Panel Of Immunohistochemical Markers Research Articles

Cytohistopathological Association and the Use of a Dual Immunohistochemical Regimen in the Diagnosis of Lung Malignancies: A Cross-sectional Study

Introduction: Lung cancer is a highly aggressive malignancy that causes significant morbidity and mortality. The incidence of lung cancer has been increasing in the past few decades. Cytology aids in the initial evaluation and diagnosis of patients with lung cancer. Currently, the classification of lung carcinoma has expanded beyond small cell lung carcinoma and Non-Small Cell Lung Carcinoma (NSCLC). Precise subtyping of poorly differentiated NSCLC into adenocarcinoma and Squamous Cell Carcinoma (SCC) has a direct impact on patient management and prognosis. The morphologic diagnosis forms the basis and is further supplemented by a panel of immunohistochemical markers. Immunohistochemistry (IHC) is important in cases with poorly differentiated morphology or partial sampling. The IHC panel used includes Tumour Protein p63 (p63) and Thyroid Transcription Factor (TTF1) for subtyping lung cancer. Aim: The present study was conducted with the aim of studying the age and gender distribution, risk factors, cytohistopathological association, and formulating an effective IHC panel for the precise yet effective subtyping of poorly differentiated lung malignancies. Materials and Methods: This cross-sectional study included cases retrieved from the Archives of Pathology Department, SRM Medical College and Research Centre, Chennai, Tamil Nadu, India, between July 2012 and July 2016. The cases included had a diagnosis of lung malignancy (confirmed by cytology/biopsy) or were suspected of having malignancy based on clinical/radiological findings. The study period was from July 2015 to August 2016. The cytology and biopsy slides were reviewed, and the malignancy was classified according to the World Health Organisation (WHO) classification of lung malignancies (2021). IHC was performed on the cases using the markers p63 and TTF1 as a dual regimen. Diagnosis and subtyping of tumours were done based on histomorphology, and the tumours were reclassified based on IHC findings. The data were statistically analysed using SPSS software version 25 and the ROC curve. Results: The mean age of the patients was 60.9 years. The study included a total of 50 cases of lung carcinoma, with an average age of 60.9 years (ranging from 30 to 88 years). Among the cases, 35 (70%) had a positive smoking history. A concordant cytohistopathological association was observed in 26 (52%) of cases. Adenocarcinoma was the predominant subtype, accounting for 21 (42%) of cases. Tumour cells in adenocarcinoma showed positive staining for TTF-1, with the marker exhibiting 100% sensitivity and 83% specificity. In SCC, tumour cells were positive for p63, with the marker demonstrating 92% sensitivity and 82% specificity. Both markers showed effective sensitivity and specificity when used as a dual regimen. Conclusion: Although lung cancer is typically diagnosed in the elderly population, there has been an increase in cases among younger individuals due to urbanisation. Smoking remains an important risk factor for lung malignancy. Exfoliative cytology alone is not sufficient for the diagnosis of lung malignancies and should be supplemented with biopsy for more accurate results. Adenocarcinoma was found to be the most common subtype in our study. The IHC panel of p63 and TTF-1 proved to be an effective regimen for classifying poorly differentiated lung carcinomas.

A Case of Tubular Carcinoid of the Appendix: A Rare Entity

Carcinoid tumours of the appendix are low-grade neoplasms with neuroendocrine differentiation. They are typically found incidentally during appendectomies. Tubular carcinoid is an extremely rare, distinct, and benign form of appendiceal carcinoid. Here, we present the case of a 32-year-old male who presented with an abdominal mass and pain radiating to the right iliac fossa. Appendectomy was performed, and the gross examination revealed a congested and exudate-covered appendix. Microscopic analysis showed small tubules infiltrating the appendix wall, along with evidence of acute appendicitis. Differential diagnoses considered included carcinoid tumour with glandular differentiation and metastatic adenocarcinoma. Additional sections were examined, and a final diagnosis of tubular carcinoid was made after conducting a panel of immunohistochemical markers and Alcian blue stain. Since most tubular carcinoids are not identifiable on gross, microscopic assessment and serial sectioning play a crucial role in diagnosing this condition.

