[Show abstract][Hide abstract]ABSTRACT: Sézary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma with an aggressive clinical course. The genetic etiology of the disease is poorly understood with chromosomal abnormalities and mutations in some genes being involved in the disease. The goal of our study was to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sézary cells, fourteen of them fulfilling the diagnostic criteria of SS. We have discovered genes that could be involved in the pathogenesis of SS. Some of the genes that are affected by somatic point mutations include ITPR1, ITPR2, DSC1, RIPK2, IL6, and RAG2, with some of them mutated in more than one patient. We have observed several somatic copy number variations shared between patients, including deletions and duplications of large segments of chromosome 17. Genes with potential function in T-cell receptor signaling pathway and tumorigenesis were disrupted in SS patients, e.g. CBLB, RASA2, BCL7C, RAMP3, TBRG4 and DAD1. Furthermore, we have discovered several fusion events of interest involving RASA2, NFKB2, BCR, FASN, ZEB1, TYK2 and SGMS1. Our work has implications for the development of potential therapeutic approaches for this aggressive disease.
Full-text available · Article · Mar 2016 · Journal of Investigative Dermatology
[Show abstract][Hide abstract]ABSTRACT: Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available.
We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas.
Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients.
Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up.
This was a case series retrospective study.
Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients.
Article · Jun 2013 · Journal of the American Academy of Dermatology
[Show abstract][Hide abstract]ABSTRACT: Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), leg type can eventually disseminate to extracutaneous sites including testes. In addition, patients with testicular lymphoma can develop specific skin involvement.
We sought to describe similarities between PCDLBCL, leg type and testicular B-cell lymphoma affecting the skin.
We report two cases with typical clinicopathological and immunophenotypical features of leg type lymphoma occurring simultaneously with a testicular B-cell lymphoma. We also report an additional case of PCDLBCL, leg type with secondary testicular involvement.
All cases presented with typical red tumors exclusively located on the legs. Histologically, all cases showed a diffuse nonepidermotropic infiltrate composed of large blastic cells mainly centroblastic type. Phenotype showed strong positivity for Bcl-2, MUM-1, and FOXP1. Epstein-Barr virus stains and CD30 were negative in the 3 cases. In all cases the testicular infiltration showed the same pathological and phenotypical changes to those observed in the skin.
This was a retrospective case series study.
Skin involvement by testicular B-cell lymphomas and PCDLBCL, leg type are indistinguishable on the basis of pathologic and immunophenotypical features, therefore specific investigation and clinic correlation are needed.
Article · Aug 2011 · Journal of the American Academy of Dermatology
[Show abstract][Hide abstract]ABSTRACT: Oncogenesis in the oral cavity is believed to result from genetic alterations that cause a stepwise transformation of the mucosa to invasive carcinoma. In oral squamous cell carcinoma (OSCC) multiple cytogenetic abnormalities have been reported, but their practical significance remains uncertain.
To evaluate the usefulness of the assessment of CCND1, MYC, EGFR, ERBB2 and TP53 in OSCC and lymph node metastases.
Fifty-one consecutive samples of OSCC, nine lymph node biopsies showing metastatic spread from OSCC, 16 biopsies diagnosed as oral leucoplakia (OLK), 13 samples corresponding to oral lichen planus (OLP) and 14 samples from normal oral mucosa were included in the study. Clinical and histopathological characteristics were reviewed. The genetic and protein status of the CCND1, MYC, EGFR, ERBB2 oncogenes and the TP53 tumour suppressor gene were assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The obtained results were compared with the clinical characteristics and the outcome of the OSCCs.
TP53 gene losses and MYC, ERBB2, CCND1 and EGFR copy number gains and amplifications were detected in a higher proportion in OSCC and lymph node samples than in OLK and OLP samples (P < 0·005). Overexpression of p53, Myc, Cyclin D1, c-erbB-2 and epidermal growth factor receptor (EGFR) was more prevalent in malignant samples than benign samples (P < 0·05). Correlation between FISH and IHC results was demonstrated in MYC, EGFR and CCND1 studies. The presence of two or more genetic abnormalities in the studied loci was exclusively detected in primary and metastatic OSCC.
In our series, genetic abnormalities in TP53, MYC, CCND1, ERBB2 and EGFR detected by FISH were absent in inflammatory lesions, infrequent in precursor lesions and common in tumoral lesions. Evaluation of the genetic status of TP53, MYC, CCND1, ERBB2 and EGFR may be an additional diagnostic tool in distinguishing benign from malignant oral lesions in histopathologically challenging cases.
