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   Table of Contents - Current issue
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January-March 2017
Volume 60 | Issue 1
Page Nos. 1-144

Online since Tuesday, February 14, 2017

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EDITORIAL  

From Editor's desk p. 1
Vatsala Misra
DOI:10.4103/0377-4929.200031  PMID:28195082
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REVIEW ARTICLE Top

Progressive familial intrahepatic cholestasis: A comprehensive review of a challenging liver disease Highly accessed article p. 2
Kavita Gaur, Puja Sakhuja
DOI:10.4103/0377-4929.200040  PMID:28195083
Cholestatic liver disease in children represents a diagnostic and therapeutic challenge. The requirement of a multidisciplinary approach, high levels of professional expertise, and the costs of genetic testing are a few of the reasons why such patients may suffer for want of an accurate diagnosis. Progressive familial intrahepatic cholestasis (PFIC) is a hereditary cholestatic liver disease, afflicted children often progressing to liver failure. Despite its potential to cause significant morbidity, it has seldom been studied in India. Preliminary observations made previously at our center while dealing with such cases have suggested that PFIC may actually not be as rare as described in Western literature. A lack of understanding of actual disease burden in India and no data on genotype–phenotype correlation compounds the issue. The aim of this review is to make pathologists aware of the nuances involved in understanding this disease and its diagnostic clues. As a specific diagnosis has direct therapeutic implication for this subset of patients, the onus is on the pathologist to ensure an accurate opinion. A PubMed-based literature search using the keywords “PFIC” and “progressive familial intrahepatic cholestasis” was done to analyze and disseminate both global and Indian work in this arena.
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ORIGINAL ARTICLES Top

Calretinin expression as a reliable prognostic marker in different molecular subtypes of breast carcinoma Highly accessed article p. 8
Mayada Saad Farrag, Amro Awad El-karef, Maha Mohammed Amin, Nagwa Mokhtar Helal, Omar Farouk Ali, Nesrine Saad Farrag
DOI:10.4103/0377-4929.200046  PMID:28195084
Background: Calretinin (CR), a known mesothelial marker, is expressed in both epithelial and mesenchymal malignancies including breast cancer. Aims: We aimed to measure the frequency of CR expression in correlation with other clinicopathological parameters of different molecular subtypes of invasive breast carcinoma and to study its prognostic implications in this common cancer.Study Design: Tissue microarrays were constructed from 225 tissue samples of breast carcinoma cases. Subjects and Methods: Immunostaining for CR in addition to estrogen receptors, progesterone receptors, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor, CK5/6, and Ki-67 for molecular subtyping. Statistical Analysis Used: Chi-square and Fisher's exact tests were done using SPSS 18.0 software (IBM Inc.). Survival data were analyzed using Kaplan–Meier test, Log-rank test, and Cox proportional hazard models. Results: Cases of invasive breast carcinomas with different grades were classified into 84 luminal A, 45 luminal B, 27 HER2 positive, 40 basal-like, and 29 unclassified. High CR expression was associated with tumors of high grade (P < 0.0001), high locoregional recurrence (P = 0.005), hormonal receptors negative, and high Ki-67 indices. They frequently display a basal-like phenotype (70%, P < 0.0001), HER2 (59.3%), and luminal B (33.3%) tumors compared to luminal A (9.5%) and unclassified subtypes (17.2%). Moreover, it is associated with poor overall patient survival (P = 0.034), but it does not affect disease-free survival. Conclusions: Calretinin could be a reliable predictor marker of adverse prognosis in breast cancer.
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Histological evaluation of the possible transformation of peripheral giant cell granuloma and peripheral ossifying fibroma: A preliminary study p. 15
Ömür Dereci, Şivge Akgün, Bülent Celasun, Adnan Öztürk, Ömer Günhan
DOI:10.4103/0377-4929.200032  PMID:28195085
Aims: The objective of this study is to describe shared morphological features of peripheral giant cell granuloma (PGCG) and peripheral ossifying fibroma (POF) in detail and discuss the possible relationship between them. Materials and Methods: Ten intermediate cases with features resembling to both POF and PGCG were selected and type 3 and 1 collagen immunostainings were performed for evaluation of the connective tissue maturation. Immunohistochemical staining percentage (SP) for stromal cells in the slides of POF and PGCG counterparts of intermediate lesions was scored as 1 when the SP was above 10%, 2 when the SP was above 25%, 3 when the SP was above 50% and 4 when the SP was above 75%. Staining intensity (SI) of immunuhistochemical staining was graded and scored as 1 - mild, 2 – moderate, and 3 - severe. An immunoreactivity score was calculated by multiplying SP and SI. Results: All intermediate lesions comprised osteoclast type multinucleated giant cells and partly mineralized hard tissue component. Parts of intermediate lesions resembling POF showed higher type 1 collagen immunoreactivity compared to the PGCG counterparts of intermediate lesions (P < 0.05). PGCG counterparts showed higher type 3 collagen immunoreactivity compared to the POF counterparts of the intermediate lesions (P < 0.05). Conclusion: POF may be a later stage lesion with morphologically more mature components. A possible transformation may be considered for these two lesions.