Correlation of PD-L1 immunohistochemical expression with microsatellite instability and p53 status in endometrial carcinoma.

Endometrial carcinoma (EC) is the most common gynaecological cancer worldwide. The Cancer Genome Atlas molecular grouping of a given case of EC could be assessed by POLE gene mutation, mismatch repair (MMR) 'to reflect microsatellite instability' and p53 status, which has proved to be of prognostic value. Programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) are playing a progressively important role in tumour immunology and cancer treatment. To investigate PD-L1 immunohistochemical expression in EC in relation to MMR and p53 status. Associations between marker expression and different histopathological parameters were also investigated. This retrospective study was performed on archival biopsies of 170 cases of EC using a tissue microarray model. Immunohistochemical staining was applied using antibodies against PD-L1, MLH1, MSH2 and p53. The percentages of positivity were as follows: PD-L1, 19.6%; MLH1, 79.5%; MSH2, 78.5%; and p53 mutant, 13.8%. There was significant correlation between MLH1 expression and MSH2 expression (p=0.008). Tumour grade was significantly correlated with stage (p=0.005) and p53 mutant expression (p=0.008). Combined PD-L1 positivity and MMR deficiency showed significant correlation with the presence of lymphovascular space invasion (p=0.014). MSH2 negativity was significantly associated with poorer overall survival (p=0.014). A panel of immunohistochemical markers (PD-L1, MLH1, MSH2 and p53) could help to predict the prognosis and plan the treatment of patients with EC. MMR deficiency seems to be a good predictor for PD-L1 status, and therefore the response to potential PD-1/PD-L1 inhibitor therapy.

Immunohistochemistry on cell blocks for diagnosis of malignancy in abdomino-pelvic lesions and ascitic fluid cytology at a rural cancer center: A paradigm shift in cancer management.

Cell block preparation is routine practice in cytopathology these days because of its pivotal role in increasing diagnostic yield and ancillary studies. In the present era of personalized medicine in oncology, ancillary techniques such as immunohistochemistry (IHC) and molecular analysis are gaining more importance. A retrospective study was conducted in the Department of Pathology, over 6 months, which included 144 cases of Fine Needle Aspiration Cytology (FNAC) of abdominopelvic masses and 105 cases of ascitic fluids. Cell blocks and conventional smears were prepared simultaneously in all cases. IHC was applied on cell blocks and analyzed. IHC was performed on cell blocks in 76 cases of FNA and 53 cases of ascitic fluids. Based on IHC, liver lesions (50 cases) were categorized into metastatic carcinomas with a suggested primary site (45.0%), hepatocellular carcinoma (12.2%), neuroendocrine tumors (16.3%), and malignant melanoma (2%). Using MOC-31 and WT-1, ascitic fluid samples were categorized into benign and malignant. Forty-one out of 53 cases of fluids were diagnosed as metastatic adenocarcinomas with the ovary as the most common primary site. A panel of IHC markers, though not specific alone when applied to cell blocks in a careful clinical and morphological context leads to a rapid and accurate diagnosis. This in turn obviates the need for biopsy in severely ill patients. An astute pathologist can provide accurate results with judicious use of IHC on cell blocks and may bring a sigh of relief for many cancer patients by averting the need for biopsy.

The "hypopigmented" bitemark: a clinical and histologic appraisal.

So-called "hypopigmented" bitemark patterns, commonly seen but not limited to dark skinned individuals, can be of value in forensic investigations. The process of aging bitemarks observed on skin is controversial and without guidelines. This report analyzes tissue obtained from the site of a hypopigmented bitemark using special histochemical stains for the identification of melanin pigment, and a panel of immunohistochemical markers to aid in the aging process. Histologic evaluation clearly showed that cellular changes in the hypopigmented area were indicative of wound healing that had taken place over a period of time. This validates the hypothesis that a hypopigmented bitemark is an indication of a wound inflicted some days previously. These findings have value in forensic investigations, particularly in cases of suspected long-term physical abuse.

