Primary cutaneous lymphomas are a heterogeneous group of T- and B-cell lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. The 2005 World Health ...Organization–European Organization for Research and Treatment of Cancer (WHO-EORTC) consensus classification has served as a golden standard for the diagnosis and classification of these conditions. In September 2018, an updated version of the WHO-EORTC was published in the fourth edition of the WHO Classification of Skin Tumours Blue Book. In this classification, primary cutaneous acral CD8+ T-cell lymphoma and Epstein-Barr virus positive (EBV+) mucocutaneous ulcer are included as new provisional entities, and a new section on cutaneous forms of chronic active EBV disease has been added. The term “primary cutaneous CD4+ small/medium T-cell lymphoma” was modified to “primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder” because of its indolent clinical behavior and uncertain malignant potential. Modifications have also been made in the sections on lymphomatoid papulosis, increasing the spectrum of histologic and genetic types, and primary cutaneous marginal zone lymphomas recognizing 2 different subtypes. Herein, the characteristic features of these new and modified entities as well as the results of recent molecular studies with diagnostic, prognostic, and/or therapeutic significance for the different types of primary cutaneous lymphomas are reviewed. An update of the frequency and survival of the different types of primary cutaneous lymphomas is provided.
Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. ...Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISG
) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISG
), low viral loads and abundant infiltrating activated CD8
T cells and macrophages. ISG
patients die significantly earlier after hospitalization than ISG
patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.
CD30+ lymphoproliferative disorders of the skin (CD30+ LPD) represent a well‐defined spectrum of primary cutaneous T‐cell lymphomas which have been recognized as distinct entities in recent lymphoma ...classifications. Lymphomatoid papulosis and anaplastic large‐cell lymphoma share the expression of CD30 antigen as a common phenotypic hallmark but differ in regard to their clinical and histologic features as well as their biologic behavior. This article summarizes the histologic features of CD30+ LPD and presents recently identified new clinicopathologic variants of CD30+ LPD. There is an increasing number of reactive inflammatory disorders and neoplastic diseases which are composed of or contain a significant number of CD30+ cells and mimic LyP or anaplastic large cell lymphoma clinically or histologically. Differential diagnostic considerations focus on other lymphoproliferative processes with CD30+ tumor cells as well as non‐lymphoid neoplasms and inflammatory simulators. The term CD30+ pseudolymphoma is proposed to designate inflammatory processes with CD30+ T cells. The final diagnosis of CD30+ LPD is based on a synthesis of clinical, histologic, phenotypic, and molecular genetic findings.
Primary cutaneous CD30+ lymphoproliferative disorders (CD30+ LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic ...large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30+ LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30+ LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30+ LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30+ LPDs.
Aims
Immune checkpoint inhibitors have become a successful treatment in metastatic melanoma. The high response rates in a subset of patients suggest that a sensitive companion diagnostic test is ...required. The predictive value of programmed death ligand 1 (PD‐L1) staining in melanoma has been questioned due to inconsistent correlation with clinical outcome. Whether this is due to predictive irrelevance of PD‐L1 expression or inaccurate assessment techniques remains unclear. The aim of this study was to develop a standardised digital protocol for the assessment of PD‐L1 staining in melanoma and to compare the output data and reproducibility to conventional assessment by expert pathologists.
Methods and results
In two cohorts with a total of 69 cutaneous melanomas, a highly significant correlation was found between pathologist‐based consensus reading and automated PD‐L1 analysis (r = 0.97, P < 0.0001). Digital scoring captured the full diagnostic spectrum of PD‐L1 expression at single cell resolution. An average of 150 472 melanoma cells (median 38 668 cells; range = 733–1 078 965) were scored per lesion. Machine learning was used to control for heterogeneity introduced by PD‐L1‐positive inflammatory cells in the tumour microenvironment. The PD‐L1 image analysis protocol showed excellent reproducibility (r = 1.0, P < 0.0001) when carried out on independent workstations and reduced variability in PD‐L1 scoring of human observers. When melanomas were grouped by PD‐L1 expression status, we found a clear correlation of PD‐L1 positivity with CD8‐positive T cell infiltration, but not with tumour stage, metastasis or driver mutation status.
Conclusion
Digital evaluation of PD‐L1 reduces scoring variability and may facilitate patient stratification in clinical practice.
