Different Stages Of Mycosis Fungoides Research Articles

Effectiveness and tolerability of chlormethine gel for the management of mycosis fungoides: a multicenter real-life evaluation.

Topical chlormethine (CL) is recommended as a first-line treatment for early-stage mycosis fungoides (MF) and in 2017, the European Medicines Agency approved the CL gel formulation to treat adult patients. More recently, to increase patient compliance and adherence, clinicians have developed flexible protocols that allow the concomitant use of CL gel with topical corticosteroids in daily practice regimens. Therefore, sharing real-life data on CL gel use and side effects management may help improve the use of this agent. To expand knowledge about the actual use of CL gel in patients with MF, the present study assessed the improvement of MF skin lesions after CL gel treatment and provided information on the management of cutaneous adverse events (AEs) in a real-life setting. This was an Italian retrospective study conducted among six dermatology referral centers. Patients ≥18 years affected by MF and in treatment with CL gel (160 µ/g), alone or in combination according to routine clinical practice, between December 2019 and December 2021 were considered. The study's primary aim was to evaluate the effectiveness of CL gel in terms of overall response rate (ORR) after 3 months of treatment. A total of 79 patients (61% male) with different stages of MF (84% early stage) were included. CL gel was prescribed mainly in association with topical corticosteroids (66% of patients). ORR after 3 months of treatment was 42%, with no differences between early- and advanced-stage MF. Response rates improved over time up to 97% after 18 months of treatment. Overall, 66 AEs were reported in 67% of patients; most were hyperpigmentation (45%) and irritant contact dermatitis (37%). Six AEs led to treatment discontinuation, and five out of six (83%) patients who reported these events resumed treatment after interruption. No AEs were classified as severe. Our observations support the use of CL gel in patients with early- and advanced-stage MF, making it a valuable treatment option.

YKL-40 immunoexpression as a prognosticator of mycosis fungoides.

YKL-40 is a 40 kDa chitinase-like glycoprotein that is predicted to contribute to the pathogenesis of several inflammatory and neoplastic conditions. To assess YKL-40 immunoexpression in different stages of mycosis fungoides (MF) to find out if YKL-40 is playing a possible role in disease pathophysiology and progression. This work included 50 patients with different stages of MF diagnosed on the basis of clinical, histopathological, and both CD4 and CD8 immunophenotyping, in addition to 25 normal control skin. The Immune Reactive Score (IRS) of YKL-40 expression was determined in all specimens and statistically analyzed. YKL-40 expression reported a significant rise in MF lesions compared to control skin. Among MF specimens, the mildest expression was observed in the early patch stage followed by the plaque stage, while the strongest was in tumor stages. Positive correlations were discovered between IRS of YKL-40 expression in MF specimens and patients' age, disease chronicity, clinical staging, and TNMB classification. YKL-40 might participate in MF pathophysiology, and the highest expression is associated with advanced stages of the disease and poor outcomes. Therefore, it might be of value as a prognosticator for monitoring high-risk MF patients and follow-up assessment of treatment success.

Role of Neutrophil-to-Lymphocyte Ratio (NLR) in Patients with Mycosis Fungoides.

The neutrophil/lymphocyte ratio (NLR) at baseline has been demonstrated to correlate with higher stages of disease and to be a prognostic factor in numerous cancers. However, its function as a prognostic factor for mycosis fungoides (MF) has not been yet clarified. Our work aimed to assess the association of the NLR with different stages of MF and to outline whether higher values of this marker are related to a more aggressive MF. We retrospectively calculated the NLRs in 302 MF patients at the moment of diagnosis. The NLR was obtained using the complete blood count values. The median NLR among patients with early stage disease (low-grade IA-IB-IIA) was 1.88, while the median NLR for patients with high-grade MF (IIB-IIIA-IIIB) was 2.64. Statistical analysis showed positive associations of advanced MF stages with NLRs higher than 2.3. Our analysis demonstrates that the NLR represents a cheap and easily available parameter functioning as a marker for advanced MF. This might guide physicians in recognizing patients with advanced stages of disease requiring a strict follow-up or an early treatment.

