Liver transplantation is now a well-established therapeutic strategy for irreversible acute and chronic liver diseases. There is a broad spectrum of complications encountered in early and late period after transplantation and these contribute to significant morbidity and mortality. Distinguishing among these complications often requires interpretation of allograft biopsies. Histology is the gold standard for the diagnosis of rejection. However, interpretation of these biopsies is quite challenging due to the atypical and complex histomorphology. Multiple simultaneous insults, effects of immunosuppression (IMS), de novo complications, and presentations distinct from non-transplant setting are a few cardinal concerns. Awareness of the time period of occurrence of various complications, the most characteristic histological features or patterns, and distinguishing features between various complications are crucial. The management can be completely divergent; hence, recognition of dominant problem and interpretation in appropriate clinical context is much needed. This review focuses on histopathology of major complications accountable for early and late graft dysfunction. Tabulation of clinico-pathological features to distinguish various complications helps to solve the conundrums and arrive at the correct diagnosis.

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Background: The dismal survival of one of the commonest malignancies of the world, head neck squamous cell carcinomas (HNSCC), has prompted researchers to probe into its various characteristics, especially those which reflect the outcome. Over the years, even though epidermal growth factor receptor (EGFR) and tumor-infiltrating lymphocytes (TIL) have emerged as useful biomarkers of the disease, the two parameters have rarely been considered in conjunction. Aims and Objectives: The study aimed to assess if there is any correlation between TIL levels (both stromal and intratumoral) and site, grade, stage, and EGFR score of HNSCC. Materials and Methods: A retrospective observational study was conducted in which histopathologically confirmed cases of HNSCC were included. The site of tumor, grade, stage, stromal and intratumoral TIL levels, and EGFR score were noted for each case. The data were analyzed using standard statistical tests. Results: The study population consisted of 122 patients with a mean age of 53.8 ± 9.2 years. The oral cavity was the commonest site of tumor (109 cases, 89.3%). Most cases were moderately differentiated (75, 61.5%). Pathological staging showed 66 cases (54%) to be in pT1, and 92 cases (75.4%) to be in pN0. In 68 cases (55.7%), stromal TIL level was high, and intratumoral TIL was low in 102 cases (83.6%). A statistically significant correlation was found between TIL levels and site, grade, pathological stage, and EGFR score of HNSCC. Conclusion: This pioneering study is unique in its exploration of the correlation between two significant biomarkers of HNSCC – TIL and EGFR score.

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The large-scale celebration of National Pathology Day on the birth anniversary of Dr. VR Khanolkar would help pathologists to showcase their role in patient care, medical education, and research, change the image of pathology, and bring this specialty to the forefront.

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Background: Invasive solid papillary carcinomas (ISPC) are rare malignant neoplasms in the classification of WHO 2019 breast tumors. Aims: We aimed to investigate the correlations between programmed cell death ligand-1 (PD-L1) expression status of tumor and immune cells and clinicopathological parameters by molecular classification of this rare morphological subtype. This study will contribute to the literature about the PD-L1 expression state of ISPCs for the first time. Material and Methods: The study included 19 invasive solid papillary carcinoma cases diagnosed between 2009 and 2019 in Pathology Department. Molecular subtyping was performed in 19 cases by immunohistochemical studies (ER/PR, Her-2/neu, Ki-67), and PD-L1 expression was evaluated in neoplastic and immune cells. Results: PD-L1 expression was detected in 4 (21%) cases, 3 (75%) of them were in luminal B and 1 (25%) were in the luminal A group. The correlation between molecular subtypes and PD-L1 expression was statistically significant (P = 0.016). Patients with PD-L1 expression had a higher Ki-67 index than patients without PD-L1 expression (P = 0.037). In addition, there was a statistically significant correlation between PD-L1 expressions of intratumoral lymphocytes and PD-L1 expressions of neoplastic cells (P = 0.004). Conclusions: While predicting the group that will benefit more from immunotherapy in solid papillary carcinoma cases, not only PD-L1 expression of tumor cells but also PD-L1 expression in tumor infiltrating lymphocyte (TIL) can help. In addition, PD-L1 staining rates of tumor cells as well as clinicopathological parameters (molecular subtype, high Ki-67 index, presence of TIL) can be predictive about immunotherapy.

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Introduction/Context: Hypertensive disorders of pregnancy (HDP) are major complications of pregnancy and seen in about 5% to 10% of all pregnancies. Among these, pre-eclampsia is a leading cause of perinatal and fetal morbidity and mortality. It is a multifactorial and multisystemic disorder that results in a variety of histomorphologic features, some of which may be missed if a diligent examination is not performed. Aims and Objectives: The present study aimed to propose a checklist and novel scoring system to ensure comprehensive placental examination. We also aimed to evaluate the correlation, if any, between histopathological and morphometric findings in HDP and with fetal growth. Materials and Methods: A total of 100 placentas of women diagnosed with hypertensive disorders of pregnancy were included in our cross-sectional, observational study. Morphometric features and histological features that are known to be seen in HDP were analyzed, and each of them was given a numerical score based on their severity. Statistical Analysis Used: Pearson correlation coefficient test was applied to correlate these findings, and ANOVA test was used to assess the correlation of these findings with fetal growth restriction (FGR). Results: More than 50% of the placentas studied recorded maximum scores for weight and volume. At least 25% of the placentas showed the presence of all histo-pathological features under study. The association of total morphometric and histological scores was not found to be statistically significant (P-value = 0.239). We found a significant difference between means of morphometric scores of cases with normal fetal growth and cases showing FGR (P-value = 0.008). Conclusion: Uneven distribution and presentation of the lesions in these cases may lead to the absence of correlation between morphometry and histopathology, as seen in our study. Morphometric derangements in the placenta correlate with FGR. Our proposed checklist and scoring system can be utilized to standardize reporting of placental specimens in the evaluation of placentas with HDP, in order to facilitate and standardize the placental reporting.

