Primary Cutaneous CD30 Research Articles

Posttransplant Primary Cutaneous CD30+ Anaplastic Large T Cell Lymphoma: A Case Report

Recipients of organ transplants are at an increased risk of secondary malignancies. An anaplastic large cell lymphoma that was positive for CD30 presented as a several tumors on the forehead in a 60-year-old man 12 years after kidney transplantation. A pulmonary adenocarcinoma was also discovered during the extension workup. Systemic chemotherapy was decided but the patient died from COVID infection. This case highlight that strict screening programs after kidney transplantation are key factors for an early diagnosis and to allow for prompt treatment resulting in a better outcome.

Evaluation of Associated Lymphomas and Their Risk Factors in Patients with Lymphomatoid Papulosis: A Retrospective Single-Center Study from Turkey

Objective:Lymphomatoid papulosis (LyP) is an indolent skin disease with variable clinical features classified among the primary cutaneous CD30+ T-cell lymphoproliferative disorders. It may show association with cutaneous and systemic lymphomas. We aimed to identify the frequency and characteristics of associated lymphomas among Turkish patients with LyP and to determine the risk factors for secondary lymphomas.Materials and Methods:The files of patients diagnosed with LyP between 1998 and 2018 in a tertiary dermatology clinic were retrospectively analyzed. Univariate and multivariate models were used to assess the possible risk factors for secondary lymphomas, such as demographic and clinical characteristics of the patients.Results:Among 61 patients (47 adults, 14 children) with LyP, a total of 22 secondary lymphomas were observed in 20 patients. Nineteen of them were adults. Mycosis fungoides (MF) was the major associated lymphoma (n=19) followed by systemic anaplastic large cell lymphoma (ALCL) (n=2) and primary cutaneous ALCL (n=1). The most common stage in patients with accompanying MF was stage IB (n=11). While 18 patients showed the classical type of MF, one patient had folliculotropic MF. When the risk factors for association between LyP and other lymphomas were evaluated, only older age was found to be a significant risk factor and existence of ulcerated lesions was found to be a negative indicator.Conclusion:LyP is not rare in the pediatric population. MF is the most common associated lymphoma in patients with LyP. Adult LyP patients are more commonly associated with secondary lymphomas than pediatric patients. Older age at the time of diagnosis of LyP is a significant risk factor for associated lymphomas.

Primer cutan CD4 + kis/középnagy T-sejtes lymphoproliferatív megbetegedés: Esetbemutatás a Semmelweis Egyetem Bőr-, Nemikórtani és Bőronkológiai Klinika anyagából irodalmi áttekintéssel

In the updated 2018 WHO-EORTC classification, the name of the disease was changed to primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder instead of the former primary cutaneous CD4+ small/medium T-cell lymphoma, because of its indolent behaviour and uncertain malignant potential. The authors present five cases of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, through which they show the various clinical appearances, and the histological features of the disease, and review the literature. The authors point out that the disease, except for a few cases, presented with a solitary lesion, has a particularly good prognosis, remains localized and shows a tendency to regress despite the monoclonal T-cell receptor gene rearrangement.

Primary cutaneous CD30+ Anaplastic large cell lymphoma

Defining features of Anaplastic large cell lymphoma (ALCL) consist of a proliferation of predominantly large lymphoid cells with a strong expression of the cytokine receptor CD30 and a characteristic growth pattern.

Challenges in early diagnosis of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma: a case series of four patients

Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma (AECTCL) is a rare and aggressive lymphoma characterised by ulcerated lesions and a poor prognosis. To present a case series of four previously misdiagnosed AECTCL patients and discuss the importance of early diagnosis. All patients in this study were identified from the database of the Dermatology Department of the Medical School of Bezmialem Vakif University, based on clinical and histopathological diagnosis of AECTCL between 2010 and 2018. AECTCL cases may mimic many benign dermatoses and accurate diagnosis may be delayed. Because of its poor prognosis, early diagnosis of AECTCL may be helpful in improving the likelihood of patient survival, but further study is needed to address the challenges in diagnosing this rare and aggressive lymphoma.

145 Loss of 5-hydroxymethylcytosine in CD4+ small /medium T-cell lymphoproliferative disorder

Primary cutaneous CD4+ small /medium T-cell lymphoproliferative disorder (PC-SMTLD) has recently been considered as a distinct clinicopathological entity. Because of a considerable degree of overlap with pseudolymphoma, diagnosis of PC-SMTLD is often challenging. The methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, this epigenetic marker has never been studied in cutaneous lymphomas.

