Brentuximab vedotin in ALK-negative anaplastic large cell lymphoma presenting with alar mass: A case report

@#Anaplastic large cell lymphoma (ALCL) is a rare subtype of T-cell non-Hodgkin lymphoma (NHL) primarily involving the lymph nodes; however, extra-nodal manifestations are also common. Diagnosis can be confirmed by a combination of histopathology and immunohistochemical staining. Complete workup and staging include imaging and bone marrow examination. This presents a case of a 55-year-old male with anaplastic lymphoma kinase (ALK) - negative ALCL presenting with an alar mass. ALCL patients often present with rapidly progressing lymphadenopathy. Extra-nodal manifestations commonly involve the skin, liver, lung, and gastrointestinal tract. Biopsy of the mass showed small to medium-sized anaplastic lymphoid cells that stained positive for CD30, LCA (CD45), CD99, and negative for CD20, ALK (CD246), neuron-specific enolase, CD34, CD5, PAX5, TdT, MPO, CD138, EMA, pancytokeratin, CD3 and synaptophysin. These findings were most compatible with an ALK-negative ALCL. The patient was started on a combination of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (BV + CHP) every 21 days for 6 cycles. There was a progressive decrease in the size of the mass, and a resolution was noted after the 5th cycle. FDG-PET/CT scan was done after the 6th cycle of chemotherapy and 6 months after completion of treatment. Both scans showed no evidence of metabolically active nodal or extra-nodal lymphomatous disease. This case showed a unique extra-nodal manifestation of an ALK-negative ALCL presenting as an alar mass with a good response to BV + CHP. However, more evidence is necessary to further establish the role of BV as the first-line treatment regimen for CD30-positive peripheral T-cell lymphoma (PTCL), including ALK-negative ALCL.

Prótesis mamarias texturizadas y linfoma anaplástico de células grandes / Breast implant associated anaplastic large cell lymphoma (BIA-ALCL)

Resumen En los últimos años, han aparecido evidencias que relacionan a un tipo de linfoma mamario con los implantes de silicona, lo que ha causado gran conmoción a nivel mundial. Este linfoma anaplástico de células grandes no Hodgkin (células T monoclonales), se ha visto asociado en mayoría de los casos, a las prótesis mamarias texturizadas. Es relativamente raro, ya que se puede presentar en 1 de cada 2.832 operados (as) y se puede manifestar como un seroma periprotésico o como una tumoración de la cápsula cicatrizal mamaria con o sin compromiso de la glándula y de los tejidos adyacentes.

In recent years, evidence has appeared linking a type of breast lymphoma with silicone implants, which has caused great commotion worldwide. This anaplastic large cell non-Hodgkin lymphoma (monoclonal T cells) has been associated in most cases with textured breast implants. It is relatively rare, since it can occur in 1 in 2832 operated on and it can manifest as a periprosthetic seroma or as a tumor of the mammary scar capsule with or without involvement of the gland and adjacent tissues.

Linfoma anaplásico de células grandes asociado a implante mamario. Reporte de un caso y revisión de la literatura. / Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL) - Argentinian case

El linfoma anaplásico de células grandes asociado a implantes mamarios LACG-AI o BIA-ALCL, abreviatura en inglés de "Breast Implant Associated-Anaplastic Large Cell Lymphoma", es una nueva entidad reconocida por la OMS desde el 2016, de rara incidencia y que aún plantea muchos interrogantes. Desde su primera mención en 1997 (J. Keech - B. Creech) su incidencia ha ido en aumento. En julio de 2020, 953 casos en el mundo según el Registro de la Sociedad Americana de Cirujanos Plásticos (PROFILE), y las publicaciones se multiplican exponensialmente año a año demostrando el interés que suscita. Se ha descripto una fuerte asociación con las superficies texturizadas de los implantes mamarios y con el tipo de material (mayor textura "grado 4" y cubierta de poliuretano mayor riesgo) llegando a describirse tasas tan altas omo 1/2830 en Australia/Nueva Zelanda. Su presentación clínica en casi el 75% es bajo la forma de un seroma tardío y el tiempo de exposición promedio ronda entre los 7 a 11 años. El diagnóstico histo-patológico integra el examen morfológico con la caracterización molecular, visualizándose grandes célular anaplásicas CD30 (+), ALK (-). El tratamiento quirúrgico, capsulectomía bilateral en estadios tempranos es el gold standard. Su pronóstico es excelente con exérsis completas. Objetivo: actualizar la información sobre esta novel enfermedad y comentar un caso propio que presenta todas las características descriptas en la literatura, siendo el 14° registrado en Argentina

