Paraneoplastic Pemphigus Is a Life-Threatening Disease

Paraneoplastic pemphigus is a multiorganic autoimmune disease, usually triggered by neoplasias, mainly of lymphoproliferative origin such as chronic lymphocytic leukemia, multiple myeloma, non-Hodgkin’s lymphoma, Castleman disease, and thymoma. This disorder is characterized by the presence of autoantibodies that react against proteins, such as desmoplakins, desmocollins, and others existing in cell junctions. The prognosis is reserved, and the mortality rate of the disease is very high, thus proving to be an additional challenge in the therapeutic management of onco-hematological diseases. The objective of this chapter is to solve the main clinical aspects of paraneoplastic pemphigus in lymphoproliferative hematological diseases, anatomopathological and immunofluorescence characteristics, as well as associations with the main differential diagnoses and therapeutic management. We will also describe the main differential diagnoses of paraneoplastic pemphigus, such as various types of pemphigus including induced drug, bullous pemphigoid, drug eruption, lichen planus, graft versus host disease, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. In addition, the prognosis and quality of life will be mentioned

Paraneoplastic pemphigus associated with chronic lymphocytic leukemia: a case report

Abstract Background Paraneoplastic pemphigus is a rare multiorgan disease of autoimmune causes, usually triggered by neoplasias, mainly of lymphoproliferative origin, such as leukemia and lymphoma. This disorder is categorized by the presence of autoantibodies that react against proteins, such as desmoplakins, desmogleins, desmocollins, and others that exist in cellular junctions. Paraneoplastic pemphigus can manifest clinically in a variety of ways, ranging from mucositis to lesions involving the skin and pulmonary changes. The diagnosis depends on the correlation between the clinical and histopathologic evaluations. Currently, the treatment of this disease is still very difficult and ineffective. The prognosis is poor, and the mortality rate is very high. Case presentation We report a case of a Caucasian patient who had chronic lymphocytic leukemia and developed paraneoplastic pemphigus with severe impairment of skin and mucosa. The initial diagnostic hypothesis was Stevens-Johnson syndrome. The histopathological examination of the skin biopsy was compatible with paraneoplastic pemphigus, and the definitive diagnosis was made on the basis of clinical-pathological correlation. Conclusions With the presence of multiorgan lesions in patients with lymphoproliferative neoplasia, paraneoplastic pemphigus should always be considered among the possible diagnostic hypotheses, because diagnosis and early treatment may allow a better prognosis for the patient

Biological and therapeutic implications of RKIP in Gastrointestinal Stromal Tumor (GIST): an integrated transcriptomic and proteomic analysis

Abstract Background Gastrointestinal stromal tumors (GIST) represent a significant clinical challenge due to their metastatic potential and limited treatment options. Raf kinase inhibitor protein (RKIP), a suppressor of the MAPK signaling pathway, is downregulated in various cancers and acts as a metastasis suppressor. Our previous studies demonstrated low RKIP expression in GIST and its association with poor outcomes. This study aimed to expand on the previous findings and investigate the biological and therapeutic implications of RKIP loss on GIST. Methods To validate the RKIP prognostic significance, its expression was evaluated by immunohistochemistry in 142 bona fide GIST cases. The functional role of RKIP was evaluated in vitro, using the GIST-T1 cell line, which was knocked out for RKIP. The biological and therapeutic implications of RKIP were evaluated by invasion, migration, apoptosis, and 2D / 3D viability assays. Additionally, the transcriptome and proteome of RKIP knockout cells were determined by NanoString and mass spectrometry, respectively. Results Immunohistochemical analysis revealed the absence of RKIP in 25.3% of GIST cases, correlating with a tendency toward poor prognosis. Functional assays demonstrated that RKIP knockout increased GIST cells’ invasion and migration potential by nearly 60%. Moreover, we found that RKIP knockout cells exhibited reduced responsiveness to Imatinib treatment and higher cellular viability in 2D and 3D in vitro models, as assessed by apoptosis-related protein expression. Through comprehensive genetic and proteomic profiling of RKIP knockout cells, we identified several putative RKIP-regulated proteins in GIST, such as COL3A1. Conclusions Using a multidimensional integrative analysis, we identified, for the first time in GIST, molecules and pathways modulated by RKIP that may potentially drive metastasis and, consequently, poor prognosis in this disease