Hemophagocytic Lymphohistiocytosis in Cutaneous T-Cell Lymphoma.

Importance: Hemophagocytic lymphohistiocytosis (HLH) has been reported as a serious complication of cutaneous T-cell lymphoma (CTCL). Despite available diagnostic guidelines, it remains a diagnostic and therapeutic challenge in this patient population. Objectives: To examine the characteristics of CTCL associated with HLH and analyze the presenting signs and symptoms, therapeutic options, and outcome. Design, Setting, and Participants: In this case series, patients diagnosed with CTCL and HLH who were treated at a single institution from January 1, 2014, through December 31, 2017, were studied. Exposures: The HLH-2004 trial criteria, HScore, and various clinical and histopathologic variables were applied to and analyzed in the cohort. Main Outcomes and Measures: Subtype of CTCL, treatment administered for HLH, and patient outcome were assessed. Results: Seven patients (4 men and 3 women; median age, 50 years; range, 34-77 years) were identified from the database and included in the study. Cytotoxic subtypes of CTCL that involve the deep dermis and subcutaneous tissue were most commonly associated with HLH. Four patients met 5 or more HLH-2004 trial criteria, and 5 had an HScore probability greater than 85% at presentation. Common presenting HLH symptoms were fever and malaise. Cyclosporine, polychemotherapy, and systemic corticosteroids were the most common treatments. Patients receiving allogeneic stem cell transplants had the best outcomes, with all 3 of these patients alive and in complete remission. Conclusions and Relevance: Hemophagocytic lymphohistiocytosis is a life-threatening complication of CTCL associated with rare cytotoxic CTCL subtypes that primarily involve the subcutaneous tissue. Because these cases may resemble a granulomatous or infectious condition, the diagnosis and appropriate management are often delayed. The results of this study demonstrate the need for high awareness of HLH in patients with panniculitic lymphomas and indicate that allogeneic stem cell transplantation may be the best option for a sustained remission.

Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas.

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αß T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αß/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases.

Durable Responses With Maintenance Dose-Sparing Regimens of Romidepsin in Cutaneous T-Cell Lymphoma.

IMPORTANCE: Romidepsin is a histone deacetylase inhibitor approved for the treatment of cutaneous T-cell lymphoma (CTCL). Durable responses have been published without establishing a standard recommendation about duration of treatment. OBJECTIVE: To review the long-term use of romidepsin in responders who received a dose-sparing regimen. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of medical records of patients with a diagnosis of CTCL, including mycosis fungoides (MF), Sézary syndrome (SS), or CTCL not otherwise specified seen at a multidisciplinary clinic at Northwestern University from 2009 until December 2014. EXPOSURES: Doses administered and different regimens of romidepsin were reviewed. MAIN OUTCOMES AND MEASURES: Duration of treatment, participants receiving dose-sparing regimen. RESULTS: Of 47 patients identified, 23 had MF, 15 had SS, and 9 had other types of CTCL. None of these 9 (mostly cytotoxic lymphomas) achieved a durable response. Of the remaining 38 patients, 17 were considered long-term responders (>6 months of treatment). Nine of these patients received a dose-sparing regimen. The median (range) duration of treatment was 15 (7-34) months; the frequency of patients with SS (10 of 15) in the long-term group was significantly higher than that of patients with MF (7 of 23; P = .046). Adverse events were reported in 29 (69%) of 42 patients for whom data were available. There was no significant difference in the incidence of AEs between the short-term and long-term groups (12 of 21 vs 12 of 17; P = .50). CONCLUSIONS AND RELEVANCE: Decreasing the frequency of infusions in patients with MF or SS who achieve a response with romidepsin therapy may provide a practical strategy to prolong response.

Cutaneous Involvement in a Case of Intravascular T-Cell Lymphoma With a γδ Phenotype.

Intravascular lymphomas (IVL) are uncommon variants of extranodal non-Hodgkin which are usually difficult to diagnose because of their lack of clinical uniformity. Most cases are of B-cell differentiation followed by natural killer/T-cell differentiation and underlying CD30 lymphoproliferative conditions. Epstein-Barr virus is pathogenically related in most of the natural killer/T-cell variants, and the skin is a common site of presentation noted in approximately 40% of cases. Recently, cases with uncommon phenotypes have been described, expanding our understanding of the pathogenesis of this condition. In this report, we describe a 67-year-old man with a 3-month history of constitutional symptoms associated with linear purpuric macules on the trunk, pancytopenia, and high levels of serum lactate dehydrogenase. He had been followed for longstanding adenopathy and hepatosplenomegaly. Skin biopsy demonstrated a intravascular lymphocytic proliferation with positivity for CD3, CD2, CD5, and γδ T-cell receptor marker; in situ hybridization Epstein-Barr virus RNA was negative. The patient was subsequently treated with chemotherapy and allogenic stem cell transplant. He remains in complete remission 6 months posttransplant. Although the presence of hepatosplenomegaly led to consideration of a hepatosplenic T-cell lymphoma, it was pre-existing for several years making the diagnosis doubtful. To our knowledge, this is the first case report of an IVL γδ T-cell lymphoma.

