Clinicopathological Correlation Research Articles

Cytologic presentation and clinicopathologic correlation of Mullerian carcinosarcoma on serous fluid samples.

Limited data are present to study the cytologic findings of Mullerian carcinosarcoma (MCS) in serous fluid samples and clinicopathologic features that are associated with cytology yield. We studied 30 MCS patients diagnosed on surgical resection samples, and reviewed their cytomorphology and immunophenotypes on concurrent serous fluid cytology samples. Clinicopathologic features were also compared between cases with positive or negative cytology. Fourteen out of 30 patients showed positive cytology, including 12 patients with only carcinomatous components and 2 with sarcomatous cells. Cytomorphology of MCS was mostly consistent with adenocarcinoma, with psammoma bodies occasionally present. The 2 cases with sarcomatous cells showed spindle cells without signs of heterologous differentiation. PAX8 was positive in 10 of 11 cases, and WT1 was positive in 8 of 11 cases including the case with negative PAX8. In 1 case, PAX8 and WT1 were only positive in the sarcomatous but not in carcinomatous cells. MOC31 showed consistent positivity in carcinomatous cells, which appeared to be more sensitive than B72.3 (positive in 72.7%). In addition, sarcomatous cells showed CD10 positivity in 1 case. Clinically, patients who developed body cavity effusions or with higher stage diseases were more likely to have positive cytology. Cytologic diagnosis of MCS in the serous fluid is challenging due to the rare presence of sarcomatous component. Staining both PAX8 and WT1 is recommended to confirm their Mullerian origin, although both markers may be positive only in sarcomatous cells. Cytology yield of MCS is highly associated with the disease stage.

Clinicopathological Correlation of Microbial Keratitis and Ahead: Is There a Corneal Sepsis?

Microbial, infectious keratitis is a relevant indication for penetrating keratoplasty. The requirement for transplantation results in histopathological examination of the entire thickness of the cornea. Although the clinical diagnosis is not always possible to confirm, pathology can support diagnostic evidence of clinical presentation and pathogenesis. This is achieved with multiple methods from cytology, histochemistry, immunohistology, molecular pathology and in rare cases electron microscopy. These allow tissue-based detection of previous and parallel diseases and the responsible pathogens. The failure of satisfactory clinicopathological correlation raises the question whether a suspected pathogen was not ultimately responsible for destroyed corneal tissue. The pathogenesis of keratitis requiring transplantation is not yet completely understood, also on the experimental level. The development of such a keratitis can lead to a clinical symptomatology which can be described as "threatening organ dysfunction", a term used in sepsis research. Considering recent literature, possible correlations between sepsis and microbial keratitis and their relation to histopathology are discussed.

To Evaluate the Expression of p53 and Ki67 in Breast Cancer and Their Clinicopathological Correlation with ER PR and HER2/neu

Background: Breast cancer is the most common cancer among women in India and with an increasing trend. The combined estrogen receptor (ER), progesterone receptor (PR), and HER2/neu biomarker expression is a predictor of breast cancer status for therapeutic guidance. Studies have demonstrated that these biomarkers are unstable throughout their tumor progression. Varying concordance and discordance in the biomarker expression between ER, PR Her2neu and its correlation with p53 and ki67 status are reported. Aim: This study was conducted for studying and comparing the expression of immunohistochemistry (IHC) markers, i.e., ER, PR, HER2/neu, p53, and Ki67 for clinicopathological features and interrelation purpose. Methods: Fifty one cases of female breast carcinoma between years December 2019 and April 2021 were included in the study. IHC was applied on the sections from tru-cut/excisional biopsies and subsequent mastectomy specimens. Analyses of the expression of IHC markers were attempted. Results: Substantial agreement was observed for biomarker ER, PR, HER2/neu, p53, and Ki67 expression with respect to age of the patient, size of the lump, histologic grade and diagnosis. Conclusion: This study demonstrated a significant association between tumor size with advanced histological grade, high cell proliferation (Ki-67 expression) and p53. Thus, there is a need to perform ER, PR, HER2/neu, p53, and Ki67 IHC studies routinely to help design therapies that are tailored to target the specific tumor clones and render maximum benefit to patients.

