Immunohistochemical analysis of small plaque parapsoriasis: involvement of dendritic cells.

Small plaque parapsoriasis (SPP) is one of the cutaneous T-cell lymphoproliferative disorders. The aim of the present study was to show the antigenic profile of a subset of dendritic cells and lymphocytes in SPP in comparison with normal cells to provide data on the role of these two cell types in the pathogenesis of SPP. Skin biopsy specimens of lesions were obtained from 8 patients with SPP. Biopsies of the healthy skin from 9 control individuals were also analyzed. Immunohistochemistry was performed on the frozen tissue sections to reveal binding of anti-HLA Class II, anti-CD1a, anti-CD4, anti-CD8, anti-CD44, anti-CD45, and anti-CD68 monoclonal antibodies. There was a statistically significant increase in the number of CD1a(+), Langerhans cells (LCs), HLA-DR-immunoreactive and, CD1a-positive dermal dendritic cells and CD68(+) macrophages in the SPP group (p=0.008, 0.008, 0.002 and <0.0009, respectively). The number of lymphocytes positive for CD4, CD8 and CD45 was significantly higher than normal in the SPP group (p=0.015, <0.0009 and <0.0009, respectively). Our study demonstrates that both peptide- and lipid-based antigens are involved in the persistent antigenic exposure in SPP. Dendritic cells play a pivotal role in SPP by presenting antigens by both LC and dermal dendritic cells via MHC Class II and CD1a molecules. The CD68(+) macrophages are thought to be involved in the immune response in this pathology as an antigen-presenting cell.

Assessment of TCR-beta clonality in a diverse group of cutaneous T-Cell infiltrates.

While some unequivocally benign infiltrates are easy to distinguish from cutaneous T-cell lymphoma (CTCL), drug-associated lymphomatoid hypersensitivity reaction and cutaneous lesions of collagen vascular disease can show cytologic atypia, clonality and an immunophenotypic profile that closely simulates CTCL and cause diagnostics difficulties. Similar immunophenotypic and molecular abnormalities to those of malignant lymphoma can also be observed in pityriasis lichenoides chronica (PLC), large plaque parapsoriasis (LPP), pigmented purpuric dermatosis (PPD) and atypical lymphocytic lobular panniculitis leading one to consider these entities as forms of cutaneous lymphoid dyscrasia. The purpose of our study was to evaluate the distinction of these various subcategories of cutaneous T-cell infiltrates by assessment of T-cell receptor (TCR)-beta gene rearrangement. Formalin-fixed paraffin-embedded skin biopsies from 80 patients containing a T-cell dominant lymphocytic infiltrate were analyzed for TCR-beta gene rearrangement. Our findings indicate that monoclonality is a reliable characteristic of CTCL with polyclonality being very infrequent. However, some cases of drug associated lymphomatoid hypersensitivity, collagen vascular disease and the various cutaneous lymphoid dyscrasias (i.e. PLC, PPD and atypical lymphocytic lobular panniculitis) could manifest restricted molecular profiles in the context of an oligoclonal process or frank monoclonality.

Expression of proliferation markers and cell cycle regulators in T cell lymphoproliferative skin disorders.

