The Revised European-American Classification of mature lymphoid neoplasms published in 1994 and the 2001, 2008 and 2016 WHO classifications that followed, were the product of international ...collaboration and consensus amongst haematopathologists, geneticists, molecular scientists and clinicians. Primary cutaneous lymphomas were fully incorporated into this process following the publication of the WHO-EORTC classification of cutaneous lymphomas in 2005. The definition, diagnostic criteria and recommended studies for primary cutaneous lymphoma continue to be refined. The 2022 International Consensus Classification represents the most recent update and an overview of all the main entities presenting primarily in the skin, together with the major changes in classification, are summarized herein. Primary cutaneous marginal zone lymphoma is segregated from other extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma) and downgraded to a lymphoproliferative disorder in line with its markedly indolent behaviour. In addition, two subtypes are recognised, based largely but not exclusively on whether they are heavy chain class-switched or IgM positive. Similarly, in keeping with a trend to greater conservatism, primary cutaneous acral CD8 positive T cell lymphoma is now also classified as a lymphoproliferative disorder. In addition, significant new insights into the biology of primary cutaneous lymphoma have also recently been forthcoming and will be presented. These studies have enhanced our knowledge of genetic, epigenetic and transcriptional changes in this group of diseases. They not only identify potential targets for novel therapies, but also raise as yet unanswered questions as to how we categorise cutaneous lymphomas, particularly with respect to relationships with similar lymphomas at extracutaneous sites.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease of controversial origin recently recognized as a neoplasm deriving from plasmacytoid dendritic cells (pDCs). Nevertheless, it ...remains an orphan tumor with obscure biology and dismal prognosis. To better understand the pathobiology of BPDCN and discover new targets for effective therapies, the gene expression profile (GEP) of 25 BPDCN samples was analyzed and compared with that of pDCs, their postulated normal counterpart. Validation was performed by immunohistochemistry (IHC), whereas functional experiments were carried out ex vivo. For the first time at the molecular level, we definitely recognized the cellular derivation of BPDCN that proved to originate from the myeloid lineage and in particular, from resting pDCs. Furthermore, thanks to an integrated bioinformatic approach we discovered aberrant activation of the NF-kB pathway and suggested it as a novel therapeutic target. We tested the efficacy of anti-NF-kB-treatment on the BPDCN cell line CAL-1, and successfully demonstrated by GEP and IHC the molecular shutoff of the NF-kB pathway. In conclusion, we identified a molecular signature representative of the transcriptional abnormalities of BPDCN and developed a cellular model proposing a novel therapeutic approach in the setting of this otherwise incurable disease.
Diagnosis and differential diagnosis of cutaneous lymphoproliferative disorders is one of the most difficult areas in dermatopathology, and biopsies are often taken to rule out a cutaneous lymphoma ...in patients with “unclear” or “therapy-resistant” skin lesions. Histopathological features alone often enable a given case to be classified to a diagnostic group (eg, epidermotropic lymphomas), but seldom allow a definitive diagnosis to be made. Performing several biopsies from morphologically different lesions is suggested, especially in patients with suspicion of mycosis fungoides. Immunohistochemistry is often crucial for proper classification of the cases, but in some instances is not helpful (eg, early lesions of mycosis fungoides). Although molecular techniques provide new, powerful tools for diagnosing cutaneous lymphoproliferative disorders, results of molecular methods should always be interpreted with the clinicopathological features, keeping in mind the possibility of false positivity and false negativity. In many cases, a definitive diagnosis can be made only on careful correlation of the clinical with the histopathological, immunophenotypical and molecular features.
The classification of primary cutaneous lymphomas and lymphoproliferative disorders (LPD) is continuously evolving by integrating novel clinical, pathological and molecular data. Recently two new ...classifications for haematological malignancies including entities of cutaneous lymphomas were proposed: the 5th edition of the WHO classification of haematolymphoid tumours and the International Consensus Classification (ICC) of mature lymphoid neoplasms. This article provides an overview of the changes introduced in these two classifications compared to the previous WHO classification. The main changes shared by both classifications include the downgrading of CD8+ acral T-cell lymphoma to CD8+ acral T-cell LPD, and the recognition of entities that were previously categorized as provisional and have now been designated as definite types including primary cutaneous small or medium CD4+ T-cell LPD, primary cutaneous gamma/delta T-cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, Epstein-Barr virus-positive mucocutaneous ulcer. Both classifications consider primary cutaneous marginal zone B-cell clonal neoplasm as an indolent disease but use a different terminology: primary cutaneous marginal zone lymphoma (WHO) and primary cutaneous marginal zone LPD (ICC). The 5th WHO classification further introduces and provides essential and desirable diagnostic criteria for each disease type and includes chapters on reactive B- or T-cell rich lymphoid proliferations formerly referred as cutaneous pseudolymphomas, as well as histiocyte and CD8 T-cell rich LPD in patients with inborn error of immunity. As already emphasized in previous lymphoma classifications, the importance of integrating clinical, histological, phenotypic and molecular features remains the crucial conceptual base for defining cutaneous (and extracutaneous) lymphomas.
Summary
Background The influence of phenotype and detection of clonality on prognosis in early mycosis fungoides has never been addressed in large studies.
Objectives To correlate immunophenotype ...and detection of clonality with clinical outcome.
Methods We analysed 73 biopsy specimens from 68 patients with early mycosis fungoides (stage Ia or Ib) and at least 10 years of follow up (or dead of disease).
