Anaplastic large cell lymphoma with ALK::ATIC fusion mimicking a histiocytic sarcoma debuting as an anterior thoracic soft tissue tumor with exceptional clinicopathological, morphological and molecular features.

A 56-year-old woman debuted with a palpable painless mass in the anterior thorax wall at the level of the second and third right parasternal intercostal space, which progressively increased in size over 5 months accompanied by localized skin rash, mild dyspnea and chest pain when changing position. Imaging studies showed a soft tissue mass measuring 75 × 62 mm and a density of 34 Hounsfield Units that had caused the lysis of the costal arches and grew expansively towards the anterior mediastinum, without identifying mediastinal adenopathies only by this imaging method. Core biopsy was performed, which was initially diagnosed as histiocytic sarcoma (HS); however, when the diagnostic panel was expanded to include molecular and NGS studies, the final diagnosis was anaplastic large cell lymphoma with ALK::ATIC fusion. Here, we report a very rare neoplasm with unusual clinical presentation, histopathology and molecular features.

Breast Implant-Associated Anaplastic Large-Cell Lymphoma in Brazil: What Are We Missing?

BACKGROUND: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) has been diagnosed in more than 1000 patients in more than 30 countries, although only a few cases have been reported in Latin America and the Caribbean to date. As the second-largest global market for breast implants with a predominance of textured-surface implants, Brazil is a major global market for cosmetic augmentations, making it unlikely that cases of BIA-ALCL are actually scarce. METHODS: A local and voluntary registry of patients with BIA-ALCL was initiated in 2018. All patients diagnosed with BIA-ALCL were confirmed by the World Health Organization criteria. Implant characteristics, disease symptoms, treatment, and oncologic outcomes were assessed. RESULTS: Fourteen cases of BIA-ALCL in a Brazilian population were identified in the Paraná state. Disease-specific diagnostic tests were omitted before surgical intervention in 50 percent of patients. With additional cases from a literature review, the treatment and outcomes of 29 cases of BIA-ALCL in Brazil were assessed. CONCLUSIONS: Compared with other populations, these initial observations suggest that awareness of the disease by the local breast surgery community remains low and that a number of cases may remain undiagnosed. Lack of preoperative diagnostic testing compromises disease treatment, oncologic outcomes, and both short- and long-term surveillance.

Use of flow cytometry and cytology to differentiate breast implant-associated anaplastic large cell lymphoma from reactive seromas in Brazilian patients.

INTRODUCTION: The combination of cytology and multiparametric flow cytometry (MFC) may be useful in the diagnosis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and may be a practical way to differentiate lymphoma from benign and reactive seromas. Although the Brazilian breast implant market is the second largest in the world, with several manufacturers and the almost exclusive use of textured implants, the occurrence of BIA-ALCL in Brazil is underreported. METHODS: One hundred seventeen sequential collections of suspicious periprosthetic fluid (PF) from 105 Brazilian patients registered between March/2018 and March/2021 were evaluated by routine cytomorphology and flow cytometry. The combination of CD30, HLA-DR, and CD25 was used together with T and B lymphocyte and monocyte evaluation. The PF samples were divided into positive, acute reactive (neutrophilic exudate), or chronic reactive (macrophage or lymphocyte rich), and unavailable samples. RESULTS: Nine BIA-ALCL positive cases (7.7%) were identified, with typical morphology and increased FSC/SSC dispersion, bright expression of CD30, CD25 and HLA-DR, and absence or weakness of T-cell antigens (CD3, CD8, CD4, CD5, and CD7). Reactive samples were acute (n = 18, 15.4%) and chronic (n = 70, 59.8%). Twenty samples were excluded. The mean age of BIA-ALCL patients was 50 years (31-57 years) and 35 years in reactive patients (20-69 years). CONCLUSION: Use of MFC with a comprehensive antibody panel consisting of CD30 in conjunction with CD25 and HLA-DR can discriminate anaplastic cells of BIA-ALCL from lymphoid or neutrophilic reactive cells and should be considered in the initial evaluation of seroma.

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.

Immunophenotypic shifts during minimal residual evaluation in a case of leukemic form of anaplastic large cell lymphoma ALK.

