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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.

The ACOSOG Z0011 study, heralded as a "practice changing" trial, suggested that women with T1-2 breast cancer with 1-2 SLN+, undergoing breast conservation therapy, need not be offered further ALND. However, whether these results are applicable to all women in the Indian setting, it remains debatable. A retrospective audit of all cN0 operated from 2013 to 2018 was conducted. We analyzed the percentage of additional LN positive (LN+) in the ALND group and compared it to the ACOZOG Z11 trial. Of the 2350 cN0 with EBC who underwent LAS, 687 (29%) had positive lymph nodes on final histopathology. Five hundred ninety-seven (86.9%) patients had 1-2 LN+, 40 (5.8%) patients had 3 LN+, and 50 (7.3%) had 4 or more nodes positive. Demographic features in the ACOSOG Z11 are different from those in our study, looking at ACOZOG Z11 versus our cohort-median pT 1.7 cm versus 3 cm, 45% micrometastasis versus 99.16% macrometastasis, and 28-30% grade 3 tumors versus 73.7%. In our cohort 31.82% of the 1-2 LN positive had additional LN+ on ALND. Keeping in mind the difference in clinicopathological features between our cohort and that of ACOZOG Z0011 and that 31.82% of women had additional LN+ on ALND, it may not be appropriate to apply the results of the ACOSOG Z0011 trial directly to our general population. Possibly, only a select subset of patients who match the trial population of the ACOSOG Z11 could be offered observation of the axilla and validated nomograms can be used to identify high-risk patients.

Background: Ductal carcinoma in situ (DCIS) identified by screening mammography accounts for 20% of breast cancer diagnoses, and microinvasion (DCIS-M) is found in 5%-10%. There are no defined treatment guidelines for palpable DCIS or DCIS-M. The role of screening mammography is now being questioned across the world and in the developing world with no national screening programs, women with DCIS present with a palpable lump in the breast. We conducted a retrospective audit of women with DCIS treated at our institution to classify palpable DCIS and DCIS-M as distinct clinical stages and emphasize the need for a change in management of ‘palpable DCIS’ Methods: Annually we register approximately 1700 new cases of early breast cancer of which DCIS and DCIS-M constitutes less than 1%. Between 2005-2016 we registered 784 cases of with DCIS, DCIS-M and early invasive cancer with extensive intraductal component (EIC) at our centre. A retrospective analysis of these cases was performed. Results: Of the 784 patients case records reviewed, 113 (14.4%) had Tis, 87 (11.1% of all early cases and 43.5% of DCIS) had T1mic, the rest had invasive cancer with EIC, of which 46 (5.9%) wereT1a, 28(3.6%) were T1b, 146 (18.6%) were T1c and 364 (46.4%) wereT2. The median age at presentation was 48 years, median clinical tumour size was 3cm; 740 (94.4%) presented with palpable breast lumps.At a median follow up of 86 months , the disease free survival was 95.6% for Tis, 96.6% T1mic, 90.5% T1 and 82.7% T2 (p=0.00). On follow up distant recurrences were noted in 5(4.4%) patients with Tis, 3(3.4%) with T1mic, 21(9.5%) with T1 and 63(17.3%) with T2, (p=0.00). Limited use of adjuvant chemotherapy in Tis and T1mic may have contributed to the high distant recurrences in that group. Also palpable Tis,T1mic and T1a had higher percentage of HR negative compared to those with larger invasive tumours. Conclusions: DCIS presenting in palpable lesions poses a clinical dilemma for the use of adjuvant therapy. In our cohort 43.5% of the palpable DCIS showed evidence of microinvasion with high risk of distant recurrence compared to screen detected DCIS. We thus need to reconsider grossing techniques to accurately identify foci of invasion, redefine DCIS-M based on number and size of foci of invasion and explore the possible role of adjuvant chemotherapy in treating large palpable DCIS. ResultsTis (N%)T1mic (N%)T1a (N%)T1b (N%)T1c (N%)T2 (N%)cT >2 cm63 (55.8)68 (78.2)28 (60.9)6 (21.4)1 (0.7)363 (99.7)Palpable lump85 (75.2)81 (93.1)39 (83)28 (100)144 (98.6)363 (99.7)Nipple discharge26 (23)6 (6.8)7 (14.9)0 (0)2 (1.3)1 (0.3)Hormone receptor positive (HR+ve)60 (53.1)18 (20.7)18 (38.3)15 (53.6)92 (63)218 (60.6)HER2neu +ve31 (27.4)41 (47.1)13 (27.7)8 (28.6)27 (18.5)93 (25)Axilla +ve6 (5.3)9 (10.3)9 (19.1)9 (32.1)50 (34.2)184 (50.7) Citation Format: Karishma Kirti, Nita Nair, Tanuja Shet, Rohini Hawaldar, Vani Parmar, Seema Gulia, Shalaka Joshi, Sridevi Murali, Vaibhav Vanmali, Bipin Bandre, Sudeep Gupta, Rajendra Badwe. Reconsidering the management of palpable DCIS - A single institution audit [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-23.