Article · Nov 2010 · British Journal of Dermatology
[Show abstract][Hide abstract]ABSTRACT: Mycosis fungoide (MF) patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present European Organization for Research and Treatment of Cancer (EORTC) multicenter study, the genomic profile of 41 skin biopsies from tumor stage MF (MFt) was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter, and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2, and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21, and 10q26qter, were defined as prognostic markers showing a significant correlation with overall survival (OS) (P=0.042, 0.017, and 0.022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (>5 DNA aberrations), showing that the genomic unstable group had a shorter OS (P=0.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B, and MTAP) and 10q26qter (MGMT and EBF3) may have an important role in prognosis. In addition, we describe the MFt genomic instability profile, which, to our knowledge, has not been reported earlier.
Full-text available · Article · Sep 2009 · Journal of Investigative Dermatology
[Show abstract][Hide abstract]ABSTRACT: Epithelioid granuloma formation has rarely been observed in specific cutaneous lesions from T-cell lymphomas other than those of mycosis fungoides/Sézary syndrome (MF/SS). Three patients diagnosed with nodal and/or extranodal (tonsillar) non-Hodgkin's peripheral T-cell lymphoma (PTCL) and one patient with angioimmunoblastic T-cell lymphoma (AILD), developed specific cutaneous involvement showing prominent epithelioid cell and/or granulomatous inflammation. The original diagnostic lesions had no granulomatous features. In addition to a specific lymphomatous infiltrate, prominent dermal and/or subcutaneous granulomatous infiltrates were observed. Sarcoid-like granulomas were observed in two patients (one of them presented a granuloma annulare-like pattern in early lesions), granulomatous panniculitis was noted in one patient and in one patient with AILD, masses of epithelioid cells were noted. The clinicopathological features of cutaneous involvement by PTCL showing a florid epithelioid and/or granulomatous cell reaction are reviewed. Various histopathological patterns can be observed. The diagnostic difficulties of these cases are stressed.
[Show abstract][Hide abstract]ABSTRACT: Biología Molecular Hospital del Mar-IMAS. 4 Hospital Clínic, IDIBAPS. 5 Ciutat Sanitària i Universitària de Bellvitge. 6 Hospital Santa Creu i Sant Pau. Barcelona. España. El estudio de los reordenamientos de los genes del receptor de la célula T (TCR) y de las cadenas pesadas de las inmunoglobulinas (IgH) (análisis genotípico) mediante PCR representa el método diagnóstico más utilizado para la demostración del carácter monoclonal o policlonal de una proliferación linfoide cutánea y extracutánea. Representa en la actualidad un elemento importante en el diagnóstico definitivo de un linfoma cutáneo. Sin embargo, el resultado del análisis genotípico debe siempre valorarsedentro de un contexto clínico, histopatológico e inmunofenotípico particular. El objetivo del trabajo es analizar la sensibilidad en la detección de clonalidad (reordenamiento del TCR-g e IgH obtenidos mediante PCR) en una serie de linfomas cutáneos primarios células T y B en material de archivo parafinado empleando un sistema automatizado de análisis de fragmentos de ADN (Genescan [GS]).
[Show abstract][Hide abstract]ABSTRACT: 1)Servicio de Dermatología y (2) Patología Hospital del Mar-IMAS, Barcelona. (3)Hospital Clínic, (4)Hospital de Sant Pau, (5)Hospital de Bellvitge, (6)Servicio de Hematología, Hospital del Mar-IMAS, Barcelona. Red temática de linfomas cutáneos de Cataluña. Casos clínicos Comentario La afectación cutánea específica por linfoma de Hodgkin (LH) es un fenómeno poco frecuente, que se observa en aproximadamente un 0,5-7,5% de los casos, y de forma casi exclusiva en estadíos avanzados. Puede ser la consecuencia de una diseminación linfática retrógrada (el mecanismo más habitual), de una extensión directa de la progresión de la masa tumoral a la piel o bien por diseminación hematógena. Presentamos las características clínico-patológicos de 4 pacientes con afectación cutánea loco-regional secundaria a un LH. Caso 1: Varón de 29 años sin antecedentes de interés, que presenta una placa eritematosa, asintomática, de bordes mal definidos y discretamente infiltrada al tacto en la región torácica anterior de unos 4 meses de evolución. (Figura 1) No refería ninguna otra sintomatología sistémica acompañante. La exploración física no evidenciaba la presencia de adenopatías ni visceromegalias. La lesión planteaba un diagnóstico diferencial clínico amplio: lupus eritematoso subagudo, infiltración linfocitaria de Jessner, granuloma anular, proceso linfoproliferativo cutáneo primario, etc. El estudio histopatológico e inmunohistoquímico de una biopsia cutánea fue interpretado como compatible con infiltración cutánea por LH. (Figura 2A-D) (Figuras 3,4) El estudio de extensión mediante TAC/PET evidenció la presencia de múltiples adenopatías mediastínicas con infiltración directa por masa tumoral de la región preesternal. (Figura 5) La biopsia de la masa mediastínica fue concluyente con el diagnóstico de LH clásico. Un año después del tratamiento con 8 ciclos de ABVD (adriamicina, bleomicina, vinblastina, dacarbacina) el paciente permanece en remisión completa.