Lymphomatoid Papulosis Type Research Articles

Clinical and Histologic Variants of CD8+ Cutaneous T-Cell Lymphomas.

Although the vast majority of CTCL subtypes are of the CD4+ T-helper cell differentiation phenotype, there is a spectrum of CD8+ variants that manifest wide-ranging clinical, histologic, and phenotypic features that inform the classification of the disease. CD8, like CD4, and cytotoxic molecules (including TIA and granzyme) are readily detectable via IHC staining of tissue and, when expressed on the phenotypically abnormal T-cell population, can help distinguish specific CTCL subtypes. Nonetheless, given that the histopathologic differential for CD8+ lymphoproliferative disorders and lymphomas may range from very indolent lymphomatoid papulosis (LyP) to aggressive entities like CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (AECTCL), CD8 and/or cytotoxic molecule expression alone is insufficient for diagnosis and is not in itself an indicator of prognosis. We present a review of CTCL subtypes that can demonstrate CD8 positivity: CD8+ mycosis fungoides (MF), LyP type D, subcutaneous panniculitis-like T-cell lymphoma (SPTCL), primary cutaneous gamma/delta T-cell lymphoma (PCGDTL), CD8+ AECTCL, and acral CD8+ T-cell lymphoproliferative disorder (acral CD8+ TCLPD). These diseases may have different clinical manifestations and distinctive treatment algorithms. Due to the rare nature of these diseases, it is imperative to integrate clinical, histologic, and immunohistochemical findings to determine an accurate diagnosis and an appropriate treatment plan.

Lymphomatoid Papulosis Type D in a Stem-Cell Transplant Recipient: A Rare but Diagnostic Pitfall: Answer

Lymphomatoid Papulosis Type D in a Stem-Cell Transplant Recipient: A Rare but Diagnostic Pitfall: Answer

Vesicular Lymphomatoid Papulosis With DUSP22-IRF4 Rearrangement on Chromosome 6p25.3: A Case Report.

Lymphomatoid papulosis (LyP) with DUSP22-IRF4 rearrangement on chromosome 6p25.3 is a newly identified subtype of LyP. It is characterized by an older age of onset, localized skin lesions, with good prognosis, and it resembles a hybrid of LyP types B and C in histopathology. A limited number of cases have been reported so far. In this article, we reported a case of a 72-year-old man with recurrent episodes of widespread multiple discrete papular or vesicular eruptions on a region of the head, trunk, and 4 extremities for about 3 years. Histopathological examination of a vesicle revealed a subepidermal blister with abundant atypical lymphocytes in the vesicular space, band-like infiltrates in the papillary dermis, along with epidermotropism and pilosebaceous structure involvement. Fluorescence in situ hybridization analysis further demonstrated DUSP22-IRF4 rearrangement on chromosome 6p25.3. A diagnosis of vesicular LyP with this rare subtype was made according to the clinical and pathological findings.

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.

27128 An atypical presentation of lymphomatoid papulosis in a child

Lymphomatoid papulosis (LyP) is a rare CD30+ T-cell lymphoproliferative disorder. It classically presents as a chronic eruption of ulcerating erythematous papules on the trunk and extremities. While most cases are benign, 10-20% of patients may develop mycosis fungoides, anaplastic large cell lymphoma, and Hodgkin lymphoma. There are several histologic types of LyP; the three best-described are types A-C. Type A shows scattered atypical CD30+ T-cells among a diffuse inflammatory infiltrate of histiocytes, neutrophils and eosinophils.

Lymphomatoid papulosis types D and E: a multicentre series of the French Cutaneous Lymphomas Study Group.

Lymphomatoid papulosis (LyP) type D (LyP D) and type E (LyP E) have recently been described in small series of cases or isolated case reports. To further describe the clinical and histological features of LyP D and E based on a retrospective multicentre study. The clinical and histopathological features of 29 patients with an initial diagnosis of LyP D or LyP E were retrospectively assessed using standardized forms. After exclusion of 5 cases, 24 patients (14 LyP D, 10 LyP E) were enrolled in the study. The median follow-up was 2.5 years (range 1 month to 13 years). LyP D was characterized by multiple recurrent self-regressing small papules that developed central erosion or necrosis, whereas LyP E presented as papulonodular lesions that rapidly evolved into necrotic eschar-like lesions > 10 mm in size. Epidermal changes were more frequent in LyP D, whereas dermal infiltrates were deeper in LyP E. Anaplastic cytology was rare and the DUSP22 rearrangement was never observed. Two patients (8%) had an associated cutaneous lymphoma. LyP D and E have distinct clinical findings and may be associated with other cutaneous lymphomas.

