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   Table of Contents - Current issue
Coverpage
October-December 2020
Volume 63 | Issue 4
Page Nos. 513-686

Online since Wednesday, October 28, 2020

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EDITORIAL  

From Editor's desk p. 513

DOI:10.4103/IJPM.IJPM_1241_20  
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EDITORIAL INSIGHT Top

Journal indexing: Myths and facts Highly accessed article p. 515

DOI:10.4103/IJPM.IJPM_1265_20  
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NEW HORIZON Top

Dr. R. K. Gadgil - An eminent Indian pathologist, pioneer in starting rural medical camps and a researcher who discovered an endemic focus of schistosomiasis in Maharashtra, India p. 518
Dhaneshwar N Lanjewar, Ulhas L Wagholikar, Vijay V Joshi
DOI:10.4103/IJPM.IJPM_686_20  
Dr. Ramchandra Krishnaji Gadgil (RKG) was a pioneer and an eminent researcher. Along with clinician colleagues, he started rural medical camps in 1952, in Maharashtra, India. Through his meticulous research, he discovered in the same year an endemic focus of schistosomiasis in the village, Gimvi, and in 1956, went on to establish a life cycle of the Schistosoma hematobium, involving a completely new intermediate Mollusk host “Ferrisia tenuis”, a rather epoch making discovery in the realm of Mollusk intermediate host in relation to human schistosomiasis. His instructions and guidance to the Government Public Health department led eventually to eradication of the schistosomiasis focus in that village in 1969, thereby setting an example for pathologists to head out into the field, do clinical work and pursue with disciplined curiosity a new pathological finding in the laboratory. The fascinating story of his life, education and research is described in this paper.
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ORIGINAL ARTICLES Top

Circulating free DNA as a marker of response to chemoradiation in locally advanced head and neck squamous cell carcinoma Highly accessed article p. 521

DOI:10.4103/IJPM.IJPM_28_20  
Context: Liquid biopsy has moved from bench to bedside as a non-invasive biomarker for early diagnosis and monitoring treatment response. Objective: This study investigated the role of circulating free DNA (cfDNA) as a diagnostic marker in locally advanced head and neck squamous cell carcinoma (HNSCC) and in monitoring response to chemoradiation therapy. Materials and Methods: Serum was collected from treatment naïve, histopathologically diagnosed tumors in 24 HNSCC cases and 16 normal controls. CfDNA levels were quantified using β globin gene amplification. Results: The cfDNA level was significantly elevated in HNSCC (992.67 ± 657.43 ng/mL) as compared to healthy controls (60.65 ± 30.42 ng/mL, P = <0.001). The levels of cfDNA did not significantly correlate with TNM stage, lymph node involvement and grade. In responders, percentage decrease in cfDNA levels was 9.57% and 29.66%, whereas in nonresponders percentage increase was 13.28% and 24.52% at the end of three months of follow-up. Conclusion: Our study adds to the evidence that cfDNA levels are significantly higher in HNSCC cases and provides some evidence that levels increase with tumor progression. CfDNA may be a promising prospective non-invasive marker to predict response in patients undergoing chemo-radiotherapy.
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Worst pattern of invasion – type 4 (WPOI-4) and Lymphocyte host response should be mandatory reporting criteria for oral cavity squamous cell carcinoma: A re-look at the American Joint Committee of Cancer (AJCC) minimum dataset Highly accessed article p. 527

DOI:10.4103/IJPM.IJPM_662_19  
Background: A proportion of early-stage node-negative oral squamous carcinoma patients fail despite complete surgical resection. Adjuvant treatment in early oral cancer is controversial and is often individualized based on stage, depth, and margin status. Aims: We reviewed various histological markers in pT1/T2N0 cases, resected upfront with elective nodal dissection, with an emphasis on tumor-tissue interface characteristics of the worst pattern of invasion (WPOI), tumor cell nest size (sCNS), budding and lymphocytic host response (LHR), to assess their prognostic significance. Materials and Methods: Archived blocks of 95 cases were reviewed. Tumor stage, grade, size, depth of invasion, lymphovascular, and perineural invasion, WPOI, LHR, sCNS, and tumor bud (single cells or <5 cell clusters) score were recorded. Statistical Analysis: Prognostic significance was statistically analyzed using SPSS software version 20. Results: Depth of invasion (P = 0.008), WPOI- 4 and 5 (P = 0.033), sCNS (<5 cells) at tumor interface (P = 0.010), high bud count (≥3 buds/40 × hpf) (P = 0.021) and poor LHR (P = 0.019) correlated significantly with poor disease-free survival on univariate analysis. However, on multivariate analysis only LHR and WPOI-4 (that is presence of small cell nests or buds) were significant, with high hazard ratio of 4.351 (95% CI 1.290–14.676, P = 0.018) and 5.019 (95% CI 1.212–20.789, P = 0.026), respectively. Conclusion: We propose mandatory reporting of WPOI-4 at the tumor interface and absence of LHR, as significant markers of poor prognosis in early-stage oral cavity squamous carcinoma.
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Assessment of apoptotic index in various grades of oral epithelial dysplasia: A cross-sectional study p. 534