A Clinico Pathological Correlation of FNAC and Histopathology of Thyroid Swellings: A Hospital-Based Prospective Study

Background: Fine needle aspiration cytology is a diagnostic tool in which cells are extracted from palpable swelling using FNAC gun or syringe and needle. It is a simple, speedy, safe, cost effective and accurate technique being used worldwide. But, pitfalls come along making the correlation with histopathology often necessary. Materials and Methods: This study was a prospective study conducted among 30 patients undergoing thyroidectomy for thyroid swellings in ENT department, Bangalore Medical College and Research Institute, Bangalore. Patients were evaluated by detailed history, clinical examination, preoperative FNAC, thyroid function tests. Results: Thirty patients who underwent thyroidectomy for thyroid swelling during the study period was selected. Among 30 cases all specimen was sent for gross and microscopic examination. Two cases of malignant neoplasms were detected, one of which was benign according to FNAC. Most common lesion was multinodular goiter. Correlation of FNAC and histopathology for benign and malignant lesions, sensitivity of FNAC was found to be 50%, specificity 100%, negative predictive value of 96.5 % and positive predictive value of 100%. p-value<0.01, showing that there is a strong positive correlation between FNAC and histopathology findings. Conclusion: Thyroid pathologies are frequently encountered in otolaryngology clinics. Often the initial FNAC is a cost effective and minimally invasive procedure for the preoperative assessment of patients with thyroid swelling. Even though the clinical presentation may be similar in benign and malignant thyroid swellings, FNAC is the key to initial evaluation of thyroid swellings as well as to plan the surgery. Keywords: Fine Needle Aspiration Cytology, Histopathology, Thyroid swellings.

The m7G-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Tumour Immune Infiltration in Colon Cancer.

With high morbidity and mortality, colon cancer (CC) is considered as one of the most often diagnosed cancers around the world. M7G-related lncRNA may provide a regulatory function in the formation of CC, but the principle of regulation is still unclear. The purpose of this research was to establish a novel signature that may be used to predict survival and tumour immunity in CC patients. Data about CC in TCGA was collected for analysis, coexpression analysis and univariate Cox analysis were used to screen prognostic m7G-related lncRNAs. A consensus clustering analysis based on prognostic m7G-related lncRNAs was applied, and a prognosis model based on least absolute shrinkage and selection operator (LASSO) regression analysis was established. Independent prognostic analysis, nomogram, PCA, clinicopathological correlation analysis, TMB, survival analysis, immune correlation analysis, qRT–PCR and clinical therapeutic compound prediction were also applied. 90 prognostic m7G-related lncRNAs were found, GO and KEGG analysis showed that prognostic m7G-related lncRNAs were mainly related to cell transcription and translation. The results of the consensus clustering analysis revealed substantial disparities in survival prognosis and tumour immune infiltration between two clusters. We built a risk model with 21 signature m7G-related lncRNAs, patients in the high-risk group had a considerably poorer prognosis than those in the low-risk group. Independent prognostic analysis confirmed that patients’ prognosis was linked to their tumour stage and risk score. PCA, subgroups with distinct clinicopathological characteristics were studied for survival, multi-index ROC curve, c-index curve, the survival analysis of TMB, and model comparison tested the reliability of risk model. A tumour immunoassay revealed a substantial difference in immune infiltration between high-risk and low-risk individuals. Five chemicals were eliminated, and qRT–PCR indicated that the four lncRNAs were expressed differently. Overall, m7G-related lncRNA is closely related to colon cancer and the 21 signature lncRNAs risk model can efficiently evaluate the prognosis of CC patients, which has a possible positive consequence for the future diagnosis and therapy of CC.

Histopathological and clinical correlation of cutaneous adverse drug reaction

<p><strong>Background:</strong> The aim was to study the histopathological features of cutaneous adverse drug reactions (ADRs) and its correlation to clinical presentation.</p><p><strong>Methods:</strong> We carried our study on 80 patients of drug reactions presented in OPD over a period of 24 months. We noted offending drug, time gap between drug intake and appearance of lesion clinically and performed biopsy to study histopathological patterns and their utility as an aid to diagnosis. WHO-UMC causality assessment method was used in few cases with due diligence. AGEP (acute generalized exanthematous pustulosis) validation score of the EuroSCAR study group was used and SCORTEN for prognosis of SJS/TEN (Stevens-Johnson syndrome/toxic epidermal necrolysis). Histopathological correlation and clinical correlation were statistically analysed.</p><p><strong>Results:</strong> The most common histopathological finding was vacuolar interface dermatitis and presence of eosinophils. The most common drug responsible was antimicrobials. Histopathological findings were most consistent in cases of FDE and AGEP and differentiating viral exanthems from maculopapular rash was challenging. Erythroderma showed varying patterns of histopathology</p><p><strong>Conclusions:</strong> Identification of histopathological patterns and clinical correlation is important for distinguishing between cutaneous ADR and the other inflammatory dermatoses. Drug reactions pose clinical challenge thus clinicopathological correlation can help in reaching diagnosis.</p>

