Two Cases of Renal Cell Carcinoma Harboring a Novel STRN-ALK Fusion Gene

Abstract

Anaplastic lymphoma kinase (ALK) translocation renal cell carcinomas (RCCs) have been reported by several independent groups in recent times. The clinical behavior and histopathologic characteristics of these carcinomas are not fully understood because of the paucity of cases reported. Here, we describe 2 cases of RCC harboring a novel striatin (STRN)-ALK fusion. The first case was a 33-year-old woman with no sickle cell trait who underwent nephrectomy for right renal mass and had late recurrence in para-aortic lymph nodes twice 10 and 12 years after initial surgery. After the second recurrence, she was carefully observed without any treatment. Twenty-six years after the initial nephrectomy, the second para-aortic lymphadenectomy was performed, and gastrectomy was performed for newly developed primary gastric cancer. The resected para-aortic lymph nodes were largely replaced by metastatic carcinoma. The second case was a 38-year-old man with no sickle cell trait who underwent cytoreductive nephrectomy followed by sunitinib therapy for metastatic RCC. In both cases, the tumor showed solid, papillary, tubular, and mucinous cribriform structures. Psammoma bodies were occasionally seen in the stroma. Tumor cells had a large nucleus and prominent nucleoli with predominantly eosinophilic cytoplasm. Rhabdoid cells and signet-ring cells were also observed. Intracytoplasmic mucin deposition and background mucinous stroma were confirmed. In the second case, tumor necrosis was seen in some areas. Tumor cells exhibited diffuse positive staining for ALK in both cases. ALK translocation was confirmed by fluorescent in situ hybridization, and further gene analysis revealed a STRN-ALK fusion. These cases provide great insights into ALK translocation RCCs.

Expanding the spectrum of ALK‐rearranged renal cell carcinomas in children: Identification of a novel HOOK1‐ALK fusion transcript

“…Indeed, besides the case reported here, two additional cases of ALK -rearranged RCC have been reported in adult patients since the publication of our study, both corresponding to STRN-ALK fusions (Kusano et al, 2016). In addition to our pediatric cases, seven adult cases have been reported (Sugawara et al, 2012, Sukov et al, 2012; Lee et al, 2013; Kusano et al, 2016). Within the total of 13 reported cases, the fusion partners include TPM3 (4 cases, 3 pediatric and 1 adult), VCL (3 pediatric cases, all with sickle cell disease or trait), STRN (2 adult cases) and EML4 (1 adult case).…”

Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence

“…This involves the entire ALK kinase domain, which leads to constitutive activation of ALK kinase via dimerization mediated by the coiled-coil domain of STRN (22). This rare rearrangement has been reported in thyroid cancer before (2) as well as renal cell carcinoma (23) and colorectal adenocarcinoma (24). Patients with this fusion have shown significant initial clinical response to the ALK inhibitors crizotinib and TAE864.…”

Morphologic, Molecular, and Taxonomic Evolution of Renal Cell Carcinoma: A Conceptual Perspective With Emphasis on Updates to the 2016 World Health Organization Classification

“…[75][76][77][78][79][80] ALK-rearranged RCCs in young patients with hemoglobinopathy often show a medullary location, are composed of spindled-to-polygonal cells with eosinophilic cytoplasm and intracytoplasmic vacuoles, and are positive for ALK expression (with concomitant retained nuclear INI-1 staining). At the genomic level, these tumors typically harbor ALK fusions with vinculin (VCL), whereas other reported ALK-rearranged RCCs show variable fusion partners (and morphology).…”

“…In perhaps no tumor type has this been more evident than renal cell carcinoma (RCC), which has expanded from 4 subtypes in the 1997 Heidelberg classification 1 to 12 recognized subtypes and several provisional entities in the recent 2016 World Health Organization (WHO) Classification of Tumours of the Urinary System and Male Genital Organs 2,3 (Table). Although these insights have improved our ability to identify molecularly distinct RCC entities from within a group of morphologically heterogeneous tumors, RCC classification may also carry significant clinical implications for patients, including prognostic risk stratification, selection of targeted therapeutics, and identification for subsequent genetic testing (with associated familial ramifications).…”