Janyana M.D. Deonizio

Cutaneous γδ T-cell lymphomas: a spectrum of presentations with overlap with other cytotoxic lymphomas.

We reviewed our multicenter experience with gamma-delta (&ggr;&dgr;) T-cell lymphomas first presenting in the skin. Fifty-three subjects with a median age of 61 years (range, 25 to 91 y) were diagnosed with this disorder. The median duration of the skin lesions at presentation was 1.25 years (range, 1 mo to 20 y). The most common presentation was deep plaques (38 cases) often resembling a panniculitis, followed by patches resembling psoriasis or mycosis fungoides (10 cases). These lesions tended to ulcerate overtime (27 cases). Single lesions or localized areas of involvement resembling cellulitis or pyoderma were reported in 8 cases. The most common anatomic site of involvement was the legs (40 cases), followed by the torso (30 cases) and arms (28 cases). Constitutional symptoms were reported in 54% (25/46) of the patients, including some with limited skin involvement. Significant comorbidities included autoimmunity (12 cases), other lymphoproliferative disorders (5 cases), internal carcinomas (4 cases), and viral hepatitis (2 cases). Lymphadenopathy (3/42 cases) and bone marrow involvement (5/28 cases) were uncommon, but serum lactose dehydrogenase (LDH) was elevated in 55% (22/39) of the patients. Abnormal positron emission tomography and/or computed tomography scans in 20/37 subjects mostly highlighted soft tissue or lymph nodes. Disease progression was associated with extensive ulcerated lesions resulting in 27 deaths including complications of hemophagocytic syndrome (4) and cerebral nervous system involvement (3). Median survival time from diagnosis was 31 months. Skin biopsies varied from a pagetoid pattern to purely dermal or panniculitic infiltrates composed of intermediate-sized lymphocytes with tissue evidence of cytotoxicity. The most common immunophenotype was CD3+/CD4−/CD5−/CD8−/BF1−/&ggr;-M1+/TIA-1+/granzyme-B+/CD45RA−/CD7−, and 4 cases were Epstein-Barr virus positive. This is the largest study to date of cutaneous &ggr;&dgr; T-cell lymphomas and demonstrates a variety of clinical and pathologic presentations with a predictable poor outcome.

γδ T-cell-rich variants of pityriasis lichenoides and lymphomatoid papulosis: benign cutaneous disorders to be distinguished from aggressive cutaneous γδ T-cell lymphomas

T cells with a γδ phenotype have been associated with aggressive lymphomas. Yet, inflammatory skin disorders and low‐grade lymphoproliferative disorders have rarely been described with a predominant γδ T‐cell infiltrate.

Multicenter case series of indolent small/medium-sized CD8+ lymphoid proliferations with predilection for the ear and face.

Abstract:We report 7 cases of a CD8+ lymphoid proliferation of the ear and face with a cytotoxic T-cell phenotype, but an indolent clinical course. All patients presented with stable or slowly growing asymptomatic lesions on the ear, nose, or lower eyelid. Histopathology showed a dense diffuse dermal infiltrate of small- to medium-sized atypical lymphocytes without destructive features. The lymphocytes were positive for CD3, CD8, &bgr;-F1, and TIA-1 and negative for CD4, CD30, CD56, granzyme B, and PD-1. Of note, the proliferation index was low in available cases. All patients remained in complete remission at median follow-up of 14 months regardless of treatment modality. Staging was negative for extracutaneous disease in all patients. The clinically indolent behavior and histopathologic phenotype together with a low proliferation index (10%–15%) emphasize the importance of accurate diagnosis and appropriate clinical management to avoid overtreatment and complications of therapy.

