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   Table of Contents - Current issue
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April-June 2018
Volume 61 | Issue 2
Page Nos. 169-305

Online since Friday, April 20, 2018

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EDITORIAL  

From the Editor's Desk Highly accessed article p. 169
Ranjan Agrawal
DOI:10.4103/0377-4929.230586  
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ORIGINAL ARTICLES Top

Evaluation of p53 protein expression in Barrett esophagus p. 170
Mahathi Krothapalli, Jyoti Ramnath Kini, Hema Kini, Kausalya Kumari Sahu, Suresh Shenoy, Sandeep Gopal Krishna, BV Tantry
DOI:10.4103/IJPM.IJPM_369_16  
Background: Loss of heterozygosity of p53 along with aneuploidy is deemed to be the early molecular steps in Barrett metaplasia-dysplasia-adenocarcinoma sequence. Objective biomarkers need to be used along with microscopy for risk stratification to predict the progression of Barrett esophagus (BE) to carcinoma. Aim: This study aims to study p53 protein expression in dysplasia and correlate the same with morphology in BE. Materials and Methods: A time-bound study was conducted from January 2011 to June 2015. All esophageal biopsies showing histological evidence of columnar epithelium with the presence of goblet cells were included. The cases which showed dysplasia were graded on hematoxylin and eosin stain. Evaluation of p53 immunohistochemistry staining was done on all the cases of BE. Dysplasia was correlated with the expression of p53 using Chi-square value (χ2) and Fischer's exact test wherever appropriate. P < 0.05 was considered to be statistically significant. Results: Of 829 esophageal biopsies received, 119 were endoscopically suspected to be BE, of which 85 cases were confirmed on microscopy. In our study, there were 75 cases negative for dysplasia (88.2%), 8 with low-grade dysplasia (LGD) (9.4%), and two with high-grade dysplasia (HGD) (2.4%). Three cases of BE had associated adenocarcinoma. Immunostaining with p53 done on all the 85 cases showed positive staining in all cases with LGD, one with HGD and two with adenocarcinoma. In the present study, immunostaining with p53 showed 90% sensitivity, 89.3% specificity, positive predictive value of 52.9%, and negative predictive value of 98.5%. Conclusion: The technical simplicity, easy availability, and comparatively lower cost enhance the role of p53 as a biomarker in risk stratification for patients with BE.
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Comparison of lymphangiogenesis, lymphatic invasion, and axillary lymph node metastasis in breast carcinoma p. 176
Prerna Guleria, V Srinivas, D Basannar, Vibha Dutta
DOI:10.4103/IJPM.IJPM_774_16  
Context: Lymphangiogenesis correlates with poor prognosis in Invasive Ductal Carcinoma (IDC) breast. D2-40 antibody, a specific marker for lymphatic endothelium, differentiates lymphatic from vascular endothelium. Therefore, the aims of this study were to estimate lymphangiogenesis using D2-40 antibody and correlate with lymphatic invasion (LI) and axillary lymph node (LN) status and compare lymphatic mean vessel density (LMVD) with Tumor (T) and Node (N) stages and grade of tumor. Methods and Material: The study was conducted on fifty consecutive cases of IDC breast who underwent modified radical mastectomy (MRM) from Jan 2009 to March 2011. Hematoxylin-eosin sections and Immunohistochemistry (IHC) slides were studied along with their LN status. LMVD was counted after D2-40 immunostaining (100x magnification) in three hot spots in peritumoral areas and averaged. LI as opposed to vascular invasion (BVI), and LN status for all cases were assessed. Statistical Analysis: Statistical analysis was done using SPSS software (version 14.0 for Windows). Pearson's correlations, χ2 tests and Mann-Whitney U test were used. Results: Lymphangiogenesis varied from 0 to 58 with mean LMVD of 11. Of 50 cases, five showed no lymphatic vessels in peritumoral areas; of these five, three had positive LNs. 21/50 cases had LI. No statistical significant association was seen between lymphangiogenesis and LI. 34/50 cases had positive LNs. Mean LMVD was higher in patients with N2/N3 stage as compared to N0/N1 stage and was statistically significant (P = 0.013). Conclusions: D2-40 is specific marker for lymphatic endothelium. LI and lymphangiogenesis, as opposed to BVI, are better prognostic indicators in IDC breast.
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Interobserver reproducibility of tumor-infiltrating lymphocyte evaluations in breast cancer p. 181
Fatmagul Kusku Cabuk, Fatma Aktepe, Fatma Nilgun Kapucuoglu, Ipek Coban, Dauren Sarsenov, Vahit Ozmen
DOI:10.4103/IJPM.IJPM_131_17  
Aim: Tumor-infiltrating lymphocytes (TILs) have a prognostic value in breast cancer (BC); however, because of the lack of standard evaluation methods, we aimed to assess the interobserver agreement of stromal TILs (sTILs) and intratumoral TILs (iTILs) as well as the effect of hot spot areas and molecular subtyping on the overall agreement. Methods: The study consisted of 121 haematoxylin and eosin (H and E)-stained slides of invasive BC samples obtained from the pathology archives. The TIL assessment was based on the International TIL Working Group recommendations for the percentage of sTILs and was conducted by four pathologists. The percentage of iTILs, the number of lymphocytes in hot spot areas (iTILs-HS), and the overall interobserver agreement for the molecular subtypes were evaluated. The interclass correlation coefficient (ICC) was used to assess interobserver agreement among the four pathologists. Results: The ICC score among the observers for the sTIL percentages was 0.74, and the individual ICC values for each molecular subtype were 0.55, 0.88, and 0.79 for luminal, HER2-positive, and triple-negative tumors, respectively. The compliance value for the iTILs was 0.29 (95% confidence interval (CI) = 0.06–0.48], whereas the compliance value for the iTILs-HS was 0.63 (95% CI = 0.49–0.71). The compliance values for the iTILs-HS subtypes were 0.72, 0.43, and 0.55 for luminal, HER2-positive, and triple-negative tumors, respectively. Conclusion: The IWTILG recommendations are reproducible and reliable. The interobserver agreement of the sTIL percentages was considerably higher for the triple-negative and HER2-positive cases than the luminal cases, whereas the interobserver agreement for the assessment of iTILs-HS in tumors was higher for the luminal subtype.
