Langerhans cell hyperplasia in the tumor stage of mycosis fungoides: a mimic of Langerhans cell histiocytosis

Mycosis fungoides is a form of cutaneous T-cell lymphoma (CTCL). Malignant CD4⁺ T cells have been found to adopt the T-regulatory (Treg) cell phenotype and function. We present the case of a 66-year-old man diagnosed with mycosis fungoides that was progressing from the plaque to the tumor stage. The histopathological examinations showed that the Langerhans cell (LC) infiltration in the skin lesion of the tumor stage was greater than that in the patch/plaque stage; the tumor stage lesions resembled LC histiocytosis pathologically. The associations among LCs, apoptotic tumor cells, Treg CTCL cells, and relevant cytokines are complex. Treg CTCL cells produce the immunosuppressive cytokines interleukin-10 and transforming growth factor beta, which facilitate continuous recruitment of LCs and maintenance of long-term dendritic cell immaturity, thereby explaining the remarkable LC infiltration in the tumor stage samples from our patient. This phenomenon indicates that LCs accompanied by Treg CTCL cells may play an important synergistic role in the tumor progression. The development of immunotherapy directed against Treg CTCL cells and LCs overproduction and other immunosuppressive cytokines may be a potent useful adjuvant and worthy of further investigation.     

Distribution of T cell subsets and Langerhans cells in mycosis fungoides, and the effect of PUVA therapy

Twenty-three patients with histologically proven mycosis fungoides (MF) were followed sequentially using cell marker studies to investigate the possibility of specific patterns of T cell and Langerhans cell (LC) involvement. Fifty-five skin biopsies, taken before and during PUVA therapy, were studied using monoclonal antibodies directed against T cell subsets. Both T-helper (Tn) and T-suppressor/cytotoxic (Tsc) cells were present in all biopsies, and the epidermal infiltrate contained proportionally more T_sc than the dermal infiltrate. Epidermal LC numbers were counted in 60 biopsies and were increased in early disease but fell dramatically during PUVA; some biopsies had large numbers of dermal LC, usually in focal aggregates.     

The role of Langerhans cells in the sexual transmission of HIV

Sexual transmission of HIV is the most common mode of infection in the global HIV epidemic. In the absence of an effective vaccine, there is an urgent need for additional strategies to prevent new HIV infections. An emerging body of evidence now indicates that Langerhans cells (LC) are initial cellular targets in the sexual transmission of HIV, and CD4- and CCR5-mediated infection of LC plays a crucial role in virus dissemination. However, interactions between HIV and LC are complex. For example, it is evident that HIV can interact concomitantly with non-LC dendritic cells in two separate and distinct ways: a CD4- and CCR5-dependent infection pathway and a CD4- and CCR5-independent capture pathway mediated by DC-SIGN, a C-type lectin molecule. Thus, there may be multiple ways by which HIV interacts with target cells in the genital mucosa. This review focuses on the recent advances regarding the cellular events that may occur during heterosexual transmission of HIV.     

Decreased presence of Langerhans cells is a critical determinant for Indian Post kala‐azar dermal leishmaniasis

Post kala‐azar dermal leishmaniasis (PKDL) is the dermal sequel of visceral leishmaniasis (VL) and occurs after apparent cure or alongside with VL. It is confined to South Asia (India, Nepal and Bangladesh) and East Africa (mainly Sudan), the incidence being 5‐10% and 50‐60% respectively. In South Asia, as the transmission of VL is anthroponotic, PKDL patients are the proposed disease reservoir, thus assuming epidemiological significance, its eradication being linked to the control of leishmaniasis. In the absence of an animal model and its low incidence, factors contributing towards the immunopathogenesis of PKDL remain an open‐ended, yet pertinent question. This study delineated the lesional immunopathology in terms of granuloma formation, Langerhans cells, tissue macrophages along with mRNA expression of IL‐12p40 and IL‐10. Our study in Indian PKDL for the first time identified that the number of CD1a⁺/CD207⁺ Langerhans cells are decreased and CD68⁺ macrophages are increased along with the absence of an epitheloid granuloma. Importantly, this decrease in Langerhans cells was associated with decreased mRNA expression of IL‐12p40 and increased IL‐10. This was reverted with treatment allowing for elimination of parasites and disease resolution along with an increase in Langerhans cells and decrease in macrophages. Thus, in Indian PKDL, absence of a granuloma formation along with a decrease in Langerhans cells collectively caused immune inactivation essential for parasite persistence and disease sustenance.     

