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   Table of Contents - Current issue
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April-June 2019
Volume 62 | Issue 2
Page Nos. 193-363

Online since Wednesday, April 10, 2019

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EDITORIAL  

From Editor's desk Highly accessed article p. 193
Ranjan Agrawal
DOI:10.4103/0377-4929.255846  
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GUEST EDITORIALS Top

Expanding the scope of tumor budding p. 195
Antonio DAntonio, Alessandro Caputo
DOI:10.4103/IJPM.IJPM_151_19  
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Prognostic value of lymph node ratio in cancer Highly accessed article p. 197
Asaranti Kar
DOI:10.4103/IJPM.IJPM_159_19  
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REVIEW ARTICLE Top

Small round cell lesions of the bone: Diagnostic approach, differential diagnoses and impact on treatment Highly accessed article p. 199
Bharat Rekhi, Asit Mridha, Jayashree Kattoor
DOI:10.4103/IJPM.IJPM_675_18  
Small round cell lesions of the bone encompass a heterogeneous group of tumors and tumor-like lesions, including Ewing sarcoma, small cell osteosarcoma, mesenchymal chondrosarcoma, neuroblastoma, non-Hodgkin's lymphoma (NHL), “Ewing-like” undifferentiated round cell sarcomas, metastasizing small cell carcinoma, along with plasma cell dyscrasia and Langerhan's cell histiocytosis. At the same time, there are tumor mimics, for example, chronic osteomyelitis, which has overlapping radiologic features with Ewing sarcoma and a primary intraosseous NHL. An exact diagnosis necessitates integration of clinical, radiologic, pathologic, and ancillary test results, including immunohistochemical and molecular results. Currently, there are several immunohistochemical markers and specific molecular signatures, driving most of these tumors, available, for an exact diagnosis. This review focuses on a pragmatic approach towards uncovering specific small round cell lesions of the bone, emphasizing upon integration of traditional morphology with ancillary techniques, including immunohistochemical markers and molecular techniques, the latter, especially in cases of Ewing sarcoma, Ewing-like undifferentiated round cell sarcoma, mesenchymal chondrosarcoma, and neuroblastoma. Subsequent to the diagnostic approach, including an impact on treatment, individual intraosseous round cell lesions have been described in detail. The references include updated articles from PUBMED.
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ORIGINAL ARTICLES Top

The diagnostic significance of trophoblast cell-surface antigen-2 expression in benign and malignant thyroid lesions p. 206
Canan Sadullahoğlu, Alper Sayıner, Dinç Süren, Hülya Tosun Yıldırım, Döndü Nergiz, Cem Sezer, Mehmet Tahir Oruç
DOI:10.4103/IJPM.IJPM_202_18  
Context: Thyroid cancers are the most common malignancy of the endocrine system. Over-expression of trophoblast cell-surface antigen 2 (TROP-2) in various tumors has been found to correlate with poor prognosis and aggressive tumor behavior. Aims: The aim of this study was to evaluateTROP-2 expression in thyroid neoplasms. Subjects and Methods: This study contained 152 cases, including 48 follicular nodular disease (FND), 29 follicular adenoma (FA), 57 papillary thyroid carcinoma (PTC), 12 follicular thyroid carcinoma (FTC), 3 medullary thyroid carcinoma (MTC), 2 poorly differentiated thyroid carcinoma (PDTC) and 1 undifferentiated thyroid carcinoma (UDTC). TROP-2 expression was investigated via immunohistochemistry in sections prepared from paraffin blocks of the cases. Results: The cases comprised 32 (21%) males and 120 (79%) females with a mean age of 46.8 years (range, 15-85 years). TROP-2 expression was observed in 74.6% of the malignant lesions of the thyroid except for medullary carcinoma, poorly differentiated and undifferentiated thyroid carcinoma. Immunoreactivity was 3.4% in FA, 41.7% of cases with FTC and 81.8% in PTC follicular variant (PTC fv). The difference between FA/FTC and FA/PTC follicular variant were both significant (P < 0.005, P < 0.001, respectively). There was no difference between FTC/PTC fv (P = 0.089). Conclusion: TROP-2 can be considered a useful marker for distinguishing PTC fv cases from follicular nodular disease and follicular adenoma cases because of its high sensitivity in the identification of papillary carcinomas of the thyroid.
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Incidental papillary thyroid microcarcinomas in thyroidectomy specimens: A single-center experience from Turkey p. 211
Fatma Senel, Hatice Karaman, Aynur Aytekin, Güler Silov, Ali Bayram
DOI:10.4103/IJPM.IJPM_439_18  
Background: Papillary thyroid microcarcinoma (PTM) is a relatively common entity in the general population. PTM is often asymptomatic and is detected incidentally during the histopathological examination of thyroidectomy specimens from operations because of benign thyroid disease. Aims: The aims of the study are to determine the incidence of incidental papillary thyroid microcarcinomas (IPTMs) in our center, to examine the clinicopathologic characteristics of these tumors, and to present our experiences. Materials and Methods: This study includes 827 patients who underwent thyroidectomy operation in our center between January 2013 and June 2017 and were examined histopathologically in the Pathology Clinic. Patients' demographic characteristics, preoperative diagnoses, operative procedure, histopathological findings, and postoperative prognostic indexes are presented. Results and Conclusion: Of the 827 patients, 138 (16.6%) were diagnosed with a malignancy. Of these, 124 were papillary carcinoma, 5 were follicular carcinoma, 4 were lymphoma, 2 were medullary carcinoma, 2 were anaplastic carcinoma, and 1 was poorly differentiated carcinoma. The IPTM incidence rate was 8.01%; the multifocality and bilaterality rates were 23.3% and 13.3%, respectively. In 98.3% of IPTM cases, total thyroidectomies were performed, and in 1.7% of cases, subtotal thyroidectomy was performed followed by complementary thyroidectomy. No relapse or metastasis was detected in any of these cases. A careful histopathological examination of the thyroidectomy specimen is essential because IPTM is frequently skipped in fine needle aspiration cytology. We consider it best to perform total thyroidectomies because bilaterality and multifocality rates are high in IPTM. Long-term life expectancy in these tumors is quite good.
