Background: Inflammatory bowel diseases (IBDs) mainly consist of Crohn's Disease (CD) and Ulcerative Colitis (UC). These two categories have overlapping histopathological features and sometimes it is difficult to diagnose them into distinct category and such biopsies are categorised as Inflammatory Bowel Disease (IBD-U). Recently, there has been an increase in interest to discover new biomarkers of IBD to differentiate UC and CD and predict their prognosis. Method: In the present study, 273 non-neoplastic colonic biopsies with clinicoendoscopic features of IBD were studied and categorized into UC (88; 32.3%) and CD (03; 1.1%) but a major chunk remained in category of IBD-U (182; 66.6%). 161 (58.9%) of these biopsies were then subjected to IHC for RB protein and β-catenin and Serology for pANCA and ASCA was done in only 85 (31.13%) of these selected cases for identification of UC and CD on colonic biopsies. Result: 161 biopsies that were subjected to IHC analysis included 57 cases of UC, 03 cases of CD, and rest 101 cases of IBD-U. Out of 101 cases of IBD-U, 87 (86.13%) cases were reclassified as UC (61; 60.3%) and CD (14; 13.86%) on the basis of results of IHC and Serology. Conclusion: The two major tools IHC for β-catenin and RB protein and the assay of serum ASCA and p-ANCA along with proper history and clinical presentation can act as a good adjunct to conventional H and E in subclassifying cases of IBD-U into UC and CD.

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Background: H. pylori-associated gastritis in patients from the high-altitude area of Ladakh showed severe gastritis, mucosal nodularity, atrophy, and cancer in comparison to those from North India. This study served to analyze if differences in the H. pylori virulence genotypes decide the extent of gastric mucosal inflammation. Methods: Fifty gastric biopsies each from patients with H. pylori-associated gastritis from Ladakh and a tertiary care center in North India were included. The presence of H. pylori strain was confirmed with Warthin starry stain and polymerase chain amplification of the H. pylori-specific 16S rRNA. The cagA, vacA s1, s2, and m1, m2 alleles, and dupA virulence genotypes were studied in all archival samples, followed by their histological correlations. Results: cagA (P 0.009) and vacAs1 m1 (P 0.009) genes were distinctly more in H. pylori strains colonizing the biopsies of North Indian patients. In contrast, the cagA -ve vacAs2 m2 strains were significantly more in H. pylori strain colonizing the biopsies from Ladakhi patients. dupA genotype was almost similarly present in strains from both regions. Among these, only cagA and dupA virulence genes were associated with severe mucosal neutrophilic activity and deep infiltration of H. pylori strains in North Indian patients. Conclusions: Differences in virulence genotypes of H. pylori in gastric biopsies from North Indian and Ladakhi patients were found not significant in deciding the severity of H. pylori-associated gastritis.

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Background: Gastric neuroendocrine tumors (G-NETs) are classified into well-differentiated NETs with three grades and poorly differentiated neuroendocrine carcinomas based on morphology and the Ki-67 index. Besides, G-NETs are broadly classified into four types based on clinical and pathophysiological features. Aim: To study clinical and pathological features of different types and grades of G-NET. Materials and Method: All G-NETs, diagnosed from January 2011 to December 2020, were included. Clinical presentation, peritumoral findings, lymph node status, and liver involvement were obtained and correlated with different grades and types of G-NETs. Results: NET was diagnosed in 88 cases. Tumors were graded as I, II, III, and carcinoma in 58, 14, 12, and 4 cases, respectively. Type I NET (49.2%) in the background of chronic atrophic gastritis was the most common type followed by type III (33.3%). Type I tumors were predominantly graded I (91.1%) and limited to the mucosa and submucosa. MEN-1-associated G-NET (type II) was seen in eight cases. All except one type II tumor was associated with ZES syndrome. Remarkably, peritumoral mucosa showed atrophy and intestinal metaplasia in 52.1% and 24.6% cases, respectively. Two cases were associated with adenocarcinoma. Lymph node metastasis was seen in all carcinoma and grade III cases. All carcinoma cases and 58.3% of grade III tumors showed liver metastasis. Conclusion: Biological behavior of G-NET varies with different types and grades of tumor. Typing and grading of G-NET should be done whenever possible to predict the aggressiveness of the tumor.

