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Orbital mucosa-associated lymphoid tissue (MALT) lymphoma, which are rare and indolent, often present at an early stage. We report the efficacy and safety outcomes of treatment in these patients.We analyzed adult patients with stage IE or IIE orbital MALT lymphoma between 1999 and 2017 treated at our institute. We assessed local control (LC) rates, overall survival (OS), relapse-free survival (RFS) using Kaplan Meier method and the incidence of late toxicities.Seventy patients were analyzed for clinical outcomes. The median age at diagnosis was 52 years (IQR-45-62 years). Radiotherapy was offered to 97% of patients and the dose ranged from 36 to 45 Gy. Chemotherapy was administered in 5(7.1%) patients. Relapse occurred in 8 patients (local: 2, distant: 6). At a median follow-up of 101 months (IQR-47-146 months), the median OS and RFS was not reached. 8-year OS, RFS and LC rates were 96.5%, 88.5%, 96.7% respectively. Univariate analysis showed age ≤60 years and lacrimal involvement significantly correlated with better OS (P = .01 and .04, respectively). Cataract was the most common sequelae observed in 31 patients (44.3%).Moderate doses of radiotherapy are curative in early-stage orbital MALT lymphoma with favorable clinical outcomes. Lower doses of radiation can reduce the toxicity further, without compromising efficacy.

BACKGROUND: Diagnosis of MALT lymphoma in the oral cavity is challenging. There is a great overlap in the histopathologic, immuno-histochemical and molecular features of MALT lymphoma with reactive lymphoid proliferations. The literature shows a very few case reports of primary MALT lymphoma of oral cavity. METHODS: We discuss the histopathologic, immuno-histochemical, cytogenetic features, treatment and behavior of 3 cases of primary MALT lymphoma oral cavity along with review of literature. RESULTS: The age ranged from 40 to 57 years (male to female ratio = 2:1). The sites involved were hard palate, bilateral gingivobuccal sulcus and right buccal mucosa. The most common histology was centrocyte-like (2 cases). Lymphoepithelial lesions were absent. On immunohistochemistry, all tumors showed diffuse strong CD20 and bcl2 expression with strong and diffuse MNDA staining in one case. IgH; MALT1 translocation was not seen in any of these cases. One patient received local radiotherapy, one received steroids; while the case 3 received RCHOP (Rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine and prednisone) chemotherapy. Two patients had complete remission while one had recurrence. CONCLUSION: MALT lymphoma of oral cavity shows a wide spectrum of morphology with presence of transformed cells, that may lead to misdiagnosis of DLBL. Treatment guidelines are not well established but a tendency to excise MALT lymphomas of oral cavity has been observed. Nevertheless, MALT lymphoma of oral cavity appears to be an indolent disease.

Triple negative Breast tumor (TNBC) is an aggressive tumor with sparse data worldwide.We analyzed non-metastatic TNBC from 2013 to 2019 for demographics, practice patterns, and survival by the Kaplan Meir method. Prognostic factors for OS and DFS were evaluated using Cox Proportional Hazard model estimator for univariate and multivariable analysis after checking for collinearity among the variables.There were 1297 patients with median age of 38 years; 41 (33.3%) among 123 tested were BRCA-positives. Among these 593 (45.7%) had stage III disease, 1279 (98.6%) were grade III, 165 (13.0%) had peri-nodal extension (PNE), 212 (16.0%) lympho-vascular invasion (LVI), and 21 (1.6%) were metaplastic; 1256 (96.8%) received chemotherapy including 820 (63.2%) neoadjuvant with 306 (40.0%) pCR. Grade ≥3 toxicities occurred in 155 (12.4%) including two deaths and 3 s-primaries. 1234 (95.2%) underwent surgery [722 (55.7%) breast conservations] and 1034 (79.7%) received radiotherapy. At a median follow-up of 54 months, median disease-free (DFS) was 92.2 months and overall survival (OS) was not reached. 5-year estimated DFS and OS was 65.9% and 80.3%. There were 259 (20.0%) failures; predominantly distant (204, 15.7%) - lung (51%), liver (31.8%). In multivariate analysis presence of LVI (HR-2.00, p-0.003), PNE (HR-2.09 p-0.003), older age (HR-1.03, p-0.002) and stage III disease (HR-4.89, p-0.027), were associated with poor OS.Relatively large contemporary data of non-metastatic TNBC confirms aggressive biology and predominant advanced stage presentation which adversely affects outcomes. The data strongly indicate the unmet need for early detection to optimize care.

PURPOSE There are sparse data in patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer with brain metastases from real-world settings, especially where access to newer targeted therapies is limited. METHODS This was a single institution, retrospective cohort study of patients with HER2-positive breast cancer diagnosed between January 2013 and December 2017 to have brain metastases and treated with any HER2-targeted therapy. The main objectives were to estimate progression-free survival (PFS) and overall survival (OS) from the time of brain metastases. RESULTS A total of 102 patients with a median age of 52 (interquartile range, 45-57) years were included, of whom 63 (61.8%) had received one line and 14 (13.7%) had received two lines of HER2-targeted therapies before brain metastasis, 98 (96.1%) were symptomatic at presentation, 22 (25.3%) had solitary brain lesion, 22 (25.3%) had 2-5 lesions, and 43 (49.4%) had ≥ 5 lesions. Local treatment included surgical resection in nine (8.9%) and radiotherapy in all (100%) patients. The first HER2-targeted therapy after brain metastasis was lapatinib in 71 (68.6%), trastuzumab in 19 (18.6%), lapatinib and trastuzumab in three (2.9%), trastuzumab emtansine in four (3.9%), and intrathecal trastuzumab in five (4.9%) patients. At a median follow-up of 13.9 months, the median PFS and OS were 8 (95% CI, 6.2 to 9.8) months and 14 (95% CI, 10.8 to 17.2) months, respectively, with a 2-year OS of 25% (95% CI, 16.7 to 34.4). The median PFS in patients who received lapatinib-capecitabine regimen (n = 62) was 9.0 (95% CI, 7.3 to 10.7) months. CONCLUSION There was a substantial clinical benefit of local and systemic therapy in patients with brain metastases and HER2-positive disease in a real-world setting with limited access to newer HER2-targeted drugs.

Surgery is the primary treatment of phyllodes tumor of the breast, and margins are the most important risk factor associated with local recurrence. We conducted a retrospective audit of 433 patients treated at our center.Women who presented with phyllodes tumors between 1999 and 2017 were included in the analysis. Data was collected from the hospital medical records, telephonic interviews, and electronic mail.Of the 433 women included in this study, 177 (40.9%) had benign phyllodes tumors, 84 (19.4%) were borderline, 131 (30.3%) were malignant, and 41 (9.5%) had sarcoma. A history of previous excision was noted in 154 (35.6%) patients, of which 104 presented with local recurrence. Of the total patients, 209 (48.3%) underwent breast conservation surgery; the median pT was 6 cm. At a median follow-up of 37.9 months, the 5-year disease-free survival (DFS) was 82.9%. On multivariate analysis, the factors that impacted DFS were histology (hazard ratio, 4.1; 95% confidence interval [CI], 1.5-10.9; P = .005) and history of previous excision biopsy (hazard ratio, 3.39; 95% CI, 1.76-6.52; P .001). We analyzed 231 women who presented without any prior excision separately, wherein at a median follow-up of 44.1 months, the DFS was 92.1% (95% CI, 92.05%-92.15%). In addition, less recurrences were noted in this cohort (5.6% [13/231] in no-excision biopsy vs. 12.5% with surgery done prior to presentation to our institute).A previous history of excision and the histologic subtype of phyllodes tumor are factors that have an impact on DFS, thus emphasizing the need for appropriate surgical planning and en bloc excision of the phyllodes at presentation.

We present the findings of 18 F-FDG PET and 68 Ga-fibroblast activation protein PET scans done in a case of bilateral breast carcinoma with 2 different histopathology, left breast tubulolobular carcinoma and right breast invasive breast carcinoma of no special type.