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Introduction: Despite the commendable advancements in oral squamous cell carcinoma (OSCC) diagnostics and therapeutics, it remains a considerable medical challenge. Recent evidence suggests that small populations of stem-like cancer cells are responsible for tumor initiation, progression and metastasis. These cancer stem cells (CSCs) have been identified and characterized in various types of cancers, including OSCCs. CSC hypothesis has been supported by the expression of CD44, CD133, ALDH1 and ABCG2. Amongst them, CD44 (a transmembrane glycoprotein), is the most reported CSC marker in OSCCs. The increasing incidence of OSCC combined with its poor survival rates motivates a need for research into the expression of adhesion molecules and may play a pivotal role in studying tumor biology related to invasion and distant metastasis. Objective: To quantify the expression of CD44 in the different grades of OSCC and to correlate the expression of CD44 with clinicopathological parameters. Method: A total of 20 formalin-fixed paraffin-embedded tissues of OSCC were retrieved from department archives. Immunohistochemical staining was performed using anti-CD44 antibody (Biogenex). The expression was assessed semi-quantitatively in varying histopathological grades of OSCC and were correlated with tumor, node, metastasis (TNM) staging which were obtained from the department records. The results were statistically evaluated. Result: Overexpression of CD44 was detected in 48% of well-differentiated OSCCs followed by a linear decrease in moderately differentiated and poorly differentiated OSCCs and the expression correlated with the tumor size (T) in 23% cases and with lymph node metastases (N) in 42% of cases (P ≤0.05). Conclusion: The results of the present study suggested an altered expression of CD44 in OSCC. This depicts an association of CD44 with tumor aggressiveness and Epithelial Mesenchymal Transition (EMT) related to loss of cell adhesion in a subset of OSCC—clearly stating tumor cell stemness as a key factor in malignant potential of OSCC.

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Background: Deregulation of long noncoding RNAs (lncRNAs) was considered one of the main characteristics of several human cancers. However, detailed genome-wide expression and functional significance studies of lnc RNAs in lung adenocarcinoma are still limited. This study aims to discover a new lncRNA that may play an important role in regulating the pathogenesis of lung adenocarcinoma (ADC). Methods: We conducted a comprehensive analysis of three Gene Expression Omnibus (GEO) microarray datasets and TCGA datasets. Differentially expressed lncRNAs between ADC and normal tissues were screened and verified using Gene Expression Profiling Interactive Analysis (GEPIA). Moreover, Kaplan-Meier plotter was used to construct the gene prognosis profile. The downstream targets of miRNA and related functional pathways were predicted and validated. Results: With microarray gene expression analysis, we found that only lncRNAs-PCAT6 was commonly upregulated among four datasets, and four lncRNAs (LINC00968, PGM5-AS1, LHFPL3-AS2 and SFTA1P) were significantly downregulated in the ADC samples as compared to the normal tissues. Meanwhile, for LHFPL3-AS2, high-risk patients showed better overall survival (HR=0.6 or 0.62; P < .0001 or P = 0.0014), overall survival from TCGA datasets (HR=0.72; P = 0.015) and recurrence-free survival (HR=0.72; P = 0.015). Then, LHFPL3-AS2 was predicted to bind to two miRNAs, miR-127-5p and miR-424-5p. Finally, validation and functional enrichment analysis of the downstream key mRNAs showed significant enrichment in some cancer-related pathways, such as cell adhesion in cancer and small cell lung cancer. Conclusions: Taken together, our study indicated that LHFPL3-AS2 was associated with tumorigenesis, and it could be used as a useful biomarker in the diagnosis, prognosis and treatment of ADC.

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Introduction: Helicobacter pylori infection is a chronic bacterial infection associated with some extragastric diseases as well as gastric involvements that occur most commonly worldwide. In our study, we aimed to investigate the usability of immature granulocytes as a basic indicator that can reflect the severity of helicobacter pylori inflammation, to the best of our knowledge, for the first time. Materials and Methods: Patients who underwent upper gastrointestinal endoscopy between April 2019 and April 2020 and were diagnosed with antral gastritis were included in this study. The relationship between helicobacter infection and its severity detected in gastric biopsies of patients and immature granulocyte count (IGC), immature granulocyte percentage (IG%), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) were investigated. Results: Of the 868 patients, 210 were HP negative, 658 were HP positive (218 mild HP positive, 293 moderate HP positive, and 147 severe HP positive). There were statistically significant differences between the HP negative and HP positive groups in terms of IGC, IG%, NLR, and PLR. However, IG% and IGC were not clinically useful because the median IG% (0.3 vs 0.3) and IGC (0.02 vs 0.02) were the same in the HP negative and total HP positive groups. Conclusion: In our study, IGC and IG% were not found useful to detect H. pylori intensity and severity of inflammation.

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Background/Aims: As targeted therapies are promising in the treatment of lung cancer (LC), it is important to identify the genetic variations in tumors. The present research aimed to determine the regional prevalence of alterations in ALK, ROS1, and EGFR genes. Materials and Methods: ALK rearrangement in 1152, ROS1 rearrangement in 390, and EGFR mutations in 1054 cases with LC were evaluated. Results: Alteration rates of ALK, ROS1, and epidermal growth factor receptor (EGFR) genes were 3.5%, 0.4%, and 11.2% in the samples, respectively. ALK rearrangements were mainly detected in young patients (P < 0.01) and in females (P < 0.01). Females were also more often inflicted by EGFR variations, especially from the exon 19 deletion. Exon 21 L858R mutations were more frequently found in men. However, any statistical significance between EGFR alterations and gender or age was not discovered. Conclusion: In this study, molecular changes were less frequent than expected. We thought that this low rate confirmed the aphorism of “smokes like a Turk, ” which could be because almost all patients were active or passive smokers.

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Background: Colorectal cancer (CRC) is the third most commonly occurring cancer in men and the second most common cancer in women. Despite advances in surgical techniques and chemotherapeutic regimens, CRC continues to be one of the main causes of cancer-related deaths in the world. Aims: The aim of the study was to evaluate the immunohistochemical expression of human epidermal growth factor receptor 2 (HER2) and the relationship between HER2, clinicopathological parameters, and microsatellite instability (MSI). Materials and Methods: Two hundred and forty resected CRCs at our institution between 2016 and 2019 were included in the study. Tumors were re-evaluated and classified according to the World Health Organization. Tissue macroarray techniques were used to generate tissue samples. HER2 antibody was performed using the automated system. Results: HER2 antibody was score 3 positive in only 5 cases. Score 2 was observed in 13 cases, score 1 in 27, score 0 in 195. All of the HER2-positive cases were metastatic. All of them were tubular adenocarcinoma. HER2 positive cases were well and moderately differentiated. Four of the HER2 positive cases were T3 stage, and one was T4. Conclusion: A total of 2.1% of CRCs were positive for HER2 antibody. There was a positive correlation between HER2 and distant metastasis. There was no significant relationship between MSI, other prognostic parameters, and HER2.