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.

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.

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.

Introduction Rosai-Dorfman disease (RDD) is a rare, idiopathic, proliferative disorder of histiocytes usually involving head-neck lymph nodes. It can also involve extra nodal sites like skin, nasal sinuses, and soft tissue. It rarely affects the breast. Case presentation We present three unusual case scenarios of breast RDD. One presented with breast lump, clinico-radiologically mimicking early breast cancer. The second case was thought to be de-novo metastatic breast cancer, but was found to have disseminated RDD of breast, lymph nodes and bones. The third patient was that of cervical lymphadenopathy in a breast cancer survivor masquerading as recurrence. In all 3, histopathology showing emperipolesis and immunohistochemical staining with S100 clinched the diagnosis. Discussion The diagnosis of RDD is made by histopathology. The classic histological picture consists of a lymphoid rich associated infiltrate, atypical nuclei of the histiocytes and lack of fat necrosis or acute inflammatory cells. These histiocytes typically stain positive with S100 and CD168 on immunohistochemistry. Hence, an excision biopsy is often necessary, and mostly the only treatment needed. However, if the disease is disseminated or has massive lymphadenopathy, a course of oral steroids or chemotherapy is indicated. Conclusion RDD of the breast usually has an indolent, benign, and non-aggressive course that requires minimum treatment. A high index of suspicion and accurate histopathological diagnosis is utmost important for proper management.

Epithelioid Hemangioendothelioma (EHE) is a vascular tumour with intermediate malignant potential which rarely occurs in the breast. We report a unique case of EHE of breast that presented with nodal metastases along with the review of literature. This case was initially misdiagnosed on fine needle aspiration cytology (FNAC) as breast carcinoma; however, histopathology revealed the characteristic short strands and single cell infiltrating pattern by epithelioid cells embedded in a myxohyaline matrix. The typical intracytoplasmic vacuoles with red blood cells were seen in occasional cell hinting at the vascular nature of tumor. Patchy foci of nuclear atypia, pleomorphism and frequent mitoses were seen. Although focal reactivity for AE1/AE3 initially did lead to a differential diagnosis of carcinoma, diffuse positivity for vascular differentiation markers like CD31, CD34 and FLI-1 clenched the diagnosis of EHE. The patient underwent modified radical mastectomy with axillary dissection with post-operative locoregional adjuvant radiation therapy. Till date, with a follow-up of 36 months patient is fine with no event. To conclude EHE can occur in breast and show nodal metastasis like breast carcinomas. However awareness of histologic features with typical immunohistochemistry (IHC) will assist the diagnosis. Inspite of nodal metastasis patient has an uneventful follow up indicating a non-aggressive behavior of this tumor.

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 (

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.

