Background and Aims: Inflammation is considered to be the seventh hallmark of cancer and plays a pivotal role in all stages of tumor development. Systemic inflammatory responses in particular neutrophil to lymphocyte ratio (NLR) have garnered immense attention of current researchers and its role is well proven in various solid malignancies. Its prognostic role in oral cancer have been extensively studied. However, its diagnostic role is yet to be explored. The current study aims to investigate diagnostic utility of NLR in oral potentially malignant disorders and oral cancer, when compared to normal subjects. Methods: A total of 150 subjects were involved in the study, a total of 2.5 ml of blood was drawn from the median cubital vein of the patient in an EDTA vial and hematological parameters were assessed using Erba-Transasia B7256 Autoanalyzer and reassessed manually by two experts. Statistical Analysis: The NLR values were recorded and tabulated as Mean ± S.D. and comparisons were analyzed using Kruskal Wallis and Mann Whitney post hoc U test. ROC curve analysis was performed to estimate cut-off values. Results: The NLR values when compared between the 3 groups were statistically significant (P < 0.001). The cut off value between disease and normal subject was 2.33, while the cut-off value between potentially malignant and malignant condition is 3.20. Conclusion: NLR can be a valuable diagnostic adjunct in oral cancer and potentially malignant disorders of oral cavity.

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Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial neoplasm, which is generally regarded as benign or indolent in terms of its clinical behavior. However, details about WDPM have remained relatively unknown. Therefore, in this study, we examined six incidentally detected cases of WDPM of the peritoneum. All six cases were surgically excised, without any additional therapeutic measures. None of the cases showed recurrence. All six cases presented single lesions and the tumor sizes ranged from 2 to 10 mm. Histologically, all six cases exhibited papillary proliferation of cytologically bland mesothelial cells with a fibroconnective tissue core. One of the cases (Case 6) presented small invasive foci in the stalk. The tumor cells were immunohistochemically positive for mesothelial markers and negative for GLUT-1, p53, and CD146. The Ki-67 labeling index of the tumor cells was lower than 5% at the hot spots. All samples were BAP1-positive. None of the samples presented p16 homozygous deletion, as assessed by fluorescence in situ hybridization (FISH). None of the patients deceased due to WDPM. However, in Case 3, death occurred due to pancreatic cancer. The results of this study indicate the importance of analyzing immunohistochemical markers and p16 status to diagnose WDPM accurately.

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Background: Circulating tumor cells (CTCs) are cells present in the blood stream that are antigenically or genetically similar to a specific tumor type and are markers of tumor diagnosis, prognosis, residual disease and metastasis. The ever-increasing burden of breast cancer globally warrants the incorporation of this all-inclusive marker in the diagnostic repertoire using the simplest of techniques. Aims: To identify CTCs in peripheral blood by cell block (CB) technique in cases of breast cancer diagnosed on fine-needle aspiration (FNA) or core needle biopsy (CNB) and to correlate their presence with nodal metastasis. Material and Methods: This study was conducted in the Department of Pathology, at a tertiary care hospital. Peripheral blood samples from a total of 30 cases of primary breast carcinoma diagnosed on FNA or CNB without prior neoadjuvant chemotherapy were analyzed using the CB technique. Results: The age ranged between 29-74 years with the most common presenting complaint being a palpable, single, unilateral breast lump. CTCs were detected in 2 (6.7%) cases with a <5 cell cluster with both the cases being grade I breast carcinomas and also displaying nodal metastasis.

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Immature platelet fraction (IPF) is a quantification of immature platelets in the circulation reflecting the state of thrombopoiesis in the marrow. Normal reference range for IPF has been established in adults. Reference intervals in neonates are highly dependent on gestational age of the neonate. Complete blood counts (CBC) with IPF of all neonates admitted in neonatal intensive care unit (NICU) were analyzed using Mindray BC-6800 Auto Hematology analyzer. Platelet count of less than 150 × 10^9/L was assigned as thrombocytopenia. Neonates were divided into four groups as per the corrected gestational age (CGA) on the day of CBC analysis: 28–32 weeks, 32–34 weeks, 34–37 weeks, and >37 weeks according to World Health Organization (WHO) classification. Mean, standard deviation, and 95% confidence interval for IPF was calculated in each group and reference range for IPF was derived. Mean IPF in neonates with normal platelet count was term––3.58 (95% CI 3.29 to 3.87), late preterm Neonates (34–37 weeks)––4.14 (95% CI 3.82 to 5.0), moderate preterm neonates (32–34 weeks)––4.14 (95% CI 3.46 to 4.82), and in Very Preterm neonates (28–32 weeks)––IPF of 5.51 (95% CI 3.95 to 7.07). We aimed to establish a reference range for IPF in neonates of different gestational age groups. The IPF values in neonates were comparable between hematology analyzers in neonates with normal platelet counts.