Clinicopathological Correlation in Dermatopathology

Introduction and aim: Getting an accurate diagnosis in dermatopathology requires a combination of clinical and pathological information. Our aim was to assess the importance of the correlation between clinical and histopathological diagnosis in various cutaneous diseases. Materials and Methods: One-hundred cases of variable skin diseases were studied clinically by dermatologist and histopathologically by general pathologists. Cliniopathological correlation was done by direct communication between the dermatologist and the pathologist. Results: Concordance between pathological and clinical diagnoses was seen in 84%, a new pathological diagnosis was issued in 3% and non-diagnostic report in 13 %. After clinicopathological correlation; out of 84%, we accept only 65% as final diagnosis. In addition, the correlation was helpful and provide a diagnosis in another 20% of cases. One new pathological diagnosis was accepted whereas in the remaining cases (14%) further workup were required. Conclusions: Accurate diagnosis of cutaneous disorders depends on clinical skills as well as careful histopathological assessment and best results can be obtained if the patient and biopsy sections are viewed together. Electron microscopy, immunofluorescence assay, immunohistochemistry techniques and molecular pathology are important adjuncts for definite diagnosis of many skin diseases.

Tropomyosin receptor kinase protein expression in Thai cholangiocarcinoma: Clinicopathological correlation, expression pattern, and prognosis

ObjectiveTropomyosin receptor kinase (TRK) gene fusion was found in association with many tumors and could be a target of treatment. Immunohistochemistry (IHC) expression of TRK is widely used to screening this alternation. AimTo investigate the expression of TRK protein detected by IHC in Thai cholangiocarcinoma (CCA) whereas the high endemic area of liver fluke infection and correlate with clinicopathological and survival data. MethodsRetrospective study of CCA patients who diagnosed from January 2011 to December 2015. The TRK IHC was performed on paraffin-embedded tissues. ResultsA total of 85 CCA patients were enrolled. The mean age of the patients was 59 y (range; 35–79). Tumors were situated at intrahepatic (42 cases, 49.4 %), perihilar (41 cases, 48.2 %) and extrahepatic (2 cases, 2.4 %). The TRK IHC was expressed in 26 cases (31 %) and most of them (25 cases, 96.2 %) showed focal cytoplasmic expression with weak intensity. TRK IHC expression was not correlated with clinicopathological findings. Nevertheless, the median survival time of the TRK IHC positive and negative groups were 1.88-year and 1.30-year, respectively (p = 0.041) with the hazard ratio of 0.564 (p = 0.039, 95%CI 0.328–0.971). ConclusionIn Thai CCA, TRK IHC was detected about 1/3 of the patients and most expressed focally in the cytoplasm with weak staining. TRK expression showed better overall survival and was an independent prognostic factor. As the screening assays, the TRK IHC is wildly available with rapid, and high sensitivity but the confirmatory testing is necessary in tumors with low incidence of NTRK gene fusion.

Prominent Pseudoacini in Focal Nodular Hyperplasia: A Potential Diagnostic Pitfall.

Pseudoacini are generally a morphologic feature of hepatocellular carcinoma (HCC), being absent or rare in benign hepatocytic tumors, such as hepatocellular adenoma. However, rarely these can be seen in focal nodular hyperplasia (FNH) and may pose diagnostic challenges, especially when prominent. The study was aimed to evaluate the occurrence of pseudoacini in FNH and their clinicopathologic correlations. A total of 95 FNH cases diagnosed from 2005 to 2020 were included in the study. A pseudoacinus was defined as a circular arrangement of hepatocytes around a central dilated lumen present within the lobular parenchyma of the lesion with or without inspissated bile. Among the 95 FNH cases, 28 (29.5%) showed pseudoacini, which were prominent in 12 (12.6%) cases. Of these 3 occurred in patients above 50 years old. The pseudoacini were numerous in 3 cases, leading to an initial consideration of HCC in the differential diagnosis, and 1 case was diagnosed as well-differentiated hepatocellular neoplasm on initial biopsy. All 12 cases showed map-like staining pattern for glutamine synthetase. The hepatocytes forming the pseudoacini were positive for CK7 and HepPar1, while the inner lumina were highlighted by CD10 and bile salt export pump immunostains similar to adjacent canaliculi. The presence of prominent pseudoacini was not significantly associated with any clinical or pathologic features. The findings suggest that pseudoacini are likely manifestation of hepatocyte biliary transdifferentiation associated with chronic cholestasis in the lesion. This feature may pose a potential diagnostic pitfall especially on needle biopsies and awareness is needed to avoid misdiagnosing this as HCC.

