Linfomas cutáneos: serie de casos en México / A case series of cutaneous lymphomas in Mexico

Resumen Introducción: Los linfomas cutáneos primarios son un grupo heterogéneo de neoplasias de células T y B que se presentan en la piel, sin ninguna evidencia de enfermedad extracutánea en el momento del diagnóstico, y muestran diferencias considerables en histologia, fenotipo y pronóstico. Se consideran neoplasias poco frecuentes. Casos clínicos: Se presentan cinco casos de linfomas cutáneos diagnosticados en el Hospital Infantil de México Federico Gómez durante el periodo de 2010 a 2018. Las presentaciones clínicas más frecuentes en estos pacientes fueron dermatitis, costras hemáticas y úlceras necróticas. El inmunofenotipo más común fue el linfoma cutáneo no Hodgkin T/NK extranodal nasal primario. El esquema de tratamiento que se utilizó en la mayoría de los pacientes fue SMILE. El promedio de tiempo al diagnóstico fue de 7 meses. Conclusiones: El pronóstico depende del estadio de la enfermedad al diagnóstico, grado de afectación de la piel y presencia o ausencia de enfermedad extracutánea. Los linfomas cutáneos primarios son neoplasias poco frecuentes. Debido al diagnóstico tardío, el estadio de la enfermedad suele ser avanzado, por lo que, generalmente, el comportamiento es agresivo.

Abstract Background: Primary cutaneous lymphomas are a rare heterogeneous group of T and B cell skin neoplasms without any evidence of extracutaneous disease at the time of diagnosis, which show considerable differences in histology, phenotype and prognosis. Case reports: Five cases of cutaneous lymphomas treated at the Hospital Infantil de México Federico Gómez from 2010 to 2018 are described. The most frequent clinical presentations in these patients were dermatitis, blood scabs, and necrotic ulcers. The most common immunophenotype was non-Hodgkin T/NK primary nasal extranodal cutaneous lymphomas. The treatment scheme used in most patients was SMILE. The average time to diagnosis was 7 months. Conclusions: The prognosis depends on the stage of the disease at diagnosis, the degree of skin involvement, and the presence of extracutaneous disease. As primary cutaneous lymphomas are infrequent neoplasms, the stage of the disease is usually advanced and generally shows an aggressive behavior due to a late diagnosis.

Cutaneous T-cell lymphomas in the revised 4th edition of World Health Organization classification of tumors of hematopoietic and lymphoid tissues (2017)

Abstract: Recently, the World Health Organization published the revised 4th edition of its classification of tumors of hematopoietic and lymphoid tissues. The present paper is a concise comparative review of the main primary cutaneous T-cell hematopoietic tumors, with emphasis on their immunohistochemical profiles.

Primary cutaneous T-cell lymphoma: experience from the Peruvian National Cancer Institute

Abstract: Background: Primary cutaneous T-cell lymphomas constitute a heterogeneous and rare group of diseases with regional particularities in Latin America. Objective: To determine the clinicopathological features, relative frequency and survival among patients from a Peruvian institution. Methods: Primary cutaneous T-cell lymphomas were defined based on the absence of extracutaneous disease at diagnosis. Classification was performed following the 2008 World Health Organization Classification of Neoplasms of the Hematopoietic and Lymphoid tissues. Risk groups were established according to the 2005 World Health Organization-EORTC classification for cutaneous lymphomas. Data of patients admitted between January 2008 and December 2012 were analyzed. Results: 74 patients were included. Mean age was 49.5 years. In order of frequency, diagnoses were: mycosis fungoides (40.5%), peripheral T-cell lymphoma not otherwise specified (22.95%), adult T-cell lymphoma/leukemia (18.9%), CD30+ lymphoproliferative disorders (6.8%), hydroa vacciniforme-like lymphoma (5.4%), extranodal NK/T-cell lymphoma (4.1%) and Sézary syndrome (1.4%). Predominant clinical patterns were observed across different entities. Mycosis fungoides appeared mainly as plaques (93%). Peripheral T-cell lymphoma not otherwise specified and adult T-cell lymphoma/leukemia presentation was polymorphic. All patients with hydroa vacciniforme-like lymphoma presented with facial edema. All cases of extranodal NK/T-cell lymphoma appeared as ulcerated nodules/tumors. Disseminated cutaneous involvement was found in 71.6% cases. Forty-six percent of patients were alive at 5 years. Five-year overall survival was 76.4% and 19.2%, for indolent and high-risk lymphomas, respectively (p<0.05). High risk group (HR: 4.6 [2.08-10.18]) and increased DHL level (HR: 3.2 [1.57-6.46]) emerged as prognostic factors for survival. Study limitations: Small series. Conclusion: Primary cutaneous T-cell lymphomas other than mycosis fungoides or CD30+ lymphoproliferative disorders are aggressive entities with a poor prognosis.