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Altered expressions of Notch-1 signaling proteins and beta-catenin in progression of carcinoma in situ into squamous carcinoma of uterine cervix p. 21
Na-Hye Myong
DOI:10.4103/0377-4929.200045  PMID:28195086
Background: Activation of Notch-1 signaling pathway and loss of membranous beta-catenin have been known to play key roles in the progression of uterine cervix cancer and thus this study focused any alteration in the expression patterns for Notch-1, p53, and cyclin D1 as well as beta-catenin in squamous carcinoma in situ (CIS) and invasive squamous carcinomas to investigate their roles in the progression of CIS to squamous carcinomas. Materials and Methods: Three Notch-1 signaling proteins, such as Notch-1, TP53, and cyclin D1, and a component of cell adhesion complex, beta-catenin, were immunohistochemically stained in 112 uterine cervical tumors including 74 CIS and 38 invasive squamous carcinomas (11 microinvasive and 27 invasive carcinomas). Each immunohistochemical result was compared between CIS and squamous carcinoma groups and the difference was statistically analyzed. Results: Notch-1 protein expression was significantly higher in the microinvasive and invasive carcinomas than in CIS lesions (P = 0.001). Cyclin D1 and p53 immunoreactivities tended to be expressed higher in the invasive group than in CIS (P = 0.056 and 0.060). Membranous beta-catenin expression was significantly reduced in squamous carcinomas compared to CIS (P = 0.000). However, both CIS and squamous carcinoma groups revealed no interrelationship among Notch-1 signaling proteins and beta-catenin. Conclusion: Altered expressions of Notch-1 signaling proteins and beta-catenin in the progression of CIS into squamous carcinoma of uterine cervix suggests that Notch-1 signaling pathway and cell adhesiveness might play key roles in the stromal invasion of CIS cells.
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Perineural invasion is a valuable prognostic factor in advanced stage and/or Node (+) cervical cancer p. 27
Cigdem Vural, Busra Yaprak Bayrak, Bahar Muezzınoglu, Izzet Yucesoy
DOI:10.4103/0377-4929.200021  PMID:28195087
Background: Perineural invasion (PNI) is correlated with adverse survival in several malignancies, but its significance cervical cancer remains to be clearly defined. The objective of this study was to determine the association between PNI status and clinical outcomes in clinically localized surgically treated cervical cancers. Materials and Methods: We reviewed clinical records and pathology slides of 111 patients with cervical cancer treated with surgery at a single academic center. PNI was evaluated for presence, number of foci per slide, involved largest nerve size, and topographically (intratumoral vs. extratumoral). Association with these parameters, clinicopathologic characteristics and survival were analyzed. Results: The analysis demonstrated that PNI in cervical cancer was significantly correlated with parametrial invasion, tumor size, resection margin involvement, lymphovascular invasion, lymph node (LN) metastasis, depth of stromal invasion, necrosis, and higher stage disease (P < 0.005). Similarly, PNI density and mean size of the nerve involved were also associated with advanced stage (P < 0.005). In the multivariate analysis, PNI was not an independent prognostic factor for disease-free and overall survival. However, in the advanced stage cases and LN (+) cases, PNI is significantly associated with lower overall survival (43 vs. 58 months and 36 vs. 60 months, respectively, P < 0.005). Conclusions: The presence of PNI is accompanied by high-risk factors for recurrence. Overall survival rate is significantly reduced in PNI (+) patients. Although PNI itself is not an independent prognostic factor, PNI has a significant prognostic impact on overall survival in patients with advanced stage and/or Node (+) cervical cancer.
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Serotonin receptor 4 (5-hydroxytryptamine receptor Type 4) regulates expression of estrogen receptor beta and cell migration in hormone-naive prostate cancer p. 33
Yasuhiro Nakamura, Kazue Ise, Yuto Yamazaki, Fumiyoshi Fujishima, Keely M McNamara, Hironobu Sasano
DOI:10.4103/0377-4929.200022  PMID:28195088
Background: Estrogens are considered to potentially play some roles in the development and progression of prostate cancer through estrogen receptor beta (ERβ). However, additional factors which could influence the clinical outcome of the patients through modulating these steroid signalings have also been proposed. Among these, increased expression of serotonin receptor especially that of 5-hydroxytryptamine receptor Type 4 (5-HTR4) has been recently proposed to be involved in autocrine/paracrine mechanisms of castration-resistant prostate cancer, but the presence and clinical significance of 5-HTR4 in hormone-naive prostate cancer (HNPC) and its interaction with hormonal signaling pathways have remained virtually unknown. Materials and Methods: We evaluated the status of 5-HTR4 in 112 human HNPC cases (acinar adenocarcinoma) using immunohistochemistry and correlated the findings with clinicopathological features of individual patients and the status of androgen receptor (AR) and ERβ. To further elucidate its underlying mechanisms, androgen-dependent human prostate carcinoma cell line, LNCaP, expressing 5-HTR4, was treated by 5-HTR4 agonist. Results: 5-HTR4 immunoreactivity was detected in 34% of prostate cancer cases examined (38/112) and was significantly correlated with the status of ERβ but not with that of AR and other clinicopathological factors of the patients. Results of in vitro studies demonstrated that 24 h incubation with 5-HTR4 agonist (10 nM) increased the expression level of ERβ messenger RNA compared to controls. 5-HTR4 agonist (100 nM) significantly inhibited LNCaP carcinoma cell migration (P < 0.05). Conclusion: Results of our present study indicated that 5-HTR4 signaling upregulated ERβ expression in HNPCs and could impact on biological processes in HNPC.