Abstract 3776: Frequent alteration of mitochondria functional pathways in lung cancer

Abstract Lung cancer killed 1.8 million people globally in 2020. In the United States, there will be over 235,760 cases of lung cancer with an estimated death of 131,880 individuals in 2021. Despite significant improvement in multimodal therapeutic approaches, overall 5-year survival rate is only 21.7%. Lung cancer appears to be mitochondria enriched cancer, however, alteration pattern of hallmark molecular pathways associated with diverse mitochondrial functions remain largely unknown in lung tumorigenesis. Utilizing high-throughput genomic profiling, we identified altered copy number of a panel of 40 mitochondria targeted molecules in primary lung cancer patients and their histologically normal appearing follow up mucosal biopsies. These altered molecules are critical components of the mitochondrial protein carrier, OXPHOS, stress response, amino acid metabolism and apoptosis pathways. This finding suggests for clonal genetic relationship between multifocal lesions and potential role of these alterations in the evolution of second primary tumors, which is an existing problem among lung cancer patients. The Human Cancer Genome Atlas database was utilized to further assess the mRNA expression pattern of these 40 molecules and determine their clinico-pathological correlations. Immunohistochemistry and digital pathology system based evaluations were performed to validate expression pattern of key altered molecules. We identified overexpression of various critical mitochondria pathway molecules including AARS2, AGMAT, SDHA, NDUFB7, LONP1, DGUOK, MRM1 and GCAT in both lung adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC), predicting poor prognosis. Significant loss of expression of ACSF2, ACSS1, MTCH1, SLC25A4, ACAD8 and NAGS was evident in both adenocarcinoma and squamous cell carcinoma subtypes. Molecular characterization of both LUAD and LUSC tumor subtypes identified significant association of various key molecules including ACAD8, AGMAT, DGUOK and NDUFAB1 with proximal-inflammatory, proximal-proliferative and terminal respiratory unit pathways in LUAD; and an association of DGUOK, MDH2, MRM1 and MRPL10 with basal, classical, primitive and secretory pathways in LUSC. Significant loss of SLC25A4 protein expression was evident in lung cancer tissues, which predicted poor survival of the lung cancer patients. Capturing the compendium of hallmark mitochondrial alterations in lung tumorigenesis may open up novel avenues for therapeutic and biomarker interventions to improve the overall survival of the lung cancer patients. Citation Format: Kate L. Hertweck, Brian Persing, Pranitha Prodduturvar, Seema Singh, Ajay Singh, Santanu Dasgupta. Frequent alteration of mitochondria functional pathways in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3776.

Abstract 520: MYB exhibits racially disparate overexpression and clinicopathologic association in prostate cancer: significance as a predictor of biochemical recurrence

Abstract Prostate cancer (PCa) is the most diagnosed non-cutaneous malignancy and the second leading cause of cancer-related death in American men. Significant racial disparities also exist in incidence and clinical outcome. African American (AA) men are nearly two times more likely to be diagnosed with PCa and have more than twice mortality rate than their Caucasian American (CA) counterparts. Despite an early diagnosis in majority of the cases, about one-third patients face biochemical recurrence following local therapy, with a likelihood of developing distant metastasis. Gleason score used as a prognosticator exhibits discrepancy between AA and CA men highlighting the need for better predictive markers. We previously demonstrated functional significance of MYB in PCa growth, aggressiveness, and castration-resistance. We also showed a role of MYB in sustained androgen receptor (AR) signaling under androgen-deprived condition and prostate-specific antigen (PSA) expression. Here, we studied the expression of MYB in PCa by immunohistochemistry and examined if it varied between AA and CA PCa cases and had any clinicopathological correlation. A total of 105 PCa [CA (n=50) and AA (n=55)] cases with available clinicopathologic data were included. MYB expression was also studied in adjacent benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplastic (HGPIN) lesions. Stained slides were scanned and digitally analyzed for the measurement of percent positivity (0-100%) and staining intensity (1+, 2+ and 3+). Significant overexpression of MYB (p<0.0001) was reported in PCa relative to HGPIN and BPH. PCa predominantly exhibited moderate to strong staining, compared to weak to moderate staining with low precent positivity rate in HGPIN and weak MYB staining with low percent positivity in BPH. A significantly higher expression of MYB (p<0.0001) was noted in high Gleason score (8-9) PCa, compared to the low-medium Gleason score (≤7) PCa. Interestingly, MYB expression was significantly (p= 0.024) higher in AA PCa than CA PCa in overall and Gleason score wise comparisons. Correlation analysis of MYB showed its inverse association with time to BCR (r =-0.467, 95% CI=-0.675 to -0.190, p=0.002). Altogether, our findings establish MYB as a potentially useful biomarker for PCa diagnosis and prognosis and provide clinical support to our prior findings on the pathobiological role of MYB in PCa. Citation Format: Mohammad Aslam Khan, Srijan Acharya, Shashi Anand, Fnu Sameeta, James E. Carter, Oliver J. Semmes, Dean A. Troyer, Seema Singh, Santanu Dasgupta, Ajay P. Singh. MYB exhibits racially disparate overexpression and clinicopathologic association in prostate cancer: significance as a predictor of biochemical recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 520.