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Diagnostic and prognostic impact of mucin 1–6 expression in non-small cell lung cancer p. 187
William Sterlacci, Michael Fiegl, Lothar Veits, Alexandar Tzankov
DOI:10.4103/IJPM.IJPM_678_17  
Background: The prognostic significance and clinico-pathological characterization of mucin (MUC) expression in non-small cell lung cancer (NSCLC) is controversial and little studied. Aims: This study aims at elucidating this issue on the largest and most detailed cohort so far. Settings and Design: We examined the expression of MUC 1, 2, 4, 5AC and 6 on 371, well documented, surgically resected NSCLC cases. Materials and Methods: Immunohistochemical results were correlated with several of our previously studied, relevant parameters on this cohort including a follow-up period of up to 20 years. An additional point we examined for practical reasons that has not been addressed so far, was the possible assistance of MUC expression for the differentiation between a primary lung adenocarcinoma and metastasis from a known pancreatobiliary primary tumor. Statistical Analysis Used: Cronbach's Alpha reliability correlation, Spearman's correlation, ANOVA means of comparison with additional Kruskall–Wallis H-test, and Kaplan–Meier survival analysis were employed as statistical analyses in this study. Results and Conclusions: MUCs were associated with histologic subtypes, tumor differentiation and members of the epidermal growth factor receptor signaling pathway, although they were not found to be significant for prognosis. Expression of MUC1 correlated with certain other markers and may point to a group of patients relevant for upcoming treatment strategies involving MUC1. According to our findings, we also recommend additional MUC5AC staining for a thyroid transcription factor 1-negative adenocarinoma in the lung for the differentiation of a possible metastasis in the presence of a pancreatic ductal adenocarcinoma.
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The determination of stage in nonmuscle urothelial carcinoma: Staining pattern of caspase-8 p. 192
Nilay Şen Türk, Saadettin Eskiçorapçi, Zafer Aybek, Levent Tuncay
DOI:10.4103/IJPM.IJPM_161_17  
Context: Urothelial carcinoma (UC) is one of the most frequent epithelial tumors worldwide. Aims: We aimed to investigate the protein expressions of caspase-8, p53, murine double minute 2 (mdm2), and p14ARF in nonmuscle UCs and to correlate the findings with clinicopathological characteristics. Settings and Design: A total of 50 patients who had pTa and pT1 tumors were analyzed. Subjects and Methods: The protein expressions of caspase-8, p53, mdm2, and p14ARF were analyzed by immunohistochemistry. Statistical Analysis Used: Chi-square test was done using SPSS version 16.0 (SPSS, Inc., Chicago, IL, USA). Results: Cytoplasmic caspase-8 expression was significantly higher in pT1 UCs while nuclear caspase-8 expression was significantly higher in pTa UCs (P = 0.005 and P = 0.011, respectively). Cytoplasmic caspase-8 expression was also higher in high-grade UCs (P = 0.035). The expression of p53, mdm2, and p14ARF was not also related with pathological stage or grade (P > 0.05 for all). The p14ARF expression was related with nuclear caspase-8 expression in most of the patients. Complete agreement among nonmuscle UCs for immunohistochemical expression of p14 and nuclear caspase-8 was seen in 41 cases, and the pairwise kappa agreement value was substantial (κ =0.614). The patients who had recurrence were positive for both p53 and mdm2 or either p53 or mdm2 (P = 0.025). Conclusions: These results suggested that the staining pattern of caspase-8 might be helpful for determining of the stages in nonmuscle UC. It was also showed that the expression status of p53 and mdm2 were related with the recurrence.
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Current practice in handling and reporting needle biopsies: A hospital-based survey p. 197
Paritosh Garg, Priya Pathak, Rachna Goyal, Vinod K Arora, Navjeevan Singh
DOI:10.4103/IJPM.IJPM_93_17  
Context: Core-needle biopsy (CNB) is a minimally invasive screening and diagnostic tool which provides intact tissue fragments for histopathological examination. Aims: This study was conducted to review the current practices of handling and reporting CNBs performed for core-needle biopsies from four organ systems which are frequently encountered in our institution. These include breast, prostate, soft tissues, and lymph nodes. Settings and Design: This was a retrospective study conducted at a tertiary care hospital. Materials and Methods: CNB reports of breast, prostate, soft tissue, and lymph nodes were accessed and categorized based on the site of biopsy, number, and average length of the cores. The CNB reports were categorized into diagnostic or nondiagnostic. In case of diagnosis of malignancy, reports were recorded as structured or nonstructured reports. Statistical Analysis Used: Fisher's exact test and Chi-square tests were applied to check the significance of the results obtained on comparing the number of cores and size of cores with the outcome of report. Results: Out of 16,300 surgical pathology specimens received, 400 were CNBs comprising breast (n = 211), prostate (n = 108), soft tissue (n = 50), and lymph node (n = 31). Majority of the CNBs had 2–5 cores and the size of the core was ≥0.5 cm, which accounted for most of the reports which were diagnostic. There was a lack of clinical and radiological detail in many of the cases. Out of the malignant cases diagnosed, structured reports were given in 30% of breast, 79.3% of prostate, 41.7% soft tissue, and 60% of lymph node needle biopsies. Conclusions: The audit helped to identify areas of improvement in CNB services.
