ALK-Rearranged Renal Cell Carcinoma: A Study of Three Cases With Clinicopathologic Features and Effect of Postoperative Adjuvant Immunotherapy

Abstract

Background

ALK-rearranged renal cell carcinoma (ALK-RCC) is a rare malignant epithelial tumor of the kidney. ALK-RCC has recently been listed in the 5^th edition of the World Health Organization (WHO) Classification of Tumors as a molecularly defined RCC subtype.

Patients and Methods

We describe retrospectively 3 ALK-RCCs from clinicopathologic, immunohistochemical (IHC), and molecular genetic aspects, along with postoperative adjuvant therapeutic regime and prognosis-related information.

Results

Two patients were female and one patient was male. Patients’ age ranged from 38 to 64 years (mean 51.3 years). Tumor size ranged from 32 mm to 89 mm (mean 55.3 mm, median 45 mm). All 3 tumors were diffusely positive for ALK protein. ALK fusion partners (TPM3 for case 1, VCL for case 2, and EML4 for case 3) were identified by next-generation sequencing. Histomorphologically, the tumors were heterogeneous, showing tubulocystic, papillary, trabecular, and solid growth patterns and polygonal to rhabdoid neoplastic cells. Cases 1 and 3 set in a mucinous background. Upon quantification of tumor-associated CD8⁺ T cells by IHC, tumor immune phenotypes (IPs) were defined as immune-desert in case 1, immune-inflamed in case 2, and immune-excluded in case 3. Follow-up for the 3 patients ranged from 18 to 129 months (mean, 59.3 months). Case 1 refused postoperative adjuvant therapy and was alive without disease at 129-month follow-up. Case 2 was postoperatively treated with a PD-1-targeted monoclonal antibody, being alive without disease at 18-month follow-up. Case 3 showed retroperitoneal lymph nodes and lung metastases at initial diagnosis. She was postoperatively treated with a PD-1-targeted monoclonal antibody, with no benefit suggested by computed tomography on follow-up.

Conclusion

ALK-RCC represents a distinct entity with clinicopathological, genetic, and immunophenotypic heterogeneity. ALK IHC analysis during primary screening may aid diagnosis in difficult cases. For progressive ALK-RCCs, postoperative adjuvant immunotherapy may be best selected according to IP features. Patients with immune-excluded phenotypes may not benefit from immunotherapy.