Programmed death ligand 1 (PD-L1) is expressed by 20% to 57% of systemic diffuse large B cell lymphomas (DLBCLs). PD-L1 expression in primary cutaneous DLBCL (pcDLBCL) has not been studied so far. ...Sixteen paraffin-embedded tissue samples of pcDLBCL (13 leg type LT, 3 others OT) were investigated for PD-1, PD-L1, and CD33 expression and the cellular composition of the tumor microenvironment, focusing on myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. Membrane-bound PD-L1 expression by the tumor cells was observed in all samples, albeit to a variable extent (19.9%). As expected, most DLBCL-LT (10 cases) were classified as activated B cell like type, with a higher PD-L1 score (21.9%) compared with that of the germinal center B cell like type (7.7%). The surrounding infiltrate consisted predominately of CD163(+) M2 rather than CD68(+) macrophages (CD68:CD163=1:4 to 6). Moreover, a considerable proportion of CD33(+) MDSCs with PD-L1 coexpression was admixed. Tumor cells expressed CD33 to variable degrees (2% to 60%). The number of MDSCs or M2 macrophages did not correlate with pcDLBCL subtypes LT or OT. T cells were only a minor component of the tumor microenvironment. We propose that PD-L1(+) tumor cells and PD-L1(+) MDSCs shield the tumor against PD-1(+) tumor-infiltrating lymphocytes, consequently leading to inhibition and diminution of tumor-infiltrating lymphocytes. Moreover, we found a polarization to M2 macrophages, which may contribute to the poor prognosis of DLBCL patients. Thus, targeting of tumor cells and MDSCs using anti-PD-1/anti-PD-L1 or anti-CD33 antibodies might be a worthwhile new approach to treat this aggressive form of cutaneous B-cell lymphoma.
Background Scleromyxedema is associated with a monoclonal gammopathy and other comorbidities. Its prognostic and therapeutic features are poorly documented because most reports deal with single cases ...or small series. Objective We sought to describe the characteristics of patients with scleromyxedema regarding demographics, clinical characteristics, comorbidities, therapeutic interventions, and course. Methods We conducted a retrospective and prospective multicenter study. Results We identified 30 patients with scleromyxedema (17 men and 13 women). The mean age at diagnosis was 59 years. The mean delay between disease onset and diagnosis was 9 months. Monoclonal gammopathy was detected in 27 patients. Extracutaneous manifestations were present in 19 patients including neurologic (30%), rheumatologic (23.3%), and cardiac (20%) manifestations. Two patients developed hematologic malignancies. The most common therapies included oral steroids and intravenous immunoglobulins. Although corticosteroids were ineffective, intravenous immunoglobulins (alone or in combination with other drugs) induced complete remission in 4 and partial remission in 9 patients with a mean treatment duration of 2 years. In all, 21 patients were followed up for a mean period of 33.5 months, at which time 16 patients were alive, 12 with and 4 without skin disease. Five patients died: 2 with dermatoneuro syndrome and 1 each with myeloid leukemia, Hodgkin lymphoma, and myocardial insufficiency. Limitations This is mainly a retrospective study. Conclusions Our study confirms that scleromyxedema is a chronic and unpredictable disease with severe systemic manifestations leading to a guarded prognosis. There is no specific definitive treatment. Our data support the contention that intravenous immunoglobulin is a relatively effective and safe treatment. The response is not permanent and maintenance infusions are required.
Abstract Cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ T-LPD) represent a spectrum encompassing lymphomatoid papulosis (LyP), primary cutaneous anaplastic large-cell lymphoma (pcALCL) ...and borderline lesions. They share the expression of CD30 as a common phenotypic marker. They differ however in their clinical presentation, the histological features and clinical course. Moreover, LyP and PcALCL show numerous clinical, histological and phenotypic variants. Overlapping features of LyP and pcALCL with themselves and with other cutaneous and systemic lymphomas emphasize the importance of careful clinicopathologic correlation and staging in the diagnosis of CD30+ T-LPD. Furthermore, an increasing number of inflammatory and infectious skin disorders harboring medium-sized to large CD30+ cells have to be considered in the differential diagnosis. Whereas the expression of CD30 in cutaneous CD30+ T-LPD stands for a favourable prognosis, its expression in other cutaneous and systemic lymphomas has a divergent impact. The assessment of CD30 expression does not only provide prognostic information, but is of potential therapeutic relevance as CD30 can serve as a therapeutic target. This review focuses on the clinicopathological and phenotypic spectrum of CD30+ T-LPD, its differential diagnoses and the role of CD30 as a diagnostic, prognostic and therapeutic marker.
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