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Immunogenetics of chronic lymphocytic leukemia p. 38
Nikhil Patkar, Nikhil Rabade, Pratibha Amare Kadam, Falguni Mishra, Aditi Muranjan, Prashant Tembhare, Shruti Chaudhary, Swapnali Joshi, Hasmukh Jain, Uma Dangi, Bhausaheb Bagal, Navin Khattry, Hari Menon, Sumeet Gujral, Manju Sengar, PG Subramanian
DOI:10.4103/0377-4929.200051  PMID:28195089
Introduction: Cytogenetic aberrations as well as presence of IGVH mutations are the underlying reason for clinical heterogeneity in Chronic Lymphocytic Leukemia (CLL). The presence of IGVH mutations as well as the predominant gene usage shows geographical variations. However, there is no study from India addressing immunogenetics of CLL. In a first Indian study we document the immunogenetics of CLL in a large tertiary hospital. Methods: We analyzed IGVH mutation status, VH gene usage, cytogenetic abnormalities using FISH, immunophenotyping data and correlated them with standard clinical variables in 84 patients of CLL. Results: Advanced Rai stage (Stage 3/4) was seen in 45% of our patients, where as 13q deletion was the commonest clonal cytogenetic abnormality detected in 48.4% of the cases. IGVH unmutated cases (55.2%) showed higher proportion expressing CD38 and CD49d, a preferential usage for VH1 and VH3 families (55.2%), presentation at an advanced Rai stage (52.8%) as well as more frequent presence of p53 deletions. As compared to the IGVH mutated cases greater proportion of IGVH unmutated patients (70%) required treatment. However, there was no significant difference in the time to treatment between mutated and unmutated cases which can be attributed to relatively short median follow up of 10 months. Conclusion: To summarize, we have seen a higher proportion of IGVH unmutated patients in our cohort (55.2%). The commonly used VH genes in the Indian population are IGVH 2-5, IGVH 1-2 and IGVH 1-69. Longer clinical follow up and a larger cohort is necessary to confirm the prognostic value of IGVH mutation analysis in Indian Patients with CLL.
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Mixed-phenotypic acute leukemia series from tertiary care center p. 43
Ravikiran N Pawar, Sambhunath Banerjee, Subhajit Bramha, Shekhar Krishnan, Arpita Bhattacharya, Vaskar Saha, Anupam Chakrapani, Saurabh Bhave, Mammen Chandy, Reena Nair, Mayur Parihar, Neeraj Arora, DK Mishra
DOI:10.4103/0377-4929.200057  PMID:28195090
Introduction: Mixed-phenotype acute leukemias (MPALs) are a heterogeneous group of rare leukemias constituting approximately 2%–5% of all leukemias, in which assigning a single lineage of origin is not possible. They are diagnosed by either the presence of antigens of more than one lineage or by the presence of dual population of blasts belonging to two or more lineages. We highlight the clinicopathological, immunophenotype, and genetic data of a cohort (n = 14) of patients diagnosed and treated at our center. Materials and Methods: We retrospectively analyzed consecutive cases of MPAL diagnosed in our flow cytometry laboratory from May 2012 to August 2015. These cases were diagnosed based on immunophenotyping of peripheral blood/bone marrow aspirates and morphology/genetics wherever available as per the World Health Organization (WHO) 2008 guideline. Results: Among 628 consecutive acute leukemia (AL) cases diagnosed and evaluated during this period, we identified 14 (2.2%) patients with MPAL fulfilling WHO 2008/EGIL criteria for immunological characterizing of AL criteria. Majority of these were males (n = 8, male:female ratio 1.3:1) and adults (n = 11, 78.5%). The median age of this cohort was 41 years (range 2–80). These cases were further classified as: B/myeloid (n = 9), T/myeloid (n = 4), and B/T MPAL (n = 1). Cytogenetics was available in 12 out of 14 cases, out of which, three cases had normal karyotype, three with t(9;22)(q34;q11), and two cases with complex karyotype. We also came across a rare case of B + T lymphoid MPAL who had mixed-lineage leukemia gene t(v; 11q23) rearrangement. Conclusion: MPAL is a complex entity with heterogeneous clinical, immunophenotypic, cytogenetic, and molecular features. Multiparametric flowcytometry by using comprehensive antibody panels is a valuable tool for diagnosis. Subsequent cytogenetic and molecular analysis for further prognostic stratification and treatment modalities are important.