CD8+ granulomatous cutaneous T-cell lymphoma: A potential association with immunodeficiency

BACKGROUND Granulomatous cutaneous T-cell lymphoma (G-CTCL) is a rarely encountered entity. Most G-CTCL is CD4(+), with granulomatous mycosis fungoides representing the vast majority of cases. Because of the rarity of CD8(+) G-CTCL, there is a paucity of data regarding the clinicopathologic features and expected course. OBJECTIVE To describe the clinical and histopathologic features of G-CTCL. METHODS This is a retrospective review of collected cases. RESULTS We present 4 cases of CD8(+) G-CTCL. Patients presented with papules and nodules on the trunk and extremities without antecedent patch or plaque disease. In all cases, biopsy specimens were obtained, and these revealed a dense granulomatous infiltrate accompanied by an atypical lymphoid infiltrate of CD8(+) T cells. T-cell clonality studies were positive in 3 of 4 cases. Staging was negative for nodal involvement, but lung granulomas were seen in all cases. In all 4 cases, the patients medical history was significant for immunodeficiency, either primary or iatrogenic. All 4 patients had slowly progressive disease. LIMITATIONS This is a small retrospective case series. CONCLUSIONS CD8(+) G-CTCL appears to be associated with immunodeficiency. The finding of a CD8(+) G-CTCL should prompt an evaluation for underlying immunodeficiency. Additional studies are required to validate these conclusions.

High incidence of gastrointestinal tract disorders and autoimmunity in primary cutaneous marginal zone B-cell lymphomas.

IMPORTANCE To our knowledge, this is the first comprehensive study addressing comorbidities associated with primary cutaneous marginal zone B-cell lymphomas (PCMZLs). OBJECTIVE To determine if patients with PCMZL were at risk for other medical conditions. DESIGN, SETTING, AND PARTICIPANTS Case-control study at a cutaneous lymphoma clinic and a dermatopathologic consultation service at a single academic institution using an extensive questionnaire of illnesses, symptoms, and environmental exposures for 80 sequential patients with PCMZL and 80 matched controls. MAIN OUTCOMES AND MEASURES The frequency of several morbidities was obtained in both groups from data gathered from the questionnaire and corroborated by reviewing medical records when available. RESULTS We found a high incidence of past or present gastrointestinal tract problems in 49 patients (61.2%) with PCMZL compared with 30 participants (37.5%) in the control group (CG) (P = .003). Gastroesophageal reflux was reported in 50.0% (40 vs 27 in the CG, P = .04) and gastric ulcers in 10.0% (8 vs 3 in the CG, P = .13); 20.0% of the cohort had positive Helicobacter pylori serology (16 vs 2 in the CG, P = .003). Colon disorders, including irritable bowel syndrome and inflammatory bowel disease, were more common in the PCMZL cohort (20 vs 7 in the CG, P = .01). Autoimmunity was reported in 20.0% of participants (16 vs 6 in the CG, P = .03). Eight patients had a history of Hashimoto thyroiditis. Three patients had a positive antinuclear antibody. Two had a diagnosis of lupus erythematosus and 1 had Sjögren syndrome. Sicca syndrome was noted in 12.5% (10 vs 3 in the CG, P = .052). A history of noncutaneous malignant neoplasms was observed in 21.3% of the patients (17 vs 8 in the CG, P = .050). Other notable morbidities did not reach statistical significance. CONCLUSIONS AND RELEVANCE Our results indicate a high incidence of systemic conditions in patients with PCMZL, especially involving the gastrointestinal tract, but also autoimmunity and cancer.

CD30+ cutaneous lymphoproliferative disorders with pseudocarcinomatous hyperplasia are associated with a T-helper-17 cytokine profile and infiltrating granulocytes

