Mucinous Tubular and Spindle-Cell Carcinoma of the Kidney: Clinical Features, Genomic Profiles, and Treatment Outcomes

Abstract

Background: Mucinous tubular and spindle-cell carcinoma (MTSCC) is a rare kidney cancer subtype with limited cases reported in the literature. We report on outcomes of 25 patients with this variant who were managed at our institution.

Materials and methods: The institution database was queried, and clinical data extracted for patients with MTSCC. Molecular features examined included next-generation sequencing with Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets and allele-specific copy number analysis using the Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) algorithm in a subset of patients.

Results: All patients underwent primary tumor-directed therapy (nephrectomy = 23, cryoablation = 2). Metastases were diagnosed in 6 patients (24%), 3 (12%) of whom had de novo metastatic disease. Five of 6 patients with metastatic disease had high-grade histological features compared with 0 of 19 nonmetastatic patients (83% vs. 0%; P < .001, Fisher exact test). Three-year overall survival from diagnosis was 84.8% (95% confidence interval, 59.6-94.9) with a median follow-up time of 3.9 years (range, 1 month to 10.3 years). Three deaths occurred, all from metastatic disease. Four patients received systemic therapy with time to treatment failure ≤6 months across different agents with the exception of 1 patient with prolonged response with sunitinib treatment (30.6 months). The most frequent molecular alterations were neurofibromin 2 mutations (n = 2; 40%), germline alterations (n = 2; 40%) including checkpoint kinase 2 and BRCA2 DNA repair associated mutations, multiple chromosomal copy number losses, and mismatch repair deficiency in 1 patient.

Conclusion: MTSCC is characterized by localized tumors treated successfully with primary tumor-directed therapy. However, patients with high-grade histological features were more likely to develop metastatic disease with limited responses to standard therapies.

Keywords: Genomics; MTSCC; Non–clear-cell renal cell carcinoma; Survival; Systemic therapy.

Figure 1.. Overall survival of patients with MTSCC from first pathological diagnosis.

3-year overall survival from first pathological diagnosis with MTSCC was 84.8% (95% CI: 59.6, 94.9) for all patients with a median follow-up time for survivors of 3.9 years (range: 1 months, 10.3 years). Three deaths occurred which were all from metastatic disease at 3.7, 15.0 and 29.2 months.

Figure 2.. Swimmers plot for treatment durations on all lines of therapy.

Details on all lines of systemic therapy per individual patients by coded by different colors. (*) Death from metastatic disease (†) Drug stopped due to disease progression.

Figure 3.

Oncoprint illustrating most common Genomic alterations changes detected by NGS using MSK- IMPACT analysis across 5 patients with columns representing individual patients

Figure 4.

Allelic integer copy number as estimates by FACETS of 7 samples from 5 patients. HETLOSS (LOH) A=1; B=0, HOMDEL A=0, B=0, Gain A=2, B=1, Tetraploid A=2, B=2, AMP (or if broader high copy gain) A=3+, B=1, Copy number neutral LOH (CNLOH) A=2, B=0, Reciprocal LOH (RLOH) A=3+, B=0

Picture 1:

Immunohistochemistry staining for mismatch repair (MMR) proteins for one patient in the series with deficient.MMR status. Note for the loss of MLH1 and PMS2 in tumor cell.