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Evaluation of lymph node ratio and morphologic patterns of nodal reactive hyperplasia in primary organ malignancy p. 216
Shinde V Sweety, Ashwini Sardar Narayankar
DOI:10.4103/IJPM.IJPM_62_18  
Background: Lymph node ratio (LNR) in cancer staging is the ratio of nodal metastases (LNM) to total nodes harvested (LNH). Reactive nodal hyperplasia can exhibit morphological patterns I to VI. Aims: To measure LNR and evaluate it with tumor stage, tumor grade, LN reactive patterns, and LN size. Setting and Design: Retrospective, observational study of 100 cancer resections including breast, gastrointestinal (GIT), genitourinary (GUT), and head, face, neck, and thyroid (HFNT). Materials and Methods: Total 1463 LNs were reviewed for metastases and reactivity patterns I–VI as per the World Health Organization (WHO) protocol. LNR was calculated from LNM and LNH. Statistical Analysis Used: Association between qualitative variables was assessed by the Chi-square test and Fisher's exact test, those between quantitative variables using the unpaired t-test and Mann–Whitney U test. Results: Mean LNH (23.7) was highest in HFNT and lowest (6.6) in GIT (P = 0.008). Mean LNR was highest (0.29) in breast and least (0.06) in HFNT (P = 0.861). Commonest LN reactive patterns were sinus histiocytosis (60), mixed (48), and follicular hyperplasia (46) (P = 0.000). Maximum cases of breast (59.6%), GUT (53.8%), and HFNT (45%) belonged to stage T2, while GIT (60.0%) to stage T3 (P = 0.000). Maximum well-differentiated cases belonged to HFNT (13, 59.0%), while moderately poorly differentiated cases of breast (38, 55.8% and 7, 70.0%) (P = 0.000). The largest and smallest metastatic LN was 2.4 cm and 0.4 cm (P = 0.009). LNs with thickened capsule showed nodal metastases in 75.7% (P = 0.003871). Conclusions: LNH and LNR cut-off values show organ-wise variation and need standardization. LNR shows stronger relation with tumor grade than tumor stage. Commonest LN reactive patterns include sinus histiocytosis and follicular hyperplasia. Thickened LN capsule strongly suggests nodal metastases. A longitudinal follow-up is warranted to study prognostic association between LNR and LN reactive pattern.
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Tumor budding in infiltrating breast carcinoma: Correlation with known clinicopathological parameters and hormone receptor status p. 222
Radhika Agarwal, Nita Khurana, Tejinder Singh, PN Agarwal
DOI:10.4103/IJPM.IJPM_120_18  
Introduction: Tumor budding (TB) is proposed as an essential step in the invasion and metastasis of various tumors. However, there is limited information about its role in breast cancer. This study was designed to assess the prognostic significance of TB in clinical practice. Objectives: To study and grade TB in patients with invasive breast cancer and to correlate it with known prognostic parameters. Materials and Methods: In this prospective study, 40 cases of invasive breast cancer were studied over a period of 1.5 years. Tumor buds were defined as comprising five tumor cells or less at the invasive front of the tumor. Cases were separated into two groups according to TB density as low grade and high grade. Significance and correlation between TB with established clinicopathological parameters and hormone receptor status were studied by Chi-square test. P value <0.05 was considered significant. Results: All 40 cases in this study were newly diagnosed cases, who did not receive any therapy. The majority of patients were premenopausal (55%), had small tumor size ≤5 cm (67.5%), had negative lymph nodes (67.5%), had grades 2 and 3 (75%), and presented in stages 1 and 2 pathological stage (62.5%). The majority were estrogen-receptor-negative (62.5%), progesterone-receptor-negative (65%), and human epidermal growth factor receptor-2-positive (52.5%). Higher grade TB was observed in larger tumor (P = 0.03), in higher stage (P = 0.046), and in tumor having lymphovascular emboli (P = 0.03) when compared with small size, lower stage, and tumor with no lymphovascular emboli, respectively. Conclusion: As higher grade TB was associated with larger, higher stage tumor, and in tumor having lymphovascular emboli, it can be recognized as an easily identifiable prognostic factor.
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Immunophenotyping of male breast cancer - Experience at a tertiary care centre p. 226
Sunil Pasricha, Meenakshi Kamboj, Parul Tanwar, Gurudutt Gupta, Manoj Panigrahi, Anila Sharma, Garima Durga, Anurag Mehta
DOI:10.4103/IJPM.IJPM_543_18  
Background: Male breast cancers (MBCs) are uncommon and account for 1% of all breast cancers. Medical conditions that increase the estrogen to testosterone ratio are implicated as the risk factors. Morphologically similar, but MBCs have biological differences compared with female breast cancer (FBC). Purpose: The present study was aimed to examine the immunophenotype of MBC, subsequent molecular subtypes, their association with clinicopathological features, and prognosis. Materials and Methods: We analyzed clinicopathological features of 42 cases of MBC, and classified them according to molecular classification using immunohistochemistry (IHC). This is the second largest study from India. Results and Conclusion: Median age of patients was 61 years (age range: 41-87 years). Invasive duct carcinoma comprised 95.2% of cases. Tumor grade II and III was seen in 50% and 47.6% of cases, respectively, and advanced stage disease (III/IV) was seen in 45.2% cases (n = 39). Estrogen receptor (ER) was positive in 97.6% cases, progesterone receptor (PR) in 83.3%, androgen receptor (AR) in 76.2%, HER2 in 4.8%, Cyclin-D1 in 92.9%, Bcl2 in 66.7%, GCDFP-15 in 23.8%, p53 in 16.7%, and Ki67 index was low (<14%) in 66.7% cases. Molecular subtyping of these cases revealed 64.3% of luminal A, 35.7% of luminal B, and no HER2 rich/driven category or triple negative case. There was no statistical significance between luminal A and B category pertaining to overall stage of tumor (P = 0.905). Lymph node metastasis was more commonly associated with luminal B category (P = 0.089). p53 positivity showed significant association with luminal A cases (P = 0.002) and nodal metastasis (P = 0.042). GCDFP-15 positivity showed significant association with higher tumor grade (P = 0.042) and stage (P = 0.047). Stage was the most significant prognostic marker (P < 0.0001). On follow-up (n = 27), all the six cases that showed recurrence/persistent disease were high stage (III/IV) on presentation.