Abstract 6398: Functional characterization of Androgen Receptor splice variants in breast cancer invasion and metastasis

Abstract Introduction: A growing body of evidence suggests the prognostic and therapeutic value of Androgen Receptors (AR) in Breast Cancer (BrCa), particularly Triple Negative BrCa (TNBC). The splice variants of AR (ARVs); notably full-length AR (AR-fl) of ~110 kDa and a C-terminally Ligand Binding Domain (LBD) truncated AR isoform (AR-V7) of ~67 kDa are present in a variety of tissues. The ligand-independent AR-V7 is constitutively expressed and confers castration resistance in prostate cancer. With the irrefutable role of ARVs in BrCa, we evaluated their expression profile in cell lines with their prevalence and clinicopathological correlation in BrCa patients from India. Methods: Breast Cancer cell lines MDA-MB-231, MCF7, and MDA-MB-453 were procured from American Type Culture Collection. Thirty-eight de novo cases of Breast Cancer undergoing surgical intervention at a tertiary healthcare center in India were recruited. Tumor and adjacent benign tissue were collected after informed consent. The ARVs expression at transcriptomic and proteomic levels was evaluated by qRT-PCR and western blotting & Immunohistochemistry (IHC) respectively. For functional annotation, ARVs were knocked down in vitro using differently targeting siRNAs facilitated by Lipofectamine 3000 based transfection. There was a strong complementarity observed in western blotting and IHC. Results: All the ARVs were significantly higher in MDA-MB-453 followed by MCF7 and MDA-MB-231 cells. The expression ratio of AR-V7 versus AR-fl is, however, elevated in highly aggressive TNBC cell line MDA-MB-231. 67% of patients recruited were immunostained positive for AR (n=38). A majority of patients were of Luminal phenotype (37%) expressing both the prominent ARVs. One-third of the TNBC fraction were AR positive. Following the TNBC cell line, a subset of patients' samples also exhibited a substantial upregulation of AR-V7 compared to AR-fl. These patients had poor prognoses and aggressive features. The siRNA knockdown of all the ARVs resulted in decreased invasion and Epithelial-mesenchymal transition (EMT). Interestingly knocking down of ARVs barring AR-V7, restored invasiveness suggesting the compensatory behavior of AR-V7. Conclusion: Our work demonstrates the presence of ARVs in BrCa with a particular focus on the AR-V7. The LBD truncated AR-V7 potentiates the growth in BrCa cell lines and patients. This study further encourages the ARVs expression screening with AR positive BrCa for a prognostic biomarker of aggressive phenotype and therapeutic resistance. Citation Format: Tryambak Pratap Srivastava, Ruby Dhar, Anurag Srivastava, SVS Deo, Rajinder Parshad, Subhradip Karmakar. Functional characterization of Androgen Receptor splice variants in breast cancer invasion and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6398.

