ABSTRACT
BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.
Subject(s)
Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , NF-kappa B , NFATC Transcription Factors , STAT3 Transcription Factor , Skin Neoplasms , Humans , Mycosis Fungoides/genetics , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Skin Neoplasms/genetics , T-Lymphocytes/metabolismABSTRACT
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Subject(s)
Humans , Male , Middle Aged , Eosinophilia/etiology , Folliculitis/etiology , Lymphoma, T-Cell, Cutaneous/complications , Skin Diseases, Vesiculobullous/etiology , Skin Neoplasms/complications , Monoclonal Gammopathy of Undetermined Significance/complications , Interferon-alpha/therapeutic use , CD3 Complex/analysis , CD4 Antigens/analysis , PUVA Therapy , Remission Induction , T-Lymphocyte Subsets , Tetrahydronaphthalenes/therapeutic useSubject(s)
Eosinophilia/etiology , Folliculitis/etiology , Lymphoma, T-Cell, Cutaneous/complications , Monoclonal Gammopathy of Undetermined Significance/complications , Skin Diseases, Vesiculobullous/etiology , Skin Neoplasms/complications , Bexarotene , CD3 Complex/analysis , CD4 Antigens/analysis , Eosinophilia/diagnosis , Eosinophilia/pathology , Folliculitis/diagnosis , Folliculitis/pathology , Humans , Interferon-alpha/therapeutic use , Lymphoma, T-Cell, Cutaneous/drug therapy , Male , Middle Aged , PUVA Therapy , Remission Induction , Skin Diseases, Vesiculobullous/diagnosis , Skin Diseases, Vesiculobullous/pathology , Skin Neoplasms/drug therapy , T-Lymphocyte Subsets/chemistry , T-Lymphocyte Subsets/immunology , Tetrahydronaphthalenes/therapeutic useABSTRACT
Patients with Birt-Hogg-Dube syndrome have an increased risk of developing hamartomas of the pilosebaceous unit, renal tumors of various types, lung cysts, and spontaneous pneumothorax. We present the case of a 54-year-old woman with a long history of whitish papules in the central region of the face and a family history of similar lesions. Biopsy and genetic study revealed a new mutation of the gene involved in Birt-Hogg-Dube syndrome.
Subject(s)
Birt-Hogg-Dube Syndrome/genetics , Mutation , Female , Humans , Middle Aged , PedigreeABSTRACT
El Birt Hogg Dubé es un síndrome que predispone a la aparición de hamartomas del folículo pilosebáceo y a mayor riesgo de presentar tumores renales de diversa extirpe, quistes pulmonares y neumotórax espontáneos. Presentamos el caso de una mujer de 54 años que presenta desde hace años pápulas blanquecinas centrofaciales e historia familiar de esas mismas pápulas. Tras biopsia y estudio genético de la paciente se detecta una nueva mutación en el gen implicado en este síndrome (AU)
Patients with Birt-Hogg-Dube syndrome have an increased risk of developing hamartomas of the pilosebaceous unit, renal tumors of various types, lung cysts, and spontaneous pneumothorax. We present the case of a 54-year-old woman with a long history of whitish papules in the central region of the face and a family history of similar lesions. Biopsy and genetic study revealed a new mutation of the gene involved in Birt-Hogg-Dube syndrome (AU)
Subject(s)
Humans , Female , Middle Aged , Mutation , Genetic Predisposition to Disease , Hamartoma Syndrome, Multiple/genetics , Hair Follicle/pathology , Kidney Neoplasms/genetics , Pneumothorax/geneticsABSTRACT
Patients with Birt-Hogg-Dube syndrome have an increased risk of developing hamartomas of the pilosebaceous unit, renal tumors of various types, lung cysts, and spontaneous pneumothorax. We present the case of a 54-year-old woman with a long history of whitish papules in the central region of the face and a family history of similar lesions. Biopsy and genetic study revealed a new mutation of the gene involved in Birt-Hogg-Dube syndrome.
ABSTRACT
El carcinoma de mama en el varón es muy infrecuente. Cerca de 1500 casos nuevos se diagnostican cada año en Estados Unidos. Describimos dos pacientes cuyas lesiones cutáneas fueron la primera manifestación de un carcinoma ductal infiltrante subyacente. Los dos presentaban importantes factores de riesgo descritos por otros autores: enfermedad de Hodgkin tratada previamente con radioterapia, en el primer caso, e historia familiar de cáncer de mama en el segundo. Las publicaciones dermatológicas a este respecto son muy escasas. Un mejor conocimiento de las distintas formas clínicas contribuirá a un diagnóstico y tratamiento precoz (AU)
Subject(s)
Adult , Male , Humans , Hodgkin Disease/diagnosis , Breast Neoplasms/diagnosis , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Hodgkin Disease/radiotherapy , Risk Factors , Breast Neoplasms/surgery , Mastectomy/methods , Lymph Node Excision/methods , Carcinoma, Intraductal, Noninfiltrating/surgeryABSTRACT
Plasma cell gingivitis (PCG), an infrequent benign inflammatory condition of unknown etiology, is a type of plasma cell orificial mucositis, which includes a wide spectrum of conditions. We present the case of a 13-year-old girl who had PCG with an erythematous congestive plaque on the anterior maxillary gingiva for 4 years. Occasionally, the lesion became increasingly swollen and painful and bled. Results of a histopathologic examination showed dense plasmacytic infiltrate in the dermis, affecting the dermoepidermal border, with immunohistochemical positivity in the K and A light chains and vascular proliferation. "Lozenge" keratinocytes, "watery" spongiosis, and exocytosis were seen in the epidermis. Laboratory analysis showed notably low levels of both serum IgA and secretory IgA. We consider whether secretory IgA at low levels has an important etiopathogenic role favoring the development of localized subclinical repetitive infections that could lead to chronic PCG.
Subject(s)
Gingivitis/diagnosis , Plasma Cells/pathology , Adolescent , Diagnosis, Differential , Electrocoagulation , Female , Gingivitis/etiology , Gingivitis/pathology , Gingivitis/surgery , Humans , IgA Deficiency/complicationsABSTRACT
The syphilis is a venereal disease of sexual transmission that incidence is increasing in several groups populations. We report a case of a patient with secondary syphilis who consulted for an atypical solid mass to penile. The clinical evolution, histological examination and analytical tests confirmed the diagnosis of genital syphilis having a satisfactory response to specific antibiotic treatment. The epidemiological, clinical, diagnostic aspects and therapeutic of the genital ulcer disease are discussed.
Subject(s)
Penile Diseases , Syphilis , Humans , Male , Middle Aged , Penile Diseases/diagnosis , Penile Diseases/drug therapy , Syphilis/diagnosis , Syphilis/drug therapyABSTRACT
Describimos el caso de una mujer de raza blanca, VIH positiva, que inició erupción cutánea fotosensible coincidiendo con el deterioro de su situación inmune marcada por la disminución de linfocitos CD4 y elevada carga viral. Su evolución clínica fue paralela a la inmunitaria con importante mejoría después de recibir triple tratamiento antiretroviral. Discutimos los aspectos patogénicos de estas fotoerupciones que pueden suponer un marcador clinico de la infección VIH y su progresión. Comentamos la importancia del control de la radiación ultravioleta y puvaterapia en pacientes VIH positivos (AU)
