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October-December 2017
Volume 38 | Issue 4
Page Nos. 411-565

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ORIGINAL ARTICLES  

Histopathological study of gallbladder carcinoma and its mimics with role of carcinoembryonic antigen immunomarker in resolving diagnostic difficulties p. 411
Santosh Kumar Mondal, Debashish Bhattacharjee, Palash Kumar Mandal, Saumitra Biswas
DOI:10.4103/ijmpo.ijmpo_230_15  
Background: Gallbladder carcinoma (GBC) sometimes presents with nonspecific signs, without forming a mass, mimicking benign gallbladder (GB) diseases. On the contrary, benign GB diseases may mimic GBC. Material and Methods: We retrospectively reviewed 107 cases over a period of 3 years (May 2012–April 2015), which included 41 review cases and 66 departmental cases. Carcinoembryonic antigen (CEA) immunomarker expression was done. Results: In 27 of the 41 review cases, the diagnoses were benign diseases of GB associated with mild-to-moderate dysplasia of mucosal glands; however, after review in our department, it was found that of these 27 cases, nine cases were actually well-differentiated adenocarcinoma of GB with diffuse CEA expression and were mis diagnosed as benign diseases of GB with dysplasia. In 32 out of 66 departmental cases, initial histopathological diagnoses were benign diseases of GB associated with dysplastic mucosal glands. After CEA staining, 11 out of these 32 cases turned out to be adenocarcinoma of the GB. Among the rest 34 (34/66) departmental primary GBC cases, no CEA expression was seen in six cases, focal expression was seen in 12 cases, and diffuse expression was seen in 16 cases. No diffuse CEA expression was seen in benign diseases of the GB with dysplasia. Conclusion: GBC sometimes may not be diagnosed radiologically and grossly as it often presents without any mass and specific signs, which lead to under diagnosis. Some benign cases may mimic GBC and may complicate histological diagnosis. CEA expression may aid as an additional diagnostic aid in resolving diagnostic dilemmas.
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DROSHA rs642321 polymorphism influence susceptibility to childhood acute lymphoblastic leukemia: A preliminary report p. 416
Mohammad Hashemi, Seyed-Shahaboddin Hasani, Majid Naderi
DOI:10.4103/ijmpo.ijmpo_4_15  
Introduction: It has been well known that the microRNA biogenesis is involved in the pathogenesis of various diseases. We investigated the possible association between DROSHA rs642321 variant and risk of acute lymphocytic leukemia (ALL). Materials and Methods: We genotyped 75 children diagnosed with ALL and 115 age- and sex-matched children with no history of cancer of any type (as the control group) by the tetra amplification refractory mutation system-polymerase chain reaction. Results: We found that DROSHA rs642321 C > T variant significantly decreased the risk of ALL in codominant (TT vs. CC: odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.14–0.80, P = 0.020) and dominant (TT + CT vs. CC: OR = 0.51, 95% CI = 0.27–0.94, P = 0.037) inheritance model tested. The rs642321 T allele was associated with protective against ALL (OR = 0.58, 95% CI = 0.38–0.88, P = 0.011) in comparison with C allele. Conclusion: The study findings revealed that DROSHA rs642321 variant decreased the risk of pediatrics ALL in an Iranian population. Larger sample sizes with different ethnicities are needed to validate our findings.
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Prognostic factors and survival outcomes of intracranial ependymoma treated with multimodality approach p. 420
Kunhi Parambath Haresh, Ajeet Kumar Gandhi, Supriya Mallick, Rony Benson, Subhash Gupta, Daya Nand Sharma, Pramod Kumar Julka, Goura Kisor Rath
DOI:10.4103/ijmpo.ijmpo_202_15  
Objectives: We aimed to analyze treatment outcomes of intracranial ependymoma (ICE) treated at our institute with multimodality approach. Materials and Methods: Demography, treatment details, and survival data of 40 patients (2005–2012) were collected in a predesigned pro forma. Kaplan Meier method was used to analyze disease-free survival (DFS) and the impact of prognostic factors was determined using univariate analysis (log-rank test). Multivariate analysis was performed using Cox-proportional hazard model. SPSS version 21.0 was used for all statistical analysis. Results: Male:female ratio was 29:11. Gross total resection: subtotal resection or less was 42.5%: 57.5%. A total of 16 patients (40%) had anaplastic histology. All except two patients received adjuvant radiotherapy. Four patients received concurrent chemotherapy (temozolomide [TMZ]) and 10 patients received adjuvant chemotherapy (6 carboplatin plus etoposide; 4 TMZ). Median follows up was 18 months (2–60 months). Median DFS for the entire cohort was 22.42 months. The estimated 1, 2, and 3 years DFS was found to be 58.5%, 41%, and 30.7%, respectively. On univariate analysis, patients receiving higher radiation dose (56 Gray vs. 60 Gray; hazard ratio [HR] 0.366; 95% confidence interval [CI] 0.142–0.9553; P = 0.02) and lower MIB labeling index (<20 vs. ≥20; HR 0.238; 95% CI 0.092–0.617; P = 0.001) had a better DFS. Higher radiation dose continued to be an independent prognostic factor on multivariate analysis (HR 0.212; 95% CI 0.064–0.856; P = 0.03). Conclusion: ICE has guarded prognosis. Adjuvant radiotherapy to a higher radiation dose improves survival. Higher MIB labeling index connotes a dismal survival despite the use of radiotherapy and chemotherapy.