Primary Cutaneous CD30+ Lymphoproliferative Disorders: a Comprehensive Review.

Primary cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ LPDs) are the second most common cutaneous lymphomas after mycosis fungoides and Sezary syndrome. They include primary cutaneous anaplastic large cell lymphoma (pcALCL), lymphomatoid papulosis (LyP), and borderline lesions. The purpose of this literature review is to consolidate the available evidence on the primary cutaneous CD30+ LPD in order to define the tools for correct diagnosis and appropriate treatment. The current body of knowledge regarding the clinical features, histopathologic changes, recently described genetic alterations, and therapeutic options will be covered in this comprehensive review. Primary cutaneous CD30+ LPD represent rare cutaneous lymphomas that have significant histologic overlap within the defined group as well as with other neoplastic and reactive entities. The importance of differentiating these entities is crucial, as each one has a different clinical course and prognosis.

CD30+ leukemic cutaneous T-cell lymphoma

To the Editor: CD30 is a tumor necrosis factor receptor involved in regulating apoptosis and proliferation of CD30+ tumor cells.1 CD30+ T cells are primarily expressed in conditions such as primary cutaneous CD30+ T-cell lymphoproliferative disorders and some peripheral T-cell lymphomas, and they can potentially be expressed in any type of cutaneous T-cell lymphoma (CTCL).2-4 However, CD30 expansion on the leukemic cells of patients with CTCL or Sézary syndrome is rare, and little is known regarding the natural history and prognosis of patients with leukemic CTCL expressing this cell type.

Adnexotropism as a Histopathological Clue for the Diagnosis of Primary Cutaneous CD4+ Small/Medium-Sized T-Cell Lymphoproliferative Disorder.

To the Editor: Primary cutaneous CD4+ small/medium-sized T-cell lymphoproliferative disorder (PCSM-TCLPD) is considered as a World Health Organization provisional entity, histopathologically characterized by diffuse or nodular infiltrates of small- to medium-sized pleomorphic T lymphocytes with CD3+/CD4+/CD8−/CD30− phenotype, sometimes admixed with less than a 30% of large pleomorphic cells. Recognition of this disorder requires differential with other neoplastic and inflammatory disorders in the skin, including primary cutaneous marginal zone B-cell lymphoma, insect bite inflammatory reaction, mycosis fungoides, and T cell helper follicular primary cutaneous T-cell lymphoma, a neoplastic condition that may present similarities but portends a worse prognosis We have recently reviewed all the biopsies of lymphomas in our hospital from January 2010 to January 2018 to select 33 cases with clinical or histopathological diagnosis of PCSM-TCLPD diagnosed in our department. We applied the diagnostic criteria described within the last updated World Health Organization classification of hematological malignancies.1,2 Our patients clinically correspond to 16 women and 10 men with a mean age of 55.1 years (range 29–86) and with no other epidemiological features showing differences with the previously described.FIGURE 1.: A, Panoramic view of a PCSM-TCLPD with nodular infiltrates showing a rounded interface with the subcutaneous fat, (B) atypical lymphocytes surrounding and partially destructing the hair follicle, (C) infiltration by the tumoral cells in the eccrine ducts, and (D) infiltration of the piloerector muscle by the same medium-sized atypical lymphocytes.FIGURE 2.: A, Eccrine ducts that show areas with partial destruction and (B–D) different fields showing the eccrine ducts infiltration by the tumoral cells. Double immunohistochemistry LEF1 (peroxidase)/E-cadherin (alkaline phosphatase).The more striking histopathological feature, to our eyes, was a distribution showing nodules mostly located in the dermis, which tends to embrace the adnexal structures and presenting in the deeper areas a rounded pushing interface (Fig. 1A). Moreover in a lymphoma where finding epidermotropism is an exclusion criterion, was striking to find infiltration by the tumoral cells in the eccrine ducts as well as in the hair follicle in all the cases (Figs. 1B–D). This finding, adnexotropism, was first described by Beltraminelly and cols,3 and it is also observed in the larger series, although these articles have not highlighted this finding enough.3,4 In our experience, this adnexotropism is very characteristic, and the finding of an atypical lymphocytic infiltrate with these features and with scarce or lacking epidermotropism should raise the suspicion of PCSM-TCLPD. It was also striking to find infiltration by the tumoral cells in the epithelium of the eccrine ducts involving both the superficial epithelium and the basal layer that also are hyperplastic. The gland presented a multilobulated contour due to the hyperplasia of both components. In all the cases, the affected eccrine ducts showed areas with partial destruction. It was also quite characteristic to find an infiltration of the piloerector muscle by the same atypical cells.5 In these lesions is also quite frequent to find scarce nonclustered CD30-positive cells, in less than 10% of the tumoral lymphocytes and some B-cell lymphocytes. PD1 staining showed clusters of cells in all the studied cases as previously described (Fig. 2). Is important to how that syringotropism does not equal malignancy, it may be observed in several different dermatoses.6 In conclusion, precise diagnosis of PCSM-TCLPD is still a challenge, but a multilobulated nodular infiltrate of slightly atypical lymphoid cells infiltrating hyperplastic eccrine ducts that is presence of siringotropism is a useful marker that, in the appropriate context, may facilitate its recognition of PCSM-TCLPD. In this context, an immunohistochemical panel including T-cell markers, PD1, and CD30 will confirm the correct diagnosis.

Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorders

Primary cutaneous CD4 small/medium T-cell lymphoproliferative disorder (PCSMLPD) is a recently recognized entity in the 2017 World Health Organization (WHO) classification. It belongs to the T-follicular helper (TFH) lymphoproliferations. The clinical, pathologic, and molecular features of this localized disease are underresearched. We conducted a retrospective multicentric study of 60 patients with a PCSMLPD that presented as a single cutaneous lesion. Clinical, pathologic, and targeted molecular analyses were performed. PCSMLPD presented mostly as a nodule (45%), located on the head and neck area (50%) in adults (mean age: 59 y [43.3 to 75.2]). All patients had an indolent disease course, either at initial staging or during follow-up (mean: 16.6 mo [1.3 to 31.9]). Spontaneous regression was reported in 31.9% of cases. The infiltrates were most often nodular and/or diffuse, expanding in the whole dermis (78%, Pattern 1), rather than subepidermal band-like in the superficial dermis (22%, Pattern 2). Epidermotropism, folliculotropism, and capillary hyperplasia were common. The expression of TFH lineage markers was more extensive in lesions with Pattern 2, but a substantial B-cell infiltrate was seen in both types of lesions. A clonal rearrangement of the TCR genes was identified in 68% of cases. One sample of the 13 tested revealed a mutation in the DNMT3A gene among the 9 genes studied (TET2, DNMT3A, IDH2, RHOA, SETD2, PLCG1, STAT3, STAT5B, and CD28). PCSMLPD follows a benign clinical course and can spontaneously regress after biopsy. Although PCSMLPD expresses TFH lineage markers, mutations usually found in angioimmunoblastic T-cell lymphomas are uncommon.

Nitrogen mustard gel-induced inflammation triggers lymphomatoid papulosis in patients with mycosis fungoides.

Lymphomatoid papulosis (LyP) is a paraneoplastic primary cutaneous CD30+ lymphoproliferative disorder (LPD) that has been associated with malignant lymphomas, most commonly mycosis fungoides (MF). We observed 10 patients with MF who developed severe inflammation after using nitrogen-mustard (NM) gel from 1 to 8months and who developed LyP. We hypothesized that NM gel produced local inflammation, which induced CD30 expression in malignant T cells in situ leading to the appearance of LyP papules. The high frequency of induction of LyP lesions in patients with severe inflammation while on treatment with NM gel suggests an association between inflammatory stimuli and development of LyP. Our observation provides insight into the pathogenesis of CD30+ LPD.

Evidence linking atopy and staphylococcal superantigens to the pathogenesis of lymphomatoid papulosis, a recurrent CD30+ cutaneous lymphoproliferative disorder.