Granulomatous slack skin: a rare subtype of mycosis fungoides

Abstract: We report a case of granulomatous slack skin, a rare and indolent subtype of mycosis fungoides. It affects mainly men between the third and fourth decades. It is characterized by hardened and erithematous plaques that mainly affect flexural areas and become pedunculated after some years. Histological examination shows a dense infiltrate of small atypical lymphocytes involving the dermis (and sometimes the subcutaneous tissue) associated with histiocytic and multinucleated giant cells containing lymphocytes and elastic fibers (lymphophagocytosis and elastophagocytosis, respectively). Patients affected by this entity can develop secondary lymphomas. There are several but little effective therapeutic modalities described. Despite the indolent behavior of granulomatous slack skin, its early recognition and continuous monitoring by a dermatologist becomes essential for its management and prevention of an unfavorable outcome.

Linfomas cutáneos primarios: frecuencia de los tipos histológicos en una serie de 500 pacientes / Primary cutaneous lymphomas frequency of histological types in a series of 500 patients

Objetivo: analizar las frecuencias de los tipos histopatológico de Linfomas Cutáneos Primarios (LCP) registrados por un grupo colaborativo multicéntrico (redlinfomacutaneo.org.ar). Metodología: analizamos 500 casos provenientes de 24 centros dermatológicos (públicos y privados) de Argentina y uno de Colombia, reportados entre 2010 y 2015. Se incluyeron únicamente casos histológicamente confirmados y estadificados. La información registrada cumple con la Declaración de Helsinki. Resultados: el 94,2% fueron LCP de células T (LCCT) distribuidos en: Micosis fungoide (MF), 75,4%; Desórdenes Linfoproliferativos CD30+, 5,8%; variantes de MF, 4,6%; Síndrome de Sezary, 2,6%; Linfomas T Periféricos tipo NOS, 1,0%; Linfomas de células T-NK Extranodal tipo nasal, 1,0%; Linfomas CD8+ Epidermotropo Agresivo, 1,0%; Linfomas T Pleomórfico CD4+, 0,2%; Leucemia Linfoma T del Adulto, 0,4%. Los LCP de células B (LCCB) fueron el 5,8% y se distribuyeron en: Linfomas Centrofoliculares, 2.4%; Linfomas Marginales, 1,8%; Linfomas B difusos de Células Grandes tipo pierna, 0,4% y tipo NOS, 1%. Conclusiones: confirmamos el predominio de los LCCT pero con una frecuencia de LCCT superior y de LCCB inferior a las reportadas en series europeas o de EE.UU y similar a las de países asiáticos pudiendo obedecer a un sesgo del grupo aportante que sub-registra los LCCB o a factores etiológicos y/o étnicos. (AU)

Aims: to analize the frequency of histopathological types in Primary Cutaneous Lymphoma (PCL) recorded by a multicenter collaborative group (redlinfomacutaneo.org.ar). Methodology: we analized 500 cases from 24 dermatological centers (public and private) of Argentina and one of Colombia, reported between 2010 and 2015 and only being included histological confirmed and staged cases. Recorded information complies with the Declaration of Helsinki. Results: 94,2% were PCL of T cells (CTCL) distributed as follow: Mycosis Fungoides (MF), 75,4%; CD30+ Lymphoproliferative Disorders, 5,8%; MF variants, 4,6%; Sezary Syndrome, 2,6%; Peripheral T cells Lymphoma unspecified, 1,%; Extranodal NK/T cell Lymphoma nasal type, 1,%; CD8+ aggressive epidermotropic lymphoma 1,0%; CD4+ pleomorphic lymphoma, 0,2%; Adult T-cell leukemia/lymphoma, 0, 4%. The PCL B cell (LCCB) were 5.8% and distributed into: follicle center lymphoma, 2.4%; marginal zone lymphoma, 1,8%; diffuse large B-cell lymphoma, leg type, 0,4% and others type, 1%. Conclusions: we confirmed the prevalence of CTCL but with a higher frequency of CTCL and lower of LCCB to those reported in European or US series and similar to those of Asian countries, may be due to a bias of the contributor who underreport LCCB or to etiological and / or ethnic factors. (AU)

[Revision and classification of persian patient's primary cutaneous lymphoma according to WHO-EORTC classification in Razi hospital, Tehran: a brief report]