INTRODUCTION: Primary Mediastinal B cell lymphoma (PMBCL) is a biologically and clinically distinct subset of diffuse large B cell lymphoma. We analysed the outcomes of our cohort of PMBCL patients treated with Dose adjusted (DA)-R-EPOCH regimen. PATIENTS AND METHODS: This is a retrospective analysis of consecutive PMBCL patients who received chemotherapy consisting of DA-R-EPOCH with filgrastim support. Survival analysis was done using Kaplan–Meier method. All calculations were performed using SPSS version 20 for windows. RESULTS: A total of 43 consecutive suspected PMBCL patients were reviewed for this study, 6 patients were excluded as diagnosis of PMBCL could not be established. All patients except one (97.3%) received 6 cycles of R-DA-EPOCH regimen. Median age of the patients was 27 years (range 15–58). Bulky disease (> 7 cm) was present in 97% patients and 54% patients had extranodal disease. With a median follow up of 40 months, 3-year overall survival was 80.6% (95% CI: 74.0–87.2). The 3-year event free survival was 78.4% (95% CI: 71.6–85.2). There were 6 (16.2%) relapses, 1 (2.7%) primary progression and 7 (23%) deaths. Mediastinal radiotherapy was administered to 17 (45.9%) patients. All the deaths were due to disease progression. Grade III/IV toxicities were seen in 28 (75.7%) patients, febrile neutropenia being the most common one. CONCLUSIONS: DA-R-EPOCH regimen is an effective and tolerable regimen in PMBCL patients even with adverse features.

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.

Purpose The purpose of this study was to report clinical outcomes in patients treated with accelerated partial breast irradiation (APBI), stratified as per molecular subtype and American Society for Therapeutic Radiology and Oncology/Groupe Europeen de Curietherapie and European Society for Radiotherapy & Oncology (ASTRO/GEC-ESTRO) patient selection criteria in order to determine whether molecular subtype should be recommended as one of the selection criteria for APBI. Material and methods 157 early-stage breast cancers patients, treated with APBI using multi-catheter interstitial brachytherapy with ≥ 6 months follow-up were included. Molecular subtype was assigned based on estrogen/progesterone receptor (ER/PR), Her2neu and tumor grade. Patients were stratified into ASTRO and GEC-ESTRO risk groups, as per updated ASTRO consensus statement (CS) and GEC-ESTRO recommendation, respectively. The Kaplan-Meier method was used to calculate the time to event data of clinical outcomes. Results With a median follow-up of 35 months, local control (LC) and locoregional control (LRC) were not significantly different among the different molecular subtypes (p = 0.19, p = 0.41, respectively). None of the APBI guidelines predicted risk of local or locoregional recurrence. Re-analyzing the data by replacing ER status with molecular subtype in the ASTRO-CS did not show any significant difference in LC/LRC across the various categories. Her2neu subtype was associated with significantly lower disease-free survival, cause specific survival, and overall survival than the luminal subtypes. Conclusions None of the mentioned APBI guidelines predicted local or locoregional recurrence risk in our study population. Additional follow-up will be needed to recommend inclusion of molecular subtype (or at least HER2 receptor status) in the patient selection criteria for APBI.

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.

Introduction: Biomarkers predictive of response to mechanistic target of rapamycin (mTOR) inhibitor, everolimus, in endocrine receptor (ER)-positive metastatic breast cancer (MBC) are a work in progress. We evaluated the feasibility of directly measuring mTOR activity and phosphatase and tensin homolog (PTEN) expression and correlating their expression with response and survival. Materials and Methods: MBC patients who received everolimus with endocrine therapy (ET) after progression on an aromatase inhibitor and had adequate tissue preservation for estimation of mTOR activity and PTEN expression were selected for analysis from a prospectively maintained database. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method, and correlation between mTOR activity and PTEN expression with survival was done by log-rank test. Results: Thirteen ER-positive MBC patients were available for analysis. PTEN expression was lost in 11/13 (84.6%) patients and retained in 2/13 patients (15.4%). mTOR activity was absent in four patients (30.7%), weak in six patients (46.1%), and moderate in 3 patients (23.2%). Median PFS for the entire population was 2.5 months while median OS was not reached. Patients with an absent mTOR activity showed a longer PFS (5 vs. 1.5 vs. 2 months) than those with weak and moderate activity, respectively (P = 0.043). There was no correlation between loss of PTEN expression and PFS. Conclusions: Measurement of direct mTOR activity in patients with MBC receiving everolimus/ET combination appears feasible. Absent mTOR activity may predict for longer PFS with everolimus-ET combination and requires further study.