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Expression and clinical significance of B and T lymphocyte attenuator on CD4+ and CD8+ T cells from patients with pulmonary tuberculosis p. 232
Xinghua Shen, Jianping Zhang, Peijun Tang, Huafeng Song, Xiaocao Liu, Ziyi Huang, Xueguang Zhang, Xuefeng Wang, Meiying Wu
DOI:10.4103/IJPM.IJPM_727_17  
Background: As an immune checkpoint, upregulation of B and T lymphocyte attenuator (BTLA) contributes to T-cell exhaustion in chronic infection. However, the characteristics of BTLA on T cells of patients with pulmonary tuberculosis (PTB) are still uncovered. Aims: The aim of the study was to elucidate the dynamics and clinical significance of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients. Materials and Methods: BTLA expression on T cells from PTB patients with smear positivity (n = 86) and healthy controls (HCs) (n = 40) were determined using flow cytometry. Results: The levels of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients with smear positivity were both upregulated, compared with HC. At the same time, the levels of BTLA expression on CD4+ and CD8+ T cells of patients with retreatment were both higher than that of those with initial treatment and gradually upregulated along with the increase of the bacillary load in sputum. In addition, the patients with lung cavity were discovered to present higher levels of BTLA expression on CD4+ and CD8+ T cells than those without lung cavity. Whereas we noted that there was no correlation between the levels of BTLA expression and the positivity or negativity of anti-Mycobacterium tuberculosis antibody. Conclusions: The levels of BTLA expression were upregulated on CD4+ and CD8+ T cells of PTB patients and associated with disease progression. Thereby, BTLA expression on T cells may be considered as a potential clinical indicator and utilized as a therapeutic target for PTB.
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CD105 as a tool for assessing microvessel density in renal cell carcinoma p. 239
Andreea Cioca, Diana Muntean, Catalina Bungardean
DOI:10.4103/IJPM.IJPM_773_17  
Background: Angiogenesis plays an essential role in both tumor growth and metastasis. CD105 expression was correlated with prognosis in many tumors, but its value in renal cell carcinoma (RCC) is still questionable. Materials and Methods: The aim of this study was to evaluate microvessel density (MVD) by using CD105 marker, in 95 cases of renal cell carcinoma. Results: CD105 showed positivity in 93 cases. The mean MVD value was significantly higher in clear cell carcinoma compared to papillary and chromophobe subtypes (P = 0.000). We noticed a significant correlation between MVD and ISUP grade (P = 0.007). The highest MVD value was observed in tumors with ISUP grade 1 and 2, while the lowest MVD value was noted in ISUP grade 3 tumors. A high vessel density was identified in tumors with a low Fuhrman grade, compared to those with a high grade (P = 0.010). MVD value was lower in tumors with a larger diameter, compared to small ones (P = 0.026). Conclusion: In conclusion, CD105 expression (MVD) is inversely related to tumor aggressiveness in clear cell RCC and can be used as a favorable prognosis marker. The vascularity differences between histological subtypes of RCCs could be useful for a better selection of patients that may benefit from anti-angiogenic therapies.
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Diagnostic utility of GATA3 immunohistochemical expression in urothelial carcinoma p. 244
Harshita Agarwal, Suresh Babu, Chanchal Rana, Madhu Kumar, Atin Singhai, Shiv Narayan Shankhwar, Vishwajeet Singh, Rahul Janak Sinha
DOI:10.4103/IJPM.IJPM_228_18  
Aims: This study aims to explore the utility of GATA binding protein 3, a zinc finger transcription factor, expression in genitourinary carcinoma, especially urothelial carcinoma. Settings and Design: It is a prospective study where 74 consecutive cases of urothelial carcinoma along with 10 cases each of prostatic adenocarcinoma (PC) and conventional clear cell renal cell carcinoma were included between August 2016 and January 2017. Methods and Materials: All the cases were histopathologically evaluated and immunohistochemically stained for GATA binding protein 3. Only nuclear positivity was considered as positive. Immunoreactivity score for GATA expression was calculated based on the staining intensity as well as percentage. Statistical Analysis Used: The statistical analysis was done using Statistical Package for Social Sciences Version 15.0 statistical analysis software. P value of <0.05 was considered statistically significance. Results: GATA3 expressions were seen in 77% of the cases of urothelial carcinoma, whereas none of the clear cell renal cell carcinoma and prostatic adenocarcinoma cases was GATA3 positive. GATA3 expression significantly correlated with histological grade and muscle invasion with a weaker or negative expression in high-grade muscle invasive tumor as compared to low-grade and noninvasive neoplasm. Significantly weaker expression of GATA3 was found in cases with severe nuclear pleomorphism, mitosis >10/10 hpf, presence of necrosis, and tumor-infiltrating lymphocytes. No significant change in the status of GATA3 expression was seen in follow-up cases between initial Transurethral resection of bladder tumor (TURBT) and post-recurrence TURBT or radical cystectomy specimens. Conclusions: GATA3 as a sensitive and specific marker for urothelial carcinoma can be effectively used to exclude other genitourinary malignancies, PC, and renal cell carcinoma, at metastatic site. This marker can also be effectively used in predicting the probable grade and invasion in biopsy material with poor morphological characteristics, thereby helping in appropriate management in such cases.
