Cutaneous CD30 Research Articles

Automatic CD30 scoring method for whole slide images of primary cutaneous CD30+ lymphoproliferative diseases

AimsDeep-learning methods for scoring biomarkers are an active research topic. However, the superior performance of many studies relies on large datasets collected from clinical samples. In addition, there are fewer...

Clinical features and treatment outcomes for primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder: a retrospective cohort study from the Dana-Farber Cancer Institute and updated literature review

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-TCLPD) was reclassified in 2016 as a rare benign entity with an excellent prognosis, yet its clinical features and best treatments remain poorly defined. We collected clinical data, treatments, and treatment-responses from our institution’s patients with PCSM-TCLPD through September 2018 and an identical PubMed review through June 2021. Among 36 cases (median-age 54 years; 58.3% head/neck), diagnostic biopsy resulted in sustained complete remission (CR) in 13/33 punch/shave biopsies and 3/3 excisional biopsies. The remaining 20 patients further required topical corticosteroids (n = 5); intralesional corticosteroids (n = 1); surgical-excision (n = 5); electron-beam-radiation (n = 6); or brachytherapy (n = 3). All patients ultimately achieved CR, excluding one patient continuing treatment at end-of-study. 57/59 (96.6%) of institutional and literature-reported radiation-treated patients experienced CR. No institutional cases progressed beyond skin; 5/209 (2.4%) literature-reported cases progressed to systemic/extracutaneous involvement, all pre-reclassification. PCSM-TCLPD responds well to local-directed therapy including radiation, and only rarely if ever progresses.

Expression pattern and diagnostic utility of BCL11B in mature T- and NK-cell neoplasms

BCL11B is an essential transcription factor for T-cell lineage commitment and differentiation, and its dysregulation has been shown to be associated with T-cell tumourigenesis. In this study, we investigated BCL11B expression by immunohistochemical analysis in 120 cases of mature T-cell lymphoma, 34 B-cell lymphomas, 11 NK-cell neoplasms and 17 reactive cutaneous conditions. All cases of mycosis fungoides (n=23), primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (n=8) and T-prolymphocytic leukaemia (n=6) were positive for BCL11B and the staining intensity was higher than that of reactive T-cells. Fourteen of 15 (93%) cases of angioimmunoblastic T-cell lymphoma, 10 of 12 (83%) T-large granular lymphocytic leukaemia and 14 of 20 (70%) peripheral T-cell lymphoma, not otherwise specified, were also positive for BCL11B with an intensity comparable to reactive T-cells. Other T-cell neoplasms were uncommonly positive including one of three (33%) cases of primary cutaneous gamma delta T-cell lymphoma, one of four (25%) cases of subcutaneous panniculitis-like T-cell lymphoma, one of four (25%) cases of hepatosplenic T-cell lymphoma, and one of 20 (5%) cases of anaplastic large cell lymphoma (8 ALK-positive, 12 ALK-negative). T-cells in reactive cutaneous infiltrates were also positive for BCL11B, but staining intensity was much weaker than in mycosis fungoides. All NK-cell (n=11) and B-cell neoplasms (n=34) were negative for BCL11B. In conclusion, BCL11B shows a distinct expression pattern in various T-cell neoplasms. BCL11B appears to have utility as another T-cell marker and may be useful in the differential diagnosis of lymphoid neoplasms.

Efficacy of brentuximab vedotin in patients with CD30-positive lymphoproliferative skin diseases: results of the first prospective study in the Russian Federation