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Aims: Thymectomy specimens are uncommon in routine histopathology practice. However, awareness of various pathologic entities and definite reporting of these specimens is paramount to optimal patient management. Our objective was to determine the histomorphologic spectrum of thymectomy specimens spanning the non-neoplastic, benign to malignant spectrum. Methods and Results: Thymectomies received over an 8-year period were retrospectively analyzed by reviewing clinical details and histologic findings in detail, incorporating the latest World Health Organization (WHO) 2015 histologic classification. A total of 303 thymectomy specimens (179 males/124 females, mean age 45.3 years [3–84 years]) were included. Around 51.2% (n = 155) patients had associated myasthenia gravis (MG), while 17.5% (n = 53) had incidentally detected anterior mediastinal mass (AMM). Non-neoplastic and benign pathologies comprised 31% (n = 94) cases and showed stronger association with MG (P = 0.009). Thymic follicular hyperplasia (TFH) was the commonest non-neoplastic pathology (n = 32), while the benign tumor group included thymic hemangioma/lymphangioma, thymolipoma, and ectopic parathyroid adenoma. Thymic epithelial tumors (TETs) comprised 64.7% cases, with majority being thymomas (185/303; 61.1%). Thymoma type B2 was the commonest histologic subtype and Stage I/T1 was the most frequent stage. Type A and AB thymomas affected older patients (P = 0.005) and were in lower stage (both Masaoka and American Joint Committee on Cancer [AJCC]) than type B thymomas (P = 0.007). No significant association between MG and thymoma subtype, patient sex or Masaoka stage was seen (P > 0.05). Thymic carcinomas comprised 11 cases and showed no association with MG (0/11, P < 0.001); squamous cell carcinoma was the commonest histologic type (8/11; 72.7%). Conclusion: TETs are the commonest thymic lesions; however, a diverse spectrum of pathologic processes can affect the thymus.

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Background and Aims: We aimed to investigate the prognostic importance of the microvessel density (MVD) value, the vascular endothelial growth factor (VEGF) expression, and the presence of perineural invasion (PNI) in laryngeal cancer (LSCC) patients. Methods: Pathological specimens of 62 LSCC patients were assessed for the evaluation of the MVD value, the VEGF expression level, and the presence of PNI of the tumors. The tumor characteristics and prognostic effects of these parameters on local control (LC) and overall survival (OS) were analyzed. Statistical Analysis: Descriptive analyses were done using frequencies for the demographic variables. The survival estimates were calculated by the Kaplan–Meier survival curves. The effects of the parameters on LC and OS were investigated by using the log-rank test comparing the survival rates. Cox regression analysis was used for multivariable analysis. Results: The 5-year LC and OS rates of the 62 LSCC patients were 64.5 and 53.9%, respectively. Twenty-two patients (35.5%) had PNI and the frequency of PNI was higher in the patients with a high-grade disease (P = 0.01). The MVD value was higher in the tumors of older patients (P = 0.035) and was correlated with the VEGF expression (P = 0.009). A higher tumor grade was related to a higher VEGF expression (P = 0.01) and the increase in the VEGF expression was associated with a significant decrease in the OS (P = 0.03). Conclusion: The VEGF expression, the MVD value, and the presence of PNI had no prognostic significance on the LC in the LSCC patients while only the VEGF expression was associated with the OS.

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Background: Low-grade appendiceal mucinous neoplasms (LAMN) of the appendix have bland cytological features and well-differentiated morphology. Despite this, they may cause a pseudomyxoma peritonei (PMP) disease characterized by mucinous deposits in the peritoneal cavity and may exhibit malignant behavior. Aims and Objectives: In this study, we evaluated the clinical course and histopathological findings of LAMN. The rate of progression to PMP, factors affecting its development, and the clinical course of cases with PMP were investigated. Materials and Methods: Twelve thousand and forty-seven cases who underwent appendectomy were reviewed, and 71 mucinous lesions cases whose slides are in our archive were included in the study. Histopathological findings were re-evaluated. Morphological findings that guide the differential diagnosis, the clinical course of the patients, and factors affecting PMP development were determined. Results: The cases were divided into group 1 non-neoplastic (9.9%), group 2 benign (18.3%), group 3 LAMN (60.6), and group 4 malignant neoplasms (11.3%). Age, gender, appendix diameter, gross appearance, epithelial characteristics, and presence of microcalcification were significantly different between the patient groups. The presence of mucin in the ileocecal region was found to be significant in the development of PMP. It was observed that the additional procedure performed after the appendectomy did not prevent a recurrence. Conclusion: LAMNs are lesions with characteristic findings and different behaviors. The only method to distinguish from the lesions included in the differential diagnosis is to interpret the histopathological findings correctly. Additional operations after appendectomy do not contribute to preventing recurrence.

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Background: High-grade pelvic serous carcinoma is a common cause of death in women worldwide and India. Recent evidence has clearly implicated the changes in the mucosa of the fimbrial end of the fallopian tube in its pathogenesis. Objective: 1) To study histopathology features of surgically resected specimens of fallopian tubes received with non-neoplastic lesions of the uterus and ovary for the presence of any precursor lesions [secretory cell outgrowth (SCOUT), serous tubal intraepithelial lesion (STIL), p53 signatures, and serous tubal intraepithelial carcinoma (STIC)]. 2) To confirm the findings with immunohistochemistry. 3) To correlate the prevalence of precursor lesions with clinical parameters and benign lesions of the uterus and ovaries. Materials and Methods: Assessment of histopathological changes in 100 specimens of distal fallopian tubes was done using the sectioning and extensive examination of the fimbrial end (SEE-FIM) protocol. H and E stain followed by immunohistochemistry for Bcl-2, p53, and Ki-67. The statistical significance of the difference in the mean values of precursor areas was evaluated by an unpaired t-test. Results: Among 100 specimens taken on H and E, precursor lesions were suspected in 49% of the cases. SCOUT, suspicious for STIC, suspicious for STIC with areas of SCOUT, and unequivocal for STIC with areas of SCOUT were seen in 8%, 4%, 33%, and 4% of the cases, respectively. However, on IHC, SCOUTS were confirmed in 45% of the cases, p53 signature in 2%, STIL in 9%, and STIC in 4% of the cases. Conclusion: Sectioning and extensive examination of the fimbrial end (SEE-FIM) should be routinely done as it provides the opportunity to detect the early malignant changes. It may help in evolving the strategies for early detection, management, and reducing mortality.

