IL-23 and the Tumor Microenvironment.

The tumor microenvironment (TME), which assists in the development, progression, and metastasis of malignant cells, is instrumental in virtually every step of tumor development. While a healthy TME can protect against malignancy, in an unhealthy state, it can result in aberrant cellular behavior and augment tumor progression. Cytokines are one component of the TME, therefore, understanding the composition of the cytokine milieu in the tumor microenvironment is critical to understand the biology of malignant transformation. One cytokine, interleukin (IL)-23, has received particular scrutiny in cancer research because of its ability to manipulate host immune responses, its role in modulating the cells in TME, and its capacity to directly affect a variety of premalignant and malignant tumors. IL-23 belongs to the IL-12 cytokine family, which is produced by activated dendritic cells (DC) and macrophages. IL-23 acts by binding to its receptor consisting of two distinct subunits, IL-12Rß1 and IL-23R. This, in turn, leads to janus kinase (JAK) activation and signal transducer and activator of transcription (STAT) 3/4 phosphorylation. There have been contradictory reports of pro- and antitumor effects of IL-23, which likely depend on the genetic background, the type of tumor, the causative agent, and the critical balance of STAT3 signaling in both the tumor itself and the TME. Clinical trials of IL-12/23 inhibitors that are used to treat patients with psoriasis, have been scrutinized for reports of malignancy, the most common being nonmelanoma skin cancers (NMSCs). Continued investigation into the relationship of IL-23 and its downstream pathways holds promise in identifying novel targets for the management of cancer and other diseases.

Rosai-Dorfman disease with cutaneous plaques and autoimmune haemolytic anemia.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a non-Langerhan cell histiocytosis which primarily involves lymph nodes. Extranodal involvement in the form of cutaneous plaques can occur and can pose a diagnostic challenge because of pleomorphic presentation and histopathological mimics. Rarely, systemic autoimmune involvement may complicate the disease process. We present a 28-year-old woman with slowly evolving scaly erythematous cutaneous plaques and fluctuating lymphadenopathy, associated with autoimmune haemolytic anaemia. The patient responded favourably to oral corticosteroids and acitretin with significant flattening of cutaneous plaques, reduction in size of neck nodes and improvement of anaemia.

Congenital symmetrical circumscribed patterned non-scarring alopecia of eyebrows: a variant of congenital triangular alopecia or an anatomical variation?

Triangular alopecia presents as a unilateral triangular-shaped non-scarring alopecia usually involving the temporal scalp. There are few reports of occipital scalp involvement and bilateral disease. Usually it is seen at 2-3 years of age but occasionally can be present at birth. Here we present a unique case of triangular alopecia involving the eyebrows in a 23-year-old man. He had bilateral symmetrical involvement since birth. Points in favour of triangular alopecia in our case were non-scarring alopecia, oval-to-triangular shape, fringe of terminal hair at superior margin; trichoscopy showing significant decrease in hair diameter diversity with increased number of vellus and intermediate hair and histopathology showing normal hair follicle density and increased vellus and intermediate hair (miniaturisation) with absence of inflammation on histopathology. Other differential diagnoses kept were partial duplication of eyebrows, congenital alopecia areata and mild form of ectodermal dysplasia.