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Sudden death, a catastrophic event, falls within the purview of the forensic experts. It is often caused by cardiovascular diseases, which may be evident or occult. A vast majority of sudden cardiac deaths (to the extent of 90%) are due to ischemia of the working or conducting myocardial tissues consequent to coronary artery diseases. A heterogeneous group of nonischemic myocardial disorders, most producing structural abnormalities are responsible for the remainder; they predominantly represent various cardiomyopathies. This review, in two parts, covers sudden cardiac death in medicolegal autopsies with an approach to some common and uncommon nonischemic myocardial diseases that have a genetic and/or nongenetic basis.

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Background: Follicular dendritic cell sarcomas (FDCSs) and histiocytic sarcomas (HSs) are exceedingly rare tumors. Most of the data on those entities are based on case reports or small case series. The natural history and response to different treatment modalities have not been well established. Aims: To analyze the clinicopathologic features, immunophenotypic profile, treatment responses and to add to the existing data on FDCS and HS. Study Design: Retrospective descriptive study. Materials and method: The study was conducted at the department of Oncopathology at a tertiary care cancer hospital in India, retrospectively within the time period of four years (2016-2019). Total eight (8) cases were diagnosed: four cases of FDCS and four cases of HS involving nodal and extra-nodal sites. Clinical, histopathological, immunohistochemistry (IHC) and therapeutic data of the eight cases were retrieved and analyzed. Statistics: Descriptive statistics. Result: Among the four patients of FDCS, two had nodal and two had extra-nodal disease. Mean tumor size was 6 cm. Tumor cells expressed CD23, CD21, CD45, CD68 and S100. One patient received adjuvant chemotherapy (Gemcitabine and Docetaxel). Median survival was 36 months. None of them developed distant metastasis. Two of the patients having HS, developed bone metastasis. Median survival was 8.5 months. CD68 was consistently expressed in all cases of HS. Other applied IHC markers were negative in all the eight cases. Conclusion: FDCS and HS are under-recognized and easily prone to a wrong diagnosis. Therefore, considering these rare entities in differential diagnoses and inclusion of proper IHC biomarkers are necessary to avoid potential misdiagnosis.

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Background: Primary cutaneous amyloidosis (PCA) comprises several forms of localized cutaneous amyloidosis characterized by amyloid deposits occurring at or near dermal–epidermal junctions. Immunohistochemical studies have shown the expression of cytokeratin (CK) suggesting that it has an epidermal origin. Objectives: To study the clinicopathological features of PCA and expression of CK5/6 and correlate it with Congo red stain. Materials and Methods: A total of 30 histologically proven cases of PCA were studied. Congo red staining and immunohistochemical expression of CK5/6 were analyzed. Statistical Analysis: The qualitative data has been expressed as proportions and the quantitative data has been expressed as mean ± SD. All data was analyzed using the Statistical Package for Social Sciences (SPSS) software version 22. Results: Deposits of amyloid in papillary dermis were seen in all 30 cases. Mild focal basal cell vacuolar degeneration and apoptotic bodies in epidermis were seen in six cases. The presence of pigment cells in dermis were seen in 26 cases. CK5/6 showed weak/mild immunopositivity in nine cases, moderate in 20 cases, and strong in one case. Conclusion: The presence of dermal melanophages interspersed within eosinophilic deposits gives a clue to the diagnosis. Congo red stain highlights the deposits and visualization under polarized light gives apple green birefringence which is diagnostic of amyloid. Staining of amyloid deposits by CK5/6 proves that the amyloid is of keratinocyte origin. There was 100% sensitivity with Congo red and CK5/6. Thus, CK5/6 can be used as an adjunct tool to Congo red stain in the diagnosis of primary cutaneous amyloidosis.

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Background: Xanthoceraside is a component obtained in the husks of Xanthoceras sorbifolia Bunge. Series of researches proved that xanthoceraside had functions of anti-inflammation and anti-tumor effects. However, the mechanisms of xanthoceraside against bladder cancer are unclear. Accordingly, we proposed to investigate xanthoceraside's impacts and potential mechanisms in cells of bladder cancer. Methods: By using the CCK-8 assay, we measured the viability of cells. With the use of 4,6-diamidino-2-phenylindole (DAPI) staining, we examined nuclear fragmentation and chromatin condensation in the nuclei of apoptotic cells. By using flow cytometry, we measured cell apoptosis. By using Western blotting, we tested the expressions of Caspase-9, Caspase-8, Caspase-3, Bcl-xL, P53, and PI3K/Akt/Bcl-2/Bax. Results: The proliferation of cell lines of human bladder cancer T24 and 5637 was suppressed by xanthoceraside significantly in a time- and concentration-dependent way. When cell lines 5637 and T24 were incubated as the xanthoceraside dose increased, the rates of cell apoptosis were upregulated, which was dependent on dose. According to further analysis, xanthoceraside induced apoptosis by upregulating Bax and downregulating the expression of Bcl-xL and Bcl-2. However, xanthoceraside did not change the expression of Caspase-9, Caspase-8, and Caspase-3. Interestingly, xanthoceraside also downregulated the expression of p-PI3K and p-Akt, and upregulated P53. Conclusions: Xanthoceraside induces cell apoptosis through downregulation of the PI3K/Akt/Bcl-2/Bax signaling pathway in cell lines of human bladder cancer.