Abstract C064: Prognostic impact of an immunomorphological signature integrating immune, fibroblast and tumor markers in a series of 217 patients operated on for pancreatic adenocarcinoma

Abstract An integrative approach taking into consideration the tumor microenvironment, in particular cancer-associated fibroblasts (CAFs) and tumor-infiltrating lymphocytes (TILs) and its interaction with tumor cells offers a more precise reflect of pancreatic ductal adenocarcinomas (PDACs) biology. In this setting, an immunomorphological signature established from bioinformatics data could thus represent an attractive approach. Moreover to molecular signatures, on which there is still no consensus. This study aimed to evaluate the prognostic value of a panel of morphological and immunohistochemical (IHC) markers on the immune, fibroblastic and epithelial contingents of PDACs for overall (OS) and relapse-free (RFS) survival. Two hundred and seventeen patients operated for PDAC between 2000 and 2017 were included for a tissue microarray (TMA) analysis. A panel of antibodies and special stains was selected based on a previous bioinformatics study (under review) literature data. Slides were digitized and lymphocytes expressing CD3, CD8 and CD20 were quantified. A pixel classifier was used to assess the percentage of collagen and fibroblasts expressing anti-LRRC15, HSP47, α-SMA and FAP antibodies involved in the stroma reaction. Due to the co-marking of stromal and epithelial cells of PTK7 and β-catenin, respectively implicated in embryogenesis and the canonical Wnt pathway, these markers were interpreted semi-quantitatively in a double-blind fashion. After dichotomization using the maximized log-rank method, the association of these parameters with OS and RFS was assessed by univariate and multivariate Cox models. Five years after surgical resection, 26 patients (12.0%) were free of recurrence and 56 (25.8%) were alive. In multivariate analysis, the following parameters were associated with reduced OS and RFS: poor differentiation, lymph node ratio greater than 0.2, loss of tumor β-catenin on tumor cells, a low density of tumor-infiltrating CD3 T lymphocytes and a high percentage of HSP47 fibroblasts. Reduced OS was also associated with an age greater than 65 years at the time of surgery and the absence of adjuvant treatment. In order to evaluate the joint effects of the three tumor compartments markers independentely related to OS and RFS (β-catenin, HSP47, CD3), we grouped them into 3 classes (0/1+, 2+, 3+) according to the number of good prognosis criteria (class 3+ with the greatest number of good prognosis criteria). The multivariate analysis shows an additive effect of these parameters in OS and RFS compared to class 3+ patients. These data underline the interest of simultaneously characterizing the three epithelial, immune and fibroblastic compartments in PDAC. Furthermore, we highlight for the first time the prognostic impact of HSP47 by immunohistochemistry and confirm the β-catenin one. This tissue approach with an IHC panel studied on an operating specimen could be a first step towards applicability on biopsies and lead to a better patient stratification in a therapeutic setting. Citation Format: Franck Monnien, Chloé Molimard, Marine Abad, Marie-Paule Algros, Sophie Félix, Nikolaus Zirganos, Bruno Heyd, Angélique Vienot, Christophe Borg, Frédéric Bibeau. Prognostic impact of an immunomorphological signature integrating immune, fibroblast and tumor markers in a series of 217 patients operated on for pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C064.