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Coagulation profile during induction chemotherapy in childhood acute lymphoblastic leukemia p. 50
Shivali Sehgal, Sunita Sharma, Jagdish Chandra, Anita Nangia
DOI:10.4103/0377-4929.200029  PMID:28195091
Context: Thromboembolism in children with acute lymphoblastic leukemia (ALL) is most commonly reported after the initiation of antileukemic therapy, indicating a possible interaction of disease and therapy. Aims: To study the effect of induction chemotherapy on coagulation parameters in pediatric ALL patients. Settings and Design: Thirty-seven newly diagnosed patients of ALL up to 18 years of age were evaluated along with 30 age- and sex-matched controls. Subjects and Methods: At the time of diagnosis (day 0), various coagulation parameters were tested. These were sequentially analyzed on day 14 (after the completion of L-asparaginase doses) and on day 28 of therapy (after the completion of induction). Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C (PC) activity, and protein S (PS) activity were done by a clot-based method. Antithrombin (AT) assay was performed by chromogenic method. D-dimer (D-DI), tissue plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1) levels were assayed by ELISA method. Statistical Analysis Used: The statistical analysis was done using Statistical Package for Social Sciences version 17.0. Results: No major change in PT and APTT was observed during chemotherapy; however, fibrinogen levels declined significantly (P = 0.04), following L-asparaginase treatment. D-DI levels were significantly raised at diagnosis (P < 0.001) and throughout induction therapy (P < 0.001). PC, PS, and AT were reduced in the initial part of induction, followed by a rise in the second half of therapy, reaching their respective baseline levels (P < 0.05). The tPA levels were significantly reduced in the patients at diagnosis and throughout therapy (P < 0.001). PAI-1 levels were comparable to controls at presentation and showed a rising trend during therapy. Conclusions: The results of this study indicated that both the malignant process and the drugs used in combined chemotherapy cause thrombin activation, decrease in natural inhibitors, and hypofibrinolysis, resulting in hypercoagulability. Thus, ALL per se is a hypercoagulable state and the prothrombotic condition at the time of diagnosis gets enhanced during induction chemotherapy.
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Efficacy of in-house fluorescent stain for fungus p. 57
K. R. L. Surya Kirani, V Satya Chandrika
DOI:10.4103/0377-4929.200049  PMID:28195092
Context: Mycotic infections are gaining importance in the present day medicine, and definite demonstration of fungus is essential for diagnosis. Small numbers of organisms in the smear can be identified by fluorescence microscopy. Calcofluor white (CFW) fluorescent stain is a textile brightener mixed with Evans blue. It is expensive and not easily available. Aims: (1) To assess the efficacy of in-house CFW fluorescent stain for fungus in relation to conventional CFW stain, histopathology, and culture. (2) To determine sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with culture as gold standard. Settings and Design: One hundred cases of suspected dermatophytosis and 15 cases of systemic mycosis were included in the study. Subjects and Methods: The local whitener Ranipal is added with Robin blue, another brightener, and was used to stain teased fungal cultures. Skin, hair, and nails require pretreatment with potassium hydroxide (KOH). Biopsy slides require deparaffinization and pretreatment with KOH before staining. Conventional calcofluor stain, histopathology, and culture were done. Statistical Analysis Used: Statistical analysis was performed using sensitivity, specificity, NPV, and PPV. Results: The results are consistently comparable with conventional stain. The sensitivity was 100%, specificity was 93.3%, NPV was 100%, and PPV was 85.7%. It is also cost effective when compared to commercial stains. Conclusions: In-house stain can be used for screening of fungus in direct samples, biopsies as alternative in resource-constrained laboratories.
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Molecular identification of Candida species isolated from cases of neonatal candidemia using polymerase chain reaction-restriction fragment length polymorphism in a tertiary care hospital p. 61
Akeela Fatima, Gulnaz Bashir, Tehmeena Wani, Abiroo Jan, Amrish Kohli, Mosin S Khan
DOI:10.4103/0377-4929.200023  PMID:28195093
Context: Candida spp. is an emerging cause of bloodstream infections worldwide. Delay in speciation of Candida isolates by conventional methods and resistance to antifungal drugs in various Candida species are responsible for the increase in morbidity and mortality due to candidemia. Hence, the rapid identification of Candida isolates is very important for the proper management of patients with candidemia. Aims: The aim was to re-evaluate the identification of various Candida spp. by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and to evaluate the accuracy, speed, and cost of phenotypic methodology versus PCR-RFLP. Settings and Design: Hospital-based cross-sectional study. Materials and Methods: Ninety consecutive clinical isolates of seven Candida species, isolated from blood of neonates and identified by routine phenotypic methods, were re-evaluated using universal primers internal transcribed spacer 1 (ITS1) and ITS4 for PCR amplification and Msp I restriction enzyme for RFLP. Statistical Analysis Used: Kappa test for agreement. Results: The results of PCR-RFLP were 100% in agreement with those obtained using conventional phenotypic methods. Identification could be achieved within 3 work days by both the methods. Our routine methods proved to be cost effective than PCR-RFLP. Conclusions: We can continue with our routine phenotypic methods and PCR-RFLP can be used for periodic quality control or when conventional methods fail to identify a species.
