CD34+ pigmented fibrous proliferations: the morphologic overlap between pigmented dermatofibromas and Bednar tumors

Pigmented dermatofibrosarcoma protuberans (DFSP; Bednar tumor) constitutes 5%-10% of all cases of DFSP and shows morphologic features that overlap with melanocytic and fibrous proliferations. We report 2 unusual cases of pigmented fibrous proliferations that demonstrate features of dermatofibromas and DFSP. The first case is that of a 19-year-old man with a 3-year history of a slowly growing pigmented lesion on the right arm. On clinical exam, the lesion was a 7-mm firm pigmented papulonodular lesion. The second case is that of a 31-year-old woman with a 4- to 5-year history of a slowly enlarging, asymptomatic "dark area" on the right buttock. On clinical exam, the lesion was a 2-cm darkly pigmented flat nodule. Morphologically, both lesions are primarily dermal proliferations of spindled cells admixed with pigmented dendritic melanocytes. The lesional cells trap collagen fibers at the periphery and there is basal cell hyperpigmentation. Adnexal structures are effaced, but significant trapping of subcutaneous fat is not present. By immunohistochemistry, both lesions show focal CD34 positivity but are negative for Factor XIIIa and melanocytic markers. Although overlap between standard dermatofibromas and DFSP is well documented in the literature, pigmented fibrous lesions with features of both entities are not well described.     

In vivo dynamics of intraepidermal CD8+ T cells and CD4+ T cells during the evolution of fixed drug eruption

Background Although a severe form of fixed drug eruption (FDE) clinically and histologically mimics toxic epidermal necrolysis (TEN), subsequent evolution of the two conditions is quite different. It remains unknown, however, which factors determine whether these lesions resolve spontaneously or subsequently progress to TEN. Objectives Because epidermal injury in TEN can be locally reproduced in the evolving FDE lesions, we sought to investigate how epidermal damage can be induced in the evolving FDE lesions and how disease progression to TEN can be prevented, by analysing the FDE lesions induced by clinical challenge with the causative drug. Methods We immunohistochemically investigated in vivo dynamics of T‐cell trafficking and activation that occur in the evolving FDE lesions using sequential biopsy specimens obtained at multiple time points from the FDE lesions. Results Intraepidermal CD8+ T cells, which are resident in the lesional epidermis as a stable homogeneous population of memory T cells, transiently acquire a natural killer‐like phenotype and express cytotoxic granules upon activation. The influx into the epidermis of CD4+ T cells including Foxp3+ regulatory T cells (Tregs) during the evolution serves to ameliorate epidermal damage induced by activation of the intraepidermal CD8+ T cells. Interleukin‐15 derived from the lesional epidermis could maintain the survival of the intraepidermal CD8+ T cells even in the absence of antigenic stimulus over a prolonged period of time (> 4 years). Conclusions Whether Tregs could migrate to the lesions upon activation of intraepidermal CD8+ T cells would determine whether the inflammation becomes resolved spontaneously or progresses to TEN.     

Rise in dermal CD11c+ dendritic cells associates with early-stage development of psoriatic lesions

There is limited information available regarding the phenotype and function of leukocytes involved in the earliest stages of psoriatic lesion development. In this study, we examined the presence of different types of leukocytes in psoriatic point lesions collected at three 1-week interval time points from a recent and simultaneously formed group of point lesions. The cells were quantified and compared with K16 expression and epidermal thickness, both typically increased in this disease and considered as hallmarks. We found a significant correlation between K16(+) cell increment and the increase in epidermal thickness in the timeframe of 14 days. The change in CD3(+), CD4(+), and CD8(+) T-cell numbers in the dermis showed a significant association with these two features from d7 to d14, whereas in the epidermis only CD8(+) T cells demonstrated a significant correlation. Remarkably, the relationship between T cells and disease progression was preceded by a significant correlation of CD11c(+) dendritic cells (DCs) with K16 expression and epidermal thickness from baseline onwards. Interestingly, there was also a numeric correlation of CD11c(+) DCs with the CD3(+) T-cell shifts from d7 to d14. A significant correlation was also found between dermal CD14(+) cells and K16 expression from d7 to d14. BDCA-2(+) plasmacytoid DCs were absent in non-lesional skin, but found at low numbers in most lesions. The change in plasmacytoid DC or neutrophil numbers did not correlate with lesion development. In conclusion, our study suggests a relevant role for T cells, and in particular dermal CD11c(+) DCs, in the earliest stage of psoriatic lesion development.     

