Primary cutaneous CD30+ lymphoproliferative disorders with DUSP22 translocation.

Primary cutaneous CD30+ lymphoproliferative disorders (LPD) encompass a broad category of clonal T cell proliferations with varied clinical presentations. Classically, lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (ALCL) have been recognized as distinct clinicopathological entities according to their differing clinical features. Recently, a subset of LyP and both cutaneous and systemic ALCL have been shown to carry a DUSP22 translocation [1-3], a defining molecular feature for the novel entity "LyP with DUSP22t" [1]. In cutaneous biopsies, both primary cutaneous DUSP22-translocated ALCL and LyP with DUSP22 rearrangements are characterized by a biphasic pattern with significant small cell epidermotropism. A distinct protein expression profile with preserved T Cell Receptor (TCR) expression, positivity for CD30, LEF1, HLA, and CD58, and negativity for cytotoxic marker expression as well as phospho-STAT3 protein is consistently found in these cases.

DUSP22-IRF4 Rearranged CD30-Positive Primary Cutaneous Lymphoproliferative Disorder With Gamma/Delta Phenotype.

ABSTRACT: CD30-positive primary cutaneous lymphoproliferative disorders (CD30 + PCLPD) are a heterogeneous group of cutaneous T-cell lymphoma (CTCL) that includes lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma. They exist as a clinical and pathological spectrum, which display significant overlap and variability. The diagnosis is made based on correlation between clinical and histopathologic findings. LyP with 6p25.3 rearrangement subtype represents <5% of LyP cases and is defined by DUSP22-IRF4 rearrangement on 6p25.3 locus. The reported cases express the alpha/beta T-cell receptor and follow an indolent clinical behavior typical of LyP. The same rearrangement is detected in 28% of anaplastic large cell lymphoma. We hereby present an extraordinary case of CD30 + PCLPD with DUSP22-IRF4 rearrangement and novel expression of gamma/delta T-cell immunophenotype in a young patient. Although the gamma/delta T-cell immunophenotype has been described in many other T-cell lymphomas, this is the first reported association with CD30 + PCLPD with DUSP22-IRF4 rearrangement.

Lymphomatoid papulosis associated with myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement: Successful imatinib treatment in two cases.

Lymphomatoid papulosis (LyP) is a benign condition, listed among primary cutaneous CD30+ lymphoproliferative disorders. Its typical picture consists of relapsing-remitting papular lesions and it can be encountered in the course of a hematologic disease, at times representing its first manifestation. Hypereosinophilic syndromes are a heterogeneous group of disorders characterized by persistent peripheral blood hypereosinophilia that may lead to life-threatening organ damage. Among eosinophilic disorders, the subtype identified as myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions has aroused particular interest due to its excellent response to tyrosine kinase inhibitors, including imatinib. Here, we described the case of two 33-year-old men presenting with LyP and myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement who achieved complete clinical and molecular remission of both conditions a few months after starting imatinib.

Diagnosis and management of cutaneous lymphomas and lymphoid proliferations in children, adolescents and young adults (CAYA).

Cutaneous lymphomas and lymphoid proliferations (LPD) in children, adolescents, and young adults (CAYA) are a heterogeneous group of lymphoid neoplasms that present formidable diagnostic challenges to clinicians and pathologists alike. Although rare overall, cutaneous lymphomas/LPD occur in real-world settings and awareness of the differential diagnosis, potential complications, and various therapeutic approaches will help ensure the optimal diagnostic work-up and clinical management. Lymphomas/LPD involving the skin can occur as primary cutaneous disease in a patient that characteristically has lymphoma/LPD confined to the skin, or as secondary involvement in patients with systemic disease. This review will comprehensively summarize both primary cutaneous lymphomas/LPD that occur in the CAYA population as well as those CAYA systemic lymphomas/LPD with propensity for secondary cutaneous involvement. Focus on the most common primary entities occurring in CAYA will include lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma, mycosis fungoides, subcutaneous panniculitis-like T-cell lymphoma, and hydroa vacciniforme lymphoproliferative disorder.

A case report of T cell/histiocyte-rich large B cell lymphoma misdiagnosed as lymphomatoid papulosis.