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Is a diagnostic lumbar puncture indicated in intraocular retinoblastoma? p. 201
Sidharth Totadri, Vinay Munikoty, Usha Singh, Radhika Srinivasan, Amita Trehan, Richa Jain, Nandita Kakkar, Akshay Kumar Saxena, Arvind Rajwanshi, Deepak Bansal
DOI:10.4103/IJPM.IJPM_475_17  
Background: Lumbar puncture (LP) is frequently performed in patients with advanced intraocular retinoblastoma. However, this may not be necessary in a significant proportion of patients. Materials and Methods: A file review of patients who were diagnosed with retinoblastoma over a 13-year-period was performed. Patients who underwent LP as part of staging were included in the study. Results: The study included 223 patients. One-third had bilateral retinoblastoma. The grouping was C, D, and E in 4 (2.9%), 41 (29.9%), and 92 (67.2%) patients, respectively. The stage was 0, I, II, III, and IV in 14 (6.3), 123 (55.2%), 13 (5.8%), 70 (31.4%), and 3 (1.3%) patients, respectively. Eight (3.6%) patients had a positive cerebrospinal fluid (CSF) cytology. None of the patients with intraocular disease and 7 (10%) patients with extraocular disease had a positive CSF. Conclusions: A diagnostic CSF is not indicated in patients with intraocular retinoblastoma.
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Frequency, distribution, and immunomorphologic characteristics of peripheral T-cell lymphoma, not otherwise specified in a tertiary care center in Southern India p. 204
Archana Lakshmanan, Deeksha Sikri, Sushama Patil, Ann Kurian, S Annapurneswari, Sheila Nair
DOI:10.4103/IJPM.IJPM_405_17  
Aims: In world literature, Peripheral T-cell lymphomas (PTCLs) constituted about 12% of non-Hodgkin's lymphomas (NHL) of which PTCL not otherwise specified (NOS) was the most common subtype. This study was undertaken to ascertain the frequency and to assess the morphologic and immunophenotypic characteristics of PTCL, NOS over a period of 5 years in a tertiary care referral center in Southern India. Materials and Methods: Slides and blocks of all PTCL, NOS were retrieved, and a detailed morphologic and immunophenotypic study using a wide panel of antibodies was done. Results: During this study, NHL constitutes 77.61% of all lymphomas. PTCL formed about 12.55% (251 cases) of all NHL. PTCL NOS was the most common subtype (30.68%). The most common site of involvement was lymph nodes (75%) followed by extranodal sites such as soft tissue (8.33%), gastrointestinal tract including oral cavity (6.67%), nasal cavity (5%), central nervous system (1.67%), lung (1.67%), and spleen (1.67%). PTCL, NOS showed a broad morphologic spectrum and had varied morphologic patterns with some mimicking reactive hyperplasia and some mimicking known type of T-cell lymphomas, B-cell lymphomas, and Hodgkin's lymphoma. Conclusions: PTCL, NOS constituted about 30.68% of all PTCLs in our institution during a 5-year period and was the second most common type of PTCL. Immunophenotyping using a wide panel of T-cell antibodies is necessary to distinguish PTCL, NOS from other lymphomas which they mimic, as they are known to carry a worse prognosis.
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Molecular genetics of BCR-ABL1 negative myeloproliferative neoplasms in India p. 209
Nikhil Rabade, PG Subramanian, Rohan Kodgule, Goutham Raval, Swapnali Joshi, Shruti Chaudhary, Russel Mascarenhas, Prashant Tembhare, Sumeet Gujral, Nikhil Patkar
DOI:10.4103/IJPM.IJPM_223_17  
Introduction: Over the past decade, we have moved on from a predominantly morphological and clinical classification of myeloproliferative neoplasms (MPN) to a more evolved classification that accounts for the molecular heterogeneity that is unique to this subgroup of hematological malignancies. This usually incorporates mutations in Janus kinase 2 (JAK2), MPL, and calreticulin (CALR) genes. In this manuscript, we report the frequency of these mutations in a cohort of Indian patients at a tertiary cancer center. Materials and Methods: One hundred and thirty cases of MPN were included in this study. These cases were diagnosed and classified based on the World Health Organization 2008 criteria. JAK2 and MPL mutations were detected using high sensitivity allele-specific polymerase chain reaction using fluorescent labeled primers followed by capillary electrophoresis. A subset of JAK2 and CALR mutations were assessed using a fragment length assay. Results: Among the MPN, we had 20 cases of polycythemia vera (PV), 34 cases of essential thrombocythemia (ET), and 59 of myelofibrosis (MF). JAK2, MPL, and CALR mutations were mutually exclusive of each other. Seventeen cases were categorized as MPN unclassifiable (MPN-U). JAK2p.V617F and MPL mutations were present in 60% (78 of 130) and 5.3% (7 of 130) of all MPN. All the PV cases harbored the JAK2 p.V617F mutation. A total of 23.8% (31 of 130) of patients harbored CALR mutations. CALR exon 9 mutations were detected in 60.8% (14 of 23) and 50% (5 of 10) of JAK2 and MPL negative MF and ET cases, respectively. MPN-U cases included three JAK2 p.V617F positive, two MPL p.W515 L, and 12 CALR positive cases. Ten different types of CALR indels (8 deletions and 2 insertions) were detected of which Type I and Type II mutations were the most common, occurring at a frequency of 45.1% (14 of 31) and 22.5% (7 of 31), respectively. Discussion and Conclusion: We report frequencies of JAK2 p. V617F, MPL exon 10 and CALR mutations in 130 patients similar to those reported in western literature. These mutations carry not only diagnostic but also prognostic relevance.