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Histomorphological study of prostatic adenocarcinoma and its mimics p. 251
Qury S Mahapatra, Pranati Mohanty, Annu Nanda, Lity Mohanty
DOI:10.4103/IJPM.IJPM_322_18  
Context: Prostate adenocarcinoma (PC) is one of the common cancers in India and world over. Numerous prostatic, nonprostatic lesions, and normal structures can be very similar to adenocarcinoma. A pathologist's awareness of the benign mimics is important for the diagnosis of PC. Aim: The aim of this study was to determine the prevalence, clinical, and histopathological features of PC, and its common mimics, and to study the criteria for their distinction from PC. Materials and Methods: A prospective study of histopathological features of radical prostatectomy and transurethral resection of the prostate specimens, sent to the department of pathology in a medical college, for a period of 2 years was done. A brief clinical history followed by a clinical examination, including per-rectal findings and serum prostate-specific antigen (PSA) levels, was noted. Results: After excluding all the cases of benign hyperplasia of prostate without any associated findings, 50 cases of operated surgical specimens of prostate were studied. PC was the most frequent diagnosis in 28 patients of 50 cases (56.0%). Basal cell hyperplasia formed the predominant mimic (26.0%), followed by prostatic intraepithelial neoplasia (8%), prostate atrophy (4%), clear-cell cribriform hyperplasia(4%),, and one case of atypical adenomatous hyperplasia (2%). Serum PSA was >4 ng/mL in all the cases of PC. In three of the mimics, PSA was >4 ng/mL and in the rest it was <4 ng/mL. Immunohistochemistry (IHC) was not applied in our study. Conclusion: Biopsy still remains a gold standard for diagnosis of PC and its mimics. All the lesions in the above study were diagnosed on routine hematoxylin and eosin staining. IHC is useful especially for lesions in the grey zone but not in routine histopathological study and should not be used as a screening test but should be applied in specific selected cases only.
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Distribution of common BCR-ABL fusion transcripts and their impact on treatment response in Imatinib treated CML patients: A study from India Highly accessed article p. 256
Sudha Sazawal, Sunita Chhikara, Kanwaljeet Singh, Rekha Chaubey, Manoranjan Mahapatra, Tulika Seth, Renu Saxena
DOI:10.4103/IJPM.IJPM_726_17  
Background: Philadelphia chromosome (Ph): Hallmark of CML is caused by reciprocal translocation between chromosomes 9 and 22 resulting in BCR-ABL fusion protein. Most commonly associated breakpoint with CML is M-bcr in exon 13 or exon 14, producing splice variant b2a2 or b3a2 respectively. The distribution of these transcripts and their influence on clinico-hematological parameters is variable. Impact of the fusion transcripts on treatment outcome in Imatinib treated CML patients is still a matter of debate. Aims/settings and design: We conducted this study on 400 CML-CP patients to look for the distribution of fusion transcripts i.e. b3a2 and b2a2, their clinico-hematological profile and impact on treatment response in patients treated with Imatinib. Material and Methods: CML-CP was diagnosed by reverse transcriptase PCR (RT-PCR) for the BCR-ABL fusion transcript. Real-time quantitative PCR (RQ-PCR) was performed on peripheral blood every 3-6 monthly to look for treatment response. Results: The overall frequency of b3a2 transcript was observed in 288 (72%) followed by b2a2 in 104 (26%) and hybrid fusion transcript (b3a2 + b2a2) was seen in 8 (2%) cases. MMR was attained in 198/288 (68.7%) patients with b3a2 transcript and 90/288 (31.3%) patients failed to achieve MMR after 12 months of Imatinib therapy. Among the patients with b2a2 transcript, 44/104 (42.3%) patients achieved MMR and 60/104 (57.7%) patients failed to achieve MMR after 12 months of Imatinib therapy. Conclusions: In conclusion, the frequency of b3a2 transcript was more as compared to b2a2 transcript. MMR was significantly higher in patients with b3a2 transcript as compared to patients with b2a2.
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BRIEF COMMUNICATIONS Top

Focal nodular hyperplasia of the liver in children: A report of 2 cases p. 261
Nelofar Islam, Aniket Halder, Ranajoy Ghosh, Sugato Banerjee, Prafulla Kumar Mishra, Uttara Chatterjee
DOI:10.4103/IJPM.IJPM_396_18  
Focal nodular hyperplasia (FNH) is a benign non-neoplastic lesion of the liver usually found in adults. It is uncommon in children, comprising 2-10% of all pediatric liver tumours. In children, it can occur at all ages, with increased frequency between 6-10 years. We present two cases of FNH in childhood- the first being that of a 5-month-old infant, and the second in a 6-year-old boy. The possibility of congenital FNH had been excluded in the first case. The second case posed diagnostic difficulty initially and was wrongly treated for hepatoblastoma by neoadjuvant chemotherapy, but later correctly diagnosed to be FNH. Both the children are doing well on follow-up. Paediatric FNH though rare, should be kept in mind while dealing with a hepatic mass. Radiological features can be variable and needle sampling may not be sufficient to reach to a diagnosis. Histological examination with glutamine synthetase immunostaining should be performed in doubtful cases to differentiate FNH from other paediatric liver masses, as management differs.
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Post therapy Wilms tumour or ectopic immature renal tissue: A pathologist's diagnostic dilemma p. 266
Vinay Anand Guntiboina, Nelofar Islam, Sugato Banerjee, Uttara Chatterjee
DOI:10.4103/IJPM.IJPM_112_18  
Post chemotherapy Wilms Tumour (PCWT) is a diagnostic conundrum both for the clinician and the pathologist, in view of its morphological similarity with ectopic immature renal tissue (EIRT). However, due to their varying prognoses and different lines of management, it is important to distinguish between the two. Here, we discuss clinical presentation and pathology of a case of PCWT, arising in a horse shoe deformity of the kidney in a 5 year old girl. The discussion focuses on the pathogenesis of Extra Renal Wilms Tumour (ERWT) as well as its distinguishing morphological features and chemotherapy induced changes in Wilms tumour.
