CD56 staining in Merkel cell carcinoma and natural killer‐cell lymphoma: magic bullet,diagnostic pitfall,or both?

Background: Antibodies to CD56 label natural killer (NK) cell lymphomas and neuroendocrine tumors such as Merkel cell carcinoma (MCC). In MCC altered by crush artifact or obscured by lymphocytes, the histologic features coupled with CD56 positivity can lead to an erroneous impression of NK‐cell lymphoma. Methods: Eighteen cases of MCC were stained for CD56, CK20, MNF116, and pankeratin. The results were compared to histologic features and CD56 staining pattern of three NK‐cell lymphomas. Results: Three of 18 cases of MCC histologically resembled lymphoma, and CD56 positivity with CD3 and CD20 negativity initially raised the possibility of NK‐cell lymphoma. Two additional cases were obscured by dense inflammation, again suggesting the diagnosis of lymphoma. Seventeen of 18 MCC labeled for CD56 and an equal number stained for CK20. All MCC tested were positive for CAM5.2 (14/14) and MNF116 (17/17). Antibodies to pankeratin labeled only one of 18 MCC. Staining for CD56 was stronger in MCC than NK‐cell lymphomas. Conclusions: CD56 is a sensitive marker for MCC as well as for NK‐cell lymphoma, but is not specific. Importantly, CD56 positivity in crushed or inflamed biopsies of MCC may lead to an erroneous impression of NK lymphoma. Awareness of this potential pitfall will prevent misdiagnosis.     

Blastic natural killer‐cell lymphoma of the skin associated with myelodysplastic syndrome or myelogenous leukaemia: a coincidence or more?

We report three patients with blastic natural killer (NK)-cell lymphoma of the skin associated with myelodysplastic syndrome (MDS) (two patients) or subacute myelomonocytic leukaemia (one patient). In two patients MDS was diagnosed before skin lesions; the patient with leukaemia initially presented with skin lesions. Our patients had several clinical features in common, namely multiple skin lesions with a bruise-like appearance, involvement of the oral mucosa, and good general status at presentation but very rapid deterioration in the course of the disease. All patients died of disease 4-14 months after the diagnosis. Histopathologically, there were cutaneous infiltrates of slightly pleomorphic medium-sized cells expressing CD4, CD56, terminal deoxynucleotidyl transferase (focally) and being negative for surface CD3, cytotoxic molecules, B-cell-associated markers and myelomonocytic markers. Erythrocyte extravasation was seen in all patients. T-cell receptor genes were in germline configuration. MDS was classified as refractory cytopenia with multilineage dysplasia and ring sideroblasts and refractory anaemia with transition to refractory anaemia with excess of blasts. We reviewed similar cases reported in the literature showing coexistence of blastic NK-cell lymphoma/leukaemia and MDS or myelogenous leukaemia. We conclude that given an overall limited number of reported cases of blastic NK-cell lymphoma/leukaemia, its association with various myelodysplastic/myeloproliferative disorders seen in a subset of patients ( approximately 15-20%) is more than coincidental and may indicate their common origin.     

Psoriasis associated with idiopathic CD4+ T‐cell lymphopenia: a regulatory T‐cell defect?

Idiopathic CD4⁺ lymphocytopenia (ICL) is a rare immunodeficiency syndrome of unknown origin for which the increased risks of opportunistic infections and of malignancies have been well established; however, skin dysimmune diseases, including psoriasis, have been scarcely reported up to now. We report herein the severe course of psoriasis in four patients with ICL, and show evidence for a defect in the skin recruitment of regulatory CD4⁺FoxP3⁺ T cells. These data raise the apparent paradigm of the occurrence of a severe immunomediated disease together with a profound T‐cell defect, a model that might also apply to other immune deficiencies associated with psoriasis.     

Indolent CD8+ lymphoid proliferation of the ear: A phenotypic variant of the small‐medium pleomorphic cutaneous T‐cell lymphoma?