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Association of interleukin-2, -4 and -10 with dengue severity p. 66
Kumar S Abhishek, Anita Chakravarti, CP Baveja, Naresh Kumar, Oves Siddiqui, Suman Kumar
DOI:10.4103/0377-4929.200027  PMID:28195094
Background: Dengue is an arboviral disease caused by four distinct serotypes of dengue virus. The pathogenesis of dengue is not very clearly understood. Various pro- and anti-inflammatory cytokines are involved in the immune pathogenesis of dengue. Interleukin (IL)-2/IL-2 receptor interaction is supposed to play a protective role, while IL-4 acts as pro-inflammatory whereas IL-10 acts as anti-inflammatory cytokines. So far, not much information is available regarding the established role of these cytokines with dengue infection and severity. Aims: our study aimed to show the association of IL-2, -4, and -10 with severity of dengue infection. Settings and Design: This was a cross-sectional study. Materials and Methods: The study was conducted in the year 2015; 150 blood samples from suspected dengue cases were confirmed for dengue and then with an equal number of healthy control samples were tested for cytokines levels (IL-2, -4, and -10) by ELISA. Severity of the dengue infection was determined on the basis of clinical manifestations based on the WHO criteria.Statistical Analysis: for statistical analysis, SPSS version 21 (IBM, New York, United States) was used. Results: Out of 150 samples, 56 samples came to be dengue positive. Thirty-eight (67.85%) cases were classified as nonsevere dengue and 18 (32.15%) were severe dengue. The serum levels of IL-4 and -10 were significantly raised in severe dengue cases as compared to nonsevere dengue cases. No significant association was observed between serum IL-2 levels and the severity of dengue. Conclusion: IL-4 and -10 levels can be used as marker of severe dengue and help in early preparedness to start the treatment in the line of severe dengue.
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Molecular detection of Orientia tsutsugamushi from suspected scrub typhus cases p. 70
Seethalakshmi Srinivasan, Thangam Menon
DOI:10.4103/0377-4929.200043  PMID:28195095
Context: Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. The disease is under-diagnosed in India, because of low index of suspicion and also due to its nonspecific presentation, and lack of confirmatory diagnostic tests. Aims: This study was undertaken to diagnose scrub typhus in patients with undifferentiated fevers by serology and molecular methods. Materials and Methods: A total of 68 blood samples were collected from patients clinically suspected to have scrub typhus. After transportation to the laboratory, the serum was separated from the blood and subjected to rapid card test. The ethylenediaminetetraacetic acid blood samples were subjected to DNA extraction using QIAamp DNA Mini Kit followed by nested polymerase chain reaction (nPCR). Results: 24/68 (35.29%) cases showed the presence of antibody against scrub typhus by serology. 6/68 (8.8%) patients showed the presence of outer membrane protein antigen gene 56 kDa by nPCR. 5/24 serology positive cases showed the presence of 56 kDa outer membrane protein antigen gene by nPCR. A large number of cases positive by serology were negative by PCR which may indicate a low sensitivity of this test either due to low copy numbers or due to excess host DNA. Conclusion: Delay in treatment may increase disease severity and leads to higher mortality. Thus, molecular methods of diagnosis may aid in the early diagnosis of infection and enable prompt treatment. This is the first report on the diagnosis of scrub typhus in the suburbs of Chennai using molecular methods and reemphasizes the need for increased awareness of rickettsial infections in rural areas.
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Genotyping of clinical and environmental multidrug resistant Enterococcus faecium strains p. 74
Leili Shokoohizadeh, Ashraf Mohabati Mobarez, Masoud Alebouyeh, Mohammad Reza Zali, Reza Ranjbar
DOI:10.4103/0377-4929.200048  PMID:28195096
Context: Multidrug resistant (MDR) Enterococcus faecium is a nosocomial pathogen and clonal complex 17 (CC17) is the main genetic subpopulation of E. faecium in hospitals worldwide. Aims: There has thus far been no report of major E. faecium clones in Iranian hospitals. Subjects and Methods: The present study analyzed strains of MDR E. faecium obtained from patients and the Intensive Care Unit environments using pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to determine the antibiotic resistance patterns and genetic features of the dominant. Results: clones of E. faecium. PFGE and MLST analysis revealed the presence of 17and 15 different subtypes, respectively. Of these, 18 (86%) isolates belonged toCC17. Most strains in this clonal complex harbored the esp gene and exhibited resistance to vancomycin, teicoplanin, ampicillin, ciprofloxacin, gentamicin, and erythromycin. The MLST results revealed 12 new sequence types (ST) for the first time. Approximately 50% of the STs were associated with ST203. Conclusion: Detection of E. faecium strains belonging to CC17 on medical equipment and in clinical specimens verified the circulation of high-risk MDR clones among the patients and in hospital environments in Iran.
