Background: Signet-ring sinus histiocytosis is a rare and distinctive reactive disorder recently observed in the axillary lymph nodes of patients with breast carcinoma. This form of sinus histiocytosis closely resembles and can easily be confused with metastatic adenocarcinoma.
Methods: To determine the incidence of this reactive process in lymph nodes from different anatomic sites, broaden its morphologic spectrum, and discuss the differential diagnosis, the authors examined lymph nodes from 316 radical prostatectomy specimens, 184 modified radical mastectomy specimens, 108 colectomy specimens, 57 gastrectomy specimens, and 27 radical hysterectomy specimens. These surgical procedures were performed to treat carcinoma of the prostate, breast, colon, stomach, and uterine cervix, respectively. A total of 9741 lymph nodes were histologically examined. The lymph nodes containing sinus signet-ring cells were stained with mucicarmine, Alcian blue, and periodic acid-Schiff stains (PAS). Immunostains for epithelial, lymphoid, and histiocytic markers were also performed. In two cases, tissue was retrieved from the paraffin block and subsequently processed for electron microscopic examination.
Results: Only 4 of 316 radical prostatectomy specimens (1.2%) and 2 of 184 axillary dissections (1.08%) contained lymph nodes with signet-ring sinus histiocytosis. Of 9741 lymph nodes reviewed, 37 (24 pelvic and 13 axillary lymph nodes) had signet-ring sinus histiocytosis, for an incidence of 0.38%. Microscopically, the signet-ring histiocytes lacked nuclear atypia and were mucin negative. In two cases, clusters of histiocytes with rounded, eosinophilic, diastase resistant, PAS positive cytoplasmic globules were observed. Both types of signet-ring cells showed reactivity for histiocytic markers and were negative for cytokeratin and lymphoid markers. By electron microscopy, most histiocytes were shown to have a large empty vacuole that displaced the nucleus. Granular material was observed in some of the vacuoles. Some histiocytes exhibited a rounded cytoplasmic body composed of central electron dense, granular material and a rim of microfibrils. No lipid droplets were identified.
Conclusions: Signet-ring sinus histiocytosis is a rare and distinctive reactive disorder found incidentally in the pelvic and axillary lymph nodes of patients with carcinoma of the prostate and breast, respectively. Although this histiocytic reaction mimics metastatic adenocarcinoma and signet-ring cell lymphoma, it can be identified by careful cytologic analysis together with positive reactivity for histiocytic markers, negative mucin stains, and lack of reactivity for epithelial and lymphoid markers. The etiology and pathogenesis of this unusual form of sinus histiocytosis remains unclear.