15573 Angioinvasive lymphomatoid papulosis (type E)

Background: Lymphomatoid papulosis (LyP) is an indolent CD30 positive lymphoproliferative disorder characterized by recurrent, self-healing papulo-nodules. LyP type E is a recently described rare subtype of lymphomatoid papulosis. It is distinguished by its angiocentric and angiodestructive histologic features and larger, eschar-like ulcerations. The diagnosis of LyP type E depends on clinical, histologic, and immunohistochemical findings rather than TCR clonality studies.

An Unusual Type of Lymphomatoid Papulosis Presenting in Pregnancy: Risk-Benefit Analysis of Antepartum Treatment [18H

INTRODUCTION: Lymphomatoid papulosis (LyP) has an incidence of 2 per 1,000,000 and is associated with lymphoproliferative disorders. Type E, characterized by angioinvasion, is the rarest subtype and is associated with CD30 and CD8 expression. LyP is associated with immune compromising disorders, making pregnancy a potential setting for presentation. We present one of the first cases of LyP type E in pregnancy. METHODS: Case: 30-year-old G5P3, with a pregnancy complicated by a history of hemolysis, elevated liver enzymes and low platelet count syndrome in a previous pregnancy, presented in early pregnancy with a two month history of diffuse painful skin lesions. As the pregnancy progressed, the lesions spread and would blister and ulcerate before resolving. Biopsy returned with CD30+ angioinvasive LyP type E. Prednisone and topical steroids provided minimal symptomatic improvement. Peginterferon alfa-2a was offered as an alternative therapy; however, was deferred until after delivery. CONCLUSION: Appropriate diagnosis of LyP and subtype as well as multi-disciplinary follow-up is essential given possible associated lymphoproliferative disorders. Treatment may involve more risk than benefit and has not been proven to prevent associated malignancy necessitating individualized risk-benefit analysis. Conservative treatment is preferred, even in significantly symptomatic pregnant patients. In some severely symptomatic patients, peginterferon alfa-2a may be considered with a better safety profile compared to other agents in pregnancy. The angiodestructive nature of type E may be associated with pregnancy complications including those on the preeclampsia spectrum. These pregnancies may require closer monitoring and the consideration of aspirin prophylaxis. Early diagnostic biopsy will allow for timely intervention.

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).

Clinical and Immunomorphological Characteristics of Lymphomatoid Papulosis Type E (Literature Review and Case Report)

Lymphomatoid papulosis (LP) is a rare variant of benign lym-phoproliferative disease with skin involvement. Based on clinical, morphological, and immunobiological characteristics, WHO hematopoietic and lymphoid tissue tumor classification (2016) differentiates between several LP types: А, В, С, D, Е, and with 6p25.3 rearrangement. The present article reviews the literature on clinical course, pathomorphologi-cal, immunological, and biomolecular characteristics of LP in adults and children. For the first time in the domestic literature, it provides a case report of LP, type E, in a 2-year-old child. Differential diagnosis and optimal disease management of LP are also described in detail.

To be a “Lymphomatoid Papulosis Type E” or not to be? That Is a Question

Lymphomatoid papulosis (LyP) Type E is a recently introduced subtype of LyP presenting with escar-like lesions and characterized with angiocentric invasion of dermal blood vessels by CD30 positive atypical lymphocytes resulting necrosis of their walls. Owing to its considerable histologic characteristics such as dense dermal infiltration of CD30 positive large atypical lymphocytes showing high mitotic activity, and angiodestructive invasion, it is challengible to discriminate LyP Type E to aggressive cutanoues lymphomas.