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Cytological evaluation of pericardial fluids: A 5 years experience in tertiary care center p. 270
Surekha Yadav, Meeta Singh, Pomilla Singh, Sharmana Mandal, Nita Khurana, Shyam Lata Jain
DOI:10.4103/IJPM.IJPM_360_18  
Background: Cytological examination of pericardial effusion fluids is important in diagnosing the etiology of underlying disease, staging, and prognosis of cancer. Aims and Objectives: (1) To study cytological evaluation of pericardial effusions in various pathological conditions in a tertiary care center. (2) To analyze their frequency and clincopathological correlation of the diagnosis. Materials and Methods: Our study was a retrospective study performed in the Department of Pathology from 1st January 2012 to 31st December 2016. The study sample included all the pericardial effusions submitted in the pathology department for cytological evaluation. Clinical details and relevant parameters correlated with clinical findings. Each fluid underwent cytospin and cytocentrifuge along with preparation of conventional smears. Results: Of 120 cases, 80% were of benign effusion and 20% were of malignant effusion. Male-to-female ratio was 1.44:1 with patient age ranging from 3 to 90 years. Conclusion: Benign effusions can been seen in younger age group and malignant ones in the older age group. The preliminary pericardial fluid analysis in resource-limited settings is the most convenient and cost-effective method for accurate diagnosis. It reduces the demand of invasive investigations and its complications. At times, it is the first test to point toward underlying malignant process thereby affecting the prognosis, survival, and treatment outcome of the patient.
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Xylene-free staining: Is it possible and practical? p. 274
Surekha Yadav, Varuna Mallya, Nita Khurana
DOI:10.4103/IJPM.IJPM_39_18  
Good paraffin sections are key to correct histopathological diagnosis. Xylene is hazardous to health, expensive, and difficult to dispose. Various substitutes have been tried without success. We aimed to examine if 1.7% dishwasher soap (DWS) aqueous solution and refined mineral oil (RMO) for deparaffinization can replace xylene. Fifty tissue blocks consisting of benign and malignant lesions were processed using xylene (A), 1.7% DWS (B), and RMO (C). Each section was evaluated, scored as 0 (inadequate) and 1 (adequate) by two independent pathologists who were blinded to agent used. Following criteria were considered: nuclear staining, cytoplasmic staining, clarity, crispness, and uniformity. Total score of <2 was graded as inadequate for diagnosis and 3–5 as adequate. Statistical analysis was done using the SPSS software by applying chi-square test. Among three methods, B had the best scores in adequacy for cytoplasmic staining (P = 0.001), clarity (P = 0.004), and crispness (P = 0.003). About 1.7% DWS and RMO were found to be effective methods for deparaffinization and can replace xylene.
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Hematopoietic stem cell transplantation in children with Griscelli Syndrome type 2: Experience and outcomes p. 279
Devika Gupta, Deepshi Thakral, Sameer Bakhshi, Sushil Kumar Kabra, Dipendra Kumar Mitra
DOI:10.4103/IJPM.IJPM_645_18  
Griscelli syndrome is a rare autosomal recessive inherited disorder characterized by hypopigmentation, silver colored hair, and associated immunological deficiency, which proves fatal in the absence of timely intervention. Our patients diagnosed with Griscelli syndrome-2 presented with fever, hepatosplenomegaly, and deranged hematological and biochemical parameters. Both cases underwent detailed investigations comprising of hair mount microscopic examination, degranulation assay, and mutational studies. Our cases showed defective degranulation activity by NK cells and gene mutation analysis revealed RAB27A mutation that causes defect of cytotoxic granule exocytosis from natural killer (NK) and T-cells, manifesting clinically as hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplantation in one of the patients resulted in stable chimerism; however, the second case relapsed within a month after SCT. Stem cell transplantation is the only curative therapeutic option for GS2; thus, improvement in posttransplantation management may reduce mortality and posttransplant complications. Hence, any child who presents with partial albinism and clinical features suggestive of HLH, a peripheral blood, hair shaft mount examination along with basic immunological NK and T-cell cytotoxicity assay by flow cytometry will help clinch the diagnosis early. It can subsequently be confirmed by molecular study. Timely therapeutic intervention can prevent relapses and severe infection and improve outcome in these cases.
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CASE REPORTS Top

Rare association of cyclopia with craniospinal rachischisis p. 283
Lynda D Rodrigues, Surekha U Arakeri, Raga S Dwarampudi
DOI:10.4103/IJPM.IJPM_275_17  
Cyclopia is a severe form of holoprosencephaly which results in children being born with just one eye, absence of nose and presence of a proboscis above the median eye. Incidence of cyclopia is around 1.05 in 1, 00,000 births, including stillbirths. The association of anencephaly with spinal rachichisis varies from 17-50%. However, the existence of cyclopia with anencephaly and spinal rachischisis has been reported only in 9 cases till date. We report one more case of cyclopia with anencephaly and spinal rachischisis. Awareness of this spectrum of association with cyclopia, albeit rare, will help in early antenatal diagnosis by fetal ultrasonography. Public education and strict adherence to folic acid supplementation can prevent this unfortunate anomaly.
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A unique case of eyelid metastasis from chondroid chordoma p. 287
Huayan Ren, Xueyan Zhao, Na Wei, Huifen Huang, Wencai Li, Huixiang Li
DOI:10.4103/IJPM.IJPM_387_18  
A unique case of eyelid metastasis from nasopharyngeal chondroid chordoma in a 63-year-old woman was reported. Chordomas are rare tumors of the bone deriving from remnants of the embryonic notochord. Histologically, the tumor showed lobulated structure and concludes two types of cells: liquid drop cell and small round/cubic cell. Immunohistochemically, AE1/AE3, epithelial membrane antigene (EMA), and S100 showed a uniform and strong positivity. It has a great capacity for recurrence and malignant transformation, despite their slow-growing nature. The most common sites of metastases are liver, lungs, and bones. The eyelid metastasis from chordoma is an extremely rare finding, which may suggest a poor prognosis for the patient. Its significant clinicopathological characteristic could prompt us to take it into consideration when assessing the patient's prognosis.