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Context: Breast cancer is the most common cause of cancer mortality among women worldwide. It is a heterogeneous disease partly responsible for treatment failure in luminal B patients. Deregulation of fibroblast growth factor signaling has been found and its therapeutic/prognostic value is explored. Aims: Most of the research has studied the FGFR1 gene while our study explored its protein expression by immunohistochemestry and examined the association with clinicopathological features, different molecular subtypes and survival. Subjects and Methods: Formalin-fixed and paraffin-embedded samples of invasive breast carcinomas were used to analyze FGFR1 expression. FGFR 1 was scored by percentage and intensity of cell cytoplasm staining, correlations were investigated and survival curves were constructed. Statistical Analysis Used: Chi-square test was used to assess the relationship between the marker expression and the clinicopathological characteristics. Overall specific survival curves were estimated using the Kaplan-Meier method and statistical significance was assessed using the log-rank test. Results: FGFR1 was associated at different staining threshold cut-offs with tumor size (P = 0.002), infiltrating lymph node (P = 0.022), distant metastasis (P = 0.003), positive estrogen receptor (P = 0.000), HER2 overexpression (P = 0.044) and luminal phenotypes (P = 0.026). The results also emphasize FGFR1 correlation expression with distant metastasis in luminal B tumors (P = 0.035) but not with luminal A and with overexpressed HER2 protein in both luminal tumors. FGFR1 expression affect luminal B patients survival with poor outcome. Conclusions: FGFR1 expression may serve as a prognostic and predictive factor in luminal breast cancers, it can also be considered as a potential therapeutic target in luminal B cases.

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Diffuse Midline Glioma-H3K27M mutant is a specific entity added to the 2016 updated WHO classification of CNS tumours that represents the majority of diffuse intrinsic pontine gliomas, although identical tumours are also found elsewhere in the midline. They are aggressive tumours with a poor prognosis and considered WHO GRADE IV regardless of histological features.^[1],[2] Patients with H3K27M–mutant gliomas in unusual anatomical locations have a better prognosis than those with corresponding tumors in the brainstem and this helps in the treatment stratification of diffuse gliomas. Extrapolating from the clinicopathologic features of diffuse pontine gliomas and the poor prognosis seen in pediatric diffuse midline gliomas with H3 K27M mutations, the presence of an H3 K27M mutation in an infiltrating astrocytoma of the midline automatically confers a grade IV status.^[2],[3] This case emphasizes the need for Immunohistochemistry using a mutation-specific H3K27M antibody in all cases of midline gliomas.

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Background and Aim: Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder manifesting as multiple lymphadenopathy, multiorgan involvement, and inflammatory symptoms. This study aims at highlighting some unique features of MCD in Indian patients. Materials and Methods: These 17 patients from review of 78 cases of Castleman's disease (CD) diagnosed. Besides routine tissue sections were stained for Human Herpes Virus 8 latency associated nuclear antigen (HHV8-LANA) by immunohistochemistry (IHC) and Epstein Barr virus latent membrane protein (EBV-LMP) or Epstein Barr Virus by in situ hybridization (EBER-ISH). Result: The cases included Plasma cell variant (11 cases), mixed MCD (4 cases) and two concurrent MCD with large B cell lymphoma in HIV positive patients. Median age of disease onset was 47 years and female predominance was seen. Out of 15 MCD uncomplicated by lymphoma, 5 had POEMS (Polyneuropathy, organomegaly, endocrinopathy, myeloma protein, skin changes) and one also had TAFRO (Thrombocytopenia, anasarca, fever, marrow reticulin fibrosis, organomegaly, normal or slightly elevated immunoglobulin) syndrome. Out of 10 MCD without lymphoma, 2 cases showed few EBV positive large cells, both have features of POEMS. All 17 MCD cases were negative for HHV8-LANA IHC. Two HIV patients with MCD had large cell lymphoma, intrasinusoidal pattern, of which one was EBV positive. Though four relapses were seen, none died from disease. One of the two patients complicated by lymphoma died from disease. Conclusion: Indian patients with MCD show female preponderance and are negative for HHV8 but show EBV positive cells. This makes a case for role of EBV in etiopathogenesis of MCD in India.