Morphological spectrum of Xp11. Translocation-Associated Renal Cell Carcinoma in a Developing Country

Objective: to determine unusual morphological features and a panel of immunohistochemical markers to diagnose Xp11 translocation carcinoma.
 Study Design: Retrospective longitudinal study.
 Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital, Lahore Pakistan, from Jun 2015 to Feb 2020.
 Methodoldogy: We analyzed clinicopathological features, and evaulated intensity and extent of TFE 3 immunoreactivity of 18 cases with suggested diagnosis of xp11 translocation associated renal cell carcinoma from 2015-2020.
 Results: Different morphological pattern includes papillary (8/18, 44%), nested (2/18, 11.1%), alveolar (3/18, 16.7%), nested and papillary (3/18, 16.7%), solid and nested (1/18, 5.6%), cystic and nested (1/18, 5.6%). Four cases show papillary architecture with a linear array of nuclei away from the basement membrane, a pattern seen in SFPQ-TFE3 renal cell carcinoma and NONO-TFE3 renal cell carcinoma. Strong nuclear TFE3 expression was seen in 9/18 (50%) cases. Cathepsin k expression was seen in 6/11 (54%) cases, Ck7 was focal weak positive in 4/12 (25%) cases, PAX8 was positive in 8/8 (100%) cases, and CA IX was focal weak positive in 1/5 (20%) case. According to follow-up data, disease progression was seen in only one case with the low-stage disease. No death was reported due to renal cell carcinoma to date of follow-up.
 Conclusion: We have suggested that young patient age, unusual morphological features and an immunohistochemical panel may help reach the diagnosis in countries with limited resources.

Utility of GATA-3 and associated immunohistochemical markers in the differential diagnosis of poorly differentiated urothelial carcinoma.

The aims are to study the utility of GATA-3 along with panel of immunohistochemical (IHC) markers in the differential diagnosis of primary and metastatic poorly differentiated urothelial carcinoma (UC). This is a prospective and retrospective observational study. Poorly differentiated carcinomas of urinary tract and metastatic sites from January 2016 to December 2017 were subjected to a panel of four IHC markers including GATA-3, p63, Cytokeratin (CK) 7, and CK20. Additional markers such as p16, an enzyme called alpha-methylacyl-CoA racemase, CDX2, and thyroid transcription factor 1 were also done depending on the morphology and site. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of GATA-3 in making the diagnosis of UC were calculated. Forty-five cases were included in the study and after appropriate IHC, the diagnosis was resolved as UC in 24 cases. GATA-3 was positive in 83.33% of UC; all the four markers positive in 33.33% and all negative in 4.17% of UC. However, at least one of the four markers was present in 95.83% of UC, except in sarcomatoid UC. GATA-3 had 100% specificity in differentiating from prostate adenocarcinoma. GATA-3 is a useful marker in the diagnosis of UC in the primary and metastatic sites with a sensitivity of 83.33%. GATA-3 along with other IHC markers in correlation with clinical and imageological features is necessary for making specific diagnosis of poorly differentiated carcinoma.

A Metastatic Papillary Thyroid Carcinoma Could be Confused Clinically with a Primary Renal Neoplasm; A Case Report and Literature Review

Background: Papillary thyroid carcinoma is the most common thyroid neoplasm. It has a very high incidence of regional lymph node metastasis at the initial presentation. However, vascular spread is a very uncommon event. Lungs and bones are the most frequent sites of vascular metastasis from papillary thyroid carcinoma. Case concerns: The currently discussed case was obtained from the archive of Pathology laboratory, Sohag University. A 46-year-old female patient admitted to Urology Department, Sohag University, in 2015. The patient had a left loin pain, no other clinical data included in her referral sheet . Radiological findings revealed a renal mass and left radical nephrectomy was performed. Histopathological evaluation revealed a circumscribed neoplasm, formed of densely packed acini with scanty stroma. The patient was diagnosed as renal oncocytoma. On re-evaluation of the Hematoxylin and Eosin-stained slides; the nuclear features were different from those described in renal oncocytomas. So, a panel of immunohistochemical markers was performed (anti-CK7, anti-EMA, anti-Vimentin, anti-Thyroglobulin and anti-TTF1). Results: The neoplastic cells showed strong and diffuse cytoplasmic expression for Thyroglobulin and CK7 and nuclear expression for TTF1. The neoplastic cells didn’t express EMA or Vimentin. Based on the characteristic nuclear features detected by Hematoxylin and Eosin-stained slides and the obtained immunohistochemical results; the diagnosis of metastatic papillary thyroid carcinoma to the kidney was confirmed. Conclusions: Papillary thyroid carcinoma may metastasize to the kidney and form a solitary mass, that could be confused as a primary renal neoplasm.

