Topical rapamycin for acanthosis nigricans in the Fitzpatrick IV/V adolescent population.

Dermatologically, FGFR3 mutations can lead to acanthosis nigricans (AN), epidermal nevi, and seborrheic keratosis. A recent case report found that topical rapamycin (sirolimus) can improve FGFR3-induced epidermal nevi with AN features in children, specifically with Fitzpatrick skin type (FST) I/II, and we would like to expand these findings to skin plaques with extensive AN-like features in the FST IV/V adolescent population. An 18-year-old female with FST IV/V and FGFR3-induced hypochondroplasia presented to our clinic with extensive AN-like plaques. Significant improvement with lightening and thinning of the plaques was observed after applying 1% topical rapamycin cream twice daily. Topical rapamycin should be considered as a treatment option for AN, particularly in FST IV/V adolescents with FGFR3-induced AN.

Prognosis for women diagnosed with melanoma during, before, or after pregnancy: Weighing the evidence.

Approximately one third of women who are diagnosed with malignant melanoma are of childbearing age. Therefore, it is not surprising that some studies have found malignant melanoma to be one of the most common malignancies diagnosed in pregnant women. The impact of pregnancy-related hormonal changes on melanoma development and progression remains controversial. Women undergo immunologic changes during pregnancy that may decrease tumor surveillance. Additionally, hormone receptors are found on some melanomas. Unfortunately, many of the past and even recent studies that have been published and are reviewed herein did not uniformly use appropriate control groups, account for confounding covariates, or employ appropriate statistical analysis, which makes it difficult to rely on the conclusions they reach. However, a review of the better controlled and preponderant studies demonstrates that pregnancy-associated melanomas are not associated with a poorer prognosis.

Expression of functional P-selectin glycoprotein ligand 1 on hematopoietic progenitors is developmentally regulated.

T cell development requires periodic importation of hematopoietic progenitors into the thymus. The receptor-ligand pair P-selectin and P-selectin glycoprotein ligand 1 (PSGL-1) are critically involved in this process. In this study, we examined the expression of functional PSGL-1 on bone marrow hematopoietic progenitors. We demonstrate that functional PSGL-1 is expressed at low levels on hematopoietic stem cells, but upregulated on the cell surface of progenitors that bear other homing molecules known to be important for thymic settling. We found that progenitors able to home to the thymus expressed high levels of PSGL-1 transcripts compared with hematopoietic stem cells. We further demonstrate that hematopoietic progenitors lacking fucosyltransferase 4 and 7 do not express functional PSGL-1, and do not home efficiently to the thymus. These studies provide insight into the developmentally regulated expression of a critical determinant involved in progenitor homing to the thymus.

Delivery of progenitors to the thymus limits T-lineage reconstitution after bone marrow transplantation.

T-cell production depends on the recruitment of hematopoietic progenitors into the thymus. T cells are among the last of the hematopoietic lineages to recover after bone marrow transplantation (BMT), but the reasons for this delay are not well understood. Under normal physiologic conditions, thymic settling is selective and either CCR7 or CCR9 is required for progenitor access into the thymus. The mechanisms of early thymic reconstitution after BMT, however, are unknown. Here we report that thymic settling is briefly CCR7/CCR9-independent after BMT but continues to rely on the selectin ligand PSGL-1. The CCR7/CCR9 independence is transient, and by 3 weeks after BMT these receptors are again strictly required. Despite the normalization of thymic settling signals, the rare bone marrow progenitors that can efficiently repopulate the thymus are poorly reconstituted for at least 4 weeks after BMT. Consistent with reduced progenitor input to the thymus, intrathymic progenitor niches remain unsaturated for at least 10 weeks after BMT. Finally, we show that thymic recovery is limited by the number of progenitors entering the thymus after BMT. Hence, T-lineage reconstitution after BMT is limited by progenitor supply to the thymus.