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Detection of immunoglobulin M and immunoglobulin G antibodies to Mycoplasma pneumoniae in children with community-acquired lower respiratory tract infections p. 214
Surinder Kumar, Indu Bala Garg, Gulshan Rai Sethi, Sanchit Kumar, Sanjeev R Saigal
DOI:10.4103/IJPM.IJPM_21_17  
Context: Mycoplasma pneumoniae (M. pneumoniae) causes up to 40% of community-acquired pneumonia in children. It is impossible to identify M. pneumoniae infection on the basis of clinical signs, symptoms, and radiological features. Therefore, correct etiological diagnosis strongly depends on laboratory diagnosis. Aims: This study aims to investigate the role of M. pneumonia e in pediatric lower respiratory tract infections (LRTIs) employing enzyme-linked immunosorbent assays (ELISA) and particle agglutination (PA) test. Settings and Design: Two hundred and eighty children, age 6 months to 12 years with community-acquired LRTIs were investigated for M. pneumoniae etiology. Materials and Methods: We investigated 280 children hospitalized for community-acquired LRTIs, using ELISA and PA test for detecting M. pneumoniae immunoglobulin M (IgM) and immunoglobulin G antibodies. Statistical Analysis Used: The difference of proportion between the qualitative variables was tested using the Chi-square test and Fischer exact test. P ≤ 0.05 was considered as statistically significant. Kappa value was used to assess agreement between ELISA and PA test. Results: M. pneumoniae was positive in 51 (23.2%) <5 years and 33 (54.0%) children in ≥5 years of age group, and this difference was statistically significant (P < 0.001). Clinical and radiological findings in M. pneumoniae positive and negative groups were comparable. ELISA detected M. pneumoniae in 78 (27.8%) and PA test 39 (13.9%) patients; 33 (84.6%) ELISA positive and 6 (15.4%) ELISA negative. ELISA/PA test together detected M. pneumoniae infection in 84 (30%) children. Conclusions: Our data underline that M. pneumoniae plays an important role in children with community-acquired LRTIs and more particularly in children >5 years of age.
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CLINICO-PATHOLOGY CONFERENCE Top

A 37-year-old male with extensive cerebral venous thrombosis: Clinicopathological correlation of a rare case p. 219
Deepti Mutreja, Rajeev Saxena, T V. S. V. G K. Tilak, Vanmalini Tewari, Nikhil Moorchung, Bhaskar Nandi
DOI:10.4103/IJPM.IJPM_232_17  
We present the autopsy findings and differential diagnosis of a 37-year-old immunocompetent male patient who presented primarily with extensive cerebral vein thrombosis and was found to have a rare association with JAK2V617F mutation positivity.
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BRIEF COMMUNICATIONS Top

Expression of E-cadherin, syndecan 1, Ki-67, and maintenance minichromosome 3 in tissue lesions of actinic prurigo obtained by incisional biopsy p. 225
Alexandra Mancheno-Valencia, Ronell Eduardo Bologna-Molina, Sonia Toussaint-Caire, María Elisa Vega-Memije, Juan Carlos Cuevas-González
DOI:10.4103/IJPM.IJPM_574_17  
Actinic prurigo (AP) is an idiopathic photodermatosis; the initial manifestations usually occur during the first decades of life but can appear at any age. Cases are usually diagnosed late once the lesions have exacerbated; due to the extensive involvement of the vermilion border and the etiology, it has been confused with and related to a potentially malignant process. Syndecan-1 and E-cadherin were positive in the epidermis, with moderate-to-intense staining in 100% of samples. Ki67 and MCM3 were expressed in the lower third of the epidermis and showed greater immunolabeling in samples that contained lymphoid follicles (Ki 67: epidermis [17.7% ± 6.79%] and dermis [7.73% ± 6.69%]; MCM3: epidermis [22.92% ± 10.12%] and dermis [6.13% ± 6.27%]). In conclusión AP is a disease in which there is no evidence that the lesions are potentially cancerous. AP cheilitis should not be confused with actinic cheilitis because they are separate entities.