Primary cutaneous CD30+ lymphoproliferative disorders (CD30CLPD) are the second most common type of cutaneous T cell lymphoma (CTCL) and include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Case reports and small patient series suggest an association of CD30CLPD with atopic disorders. However, the prevalence of atopy in patients with CD30CLPD in retrospective studies depends on patients' recall which is not always reliable. More objective criteria of atopy include evidence of skin reactivity to allergens (positive prick test) and evidence of allergen-specific IgE in serum. This study was undertaken to test the hypothesis that atopy is prevalent in patients with CD30CLPD using serologic criteria of allergen-specific IgE antibodies to aeroallergens and Staphylococcal aureus enterotoxin superantigens (SSAgs). We tested serum samples of CD30CLPD for common IgE-specific airborne allergens with the Phadiatop test, which if positive, is regarded as serologic evidence of atopy in adults. Sera were also tested for IgE antibodies reactive to three Staphylococcal enterotoxins with superantigenic properties (SSAg-IgE). Control sera were obtained from adult subjects evaluated for rhino-sinusitis and a negative Phadiatop test. Patients' history of an atopic disorder was obtained by retrospective chart review. Nearly 50% of patients with the most common LyP types (A and C) had a positive Phadiatop test for allergic sensitization to common airborne allergens, and total serum IgE (IgE-t) was increased compared to non-atopic controls. At the IgE antibody concentration generally used to define serologic atopy (≥ 0.35 kUA/L), 8/31 (26%) samples of CD30CLPD and 7/28 (25%) samples of LyP were reactive to at least one SSAg-IgE compared to 3/52 (6%) control specimens (P = 0.016 and P = 0.028, respectively). TSST1-IgE was detected in 7 (23%) specimens of CD30CLPD, often together with SEB-IgE; SEA-IgE ≥ 0.35 kUA/L was not detected. For control specimens, TSST1-IgE exceeded the 0.35 kUA/L threshold in 3 (6%) specimens. Patients with LyP types A and C have serologic evidence of atopy against common airborne antigens and SSAgs when compared to control adult subjects who had rhino-sinusitis and a negative Phadiatop test for aero-IgEs. Serologic evidence of atopy exceeded that determined by LyP patients' personal history. The findings support our hypothesis that an atopic diathesis may contribute to the pathogenesis of the most common types of LyP (A and C).

Cutaneous lymphoma in Japan, 2012–2017: A nationwide study

BackgroundThe types of cutaneous lymphoma (CL) and their incidences can vary among geographic areas or ethnic groups. ObjectiveThis study aimed to investigate the incidence of various CL types in Japan using epidemiological data from a nationwide registration system for CL. MethodsA questionnaire was sent to participating hospitals, all of which had been approved to conduct residency programs for board-certified dermatologists by the Japanese Dermatological Association. Data from patients newly diagnosed with CL were collected electronically. ResultsBetween 2012 and 2017, 2547 new patients with CL from the dermatological institutes were registered. In total, 2090 patients had primary CL and 453 had secondary CL. Those with primary CL included 1609 (77.0 %) patients with mature T- and natural killer (NK)-cell neoplasms, 442 (21.1 %) with B-cell neoplasms, and 39 (1.9 %) with blastic plasmacytoid dendritic cell neoplasms. Mycosis fungoides (MF) was the most common CL subtype in the present study (1003 patients, 48.0 %), and 72.4 % of MF patients had early-stage disease, similar to observations in previous studies on other cohorts. Primary cutaneous CD30+ T-cell lymphoproliferative disorders and adult T-cell leukemia/lymphoma were the second and third most common subtypes, respectively. ConclusionCompared to that in our previous cohort (2007–2011), the number of registered T- and NK-cell CL cases decreased, whereas that of B-cell CL cases increased from 44.8–73.7 patients/year. These results provide insight into CL trends within the Japanese population, which might contribute to a better understanding of the disease.

Radiotherapy of primary cutaneous anaplastic large cell lymphoma: our experience in 30 cases

Since the observation of new cases of primary cutaneous anaplastic large cell lymphoma (PCALCL) with a seemingly aggressive clinical presentation and a favorable response to radiation therapy (RT), a review of our series has been performed to evaluate the results of RT. The study is a retrospective analysis of 30 patients with PCALCL treated with conventional energy RT. About 55 fields of irradiation were performed. Complete clinical response (CCR) was obtained in 29 cases and a partial clinical response (PCR) in one. Two lesions had a marginal relapse at 7 and 37months, respectively. In eight cases, new lesions appeared in the same body district and in six cases, in body sites at distance from the field of treatment. Total radiation dose ranged from 15 to 35Gy (median 25Gy). Follow-up range was 2-218months (median 38.5months) with a local control rate of 85% and a relapse-free rate of 49% at 5years from RT. Three cases developed a nodal involvement. PCALCL belongs to the group of primary cutaneous CD30+ lymphoproliferative disorders, accounting for 25-30% of cutaneous T-cell lymphomas. RT is considered of choice as alternative to surgical excision of solitary lesions. Recent studies have focused on ideal dose to obtain local control indicating 30Gy as adequate, but others have hypothesized that lower doses may suffice. Our study confirms the excellent role of RT in the local control of the disease with total doses ≤25Gy.

Primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoproliferative disorder in a woman successfully treated with intralesional interleukin injection and occlusive corticosteroid

Primary cutaneous CD4⁺ small/medium pleomorphic T-cell lymphoproliferative disorder in a woman successfully treated with intralesional interleukin injection and occlusive corticosteroid

Update on peripheral T-cell lymphomas with T-helper phenotype: Are there too many subtypes?

