[Primary cutaneous anaplastic large cell lymphoma with systemic progression responding to low-dose methotrexate therapy].

The standard therapies for primary cutaneous anaplastic large cell lymphoma (pcALCL) in an advanced stage remain undefined. A 71-year-old man presented with multiple erythema and nodules. He was diagnosed with lymphomatoid papulosis (LyP) through a skin biopsy from the left postauricular area. All skin lesions achieved complete response by electron beam irradiation. However, nodular lesions appeared in both inner canthi 5 months later. Histopathological evaluation of the lesional biopsy revealed dominant infiltration of CD30-positive large cells. Positron emission tomography/computed tomography revealed fluorodeoxyglucose-positive cervical and inguinal lymph node swelling and right tonsillitis, followed by the diagnosis of pcALCL and TNM classification T3bN3M0. Since the patient had severe chronic obstructive pulmonary disease and recurrent pneumonia, he received low-dose methotrexate (MTX) (15 mg/week) therapy. Low-dose MTX effectively debulked the lymphadenopathies over time without particular adverse effects. Although the standard therapies for pcALCL are not established, low-dose MTX was effective and considered safe for patients with frailty and compromised respiratory function. Further study is warranted on the pathophysiology of pcALCL after the development of LyP and mechanisms of action of low-dose MTX against LyP and pcALCL.

Remission of refractory granulomatous primary cutaneous anaplastic large cell lymphoma to brentuximab vedotin.

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a rare non-Hodgkin's lymphoma that arises as a single, or multiple dome-shaped tumours on the skin. The histology is characterised by the presence of atypical lymphocytes with large irregularly shaped nuclei that express the surface marker CD30. There can be significant heterogeneity in clinical manifestation and histological pattern and in rare cases accurate diagnosis can be a challenge. Here, we present an unusual case presentation of cutaneous CD30+ anaplastic large cell lymphoma with significant granulomatous histology pattern that mimicked sarcoid. After a lack of durable response to treatments that included glucocorticoid and methotrexate, targeted treatment with anti-CD30 monoclonal antibody drug conjugate (brentuximab vedotin) yielded long-term clinical remission.

Linfoma anaplásico de células grandes primario cutáneo del canto medio palpebral / Primary cutaneous anaplasic large-cell lymphoma involving medial canthus of the eyelid

El linfoma anaplásico de células grandes primario cutáneo (LACGc) forma parte del espectro de la enfermedad linfoproliferativa cutánea CD30+. Su afectación palpebral es muy rara, y en todos los casos descritos en la literatura afecta al párpado superior. En el presente caso clínico se describe un LACGc palpebral de localización atípica. Una mujer de 39 años sin antecedentes de interés presentó una lesión de crecimiento rápido en canto medio palpebral de aspecto inflamatorio-infeccioso. Tras una semana de antibioterapia oral sin respuesta, se realizó una biopsia excisional. Con análisis anatomopatológico compatible y estudio de extensión negativo, se catalogó como LACGc. Tras 2 años de seguimiento la paciente no ha presentado recidiva de la enfermedad. La afectación de los párpados por un LACGc es poco frecuente y potencialmente grave. Por ello, es necesario ampliar la información sobre el diagnóstico, tratamiento y curso de esta enfermedad

Cutaneous anaplastic large-cell lymphoma (cALCL) is a condition within CD30 lymphoid proliferations spectrum. Involving the eyelid is unusual and all cases found in the literature are located in the upper eyelid. In this case we report an cALCL atypical presentation. A 39 year-old woman with no significant medical history, presents a fast-growing mass in the medial canthus, with inflamatory-infectious appearance. After a week with antibiotics with no response, an excisional biopsy was practiced. The hystopathology analysis with a negative systemic work up confirmed the diagnosis of a cALCL. After two-year follow up, patient is asymptomatic. cALCL involving the eyelid are rare but potentially life-threatening disorders, so more information about diagnosis, treatment and follow up is needed

Low-dose Methotrexate Treatment for Solitary or Localized Primary Cutaneous Anaplastic Large Cell Lymphoma: A Long-term Follow-up Study.