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Background: Increased acetylcholinesterase (AChE) activity on frozen sections of rectal mucosal biopsies accurately diagnoses Hirschsprung disease (HD). But the quest for a biomarker in blood as a screening test prompts one to look for AChE in blood and study its role in HD diagnosis. Aim: To develop a low-cost reliable method to estimate the AChE activity in plasma and red blood cells (RBCs) in normal children (control) and study its role in HD (test). Materials and Methods: Optimized method derived after modifying and standardizing known AChE assay protocols for blood were employed on 30 controls to define the AChE cut-off range, on 40 suspected HD cases to categorize them as HD/non-HD based on cut-off values and later compared with gold standard tissue AChE histochemistry of rectal mucosal biopsies. Results: An optimal in-house modified methods of Ellman's was found best suited to analyze plasma AChE activity, method by Wilson and Henderson was optimal for extraction and AChE estimation in RBCs. AChE levels (controls) obtained were 1.03 ± 0.31 U/mL and 5.17 ± 1.52 U/mL in plasma and RBCs, respectively while the plasma AChE was 1.35 ± 0.84 U/mL (HD) and 1.62 ± 0.85 U/mL (non-HD) while RBC AChE was 4.29 ± 3.2 U/mL (HD) and 6.48 ± 4.31 U/mL (non-HD). Sensitivity was 66.67% and 55.56%, specificity was 22.73% and 45.45%, and an accuracy rate of 42.5% and 50% for plasma and RBC, respectively. Conclusions: Mutually exclusive AChE activity range identified for test blood samples overlapped with the normal and hence, not considered a diagnostic tool for HD.

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Background and Aims: The objective of this study was to analyze and review the clinical and histopathological aspects of oro-facial tuberculosis. Methods: Sixteen cases of oral mucosal biopsies diagnosed as granulomatous pathology consistent with tuberculosis were retrieved from the data base and clinical information and histopathological findings were analyzed retrospectively. Results: Of the total 16 cases, 12 were males while 4 were females. The age ranged from 15-70 years (mean of 39.6 years). Buccal mucosa, as an involved site, was seen in 31% of cases, while tonsil and soft palate constituted 3 cases each. Duration of symptoms ranged from 01-12 months (mean of 5.3 months). Oral examination revealed ulceroproliferative lesions in majority of the cases. Of sixteen cases, six cases (37.5%) each primarily as well as secondarily involved oral cavity while in 25% (4/16) of cases the status could not be evaluated. On histopathology, caseating granulomas were seen in 7 of 16 cases (43.75%) and non-caseating granulomas were seen in rest 56.25% of cases. Ziehl Neelsen stain for acid fast bacilli was positive in 31.25% (5/16) of cases. Conclusion: Though unusual, tuberculosis should always be included in the differentials of oral lesions in a country endemic to tuberculosis like India. Histopathological evaluation of the biopsy remains the indispensible tool to diagnose oro-facial tuberculosis.

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Background: Proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID) is an entity with a variable clinical and histological spectrum, which mimics immune-complex mediated glomerulonephritis on light microscopy. In this article, we aim to describe the clinical and pathological features of six cases of PGNMID that we encountered during our routine practice. Materials and Methods: The study was of the prospective type carried out from February 2018 to August 2019. The renal biopsies that we received in our department, were processed for light microscopy, immunofluorescence microscopy, and electron microscopy. Light microscopic findings were carefully re-evaluated by two experienced renal pathologists. Key diagnostic features were 1) Monoclonal staining of glomeruli for one immunoglobulin (Ig) subclass and single light chain, 2) Membranoproliferative glomerulonephritis (MPGN) pattern (rarely membranous or crescentic), 3) Subendothelial and mesangial (rarely subepithelial) deposits. Results: We diagnosed five cases of IgG PGNMID and one case of IgA PGNMID with a mean age 53 ± 10.33 years. The most common histological pattern, seen in three cases was MPGN. IgG3 deposits were identified in five cases out of which k light chain restriction was present in four cases and λ light chain restriction was present in one case. IgA deposits were identified in one case that had λ light chain restriction. One patient suffered from multiple myeloma. Conclusions: The renal biopsy especially immunofluorescence analysis is the key modality for diagnosis of PGNMID where it shows staining of the glomerulus for a single heavy-chain subclass and a single light-chain isotype. Electron microscopic evaluation is necessary to differentiate PGNMID from other renal diseases with monoclonal immunoglobulin deposits.

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Glomus tumor is a rare mesenchymal tumor composed of perivascular glomus bodies. The most common presentation area of these tumors is peripheral soft tissue, particularly in the distal part of extremities. They rarely can occur in the gastrointestinal tract and the most common location is the stomach. Preoperative diagnosis of this tumor can be difficult because of rarity and overlapping features with other mesenchymal lesions with regard to clinical and pathological findings. Therefore, to exclude differential diagnosis and make a definitive diagnosis is possible only with histopathological examination. In this case, we evaluated glomus tumor of stomach according to 2019 WHO Digestive System Tumors and accurate diagnosed was Uncertain Malignant Potential Gastric Glomus Tumor.