The anaplastic large cell lymphoma associated with breast implants, LACCG-AI o BIA-ALCL abbreviation in English, is an entity recognized by the WHO since 2016 of rare incidence and that still raises many questions. Since its firts mention in 1997 (J. Keech - B. Creech) its incidence has been increasing, In july 2020, 953 cases in the world according to the Registry of the America Society of Plastic Surgeons (PROFILE), and the publications multiply exponentially year after year, demonstrating the interest it arouses, A strong association has been described with the textured surfaces of breast implants and with the type of material (greater texture "grade 4" and higher risk polyurethane cover), reaching rates as high as 1/2830 in Australia / New Zealand. Its clinical presentation in almost 75% is in the form of a late seroma and the average exposure time is between 7 to 11 years. The pathological anatomical diagnosis integrates the morphological examination with the molecular characterization, visualizing large anaplastic CD30 (+), ALK (-) cells. Surgical treatment, bilateral capsulectomy in early stages, is the gold standard. Her prognosis is excellent with complete exeresis. Objetive: to update the information on this novel disease and comment on an own case that presents all the characteristics described in the literature, the 14th being registered in Argentina

Systemic ALK-positive anaplastic large cell lymphoma involving implant site: a fortuitous association

Anaplastic lymphoma kinase (ALK) positive, anaplastic large cell lymphoma involving the non-mammary implant is an extremely rare presentation. Irrespective of the type or site, the implant-associated primary ALCL is morphologically and immunophenotypically similar to ALK-negative ALCLs. Herein, we present the case of a 42-year-old male who developed a lytic lesion after an implant for a right femur fracture. The lytic lesion biopsy revealed anaplastic large cell lymphoma with ALK protein expression. Imaging findings showed the widespread dissemination of disease all over the body, entrapping the implant too. ALCL involving the bone implant is a very unusual and rare presentation that needs to be documented.

ALK+ Anaplastic large cell lymphoma with extensive cardiac involvement: A rare case report and review of the literature

Cardiac lymphoma is a rare entity. In this setting, the secondary involvement of the heart is far more frequent than the primary cardiac lymphoma. Herein, we present an autopsy case of a disseminated anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma with a dominant mediastinal involvement. Extensive cardiac infiltration with the near replacement of the myocardial wall by the neoplastic cells was observed. A total of nine isolated case reports of anaplastic large cell lymphoma with cardiac involvement were found in the English-language literature, and a widespread cardiac and thymic infiltration by the systemic ALK-positive anaplastic large cell lymphoma has not been documented. An incidental regenerative nodule was also identified in the liver. The patient died of pulmonary thromboembolism and cardiac arrest.

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 grandes células relacionado ao implante mamário: revisão sistemática da literatura / Breast implant-associated anaplastic large-cell lymphoma: a systematic literature review

O linfoma anaplásico de grandes células associado ao implante de mama (Breast Implant Associated Anaplastic Large Cell Lymphoma - BIA-ALCL) é uma doença maligna recentemente descoberta, rara e possivelmente associada aos implantes mamários texturizados. Essa revisão da literatura teve como objetivo trazer novas atualizações acerca da epidemiologia, fisiopatologia e fatores de risco para desenvolvimento do BIAALCL. Foi realizado o levantamento de dados do período de dezembro de 2018 a fevereiro de 2019, através das bases de dados PUBMED, LILACS e Scielo sendo selecionados 10 artigos publicados entre 2016 e 2018. Foi encontrada uma incidência variando entre 2,8:100.000 a 1:3 milhões de pacientes com implantes mamários. Os dados coletados corroboram para a teoria de que não há uma relação direta de causa e efeito entre os implantes mamários, mormente os texturizados, e o desenvolvimento do BIA-ALCL, podendo esses ser considerados somente como fatores de risco e não agentes causadores. A teoria fisiopatológica mais aceita é a de que os implantes mamários com maior área de superfície levariam a formação de maior biofilme por maior adesão bacteriana gerando inflamação crônica mais proeminente, levando ao gatilho para a transformação maligna das células T. As informações explicitadas nessa revisão devem auxiliar na ampliação de estudos acerca da doença e criação de políticas públicas para a prevenção e diagnóstico precoce de tal enfermidade. Pelos dados encontrados há necessidade de que cirurgiões plásticos realizem acompanhamento mais próximo de seus pacientes, assim como orientem os pacientes antes das cirurgias sobre a existência da doença.