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Background: Neuroblastoma (NB) is the fourth most common tumor of childhood. There is a paucity of literature on its subtyping of cytology and prognostic utility. Aims: We aimed to study the cytopathological features of NB on the aspirated material, subtype it, and assess the role of International Neuroblastoma Pathology Classification (INPC) classification on cytology smears in the preoperative prognosis of NB. Materials and Methods: Fifteen cases of NB reported on fine-needle aspiration cytology (FNAC) in the past 3 years were included. Detailed clinical, radiological, and cytological features were noted. Smears were assessed for characteristics such as cellularity, neuroblasts (cytoplasmic, nuclear details), rosettes, neuropil, Schwann cells, fibroblasts, calcification, and necrosis. Afterward, cases were categorized as undifferentiated (UD), poorly differentiated (PD), and differentiating (D) subtypes. Mitotic-karyorrhectic index (MKI) was calculated and correlated with histopathology. Follow-up was done to date. Results: The age ranged from 19 days to 10 years with an M: F ratio of 3:1. Twelve cases were retroperitoneal, two cervical, and one mediastinal. Metastatic disease was seen in six cases, one to the cervical, four to the bone marrow, and two to the scalp. The International Neuroblastoma Risk Group (INRG) staging system was available in all cases, out of which three were in stage L1, six in stage L2, four in stage M, and two in stage Ms. On cytology, four cases were differentiating NB, five PD NB, and six UD NB. The MKI was high (>4%) in 80% of UD, intermediate (2–4%) in 100% of PD, and low (<2%) in 75% of D cases. MKI corroborated in both histology and cytology, except in one case. Conclusion: NB can be subtyped on cytology on the basis of characteristics of neuroblasts, presence of neutrophils, rosettes, and necrosis. UD NB has a high MKI and is associated with a poor prognosis. A preoperative comprehensive reporting of NB on cytology can be very useful in guiding appropriate chemotherapy with some increment in survival. However, larger studies are needed to validate the calculation of MKI on FNA smears.

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Background: Targeted therapy using tyrosine kinase inhibitors in cases of non-small-cell lung carcinoma (NSCLC) that harbor epidermal growth factor receptor (EGFR) mutations has drastically improved the overall survival rate. The current study estimated the frequency of EGFR mutations in the Indian population by analyzing the diagnostic parameters of various techniques available for the detection of these mutations. Materials and Methods: A case series of 100 histologically diagnosed and immunohistochemically confirmed NSCLC with the adenocarcinoma phenotype comprises the study sample. EGFR mutations were detected using clone-specific immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), and Sanger sequencing. Results: EGFR mutations were identified in 48% cases with 72.78% mutations involving exon 19. Clone-specific IHC had a low sensitivity of 46.43%, and the specificity was 79.17%. Sanger sequencing yielded interpretable results in 16% cases only, which were in concordance with the results of real-time PCR. Conclusion: EGFR mutations are increasingly being explored for targeted therapy and personalized medicine. Real-time PCR was found to be the best and the most accurate method for the detection of somatic EGFR mutations in adenocarcinoma primarily in the lungs.

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Objectives: To investigate clinical implications of epithelial mesenchymal transition (EMT) expression in oral cavity squamous cell carcinoma (OSCC). Materials and Methods: E-cadherin and vimentin expression was studied in 50 newly diagnosed cases of OSCC who underwent surgical excision. EMT expression at non cold spot infiltrative margin and cold spot was studied and correlated with prognostic factors and disease-free survival (DFS). Results: EMT expression at the cold spot and non-cold spot infiltrative margin showed significant results with nodal status (P < 0.001, P < 0.009 respectively). On multivariate analysis, only EMT at the cold spot correlated significantly with prognostic factors (P < 0.030). The factors affecting DFS on Kaplan Meier index were EMT expression and differentiation (P < 0.002, P < 0.016 respectively) which proved significant in cox regression analysis. Conclusion: The study reveals that EMT expression at the cold spot is a significant biomarker for predicting lymph-node metastasis and tumor recurrence in OSCC.

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Context: p16 is an important tumor suppressor gene and responsible for regulating the cell cycle. Diffuse positivity with p16 in the cervix and head/neck carcinomas can be regarded as a surrogate marker of the presence of high-risk human papillomavirus (HPV). Aim: The aim of our study was to search the existence of p16 expression in pterygium. We also analyzed the association of p16 expression with epithelial dysplasia and HPV expression. Subjects and Methods: The study enrolled 75 cases of pterygium. The conjunctival tissues of 10 patients excised by the strabismus surgery were used as control group. All of the slides were stained with p16 via the immunohistochemical method. Results: 49 (65%) of pterygiums showed low-grade epithelial dysplasia. None of the control groups showed dysplasia. Positive expression of p16 in patient group was significantly higher (P < 0.001). Staining percentage (SP) of p16 was between 0 and 26% in pterygium; mean SP was 5.1%. There was no staining in the control group. A total of 59 (72%) pterygium cases were positive with p16. Appoximately 42 of 49 (85%) cases with dysplasia showed p16 staining. There was a significant relation between dysplasia and positive expression of p16 (P < 0.001). Conclusions: P16 is significantly expressed in pterygium and correlated with epithelial dysplasia. Furthermore, the existence of p16 expression suggests that HPV is a possible ethiological factor in pterygium. We think that examination of p16 expression and analysis of HPV DNA in p16 positive cases can help us to understand the etiopathogenesis of the disease better.

