Multiple clustered dermatofibroma: case report and review of the literature.

The presence of multiple dermatofibromas is rare and is defined as more than 15 lesions. Multiple clustered dermatofibroma (MCDF) is a distinct entity with only 12 reported cases in the literature. MCDF occurs in healthy individuals of both sexes in the first to third decades on the lower half of the body and portends an excellent prognosis. On histology, MCDF is consistent with benign dermatofibromas. We report a 31-year-old healthy Hispanic woman with a 14-year history of slowly progressive MCDF located on her right hip initially misdiagnosed as dermatofibrosarcoma protuberans. We believe this case represents the 13th report of MCDF in the literature and the second from North America.

Signet-ring cell carcinoma of the gallbladder with skin metastases.

Cutaneous metastasis from gallbladder cancer is extremely rare. We present a case of signet-ring cell carcinoma of the gallbladder metastatic to the skin in a 38-year-old man. The skin nodules on the face, scalp and perianal area occurred approximately 1 year after the resection of the neoplasm. Skin metastases from gastrointestinal cancers are usually detected around surgical scars or on the abdominal wall, especially in the periumbilical region, and rarely present at other sites. Multiple imaging studies revealed the presence of metastatic bony involvement in the spine and left orbit. Visceral metastases have not been demonstrated in our patient in 20 months of follow up since the initial diagnosis of gallbladder cancer was made. We also briefly discuss other primary and metastatic skin tumours with signet-ring cell morphology.

Prostate cancer diagnosed after initial biopsy with atypical small acinar proliferation suspicious for malignancy is similar to cancer found on initial biopsy.

OBJECTIVES: To compare matched clinical and prostatectomy data between (a) men with an initial biopsy diagnosis of atypical small acinar proliferation (ASAP) suspicious for malignancy whose cancer was diagnosed subsequently, and (b) men with a cancer diagnosis not preceded by an ASAP diagnosis. ASAP diagnoses apply to 1.5%-9.0% of prostatic biopsies and predict definite cancer in about 45% of repeat biopsies. METHODS: At our hospitals, during overlapping intervals from 1990 to 2001, 7081 men underwent prostate biopsy, and 227 (3.2%) had an overall diagnosis (based on all cores sampled) of ASAP. We concurred with the ASAP diagnosis in 184 cases (81%). Repeat biopsy was performed in 129 (57%), with 22 again having ASAP and 51 (40%) adenocarcinoma. Nineteen men underwent prostatectomy at our hospitals. The controls comprised men who underwent prostatectomy before and after each man with an initial ASAP diagnosis (2:1 match with cases). Findings included grade, pathologic stage, measured maximum dimension of tumor, resection margin status, patient age, and latest preoperative serum prostate-specific antigen. RESULTS: Men in the initial-ASAP group did not differ significantly from controls with respect to age (63 vs. 61, P = 0.08). Initial-ASAP and control groups had serum prostate-specific antigen levels of 5.9 and 7.4 ng/mL (P = 0.32), respectively; mean Gleason scores were 6.2 and 6.6 (P = 0.11); mean stages were pT2b and pT2b; and tumor size averaged 0.9 and 1.2 cm (P = 0.36). Fewer men with initial-ASAP diagnosis on biopsy had positive margins (5%) than did those in the control group (30%, P < 0.05). CONCLUSIONS: An ASAP diagnosis represents undersampled cancer in at least 40% of cases and places men at risk of prostate cancer with similar clinicopathologic findings as in other men with cancer.

Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease.

Humans and mice deficient in Fas, a tumor necrosis factor (TNF)-receptor family member, cannot induce apoptosis of autoreactive cells, and consequently develop progressive lymphoproliferative disorders and lupus-like autoimmune diseases. Previous studies have shown that short-term administrations of agonistic monoclonal antibodies against CD137, another TNF-receptor family member, activate T cells and induce rejection of allografts and established tumors. Here we report that treatment with an agonistic monoclonal antibody to CD137 (2A) blocks lymphadenopathy and spontaneous autoimmune diseases in Fas-deficient MRL/lpr mice, ultimately leading to their prolonged survival. Notably, 2A treatment rapidly augments IFN-gamma production, and induces the depletion of autoreactive B cells and abnormal double-negative T cells, possibly by increasing their apoptosis through Fas- and TNF receptor-independent mechanisms. This study demonstrates that agonistic monoclonal antibodies specific for costimulatory molecules can be used as novel therapeutic agents to delete autoreactive lymphocytes and block autoimmune disease progression.

Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of experimental autoimmune encephalomyelitis.

4-1BB, a member of the TNFR superfamily, is a costimulatory receptor primarily expressed on activated T cells. It has been shown that the administration of agonistic anti-4-1BB Abs enhances tumor immunity and allogenic immune responses. Paradoxically, we found that the administration of an agonistic anti-4-1BB mAb (2A) dramatically reduced the incidence and severity of experimental autoimmune encephalomyelitis (EAE). Adoptive transfer of T cells from such treated mice failed to induce EAE, whereas anti-4-1BB treatment following adoptive transfer of encephalitogenic T cells did not prevent EAE pathogenesis. These results suggest that anti-4-1BB treatment during the induction phase inhibits autoreactive T cell immune responses rather than preventing T cell trafficking into the CNS. This was substantiated by the observations that draining lymph node cells from anti-4-1BB-treated mice failed to respond to Ag stimulation in vitro. In addition, we found that such treatment initially promotes the activation and proliferation of Ag-specific CD4+ T cells but subsequently increases their probability of undergoing activation-induced cell death, thereby inhibiting effector T cell responses. More importantly, 2A treatment also inhibits the relapse of EAE in a clinically relevant murine model of multiple sclerosis. This study indicates that the agonistic Ab against 4-1BB can potentially be used as a novel immunotherapeutic agent for treating autoimmune diseases.