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Rational use of imaging to stage breast cancer: Evidences for a selective approach p. 427
S G D Gangadaran
DOI:10.4103/ijmpo.ijmpo_113_16  
Introduction: Staging investigations at diagnosis are customary to accurately assign a clinical stage before therapy. The practice of routine imaging in patients asymptomatic for metastasis is not recommended but widely adopted. This study was done to reexamine the basis behind guideline recommendations and to identify the factors predictive of asymptomatic metastasis. Methods: Oncology records of 200 breast cancer patients in clinical Stages I-III at diagnosis were prospectively reviewed. Baseline demographic information, tumor characteristics, and pathological data including molecular typing were collected. The prevalence of metastasis deduced and accuracy of bone scan, chest X-ray (CXR), liver ultrasound, and computed tomography (CT) chest analyzed. Patient and tumor characteristics predictive of asymptomatic metastasis tested for significance using appropriate statistical tests. Results: The prevalence of asymptomatic metastasis was 13.5%. Bone lesions (8%) were the most common metastatic site followed by lungs (7%) and liver (1%). Sensitivity, specificity, positive- and negative-predictive values of bone scans and CT chest were 100%, 97%, 74%, 100%, and 92%, 99%, 87, 3%, 99.4%, respectively. The above values for ultrasound abdomen and CXRs were 100%, 99%, 93%, 100% and 21%, 94%, 20%, 94%, respectively. Tumor size (P = 0.001), tumor Stage T1/T2 versus T3/T4 (P = 0.0002), nodal stages N0/N1 versus N2/N3 (P = 0.001), high histological Grade G I versus GII/GIII (P = 0.0001) and molecular types were strongly predictive of metastatic disease. Conclusion: The routine use of imaging to detect distant metastasis in asymptomatic patients is not recommended in newly diagnosed breast cancer. A selective approach may be adopted in individuals with tumor more than 5 cm, advanced nodal disease, higher histological grade, and aggressive molecular types.
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Utility of cluster of differentiation 5 and cluster of differentiation 117 immunoprofile in distinguishing thymic carcinoma from pulmonary squamous cell carcinoma: A study on 1800 nonsmall cell lung cancer cases p. 430
Vidya Jha, Preeti Sharma, Ashish Kumar Mandal
DOI:10.4103/ijmpo.ijmpo_148_16  
Background: Mediastinum harbors a mixed bag of neoplastic lesions with varied therapeutic and prognostic implications. Distinguishing pulmonary squamous cell carcinoma from thymic carcinoma is a challenging task owing to rather nonspecific clinicoradiological features and a considerable overlap in histomorphological features. Thus, we evaluated the diagnostic utility of cluster of differentiation 5 (CD5) and CD117 immunohistochemical markers in distinguishing these tumors. Materials and Methods: The archives of department of histopathology were retrospectively reviewed from June 2012 to May 2016. Formalin-fixed paraffin-embedded blocks of 1800 cases diagnosed as nonsmall cell lung carcinoma were retrieved, and immunohistochemical expression of CD5 and CD117 was evaluated in these cases. Results: Adenocarcinoma (980; 54.44%) was the most common histological subtype of lung carcinoma observed in our study. CD117 was positive in 171 out of 1800 cases (9.5%) of which 120 cases (70.17%) were adenocarcinoma, followed by 40 cases (23.4%) of squamous cell carcinoma. Immunoreactivity for CD5 was observed in 209 cases (11.61%), 200 (95.7%) cases of which were diagnosed as adenocarcinoma. None of the cases diagnosed as squamous cell carcinoma on histomorphology showed CD5 immunoexpression. Conclusion: While thymic squamous cell carcinomas are well known for CD5 and CD117 coexpression, none of the cases of squamous cell carcinoma arising in lung express CD5. These markers are a diagnostic tool to distinguish a primary lung squamous cell carcinoma from thymic carcinoma, particularly in the setting of a central pulmonary lesion with mediastinal involvement.
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Metabolic syndrome and breast cancer risk p. 434
Burhan Wani, Shiekh Aejaz Aziz, Mohammad Ashraf Ganaie, Mohammad Hussain Mir
DOI:10.4103/ijmpo.ijmpo_168_16  
Objective: The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Materials and Methods: Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Results: Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group (P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214–7.597). Conclusions: Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.
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Peripheral and central giant cell lesions in children: Institutional experience at Subharti Dental College and Hospital p. 440
Preetika Chandna, Nikhil Srivastava, Vishal Bansal, Vijay Wadhwan, Prajesh Dubey
DOI:10.4103/ijmpo.ijmpo_17_16  
Introduction: Giant cell lesions (GCG) are a group of varied lesions that contain a multitude of multinucleated, osteoclast like giant cells within connective tissue stroma. These include giant cell granulomas which may be central (CGCG), if they lie within the jaw bone, or, peripheral (PGCG) if they lie within the soft tissue. Giant cell granulomas comprised 9.29% of all oral lesions. This case series comprises of 5 giant cell lesions in children between the ages of 4 to 12 years. Materials and Methods: A retrospective analysis was conducted of all patients who were diagnosed with giant cell lesions and treated over a period of 10 years (from August 2004 to August 2014) at Subharti Dental College and Hospital, Meerut, India. Results: A total of 5 giant cell lesions were identified in this case series, of which 2 cases were diagnosed as PGCG and 3 cases as CGCG. Surgical excision and curettage was performed for 2 peripheral lesions under local anesthesia while 1 central lesion was excised under general anesthesia. Two central lesions were treated with a non-surgical approach using intralesional corticosteroid. Conclusion: Our experience suggests that a correct diagnosis and complete surgical excision with curettage is effective in complete management of oral giant cell lesions in the pediatric age group.