Immunoexpression of Programmed Death-1 Receptor (PD-1) and Programmed Death-Ligand 1 (PD-L1) in Non-Small-Cell Lung Carcinoma and Its Correlation With Other Clinicopathological Parameters: A Cross-Sectional Study From North India.

AimTo study the prevalence of programmed death-1 receptor (PD-1) and programmed death-ligand 1 (PD-L1) positive cases in non-small-cell lung carcinoma (NSCLC) and their association with other clinicopathological parameters in a tertiary care setting in North India.Material and methodsOne hundred histologically proven NSCLC cases having sufficient tumor material from July 2016 to July 2018 were examined, and the prevalence of PD-1 and PD-L1 positivity in NSCLC was studied. In addition, H&E-stained sections were reviewed, and 100 consecutive cases meeting study criteria were identified as study cases. Histopathological categorization was done using a panel of immunohistochemical markers.Statistical analysis and resultsThe PD-1 positivity in lymphocytes was 29% (95% CI: 20.4%-38.9%). Membranous positivity for PD-L1 in tumor cells was 27% (95% CI: 18.6%-36.8%) and in tumor-infiltrating lymphocytes was 22% (95% CI: 14.3%-31.4%). There was no statistically significant association between PD-1 or PD-L1 status with age, gender, smoking, pleural effusion, clinical stage, histological type, or lymphocyte infiltration.ConclusionThe moderately high prevalence may justify routine testing for PD-1 or PD-L1 in NSCLC, which should preferably be carried out in all cases rather than any selected subsets. However, there was no significant correlation between PD-1 and PD-L1 with the clinical parameters studied.

CD117, BAP1, MTAP, and TdT Is a Useful Immunohistochemical Panel to Distinguish Thymoma from Thymic Carcinoma.

Simple SummaryThymic epithelial tumors, including thymomas and thymic carcinomas are malignant neoplasms that occur in the prevascular (anterior) mediastinum. Thymic carcinomas have a worse outcome than thymomas, and, therefore, management and treatment may differ. However, the morphologic distinction between thymomas and thymic carcinomas can be challenging, as has also been shown in reproducibility studies. We aimed to identify immunohistochemical markers that aid in the distinction between thymomas and thymic carcinomas. We found that a panel of CD117 with a cut-off of 10% tumor cell expression, BAP1, mTAP, and TdT was able to predict 88.9% of thymic carcinomas and 77.8% of thymomas (among the studied types A and B3 thymomas and micronodular thymomas with lymphoid stroma). Only a small subset of thymic carcinomas (11.1%) and thymomas (22.2%) could not be predicted with that model.Background: The morphologic distinction between thymic carcinomas and thymomas, specifically types B3, A, and occasionally micronodular thymomas with lymphoid stroma (MNTLS) can be challenging, as has also been shown in interobserver reproducibility studies. Since thymic carcinomas have a worse prognosis than thymomas, the diagnosis is important for patient management and treatment. This study aimed to identify a panel of immunohistochemical (IHC) markers that aid in the distinction between thymomas and thymic carcinomas in routine practice. Materials and Method: Thymic carcinomas, type A and B3 thymomas, and MNTLS were identified in an institutional database of thymic epithelial tumors (TET) (1963–2021). IHC was performed using antibodies against TdT, Glut-1, CD5, CD117, BAP1, and mTAP. Percent tumor cell staining was recorded (Glut-1, CD5, CD117); loss of expression (BAP1, mTAP) was considered if essentially all tumor cells were negative; TdT was recorded as thymocytes present or absent (including rare thymocytes). Results: 81 specimens included 44 thymomas (25 type A, 11 type B3, 8 MNTLS) and 37 thymic carcinomas (including 24 squamous cell carcinomas). Using BAP1, mTAP, CD117 (cut-off, 10%), and TdT, 88.9% of thymic carcinomas (95.7% of squamous cell carcinomas) and 77.8% of thymomas could be predicted. Glut-1 expression was not found to be useful in that distinction. All tumors that expressed CD5 in ≥50% of tumor cells also expressed CD117 in ≥10% of tumor cells. In four carcinomas with homozygous deletion of CDKN2A, mTAP expression was lost in two squamous cell carcinomas and in a subset of tumor cells of an adenocarcinoma and was preserved in a lymphoepithelial carcinoma. Conclusion: A panel of immunostains including BAP1, mTAP, CD117 (using a cut-off of 10% tumor cell expression), and TdT can be useful in the distinction between thymomas and thymic carcinomas, with only a minority of cases being inconclusive.