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Context: Ascertaining the role of cytokeratin-19 (CK19) and its staining pattern helps to differentiate papillary carcinoma from other thyroid lesions. Aims: To correlate fine needle aspiration cytology (FNAC) and cell block study of equivocal cases (Category III, IV, and V) with the role of CK19 staining in it. Settings and Design: A hospital-based cross-sectional observational study was designed and conducted at North Bengal Medical College and Hospital, Shusrutnagar, Darjeeling. Methods and Material: The FNAC performed and reported as per TBSRTC-2017.50 cases of Category III, IV, and V was selected for cell block study and CK19 staining followed by immunohistochemical scoring. Results: Out of 50 cases, 17 were follicular neoplasm, 21 papillary carcinoma, 6 lymphocytic thyroiditis, 1 Hürthle cell adenoma, 1 medullary carcinoma, 1 lymphoma, and 3 undifferentiated carcinomas. Among cases of papillary carcinoma, 10 showed 4+ positivity, 9 showed 3+ positivity, 2 showed focal 1+ and 2+ positivity. In the case of follicular neoplasm, 1 showed 3+ positivity, 3 cases had 1+ 2+ positivity, and 13 cases revealed negative staining. Conclusion: Role of CK19 in distinguishing papillary carcinoma of thyroid from other lesions in cytologically diagnosed Category III, IV, and V (TBSRTC-2017) cases can be demonstrated.

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Context: The diagnosis of giant cell tumor of bone (GCTB) is difficult in small biopsies with unusual age of presentation, location, and extensive secondary changes. Most of the GCTBs harbor H3F3A G34W mutations with a subset of cases showing alternate G34V, G34R, and G34L mutations. Objectives: To analyze the expression of anti-histone H3.3G34W antibody in different cellular components of GCTB across different locations and presentations (including the unusual ones) and validate the utility of this antibody in the diagnosis of GCTB and differentiate it from the other osteoclast-like giant-cell-rich lesions. Design: Immunohistochemistry was performed using anti-histone H3.3G34W antibody in the diagnosed cases of GCTB (136 cases of GCTB from 133 patients, including two malignant GCTBs) and other giant cell-containing lesions (62 cases). The presence of unequivocal crisp nuclear staining was considered positive. Results: Immunohistochemistry revealed unequivocal nuclear positivity in the mononuclear cells in 87.3% of the cases of GCTB. Of these, most showed diffuse expression with moderate to strong intensity staining. The positive staining was restricted to the nuclei of mononuclear cells with the nuclei of osteoclastic giant cells being distinctly negative. In addition to conventional GCTBs, two cases each of multicentric and malignant GCTB showed positive staining. The other giant-cell containing lesions were distinctly negative. The present study showed a sensitivity of 87.3% with specificity and positive predictive value of 100%. Conclusion: The anti-histone G34W antibody is a highly sensitive and specific marker for the diagnosis of GCTB and differentiating it from its mimics. The positive staining is restricted to the mononuclear cell component of GCTB with sparing the osteoclastic giant cells further reiterating the fact that the mononuclear stromal cells are the true neoplastic component of GCTB.

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Objective: Cancer cells activate either telomerase or alternative lengthening of telomeres (ALT) to maintain telomere length and achieve immortalization. Alpha thalassemia/mental retardation X-linked (ATRX) is involved in chromatin remodeling. Mutations in ATRX genes are associated with the loss of nuclear expression and correlated with the ALT phenotype. ATRX expression has been evaluated in various cancers, especially sarcoma and neuroendocrine tumors, and its clinical significance has been shown to be diverse, depending on the tumor types. The role and prognostic value of ATRX expression in clear cell renal cell carcinoma (CCRCC) have not been elucidated. Methods: We investigated the messenger RNA (mRNA) expression levels of ATRX using the gene expression profiling interactive analysis (GEPIA) database and evaluated the expression of ATRX using immunohistochemical (IHC) staining in 302 CCRCC cases. Results: Loss of ATRX expression was significantly associated with larger tumor size, higher nuclear grade (NG), lymphovascular invasion (LVI), pathologic T (pT) stage, recurrence/metastasis, and stage. Although ATRX was not an independent prognostic factor, patients with loss of ATRX expression showed poor survival. Conclusion: Our findings suggest that loss of ATRX expression could be a potential biomarker for predicting aggressive tumor behavior and poor clinical outcomes in CCRCC.