Background Therapeutic decisions in breast carcinoma are being made on the basis of tumor cell proliferation using exorbitant genomic tests. The 2013 St Gallen meeting advocated surrogate definitions for classifying tumors into luminal subtypes on the basis of immunohistochemical (IHC) markers. We studied the classification of estrogen receptor (ER)-positive tumors using these definitions as well as different methods for Ki-67 labeling index (LI) estimation. Patients and Methods A total of 541 ER+ invasive breast carcinoma cases from January 2012 to December 2012 were evaluated for Ki-67 LI by the average and hot spot methods. The IHC results of ER, PR, and human epidermal growth factor receptor 2 (HER2) were noted. HER2 IHC equivocal (2+) samples were subjected to HER2 fluorescence in-situ hybridization testing. Luminal subgroups created on the basis of the 2013 St Gallen meeting guidelines were correlated with clinicopathologic variables and disease-free survival. Results The distribution of luminal subtypes was as follows: luminal A–like, 13.3%; luminal B–like (HER2−), 57.9%; and luminal B–like (HER2+), 28.8%. Approximately 6% of cases were recategorized into different subgroups when the average method was used instead of the hot spot method for Ki-67 LI assessment. Younger patients (≤ 50 years), grade 3 tumors, positive axillary nodes, recurrence, and distant metastasis had a positive statistical correlation with luminal B–like (HER2−) subtype. Patients with luminal B–like (HER2−) tumors had a shorter disease-free survival compared to patients with luminal A–like tumors. Conclusion Ki-67 LI, irrespective of the method of assessment, along with PR, can be efficiently used to divide ER+ tumors into prognostic subgroups in Indian patients.

Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) in the elderly aims to achieve disease remission while minimizing treatment-related toxicities. The use of anthracycline in the elderly is associated with increased risk of cardiotoxicity and myelosuppression. Non-anthracycline-based regimens have commonly been used in patients with cardiac contraindications or anticipated severe toxicities to anthracyclines.We retrospectively analyzed the treatment outcomes of patients, aged 60 years and above, newly diagnosed with DLBCL at our center. Of a total of 218 patients, 71 patients received the R-CHOP regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone) and 137 received R-CE (Etoposide) OP chemotherapy. The decision to substitute etoposide for doxorubicin was based on physician's discretion depending on the performance status, cardiac comorbidities and frailty as well as available resources for supportive care.The 2-year progression-free survival (PFS) rate in the R-CHOP group was higher than that in the R-CEOP group (79.1% vs 49.6%, P-value.001) and this superiority of R-CHOP was seen in both early and advanced disease. The incidence of febrile neutropenia and grade III/IV hematological toxicities was significantly higher in the R-CHOP group in the age group of 60 to 65 years'. ECOG PS at presentation, NCCN-IPI and the chemotherapy regimen were found to be significant factors for 2-year PFS rate by multivariate analysis.Anthracycline-based regimen should be used in elderly fit patients without absolute cardiac contraindications wherever feasible with adequate access to supportive care.

Pediatric B-cell lymphoblastic lymphoma (LBL) is a rare entity, and appropriate treatment for pediatric B-cell LBL is not well defined. While intensive ALL type regimens achieve long term survival of 90% across Western co-operative group trials, published data from Asian studies on long term outcomes are scarce. We retrospectively analyzed the data of pediatric B-cell LBL patients treated between January 2010 and December 2017 on a uniform protocol (modified BFM 90). Kaplan-Meier method was used to estimate the survival and Cox regression models to identify prognostic factors. Of 21 patients who received treatment on the modified BFM-90 protocol, 17(81%) were alive in remission, 3(14%) had relapse, and 1(4%) had treatment-related mortality (TRM) while in remission. Two of 3 relapsed patients subsequently expired. With a median follow-up of 66 months (range 6–114), 5-year event free survival (EFS) and overall survival (OS) were 80% (95% CI:71–89%) and 91% (95% CI:85–97%), respectively. While delayed presentation from symptom onset (p=0.030), and partial response at early (D35) interim assessment (p=0.025) had inferior EFS, patients with elevated baseline LDH had a worse OS (p=0.037). Outcomes of pediatric B-cell LBL patients treated on a modified BFM-90 protocol at a single center in India were excellent. In our study, higher disease burden manifested by elevated baseline LDH and delayed presentation (≥3months) and partial interim response portend poorer survival. Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.2005725

Extra-nodal natural killer (NK)/T-cell lymphoma is a rare, distinctive clinicopathologic entity with an aggressive clinical course. High expression of multidrug-resistant (MDR) P-gp on NK lymphoma cells renders this disease resistant to anthracycline-based chemotherapy regimens. Over the years, based on retrospective analysis and phase II studies, regimens with L-asparaginase and non-MDR drugs have been used.To evaluate the outcome of patients with extra-nodal NK/T-cell lymphoma treated in a tertiary cancer care center in India from 2012 to 2021.Retrospective, observational, single-center study.Hematolymphoid Department, Tata Memorial Hospital.From January 2010 to December 2021, all consecutive patients with NK/T-cell lymphoma were analyzed.Relapse-free survival and overall survival.A total of 78 patients with a diagnosis of extra-nodal NK/T-cell lymphoma were treated from 2010 to 2021. Amongst them, 56 (71.8%) were male, with a median age of 40 years (15-71 years). The most common presenting symptom was nasal swelling (9%), followed by dysphagia (3.8%). B symptoms were present in 35 patients (45%). Only 5% had HLH anytime during the treatment. One-third of the patients had an ECOG performance status1. Nasal type constituted 80% of the cohort, regional node was involved in 60%, distant node was involved in 28%, 33% had more than 1 extra-nodal site involved, 23% had bulky disease, and 40% had advanced stage (stage 3-4) at presentation. EBV LMP1 was positive in 19 patients (24%). EBERISH was available in 9 patients, of which 7 were positive. Fifteen patients received treatment prior to presentation to our center (CHOP in 10 patients). At our center, the SMILE chemotherapy protocol was administered to 52 patients (66.7%). Consolidative radiation therapy was administered in 43 patients (55.1%). The best radiological response of CR was achieved in 49 patients (62.8%). After a median follow-up of 30 months, 30 (38.5%) patients relapsed and 30 (38.5%) died. Median relapse-free survival was 45 (95%CI: 5.1-84.8) months. Overall survival at 36 months was 53.4% (95%CI: 41.7%-68.4%).The outcome of NK/T-cell lymphoma in our cohort is comparable to the outcomes found in the literature.

Background Molecular tests in solid tumours for targeted therapies call for the need to ensure precision testing. To accomplish this participation in the External Quality Assessment Program (EQAS) is required. This evaluates the consistency of diagnostic testing procedures and offers guidance for improving quality. Outbreak of COVID-19 pandemic led to worldwide lockdown and disruption of healthcare services including participation in EQAS.The present study describes the extended scope of EQAS offered byMPQAP (Molecular Pathology Quality Assurance Program), the first proficiency test provider for solid tumor diagnostics in India. The study surveys the preparedness of molecular testing laboratories in routine diagnostics and participation for quality assessment scheme. Methods A documented guideline for measures and precautions to be carried by testing laboratories in performing routine diagnostic tests during the lockdown period were charted and distributed to all MPQAP participant centres. A survey was conducted for MPQAP participants to check whether laboratories were involved in COVID-19 testing and to evaluate the impact of lockdown on the operations of diagnostics procedures. From the acquired response of the survey, 2 cycles out of initially proposed 11 cycles were executed with transformed approach using digital tools and image interpretation modules. Findings Out of 25 solid tumour testing laboratories registered as participants, 15 consented to participate in survey. The summary of survey conveyed the impact of COVID-19onroutine operations of diagnostics tests such as shortcomings in inventory and human resource management. Thirteen participants showed active willingness and consented to participate in EQAS test scheme. Interpretations The survey findings and assessment of EQAS cycles endorsed the quality testing procedures carried by participating laboratories throughout the lockdown. It highlighted the utility of EQAS participation during pandemic along with emphasis on safety measures for continual improvement in quality of diagnostic services.

Anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin lymphoma (NHL) in children. Most treatment regimens include high-dose methotrexate (HDMTX), which is logistically difficult to administer in resource-limited settings. We evaluated the outcomes of pediatric ALCL patients treated on a uniform protocol (Modified Multicentric Protocol, MCP-842 regimen) at our hospital between January 2005 and December 2016. Of the 68 patients who received treatment on the Modified MCP842 protocol, 46 patients are alive in remission, 11(16%) had disease progression, 9(13%) relapsed after achieving remission, and 5(7%) had treatment-related mortality (TRM). Seventeen of 20 relapsed/progressed patients subsequently expired. With a median follow-up of 55 months (range 2-165 months), the 4-year event-free survival (EFS) and overall survival (OS) are 63% (95% CI of 50-73%) and 70%(95% CI of 57-79%), respectively. An indigenous protocol using vinblastine (without HDMTX and steroids) is feasible in a resource-limited setting and achieves outcomes comparable to regimens incorporating HDMTX, with lower toxicity.

T cell lymphomas encompass a diverse group of Non-Hodgkin lymphomas with a wide spectrum of clinical, immunological and pathological manifestations. In the last two decades there has been a progress in our understanding of the cell of origin, genetic abnormalities and their impact on behaviour in T cell lymphomas. Genetic alterations are one of the critical drivers of the pathogenesis of T cell lymphoma. Disease progression has been correlated with multiple genetic abnormalities where malignant clones arise primarily out of the host immune surveillance arsenal. There are many cellular processes involved in disease development, and some of them are T cell signaling, differentiation, epigenetic modifications, and immune regulation. Modulation of these crucial pathways via genetic mutations and chromosomal abnormalities possessing either point or copy number mutations helps tumor cells to develop a niche favourable for their growth via metabolic alterations. Several metabolic pathways especially regulation of redox homeostasis is critical in pathogenesis of lymphoma. Disruption of redox potential and induction of oxidative stress renders malignant cells vulnerable to mitochondrial damage and triggers apoptotic pathways causing cell death. Targeting genetic abnormalities and oxidative stress along with current treatment regime have the potential for improved therapeutics and presents new combination approaches towards selective treatment of T cell lymphomas.

Plasmablastic lymphoma (PBL) is an aggressive non-Hodgkin lymphoma occurring commonly in the oral mucosa and jaw of human immunodeficiency virus (HIV) positive adult males. PBL is not a common occurrence in children and a presentation with malignant effusion is rarely reported. Herein, we share our experience in the challenges confronted in the diagnosis of PBL in a 6-year-old, HIV positive boy presenting with malignant pleural and peritoneal effusions along with gum hypertrophy, lymphadenopathy and paranasal sinus mass. Amenability of pleural effusion to exfoliative cytology led to an initial cytological examination demonstrating large atypical lymphoid cells with plasmacytoid morphology and a plasmablastic variant of Burkitt lymphoma was initially considered. However immunophenotyping by flowcytometry (FCM) and a cell block immunohistochemical evaluation of the serous effusion suggested a plasma cell immunophenotype and a diagnosis of PBL was favored. A subsequent biopsy from the paranasal sinus mass confirmed the diagnosis of PBL but showed tumour cell angiocentricity on morphology and CD45 expression on immunohistochemistry (IHC), both unusual features in PBL. A CD20 negative/MUM-1 positive immunoprofile and presence of a solid tumour mass in a typical location in addition to malignant effusion substantiated the diagnosis of PBL. The patient was offered HAART (highly active antiretroviral therapy) and chemotherapy and is on follow-up. Paediatric PBL with malignant effusion is rarely reported and this case stresses the importance of use of a multimodality diagnostic approach for an accurate diagnosis.

Clinicopathologic profile and outcome of 15 children (15 years or above) with diffuse large B-cell lymphoma treated with MCP-842 protocol are reported. Eleven of 15 presented with advanced (stage-III/IV) disease. Post-2 cycles of chemotherapy, complete metabolic and morphologic response was documented in 10 (66%) and rest 5 (33%) with partial response achieved complete metabolic remission by end of treatment. At a median follow-up of 44 months (range: 16 to 79 mo), the 3-year event-free survival and overall-survival were 77.1%±11.7% and 85.7%±9.4%, respectively. Though majority of our patients had advanced disease, outcome on MCP-842 protocol was satisfactory.

There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment.This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity.A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6-90 months), the median age was 46 (24-65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56-75%) and the OS was 76% (95% CI 67-85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients.The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

In a previous retrospective audit from our institution we reported that patients had limited access to HER2-targeted therapy due to financial constraints. Subsequently, the advent of biosimilar versions of trastuzumab and philanthropic support has potentially changed this situation. Herein, we reanalyzed and reported access to HER2-targeted therapy in a more recent cohort of patients.Medical records of new breast cancer patients registered in one calendar year were retrospectively reviewed, supplemented by online pharmacy data to extract information on receptor status, use of HER2-targeted therapy, and other relevant variables. Since not all HER2 immunohistochemistry (IHC) 2+ tumors underwent fluorescent in-situ hybridization (FISH) testing, we estimated the probable HER2 amplified from this group based on a FISH amplified fraction in those HER2 2+ tumors who did undergo FISH.Between January 2016 and December 2016, 4717 new BC patients were registered at our institution, of whom 729 (20.04%) had HER2 IHC 3+ tumors while 641 (17.62%) had HER2 IHC 2+ tumors. The final number of HER2 overexpressing/amplified tumors was estimated to be 928 (729 HER2 IHC 3+, 105 known FISH amplified, and 94 estimated FISH amplified), of whom 831 received treatment at our institution. Overall 474 (57.03%, 95% confidence interval [CI] 53.6-60.4) of these 831 patients received trastuzumab for durations ranging from 12 weeks to 12 months in the (neo)adjuvant setting or other durations in metastatic setting compared to 8.61% (95% CI 6.2-11.6) usage of HER2-targeted therapy in the 2008 cohort.Access to HER2-targeted therapy has substantially increased among patients treated at a public hospital in the past decade, likely due to the advent of biosimilars, the use of shorter duration adjuvant regimens, and philanthropic support. However, further efforts are required to achieve universal access to this potentially life-saving treatment.

Purpose: There is lack of consensus on management of adolescent and young adult (AYA) Hodgkin lymphoma with respect to chemotherapy approach (adult or pediatric). Hence we sought to evaluate the efficacy and safety of Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy in AYA Hodgkin lymphoma. Patients and Methods: It is a retrospective, observational, single-center study. From January 2013 to December 2016, all consecutive patients with AYA (15-25 years, all stages) were analyzed. The primary endpoint of the study was event-free survival (EFS). Secondary endpoints were complete response rates (CR) and overall survival (OS). Results: A total of 220 patients (70% men) with median age 20 years were evaluated. A significant proportion of patients had adverse features such as stage III/IV disease (63%), bulky disease (63%), extranodal involvement (37%), and marrow involvement (22%). After two cycles and end of therapy, 77% patients achieved complete response. Primary progressive disease was seen in 6% patients. With a median follow-up of 2.6 years, 19 (8.6%) patients relapsed, 1 patient developed second malignancy, and 6 patients died. Three-year EFS and OS were 81.3% and 97%, respectively. Bleomycin-induced lung injury was seen in 16% patients. On multivariate analysis stage at presentation, bone marrow involvement, partial response at interim positron emission tomography and International prognosis score (IPS) >3 were predictors of poor EFS. Conclusion: ABVD is an effective and safe regimen in AYA Hodgkin lymphoma. Advanced disease with high IPS (>3) score needs an early escalation approach to escBEACOPP regimen.