Although low-dose methotrexate (MTX) has been used widely in treatment of a variety of dermatological diseases, including multifocal primary cutaneous anaplastic large cell lymphoma (PCALCL), it has not been established for use in the treatment guidelines for solitary or localized PCALCL. Furthermore, there has been no report of long-term follow-up data in Asian patients with PCALCL treated with low-dose MTX. To investigate the effectiveness and clinical outcome of treatment with low-dose MTX, clinical and long-term follow-up data of 7 patients with solitary or localized PCALCL were analysed retrospectively. Of the 7 patients, 6 (85.7%) showed a complete response and 1 (14.3%) showed partial remission. During follow-up, mean duration of 92.1 months, 5 patients developed one or more cutaneous relapses. At the last follow-up, all of the patients with PCALCL were alive without disease. These results indicate that low-dose MTX is a highly effective and safe treatment for solitary or localized PCALCL as well as multiple relapsed lesions.

FR - Brentuximab como tratamiento de los linfomas cutáneos primarios CD30 / RF - Brentuximab as Treatment for CD30+ Primary Cutaneous Lymphoma

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Sarcomatoid Variant of Primary Cutaneous Anaplastic Large Cell Lymphoma.

Sarcomatoid variant of primary cutaneous anaplastic large cell lymphoma is rare and is a diagnostic challenge. Clinical manifestation often mimics that of an infectious disease. Predominance of spindle cells in the biopsy specimen prevents from suspecting lymphoma. Here, we report the fourth case of this entity with good prognosis. A 30-year-old woman presented with several nodules on the whole body. The biopsy revealed infiltration of spindle cells in the dermis with myxomatous background. The spindle cells were positive for CD4 and CD30 and negative for CD3, CD8, CD20, and anaplastic lymphoma kinase. Although most of the skin lesions spontaneously resolved, a new red nodule progressively expanded on the left axilla. Finally, the patient received chemotherapy, which resulted in complete remission. The patient is free of disease for 18 months.

Recent Advances in Cutaneous T-cell Lymphoma: Diagnostic and Prognostic Considerations.

This review describes the latest advances in the diagnosis of cutaneous T-cell lymphoma focusing on the most clinically useful features introduced since the publication of the World Health Organization revision in 2017. Clinical entities described include mycosis fungoides, Sézary syndrome, lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma, primary cutaneous gamma delta T-cell lymphoma, primary cutaneous acral CD8+ T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, and hydroa-vacciniforme-like lymphoproliferative disorder. Distinguishing histologic clues to diagnosis are discussed, and important molecular advances are described. Key prognostic indicators that may assist clinicians with timely and appropriate management options are presented.

Complete Resolution of Primary Cutaneous Anaplastic Large Cell Lymphoma With Topical Imiquimod

Primary cutaneous anaplastic large cell lymphoma (pc-ALCL) is a CD30+ subtype of cutaneous T-cell lymphoma. It typically has a very favorable prognosis; however, traditional treatment can be expensive, invasive, and associated with significant adverse events. Imiquimod is a topical toll-like receptor approved by the Food and Drug Administration (FDA) for genital warts, actinic keratosis, and primary superficial basal cell carcinoma. In previous case reports, imiquimod has been shown to be effective against pc-ALCL. We present a case of complete resolution of pc-ALCL within 8 weeks with topical imiquimod and review the current literature. J Drugs Dermatol. 2019;18(5):460-462.

Long-term efficacy and safety of bexarotene for Japanese patients with cutaneous T-cell lymphoma: The results of a phase 2 study (B-1201).