DOI:10.4103/IJPM.IJPM_565_19  
Context: Oral cancer is a major health problem worldwide. In cancer, the equilibrium between cell proliferation and apoptosis is disturbed. The defect in the apoptotic pathway allows cells to proliferate with genetic abnormalities. Thus, the apoptotic index (AI) can be used to assess the significance of apoptosis as a proliferative marker in oral epithelial dysplasia. Aims: To assess the apoptotic index in various grades of epithelial dysplasia. Objectives: 1) To calculate the apoptotic index in various grades of oral epithelial dysplasia, 2) To compare the apoptotic index between various grades of oral epithelial dysplasia, 3) To predict the biologic behavior of oral epithelial dysplasia based on an apoptotic index. Settings and Design: Cross-sectional tissue analyzing study. Methods and Materials: This study constituted 30 cases, previously diagnosed with various grades of oral epithelial dysplasia (OED). AI was calculated as the number of apoptotic bodies/cells expressed as a percentage of the total number of cells counted in each case. Statistical Analysis Used: Statistical analysis was carried out using ANOVA test. Results: A statistically significant difference was observed between mild dysplasia and severe dysplasia where P = 0.002. The mean AI was increased progressively with increasing grades of OED. Conclusions: This study demonstrated the clinical significance of apoptosis in assessing disease progression in Oral Potentially Malignant Disorder (OPMD) which may be used as a prognostic indicator in OED. This would, in turn, help in knowing the prognosis of the disease and to develop targeted drug therapy.
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Impact of ERCC1 gene polymorphisms on response to cisplatin based therapy in oral squamous cell carcinoma (OSCC) patients p. 538

DOI:10.4103/IJPM.IJPM_964_19  
Background and Objectives: Cisplatin is one of the major drugs that used in the treatment of oral cancer.Excision repair cross-complementation group 1 (ERCC1) is a key DNA repair gene in the nucleotide excision repair pathway which is activated in the repair of intra- and interstrand DNA crosslink caused by platinum-based treatment. The aim of this study was to investigate the association between polymorphisms in ERCC1 (C118T & C8092A) genes and the response to cisplatin-based chemotherapy. Methods: ERCC1polymorphisms (C118T & C8092A) were studied using PCR-RFLP method from 150 OSCC patients as cases as well as 150 normal tissues from the same patients were collected as controls for this study. Results: Frequencies of ERCC1 C118C, C118T and T118T genotypes were 60%, 28% and 12% in OSCC patients and 78%, 19% and 3% in the controls, respectively. The C118T & T118T genotype had a 1.69 and 4.97 -folds increased risk for OSCC. Frequencies of ERCC1 C8092C, C8092A and A8092A were 78%, 18% and 4% in the OSCC patients and 89%, 10%, amd 1% in the controls, respectively. The C8092A genotype showed a 1.97-fold increased risk for OSCC. Interpretation & Conclusions: In conclusion, this study highlights the DNA repair gene polymorphisms that might play a role in mediating susceptibility to oral squamous cell carcinoma and cisplatin therapy. Our data suggest that the ERCC1 C118T, T118T and ERCC1 C8092A genotypes are genetic risk factors for Oral squamous cell carcinoma and ERCC1 118 C/T and C8092A polymorphisms have significant influence on clinical outcome.
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The clinical usefulness of chemokine C-X-C Motif Ligand 12 as a diagnostic marker for Papillary Thyroid Carcinoma p. 544
Sang Ah Lee, Jae Hyuck Choi, Suk Ju Cho, Jee Won Chang, Young Hee Maeng
DOI:10.4103/IJPM.IJPM_722_19  
Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer worldwide. It is essential to develop methods for the accurate diagnosis of PTC to avoid unnecessary surgery. The chemokine C-X-C motif ligand 12 (CXCL12) is associated with various cancers. We aimed to investigate the efficacy of CXCL12 in the diagnosis of PTC in fine-needle aspiration (FNA) specimens. Methods: We prospectively collected samples from 58 patients who were scheduled for surgical treatment of PTC from 2013 to 2015. Tissue samples of 31 people with benign thyroid conditions were used as controls. Immunocytochemical and immunohistochemical staining for CXCL12 was performed on FNAs and corresponding tissue specimens. B-type Raf kinase (BRAF) V600E mutant protein expression and gene mutation were also analyzed to compare the clinical usefulness. Results: The mean age of the patients was 49.1 ± 1.4 years and 88.1% were women. Positive CXCL12 staining was observed in 6.5% of benign and in 98.3% of PTC samples; positive BRAF V600E mutant protein expression was found in 19.4% of benign and 93.1% of PTC samples. For the diagnosis of PTC for CXCL12 staining of FNA specimens, the calculated values were 93.1% sensitivity, 90.3% specificity, 94.7% positive predictive value, 87.5% negative predictive value, and 89.1% accuracy. CXCL12 had 100% sensitivity and specificity for the 12 cases of atypia of undetermined significance (AUS) diagnosed in FNA specimens. Conclusions: CXCL12 may be a useful diagnostic tool for PTC, especially when the FNA specimen is classified as AUS.
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Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas p. 551

