Id-like reaction to BCG therapy for bladder cancer.

Id reaction, also known as autoeczematization, is the development of dermatitis that is distant to an initial site of infection or sensitization. Clinical findings typically include an acute, intensely pruritic maculopapular or papulovesicular eruption that most frequently involves the extremities. Histology typically reveals spongiotic dermatitis that often is vesicular, and eosinophils may be present in the infiltrate. Id reactions can result from inflammatory skin conditions such as stasis dermatitis as well as infectious entities including mycobacterial infections. BCG live therapy consists of an attenuated strain of Mycobacterium bovis that is utilized as a first-line treatment of superficial transitional cell carcinomas. We report the case of an id-like reaction in a 90-year-old man who developed an intensely pruritic, scaly, erythematous eruption on all 4 extremities 2 weeks after starting weekly intravesical use of BCG therapy for superficial transitional cell carcinoma. A representative biopsy demonstrated spongiotic dermatitis with overlying scaling and an eosinophilic infiltrate. The eruption resolved after discontinuation of BCG therapy and treatment with topical corticosteroids.

Treatment-refractory actinic keratoses successfully treated using simultaneous combination topical 5-fluorouracil cream and imiquimod cream: a case-control study.

BACKGROUND: Most actinic keratoses (AKs) respond to standard treatments, but a subset persist and require further intervention. We report a series of 10 patients with AKs that failed to respond to conventional treatment with cryotherapy and topical monotherapy but responded completely to simultaneous therapy with topical 5-fluorouracil (5-FU) and imiquimod creams. OBJECTIVE: To report the success of this combination therapy in refractory AKs and to determine whether any clinical or histologic features predict for treatment resistance. METHODS: Case-control study with two control groups matched to each patient according to lesion location and sex. RESULTS: Mean lesion diameter (p < .001), lesion diameter greater than 1 cm (p < .001), and the presence of pain (p = .01) were statistically associated with failure of cryotherapy and topical monotherapy. None of the histologic features evaluated were found to be statistically significant, although thicker epidermis was nearly so (p = .054). CONCLUSIONS: In patients who have failed standard therapy for AKs, combination treatment using topical 5-FU and imiquimod cream may be an effective alternative therapeutic strategy. Larger lesion diameter, specifically greater than 1 cm, and the presence of pain predict conventional treatment resistance.

Aberrant expression of LMO4 induces centrosome amplification and mitotic spindle abnormalities in breast cancer cells.

The LIM-only protein, LMO4, is a transcriptional modulator overexpressed in breast cancer. It is oncogenic in murine mammary epithelium and is required for G2/M progression of ErbB2-dependent cells as well as growth and invasion of other breast cancer cell types. However, the mechanisms underlying the oncogenic activity of LMO4 remain unclear. Herein, we show that LMO4 is expressed in all breast cancer subtypes examined and its expression level correlates with the degree of proliferation of such tumours. In addition, we have determined that LMO4 silencing induces G2/M arrest in cells from various breast cancer subtypes, suggesting that LMO4 action in the cell cycle is not restricted to a single breast cancer subtype. This arrest was accompanied by increased cell death, amplification of centrosomes, and formation of abnormal mitotic spindles. Consistent with its ability to positively and negatively regulate the formation of active transcription complexes, overexpression of LMO4 also resulted in an increase in centrosome number. Centrosome amplification has been shown to prolong the G2/M phase of the cell cycle and induce apoptosis; thus, we conclude that supernumerary centrosomes mediate the G2/M arrest and cell death in LMO4-deficient cells. Furthermore, the correlation of centrosome amplification with genomic instability suggests that the impact of dysregulated LMO4 on the centrosome cycle may promote LMO4-induced tumour formation.

FOXA1 is an essential determinant of ERalpha expression and mammary ductal morphogenesis.

FOXA1, estrogen receptor alpha (ERalpha) and GATA3 independently predict favorable outcome in breast cancer patients, and their expression correlates with a differentiated, luminal tumor subtype. As transcription factors, each functions in the morphogenesis of various organs, with ERalpha and GATA3 being established regulators of mammary gland development. Interdependency between these three factors in breast cancer and normal mammary development has been suggested, but the specific role for FOXA1 is not known. Herein, we report that Foxa1 deficiency causes a defect in hormone-induced mammary ductal invasion associated with a loss of terminal end bud formation and ERalpha expression. By contrast, Foxa1 null glands maintain GATA3 expression. Unlike ERalpha and GATA3 deficiency, Foxa1 null glands form milk-producing alveoli, indicating that the defect is restricted to expansion of the ductal epithelium, further emphasizing the novel role for FOXA1 in mammary morphogenesis. Using breast cancer cell lines, we also demonstrate that FOXA1 regulates ERalpha expression, but not GATA3. These data reveal that FOXA1 is necessary for hormonal responsiveness in the developing mammary gland and ERalpha-positive breast cancers, at least in part, through its control of ERalpha expression.

Pagetoid reticulosis in a 5-year-old boy.

We present a rare case of pagetoid reticulosis arising in a 5-year-old white boy. He had a history of a large chronic erythematous, scaly patch on his left buttock that had shown intermittent partial response to a topical antifungal medication. A punch biopsy specimen revealed dramatic epidermal hyperplasia, with parakeratosis and prominent exocytosis of single and clustered mononuclear cells (Pautrier's microabscesses) into the epidermis. Some of these exhibited hyperchromatic nuclei with irregular contours. They stained prominently for CD3, CD4, and CD8, with a predominance of CD8(+) cells. T-cell receptor gene rearrangement by polymerase chain reaction was negative for a clonal process on a second biopsy specimen that was nondiagnostic on routine sections. Pagetoid reticulosis is an indolent, unilesional variant of mycosis fungoides, in which the atypical T cells may express a CD4(-)/CD8(+) phenotype. This is in contrast to primary cutaneous epidermotropic CD8(+) cytotoxic T-cell lymphoma, which is often very aggressive with a poor outcome. Pagetoid reticulosis is exceedingly rare in children and adolescents. Two features predict a benign course in this 5-year-old child: the unilesional clinical presentation and the CD8 predominance of the epidermal lymphocytes.