The present study (B-1201 clinical trial) was conducted as a multicenter, open-label, single-arm phase II study to evaluate the long-term safety, tolerability and efficacy of bexarotene. This study enrolled 10 Japanese adults aged more than 20 years with cutaneous T-cell lymphoma (CTCL) who completed the 24-week study period of the B-1101 trial. The objective response rate (ORR) was 53.8% (95% confidence interval, 25.1-80.8). In the early stage (IB), the ORR was 60% (3/5 cases). In the advanced stage (IIB and IIIA), the ORR was 57.1% (4/7 cases). The median time to response was 58 days (range, 27-168). The median treatment duration was 380 days (range, 33-1674). The median duration of response (DOR) could not be reached during the study period. The longest DOR reached 1618 days at the end of the B-1201 trial. Nine patients (56.3%) in the full analysis set (FAS) population experienced dose reduction of bexarotene. Common drug-related adverse events in the FAS population included hypothyroidism (93.8%), hypertriglyceridemia (81.3%), hypercholesterolemia (81.3%), leukopenia (68.8%) and neutropenia (56.3%). Dose-limiting toxicity (DLT) was present in five (38.5%) of the 13 patients in the 300 mg/m2 cohort. Of the five patients, four developed grade 3 neutropenia and one developed grade 4 hypertriglyceridemia. All DLT cases recovered after the discontinuation of bexarotene. None of the five patients discontinued this trial because of DLT. The B-1201 trial shows the long-term safety of oral bexarotene for Japanese patients with CTCL, despite frequent dose reduction.

Eficacia y seguridad de brentuximab en pacientes adultos con linfoma cutáneo primario anaplásico de células grandes con diseminación extracutánea, progresivo o refractario a al menos una línea de quimioterapia / Efficacy and safety of brentuximab in adult patients with anaplastic primary cutaneous lymphoma of large cells with extracutaneous, progressive or refractory dissemination to at least one chemotherapy line