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a newly discovered and rare cancer possibly associated with textured breast implants. This literature review investigates its epidemiology, pathophysiology, and risk factors. PubMed, LILACS, and SciELO databases were searched from December 2018 to February 2019, and 10 articles published between 2016 and 2018 were selected. The incidence of BIA-ALCL ranged from 2.8:100,000 to 1:3 million breast implants. The obtained data corroborate the hypothesis that there is no direct cause and effect relationship between breast implants, especially textured implants, and BIA-ALCL, and these implants can be considered risk factors but not causative factors. The most accepted hypothesis on disease pathophysiology is that breast implants with larger surface areas may promote bacterial adhesion and biofilm formation, leading to severe chronic inflammation, triggering the malignant transformation of T cells. This review provides knowledge on BIA-ALCL and helps develop and implement public policies for disease prevention and timely diagnosis. The data highlight that long-term follow up is necessary and that surgeons should advise patients of the potential risk of developing BIA-ALCL before performing the implant surgery.

Primary multifocal anaplastic large cell lymphoma with eyelid involvement: a case report / Linfoma anaplásico de grandes células primário multifocal com envolvimento de pálpebra: relato de caso

ABSTRACT Ocular adnexal involvement in CD30+ lymphoproliferative disorders is rare. We report the case of a 73-year-old woman with a relapsing primary cutaneous anaplastic large cell lymphoma on her eyelid. A systemic extension study excluded extracutaneous involvement. Systemic chemotherapy resulted in an optimal response, with complete regression of the cutaneous lesions. There has been no recurrence during the 2 years of follow-up.

RESUMO O acometimento ocular adicional nos distúrbios linfoproliferativos CD30+ é raro. Relatamos o caso de uma mulher de 73 anos com linfoma de grandes células anaplásicas primárias recidivantes em sua pálpebra. A avaliação sistêmica excluiu envolvimento extracutâneo. A quimioterapia sistémica resultou em uma resposta ótima, com regressão completa das lesões cutáneas. Não houve recidiva durante 2 anos de acompanhamento.

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.

ALK-positive anaplastic large cell lymphoma with a monomorphic small-cell pattern masquerading as inflammatory gastric lesions

@#Introduction: Anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) with a non-common pattern can be diagnostic challenging. Pathologists can be unavoidably and unintentionally blind to non-descript tumor cells in a lymphohistiocytic- (LH) or small-cell (SC)pattern. We report a case of primary systemic ALK+ ALCL with a SC pattern that presented as secondary gastric lesions with a mixed LH and SC pattern that was masqueraded as inflammatory lesions. Case Report: A 34-year-old woman with intractable epigastric pain was referred to have repeated endoscopy with biopsy. She was found to multiple gastric erosions and nodules that were diagnosed as inflammatory lesions both endoscopically and histologically. Meanwhile, she developed an acute onset of severe back pain associated with a pathologic compression fracture in the T3 thoracic vertebral body. Imaging studies disclosed a disseminated systemic disease involving abdominopelvic lymph nodes and cervical and thoracic vertebral bodies. The needle biopsy of the pelvic lymph node disclosed diffuse proliferation of monomorphic small round cells that were diffusely positive for CD30 and ALK. A diagnosis of ALK+ ALCL with a monomorphic SC pattern was rendered. Discussion: A retrospective review of the gastric biopsies with the aid of immunohistochemistry enabled us to recognise the presence of lymphomatous infiltrates with a mixed LH and SC pattern in every piece of gastric biopsies that were repeatedly misdiagnosed as inflammatory lesions. This case illustrates a significant diagnostic pitfall of the LH- and SC-patterns in ALK+ ALCL, in which the tumour cells featuring lymphoid, plasmacytoid or histiocytoid appearance can be masqueraded as inflammatory cells.

