Secondary syphilis presenting as pseudolymphoma of the skin.

Secondary syphilis most commonly presents with a papulosquamous eruption that involves the palms, soles, and mucous membranes. The papulonodular variant has only been described 11 times in the literature. We describe a case of papulonodular secondary syphilis presenting as an atypical lymphoid hyperplasia suggestive of cutaneous lymphoma

Expression of Thymidine Phosphorylase in Lymph Nodes Involved with Mycosis Fungoides and Sézary Syndrome

Thymidine phosphorylase may be overexpressed in both neoplastic cells and tumor stromal cells in a variety of malignancies. Our study explores thymidine phosphorylase expression in lymph nodes (LNs) from patients with mycosis fungoides (MF) or Sézary syndrome (SS). In MF/SS, the LNs may have a pathologic diagnosis of either dermatopathic lymphadenopathy (LN-DL) or involvement by MF/SS (LN-MF). We performed immunohistochemical staining on MF/SS lymph nodes using antibodies to thymidine phosphorylase, CD68, CD21, CD3, and CD4. In both LN-DL and benign nodes, thymidine phosphorylase staining was noted only in macrophages, dendritic cells, and endothelial cells. In LN-MF, thymidine phosphorylase expression was also noted in subsets of intermediate to large neoplastic T cells. Concurrent CD68, CD21, CD3, and CD4 staining supported the above observations. Similar results were noted in the skin and in LN-MF with large cell transformation. Other T-cell lymphomas were also examined (total 7 cases); only enteropathy-type T-cell lymphoma (1 case) showed TP positivity in neoplastic T lymphocytes. We demonstrated that thymidine phosphorylase staining is present in neoplastic T cells in mycosis fungoides. The exact mechanism needs further investigation

DNA-Cytophotometry of Lymph Node Touch Imprints in Cutaneous T-Cell Lymphoma

Scanning DNA-cytophotometry was performed on touch imprints of 26 lymph nodes (LN) obtained from 25 patients with cutaneous T-cell lymphoma (CTCL), stained by the Feulgen technique, and interpreted without knowledge of histopathologic diagnosis. Four patterns of DNA distribution were identified, but only histograms that demonstrated cells containing nuclei with more than 4C DNA content (hypertetraploidy) reliably distinguished LN involved with CTCL from LN with reactive changes; for example, dermatopathic lymphadenitis. An abnormal DNA histogram with evidence of hypertetraploidy was demonstrated in 9 of 12 LN showing histopathologic evidence of involvement compared with no abnormal histograms in 14 LN without histopathologic involvement. One LN that was diffusely involved with CTCL had a DNA distribution characteristic of a relatively high level of cell proliferation, but without definite hypertetraploidy. Cytogenetic studies on the blood of this patient, who had Sézary syndrome, demonstrated a clone of lymphocytes with a pseudodiploid karyotype without a related polyploid subline. The remaining two histopathologically involved LN had normal DNA histograms; these LN were only focally involved with CTCL. These observations indicate that DNA-cytophotometry correlates well with the histopathologic findings in LN diffusely involved with CTCL, but may be normal in LN with focal involvement or in those that contain cytogenetically abnormal cells with a near-dip- kid DNA content

Classification and Prediction of Survival in Patients with the Leukemic Phase of Cutaneous T Cell Lymphoma

We have used cDNA arrays to investigate gene expression patterns in peripheral blood mononuclear cells from patients with leukemic forms of cutaneous T cell lymphoma, primarily Sezary syndrome (SS). When expression data for patients with high blood tumor burden (Sezary cells >60% of the lymphocytes) and healthy controls are compared by Student's t test, at P < 0.01, we find 385 genes to be differentially expressed. Highly overexpressed genes include Th2 cells–specific transcription factors Gata-3 and Jun B, as well as integrin β1, proteoglycan 2, the RhoB oncogene, and dual specificity phosphatase 1. Highly underexpressed genes include CD26, Stat-4, and the IL-1 receptors. Message for plastin-T, not normally expressed in lymphoid tissue, is detected only in patient samples and may provide a new marker for diagnosis. Using penalized discriminant analysis, we have identified a panel of eight genes that can distinguish SS in patients with as few as 5% circulating tumor cells. This suggests that, even in early disease, Sezary cells produce chemokines and cytokines that induce an expression profile in the peripheral blood distinctive to SS. Finally, we show that using 10 genes, we can identify a class of patients who will succumb within six months of sampling regardless of their tumor burden

Evidence linking atopy and staphylococcal superantigens to the pathogenesis of lymphomatoid papulosis, a recurrent CD30+ cutaneous lymphoproliferative disorder.

