Lymphomatoid Granulomatosis

General: Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disorder typically involving lung and other extranodal sites such as skin, kidney, and central nervous system. It is an angiodestructive and angioproliferative lesion that only recently has been understood to be an EBV driven B-cell lymphoprolifer-ative disorder. A previous term in the literature that likely represent LYG is angioimmunoproliferative lesion. Patients present with respiratory symptoms such as cough, chest pain, and dyspnea. Constitutional "B" symptoms are also common. This presents in adults with a median age of 40 years and a male pre-dominance.69 Patients with immunodeficiency states are at increased risk for LYG.70-72 The clinical course is variable and spontaneous regression of some low-grade lesions may occur. Treatment with multiagent chemotherapy and interferon has been used with some success.73

Pathology: LYG appears as a polymorphous lym-phoid infiltrate with necrosis. The cells are, for the most part, small to intermediate in size with angulated nuclei. The infiltrate is angiocentric and infiltration of the vasculature occurs. Destruction of the vessels may contribute to the necrosis. Rare larger atypical transformed cells are present with the appearance of immunoblasts or sometimes demonstrating more atypia. Mitotic figures are present to varying degrees. A three-tier histologic grading scheme has been pro-posed74 based upon the number of proliferating large B-cells.75 Grade 3 lesions correspond to an overt large cell lymphoma.

Immunophenotype: Immunophenotyping shows the majority of small lymphocytes are T-cells with a CD4 predominance compared to CD8. The large cell are now shown to be CD20+ B-cells.

Molecular genetics: In situ hybridization (ISH) shows that the large B-cells are EBV-positive in the higher grade lesions.69 76 Gene rearrangement studies are often negative due to the low level of neoplastic B-cells in the infiltrate. Higher grade lesions more frequently have monoclonal IGH rearrangements. Grading is aided by EBER ISH. Grade 1 lesions have less than 5 cells/hpf. Grade 2 has 5-20 cells and grade 3 tumors have numerous EBV-positive cells that can form sheets.

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