DOI:10.4103/IJPM.IJPM_637_18  
Aims: The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters. Materials and Methods: We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas. Results: In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion. Conclusions: Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.
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Neuroendocrine carcinomas of the breast: Case series with review of literature Highly accessed article p. 559

DOI:10.4103/IJPM.IJPM_908_19  
Background: The breast tumors with neuroendocrine differentiation show features similar to their counterparts in other organs. Neuroendorine carcinomas account for less than 0.1% of all breast carcinomas. Aims: To study the demographics and clinicopathological prameters ten cases showing neuroendocrine carcinoma breast. Material and Methods: Ten cases showing neuroendocrine carcinoma were studied. The data was analysed for demographics and clinicopathological prameters. The Immunohistochemistry for ER, PR, Her2neu, Synaptophysin, Chromogranin, NSE, Ki67 index and EMA were done in these cases. Results: Nine Trucut biopsies were reported as infiltrating duct carcinoma and one case as IDC with neuroendocrine differentiation with focal mucinous areas.The histopathological slides of breast excision specimens revealed clusters of cells arranged in sheets and small nests separated by thin fibrous septae in eight of the cases. Trabeculae were noted in two case and in another rosettes were noted. DCIS component was noted in two cases. Infiltration into fat in five of the cases. One case showed pools of mucin. The tumour cells were positive for synaptophysin in 5/10 cases, chromogranin in 8/10 cases and NSE in 9/10 cases. Estrogen receptor positivity was noted 6 cases (6/10), progesterone receptor positivity in 8 cases (8/10) and Her2neu positivity in 5 cases (5/10). Conclusion: NECB cases are more likely to ER/PR positive with variability of expression of neuroendocrine markers. These tumors are more aggressive with propensity for distant metastasis. Endocrine therapy may be more beneficial than standard chemotherapy. Anti-angiogenic markers are an exciting new approach for these case, which is yet to be explored.
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Role of platelet aggregation in metastatic breast cancer patients p. 564

DOI:10.4103/IJPM.IJPM_817_19  
Background and Aims: Breast cancer is the most common female cancer in the world. Although early detection and systematic adjuvant therapy has improved survival, distant metastasis remains the leading cause of breast related mortality. The relationship between tumor and the hemostatic system is increasingly recognized as an important regulator of breast cancer progression. Tumors have the ability to induce platelet aggregation which is referred as tumor cell induced platelet aggregation (TCIPA). This study highlights that increased platelet aggregation plays an important role in metastasis of breast cancer. The aim here is to study the role of platelet aggregation in metastatic breast cancer patients using: • ADP • Thrombin. Methods: 30 cases (n = 30) of metastatic breast cancer and 30 controls (n = 30) of non-metastatic breast cancer which were clinically diagnosed and histopathologically confirmed were included in this study. Platelet aggregation studies in vitro using ADP and Thrombin were performed using an optical aggregometer in both cases and controls. Other parameters like platelet count, histological grade and surrogate molecular classification was also correlated with platelet aggregation. Results: In this study, increased aggregation was seen with ADP and thrombin in the metastatic cases and none showed increased aggregation in the non-metastatic breast cancer patients. Also, high platelet count and higher histological grade correlated with increased aggregation. However, no correlation was seen between platelet aggregation and the surrogate molecular classification. Conclusion: It was concluded from this study that platelet aggregation has an important part to play in the tumor metastasis of breast cancer patients.
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Gallbladder stone formation in Iraqi patients is associated with bacterial infection and HLA class II-DRB1 antigens p. 570

DOI:10.4103/IJPM.IJPM_841_19  
Background: Gallbladder stone is recently increased among the Iraqi society due to many risk factors such as bacterial infection and some HLA class II antigens. Aim(s): This study investigates the types of bacterial infection and HLA-DRB1 antigens' ratio that may be correlated with gallbladder stone formation. Setting and Design: The study included 45 patients and the same number of healthy individuals as a control group. Patients were with multiple gallstones. Gallstone bacterial culture was demonstrated to diagnose viable bacteria. HLA-DRB1 alleles' frequency was investigated using sequence-specific oligonucleotide probes (PCR-SSOP). Results: Irrespective of gallstone type and size, different types of living viable bacteria were isolated from the cores of the studied gallstones in 80% of the studied cases versus 20% of sterile gallstones. Gram-negative bacteria cultures were the dominant (89.3%), including Escherichia coli, Klebsiella spp., Proteus spp., Acinetobacter spp., and Enterobacter spp. Mixed infection of Gram-positive and negative bacteria was noted: Escherichia coli and Enterococus spp. and the others of Escherichia coli and Acitobacter spp., and Klebsiella spp. and Pseudomonas spp. Gram-positive bacteria cultures were also detected at lower rate (10.7%) including Staphylococci spp. The frequency of HLA-DRB1*03:01, HLA-DRB1*4:03, HLA-DRB1*13:22, and HLA-DRB1*15:10 alleles was significantly elevated in patients compared to the healthy control group. Conclusion: Results ensured the viability of the bacteria isolated from the core of gallstones and showed positive correlation between gallbladder stone and different bacterial infection. In addition, HLA-DRB1 alleles were significantly high in patients compared to healthy control group suggesting them as risk factors (P < 0.05).
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High expression of lncRNA SNHG1 in prostate cancer patients and inhibition of SNHG1 suppresses cell proliferation and promotes apoptosis p. 575