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Context: Soft tissue neoplasms are infrequent in children with sarcomas accounting for approximately 7% of all pediatric malignancies. Morphologic diagnosis is challenging due to overlapping features. Subtyping and categorization of these lesions are difficult on fine-needle aspiration cytology (FNAC) alone owing to tumor heterogeneity and limited material in some cases. Tru-cut biopsies obtain adequate tumor tissue for ancillary studies besides conventional histology. Aim: The study aims to explore the role of tru-cut biopsy to arrive at a definitive diagnosis. The study also highlights the correlation between FNAC and histopathology on tru-cut biopsy besides explaining the significance of a panel of immunohistochemistry (IHC) markers for histological categorization and subtyping. Materials and Methods: A total of 61 children from infancy to 18 years were included in the study. Closed biopsy procedures like FNAC and tru-cut biopsy were performed, and the tru-cut biopsy specimen was subjected to a panel of immunohistochemical markers. Results: Fisher's exact test for sensitivity and specificity towards detection of malignancy was 83% and 86%, respectively for FNAC. For tru-cut biopsy, sensitivity was 94% and specificity was 91%. The two-sided P value (<0.0001) was extremely significant. Cohen's Kappa coefficient value for tru-cut biopsy was 0.772 suggesting a substantial strength of agreement. Tru-cut with IHC had a Kappa value of 0.866 suggesting greater agreement with histopathology. Conclusion: Tru-cut biopsy is a simple, safe, and reliable adjunct to the FNAC. Instead, immunohistochemistry enhances the diagnostic accuracy.

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Purpose: To investigate the clinicopathological features of mature teratoma with malignant transformation. Methods: Retrospectively analysis of 1179 cases mature teratoma was done from August 1999 to December 2019 in Institution. 14 cases of mature teratoma with malignant transformation were discussed mainly for the pathological characteristics and clinical manifestations. Results: 4 of them were less than 40 years old. All but one occurred in the ovaries, and the one was in the left anterior mediastinum which was the only male. The clinical manifestations of the patients were atypical. Imaging showed cystic solid mass. Surgery was performed. Polypoid mass, solid nodule and thickened area of cyst wall can be seen on the section of tumor. Pathological results show that there were 5 cases of squamous cell carcinoma, 3 cases of carcinoid, 2 cases of serous carcinoma and 2 cases of thyroid papillary carcinoma, 1 case of carcinosarcoma and 1 case of strumal carcinoid. Two cases of squamous cell carcinoma had pelvic and abdominal metastasis. Immunohistochemistry of case 14 showed that AE1/AE3, CD56, SYN, NSE, PSAP, CDX2 were positive in carcinoid. EMA and CK20 were positive in mucinous glands around carcinoid. Calretinin and inhibin were positive in the mesenchyme adjacent to intestinal mucinous gland. Conclusions: Teratoma with malignant transformation is a rare malignancy, although teratoma is a common germ cell tumor. And it's more common in patients over 40 years, especially those patients who were in menopause. Squamous cell carcinoma is the most common type and prone to metastasis. Strumal carcinoid was well-defined, but as an endocrine tumor, it may cause a series of digestive, respiratory or hormonal disorders. Therefore, the mature teratomas should be removed in time after detection.

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Background: Malignant melanoma (MM) is an aggressive tumor characterized by high metastatical potential and is sometimes diagnosed by distant organ metastasis such as liver. Morphologically it may mimic many other tumors and cause diagnostic challenges. In this paper, eleven MM cases metastasized to the liver with different morphologic patterns were analyzed in the light of literature. Materials and Methods: Histopathological and immunohistochemical findings of the cases diagnosed as MM metastasis in liver were reevaluated in the light of clinical data. Results: We obtained 11 MM cases with hepatic metastasis. In slides of the first four cases, morphologic features similar to epithelioid variant of MM with different amounts of melanin deposition were observed. In the fifth and sixth cases, fascicular patterned tumoral lesion composed of spindled cells were detected; and in the seventh and eighth cases, nested and sheet-like patterned tumoral lesion consist of giant bizarre and spindled cells with hyperchromatic nuclei were observed. The last three cases consisted of plasmacytoid cells with eccentric nuclei in pseudoalveolar pattern; and the exact diagnosis was possible with the help of immunohistochemistry. Conclusion: MM should always be kept in mind in differential diagnosis of metastatic hepatic tumors with unknown primary because of its various morphological characteristics.

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Background and Aim: Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphomas (ALK⁺-LBCLs) are aggressive CD20-negative lymphomas, accounting for <1% of diffuse LBCLs. Being rare and with peculiar immunophenotypic characteristics, these can be easily misdiagnosed. We present 11 cases of ALK⁺-LBCLs diagnosed over a period of 11 years at a tertiary care hospital in South India to analyze the clinical, morphological, and immunophenotypic profile of these tumors. Subjects and Methods: ALK⁺-LBCL cases diagnosed from September 2009 to August 2020 were included. Clinical details were obtained from stored electronic records and summarized. Available hematoxylin and eosin (H and E) stained slides and immunohistochemistry slides were reviewed and observations tabulated. Results: Eleven patients (nine males and two females) were diagnosed with ALK⁺-LBCLs in the study period with seven presenting primarily with extranodal disease manifestations. Tumors in the lymph nodes showed diffuse architecture effacement and variable sinusoidal invasion. All tumors showed immunoblastic and plasmablastic-type large lymphoid cells with scattered anaplastic/multinucleate large cells, including rare Reed–Sternberg-like cells. Cytoplasmic granular ALK-1 staining, CD20 negativity, and immunohistochemical features of plasmablastic differentiation were noted in all. Of eight patients treated, only one achieved remission with multi-agent chemotherapy but relapsed after 6 months. Two patients died of disease and five others had progressive/persistent disease and were lost to follow-up. Conclusion: Although rare, these tumors should always be in the differential diagnoses of tumors with plasmablastic and immunoblastic morphology, especially in extranodal sites to avoid diagnostic delay/misdiagnosis.