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Lymphomatoid granulomatosis: A case series from South India p. 228
Elanthenral Sigamani, Jagan Chandramohan, Sheila Nair, Geeta Chacko, Meera Thomas, Leni Grace Mathew, Susanne Pulimood, Marie Therese Manipadam
DOI:10.4103/IJPM.IJPM_471_17  
Context: Lymphomatoid granulomatosis (LYG) is a rare B-lymphoproliferative disorder characterised by an angiocentric and angiodestructive pattern along with Epstein - Barr virus (EBV) association. It is one of the diagnostic challenges in lymphoma pathology. Deregulation of EBV immune surveillance is one of the narrated hypotheses in the literature. Extrapulmonary manifestations are rare with LYG. Morphological grading is done based on the number of EBV-positive B cells, which is useful to strategize treatment protocol. Aims: We report here a series of nine cases of LYG to discuss the clinical, histological, and immunohistochemistry findings. Settings and Design: This is the first case series from India in published literature. Subjects and Methods: We reviewed cases of LYG diagnosed at our center for the past 11 years (2006-2016). A total of nine cases were included in this study. Histomorphology was studied in conjunction with immunohistochemistry and clinical details. Cases without classical morphology and negative for EBV immunostain were excluded from the study. Results: There were nine patients in our study (7 males and 2 female; M:F ratio 3.5:1). The age of these patients ranged from 4 years to 57 years (mean age: 30 years). The most common site involved was the lung (4, 44%), followed by the skin (2, 22%), central nervous system (2, 22%) and lymph node (1, 11%). One patient had primary immunodeficiency. Another patient had undergone renal transplant 11 years before the development of the lesion. Angiocentricity and angioinvasion were appreciated in all nine cases (9/9) with necrosis in four cases (44%) and ill-defined histiocytic aggregates in three cases (33%). The histological features were as follows: Grade 1(4 cases, 44%), Grade 2(2 cases, 22%), and Grade 3(3 cases, 33%). Conclusion: LYG is a rare EBV driven angiodestructive disease with predominantly lung involvement as well as isolated extrapulmonary sites as seen in our study. It is often progressive and ultimately fatal in the absence of appropriate treatment. Grading of the lesion helps to initiate the appropriate treatment of choice.
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Qualitative defects with normal sperm counts in a patient attending infertility clinic Highly accessed article p. 233
Rachna Goyal, Mrinalini Kotru, Aarti Gogia, Sonal Sharma
DOI:10.4103/IJPM.IJPM_460_17  
Background: Sperm morphology is an important qualitative parameter in semen analysis. Aim: To assess qualitative defects in the semen with normal sperm counts. Setting and Design: This was a prospective and descriptive study done in a tertiary care center. Materials and Methods: Seventy-five semen samples with normal sperm counts were evaluated. Qualitative defects of sperms on Papanicolaou-stained slides were assessed. The defects were noted as follows: head (tapering head, large head, small head, round head, bifid head), middle piece (bent neck, broad middle piece, excess residual cytoplasm), and tail (coiled tail). Results: All cases showed the qualitative defects in spite of the normal counts. The defects found in head – pointed/tapering head (1%–20%), round head (1%–7%), large head (1%–3%) and others (0%–2%); in middle piece – bent neck (1%–8%), excess cytoplasm (1%–3%) or broad middle piece (1%–12%); and in tail – coiled tail (1%–5%). Conclusions: Qualitative defects are often seen even in cases with normal sperm counts.
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Rapid detection of respiratory syncytial virus in community-acquired lower respiratory tract infections in children by chromatographic assay p. 236
Surinder Kumar, Bhanu Mehra, Gulshan Rai Sethi, Sanjeev R Saigal
DOI:10.4103/IJPM.IJPM_789_16  
Respiratory syncytial virus (RSV) is the single most important viral agent causing pediatric lower respiratory tract infections (LRTIs) worldwide. To evaluate the role of RSV in pediatric LRTIs, we studied 85 children <2 years of age hospitalized for community-acquired LRTIs. Nasopharyngeal aspirates were obtained on admission for the detection of RSV antigen by immunochromatographic assay. Demographic, clinical, and radiological findings for RSV antigen were compared. Data analysis was performed by Chi-square test. A relatively higher number of RSV-infected children 32 (60.4%) were below 6 months of age. Clinical and radiological findings in both RSV-positive and RSV-negative groups were comparable. RSV antigen was positive in 53 (62.4%) with immunochromatography. Our study confirms that RSV plays a significant role in community-acquired LRTIs in children.
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CASE REPORTS Top

Pindborg tumor: Pathology with special stains p. 239
Swati Shrikant Gotmare, Treville Pereira, Subraj Shetty, Kashmira S Kesarkar
DOI:10.4103/IJPM.IJPM_143_17  
Odontogenic tumors constitute a wide spectrum of lesions ranging from malignant and benign neoplasms to dental hamartomas, all derived from the epithelial and ectomesenchymal remnants of the tooth forming apparatus. Calcifying epithelial odontogenic tumor (CEOT) is an uncommon, benign epithelial odontogenic tumor first described by Pindborg in 1956. It is a universally accepted eponym for this neoplasm. Pindborg tumor or CEOT is a locally aggressive neoplasm that accounts for 1% of the total odontogenic tumors, with recurrence in 14% of cases. The etiology of this tumor remains an enigma to the clinician. Pindborg suggested that the tumor arises from the remnants of reduced enamel epithelium of an unerupted tooth. Recent studies in literature report that the tumor arises from stratum intermedium. We report a case of Pindborg tumor in a 22-year-old male patient in the left mandibular posterior region. Radiographically, a well-defined radiolucency was associated with unerupted mandibular second molar which was displaced to the inferior border of the mandible. Along with routine haematoxylin and eosin stains, this case reports histopathological findings using Congo red stain and modified Gallegos stain.