Primary cutaneous anaplastic large cell lymphoma in a 73-year-old Filipino male

Introduction@#Primary cutaneous anaplastic large cell lymphoma (PCALCL) is an uncommonly encountered subtype of cutaneous lymphoma under the classification of CD30-positive lymphoproliferative disorders which presents histologically as large atypical lymphocytes with pleomorphic and anaplastic cytology that localizes to the dermis. Although recurrent, PCALCL usually carries a good prognosis, with 5-year survival rates ranging from 85% to 95%.@*Case Summary@#We report a 73-year-old elderly male who consulted at our out-patient department with a 3-year and 6-month history of multifocal, gradually enlarging, erythematous nodules with dry, necrotic areas on the scalp, right auricular area, left axillary area, right forearm, and right thigh, accompanied by loss of appetite and nontender cervical, left axillary, and right inguinal lymphadenopathy. Previous skin punch biopsy and immunohistochemical stain done by the patient’s preceding dermatologist was signed out as “suggestive” of pseudolymphoma. However, management with intralesional corticosteroid injections provided no improvement. Skin punch biopsy done at our institution revealed ALK negative (-) anaplastic large cell lymphoma. Patient was then referred to an oncologist, however, the patient was lost to follow-up and succumbed to community acquired pneumonia.@*Conclusion@#This case highlights the importance of a thorough diagnostic assessment as recent studies indicate a poorer prognosis of ALK (-) cases, with overall 5-year survival rates consistently below 50%.

Clinical Features and Prognostic Factors of 18 Children with Anaplastic Large Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical features and to explore the therapeutic efficacy and prognostic factors of children with anaplastic large cell lymphoma (ALCL).@*METHODS@#The clinical data of 18 children with ALCL admitted in Department of Pediatric Hematology, Union Hospital of Fujian Medical University from April 2011 to November 2017 was collected and analyzed.@*RESULTS@#The male to female ratio was 2∶1, the median age of onset was 6 (0.9-11.3) years old, and the B symptom was positive in 13 cases. The most common initial symptom was lymphadenopathy (in 17 cases). All patients were manifested with multiple organ involvements. 4 cases were classified as clinical stage Ⅱ, 11 cases as stage Ⅲ, and 3 cases as stage Ⅳ. Laboratory tests revealed 9 cases with leukocytosis and 8 cases with CRP＞20 mg/L. The pathological results showed all ALK-positive anaplastic large cell lymphoma with Ki-67 rate between 40%-90%. The median follow-up time was 41 months. 2 patients died before treatment, 1 patient was lost to follow-up. 15 patients accepted chemotherapy protocol of CCCG-BNHL-2011. 2 patients relapsed early, the 3 year event-free survival rate was (76.7±10.2)%. Kaplan-Meier survival analysis showed leukocytosis, increased CRP level, bone involvement and clinical stage were factors affecting prognosis.@*CONCLUSION@#ALCL is a relatively rare subtype of childhood non-Hodgkin's lymphoma with high invasiveness. Leukocytosis, increased CRP level, bone involvement and clinical stage are poor factors affecting the prognosis of patients.

A Case of Multifocal Primary Cutaneous Anaplastic Large Cell Lymphoma Managed without Surgical Treatment / 대한두경부종양학회지

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is rare among skin malignancies. C-ALCL usually manifests as reddish or violet nodules. Surgical excision or radiation therapy is generally considered as first-line therapy, but a clinically aggressive disease may require multiagent chemotherapy. Establishing a proper diagnosis of C-ALCL is challenging but should be made to avoid inappropriate treatment and its consequences. The authors report a case of medically resolved C-ALCL in an 81-year-old man presented with well-defined nodular lesions on the forehead.

Anaplastic Large Cell Lymphoma of the Duodenum in a Teenage Girl: Misdiagnosed as an Intramural Duodenal Hematoma / 대한소아소화기영양학회지

We report a case of a 13-year-old girl who presented with a 2-month history of intermittent abdominal pain. Laboratory examination showed hepatitis and pancreatitis. Because of persistent vomiting, computed tomography (CT) was performed, which revealed a circumferential soft tissue density in the duodenal wall, causing partial obstruction. Supportive therapy failed. Repeat CT showed no significant change from the initial study. The patient underwent upper endoscopy, which revealed a mass in the second portion of the duodenum, which occluded most parts of the lumen. The histopathological finding was consistent with an anaplastic large cell lymphoma, a rare form of small bowel neoplasm. After the third course of chemotherapy, complete resolution of the mass was noted, and her symptoms were relieved.

