Yun-Tsan Chang

Expression of CD164 on Malignant T Cells in Sézary Syndrome

Sézary syndrome is a primary cutaneous T-cell lymphoma characterized by pruritic erythroderma, peripheral lymphadenopathy and the presence of malignant T cells in the blood. Unequivocal detection of malignant cells in patients with Sézary syndrome is of important diagnostic, prognostic and therapeutic value. However, no single Sézary syndrome specific cell surface marker has been identified. In a cohort of patients with Sézary syndrome, CD164 expression on total CD4+ lymphocytes was significantly upregulated compared with healthy controls. CD164 expression was in most cases limited to CD4+CD26- malignant T lymphocytes, unequivocally identified using flow-cytometry by the expression of a specific Vβ clone for each patient. Increased expression of CD164 may be a promising diagnostic parameter and a potential target for a CD164-linked therapeutic approach in Sézary syndrome.

Interleukin-1 receptor antagonist (anakinra) for Schnitzler syndrome

Abstract Schnitzler syndrome is a rare autoinflammatory disease, which is defined by the presence of two major criteria: chronic urticaria and monoclonal immunoglobulin M (IgM) or immunoglobulin G gammopathy, in combination with at least two additional minor criteria: recurrent fever, leukocytosis and/or elevated C-reactive protein (CRP), objective signs of abnormal bone remodelling and a neutrophilic infiltrate in skin biopsy. We report on a 68-year-old female patient with a 10-year medical history of chronic urticaria, recurrent fever, severe arthralgia and increased CRP. Over the years, multiple diagnostic investigations were performed without conclusive findings, and therapeutic attempts with anti-histamines and several immunosuppressive agents had failed. The decision to initiate monotherapy with interleukin-1 (IL-1) receptor antagonist was based on immunohistochemical detection of the abundance of IL-1β positive cells in the patient’s skin biopsy. After starting treatment with anakinra, disappearance of symptoms could be observed within 24 h. Discontinuation of the treatment resulted in a rapid relapse of the symptoms. Finally, already after the initiation of therapy with anakinra, the suspected diagnosis of Schnitzler syndrome could be confirmed by detection of IgM-gammopathy that was initially absent.

PD-L1 expression is an independent predictor of favorable outcome in patients with localized esophageal adenocarcinoma

ABSTRACT Background. The outcome of patients with adenocarcinoma of the esophagogastric junction (AEG) remains poor. The programmed cell-death-protein-1 (PD-1), a co-inhibitory receptor primarily expressed by T-cells, represents a potential new therapeutic target. PD-1, PD-1 ligand 1 (PD-L1), and PD-L2 expression have all been described as prognostic factors in a variety of cancers. Their expression patterns in AEG, however, are poorly understood. We analyzed PD-L1, PD-L2 and PD-1 expression by tumor-infiltrating lymphocytes (TILs) and cancer-cells in tumor-biospecimens in AEG-patients. Methods. 168 patients who underwent esophagectomy because of AEG between 1992–2011 were included in this study. PD-L1, PD-L2 and PD-1 expression were evaluated by immunohistochemistry and correlated with various clinicopathological parameters, disease-free survival (DFS) and long-term overall survival (OS). Results. PD-L1 expression by cancer-cells (cancer-cell-PD-L1+) was found in 43.5% of patients whereas PD-L1 expression by TILs (TILs-PD-L1+) was observed in 69%. PD-L2 expression by cancer-cells and TILs was only found in 3.5% and 1.8%, respectively. Additionally, 77.4% of tumors contained PD-1+-cancer-cells and 81% PD-1+-TILs. Patients with increased expression of PD-1 by cancer-cells and TILs showed significantly reduced OS and DFS, as determined by univariate, but not multivariate analysis. Expression of PD-L1 by cancer-cells was found to be an independent predictor for improved DFS (p = 0.038) and OS (p = 0.042) in multivariate analysis. Conclusions. Cancer cells and TILs displayed PD-L1 expression in around 50% and PD-1 expression in around 80% of tumor-biospecimens obtained from AEG patients. Expression of PD-L1 is an independent predictor of favorable outcome in AEG, whereas PD-1 expression is associated with worse outcome and advanced tumor stage.

Aggressive Rare T-cell Lymphomas with Manifestation in the Skin: A Monocentric Cross-sectional Case Study

Rare T- or NK-cell lymphomas with cutaneous manifestation may display a highly aggressive clinical course and major diagnostic/therapeutic challenges. This report describes our experiences with different lymphomas of this rare category and the therapeutic options used. This retrospective, descriptive, monocentric, cross-sectional case study, identified 4 rare aggressive T-/NK-cell lymphomas with manifestation in the skin, which were diagnosed in a tertiary care centre over a period of 4 years. Two patients had an Epstein-Barr virus-associated extranodal NK/T-cell lymphoma and 2 patients had a primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma. Concomitant extracutaneous involvement was observed in 2 of all 4 patients. Two patients had fulminant disease progression and resistance to chemotherapy. Two patients underwent allogeneic haematopoietic stem cell transplantation, which resulted in one complete remission and one partial remission. This report emphasizes the importance of an early diagnostic work-up and a prompt aggressive therapeutic approach.