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Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland: Not so indolent a neoplasm? p. 242
Anila Kunjulekshmi Amma Raveendran Nair, Nebu A George, Rejnish Kumar, A Sreekumar, K Jayasree
DOI:10.4103/IJPM.IJPM_169_17  
A 58-year-old female, a known diabetic and hypertensive, presented with left-sided swelling on the anterior aspect of the neck of 1-year duration, which was rapidly increasing in size for the past 6 months. She was on Eltroxin for hypothyroidism for the past 1 year. Computed tomography study of the neck showed a nodule in the left lobe of thyroid which on fine-needle aspiration was suspicious for malignancy. Total thyroidectomy with left posterolateral lymph node dissection was done. Histopathological examination showed sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) of the thyroid gland with lymph node metastasis. SMECE of the thyroid was initially thought to be a low-grade malignancy with indolent clinical behavior. However, our case showed extra thyroidal spread with lymph node metastasis, necessitating adjuvant therapy for our patient. Such aggressive behavior has been noted in few earlier case reports also.
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Clear cell sarcoma arising from paraspinal ligament of thoracic spine: Report of an unusual case p. 245
Ranjan Agrawal, Prabal Deb, Jagdamba Sharan, Parbodh Kumar
DOI:10.4103/IJPM.IJPM_516_17  
Clear cell sarcoma (CCS) is an unusual but aggressive soft-tissue tumor with an incidence of <1% of all soft-tissue sarcomas. It was previously termed “malignant melanoma of soft parts” due to its resemblance clinically and morphologically. Normally CCS is seen in patients aged 20–40 years. A rare case of CCS of paraspinal ligament in a 5-year-old boy is being reported. Histopathology and immunohistochemistry markers confirmed the diagnosis. The present case is unique since the entity itself is rare and also due to its occurrence in a child.
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A mesenteric primary peripheral Ewing's sarcoma/primitive neuroectodermal tumor with molecular cytogenetic analysis: Report of a rare case and review of literature p. 248
Yi-Shu Liao, I-Han Chiang, Hong-Wei Gao
DOI:10.4103/IJPM.IJPM_546_17  
Rare cases of Ewing's sarcoma/primitive neuroectodermal tumors (EWS/PNETs) arising from mesenteric tissue have been reported. This report describes an EWS/PNET in a 25-year-old woman who presented with abdominal pain lasting 3 days. Radiologic evaluation revealed a 9 cm × 6 cm homogeneous mass in the lower abdomen with homogeneous enhancement and invasion of the ileum. Surgical resection was completed during exploratory laparotomy. Immunohistochemically, the tumor cells revealed CD99, friend leukemia virus integration-1 and NKX2.2 (NK2 Homeobox 2, a protein coding gene) and subsequently showed EWSR1 rearrangement. The histological feature, immunohistochemical results and genetic fluorescence in situ hybridization analysis of this case were confirming the diagnosis of EWS/PNET. Adjuvant chemotherapy was suggested, but the patient was lost to follow-up.
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Primary primitive neuroectodermal tumor of the kidney p. 252
Sunil Vitthalrao Jagtap, Pradnya Pandurang Kale, Anil Huddedar, Atul Bhanudas Hulwan, Swati S Jagtap
DOI:10.4103/IJPM.IJPM_277_16  
Renal primitive neuroectodermal tumor (PNET) is a rare entity. It should be differentiated from other primary renal malignancies. The differentiation of the malignant small round cell tumors may be challenging; however, it is essential for better management of the patient. We report a 45-year-old male having complaints of pain in the abdomen, hematuria, and mass in the abdomen for 6 months. Abdominal and pelvic sonography finding showed cystic-solid, right renal mass suggestive of malignancy. On histopathology diagnosed as malignant small round blue cell tumor suggestive of primitive neuroectodermal tumor. On immunohistochemistry, CD99 positivity confirmed the diagnosis of primary PNET of the kidney. We are presenting this case for its rarity, clinical presentation, and pathological findings.
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Methotrexate-associated Epstein–Barr virus mucocutaneous ulcer: A case report and review of literature p. 255
Priyanka Yogendra Ravi, Elanthenral Sigamani, Yasir Jeelani, Marie Therese Manipadam
DOI:10.4103/IJPM.IJPM_135_16  
Epstein–Barr virus-positive mucocutaneous ulcer (EBVMCU) comprises part of the spectrum of B-cell lymphoproliferative disorders, reported in settings of immunosenescence and iatrogenic immunosuppression, affecting the oropharyngeal mucosa, skin, and gastrointestinal tract. We report a case of a 59-year-old female, known case of rheumatoid arthritis on methotrexate (MTX) for 15 years, who presented with an ulcer in the inner aspect of her cheek region for 2 years. Clinical examination revealed an infiltrative lesion involving the lower gingivobuccal sulcus of size 2 cm × 3 cm extending to the alveolus with level I lymph nodes, suspicious for carcinoma buccal mucosa. Anti-EBV-capsid antigen-immunoglobulin M and qualitative EBV polymerase chain reaction of peripheral blood were negative. Histopathological examination revealed atypical lymphoid cells with enlarged vesicular nuclei, prominent nucleoli, and moderate eosinophilic cytoplasm, few with binucleation (CD20 focally positive, CD79a focally positive, CD30+, EBV LMP-1+, MIB-I 60%) consistent with EBVMCU, MTX-associated. This is the first case report from India.