Topical chlormethine gel in the treatment of mycosis fungoides: A single-center real-life experience and systematic review of the literature.

Gel formulation of chlormethine (CG) has gained a preeminent role among therapies available for mycosis fungoides (MF). To evaluate the frequency of use of CG for MF treatment and to determine the limits and potentialities of CG in a real-world setting. A systematic review of articles published prior to October 2021 was performed. Articles were included in the review if a full-text English version was available. MEDLINE (PubMed), Scopus, and Web of Science were each queried from their date of inception with the following terms: "mechlorethamine gel", "chlormethine gel", and "mycosis fungoides". The reference lists of the studies retrieved were searched manually. Moreover, this study included all consecutive patients with different stages of MF (from IA to IIB) who started treatment with CG gel between July 2020 and May 2021. Data of the literature were compared to our single-center real-life experience. Of the surveyed literature, 11 publications were included in the final analysis describing a total of 548 patients with MF. Eleven patients with a median (standard deviation) age of 66 years (15.1) were enrolled and followed up, receiving CG (0.02% chlormethine HCl). Response to treatment resulted higher (90.1%) in our study population than in other real-world experiences published in literature. This systematic review supports the role of CG for MF treatment, showing its limits and potentialities. Our single-center real-life experience revealed an elevated percentage of clinical response with high safety and tolerance, demonstrating its versatile use with dose and application rate adaptability.

Proteomic Screening and Verification of Biomarkers in Different Stages of Mycosis Fungoides: A pilot Study

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma; in advanced stages, it can involve multiple organs and has a poor prognosis. Early detection of the disease is still urgent, but there is no optimal therapy for advanced MF. In the present study, quantitative proteomic analyses (label-free quantitation, LFQ) were applied to tissue samples of different stages of MF and tissue samples from controls (eczema patients and healthy donors) to conduct preliminary molecular analysis to clarify the pathogenesis of the disease. Differential protein expression analysis demonstrated that 113 and 305 proteins were associated with the early and advanced stages of MF, respectively. Gene ontology (GO) enrichment analysis was conducted to determine the potential functions of the proteins, which could be classified into three categories: biological process, cellular component, and molecular function. The results revealed that a series of biological processes, including “initiation of DNA replication” and “nucleosome assembly,” were involved in the disease. Moreover, cellular components, including the “desmosome” and “integrin complex,” may affect the invasion and metastasis of MF via molecular functions, including “integrin binding” and “cadherin binding”. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis demonstrated that “focal adhesion DNA replication,” “Toll-like receptor signalling pathway” and other pathways were also involved. A parallel reaction monitoring (PRM) assay was applied to validate the identified differentially expressed proteins. In conclusion, the above proteomic findings may have great diagnostic and prognostic value in diverse malignancies, especially MF. Nevertheless, further studies are still needed to explore the precise mechanisms of MF.

Potential role of tumor-associated macrophages and CD163/CD68 ratio in mycosis fungoides and Sézary syndrome in correlation with serum sCD163 and CCL22.

Currently, there are no curative treatment options for mycosis fungoides (MF) and Sézary syndrome (SS) other than stem cell transplant. Understanding the interplay between tumor cells and tumor microenvironment could aid in the development of new therapies. Tumor-associated macrophages (TAMs) mostly have M2 phenotype that promotes tumor progression. This study investigated CD68+ and CD163+ TAMs as well as CD163/CD68 ratio in skin lesions from different stages of MF, large-plaque parapsoriasis, and SS. Moreover, we analyzed serum levels of sCD163 and CCL22 in correlation with TAMs count and CD163/CD68 ratio. CD68+ and CD163+ TAMs count significantly increased as the disease progressed. CD163/CD68 ratio was highest at MF tumor stage and SS indicating M2 polarization with disease progression. Significant positive correlations were detected between serum levels of sCD163 and CCL22 and CD68+ and CD163+ TAMs count and CD163/CD68 ratio. We concluded that TAMs play an important role in MF progression. High CD163/CD68 ratio in tumor stage MF and SS indicates M2 polarization of TAMs with tumor progression. CD163/CD68 ratio should be considered in assessing TAMs rather than total TAMs count. Also, sCD163 and CCL22 serum levels reflect M2 load and thus could be used as markers to assess disease progression.