Background: Recently, Petrella et al. described four patients with an unusual CD8+ lymphoid proliferation arising on the ear. These cases do not correspond clearly to any recognized category of cutaneous T-cell lymphoma (CTCL) described in the World Health Organization (WHO)/European Organization for Research and Treatment of Cancer (EORTC) 2005 classification.
Methods and Results: Three patients (all men; median age 64; range: 61-69) presented with plaques or small tumors localized on the ears. All lesions showed histopathologically a dense, diffuse infiltration of lymphocytes within the entire dermis without epidermotropism. Cytomorphology revealed predominance of medium-sized pleomorphic lymphocytes. Immunohistochemistry showed a cytotoxic phenotype (CD3 + /CD4 −/CD8 +). Polymerase chain reaction (PCR) analysis of the T-cell receptor (TCR)-gamma gene revealed a monoclonal rearrangement in two of three patients. Follow-up data of two patients were available; one is alive without skin or systemic manifestations of the disease after 28 months, whereas the other is alive with persistent skin disease after 7 months.
Conclusions: Our observation confirms that some patients present with a peculiar lymphoid proliferation of small-medium pleomorphic cytotoxic lymphocytes located on the ear, probably representing a phenotypic variant of the cutaneous small/medium pleomorphic T-cell lymphoma (CSMPTCL). These cases should not be misinterpreted as a high-grade cytotoxic lymphoma.     

Indolent CD8‐positive lymphoid proliferation on the face: part of the spectrum of primary cutaneous small‐/medium‐sized pleomorphic T‐cell lymphoma or a distinct entity?

We report two cases of a CD8‐positive lymphoid proliferation presenting as solitary lesions on the ear and nose, respectively. Histopathologically, both cases were characterized by a diffuse non‐epidermotropic dermal proliferation of clonal medium‐sized CD8‐positive T‐lymphocytes with a lymphoblast‐like appearance, having cells with large folded nuclei, prominent nucleoli and ample amphophilic or pale eosinophilic cytoplasm. Staging procedures excluded systemic involvement, and both lesions were successfully treated with localised radiotherapy without evidence of recurrence after 12 and 24 months' follow up, respectively. Previously reported cases on the ear had similar clinicopathological and immunophenotypical features, and together raise the possibility of a distinct entity, an indolent CD8‐positive lymphoid proliferation. Suchak R, O'ConnorS, McNamara C, Robson A. Indolent CD8‐positive lymphoid proliferation on the face: part of the spectrum of primary cutaneous small‐/medium‐sized pleomorphic T‐cell lymphoma or a distinct entity?     

Factors Influencing [F‐18] 2‐Fluoro‐2‐Deoxy‐d‐Glucose (F‐18 FDG) Accumulation in Melanoma Cells: Is FDG a Substrate of Multidrug Resistance (MDR)?

In order to specify the influence of multidrug-resistance (MDR) on the accumulation of the PET tracer, F-18 FDG ([Fluorine-18] 2-fluoro-2-deoxy-D-glucose, in melanoma cells, both the MDR function and expression of two human melanoma cell lines SK-MEL 23 and 24, were evaluated. The effects of MDR modulators on FDG accumulation and efflux were also investigated. A functional analysis using representative MDR fluorescent substrates and inhibitors clarified the following characteristics: 1) SK-MEL 23 possesses a highly active function of MRP, but not P-gp. 2) SK-MEL 24 possesses weak functions of both MRP and P-gp. Western blot analysis using monoclonal antibodies for MDR expression demonstrated an exceedingly high MRP expression of SK-MEL 23 and only slight P-gp and MRP expression of SK-MEL 24, corresponding to the functional data. The efflux inhibition assay using F-18 FDG revealed a considerable retention of FDG in SK-MEL 23 in the presence of the MRP inhibitor probenecid. It was also found that the P-gp inhibitor verapamil depressed the FDG efflux of SK-MEL 24. Our present in vitro study suggests that FDG may be a substrate of MDR in some melanoma cells and further MDR may be one of the important factors affecting FDG-PET melanoma imaging.     