Primary cutaneous lymphoma is separated into two groups, cutaneous lymphoma [CTCL] and cutaneous B-CELL Lymphoma [CBCL]. This study was performed to classify histopathologically and define demographic features of Persian patients with primary cutaneous lymphoma. Twenty hundred and thirty four patients with primary cutaneous lymphoma who have been referred to Razi Hospital in Tehran, Iran during at four year period [October 2005 to October 2009], were investigated in this study. The data were gathered by reviewing their medical records and examined again extant evidence and histology slides. Among 234 Patients, the only clinical feature that could be assessed was itching. The most common involves location of disease was generalized. 189 [80.77%] cases of the patients had CTCL and 45 [19.23%] cases of the patients had CBCL. Age of patients with two lymphoma type were similar at the this time of diagnosis. Sex supremacy was with men in two groups. This study provides histopathologic classification and demographic data

Linfoma de células cutáneas de células T, tipo micosis fungoide folicular: reporte de un caso / Cutaneous T-cell lymphoma type mycosis fungoides follicular: case report

La Micosis Fungoide (MF) es el linfoma cutáneo más común de células T. Tiene un comportamiento indolente, llevando a algunos a utilizar el término de linfoma cutáneo de células T (LLCT) como sinónimo de la MF. Se caracteriza por una erupción cutánea crónica, generalizada, y clínicamente por la evolución de los parches en placas y tumores. A continuación se presentará un caso clínico que tras un diagnóstico de liquen plano refractario a tratamiento, se diagnostica micosis fungoide folicular.

Mycosis fungoides (MF) is recognized as the most common cutaneous T-cell lymphoma (CTCL). It has an indolent behavior, leading some to use the term cutaneous T-cell lymphoma as synonymous of MF. It is characterized by chronic, widespread rash, and clinically by the evolution of patches in plaques and tumors. We describe our experience with a case that after a diagnosis of lichen planus refractory to treatment, we diagnosed follicular mycosis fungoides.

Diagnóstico y manejo del linfoma cutáneo de células T de tipo micosis fungoides y síndrome de Sèzary / Diagnosis and treatment of cutaneous T cells lymphoma

La micosis fungoides y el síndrome de Sèzary constituyen el grupo más frecuente de linfomas cutáneos de células T; tienen un curso lento y progresivo y un impacto negativo en la calidad de vida del paciente. En los estadios iniciales, la curación es anecdótica y en los casos avanzados pueden comprometer la vida del paciente; con las opciones terapéuticas actuales se consigue disminuir la sintomatología y se logran remisiones temporales. Para los estadios tempranos se propone el uso de terapias dirigidas a la piel, como los esteroides tópicos, la fotoquimioterapia PUVA y la radioterapia localizada, y otros no disponibles en nuestro medio, como la quimioterapia tópica y el bexaroteno, mientras que, para los estadios más avanzados, se recomiendan terapias que combinan las dirigidas a la piel con tratamientos sistémicos, como el interferón alfa, el vorinostat y la poliquimioterapia.

Cutaneous CD30 positive anaplastic large cell lymphoma

An adult Caucasian male presented with a solitary abscess-like lesion on his left thigh. The lesion later on ulcerated and developed a central eschar. The initial differential diagnoses included deep mycosis, insect bite reaction or atypical mycobacterial infection. Histology confirmed it to be a CD30 positive anaplastic large cell lymphoma. Haematologyoncology screen was carried out and the patient started on local field radiotherapy. Localized lymphomatous lesions can be treated with surgical excision or local radiotherapy. Systemic treatments are reserved for generalized disease. The prognosis depends on the extent of involvement

Aplicación de la citometría de flujo en el diagnóstico inmunológico de los linfomas cutáneos T / Application of flow cytometry in the immunological diagnosis of cutaneous T-cell lymphomas

Se comunican las características inmunofenotípicas de 7 pacientes (5 del sexo masculino y 2 del femenino) con el diagnóstico clínico-morfológico de linfomas cutáneos de células T, atendidos en la consulta de Hematología del Instituto de Hematología e Inmunología. La edad de los pacientes osciló entre 17 y 88 años. El inmunodiagnóstico se realizó por inmunofluorescencia directa con un panel de anticuerpos monoclonales que incluyó marcadores linfoides B y T: CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD22 y CD25. La lectura se realizó en un clitómetro de flujo FaCScan (Becton-Dickinson ). Cada marcador se consideró positivo si un porcentaje mayor al 20 por ciento de los linfocitos expresaba el antígeno. Nuestros resultados mostraron que en la mayoría de los pacientes predominó el patrón general de los linfocitos T con función auxiliadora (CD3+, CD4+, CD8-). Se corrobora que la citometría de flujo es un procedimiento más rápido y menos laborioso que otros métodos de inmunofenotipaje celular, que nos permite un diagnóstico de certeza y la aplicación de una terapia efectiva.