Mapping signal transducer and activator of transcription (STAT) activity in different stages of mycosis fungoides and Sezary syndrome.

Deregulation of signal transducer and activator of transcription (STAT) signaling is known to participate in the pathogenesis of cutaneous T-cell lymphomas (CTCLs). However, published results regarding STAT expression in different stages of CTCLs are conflicting. The aim of the study was to define the pattern of STAT expression in skin and detect any differences between pruritic and nonpruritic patients but also different stages of disease. Thirty-nine skin biopsies from CTCL patients and 24 biopsies from healthy volunteers were taken. Immunohistochemical staining for STAT 3, 5a, 5b, and 6 was performed in formalin-fixed paraffin-embedded sections of mycosis fungoides (MF) and Sezary syndrome (SS) specimens. We found increased expression of STAT proteins in CTCL: MF and SS skin in comparison to the control group. STAT5 but also STAT6 and to a lesser extent STAT3 seems to be constitutively activated in MF and SS. Moreover, also downregulation of STAT5b protein in advanced-stage CTCL appears to contribute to its pathogenesis. There were no significant associations between expression of STATs and pruritus severity. Our results confirm the possible pathogenetic role of STATs in CTCL. STATs seem to be a promising target for new effective therapeutic agents in CTCL.

Podoplanin as a Predictive Marker for Identification of High-Risk Mycosis Fungoides Patients: An Immunohistochemical Study.

Background:Podoplanin, an important protein, has been implicated in various cellular processes, including lymphangiogenesis. Podoplanin is a mucin-type transmembrane glycoprotein that is accepted as a novel marker of lymphatic endothelial cells.Objectives:To study the immunohistochemical expression of podoplanin in the different stages of mycosis fungoides (MF) in comparison to control and to correlate their expression with disease severity and progression.Materials and Methods:The study included 50 patients of MF, clinically diagnosed and assessed by World Health Organization/European Organization for Research And Treatment Of Cancer Consensus and 20 normal persons as control. Skin biopsy specimens were taken from all and examined for expression of podoplanin immunohistochemically.Results:Significant upregulation of podoplanin expression was detected in all studied patients of MF in comparison to control group. Podoplanin expression in malignant lymphocytes and also lymph vessel density showed significant upregulation in the aggressive clinical presentations as well as the highest stages regarding TNMB staging of MF.Conclusions:Evaluation of podoplanin expression may be taken into consideration in the future as a useful tool to identify high-risk MF patients. Furthermore, it may open new therapeutic options for the clinical management of those patients.