BACKGROUND: This study aims to describe immunophenotypic explorations at diagnosis and follow up of a pediatric patient with leukemic phase of ALK+ anaplastic large cell lymphoma (ALCL) by multiparametric flow cytometry (MFC). CASE: An 8-color MFC combination of antibodies allowed to identify neoplastic cells in concentrations until 0.02% during minimal residual disease (MRD) monitoring. Immunophenotypic shifts occurred in key markers as CD30, CD7, CD2, and CD5, however neoplastic cells were clearly discriminated from normal populations. CONCLUSION: MFC can be a useful tool for ALCL diagnosis and MRD monitoring and may support therapeutic decisions.

Linfoma anaplásico de células grandes asociado a implantes mamarios diagnosticado mediante punción por aguja fina. Caso clínico

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin T-cell lymphoma, recently defined in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms. It occurs more commonly when textured implants are used and appears clinically as a late seroma. Cytologically, these lesions are composed of large atypical cells with pleomorphic nucleus and an immunophenotype positive for T cell markers and CD30, and negative for ALK1. We report a 56-years-old woman with breast implants who developed a periprosthetic seroma three years after surgery. A fine needle aspiration of the lesion was carried out. Cytology and the immunocytochemical study revealed cells compatible with BIA-ALCL. The flow cytometric study was negative. Excisional biopsy of the capsule was performed, observing that the neoplastic cells were confined to the inner surface of the capsule. Imaging studies did not find evidence of disseminated disease. The present case demonstrates the importance of the study of any late periprosthetic effusion, which can be performed using fine needle aspiration.

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) and the Textured Breast Implant Crisis.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon T-cell, CD-30+/ALK lymphoma. Late (9 years) periprosthetic fluid (seroma) is the most common presentation (90% of the cases). A combination of textured breast implant, bacterial contamination, and genetic predisposition seems to be necessary for BIA-ALCL to occur. There are 35 million patients with implants in the world, and at the present moment, 573 cases of BIA-ALCL have been reported. The risk of developing BIA-ALCL in Australia varies from 1:2832 to 1:86,029, with texture grades 3 and 4 seeming to pose a higher risk than grades 2 and 1. NCCN has established guidelines for diagnosis and treatment, and early diagnosis is the key to cure. At an early stage and for the vast majority of patients, the treatment consists of capsulectomy and implant removal. However, at stages II to IV, a systemic treatment is warranted, including chemotherapy, radiotherapy (residual disease), and brentuximab vedotin. The majority of patients can be cured, and complete capsular removal is the most important factor. So far, 33 patients have died from BIA-ALCL worldwide, with deaths related to delay in diagnosis and treatment. Textured implants have been in the midst of the current implant crisis, and Biocell was recalled worldwide after the latest FDA update on the disease. At the present moment, no medical society or regulatory agency has recommended implant removal. It is about time that we start robust breast implant registries to determine risks. Besides, based on scientific criteria, we must consider all the benefits and risks associated with the available breast devices.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

[Anaplastic large cell lymphoma associated with breast implants, diagnosed by fine needle aspiration. Report of one case]. / Linfoma anaplásico de células grandes asociado a implantes mamarios diagnosticado mediante punción por aguja fina. Caso clínico.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin T-cell lymphoma, recently defined in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms. It occurs more commonly when textured implants are used and appears clinically as a late seroma. Cytologically, these lesions are composed of large atypical cells with pleomorphic nucleus and an immunophenotype positive for T cell markers and CD30, and negative for ALK1. We report a 56-years-old woman with breast implants who developed a periprosthetic seroma three years after surgery. A fine needle aspiration of the lesion was carried out. Cytology and the immunocytochemical study revealed cells compatible with BIA-ALCL. The flow cytometric study was negative. Excisional biopsy of the capsule was performed, observing that the neoplastic cells were confined to the inner surface of the capsule. Imaging studies did not find evidence of disseminated disease. The present case demonstrates the importance of the study of any late periprosthetic effusion, which can be performed using fine needle aspiration.

Linfoma anaplásico de células T grandes primario cutáneo CD30+. Serie de nueve casos.

