Investigator

Si Kei Lou

University Of Toronto

SKLSi Kei Lou
Papers(2)
Validation of <i>BRCA…Cytologic Histotyping…
Collaborators(1)
Heather M. Ruff
Institutions(1)
University Of Toronto

Papers

Validation of BRCA testing on cytologic samples of high‐grade serous carcinoma

BackgroundTesting for BRCA1/2 gene alterations in patients with high‐grade serous carcinoma (HGSC) is a critical determinant of treatment eligibility for poly(adenosine diphosphate‐ribose) polymerase inhibitors in addition to providing vital information for genetic counselling. Many patients present with effusions necessitating therapeutic drainage, and this makes cytologic specimens (CySs) the initial diagnostic material for HGSC, often before histologic sampling. Initiating somatic BRCA testing on a CyS allows the BRCA status to be determined sooner, and this affects clinical management.MethodsRetrospectively, 8 cases of formalin‐fixed, paraffin‐embedded (FFPE) CySs of peritoneal or pleural fluid from patients with HGSC and known BRCA1/2 alterations previously established by the testing of FFPE surgical specimens (SpSs) underwent next‐generation sequencing (NGS). Prospectively, 11 cases of peritoneal or pleural fluid from patients with HGSC but an unknown BRCA1/2 status underwent NGS with fresh, alcohol‐fixed, and FFPE CySs, and they were compared with subsequent NGS on 4 SpSs.ResultsCySs yielded high‐quantity and high‐quality DNA for NGS analysis when sufficient tumor cellularity was present. Fresh, alcohol‐fixed, and FFPE CySs were all suitable for NGS and provided identical NGS results. SpS and CyS BRCA testing was concordant in 10 of 12 cases. The 2 discordant cases showed low tumor cellularity and quality in the CyS and the SpS, respectively.ConclusionEffusion CySs of HGSC are excellent sources for NGS testing for BRCA1/2 genetic alterations when sufficient tumor cellularity is present. Fresh, alcohol‐fixed, and FFPE CySs are equivalent for NGS of BRCA1/2. NGS testing of HGSC CySs demonstrates good concordance with SpSs for the BRCA1/2 status.

Cytologic Histotyping of Gynecologic Malignancies in Peritoneal Fluids Is Reliable When Compared to Its Corresponding Surgical Specimen

ABSTRACTBackgroundCytologic examination of peritoneal fluid (PTFL) often represents the first and only pathologic specimen available to guide management of gynecologic malignancies (GMs). This study examines the cytohistologic correlation between histotyping of GM in PTFL and its corresponding surgical specimen (SS).MethodsThe study retrospectively identified positive PTFL with a GM between 2017 and 2022. Cytologic specimens (CSs) that were obtained after or concurrently with its diagnostic SS (biopsy/resection) were excluded. Root cause analysis of discordant cases was performed by reviewing morphology, specimen characteristics, and immunophenotype of CS.ResultsGM affected 55.8% (502/899) of malignant PTFL, of which 15.7% (79)/22.3% (112) was the only/initial diagnostic sample, respectively. Compared to SS, when a subtype was rendered on CS (91.9%), the concordance rate is 91.2% (almost perfect agreement, K = 0.842). Factors contributing to incorrect/inadequate subtyping include specimen limitations (low volume and/or cellularity), cytopathologist preference, and insufficient immunophenotyping. In seven patients (1.4%), the CS was able to render a more definitive diagnosis than its preceding nondiagnostic SS due to the paucity of lesional cells.ConclusionWhen compared to SS, histotyping of GM in PTFL is reliable and, at times, can be more definitive than its surgical counterpart. In some cases, subtyping is limited by extrinsic factors (i.e., specimen limitations). In other cases, the responsible cytopathologist prefers not to subtype despite supportive morphologic and immunohistochemical features. This highlights an opportunity for improvement in the diagnosis/subtyping of GM in PTFL, which may be the initial or only diagnostic specimen prior to patient treatment.

2Papers
1Collaborators