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Sinusoidal obstruction syndrome during treatment for wilms' tumor: A life-threatening complication p. 447
Sidharth Totadri, Amita Trehan, Deepak Bansal, Richa Jain
DOI:10.4103/ijmpo.ijmpo_188_16  
Context: Survival rates exceed 90% in Wilms' tumor (WT). Actinomycin-D (ACT-D) which is indispensable in the management of WT is associated with the development of sinusoidal obstruction syndrome (SOS), a potentially fatal complication. Aims: The aim is to study the presentation, management, and outcome of SOS complicating ACT-D administration in WT. Settings and Design: Retrospective file review conducted in a Pediatric Hematology-Oncology unit. Materials and Methods: Patients diagnosed and treated for WT from January 2012 to December 2015 were analyzed. SOS was diagnosed clinically, based on McDonalds criteria, requiring two of the following: jaundice, hepatomegaly and/or right upper quadrant pain, weight gain with or without ascites. Results: Of 104 patients treated, SOS occurred in 5 (4.8%). Age: 6 months to 5 years, 3 were girls. Tumor involved left kidney in 3, right in 1 and a horseshoe kidney in 1. Histopathology was consistent with WT in 4 and clear cell sarcoma kidney in 1. One had pulmonary metastases. Three developed SOS preoperatively and two during adjuvant chemotherapy. None received radiotherapy. Clinical manifestations comprised of jaundice, hepatomegaly, ascites/weight gain, respiratory distress, hypotension, and encephalopathy. Laboratory findings included thrombocytopenia, elevated serum transaminases, and coagulopathy. Treatment included fluid restriction, broad spectrum antibiotics, and transfusional support. Two children received N-acetyl cysteine infusion. Defibrotide was administered to two patients. Four recovered and one succumbed to multi-organ failure. Two patients were safely re-challenged with 50% doses of ACT-D. Conclusions: SOS is a clinical diagnosis. Systematic supportive care can enable complete recovery. Under close monitoring, re-challenge of ACT-D can be performed in gradually escalating doses.
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Oral verrucous carcinoma: Ten year experience from a Tertiary Care Hospital in India p. 452
Joshua Franklyn, Rajinikanth Janakiraman, Amit J Tirkey, Cecil Thankachan, John Muthusami
DOI:10.4103/ijmpo.ijmpo_153_16  
Background: Verrucous carcinoma of the oral cavity (OVC) is an uncommon variant of oral squamous cell carcinoma (OSCC). The clinical presentation and surgical outcomes of OVC are unique; however, the management protocols for OVC are largely extrapolated from OSCC. Objectives: The aim is to study the clinical, histopathological demographics, and outcome of OVC at a tertiary care referral hospital in South India. To study the need for lymph node dissection and the role of adjuvant therapy for close resection margins. Materials and Methods: A retrospective review of all patients diagnosed to have OVC between January 2005 and April 2015 was undertaken. Data were collected from hospital records and telephonic interview when possible. Results: Thirty patients were diagnosed to have OVC. The most common site of the presentation was the buccal mucosa. Twenty-three patients had wide local excision of the primary tumor and seven patients had neck dissection as well. None of the patients who underwent neck dissection had node-positive disease pathologically. The margins were considered close in nine patients, only one of these patients received adjuvant radiation therapy; despite among the patients with close resection margins, there was no recurrence or disease-related mortality. Among the thirty patients, there was only one patient who had recurred locally and there was no disease associated mortality. Conclusions: OVC is a unique variant of OSCC which has a good prognosis. Routine lymphadenectomy can be avoided.
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Squamous cell carcinoma lung with skeletal muscle involvement: A 8-year study of a Tertiary Care Hospital in Kashmir p. 456
Javvid Muzamil, Shumail Bashir, Faisal R Guru, Firdousa Nabi, Gull Mohammad Bhat
DOI:10.4103/ijmpo.ijmpo_169_16  
Aims: Lung cancer is the most common malignancy throughout the world. Nonsmall cell lung cancer (NSCLC) is the most common type, and squamous cell type is most common in India. Mostly, patients present with chest-related symptoms and signs. Isolated skeletal muscle metastasis (ISMM) is rarely seen. The aim was to see muscle metastasis and its prognosis. Materials and Methods: We are presenting our data of 8 years about this common malignancy with relation to muscle metastasis, either alone or with other system metastasis. Results: Muscle metastasis is seen 1.5% of patients, with male: female of 8:1. Overall median survival was 15 months and progression-free survival was 12 months. Conclusion: One peculiarity seen was ISMM with no pulmonary system and severe paraneoplastic hypercalcemia. Local therapy may be having an impact on overall survival in metachronous muscle involvement.
