INCREASED NUMBERS OF CYTOKERATIN-POSITIVE INTERSTITIAL RETICULUM CELLS (CIRC) IN REACTIVE, INFLAMMATORY AND NEOPLASTIC LYMPHADENOPATHIES - HYPERPLASIA OR INDUCED EXPRESSION

A total of 291 enlarged lymph nodes showing a range of reactive-inflam matory processes, primary and metastatic neoplasms were studied to det ermine the distribution and immunoprofile of their cytokeratin-positiv e interstitial reticulum cells (CIRC) in comparison with normal nodes. In 258/291 nodes (89%), CIRC numbers were distinctly increased in the subcapsular, paracortical and, occasionally, in the medullary zones; often, these increased CIRC formed networks around follicles, sinuses and vessels. CIRC had comparatively small, irregularly shaped bodies a nd dendritic processes; occasionally, giant forms were noted. CIRC con tained cytokeratins (CK) 8 and 18 but not 19, as shown by immunohistoc hemistry, and by gel electrophoresis with subsequent immunoblotting. T hey co-expressed vimentin consistently, alpha-smooth-muscle actin freq uently, and desmin less frequently. They did not contain desmoplakins, Factor VIII, S-100, LCA, B and T lymphocyte- and macrophage-associate d antigens, chromogranin A, synaptophysin or the A-80 glycoprotein. We found no clear correlation between the increased CIRC and given nodal disease processes. However, CIRC were most abundant in nodes free of but draining malignant tumours; bizarre CIRC assemblies were noted in HIV lymphadenopathy. CIRC appear to represent a subset of the so-calle d ''fibroblastic reticulum cells'' of lymph nodes. Their function rema ins undetermined; their increase in diverse lymphadenopathies suggests that they partake in nodal reactions to injury. It remains unclear wh ether the increase in CIRC relative number is due to proliferation or to CK gene induction processes but their presence and potential capabi lity to undergo hyperplasia with dysplastic forms should alert patholo gists to possible diagnostic pitfalls. In addition, we discuss that CI RC may undergo transformation and represent the ''cell of origin'' of certain CK-positive tumours restricted to lymph nodes.