INTRODUCTION: CD30+ anaplastic large T cell lymphoma is a cutaneous primary lymphoma in which there is no evidence of systemic disease; histopathological study is required for its diagnosis. OBJECTIVE: To present the cases diagnosed with primary cutaneous CD30+ anaplastic large T-cell lymphoma over a 24-year period in Hospital General "Dr. Manuel Gea González" Department of Dermatology. METHOD: Retrospective study. Descriptive statistics was carried out. Information was collected on gender, age, clinical characteristics, complementary test results, previous and current treatments, histopathological studies reports and immunohistochemistry test results. RESULTS: Of 29 309 records, nine patients (0.000034%) with a diagnosis of CD30+ anaplastic T cell lymphoma were found. Histopathological and immunohistochemical diagnosis was confirmed by two certified dermatopathologists. Average age was 61.2 years, and there was a predominance of the female gender, with initial clinical presentation as a papular or nodular lesion and varied topography. CONCLUSIONS: The prognosis of CD30+ anaplastic large T cell lymphoma in the studied population was dependent on clinical stage. The treatment at early stages has favorable results.

INTRODUCCIÓN: El linfoma anaplásico de células T grandes CD30+ es un linfoma primario cutáneo en el cual no hay evidencia de enfermedad sistémica; para su diagnóstico es necesario el estudio histopatológico. OBJETIVO: Presentar los casos diagnosticados en el Departamento de Dermatología del Hospital General "Dr. Manuel Gea González" con linfomas anaplásicos de células T grandes primarios cutáneos CD30+ durante un periodo de 24 años. MÉTODO: Estudio retrospectivo en el que realizó estadística descriptiva. Se recopiló información de sexo, edad, características clínicas, resultados de pruebas complementarias, tratamientos previos y actuales, reportes de los estudios histopatológicos y de inmunohistoquímica. RESULTADOS: Entre 29 309 expedientes, se encontraron nueve casos (0.000034 %) con diagnóstico de linfoma anaplásico de células T CD30+. Se hizo la confirmación del diagnóstico histopatológico e inmunohistoquímico por dos dermatopatólogos certificados. La edad promedio fue de 61.2 años, hubo predominio del sexo femenino y de lesión papular o nodular y topografía variada como presentación clínica inicial. CONCLUSIONES: El pronóstico del linfoma anaplásico de células T grandes CD30+ en la población estudiada fue dependiente del estadio clínico. El tratamiento en etapas tempranas tiene resultados favorables.

Linfoma anaplásico de células T grandes primario cutáneo CD30+. Serie de nueve casos / Primary cutaneous CD30+ anaplastic large T-cell lymphoma. Series of nine cases

Resumen Introducción: El linfoma anaplásico de células T grandes CD30+ es un linfoma primario cutáneo en el cual no hay evidencia de enfermedad sistémica; para su diagnóstico es necesario el estudio histopatológico. Objetivo: Presentar los casos diagnosticados en el Departamento de Dermatología del Hospital General "Dr. Manuel Gea González" con linfomas anaplásicos de células T grandes primarios cutáneos CD30+ durante un periodo de 24 años. Método: Estudio retrospectivo en el que realizó estadística descriptiva. Se recopiló información de sexo, edad, características clínicas, resultados de pruebas complementarias, tratamientos previos y actuales, reportes de los estudios histopatológicos y de inmunohistoquímica. Resultados: Entre 29 309 expedientes, se encontraron nueve casos (0.000034 %) con diagnóstico de linfoma anaplásico de células T CD30+. Se hizo la confirmación del diagnóstico histopatológico e inmunohistoquímico por dos dermatopatólogos certificados. La edad promedio fue de 61.2 años, hubo predominio del sexo femenino y de lesión papular o nodular y topografía variada como presentación clínica inicial. Conclusiones: El pronóstico del linfoma anaplásico de células T grandes CD30+ en la población estudiada fue dependiente del estadio clínico. El tratamiento en etapas tempranas tiene resultados favorables.

Abstract Introduction: CD30+ anaplastic large T cell lymphoma is a cutaneous primary lymphoma in which there is no evidence of systemic disease; histopathological study is required for its diagnosis. Objective: To present the cases diagnosed with primary cutaneous CD30+ anaplastic large T-cell lymphoma over a 24-year period in Hospital General "Dr. Manuel Gea González" Department of Dermatology. Method: Retrospective study. Descriptive statistics was carried out. Information was collected on gender, age, clinical characteristics, complementary test results, previous and current treatments, histopathological studies reports and immunohistochemistry test results. Results: Of 29 309 records, nine patients (0.000034%) with a diagnosis of CD30+ anaplastic T cell lymphoma were found. Histopathological and immunohistochemical diagnosis was confirmed by two certified dermatopathologists. Average age was 61.2 years, and there was a predominance of the female gender, with initial clinical presentation as a papular or nodular lesion and varied topography. Conclusions: The prognosis of CD30+ anaplastic large T cell lymphoma in the studied population was dependent on clinical stage. The treatment at early stages has favorable results.