Malodorous Skin Lesions in a Diabetic Patient: Infectious Versus Neoplastic

Abstract Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma is a rare entity accounting for <1% of all cutaneous T-cell lymphomas. Almost all patients present with generalized skin lesions. This type of lymphoma has an extremely aggressive course with a median survival of 12 months. It tends to spread to other visceral sites, but lymph nodes are usually spared. We describe a case of a 59-year-old male with multiple necrotic malodours ulcers for several months. The first lesion was on his left thigh, followed by another lesion on his right chest and right eyelid. Medical history revealed newly diagnosed diabetes mellitus. The patient received antibiotics, presumptively for infectious etiology of the skin lesion, with no improvement. The right thigh lesion was excised and histomorphologic examination revealed a deep dermal proliferation of large-sized pleomorphic cells with marked pagetoid epidermotropism and skin ulceration. The adnexal skin structures were invaded by the lesion. The lesional cells were immunoreactive for CD3, CD7, CD8, and granzyme B; they were negative for CD4, CD5, CD56, and CD30. The immunophenotype confirms the entity that we have at hand in addition to the similar clinical picture that the patient presented with. This disease usually shows clonal TR gene rearrangements; nonetheless, no specific mutational aberration has been described. Our patient received chemotherapy; however, new lesions continued to erupt and he opted to proceed with palliative care. Clinical information is needed to give this diagnosis as it may look identical to a variant of lymphomatoid papulosis (type D), CD8-positive cutaneous T-cell lymphoma. We present this case due to the importance of clinical pathologic coloration to prevent misdiagnosis with mimickers as the ones pointed out earlier, and it is a provisional rare entity in the 2018 WHO classification of Tumors of Haematopoietic and Lymphoid Tissues.

061 - Lymphomatoid papulosis type E with subcutaneous tissue infiltration and prominent rimming

061 - Lymphomatoid papulosis type E with subcutaneous tissue infiltration and prominent rimming

053 - Lymphomatoid papulosis types D and E: a multicentric series on 21 patients

053 - Lymphomatoid papulosis types D and E: a multicentric series on 21 patients

Papulose linfomatóide em idade pediátrica: desafios no diagnóstico e follow-up

A papulose linfomatóide (PL) é uma doença linfoproliferativa cutânea primária, pouco comum que, na maioria dos casos, surge na idade adulta. Apesar de ter a imagem histológica de uma condição maligna, a PL é, na maioria dos casos, uma doença autolimitada e tem prognóstico favorável. Descreve-se o caso de um menino de 8 anos de idade, saudável, observado por lesões cutâneas polimórficas disseminadas por todo tegumento com 4-6 semanas de evolução. O exame histológico e imunohistoquímico confirmou o diagnóstico de PL tipo A. Discutem-se os principais desafios no tratamento, follow-up e o risco de progressão da PL para linfomas secundários nesta faixa etária.

Lymphomatoid papulosis: a clinicopathologic analysis and whole exome sequencing

Objective: To study the clinicopathologic characteristics and immunophenotype of lymphomatoid papulosis(LyP), followed by exon mutation analysis with focus on gene mutations involved in apoptosis pathway and other possible pathogenic genes. Methods: Clinical data analysis and immunohistochemical staining were carried out in 20 cases of LyP. Whole exome sequencing technology was employed in 2 cases of type C of LyP. Results: Of the 20 cases, there were 9 males and 11 females with a median age of 28.6 years. Nineteen patients presented with multiple papules and nodules, and one case presented with only one tumor nodule. Of the fifteen cases with available followed-up data, all were alive (20-155 months). Histologically, the tumors primarily involved the dermis and subcutaneous layer, in which 6 were type A, 3 were type B, 10 were type C and 1 was type D. Main infiltration patterns included wedge-shaped, band-like, sheets and large nodular. Immunohistochemistry showed that most cases expressed CD30 in the large tumor cells. Sixteen cases expressed CD3, 17 cases expressed CD4 and 8 cases expressed CD8. Sixteen cases expressed TIA1. Ten cases expressed GrB and 1 case expressed CD15. All but one case did not expressed CD20. All cases did not express ALK1.A total of 101 common non-synonymous mutations were detected in 2 cases of LyP type C by whole exome sequencing, including 87 missense mutations, 6 missense mutation/frame-shift deletions, 2 missense mutation/nonframe-shift deletions, 5 frame-shift deletions, 1 missense mutations/synonymous mutation. Syndecan-1(SDC1), COL4A1, Laminin-5 were involved in the extracellular matrix receptor pathway. Conclusions: Clinical presentations are crucial for the diagnosis of LyP. LyP has a favorable prognosis. SDC1, COL4A1 and Laminin-5 gene mutations may be associated with tumor recurrence or progression into a higher gradelymphoma.