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Urothelial carcinoma of urinary bladder with exclusive heterologous component of epithelioid rhabdomyosarcoma at metastatic site p. 258
Poojan Agarwal, Sunil Pasricha, Gurudutt Gupta, Anila Sharma, Anurag Mehta
DOI:10.4103/IJPM.IJPM_785_17  
Urothelial carcinoma of urinary bladder with divergent differentiation into rhabdomyosarcoma (RMS) is an extremely uncommon aggressive phenomenon. We present a case of a 74-year-old male with bladder carcinoma which metastasized to the abdominal wall as epithelioid RMS. To the best knowledge of our literature searches, an oligometastasis of exclusive heterologous component has not been described before. The clinical, radiological, and immunohistochemistry profile of the patient supported the monoclonal nature of the tumor.
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Ovarian borderline mucinous tumor with squamous overgrowth: An unusual finding with review of literature p. 261
Geetha Vasudevan, Padmapriya Jaiprakash, Shyamala Guruvare, Nivedita Samanta
DOI:10.4103/IJPM.IJPM_30_17  
Borderline mucinous tumor (BMT) is often associated with other entities such as dermoid cyst, Brenner tumor, and endometriosis. Squamous areas are often associated which may be a part of BMT or its associated conditions. Here, we describe squamous overgrowth in a case of intestinal type of mucinous borderline tumor in a 29-year-old uniparous female and discuss the diagnostic difficulties.
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Ovarian fibroma with luteinized thecal cells and minor sex cord element: A rare case report p. 264
Anjali Mathur, Ankit Seth, Leela Pant
DOI:10.4103/IJPM.IJPM_446_17  
Ovarian fibroma with minor sex cord element (MSCE) is a rare tumor. The increased estrogen production due to the presence of MSCE and/or luteinized thecal cells within fibroma can be a risk factor for endometrial hyperplasia or carcinoma.
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Bone marrow oxalosis: An unusual cause of cytopenia in end-stage renal disease; report of two cases p. 268
Seema Sharma, Ram Nawal Rao, Krushna Chandra Pani, Paramita Paul
DOI:10.4103/IJPM.IJPM_572_17  
Systemic oxalosis can be either primary or secondary hyperoxaluria. Oxalosis is a phenomenon in which calcium oxalate crystals deposit in various visceral organs leading to bone marrow (BM) failure and recurrent renal stones. We describe two rare cases of BM oxalosis. Hyperoxaluria is strongly associated with nephrolithiasis and nephrocalcinosis. Both the patients presented with recurrent renal stones and a variable degree of BM failure. BM oxalosis should be considered as a possible diagnosis in patients in recurrent nephrolithiasis and cytopenia.
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An unusual presentation of large B-cell lymphoma with interferon regulatory factor 4 gene rearrangement p. 271
Anuj Verma, Sridhar Epari, Sumeet Gujral, Tanuja Shet
DOI:10.4103/IJPM.IJPM_194_17  
Rearrangements involving interferon regulatory factor 4 (IRF4) gene has been recently described in a subtype of diffuse large B-cell lymphoma (DLBCL). They occur in a typical clinical setting of a pediatric age group, predominantly with tonsillar mass, usually as a low-stage disease and with good response to chemotherapy. Histomorphologically, they show nodular/follicular architecture with diffuse strong immunopositivity for multiple myeloma oncogene 1. Here, the authors describe one such unusual case of large B-cell lymphoma with IRF4 gene rearrangement in a young child with the unusual location of inguinal region and detailed pathological (histological, immunohistochemical, and molecular) findings.
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Expect the unexpected – Loss of surface CD3 on flow cytometry in hepatosplenic T-cell lymphoma: An eye opener p. 275
Richa Chauhan, Seema Tyagi, Sumeet Mirgh, Priyanka Mishra, Tulika Seth, Manoranjan Mahapatra, Haraprasad Pati, Renu Saxena
DOI:10.4103/IJPM.IJPM_442_17  
Hepatosplenic T-cell lymphoma (HSTCL) is a rare extranodal T-cell lymphoma that shows preferential sinusoidal infiltration of spleen and liver. It usually shows bright expression of surface CD3 (sCD3) with restriction for γδ-T cell receptors (TCR). We present a case of a 34-year-old male who presented with hepatosplenomegaly and B symptoms. His peripheral blood and bone marrow (BM) was involved by atypical lymphoid cells that were CD2+, CD7+, CD56+, cytoplasmic CD3+, and sCD3− on immunophenotyping by flow cytometry. As sCD3 is a lineage marker for T-cell lymphomas, the loss of sCD3 posed a diagnostic dilemma. However, typical pattern of sinusoidal BM and liver involvement by CD3+ cells and TCR gene rearrangement positivity led to final diagnosis of HSTCL. The differential diagnosis, workup, and clinical course of the case are discussed. To the best of our knowledge, only one case of de novo HSTCL with negative sCD3 has been reported before in the literature.