CD4+ CD56+ hematodermic neoplasm

We report a case of a 75-year-old man with a cutaneous CD4+CD56+ hematodermic neoplasm. CD4+CD56+ hematodermic neoplasms are rare and commonly present as cutaneous lesions. This is an important diagnosis in the differential diagnosis of cutaneous hematologic malignancies because of the extremely poor prognosis.     

Fusariosis occurring in an ulcerated cutaneous CD8+ T cell lymphoma tumor

Fusarium species have recently emerged as the second most common pathogenic mold in immunocompromised patients, and they are moderately resistant to most antifungal agents. The skin lesions of disseminated fusariosis typically manifest as multiple red or violaceous macules or nodules, often ulcerated and covered by a black eschar. We report a case of cutaneous fusariosis in a patient with long-standing hypopigmented mycosis fungoides. The infection was successfully treated with a 3-month course of oral voriconazole. The present case is unusual in that the infection occurred within a pre-existing, ulcerated lesion of cutaneous CD8+ lymphoma, resulting clinically in confusion with pyoderma gangrenosum and necrosis of lymphoma. A high index of suspicion will prompt a timely biopsy as well as isolation of the fungus, and early institution of systemic antifungal therapy.     

Congenital CD34-positive granular cell dendrocytosis

Granular cell tumors involving the skin are mostly acquired lesions. The Schwann cell origin of these lesions is supported by positive immunostaining for S-100 protein and myelin basic protein. S-100- granular cell lesions rarely have been described in association with fibrous papules or dermatofibromas. The congenital variety of S-100- granular cell tumors occurs almost exclusively in the gingiva. The cell origin of these lesions is not well delineated. We report a hitherto undescribed case of a congenital cutaneous lesion which is histologically characterized by diffuse dermal infiltrates of S-100- but CD34+ granular dermal dendrocytes. The granular appearance of these CD34+ dendrocytes is attributed to an abundance of phagolysosomes. The pathogenetic mechanism of this unusual lesion remains to be elucidated.     

Primary cutaneous CD30+ anaplastic large-cell lymphoma in a young patient with psoriasis

Psoriasis is a common chronic inflammatory cutaneous disease, while primary cutaneous CD30+ anaplastic large-cell lymphoma (PC-ALCL) is a rare T-cell lymphoma which always has an excellent prognosis, although multifocal PC-ALCL tends to relapse after systemic chemotherapy. Psoriasis associated with PC-ALCL is exceptionally rare. We report a 29-year-old Chinese female with a 5-year history of psoriasis treated with Chinese herbs alone, who was referred to our institution with a tumor on the left clavicular region for 1 year and another one on the left palm for 2 months. Skin biopsies of both lesions showed diffuse infiltration of tumor cells, composed of large atypical cells with marked nuclear pleomorphism, prominent nucleoli, and eosinophilic cytoplasm. Large numbers of neutrophilic infiltrations were also noted in the lesion. Immunostaining revealed the lesion to be positive for CD30, vimentin, CD45, and CD68, and weakly positive for epithelial membrane antigen, but negative for anaplastic lymphoma receptor tyrosine kinase. The patient was diagnosed to have psoriasis associated with PC-ALCL; she died 18 months after the final diagnosis with unknown cause. We consider that immune dysregulation and/or Chinese herbs may play roles in the development of the present PC-ALCL.     

CD34+ dermal dendritic cells and mucin deposition in dermatomyositis

Dermal mucinosis is often associated with collagen diseases such as rheumatoid arthritis, lupus erythematosus, and dermatomyositis, in addition to autoimmune thyroiditis. We report eight cases of dermal mucin deposition secondary to typical dermatomyositis with cutaneous lesions known as heliotrope rash and Gottron’s papules. Striking mucin deposition was observed in both the papillary dermis and reticular dermis of all biopsy specimens. Immunohistochemical analysis showed that CD34+ dermal dendritic cells (DDCs) in the perilesional area in combination with vimentin+ cells within the mucinous lesion might be important in giving rise to abnormal deposition of dermal mucin. On the other hand, numbers of factor XIIIa+ DDCs and tryptase+ mast cells were reduced within and surrounding the mucin deposition, as compared with those in the dermis of normal controls. A pathogenic mechanism of dermal mucin deposition is proposed.     

