Conventional Cytogenetic Analysis of Solid Tumor Abnormalities: A 25-Year Review of Proficiency Test Results from the College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee

Abstract

Background: The joint College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee works to ensure the competency and proficiency of clinical cytogenetic testing laboratories through proficiency testing (PT) programs for various clinical tests offered by such laboratories, including the evaluation of cytogenetic abnormalities in solid tumors. Methods: Review and analyze 25 years (1999-2023) of solid tumor chromosome analysis PT results, utilizing G-banded karyograms. A retrospective review of results from 1999 to 2023 was performed, identifying the challenges addressing solid tumors. The chromosomal abnormalities and overall performance were evaluated. Results: A total of 21 solid tumor challenges were administered during the period 1999-2018. No solid tumor challenges were administered during the period 2019-2023. Challenges consisted of metaphase images and accompanying clinical history for the evaluation of numerical and/or structural abnormalities. All 21 cases reached 80% grading consensus for abnormality recognition. However, five cases (24%) failed to reach consensus for nomenclature reporting by participating laboratories. These cases illustrate errors in reporting chromosomal abnormalities, including whole-arm translocations and those involving sex chromosomes. In addition, they highlight the challenges with differentiation of terminal and interstitial deletions, difficulties in identifying correct breakpoints, and omission of brackets in neoplastic cases. Conclusions: This comprehensive 25-year review demonstrates the exceptional proficiency of cytogenetic laboratories in accurately identifying chromosome abnormalities in solid tumors, while also highlighting the challenges of reporting specific types of chromosomal abnormalities.

Keywords: conventional chromosome analysis; karyotype; proficiency testing; solid tumors.

Figure 1

Representative metaphase cell that demonstrates t(11;22;15)(q24;q12;q15). This abnormality was challenged twice (2003B-7 and 2008A-4) and represents the variant t(11;22) that is observed in Ewing sarcoma.

Figure 2

Representative metaphase cell from challenge 2006B-8. This challenge failed to meet 80% consensus for karyotype nomenclature. Three karyotypes were acceptable: 45,XX,der(3;8)(q10;q10)[5], 45,XX,der(3)t(3;8)(p11;q11.1),-8[5], and 45,XX,-3,der(8)t(3;8)(q11.1;p11.1)[5]. Most participants correctly identified and described a whole-arm translocation.