Answer: Langerhans cell histiocytosis

Histology: The biopsy shows diffuse effacement of the lymph node architecture by an infiltrate of large, pale cells with abundant ill-defined, slightly eosinophilic cytoplasm. The nuclei are vesicular, and many have a characteristic longitudinal crease or “groove”. Mitoses are not prominent, and nucleoli are inconspicuous. Multi-nucleated giant cells are not an uncommon feature, but were not present in this particular case. Eosinophils are not a prominent feature in this particular biopsy, immunostains for CD1a and S-100 were strikingly positive in the pale inlfiltrating cells.

Discussion: Langerhans Cell Histiocytosis (“Histiocytosis-X”) is a disorder characterized by a clonal proliferation of cells that exhibit morphologic, histochemical and immunologic features similar to those of the epidermal Langerhans’ cell. In the past, there was a confusing nomenclature for their proliferations, including Histiocytosis-X, Hand-Schuller Christian disease and Letterer-Siwe disease. In fact, all of these entities appear to represent variations in histologic features, and extent of organ involvement by the same basic process. A wide variety of organ system involvement has been described in Langerhans’ cell Histiocytosis with bone and skin being most commonly involved. A few areas of the body, however, appear to be exempt. In this particular case, a biopsy of the patient’s rash revealed the same infiltrate of histiocytes. A review of the contemporary classification of histiocytic disorders by Blaise Favara and members of the World Health Organization Committee on Histiocytic/Reticulum Cell Proliferations and the reclassification working group of the Histiocyte Society can be found in Medical and Pediatric Oncology (29:157-166, 1997.) A more recent immunohistochemical study and approach to classification from the International Lymphoma Study Group can be found in Histopathology (41:1-29, 2002.)

The differential diagnosis in cases of lymph node involvement by Langerhans Cell Histiocytosis-X would include other lymphoid and histiocytic neoplasms, infection (especially in cases with prominent giant cell formation) and other reactive processes. Massive Sinus Histiocytosis (Rosai-Dorfman) Disease occurs in children, but is characterized by a distinct, sinusoidal proliferation of histiocytes, including giant cells in which prominent collections of intracytoplasmic lymphocytes can be found. The infiltrating cells in this condition may be focally a S-100 positive, but not to the extent seen in LCH and they should not react with antibodies to CD1a. Metastatic melanoma might have a similar histologic appearance, however, the age of the patient and the lack of mitotic activity would be features against the diagnosis. Melanocyte markers other than S100 should be negative in LCH. Malignant lymphoma would seem unlikely because of the bland nature of the infiltrating cells and the lack of nucleoli and mitosis. In equivocal cases, immunohistochemical staining should resolve the issue.