PURPOSE We tested low axillary sampling (LAS) and sentinel node biopsy (SNB) performed in the same patient to predict axillary nodal status post–neoadjuvant chemotherapy (NACT) in women undergoing elective breast surgery, clinically N0 after NACT. PATIENTS AND METHODS A total of 751 women clinically node negative post-NACT underwent LAS (excision of lymph node [LN] and fat below first intercostobrachial nerve). Of these women, 730 also underwent SNB by dual technique (methylene blue plus radioisotope). SNB (defined as targeted plus palpable LNs) and LAS specimens were distinctly examined for metastasis. All patients underwent completion axillary lymph node dissection. Post-NACT, 290 (38.6%) of 751 women had residual positive lymph nodes on pathology. RESULTS The median clinical tumor size was 5 cm (range, 1-15 cm), and 533 (71%) of patients were N1 or N2 at presentation. Targeted sentinel node (SN) identification was 85.7% (626 of 730; median, two LNs); SN with palpable nodes was found in 95.2% (695 of 730; median, five LNs); LAS node was identified in 98.5% (740 of 751; median, seven LNs). In all but one case, the SN was found within the LAS specimen. The false negative rate (FNR) of SNB (blue, hot, and adjacent palpable nodes) was 19.7% (47 of 238; one-sided 95% CI upper limit, 24.0), compared with an FNR of 9.9% for LAS (29 of 292; one-sided 95% CI upper limit, 12.8; P < .001). If SNB was confined to blue/hot node, excluding adjacent palpable nodes, the FNR was 31.6% (74 of 234; one-sided 95% CI upper limit, 36.6). The FNR could be brought down to < 8.8% if three or more LNs were identified by LAS. CONCLUSION LAS is superior to SNB in identification rate, FNR, and negative predictive value in predicting node-negative axilla post-NACT. LAS can be safely used to predict negative axilla with < 10% chance of leaving residual disease.

Indian studies on EBV in childhood classic Hodgkin Lymphoma (cHL) have mainly analyzed the epidemiology of EBV-positive [EBV(+)HL] or negative HL [EBV(-)HL], with limited data on outcomes. We studied a large cohort of children with intermediate and high-Risk cHL for tumor EBV status and its impact on outcomes retrospectively. Of evaluable 189 patients, 84.7% had EBV(+)HL. Positive status was significantly associated with age ≤ 10 years (

The management of T-lymphoblastic lymphoma (T-LBL) in adults poses uncertainties, including optimal chemotherapy regimen, need for radiotherapy, and the benefit of stem cell transplant. This retrospective case series investigated the efficacy of the pediatric BFM-90 regimen in adult patients and evaluated the role of early response assessment by positron emission tomography with computed tomography (PET-CT) in predicting outcomes.Patients aged 15 years or older with T-LBL diagnosed at Tata Memorial Hospital, Mumbai, India were given chemotherapy according to the European BFM-90 protocol (n = 38). The patients were evaluated for early response by interim PET-CT, post-induction and monitored for toxicity and long-term outcomes.Thirty-eight consecutive patients (median age 23.5 years) were analyzed. After a median follow-up of 33.5 (1-77) months, following induction, 35 out of 38 patients (92.1%) had achieved complete response (CR) on PET-CT. Thirty (78.9%) patients treated according to BFM-90 were alive in first remission. Three-year event-free survival for those with CR on PET-CT was 78%, against no survivors for those who remained PET-positive.This study demonstrates the feasibility and efficacy of BFM-90 approach in adults with T-LBL. We found an early PET response to be highly predictive of outcome.

PURPOSE The role of axillary conservation after neoadjuvant chemotherapy (NACT) is debatable. We routinely carry out complete axillary lymph node dissection (ALND). This study was conducted to understand the pathologic axillary complete response (pAxCR) after NACT. MATERIALS AND METHODS We evaluated a prospective database of patients with breast cancer who underwent surgery after NACT in the year 2017 at our institution. NACT was administered to downstage locally advanced breast cancer or facilitate breast-conservation surgery. RESULTS Of 793 patients who underwent surgery after NACT, 97(12.2%) had cN0 disease, 407 (51.3%) had cN1, 262 (32%) had cN2, and 27 (3.4%) had cN3 at presentation. Eighty-eight patients (11.1%) had cT1-2 primary tumor stage, and 623 patients (78.6%) had cT3-4 primary tumor stage; primary tumor stage details were unavailable for 82 patients (10.3%). The median age was 46 years (range, 21-74 years). On histopathology, the overall pAxCR rate was 52.8%. In the cN1 and cN2 settings, 58.7% and 36.6% of patients achieved ypN0 status, respectively. The overall pathologic complete response rate was 22.64% (161 of 711 patients). On univariable analysis, cN stage, histologic grade, hormone receptor status, NACT duration, and lymphovascular invasion were significantly associated with pAxCR ( P CONCLUSION At least half of patients with cN1 and a third of patients with cN2 breast cancer who develop pAxCR may be suitable candidates for axillary conservation. A careful postchemotherapy assessment followed by a conservative axillary procedure may be an alternative to ALND, but this needs to be studied prospectively.

A histopathology report offers important prognostic and predictive information that helps plan systemic therapy in breast cancer. However, in many cases a pathologist fails to provide relevant information chiefly due to the lack of awareness of the impact of these parameters in clinical decision-making. This review seeks to put forth common practice points in grossing and reporting of specimens harboring breast cancer with focus on latest revisions in the same. Just as it is important to document tumor size, tumor type, margins, estrogen receptor/progesterone receptor, and human epidermal growth factor (ER/PR/HER2) in breast cancer, we need to also focus on sentinel node grossing, nodal burden, size of nodal metastasis, and extranodal extension. In parallel, increasing number of patients are getting neoadjuvant chemotherapy in breast cancer and points in grossing and reporting of such specimens are also alluded to. This article will serve as reference guide to pathologists on what we do and why we do the same.

The purpose of the study was to report dosimetric differences for breast brachytherapy plans optimized for clinical target volume (CTV) generated using conventional isotropic expansion of tumor bed volume (TBV) and Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) recommendations to expand the TBV anisotropically to achieve a total safety margin of 2 cm (resection margin size + added safety margin).Institutional records of 100 patients who underwent accelerated partial breast irradiation using multicatheter interstitial brachytherapy from May 2015 to March 2020 were reviewed retrospectively. Two sets of CT-based plans were made, one with 1-cm isotropic margins around the tumor bed (CTV_ISO) and the other with anisotropic margins (CTV_GEC). Plans were evaluated and compared using the American Brachytherapy Society and GEC-ESTRO guidelines.The median TBV was 36.97 cc. The median margin widths were as follows: anterior 1.2, posterior 1.0, superior 1.0, inferior 0.9, medial 1.2, and lateral 1.2 cm. The mean tumor bed coverage index was 0.94; 0.93 [p.066], the CTV coverage index 0.86; 0.84 [p 0.001], the dose homogeneity index (DHI) 0.77; 0.75 [p 0.001] and the conformity index 0.66; 0.64 [p 0.001] in CTV_ISO and CTV_GEC plans, respectively. In smaller volume implants (TBV35 cc), the DHI was 0.76; 0.75 [p 0.008] and the conformity index was 0.66; 0.62 [p 0.001], whereas in larger volumes35 cc, the CTV coverage index was 0.86; 0.84 [p 0.003] and the DHI 0.78; 0.76 [p 0.001] in CTV_ISO and CTV_GEC plans, respectively.In this cohort of patients who underwent accelerated partial breast irradiation, plans with anisotropic margins had lower conformity, the impact of which was predominantly seen in smaller implants. Rest of the dosimetric constraints were achieved in both the plans as per the American Brachytherapy Society and GEC-ESTRO guidelines.