Need for Panel of Immunohistochemical Markers in Primary Intraosseous Squamous Cell Carcinoma Ex Odontogenic Keratocyst

Need for Panel of Immunohistochemical Markers in Primary Intraosseous Squamous Cell Carcinoma Ex Odontogenic Keratocyst

Prometastatic CXCR4 and Histone Methyltransferase EZH2 Are Upregulated in SMARCB1/INI1-Deficient and TP53-Mutated Poorly Differentiated Chordoma

Background: Chordoma is a rare tumor most commonly arising in the sacrococcygeal region from notochord remnants. Usually, these tumors are locally invasive and recurrent, and they have a 5–43% ability to metastasize. A newly-described aggressive variant called poorly differentiated chordoma is different from conventional chordoma in that it does not have the well-differentiated histologic appearance of conventional chordoma and also exhibits the loss of SMARCB1/INI1. Herein, we describe a case of poorly differentiated chordoma with SMARCB1/INI1 loss, a concurrent TP53 mutation, and Rb1 loss. Methods: The patient is a middle-aged man with a history of previously resected sacrococcygeal chordoma, who was found to have new hepatic, lung, and adrenal lesions. Results: Biopsy of the liver lesion showed sheets of malignant epithelioid cells with vacuolated cytoplasm, areas of necrosis, and up to five mitoses in one high-power field. No physaliferous cytologic features or matrix material was seen. After reviewing an extensive panel of immunohistochemical markers, the origin of the metastatic tumor could not be determined; the tumor was only positive for Cam5.2, EMA, and CD56. Brachyury was performed due to the patient’s previous history and was positive. Genomic testing showed a SMARCB1 mutation, TP53 mutation, and RB1 loss. Additional markers were performed, and the tumor showed a Ki-67 proliferation index of approximately 80%, mutant p53 protein, loss of INI1, and strong expression of both the histone methyl transferase EZH2 and the chemokine receptor CXCR4. Conclusions: Poorly differentiated chordoma is a highly aggressive variant of chordoma with few cases reported. This case of SMARCB1/INI-deficient, poorly differentiated chordoma also showed a concurrent TP53 mutation and loss of RB1, which resulted in malignant transformation with upregulation of both prometastatic CXCR4 and the histone methyltransferase EZH2, causing aggressive behavior and metastasis.

Sinonasal Mucosal Melanoma: An Update and Review of the Literature.

Primary sinonasal mucosal melanoma (SNMM) is an aggressive tumor with high metastatic potential and poor outcomes. Presenting symptoms are nonspecific, and the nasal cavity is the most common site of origin followed by the maxillary and ethmoid sinuses. Histopathologically, SNMMs are pleomorphic and predominantly composed of epithelioid cell type. Identifying these tumors requires a high index of suspicion for melanoma and the use of a panel of immunohistochemical markers when typical histopathological features are missing. Not infrequently, these tumors are undifferentiated and/or amelanotic. Currently, SNMM falls into 2 different staging systems proposed by the American Joint Committee on Cancer, one for carcinoma of the nasal cavity and sinuses and the other for head and neck melanoma. Although therapeutic standards do not exist, surgical resection with adjuvant radiotherapy and/or systemic therapy may offer the best outcome. Lymphadenectomy including possible parotidectomy and neck dissection should be considered in patients with regional lymph node metastasis. However, the role of elective lymph node dissection is controversial. Genetic profiling has identified a number of recurrent gene mutations that may prove useful in providing targets for novel, emerging biological treatments. In this article, we provide an update on clinicopathological features, staging, molecular discoveries, and treatment options for SNMM.