Background. Primary cutaneous lymphomas are the second most common group of extranodal lymphomas. Unlike nodal lymphomas, which are characterized by predominant B-cell proliferation, primary cutaneous T-cell lymphomas account for 6575% of all cutaneous lymphomas. About 50% of all cutaneous T-cell lymphomas are mycosis fungoides (MF). CD30-positive lymphoproliferative disorders (CD30+ LPD) occupy the second place in the incidence of cutaneous T-cell lymphomas, while 10% are rare disease forms such as primary cutaneous peripheral T-cell lymphoma not otherwise specified (PTLNOS), Szary syndrome (SS), etc.
 Treatment of MF/SS patients in the Russian Federation shows that about 30% of individuals are resistant to various therapeutic effects, especially in the later stages. The problem of CD30+ LPD treatment is extracutaneous dissemination in the case of primary cutaneous anaplastic large cell lymphoma (pcALCL) and steadily relapsing lymphomatoid papulosis (LyP) without symptom-free intervals. These aspects of the therapy of cutaneous lymphomas highlight the need to search for new treatment options.
 According to the results of the international randomized ALCANZA trial, brentuximab vedotin (BV) has shown high efficiency in the treatment of cutaneous T-cell lymphoproliferative disorders.
 Study objective. The study aim is to evaluate BV efficacy in the group of poor prognosis patients with cutaneous T-cell lymphomas who has received at least one line of systemic therapy.
 Materials and methods. The study included 21 patients: 16 men and 5 women. There were 8 patients with MF, 5 patients with SS; 6 individuals had cutaneous CD30+ LPD (including 5 patients with pcALCL and 1 individual with LyP) and 2 patients were diagnosed with PTLNOS. Cutaneous T-cell lymphoma was confirmed based on the medical history, nature of cutaneous lesions, as well as histological, immunohistochemical, and, in some cases, molecular genetic testing of the skin biopsy sample (analysis of T-cell receptor gene rearrangement).
 Results. Late stages of the disease were diagnosed in 12 out of 13 patients with MF/SS. Extracutaneous lesions were diagnosed in 57% of cases. The median of prior lines of therapy was 3 (18 variants of treatment). The overall response to the treatment was achieved in 91% of cases (19 out of 21 patients): complete remission was observed in 53% of patients, very good partial remission was achieved in 31% of individuals, and partial remission was noted in 16% of cases. Disease progression was found in 2 patients (after cycles 1 and 4). Some patients with partial remission after BV therapy underwent additional therapy (radiation therapy, interferon therapy, and cycles of systemic therapy), which made it possible to achieve a more pronounced antitumor response. Early relapse was diagnosed in 2 out of 19 patients who had responded to the treatment. The treatment tolerability was acceptable, and the toxicity did not exceed that described in the previous studies. Thus, the overall stable antitumor response persisted in 89% of patients (the median follow-up was 10 months).
 Conclusion. The use of targeted therapy with BV made it possible to achieve high treatment results in patients with advanced stages of the disease and the absence of response to several lines of therapy.

Improved understanding about different types of CD8 + cutaneous lymphomas

British Journal of DermatologyVolume 186, Issue 5 p. 208-208 Plain Language Summary Improved understanding about different types of CD8+ cutaneous lymphomas First published: 02 May 2022 https://doi.org/10.1111/bjd.21261AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Kempf et al. Br J Dermatol 2022; 186:887–897. CD8+ cutaneous lymphomas are skin cancers that arise from types of cells that are important in immune defences called CD8+ T-lymphocytes. CD8+ cutaneous lymphomas are rare cancers. There are several different types – they share some histological features (features that can be seen under the microscope) but some types are more serious than others. Knowing more about them will help with diagnosis and treatment. This study, with authors and patients from around the world, set out in improve our understanding about the clinical and histological features of these cancers, their outcome and their differences. Knowing more about their differences will help make sure patients receive the best treatment for the specific type of CD8+ cutaneous lymphoma they have. Data about 46 patients with 55 skin biopsies (where a small section of tissue is removed for testing) were analysed by the international European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Group. They found that these cancers could be divided into three distinct groups. The first group is: cutaneous acral CD8+ T-cell lymphoma. There were 31 patients with this type. The outcome for this type is generally good. The second group is: primary cutaneous CD8+ peripheral T-cell lymphoma, unspecified/not otherwise specified. There were 11 patients with this type. The third group is: cutaneous CD8+ tumours associated with congenital or acquired immunodeficiency syndromes. There were four patients with this type. The findings of this study will help doctors to diagnose the specific type of CD8+ cutaneous lymphoma patients have so that they can receive the most appropriate treatment. Volume186, Issue5May 2022Pages 208-208 RelatedInformation

Clinical, histopathological and prognostic features of primary cutaneous acral CD8+ T-cell lymphoma and other dermal CD8+ cutaneous lymphoproliferations: results of an EORTC Cutaneous Lymphoma Group workshop.