Linfoma anaplásico de columna cervical: doble reto diagnóstico para el otorrinolaringólogo / Cervical spine anaplastic lymphoma: double diagnostic challenge for the otorhinolaryngologist

RESUMEN Las metástasis de la columna vertebral cervical no se ven comúnmente en el área otorrinolaringológica, y por lo tanto corren el riesgo de pasar por alto durante la evaluación del paciente. Presentamos un caso inusual evaluado debido a las metástasis de la columna cervical de un tumor primario desconocido. Después de extensos procedimientos de estudio que no eran diagnósticos, se obtuvo una biopsia mediante un abordaje cervical extendido. El paciente fue diagnosticado con un linfoma anaplásico, una enfermedad muy rara en la región de cabeza y cuello. Discutimos los hallazgos histológicos y la presentación clínica de esta condición.

ABSTRACT Cervical spine metastases are not commonly seen in the otolaryngology clinic and therefore run the risk of being overlooked during patient evaluation. We report an unusual case evaluated due to cervical spine metastases from an unknown primary tumor. After extensive workup procedures that were non-diagnostic, a biopsy was obtained through an extended cervical approach. The patient was diagnosed with an anaplastic lymphoma, a very rare disease in the head and neck region. We discuss the histologic findings and clinical presentation of this condition.

Hallazgo incidental de microfilarias de Mansonella ozzardi en un paciente pediátrico con linfoma T anaplásico / Incidental finding of Mansonella ozzardi in a paediatric patient with anaplastic lymphoma

Resumen Las filariasis son parasitosis producidas por nemátodos hemáticos de la familia Filariidae, la Mansonella ozzardi, es uno de los agentes etiológicos distribuido ampliamente en el continente americano y en el Caribe. Presentamos el caso de una paciente de 13 años de edad, previamente diagnosticada con linfoma T de célula grande anaplásico. Como parte de la evaluación antes del segundo ciclo B de quimioterapia, se realizó un extendido de sangre periférica en el que se encontró una microfilaría tipificada como Mansonella ozzardi, se dio manejo con una dosis única de ivermectina y se logró resultado negativo en el control a las 24 horas. Actualmente la paciente se encuentra asintomática y sin evidencia de recurrencia de la parasitemia y terminando su tratamiento oncológico.

Abstract Filariasis is caused by nematodes in the blood. Mansonella ozzardi is one of the aetiological agents widely distributed in the Americas and the Caribbean. The case is presented on a paediatric patient previously diagnosed with T-cell anaplastic large cell lymphoma. As part of the evaluation before the second cycle B chemotherapy, a peripheral blood smear was performed, in which were found microfilaria, identified as Mansonella ozzardi. The treatment was a single dose of ivermectin, with a negative result being obtained at 24 hours. The patient is currently asymptomatic and with no evidence of recurrence of the parasitaemia, and able to finish the cancer treatment.

Linfoma anaplásico de células grandes CD30+ y ALK+ con manifestación oral: revisión de literatura y reporte de caso / Anaplastic large cell lymphoma CD30+ and ALK+ with oral manifestation: review of the literature and case report

Introducción: Los linfomas son neoplasias del sistema linfoide clasificadas en Hodgkin y No-Hodgkin. Los linfomas de cabeza y cuello se originan en tejido linfoide regional, pero también en otros sitios como encía, paladar, etc. Objetivo: Describir el Linfoma Anaplásico de Células Grandes (LACG) como un subgrupo de linfomas No-Hodkin de células T, positivo o negativo para la expresión de las proteínas CD30 y AKL, el cual puede afectar numerosas partes del cuerpo incluyendo la cavidad oral. Se reporta un caso de LACG de células T CD30+ALK+. Diseño: Reporte de caso. Metodología: Se realizó una búsqueda sistemática en PubMed, MEDLINE, EMBASE, LILACS y Ovid. Se seleccionaron los artículos que reportaron casos de Linfoma No-Hodkin de células T con manifestaciones orales, limitándose al idioma Inglés. Reportamos el caso de una paciente de 9 años con LACG de células T, CD30+ALK+ con manifestaciones orales y sistémicas. Resultados: De los artículos obtenidos ninguno reporta casos de LACG de células T CD30+ ALK+ con manifestaciones orales, por la cual no fue posible realizar el análisis sistemático. Discusión: El LACG representa 2-3% de los Linfomas No-Hodkin, se divide en cutáneo primario y sistémico (ALK+/ALK-). El ALK+ también puede afectar sitios extranodales. Los pacientes a menudo presentan síntomas sistémicos, como fiebre y sudoración nocturna. Los casos de LACG sistémico primario ALK+ suelen responder bien a la quimioterapia y tienen mejor pronóstico que los casos ALK-. Conclusiones: El Linfoma anaplásico de células grandes de células T, CD30+ALK+ es una entidad poco frecuente en la cavidad oral.