INTRODUCCIÓN: Los linfomas cutáneos primarios de células T (LCCT) son un grupo heterogéneo de neoplasias linfoides de células T que se originan en la piel. La entidad más frecuente es la micosis fungoide (MF), seguida de los desórdenes linfoproliferativos CD30+, que incluye al linfoma cutáneo primario anaplásico de células grandes (LCPCG). Se desconoce la frecuencia de LCPCG, pero en general representa un 9 % de todos los LCCT. En Perú, en un estudio llevado a cabo en el Hospital Nacional Edgardo Rebagliati Martins de EsSalud en el 2008, se reportó que de una cohorte de 67 pacientes con LCCT, dos de ellos presentaron LCPCG. La sobrevida global (SG) del LCPCG a los cinco años es del 90 %. Y alrededor del 10 % de los casos de LCPCG se presentan o cursan con diseminación extracutánea (DEC), en su mayoría a los ganglios linfáticos regionales y en menor frecuencia, a otros órganos. TECNOLOGÍA SANITARIA DE INTERÉS: Brentuximab es un anticuerpo conjugado, el cual está formado por un anticuerpo monoclonal dirigido contra el antígeno CD30 (IgG1), unido de forma covalente a MMAE (monomethyl auristatin E), un agente anti-microtúbulos. Este anticuerpo conjugado es producido mediante tecnología ADN recombinante en células de ovario de hámster chino. Es elaborado por la compañía farmacéutica Millennium Pharmaceuticals, Inc. ®. Se comercializa con el nombre de Adcetris ®, y sus derechos de comerciales le pertenecen a Seattle Genetics ® en Estados Unidos y Canadá, y a Takeda Group ® para el resto del mundo. METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica jerárquica de la literatura con respecto a la eficacia y seguridad de BV, comparado con metotrexato, para pacientes con LCPCG y DEC, progresivo o refractario a al menos una línea de quimioterapia. La búsqueda se inició revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras como FDA, EMA, y DIGEMID en el Perú. RESULTADOS: A partir de la búsqueda sistemática de la literatura llevada a cabo hasta enero de 2019, se incluyeron dos guías de práctica clínica (GPC) elaboradas por la National Comprehensive Cancer Network (NCCN) de Estados Unidos, y la European Society for Medical Oncology (ESMO) de Europa, y un ensayo clínico aleatorizado (ECA) fase III, como evidencia indirecta para responder a la pregunta PICO. No se identificaron evaluaciones de tecnologías sanitarias o revisiones sistemáticas que hayan evaluado BV en la población de interés del presente dictamen. CONCLUSIONES: El presente dictamen evaluó la evidencia científica disponible a la actualidad en relación a la eficacia y seguridad de BV comparada con metotrexato en pacientes adultos con LCPCG y DEC, progresivo o refractario a al menos una línea de quimioterapia, en términos de SG, calidad de vida, TRO, SLP y EA.  Nuestra revisión de la evidencia disponible hasta enero del 2019, permitió identificar al estudio ALCANZA como la principal fuente de información para la evaluación de los efectos de BV en nuestra población de interés.  El ECA ALCANZA es un estudio de etiqueta abierta de fase III financiado por la industria que comparó BV vs. terapia estándar de elección del investigador (i. e. metotrexato y bexaroteno) en pacientes adultos con LCCP CD30+ (LCPCG y MF CD30 +) con uso previo de al menos una línea de terapia sistémica. El ECA ALCANZA constituye evidencia indirecta para derivar las conclusiones del presente dictamen, dado que solo el 8.5 % de la población del estudio corresponde a los pacientes con LCPCG y DEC que habían recibido al menos una línea de terapia sistémica previa. Además, el comparador constituyó un análisis combinado de dos medicamentos, de cual sólo metotrexato es de interés. Sus resultados no mostraron un beneficio neto con BV, comparado con metotrexato, en la población de interés del presente dictamen. Primero, dado el diseño de etiqueta abierta y el uso de desenlaces blandos o subjetivos, como los de TRO4, TRO y SLP, los resultados podrían encontrarse potencialmente afectados por sesgos asociados con el investigador. Además, estos desenlaces subrogados (i. e. TRO4, TRO y SLP) no han demostrado ser predictores de una mejor calidad de vida o una mayor SG en los pacientes con linfomas cutáneos. Sumado a ello, no se han reportado resultados específicos para los desenlaces de SG o calidad de vida en la población con LCPCG, ni en la población de interés del presente dictamen, lo que genera una incertidumbre alrededor de un beneficio de BV, comparado con metotrexato, sobre los desenlaces clínicamente importantes desde la perspectiva del paciente. Asimismo, dada la incertidumbre alrededor de la seguridad con BV, evidenciada en el estudio ALCANZA, no es posible identificar un balance favorable del riesgo-beneficio con BV en comparación con metotrexato. En el contexto de EsSalud, se requiere de inversiones en tecnologías costo-oportunas favorables, que muestren un claro beneficio en los desenlaces de relevancia clínica para el paciente. Este no es el caso de BV para la población de la pregunta PICO. Por lo expuesto, el Instituto de Evaluaciones de Tecnologías en Salud e Investigación - IETSI, no aprueba el uso de BV para el manejo de los pacientes adultos con LCPCG y DEC, con progresión o refractariedad a al menos una línea de quimioterapia.

Primary cutaneous anaplastic large cell lymphoma arising from a long-standing erythema nodosum: A case report.

RATIONALE: Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a rare subtype of non-Hodgkin lymphoma, which is rarely associated with erythema nodosum (EN). PATIENT CONCERNS: A 57-year-old woman complained of recurrent rashes involving her abdomen, back, upper and lower limbs for over 20 years, with severity in symptoms for 2 weeks. DIAGNOSES: The first skin biopsy was performed in 2011 in another hospital and she was diagnosed idiopathic EN. The second skin biopsy was performed in 2014 and she was diagnosed as pcALCL with stage IA. INTERVENTIONS: She was treated with oral prednisone, cyclosporine, and thalidomide. OUTCOMES: One month later, the ulcerative lesion was decreased in size and became smooth and the patient achieved partial remission. She is still under treatment and has been monitored closely for 4 years. LESSONS: The case suggested that stimulation of inflammation in the skin lesions for a long period might be related to clonal transformation into pcALCL and hence should be closely monitored. Immunosuppressive treatment may be effective and safe for patients with pcALCL at early stages.

[Long-term administration of brentuximab vedotin in a patient with primary cutaneous anaplastic large cell lymphoma with peripheral blood involvement with leukemic change].