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Brunner's gland hamartoma with dysplasia, presenting as multiple duodenal polyps: An unexplored entity with literature review p. 290
Mitali M Rath, Debahuti Mohapatra, Sandip K Mohanty, Subhashree Shantisudha
DOI:10.4103/IJPM.IJPM_69_18  
Brunner's gland hamartomas (BGHs) are uncommon lesions of duodenum which show hyperplasia of these glands along with smooth muscle bundles, adipose tissue and lymphoid aggregates. These are usually benign, solitary, pedunculated, polypoidal lesions. Dysplastic changes in BGH are extremely rare and even rarer is the multiplicity of this lesion. We hereby report an index case of BGH showing features of high-grade dysplasia, presenting as multiple duodenal polyps.
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Multifocal Epstein–Barr virus-associated miliary post-transplant smooth muscle tumors p. 293
Pradeep Vaideeswar, Subhash Yadav
DOI:10.4103/IJPM.IJPM_485_18  
Epstein–Barr virus (EBV) promotes the development of undifferentiated carcinomas of the upper aerodigestive tract and different types of lymphomas. This ability of tumorigenesis is heightened in many immunocompromised patients who have an increased incidence of lymphoproliferative disorders. The virus also induces smooth muscle proliferation, and those occurring following transplantation are designated as EBV-associated post-transplant smooth muscle tumors. We report multifocal miliary-sized leiomyomas in the lungs in a renal transplant recipient as an incidental finding.
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Composite pleomorphic xanthoastrocytoma-ganglioglioma; assessing and addressing the dilemma of differential expression of neuronal markers: Case report with diagnostic perspective p. 296
Kavita Gaur, Rakesh Kumar Gupta, Ravindra K Saran, Mehar C Sharma
DOI:10.4103/IJPM.IJPM_458_18  
We report the case of a 5-year-old male child presenting with seizures for 4 months. Magnetic resonance imaging (MRI) revealed a cortical-based solid cystic lesion in the right parietal lobe. Histopathological examination showed a tumour comprised of spindled glial fibrillary acid protein (GFAP) positive neoplastic cells interspersed with bizarre pleomorphic cells showing nuclear pseudoinclusions and intermingled dysplastic ganglion cells variably immunopositive for synaptophysin, chromogranin, Neu-N and immunonegative for neuron filament protein (NFP). This report highlights the occurrence of the rare composite pleomorphic xanthoastrocytoma-ganglioglioma and the vagaries of immunohistochemical analysis in highlighting neuronal differentiation in such a case setting. In addition, to the best of our knowledge this is the youngest patient till date to present with this entity.
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Juvenile hyaline fibromatosis in siblings p. 300
Valkodai Ramanathan Ravikumar, Ram Ganesh Veerappan Ramamoorthi, Sivakumar Manisankar
DOI:10.4103/IJPM.IJPM_76_17  
Background: Juvenile Hyaline Fibromatosis is a rare autosomal recessive connective tissue disorder. Case Characteristics: Three year old girl with multiple facial nodules, gingival hypertrophy and multiple joint contractures. Her sibling, male child also had similar findings which was progressive and he died at 2 years. Outcome: Nodule biopsy showed extensively hyalinised dermis with PAS positivity. Message: Juvenile Hyaline Fibromatosis is a differential diagnosis for children presenting with multiple nodular lesions.
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Posttransplant epithelioid inflammatory myofibroblastic sarcoma: A case report p. 303
Ritu Garg, Sumaid Kaul, Deepshikha Arora, Vikas Kashyap
DOI:10.4103/IJPM.IJPM_284_17  
Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare entity and a novel variant of inflammatory myofibroblastic tumor (IMT), usually seen in children and nonsmoking young adults. Their occurrence in a posttransplant setting is still rare. These tumors are characterized by prominent epithelioid morphology, large histiocytoid “Reed Sternberg”-like cell, unique pattern of ALK immuno-reactivity, and aggressive clinical behavior. Their etiology and metastatic potential is controversial. In a post-transplant setting, many factors such as trauma, infections with EBV, HIV, Hepatitis C, mycobacteria, fungus, and chemotherapy-induced immunosuppression have been implicated in their etiology. We present the case of a 2-year-old female child who developed multiple omental and mesenteric tumor nodules, 8 months post liver transplant for progressive familial intrahepatic cholestasis (PFIC). Following a histopathological diagnosis of “mesenchymal neoplasm of possible malignant nature” on a trucut biopsy and frozen section, tumor debulking was performed. A final histological diagnosis of EMIS was made on the completely resected tumor. The patient remains in remission nearly 7 months after presentation, without any follow-up systemic chemotherapy. IMT after a solid organ transplant is rare, only 5 cases have been reported in the literature until now. Similar phenomenon has also been noted with hematopoietic stem cell transplant. However, to our knowledge, this case of EMIS in a post liver transplant patient is first of its kind.
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Epithelioid sarcoma of paratesticular region: A case report of an unusual case p. 306
Jaydeep N Pol, Zeba Nisar, Madhura D Phadke, Girish A Kadkol
DOI:10.4103/IJPM.IJPM_431_18  
Primary tumors of the paratesticular region are rare, with sarcomas constituting a major proportion, particularly in the old age. The paratesticular region consists of mesothelial, various epithelial, and mesenchymal cells and may therefore give rise to a variety of tumors. Epithelioid sarcoma usually occurs at the distal extremities of young adults. The proximal-type variant is characterized by a more aggressive course and resistance to treatment. We herein report a case of 32 years male with scrotal swelling diagnosed as proximal-type epithelioid sarcoma of paratesticular region after histopathological examination and immunohistochemistry. To the best of our knowledge, this is only the second case of proximal epithelioid sarcoma of paratesticular region in the English literature. As these tumors are rare, it has been difficult to establish their optimal treatment. Also, these can be easily misdiagnosed as other epithelioid lesions.
