No abstract

Psoriasis is a chronic inflammatory skin disease triggered by interplay between immune mediators from both innate and adaptive immune systems and skin tissue, in which the IL-23/IL-17 axis is critical. PI3Kδ and PI3Kγ play important roles in various immune cell functions. We found that mice lacking functional PI3Kδ or PI3Kγ are largely protected from imiquimod (IMQ)-induced psoriasis-like dermatitis, correlating with reduced IL-17 levels in the lesions, serum, and the draining lymph nodes. TCRγδ T cells were the major IL-17–producing population in the draining lymph nodes and were significantly diminished in IMQ-treated PI3Kδ knockin and PI3Kγ knockout mice. We also show that PI3Kδ and PI3Kγ inhibitors reduced IFN-γ production by human TCRγδ T cells and IL-17 and IFN-γ production by PBMCs from psoriatic or healthy donors. In addition, inhibition of PI3Kγ, but not PI3Kδ, blocked chemotaxis of CCR6+IL-17–producing cells from IMQ-treated mice or healthy human donors. Taken together, these data indicate that PI3Kδ and/or PI3Kγ inhibitors should be considered for treating IL-17–driven diseases, such as psoriasis.

Reactive angioendotheliomatosis (RA) is a rare self-limited skin condition characterized histopathologically by a proliferation of endothelial cells within vascular lumina, usually as a result of different stimuli such as systemic infections, cryoproteinemias, monoclonal gammopathies, allergic conditions, severe peripheral vascular atherosclerotic disease, and iatrogenic arteriovenous fistulas. We report on a 67-year-old woman with a 20-year history of seropositive rheumatoid arthritis who presented with violaceous swelling of her left forearm. A skin biopsy revealed the histopathologic finding of RA with focal glomeruloid features and deposition of periodic acid-Schiff-positive material. In this systemic disorder, cutaneous manifestations may occur secondary to an immune complex-mediated vasculitic mechanism.

A 27-year-old woman presented with multiple nodules closely grouped on her right upper distal extremity. The lesions, dating from childhood, increased slowly in time. Microscopic examination of one nodule showed the histologic features of spindle cell hemangioendothelioma (SCH). At the periphery of the nodule there were also some features of the so-called sinusoidal hemangioma. Clinically, SCH can present as a solitary lesion or as multiple lesions in zonal distribution. When the lesions are multiple, the diagnosis of Maffucci’s syndrome should be considered. SCH may be interpreted as a reactive process secondary to thrombosis and recanalization occurring in angiomatous lesions with different clinical presentations. Spindle cells are probably mesenchymal cells modified by blood pressure. For this entity the term hemangioma seems to be preferable to that of hemangioendothelioma.

Metastatic breast carcinoma may assume many clinicopathological patterns. We here describe a case of histiocytoid breast carcinoma metastasis in the eyelids of a 73-year-old woman. Clinically, the patient presented painless swelling and nodular infiltration of the lateral and medial portions of the eyelids recalling a xanthomatous process or cystic lesions. Physical examination revealed similar lesions on the neck and right thigh. Medical history had revealed breast carcinoma 5 years previously. A biopsy specimen taken from a nodule on the eyelids revealed a relatively symmetric dermal tumor composed mainly of large, uniform, round-to-oval cells embedded in a fibrous stroma with moderate mucin deposits. The cells had abundant, coarsely granular eosinophilic cytoplasm and scant or absent nuclear atypia. No lobular arrangement of the cells or overt ductal formation were seen. Only occasional intracytoplasmic lumina were observed. Most cells demonstrated a positive immunoreaction for carcinoembryonic antigen. It is important to recognize histiocytoid breast carcinoma metastasis in the eyelids, because it may easily be overlooked clinically and histopathologically. This tumor should not be confused histopathologically with other benign and malignant skin tumors containing similar granular cells, but which have a different significance or a different prognosis. The immunohistochemical study, in conjunction with the medical history of the patient, facilitated the diagnosis.