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BRIEF COMMUNICATIONS Top

Phenotypic expression of HbO Indonesia in two Indian families and its interaction with sickle hemoglobin p. 79
Amar Das Gupta, Anita Nadkarni, Pallavi Mehta, Manju Goriwale, Manisha Ramani, Pradnya Chaudhary, Vishal Mehrotra, Roshan Colah
DOI:10.4103/0377-4929.200030  PMID:28195097
Background: Alpha globin chain variants are clinically significant since they directly influence the structure and function of the hemoglobin (Hb) molecules they constitute, either in combination with normal beta globin chains or with variant beta chains, thereby altering the morbidity and mortality associated with the resultant hemoglobinopathies. We describe here two unrelated families from Madhya Pradesh who had a nondeletional alpha-chain variant, HbO Indonesia (CD116 G → A). Members of one of the two families also had coinheritance of sickle hemoglobin (HbS). Aims: The aim was to study the phenotype of HbO Indonesia and its interaction with HbS. Materials and Methods: Hb electrophoresis, high-performance liquid chromatography (HPLC), covalent reverse dot blot hybridization, amplification refractory mutation system, multiplex polymerase chain reaction, and direct gene sequencing were used to identify and characterize the variant Hbs. Results: The abnormal Hb moved in HbS region in Hb electrophoresis at alkaline pH but gave an abnormal peak in HPLC with a retention time (RT) of 4.86–4.89 min. In two members of the family with coinheritance of HbS, it produced small additional abnormal Hb peaks (4.6% in heterozygous and 11.9% in homozygous member) in HPLC with a longer RT (5.15–5.17 min) possibly resulting from a combination of HbO Indonesia alpha chain with HbS beta chain. Conclusions: It appears that depending on the zygosity of HbS, HbO Indonesia would subtract a variable amount of HbS beta chain from the total pool, thereby potentially reducing the clinical severity of HbS disease. HbO Indonesia per se does not cause anemia or alter the red cell indices.
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Biclonal chronic lymphocytic leukemia: A study of two cases and review of literature p. 84
Kiran Ashok Ghodke, Nikhil V Patkar, PG Subramanian, Sumeet Gujral, Pratibha Aamre Kadam, Prashant R Tembhare
DOI:10.4103/0377-4929.200019  PMID:28195098
Chronic lymphocytic leukemia (CLL) is a common, immunophenotypically well-defined mature B-cell neoplasm. Demonstration of more than 5000/μL CD5+ B-cell population with co-expression of CD23, weak expression of CD20, and one type of immunoglobin light chain (either kappa or lambda) is necessary for the diagnosis of CLL. However, CLL with two populations of B-cells expressing both kappa as well as lambda (biclonal) light chains are extremely rare and has not been reported from India. We report two cases of biclonal CLL presented with leukocytosis, typical morphological features, and distinct immunophenotype of CLL. These cases are also an example which suggests that careful attention to the morphology of the blood smear and the entire immunophenotype panel is a must and will aid the proper diagnosis as only light chain ratios can be misguiding.
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Identification of prognostic factors in patients with diffuse large B-cell lymphoma p. 87
Fang Peng, Liang Guo, Wei-Kai Yao, Yan Zheng, Ye Liu, Xiu-Mei Duan, Yin-Ping Wang
DOI:10.4103/0377-4929.200056  PMID:28195099
To identify prognostic factors for patients with diffuse large B-cell lymphoma (DLBCL), specifically those classified into conflicting subgroups by Hans' and Choi's classification algorithms. We retrospectively reviewed clinical and pathological data of 154 patients diagnosed with de novo DLBCL in the First Hospital of Jilin University from January 2004 to September 2011. All cases were classified into subgroups based on Hans' and Choi's algorithms with immunohistochemical markers. Statistical Analysis Used: The correlation between various clinicopathological factors and 5-year survival rate, the correlation between those factors with the International Prognostic Index, the concordance between Hans' and Choi's approach was evaluated. The survival in different subtypes as classified by Hans' or Choi's approach was mapped. Results: The Eastern Cooperative Oncology Group (ECOG) performance score 2–5, positive Bcl-2 expression, negative CD10 expression or negative Bcl-6 expression significantly correlated with worse prognosis. The two algorithms showed good consistency (83% concordance, Kappa = 0.660, P < 0.001). By both classifications, the 5-year overall survival rate in germinal center B-cell-like subtype (GCB) lymphoma is significantly higher than that in the non-GCB subtype. There were 25 cases assigned to conflicting subtypes by the two approaches. Among these 25 cases, ECOG 2–5, positive Bcl-2 expression, negative CD10 expression, or negative Bcl-6 expression significantly correlated with worse prognosis. Conclusions: ECOG 2–5, positive Bcl-2 expression, negative CD10 expression, or negative Bcl-6 expression are independent markers for poor prognosis of DLBCL patients. There were 15% cases assigned to conflicting subgroups based on the two algorithms. For these cases, ECOG 2–5, positive Bcl-2 expression, negative CD10 expression, or negative Bcl-6 expression still significantly correlate with poor prognosis.
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CLINICOPATHOLOGIC CONFERENCE Top

A 54-year-old male with rapidly progressive neurologic syndrome: Clinicopathologic correlation of a rare diagnosis p. 92
Deepti Mutreja, Nikhil Moorchung, Salil Gupta, Rajeev Saxena, Rohini S Doshetty, Bhaskar Nandi
DOI:10.4103/0377-4929.200026  PMID:28195100
Diagnosis of systemic lupus erythematosus (SLE) as primary presentation with central nervous system involvement as a rapidly progressive neurologic syndrome is extremely rare. We present a rare case of a 54-year-old hypertensive male patient, who presented with a fulminant neurologic syndrome. He presented with cerebellar and meningeal signs, aseptic meningitis and had a rapid downhill course following admission. A postmortem revealed feature of systemic connective tissue fulfilling diagnostic criteria of SLE with lupus cerebritis.