Primary cutaneous T-cell lymphomas: a review.

Primary cutaneous T-cell lymphomas (CTCLs) represent a number of extranodal lymphomas arising from a malignant population of lymphocytes in the skin, with the most common type being mycosis fungoides (MF) representing half of all primary CTCLs. Despite advances in immunohistochemistry and molecular methodology, significant diagnostic challenges remain due to phenotypic overlap of primary CTCLs with several inflammatory dermatoses, secondary lymphomas, among other conditions. Clinical features such as presentation and morphology, staging, histology, immunophenotype and molecular features must be considered in detail before a diagnosis is made in order to minimise false-positive, false-negative and indeterminate diagnoses. Herein, we review primary CTCLs, including epidemiological data, a brief summary of clinical presentations, immunophenotype, molecular signatures and differential diagnoses.

Temperature thresholds in assessment of the clinical course of acquired cold contact urticaria: a prospective observational one-year study.

Cold contact urticaria is the second most common subtype of physical urticaria. Cold stimulation standardized tests are mandatory to confirm the diagnosis. The aim of this study is to define the utility of determining thresholds (critical time and temperature) in assessment of the clinical course of typical acquired cold contact urticaria. Nineteen adult patients (10 women and 9 men; mean age 45 years) were included in the study and the diagnosis was confirmed with the ice-cube test and TempTest 3.0. Patients were treated continuously for 1 year with 20 mg/day rupatadine (anti-H1). Thresholds measurements were made before and after treatment. Improvements in temperature and critical time thresholds were found in the study sample, demonstrating the efficacy of continuous treatment with rupatadine. In most cases association with a clinical improvement was found. We propose an algorithm for the management of acquired cold contact urticaria based on these results.

Chronic actinic dermatitis/actinic reticuloid: a clinicopathologic and immunohistochemical analysis of 37 cases.

Chronic actinic dermatitis/actinic reticuloid (CAD/AR) is an eczematous hypersensitivity reaction to ultraviolet rays that can vary from mild eczematous cases to AR, the most severe cases which may resemble cutaneous T-cell lymphoma. Diagnosis is based on clinical, histopathologic, and photobiologic features. In this study, we characterize the histopathologic and immunohistochemical features of 40 biopsies from 37 patients with established CAD. The cohort included 30 men and 7 women, ranging in age from 38 to 84 years (median, 62 years) and with a median duration of symptoms at presentation of 3 years (range, 1 to 40 years). All patients presented with erythematous lichenified plaques on sun-exposed areas. Severe cases (12/37) had extension to non-exposed areas. Positive photo-testing (20/20) and patch-testing (10/10) results, and cases with a high peripheral blood eosinophila (7/24) and HIV positivity (4/37) were noted. Skin biopsies demonstrated eczematous features including parakeratosis, acanthosis, spongiosis, and prominent dermal fibroplasia. Dermal dendrocytes were prominent in all cases with frequent multinucleated giant cells positive for factor XIIIa and S100 protein. Most cases displayed a brisk lymphocytic infiltrate with subtle exocytosis, atypical lymphocytes, and increased numbers of Langerhans cells, eosinophils, and plasma cells. There was a predominance of CD8 T cells within the epidermis (20/25) and a low CD4:CD8 ratio was noted in 20 of 25 cases. T-cell clonality studies were negative in 10 of 10 cases. CAD/AR may be difficult to distinguish from eczematous variants of cutaneous T-cell lymphoma. Important clues to differentiate both conditions include the identification of prominent dermal dendrocytes with multinucleated giant cells, eosinophils, plasma cells, and a low CD4:CD8 ratio.

Mycosis Fungoides Variants.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that usually manifests as patches and plaques with a propensity for nonphotoexposed areas. MF is a common mimicker of inflammatory and infectious skin diseases, because it can be manifested with a wide variety of clinical and pathologic presentations. These atypical presentations of MF may be difficult to diagnose, requiring a high level of suspicion and careful clinicopathologic correlation. Within this array of clinical presentations, the World Health Organization classification recognizes 3 MF variants: folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin. These 3 variants, as well as hypopigmented MF, are addressed in this article.