PUVA AND INTERFERON α2b COMBINED THERAPY FOR PATIENTS WITH MYCOSIS FUNGOIDES: A SEVEN‐YEAR RETROSPECTIVE STUDY IN RUSSIA

Introduction: Cutaneous T-Cell Lymphomas (CTCLs) are characterized by proliferation and accumulation of malignant monoclonal T lymphocytes or Natural Killer cells in the skin, which may also sequentially involve lymph nodes, internal organs and bone marrow. There are still only a limited number of controlled studies to support treatment decisions for MF patients with therapy being frequently determined by institutional experience and availability. The aim of our survey was to investigate the efficacy and tolerability of combined PUVA and IFN-α2b therapy in patients with different stages of MF, refractory to first line treatment with PUVA. Methods: We observed 31 patients with MF. The diagnoses were verified with histological, immunohictochemical methods and molecular analysis. The following combined IFN-α2b - PUVA treatment protocol was used: IFN-α2b was administered at a dose of 3 MU three times weekly. The dose was increased according to patient's tolerance up to 6 MU three times weekly. For PUVA therapy, 0.8 mg/kg oral 8-methoxypsoralen was given 1.5 hours before UVA radiation, three times a week with gradually increasing dose of 0.5-1.0 J/cm2 in every 2 sessions starting from a dose of 0.5-2 J/cm2 depending on skin phototype. Treatment toxicity was graded according to World Health Organization (WHO) criteria. Results: In terms of the stage of the disease, patients were distributed as follows: IB – 3 (10%), IIA – 7 (23%), IIB – 6 (19%), IIIA – 4 (12%), IIIB – 3 (10%), IVA – 3 (10%), IVB – 5 (16%). The mean total IFN-α2b dose was 275 MU (range 171-576 MU). Conversely, the median PUVA sessions for the entire group of patients was 81 with the median joules/ cm2 being 177.13 (range 127-204 joules/ cm2) and the median combination treatment period being 189 days (range 133–254 days). The overall response rate was 93%, including complete response (CR) (73%) and partial response (PR) (20%). CR was found in 100% stage IIB-IIIA group respect 0% in stage IIIB-IV, P<0.05; the CR rate was in line with the mean CR percentage reported in previous studies (76.5%). Patients with early stage disease had a 2-year progression free survival of 100% vs. 82% for the advanced stage group (P<0.001). In our study, combined treatment showed a 2- and 5-year progression free survival (PFS) of 90% and 43%, respectively; obviously, patients with early stage disease had a superior 2-year PFS respect to the advanced stage group (100% vs 82%) (P < 0.001). Сonclusion: IFN-α2b + PUVA combined treatment seemed to be an efficacious therapy option for MF patients refractory to PUVA ± topical corticosteroids, presenting also a convenient tolerability profile, especially in patients with IB-IIB stage. This combined therapy protocol showed to be effective in both early and advanced MF disease stage, even if significantly better outcomes were observed for early stage disease. Keywords: interferon (INF); mycosis fungoides (MF); phototherapy.

Serum Vitamin D and Vitamin D Receptor Gene Polymorphism in Mycosis Fungoides Patients: A Case Control Study.

BackgroundVitamin D has been considered a key player in various malignancies including cutaneous cancers. To date, mycosis fungoides (MF) has been the least studied in relation to vitamin D. Furthermore, the vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) have not been tackled before in the context of MF, despite their incrimination in numerous diseases.Aim of studyTo assess the role of vitamin D in MF by measuring its serum level, and studying VDR SNPs (TaqI, BsmI, FokI) in different stages of MF.Patients and Methods48 patients with various stages of MF, and 45 healthy controls were included. Complete history, full clinical examination and a five mm punch skin biopsy were performed to all recruited patients. Venous blood samples were withdrawn from both patients and controls to determine the serum vitamin D level and VDR gene polymorphisms.ResultsSerum vitamin D level was significantly lower in patients (5.3–33.7 nmol/L)] compared to controls (8.3–90.1 nmol/L)] (P<0.001). A significant difference was observed between patients and controls regarding the FokI polymorphism only, being higher in patients (P = 0.039). Also Vitamin D serum levels differed significantly in patients with FokI genotypes (P = 0.014). No significant correlations were detected between any of the studied parameters and the demographic and clinical data of the included subjects.ConclusionDepressed vitamin D and FokI polymorphism are potentially involved in the context of MF. VDR gene polymorphisms warrant further larger scale investigations to detect the exact genes involved in the pathogenesis of such an enigmatic disease.

The possible interaction between periostin expressed by cancer stroma and tumor-associated macrophages in developing mycosis fungoides.

Mycosis fungoides (MF) starts as an indolent disease, progresses from a patch stage to confluent plaques and ultimately develops skin tumors. Tumor-associated macrophages (TAMs) play roles in maintaining the tumor microenvironment in MF. The purpose of this study was to elucidate the involvement of TAMs in the lesional skin of different stages of MF. First, we immunohistologically examined the percentage of CD163+ macrophages and CD206+ cells, as well as the levels of periostin and IL-4 in cancer stroma. The percentage of CD206+ cells increased in parallel with tumor progression, while there was no significant difference in the percentage of CD163+ cells. Periostin was prominent in the stromal area at the patch and plaque stages but decreased at the tumor stage. In contrast, IL-4 was prominently stained at both plaque and tumor stages. To further elucidate the molecular mechanisms of the effects of these stromal factors on TAMs, we examined their effects on mRNA expression in monocyte-derived macrophages in vitro. Based on microarray analysis and gene ontology, we examined a series of chemokines and MMPs whose expression was strongly connected with periostin stimulation. The DNA microarray results were verified in M2 macrophages using real-time PCR. We further examined the mRNA expression of these chemokines and MMPs in the presence of periostin and IL-4 to simulate the advanced stages of MF and validated their protein expression by ELISA. Our present report suggests possible roles of periostin on TAMs in establishing the tumor microenvironment in MF.