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Context: HER2-targeted therapy has been shown to benefit HER2-positive gastric cancer. It is very important to determine the HER2 expression level correctly to select the appropriate test and sampling method. Aim: In this study, we investigated the frequency of overexpression of HER2 and intratumoral heterogeneity of HER2-positive cases, comparison of HER2 used immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) performance in biopsy and resection specimens, the correlation of HER2 status between biopsy and resection specimens, and its relationship with clinicopathological findings. Materials and Methods: Formalin-fixed, paraffin-embedded specimens of a total of 40 surgically resected and biopsy specimens of gastric cancer were analyzed. HER2 status was examined using both IHC and FISH techniques, and the findings and their association with different clinicopathological parameters were evaluated. Results: The concordance rate between the results of IHC and FISH in biopsy and resection specimens was 96.6% and 86.6%, respectively. In paired 20 cases, the overall concordance rate of HER2-IHC and HER2-FISH status between biopsy and resection specimens was 90% and 100%, respectively. HER2-IHC analysis revealed that 5/40 cases were IHC 2+ and only 1 of 5 IHC 2+ cases demonstrated HER2-FISH amplification. Conclusion: Our results showed that HER2-IHC was well concordant with FISH in cases with a score of 0/1+ or 3+ and demonstrates strong concordance between biopsy and resection specimens. FISH should be performed when the IHC result is equivocal. In our study, no statistically significant correlation was observed between HER2 positivity and clinicopathological parameters. Overall, both biopsy and resection specimens are appropriate for HER2 testing.

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A 13-year-old girl child with B-cell precursor acute lymphoblastic leukemia presented with complaints of fever, fatigue and left-sided iliac mass of 20 days duration. Preliminary blood culture from the peripherally inserted central catheter (PICC) demonstrated the presence of budding yeast cells. This is a rare form of “Disseminated cryptococcosis”. Budding yeast cells emphasizes the significance of various differentials of yeast in positive blood cultures bottles, as identifying Cryptococcus from gram stain can be complicated. This manuscript also highlights the presence of crystalloid geometric appearance like “Buckminsterfullerene”, which is derived from the mucopolysaccharide capsule in Cryptococcus. These structures are rarely observed, and in this case, are exceptionally remarkable.

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Tumors of the pituitary gland and sellar region represent about 15% of all brain tumors, with pituitary adenoma being the commonest and pituitary carcinoma being very rare. Pituitary tumors in children are even rarer. Pituitary blastoma, a pediatric adenohypophysial tumor, is a new entity described in the 2017 WHO classification of pituitary tumors. This is a very rare tumor with only 21 cases reported so far. Hence, we are reporting this unusual case seen in a 7-month-old infant who presented with a large sellar/suprasellar mass with pressure symptoms of short duration. Typically, they present between 7–24 months of age. On histopathology, a cellular tumor was seen with primitive-looking round cells with scanty cytoplasm with few well-defined gland or rosette-like structures. The immunohistochemical stains showed diffuse strong staining for synaptophysin with a very high MIB-1 index. Other markers for common round cell tumors in this age group and hormonal markers of pituitary tumors were negative with INI-1 being intact. The initial cases described by Scheithauer presented with Cushing's disease and at least focally expressed adrenocorticotrophic hormone on immunohistochemistry. However, nonfunctioning tumors are also seen, albeit rarely. These are known to be associated with DICER 1 mutations and have a poor prognosis. Hence, morphologic recognition in the right clinical context and excluding other differential diagnoses in infants help make the correct diagnosis.

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Metastases to the testis are uncommon. Signet-ring cell carcinomas from the gastrointestinal tract (GIT) can rarely disseminate to the testicles, mimicking primary testicular malignancies with signet-ring cells. We hereby describe a case of a 26-year-old male who presented with left testicular swelling, multiple lymphadenopathies, and normal serum tumor markers. Lymph node biopsy revealed clusters and singly lying signet-ring cells. Judicious use of immunohistochemistry confirmed the tumor to be GIT primary. Further investigations confirmed a gastric tumor extending to the duodenum. Although rare, metastatic tumors to the testis should be considered in differential diagnoses of testicular masses in a young patient, particularly when serum germ cell tumor markers are normal or mildly deranged.

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Clear cell chondrosarcoma (CCC) is an uncommon variant constituting less than 2% of all chondrosarcomas. CCC arises most commonly in the proximal end of the femur, followed by the humerus, and other small bones. CCC involving the tarsal bone is very rare, and to the best of our knowledge, only one case has been described involving the calcaneum in the English literature to date. In this article, we discuss a case of CCC involving the right calcaneum with complete clinico-immuno-histomorphological features, which is successfully managed by below-knee amputation. We also reviewed the reported cases of chondrosarcomas involving the calcaneum with special reference to clinical features, therapy, morphology, and follow-up data.

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Background: NOTCH1 pathway activation has been recently described to be a key player in gastric carcinogenesis, enhance the survival and proliferation of cancer stem cells (CSCs) and mediate chemoresistance in several malignancies. Aim: This study investigated the correlation between NOTCH1 and CSC marker OCT4 (octamer binding transcription factor-4) expression and the clinicopathological properties, survival and treatment outcome in patients with gastric carcinoma (GC) receiving adjuvant chemotherapy. Materials and Methods: NOTCH1 and OCT4 were immunohistochemically detected in 50 post-operated specimens of GC. Patients' data regarding disease-free survival (DFS), overall survival (OS), and the response to the chemotherapy was statistically analyzed. Results: NOTCH1 and OCT4 overexpression was detected in 60% and 52% of GC tissues, respectively, and that was significantly higher than the rates in adjacent non-neoplastic gastric mucosa (P < 0.05). A significant correlation was detected between overexpression of NOTCH1 and OCT4 in GC and aggressive clinicopathological features; poor differentiation (P = 0.021, P = 0.037, respectively), depth of tumor invasion (P < 0.001 for both), TNM stage (P < 0.001 for both), lymph node metastasis (P = 0.002, P = 0.003, respectively) and distant metastasis (P < 0.001 for both). NOTCH1 was positively correlated with OCT4 (P = 0.002). Survival analysis disclosed that upregulation of NOTCH1 and OCT4 was associated with worse DFS (P = 0.013, P < 0.001, respectively) and OS (P < 0.001 for both). Overexpression of NOTCH1 and OCT4 correlated with poor response to chemotherapy (P = 0.013, P = 0.005, respectively) and worse clinical outcome. Conclusion: Combined detection of these proteins might disclose even better predictive value for shorter survival and resistance to chemotherapy.