The differential diagnosis of atypical dermal nonepidermotropic CD8+ lymphocytic infiltrates includes a heterogeneous spectrum of lymphoproliferations with overlapping histological and phenotypic features, but divergent clinical manifestations and prognoses. As these neoplasms are rare, more data on their clinicopathological presentation and course are needed. To assess the clinical, histological and immunophenotypic features; outcomes of; and differences between dermal CD8+ lymphoproliferations. Retrospective analysis of a series of 46 patients and biopsies by the international EORTC Cutaneous Lymphoma Group. The dermal CD8+ lymphoproliferations (n = 46) could be assigned to one of three groups: (i) cutaneous acral CD8+ T-cell lymphoma (n = 31), characterized mostly by a solitary nodule arising at acral sites, a monotonous dermal infiltrate of small-to-medium-sized CD8+ lymphocytes with a characteristic dot-like pattern of CD68, a low proliferation rate and an excellent prognosis; (ii) primary cutaneous CD8+ peripheral T-cell lymphoma, unspecified/NOS (n = 11), presenting with one or multiple rapidly evolving tumours, mostly medium-sized pleomorphic CD8+ tumour cells with expression of several cytotoxic markers, and high proliferative activity; and (iii) cutaneous CD8+ lymphoproliferations (n = 4), associated with congenital immunodeficiency syndromes in two patients with persisting localized or disseminated violaceous to brownish plaques on the extremities, a histiocyte-rich infiltrate of mostly small CD8+ lymphocytes with subtle atypia and a protracted course; and papular CD8+ eruptions in two patients with acquired immunosuppression. A constellation of distinct clinical, histopathological and phenotypic features allows discrimination and assignment of dermal CD8+ infiltrates into distinct disease entities. Primary cutaneous acral CD8+ lymphoma, assigned a provisional category in current lymphoma classifications, is a distinct and reproducible entity. A correct diagnosis is essential to avoid unnecessarily aggressive treatment for indolent CD8+ lymphoproliferations and to identify cases with underlying immuno-deficiency or potential for dismal outcome.

Cutaneous CD4+ T cell subsets promote distinct outcomes in human keratinocytes and fibroblasts

Abstract Epithelial, stromal, and immune cells in the skin cooperate to ensure appropriate response to pathogens and environmental damage. Recent single cell transcriptional analyses of healthy and fibrotic human skin revealed a wide range of phenotypes that arise in response to distinct cytokine milieu. Cutaneous T cells promote host defense and the subsequent resolution of inflammation and repair of damaged skin through the production of cytokines, but the precise mechanisms T cells use to impact the differentiation and function of skin cells involved in inflammatory and tissue-repair responses remain understudied. To assess the functional capacity of cutaneous lymphocytes we isolated skin-tropic and skin-resident T helper cells including a novel population of pro-fibrotic migratory tissue resident memory cells we recently discovered. We measured both quantitative T cell cytokine production following TCR stimulation, and the impact of T cell derived cytokines on human keratinocyte and fibroblast transcriptional profile and morphology. We find that phenotypically and functionally distinct circulating and skin-resident T cell subsets have the capacity to promote discrete cytokine-dependent transcriptional and cellular outcomes in the skin including the induction of metabolic, proliferative, and inflammatory gene profiles. Thus, cutaneous T cells support host-protective and tissue-repair responses through direct activity on keratinocytes and dermal fibroblasts.

Intestinal inflammation alters the antigen-specific immune response to a skin commensal.

SUMMARYResident microbes in skin and gut predominantly impact local immune cell function during homeostasis. However, colitis-associated neutrophilic skin disorders suggest possible breakdown of this compartmentalization with disease. Using a model wherein neonatal skin colonization by Staphylococcus epidermidis facilitates generation of commensal-specific tolerance and CD4+ regulatory T cells (Tregs), we ask whether this response is perturbed by gut inflammation. Chemically induced colitis is accompanied by intestinal expansion of S. epidermidis and reduces gut-draining lymph node (dLN) commensal-specific Tregs. It also results in reduced commensal-specific Tregs in skin and skin-dLNs and increased skin neutrophils. Increased CD4+ circulation between gut and skin dLN suggests that the altered cutaneous response is initiated in the colon, and resistance to colitis-induced effects in Cd4creIl1r1fl/fl mice implicate interleukin (IL)-1 in mediating the altered commensal-specific response. These findings provide mechanistic insight into observed connections between inflammatory skin and intestinal diseases.

Primary cutaneous lymphoma: the 2018 update of the WHO-EORTC classification

Primary cutaneous lymphomas are a heterogeneous group of cutaneous T-cell lymphomas (CTCL) and cutaneous B-cell lymphomas (CBCL) that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. In the last decade the 2005 WHO-EORTC consensus classification has served as a golden standard for the diagnosis and classification of these conditions. Recently, an updated version of the WHO-EORTC was published. This classification contains several new entities, including primary cutaneous acral CD8+ T-cell lymphoma and EBV-positive mucocutaneous ulcer, while other conditions were slightly modified. Herein, the characteristic features of the different types of CTCL and CBCL are presented, differences with previous classification schemes discussed and the results of more recent molecular studies with clinical implications for these conditions reviewed. In addition, an update of the frequency and survival of the different types of primary cutaneous lymphomas is provided.