RATIONALE: T cell/histiocyte-rich large B cell lymphoma (THRLBCL) is an uncommon B cell lymphoma characterized by < 10% large neoplastic B cells in a background of abundant T cells and frequent histiocytes. If a skin lesion is the first clinical sign of lymphoma, the diagnosis might be difficult and misdiagnosed. PATIENT CONCERNS: A 60-year-old woman presented with multiple erythematous umbilicated nodules on her left upper back for 3 months. DIAGNOSES: Through punch biopsy of the back lesion and additional excisional right inguinal lymph node biopsy, the patient was diagnosed with cutaneous metastasis of THRLBCL. INTERVENTIONS: The patient was referred to the Hemato-oncology Department for chemotherapy. OUTCOMES: R-CHOP chemotherapy is currently in progress, and some skin lesions show improvement. LESSONS: Skin lesions might be the first clinical sign of THRLBCL and when THRLBCL is suspected, careful further evaluation is essential for accurate diagnosis and treatment.

CD30-positive lymphoproliferative disorders-An Australian Clinical Practice Statement from the Peter MacCallum Cancer Centre.

The CD30-postive lymphoproliferative disorders, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, account for up to 30% of all cutaneous T-cell lymphomas (CTCLs) and are the second most common form of CTCLs after mycosis fungoides. Both conditions differ in their clinical presentations; however, they share the expression of the CD30 antigen as a common immunophenotypic hallmark. There is a wide spectrum of management options depending on factors such as extent of disease, staging and treatment tolerability. This Clinical Practice Statement is reflective of the current clinical practice in Australia.

Etiopathogenesis, Diagnosis, and Treatment Strategies for Lymphomatoid Papulosis with Particular Emphasis on the Role of the Immune System.

Lymphomatoid papulosis (LyP) is a very rare disease that belongs to the group of CD30+ lymphoproliferative skin diseases. LyP is localized or generalized and usually presents as isolated or clustered red/brown-red lesions in the form of nodules and/or papules. The course of the disease is in most cases mild; however, depending on concomitant risk factors and history, it may progress to lymphoma, significantly reducing the survival rate and prognosis. Importantly, the clinical picture of the disease remains somewhat ambiguous, leading to a large number of misdiagnoses that result in inappropriate treatment, which is usually insufficient to alleviate symptoms. In addition to clinical manifestations, the histological characteristics vary widely and usually overlap with other conditions, especially those belonging to the group of lymphoproliferative disorders. Although diagnosis remains a challenge, several recommendations and guidelines have been introduced to standardize and facilitate the diagnostic process. This article reviews the available literature on the most important aspects of etiopathogenesis, clinical and histopathological features, diagnostic criteria, and possible treatment strategies for LyP, with particular emphasis on the role of the immune system.

Type D lymphomatoid papulosis with pityriasis lichenoides et varioliformis acuta-like features in a child with parvovirus infection: a controversial diagnosis in the spectrum of lymphoid proliferations: case report and literature review.

BACKGROUND: Lymphomatoid papulosis (LyP) is a rare condition in pediatrics; LyP histological type D has been reported in only 7 children. The differential diagnosis of LyP in the spectrum of lymphoid proliferation remains controversial. CASE PRESENTATION: A 6-year-old boy presented to Emergency Department with a 3-week history of an erythematous papulo-vesicular itchy eruption over the submandibular regions, trunk and extremities. History, symptoms and laboratory tests were unremarkable. SARS-CoV-2 antigen was negative. The clinical suspicion of pityriasis lichenoides et varioliformis acuta (PLEVA) was posed, and topical steroids were introduced. One week after, he returned with an extensive painful scaly papulo-erythematous rash, with some ulcerated and necrotic lesions, and fever; therefore the child was hospitalized. Biochemical results were within reference limits, except for high level of C-reactive protein, aspartate aminotransferase, alanine transaminase and bilirubin. Due to a persistently high fever, systemic corticosteroid treatment was administered, with a good clinical response and an improvement of the skin lesions. Anti-PVB-19 Immunoglobulin M was detected. Elevated levels of IL-6, IL-10 and IFN-γ were also recorded. Five days post-admission, most of the lesions had cleared, and the child was discharged. Methotrexate was started, with a positive response. At skin biopsy a "PLEVA-like" pattern was apparent, with a dense, wedge shaped lymphoid infiltrate featuring epidermotropism and morphologically comprising pleomorphic and blastic cells. The pattern of infiltration was highlighted by immunohistochemical stains, which prove the process to feature a CD8+/CD30 + phenotype, the latter being intense on larger cells, with antigenic loss. Polymerase chain reaction for T-cell receptor gamma (TCRG) chain clonality assessment documented a monoclonal peak. A diagnosis of LyP type D was favored. CONCLUSION: The reported case encompasses most of the critical features of two separated entities-PLEVA and LyP-thus providing further support to the concept of them representing declinations within a sole spectrum of disease. Studying the role of infectious agents as trigger potential in lymphoproliferative cutaneous disorders and detecting novel markers of disease, such as cytokines, could have a crucial impact on pathogenic disease mechanisms and perspective therapies.

