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Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin lymphomas that predominantly affect older patients. Onset of cutaneous lymphoma in childhood is rare, but it can present as early as the first decade of life. In both adults and children, the diagnosis of cutaneous lymphoma can be challenging because inflammatory dermatoses can mimic CTCL both clinically and histologically. The clinicopathologic manifestations can be similar in adults and younger individuals; however, differences in the prevalence of certain CTCL variants among age groups exist. Whereas the classic Alibert-Bazin-type mycosis fungoides (MF) and Sézary syndrome represent the overwhelming majority of adult cutaneous T-cell lymphomas, in younger individuals, certain mycosis fungoides variants, such as hypopigmented MF, are over-represented and Sézary syndrome is extremely rare. CD30 + lymphoproliferative diseases, which include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (ALCL), represent the second most common subtype of CTCL in both adults and children; however, in the pediatric population, most of these are represented by LyP, and primary cutaneous ALCL is very rare. The prognosis is stage dependent, and the most significant prognostic factor in MF is the extent of skin involvement and the presence or absence of extracutaneous disease. The overwhelming majority of pediatric patients present with early-stage disease, and progression to more advanced stages, such as tumor stage, erythrodermic MF, and large cell transformation, which can be seen in adults, is very rare. The choice of treatment, regardless of age, is dependent on the extent of skin involvement and the presence or absence of extracutaneous disease., (Published by Elsevier Inc.)

Extranodal nasal natural killer (NK)/T-cell lymphoma is a very rare lymphoma characterized by strong association with Epstein-Barr virus infection, very aggressive clinical behavior, and poor prognosis. The typical phenotype of neoplastic natural killer cells in this entity is as follows: CD2+, CD56+, surface CD3-, cytoplasmic CD3epsilon+, and cytotoxic granule-associated protein positive. CD30 expression, a phenotype characteristic of anaplastic large-cell lymphomas, is not a typical feature of nasal NK/T-cell lymphomas. We describe the case of a 42-year-old woman with chronic nasal congestion and septal deviation who presented with progressive generalized tender erythematous plaques. A skin biopsy revealed an atypical angiocentric mononuclear cell infiltrate. Strong CD30 and CD3e immunoreactivities were noted in large atypical mononuclear cells within the infiltrate initially suggestive of a CD30+ T-cell lymphoma. However, flow cytometry of the skin lesion indicated that the cells were CD2+, CD4-, CD8-, and lacked surface CD3 more typical of a neoplasm of natural killer cells. Further studies revealed that the cells were CD56+, T-cell-restricted intracellular antigen-1+, and contained Epstein-Barr virus sequences consistent with a nasal-type NK/T-cell lymphoma. High titers of Epstein-Barr virus in the blood, evidence of sinonasal disease, and absence of a T-cell receptor gene rearrangement were additional features consistent with the diagnosis. The patient had a very aggressive clinical course and, despite combination chemotherapy, died 8 months after the onset of skin lesions. This case represents an example of nasal-type NK/T-cell lymphoma with expression of CD30. When presenting in the skin, the phenotypic and morphologic features of this lymphoma may lead to an erroneous diagnosis of a CD30+ large-T-cell lymphoma.

Purpose: The T cell repertoire in patients with advanced cutaneous T cell lymphoma (CTCL) is significantly contracted despite the presence of relatively normal absolute numbers of T cells. We propose that many normal T cells were being lost in patients with CTCL, with the remaining normal T cells expanding clonally to fill the T cell compartment. T-cell receptor excision circles (TREC) form as a result of the initial gene rearrangement in naïve T cells. Although they are stable, they do not replicate and are subsequently diluted with the expansion of a population of T cells. Their concentration is therefore a measure of unexpanded naïve T cells relative to T cells that have undergone expansion., Experimental Design: We analyzed TRECs from unfractionated peripheral blood T cells from 108 CTCL patients by quantitative PCR. In patients with obvious peripheral blood involvement, we also analyzed TRECs from clonal and nonclonal T cells., Results: We found a decrease in the number of TRECs in peripheral blood of patients with CTCL at all stages of disease, and this decrease was proportional to the loss of complexity of the T cell repertoire as measured by complementarity-determining region 3 spectratyping. In patients with leukemic CTCL and a numerically expanded clone, we also found a significantly lower-than-expected number of TRECs in the nonclonal normal T cells., Conclusions: We hypothesize that the nonmalignant T cells have proliferated to fill the empty T cell repertoire space left by the loss of other T cells, leading to diminished TRECs and loss of T-cell receptor diversity.

Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing T cells. A major feature of CTCL is profound immunosuppression, such that patients with advanced mycosis fungoides or Sézary syndrome have been compared with patients with advanced HIV disease and are susceptible to opportunistic infection. The etiology of this immunosuppression is unclear. We analyzed peripheral blood T cells of patients with CTCL with stage I to IV disease, using a sensitive beta-variable complementarity-determining region 3 spectratyping approach. Our data revealed a profound disruption of the complexity of the T-cell repertoire, which was universally observed in patients with advanced disease (stages III and IV), and present in up to 50% of patients with early-stage disease (stages I and II). In most patients, multiple monoclonal and oligoclonal complementarity-determining region 3 (CDR3) spectratype patterns in many different beta-variable families were seen. Equally striking was a reduction of normal T cells (as judged by absolute CD4 counts) across multiple beta-variable families. In general, CTCL spectratypes were reminiscent of advanced HIV spectratypes published elsewhere. Taken together, these data are most consistent with a global assault on the T-cell repertoire in patients with CTCL, a process that can be observed even in early-stage disease.

Background: The prognosis of patients with stage IV cutaneous T-cell lymphoma (CTCL) is grim and therapeutic options are limited. Treatment of advanced-stage CTCL is aimed at suppressing the dominant T-cell clone, which is typically present in the skin, peripheral blood, and lymph nodes., Observations: We detected the expansion of 1 T-cell clone expressing the T-cell receptor V beta 14 in the peripheral blood of a patient with stage IVA CTCL. Before initiation of combination therapy with photopheresis and low-dose interferon alpha, the dominant T-cell clone represented 84% of the total T-cell population. After successful therapy, this clone showed a dramatic decrease to 6% of the T-cell population after 6 months of treatment. This reduction in the percentage of the malignant T-cell population in response to therapy was paralleled by clinical skin improvement from initial generalized erythroderma to undetectable skin disease., Conclusions: This case demonstrates that response to combination treatment with photopheresis and low-dose interferon alpha in patients with advanced CTCL may be accurately and quantitatively followed up by monitoring the percentage of the malignant T-cell clone (when identifiable) within the total circulating T-cell population by flow cytometry.

Chemokines are critical molecules in leukocyte trafficking, promoting site-specific migration to various tissues. The chemokine receptor CCR4 has recently been associated with skin-homing T cells. In view of the potential importance of CCR4 in skin homing of T cells, we investigated the expression pattern of CCR4 and its ligands TARC/CCL17 and MDC/CCL22 in the peripheral blood and skin of patients with cutaneous T cell lymphoma, a putative malignancy of the skin-homing T cells. In this study we analyzed the pattern of coexpression of the skin-homing molecules cutaneous lymphocyte antigen (CLA) and CCR4 in the blood and skin of patients with cutaneous T cell lymphoma. In the blood of cutaneous T cell lymphoma patients with peripheral blood involvement we found significantly increased percentages of T cells displaying the skin-homing phenotype (CLA+CCR4+) compared with healthy individuals. T cells expressing CLA and CCR4 were also found at high levels in cutaneous T cell lymphoma lesions along with abundant expression of the two CCR4 ligands TARC/CCL17 and MDC/CCL22. These data may explain, in part, why these T cells accumulate in the skin, a diagnostic feature of cutaneous T cell lymphomas.