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CASE REPORTS Top

Trichoblastic carcinoma of the scalp with rippled pattern p. 97
Cem Leblebici, Dincer Altinel, Merdan Serin, Oguzhan Okcu, Sevgi Kurt Yazar
DOI:10.4103/0377-4929.200024  PMID:28195101
Trichoblastic carcinoma (TC) is a rare type of malignancy which is derived from the hair follicles. In this paper, we report a case with TC on the scalp characterized with rippled pattern. There have been reports of rippled pattern in trichoblastomas, sebaceomas, and basal cell carcinomas. To the best of our knowledge, this is the first case in the literature to report a rippled pattern in TCs.
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Atypical parathyroid adenoma p. 99
Anikode Subramanian Ramaswamy, Thinakaran Vijitha, BN Kumarguru, Prashant Basavaraj Mahalingashetti
DOI:10.4103/0377-4929.200055  PMID:28195102
Parathyroid lesions clinically manifest themselves in the form of primary hyperparathyroidism most of the times. Parathyroid adenoma constitutes one of the important causes of the same. Although rare, they pose considerable diagnostic dilemma to the pathologist. A 50-year-old female presented to the surgical outpatient of our hospital with a history of recurrent pancreatitis. Clinical examination revealed a mass in the neck which was radiologically demonstrated as right inferior parathyroid mass. The same mass was surgically excised and histopathological features are discussed in this report.
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Malignant melanocytic neoplasm of pancreas with liver metastasis: Is it malignant melanoma or clear cell sarcoma? p. 102
Thomas Alex Kodiatte, Sam Varghese George, Raju Titus Chacko, Banumathi Ramakrishna
DOI:10.4103/0377-4929.200054  PMID:28195103
Malignant melanocytic neoplasm, usually seen in soft tissues, is rare in a visceral location and presents as a diagnostic dilemma. We present a case of pancreatic malignant melanocytic neoplasm with liver metastasis. A 58-year-old man presented with left upper abdominal swelling and loss of appetite. Imaging revealed a large mass arising from the pancreatic tail, and this was diagnosed as malignant neoplasm with melanocytic differentiation on biopsy with the possible differentials of malignant melanoma, clear cell sarcoma (CCS), and perivascular epithelioid cell neoplasm. The patient underwent distal pancreatectomy and splenectomy for the same. Follow-up imaging 6 months later showed a metastatic liver lesion, for which he also underwent a liver resection. BRAF mutational analysis was found to be negative. Both CCS and malignant melanoma have similar morphological features and melanocytic differentiation, but each harbors a distinct genetic background. Differentiation of both has diagnostic and therapeutic implications.
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Well differentiated neuroendocrine tumor of the kidney: Report of a rare case with review of literature p. 105
Kavita Mardi, Lalita Negi, Srijan Srivastava
DOI:10.4103/0377-4929.200020  PMID:28195104
Neuroendocrine tumors (NETs) are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC), and large cell neuroendocrine carcinoma (LCNEC) are exceedingly rare. Renal carcinoids are typically slow-growing tumors and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. We herein report a rare cases of well-differentiated NET (carcinoid) in a 39-year-old male along with the immunohistochemical features. The rarity of these tumors poses a diagnostic and therapeutic challenge.
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Hereditary leiomyomatosis and renal cell cancer syndrome associated renal cell carcinoma p. 108
Shraddha Adamane, Sangeeta Desai, Santosh Menon
DOI:10.4103/0377-4929.200025  PMID:28195105
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a recently described entity with unknown exact prevalence. The affected individuals are predisposed to have multiple leiomyomas and renal cancer due to germline mutation in fumarate hydratase gene on chromosome 1. The knowledge of this rare tumour is essential for early recognition and institution of appropriate therapy, since they have a grave prognosis. Herein, we present the first case from India of HLRCC in a 42 year old lady who presented with a renal mass and metastasis with consequent fulminant course of disease. We discuss the detailed histomorphologic features and iunique immunohistochemical signature of this unusual renal tumour with discussion of differential diagnosis.
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Dual tumor – Clear cell sarcoma of kidney with differentiating neuroblastoma: A rare case with review of literature p. 111
Preeti Rajeev Doshi, Manjiri N Karandikar, Ravi C Swami, Harvinder A Singh, Ravindra C Nimbargi
DOI:10.4103/0377-4929.200047  PMID:28195106
Occurrence of two distinct synchronous primary tumors is a rare event in children as well as in adults. Here, we report an extremely rare case of an infant found to have two synchronous Tumours namely clear cell sarcoma of kidney(CCSK) and differentiating neuroblastoma of preaortic region. To our knowledge, this may be the first case of synchronous CCSK and differentiating neuroblastoma being reported.
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COMMENTARY Top

Concurrent occurrence of neuroblastoma and clear cell sarcoma of kidney in an infant: Is it a random event? p. 115
Ramesh B Deshpande
DOI:10.4103/IJPM.IJPM_663_16  PMID:28195107
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CASE REPORTS Top

Mucoepidermoid carcinoma in a mature cystic teratoma: A rare case report with review of literature p. 117
Yasmin Altaf Momin, Medha Pradip Kulkarni, Amitkumar Bapuso Pandav, Kalpana Ranjitsingh Sulhyan
DOI:10.4103/0377-4929.200038  PMID:28195108
Mature cystic teratoma, also known as dermoid cyst, is the most common germ cell tumor of the ovary with a relative incidence of 20%. Rarely, dermoid cysts undergo malignant transformation (0.94%–2%). We report a case of mucoepidermoid carcinoma within a mature cystic teratoma in a 35-year-old female.