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Rhabdomyolysis is a potentially life-threatening clinical syndrome characterized by the breakdown of skeletal muscle cells and release of creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin into the plasma and interstitial space. Rhabdomyolysis can occur due to a variety of causes and acute kidney injury (AKI) is one of its most dreaded complications occurring in 33%–50% patients. The main pathophysiology of renal injury is due to vasoconstriction, intraluminal casts, tubular obstruction, and direct myoglobin toxicity. As the symptoms are nonspecific, a high level of suspicion is required in the mind of the treating physician. Early diagnosis and prompt management with fluid resuscitation, initiation of renal replacement therapy (RRT), and elimination of causative agents can help prevent complications. We hereby report four interesting cases of this clinical syndrome with emphasis on the causative agents.

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The carcinoids are the most frequent tumors arising from the appendix, in majority of the cases, these are asymptomatic and are discovered after appendectomy. The lipid-rich carcinoid, also known as clear cell carcinoid; is histologically characterized by the presence of clear vacuoles in the cytoplasm of tumor cells. Only 24 cases of lipid-rich carcinoid of the appendix are described in the English literature, and there is no report of this entity in the Indian literature. In this report we describe a first case of lipid-rich carcinoid of the appendix in India and also present a review of the literature.

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Intraosseous hemangiomas are uncommon, constituting less than 1% of all osseous tumors. The most frequent sites are the calvaria and the vertebral column. The involvement of the facial bones is rare, and if occurs, it can involve maxilla, mandible, nasal bones and zygomatic bone. Zygomatic hemangioma is a benign, slow-growing tumor occurring mostly in adult women. The radiographic findings are diagnostic. Total excision of the tumor with the primary reconstruction of the defect is the preferred treatment modality. Here, we are reporting a case of a 37-year-old woman who presented with a painless hard swelling in the right zygomatic prominence, which was diagnosed as intraosseous hemangioma after the radiological examination because of its characteristic radiological picture. An Excisional biopsy also proved the swelling to be a cavernous hemangioma.

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Introduction: Kayexalate (Sodium Polystyrene Sulfonate/SPS) and K-bind (Calcium Polystyrene Sulfonate/CPS) are cation exchange resins, commonly used for treatment of hyperkalaemia. SPS/CPS induced injury of the gastrointestinal tract(GIT) is rare, can be potentially life threatening but is under-recognized. This study aims to increase awareness of pathologists and clinicians of this under-reported complication of a drug commonly used to treat hyperkalaemia. Materials: Study population comprised patients with SPS/CPS (Kayexalate or its analogues) crystals identified in gastrointestinal specimens from 2017-2019 at a tertiary care centre. Clinical details, relevant investigations, imaging and endoscopic findings, patient follow up details were obtained from the hospital electronic information system. Results: A total of 10 patients with SPS/ CPS crystals in the GIT were encountered over 2 years. Male to female ratio was 9:1, with mean age 66.5years (range 52-82 years). Eight cases were mucosal biopsies and 2 were resection specimens. Additional pathology (tumours, colonic perforation) was present in 80% of patients. The characteristic morphological appearance of the CPS/SPS crystals on H&E stains were supported by special stains -Periodic acid Schiff(PAS) and Acid fast Bacilli(AFB). In all cases, the treatment history with SPS/CPS for hyperkalaemia was obtained only after the histological examination. Most common etiology of hyperkalaemia encountered was chronic kidney disease(CKD)/ Acute on chronic kidney disease. Conclusion: It is important for pathologists to recognise the presence of these crystals especially in small biopsies as early feedback to clinicians can help in appropriate management and avoidance of more serious adverse outcome. To the best of our knowledge, this is the first series of 10 consecutive cases of SPS/CPS crystals encountered in gastrointestinal tract to be reported from India.

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Background and Aims: Molecular analysis is gold standard for diagnosis of synovial sarcoma (SS) but use of these ancillary techniques is limited by many practical issues like cost and limited resources. Several studies analyzed TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma and few studies disagreed. The objective of the study was to evaluate immunohistochemical expression of TLE1 in synovial sarcoma and its histological mimics. Methods: The study included a total of 63 cases; of which 28 were synovial sarcomas (SS) and 35 its histologic mimics. A tissue microarray was constructed from these cases and subjected to TLE immunostaining. Nuclear immunoreactivity of TLE1 was graded as 0, 1+, 2+ and 3+ based on intensity and percentage of cells. Results: All SS except one (27/28; 96.4%) were positive for TLE 1. These included 18 of monophasic spindle cell type (94.7%), 5 biphasic type (100%), followed by two each (100%) of poorly differentiated and calcifying type of SS. Of the other tumours 2 GISTs (50%), 2 haemangiopericytoma (66.7%), 2 schwannomas (50%) and one mesenchymal chondrosarcoma (33.3%) were positive for TLE1. Conclusion: TLE 1 is a highly sensitive marker with reasonable specificity for synovial sarcoma. Awareness of TLE1 expression in other tumours, is important to avoid misdiagnosis.