DOI:10.4103/IJPM.IJPM_612_19  
Objective: This study aimed to investigate the expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in prostate cancer (PCa) patients and to assess the effects of SNHG1 on PCa cell proliferation and apoptosis. Materials and Methods: A total of 134 PCa patients were randomly included from patients who underwent surgical resection at our hospital from October 2015 to December 2016. The SNHG1 expression levels in PCa tissues and paired adjacent non-cancerous tissues were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The association of the SNHG1 expression with clinical-pathological features of PCa patients was summarized and evaluated. A short interfering (si) RNA targeting SNHG1 and pcDNA3.1-SNHG1 were transfected into PC3 and DU145 PCa cell lines, and transfection efficiency was verified by qRT-PCR. Cell proliferation and apoptosis were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, respectively. Results: The SNHG1 expression was significantly upregulated in PCa tumor tissues compared with paired adjacent non-cancerous tissues. The SNHG1 expression was obviously associated with the TNM stage, Gleason Score, lymph node invasion, and long-term metastasis mortality rate. Silencing of SNHG1 inhibited cell proliferation and promoted apoptosis in PC3 and DU145 PCa cell lines in vitro, while overexpression of SNHG1 led to opposite results. Conclusion: LncRNA SNHG1 was upregulated and associated with aggressive malignant behavior in PCa progression. SNHG1 might serve as a potential prognostic biomarker and potential therapeutic target for PCa.
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Utility of cell block as an adjunct to liquid-based cytology for diagnosing papillary thyroid carcinoma p. 581

DOI:10.4103/IJPM.IJPM_999_19  
Background: Although liquid-based cytology (LBC) has gained popularity among clinical laboratories, it is unclear whether it is equivalent to conventional smears for making a definite diagnosis of papillary thyroid carcinoma (PTC). The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) suggests a definite diagnosis of PTC is preferred when there are at least one of three features (papillary architecture, psammomatous calcifications, and frequent pseudonuclear inclusions) plus other typical cytomorphological findings. This study evaluated whether an additional cell block (CB), prepared from the residual LBC material, could help improve the diagnosis of PTC. Materials and Methods: A total of 62 cases with both ThinPrep LBC and CB preparations and histopathological follow-up of PTC were retrieved between November 2016 and March 2019. The ThinPrep LBC and CB slides were reviewed separately to identify any papillary architecture, psammomatous calcifications, or pseudonuclear inclusions for diagnosing PTC. Results: Among the 51 cases with cytological diagnosis of PTC in the LBC+CB slides, the CB provided additional diagnostic information in 15 cases, which were initially diagnosed as suspicious for PTC based on the LBC slides alone. This information included papillary architecture (n=11), psammomatous calcification (n=1) and pseudonuclear inclusions (n=5). The number of specimens in the 51 cases containing at least one of the three features increased from 42 (LBC) to 51 (LBC+CB). The accuracy for diagnosing PTC increased from 58.1% for LBC alone to 82.3% for the LBC+CB examination. Conclusion: An adjunctive CB preparation may improve the LBC technique for diagnosing PTC.
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Fungal infection in post-renal transplant patient: Single-center experience p. 587

DOI:10.4103/IJPM.IJPM_306_19  
Introduction: Fungi are ubiquitous organisms and significantly alter the post-transplant course. They are a major cause of morbidity and mortality and more so in developing countries. Aims: To study the clinical profile, etiology, risk factors, treatment, and outcome of fungal infections in post-renal transplant recipients. Materials and Methods: This was a cross-sectional observational retrospective study from January 2014 to June 2017 wherein renal transplant recipients with invasive fungal infection were included and were followed. Results: Amongst 550 renal transplant recipients, 56 (10.2%) patients developed invasive fungal infection. Mean age of patients was 40.61 ± 10.06 (13-66) years and mean duration of acquiring infection post-transplant was 25.33 ± 23.65 (1-96) months. Male to female ratio was 3:1. Fever was the commonest presentation observed in 89.3% patients. Cough (76.8%), breathlessness (64.3%), sputum (55.3%), hypoxia (50%), and hemoptysis (10.7%) were other common clinical symptoms at presentation. Mean serum creatinine at presentation was 1.70 mg/dl. Most common invasive fungal infection isolated was Mucormycosis 15 (26.7%), foolwed by Aspergillosis 13 (23.2%), Pneumocystis jiroveci 12 (21.4%), Cryptococcus 6 (10.7%), Candida 4 (7.1%), Histoplasmosis 3 (5.3%), Phaeohypomycosis 2 (3.5%), and 5 (8.9%) patients had undetermined fungal etiology. Twenty (35.7%) patients had evidence of dual infection. Use of antithymocyte globulin 27 (48.2%), post-transplant diabetes mellitus 18 (32.1%), Cytomegalovirus (CMV) infection 16 (28.5%), anti-rejection therapy 9 (16%), and Hepatitis C infection 7 (12.5%) were some identified risk factors. Ten (17.8%) patients had graft loss and 12 (21.4%) patients died in the study period. Conclusions: Invasive fungal infection is a serious threat to renal transplant recipients. Patient and graft survival is significantly affected by fungal infection in developing world.
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Prevalence of constitutional macrothrombocytopenia in the immigrants of Northern and Eastern states of India p. 593