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The novel coronavirus disease (COVID-19) has spread to all the continents posing a serious threat to global health. It can present with myriad symptoms and complications including susceptibility to fungal co-infections. We hereby describe a case of mucormycosis in a 17 year old COVID-19 positive female with no known comorbidities presenting with abdominal pain and distention and ultimately developing intestinal perforation. Early identication of the symptoms is essential to make a correct and early diagnosis to prevent complications.

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Pulmonary tuberculosis is one of the most common immunosuppressive infections in India, seldom accompanies other parasitic and fungal infections. In our case, we describe the three coexistent infections and their clinical presentation in a 53-year-old woman. A fibro-cavitary lesion in lung with superadded infections of hydatid cyst and aspergillus which is rare has been elaborated in the present case.

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Introduction: Loop electrosurgical procedure of the transformation zone of the cervix (LEEP) is the preferred method for many investigators for early detection and treatment of high grade intraepithelial neoplasia(HGCIN). Histopathology reports of LEEP should contain information about the diagnosis, presence or absence of neoplasia ( with its grade) and comment on excison margins. Aim: Our aim was to study LEEP reports for its contents and to see their correlation with preprocudure histology and/or cytology report. Results: Between 2011 and 2017, 44 LEEP reports were archived and studied for their contents from our records. Slides were not reviewed. Mean age was 47.66 years (median 47 years). Forty two (( 95.45%) reports mentioned that all the tissue was examined. Deep cut examination was mentioned in 17/44 cases (38.64%). The concordance rate between LEEP and preprocudure histology and /or cytology for CIN II plus diagnosis is 65.9%. A strict definition is used. If, however, diagnoses between inflammation and CIN I, ASC-H and inflammation, and ASC-H and CIN I are considered non discordant, then the concordance rate rises to 72.7 %. The breakup of discordant cases is given. Conclusion: Literature shows wide range of concordance due to variable definitions and variety of reasons; possible reasons are discussed.

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The most common cause of granulomatous lymphadenitis in countries like ours is mycobactrium tuberculosis followed by atypical mycobacterial infection, fungal infections, parasitic infection, cat scratch disease, lymphogranuloma venereum (inguinal lymphadenopathy), and leprosy Here, we present three cases of lymphadenopathy due to histoplasmosis in immunocompetent children. Two of them presented with fever, lymphadenopathy, initially diagnosed as granulomatous lymphadenitis consistent with tuberculosis on FNAC and were put on antitubercular drugs. However, their condition gradually became worse. As the patients continued to deteriorate, subsequent lymph node biopsies were done and diagnosed as histoplasmosis. Third case presented with acute loss of vision with hepatosplenomegaly and lymphadenopathy. Initially considered as acute leukemia, but eventually established as histoplasmosis. Histoplasmosis should be considered as one of the possible causes of granulomatous lymphadenitis in children.

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Background: Laryngeal squamous cell carcinoma (SCC) which is the most common carcinoma of the respiratory system after lung carcinomas is graded by the World Health Organization (WHO) into three groups as grades 1, 2, and 3. This system does not correlate with the prognosis and has a low reproducibility among the pathologists. Searching for a new grading system, in this study, we investigated the relationship between tumor budding and histomorphological parameters and survival status. We examined the new grading system based on cell nest size and tumor budding. Methods: Partial and total laryngectomy materials of 130 patients diagnosed as laryngeal SCC between 2012 and 2018 in our clinic were evaluated retrospectively by two pathologists. Tumor budding activity and cell nests were scored and a new score was obtained by summing the scores. According to the scores obtained, a new grading system was created. Results: There was a statistically significant difference between the tumor budding activity and the overall and disease-free survival times of the groups. The overall and disease-free survival time of the patients with high tumor budding significantly reduced. Tumor budding was found to be low in the presence of an intense lymphocytic host response (P < 0.05). There was no relationship between the new grade system and cell nest size and life expectancy (P > 0.05). Conclusions: Tumor budding provides significant clues in predicting the life expectancy of the patients. Therefore, tumor budding might be a component of new grading systems and should take place in pathology reports.

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Background: The present study aimed to explore the effect of neoadjuvant therapy and tumor regression grade (TRG) on the shrinkage in the distal surgical margin (DSM) induced by formalin fixation in rectal cancer. Materials and Methods: In this prospective study, the DSM of resected 61 specimens of rectal and rectosigmoid junction adenocarcinoma were measured following fresh and formalin fixation. The measurements were performed within the first 15 min after resection and at 24 h after formalin fixation without pinning and were compared with regard to neoadjuvant treatment status and TRG. Results: In the patients that received neoadjuvant therapy, the fresh and postfixation DSM values were 32.2 mm and 22.7 mm, respectively, and the mean shrinkage rate was 34.7% (P < 0.001). In the patients that did not receive neoadjuvant therapy, the fresh and postfixation DSM values were 54.03 mm and 41.9 mm, respectively, and the mean shrinkage rate was 23.7% (P < 0.001). The mean shrinkage rate was 41.9% in TRG 1, 29.4% in TRG 2, and 31.9 in TRG 3 specimens. The mean shrinkage rate was higher in specimens with a DSM of ≤20 mm compared to specimens with a DSM of >20 mm (46.2% vs. 24.9%). Conclusion: A complete or near-complete tumor regression in patients with rectal cancer undergoing neoadjuvant therapy increases the shrinkage of DSM. Moreover, this shrinkage rate is likely to be higher and the pathological DSM is likely to be closer than expected in cases that present a better clinical response to neoadjuvant therapy, particularly in distal rectal cancer.

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Parasitic infection of the central nervous system could be fatal, and its incidence is rising due to increasing worldwide travel. Amongst the various nematodes, Angiostrongylus contonensis is the commonest and causes eosinophilic meningitis. It is a zoonotic disease produced due to the ingestion of raw or undercooked snails or slugs. Most cases of angiostrongyliasis are mild and self-limiting, but death can occur in severe cases lacking timely and proper treatment. Very few autopsy cases of A. cantonensis are reported. We present the case of a 32-year-old mentally challenged orphan male with eosinophilic meningitis at autopsy.