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Comparative study of imprint cytology and histopathology of soft tissue tumors p. 461
Sujit Kumar Dutta, Senjuti Dasgupta, Nirmal Kumar Bhattacharyya, Parul Jain, Debdas Bose, Pranab Kumar Biswas
DOI:10.4103/ijmpo.ijmpo_132_16  
Background: The components of soft tissue are fibroblasts, collagen, vascular structures, fatty tissue, skeletal muscles, smooth muscles, and neural tissue. The real incidence of soft tissue tumors (STTs) is difficult to estimate because most of them are benign (Benign: Malignant-100:1). Aims: The aim of the present study was undertaken to note the patterns of presentation of patients with STTs and to evaluate the findings of imprint cytology (IC) and histopathological examination (HPE) of STTs. Materials and Methods: The present study was undertaken for 1 year. A total of 41 patients with clinically and radiologically diagnosed STTs were included in the study. Following surgery, imprint smear was taken for each tumor, before delivering the tissue to 10% formalin. HPE was subsequently performed. Results: The age of the patients ranged from 4 months to 80 years with a mean of 35.6 ± 17.5 years. The ratio of males to females was 1.05:1. HPE revealed that 21 (51.2%) tumors were benign and 20 (48.8%) malignant. Imprint smears revealed 16 (39%) tumors to be benign and 20 (48.8%) malignant. IC was inconclusive in 5 (12.2%) cases. The sensitivity of IC was found to be 89.5% and specificity 82.35%. The positive predictive value of IC was 85%. The accuracy of IC for diagnosis of both benign and malignant tumors was found to be 75%. Conclusion: IC of STTs is a rapid and simple method of intraoperative diagnosis, and it can serve as a viable alternative to frozen section biopsy, particularly in rural settings.
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Is colorectal cancer in young (<40 Years) different from those in the elderly (>40 Years): Experience from a regional care center p. 466
Rudresha A Haleshappa, Suparna Ajit Rao, Sunny Garg, C Lakshmaiah Kuntegowdanahalli, Govinda Babu Kanakasetty, Lokanatha Dasappa
DOI:10.4103/ijmpo.ijmpo_187_16  
Background: Colorectal cancer (CRC) is considered a disease of elderly. There has been a steady decrease in the incidence in those aged >50 years, with an alarming increase noted in adults aged <50 years. Subjects and Methods: We retrospectively analyzed 89 patients diagnosed with CRC aged <40 years between the years 2010 and 2014. Their clinical profile, treatment, and outcomes were studied. Results: The median age was 33 years with a male preponderance (56.2%). Most common symptoms were lower gastrointestinal bleed (48.3%) followed by abdominal pain (46.1%). Most common sites were rectum (50.6%) followed by colon. Histology in all was adenocarcinoma. Most tumors were moderately differentiated (54%) and were stage 4 (36%). Most common sites of metastases were liver (46.9%) followed by peritoneum and ovaries. Majority underwent surgery with adjuvant chemotherapy, with/without radiotherapy. Chemotherapy was administered in 70 patients, majority receiving FOLFOX-4 regimen (88.6%). Median survival was 23 months. Survival in early stage[1],[2] was significantly higher than in advanced stages (3 and above), 34 and 19 months (P = 0.0287), in those aged >40 years compared to <40–35 versus 23 months (P = 0.0029), nonmetastatic compared to metastatic disease – 26 versus 14 months (P = 0.00196), and females compared to males – 26 and 18 months (P = 0.0242). There was no significant difference in survival with respect to tumor grade or site of metastases (hepatic versus extrahepatic). Conclusions: Colorectal carcinoma in young seems to be an emerging problem in India. Any young patient presenting with symptoms suggestive of a colonic malignancy should be evaluated promptly and treated aggressively.
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A profile of pediatric solid tumors: A single institution experience in Kashmir p. 471
Namita Sharma, Ayesha Ahmad, Gull M Bhat, Sheikh A Aziz, Mohammad Maqbool Lone, Nisar A Bhat
DOI:10.4103/ijmpo.ijmpo_95_16  
Aims: The purpose of this retroprospective study was to study the epidemiological characteristics and outcomes of children with solid tumors at our institution. Subjects and Methods: Three hundred and three pediatrics patients registered at Regional Cancer Centre (RCC), Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Kashmir, between January 2008 and June 2014, were analyzed with regard to demographic status, presenting complaints, investigations, treatment, morbidity, and outcomes. Standard statistical methods were used for analysis. Results: Among 19,880 patients registered at RCC, SKIMS from January 2008 till June 2014, 986 (4.9%) were of pediatric age group. Of these, 303 (30.7%) patients had pediatric solid tumors. The male-to-female ratio was 1.04, there were no infants (up to 27 days), 6% were infants and toddlers (28 days–23 months), 39% were children (2–11 years), and 55% were adolescents (12–19 years). There were 86% rural patients and 14% urban patients. Most common were central nervous system tumors (25.74%), followed by germ cell tumors (14.52%), primitive neuroectodermal tumor/Ewing sarcoma (13.86%), Wilms' tumor (8.9%), osteosarcoma (6.6%), rhabdomyosarcoma (5.6%), colorectal cancer (5.28%), neuroblastoma (4.9%), and retinoblastoma (2.6%). Outcomes: 33.9% patients went into remission, 35.64% were defaulters, 2.97% had stable disease, 2.31% had partial response, 20.79% expired, and 3.96% were still on treatment. Of all these patients, 5.28% had a relapse. Conclusions: Across the series, advanced stage of presentation, a high incidence of default and poor follow-up was seen. Multiple interrelated factors are responsible for the poorer outlook of childhood cancer in Kashmir.