Spectrum of Germ Cell Tumor (GCT): 5 Years' Experience in a Tertiary Care Center and Utility of OCT4 as a Diagnostic Adjunct.

Germ cell tumors (GCT) are an intriguing group of neoplasm having myriad clinical and morphological presentation. More and more transcription factors are being evaluated for identification of same. To study the spectrum of GCTs in a tertiary care center and the use of a stem cell marker OCT4 as a diagnostic adjunct, a retrospective 5-year (2008-2013) study was carried out. Immunohistochemistry (IHC) with OCT4 was performed on all cases and IHC for α feto protein (AFP), CD30, and epithelial membrane antigen (EMA) as per requirement. Cohort included 73 cases (23 males and 50 females). Testicular and ovarian GCTs accounted for 95.83% and 35.71% respectively. In males, seminoma was the commonest (34.78%) followed by mixed GCT (26%). 17.85% of ovarian GCTs were malignant mostly constituted by dysgerminoma (18%). Benign mature cystic teratoma (MCT) constituted 50% of ovarian GCTs. OCT4 immunoexpression was seen in all cases of seminoma/dysgerminoma, embryonal carcinoma, immature teratoma, and seminomatous/embryomatous component of mixed GCTs. Pure yolk sac tumor (YST) and MCT were consistently negative. OCT4 was especially helpful in identification of mixed GCT. A panel of immunohistochemical markers would be a more ideal way to identify and clarify the components because correct identification of the components is important for therapeutic intervention and prognostication. OCT4 being a primordial germ cell marker predicts aggressive behavior and targeted therapy against this should be investigated.

Primary testicular T cell Non Hodgkin Lymphoma with unusual histomorphology: A rare case

Primary testicular non-Hodgkin lymphoma (NHL) is an uncommon extra nodal lymphoma presentation, constituting 1-2% of all lymphomas. Majority are of B-Cell type, with very few cases being primary T-Cell phenotype. A 28 years male presented with painless, unilateral testicular swelling with elevated serum LDH levels, beta HCG and AFP serum levels were within normal limits. Gross evaluation of high inguinal orchidectomy specimen showed an enlarged homogenous, grey white lobulated mass with adjacent entrapped testicular parenchyma. Microscopy showed diffuse sheets of medium sized, monomorphic atypical lymphoid cells with sparing of adjacent seminiferous tubules. A panel of Immunohistochemistry markers done were suggestive of T-Cell Non-Hodgkin Lymphoma. Testicular T cell NHL are extremely rare amongst the testicular lymphomas, constituting for 5% of all testicular tumours. This case is being presented for its rarity in literature, especially in young age group and the unusual histomorphology.

Cytological Diagnosis of Malignant Mesothelioma: A Case Series.

Background:Mesotheliomas are neoplasms of the serosal lining of the body cavities. Diagnosis requires a multimodal approach of clinical findings, cytology, and histopathology with immunohistochemistry (IHC). The published sensitivity of cytology for diagnosing mesothelioma ranges from 30% to 75%.Aim and Objectives:This study aimed to calculate the incidence of malignant mesothelioma (MM) at our institute and to study the cytological features of MM.Materials and Methods:A retrospective study of pleural, peritoneal, and pericardial fluids submitted at our institute was done. The duration of the study was 8 years (2011–2019). Apart from examining Giemsa smears, a panel of immunocytochemical (ICC) and cell block immunohistochemical (IHC) markers was applied to achieve the diagnosis. These included calretinin, mesothelin, CK5/6, Hector Battifora mesothelial cell antibody (HBME), WT1, MOC31, CK7 and CK20. Histopathological correlation was done wherever possible.Result:In the present study, we compiled four cases of MM over 8 years diagnosed on serous effusion cytology and confirmed by immunocytochemistry (ICC)/cell block immunohistochemistry (IHC)/biopsy. This indicates a rare incidence of MM. The Cytological features of MM were studied.Conclusion:The diagnosis of MM is difficult, especially cytologically. It was found to be a rare entity in the malignant cases diagnosed on effusion cytology.

