Answer: Langerhans cell histiocytosis

Histology: Sections show ulcerated skin with dense superficial and deep dermal infiltrate of epithelioid cells with round to oval shaped, folded or indented nuclei with characteristic longitudinal grooves and intermixed eosinophils, histiocytes and smalllymphocytes. Immunostains demonstrate that the epithelioid cells are S-100 and Cd1a positive.

Discussion: Langerhans cell histiocytosis is a neoplastic proliferation of Langerhans cells that has also been referred to histiocytosis X and Langerhans cell granulomatosis. Clinically, it may present as unifocal disease (solitary eosinophilic granuloma) usually in the bone or less often in the skin, lymph node or lung. Multifocal disease within one organ system is referred to as Hand-Schuller-Christian disease (usually involvement of multiple bones). If disease is multifocal and is seen in multiple organs the term Letterer-Siwe disease is used. The etiology is unknown. No grading system is used for describing cytologic atypia because of poor correlation with clinical outcome. Lesios with frank malignant features are rare and are diagnosed as Langerhans cell sarcoma.

The neoplastic Langerhans cells express CD1a and S-100 and usually are also positive for vimentin, HLA-DR and placental alkaline phosphatase. There is variable positivity for CD45, CD68 and lysozyme. The cells are positive for CD4 but negative for most other B and T-cell markers, CD30, myeloperoxidase, CD34, EMA and follicular dendritic cell markers (CD21, CD35). Characteristic ultrastructural finding is the presence of cytoplasmic Birback granules (200-400 nm long and 33 nm wide tennis racket shaped granules).

The clinical course depends on the number of organs affected at presentation. Overall survival is greater than 95% with unifocal disease that drops to 75% if two organs are involved and is even lower if more than two organ systems are involved.