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Background: The purpose of the study was to analyze the expression of nucleophosmin (NPM1), CCAT/enhancer-binding protein alpha (CEBPA), and FMS-like tyrosine kinase 3 (FLT3) with immunohistochemistry and evaluate the relationship with clinicopathologic data with special emphasis on prognosis in bone marrow biopsy specimens diagnosed with acute myeloid leukemia (AML). Materials and Methods: Bone marrow biopsies of 104 patients who were diagnosed with AML were re-evaluated for diagnosis and subclassification. Immunohistochemically, anti-NPM1, anti-CEBPA, and anti-FLT3 antibodies were applied to slides prepared from formalin-fixed paraffin-embedded tissues. Sixty-three of these patients had their follow-up in our institutional hematology clinic and these patients' clinical, biochemical, and radiological data were obtained and analyzed from patient files. These data were analyzed with survival times statistically. Results: Except for age, no significant effect of clinical data on prognosis was detected. Immunohistochemical results were also statistically compared with clinical data. No correlation was found between overall survival and disease-free survival with the expression of anti-CEBPA or anti-NPM1 antibodies. However, immunohistochemical reactivity for anti-FLT3 antibody was found to be a poor prognostic factor and statistically significant. Also, when the expression of FLT3 was analyzed with that of NPM1 or CEBPA, a correlation (dependent on the expression of FLT3) was found with disease-free survival. Conclusions: FLT3 is an independent prognostic factor for AML. CEBPA and NPM1 should be considered as good prognostic factors only in the absence of FLT3 abnormalities.

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Purpose: The present study aims to identify basaloid and luminal molecular groups and the p53-like sub-group, which is a sub-group of the luminal group, using a specific immunohistochemical panel and investigate human epithelial growth factor receptor 2 (HER2)/Neu and Fascin expression in these groups to analyze their relationship with clinicopathological features and prognosis in a cohort of cases with muscle-invasive urothelial bladder carcinoma (MIBC). Material and Methods: An immunohistochemical panel that included GATA-3, CK20, CD44, and CK5/6 was used to identify molecular sub-groups based on expression in 44 cases of MIBC. HER2/Neu and Fascin expression in basal, luminal, and p53-like groups and the relationship with clinicopathological features and prognosis were investigated. Results: The distribution of the molecular sub-groups determined by immunohistochemistry was as follows: 23 luminal cases (52.3%), 16 basal cases (36.4%), and 5 (11.4%) p53-like cases. There was a statistically significant difference in tumor size across the groups, with the greatest size in the p53-like group (p = 0.001). A statistically significant difference was observed in HER2/Neu expression between the molecular sub-groups (p = 0.017). Comparison of survival and HER2/Neu scores revealed shorter survival in patients with an HER2/Neu score of 3 + compared to those with scores of 0, 1+, and 2+ (p = 0.109). Fascin immunoreactivity was more common in the p53-like and basal groups compared to the luminal group (p = 0.036). Conclusion: Despite the limited number of cases in the MIBC group, our results support that HER2/Neu expression in the luminal sub-group and Fascin expression in basal and p53-like groups may be used as a negative prognostic marker. Multi-center studies that include large case series are warranted in this field.

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Introduction: There are few reports of nocardial infections among the Indian population. We report this case because of its rarity and unique presentation and to highlight the role of cytology in diagnosis. Case Details: A 74-year-old woman presented with fever and chest pain of a duration of 15 days. In view of the coronavirus disease (COVID) pandemic, she was given steroids. She developed breathlessness and was referred to a tertiary care hospital. Her pleural fluid cytology showed filamentous bacteria. A diagnosis of nocardia was confirmed by culture. Discussion: Nocardiosis refers to the localized or disseminated infection caused by filamentous aerobic bacteria of the genus Nocardia. The clinical presentation of nocardiosis is highly variable. In our case, clinical misdiagnosis as COVID-19 and steroid treatment would have caused deterioration of nocardiosis. Conclusion: All patients with pulmonary symptoms should be thoroughly evaluated before considering a diagnosis of COVID-19. Pleural fluid cytology can be of help in the diagnosis of nocardiosis.

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We describe three postmortem open lung-biopsy findings among patients with COVID-19 pneumonia who were on anticoagulant therapy. The spectrum of histopathological findings included lung inflammation in the form of diffuse alveolar damage (DAD) in exudative and organizing phases, with or without pulmonary artery thrombosis in different stages of evolution. This spectrum of inflammation and thrombosis may be indicative of a natural history of severe COVID-19 pneumonia or demonstrative of variation in therapeutics.