Brentuximab vedotin therapy for CD30-positive cutaneous T-cell lymphoma: a targeted approach to management

CD30-positive primary cutaneous T-cell lymphoma (CTCL) includes mycosis fungoides, anaplastic large-cell lymphoma and lymphomatoid papulosis type A. Brentuximab vedotin (BV) consists of an antibody targeting CD30 with a protease-cleavable linker to vedotin. CD30 binding allows internalization of BV inducing cell-cycle arrest and apoptosis. Response rates >75% with manageable adverse effects in refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma led to accelerated approval for both. Phase II studies in CD30-expressing CTCL followed and showed similar efficacy, which was ratified in a Phase III trial of BV versus physician's choice (methotrexate or bexarotene) showing significant improved responses without increase in severe adverse effects although peripheral neuropathy is frequent. BV provides an effective targeted therapy for CD30-expressing cutaneous lymphomas and welcome addition to our anti-CTCL armory.

Mycosis fungoides preceding lymphomatoid papulosis

Lymphomatoid papulosis (LyP) is defined as a chronic, recurrent, self-healing papulonecrotic or papulonodular skin disease with histologic features suggestive of a (CD30-positive) malignant lymphoma. In up to 20% of patients, LyP are preceded by, associated with, or followed by another type of cutaneous or systemic lymphoma, generally mycosis fungoides (MF), primary cutaneous anaplastic large cell lymphoma (C-ALCL). In this case, we describe a case of MF that preceded and continued to coexist with LyP type C.

Lymphomatoid papulosis - making sense of the alphabet soup: a proposal to simplify terminology.

Clinically, lymphomatoid papulosis (LYP) is characterized by recurrent papulonodular lesions. Unlike this stereotypical clinical presentation, the histological spectrum of LYP is very wide, comprising distinct growth patterns, variably sized neoplastic cells, and different immunophenotypes. The revised 2016 WHO classification includes the histological LYP types A to E as well as another type characterized by a specific chromosomal alteration. In addition, new LYP types are going to be proposed, based not only on histological but also on clinical and genetic features. The ensuing expansion of the alphabetical list of histological types will add to the complexity of the terminology of LYP, thereby potentially increasing the risk of complicating rather than facilitating the diagnostic approach to the disease. Moreover, there may be overlap between individual disease types. This development raises the question as to how to simplify the terminology of LYP while still respecting its histological complexity. Herein, we advocate a practical approach to the terminology of LYP based on descriptive terms rather than the designation of LYP types by alphabetical characters. Our proposal aims to contribute to a pragmatic and user-friendly approach, thus not only facilitating the diagnostic process but also the communication between clinicians and pathologists.

Histopathological aspects and differential diagnosis of CD8 positive lymphomatoid papulosis

Lymphomatoid papulosis (LyP) belongs to CD30+ lymphoproliferative disorders with indolent clinical course. Classic histological subtypes, A, B and C are characterized by the CD4+ phenotype, while CD8+ variants, most commonly classified as type D, were reported in recent years. We present 14 cases of CD8+ LyP. In all patients, self-resolving or treatment-sensitive papules were observed. Of 14 cases 7 produced results with typical microscopic features of LyP type D mimicking primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma. The infiltration pattern in 4 of 14 cases were consistent with classic LyP type B, without CD30 expression in two cases, resembling mycosis fungoides (MF). The morphology of 2 of 14 cases shared a certain consistency with classic type A and C, lacking eosinophils and neutrophils. Extensive folliculotropism characteristic to type F was observed in 1 of 14 case. Significant MUM1 and PD1 expression were detected in 2 of 14 and 3 of 14 cases, respectively. We concluded that CD8+ LyP may present with different histopathological features compared with type D, similar to CD4+ LyP variants. Differential diagnoses include CD8+ papular MF, folliculotropic MF and anaplastic large cell lymphoma in addition to primary cutaneous aggressive epidermotropic T-cell lymphoma. We emphasise that rare CD8+ LyP cases may exist with CD30-negativity.