Assessment of Tissue Level of Histone Deactylase-2 (HDAC-2) in Patients With Mycosis Fungoides.

Histone deactylases (HDAC) have a role in the pathogenesis of mycosis fungoides (MF) through their actions on different apoptosis pathways. To assess the possible role played by HDAC-2 in MF by estimating the tissue expression of HDAC2 mRNA in different stages of MF. This study included 28 MF patients and 30 controls. The HDAC-2 levels were detected by real-time polymerase chain reaction (PCR). Correlations of HDAC-2 levels with clinical presentation and different stages of MF were analyzed. Mean HDAC-2 level was significantly higher in patients (P < .001) than in controls. HDAC-2 highest mean value was significantly detected in patients with stage IIb, and the lowest mean value was detected in patients with stage Ia (P < .001). Up-regulation of tissue HDAC-2 in MF patients might develop a new approach in the understanding of the pathogenesis of MF. Histone deactylases are important targets for molecular cancer therapeutics.

Aberrant expression of BCL11B in mycosis fungoides and its potential role in interferon‐induced apoptosis

BCL11B is a Kruppel-like C2H2-type zinc finger transcription factor, which has been associated with several human malignancies. Recent evidence showed that overexpressed BCL11B conferred chemoresistance to malignant T cells and that inhibiting BCL11B led to increased apoptosis, suggesting its potential pathogenic relevance in cutaneous T-cell lymphomas (CTCL), which were characterized by the resistance to chemotherapy-induced apoptosis. To investigate the expression pattern of BCL11B in different stages of mycosis fungoides (MF), quantitative reverse transcription polymerase chain reaction and immunohistochemistry were performed to compare the mRNA and protein expression among different stages of MF and benign inflammatory dermatoses (BID), respectively. BCL11B demonstrated significant upregulation in all stages of MF, compared with BID, in both mRNA expression level and protein level. In addition, BCL11B expression increased with advancing lesion tumor stage and overall disease stage. Further, to evaluate the dynamic expression of BCL11B under CTCL-directed treatment, BCL11B expression and cell apoptosis were evaluated after interferon (IFN)-α-2b and methotrexate treatment on CTCL cell line Hut78 cells. IFN-α-2b, but not methotrexate, induced BCL11B inhibition and cell apoptosis, suggesting that BCL11B may play important roles in the anti-CTCL effect of IFN-α-2b. In conclusion, our study demonstrated the overexpression of BCL11B in MF lesions and its potential relevance to disease progression. In addition, we provided evidence for BCL11B inhibitory approaches as a potential treatment to target chemoresistant tumor cells in advanced MF.

FOXP3 in Sequential Biopsies of Progressive Mycosis Fungoides

A recent report has suggested that the numbers of regulatory T cells correlate with stage of disease and prognosis in mycosis fungoides (MF). To evaluate the role of FOXP3+ Tregs in different stages of MF, we investigated sequential biopsies in 14 patients with patch/plaque and subsequent tumor stage using FOXP3 antibody. Our data neither show a significant difference in the percentage of FOXP3+ cells between patch/plaque and tumor stage biopsies of MF nor demonstrate a predictable shift of Tregs in the course of disease progression. Additionally, we could observe FOXP3-expressing neoplastic cells in 4 patch/plaque stage biopsies, where they represented almost 100% of the epidermotropic infiltrate. Only in one of these patients, FOXP3+ cells could also be detected in the tumor stage biopsy, indicating that FOXP3 expression can be acquired or lost during the course of the disease, comparable to other phenotypic markers.