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

Background: The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR’s prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC, whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients’ prognosis. Methods: We evaluated the prognostic value of AR in resected primary tumors from TNBC patients from six international cohorts {US (n = 420), UK (n = 239), Norway (n = 104), Ireland (n = 222), Nigeria (n = 180), and India (n = 242); total n = 1407}. All TNBC samples were stained with the same anti-AR antibody using the same immunohistochemistry protocol, and samples with ≥1% of AR-positive nuclei were deemed AR-positive TNBCs. Results: AR status shows population-specific patterns of association with patients’ overall survival after controlling for age, grade, population, and chemotherapy. We found AR-positive status to be a marker of good prognosis in US and Nigerian cohorts, a marker of poor prognosis in Norway, Ireland and Indian cohorts, and neutral in UK cohort. Conclusion: AR status, on its own, is not a reliable prognostic marker. More research to investigate molecular subtype composition among the different cohorts is warranted.

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.

The Incidence of breast cancer has been steadily increasing in the last two decades, more so in urban areas of the sub-continent. Cancer ceters across the country have large numbers of patients being treated with multiple publications in this field. Inspite of paucity of prospective data and randomised clinical trials from India, there are large number of retrospective publications on various aspects of the disease including pathology, radiology, surgery, chemotherapy, radiation, palliative care and alternatitive treatment modalities. These published data provide an insight into the trends of breast cancer in the country and this comprehensive data review of Indian data will provide a basis for designing trials relevant to our population and planning health care.

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.

Background: African American (AA) triple-negative breast cancer (TNBC) patients experience worse clinical outcomes and exhibit 40% higher mortality rate than their European Americans (EAs) counterparts. There are currently no distinctions in inherent tumor biology between the ethnically distinct TNBC patients that serve as risk-predictive markers allowing new tailored treatments. Recently, androgen receptor (AR) has emerged as a new target for treating TNBC. However, the prognostic value of AR in TNBC remains controversial. To reconcile conflicting reports about the impact of AR loss on prognosis of TNBC and uncover the molecular pathways that may underlie the racial disparity in outcomes among AR-negative TNBCs, we determined the prognostic value of AR in diverse TNBC cohorts. Since loss of AR is associated with worse clinical outcome and African and AA women are more prone to aggressive disease course, we hypothesized that AR loss may underlie the global disparate burden in TNBC. Methods: We evaluated AR expression in well-annotated formalin-fixed, paraffin-embedded TNBC resection samples (n=1351) obtained from multiple hospitals from US, UK, Norway, Ireland, Nigeria and India. Samples with ≥1% nuclei staining positive for AR were deemed to be AR-positive. Associations between AR status, clinicopathologic variables and overall survival (OS) were evaluated. We performed gene set enrichment analysis for AR low and high group in AA and EA TNBCs. In vitro experiments were performed to examine whether AR loss increased the metastatic potential of TNBC cells. Results: We observed a significant difference in AR expression among EA and AA TNBCs (p=0.02) with AR loss associated with women of African ancestry (>90%, p14%) (HR=1.72; p=0.095) AA TNBC (n=98) when compared to EA TNBCs (n=80). Furthermore, AR status retained its significant prognostic value (HR=1.549, p=0.036) after controlling for age, grade, Ki67, race and chemotherapy status. Gene set enrichment analysis revealed that Wnt/β-catenin signaling was the top-enriched gene ontology in the AR-low TNBC subgroup. Moreover, β-catenin protein levels are higher in AA AR-low TNBCs compared with AA AR-high TNBCs (p Conclusion: Our study suggests a striking association of AR loss in TNBC with women of African ancestry. Our data offer compelling evidence that oncogenic Wnt/β-catenin signaling may link AR loss to more aggressive disease course and represent actionable biology in AA AR-negative TNBCs for whom no targeted treatments are currently on the horizon. This abstract is also being presented as Poster C102. Citation Format: Shristi Bhattarai, Sergey Klimov, Karuna Mittal, Uma Krishnamurthi, Xiaoxian Bill Li, Deepika Wali, Ceyda Sonmez Wetherilt, Ansa Riaz, Mohammad A. Aleskandarany, Andrew R. Green, Ian O. Ellis, Meenakshi Gupta, Lauren E. McCullough, Upender Manne, Johnson Agboola, Brett Baskovich, Emiel A. Janssen, Grace Callagy, Anurag Mehta, Tanuja Shet, Rakha A. Emad, Padmashree C.G. Rida, Ritu Aneja. Prognostic role of androgen receptor in triple-negative breast cancer: A global multi-institutional experience [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr PR18.