Pediatric Cutaneous Hematologic Disorders: Cutaneous Lymphoma and Leukemia Cutis-Experience of a Tertiary-Care Pediatric Institution and Review of the Literature.

Cutaneous hematologic malignancies are rare in children, and the literature about them is still sparse. The purpose of our study was to report our experience with pediatric cases of cutaneous hematologic disorders and describe their clinical and histological features. Data were retrospectively collected from the histopathologic database of the CHU Sainte-Justine, University of Montreal, Montreal, Canada. All patients up to 18 years of age with a diagnosis of a primary cutaneous lymphoma (including lymphomatoid papulosis), secondary cutaneous lymphoma or cutaneous manifestations of leukemia, followed from 1980 to 2019 at our center were reviewed. Thirty-six patients were included. Age at presentation ranged from birth to 18 years of age (mean 7.83 ± 5.16; median 7.0). Ten different hematologic disorders were identified according to the WHO-EORTC classifications: lymphomatoid papulosis (10 cases), mycosis fungoides (6 cases), anaplastic large cell lymphoma (4 cases), pre-B acute lymphoid leukemia (5 cases), primary cutaneous marginal zone B-cell lymphoma (4 cases), primary cutaneous CD4+medium T-cell lymphoproliferative disorder (1 case), extranodal NK/T-cell lymphoma (1 case), hydroa vacciniforme-like lymphoproliferative disorder (1 case), B-cell lymphoblastic lymphoma (1 case) and acute myeloid leukemia (3 cases). The most common subtype of cutaneous hematologic disease in our single institution study was lymphomatoid papulosis (type A and type C), followed by mycosis fungoides. Recognition of this large clinical and histological spectrum by dermatologists is important because diagnosis is often established by biopsy of skin lesions, even in secondary cutaneous cases. Moreover, the clinicopathological correlation is of utmost importance for the final diagnosis of those pathologies.

CD8+ mycosis fungoides: A wolf in sheep’s clothing?

Sir, CD8+ mycosis fungoides (MF) is a rare form of MF with an indolent course. Herein, we report a rare case of CD8+ fungoid mycosis preceded by lymphomatoid papulosis type D with an aggressive course. A 36-year-old female presented with several papular lesions on the trunk and extremities with a relapsing–remitting course. Histopathology and an immunohistochemical study confirmed CD8-positive lymphomatoid papulosis type D and methotrexate at 25 mg/week was initiated. After a temporary clinical improvement, the lesions worsened, became infiltrated, and grouped as vaguely annular and angular patches with serpiginous borders (Fig. 1). A second scalp biopsy was performed and a diagnosis of CD8+ MF was established. An extension workup was normal, and MF was classified as stage IB. PUVA therapy was started with acitretin at 25 mg/day. After four weeks from the beginning of treatment, the patches completely disappeared but with the concomitant appearance of four subcutaneous tumors. The evolution was spectacular in fifteen days, with the tumors rapidly increasing in size, becoming ulcerative and necrotic, and one being localized in the left cervical area compressing the upper respiratory tract (Fig. 2). A subsequent biopsy revealed massive epidermal and dermal large cell infiltration (Fig. 3a); the tumor cells were positive for CD3, CD8, and CD7 (Fig. 3b) and negative for CD4, CD5, CD3, CD2, and CD30. Antigen Ki-67 was expressed by more than 80% of T-cells (Fig. 3c). A cerebral and thoraco-abdominal CT scan revealed multiple axillary lymph nodes with hypermetabolism on a PET scan. An osteomedullar biopsy was normal, and lactate dehydrogenase (LDH) was increased to 358 U/L. Chemotherapy was performed, but the patient died after two cycles of CHOEP. In contrast to classical CD4+ mycosis fungoides, CD8+ MF is a rare cytotoxic phenotype constituting about 5% of all cases of MF [1]. It belongs to the first group of primary cytotoxic cutaneous lymphomas (PCCL) with a good prognosis, an indolent course, and a slow progression of the lesions over several years [2]. However, rare cases with a more aggressive course have been reported in the literature [3]. The main differential diagnosis of aggressive CD8+ MF is an aggressive epidermotropic cutaneous CD8+ lymphoma that is a rare cutaneous lymphoma with a poor prognosis due to rapid extracutaneous dissemination [4]. The prognosis of the CD8+ subtype of mycosis fungoides (MF) is controversial. More studies are necessary to clarify this subject.