Follicular helper T (TFH) cells are the providers of T-cell help to B-cells in the development of germinal centers and for the generation of most class-switched antibodies. The markers most commonly associated with TFH activity are IL21, IL4, CD40L, BCL6, SAP, CXCR5/CXCL13, and ICOS. T-cell lymphoma genomic studies have shown that different T-cell lymphoma types express signatures typical for TFH cells, this including angioimmunoblastic T-cell lymphoma (AITL), a related condition termed peripheral T-cell lymphoma with TFH phenotype and primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder. Angioimmunoblastic T-cell lymphoma is a well-established entity, a clinically aggressive disease with a survival of 30% OS after 5 years. Molecular and clinical studies have confirmed this as a well-established clinicopathological entity with relatively specific gene mutations, including mutations found in hematopoietic precursor cells and others. Peripheral T-cell lymphoma with TFH phenotype is an associated disorder with histology of PTCL but a TFH phenotype, as defined by the expression of 2-3 immunohistochemical markers. Molecular studies on this entity are showing a partial overlap with AITL. Primary cutaneous CD4+ small/medium lymphoproliferative disorder is an entirely different process that takes place in the skin, showing frank cytologic atypia, monoclonal TCR rearrangement and TFH phenotype in the context of a clinically benign lesion. Here we review the main clinical, molecular and diagnostic features of these three lymphoproliferative processes.

Phase 2 Study of E7777, a Diphtheria Toxin Fragment-Interleukin-2 Fusion Protein, in Japanese Patients with Relapsed or Refractory Peripheral and Cutaneous T-Cell Lymphoma

Phase 2 Study of E7777, a Diphtheria Toxin Fragment-Interleukin-2 Fusion Protein, in Japanese Patients with Relapsed or Refractory Peripheral and Cutaneous T-Cell Lymphoma

Classification for primary cutaneous lymphoproliferative disorders: an update

Primary cutaneous lymphoproliferative disorders are a group of heterogeneous diseases that mainly involve the skin and are completely different from lymph node lymphomas. Although rare, they are still an important part of lymphoid and hematopoietic tumors. In the 2017 World Health Organization (WHO) classification for tumors of hematopoietic and lymphoid tissues and the 2018 updated version of WHO-European Organization for the Research and Treatment of Cancer (EORTC) classification for cutaneous lymphomas, classifications of most diseases do not change, but the understanding of some diseases such as Epstein-Barr virus-associated lymphoproliferative diseases and primary cutaneous CD4 positive small/medium T-cell lymphoproliferative disorder has been changed, and new diseases have been added. This article introduces updates on the classification of primary cutaneous lymphoproliferative disorders based on the 2017 WHO and 2018 WHO-EORTC classification systems. Key words: Lymphoproliferative disorders; Lymphoma, T-cell, cutaneous; Lymphoma, extranodal NK-T-cell; Lymphoma, B-cell

Primary Cutaneous Acral CD8+ T-Cell Lymphoma—A Single Center Review of 3 Cases and Recent Literature Review

The recently published 2016 revision of the WHO classification of lymphoid neoplasms includes primary cutaneous acral CD8-positive T-cell lymphoma (PCATCL) as a provisional entity. This is a rare indolent lymphoma characterized by papules or nodules on the ear and a dermal infiltrate of CD8-positive T-lymphocytes with cytotoxic marker expression. A retrospective review of a single institutional experience with PCATCL identified 3 patients (mean age 54; range 49-62) with papules or nodules on the ear. Lesional biopsies demonstrated a dense diffuse dermal infiltrate of atypical lymphocytes with a Grenz zone in 2 cases and focal epidermotropism in 1 case. The atypical lymphocytes were predominantly CD3 and CD8 positive with expression of cytotoxic marker TIA1. Staging evaluation failed to reveal systemic disease. Two patients underwent local excision, and the third received local radiation therapy all with complete response and no disease recurrence at last follow-up 3 months (range 2-5 months). Our cases add to the existing limited literature on the clinical and histopathological features of PCATCL. We also performed an updated systematic literature view of the entity.

Primary cutaneous CD8+ CD30+ lymphoproliferative disorder in a patient with acquired CD4 immunodeficiency

article: Primary cutaneous CD8+ CD30+ lymphoproliferative disorder in a patient with acquired CD4 immunodeficiency - Giornale Italiano di Dermatologia e Venereologia 2019 Jun 12 - Minerva Medica - Journals