Folate Receptor Alpha (FRA) is a membrane protein expressed on the apical surface of epithelial cells. Its expression in increased in certain tumors, where it can serve as a target for therapy. Triple Negative Breast Carcinoma (TNBC) are a heterogeneous group of tumors, with limited therapy options and poor prognosis. We aimed to study the expression of FRA in TNBC. Tissue microarrays were prepared from archived paraffin blocks of 300 TNBC resection specimens. Staining for FRA immunohistochemistry was carried out using the clone 26B3.F2. Clinical and pathologic details of the patients were obtained from the electronic medical records. Chi square test was performed for correlation of clinicopathological features with FRA expression. Kaplan Meir and Cox Regression analysis were carried out to study the Disease Free Survival (DFS) and Overall Survival (OS). FRA showed positivity in 43% (129/300) of TNBCs in our study. In univariate analysis, TNBC expressing FRA had a significantly better OS compared to FRA negative tumors (p – 0.035). Also, FRA positive tumors showed a trend towards longer DFS, though this was not statistically significant. In multivariate analysis however, FRA expression did not emerge as a significant factor. To conclude, TNBCs in our study showed FRA expression and though this did not emerge as an important prognostic factor, it can represent a therapeutic target for future clinical trials.

Bilateral breast cancer (BBC) is an uncommon presentation. The characteristics and outcomes of synchronous and metachronous BBC were compared within an Indian cohort.This was a retrospective audit of 193 BBC patients treated at a tertiary hospital in India over a period of 10 years from January 2004 to December 2014. The demographic, tumor and treatment characteristics were compared between synchronous (n = 131 patients) and metachronous tumors (n = 62 patients) using descriptive analysis. The survival outcomes were assessed using Kaplan-Meier survival curves and compared using the log rank test. Univariate and multivariate analysis was done using a Cox proportional hazards model to assess the effect of the prognostic factors on survival.The mean age of presentation in synchronous BBC (SBBC) and metachronous BBC (MBBC) was 55 years (SD, 12.5) and 51 years (SD, 9.5), respectively. The median time to contralateral presentation in MBBC was 3.8 years. Mean tumor size was larger in SBBC (P = .01). Breast Cancer gene mutation was positive in 13 of 38 evaluated patients (of whom 12 had MBBC). The concordance rates for the estrogen receptor (ER) and progesterone receptor negativity and triple-negative receptor status were higher in MBBC compared with SBBC (P .001). Grade III tumor was more frequently seen in MBBC (P = .03). The median follow-up of the entire cohort was 42 months (range, 30-60 months): 45 months for SBBC and 35 months for MBBC. The 3-year rates of overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) for SBBC and MBBC was 88% and 90%, 74% and 64% and 90% and 84%, respectively. There was no difference in overall OS, DFS, and LRC between SBBC and MBBC.BBC is an uncommon presentation. Synchronous presentation was more common. Metachronous tumors differ from synchronous with higher Grade of presentation and less expression of ER. There was no difference in outcome between patients with synchronous and metachronous tumors.

Context PathVysion—a US Food and Drug Administration–approved dual-probe human epidermal growth factor receptor (HER2) fluorescence in situ hybridization (FISH) assay—provides the HER2:CEP17 ratio, a centromeric enumeration probe ratio for determining HER2 status in breast cancers. However, pericentromeric amplifications might then skew the HER2:CEP17 ratio, underestimating the HER2 status, which calls into question the use of CEP17 as the reference probe. Objective To analyze the utility of a noncentromeric chromosome 17 reference locus (D17S122) to assess HER2 gene status in cases showing “nonclassical” FISH patterns with the CEP17 probe. Design The HER2 status of breast cancers accessioned in the years 2015–2017, displaying “nonclassical” or “equivocal” results by the PathVysion (Abbott Molecular Inc, Des Plaines, Illinois) HER2 DNA Probe Kit were reflex tested using an alternate FISH probe (ZytoLight SPEC/D17S122, ZytoVision, Bremerhaven, Germany) and interpreted with American Society of Clinical Oncology/College of American Pathologists 2013 guidelines. Results Of 37 cases, 17 were FISH equivocal. With the alternate D17S122 probe, 13 (76.4%) were reclassified as amplified, 3 (17.6%) as nonamplified, and a single case retained an equivocal result. Of the 17 cases with a chromosome 17 polysomy pattern, disomy, polysomy, and monosomy patterns were seen with 14 cases, 2 cases, and 1 case, respectively. Within the 17 cases with polysomy pattern, 3 (17.6%) demonstrated an unusual colocalization pattern of HER2 and CEP17, which was not observed with the alternate probe. Conclusions The denominator-stable alternate probe is a useful adjunct in the diagnostic armamentarium to analyze HER2 status in cases with FISH equivocal and complex patterns.

Background: 2008 World Health Organization (WHO) classification of hematolymphoid neoplasms (HLN) has classified them based on morphology, results of various ancillary techniques, and clinical features.[1] There are no studies looking at the applicability of WHO classification. Aims: The aim of the study was to calculate proportions of all HLN subtypes seen during 1-year period based on 2008 WHO classification of HLN and study applicability and also shortcomings of practices in a tertiary care center in India. Materials and Methods: This was a 1-year retrospective study (January 1st, to December 31st, 2010) where cases were identified using hospital/laboratory electronic records. Old follow-up and referral cases were excluded from the study. Only newly diagnosed cases classified into categories laid down by 2008 WHO classification of HLN included. Results: Out of 2118 newly diagnosed classifiable cases, 1602 (75.6%) cases were of lymphoid neoplasms, 489 (23.1%) cases of myeloid neoplasms, 16 (0.8%) cases of histiocytic and dendritic cell neoplasms, and 11 (0.5%) cases of acute leukemias of ambiguous lineage. Overall, most common HLN subtype was diffuse large B-cell lymphoma (n = 361, 17.0%). Precursor B-lymphoblastic leukaemia/lymphoma (n = 177, 48.2%) was the most common subtype within pediatric age group. Conclusions: All major subtypes of HLN were seen at our center and showed trends almost similar to those seen in other Indian studies. Molecular/cytogenetic studies could not be performed on a significant number of cases owing to logistic reasons (unavailability of complete panels and also cost-related issues) and such cases could not be classified as per the WHO classification system.

Purpose The purpose of this study is to evaluate long-term clinical outcomes of women treated with accelerated partial breast irradiation (APBI) using multicatheter interstitial brachytherapy (MIB-APBI) with risk groups defined by Groupe Europeen de Curie-therapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO), American Society for Radiation Oncology (ASTRO), updated ASTRO, and American Brachytherapy Society (ABS) guidelines and to elucidate the most appropriate guideline that could differentiate outcomes among its risk groups. Methods and Materials Two hundred forty women underwent MIB-APBI during July 2000 to March 2013. Comparisons of long-term clinical outcomes (local control [LC], disease-free survival [DFS], cause-specific survival [CSS], and overall survival [OAS]) stratified by the risk groups proposed by the aforementioned patient selection guidelines were carried out on a prospectively maintained database. Results At a median follow-up of 114 months, 10-year LC, DFS, and OAS were 90%, 81%, and 83.5%, respectively, for the entire group. There was no statistically significant difference in the LC rates for risk groups by ESTRO, ASTRO, updated ASTRO and ABS guidelines. The 10-year DFS and OAS for GEC-ESTRO low-, intermediate-, and high-risk group was 75%, 88%, and 60% (p = 0.02) and 86%, 93%, and 62% (p = 0.001), respectively. Ten-year DFS and OAS in the ABS 2018–acceptable and ABS 2018–unacceptable group were 78% and 67% (p = 0.01) and 88% and 69% (p = 0.001), respectively. No significant difference in any of the outcomes was observed with risk groups suggested by ASTRO or updated ASTRO consensus guidelines. Conclusions None of the current patient selection guidelines for APBI could differentiate LC (main APBI endpoint) among its risk groups, whereas GEC-ESTRO and ABS guideline could differentiate DFS and OAS.

