The extranodal lymphoid infiltrate: a diagnostic dilemma

Lymphoid infiltrates that originate outside of the major lymphoid tissue-bearing sites have often represented a difficult diagnostic problem, and the histopathologic criteria employed to distinguish between benign and malignant extranodal lymphoid infiltrates have not always resulted in accurate prognostication. In part, this has been due to the failure to recognize the existence of primary, extranodal, well-differentiated, small lymphocytic (WDL) lymphoma unassociated with systemic lymphoma or chronic lymphocytic leukemia, the presence of pseudofollicular proliferation centers within WDL lymphoma, and the existence of intermediate differentiated and mantle zone lymphomas that contain residual, atrophic, benign-appearing germinal centers. More recently, the determination of the mono- or polyclonality of extranodal lymphoid infiltrates has given us a new perspective on these lesions. Revisions of the histopathologic criteria and advances in immunology have increased our comprehension of the lymphoid proliferations that originate in the ocular adnexa, skin, lung, and gastrointestinal tract.