A monoclonal antibody technique to demonstrate an increase in Langerhans cells in cutaneous lesions of mycosis fungoides

Two monoclonal antibodies raised against cortical thymocytes have been found to react with epidermal Langerhans cells in normal human skin. Using these antibodies, an increase in the number of Langerhans cells was seen in the epidermis and dermis of ten biopsies from patients with mycosis fungoides.     

A question of persistence: Langerhans cells and graft‐versus‐host disease

Langerhans cells (LCs) have been scrutinized many times in studies of the pathogenesis of graft‐versus‐host disease (GVHD). As migratory dendritic cells, LCs are capable of direct antigen presentation to cytotoxic T cells. Their self‐renewal capacity has led to speculation that persistent recipient LCs could provide a continuous source of host antigen to donor T cells infused during hematopoietic stem cell transplantation (HSCT). In this issue of Experimental Dermatology, a new study examines at the relationship between recipient LCs and chronic GVHD.     

Risk of mycosis fungoides in psoriatic patients: a critical review

Psoriasis has been controversially associated with risk of non-Hodgkin lymphoma (NHL) and mycosis fungoides (MF). Also patients who developed MF after systemic treatment for psoriasis have been reported, and some authors suggested that the association between MF and psoriasis is not infrequent. We performed an extensive literature review in order to examine the risk of developing MF in psoriatic patients with a systematic search of the English-language databases. An increased risk for lymphoma overall in psoriatic patients has been found only by three out of seven studies. The risk of developing MF in psoriatic patients has been investigated by different studies in different populations and with different methodologies presenting bias and limitations, and it seems reasonable that misclassification between psoriasis and MF may explain the association reported. In contrast to the large number of psoriatic patients treated with biologicals, only 27 case reports of MF after biological therapy for psoriasis have been reported, and in 10 cases, the initial psoriasis diagnoses were then revised as MF. A true association between MF and psoriasis is possible, but the real incidence and prevalence are still unknown. The reported higher risk of developing MF in psoriatic patients should be reconsidered in the light of the bias of misclassification and the low magnitude reported in previous studies. There is not enough evidence to support a causal relation among biological therapies and MF in psoriatic patients.     

A subpopulation of Langerhans cells (CD1a+Lag-) increased in the dermis of plaque lesions of mycosis fungoides.

The population of CD1a+ cells and the quantity of Birbeck granules were evaluated in comparison with the population of T lymphocytes in a variety of clinical lesions of mycosis fungoides. Anti-CD1a and Lag antibodies that specifically react with Birbeck granules and related structures of human Langerhans cells were used immunohistochemically. CD1a+ cells in the dermis of lesions of mycosis fungoides significantly increased in plaques of the plaque stage and in plaques of the tumor stage. They were most frequent in lesions with CD4+ cells ranging in number from 100 to 150/mm2. These lesions were suspected to be progressing from the plaque to the tumor stage. During the course of the disease, most of the dermal CD1a+ cells had few Lag antigens. These results suggest that dermal CD1a+Lag- cells may promote the progression of mycosis fungoides from the plaque to the tumor stage.     

Do OKT6 positive Langerhans cells play a role in the suppression of ultraviolet-induced carcinogenesis?