BACKGROUND:Primary cutaneous CD30+ lymphoproliferative disorders (CD30CLPD) are the second most common type of cutaneous T cell lymphoma (CTCL) and include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Case reports and small patient series suggest an association of CD30CLPD with atopic disorders. However, the prevalence of atopy in patients with CD30CLPD in retrospective studies depends on patients' recall which is not always reliable. More objective criteria of atopy include evidence of skin reactivity to allergens (positive prick test) and evidence of allergen-specific IgE in serum. This study was undertaken to test the hypothesis that atopy is prevalent in patients with CD30CLPD using serologic criteria of allergen-specific IgE antibodies to aeroallergens and Staphylococcal aureus enterotoxin superantigens (SSAgs). METHODS:We tested serum samples of CD30CLPD for common IgE-specific airborne allergens with the Phadiatop test, which if positive, is regarded as serologic evidence of atopy in adults. Sera were also tested for IgE antibodies reactive to three Staphylococcal enterotoxins with superantigenic properties (SSAg-IgE). Control sera were obtained from adult subjects evaluated for rhino-sinusitis and a negative Phadiatop test. Patients' history of an atopic disorder was obtained by retrospective chart review. FINDINGS:Nearly 50% of patients with the most common LyP types (A and C) had a positive Phadiatop test for allergic sensitization to common airborne allergens, and total serum IgE (IgE-t) was increased compared to non-atopic controls. At the IgE antibody concentration generally used to define serologic atopy (≥ 0.35 kUA/L), 8/31 (26%) samples of CD30CLPD and 7/28 (25%) samples of LyP were reactive to at least one SSAg-IgE compared to 3/52 (6%) control specimens (P = 0.016 and P = 0.028, respectively). TSST1-IgE was detected in 7 (23%) specimens of CD30CLPD, often together with SEB-IgE; SEA-IgE ≥ 0.35 kUA/L was not detected. For control specimens, TSST1-IgE exceeded the 0.35 kUA/L threshold in 3 (6%) specimens. CONCLUSIONS:Patients with LyP types A and C have serologic evidence of atopy against common airborne antigens and SSAgs when compared to control adult subjects who had rhino-sinusitis and a negative Phadiatop test for aero-IgEs. Serologic evidence of atopy exceeded that determined by LyP patients' personal history. The findings support our hypothesis that an atopic diathesis may contribute to the pathogenesis of the most common types of LyP (A and C)

Natural Cell-Mediated Cytotoxicity in Cutaneous T-Cell Lymphomas

Natural cell-mediated cytotoxicity was studied in 24 patients with cutaneous T-cell lymphomas and in 18 age- and sex-matched controls studied concomitantly. Percent cytotoxicity was determined by 4-h 51Cr release assay using K562 targets at effector to target ratios of 100:1, 50:1, and 25:1. Mean percent cytotoxicity was significantly lower in patients than in controls at an effector to target cell ratio of 100:1. Likewise, decreased cytotoxicity was found at effector to target ratios of 50:1 and 25:1, although this difference was not significant. When natural killer activity was analyzed separately for males and females, cytotoxicity was lower in both, although the decrease was significant only for male patients. Impairment of natural killer activity did not correlate with blood zinc levels, but appeared to correlate with stage of disease

Sezary T Cell Activating Factor is a Chlamydia pneumoniae Associated Protein

Séezary T cell-activating factor (SAF) was originally defined as an inducer of functional interleukin-2 (IL-2) receptors on normal and malignant T cells in patients suffering from Sézary syndrome. In fact, a combination of SAF and IL-2 stimulated the propagation of T cell lines from the peripheral blood mononuclear cells (PBMC) of those patients, with approximately one third of those cell lines containing the predominant malignant clone as determined via cytogenetic and/or T cell receptor gene rearrangement analysis. Although the primary source of SAF was mitogen-stimulated PBMC of a patient with Sézary syndrome, we were unable to isolate the gene encoding SAF from eukaryotic libraries. However, we observed SAF activity in the cytoplasm of one of the malignant cell lines in a complex containing RNA and DNA. This observation led us to consider the possibility that SAF is not of eukaryotic origin. Intracellular pathogens replicate in the cytoplasm of host cells and contain proteins, DNA, and RNA. Using a panel of antichlamydial antibodies with confirmation from polymerase chain reaction primers, we found that most patients with mycosis fungoides were positive for these determinants. Immunoelectron microscopy and protein blotting further confirmed antibody reactivity. We showed thatChlamydia pneumoniae were capable of infecting normal human keratinocytes in culture. We also demonstrated that C. pneumoniaeantigen expression was associated with active disease because these determinants were not expressed after psoralen and ultraviolet A therapy. We hypothesize that chronic infection by C. pneumoniae leads to expansion of C. pneumoniae-specific T cells, thereby potentiating the development of cutaneous T cell lymphoma

The radiation therapy of early stage cutaneous T-cell lymphoma

Results of different radiotherapy schedules used for early stage (T1-2, N0-1, M0) cutaneous T-cell lymphoma (CTCL) are compared in a series of 45 patients (22 patients treated with high dose total skin electron beam therapy (TSEB) with curative intent, 18 patients treated with palliative radiotherapy, and 5 patients treated with high dose local electron beam). At 3, 5, and 10 years after diagnosis the high dose TSEB treatment group had a probability of overall survival of 91%, 86%, and 75%, respectively, compared with 94%, 88%, and 88% for the palliative treatment group. The complete response (CR) rate for the high dose TSEB treatment group was 82% ( 18 22 ), compared with a 57% ( 4 7 ) complete response rate for seven patients in the palliative group who received low dose TSEB (<25 Gy in 6–7 weeks) followed by daily application of topical mechlorethamine hydrochloride (HN2). However, the probability of continued remission at 3, 5, and 10 years was 44%, 44%, and 33%, respectively, for the high dose TSEB group and 25%, 25%, and 0%, respectively, for the low dose TSEB + HN2 group. The median disease-free survival was 17.5 months for the high dose TSEB group versus 5.5 months for the low dose TSEB + HN2 group. The five patients who were treated with high doses of local electrons to a single local field had an overall survival rate of 80%, a median survival rate of 64 months, and a median length of continued remission of 31 months. These results indicate that high-dose electron beam can result in long-term disease-free survival in patients with localized and limited extent skin involvement with cutaneous T-cell lymphoma