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Clinicopathological features and outcomes in primary central nervous system lymphoma: A 10-year Experience p. 478
Chaitanya Krishna Puligundla, Stalin Bala, Ashok Kumar Karnam, Sadashivudu Gundeti, Tara Roshni Paul, Megha S Uppin, Lakshmi Srinivas Maddali
DOI:10.4103/ijmpo.ijmpo_202_16  
Context: Primary central nervous system lymphoma (PCNSL) is a variant of extranodal lymphoma, accounting for 4% of primary central nervous system tumors. PCNSL was more common in immunocompetent individuals. International Extranodal Lymphoma Study Group (IELSG) scoring was used for prognostication. High-dose methotrexate regimens along with radiotherapy improved outcomes in PCNSL. Aims: The aim of this study is to analyze the clinical and pathological features, progression-free survival (PFS), and overall survival (OS) in patients with PCNSL. Materials and Methods: Data of patients with PCNSL between 2005 and 2016 were retrospectively analyzed. Outcome was analyzed in patients who received chemotherapy. GraphPad Prism software for Windows Version 6 was used to plot the Kaplan–Meier curves for PFS and OS. Log-rank test was used to calculate P values. P < 0.05 was considered as statistically significant. Results: A total of 42 patients were available for analysis. Of these, 34 patients who received chemotherapy were evaluable for outcome parameters. The median age at presentation was 46 years (range, 10–75) with male-to-female ratio of 2.2:1. Only 2 (4.7%) patients were HIV positive. Diffuse large B-cell lymphoma (DLBCL) was the most common histology seen in 41 (97.6%) patients. Using IELSG risk scoring, scores of 8 (19%), 19 (45.2%), and 15 (35.8%) were stratified into low, intermediate, and high risk. The median PFS and OS were 11 months (range, 2–72) and 15.9 months (2.4–80.4), respectively. The median OS was 36.2 months (range, 8.8–72), 15.6 months (2–36), and 6.1 months (2.6–12.7) in low-, intermediate-, and high-risk groups, respectively, which was statistically significant (P = 0.0002). Conclusions: Immunocompetent patients with PCNSL outnumber immunocompromised patients. DLBCL was the most common histology, and IELSG risk stratification significantly predicts the outcome in PCNSL.
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Correlation of hormone receptor and human epidermal growth factor Receptor-2/neu expression in breast cancer with various clinicopathologic factors p. 483
Cherry Bansal, Aarti Sharma, Mukta Pujani, Meenu Pujani, Kiran Lata Sharma, AN Srivastava, US Singh
DOI:10.4103/ijmpo.ijmpo_98_16  
Background: A significant development in the breast carcinoma management is the correlation between the presence of hormone receptors in the tumor and response to hormonal therapy and chemotherapy. Human epidermal growth factor receptor-2/neu (Her-2/neu) overexpression also serves as a very useful parameter to predict response to herceptin. Aim of Study: The study was conducted to correlate immunohistochemical expression of markers such as estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu with various clinicopathologic parameters. Materials and Methods: The study included 509 cases of breast carcinoma over a period of 5 years (from May 2009 to May 2014). Immunohistochemistry (IHC) for ER, PR, and her-2/neu was performed. Results: ER positivity was observed in 42.8% (218/509) cases, PR positivity in 31.8% (194/509) cases whereas her-2 neu positivity was seen in 40.7% (203/509) cases. Triple marker (ER, PR, and Her-2/neu) negative cases were 23.6% (120/509) cases. ER and PR expression was found to have a statistically significant correlation with tumor grade. Statistically significant correlation was observed between tumor size and tumor grade and her-2/neu expression. Her-2/neu expression showed statistically significant association with tumor stage. As the tumor grade increased, the proportion of triple-negative cases went on increasing, which was statistically significant. Conclusion: IHC has an increasingly important prognostic role in determination of factors that affect clinicopathologic features. Nevertheless, the results of this large series showed different patterns of findings with respect to clinicopathologic features.
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Induction chemotherapy in technically unresectable locally advanced T4a oral cavity squamous cell cancers: Experience from a regional cancer center of South India p. 490
AH Rudresha, Tamojit Chaudhuri, KC Lakshmaiah, K Govind Babu, Lokanatha Dasappa, Linu Abraham Jacob, MC Suresh Babu, KN Lokesh, LK Rajeev
DOI:10.4103/ijmpo.ijmpo_185_16  
Objectives: The present study aimed to investigate the efficacy, toxicity, and impact of induction chemotherapy (IC) in technically unresectable T4a oral cavity squamous cell cancers (OSCCs). Materials and Methods: Patients diagnosed with technically unresectable locally advanced T4a OSCC from January 2013 and November 2016 at our center, who received 2–3 cycles of IC and then assessed for resectability, were reviewed retrospectively. Patients' profile, response rates and toxicity of IC, resectability status, and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). Results: Totally 80 patients received IC, and of them 58 (72.5%) were males. Median age at diagnosis was 44 years (range, 34–62 years). All our patients received IC with doublet regimen. Majority of the patients had buccal mucosa cancers (73.8%), followed by gingivobuccal complex (21.2%) and oral tongue (5%) primaries. After IC, partial response was achieved in 17 (21.3%) patients, stable disease in 49 (61.3%) patients and disease progression was noted in 14 (17.4%) patients. Post-IC, resectability was achieved in 19 (23.8%) of 80 patients, but 4 of them did not undergo surgery due to logistic and personal reasons. The median OS of patients who underwent surgery followed by adjuvant local therapy (n = 15) was 16.9 months (95% CI: 15.2–19.8 months) and for those treated with nonsurgical local therapy (n = 65) was 8.8 months (95% CI: 6.8–10.6 months) (log-rank P = 0.000). Conclusions: IC had a manageable toxicity profile and achieved resectability in 23.8% of our patients with technically unresectable T4a OSCC. Patients underwent resection had a significantly better median OS than those who received nonsurgical local treatment.