We report a case of long-term administration of brentuximab vedotin (BV) for primary cutaneous anaplastic large cell lymphoma (pc-ALCL) with leukemic change. A 67-year-old man with lymphadenopathy was admitted to our hospital. Six years ago, he was diagnosed with pc-ALCL at another hospital, and complete remission was achieved with radiation therapy. We performed a biopsy of his lymph node and diagnosed the recurrence of pc-ALCL with leukemic change. Initially, CHOP and GCD regimens were ineffective; however, partial remission was achieved following BV therapy. Thus far, he has received 42 courses of BV; he has responded well to the treatment and no serious side effects have been observed.

A rare and isolated presentation of primary cutaneous anaplastic large cell lymphoma.

Primary cutaneous anaplastic large cell lymphoma is a CD30+ lymphoproliferative disorder of the skin characterized by the absence of nodal and visceral involvement, low recurrence rate, spontaneous remission, and tendency to occur in patients older than 20 years. The case presented here is of a 15-year-old boy with grouped papular lesions arranged in an annular fashion with a central clearing on his right arm for 4 months that was diagnosed with a case of anaplastic lymphoma kinase-negative primary cutaneous CD30+ anaplastic large cell lymphoma. The CT scan, bone marrow biopsy, and laboratory data ruled out systemic involvement. He was treated with oral methotrexate 10 mg once a week, but was lost to follow-up.

CD30-positive primary cutaneous anaplastic large cell lymphoma with coexistent pseudocarcinomatous hyperplasia.

CD30-positive primary cutaneous anaplastic large cell lymphoma (C-ALCL) is an indolent type of cutaneous lymphoma with favourable clinical prognosis. Pseudocarcinomatous hyperplasia (PCH) is a rare benign epithelial condition that can resemble invasive squamous cell carcinoma both clinically and histopathologically. PCH predominantly occurs in CD30-positive lymphoproliferative disorders. We report a 75-year-old woman with PCH in a multifocal C-ALCL located on the scalp and right retroauricular area, which rapidly responded to treatment with psoralen ultraviolet A photochemotherapy. Comprehensive virological analyses for potential oncogenic viruses, including Epstein-Barr virus, human herpesvirus-8, human papillomaviruses, the recently discovered cutavirus and nine different human polyomaviruses, were negative.

Brentuximab vedotin in CD30+ primary cutaneous T-cell lymphomas: a review and analysis of existing data.

BACKGROUND: The utility of brentuximab vedotin (BV) in CD30+ systemic lymphomas is established, however evidence for treating primary cutaneous lymphoma remains limited. This study aimed to evaluate BV in treating CD30+ transformed mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (PC-ALCL). METHODS: A literature review was conducted, and we analyzed data from published trials and case reports obtained via search of Ovid-MEDLINE® and PubMed databases. The search yielded 372 reports, and 10 publications met inclusion criteria. Sixty-one patients with CD30+ transformed MF and seven with PC-ALCL were included. RESULTS: Mean age at BV initiation was 60.8 years (67 - PC-ALCL; 60.1 - MF), and 4.1 therapies were attempted prior to BV (3.1 - PC-ALCL; 4.2 - MF). The overall response rate was 67.7% (100% - PC-ALCL; 63.9% - MF), with 16.2% of patients experiencing complete response (100% - PC-ALCL; 6.6% - MF). Mean time to clinical response was 5.3 and 9.3 weeks for PC-ALCL and MF, respectively. Mean response duration for patients with PC-ALCL was 7.6 and 7.8 months for MF. Peripheral neuropathy (57.2%) and fatigue (35.6%) were the most commonly reported adverse effects. CONCLUSIONS: This analysis summates the current evidence regarding the use of BV in treating CD30+ MF and PC-ALCL. Preliminary results indicate that BV is effective for CD30+ CTCL, however additional studies with larger sample sizes are necessary. The study provides clinicians with the clinical context in which BV may be appropriate as well as information regarding therapeutic expectations and outcomes.