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Introduction: Previous studies have shown that the long intergenic non-protein coding RNA regulator of reprogramming (linc-ROR) is abnormally expressed in a variety of malignancies and plays an important role in tumor progression. However, little is known about the role of linc-ROR in gastric cancer. In this study, the relationship between the expression of linc-ROR and clinicopathological factors in gastric cancer and its potential mechanism were explored. Materials and Methods: The cells were classified into two groups: ROR small interfering RNA(si-ROR) and the Negative control siRNA (si-NC).Linc-ROR was knockdown in si-ROR group by small interfering RNA (siRNA). Detect the expression of linc-ROR in gastric cancer tissues and normal tissues and its relationship with clinicopathologic characteristics by RT-PCR. the invasion ability was studied by wound healing assay and transwell assay. The expression levels of EMT-related molecules was detected by RT-PCR and Western blotting. Result: Showed that the expression of lincROR in gastric cancer tissues was significantly higher than that in the adjacent normal tissues. The lincROR expression level was significantly related to the tumor grade, lymph node metastasis, and TNM stage in cancer tissues. The lincROR knockdown in gastric cancer cell lines significantly inhibited cell invasion and metastasis. It affected its malignant biological behavior by activating the epithelial-mesenchymal transition through increasing expression of vimentin as well as decreasing E-cadherin levels in gastric cancer cells. The lincROR silencing significantly decreased the expression of β-catenin and c-myc. Conclusion: Linc-ROR can regulate cell invasion and metastasis by activating the epithelial-mesenchymal transition process partially through Wnt/β-catenin signal pathway in the gastric cancer cells. Link-ROR may be an important molecule for the metastasis of gastric cancer.

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Aims: We aimed to determine whether lymphocyte activation gene 3 (LAG-3), also known as CD223, is associated with microvessel density (MVD) in primary hepatocellular carcinoma (HCC), as well as their clinical significance in predicting survival. Materials and methods: One hundred and twenty-seven patients were enrolled in the study. Samples were obtained on resection at the Department of Hepatobiliary Surgery of the Qingdao Municipal Hospital from June 2014 to June 2016. Immunohistochemistry was used to determine vessel density and LAG-3 abundance. Statistical analyses were performed to test for correlation of LAG-3 density and other clinicopathological variables with overall survival (OS). Results: High LAG-3 abundance was significantly correlated with increased MVD in primary HCC (P < 0.05). The χ² test revealed a significant association of LAG-3 with preoperative AFP level, tumor diameter, N stage, and the presence of HBV infection (P < 0.05). Patients with high LAG-3 expression had shorter OS compared to those with low LAG-3 expression (P < 0.05). The Cox proportional hazards model showed that both higher LAG-3 and MVD density, age, the number of tumors, preoperative AFP level, tissue differentiation, Child–Pugh grade, and lymph node metastasis correlated with survival. Conclusions: High expression of LAG-3 is associated with angiogenesis and poor prognosis in HCC patients. With the deepening of research, LAG-3 is likely to become a novel biomarker for clinical diagnosis and prognosis and can even be a therapeutic target of HCC.

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Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in Egypt. HCCs usually have a poor prognosis because of late diagnosis, aggressive metastasis, and early invasion. Heterogeneous ribonucleoproteins (HnRNPs) are nuclear proteins that play a variety of roles in telomere formation, DNA repair, cell signaling, and gene regulation. Zincfinger Eboxbinding homeoboxes (ZEBs) are transcription factors that have a consistent inverse correlation with Ecadherin in numerous types of cancer and associated with poor prognosis. Aim: This study aimed to verify the prognostic expression of HnRNP A1, ZEB1, and E-cadherin in HCC. Settings and Design: The retrospective study consisted of 54 formalin-fixed paraffin-embedded tissue blocks of hepatocellular carcinoma. Methods and Material: Immunohistochemical staining was performed using antibodies against HnRNP A1, ZEB1, and E-cadherin. The patients were followed at the Clinical Oncology Department from May 2018 to July 2021. Statistical Analysis: SPSS version 20 using the Chi-square test to compare data and the Kaplan–Meier plot for comparing survival. Results: HnRNP A1 high positivity was detected in 59.3% of the cases, whereas negative E-cadherin and ZEB 1 expression presented in 37% and 70.4% of the patients, respectively. A statistically significant relation was present between HnRNP A1, ZEB1, E-cadherin, and various clinicopathological variables. The mean progression-free survival and overall survival in low HnRNP A1 and negative ZEB1 expressions were longer than those exhibited in high HnRNP A1 and positive ZEB1 expressions. Conclusion: HnRNP A1 and ZEB1 expressions are poor prognostic factors of HCC. E-cadherin has an important role in the development of differentiated HCCs and favorable outcome.

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Adrenal oncocytic tumors are rarely encountered. Most of the oncocytic tumors are benign and rarely malignant. Here we report a case of a 10-year-old male child presented with abdominal mass whose Contrast-Enhanced Computed Tomography (CECT) shows well-circumscribed tumor. Right adrenalectomy was carried out. Histopathologically, it was diagnosed as adrenal cortical oncocytic neoplasm of uncertain malignant potential (AONUMP). This case highlights that although adrenal oncoytic tumors are rare, we should consider this as a differential diagnosis while evaluating the patient for adrenal masses. The case is presented in view of its rarity, and distinguishing gross and microscopy appearance, the diagnosis of which was further confirmed with immunohistochemistry markers.