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Harlequin ichthyosis (HI) is the most severe type of congenital ichthyosis. It is extremely rare with very few cases reported in India. It is inherited in an autosomal recessive fashion. The importance of antenatal diagnosis by ultrasonography, DNA-based molecular studies on chorionic villus sampling, and amniocentesis has been emphasized. We report a new case of HI in an infant, diagnosed postnatally by correlation of clinical and histopathological features on skin biopsy. The infant succumbed on the second day of birth despite intensive supportive care. A short review of the literature regarding the condition is also presented.

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Adenoid cystic carcinoma (ACC) is an uncommon malignant neoplasm usually confined to the salivary glands, lungs, and breasts. Primary cutaneous adenoid cystic carcinoma (PCACC) is an extremely rare entity with solitary cases reported at sites away from the scalp and chest. Hence, one must follow the multidisciplinary approach to exclude any primary ACC elsewhere in the body. We report a rare case of PCACC arising from the skin of the left lower limb in a 55-year-old woman with a history of recurrent swelling, clinically diagnosed as a metastatic tumor.

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Inflammatory myofibroblastic tumors (IMTs) are uncommon; intermediate grade soft tissue tumors occurring in young individuals with an uncertain behaviour. The incidence of pulmonary lymphangitis carcinomatosis (PLC) is around 6-8% of all pulmonary metastases. However, PLC due to papillary thyroid carcinoma (PTC) is very uncommon. We present a case of a 26-year-old male, who presented with a solitary left lung nodule on radiological scans. There was also a past history of thyroid surgery done two years back for PTC. Histology revealed a soft tissue tumor reminiscent of IMT. The periphery of the IMT nodule showed metastatic PTC in the form of extensive PLC. In view of this unusual histology, a diagnosis of PTC with nodular fasciitis-like stroma (PTC-NFS) was initially considered. However, molecular studies for anaplastic lymphoma kinase (ALK) gene rearrangement confirmed the diagnosis of IMT. This case highlights the unusual occurrence of tumor-to-tumor metastasis causing diagnostic challenges and also the importance of molecular testing.

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Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant vascular neoplasm with unpredictable clinical behavior. These lesions are frequently misdiagnosed owing to its non-specific symptomatology, ambiguous radiological features, and overlapping histomorphology. We report three cases of hepatic EHE, of which one was male and two were female patients. While all three patients presented with abdominal pain, the male patient gave an additional history of weight loss and was jaundiced. The radioimaging showed multiple nodules in the liver and two of the patients also had pulmonary metastasis. The biopsies of the liver nodules revealed a tumor composed of spindle, epithelioid, and stellate tumor cells, some with characteristic intracytoplasmic vacuolations/lumina surrounded by myxohyaline stroma. Some of these intracytoplasmic vacuoles/lumina showed erythrocytes, suggesting its vascular origin which was confirmed by CD31 and CD34 positivity. The article highlights the importance of histopathology and IHC in the precise diagnosis of EHE.

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Prostate cancer being the world's leading cause of cancer and also the second most common cancer in men is posing challenges in its diagnosis. Immunohistochemistry with markers like high molecular weight cytokeratin, p63 aid in the diagnosis. The absence of p63 and high molecular weight cytokeratin and presence of p504s in the biopsies indicate malignant lesions. Yet, there is a loophole to this too. A rare case of p63-positive prostatic adenocarcinoma in an 87-year-old patient, with immunohistochemistry results showing overexpression of p63 in the nuclei of the malignant glands. This tumor shows high molecular weight cytokeratin negativity, and p504s positivity. Prognosis of this variant of the tumor is mostly favorable. Prompt treatment will halt the progression of this tumor and prevent paraplegia. Radical prostatectomy could be avoided by treatment modalities like androgen blockade and brachytherapy, as morbidity is very high with radical prostatectomy surgery.

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Synchronous endometrial and ovarian carcinoma is a rare instance and it accounts for 50 to 70% of all synchronous female genital tract tumors. However, it is very rare to find synchronous endometrial carcinoma and ovarian sex cord–stromal tumor (thecoma). The present case is a 75-year-old woman with a complaint of post-menopausal vaginal bleeding. Radiologically, the magnetic resonance imaging (MRI) pelvis revealed altered signal intensity mass in the uterus. Frozen section and routine histopathological examination were done on radical hysterectomy. Microscopically, serous carcinoma involving uterine corpus and left Fallopian tube was identified along with the unusual finding of contralateral ovarian sex cord–stromal tumor (thecoma), which was confirmed on immunohistochemical examination. It is a very rare association and is first reported in the present study after a thorough search of the published literature. Their relationship based on a high level of estrogen produced by the hyperactive ovary is controversial as serous carcinomas are less hormone-dependent.

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Epithelioid hemangioma of bone is a rare and locally aggressive vascular neoplasm of bone associated with a good prognosis. Because of its worrisome histomorphologic features and aggressive clinicoradiologic findings, at times with multifocal presentation, they tend to simulate malignant tumors. We report a series of four cases of epithelioid hemangioma of bone with their clinicopathologic characteristics. All had adjacent soft tissue involvement and two had multifocal bone disease. Microscopically, all cases had a tumor in lobular configuration, composed of epithelioid endothelial cells with the formation of well-formed vessels or grew in solid sheets. The tumor cells lacked significant cytologic atypia, necrosis, and increased mitosis. All cases were immunohistochemically positive for vascular markers CD34, CD31, ERG1, whereas negative for CK. Two of the cases were treated with excision, and the other two underwent curettage. None had local recurrence or metastasis on follow-up. This study highlights the importance of recognizing histomorphological and clinicoradiological features for distinguishing epithelioid hemangiomas from malignant vascular neoplasms of bone because of their distinct therapeutic implications and clinical outcomes.

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Carcinoma cervix usually spreads directly to contiguous structures, such as the vagina, urinary bladder, ureter, and rectum. Intestinal metastasis from cervical cancer is very uncommon and accounts for less than 4% of cases and to date, 24 cases have been reported in Medical literature. These may be asymptomatic or present with features of intestinal obstruction, bowel wall perforation, and mimic acute abdomen. Intestinal metastasis is a late occurrence and carries a poor prognosis, hence a high index of suspicion with prompt diagnosis and management is essential. We report a series of five patients with squamous cell carcinoma (SCC) of the cervix with intestinal metastasis diagnosed in our hospital.