Langerhans cells (LC) in epidermis are antigen presenting cells. LC may play a role in immune surveillance system and are considered to suppress development of ultraviolet (UV) induced skin cancers. We studied effect of UVB irradiation to LC of xeroderma pigmentosum (XP) and normal subjects by using OKT6 monoclonal antibody. When 3 minimal erythema dose (MED) of UVB were irradiated, density of OKT6 positive LC of XP began to decrease 6 hours after irradiation, and showed the least numbers on day 2 and returned completely to the pre-irradiation level on day 14. Further, after 3 MED irradiation, LCs of both normal subjects became the least on day 3 and returned to the pre-irradiation level on day 14. In XP variant and normal subjects, the number of LC in chronic sun-exposed skin decreased significantly in a similar way comparing to that of non-exposed skin. These results suggest that epidermal LC may not play an essential role in prevention of UV-induced tumor development.     

Histologic criteria for the diagnosis of erythrodermic mycosis fungoides and Sézary syndrome: a critical reappraisal

It is often difficult to make a clinical or histologic diagnosis of erythrodermic mycosis fungoides (MF) and Sézary syndrome (SS). Whereas the histologic parameters for making a diagnosis of MF with well-developed patch and plaque stage lesions are clearly defined, the same criteria appear to be less relevant for diagnosing MF in patients with erythroderma secondary to the disease. In order to better define the histologic features of erythrodermic MF and SS, we studied 28 routine histologic sections of 17 patients with known erythrodermic MF or SS. Sections were reviewed independently by 2 dermatopathologists. Each of 24 parameters was scored semi-quantitatively and the data were compared to data previously reported from a group of 64 patients with limited patch and plaque stage lesions of MF. When compared to biopsies from patients with limited patch/plaque lesions, biopsies taken from erythrodermic patients displayed more parakeratosis (p=0.0492) and acanthosis (p=0.0046), less disproportionate epidermotropism, fewer lymphocytes aligned within the basal layer (p=0.0045), fewer hyper-convoluted cells in the epidermis, more dermal hyperconvoluted cells (p=0.0191), more papillary dermal fibrosis (p=0.0002), more prominent teleangiectasias (p=0.0028) and more mitotic figures.
The histologic features of erythrodermic MF and Sézary syndrome are even more subtle than the features of patch and plaque stage MF, thus rendering the histologic diagnosis more difficult.     

Pagetoid reticulosis, epidermotropic mycosis fungoides and mycosis fungoides: a disease spectrum

Using a standard technique involving monoclonal antibodies against T-cell subsets, we have shown that almost all the infiltrating T-cells in the epidermis of a patient with Pagetoid reticulosis (PR), one with epidermotropic mycosis fungoides (EMF) and one with poikiloderma atrophicans vasculare (PAV), were OKT8 positive (presumed cytotoxic/suppressor) T-cells. The infiltrating T-cells in the epidermis of a patient with limited plaque stage mycosis fungoides (MF), however, were almost exclusively Leu 3a-positive (presumed helper/inducer) T-cells as is usually found in this condition. The keratinocytes in the patients with PR, EMF and PAV were HLA-DR-positive whilst those in the patient with MF were HLA-DR-negative. We consider these four diseases to be part of the spectrum of mycosis fungoides, the first three conditions representing the early or benign end of the spectrum.     

4 018例浅部真菌病及其致病菌种分析

 目的 了解广州及周边地区浅部真菌病病种及其致病菌种的构成与分布情况。方法 对2013年1月至2020年12月来南方医科大学皮肤病医院就诊并且真菌培养鉴定阳性的4 018例病例进行病种及致病菌分析。结果 4 018例浅部真菌病病种前三位依次是甲真菌病2 353例（58.00%）、足癣546例（13.46%）、股癣319例（7.86%）;致病真菌前三位分别是红色毛癣菌2 197株（54.15%）,念珠菌1 161株（28.62%）,须癣毛癣菌316株（7.79%）;男性体癣、股癣、头癣和足癣的比例均高于女性(均P<0.05),而女性甲真菌病的比例高于男性（X²=189.23,P<0.05）。结论 广州及周边地区浅部真菌病及致病菌谱的分布大体符合国内的流行趋势,主要致病菌为红色毛癣菌,0～10岁年龄段是头癣和面癣的发病高峰。临床应重视以上特点,有针对性地为浅部真菌病的防治提供指导。