Expressions of CXCR3 and CD1a in lesions of mycosis fungoides at tumor and non-tumor stages

Objective To investigate the expressions of CXC chemokine receptor 3 (CXCR3) and CD1a in skin lesions of different stages of mycosis fungoides (MF). Methods The expression and distribution profiles of CD1a and CXCR3 were detected by immunohistochemistry in the epidermis of skin samples from 16 normal human controls, 16 patients with non-tumor (patch/plaque) stage MF and 8 patients with tumor stage MF. Results With the progression of MF from patch/plaque stage to tumor stage, the positivity rate of CXCR3 in intraepithelial neoplastic cells in lesions dropped from 38.9% to 17.5% (P ＜ 0.05). The average number of intraepithelial Langerhans cells (LCs) per high power field (HPF) in skin samples was 10.6 in patch/plaque stage MF, significantly higher than that in normal control (7.3) and tumor stage MF (6.7), while no significant difference was found between normal control and tumor stage MF specimens. Conclusion The epidermotropism in MF may be associated with the expression of T-helper (Th) 1-associated chemokine receptor (CXCR3) and quantity of intraepithelial LCs. Key words: Mycosis fungoides; Lymphoma, T-cell; Receptors, chemokine; Langerhans cells

Thymus and activation-regulated chemokine in different stages of mycosis fungoides: Tissue and serum levels

Thymus and activation-regulated chemokine (CCL17) is a member of the CC chemokines known to attract T-helper 2 type memory T cells and to participate in different T-helper 2 diseases. The aim of this study is to determine both serum and tissue levels of thymus and activation-regulated chemokine in patients with different stages of mycosis fungoides. Thirty-two patients with different stages of mycosis fungoides and 10 controls were included in the study. Skin biopsies and blood samples were taken to evaluate both tissue and serum levels of thymus and activation-regulated chemokine using the enzyme-linked immunosorbent assay method. The mean tissue level of thymus and activation-regulated chemokine in 10 tumour-stage patients was significantly higher (P = 0.002) than in the controls. The mean serum level of thymus and activation-regulated chemokine in all stages of mycosis fungoides patients was not significantly elevated (P = 0.131, 0.725 and 0.622) compared with controls. Both tissue and serum levels of thymus and activation-regulated chemokine correlated significantly with both the disease extent and duration in the three different stages of mycosis fungoides. Thymus and activation-regulated chemokine may be a marker for disease activity of mycosis fungoides, and may have a role in monitoring disease progression.

Immunohistochemical Study of the Expression of Matrix Metalloproteinase-9 in Skin Lesions of Mycosis Fungoides

Matrix metalloproteinase-9 (MMP-9) has been correlated with poor clinical outcome in various malignancies and is associated with enhanced tumor growth and dissemination through its role in angiogenesis. This study was carried out to review the immunohistological staining of MMP-9 in skin lesions of different stages of mycosis fungoides (MF). The study was carried on 22 patients with MF and 10 healthy controls. Immunohistochemical staining using MMP-9 monoclonal anti-human antibodies was performed to determine the intensity of expression and distribution pattern of MMP-9 in MF lesions and in normal control skin. The general intensity of expression of MMP-9 was found to be significantly higher in cases with MF than in controls, and it increased in direct proportion to the increase in disease severity, being greatest in the tumor stages. A significantly greater number of blood vessels were found in cases with MF when compared with controls, and the MMP-9 expression by endothelial cells was significantly higher in endothelial cells within tumor cell aggregates than in endothelial cells outside the tumor cell aggregates. This study raises the possibility that MMP-9 may play an important role in the development of MF lesions, and its significantly higher expression in tumor stages may point to a possible role in disease progression. Further studies are needed to validate these findings and to assess the possible therapeutic role of drugs targeting MMP-9 in the treatment of MF.