BACKGROUND: Abnormal cell proliferation, which results from deregulation of the cell cycle, is fundamental in tumorigenesis. OBJECTIVES: To investigate the expression of proliferation markers and cell cycle regulators in a range of T cell lymphoproliferative skin diseases. METHODS: We studied skin specimens of 51 patients with parapsoriasis (PP), mycosis fungiodes (MF), or lymphomatoid papulosis (LyP). Immunohistochemistry was performed for Ki-67, proliferating cell nuclear antigen (PCNA), minichromosome maintenance protein 7 (MCM7), and p21. RESULTS: MF with stage IIB-IV and LyP showed a significantly greater number of Ki-67-positive cells than PP (P=0.02 and 0.001) and MF I-IIA (P=0.019 and 0.003), respectively. MCM7 staining revealed significantly higher labeling indices for MF IIB-IV and LyP when compared to PP (P=0.002 and 0.04) and MF I-IIA (P=0.0005 and 0.01), respectively. Compared to PP and MF I-IIA, MF IIB-IV was associated with significantly higher labeling indices for PCNA (P=0.006 and 0.0004). p21 staining was significantly increased in MF IIB-IV and LyP when compared to PP (P=0.006 and 0.003) and MF I-IIA (P=0.003). However, p21 staining was all in all very weak. CONCLUSIONS: Ki-67 and PCNA seem to be useful immunohistological parameters for the correlation with the clinical stage of MF. In the differentiation and prognostication of T cell lymphoproliferative skin disorders, MCM7 may serve as a novel biomarker which is, in contrast to Ki-67 and PCNA, stable throughout the cell cycle.

CD13 and TCR clone: markers of early mycosis fungoides.

Making a differential diagnosis between early mycosis fungoides and parapsoriasis is often difficult at the clinical and histological level. The aim of this study was to explore markers that could help in this process. A total of 88 patients were included in 2 categories: large plaque parapsoriasis and digitiform parapsoriasis. A histological examination was performed for each patient, and expression of the antigen My7 (CD13), which is lacking in cutaneous T-lymphomas (but not in inflammatory lesions) and rearrangement of the T-cell receptor gene were analysed. A histological aspect of epidermotropic cutaneous T-cell lymphoma was observed in 23.5% of cases of large plaque parapsoriasis and 15% of cases of digitiform parapsoriasis. A disappearance of My7 antigen was noted in the 2 forms of parapsoriasis, more frequently when there was cutaneous T-cell lymphoma histology. A cutaneous clone was observed in 10.3% of cases of large plaque parapsoriasis, but not of digitiform parapsoriasis. For 3 patients, a cutaneous clone and a disappearance of My7 were associated with a non-specific histology. Considering these histological, immunological and molecular biological data, it appears that My7 antigen combined with T-cell clone may help the dermatologist to confirm the diagnosis of early mycosis fungoides. Moreover, further studies will determine whether CD13 is an early prognostic marker of evolution of a parapsoriasis to mycosis fungoides. Finally, these results demonstrate that digitiform parapsoriasis can be an early stage of MF.

Expression of cancer/testis antigens in cutaneous T cell lymphomas.

Cancer/testis-antigens (CTA), a novel and expanding family of immunogenic proteins detected by serological screening of recombinant cDNA expression libraries, encompass promising candidate targets for T-cell based immunotherapy. We screened kryo-preserved tissue of cutaneous T cell lymphoma (CTCL, n=36) such as mycosis fungoides (MF, n=17), pleomorphic cutaneous T-cell lymphoma (n=8) and Sezary's syndrome (SS, n= 11) as well as a non-malignant entity (small plaques parapsoriasis, SPP, n=5), for the expression of CTA by RT-PCR and Northern blot hybridization. From a panel of eleven CTA (MAGE-1, MAGE-C1, MAGE-3, BAGE, GAGE, SSX-1, SSX-2, SSX4, SCP-1, NY-ESO-1 and TS85) (HOM-Tes-85), mRNA expression could be detected for SCP-1 in 8/17 MF and 6/8 pleomorphic CTCL patients but was completely absent in small plaques parapsoriasis. SS patients had a more heterogeneous antigen expression pattern: Gage (1/11), MAGE-1 (3/11), MAGE-3 (6/11), MAGE-C1 (5/11), NY-ESO-1 (7/11) and TS85 (5/11), with expression of MAGE-3 confirmed by immunohistochemistry. CTA could provide defined targets for antigen-based vaccination in a high percentage of cases with CTCL. SCP-1 might serve as an additional diagnostic indicator in early and clinically indistinct lesions suspicious for cutaneous T-cell lymphoma.

[The pathogenesis of small-plaque parapsoriasis]. / O patogeneze melkobliashechnogo parapsoriaza.