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Modulated radiotherapy with concurrent and adjuvant temozolomide for anaplastic gliomas: Indian single-center data p. 495
Tejinder Kataria, Trinanjan Basu, Deepak Gupta, Shikha Goyal, Shahida Nasreen, Shyam S Bisht, Ashu Abhishek, Susovan Banerjee, Kushal Narang, Ajaya N Jha, Ishani Mohapatra, Jayesh A Modi
DOI:10.4103/ijmpo.ijmpo_200_16  
Objective: To evaluate early clinical outcome for anaplastic gliomas (AG) treated in the era of modulated radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ) in an Indian setting. Materials and Methods: Fifty-three patients with AGs treated with modulated RT and concurrent (95%) and adjuvant TMZ (90%) were analyzed. About 80% of patients had Karnofsky performance status (KPS) at least 90 with 30% seizure at presentation. Postoperative magnetic resonance imaging was available in 65% cases and RT dose was 60 Gy in 30 fractions. First posttreatment imaging was performed at 1 month and then at 3 and 6 months post-RT and then every 3 months. Kaplan–Meier analysis was used to estimate disease-free survival (DFS) and overall survival (OS), and analysis was done using SPSS version 18.0. Results: With median follow-up of 25 months, 2-year DFS and OS were 75% and 88%. There were only 5% symptomatic central nerves system and 8% symptomatic hematological toxicities. At the 1st evaluation, 30.4% had complete response (CR), at 3 months 40%, and at 6 months 43%. At 6 months, only 4% had progressive disease. Forty-six patients were evaluable till the last follow-up with and 55% had stable to CR. On univariate analysis for DFS, KPS at presentation >90 (P = 0.001) and response at 6 months (P = 0.02) were significant and for OS KPS at presentation (P = 0.004) alone. Conclusion: Modulated RT with TMZ among Grade III glioma patients resulted in minimum treatment-related toxicities and encouraging survival. Molecular prognostic markers will determine most favorable groups in future.
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Oxaliplatin-induced peripheral neuropathy in south indian cancer patients: A prospective study in digestive tract cancer patients p. 502
Sreenivasulu Palugulla, Steven Aibor Dkhar, Smita Kayal, Sunil K Narayan
DOI:10.4103/ijmpo.ijmpo_143_17  
Purpose: The aim of the current study is to report our prospective experience on the prevalence of oxaliplatin-induced peripheral neuropathy (OXAIPN) in patients with digestive tract cancers treated with oxaliplatin-based combination therapy. Materials and Methods: A total of 219 patients scheduled to be treated with oxaliplatin-based combination therapy were prospectively examined at baseline and follow-up during the therapy between November 2014 and December 2016. The incidence of acute OXAIPN was measured using a descriptive questionnaire (yes/no question) based on sum of number of symptoms present and NCI-CTCAE version 4.03 was applied to clinically grade the severity of chronic OXAIPN. Results: Acute and chronic OXAIPN was found in 108 of 219 (49.3%) and 127 of 219 (58%) patients, respectively. Out of 11 acute OXAIPN symptoms, the vast majority of patients manifested cold-induced pharyngolaryngeal (63.8%) dysesthesias or perioral (61.1%) paresthesias. Development of acute OXAIPN was predictive of subsequent development of chronic OXAIPN (P = 0.0001). All the patients received a median cumulative dose of 780 mg/m2 (range: 130–1040 mg/m2). There was a significant correlation between the patients who received the median cumulative dose and the development of chronic OXAIPN. The incidences of OXAIPN in patients with median cumulative dose of ≤780 mg/m2 was 51/120 (42.5%) and >780 mg/m2 was OXAIPN 76/99 (76.7%) (P = 0.0001). Conclusion: The current study results demonstrate that the vast majority of patients who receive oxaliplatin-based combination chemotherapy will manifest acute OXAIPN that may contribute to the development of chronic peripheral neuropathy on repeated courses of drug administration.
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Efficacy and safety of ibrutinib in indian patients with relapsed or refractory chronic lymphocytic leukemia and mantle cell lymphoma: Cases from a named patient program p. 508
Mohan B Agarwal, Dinesh Bhurani, Chirag Shah, Nitin Sood, Manish Singhal, Anil Kamat, Subash Chezhian, Suryaprakash Mishra, Dinesh Nagrale
DOI:10.4103/ijmpo.ijmpo_43_17  
Context: This named patient program evaluated the safety and efficacy of ibrutinib, a selective inhibitor of Bruton's tyrosine kinase in Indian patients with relapsed/refractory chronic lymphocytic leukemia (CLL, with/without chromosome 17 deletion [del17p]) and mantle cell lymphoma (MCL). Subjects and Methods: The eight enrolled patients (relapsed/refractory CLL: n = 6 [4/6 patients with del17p] and relapsed/refractory MCL: n = 2) had median age of 55 years (range, 52–60) and had received a median of 3 (CLL patients) and 4 (MCL patients) prior therapies. Patients received once-daily dose of ibrutinib (420 mg: CLL, 560 mg: MCL). Results: In CLL patients, the median time to response was 3 months (range, 0.5–7) and five of six patients had partial response (PR) whereas one achieved complete response (CR). Median time on treatment was 11.5 months (range, 8–14); five patients continued treatment and one was recommended stem cell transplantation (SCT). Of the two MCL patients, one achieved PR and one showed CR and advanced to SCT. In CLL patients, the median (range) hemoglobin level improved from 9.8 g/dL (7.2–11) at baseline to 12.0 g/dL (9.5–13.2) and median (range) platelet count improved from 150,000 cells/μL (21,000–195,000) at baseline to 190,350 cells/μL (130,000–394,000) at the time of analysis (July 2016). Most adverse events (AEs) reported were infections (n = 2). No Grade 3-4 or serious AEs, dose reductions, or treatment discontinuation due to AEs were reported. Conclusions: In this first real-world experience in Indian patients, ibrutinib demonstrated therapeutic efficacy in relapsed/refractory CLL (with/without del17p) and MCL. Safety results were consistent with the current known profile of ibrutinib.