High Association of Human Herpesvirus 8 in Large-Plaque Parapsoriasis and Mycosis Fungoides

To investigate the presence of human herpesvirus 8 (HHV-8) in lesional skin of German patients with large-plaque parapsoriasis (LPP) or mycosis fungoides (MF). The pathogenetic relevance of HHV-8 in cutaneous T-cell lymphoma is controversial. Recently, a highly significant association of HHV-8 in LPP was found, which suggests a role in the pathogenesis of this disease. Retrospective study of the presence of HHV-8 in German patients with lymphoproliferative diseases. Dermatologic clinic at a university hospital of the Ruhr University Bochum, Bochum, Germany. Fifty-three patients treated for lymphoproliferative skin diseases were included in the study, including 14 patients with LPP, 31 with different stages of MF, and 8 with lymphomatoid papulosis (LyP). Twenty-three patients with Kaposi sarcoma (KS) made up the positive control group, and 10 patients with atopic dermatitis served as negative controls. The presence of HHV-8 was analyzed from paraffin-embedded lesional tissue samples using a nested polymerase chain reaction for the open reading frame (ORF) 26 and with immunohistochemical staining for the latency-associated nuclear antigen (LANA) encoded by ORF 73. A high association of HHV-8 infection in both lymphoproliferative skin diseases was observed: 87% of LPP and 70% of MF tissue samples tested positive for HHV-8 DNA from ORF 26. However, HHV-8 was not detectable in LPP and MF by using the immunohistochemical marker LANA. A virus unambiguously associated with KS, HHV-8 was frequently detected at low amounts in LPP and MF specimens. However, based on the methods of HHV-8 detection used in this study, no conclusion can be drawn on the etiologic and pathogenetic role of HHV-8 in these diseases.

Chemokine Receptor Expression on Neoplastic and Reactive T Cells in the Skin at Different Stages of Mycosis Fungoides

We analyzed the expression of 13 chemokine receptors in mycosis fungoides, in order to assess the contribution of chemotaxis to the pathogenesis of the disease. Material from skin biopsies of six patients with early disease and six patients at the tumor stage of mycosis fungoides was analyzed by immunohistochemistry and partly also by flow cytometry. The receptors CCR1, CCR2, CCR3, CCR5, CCR6, CXCR1, CXCR2, CXCR5, and CX3CR1 were rarely and inconsistently detected in lesional skin and thus their participation in mycosis fungoides could largely be ruled out. In contrast, CCR4, CXCR3, and CXCR4 were substantially expressed on both mycosis fungoides cells and the surrounding reactive T cells in the early patch and plaque stages of the disease, indicating an involvement of these chemokine receptors in the disease process. In the tumor stage of mycosis fungoides, we interestingly observed a loss of a relevant chemokine receptor in four out of six patients. In three patients CXCR3 and in one patient CCR4 was absent on tumor mycosis fungoides cells, whereas the reactive T cells showed normal levels of expression. Within these samples, tumor mycosis fungoides cells exhibited high levels of CCR7, a chemokine receptor central for the entry of T cells to lymphatic tissue. Taken together, our data suggest that the loss of one or more of the chemokine receptors involved in the homing of the mycosis fungoides cells to the skin may trigger the latent potential of these cells to metastasize into regional lymphatic tissue.

Towards a Better Understanding of Cellular Events in Mycosis Fungoides: An Immunohistochemical Study

In the present work, we have attempted to pay special attention to epidermal and dermal cellular events in Mycosis fungoides (MF). In the epidermis, the two dendritic cell populations, CD1+ and OKM5+, HLe-1+, the adhesion molecules OKM5 and DR on the surface of epidermal cells (Ecs), and cytoskeletal proteins were studied. CD1+ dendritic epidermal cells were generally more abundant than OKM5+, HLe-1+ ones with no interrelationship in their presence. OKM5+, HLe-1+ dendritic cells prevailed in the second stage plaques. The staining pattern with anti-spectrin polyclonal antibody gradually presented increased intensity from Pre-MF to tumor stage. The activation-proliferation related immunophenotype was also examined, as well as other useful markers, in an attempt to correlate their presence in different stages of MF. Special emphasis was given to the staining pattern with the epidermal growth factor receptor (EGF-R) monoclonal antibody against three targets: epidermal, endothelial, and lymphoid cells. The presence of Ki-67 proliferation marker in suprabasal epidermal layers and lymphoid cells in the dermal infiltrate was also of interest.