568 Background: Axillary lymph node metastasis is still the important prognostic factor in the management of breast cancer (BC). Where we have moved towards axillary conservation in clinically node negative (cN0), the debate on what after 1-2 sentinel lymph nodes positive (SLN+ve) still continues. The ideal situation would be wherein we can accurately predict which patient has a risk of additional non SLN+ve. Several nomograms have been developed to predict the risk of NonSLN+ve. But in view of the differences in tumor size and nodal burden between our patients and the western data, we conducted a study to validate some of these nomograms in our cohort of early BC with positive LN on Low axillary sampling (LAS). Methods: Clinico-pathological data was collected for operable BC (OBC) with cN0 who underwent upfront SLNB or AS. This was entered into the various nomograms and the probability of the Non SLN+ve was calculated. Nomograms with AUC of greater than 0.7 were pre-defined as considerable discrimination. Results: From 2013 to 2018, 2350 women with cN0 OBC underwent LAS. Of which, 670 (28.5%) had a positive node on LAS. Median pT size was 3 cm with 327 (48%), LVI +ve 152 (77%) ENI +ve, 525 (78.4%) Hormone receptor +ve and 485 (72.4%) grade 3 tumors. Of 670, 239 (35.7%) had a NonSLN+ve on completion axillary dissection. The AUC values for nomograms included,ie. MSKCC, MDAnderson, Tenon, Cambridge, Shanghai, Mayo clinic and Turkish were 0.769, 0.77, 0.55, 0.74, 0.65, 0.529, 0.563 respectively. Only three nomograms, MDA, MSKCC and Cambridge had an AUC of more than 0.7. However, they were associated with poor sensitivity and specificity and high FNR (Table) making them clinically unreliable for this cohort. Conclusions: All 7 nomograms were not validated in our study. The larger T size and higher nodal burden of our cohort may be responsible for the same. We thus need to develop an Indian nomogram to predict the risk of non SLN+ve for our patients. [Table: see text]

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.

Background The purpose of this study was to explore urinary Epstein–Barr virus (EBV)-DNA as a potential biomarker in patients with nasopharyngeal carcinoma (NPC). Methods EBV-DNA copies were estimated in plasma/urine of patients with NPC (n = 76) by real-time polymerase chain reaction (PCR) at baseline, during therapy, and at follow-up. Their correlation with EBV-RNA expression in tissues (n = 53) was used to assess sensitivity and specificity of plasma/urine EBV-DNA. Correlation of urine and plasma EBV-DNA with each other and with radiological response was evaluated. Results This study demonstrated that urine EBV-DNA has high sensitivity (96%) at diagnosis and it correlates well with plasma EBV-DNA at baseline and after neoadjuvant chemotherapy. The EBV-DNA copies reduced significantly with therapy (plasma: p < .001; urine: p = .011). Patients with low EBV-DNA copies demonstrated improved survival (plasma: p = .023; urine: p = .083). Conclusion Plasma EBV-DNA is a good prognostic marker, whereas further study on a larger cohort may help in developing urine EBV-DNA as a surrogate prognostic marker for patients with NPC. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

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.

Castleman's disease (CD) is a relatively singular disorder. Usually presenting as a mediastinal mass, peri pancreatic localization of CD is even rarer. Diagnosis is seldom established pre-operatively. We report two such cases of CD in which peri pancreatic region was involved and were diagnosed on biopsy, hence avoiding complex and high risk surgery.

