transforming-growth-factor-beta and Paraneoplastic-Syndromes

Topics: Adenocarcinoma; Aged; Colonic Neoplasms; Dermatomyositis; Female; Humans; Lymphatic Metastasis; Lymphocytes; Paraneoplastic Syndromes; Signal Transduction; Smad4 Protein; Transcription Factors; Transforming Growth Factor beta

Systemic plasma cell dyscrasias have diverse manifestations in the skin and include an inflammatory paraneoplastic process. We encountered cases of scleroderma and eosinophilic fasciitis in the setting of an underlying plasma cell dyscrasia.. Ten cases of scleroderma-like tissue reactions in the setting of an underlying plasma cell dyscrasia were encountered. The biopsies were stained for Transforming growth factor (Transforming growth factor) beta, IgG4, kappa, and lambda.. Patients presented with a sclerodermoid reaction represented by eosinophilic fasciitis (5 cases), morphea (3 cases), and systemic scleroderma (2 cases). The mean age of presentation was 70 years with a striking female predominance (4:1). Acral accentuation was noted in 8 cases. In 6 of the cases, the cutaneous sclerosis antedated (4 cases) by weeks to 2 years or occurred concurrently (2 cases) with the initial diagnosis of the plasma cell. The biopsies showed changes typical of eosinophilic fasciitis and/or scleroderma. In 5 cases, light chain-restricted plasma cells were present on the biopsy. There was staining of the plasma cells for Transforming growth factor beta in 3 out of 5 cases tested.. In any older patient presenting with a sudden onset of eosinophilic fasciitis or scleroderma especially with acral accentuation, investigations should be conducted in regards to an underlying plasma cell dyscrasia.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Eosinophilia; Fasciitis; Female; Humans; Immunoglobulin G; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunohistochemistry; Male; Middle Aged; Paraneoplastic Syndromes; Paraproteinemias; Prognosis; Scleroderma, Localized; Scleroderma, Systemic; Skin; Transforming Growth Factor beta

Focusing on CD4(+)CD25(+) regulatory T lymphocytes (T(reg)), we studied the gene expression of T(reg) functional molecules in peripheral blood lymphocytes of patients with paraneoplastic neurological syndrome (PNS), including Lambert-Eaton myasthenic syndrome (LEMS) with small cell lung carcinoma (SCLC) and anti-Hu- or anti-Yo-antibody-positive PNS. T(reg)-rich subsets were sorted from the patients' peripheral blood mononuclear cells, and the mRNA expression levels of their functional genes were measured. The expression levels of FOXP3, TGF-beta and CTLA4 mRNA in T(reg)-rich subsets of PNS patients were down-regulated compared with that of SCLC patients without PNS. These results suggest that T(reg) dysfunction plays a role in PNS development.

Topics: Adult; Antibodies; Antigens, CD; CTLA-4 Antigen; ELAV Proteins; Female; Flow Cytometry; Forkhead Transcription Factors; Gene Expression Regulation; Humans; Interleukin-2 Receptor alpha Subunit; Male; Middle Aged; Nerve Tissue Proteins; Paraneoplastic Syndromes; RNA, Messenger; T-Lymphocytes, Regulatory; Transforming Growth Factor beta