Abstract 5178: Multifocality is an independent predictor of regional lymph node metastasis in Middle Eastern papillary thyroid carcinoma

Abstract Background: Papillary thyroid carcinoma (PTC) is treatable, with favorable prognosis and very low disease-specific mortality. However, PTC recurrence is relatively common in loco-regional and distant sites. Although multifocality is a common occurrence in PTC, its prognostic impact remains controversial. In addition, data on prevalence and prognostic significance of multifocality in PTC from Middle Eastern ethnicity is unknown. Therefore, the aim of this study was to investigate the prognostic value of multifocality in PTC larger than 1cm and papillary thyroid microcarcinoma (PTMC) in our center. Methods: A cohort of 1515 patients who underwent total thyroidectomy were retrospectively reviewed. Aggressive histopathologic variants of PTC were excluded to avoid their potential confounding effect on clinical outcomes. We identified 1087 patients who had PTC with primary tumor exceeding 1cm and 150 patients with PTMC, with medium follow up of 9.2 years. In each group, we compared patients with unifocal and multifocal disease. Clinico-pathological and molecular correlations were analyzed. Logistic regression analysis was used to assess the relation between multifocal tumors and lymph node metastasis. Results: The incidence of multifocality in PTC larger than 1cm was 48.3% (525/1087), whereas it was 38.7% (58/150) in PTMCs. In patients with PTC > 1cm, multifocality was significantly associated with aggressive markers such as extrathyroidal extension (p < 0.0001), lymphovascular invasion (p = 0.0047), lymph node (LN) metastasis (p = 0.0006), distant metastasis (p = 0.0305) and BRAF mutation (p = 0.0113). In analogous analysis of patients with PTMC, multifocality was significantly associated with extrathyroidal extension (p < 0.0001), LN metastasis (p = 0.0005) and BRAF mutation (p = 0.0006). In both sub-groups, disease recurrence and overall survival did not differ between unifocal and multifocal group. Multivariate analysis showed that multifocality was an independent predictor of LN metastasis (Odds ratio (OR) = 1.31; 95% confidence interval (CI) = 1.00 - 1.71; p = 0.0472 for PTC > 1cm and OR = 1.88; 95% CI = 1.00 - 3.54; p = 0.0491 for PTMC). Conclusions: Tumor multifocality is frequently observed in Middle Eastern PTC and PTMC and is a predictive factor for LN metastasis in PTC. Given the predictive value of multifocality in Middle Eastern ethnicity, aggressive therapy and intensive follow-up should be considered for both PTC and PTMC with multifocality. Regional LN metastasis should be closely monitored and prophylactic central lymph node dissection could be considered in these patients. Citation Format: Pratheeshkumar Poyil, Abdul K Siraj, Sandeep Kumar Parvathareddy, Divya Padmaja, Saravanan Thangavel, Rafia Begum, Roxanne Diaz, Khadija Al-Obaisi, Khawla S. Al-Kuraya. Multifocality is an independent predictor of regional lymph node metastasis in Middle Eastern papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5178.

Humoral and cellular immune response to Sars-CoV-2 wild-type and variants of concern following 3-dose vaccination in a large cohort of adults with cancer: The SerOzNET study.

LBA12065 Background: COVID-19 infection has poor outcomes for patients (pts) with cancer. Understanding vaccine response as a correlate of protection from severe infection is essential to advise pts regarding protective behaviours and optimal vaccine schedule. This Australian cohort is unique due to low rates of COVID-19 exposure at study entry (July-November 2021). and use of a 3 dose schedule. Pts initially received 2 doses of either BNT162b2 (Pf) at a 3 week interval, or ChadOx1-S (AZ) at a 6 week interval, all then received a 3rd dose, either mRNA-1273 (Mod) or Pf after 2-4 months, and finally a 4th dose at an interval of a further 3 months, for a subset. Methods: SerOzNET (ACTRN12621001004853) has enrolled pts with solid and haematological (haem) cancers prior to initial vaccination. Serial blood samples were processed for serum, PBMC and PMN at timepoints: 0, then 3-4 weeks post dose 1 then 2 then 3 then 4 (where administered). We report here neutralizing antibodies (nAb) against wild type (wt) and delta and omicron variants of concern (VOC); quantitative S-protein IgG antibody (Abbott); T-cell correlates measured by levels of interferon-g (IFN g), tumour necrosis factor-a, interleukins (IL-) 2/4/5/13; and epigenetic profiling of T cells. Results: The cohort consists of 401 pts with median age 58 (range 18-85); 59% female; 128 (32%) haem cancers. 377 (94%) are on current or recent (< 12 months) systemic therapy: 162 (43%) chemotherapy, 62 (16%) immunotherapy, 40 (10%) combined chemo/immunotherapy, 113 (29%) hormonal or targeted therapy. 42 (10%) received anti-CD20 therapy < 12 months, 6 (1.4%) had allogeneic stem cell transplant. NAb levels against wt are available for 256 pts post dose 1, 245 pts post dose 2 and 159 pts post dose 3 (will be updated). Response rates post dose were respectively 27%, 77% and 88%. Pts with haem cancer were less likely to respond to vaccination at any time compared to pts with solid cancer (p < 0.001, chi-squared test). After 3 doses, 3.8% of pts with solid cancer and 27.8% with haem cancer lacked NAb. NAb results to VOC delta are available for 92 pts post dose 2: 25/92 (27%) were negative, compared with a non-response rate to wt of 15% at same time in same pts. IFN-γ-Spike response was detectable in 18/31 (58%) and 24/30 (80%) pts post dose 1 and 2 respectively. 101 pts to date have received a 4th dose; data will be available at the meeting, as will epigenetic profiles and detailed clinicopathological correlations. Conclusions: This interim analysis shows that a significant proportion of pts with haem cancers (27.8%) lack protective Sars-CoV-2 antibodies following 3 vaccinations, whereas only 3.8% of solid cancer pts lack detectable response. Results from other B and T cell parameters may also be important in identifying pts less well protected by vaccination. Follow up is ongoing, response rate post 4th dose will be presented at the meeting. Clinical trial information: ACTRN12621001004853.