Background Brain metastases (BM) is a commonly encountered clinical scenario in patients with HER2 positive breast cancer (BC). We report here the clinical profile and outcome of patients with HER2 positive breast cancer with brain metastasis (BCBM) who were treated with HER2 targeted therapy at a single institution. Methods Clinical and outcome data of patients with HER2 positive BCBM treated with HER2 targeted agents were retrospectively collected. Efficacy variables were progression-free survival (PFS, time from diagnosis of BM to first progression or death due to any cause, whichever was earlier) and overall survival (OS). Results Between 2013 and 2017, 102 HER2 positive BCBM patients with median age 52 (IQR 45-57) years were treated with HER2 targeted therapy. Of these, 40 (39.2%) had ER positive disease, 98 (96.1%) were symptomatic at diagnosis of BM, 69 (67.6%) had received ≥2 lines of chemotherapy before BM, 22 (25.3%) had solitary brain lesion, 22 (25.3%) had 2-5 lesions and 43 (49.4%) had > 5 lesions. After BM diagnosis, whole brain radiotherapy (WBRT) was administered in 93 (91.2%) patients, stereotactic radiosurgery (SRS) in 4 (4.0%), WBRT and SRS in 4 (4%), and 9 (8.9%) patients underwent surgical resection of BM. The first HER2 targeted therapy after BM diagnosis was lapatinib in 70 (68.6%), trastuzumab in 19 (18.6%), lapatinib and trastuzumab in 3 (2.9%), trastuzumab emtansine in 4 (3.9%) and intrathecal trastuzumab in 5 (4.9%), patients. After diagnosis of BM, 17 (16.7%) patients received ≥3 lines of therapy. At a median follow-up of 13.5 months, there were 91 PFS events and 80 deaths. The median PFS after BM was 8 [95% confidence interval (CI), 6.2-9.8] months and median OS was 14 (95%CI, 10.8-17.2) months with a 2-year OS of 25% (95% CI, 16.7-34.4%). Median PFS in patients who received lapatinib-capecitabine regimen (n = 62) was 9.0 (95%CI, 7.3-10.7) months. Conclusions The median OS in patients with HER2 positive BCBM, treated with HER2 targeted therapy, is good and exceeds that reported in metastatic triple negative breast cancer. The difference between median PFS and OS suggests that continued treatment after first or subsequent progression may be therapeutically beneficial in some patients. Legal entity responsible for the study Sudeep Gupta. Funding Has not received any funding. Disclosure J. Bajpai: Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Samsung Bioepis; Research grant / Funding (institution): Sun Pharma. S. Gupta: Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Johnson & Johnson; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Celltrion; Advisory / Consultancy, Research grant / Funding (institution): Oncosten; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Intas; Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Biocon; Advisory / Consultancy: Dr. Reddy’s Laboratories; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Core Diagnostics. All other authors have declared no conflicts of interest.

Introduction There is no safe method of avoiding complete axillary lymph node dissection in women with breast cancer after neo-adjuvant chemotherapy. sentinel node biopsy (SNB) has had prohibitively high false negative rate. We tested low axillary sampling (LAS) and SNB performed in same patient to predict axillary lymph node status in clinically node negative women undergoing breast conservation or modified radical mastectomy after neo-adjuvant chemotherapy. Methodology Post neo-adjuvant chemotherapy 751 women who had no palpable axillary lymph node underwent LAS (all lymph nodes below intercosto-brachial nerve). Of these 751 women, 730 also underwent SNB by dual technique after injection of blue dye as well as radio-isotope. SN was identified within and outside axillary sampling specimen. SN as well as LAS specimens were distinctly examined for nodal metastasis. The rest of the axillary dissection was completed in all patients. Post NACT 292/751(38.9%) had residual positive lymph nodes on pathology. The identification rate, false negative rate (FNR), and negative predictive value (NPV) of SNB and LAS were compared for predicting negative axillary lymph node status. Results The median clinical tumor size was 5cm (1-15cm) and 533(71%) patients were N1 or N2 at presentation. The SNB identification rate was 87.1% (636 of 730), with a median of 5 nodes and node positive in 238 of 636 (37.4%). LAS identification rate was 98% (736 of 751), with a median of 7 nodes and node positive in 292 of 736 (39.6%). In all but one case, the SN was found within the LAS specimen. The FNR of SNB (blue, hot and adjacent palpable nodes) was 19.7% (47 of 238, one sided 95% upper CI 24.0) compared to LAS with FNR of 9.9% (29 of 292, one-sided 95% upper CI 12.8) (p Conclusions LAS is superior to SNB in identification rate, FNR and NPV in predicting node negative axilla post-neoadjuvant chemotherapy. LAS can be safely used to predict negative axilla with less than 10% chance of leaving residual disease. Citation Format: Parmar V, Nair NS, Vanamali V, Hawaldar RW, Siddique S, Shet T, Desai SB, Rangarajan V, Patil A, Gupta S, Badwe RA. Sentinel node biopsy (SNB) vs Low axillary sampling (LAS) in predicting nodal status of post-chemotherapy axilla in women with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-03.