CD30+ lymphoproliferative disorder: primary cutaneous anaplastic large cell lymphoma followed by lymphomatoid papulosis

CD30+ large anaplastic lymphoid cells are seen in anaplastic large cell lymphoma (ALCL), and also in lymphomatoid papulosis (LyP) and other lymphoproliferative disorders. It can be difficult precisely to categorize these disorders with CD30+ cells. We report a case of primary cutaneous CD30+ ALCL with systemic metastases in whom the clinical disease subsequently evolved into LyP. The patient was initially administered cisplatin and etoposide and made a good response. Eighteen months later, recurrent, self-healing cutaneous small nodules appeared around the original tumour site without any systemic involvement. Histopathological examination of the recurrent lesions revealed infiltration with a mixture of cells that included neutrophils, eosinophils and CD30+ large anaplastic cells cytologically identical with those in the primary lesion. The anaplastic cells in both the primary and recurrent lesions were positive for monoclonal antibodies CD30, CD25 and a monoclonal antibody directed against the chimeric protein p80(NPM-ALK). These observations suggest the possibility that the ALCL and the subsequent LyP represent different clinical manifestations of proliferation of the same clone.     

Childhood mycosis fungoides with a CD8+ CD56+ cytotoxic immunophenotype

Primary cutaneous T‐cell lymphomas mostly occur in patients of middle and higher age. Their rarity and an oftentimes atypical clinical presentation in childhood as well as the reluctance of taking biopsies in children are reasons for a delayed diagnosis. We report the case of an 11‐year‐old boy with a 7‐year history of slowly progressive CD8+CD56+ mycosis fungoides of the cytotoxic immunophenotype. His trunk and extremities were affected by extensive pale‐erythematous patches and plaques with fine scaling. In addition, several poikilodermatous lesions were present on his thighs. Improvement was achieved by topical mometasone furoate treatment. On the basis of our observation, a brief review on cutaneous T‐cell lymphomas in childhood and on CD8+ subtypes in particular is given. Clinicopathological correlation is crucial for establishing the correct diagnosis and for estimation of the prognosis.     

带状疱疹患者外周血CD4+ T淋巴细胞及皮损组织中自噬水平的检测

【摘要】 目的 观察带状疱疹患者外周血CD4+ T淋巴细胞、皮损组织表皮中自噬蛋白表达的变化及皮损组织表皮细胞中自噬囊泡的生成情况,探讨水痘-带状疱疹病毒感染与细胞自噬之间的关系。方法 选取2017年12月至2018年12月在解放军南部战区总医院皮肤科就诊的35例带状疱疹患者,男20例、女15例,年龄18 ~ 79（59.23 ± 9.27）岁,疼痛时间（5.14 ± 2.28） d,出疹时间（3.45 ± 1.77） d。流式细胞仪检测患者外周血CD4+ T淋巴细胞中自噬蛋白微管相关蛋白1轻链3B（LC3B）、Beclin-1、p62的表达,30例健康成人作为对照组。获取12例带状疱疹患者的皮损组织,免疫组化检测表皮中LC3B、Beclin-1、p62的表达,透射电镜观察表皮细胞中自噬囊泡的生成,以同一患者皮损周围未受累皮肤组织作为对照。组间比较采用两独立样本t检验。结果 带状疱疹患者外周血CD4+ T淋巴细胞中LC3B、Beclin-1阳性表达率（61.23% ± 7.61%、35.84% ± 4.22%）明显高于对照组（36.56% ± 4.27%、15.34% ± 1.89%;t = 15.75、24.56,均P < 0.01）,而p62阳性表达率（5.75% ± 0.67%）明显低于对照组（10.03% ± 1.15%,t = 18.65,P < 0.01）。12例带状疱疹患者皮损组织表皮中LC3B、Beclin-1的表达明显高于周围正常皮肤组织,而p62的表达明显低于周围正常皮肤组织（t = 2.86、4.58、2.43,均P < 0.05）。透射电镜观察示,12例带状疱疹患者皮损区表皮细胞中有较多包饶着病毒颗粒的自噬囊泡生成,皮损区自噬囊泡计数明显高于周围正常皮肤（t = 9.67,P < 0.01）。结论 带状疱疹患者外周血CD4+ T淋巴细胞与皮损组织表皮中自噬水平升高。     

Successful desensitization to fixed drug eruption: the presence of CD25+CD4+ T cells in the epidermis of fixed drug eruption lesions may be involved in the induction of desensitization