Primär kutane CD4+ klein‐ bis mittelgroßzellige pleomorphe T‐Zell‐Lymphoproliferation: Wo stehen wir? Eine systematische Übersicht

Primary cutaneous CD4+ small/medium pleomorphic T‐cell lymphoproliferative disorder (PCSMP‐TLPD) is a provisional entity with uncertain malignant potential according to the latest revision of the WHO classification for lymphoid neoplasms. We conducted a systematic literature review of all previously reported cases of PCSMP‐TLPD to highlight their typical and atypical features. The main features of PCSMP‐TLPD and its possible clinicopathologic overlap with similar disorders are also discussed. It is hoped that this review will provide a useful outline of this condition and the most important differential diagnoses. Finally, we recommend a rigorous consensus among cutaneous lymphoma experts in drafting diagnostic criteria and the best case definition.     

Schützen langkettige Omega‐3‐Fettsäuren vor atopischer Dermatitis?

Long‐chain polyunsaturated fatty acids are essential for human nutrition. The number of double bonds determines whether a given fatty acid is termed two, three, or x times unsaturated. Depending on the distance of the first double bond from the fatty acid's methyl group, one distinguishes omega‐3 fatty acids from omega‐6 fatty acids. While the use of gamma linolenic acid, a long‐chain fatty acid of the omega‐6 family, has proven unsuccessful in the prevention or treatment of atopic dermatitis, supplementation of long‐chain omega‐3 fatty acids may represent a promising approach in the prevention of allergic disorders, especially atopic dermatitis. Whether the concept of long‐chain omega‐3 fatty acid administration will also become established in a therapeutic setting, depends on whether the beneficial effects observed so far can be substantiated in randomized controlled intervention studies.     

长期抗病毒治疗的艾滋病患者CD4^+/CD8^+比值影响因素分析

目的探讨艾滋病患者抗病毒治疗后影响CD4^+/CD8^+比值恢复的因素。方法回顾性分析455例患者的基线及随访资料,观察期60个月,对60个月时CD4^+ T细胞数大于350/μL的患者,用Logistic回归分析影响其CD4^+/CD8^+比值恢复的影响因素,同时分析基线CD4^+/CD8^+、CD4^+T细胞数的差异。结果治疗60个月,影响CD4^+ T细胞数大于350/μL的患者CD4^+/CD8^+比值恢复的独立危险因素为年龄、基线CD4^+ T细胞数小于100/μL、基线CD8^+ T细胞数。CD4^+ T细胞数大于350/μL组,与CD4^+ T细胞数小于350/μL组,基线CD4^+/CD8^+比值比较差异有统计学意义(P=0.00),基线CD4^+ T细胞数比较差异有统计学意义(P=0.00)。结论抗病毒治疗可改善CD4^+/CD8^+比值,治疗时间越早,长期治疗后免疫功能恢复情况越好。但高龄、低CD4^+ T细胞数、高CD8^+ T细胞数是长期治疗的HIV/AIDS患者免疫功能重建的影响因素。     

Hepatosplenisches T‐Zell‐Lymphom unter Therapie mit TNF‐α‐inhibierenden Biologics: (k)ein Risiko für Patienten mit Psoriasis?

Tumor necrosis factor (TNF)‐α antagonists have considerably improved the therapeutic approach to chronic inflammatory disorders including psoriasis vulgaris. Recently, some cases of highly aggressive hepatosplenic T‐cell lymphoma (HSTCL) have developed in patients with inflammatory bowel diseases (IBD) being treated with infliximab or adalimumab. Analysis of the published data suggests that the emergence of HSTCL is favored by the combination of purine analogues and infliximab or adalimumab in the therapy of a granulomatous inflammation involving Vδ1⁺γδ T cells. Because psoriasis vulgaris is different from IBD in regard to the type of inflammation, the concomitant therapies used and the tissue‐specific subsets of γδ T cells, the use of infliximab or adali‐mumab in psoriasis may not necessarily be associated with an increase in the risk of HSTCL.