BACKGROUND Classical Hodgkin lymphoma (cHL) has excellent survival rates, but late effects are an issue and dictate modern approaches. We analyzed the clinical profile and outcome of cHL treated on a risk-adapted approach aimed at reducing late effects while improving historical outcomes at our center. PROCEDURE Children (≤15 years) consecutively treated for cHL from January 2013 through December 2016 were retrospectively analyzed. 18 FDG-PET-CT-based staging and response assessment was done after two cycles for early response (ERA) and end of chemotherapy (late-response assessment [LRA]) if not in complete response (CR; Deauville

Immune dysfunction is critical in pathogenesis of cutaneous T-cell lymphoma (CTCL). Few studies have reported abnormal cytokine profile and dysregulated T-cell functions during the onset and progression of certain types of lymphoma. However, the presence of IL9-producing Th9 cells and their role in tumor cell metabolism and survival remain unexplored. With this clinical study, we performed multidimensional blood endotyping of CTCL patients before and after standard photo/chemotherapy and revealed distinct immune hallmarks of the disease. Importantly, there was a higher frequency of “skin homing” Th9 cells in CTCL patients with early (T1 and T2) and advanced-stage disease (T3 and T4). However, advanced-stage CTCL patients had severely impaired frequency of skin-homing Th1 and Th17 cells, indicating attenuated immunity. Treatment of CTCL patients with standard photo/chemotherapy decreased the skin-homing Th9 cells and increased the Th1 and Th17 cells. Interestingly, T cells of CTCL patients express IL9 receptor (IL9R), and there was negligible IL9R expression on T cells of healthy donors. Mechanistically, IL9/IL9R interaction on CD3+ T cells of CTCL patients and Jurkat cells reduced oxidative stress, lactic acidosis, and apoptosis and ultimately increased their survival. In conclusion, coexpression of IL9 and IL9R on T cells in CTCL patients indicates the autocrine-positive feedback loop of Th9 axis in promoting the survival of malignant T cells by reducing the oxidative stress. Implications: The critical role of Th9 axis in CTCL pathogenesis indicates that strategies targeting Th9 cells might harbor significant potential in developing robust CTCL therapy.

PURPOSE A complete axillary lymph node (ALN) dissection is therapeutic in node-positive breast cancer. Presently, there is no international consensus regarding anatomic levels to be addressed in complete axillary dissection. We assessed the burden of disease in level III axilla. MATERIALS AND METHODS A prospectively maintained database was assessed for 1,591 consecutive patients with nonmetastatic breast cancer registered at Tata Memorial Center, Mumbai, between January 2009 and December 2014. RESULTS A median of four (zero to 20) level III ALNs were dissected and a median of two (one to 17) nodes were positive. A total of 27.3% (434 of 1,591) patients had level III ALN metastasis, and 4.7% of patients had positive interpectoral nodes. Some 53.2% of patients had level III metastases in the presence of four or more positive level I and II ALNs. A total of 9.4% of patients had level III involvement when one to three ALNs were positive in level I and II ( P < .001). Some 53.2% of patients had level III metastases in the presence of four or more positive level I and II ALNs. On logistic regression analysis, four or more positive ALNs in level I or II ( P < .001), inner/central quadrant tumor location ( P = .013), and perinodal extension ( P < .001) were associated with level III ALN involvement. At a median follow-up of 36 months, the disease-free survival was significantly worse for level III ALN metastases on univariate analysis ( P < .001). On multivariate Cox regression analysis, histologic grade ( P = .006), four or more positive ALNs ( P < .001), hormone receptor status ( P < .001), and tumor size ( P = .037) were independent prognostic factors for disease-free survival. CONCLUSION The axillary nodal burden is high in patients with breast cancer in developing countries like India. One of two women with four or more positive level I and II ALNs may have residual disease in level III if it is not cleared during surgery. Intraoperative interpectoral space clearance should be considered in the presence of either palpable interpectoral lymph nodes or multiple positive ALNs.

Introduction: Systemic anaplastic large cell lymphoma (ALCL) accounts for 5%–10% of adult non Hodgkin's lymphoma (NHL) and 10%–30% of childhood NHL. Owing to significant differences in survival and gene expression profile, current WHO classifies ALCL into two distinct entities as anaplastic lymphoma receptor tyrosine kinase (ALK) positive and ALK negative ALCL with ALK expression by tumour as a good prognostic indicator. However, in our institute which is a cancer referral institute, our preliminary experience was that even ALK positive tumours did not fare well as compared to ALK- negative ALCL. So, the current study aims at exploring more clinical and pathological factors impacting survival in ALCL patients. Objective: To study clinical and pathological prognostic factors in cases of ALCL. Methods: 102 cases of ALCL were retrieved from pathology database. Pathological features and clinical features of these cases were recorded and factors found to impact overall survival (OAS) and disease-free survival (DFS) curves were identified based on univariate and multivariate analysis. Results: ALK 1 expression was seen in 71/102 (69.6%) cases and was not found to impact OAS or DFS. The 2 year OAS rate for ALK positive patients was 63.5% and DFS rate was 54.4%, while for ALK negative patients, the OAS was 60.5% and DFS was 43.5%. The Ann Arbor stage, performance status, international prognostic index, histological subtype, and the degree of the background inflammatory infiltrate were found to impact the OAS significantly. Increased reactive inflammatory component also negatively impacted DFS. In the multivariate analysis, only the histologic type emerged as significant for OAS. Conclusion: Though ALK plays a role in prognostication of systemic ALCL, advanced stage disease and an inflammatory milieu may modulate the final outcome. We report a study of clinical and pathologic prognostic features in 102 cases of anaplastic large cell lymphoma (ALCL) from a cancer referral institute in India. Anaplastic lymphoma receptor tyrosine kinase (ALK-1) expression was seen in 71/102 (69.6%) cases and was not found to impact overall survival (OAS) or disease-free survival (DFS). The 2-year OAS rate for ALK-positive patients was 63.5% and DFS rate was 54.4%, while for ALK-negative patients, the OAS was 60.5% and DFS was 43.5%. The Ann Arbor stage, performance status, international prognostic index, histological subtype, and the degree of the background inflammatory infiltrate were found to impact the OAS significantly. Increased reactive inflammatory component also negatively impacted DFS. In the multivariate analysis, only the histologic type emerged as significant for OAS. Thus, though ALK plays a role in prognostication of systemic ALCL, advanced stage disease and an inflammatory milieu may modulate the final outcome.

This is a largest series of 5 cases of lymphoepithelioma-like carcinoma (LEC) of the breast attempting to look at the expression of basal cytokeratins (CKs), human papillomavirus, and Epstein-Barr virus-encoded RNAs in these tumors. Five cases were selected after stringent evaluation of all breast carcinomas showing dense lymphoid infiltration. Histologically, all these tumors showed the typical histology except 1 tumor that showed an unusual granulomatous response. All tumors were negative for estrogen and progesterone receptors and HER2 (triple negative). Three tumors expressed CK5/6 and high-molecular-weight CK, whereas only the case with nodal metastasis expressed CK14. Analysis for in situ hybridization for Epstein-Barr virus-encoded RNAs and human papillomavirus DNA on paraffin-processed tissues was negative in all tumors. All of these patients received adjuvant therapy. One patient with tumor expressing basal marker, CK5/6, had contralateral breast malignancy after a duration of 53 months of treatment completion. The rest were disease free with the follow-up period in the range of 6 to 105 months. The lymphoepithelioma-like carcinoma of breast expressed basal CK profile that is more CK5/6 positive than CK14. Analysis of basal markers within these tumors may help in refining the definition of these tumors and in classifying them into prognostically relevant groups.