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Extranodal histiocytic sarcoma in a child with acute lymphoblastic leukemia: Cytomorphological features of a rare entity with brief review of literature p. 278
Krushna Chandra Pani, Mahima Yadav, Shaleen Kumar, Vinita Agrawal
DOI:10.4103/IJPM.IJPM_67_16  
Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic evidence of histiocytic differentiation. We describe a rare case of synchronous HS in a patient of B-cell acute lymphoblastic leukemia (ALL). A 16-year-old boy diagnosed as ALL also presented with a swelling over the right Achilles tendon. The cytological features of the swelling suggested a histiocytic lesion. Histological and immunohistochemical examination clinched the diagnosis of HS. The available 5-year follow-up showed no recurrence. It was a diagnostic dilemma on fine-needle aspiration. We discuss the cytological features of HS which can help in reaching a diagnosis and emphasize that it should be considered in the differential diagnosis for unexplained swellings in patients of hematological malignancies. Wide local excision of localized HS is associated with a long-term favorable outcome.
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Hemophagocytic lymphohistiocytosis presenting with acute liver failure and central nervous system involvement in early infancy p. 281
Mukesh Kumar, Nirupama Kothari, BD Gupta, Neeraj Gupta
DOI:10.4103/IJPM.IJPM_264_17  
Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal and likely underdiagnosed disease characterized by unregulated histiocyte proliferation, hypercytokinemia and hemophagocytosis, causing life-threatening tissue damage and organ failure. We report a case of a 56-day-old infant presenting with fever, acute liver failure, and neurological manifestations as presenting features that succumbed to rapidly progressive HLH. Our objective is to emphasize the importance of early diagnosis by high suspicion in varied initial presentation of HLH so that life-saving therapy may be instituted in time.
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Fatal meningococcal septicemia without meningeal signs, contribution of the peripheral smear in diagnosis: Report of a case p. 284
Deepti Mutreja, Nikhil Moorchung, SJ Manasa, Jeenu Varghese
DOI:10.4103/IJPM.IJPM_209_17  
Acute meningococcemia is characterized by extensive purpurae consisting of both petechiae and ecchymoses. This condition can be rapidly fatal without treatment due to shock and severe consumptive coagulopathy. We report a case of fatal meningococcal septicemia in a military recruit who presented with fever and associated rapidly progressive purpuric rash (purpura fulminans) without any meningeal signs. Evaluation revealed evidence of disseminated intravascular coagulopathy and multiorgan failure. Diplococci were demonstrated in peripheral blood neutrophils and monocytes. On autopsy, extensive hemorrhages were found in both adrenals, lungs, liver, skin, and kidneys with secondary hemophagocytic lymphohistiocytosis in bone marrow. This report highlights useful information obtained from examination of peripheral blood smear in purpura fulminans.
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Ectopic hidradenoma papilliferum of eyelid: A rare entity with diagnostic challenge p. 287
Prakriti Shukla, Anil K Malaviya
DOI:10.4103/IJPM.IJPM_686_16  
Hidradenoma papilliferum is a rare cutaneous adnexal tumour of middle aged females arising mainly in the apocrine sweat glands of perianal and genital region. Ectopic forms of this entity have been described with majority of them occurring on the head and neck region. We report a case of 16 years young male who presented with two small, well circumscribed, greyish-brown, firm, nodules on his left upper and lower eyelid. A clinical impression of basal cell carcinoma was assumed but on histopathological examination it was diagnosed as hidradenoma papilliferum of eyelid. Immunohistochemistry was performed to support the diagnosis due to its unusual clinical presentation. To the best of our knowledge, only six cases in the upper eyelid and one case in the lower eyelid have been reported in the English literature. This is the first case report of hidradenoma papilliferum involving both upper and lower left eyelid in an adolescent boy.
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IMAGES Top

Peripheral variant of calcifying epithelial odontogenic tumor with clear cell changes: An enigma p. 290
Manas Bajpai
DOI:10.4103/IJPM.IJPM_679_17  
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Leukemic conversion of hepatosplenic T-cell lymphoma with pleomorphic morphology and an aggressive course p. 292
Praveen Sharma, Ram V Nampoothiri, Prashant Sharma, Shano Naseem, Pankaj Malhotra, Neelam Varma
DOI:10.4103/IJPM.IJPM_495_17  
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LETTERS TO EDITOR Top

Intracranial chondrosarcoma: Series of three cases with varied and unusual presentations p. 294
Charu Agarwal, Minakshi Bhardwaj, Palak Agarwal, Arvind Ahuja
DOI:10.4103/IJPM.IJPM_179_17  
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Sunray appearance in lacrimal canaliculitis p. 296
Manpreet Singh, Hiruni Wijesinghe, Nandita Kakkar
DOI:10.4103/IJPM.IJPM_621_17  
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Fluorodeoxyglucose avid malakoplakia of the laryngohypopharynx masquerading as malignant tumor: A pathological enigma and clinical dilemma p. 298
Deepa Goel, Dinesh Pradhan, Amrita Tiwary
DOI:10.4103/IJPM.IJPM_156_17  
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Primary squamous cell carcinoma of the ampulla p. 300
Radhika Sekhri, Meenakshi Kamboj, Gurudutt Gupta, Sunil Pasricha
DOI:10.4103/IJPM.IJPM_340_17  
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Liver histology in cholesteryl ester storage disease p. 302
Mukul Vij, Prashant Bachina
DOI:10.4103/IJPM.IJPM_260_17  
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Quality does not reside in files: Its a way of life Highly accessed article p. 304
Nadeem Tanveer
DOI:10.4103/IJPM.IJPM_530_17  
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