lymph node dissection was performed. The pathologic stage of the tumor was pT1bN1Mx and postoperative pathology showed that the tumor corresponded to WHO/ISUP grade 3–4. Immunohistochemistry (IHC) demonstrated moderate nuclear expression of TFE3 protein. Interestingly, ALK gene rearrangement rather than TFE3 gene rearrangement was observed by fluorescence in situ hy..... READ ARTICLE

Pathology - Research and Practice DOI:10.1016/j.prp.2020.153286

Authors: Yiqi Zhu, Ning Liu, Wei Guo, Xiaohong Pu, Hongqian Guo, Weidong Gan, Dongmei Li

Case StudyKirk SmithDecember 1, 2020Renal cell carcinoma, Translocation, FISH, ALK, HOOK1, TFE3

ALK-rearranged renal cell carcinomas in Polish population

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, the activation of which is considered an important event in the pathogenesis of several neoplasms and a predictive factor for the targeted therapy with ALK inhibitors. Thus far, ALK rearrangements have been identified in 22 renal cell carcinomas in both pediatric and adult patients. We evaluated the incidence of ALK rearrangement-associated RCC in adult Central European population. An immunohistochemical evaluation of 1019 kidney tumors was performed with use of three different clones of anti-ALK antibodies. None of the tested samples showed positive staining, which suggests that the incidence of ALK rearrangement-associated renal cell carcinomas is significantly lower in the Polish population, and indicates a potential association between ethnicity and occurrence of these rare neoplasms. READ ARTICLE

Pathology - Research and Practice DOI:10.1016/j.prp.2019.152669

Authors: Adam Gorczynski, Piotr Czapiewski, Aleksandra Korwat, Lukasz Budynko, Monika Prelowska, Krzysztof Okon, Wojciech Biernat

Targeted next-generation sequencing revealed distinct clinicopathologic and molecular features of VCL-ALK RCC

Anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC) is a novel entity of rare tumors with only 10 cases reported in the literature. Three RCC cases bearing VCL-ALK gene fusion were all young African American patients and associated with sickle cell trait notably. In contrast to the 3 reported cases, this neoplasm occurred in a middle-age woman (57 years old) without any evidence of sickle cell trait and demonstrated an infiltrating growth pattern with tubular, tubulopapillary, and tubulocystic structures, overlapping with collecting duct carcinoma and renal medullary carcinoma. Abundant intraluminal mucin was also noted significantly in the histologic sections. Immunostaining showed strong membranous labeling for ALK protein. We applied a large panel-targeted next-generation sequencing to explore the molecular alterations in the current case, revealing a driver oncogene VCL-ALK gene fusion co-occurring with pathogenic mutations in EP300 and TRRAP genes. Thereafter, f..... READ ARTICLE

Pathology - Research and Practice DOI:10.1016/j.prp.2019.152651

Authors: Xiao-tong Wang, Ru Fang, Sheng-bing Ye, Ru-song Zhang, Rui Li, Xuan Wang, Rong-hao Ji, Zhen-feng Lu, Heng-hui Ma, Xiao-jun Zhou, Qiu-yuan Xia, Qiu Rao