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Skeletal muscle infiltration in carcinoma is a rare entity. Intramyofiber skeletal muscle invasion is the rarest type of muscle infiltration. Here we present one such case of intramyofiber skeletal muscle invasion in a case of breast carcinoma.

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Ewing sarcoma is a rare aggressive malignant round cell tumor, primarily presenting in bone and soft tissues. This study presents two cases of this tumor in unusual locations, one in right colon which presented with intussusception and other in ovary which presented clinically as carcinoma ovary. Both the cases showed histomorphology of primitive round cell tumor with characteristic immunohistochemical profile and was confirmed on molecular analysis. We aim to highlight the importance of considering Ewing sarcoma in the differential diagnoses in these locations as they have dismal prognosis with no standard treatment modality.

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Childhood orbital teratomas are usually congenital lesions that are most often present at birth with progressive, massive unilateral proptosis. During the routine controls of 27-year-old woman between 26–27^th weeks of pregnancy her fetal ultrasonography (USG) revealed a mass in the eye of the fetus, and termination was recommended. The family refused the termination option and in the 37^th week of pregnancy, vaginal delivery is performed in an external medical center. The mass in the baby's eye was surgically removed. Microscopic examination revealed disorganized ocular tissues, adipose tissue, microcalcification, nerve plexuses as well as areas of neuronal nodules including hypercellular areas, palisatic necrosis, and microvascular proliferation. The immunprofile––patchy GFAP staining in the areas of cellular epithelioid and spindled cells that also show an focal and sparse expression p53 staining and a high proliferation rate in Ki67 staining––confirmed the hematoxylin–eosin (HE) impression of a teratoma with a component of glioblastoma (GBM). In this unique presentation of a malignant orbital teratoma with a GBM, we have identified three tumor components: (1) GBM component, (2) nodules of neuroglial tissue with mature neurons and BRAF mutation, and (3) papillary proliferation possibly representing a choroid plexus papilloma.

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Aım: Superficial urothelial urinary bladder tumors are neoplasms that frequently recur and have a potential for invasion and metastasis. REG gene family is composed of various acute phase reactants, lectins, antiapoptotic factors, and growth factors that are effective on pancreatic island cells, neural cells, and epithelial cells. REG1A and REG1B are two forms of the human REG1 gene. It is reported that they are expressed in several cancers and are correlated with the prognosis of the patient. Claudins are integral transmembrane proteins that interconnect cells. However, their role in human tumorigenesis is extremely controversial. The aim of this study is to evaluate the relationship of REG1A, claudin 7 protein expressions, and Ki67 proliferation index in superficial urothelial urinary bladder tumors with well-known parameters of prognosis and tumor recurrence, and also to clarify whether these parameters are independent prognostic factors or not. Materials and Methods: A hundred and eleven patients diagnosed with superficial urothelial carcinoma between 2011 and 2016 years in our hospital and followed up in our urology clinic were included in this study. The slides prepared from paraffin blocks were immunohistochemically stained with REG1A, claudin 7, and Ki67 antibodies. Results: REG1A showed positive staining in 37 (33%) and negative staining in 74 (67%) of urothelial tumors. Claudin 7 was positive in 24 (22%) and negative in 87 (78%) cases. REG1A expression showed a positive correlation with tumor stage and tumor recurrence; a high Ki67 proliferation index was positively correlated with tumor stage and grade. The loss of claudin 7 expression was related to tumor recurrence. Besides, tumors with REG1A expression and claudin 7 loss had a shorter survival independent of recurrence. Conclusıon: In urothelial tumors, REG1A expression and loss of claudin 7 might be significant markers of prognosis that predict tumor recurrence.

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Aneurysmal bone cyst (ABC) is a benign expansile cystic lesion that can affect any bone of the skeleton, especially the femur, tibia, and humerus. Lesions with histologic features of an ABC can be originated within soft tissue in exceedingly rare cases. Extra-skeletal ABC may mimic a variety of benign and malignant lesions and can be confused with other common or rare giant cell-rich tumors of soft tissue. Clinical, radiological and histologic correlation are crucial in reaching the correct diagnosis. Here we report a case of an extra-skeletal ABC arising in left hemithorax in a 13-year-old girl and discuss the common differential diagnosis of this rare entity.

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Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is a type of inherited cancer syndrome with a genetic predisposition to different types of cancer. There is an increased predisposition to cancers in the endometrium, colon, stomach, ovary, uterus, skin, kidney, and brain in patients of Lynch syndrome. We are reporting a 48-year-old male who presented with a pea-sized growth in his left arm which was found to be sebaceoma on histopathology. On further detailed history, examination, and genetic study, it was proved to be a familial case of Lynch syndrome. The case is being reported to stress the importance of knowledge about clinical manifestation, associated neoplasms, and molecular genetic profile of Lynch syndrome which will enable physicians and pathologists to provide highly targeted surveillance and management for patients with high cancer risk.

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Cardiac epithelioid hemangioma is extremely rare. Currently, there are only a few described cases of intraluminal hemangiomas of the aorta and the aortic valve and no described cases with extraluminal epithelioid hemangiomas of the ascending aorta. We now present a case of epithelioid hemangioma of the ascending aorta that was an incidental finding during the coronary artery bypass and successfully resected.

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A 15-month-old child was brought to the ophthalmology outpatient department with his parents complaining of a large mass located on the nasal side of his right eye since birth. On examination, an irregular mass was seen to be located on the nasal side of his right orbit, obscuring the visual axis. On a contrast-enhanced computed tomography scan, a heterogenous lesion was seen to be located on the bridge of the nose and the medial aspect of the right orbit without any bony defect or communication with the brain or sinuses. In view of the possibility of developing amblyopia, the lesion was surgically removed. On histopathological examination, a diagnosis of extranasal glial heterotopia was made. To the best of our knowledge, this is the largest extranasal glial heterotopia in the orbit to be ever reported.

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The diagnosis of myoid gonadal stromal tumor (MSGT) can represent a difficult challenge, both for the extreme rarity of this neoplasm and for the clinical-radiological characteristics similar to other neoplasms of the testicle. The case management we present suggests how a complete differential diagnosis can be obtained by integrating ultrasonographic and pathological data.

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