KERATIN SUBSETS AND MONOCLONAL-ANTIBODY HBME-1 IN CHORDOMA - IMMUNOHISTOCHEMICAL DIFFERENTIAL-DIAGNOSIS BETWEEN TUMORS SIMULATING CHORDOMA

Thirty-five chordomas and more than 100 other tumors that have to be c onsidered in the differential diagnosis, were immunohistochemically an alyzed using a panel of antibodies including those to subsets of kerat ins (K), HBME-1, a monoclonal antibody recognizing an unknown antigen on mesothelial cells, and neuroendocrine markers. The patterns of immu noreactivities in chordoma were compared with those in renal cell carc inoma, colorectal mucinous adenocarcinoma, pituitary adenoma, skeletal chondrosarcoma, and extraskeletal myxoid chondrosarcoma (ESMC). Chord omas were consistently positive for keratin cocktail AE1/AE3, and for the individual keratins K8 and K19, and nearly always positive for K5, but they showed negative or only sporadic reactivity for K7 and K20. The keratin K8 and K19 reactivity was retained in those chordomas show ing solid sheets of epithelioid, spindle cells, or cartilaginous metap lasia, and in one of two cases showing overtly sarcomatous transformat ion. In comparison, keratins were never present in skeletal chondrosar coma, although K8 and to a lesser extent K19 were seen in occasional c ases of ESMC with chordoid features, HBME-1 reacted strongly with chor doma or colorectal carcinoma. These carcinomas lacked K5-reactivity, i n contrast to chordoma. Chordomas were also consistently positive for neuron-specific enolase and occasionally focally for synaptophysin, bu t never for chromogranin. In contrast, pituitary adenomas regularly ex pressed the full spectrum of neuroendocrine markers and differed from chordoma by having a narrower repertoire of keratins, often showing ne gative or focal keratin 8- or AE1/AEJ reactivity and being almost alwa ys K19-negative. These findings indicate that chordoma can be immunohi stochemically separated from tamers that can resemble it. Immunohistoc hemistry is especially useful in the diagnosis of small biopsy specime ns that offer limited material for morphological observation. Copyrigh t (C) 1998 by W.B. Saunders Company.