Answer: Langerhans cell histiocytosis

Histology: The lymph node has a sinusoidal and nodular infiltrate of polygonal cells with fine pink cytoplasm. The nuclei are predominantly reniform and angulated in shape, with occasional nuclear grooves. There are foci of necrosis, simulating an infectious granuloma, along with neutrophils, eosinophils, and multinucleated giant cells. The histiocytic cells are diffusely immunoreactive for S100 protein and also immunoreactive for CD1a, but are essentially negative for CD68 (KP-1).

Discussion: Infectious granulomas should be characterized by macrophages that lack the cytologic features of Langerhans cells, and should label for CD68. Similarly, juvenile xanthogranuloma would have a different cytology, would also label for CD68 but not for S100 or CD1a. Monocytic leukemias may involve the paracortex of a lymph node and simulate a primary lymphoproliferative process. These cells may also have angulated nuclei, like a Langerhans cell lesion. These cells would be more primitive in their appearance, would lack the abundant cytoplasm of a Langerhans cell and should show greater mitotic activity. They should not label for CD1a and S100 protein as Langerhans cells do.
Langerhans cell histiocytoses (LCH) have several distinctive presentations. A congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker histiocytosis) is characterized by predominantly cutaneous involvement and spontaneous regression. Letterer-Siwe Disease is an acute disseminated form, which typically presents with hepatosplenomegaly, fever, thrombocytopenia and anemia. This is the form that this patient appears to have. A more chronic process is Hand-Schuller-Christian Disease, characterized by the classic triad of diabetes insipidus, exophthalmus and destructive skull lesions. Isolated Langerhans cell histiocytosis is termed eosinophilic granulomas when it involves bone or the lung. In the latter setting, this disease is associated with smoking. Importantly, the prognosis for Langerhans cell lesions is dependent on the clinical stage, not the histopathology. The presence of necrosis, atypia, and mitotic figures do not by themselves make Langerhans cell histiocytoses malignant. Adverse prognostic factors include disease onset at less than two years of age, and increasing number of involved dysfunctional organs.