The paper deals with the origin of parapsoriasis nodularis, which in its micronodular variant belongs to chronic dermatosis and has a clear-cut clinical and histological appearance. The disease arises most frequently after stress and occurs for the most part in middle-aged males. The leading role in pathogenesis of parapsoriasis nodularis is played by cellular immunity as indicated by reduced count of T-lymphocytes, active T-lymphocytes as well as the emergence of delayed hypersensitivity.

Eosinophilic histiocytosis. A subset of lymphomatoid papulosis.

A 43-year-old male with a 23-year history of small-plaque-type parapsoriasis developed a chronic recurrent self-healing papulonodular and tumoral cutaneous eruption. The microscopic findings were consistent with eosinophilic histiocytosis. Immunohistochemical and ultrastructural studies revealed a population of T lymphocytes, eosinophils and monocyte-macrophage cells in the dermal infiltrate. These findings confirm the similarities between eosinophilic histiocytosis and lymphomatoid papulosis suggesting that the former may be a clinicopathologic variant of the latter.

Early diagnosis of cutaneous T-cell lymphoma by DNA flow cytometry on skin biopsies.

Seven patients with mycosis fungoides early plaque stage with nondiagnostic histology had single-cell DNA content measured by flow cytometry for estimation of clonal ploidy. A total of 63 skin specimens were examined by histology and DNA measurements concurrently during the course of the disease. In addition, six patients had blood samples studied. All seven patients demonstrated aneuploid DNA histograms when the specimens were obtained from skin lesions. In 36 specimens the aneuploid peaks were hyperdiploid. By sequential studies one patient demonstrated two different aneuploid cell clones, one located in the hyperdiploid region and one located in the hypotetraploid region. All patients developed mycosis fungoides which were histologically confirmed, and the time from first aneuploid DNA histogram until diagnostic histology varied from 5 to 21 months (median, 12 months). In six of the patients a normal diploid DNA histogram was found of peripheral blood lymphocytes. The finding of aneuploidy in patients with early mycosis fungoides who still have a nondiagnostic histology emphasizes the value of flow cytometry as a complementary diagnostic aid which facilitates an early diagnosis.

Determination of 8-methoxypsoralen levels in plasma and skin suction blister fluid by a new sensitive fluorodensitometric method.

An improved fluorodensitometric assay for the determination of 8-methoxypsoralen (8-MOP) in plasma is described. Because of its low limit of detection (below 1 ng/spot) this method is suitable to determine the drug in skin suction blister fluid, too. The standard deviation of the procedure is 6.4% or less. Plasma and skin blister fluid levels of 8-MOP are determined 2 h following oral administration of 40-60 mg 8-MOP. They range from 0-239 ng/ml and 0-163 ng/ml, respectively. A rather close correlation (r = 0.91) between these two parameters could be observed. Thus, in cases with relatively high plasma levels sufficient skin levels can be predicted. If further investigations would prove, however, that a distinct concentration threshold required for therapeutic success exists--and recent experiments with fibroblast cultures imply that--skin blister fluid level determinations would seem highly desirable when plasma levels let us expect skin levels in the critical range. In general determination of 8-MOP skin blister fluid levels can be looked upon as a model for the evaluation of drug skin levels after systemic application in man.

Some research on parapsoriasis and lymphomas.

Thirty-five cases of benign parapsoriasis en plaques, 24 cases of prereticulotic poikiloderma (3 of which were in evolution towards polymorphous lymphomas), 15 cases of lymphoma and 10 cases of other various skin proliferative disorders were studied. For various reasons the first two conditions are preferably indicated as type 1 and type 2 parapsoriasis. Attention is drawn to the possibility of finding a dermal fibro-histiocytary proliferative condition, more often in type 2 parapsoriasis than in type 1. Dysprotidemia, signs of a reactive bone marrow condition, and changes of the tryptophan leads to niacin pathway, as signs of various degrees of damage of connective tissue, were found in type 2 parapsoriasis and lymphomas.