DOI:10.4103/IJPM.IJPM_20_20  
Background: Thrombocytopenia is generally alarming to both clinicians and patients as the consequence can be disastrous. However, some of the conditions associated with thrombocytopenia can be innocuous. Unless this is recognized, detection of thrombocytopenia results in series of further investigations and management plan by clinicians. Hematological investigation in an apparently healthy/asymptomatic individual can throw up many surprises. One of them is thrombocytopenia and giant platelets on peripheral smear examination. Asymptomatic constitutional macrothrombocytopenia (also called as Harris platelet syndrome) is increasingly recognized in north and eastern parts of India. However, this condition is nearly unknown in southern part of our country. With Increased immigrants to south India from northern and eastern states, it becomes imperative for both clinicians and lab physicians to be aware of the magnitude of the condition and interpret appropriately. This can avoid unnecessary anxiety and investigations. Materials and Methods: Blood samples from 300 north and northeastern immigrants (Cases) and equal number of healthy subjects from south India (Controls) were examined for hematological parameters. Peripheral smears were examined for the presence of giant platelets. Results: Constitutional macrothrombocytopenia was seen in 4.3% of the cases and in 0.66% of the controls. The difference was statistically significant with a Fischer exact P value of 0.0067. The prevalence of macrothrombocytopenia on subjective assessment of peripheral smear was 6.7% in the cases and 1% in the control group. Conclusions: The prevalence of Harris platelet syndrome was found to be 4.3% in the immigrants from north and northeastern states.
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BRIEF COMMUNICATION Top

Aorto-esophageal fistula – An autopsy series p. 597

DOI:10.4103/IJPM.IJPM_26_20  
Background: Fistulous tracts within the thorax are best exemplified aorto-esophageal fistulas (AEFs), which are rare exsanguinations of the upper gastrointestinal tract. Most of them are diagnosed at autopsy. Aim: This is an autopsy-based study of fatal cases of AEFs gathered over a period of 20 years. Materials and Methods: Cases of AEFs were retrieved from the autopsy records of the cardiovascular pathology sub-specialty at a tertiary care center and were studied with reference to demographic details, modes of clinical presentation, and pathological features. Results: Ten cases of AEFs (10 males and 8 females, mean age of 46.9 years) were identified in a span of 20 years. A clinical diagnosis of AEF was made in only one patient, while the rest were identified at autopsy. All the patients had a bout of massive and fatal hematemesis. The fistulous connections, involving the middle-third of the esophagus, were caused by a fishbone, esophageal ulceration and aneurismal aortic diseases of varied etiology. Conclusions: AEFs are often missed or misdiagnosed. Early recognition of this rapidly fatal condition is essential as these fistulas require quick and aggressive management.
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Histopathology of morphea: Sensitivity of various named signs, a retrospective study p. 600

DOI:10.4103/IJPM.IJPM_67_20  
Background: Morphea or localized scleroderma is characterized histopathologically by sclerosis, fibrosis, and atrophy of the skin and subcutaneous tissue. Various authors have named the characteristic findings seen in histopathology of morphea and have labeled them as specific signs, including line sign, cookie-cutter sign, and square biopsy sign. Besides, other findings mentioned include high eccrine glands and the presence of interstitial mucin. The present study was undertaken to assess the sensitivity of these tests in the histopathological diagnosis of morphea. Methods: All cases clinically diagnosed and histopathologically reported as morphea in the last 3 years (September 2016 to August 2019) were included. The slides were reviewed by two independent investigators for the presence of line sign, cookie-cutter sign, square biopsy sign, high eccrine glands, and mucin. The sensitivity of these signs in accurately diagnosing morphea was assessed. Besides, specificity, positive predictive value, and negative predictive value of these signs were assessed using 40 random histopathology slides as controls. Results: The highest sensitivity was of high eccrine glands (82.5%) followed by the presence of mucin in the dermis (77.5%). Cookie-cutter sign and square biopsy signs were seen in 70% and 62.5% patients, respectively. Line sign was least sensitive of all, seen in 45% of biopsy specimens, but was most specific (82.5%). Conclusion: A fair number of biopsies of morphea displays the presence of high eccrine glands, mucin, cookie-cutter sign, square biopsy sign, and line sign. These signs thus can be of immense help to the dermatopathology trainees.
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CASE REPORTS Top

Palisaded encapsulated neuroma in tongue – A commonly misdiagnosed peripheral nerve sheath tumor p. 604