This study attempted to review the impact of extent of squamous differentiation in 56 infiltrating duct carcinomas (IDC) with squamous differentiation (metaplastic squamous carcinomas [MSC]). Tumors showing 100% squamous elements were labeled as primary squamous carcinomas (PSC; n = 28) and compared with 28 MSC showing lesser squamous components. A clinicopathological comparison revealed that lymphovascular emboli were never seen in any PSC but were noted in 7/28 of other MSC, while perineural invasion was seen only in PSC and not in MSC. Nodal metastasis was significantly more in other MSC as opposed to PSC. Most MSC presented with 2- to 5-cm sized tumors while PSC were 5 to 10 cm in size. PSC showed cystic change while MSC did not. Disease free survival (DFS) for MSC versus PSC was 64% versus 39.8%, while overall survival (OAS) was 72.7% in MSC versus 66.7% in PSC. Tumor stage affected DFS in MSC while none of the factors affected DFS/OAS in PSC. The extent of squamous differentiation affected DFS with best behavior for metaplastic carcinomas showing 90% squamous component ( P = .024). PSC of breast is an aggressive disease and show distinct clinicopathological features from other MSC, and though the current definition of MSC does not advocate quantifying the squamous element, clearly this affects prognosis.

Aim. To identify aggressively behaving classical Hodgkin lymphoma (CHL) of mediastinum and primary mediastinal B-cell lymphoma (PMBCL) and to classify them as mediastinal gray zone lymphoma(MGZL) and to define a minimum immunopanel for the diagnosis of MGZL. Materials and Methods. Ninety-two mediastinal B-cell lymphomas were reviewed with a wide immunopanel and were classified as CHL, PMBCL, or MGZL. CHL with an expression of 3 or 4 transcription factors performed worse, and hence the CHL with ≥3 transcription factors were classified as MGZL-CHL. In PMBCL, the cases with a weak or negative CD20 and positive CD15 as well as those cases showing cyclin E positivity with a negative or focal LCA and any one of the transcription factors were classified as MGZL-PMBCL. Results. The MGZL cases expanded from 9 to 28 cases after using an extended immunopanel. CHL and PMBCL had a disease-free survival rate of 86.8% and 69.2% and an overall survival rate of 97.4% and 80.8%, respectively. MGZL-CHL and MGZL-PMBCL had a disease-free survival rate of 33% and 40% and an overall survival rate of 66.7% and 60%, respectively. Conclusion. Thus, the MGZL may be a wider category than we think and hence the use of a wide immunopanel is recommended to identify the aggressively behaving mediastinal B-cell lymphomas.

Activation of STAT3 via Y705-phosphorylation is well documented across multiple cancer types and thus forms the basis of canonical pathway to judge STAT3 activation. Recently, important roles of two other post translational modification (PTM) sites, i.e. S727-phosphorylation and K685-acetylation, leading to STAT3 activation are reported. However, their critical mode of function in controlling STAT3 dimerization and signaling, independent of canonical activation remains elusive. Therefore, to understand the functional relevance of each STAT3 PTMs in breast cancer (BC), cell models are developed by stable overexpression of PTM-site specific point mutants, i.e. Y705F, S727A or K685R, in a 3'UTR-STAT3 knockdown BC cell background. Results using this model system reveal novel findings showing that phosphorylation at S727 can lead to STAT3 activation independent of phosphoY705. We also demonstrate that loss of pS727 or K685ac significantly affects functional phenotypes such as cell survival and proliferation as well as downstream transcriptional activity (Twist 1, Socs3, c-Myc, Bcl-1 and Mcl-1) of STAT3. Thereafter, by utilizing a BRET biosensor for measuring STAT3 phosphorylation in live cells, a crucial role of pS727 in dictating STAT3 activation and homodimerization formation is uncovered. Further by performing retrospective IHC analysis of total and phospho-forms of STAT3 in a cohort of 76 triple negative breast cancer (TNBC) patient samples, a significant dominant expression of phosphoS727 over phosphoY705 PTM (p 0.001) is found in STAT3 positive cases. We also focus on validating known STAT3 inhibitor molecules for their action against both pY705 and pS727 activation. This study for the first time demonstrates that an anti-helminth drug compound, Niclosamide, is capable of inactivating both phospho-PTM sites on STAT3 and exhibits excellent anticancer efficacy in preclinical TNBC tumour model.

Introduction: There is paucity of data from India about the outcomes of patients with various hematological malignancies. Since its formation in 2009, the adult hematolymphoid disease management group of the Tata Memorial Centre is dedicated to the treatment of hematological malignancies alone. In this report, we present the outcomes of patients treated at our centre over a 5 year period for various haematological malignancies in both transplant and non-transplant setting. Methods: This is a retrospective analysis of all patients registered in adult hematolymphoid disease management group between 1st January 2010 to 31st December 2014. Patients not treated at our centre were excluded from survival analysis. The cut off date for survival analysis was 31st January 2016. Results: Overall, 1869, 3633 and 544 patients with acute leukemias, various lymphomas and myeloma respectively were registered at our centre from 1st January 2010 to 31st December 2014. Of these, 1178 (63%), 3091 (85%) and 454 (83%) respectively received treatment at our centre. The cumulative probability of 5 year overall survival for patients with acute leukemias, Hodgkin's lymphoma, non-Hodgkin lymphoma and myeloma treated at our centre is 40%, 85%, 78% and 40% respectively. Four hundred and fifteen stem cell transplants were done between 14th November 2007 to 31st December 2014 with 46% being allogeneic and 54% being autologous. The 5 year overall survival of patients with allogenic and autologous transplant was 52% and 63% respectively. Conclusions: This is the largest single centre data on outcomes of various haematological malignancies from India. This real world data identifies areas which need further attention to improve outcomes.

INTRODUCTION: The Pediatric Hematolymphoid Disease Management Group (PHL-DMG) at a tertiary cancer care hospital developed extensive patient support programs to improve retention and outcomes while focusing on protocols adapted to meet patient needs. An audit of measures and outcomes was done for a 7-year period from January 2010 to December 2016. MATERIALS AND METHODS: DMG protocols and patient support activities over the study period were documented and audited. Data was retrieved from internal databases and records. Measures taken and their impact were assessed by descriptive analytical tools. Survival outcomes were calculated using Kaplan–Meier method on SPSS v. 24™ software. RESULTS: Holistic patient support measures were undertaken through a charitable foundation entirely under pediatric oncology. Activities included infrastructure growth, socioeconomic support, provision of accommodation, nutrition, education, and multiple blood component donation drives. Patient registrations increased from 502 in 2009 to 874 in 2016, with the steepest rise in acute lymphoblastic leukemia (ALL) – 330 (2009) to 547 (2016). Treatment refusal and abandonment rates decreased from 32% to 3.4% over the same period, and male to female ratio decreased from 2.56 to 2.28:1. Early mortality in acute myeloid leukemia (AML) fell within 2 years from 26.7% in 2009 to 7%. Five-year overall survival (OS) was 69.5% for all patients registered in 2010, whereas disease-specific 5-year OS was ALL 67.1%, AML 49.3%, chronic myeloid leukemia 100%, Hodgkin lymphoma 90.4%, and non-Hodgkin lymphoma 74.2%. CONCLUSIONS: Holistic patient support-specific activities and adapted protocols made a measurable impact on patient outcomes. High survival outcomes of patients have been achieved despite relatively few receiving salvage therapies or stem cell transplant.

Rearrangements involving interferon regulatory factor 4 (IRF4) gene has been recently described in a subtype of diffuse large B-cell lymphoma (DLBCL). They occur in a typical clinical setting of a pediatric age group, predominantly with tonsillar mass, usually as a low-stage disease and with good response to chemotherapy. Histomorphologically, they show nodular/follicular architecture with diffuse strong immunopositivity for multiple myeloma oncogene 1. Here, the authors describe one such unusual case of large B-cell lymphoma with IRF4 gene rearrangement in a young child with the unusual location of inguinal region and detailed pathological (histological, immunohistochemical, and molecular) findings.

