Breast Implant-associated Anaplastic Large Cell Lymphoma: A Prospective Series of 52 Patients.

OBJECTIVE: We sought to evaluate patients at a single academic institution in a prospective manner to report patient presentation, clinical course, treatment, and outcomes in breast implant ALCL patients. BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (breast implant ALCL) is an uncommon T cell lymphoma, which is associated with textured surface breast implants. The disease has received increasing attention over the last 20 years. Previous retrospective studies have begun to outline the clinical course of breast implant ALCL. METHODS: We prospectively followed women with cytologically proven breast implant ALCL from 2014 to 2019. Demographic, clinical, treatment, and outcome data were collected and descriptive statistics were performed on variables of interest. RESULTS: We identified 52 women with pathologically confirmed breast implant ALCL. Implants were placed for augmentation in 61.5% of women and reconstruction in 36.5% of women. All of the 41 patients with known implant information had implants with textured surface. The majority of patients presented with delayed seroma (69.2%) and without systemic symptoms (86.5%). Most patients with staging information presented with Stage IA disease. Patient outcomes were excellent with 2 disease recurrence (3.8%) and all patients ultimately achieved complete remission. CONCLUSIONS: Further evaluation of the prospective and growing database of patients with breast implant ALCL will further improve our understanding of the disease and its clinical course. Robust participation in the breast implant ALCL PROFILE registry will improve our knowledge of long-term outcomes after implant placement. Finally, increasing awareness for patients and providers will lead to earlier diagnosis and improved outcomes for patients.

Breast Implant-associated Anaplastic Large Cell Lymphoma in Colombia: Report of a Multidisciplinary National Registry.

An estimated 43,390 breast augmentation surgeries (86,780 implants) and 1486 breast implant reconstructions are performed annually in Colombia, representing the second-most breast surgery destination in South America, the fourth in the western hemisphere, and the fifth country worldwide. No previous reports have evaluated the incidence of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) epidemiology or outcomes in a Hispanic population. Published data on the incidence of this disease in Colombia are unknown; therefore, a National Joint Multidisciplinary Committee was developed between the Colombian scientific societies of Mastology, Plastic Surgery, Hemato-Oncology, and the Invima (The National Food and Drug Surveillance Institute) to track national cases of BIA-ALCL. MATERIALS AND METHODS: We performed a retrospective review (survey-based study) of historical cases since 2011-2019, and a prospective collection of all patients with a confirmed World Health Organization diagnosis of BIA-ALCL identified in a newly established National Registry of BIA-ALCL. The trial was approved by Institutional Review Board (IRB). RESULTS: Eighteen cases of BIA-ALCL were identified in Colombia between 2011 and 2019. Hundred percent developed as sequelae of textured implants. Six patients (33.3%) presented either a peri-implant capsule mass or axillary lymph node involvement. Seven (38.9%) required adjuvant chemotherapy most commonly with CHOP regimen. Different brands of implants were associated with our cases. One death (5.6%) was attributed to BIA-ALCL, and one (5.6%) case displayed with relapsed with bone marrow involvement requiring a bone marrow transplantation. Six cases (33.3%) were identified with advanced stage (IIB-IV). Disease-free survival of 92.3% was achieved at 30.8-month follow-up. CONCLUSIONS: Colombia has one of the highest volumes of breast surgery and use of textured surface breast implants in the world. This study is the initial report of an implant registry in South America. A high proportion of advanced disease may be a consequence of delayed presentation, lack of disease awareness, and timely access to tertiary cancer centers for diagnosis and treatment. Brands other than Allergan and Mentor were found to be associated with BIA-ALCL in our study.

EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2020 update on diagnosis, risk-stratification and management.

DISEASE OVERVIEW: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an entity included in the 2016 WHO classification of lymphoid neoplasms. EBV+ DLBCL, NOS, is an aggressive B-cell lymphoma associated with chronic EBV infection, and a poor prognosis with standard chemotherapeutic approaches. DIAGNOSIS: The diagnosis is made through a careful pathological evaluation. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The differential diagnosis includes plasmablastic lymphoma (PBL), DLBCL associated with chronic inflammation and primary effusion lymphoma (PEL), among others. RISK-STRATIFICATION: The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers. MANAGEMENT: Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.

Differences in Human Leukocyte Antigen Expression Between Breast Implant-Associated Anaplastic Large Cell Lymphoma Patients and the General Population.

BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon T-cell lymphoma associated with textured-surface breast implants. Human leukocyte antigen (HLA) polymorphisms have been described with other forms of lymphoma, but have not been described for BIA-ALCL. OBJECTIVES: The aim of this study was to evaluate HLA polymorphisms in BIA-ALCL patients. METHODS: We prospectively evaluated HLA alleles in patients with BIA-ALCL. HLA was analyzed by probe-based sequence-specific testing and sequence-based typing. The frequencies of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 alleles were evaluated. Allele frequencies in the Caucasian European general population were obtained from the National Marrow Donor Program to serve as normative controls. We estimated the relative risk of BIA-ALCL with 95% confidence intervals from a t test. RESULTS: Thirteen patients who had undergone BIA-ALCL and HLA testing were identified from 2017 to 2018. Patients carried 10, 11, and 9 HLA-A, HLA-B, and HLA-C alleles, respectively. There were 8 DRB1 alleles and 5 DQB1 alleles in the BIA-ALCL patients. The A*26 allele occurred significantly more frequently in the general population compared with BIA-ALCL patients (0.2992 vs 0.07692, P < 0.001). CONCLUSIONS: Our results identify a difference between HLA A*26 in patients who develop BIA-ALCL and the general population, and may signify genetic susceptibility factors responsible for germline genetic variation in HLA in patients with BIA-ALCL. Further work is needed to elucidate if these alleles are predictive for BIA-ALCL in women with textured-surface breast implants.Level of Evidence: 4.

Myeloproliferative neoplasms with t(8;22)(p11.2;q11.2)/BCR-FGFR1: a meta-analysis of 20 cases shows cytogenetic progression with B-lymphoid blast phase.

Rearrangements of FGFR1 result in the 8p11 myeloproliferative syndrome, a group of rare diseases that features a myeloproliferative neoplasm (MPN) that commonly progresses to lymphoblastic leukemia/lymphoma or acute myeloid leukemia. The most common partner of FGFR1 is ZMYM2, and patients with the ZMYM2-FGFR1 fusion often present with MPN and T-lymphoblastic lymphoma. There are 14 other partners that can fuse with FGFR1, and of interest is the BCR-FGFR1 fusion that results from t(8;22)(p11.2;q11.2). Patients with t(8;22) often show leukocytosis and present with an MPN resembling chronic myeloid leukemia or very rarely, with B-lymphoblastic leukemia (B-ALL). In this study, we analyzed the clinicopathological, cytogenetic, and molecular features of 2 new patients with the t(8;22)(p11.2;q11.2)/BCR-FGFR1 who presented with B-ALL. An underlying MPN became apparent when a morphologic remission of B-ALL was achieved after chemotherapy. We subsequently reviewed the literature and identified 18 additional cases reported with B-ALL in a background MPN or with the MPN as a chronic phase. Our data suggest that the t(8;22)(p11.2;q11.2)/BCR-FGFR1 may arise from a myeloid/B progenitor cell. It is important to recognize that neoplasms carrying the t(8;22)/BCR-FGFR1, although rare, can commonly with B lymphoblastic leukemia at the initial diagnosis, which could distract one from recognizing a possible underlying 8p11 myeloproliferative syndrome.

Immunophenotypic Shifts in Primary Cutaneous γδ T-Cell Lymphoma Suggest Antigenic Modulation: A Study of Sequential Biopsy Specimens.

Primary cutaneous γδ T-cell lymphoma (PCGD TCL), an aggressive type of lymphoma, accounts for approximately 1% of all primary cutaneous lymphomas. We have occasionally observed changes in T-cell antigen expression (immunophenotypic [IP] shift) over time, a phenomenon that is considered rare in T-cell lymphoma including cutaneous T-cell lymphoma. Therefore, we assessed sequential biopsies of PCGD TCL for possible IP shifts of the lymphoma cells. We searched for cases of PCGD TCL with consecutive biopsies to perform a comprehensive immunohistochemical analysis of paired specimens. A median of 12 markers per case was tested. We evaluated the percentage of neoplastic lymphocytes and determined the differential expression of antigens (gain, loss, increase or decrease). We identified 9 patients with PCGD TCL with consecutive biopsies. All (100%) cases had IP shifts of at least 1 antigen, whereas overall 22 pairs of markers were shifted: gain of reactivity occurred in 7 (31.8%) and loss in 3 (13.6%); increased reactivity in 4 (18.2%) and decreased in 8 (36.4%). Molecular analysis of TCRγ showed identically sized monoclonal rearrangements between biopsy pairs in 4/4 (100%) patients. There was no correlation between IP shifts and the clinical appearance of lesions, histopathologic or cytologic features, or molecular rearrangements. IP shifts are common in PCGD TCL, occurring in all patients in this study and involving a variety of antigens. IP shifts do not seem to be linked to changes in the T-cell clone and are without obvious clinical or morphologic correlates. The occurrence of IP shifts in PCGD TCL suggests that antigen modulation may be involved in pathogenesis. IP shifts are somewhat frequent in T-cell lymphoma; however, it does not suggest a second neoplasm, and molecular studies can be used to determine clonal identity.

Global Adverse Event Reports of Breast Implant-Associated ALCL: An International Review of 40 Government Authority Databases.