An Automatic CD30 Scoring Method for Few Shot Whole Slide Images of Primary Cutaneous CD30 + Lymphoproliferative Diseases

An Automatic CD30 Scoring Method for Few Shot Whole Slide Images of Primary Cutaneous CD30 + Lymphoproliferative Diseases

Primary Cutaneous CD30+ Type Pleomorphic Immunoblastic Cell Lymphoma

Primary Cutaneous CD30+ Type Pleomorphic Immunoblastic Cell Lymphoma

Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorder in an Unusual Location.

Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorder in an Unusual Location.

Патоморфологическая диагностика первичного кожного CD4-позитивного Т-клеточного лимфопролиферативного заболевания из мелких и средних клеток: серия из 28 случаев

Introduction. Primary cutaneous CD4+ lymphoproliferative disorder of small and medium cells (PC CD4+ T-LPD small/medium cell) is a new entity identified in the WHO classification published in 2017. The aim of the research was to characterize morphological and immunohistochemical features of PC CD4+ T-LPD small/medium cell. Materials and methods. The study examined 28 skin biopsies from 13 males and 15 females with PC CD4+ T-LPD small/medium cell using histological and immunohistochemical methods. Results. We detected growth pattern to be of nodular, focal–diffuse, and diffuse types. Each case was characterized by significant T-cell lymphoid infiltration with an immunophenotype of follicular T-helper cells (Tfh-immunophenotype), the number of B-cells varying. Conclusion. PC CD4+ T-LPD from small and medium cells is a rare disease that requires further study to determine the criteria for diagnosis and treatment. Keywords: primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, T follicular helper cells, immunophenotype

Lack of PRAME Expression in Cutaneous T-Cell Lymphomas.

Cutaneous T-cell lymphomas (CTCLs) are rare tumors with no established markers that can reliably distinguish between benign and malignant lesions. Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen that is found in many solid and hematologic malignancies. PRAME overexpression typically portends a poor prognosis and lower chemotherapeutic response. To date, no studies have established a role for PRAME in CTCL. An analysis was performed on 47 cases definitively diagnosed as CTCL: 25 cases of mycosis fungoides, 2 of Sezary syndrome, 5 of CD30+ lymphoproliferative disorder, 7 of primary cutaneous anaplastic large T-cell lymphoma, 3 of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, 1 of subcutaneous panniculitis-like T-cell lymphoma, and 4 of angiocentric T-cell lymphoma. PRAME immunohistochemistry was completely negative in all cases. PRAME expression was not found in any CTCL subtypes, suggesting that the pathogenesis of CTCL is not mediated by PRAME. Further study is required to identify biomarkers that might aid in the diagnosis and prognostication of CTCLs.

Transcriptomic Profiling of Plaque Psoriasis and Cutaneous T-Cell Subsets during Treatment with Secukinumab

The IL-17A inhibitor secukinumab is efficacious for the treatment of psoriasis. To better understand its mechanism of action, we investigated its impact on psoriatic lesions from 15 patients with moderate-to-severe plaque psoriasis undergoing secukinumab treatment. We characterized the longitudinal transcriptomic changes of whole lesional skin tissue as well as cutaneous CD4+ and CD8+ T effector cells and CD4+ T regulatory cells across 12 weeks of treatment. Secukinumab was clinically effective and reduced disease-associated overexpression of IL17A, IL17F, IL23A, IL23R, and IFNG in whole tissue as soon as 2 weeks after initiation of treatment. IL17A overexpression in T-cell subsets, primarily CD8+ T cells, was also reduced. Although secukinumab treatment resolved 89‒97% of psoriasis-associated expression differences in bulk tissue and T-cell subsets by week 12 of treatment, we observed expression differences involved in IFN signaling and metallothionein synthesis that remained unresolved at this time point as well as potential treatment-associated expression differences involved in IL-15 signaling. These changes were accompanied by shifts in broader immune cell composition on the basis of deconvolution of RNA-sequencing data. In conclusion, our study reveals several phenotypic and cellular changes within the lesion that underlie clinical improvement from secukinumab.

Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts

BackgroundPrimary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and...