Study of Rare Hyperpigmented Lesions of the Skin in a Tertiary Care Centre in Western Maharashtra

Objectives: Hyperpigmented lesions are a common presentation in the dermatology outpatient department and causes significant burden on the dermatologist. Though they are harmless and asymptomatic in most cases they are a cause for concern because it can lead to cosmetic deformity which can cause psychological upset in the patients. Rare lesions are often misdiagnosed clinically because of overlapping clinical features. The aim of this study was to diagnose rare hyperpigmented lesions with the help of skin biopsies and correlate he findings clinically.
 Methods: All skin biopsies coming to the department of Pathology were processed and stained by routine H&E stain. Special stains were applied whenever required (Ziehl-Nelson, periodic acid Schiff, Congo red).
 Results: 56 cases were studied of which 27 rare lesions were diagnosed. All the cases were subjected to analysis according to age, sex, site of lesion, duration of lesion and clinicopathological correlation. 75% of the cases showed histopathological correlation in our study. 25% of the cases did not show concordance.
 Conclusion: Hence to conclude histopathological examination of skin biopsies forms the gold standard for the diagnosis of hyperpigmented skin lesions more so in the case of rare lesions as most of them have overlapping clinical features which can be mistaken for common lesions.

Low-Grade Invasive Triple Negative Breast Carcinoma

Triple-negative breast carcinomas (TNBCs) are defined as estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative breast carcinomas and are composed of a heterogeneous group of breast carcinomas with most of them having aggressive behavior and poor prognosis. However, some TNBC cases are low grade with indolent clinical outcome and low risk of metastasis to other organs or regional lymph nodes. Low-grade TNBCs include low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade invasive (ductal or lobular) carcinoma with apocrine differentiation, classic adenoid cystic carcinoma, secretory carcinoma, tall cell carcinoma with reversed polarity, acinic cell carcinoma, and low-grade mucoepidermoid carcinoma. This review aims to summarize the clinicopathological correlation and the molecular features of low-grade special TNBC subtypes.

Progressive ascending telangiectasias

Progressive ascending telangiectasias

P.006 Etiologic diagnoses of rapidly progressive dementia in a prospective multicenter cohort

Background: Accurate etiologic diagnoses are needed in patients with rapidly progressive dementia (RPD) to ensure access to symptomatic and disease-modifying therapies when available. Methods: Patients with RPD were prospectively enrolled and evaluated at Washington University (Saint Louis, MO; 2016-2019) and Mayo Clinic (Jacksonville, FL; 2020-2021). Etiologic diagnoses were independently assigned by two dementia specialists integrating clinical features and the results of diagnostic tests; disagreements were resolved via blinded review by a third specialist. Results: 160 RPD patients were enrolled and followed. Average age-at-symptom onset was 60.0±15.9 years; 50% were female. Inter-rater reliability (91% agreement; Cohen’s κ=0.88, p<0.001) and clinicopathologic correlation were excellent (100% agreement in 24 patients with neuropathologic data). Autoimmune encephalitis was the leading cause of RPD (39%), followed by Alzheimer disease and related dementias (29%), Creutzfeldt-Jakob disease (15%), and other causes (15%). Patients with potentially treatable causes of RPD were younger (54.5±18.2 than those with neurodegenerative causes (67.3±9.5; p<0.001), and more likely to present with altered levels of consciousness, seizures, or CSF pleocytosis (p<0.05). Conclusions: Etiologic diagnoses can be reliably established in RPD patients using available clinical data. The prevalence of autoimmune encephalitis in this series justifies routine screening for potentially treatment-responsive causes of RPD, particularly in younger patients.