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A pregnant woman with condyloma acuminatum on the vaginal orifice, areola, groin, and umbilicus p. 310
Ge Song, Xingang Zhou, Yan Wu
DOI:10.4103/IJPM.IJPM_518_18  
Condyloma acuminatum (CA) is a benign tumor primarily caused by infection with human papillomavirus (HPV) type-6 or type-11, lesions of which are most frequently found on the genital, perianal squamous mucosa, and skin. CA outside the anogenital region is not common. Here, we report a case showing simultaneous presence of CA on the vaginal orifice, areola, groin, and umbilicus in a 32-year-old pregnant woman. Histopathological examination and HPV detection are essential in making a definitive diagnosis of CA on multiple sites. The patient was treated with microwave and liquid nitrogen cryotherapy, but repeated relapse of the lesions were observed. Patients with CA during pregnancy represent a special risk group. These cases are usually characterized by fast-growing warts, multi-site or special site warts, a reduced tolerance, and poor response to treatment. Hence, we should pay more attention to CA in pregnant women in the process of diagnosis and treatment, especially cases outside the anogenital region.
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Trichoblastic carcinoma arising in trichoepithelioma in Brooke–Spiegler syndrome p. 313
Jayalakshmy P Leelamma, Sankar Sundaram, Sangeetha Kandasamy
DOI:10.4103/IJPM.IJPM_639_17  
Brooke–Spiegler syndrome (BSS) is a rare autosomal dominant disease characterized by the development of multiple cutaneous adnexal neoplasms namely cylindroma, trichoepithelioma and spiradenoma. The neoplasms associated with this syndrome are generally benign, but rarely they may undergo malignant transformation. A 63-year-old male presented with an ulcerated nodular lesion over glabella and multiple asymptomatic nodular lesions over face, scalp, chest and limbs. His father, grandfather and paternal cousins had history of similar lesions. Histopathological examination revealed trichoblastic carcinoma arising from trichoepithelioma over glabella and cylindroma on the chest. With these findings we arrived at a diagnosis of BSS with malignant transformation of trichoepithelioma. Trichoblastic carcinoma arising in trichoepithelioma in a patient with BSS is extremely rare with only a single case reported in literature.
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Pagetoid reticulosis positive for cytotoxic CD20 and CD30: A case report p. 316
Shufei Wei, Wenyong Huang, Xiao Xu
DOI:10.4103/IJPM.IJPM_717_18  
Pagetoid reticulosis is an indolent cutaneous T-cell lymphoma and presents as erythema or plaque with a well-defined border on the distal areas of the extremities. Immunophenotypic studies show that in most cases, neoplastic lymphocytes are positive for CD4, whereas CD20 and CD30 double positivity was rarely reported. In this paper, we report an 80-year-old woman who presented with erythema on the extremities for 3 years. Skin biopsy on the right forearm was performed. Histopathologically, the erythematous lesions were characterized by atypical lymphocytes with significant epidermotropism. Immunohistochemical staining showed high proliferation as evidenced by high Ki-67 index and that the tumor cells were positive for CD20 and CD30 but negative for CD7 and CD56. The patient was treated with one cycle of radiotherapy and is currently doing well.
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Non-Hodgkin's lymphoma with extensive emperipolesis mimicking Rosai–Dorfman disease: A rare case report p. 319
Sharada R Rane, Mayur Parkhi, Sharvari Vishwasrao, Leena Nakate
DOI:10.4103/IJPM.IJPM_409_18  
Emperipolesis is the hallmark finding for Rosai-Dorfman disease. Till now many studies in literatures have shown emperipolesis as a finding in other benign as well as malignant conditions. Very few cases of malignant lymphoma have this phenomenon. Herewith, we put forward a rare case of lymphoma with clinical presentation showing involvement of spleen, liver, lymph nodes as well as lleo-cecal region. Light microscopy revealed large to medium sized lymphoid cells with intervening plenty of histiocytes showing evidence of emperipolesis that mimics Rosai Dorfmann disease. Due to atypical clinical presentations we thought of lymphoma as a differential diagnosis. Further immunohistochemistry was performed using histiocytic as well as lymphoid markers. To our surprise, it turns out to be Non Hodgkin Lymphoma with extensive emperipolesis which is extremely rare in thorough literature search. This case is presented due to its unique clinical as well as histological presentations.
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Diagnostic challenges posed by a rare alpha globin chain variant Hb Fontainebleau in a pregnant female and its potential effects in her children in view of multiple globin gene defects in her husband p. 323
Kainaz Sidhwa, Manisha Ramani Daruwalla, Ravikiran Pawar, Anita Nadkarni, Priya Hariharan, Pallavi Mehta, Amar Das Gupta
DOI:10.4103/IJPM.IJPM_218_18  
Alpha globin chain variants per se do not cause severe morbidity and mortality but can modify – usually ameliorate – the clinical manifestations of beta globin chain variants when co-inherited with the latter. They also pose challenges in interpretation of high-performance liquid chromatography histograms and require molecular analysis for proper characterization. Hemoglobin (Hb) Fontainebleau is a rare alpha globin chain variant [alpha 21(B2) Ala→Pro], of which only three families have been reported from India in the past. Here, we describe a case of Hb fontainebleau detected in heterozygous condition in a 19-year-old primigravida. Her husband was found to have a double heterozygous state for HbQ India and beta-thalassemia trait. This opens up the possibility of multiple combinations of hemoglobinopathies in the offspring.