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Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare neoplasm with unknown etiology. It was previously referred to as Clear cell sarcoma of gastrointestinal tract. This tumor is characterized by a higher rate of local recurrence and metastasis. Due to its aggressive clinical course, distinguishing this entity from various other mimickers is very essential. Herein, we present a case of malignant GNET in a 33-year-old male patient.

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Acute promyelocytic leukemia (APL) is characterized by reciprocal translocation t(15;17)(q22;q21) and has a favorable prognosis upon immediate recognition and treatment. However, rare cases of APL show a cryptic insertion of retinoic acid receptor alpha (RARA) gene into promyelocytic leukemia (PML) gene which is negative both by fluorescence in situ hybridization (FISH) and conventional cytogenetics (CC). Morphology, cytochemistry and flow cytometry play a key role in early identification of such cases. Polymerase chain reaction (PCR) remains the most efficient diagnostic modality for detection of cryptic APL and other variants. It is important to identify these cases as they show beneficial response to retinoids and favourable prognosis. We herein present a rare case of cryptic APL negative by FISH and conventional cytogenetics but positive for PML-RARA by PCR.

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Objectives: To explore the effects of maternal and fetal outcomes after different diagnostic timings of placenta accreta and its types. Methods: We retrospectively collected the clinical information of 1178 pregnant women with placenta accreta in Fujian Maternity and Children Health Hospital from January 2012 to January 2017. According to the different diagnostic timings of placenta accreta, they were divided into groups of prenatal diagnosis and postpartum diagnosis; and according to the types of placenta accreta, they were divided into groups of accreta group, increta group, and percreta group. Results: 1. Women with antenatal diagnosis more often had placenta previa and history of previous cesarean section. 2. Women with antenatal diagnosis had a higher rate in blood loss and blood transfusion. 3. The rate of blood loss, blood transfusion, infection,disseminated intravascular coagulation (DIC), secondary laparotomy, hysterectomy had statistically significant differences (P < 0.05) in different types of placenta accreta. The deeper of placenta accreta, the higher the incidence of complications. Conclusion: It is important to pay attention for risk factors of the placenta accreta, then improve prenatal diagnostic rate of the placenta accreta and its types, which can forecast the severity of illness to improve maternal and fetal outcomes.

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Mature cystic teratoma of the ovary (MCT) is rare in pre and postmenopausal age patients. Among various types of malignant transformation in MCT, adenocarcinoma is a rare subtype. Dual type tumors arising from ovarian MCT have been described in the literature very rarely. A 47-year-old postmenopausal female patient presented with abdominal mass for ten years. The radiological opinion was a dermoid cyst. Grossly, a 22 × 20 × 10 cm, unilocular cystic left ovarian mass with intact capsular surface and focal thickened wall measured 3.0 cm. Microscopically, it showed components of all three germ cell layers. In addition, features of colonic type adenocarcinoma and well-differentiated neuroendocrine tumor (carcinoid) were noted and confirmed by immunohistochemistry (IHC). We report this rare case of synchronous malignancy arising from an ovarian MCT with a clinicopathological review.

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Pediatric melanomas are uncommon and sometimes arise in the background of giant congenital melanocytic nevus (GCMN). A 1-year-old girl was born with GCMN affecting her left half of the face and smaller nodules affecting trunk, hands, and feet. She developed an ulcerated lesion on the left temporoparietal scalp. The lesion showed features of GCMN along with large nests of a tumor composed of round cells with a vesicular nucleus, prominent nucleolus, plentiful mitoses, and areas of necrosis. Immunostaining for desmin, LCA, CD 20, CD 34, CD 99, BCL-2, and FLI1 was negative. Tumor cells showed immunopositivity for S-100 and HMB-45 confirming the diagnosis of melanoma. Immunostaining for BRAF V600E was negative; however, NRAS mutation was detected on next-generation sequencing. Unlike adult melanomas BRAF mutations are rare but NRAS mutations have been reported in pediatric melanomas. Adjunctive molecular testing will be important to understand the genetic basis of this disease and future targeted therapy.

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Gonadal dysgenesis is a distinct variety of Disorders of Sexual Differentiation (DSD) characterised by incomplete or defective formation of the gonads due to either structural or numerical anomalies of the sex chromosomes or mutations in the genes involved in the development of the gland. Here we present two such rare cases that presented during childhood. Both patients presented with ambiguous genitalia with a 45XO/46XY mosaic chromosome pattern. First case, an infant underwent laparoscopic excision of streak gonad, and a single stage hypospadias repair later. Second case, an adolescent who underwent gonadectomy as a child, presented with a mass which was excised and found to contain uterine and ovarian tissue; second stage hypospadias repair is being planned. Mixed gonadal dysgenesis usually presents with a unilateral testis, a streak gonad on the contralateral side and persistent mullerian structures. The most common karyotype noted is 45XO/46XY. These cases are known to have ambiguous external genitalia. The streak gonads have an increased malignant potential and thus, these patients should be carefully screened and followed up for gonadoblastoma.