18F-FDG PET Imaging in Neurodegenerative Dementing Disorders: Insights into Subtype Classification, Emerging Disease Categories, and Mixed Dementia with Copathologies.

Since the invention of 18F-FDG as a neurochemical tracer in the 1970s, 18F-FDG PET has been used extensively for dementia research and clinical applications. FDG, a glucose analog, is transported into the brain via glucose transporters and metabolized in a concerted process involving astrocytes and neurons. Although the exact cellular mechanisms of glucose consumption are still under investigation, 18F-FDG PET can sensitively detect altered neuronal activity due to neurodegeneration. Various neurodegenerative disorders affect different areas of the brain, which can be depicted as altered 18F-FDG uptake by PET. The spatial patterns and severity of such changes can be reproducibly visualized by statistical mapping technology, which has become widely available in the clinic. The differentiation of 3 major neurodegenerative disorders by 18F-FDG PET, Alzheimer disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), has become standard practice. As the nosology of FTD evolves, frontotemporal lobar degeneration, the umbrella term for pathology affecting the frontal and temporal lobes, has been subclassified clinically into behavioral variant FTD; primary progressive aphasia with 3 subtypes, semantic, nonfluent, and logopenic variants; and movement disorders including progressive supranuclear palsy and corticobasal degeneration. Each of these subtypes is associated with differential 18F-FDG PET findings. The discovery of new pathologic markers and clinicopathologic correlations via larger autopsy series have led to newly recognized or redefined disease categories, such as limbic-predominant age-related TDP-43 encephalopathy, hippocampus sclerosis, primary age-related tauopathy, and argyrophilic grain disease, which have become a focus of investigations by molecular imaging. These findings need to be integrated into the modern interpretation of 18F-FDG PET. Recent pathologic investigations also have revealed a high prevalence, particularly in the elderly, of mixed dementia with overlapping and coexisting pathologies. The interpretation of 18F-FDG PET is evolving from a traditional dichotomous diagnosis of AD versus FTD (or DLB) to a determination of the most predominant underlying pathology that would best explain the patient's symptoms, for the purpose of care guidance. 18F-FDG PET is a relatively low cost and widely available imaging modality that can help assess various neurodegenerative disorders in a single test and remains the workhorse in clinical dementia evaluation.

Prognostic value and clinicopathological correlation of the tumor regression grade in neoadjuvant chemotherapy for gastric adenocarcinoma: a retrospective cohort study.

Neoadjuvant chemotherapy (NACT) and radical gastrectomy are the gold standard treatments for resectable advanced gastric cancer (GC). However, the prognostic value of the pathological tumor regression grade (TRG) of NACT remains controversial. This retrospective study aimed to investigate the correlation between the TRG after NACT and clinicopathological features as well as its prognostic value in advanced GC. In total, 551 patients with GC who received NACT combined with surgical resection at the Zhejiang Cancer Hospital from April 2004 to December 2019 were included. The demographic characteristics, treatment response, tumor characteristics, treatment regimens, and survival data were reviewed from the medical records of all patients. The Chi-square test was used to analyze the correlation between TRG and clinicopathological factors. Kaplan-Meier univariate analysis and Cox regression multivariate analysis were used to determine the independent risk factors affecting the prognosis of GC patients. Among the 551 patients with advanced GC who accepted NACT treatment, 14 were determined to be in TRG 0, 98 in TRG 1, 257 in TRG 2, and 182 in TRG 3. Also, TRG was significantly correlated with the cT stage (P=0.015), ypT stage (P<0.001), ypN stage (P<0.001), ypTNM stage (P<0.001), vascular tumor thrombus (P<0.001), Borrmann classification (P=0.042), and lymph node ratio (LNR) (P<0.001). Furthermore, patients who had a good pathological response to NACT had a better prognosis, with a 3-year overall survival (OS) of 70.9% versus 48.8% in patients who had a poor pathological response. We also found that TRG (P=0.042, HR =1.65) was an independent prognostic factor affecting the OS of GC patients. TRG plays a significant role in the prognostic value in neoadjuvant chemotherapy for gastric adenocarcinoma. Patients with higher cT stage, higher levels of pre-CA199 and pre-CA125 may have worse pathological response.