Liquid-Based Cervical Cytology: Monitoring the Laboratory Quality Indicators.

Aim: Many developments in cervical cancer screening have happened in the past century, helping women in earlier detection of cervical cancer and its precursors. Cytology still holds the fort as being a specific test, though it suffers in sensitivity. As a part of the quality control program, the aim of the study is to determine the total number of abnormal liquid-based cervical cytology (LBC) at our center and correlate the abnormal LBC with histology and human papillomavirus (HPV) DNA test results. Method: Retrospective analysis of 4286 LBC screening cases was carried out over a period of 5 years. For cytology-histology correlation, cervical biopsy and cytology test results were analyzed. The two-tier grading system for biopsy interpretation was used. HPV DNA test results wherever available were correlated. Results: Of the 4286 LBC cases, 157 samples (3.7%) were unsatisfactory for evaluation, 3915 samples (91.3%) were negative for intra-epithelial lesion or malignancy, and 214 samples (5%) showed epithelial cell abnormality. ASC-US was reported in 60 cases (1.4%), ASC-H in 35 cases (0.8%), LSIL in 47 cases (1.1%), HSIL in 41 cases (1.0%), squamous cell carcinoma in a single case (0.02%), and atypical glandular cells in 30 cases (0.7%). The ASC/SIL ratio was 1.07:1. The CHC major discrepancy was calculated as 16.2%. The concordance of HSIL on cytology and biopsy as a measure of PPV is 94.4%. Of the epithelial cell abnormalities, 24 cases were positive for high-risk HPV (hrHPV). Molecular test results of 2737 samples showed HPV detected in 50 cases, of which 24 cases were positive for hrHPV. Conclusion: The study helped us to analyze the quality parameters of our cytopathology laboratory which are within the acceptable limits.

Distinct patterns of occurrence, common associations, and survival of patients with second primary maligancies: A 5-year single institute experience with review of literature.

BACKGROUND: Multiple primary malignancy (MPM) is defined as occurrence of two or more synchronous or metachronous primary malignancies. With the rise in cancer burden and meticulous screening of index primary malignancy (IPM) during treatment, increased incidence of second primary malignancy (SPM) is expected. This study was undertaken with an attempt to analyze the incidence, commonest associations, management strategies, and clinical outcomes of MPM. MATERIALS AND METHODS: This is an observational retrospective study carried out in a single institute with patients registered between 1st January 2015 and 31st August 2019. The International Association of Cancer Registries and International Agency for Research on Cancer (IACR/IARC) definition was used for identification of IPM and SPM. Synchronous SPM was defined as malignancy occurring within 6 months from the diagnosis of IPM. RESULTS: Out of 16,461 registered patients during the study interval, 44 (0.26%) cases were found to have MPM. A total of 31 (70.5%) cases were women and 13 (29.5%) cases were men. Median age at presentation of IPM was 48 years and of SPM was 56 years, with median duration between two primaries being 38 months. Seven patients (15.9%) had synchronous malignancies. Gynecological tumors were the most common site of IPM presentation (n = 14, 31.8%) followed by breast (n = 09, 20.5%) and head and neck tumors (n = 07, 15.9%), respectively. The most common SPM was gynecological tumors (n = 12, 27.3%) followed by gastrointestinal malignancies (n = 10, 23.3%). Curative treatment was offered to 88% of patients with IPM and 70% patients with SPM. At a median follow-up of 365 days, 21 (47.72%) patients were disease free, six (13.6%) died of disease and nine (20.5%) were lost to follow-up. CONCLUSION: The study emphasizes the importance of detecting SPM as a result of improved diagnostic and screening procedures. Clinicians should be aware of it and offer multidisciplinary management.

Prevalence estimation of microsatellite instability in colorectal cancers using tissue microarray based methods - A tertiary care center experience.

AIM: Microsatellite instability (MSI) pathway is known to be implicated in carcinogenesis of 15% colorectal carcinomas (CRC), including 2%-3% of cases of Lynch syndrome, as per western literature. MSI status has important prognostic and therapeutic implications. The prevalence of MSI in Indian CRC patients is unknown. We aimed to determine the prevalence by studying 231 consecutive unselected cases of CRC. METHODS: Tissue microarrays using duplicate cores per case for 141 cases, and whole tissue sections for 90 cases, were used. Immunohistochemistry with four mismatch repair (MMR) markers - MLH1, MSH2, MSH6, and PMS2 was performed. Molecular analysis for MSI status was performed in 18 randomly selected cases. Correlation with various clinical and histopathological features was done using univariate and multivariate analysis. RESULTS: Loss of MMR immunohistochemical (IHC) was seen in 53/231 cases, i.e. 22.94% (95% confidence interval 17.52%-28.36%). MLH1-PMS2 dual loss comprised 13.9%, MSH2-MSH6 7.4%, and isolated PMS2 loss in 1.73% of cases. Univariate analysis showed significant association with age (<60 years), right-sided tumor location, histologic type, high grade, the presence of severe intratumoral lymphocytic (ITL) and peri-tumoral lymphocytic response, and N0 nodal stage. On multivariate analysis, independent variables were age < 60 years, right-sided location, and severe ITL. Molecular testing for MSI corroborated with the IHC results. CONCLUSION: The study results show a slightly higher prevalence of MSI-H phenotype, compared to Western literature, stressing the need for more widespread testing for better clinical management and identification of possible hereditary colon cancer syndrome.

Correlation of clinicopathological outcomes with changes in IHC4 status after NACT in locally advanced breast cancers: do pre-NACT ER/PR status act as better prognosticators?

BACKGROUND: Following neoadjuvant chemotherapy (NACT) for breast cancer, changes in estrogen receptor (ER), progesterone receptor (PR), HER2 status, and Ki-67 index (IHC4 status) and its correlation with pathological complete response (pCR) or relapse-free survival (RFS) rates could lead to better understanding of tumor management. PATIENTS AND METHODS: Pre- and post-NACT IHC4 status and its changes were analyzed in 156 patients with breast cancer. Associations between pCR, RFS rates to IHC4 status pre- and post-NACT were investigated. RESULTS: pCR was found in 25.3% patients. Both ER and PR positive tumors had the lowest (14.3%) pCR compared to ER and PR negative (29%) or either ER-/PR-positive (38.6%) tumors. PR positivity was significantly associated with less likelihood of pCR (15% versus 34%). The pCR rate was low for luminal A subtype (13.68%) compared to 24.36%, 26.31%, and 33.33% for luminal B, HER2-enriched, and triple-negative subtypes, respectively. There was significant reduction in ER expression and Ki-67 index post-NACT. RFS of patients in whom the hormonal status changed from positive to negative was better compared to those of patients in whom the hormonal status changed from negative to positive. CONCLUSION: Although changes in IHC4 occurred post-NACT, pre-NACT hazard ratio status prognosticated RFS better. pCR and RFS rates were lower in PR-positive tumors.