BACKGROUND: Fixed drug eruption (FDE) is a distinct type of drug-induced eruption, in which intraepidermal CD8+ T cells in the lesional skin are the final effector cells in the epidermal injury of FDE. Desensitization is a unique approach for the management of drug eruption, which has been reported to be effective in treating FDE. However, the mechanisms underlying desensitization to FDE are quite unknown. OBJECTIVE AND METHODS: We reported a case of successful desensitization to allopurinol-induced FDE. To clarify the mechanisms underlying desensitization to FDE, we examined the phenotype of T cells in the epidermis of FDE lesions before and after desensitization using flow cytometry. RESULTS: The overwhelming majority of intraepidermal T cells in the FDE lesion before desensitization consisted of CD8+ T cells, whereas a significant number of CD25+CD4+ T cells were present in the epidermis of FDE lesions after desensitization. CONCLUSION: The presence of CD25+CD4+ T cells in the epidermis of FDE lesions may be involved in the induction of desensitization to FDE.     

Unlikely role of Epstein-Barr virus in the pathogenesis of primary cutaneous CD30+ anaplastic large cell lymphoma

BACKGROUND: Primary cutaneous CD30+ anaplastic large cell lymphoma (ALCL) is a rare subset of cutaneous lymphoma, with a much better prognosis than its nodal counterpart. The pathogenesis of both nodal and primary cutaneous CD30+ ALCL is largely unknown but experimental data support the hypothesis that the Epstein-Barr virus could play a role in the nodal subset. OBJECTIVE: To evaluate the involvement of Epstein-Barr Virus (EBV) in primary cutaneous CD30+ ALCL by searching for both nucleic acids and EBV proteins in cutaneous lesions. SETTING: Two University Hospitals in Southern France (secondary referral hospitals). PATIENTS: Eight consecutive patients with typical primary cutaneous CD30+ anaplastic large cell lymphoma were studied. METHODS: Search for the presence of DNA, RNA and EBV proteins in cutaneous lesions by PCR, in situ hybridization and immunohistochemistry. RESULTS: EBV DNA and RNA was identified in only one lesion of primary cutaneous CD30+ ALCL and in none of the normal adjacent skin samples. In situ hybridization and immunohistological studies were consistently negative in all samples. Conclusion: These results do not support an early role of EBV in the oncogenetic pathogenesis of primary cutaneous CD30+ ALCL.     

CD103+T细胞在银屑病皮损中的表达

目的：明确银屑病患者皮肤CD103+T细胞的表达及其与银屑病严重程度的关系。方法：免疫组化检测29例银屑病患者皮损和非皮损皮肤及6名健康对照皮肤中表皮及真皮CD103+T细胞的表达。计算银屑病患者PASI值。结果：CD103+T细胞主要在真皮表达。银屑病患者皮损和非皮损真皮中每个高倍视野CD103+T细胞百分率分别为（26.06%±11.72）%和（12.82±4.5）%（P<0.05）;健康人对照皮肤真皮内CD103+T细胞百分率为（7.47±1.3）%,明显低于银屑病非皮损区（P<0.05）。银屑病患者皮损中,CD103+T的表达与PASI值正相关（P<0.05）。 结论：真皮中CD103+T细胞可能与银屑病的发病及严重程度有关。     

Skin manifestations in CD4+, CD56+ malignancies

CD4+ CD56+ hematologic neoplasms were recently individualized. We report three cases of CD4+ CD56+ malignancies with cutaneous lesions in three cases and also bone marrow involvement in two cases. Two patients relapsed 2 and 3 months after polychemotherapy. Two patients died within 3-10 months. A constant immunophenotype was observed with the co-expression of CD4 and CD56, the absence of B and T-cell markers. The salient fact of this report is the presence of T-cell clonal rearrangement. The clinical and pathological features closely resemble the specific cutaneous manifestations in acute leukemia with monocytic differentiation, especially the granulocytic sarcoma. Because of the positivity of the CD56, natural killer cell proliferations were discussed. Since 1994, 50 cases of CD4+, CD56+ cutaneous neoplasms have been reported with specific clinical, cytologic and immunohistochemical features. The diagnosis is more difficult when the cutaneous location is exclusive; on the contrary, the cytological features of the blood and medullar cells with cytoplasmic vacuoles and pseudopodia are characteristic of this hematologic neoplasm. The presence of CD123 antigen in most of the cases is an argument for a plasmacytoid dendritic cell proliferation and it is also a good marker for primary cutaneous lesions.     

