Single nucleotide polymorphism (SNP) chromosomal microarray as a diagnostic tool for mucinous tubular and spindle cell carcinoma: A validation study

Hum Pathol. 2024 Apr:146:57-65. doi: 10.1016/j.humpath.2024.04.003. Epub 2024 Apr 12.

Abstract

Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA). We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays. The cohort was comprised of 8 females and males, each, with an age range of 33-79 years (median, 59), and a tumor size range of 3.4-15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally. Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of CDKN2A/B, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC. MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.

Keywords: Mucinous tubular and spindle cell carcinoma; SNP; Single nucleotide polymorphism.

Publication types

  • Validation Study

MeSH terms

  • Adenocarcinoma, Mucinous* / diagnosis
  • Adenocarcinoma, Mucinous* / genetics
  • Adenocarcinoma, Mucinous* / pathology
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Carcinoma / diagnosis
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology
  • DNA Copy Number Variations
  • Diagnosis, Differential
  • Female
  • Humans
  • Kidney Neoplasms* / diagnosis
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Reproducibility of Results

Substances

  • Biomarkers, Tumor