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2017 ASCO HIGHLIGHTS ON GASTOINTESTINAL MALIGNANCIES Top

2017 ASCO Highlights on Gastointestinal Malignancies p. 516
Ravi Kumar Paluri
DOI:10.4103/0971-5851.220133  
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REVIEW ARTICLES Top

Nivolumab – Pearls of evidence p. 520
Pratishtha B Chaudhari
DOI:10.4103/ijmpo.ijmpo_193_16  
Purpose: Nivolumab is one of the most extensively studied immune checkpoint inhibitors across various tumor types. In this narrative review, the current clinical efficacy and safety data of anti-programmed death-1 (PD-1) nivolumab for nonsmall cell lung cancer (NSCLC) and renal cell cancer (RCC) are elucidated. Methods: Systematic search was done on Pubmed, Medline, Embase, Web of Knowledge, and Cochrane Central through September 2016 for controlled prospective interventional studies of nivolumab across two indications - NSCLC and RCC. There was heterogeneity at all levels of abstraction; hence, author did not plan to provide a meta-analysis, but instead, a narrative elaboration of results structured around the conceptual frameworks. Results: Checkpoint receptor PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes. Binding of PD-1 to its ligands, programmed death-ligands 1 and 2, results in the downregulation of lymphocyte activation. Nivolumab is a fully human PD-1 immune checkpoint inhibitor. Nivolumab inhibits the interaction between PD-1 and its ligands and promotes immune responses including antitumor immune response and antigen-specific T-cell responses to both foreign antigens as well as self-antigens. In 2013, the Food and Drug Administration granted fast track designation for nivolumab in NSCLC, RCC, and melanoma. Conclusion: The encouraging literature on nivolumab lends credibility to the promise of immune checkpoint blockade, not just in terms of its feasibility as an oncotherapeutic strategy but also as a key tool of the future in the therapeutic approaches against advanced cancers.
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A risk-benefit assessment approach to selection of adjuvant chemotherapy in elderly patients with early breast cancer: A mini review p. 526
Vivek Agarwala, Neha Choudhary, Sudeep Gupta
DOI:10.4103/ijmpo.ijmpo_96_17  
Decision-making regarding the use and selection of adjuvant chemotherapy for breast cancer in elderly patients is challenging due to the presence of age-related comorbidities, frailty, and competing causes of mortality. One area, relatively neglected in most guidelines, is the effect of competing causes of mortality on presumed benefit of adjuvant chemotherapy for breast cancer in these patients. This article utilizes a clinical case to illustrate the principles of risk-benefit assessment of adjuvant chemotherapy in elderly patients. We suggest an approach that incorporates validated tools for estimating survival benefits of adjuvant chemotherapy, geriatric assessment, predicting toxicity, and estimating remaining life expectancy without cancer. Integration of all these variables provides a better picture of the possible benefits and harms of adjuvant chemotherapy in this population compared to conventional approaches that incorporate tumor-related variables and nonstandard measures of geriatric assessment.
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PRACTITIONER SECTIONS Top

Primary leiomyosarcoma of breast presenting with metastasis: An atypical presentation with dismal prognosis p. 535
Garima Singh, Deepti Sharma, Surbhi Goyal
DOI:10.4103/ijmpo.ijmpo_139_16  
Leiomyosarcoma is an extremely uncommon subtype of breast sarcoma, with <50 cases reported in the English literature till date. Patients usually present at an early stage and follow an indolent course. We reported an unusual case of leiomyosarcoma of breast in a post -menopausal female,presented with right side breast lump and pain right side hip. Histomorphological evaluation and immunohistochemistry confirmed the diagnosis. The patient received palliative radiotherapy 20 Gy in 5 fractions to right iliac bone and was started on chemotherapy comprising of docetaxel and epirubicin. Leiomyosarcoma of breast is known to have local recurrence and hematogenous metastasis, usually 10–15 years after the primary diagnosis. Aggressive behavior of leiomyosarcomas in the form of such a rapidly growing, fungating mass of 15 cm in greatest dimension with hematogenous metastasis at the time of initial presentation, as seen in our case, is extremely unusual.
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Renal Lymphoma: Primary or first manifestation of aggressive pediatric B-cell lymphoma p. 538
Pragnya Coca, Vijay Gandhi Linga, Sadashivudu Gundeti, Ashwani Tandon
DOI:10.4103/ijmpo.ijmpo_48_16  
Renal lymphoma is an uncommon renal tumor in children. Unlike renal lymphomas presenting as bilateral disease and renal failure, we report a boy who presented with unilateral renal involvement. After initial nephrectomy, he achieved remission with multiagent chemotherapy but relapsed systemically within 3 months. He was initiated on salvage chemotherapy with autologous bone marrow transplant. Even though the initial manifestation was localized lymphoma eventually, it turned out to be a systemic disease. He succumbed to disease at 14 months from diagnosis.
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CASE REPORTS Top

Ewing's sarcoma of the calcaneum p. 542
P Ajmal Sherif, A Santa
DOI:10.4103/ijmpo.ijmpo_50_16  
Ewing's sarcoma of the calcaneum is rare. Radiological features of this tumor can be misinterpreted as other benign bone tumors due to its rarity. The overall prognosis of Ewing's sarcoma of calcaneum is inferior compared to other sites of this tumor. Hence, these tumors should have extensive radiological evaluation and histological confirmation as misdiagnosis and treatment delays will have detrimental outcomes.