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The latest WHO (2017) classification describes the hematological abnormalities of Down's syndrome as a separate entity under 'Myeloid proliferations associated with Down's syndrome'. It includes Transient Abnormal Myelopoiesis and Myeloid leukemia of Down's syndrome. Here we report a case of a 3 days old neonate with Down's syndrome, presenting with a leukemic blood picture. The baby had icterus, fever and hepatosplenomagaly. Peripheral blood showed megakaryoblasts and giant platelets. A diagnosis of transient abnormal myelopoiesis was made by confirming with karyotyping and immunophenotyping. We attempt to address all the diagnostic challenges faced by a clinician and pathologist same, upon encountering such a case,by following an algorithmic approach. The mandatory need for follow up and cytogenetic studies in identifying high risk cases that will become myeloid leukemia of Down's syndrome are stressed. Our case also throws light upon the significance of identification of GATA1 mutation in diagnosing and prognostication of such cases.

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The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has led to an increased incidence of fungal infections. However, pulmonary infections are rare. COVID-associated pulmonary aspergillosis has been reported; however, there is no prior report of tracheobronchial aspergillosis with endobronchial aspergilloma as per the authors' literature search. We report such a case of a 65-year-old male with radiology and biopsy-proven endobronchial aspergilloma upon a background of tracheobronchial and pulmonary aspergillosis after having recovered clinically from severe COVID-19 disease.

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Context: Many standard books, literatures, and internet described the characteristic lineament of each salivary gland lesion. Nevertheless, there are dozens of disarray, confusion, and unmanageable morphological features regarding proper reporting. To fight with these issues, Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced in 2018, but still the third category, Atypia of undetermined significance (AUS), poses difficulties for the pathologists and clinicians for a definite interpretation. Aim: The aim is to analyze the risk of neoplasia (RON) and risk of malignancy (ROM) of Milan's category III (AUS) by subdividing into six groups based on cytolomorphology. Settings and Design: The duration of study was from March 2018 to may 2021 with the focus on ROM and RON of all Milan's categories with especial attention on AUS. Methods and Material: Result of total 329 Fine Needle Aspiration Cytology of salivary glands was categorized according to MSRSGC. On the basis of cytomorphology, further subtyping of AUS and its cytohistopathology correlation was done. The ROM and RON of each subtype was analyzed. Statistical Analysis: All data were calculated by existing formulas. Results: Out of 329 aspirates, 24 (07.29%) cases belong to AUS with availability of histology in 13 (54.17%) cases. RON and ROM was 84.62% and 53.85%, respectively. Cases of lymphocytes with nuclear atypia (L-NA) was the most prevalent (29.17%). The RON were 60.00%, 68.57,% 84.62%, 94.87%, 87.50%, 100%, 100% and the ROM were 20.00%, 11.42%, 53.85%, 05.13%, 43.75%, 83.33% and 100% in each Milan's categories I, II, III, IVa, IVb, V, and VI, respectively. ROM was the highest in cystic fluid with nuclear atypia (C-NA) (100.0%), followed by basaloid cells (75%), L-NA (66.675), and SC (50%), but ROM was zero in NA and oncocytic cells. Conclusions: Subgrouping of AUS helps to dissipate the muddiness and provide more exact and reproducible diagnostic and prognostic tool.

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Anaplastic large cell lymphoma (ALCL) is a subcategory of the mature T-cell neoplasm characterized by sheets of cluster of differentiation (CD)30-positive pleomorphic large cells mostly present as lymphadenopathy. Here, we describe a case of Small cell variant ALCL with leukemic presentation without lymphadenopathy. A 68-year-old male presented with fatigue and weakness; examination revealed a total leukocyte count of 295,000/uL. The peripheral smear showed cells having cerebriform nuclei comprising 90% of the leukocytes. The flow cytometry showed that the cells were immunopositive for CD3 (weak), CD4, CD7, and negative for the rest of the markers. The cell blocks from the peripheral blood showed cells with immunopositivity for CD30, anaplastic lymphoma kinase (ALK), and Epithelial membrane antigen (EMA). A diagnosis of the small cell variant of ALK-positive ALCL was made. Due to the presence of atypical pleomorphic cells without lymphadenopathy, the case has a diagnostic dilemma with differential diagnosis of Sezary syndrome, T-cell prolymphocytic leukemia, and adult T-cell leukemia/lymphoma. Karyotyping and additional immunohistochemistry help for the confirmation of the diagnosis.

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We report a patient who developed reactivated toxoplasmic encephalitis due to human immunodeficiency (HIV)-associated immune compromise, resulting in a breakdown of the balance between the host immunity and toxoplasma cyst. Through detailed pathological analysis, spilling of tachyzoites from the ruptured wall of toxoplasma cyst can be identified. It was also proved that Toxoplasma gondii would infect endothelial cells of blood vessels, leading to vasculitis and brain ischemic necrosis. By transmission electron microscope (TEM), apical complex of the parasite can be identified, as well as tachyzoites in rapid reproduction through fission. Rhoptry, a club-shaped specialized organelle, which is characteristic of the motile stages of Apicomplexa protozoans, was also identified. The prevention of toxoplasma infection is still an issue to be emphasized in public health. This article is special in its pathophysiology-based description of the morphology. 'Form ever follows function' is a famous quote from the architect Louis Sullivan. In this case report, we make effort to depict a pathophysiology-based or a 'form-function correlation' interpretation of the histopathological findings by light microscope, IHC and ultrastructural examination. We believe such an approach should also be included in the daily pathology resident training program.