The immunophenotypic characteristics of 7 patients (5 males and 2 females) with clinicomorphological diagnosis of cutaneous T-cell lymphomas that received attention at the Hematology Department of the Institute of Hematology and Immunology were reported. The age ot the patients ranged from 17 to 88 years old. The immunodiagnosis was obtained by direct immunofluorescence with a panel of monoclonal antibodies that included B and T lymphoid markers: CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD22 and CD25. The reading was made in a FaCScan flow cytometer (Becton-Dickinson). Each marker was considered positive if a percentage over 20 percent of the lymphocytes expressed the antigen. Our results showed the predominance in most of the patients of a general pattern of T-lymphocytes with auxiliary function (CD3+, CD4+, CD8-). It was corroborated that flow cytometry was a faster and less laborious method than other cellular immunophenotyping methods, and that it allowed to have an accurate diagnosis and to apply an effective therapy.

Diagnóstico de linfomas cutáneos mediante detección de clonalidad por PCR-heterodúplex / Diagnosis of cutaneous lymphomas by clonicity detection through PCR-heteroduplex technique

La detección de clonalidad en los síndromes linfoproliferativos mediante el estudio del reordenamiento de los genes de las inmuglobulinas y del receptor de células T, es utilizada para esclarecer si una proliferación o infiltrado de linfocitos es maligno o no. Este tipo de estudio es de particular utilidad en presencia de lesiones cutáneas cuyo origen linfoide o dermatológico resulta difícil de definir. Mediante la técnica de PCR-heterodúplex se estudiaron los genes de la cadena pesada de las inmunoglobulinas y de la cadena gamma del receptor de las células T, en 10 pacientes que presentaban manifestaciones dermatológicas atribuibles a algún tipo de linfoma cutáneo. Se observó reordenamiento clonal en 7 pacientes, lo cual permitió confirmar el diagnóstico de micosis fungoide y otros tipos de linfomas cutáneos. En 3 pacientes que no mostraron reordenamiento clonal, no fue posible confirmar por esta técnica un proceso linfoide de carácter maligno. Se demostró la utilidad del estudio cuando en presencia de una afección en la piel, es difícil diferenciar un proceso dermatológico de un síndrome linfoproliferativo con manifestaciones en piel.

The clonicity detection in the lymphoproliferative syndromes by studying the rearrangement of the immunoglobulin genes and of the T-receptor cells is used to make clear if a proliferation or infiltrate of lymphocytes is malignant or not. This type of study is particularly useful in the presence of cutaneous lesions whose lymphoid or dermatological origin is difficult to define. By the PCR-heteroduplex technique, the genes of the immunoglobulin heavy chain and of the T-cell receptor chain were studied in 10 patients that presented dermatological manifestations attributable to some kind of cutaneous lymphoma. Clonal rearrangement was observed in 7 patients, which allowed to confirm the diagnosis of mycosis fungoides and other types of cutaneous lymphomas. It was not possible to confirm a lymphoid process of malignant character by this technique in 3 patients who did not show clonal rearrangement. The usefulness of the study was proved when in the presence of a skin affection, it was difficult to differentiate a dermatological process from a proliferative syndrome with cutaneous manifestations.

Subcutaneous panniculitis-like T-cell cutaneous lymphoma.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma classified in the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification as a unique extranodal lymphoma with characteristic by T cell receptor (TCR) gene rearrangement. We report here a case of SPTCL in a 22 year-old woman who had presented with variably sized multiple nodules on both her legs. Initial differential diagnoses considered were panniculitis and lupus panniculitis. The histopathology showed a predominantly subcutaneous lobular infiltrate with atypical lymphocytes, karyorrhexis and rimming of adipocytes by lymphoid cells. Immunohistochemistry showed CD4-, CD8+, CD56- T-cell phenotype. Although TCR rearrangement studies were not done, the above T-cell phenotype and sparing of epidermis and dermis suggested the possibility of an SPTCL alpha/beta type. The patient received five cycles of a cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen which resulted in the regression in her skin lesions and constitutional symptoms.

Linfoma nasal de células T/Natural killer. Reporte de un caso / NK/T-cell lymphoma, nasal type. Case Report

El Linfoma Nasal de Células T/Natural Killer tiene baja prevalencia en occidente (1,5 por ciento), sin embargo en Asia y algunos países americanos como México, Guatemala y Perú, ésta es más alta (2,6-7 por ciento), siendo importante considerarla entre los diagnósticos diferenciales en lesiones centrofaciales en nuestro medio. El diagnóstico puede resultar difícil necesitando muchas veces varias biopsias para lograrlo, dificultad acentuada en el presente caso por el antecedente traumático coincidente con el inicio de la sintomatología.

The nasal type NK/T-cell lymphoma has low prevalence in occident (1,5%), however, in Asia and some Americancountries as Mexico, Guatemala and Peru, this is higher (2,6 - 7%), being important to consider it among thedifferential diagnoses of centrofacial lesions. The diagnosis canbe difficult, needing many times several biopsies to achieve it, accentuated in the present case for the coincident traumaticantecedent with the beginning of the sintomatology.