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Primary renal cell lymphoma: Case report, diagnosis, and management p. 545
Rajat Thawani, Amarendra Amar, Jayanta Patowary, Sumaid Kaul, Amarnath Jena, Pratap Kishore Das
DOI:10.4103/ijmpo.ijmpo_167_16  
The symptoms of primary renal lymphoma (PRL) may mimic a renal cell carcinoma. Since the diagnosis is mostly after a radical nephrectomy, we recommend a percutaneous biopsy or cytology from the renal mass in patients who have features suggestive of a lymphoma. A magnetic resonance imaging may give an image more specific for a lymphoma. There are no clinical trials for the treatment of PRL, but all previously published case reports used R-CHOP and a few patients did better than the median survival of 6 months.
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Flagellate rash: An unusual complication of bleomycin therapy – A case report with brief review of literature p. 548
Chaturbhuj Agrawal, Vineet Talwar, Rajeev Saini, Pradeep Babu
DOI:10.4103/ijmpo.ijmpo_147_16  
Chemotherapy-induced skin rashes are common toxicities encountered which require careful assessment and evaluation as rashes could be a manifestation of primary malignancy itself and a variety of drugs used in combination further complicate the clinical scenario. Bleomycin is an anticancer antibiotic derived from Streptomyces verticillus and has been commonly used in the treatment of Hodgkin's disease, germ cell tumors and for pleurodesis. There are various dermatological adverse effects of bleomycin which have been previously reported in literature including skin peeling, hyperkeratosis, nail bed changes, Raynaud's phenomenon, and palmoplantar desquamation. Bleomycin-induced skin rashes are seen infrequently now a day due to its declining use in clinical practice. We report here a 29-year-old male with Stage III germ cell tumor who developed widespread flagellate rash after receiving 3 cycles of bleomycin-based chemotherapy which responded to treatment with local steroids and omission of bleomycin from further chemotherapy cycles.
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Multiple myeloma presenting as thyroid plasmacytoma p. 552
Kaalindi Singh, Pankaj Kumar, Ritesh Pruthy, Gautam Goyal
DOI:10.4103/ijmpo.ijmpo_43_16  
Thyroid gland and thyroid cartilage infiltration in multiple myeloma (MM) are rare. Here, we discuss a patient who presented with hoarseness of voice and was found to have a hypodense lesion in right lobe of thyroid involving thyroid and cricoid cartilage. Fine-needle aspiration cytology with immunohistochemistry revealed extramedullary plasmacytoma of thyroid. MM was ruled out initially by serum protein electrophoresis, immunofixation, and bone marrow biopsy. Later, lytic lesions were found in multiple bones on radiation planning scan and he was finally diagnosed as case of MM with thyroid involvement. Treatment strategies of MM and thyroid plasmacytoma are also discussed briefly.
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A case of multifocal eosinophilic granuloma involving spine and pelvis in a young adult: A radiopathological correlation p. 555
Santosh Rai, HB Sridevi, Radha R Pai, Pulastya Sanyal
DOI:10.4103/ijmpo.ijmpo_130_16  
We present a case of multiple osteolytic lesions in a 28-year-old adult who presented with headache, back pain, and hip pain of 6 months. There was no history of localized swelling or rise of temperature, no history of weight loss or evening rise of temperature. On examination, there were no focal neurological deficits. Routine laboratory investigations, including total leukocyte counts, differential leukocyte counts, hemoglobin, and platelet counts, were within normal limits. There was a borderline elevation of erythrocyte sedimentation rate. Non enhanced computer tomography (NECT) demonstrated no abnormality in the brain or skull bones. However, incidentally, a lytic lesion involving the third cervical (C3) vertebral body and the neural arch was detected which also demonstrated a soft tissue component adjacent to the lytic lesion. These findings warranted further work up; and magnetic resonance imaging of whole spine and pelvis was performed that revealed multiple bony lesions involving the cervical vertebrae, head and neck, bilateral femur, sacrum, and iliac bones. Computed tomography-guided biopsy was performed from the C3 vertebral lytic lesion which showed features of eosinophilic granuloma on histopathological evaluation.
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Macrodystrophia lipomatosa: Clinico-patho-radiological correlation p. 559
Rakesh Mehra, Richa Bhartiya, Pallavi Agrawal, Nawanita Kumari
DOI:10.4103/ijmpo.ijmpo_65_16  
Macrodystrophia lipomatosa is a rare congenital nonhereditary developmental anomaly. It is characterized by hamartomatous proliferation of the soft tissue leading to disproportionate enlargement of the limbs and digits. Since it leads to diagnostic dilemma, it has to be differentiated from various other conditions as they differ in course, prognosis, complications, and treatment. Herein, we present two cases with localized gigantism and discuss the various differential diagnoses and need for clinico-patho-radilogical correlation for diagnosis of this rare entity.
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EDITORIAL COMMENTARY Top

Gastric teratoma: An unusual presentation and location p. 563
Jayalaxmi S Aihole, M Narendra Babu, Vinay Jadhav, Deepak Javaregowda
DOI:10.4103/ijmpo.ijmpo_182_16  
The gastric teratoma is a rare tumor that usually presents as an abdominal mass, with or without features of gastric outlet obstruction. We report two cases of gastric teratoma; one – mature in a male neonate and another – ruptured immature gastric teratoma in a female neonate.
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