[Primary cutaneous anaplastic large cell lymphoma with systemic progression responding to low-dose methotrexate therapy].

The standard therapies for primary cutaneous anaplastic large cell lymphoma (pcALCL) in an advanced stage remain undefined. A 71-year-old man presented with multiple erythema and nodules. He was diagnosed with lymphomatoid papulosis (LyP) through a skin biopsy from the left postauricular area. All skin lesions achieved complete response by electron beam irradiation. However, nodular lesions appeared in both inner canthi 5 months later. Histopathological evaluation of the lesional biopsy revealed dominant infiltration of CD30-positive large cells. Positron emission tomography/computed tomography revealed fluorodeoxyglucose-positive cervical and inguinal lymph node swelling and right tonsillitis, followed by the diagnosis of pcALCL and TNM classification T3bN3M0. Since the patient had severe chronic obstructive pulmonary disease and recurrent pneumonia, he received low-dose methotrexate (MTX) (15 mg/week) therapy. Low-dose MTX effectively debulked the lymphadenopathies over time without particular adverse effects. Although the standard therapies for pcALCL are not established, low-dose MTX was effective and considered safe for patients with frailty and compromised respiratory function. Further study is warranted on the pathophysiology of pcALCL after the development of LyP and mechanisms of action of low-dose MTX against LyP and pcALCL.

Childhood lymphomatoid papulosis Type D, a rare and challenging diagnosis.

A 10-year-old female with a several-year history of pityriasis lichenoides (PL) presented with a new, asymptomatic, large, and necrotic ulcer of her right upper arm. Skin biopsy was consistent with lymphomatoid papulosis (LyP) Type D, a recently recognized subtype of LyP that is distinguished histologically by marked epidermotropism and a perivascular infiltrate of medium-sized pleomorphic lymphocytes with a cytotoxic phenotype (CD3+, CD8+). This is only the sixth reported case of LyP Type D in a child, and while the prognosis in children appears favorable, with no reports of progression to lymphoma to date, more experience in children with longer-term follow-up is needed. Our case highlights both the challenging clinical diagnosis, since in our patient the longstanding clinical presentation was indistinguishable from PL, as well as histopathologic diagnosis, which required expert opinion and consensus.

Clinicopathological Factors Associated with the Prognosis and Chronicity of Lymphomatoid Papulosis: A Retrospective Cohort Study.

BACKGROUND: The clinical and pathological features of lymphomatoid papulosis (LYP) are diverse. The objective of this study is to evaluate the clinical and pathological features associated with the prognosis and clinical course of LYP. PATIENTS AND METHODS: The clinical and pathological features of LYP in a medical center database were retrospectively retrieved. RESULTS: Overall, 58 LYP patients were included in the study. The mean age at diagnosis was 39.1 years and the female-to-male ratio was 1:1.2. More than two-thirds (40/58, 69.0%) of the patients showed a chronic and recurrent disease course. A longer pre-diagnosis duration (odds ratio (OR), 1.01; 95% confidence interval (CI), 1.00-1.03) was significantly associated with secondary lymphoma development. Lower extremity involvement (OR, 10.40; 95% CI, 1.17-92.28) and the absence of eosinophils in the lesions (OR, 11.28; 95% CI, 1.01-126.24) were found to be significantly associated with the chronic and recurrent course of LYP. CONCLUSION: A longer pre-diagnosis duration is associated with secondary lymphoma, while a lower extremity involvement and the absence of lesional eosinophil infiltration are associated with the chronicity of LYP.

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

BACKGROUND: Cutaneous hematologic malignancies are rare in children, and the literature about them is still sparse. OBJECTIVE: The purpose of our study was to report our experience with pediatric cases of cutaneous hematologic disorders and describe their clinical and histological features. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Diagnosis and Management of Cutaneous Lymphomas Including Cutaneous T-cell Lymphoma.

The cutaneous lymphomas are malignancies of T-cell and B-cell lymphocytes in which the skin is the primary organ of involvement. The cutaneous T-cell lymphomas include variants that can mimic the presentation of common skin diseases or arthropod bites. Mycosis fungoides, the most common cutaneous T-cell lymphoma, usually presents as fixed asymptomatic patches or plaques in sun-protected areas. The cutaneous B-cell lymphomas have fewer variants that often present as papules or nodules that can mimic nonmelanoma skin cancers. Some therapies for cutaneous lymphoma have unique side effects such as central hypothyroidism, hyperlipidemia, and peripheral neuropathy.