BACKGROUND: Tracking world cases of breast implant-associated anaplastic large cell lymphoma (ALCL) is currently limited to patient registries at a few academic centers, dependent upon patient referral and case reports in the literature. The purpose of this study was to review and compare federal database adverse event reports of breast implant-associated ALCL encompassing the major breast implant markets worldwide. METHODS: Federal implantable device regulatory bodies were contacted and database queries were performed for 40 countries. Demographics, device characteristics, pathology, treatment modalities, and outcomes were assessed when available. RESULTS: For the countries queried, 363 unique cases were reported for breast implant-associated ALCL. Search terms "anaplastic" and "ALCL" were queried of the U.S. Manufacturer and User Facility Device Experience (MAUDE) database and yielded 258 unique cases as of September 2015, of which only 130 had pathologic markers performed. Implant surface was textured significantly more than smooth (50 percent versus 4.2 percent; p = 0.0001). Treatment, when reported (n = 136), included explantation [n = 125 (91.9 percent)], chemotherapy [n = 42 (30.8 percent)], radiation therapy [n = 25 (18.4 percent)], and/or stem cell transplant [n = 9 (6.6 percent)], and five deaths were reported. CONCLUSIONS: Federal reporting of breast implant-associated ALCL has limitations in providing clinical history, treatment, and oncologic follow-up. Worldwide and country-specific total and textured implant sales data are needed to determine critical incidence and prevalence analysis. International multi-institutional collaborations and centralized tissue consortiums working in concert with federal authorities are necessary to acquire accurate complete data on breast implant-associated ALCL.

Follicular lymphoma with leukemic phase at diagnosis: a series of seven cases and review of the literature.

Follicular lymphoma (FL) is a prevalent type of non-Hodgkin lymphoma in the United States and Europe. Although, FL typically presents with nodal involvement, extranodal sites are less common, and leukemic phase at diagnosis is rare. There is mounting evidence that leukemic presentation portends a worse prognosis in patients with FL. We describe 7 patients with a pathological diagnosis of FL who presented with a leukemic phase. We compared our cases with 24 additional cases reported in the literature. Based on our results, patients who present with leukemic FL tend to have higher risk disease. Leukemic FL also seems to be associated with a worse prognosis; however, larger studies are needed to confirm our findings. A discrepancy with previously reported cases of FL in leukemic phase raises the possibility of differences attributable to geographic regions.

Peripheral T-cell lymphoma with a regulatory T-cell phenotype: report of a nodal and an extranodal case from Peru.

T-cell regulatory lymphocytes (T reg) are identified by their reactivity with CD4, CD25, and FOXP3, and are variably present in the background of various neoplasms including hematopoietic tumors, and function modulating the immune response, including control of autoimmunity. Adult T-cell leukemia/lymphoma is an aggressive lymphoma associated with human T-lymphotrophic virus 1 infection characterized by the presence of neoplastic lymphocytes with a T reg phenotype; however, this phenotype is not characteristically found in other lymphomas. Here, we report 2 apparently immunocompetent human T-lymphotrophic virus 1-negative patients with nodal and extranodal peripheral T-cell lymphoma, not otherwise specified with a T reg immunophenotype, based on the strong CD25 and FOXP3 positivity of the neoplastic cells. One patient was a 48-year-old woman with an early stage tumor in the cavum, who despite of chemotherapy subsequently developed systemic disease and died of tumor progression 46 months from diagnosis. The second patient was a 65-year-old male with generalized adenopathy and B symptoms who received chemotherapy achieving a complete remission but had recurrence and died 36 months from diagnosis. The histopathology revealed a diffuse infiltrate with an interfollicular distribution in the second case, with nodal involvement, consisted of large cells with clear cytoplasm associated with vascular proliferation and abundant mitoses. Neoplastic cells of first case showed typical T reg phenotype, whereas the second case had a CD4/CD8 double negative T reg variant. Only a single similar case was found in a review of the literature. We conclude that peripheral T-cell lymphoma, not otherwise specified with a T reg phenotype may represent a distinct category of T-cell lymphoma with an aggressive clinical course and poor prognosis.

EBV-positive diffuse large B-cell lymphoma of the elderly: a case series from Peru.

EBV-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is an entity recently included in the WHO classification of lymphoid tumors. We have reviewed our experience and clinical outcomes of this distinct subtype of DLBCL. Between 2002 and 2009, cases of DLBCL were identified from medical records of the Hospital Nacional Edgardo Rebagliati Martins in Lima, Peru, and underwent pathological evaluation including immunohistochemistry for CD20, CD10, bcl-6, MUM1/IRF4, and EBV-encoded RNA in situ hybridization. Clinical data were gathered, tabulated, and reported descriptively. Survival analyses were performed using Kaplan-Meier estimates. Out of 199 cases of DLBCL, 28 cases of EBV-positive DLBCL of the elderly were identified. The median age was 75 years with male predominance (1.5:1). B-symptoms were present in 43%, advanced stage in 50% and International Prognostic Index (IPI) score > 2 in 57% of patients; 68% of patients had a nongerminal center (NGC) phenotype. The complete response rates to R-CHOP and CHOP were 63% and 33%, respectively. The median overall survival (OS) for the group was 5 months. In the univariate analysis, age ≥70 years, lymphocyte count <1.0 × 10(9) /L, and advanced clinical stage were associated with worse OS in patients treated with chemotherapy with and without rituximab. EBV-positive DLBCL of the elderly is a clinically aggressive entity with a short OS and typically presents with advanced stage, high IPI score, and a NGC phenotype. Further studies are needed to investigate if rituximab-containing regimens are associated with better response and OS rates in EBV-positive DLBCL of the elderly.