BACKGROUND The pathogenetic mechanism of CD30(+) cutaneous lymphoproliferative disorders (CLPD) associated with pseudocarcinomatous hyperplasia (PCH) and granulocytic inflammation surrounding atypical CD30(+) lymphocytes remains unclear. OBJECTIVE We sought to characterize clinical and pathological findings of a cohort of patients with PCH associated with CD30(+) CLPD and to analyze the cytokine profile of the atypical lymphocytes. METHODS We retrospectively reviewed medical records and pathological material of CD30(+) CLPD with PCH. Immunohistochemistry for T-helper (Th)17 cytokine profile was performed. RESULTS In all, 25 patients with a median age of 52 years were included. The median follow-up was 3.7 years. Histologically, an infiltrating pattern of PCH was observed in 14 cases with a neutrophilic-rich infiltrate (P = .21), and epidermal pattern in 11 cases with eosinophil-rich infiltrate (P = .03). Th17 or Th22 cytokines were detected in tumor cells in 81% cases tested. Tumor cells expressed Th17 transcription factor retinoic acid receptor (ROR)-related orphan receptor gamma-2 in 2 of 7 samples tested and 1 was positive for aryl hydrocarbon receptor. LIMITATIONS This is a retrospective study of a small sample. CONCLUSIONS PCH in CD30(+) CLPD is associated with Th17/Th22 cytokine expression in the atypical lymphocytes. Although these lesions commonly regress spontaneously and are associated with an indolent course, some cases develop a generalized process and tumor progression.

The Role of Molecular Analysis in Cutaneous Lymphomas

The purpose of this review is to summarize the most important molecular techniques for the diagnosis of cutaneous lymphomas. When making a diagnosis, we are looking for the solid clinicopathological correlation. Molecular analysis includes immunophenotyping and clonality analysis, and is important for 2 principal reasons: (1) to confirm the diagnosis in cases where the clinical and/or pathological presentations are nondiagnostic, and (2) to further characterize the nature of the lymphoma. More specifically, we are trying to discern whether the lymphoma is primarily cutaneous or systemic with secondary skin involvement, and we are also attempting to subclassify the tumor. Recently, many techniques have provided a more accurate diagnosis of cutaneous lymphomas and some prognostic implications, including polymerase chain reaction, fluorescence in situ hybridization, and flow cytometry. Fluorescence in situ hybridization is not routinely used in the diagnosis of cutaneous lymphoma, but many studies have shown potential future applications in various areas. Other techniques, such as comparative genomic hybridization, are still confined to the research arena, but have added some insight into the molecular pathogenesis of cutaneous T-cell lymphoma.

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

Abstract: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.

Diffuse large B-cell lymphoma, leg type: A matter of site?

Abstract An 81-year-old white woman with a past medical history significant for coronary artery disease and a cerebrovascular accident presented with a large ulcerated tumor on her left ankle of 3 months duration. A skin biopsy was reported as diffuse large B-cell lymphoma. The histology revealed a diffuse infiltrate composed of a monotonous population of large round lymphocytes with features of centroblasts and immunoblasts. Immunostaining showed that the tumor cells were positive for CD20, MUM-1, FOX-P1, IgM, and BCL2 but negative for CD30. Immunostaining for Ki-67 showed that the tumor cells had a high proliferative index. The lesion was treated with radiotherapy, but the patient died 8 months later. There are 3 main types of primary cutaneous B-cell lymphoma: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT). Primary cutaneous marginal zone lymphoma and primary cutaneous follicle center lymphoma are indolent lymphomas with a 5-year disease-specific survival greater than 95%, whereas PCLBCL-LT represents a more aggressive type of disease with a 5-year disease-specific survival of approximately 50%. PCLBCL-LT has a phenotype similar to the “activated” subtype of nodal diffuse large B-cell lymphoma, which is thought to be a reason for the poor prognosis. The treatment of patients with PCLBCL-LT should be aggressive and polychemotherapy is indicated in most cases.

Current understanding of cutaneous lymphoma: selected topics.

Recent epidemiology studies have identified a steady increase in the incidence of cutaneous lymphomas over the past few decades. Although possible explanations for this increased incidence include heightened awareness of these conditions as well as a more refined diagnostic acuity by dermatologists and pathologists, an increase secondary to environmental factors cannot be discounted. Our understanding of cutaneous lymphomas keeps evolving. Consequently, our knowledge and understanding of cutaneous lymphomas requires reconsideration of past dogma and critical revision of the new proposals. In this article, some hot topics and important new findings in the field are reviewed.