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The majority of bone angiosarcomas are primary tumors while secondary angiosarcomas arise after radiation therapy or bone infarctus. This article presents a case of malignant transformation of monostotic fibrous dysplasia into angiosarcoma. An 80-year-old female presented with pain on right cruris. Radiological examination revealed a lesion with lytic areas and destruction of cortical bone on right tibia. Gross and histopathological examination showed two areas with an abrupt transition. The solid component was composed of curved, immature bony trabeculae in a fibroblastic stroma. The other component involved epitheloid cells forming slit-like vascular spaces. The diagnosis of angiosarcoma and fibrous dysplasia was given. Malignant transformation of fibrous dysplasia into angiosarcoma is extremely rare; as this is the sixth case in the existing literature. Prognosis of fibrous dysplasia is generally good and less than 1% of the patients develop a malignant tumor. Therefore, patients with fibrous dysplasia should be offered a life-long follow-up.

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WHO classification of adrenal tumors. Only a handful of cases have been reported so far. A 30-year-old lady presented with cerebrovascular accident. CT scans of the abdomen and pelvis revealed a 3.5-cm well-defined, smooth margined, heterogeneously enhancing, mass lesion in the right adrenal gland. She had no endocrine symptoms and urinary metanephnines were normal. She underwent right adrenalectomy for incidentaloma. Histopathology of the excised mass showed features of an adrenal schwannoma. Diagnosis of adrenal schwannoma on imaging studies is difficult preoperatively and raises suspicion of other adrenal tumors. Surgical excision followed by histopathology confirms the diagnosis.

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Pilomyxoid astrocytoma (PMA), a distinct clinico-histopathological entity in the World Health Organization classification 2007, tends to be locally aggressive, with higher chance of leptomeningeal dissemination, recurrence, and poor prognosis. PMA is generally seen in young children and tend to occur in the hypothalamic-chiasmatic region. Their presence in other parts of the brain in the non pediatric age group is uncommon. To the best of our knowledge we are presenting first case of cerebellar PMA associated with neurofibromatosis 1 (NF1) in a 40-year- old female, with immunohistochemical study.

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Background: Renal oncocytomas are benign epithelial tumors usually detected incidentally. They are typically solid,well-circumscribed,homogenous,mahoganybrown with a central stellate scar.Sometimes,they can have cystic degenerationand rarely present as a multilocular cyst which can be mistaken for other cystic renal carcinomas. Methods: We describe a case of incidentally detected multilocular cystic renal oncocytoma having an unusual gross appearance of multiloculation with perinephric fat invasion. The tumor exhibited tubulocystic architecture posed a diagnostic dilemma. Detailed study of multiple sections coupled with immunohisto chemistry helped elucidate the diagnosis. Till date, only eight cases of multicystic renal oncocytoma have been reported in the English literature. Conclusions: We emphasize the importance of awareness of this unusual morphologic variation to ensure correct diagnosis.

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Background: Soft tissue keratocysts (SKC) are extremely rare and show similar microscopic morphology to keratocystic odontogenic tumor. The aim was to investigate immunohistochemical (IHC) features and origin of SKCs developing in buccal mucosa and lateral facial deep region. Material and Methods: Expression of CK19, CK10/13, Ki67, Cyclin D1 and Osteopontin (OPN) of 9 SKCS were investigated using IHC. Forty different types of cysts in jaw/soft tissue were used as control. Follow-up was performed. Results: CK10/13 positivity occurred more frequently and intensely in SKC and intraosseous parakeratinized odontogenic keratocysts (COKC). However, OPN positivity was observed only in COKC. Conclusion: This is the largest case series of SKCs; along with first attempt to investigate the expression of OPN on SKC. Given the microscopic and immunohistochemical features, we prefer the view that SKC is odontogenic origin but represents the soft tissue counterpart of COKC, since their expressions of OPN were extremely different.

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Hobnail variant of papillary thyroid carcinoma (HV-PTC) is an unusual entity recently included in WHO classification of endocrine tumors (2017) and proposed as an aggressive variant of PTC. Compared to patients of classical counterparts, HV-PTC frequently has extrathyroidal extension, exhibits nodal or distant metastasis, and responds poorly to radioiodine treatment, leading to increased mortality. We hereby describe the cytohistological and immunohistochemical features of a metastatic HV-PTC in 55-year-old male, previously diagnosed as poorly differentiated papillary thyroid carcinoma in thyroidectomy specimen. Five years after total thyroidectomy with radical neck dissection the patient presented with gross pleural effusion showing multiple lung parenchymal and pleural based lesions with complete collapse of lung on computed tomography scan. The conventional cytology of pleural fluid showed dyscohesive cells arranged in micropapillary form gave the suggestion of metastatic papillary carcinoma. But the cell block preparation highlighted >30% hobnail cells arranged in micropapillary pattern showing increased atypical mitosis and occasional pseudoinclusions. Supplemented with immunohistochemistry (CK19, TTF-1, and p53), final diagnosis HV-PTC was made.