Modern possibilities of therapy for primary cutaneous T-cell lymphomas: the first results of the use of brentuximab vedotin in the Russian Federation

Background. Primary cutaneous T-cell lymphomas are rare heterogeneous group of lymphoproliferative diseases characterized by primarily involving skin and subcutaneous adipose tissue. Half of these cases are mycosis fungoides (MF), for about 25% are cutaneous CD30+ lymphoproliferative diseases (CD30+ LPD): primary cutaneous anaplastic large cell lymphoma (pcALCL) and lymphomatoid papulosis (LyP). During the initiating treatment of patients with MF and Szary syndrome (SS), carried out on the territory of the Russian Federation, for about 30% of patients are resistant to various therapeutic effects, especially in the later stages. The problem of the treatment of CD30+ LPD is extracutaneous dissemination in case of pcALCL, steadily relapsing course of LyP without symptom-free intervals. These characteristics of the therapy of cutaneous lymphomas demand for the need to search for new treatment options. Brentuximab vedotin, according to the results of the international randomized ALCANZA trial, has shown high efficiency in the treatment of cutaneous T-cell lymphoproliferative diseases. Aim. To evaluate the efficacy of brentuximab vedotin application in patients with cutaneous T-cell lymphomas in adverse risk group received at least one line of systemic therapy. Materials and methods. The study included 21 patients: 16 men and 5 women. The diagnosis of MF was verified in 8 patients, SS in 5 patients, cutaneous CD30+ LPD in 6 patients (5 patients pcALCL, 1 patient LyP) and a primary cutaneous peripheral T-cell lymphoma, unspecified in 2 patients. The diagnosis of cutaneous T-cell lymphoma was verified on the basis of the anamnesis of the disease, on the character of cutaneous lesions, on histological, immunohistochemical and in some cases on molecular genetic testing of the biopted sample of the skin (the assessment of T-cell receptor gene rearrangement). Results. The late stages of the disease were diagnosed in 12 of 13 patients with MF/SS. Extracutaneous lesions were diagnosed in 57% of cases. The median of prior lines therapy was 3 (18 variants of treatment). The overall response to the treatment was achieved in 91% of cases (in 19 of 21 patients): the complete remission was obtained in 53% of cases, very good partial remission in 31% of cases and partial remission in 16% of cases. The progression of the disease was determined in 2 patients (after the first and fourth cycles). Some patients with partial remission as a result of therapy using brentuximab vedotin had the additional therapy (radiation therapy, interferon , the cycles of systemic therapy) and these acts gave an option of achieving deeper antitumor response. The early relapse was diagnosed in 2 of 19 patients who had responded to the treatment. The treatment tolerability was acceptable, and the toxicity did not exceed the already known one described in earlier studies. Thus, the stable overall antitumor response had been persisting in 89% of patients (the median of the observation was 10 months). Conclusion. The use of targeted therapy with brentuximab vedotin gave an option of achieving high treatment results in group of patients with advanced stages of the disease and inefficiency of several lines of therapy.

Genomic Analysis of Cutaneous CD30-Positive Lymphoproliferative Disorders

Primary cutaneous CD30+ T-cell lymphoproliferative disorders are the second most common cutaneous lymphomas. According to the World Health Organization, CD30+ T-cell lymphoproliferative disorders include primary cutaneous anaplastic large cell lymphoma (C-ALCL) and lymphomatoid papulosis (LyP) as well as borderline lesions. C-ALCL and LyP are thought to represent two ends of a spectrum of diseases that have different clinical presentations, clinical courses, and prognoses in their classic forms but share the same histology of medium to large CD30+ atypical lymphoid cell infiltrates. Because the behavior of these entities is different clinically and prognostically, we aim to search for oncogenic genomic variants using whole-exome sequencing that drive the development of LyP and C-ALCL. Clinical information, pathology, immunohistochemistry, and T-cell rearrangements on six cases of LyP and five cases of C-ALCL were reviewed to confirm the rendered diagnosis before whole-exome sequencing of all specimens. Both LyP and C-ALCL had recurrent alterations in epigenetic modifying genes affecting histone methylation and acetylation (SETD2, KMT2A, KMT2D, and CREBBP). However, they also harbor unique differences with mutations in signal transducer and activator of transcription gene STAT3 of the Jak/signal transducer and activator of transcription pathway and EOMES, a transcription factor involved in lymphocyte development, only noted in C-ALCL specimens. Genomic characterization of LyP and C-ALCL in this series confirms the role of multiple pathways involved in the biology and development of these lymphomatous processes. The identification of similar aberrations within the epigenetic modifying genes emphasizes common potential development mechanisms of lymphomagenesis within lymphoproliferative disorders being shared between LyP and C-ALCL; however, the presence of differences may account for the differences in clinical course.