DOI:10.4103/IJPM.IJPM_515_19  
Palisaded encapsulated (solitary circumscribed) neuromas are benign neural tumors, rarely found in oral mucosa. This case reports a 24-year-old man that presented a unique soft nodule at the left side of the tongue. An excisional biopsy was performed under local anesthesia and histopathological examination of the surgical specimen revealed a well circumscribed mass composed of spindled Schwann cells, often aligned and fasciculated, forming occasional nodules embedded in a fibrous stroma. Histopathological analysis showed the presence of positive cells for S-100, EMA, CD57, and collagen IV. Based on clinical and microscopical features, the diagnosis established was of palisaded encapsulated neuroma. This case report aims to discuss the differential diagnosis among palisaded encapsulated neuroma and the other neural tumors that affect the oral mucosa.
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Thymic amyloidoma mimicking sclerosing thymoma in a triple vessel disease patient: An incidental finding p. 608

DOI:10.4103/IJPM.IJPM_432_19  
A 65 year old man who underwent coronary artery bypass graft (CABG) for triple vessel disease was found to have enlarged thymus. Biopsy of the thymic mass revealed localised amyloid deposits demonstrating strong apple green birefringence on polarised microscopy. Localized thymic amyloidosis is an extremely rare finding with present case as the seventh in the world and the first in India. Review of literature of thymic amyloidoma and its close differential sclerosing thymoma is hereby described.
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Limited granulomatosis with polyangiitis presenting as an isolated lung lesion p. 611

DOI:10.4103/IJPM.IJPM_831_19  
Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis involving small and medium-sized blood vessels and granulomatous inflammation of upper and lower respiratory systems and/or renal system. In the limited form of GPA, there is no systemic involvement of disease with sparing of kidneys. The respiratory system is the commonly involved organ in limited GPA. Herein, we report the case of a 40-year-old male who was initially diagnosed as sarcoidosis clinically. Lung biopsy revealed necrotizing granulomatous angiitis. Diagnosis of GPA was made which was substantiated by antineutrophil cytoplasmic antibody (ANCA) positivity. This was a case of limited GPA with isolated lung involvement. The early diagnosis and initiation of treatment are critical for improved survival of patients with GPA. Tissue biopsy is necessary for the diagnosis of GPA.
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Anaplastic Lymphoma Kinase positive large B cell lymphoma of ileocaecal mesentery: A case report p. 615

DOI:10.4103/IJPM.IJPM_296_19  
ALK+ large B cell lymphoma (LBCL) is a very rare aggressive neoplasm. It accounts for less than 1% of diffuse large B cell lymphoma (DLBCL). This is a case report of ALK+ DLBCL in a 34-year-old woman with an ileocaecal mesenteric mass. Microscopically, the neoplastic cells were of high grade along with a spindle cell component. Immunohistochemistry revealed ALK+, MUM-1+, LCA+, Vimentin+, EMA+ and negative for CK 20, CK 7, neuroendocrine, melanocytic, muscle specific, and GIST panel markers. This case report, hence, presents the rarity of this tumor.
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Borderline serous papillary tumor of the testis p. 618

DOI:10.4103/IJPM.IJPM_837_19  
Ovarian epithelial type tumor of the testis is a rare entity. Herein, we report borderline serous papillary tumor of the testis in a 37-year-old male, which was clinically suspected to be a testicular malignancy.
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Florid histiocytic reaction to oxidized cellulose masquerading as ovarian malignancy: Report of two cases p. 620

DOI:10.4103/IJPM.IJPM_688_19  
Bioabsorbable hemostatic agents like oxidized regenerated cellulose (ORC) are widely used in surgical practice. Rarely, adverse events due to retained ORC may occur and can pose a diagnostic dilemma. The unique tissue response to ORC may be misdiagnosed as signet ring type of adenocarcinoma. This article aims to highlight this rare phenomenon. We report two such cases involving the ovaries. Both the patients presented with ovarian cysts and tubo-ovarian adhesions 1–2 years following surgery for benign ovarian pathology. The present biopsies were featured by sheets of large cells with abundant vacuolated cytoplasm and often small peripherally displaced nuclei having “signet ring” appearance. These cells were negative for pan-cytokeratin and strongly positive for CD68, indicating the histiocytic nature of the cells. It was confirmed that in both the patients, at the time of the initial surgeries, hemostasis was ensured by packing with ORC.
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Alveolar rhabdomyosarcoma of urinary bladder presenting as acute leukemia: A diagnostic trap p. 623

DOI:10.4103/IJPM.IJPM_850_19  
Rhabdomyosarcoma (RMS) masquerading as acute leukemia (AL) is very rare. We report a case which presented as acute leukemia subsequently diagnosed to be Alveolar RMS of Urinary Bladder. Although cases of RMS with leukemic presentation have been reported, to our knowledge this is the first case of Alveolar RMS of Urinary Bladder with leukemic picture at initial presentation. We would like to emphasize that this critical error can have serious consequences on the treatment and outcome of these patients.
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Mullerianosis of urinary bladder: The great impersonator p. 627