Clinicopathological and immunohistochemical analysis of plasma cell gingivitis- A retrospective study.

This study aims to describe the demographics and clinicopathological characteristics of the cases of plasma cell gingivitis (PCG) reported in our institute, supported by a review of pertinent literature. Further, we investigated the role of the cluster of differentiation CD138, Ki67, CD56, and CD117 immunoexpression in the differential diagnosis of PCG from plasma cell dyscrasias. All histopathologically confirmed cases of PCG, whose relevant details could be obtained, were included in this study. They were subjected to panel of immunohistochemical markers to exclude plasma cell malignancies. Further, published English literature for PCG since 1970-2020 was reviewed. Nine histopathologically confirmed cases of PCG, were retrieved from the archives of our department. The cases comprised 3 males and 6 females with their ages ranging between 14 and 82 years. The plasma cells exhibited equivocal reactivity for kappa and lambda; and immunonegativity for CD56, CD117 with low Ki67 proliferation index. Published literature in English showed 43 cases of PCG were predominantly female; the diffuse involvement of maxilla and mandible was a common finding. In addition to kappa lambda reactivity, an immunoprofile of CD138, Ki67, CD56, and CD117 may be used as a diagnostic adjunct to exclude malignant plasma cell lesions in confusing cases.

Aspirin Inhibition of Group VI Phospholipase A2 Induces Synthetic Lethality in AAM Pathway Down-Regulated Gingivobuccal Squamous Carcinoma.

Background: To elucidate the role of iPLA2/PLA2G6 in gingivobuccal squamous cell carcinoma (GB-SCC) and to ascertain the synthetic lethality-based chemoprevention role of aspirin in arachidonic acid metabolism (AAM) pathway down-regulated GB-SCC. Methods: The in vitro efficacy of aspirin on GB-SCC cells (ITOC-03 and ITOC-04) was assessed by cell proliferation, colony formation, apoptosis, cell migration, cell cycle assay and RNA-seq, while inhibition of PLA2G6 and AAM pathway components was affirmed by qPCR, Western blot and immunofluorescence staining. The in vivo effect of aspirin was evaluated using NOD-SCID mice xenografts and immunohistochemical analysis. Results: We found that aspirin, which has been reported to act through the COX pathway, is inhibiting PLA2G6, and thereby the COX and LOX components of the AAM pathway. The findings were validated using PLA2G6 siRNA and immunohistochemical marker panel. Moreover, a pronounced effect in ITOC-04 cells and xenografts implied aspirin-induced synthetic lethality in the AAM pathway down-regulated GB-SCC. Conclusions: This study reveals that aspirin induces the anti-tumor effect by a previously unrecognized mechanism of PLA2G6 inhibition. In addition, the effect of aspirin is influenced by the baseline AAM pathway status and could guide precision prevention clinical trials of AAM pathway inhibitors.

Nodular trichoblastoma or basal cell carcinoma: A diagnostic dilemma of clinical significance

Nodular Trichoblastoma (TB) is a rare and benign adnexal tumor originating from rudimentary hair follicles. Adnexal neoplasms show complex clinical and histological features. A panel of immunohistochemical (IHC) markers helps in distinguishing tumors of follicular origin from other cutaneous tumors especially Basal cell carcinoma (BCC). We herein describe the histological and immunohistochemical features of TB which clinically and histologically mimiced BCC.