Defining early mycosis fungoides.

This editorial review summarizes the results of 5 meetings sponsored by the International Society for Cutaneous Lymphoma at which the clinicopathologic and ancillary features of early mycosis fungoides were critically examined. Based on this analysis, an algorithm was developed for the diagnosis of early mycosis fungoides involving a holistic integration of clinical, histopathologic, immunopathologic, and molecular biological characteristics. A novel aspect of this algorithm is that it relies on multiple types of criteria rather than just one, for example, histopathology. Before its finalization, the proposed diagnostic algorithm will require validation and possibly further refinement at multiple centers during the next several years. It is anticipated that a more standardized approach to the diagnosis of early mycosis fungoides will have a beneficial impact on the epidemiology, prognostication, treatment, and analysis of clinical trials pertaining to this most common type of cutaneous lymphoma.

Mechanisms underlying imiquimod-induced regression of basal cell carcinoma in vivo.

BACKGROUND: Imiquimod is a local immune response modifier that has demonstrated potent antiviral and antitumor activity. It enhances innate and acquired immune responses via endogenous cytokine production and has proven efficacious in clearing superficial basal cell carcinoma (sBCC). OBJECTIVE: To evaluate the mechanisms by which topical imiquimod treatment leads to sBCC clearance in vivo. DESIGN: A pilot, open-label, nonrandomized study. SETTING: Zurich, Switzerland. PATIENTS: Six persons 18 years or older who had nonrecurrent primary tumors that had not undergone previous biopsy or treatment but were suitable for treatment by surgical excision. The tumors were located on the scalp, extremities, or trunk; had a minimum diameter of 1 cm and a maximum diameter of 2 cm; and were clinically and histologically consistent with sBCC. INTERVENTIONS: Daily application of 5% imiquimod cream 5 times per week for a maximum of 6 weeks. When the tumor began to show signs of erosion, it was surgically excised. OUTCOME MEASURES: Parameters reflecting tumor apoptotic status (Bcl-2), expression of death receptors (Fas and Fas ligand [FasL]), intercellular adhesion molecule (ICAM) 1, immunosuppressive microenvironment (interleukin 10), and antigen presentation machinery (transporter associated with antigen presentation [TAP] 1) before and after imiquimod treatment were evaluated. The changes in the interferon gamma messenger RNA (mRNA) levels relative to CD4 and CD8 mRNA were assessed using quantitative polymerase chain reaction. RESULTS: Tumor cells became more susceptible to apoptosis through decreased Bcl-2 expression after treatment with 5% imiquimod cream. Inflammatory infiltrate developed rapidly (within 3 to 5 days after treatment initiation) and was associated with the enhanced expression of ICAM-1. This early response tended to be a mixed cellular response of macrophages and lymphocytes. Interferon gamma was produced by CD4 and CD8 T cells. Imiquimod treatment induced a massive increase in macrophage peritumoral and intratumoral infiltration. Interleukin 10 was produced by infiltrating cells but was not produced by tumor cells. Tumor expression of TAP-1 and Fas/FasL appeared to be unaffected in the first 5 days of treatment.

HLA-G protein up-regulation in primary cutaneous lymphomas is associated with interleukin-10 expression in large cell T-cell lymphomas and indolent B-cell lymphomas.

Primary cutaneous lymphomas (CLs) constitute a spectrum of diseases characterized by a clonal accumulation of lymphocytes in the skin. Most CLs display a T(h)2 cytokine profile, including expression of interleukin-10 (IL-10). Because the up-regulation of HLA-G, a nonclassical class Ib molecule inducible by IL-10, might account for the immunescape of the malignant clone, HLA-G and IL-10 expression has been investigated in 45 cases of primary CL (10 of B-cell and 35 of T-cell origin) with quantitative polymerase chain reaction (PCR) and immunohistochemistry. HLA-G message was present in all cutaneous B-cell (CBCL) and T-cell (CTCL) lymphomas evaluated. Immunohistochemistry revealed HLA-G protein expression in 23 (51%) of 45 cases (7 of 10 CBCL, 16 of 35 CTCL). While in CBCL mostly indolent types displayed HLA-G positivity, in CTCL HLA-G expression was associated with high-grade histology and advanced stage of the disease. Except for neoplastic and infiltrating lymphocytes, other cells such as macrophages and dendritic cells showed HLA-G immunoreactivity. Furthermore, IL-10 protein expression was demonstrated in 16 (73%) of 22 HLA-G(+) cases, which correlated with HLA-G protein presence (P <.001). HLA-G up-regulation together with IL-10 expression in CL might additionally contribute to the evasion of immunosurveillance and facilitate the transition from low- to high-grade lymphomas.