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Cutaneous lesions are observed in approximately 25% of patients with systemic sarcoidosis. Scar sarcoidosis is a rare but peculiar cutaneous form of sarcoidosis associated with trauma, surgery, tattoos and other types of damage. We present a 32-year-old male patient with a history of unilateral facial nerve palsy, nephrolithiasis and lung involvement. A chest CT revealed multiple bilateral hilar and mediastinal lymphadenopathy and PET-CT demonstrated an inflammatory response in multiple organs and regions. Recently, the patient had developed asymptomatic papulo-nodules scattered within the areas of tattoos and previous trauma. Histopathological examination of nodules from those different areas supported the diagnosis of sarcoidosis. The lesions almost cleared after systemic therapy with oral prednisone. It is worth remembering that skin lesions in areas of tattoos and trauma may be prominent symptoms of systemic sarcoidosis. Patients with systemic sarcoidosis should avoid tattooing.

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Small intestinal medullary carcinoma (MC) is a newly recognized subclass of small intestinal carcinomas and is an exceptional entity for this site. A search of the literature for similar cases arising in the small intestine revealed only six previously reported cases. Here we present a case of MC arising in the jejunum of a 65-year-old male. The patient presented to the emergency with features of perforation peritonitis with liver metastasis and no known predisposing factors like inflammatory bowel disease and celiac disease. Studies conducted on this tumor's colonic counterpart have shown microsatellite instability (MSI) and B-type Raf kinase (BRAF) mutations; however, few exceptions are known. Also, this subtype of carcinoma is known to have a better prognosis than its other histological subtypes.

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Introduction: Ependymomas are more common in the pediatric population, in whom they are commonly infratentorial. Extra axial location of a supratentorial ependymoma is extremely rare. Diagnosis: Radiologically these tumors are often misdiagnosed as meningioma or other extra axial lesions owing to their unusual location and lack of any pathognomonic features. Hence, histopathological examination becomes imperative for proper evaluation and an adequate diagnosis. Case: Herein we report a case of a supratentorial extra axial anaplastic ependymoma misdiagnosed as a metastatic tumor on radiological examination and mimicking meningioma intra operatively, located in the frontal and temporal region in a 20 year old man.

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Leiomyosarcomas of vascular origin are very rare tumors, predominantly affecting the inferior vena cava (IVC). Although vascular leiomyosarcomas are slow-growing, their non-specific and late presentation results in delayed diagnosis which portends a very poor prognosis. Here we report a case of a 24-year-old man who presented with abdominal pain since 15 days and was found to have unresectable metastatic leiomyosarcoma of the inferior vena cava at initial diagnosis.

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Intestinal neuronal dysplasia type B in the gastrointestinal tract is a rare occurrence and may occur alone or in combination with Hirschsprung disease. Distal colon seems to be a frequent site for isolated IND-B cases; however, small bowel involvement is scarcely reported. We report a case of 9 years old boy presenting with features of intestinal pseudo-obstruction for 5 years. Exploratory laparotomy revealed narrowed distal ileum with huge proximal dilatation. Histopathology of the resected terminal ileum revealed giant submucosal ganglion, hyperplastic submucosal nerves, and ectopic ganglion cells in the lamina propria suggestive of IND-B. Although IND-B involving ileum in isolation is a rare occurrence, suspicion should be kept in cases of intestinal obstruction with minimal response to conventional treatment.

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Introduction: While disseminated intravascular coagulation (DIC) is a serious complication of COVID-19, a close differential in critically ill patients with thrombocytopenia is Thrombotic thrombocytopenic purpura (TTP). Case Report: We describe the case of a middle-aged lady admitted with COVID-19 pneumonia who developed progressive thrombocytopenia, altered sensorium and renal failure. The absence of coagulation abnormalities alerted to the possibility of TTP, strengthened by presence of schistocytes in peripheral smear. Conclusions: This case highlights the need for high index of suspicion and to pay attention to normal tests as well that might give clues to the diagnosis. New onset thrombocytopenia in COVID-19 need not always indicate DIC. A careful examination of peripheral smear may help diagnosing TTP especially if coagulation profile is normal.

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Metastatic tumors in the brain represent the most common type of intracranial neoplasm, comprising 8–10% of all brain tumors. 30% of such tumors are primarily of breast origin in females. Brain parenchymal metastasis is the more common presentation. Intraventricular spread is rare, seen in less than 5% of cases in a metastatic scenario. Here, we report a case of 41-year-old female presenting with intraventricular brain metastasis in a follow-up case of carcinoma breast. Five years post-surgery, the patient presented with complaints of headache. On evaluation, magnetic resonance imaging (MRI) brain showed an intraventricular lesion in the fourth ventricle. She was operated on for the same and the biopsy revealed a tumor with a complex papillary pattern resembling choroid plexus papilloma. On immunohistochemistry (IHC), the tumor cells were positive for cytokeratin 7 (CK7), Epithelial membrane antigen (EMA), GATA3, and mammaglobin favoring a metastasis from breast origin. Hence, a possibility of brain metastasis should be kept in mind in patients presenting with solitary ventricular masses due to the lack of definite radiological characteristics in such locations and histological overlap. Also, organ-specific IHC is a must in today's evidence-based era as is reflected in our case.