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.

Anaplastic Large Cell Lymphoma: Emerging Consent and Management Patterns among American and International Board Certified Plastic Surgeons.

BACKGROUND: Although literature and case reports regarding anaplastic large cell lymphoma (ALCL) continue to increase, changes in plastic surgery practice patterns have not been assessed. METHODS: A 19-question survey was sent electronically to U.S. and international board-certified plastic surgeons. Data were analyzed using chi-square test and logistic regression analysis. RESULTS: A total of 1383 surgeons (U.S., 715; international, 668) responded, at a rate of 13.5 percent, and 36.2 percent of U.S. physicians aspirate late seromas and send for cytologic analysis and 9.5 percent had personal experience with ALCL, equating to at least 193 self-reported cases. Overall, 26.9 percent discuss ALCL risk at the initial consultation every time, and 36.4 percent include ALCL in the informed consent. Compared to U.S. counterparts, Australian, French, and German physicians were five times as likely to include ALCL in consent. Physicians in an academic practice and those frequently (>40 percent) using textured implants were more likely to discuss ALCL in the preoperative consultation. Physicians with personal or colleague experience with ALCL were twice as likely to include ALCL in the consent process. CONCLUSIONS: Only one-third of surgeons are managing late seroma according to U.S. Food and Drug Administration guidelines. ALCL cases are likely being underreported. Collectively, plastic surgeons remain hesitant to change consent pattern. However, specific countries have adapted their consenting processes. Working in academia and frequent textured implant use makes one more likely to discuss ALCL in consultation. Personal or colleague experience makes one twice as likely to include ALCL in the consent.

Anaplastic large cell lymphoma presenting as acute liver failure: A report of two cases with review of literature.

Primary hepatic anaplastic large cell lymphoma (ALCL) of the liver is a rare entity. We present here two cases of primary hepatic anaplastic large cell lymphoma (ALCL) of the null-cell type. Both the cases had jaundice with "B" symptoms and hepatomegaly. The serum billirubin and liver enzymes were raised in both cases. The liver showed sinusoidal infiltration by atypical lymphoid cells with marked nuclear pleomorphism, dispersed chromatin and prominent nucleoli in both the cases. These cells were positive for CD30, negative for CD3, CD20 and EMA, and diagnosed as ALCL of the null-cell type. We hereby report these cases with the review of literature on primary hepatic ALCLwith their possible etio-pathogenesis & diagnostic clues which may help in timely diagnosis & management in such cases.

[Primary bone anaplastic large cell lymphoma]. / Linfoma anaplásico de células grandes. Primario de hueso.

INTRODUCTION: Anaplastic large cell lymphoma (ALCL) is a neoplasia of T-cell or null-cell origin accounting for approximately 3% of non-Hodgkin lymphomas in adults and 10-30% of lymphomas in children. It involves the lymph nodes as well as various extranodal sites, but the involvement of bone as either the primary or secondary site of spread, is rare. CASE REPORT: A 47-year-old male presented with an ALCL and multiple bone lesions involving the vertebrae, ribs, and iliac bone, with no other site of involvement. Histologic findings included interstitial and focal bone infiltrate consisting of large pleomorphic cells with an inflammatory background and marked fibrosis. There was immunohistochemical expression of CD30, EMA, CD45RO, CD43, CD8, Glut-1 and ALK-1. DISCUSSION: There are 20 reported cases of ALCL (T/null cell) arising from the bone. To diagnose primary bone lymphoma it is necessary to first exclude systemic lymphoma of the lymph nodes or the skin with bone spread. The differential diagnoses include osteomyelitis, small round cell tumors, mainly Ewing sarcoma/PNET, metastatic carcinoma, melanoma, Hodgkin lymphoma and Langerhans' cell histiocytosis. In this case, the differential FDG accumulation in the lesions observed in the PET-CT was associated with the degree of Glut-1 expression.