DOI:10.4103/IJPM.IJPM_726_19  
Müllerianosis of the urinary bladder is a rare entity with less than 30 cases reported. It encompasses a mixture of different types of Mullerian lesions like endometriosis, endocervicosis, and endosalpingiosis. It typically affects the women of reproductive age group. The symptoms vary from hematuria and dysuria, to pelvic pain, which may be associated with menstruation. It can mimic a malignant tumor clinically and radiologically; hence, it is important that a correct diagnosis is rendered in these cases to avoid unnecessary radical procedures. Herein we report a case of mullerianosis of the urinary bladder in a young female and discuss the important differential diagnosis and various treatment modalities.
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Dedifferentiated liposarcoma with heterologous spindle cell rhabdomyoblastic de-differentiation: An unusual pattern expanding the morphological spectrum p. 630

DOI:10.4103/IJPM.IJPM_936_19  
Dedifferentiated liposarcoma (DDLS) is characterized by a wide histopathological spectrum. Spindle cell type of rhabdomyoblastic dedifferentiation has been rarely described in case of DDLS. A 39-year-old male presented with a recurrent retroperitoneal tumor mass, diagnosed as well-differentiated liposarcoma, for which he underwent surgical excisions on two occasions, followed by adjuvant radiation therapy previously. Computed tomogram scan his of abdomen revealed a large-sized, fat-containing recurrent, retroperitoneal mass, measuring 18.1 cm in the largest dimension. Histopathologic examination of the resected tumor revealed distinct areas of well- and dedifferentiated liposarcoma, including areas reminiscent of a myxofibrosarcoma, further progressing into a high-grade spindle cell sarcoma with fascicular and “Herringbone-like” growth patterns (fibrosarcoma-like). Immunohistochemically, high-grade spindle cell sarcomatous (dedifferentiated) component displayed distinct positivity for desmin and MyoD1, along with focal tumor nuclei, showing nuclear positivity for myogenin. Both well-differentiated liposarcomatous and dedifferentiated components displayed diffuse, intense nuclear positivity for MDM2 (overexpression) and p16INK4A. Furthermore, upon testing tumor sections displaying spindly sarcomatous areas for MDM2 amplification, by FISH technique, nearly all tumor cells displayed MDM2 gene amplification. This case constitutes one of the rare cases of DDLS displaying spindle cell rhabdomyoblastic dedifferentiation. Its diagnostic and treatment implications are discussed herewith.
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Generalized type 2 segmental disseminated superficial actinic porokeratosis coexisted with multiple cutaneous squamous cell carcinomas: Analysis of two cases p. 634

DOI:10.4103/IJPM.IJPM_987_19  
Porokeratosis (PK) is defined as hyperpigmented macules or patches with a distinctive, ridge-like hyperkeratotic border which is histologically characterized by a cornoid lamella. Here, we report two cases of linear porokeratosis which converted to multiple cutaneous squamous cell carcinoma after long history progression. In addition, patient 2 was accompanied by secondary dermal amyloid deposits, which was rare reported.
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Ichthyosis uteri with dysplasia - A case report p. 637
Chitrawati B Gargade, Archana H Deshpande
DOI:10.4103/IJPM.IJPM_223_19  
Ichthyosis uterus is an uncommon condition in which the entire surface of the endometrium is replaced by stratified squamous epithelium. This condition most commonly develops secondary to longstanding cervical obstruction or chronic inflammation. It is considered a benign lesion, but its association with endometrial malignancy has been reported in the literature. We are reporting a case of ichthyosis uteri with dysplasia associated with cervical intraepithelial neoplasm (CIN III). The case is reported for its rarity and to aware about neoplastic potential of ichthyosis uteri.
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Granulomatous inflammation by candida presenting as a hard subcutaneous nodule: A rare case report with review of literature p. 640

DOI:10.4103/IJPM.IJPM_555_19  
Fungal infections are very important infectious causes of granulomatous inflammation. Isolated subcutaneous fungal infections are uncommon and only seen in immunosuppressed patients or in those with other comorbidities. Such cases are usually mistaken as noninfectious benign lesions and fine-needle aspiration cytology (FNAC) can be used for an adequate diagnosis.
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Diagnosis of the leukemic phase of ALK-positive anaplastic large cell lymphoma by immunohistochemistry on cell block prepared from peripheral blood buffy coat p. 642

DOI:10.4103/IJPM.IJPM_433_19  
A leukemic phase of anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK+ ALCL) is rare. The leukemic cells morphologically appear as small to intermediate-sized cells with cerebriform and cloverleaf-like nuclei and are misdiagnosed as other T-Cell lymphomas/leukemia with similar morphology. We describe a case where the diagnosis of leukemic ALK+ ALCL was aided by immunohistochemistry performed on the cell blocks prepared from the peripheral blood buffy coat specimen. The diagnosis of ALK+ ALCL was further confirmed on the biopsy of a cutaneous nodule of this patient. We found the method of immunohistochemistry on peripheral blood buffy coat cell block very useful and suggest that it may be used as an alternative method to flowcytometry in low resource settings.
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Disseminated Histoplasmosis detected on peripheral blood smear examination in immunocompetent patients from non endemic region – Report of two cases from a tertiary care hospital p. 645

