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Evaluating Mismatch Repair/Microsatellite Instability Status Using Cytology Effusion Specimens to Determine
Elizabeth M Jacobi1,2, Gene Landon1, Russell R Broaddus1,3
1The Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston.
Context.—:
The approval of pembrolizumab for treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) advanced cancers has led to increased requests for MSI and/or MMR immunoperoxidase (IPOX) testing. Diagnoses for patients with advanced-stage cancer are frequently made from cytology specimens.
Objective.—:
To investigate the feasibility of using cell block (CB) preparations of effusions for MMR IPOX evaluation.
Design.—:
Surgical pathology cases of colorectal and endometrial carcinomas with known MMR/MSI status and matched effusions with available CBs were identified. Cell block sections were evaluated for adequacy and stained with MMR IPOX (MSH2, MSH6, MLH1, and PMS2). The CBs were reviewed, the number of tumor cells quantified, and MMR IPOX was interpreted as retained, lost, suboptimal, or noncontributory.
Results.—:
We identified 748 cases with MMR/MSI testing on surgical specimens having matched effusions. Of these, 131 cases (17.5%) had an available CB and 53 were deemed adequate for MMR IPOX staining. MMR IPOX results between effusion CBs and surgical pathology specimens were concordant in 45 of 53 (85%), inconclusive in 6 of 53 (11%), and discordant in 2 of 53 (4%) cases.
Conclusions.—:
There was high concordance of MMR IPOX testing between cytologic and surgical specimens, with no false-positive and 2 false-negative CB results. Limited tumor cells, staining in cells indefinite as tumor, tumor staining heterogeneity, and lack of internal control staining were problematic in some cases. Our findings indicate that cytologic effusion specimens may be suitable substrates for MMR IPOX biomarker testing; however, inconclusive cases need to be interpreted with caution.
Insights
Cell block preparations from effusions can be used for mismatch repair (MMR) immunoperoxidase (IPOX) testing in advanced cancers. This method shows high concordance with surgical specimens, supporting its use for biomarker testing.
Area of Science:
- Oncology
- Pathology
- Biomarker Testing
Background:
- Pembrolizumab approval for MSI-H/dMMR advanced cancers increases demand for MSI/MMR IPOX testing.
- Cytology specimens are often used for advanced cancer diagnoses.
Purpose of the Study:
- To assess the feasibility of using cell block (CB) preparations from effusions for MMR IPOX evaluation.
- To determine the concordance of MMR IPOX testing between cytologic and surgical specimens.
Main Methods:
- Identified surgical pathology cases with known MMR/MSI status and matched effusions with available CBs.
- Evaluated CB sections for adequacy and performed MMR IPOX staining (MSH2, MSH6, MLH1, PMS2).
- Interpreted MMR IPOX results as retained, lost, suboptimal, or noncontributory.
Main Results:
- Out of 748 cases, 131 had available CBs, with 53 deemed adequate for staining.
- MMR IPOX results were concordant in 85% (45/53) of cases between effusion CBs and surgical specimens.
- Inconclusive results were seen in 11% (6/53) and discordant results in 4% (2/53) of cases.
Conclusions:
- Cytologic effusion specimens are suitable for MMR IPOX biomarker testing.
- High concordance was observed, with no false-positive and 2 false-negative CB results.
- Inconclusive cases require careful interpretation due to challenges like limited tumor cells and staining heterogeneity.