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There were rare clinical reports on clear cell tumor of the lung (CCTL). The clinical characteristics and underlying genetic mutation status of CCTL are poorly understood. From 2012 to 2017, patients pathologically diagnosed with CCTL in our hospital were investigated and analyzed based on clinical manifestations, pathological characteristics, prognosis and full gene mutation status through next generation sequencing (NGS) technology. During a 6-year period, four eligible patients were diagnosed with CCTL through surgical resection and were included in this study. All patients showed solitary nodules or lumps located in the left lung. The average maximum diameter of lesions was 2.5 ± 1.1 cm. Computed tomography (CT) imaging characteristics of these nodules/lumps demonstrated the features of benign tumors. The hematoxylin-eosin (HE) morphology and immunohistochemistry were consistent with the histopathological features of benign CCTL. Subsequent NGS analysis showed frame shift mutations of F2421/E2419, K1466E mutation, and p. 1450_1456 deletion mutation in mTOR gene in two of four patient samples and amplifications of MCL1 were observed in three of four samples. CCTL is a rare type of primary pulmonary mesenchymal tumor with good prognosis. Preliminary diagnosis on CT is usually sclerosing pneumocytoma. It is still unclear whether the occurrence and development of the disease are related to specific gene mutation. In this study, the genomic findings of frame shift mutation of mTOR genes and amplification of MCL1 gene in CCTL suggest that these mutations might play a role in proliferation of CCTL.

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Malignant eccrine spiradenoma is an extremely rare neoplasm of adnexal origin. It almost always originates from a preexisting long standing eccrine spiradenoma. We present a case of malignant eccrine spiradenoma arising from benign counterpart and having both carcinomatous and sarcomatous differentiation. Here we present a case of a 46 years old lady who presented with a long standing small nodule on her left leg of 7 years^' duration with suddenly increase in size. Grossly the mass was partly solid and partly cystic measuring 11.5 cm in maximum dimension with cystic area forming the deeper plane. On microscopy, the superficial dermis showed well demarcated lobules of benign eccrine spiradenoma. Deeper dermis showed tumor cells with features of malignant transformation having both carcinomatous and sarcomatous component. After wide local excision patient is now doing well. The diagnosis of malignant eccrine spiradenoma requires a thorough histopathological examination of the lesion and requires finding a focus of benign spiradenoma within or adjacent to malignant tumour. Wide local excision and close follow-up for early detection of recurrence and metastasis is the mostly recommended management modality.

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We present a case of a 48-year-old man's unexpected death affected by a relapsed clivalchordoma. After partial excision surgery of the neoplasm, he manifested 5 days later, in conditions of well-being, a sudden lethal extracranial hemorrhage from nose and mouth. The autopsy examination and the subsequent histological investigations did not allow us to clarify the exact origin of the bleeding. Based on the negativity of the accurate examinations performed, the extent of the bleeding, and the findings highlighted by the means of the nuclear magnetic resonance (NMR) carried out a few days before death, we have considered reasonable to localize the source of hemorrhage in the intrapetrous tract of the left internal carotid artery. Since this is a unique event, never previously documented, we believe that our report may be of interest to the scientific community.

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Context: Pterygium is a degenerative disease that consists of conjunctival epithelia and fibrovascular tissue. Some studies suggest that there is a defect in the regulation of apoptosis in the epithelial cell cycle characterized by the development of the disease. But, still this matter being debated. Aims: In this study, the clinical, histopathological data, and the expression of the cell cycle regulator Cyclin D1, anti-apoptotic BCL-2, tumor suppressor p53, and cell proliferation marker Ki-67 were searched in pterygium samples. Subjects and Methods: The study enrolled 62 cases of primary pterygium who underwent excision between 2014 and 2017. Recurrent and pseudo-pterygium cases were excluded from series. The clinical data were obtained from the patient files and the slides were reevaluated for the histopathological data. Slides of all were stained by Cyclin D1, BCL-2, and Ki-67 by the immunohistochemical method. For each immunohistochemical marker, first the staining was determined as negative or positive. Then if there is a staining, the hot zone (the area containing more positive cells) was determined and staining percentage (SP) was assessed by counting positive cells/100 epithelial cells). Results: Solar elastosis, edema, inflammation, and epithelial dysplasia were found statistically different between the control group and the patient group (P value <0.001, <0.001, <0.001 <0.001, respectively). A significant difference was found for staining percentage (SP) of Ki-67, p53, BCL-2 between the control group and the patient group (P values <0.001, 0.002, <0.001, respectively). There were no significant differences in the SP of Cyclin D1 between the two groups (p: 0,133). Conclusions: Our results indicate an abnormal expression of p53, BCL-2 and elevated proliferation measured by Ki-67 in pterygium samples when compared to normal conjunctiva. Besides the mesenchymal changes, the increased proliferation and the failure of apoptosis in the epithelial cells participate in the development of pterygium, as well.

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