DOI:10.4103/IJPM.IJPM_898_19  
Histoplasmosis is an opportunistic systemic infection caused by inhaling spores of a thermal dimorphic fungus Histoplasma capsulatum. Disseminated histoplasmosis is the most common form associated with acquired immune deficiency syndrome (AIDS). However, only a few cases of disseminated histoplasmosis are reported in immuno-competent hosts. Most infections in the immunocompetent hosts are asymptomatic or result in mild pulmonary disease. However the presence of Disseminated Histoplasmosis in immunocompetent host probably results due to prolonged exposure and delayed presentation We report two cases of progressive disseminated histoplasmosis in two immunocompetent patients from non-endemic region in Western Rajasthan, India. Also in both the cases, the first diagnosis was suggested by a peripheral blood smear, which is not a classical biological diagnostic method for fungal infection. Careful examination of Peripheral blood smear along with correct clinical history can aid in early diagnosis of disseminated histoplasmosis even in immunocompetent patients.
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Entomophthoromycosis in a child: Delayed diagnosis and extensive involvement p. 648

DOI:10.4103/IJPM.IJPM_20_19  
Entomophthoromycosis is a rare fungal infection of the skin and subcutaneous tissue occurring predominantly in tropical and subtropical regions. In children, it mostly affects the lower half of the body. With this, we report a case of Entomophthoromycosis in a 6-year-old girl who presented late with extensive involvement of the upper half of the body. She responded well to treatment with potassium iodide and itraconazole. We also reviewed cases of Entomophthoromycosis reported in children.
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IMAGES Top

Distal anterior cerebral artery aneurysm with bilateral fetal posterior cerebral arteries and trifurcation of anterior cerebral artery p. 651

DOI:10.4103/IJPM.IJPM_1021_19  
Developmental vascular anomalies of brain are non-modifiable risk factors for the development of aneurysms and are prone for rupture. We report one such association in a 44–year-old gentleman who succumbed to subarachnoid hemorrhage (SAH) secondary to ruptured distal anterior cerebral artery aneurysm associated with vascular anomalies in the anterior and posterior circulation that included trifurcation of anterior cerebral artery and bilateral fetal posterior cerebral arteries. We identified multiple anomalies in circle of Willis that could have contributed to the formation of aneurysm and early rupture. Knowledge of these variations is essential to plan early and optimum management with close follow-up.
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Pleomorphic lipoma of conjunctiva - An unusual tumor at unusual site p. 654

DOI:10.4103/IJPM.IJPM_480_19  
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Chondromyxoid fibroma of the nasal cavity - A rare tumor at an unusual site p. 656

DOI:10.4103/IJPM.IJPM_865_19  
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Pulmonary hyalinizing granuloma – An uncommon malignant masquerade p. 658

DOI:10.4103/IJPM.IJPM_58_20  
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Inverted condyloma of the cervix: A rare mimicker of a high-grade cervical lesion p. 661

DOI:10.4103/IJPM.IJPM_838_19  
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Hb Yaizu: A rare beta-globin chain variant posing diagnostic dilemma in high-performance liquid chromatography p. 663

DOI:10.4103/IJPM.IJPM_851_19  
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LETTERS TO EDITOR Top

Soft tissue myxoma of tongue: An infrequent case report p. 666
Jaishree Sharma, Archana B Raina, Anchal Varshney, Disha Chopra
DOI:10.4103/IJPM.IJPM_139_19  
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Painful left breast hamartoma: Underdiagnosed and under-reported entity p. 667
Renuka B Nagaraj, Arshiya Sultana
DOI:10.4103/IJPM.IJPM_915_19  
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CD10 positive benign stromal spindle cell tumor (not otherwise specified) of the male breast p. 670
Siddhi Gaurish Sinai Khandeparkar, Neha Bharti, Pradnya Saragade, Smita Pathade, Bageshri Gogate
DOI:10.4103/IJPM.IJPM_303_20  
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An unusual cause of respiratory distress in an infant p. 672
Pragati A Sathe, Pradeep Vaideeswar, Ritu Kulshrestha
DOI:10.4103/IJPM.IJPM_588_19  
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Ductal adenocarcinoma of prostate–A diagnostic dilemma p. 674
Sudha Sharma, Nandita Kakkar, Sudheer K Devana
DOI:10.4103/IJPM.IJPM_578_19  
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Clear cell carcinoma arising in a seromucinous borderline tumor with co-existing endometriosis- Case report of a rare association p. 676
Nupur Karnik, Bharat Rekhi
DOI:10.4103/IJPM.IJPM_750_19  
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Recapping error: A case of false positive result due to minuscule contamination by re-closure of vacutainer p. 678
Divya Setya, Prashant Pandey, Shweta Ranjan, Dharmender Kumar, Suryasnata Das
DOI:10.4103/IJPM.IJPM_202_20  
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Brief technical guide for conducting an online open conference in resource-limited settings p. 681
Himel Mondal, Shaikat Mondal
DOI:10.4103/IJPM.IJPM_479_20  
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NEW HORIZON Top

Catechism (Quiz 10) Highly accessed article p. 684
Bharat Rekhi
DOI:10.4103/IJPM.IJPM_1174_20  
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