Results Four phenotypic groups could be identified: group A (α/β+ CD4+ CD8− TIA1−), 51 patients; median survival time 160 months; group B (α/β+ CD4− CD8+ TIA1+), 10 patients; median survival time 195 months; group C (α/β− CD4− CD8+/− TIA1+), five patients; median survival time 165 months; and group D (α/β+ CD4− CD8− TIA1−), two patients; median survival time 130 months. Survival curves did not show statistical differences among the groups. Monoclonality was detected in 36 of 67 tested biopsies (54%), and statistical analyses did not show prognostic differences between the clonal and nonclonal cases.
Conclusions We conclude that cytotoxic phenotype and detection of monoclonal T‐cell receptor‐γ gene rearrangement in early lesions of mycosis fungoides do not have any prognostic significance.
Enlarging plaque on the sole Marovt, M.; Cerroni, L.; Marko, P. B.
Clinical and experimental dermatology,
July 2019, 2019-Jul, 2019-07-00, 20190701, Letnik:
44, Številka:
5
Journal Article
Recenzirano
Click here for the corresponding questions to this CME article.
Summary
Background
Primary cutaneous lymphomas comprise a heterogeneous group of B‐cell and T‐cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset ...of patients. Diagnosis is often delayed owing to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages compared with the inflammatory infiltrate, an interplay that is currently only insufficiently understood.
Objectives
To improve diagnostics and perform molecular characterization of a complex type of primary cutaneous lymphoma.
Methods
Single‐cell RNA sequencing (scRNA‐seq) was performed and combined with T‐cell and B‐cell receptor sequencing.
Results
We were able to diagnose a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle centre lymphoma (PCFCL), appearing in mutually exclusive skin lesions. Profiling of tumour cells and the tissue microenvironment revealed a type‐2 immune skewing in MF, most likely guided by the expanded clone that also harboured upregulation of numerous pro‐oncogenic genes. By contrast, PCFCL lesions exhibited a more type‐1 immune phenotype, consistent with its indolent behaviour.
Conclusions
These data not only illustrate the diagnostic potential of scRNA‐seq, but also allow the characterization of specific clonal populations that shape the unique tissue microenvironment in clinically distinct types of lymphoma skin lesions.
What is already known about this topic?
Patients affected by primary cutaneous lymphomas often experience significant diagnostic delay owing to clinical and histopathological similarities with benign inflammatory conditions, especially in early‐stage mycosis fungoides.
What does this study add?
This study provides a proof of concept that single‐cell RNA sequencing can be applied to diagnose primary cutaneous lymphomas, presenting a complex case of discordant lymphoma as an exemplar.
Owing to the existence of two distinct lymphomas within the same organ, we were able to separately demonstrate and compare specific effects of malignant T cells or B cells on the respective tissue microenvironment.
What is the translational message?
This study demonstrates the feasibility of single‐cell RNA sequencing for the diagnosis and characterization of complex cutaneous lymphomas.
Objectives. The aim of this in vitro study was to assess thermal changes on tooth tissues during light exposure using two different LED curing units. The hypothesis was that no temperature increase ...could be detected within the dental pulp during polymerization irrespective of the use of a composite resin or a light-curing unit. Methods. Caries-free human first molars were selected, pulp residues were removed after root resection, and four calibrated type-J thermocouples were positioned. Two LED lamps were tested; temperature measurements were made on intact teeth and on the same tooth during curing of composite restorations. The data was analyzed by one-way analysis of variance (ANOVA), Wilcoxon test, Kruskal-Wallis test, and Pearson’s χ2. After ANOVA, the Bonferroni multiple comparison test was performed. Results. Polymerization data analysis showed that in the pulp chamber temperature increase was higher than that without resin. Starlight PRO, in the same condition of Valo lamp, showed a lower temperature increase in pre- and intrapolymerization. A control group (without composite resin) was evaluated. Significance. Temperature increase during resin curing is a function of the rate of polymerization, due to the exothermic polymerization reaction, the energy from the light unit, and time of exposure.
Background
Panniculitis occurring in dermatomyositis is uncommon, with only a few cases described in the literature, most of them as case reports.
Objective
This report describes the ...clinicopathological and immunohistochemical findings in a series of 18 patients with panniculitis associated with dermatomyositis.
Methods
In each patient, we collected the clinical data of the cutaneous lesions as well as the characteristic clinical and laboratory findings. A series of histopathologic findings was recorded in the biopsy of each patient. A panel of antibodies was used in some cases to investigate the immunophenotype of the infiltrate. Data of treatment and follow‐up were also collected.
Results
Of the 18 patients, 13 were female and 5 were male, ranging in age from 13 to 74 years (median, 46.4 years). In addition to panniculitis, all patients presented pathognomonic cutaneous findings of DM and reported proximal muscle weakness prior to the diagnosis of panniculitis. Muscle biopsy was performed in 17 patients and MRI in one, all with the diagnosis of inflammatory myopathy. None of the patients presented any associated neoplasia. Panniculitis lesions were located in the upper or lower limbs. Histopathology showed a mostly lobular panniculitis with lymphocytes as the main component of the infiltrate. Most cases showed also numerous plasma cells and lymphocytes surrounding necrotic adipocytes (rimming) were frequently seen. Lymphocytic vasculitis and abundant mucin interstitially deposited between collagen bundles of the dermis were also frequent findings. Late‐stage lesions showed hyaline necrosis of the fat lobule and calcification. Immunohistochemistry demonstrated that most lymphocytes of the infiltrate were T‐helper lymphocytes, with some B lymphocytes in the lymphoid aggregates and small clusters of CD‐123‐positive plasmacytoid dendritic cells in the involved fat lobule.
Conclusion
Panniculitis in dermatomyositis is rare. Histopathologic findings of panniculitis dermatomyositis are identical to those of lupus panniculitis. Therefore, the final diagnosis requires clinic–pathologic correlation.
Linked article: This article is commented on by A. Kuhn, pp. 1231–1232 in this issue. To view this article visit https://doi.org/10.1111/jdv.15149
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