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Metastatic nasopharyngeal carcinoma presenting as an isolated breast mass: A diagnostic pitfall and a review of literature p. 119
Trupti Pai, Nita Nair, Gauri Pantvaidya, Kedar Deodhar, Tanuja Shet
DOI:10.4103/0377-4929.200058  PMID:28195109
Metastases to breast are much rarer than primary breast tumors. We now present a case of 45-year-old female, who presented with an isolated breast mass. A positron emission tomography-computed tomography (PET-CT) done revealed hypermetabolic right breast nodules, soft tissue deposits, and multiple nodal involvement. The biopsy from the breast and axillary lymph node showed dense lymphoid infiltrate and was interpreted initially as granulomatous inflammation. However, the lumps were hard and suspicious for primary breast cancer, so an immunohistochemistry for cytokeratin was performed which highlighted the epithelial cell clusters masked within the inflammatory infiltrate and the diagnosis of undifferentiated carcinoma, lymphoepithelioma-like was made. After the diagnosis was made, it was realized that the patient had been treated earlier for a nasopharyngeal carcinoma (NPC). The in situ hybridization (ISH) test for Epstein–Barr virus-encoded RNA ISH was positive in the tumor cells, and hence, a diagnosis of metastatic NPC was finally made. The patient subsequently developed extensive nodal, skeletal, and soft tissue metastatic disease but was alive till September 2015. Although extremely rare, metastatic NPC can occur in the breast and the above case highlights that it mimics an inflammatory lesion. This case highlights the importance of the multidisciplinary approach for appropriate tumor diagnosis and patient management.
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A case of gallbladder mass: Malakoplakia (The tumor mimicker) p. 122
Kanwaljeet Singh, Tathagatta Chatterjee
DOI:10.4103/0377-4929.200034  PMID:28195110
Diagnosis of malakoplakia presenting as gall bladder mass is a diagnostic dilemma faced by pathologists, radiologists, and surgeons. Malakoplakia is a rare inflammatory disorder and tumor mimicker usually occurring in the urinary tract, may occasionally be found in gall bladder. Here, we present a rare case, presenting as gall bladder mass in a known case of gallstone disease, clinically suspected as carcinoma and later turned out to be malakoplakia in gall bladder.
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IMAGES Top

Squash cytodiagnosis of synchronous papillary serous carcinoma of ovary and endometrium with demonstration of serous tubal intraepithelial carcinoma as a precursor lesion p. 125
Asaranti Kar, Tushar Kar, Ipsita Dha, Sasmita Panda
DOI:10.4103/0377-4929.200039  PMID:28195111
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Lipoleiomyoma of the uterus p. 128
Barani Karikalan, Thanikachalam Pasupathi
DOI:10.4103/0377-4929.200052  PMID:28195112
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Congenital cytomegalovirus infection in a neonate born to HIV-infected mother: A case report p. 130
Dhaneshwar Namdeorao Lanjewar, Sushma Nagsen Ramraje
DOI:10.4103/0377-4929.200028  PMID:28195113
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LETTERS TO EDITOR Top

Malignant transformation in an atypical endometrial cyst of the ovary p. 132
Manjula Jain, Shivali Sehgal
DOI:10.4103/0377-4929.200053  PMID:28195114
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Tumor-to-tumor metastasis: Small cell carcinoma lung metastasising into a follicular adenoma of the thyroid p. 133
Kiran Krishne Gowda, Amanjit Bal, Parimal Agrawal, Roshan Verma, Ashim Das
DOI:10.4103/0377-4929.200037  PMID:28195115
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Pancreatic lipomatosis in a pregnant diabetic patient p. 135
Priyanka Bhagat, Kim Vaiphei
DOI:10.4103/0377-4929.200035  PMID:28195116
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Hemophagocytic lymphohistiocytosis secondary to multiple infections: Case report of a rare entity p. 137
Ankita Jaiswal, Varuna Mallya, Vishal Singh, Mandeep Walia, Nita Khurana
DOI:10.4103/0377-4929.200033  PMID:28195117
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Crystalline inclusions in myeloma cells: Need to go beyond morphologic curiosity p. 139
Shobhana R Agashe, Jaydeep N Pol, Girish A Kadkol, Pramila P Patil
DOI:10.4103/0377-4929.200036  PMID:28195118
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The tattoo dilemma: Reading in between the ink p. 141
Kusum Jashnani, Heena Desai, Jyothi Shetty, Sweety Shinde, Vinaya Shah
DOI:10.4103/0377-4929.200050  PMID:28195119
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β-lactam susceptibility in extended-spectrum β-lactamase-producing isolates p. 142
Gopal Nandlal Agrawal, Hina Dilipsingh Rahangdale, Aparajit W Walawalkar
DOI:10.4103/0377-4929.200044  PMID:28195120
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Social media: The new frontier for pathologists p. 143
Nadeem Tanveer
DOI:10.4103/0377-4929.200041  PMID:28195121
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