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Actinomyces naeslundii causing pulmonary endobronchial Actinomycosis – A case report p. 326
BG Supriya, S Harisree, Jayanthi Savio, Priya Ramachandran
DOI:10.4103/IJPM.IJPM_706_17  
Actinomyces naeslundii is a commensal flora of the oral cavity and is generally considered as an avirulent saprophytic bacterium in immunocompetent patients. It can become an opportunistic anaerobic pathogen in oral cavity in patients with poor oral hygiene or tooth extraction and can cause periodontal disease. Pulmonary Actinomycosis is a rare manifestation and may be suspected in middle-aged male patients with cough and hemoptysis showing radiological findings of a peripheral mass or chronic consolidation in whom repeated aerobic cultures have yielded negative results. Here, we report isolation of A. naeslundii from the bronchoalveolar lavage sample from an immunocompetent patient who presented with chronic nonresolving pneumonia of 6 months duration.
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Disseminated Nocardia farcinica infection presenting as a paravertebral abscess in a patient with systemic lupus erythematosus p. 329
Yeliz Ozen, Basak Dokuzoguz, Ipek Mumcuoglu, Aysel Kocagül Çelikbas, Zeynep Ceren Karahan, Bahadir Orkun Özbay
DOI:10.4103/IJPM.IJPM_178_17  
Disseminated Nocardia infections occur particularly in immunosuppressed hosts and are most often due to Nocardia farcinica, Nocardia nova, and Nocardia cyriacigeorgica. Here, we report an unusual case of disseminated N. farcinica infection presenting as a paravertebral abscess in a patient with systemic lupus erythematosus.
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Unsuspected invasive gastrointestinal mucormycosis masquerading as inflammatory bowel disease: A pathologist's perspective p. 332
Sunitha Shankaralingappa
DOI:10.4103/IJPM.IJPM_240_18  
Mucormycosis is caused by fungi of the order Mucorales and class Zygomycetes. It is a rare opportunistic infection frequently associated with immunocompromised status. It can be disseminated disease or localized, which includes rhinocerebral, pulomonary, cutaneous, and gastrointestinal mucormycosis. Gastrointestinal mucormycosis is the most uncommon usually fatal disease accounting for 4–7% of all cases. We present a rare case of unusual presentation of angioinvasive colonic mucormycosis in a seemingly immunocompetent female masquerading as inflammatory bowel disease. It is very important to differentiate between both because treatment with steroids may lead to dissemination of disease ultimately resulting in a fatal outcome. A surgeon should maintain a high index of suspicion as timely appropriate surgical intervention along with effective antifungal treatment remains the cornerstone of treatment for this highly fatal disease. The definitive diagnosis is possible only by histopathological demonstration of tissue invasion. This requires a quantitatively and qualitatively adequate tissue biopsy.
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IMAGES Top

Signet ring: A rare morphology of metastatic neuroendocrine tumor p. 335
Manoj G Madakshira, Bishan D Radotra, Vikram Singh
DOI:10.4103/IJPM.IJPM_270_18  
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Huge tumoral calcinosis mimicking a sarcoma p. 337
Asha Sharad Shenoy, Pragati Aditya Sathe, Mona Akshay Agnihotri
DOI:10.4103/IJPM.IJPM_268_18  
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Cervical syphilitic lymphadenitis causing fever of unknown origin followed by rash of secondary syphilis p. 339
Rahul Mahapatra, Gary Clarke, Zeena Lobo, George Psevdos
DOI:10.4103/IJPM.IJPM_188_18  
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Mediastinal mixed germ cell tumor with splenic histiocytosis: A rare coincidence p. 341
Ridhi Sood, Anurag Mehta, Divya Bansal, Neha Singh, Sajjan Raj Purohit
DOI:10.4103/IJPM.IJPM_691_18  
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Bone marrow sea-blue histiocytes in a case of ITP p. 343
Nidhi S Mishra
DOI:10.4103/IJPM.IJPM_496_18  
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LETTERS TO EDITOR Top

Glandular odontogenic cyst: An unusual entity p. 345
Jaishree Sharma, Archana Bharti Raina, Anchal Varshney, Disha Chopra
DOI:10.4103/IJPM.IJPM_596_18  
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Spontaneous regression of giant cell tumor of the wrist: Myth or fact? A case report p. 346
Varuna Mallya, Latika Gupta, Nita Khurana, Lalit Maini
DOI:10.4103/IJPM.IJPM_251_18  
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Superficial acral fibromyxoma: A cytohistopathological correlation in a recurrent, nonperiungual, acral lesion p. 348
Neelam Sood, Navmeet Soin
DOI:10.4103/IJPM.IJPM_238_18  
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Embryonal carcinoma testis with extensive metastasis and IVC thrombosis p. 350
Anju Shukla, Debnandan Chowdhury, Vibhor Mahendru
DOI:10.4103/IJPM.IJPM_63_18  
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A soft tissue swelling at angle of mandible: Fine needle aspiration cytology meeting the diagnostic challenge of a rare case p. 353
Priya Sahu, Prajwala Gupta, Arvind Ahuja, Minakshi Bhardwaj, Ashish Nigam
DOI:10.4103/IJPM.IJPM_419_18  
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Co-amplification and co-localization: Rare signal pattern in human epidermal growth factor receptor 2 gene fluorescence in situ hybridization testing p. 355
Anurag Gupta, Sambasiva Rao Patibandla, Mukkanteeswara Rao Kasaragadda, Manu Goyal
DOI:10.4103/IJPM.IJPM_233_18  
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Ethical issues in laboratory medicine p. 357
Madhu Sinha, Swati Sharma, Abhijit Das, Anuj Sud, Megha Rastogi, Swati Raj
DOI:10.4103/IJPM.IJPM_533_18  
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NEW HORIZON Top

Catechism (Quiz 4) p. 360
Bharat Rekhi
DOI:10.4103/IJPM.IJPM_175_19  
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ERRATUM Top

Erratum: Clear cell myeloma artefactual or real p. 362

DOI:10.4103/0377-4929.255847  
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Erratum: Spermatocytic seminoma with rhabdomyoblastic differentiation: Case report and review of literature p. 363

DOI:10.4103/0377-4929.255848  
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