There is a global mandate even in countries with low resources to improve the accuracy of testing biomarkers in breast cancer viz. oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2neu) given their critical impact in the management of patients. The steps taken include compulsory participation in an external quality assurance (EQA) programme, centralized testing, and regular performance audits for laboratories. This review addresses the status of ER/PR and HER2neu testing in India and possible reasons for the delay in development of guidelines and mandate for testing in the country. The chief cause of erroneous ER and PR testing in India continues to be easily correctable issues such as fixation and antigen retrieval, while for HER2neu testing, it is the use of low-cost non-validated antibodies and interpretative errors. These deficiencies can however, be rectified by (i) distributing the accountability and responsibility to surgeons and oncologist, (ii) certification of centres for testing in oncology, and (iii) initiation of a national EQA system (EQAS) programme that will help with economical solutions and identifying the centres of excellence and instill a system for reprimand of poorly performing laboratories.

Background: Hodgkin's lymphoma displays distinct epidemiological attributes in Asian population thus making it relevant to study whether there are any differences in treatment outcomes too when treated with current standard of care. Aim: To evaluate the treatment outcomes of de-novo advanced stage HL in adults. Materials and Methods: This retrospective study included de-novo advanced stage HL patients (≥15 years) registered at our center from January 2004 to December 2007. Treatment outcomes were measured in terms of response rates, overall survival (OS) and progression-free survival (PFS). Overall and PFS were calculated with Kaplan-Meier methodology and Cox-proportional hazards model was used for multivariate analysis to identify prognostic factors. Results: There were 125 patients (males 77%) who received minimum one cycle of chemotherapy with median age of 32 years (Range 15-65 years). Stage IV disease was seen in (46 patients) 37%; 75% (94 patients) patients had B symptoms. International prognostic score (IPS) ≤4 was seen in 95/112 (85%) patients. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy was given to 94%. Radiation to residual/bulky sites was given to 36% (45 patients). Response data was available for 112 patients; complete response in 76%; partial response in 10 % and progressive disease in 3 patients. Nineteen deaths (progressive disease-7, toxicity-8, unrelated cause-4) were observed. At median follow-up of 28 months, estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate analysis, IPS and response to treatment were significant factors for both OS and PFS. Conclusions: The treatment outcomes in this study are comparable with the published literature with limited follow-up data.

Purpose To evaluate the impact of timing of adjuvant chemotherapy on wound healing and cosmetic outcome in women treated with accelerated partial breast irradiation (APBI). Methods and Materials Between August 2000 to December 2011, 224 women were treated with APBI using multicatheter interstitial high-dose-rate brachytherapy. Patients were treated to a dose of 34 Gy/10#/5–7 days with bid regimen. Systemic chemotherapy was administered as per the standard guidelines. Results Multicatheter interstitial brachytherapy technique was open cavity in 136 (60%) and closed cavity in 88 (40%). Adjuvant chemotherapy was given in 117 (52%). Wound complications (WCs) were observed in 24 patients (11%), which included wound infections (WIs) in 20 and wound dehiscence in 14. The median gap between chemotherapy and APBI was 13 days in women who developed WCs, 20 days for prechemo, and 32 days for postchemo APBI in its absence. On multivariate analysis, gap between APBI and chemotherapy of ≤3 weeks was the only significant factor (p = 0.03) affecting WCs. Acute WI (p = 0.01) and two-dimensional planning (p = 0.04) had significant impact on cosmesis resulting in fair to poor cosmetic outcome. Conclusions Gap of ≤3 weeks between APBI and chemotherapy resulted in increased WCs. WI and two-dimensional planning resulted in poorer cosmetic outcome. We recommend gap of at least 3 weeks for optimal outcome.

Background & objectives: Multiple myeloma (MM) is a plasma cell malignancy characterized by cytogenetic heterogeneity. In comparison with conventional karyotyping, fluorescence in situ hybridization (FISH) can efficiently detect various genetic changes in non-cycling plasma cells in 50-90 per cent of MM cases. The present study was undertaken in MM patients to evaluate the frequency and clinico-pathological significance of various cytogenetic abnormalities in the Indian population. Methods: Interphase FISH was applied on purified plasma cells of 475 patients with MM using specific probes. Interphase FISH for 1q gain/1q amplification was performed on a separate group of 250 newly diagnosed MM patients. Results: Low frequency of Δ13 [-13/del(13q)] (32%) and t(11;14) (5%) was observed in our 475 patients probably due to ethnic diversity. Clustering of Δ13, del(17) (p13.1) and IgH translocations in non-hyperdiploidy confirmed prognostic significance of ploidy in MM. t(4;14) and del(17) (p13.1) were high-risk groups due to correlation with high serum β2-microglobulin, increased plasma cells and advanced disease. Hyperdiploidy and t(14;16) were associated with higher age group. In a separate group of 250 patients, 1q amplification [amp(1q)] in combination with Δ13 and/or del(17p) with t(4;14) revealed association with adverse clinico-laboratory features, which confirmed progressive role of amp(1q) with adverse prognostic impact. Amp(1q) was clustered at 1q21 and 1q25 loci. Interpretation & conclusions: Based on our findings, it appears that comprehensive analysis of various cytogenetic aberrations by interphase FISH is a powerful strategy being adapted for risk stratification of MM.

Metastases to breast are much rarer than primary breast tumors. We now present a case of 45-year-old female, who presented with an isolated breast mass. A positron emission tomography-computed tomography (PET-CT) done revealed hypermetabolic right breast nodules, soft tissue deposits, and multiple nodal involvement. The biopsy from the breast and axillary lymph node showed dense lymphoid infiltrate and was interpreted initially as granulomatous inflammation. However, the lumps were hard and suspicious for primary breast cancer, so an immunohistochemistry for cytokeratin was performed which highlighted the epithelial cell clusters masked within the inflammatory infiltrate and the diagnosis of undifferentiated carcinoma, lymphoepithelioma-like was made. After the diagnosis was made, it was realized that the patient had been treated earlier for a nasopharyngeal carcinoma (NPC). The in situ hybridization (ISH) test for Epstein–Barr virus-encoded RNA ISH was positive in the tumor cells, and hence, a diagnosis of metastatic NPC was finally made. The patient subsequently developed extensive nodal, skeletal, and soft tissue metastatic disease but was alive till September 2015. Although extremely rare, metastatic NPC can occur in the breast and the above case highlights that it mimics an inflammatory lesion. This case highlights the importance of the multidisciplinary approach for appropriate tumor diagnosis and patient management.

Context: HER2/neu testing in breast cancer is a mandate due to availability of trastuzumab, a monoclonal antibody targeted against this biomarker. Dual-color dual-hapten in situ hybridization (D-DISH) is a new test for assessment of HER2/neu gene overexpression on light microscopy. Aims: This was a validation study for D-DISH in our laboratory and was conducted to study the concordance between fluorescence in situ hybridization (FISH) and D-DISH for HER2/neu testing in breast cancer. Materials and Methods: In all, 150 cases of invasive breast carcinoma requested for FISH analysis were selected. Immunohistochemistry by Ventana PATHWAY anti-HER2/neu (4B5) antibody, FISH by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe, and D-DISH using the Ventana INFORM HER2 Dual ISH DNA Probe Cocktail Assay was carried out. Statistical Analysis: Cohen's kappa coefficient was used to calculate concordance between FISH and D-DISH assays. The ratios and average number of signals were compared with Lin's concordance correlation coefficient. Results: About 93.1% of the cases showed concordance between FISH and D-DISH results. Cohen's kappa correlation coefficient was 0.836, indicating almost perfect level of agreement. Lin's concordance correlation coefficient (ρc) showed moderate strength of agreement for HER2/chromosome 17 ratios between FISH and D-DISH assays (ρc 0.9452). As per the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 updated guidelines, four of the cases that were nonamplified on FISH showed low-level amplification on D-DISH due to counting errors caused by faint signals or background dust. Genomic heterogeneity and larger red chromosome 17 signals on D-DISH led to discordance of the six cases amplified by FISH. D-DISH failure rate was 3.33%. Conclusion: Overall, D-DISH showed good concordance with FISH but needs expertise for reporting.