免疫表型为CD8~+,CD4~-,CD56~+的蕈样肉芽肿1例

报告1例免疫表型为CD4-,CD8+,CD56+的蕈样肉芽肿(MF)。患者男,21岁。双侧腋窝、躯干及腹股沟大片状灰红色至棕红色斑8年,呈渐进性发展,无任何自觉症状。腹部皮损组织病理示表皮轻度角化不全,真皮内致密淋巴细胞,部分细胞入侵表皮。免疫组化示CD4-,CD8+,CD3+,CD43+,CD68灶状+,CD30灶状+,CD56+,TIA-1-,EBV-。诊断:蕈样肉芽肿。给予阿维A胶囊30mg/d,顿服,糠酸莫米松乳膏及多磺酸粘多糖乳膏外用。皮损缓解,临床随访4个月,病情稳定。     

CD30 expression on CD1a+ and CD8+ cells in atopic dermatitis and correlation with disease severity

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental stimuli, resulting in increased infiltration of inflammatory cells, IgE production and enhanced expression of costimulatory molecules, cytokines and chemokines. CD30, a TNF receptor superfamily member, is a costimulatory molecule expressed on activated T and B cells. A positive correlation between soluble CD30 (sCD30) levels in patient serum and AD disease severity has been described previously. However, the relative frequencies and identities of cells expressing CD30 in AD patients and the relationship between the frequency of CD30 positive cells and serum sCD30 levels with disease severity remained unknown. To address these questions, immunofluorescence analysis of AD skin lesions representing different disease stages, was conducted. In addition to the CD4+ T cells, CD1a+ Langerhans cells and CD8+ T cells were found to express CD30 in AD lesions and the cell numbers correlated with disease severity. FACS analysis of AD patient blood samples revealed expression of CD30 on memory T-cells and a correlation with disease severity was identified. Finally, serum analysis of soluble mediators revealed positive correlations between sCD30, IgE, MDC, TARC and PARC levels with disease severity. Combined, our data provide correlative evidence that CD30+ cells, including Langerhans cells and CD8+ T-cells, may contribute to AD disease severity and that therapeutic strategies targeting CD30+ cells may provide benefit to AD patients.     

Pleomorphic CD8+ small/medium size cutaneous T-cell lymphoma

Pleomorphic small/medium-sized cutaneous T-cell lymphoma is a recently recognized rare type of cutaneous T-cell lymphoma which is clinicopathologically different from mycosis fungoides and Sezary syndrome. By definition the phenotype of the neoplastic lymphocytes in pleomorphic small/medium-sized cutaneous CD3CD4CD8 but CD8 pleomorphic small/medium sized cutaneous T-cell lymphoma cases have been occasionally described. We describe a 55-year-old female with a pruritic erythematous nodule on the lateral aspect of her right foot present for 1.5 years. Histology revealed a nonepidermotropic lichenoid infiltrate in the papillary dermis and a patchy infiltrate in the mid and lower dermis composed of small to medium-sized pleomorphic lymphocytes. The immunophenotype of these lymphocytes was CD3CD4CD8TIA-1. Staining for CD20, CD30, CD56, TdT, and LMP1 were negative, and the Ki-67 proliferation index was 5% to 10%. Gene rearrangement studies demonstrated a T-cell clone. The laboratory and imaging workup did not reveal extracutaneous involvement. The lesion was treated by local irradiation but a follow-up biopsy demonstrated only partial remission. Consequently, the lesion was treated by surgical excision.     

Primary CD30+ve cutaneous T-cell lymphoma associated with chronic burn injury in a patient with longstanding psoriasis

An increased incidence of lymphoma has been reported in psoriatic patients, but most cases are nodal B-cell lymphoma. We report a unique case of CD30-expressing cutaneous T-cell lymphoma arising from underlying psoriatic plaque after intractable caustic burns and cellulitis in the palm of a patient with generalized chronic plaque psoriasis. Molecular studies confirmed a localized clonal T-cell expansion, and the lesion responded dramatically to multiagent chemotherapy. The case highlighted the possible role of chronic systemic and local T-cell activation in the pathogenesis of primary CD30+ve cutaneous T-cell lymphoma, and the importance of histologic assessment in chronic nonhealing skin lesions.