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This case highlights the importance of histopathological examination in all cases of choristoma undergoing excision.

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IgG4-related sclerosing mesenteritis is a rare disease of mesentery of an unknown etiology which shows a constellation of histopathologic findings of lymphoplasmacytic inflammation with IgG4-positive plasma cells and marked fibrosis. This chronic inflammatory condition of mesentery forming an abdominal cocoon has never been described before to the best of our knowledge. Here, we report a patient with a history of subacute small bowel obstruction who was found to have an intra-abdominal encapsulating mass in the right iliac fossa and was finally diagnosed as IgG4-related sclerosing encapsulating peritonitis (abdominal cocoon) based on peroperative findings, histology and immunohistochemistry.

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Myeloid sarcoma (MS) is an extramedullary proliferation of immature myeloid cells which may occur as a progression of myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) and as acute myeloid leukemia (AML) relapse. Rarely may it be de novo. Lymph nodes, skin, lungs, intestine are the commonly involved sites. However, an isolated pancreatic MS is seldom reported in the literature. Herein, we report one such case which was misdiagnosed as pancreatic adenocarcinoma on the clinico-radiological examination which misled us away from preoperative diagnostic sampling, and a Whipple pancreaticoduodenectomy was performed. Histopathological examination in conjunction with immunohistochemistry revealed the final diagnosis of isolated MS of the pancreas. We emphasize that although rare, a clinical suspicion along with preoperative histopathological examination may lead to early diagnosis, targeted management, and a better clinical outcome in such cases.

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Adrenal myelolipoma is a benign tumor-like growth, composed of mature fat cells and bone marrow elements. We report a case of a 44-year lady who presented with a complaint of pain in the abdomen. The only positive finding was contrast-enhanced computed tomography (CECT) whole abdomen, which was suggestive of heterogeneously enhancing hypodense lesion of size 130 mm × 105 mm with few calcifications and 103 mm × 75 mm with intralesional fat attenuation in right and left adrenals. Rest laboratory parameters were normal. Only a few cases so far have been reported for bilateral adrenal myelolipoma but what stands out in our case is its giant size and bilaterality, managed surgically without any complications.

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Background: Neonatal cholestasis is caused by a group of diseases that cause jaundice, which can be encountered in the neonatal period. Biliary atresia (BA) and idiopathic neonatal hepatitis (INH) are among neonatal cholestasis diseases. Aims: The aim of this study was to perform histopathological and ultra-structural examinations of liver biopsy tissue samples from BA and INH patients with liver biopsies taken during laparotomy to confirm the diagnosis of biliary atresia. Settings and Design: A total of patients undergoing Kasai surgery before the age of 60 days were included in an “early” group (n = 7), whereas patients undergoing surgery after the age of 60 days were included in a “late” group (n = 11). The control group (n = 11) included INH patients. Materials and Methods: For histopathological examinations, liver tissue samples obtained intra-operatively were subjected to routine histopathological procedures after being stained with caspase-3 and cytokeratin-7 antibodies. Ultra-structural evaluations were also performed. Statistical analysis used: For comparisons between the groups, a one-way analysis of variance (ANOVA) test and the Mann–Whitney U test were used for continuous variables. Results: Histopathological findings reflected the specific liver pathologic findings seen in biliary atresia. Although there was no significant difference between the BA groups, these parameters were not detected in the control group. The histopathological evaluations revealed no significant differences in the findings of liver parenchyma damage between the early, late, and control groups. Electron microscopic examinations showed that the patients in the late group had more severe signs of intra-cellular damage to the liver. Conclusions: Although the histopathological examination revealed no significant differences in liver damage between the three groups, in ultra-structural evaluation, intra-cellular damage was found to be less in groups with better prognosis. Electron microscopy evaluations of intra-cellular damage may be more useful in this respect.

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We report a case of a 49-year-old male patient suffering from an intraspinal tumor in the lumbar vertebra. The neoplasm was composed of mono-morphic spindle cells, arrayed in a patternless pattern in a background of prominent myxoid hyaline stroma with perivascular collagen rings in hyper-cellular regions. Instead, aggregated collagen fibers arranged into nodules and apparent calcium deposition were found in hypo-cellular regions. The tumor cells showed immunopositivity with S100 and CD34, whereas lacked SOX10 expression, which were reminiscent of a group of S100 and CD34 co-expression soft tissue spindle cell lesions having recurrent fusions including RAF1, BRAF, NTRK1/2/3, and RET genes. Interestingly, a novel anaplastic lymphoma kinase (ALK)- echinoderm microtubule-associated protein-like 4 (EML4) gene fusion was revealed. To our best knowledge, it was the first time to identify such gene fusion in the Orientals among this mentioned group, and it expands the molecular genetic spectrum of this specific group. The clinical relevance of this novel fusion requires further investigations.

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The poem points toward the precautions to be followed, the COVID-appropriate behavior to fight the deadly corona pandemic.

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