Introduction: Lymphomas are neoplasms of the lymphoid system, they are classified as Hodgkin and Non-Hodgkin. Head and neck lymphomas are originated in regional lymphoid tissue, but also in other sites such as gums, lips, palate, etc. Objective: To describe the Anaplastic Large Cell Lymphoma (ALCL) as a subgroup of T-cell non-Hodgkin's lymphoma, positive or negative for expression of CD30+ and AKL+proteins, which can affect many parts of the body including tissue of oral cavity. Finally, it is pretended to report a case of ALCL T-cell, CD30+ AKL+. Design: Case report. Materials and methods: A systematic search was performed using electronic databases such as PUBMED, MEDLINE, EMBASE, LILACS and Ovid. Those papers which reported cases of T-cell NHL with oral manifestations were selected for further evaluation. This search was limited to english language. Additionally, the case of an ALCL T-cell, CD30+AKL+ with oral and systemic manifestations in a 9-year-old girl treated at the Fundación Hospital de la Misericordia is reported. Results: Of the articles obtained none report cases of ALCL T-cell, CD30+AKL+ with oral manifestations, so it is not possible to perform a systematic review of them. Discussion: ALCL is classified as primary cutaneous and systemic (ALK + and ALK-). The ALCL represents 2-3% of all NHL. The ALK+ ALCL can also affect extranodal sites. Patients often have systemic symptoms, such as fever and night sweats. Cases of ALK+ primary systemic ALCL usually respond well to chemotherapy and have a better prognosis compared to ALK- cases which have a less favorable prognosis with unpredictable clinical behavior. Conclusions: ALCL T-cell, CD30+AKL+ is an entity with presentation rare in the oral cavity.

Crizotinib in Combination with Everolimus Synergistically Inhibits Proliferation of Anaplastic Lymphoma Kinase‒Positive Anaplastic Large Cell Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Anaplastic large cell lymphoma (ALCL) is a rare aggresive non-Hodgkin lymphoma, of which over 50% of cases have an aberrant nucleophosmin (NPM)‒anaplastic lymphoma kinase (ALK) fusion protein. Both mechanistic target of rapamycin (mTOR) inhibitor everolimus and ALK inhibitor crizotinib have shown promising antitumor activity in ALK-positive cancer cell lines. However, their combined effect has not yet been investigated. MATERIALS AND METHODS: We evaluated the anti-proliferative effects of everolimus and/or crizotinib in ALK-positive ALCL cell lines, Karpas 299 and SU-DHL-1, and lung adenocarcinoma cell line, NCI-H2228. RESULTS: We found that individually, both everolimus and crizotinib potently inhibited cell growth in a dose-dependent manner in both Karpas 299 and SU-DHL-1 cells. A combination of these agents synergistically inhibited proliferation in the two cell lines. Crizotinib down-regulated aberrant AKT and ERK phosphorylation induced by everolimus. Combination treatment also significantly increased G0/G1 cell-cycle arrest, DNA damage, and apoptosis compared with everolimus or crizotinib alone in ALK-positive ALCL cells. In the Karpas 299 xenograft model, the combination treatment exerted a stronger antitumor effect than monotherapies, without significant change in body weight. The synergistic effect of everolimus and crizotinib was also reproduced in the ALK-positive lung adenocarcinoma cell line NCI-H2228. The combination treatment abrogated phosphoinositide 3-kinase/AKT and mTOR signaling pathways with little effect on the Ras/ERK pathway in NCI-H2228 cells. CONCLUSION: Crizotinib combinedwith everolimus synergistically inhibits proliferation of ALK-positive ALCL cells. Our results suggest that this novel combination is worthy of further clinical development in patients with ALK-positive ALCL.