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Pathologists routinely use histochemistry, immunohistochemistry and electron microscopy as adjuvant techniques in distinguishing epithelial mesotheliomas from pulmonary adenocarcinomas and other metastatic pleural adenocarcinomas. Epithelial mesotheliomas are characteristically mucicarmine negative, PAS--diastase (PAS-d) negative, and some are alcian blue-positive hyaluronidase sensitive, whereas approximately 60-75% of pulmonary adenocarcinomas show intracellular mucicarmine, PAS-d and alcian blue-hyaluronidase-resistant staining. Likewise, pulmonary adenocarcinomas and many non-pulmonary adenocarcinomas are carcinoembryonic antigen (CEA), LeuM1, B72.3 and BerEP4 positive, whereas mesotheliomas usually do not show immunostaining with antibodies to these substances.However, Benjamin and Ritchie studied thirty epithelial mesotheliomas with a variety of mucopolysaccharide stains, and concluded that the staining reactions of mesotheliomas with mucopolysaccharide stains were too inconsistent to be of much value in diagnosing mesotheliomas. Ernst and Atkinson reported seven of eighteen malignant epithelial mesotheliomas to be mucicarmine positive and concluded that hyaluronic acid produced by epithelial mesotheliomas. was more acidic than epithelial mucin, but may stain with mucicarmine. MacDougall. et al. reported a case of epithelial mesothelioma showing histochemical staining for mucicarmine, PAS-d and alcian blue and colloidal iron, not affected by pretreatment of the tissue sections with streptomyces hyaluronidase or bovine testicular hyaluronidase. MacDougall, et al.'s case of epithelial mesothelioma was confirmed by immunohistochemical findings (negative CEA and LeuM1) and by ultrastructural examination (long thin serpentine microvilli not covered by a glycocalyx).
Immunostaining. Approximately 10 to 15 percent
of epithelial mesotheliomas may show immunostaining for CEA, which
is usually focal and of low intensity. Otis, et al. reported a
mesothelioma that stained positive for CEA, LeuM1 and with the
B72.3 antibody, and found in one series of 14 cases that only
50% of pulmonary adenocarcinomas were LeuM1 and B72.3 positive.
More recently, Robb reported a CEA and LeuM1 positive mesothelioma
that showed no immunostaining for these antigens after predigestion
of the tissue sections with hyaluronidase, suggesting that the
substance responsible for the positive reaction for CEA and LeuM1
was hyaluronic acid. Gaffey. et al. reported focal and rarely
diffuse immunostaining of mesothelioma tumor cells for BerEP4
in 20% of epithelial mesotheliomas.During the past fifteen years,
we have observed epithelial mesotheliomas that were mucicarmine
and PAS-d positive, alcian blue positive hyaluronidase resistant,
and some that were focally CEA, LeuM1 and BerEP4 positive. These
cases initially caused diagnostic confusion, but when thoroughly
evaluated, led to a more complete understanding of the morphologic
spectrum of mesotheliomas. Because of the confusion these cases
occasionally cause, we thought it worthwhile to compare the histochemical,
immunohistochemical and ultrastructural features of ten mucin-positive
epithelial mesotheliomas with ten mucin-positive pulmonary adenocarcinomas.
Eight of the pulmonary adenocarcinomas were distinct lung masses,
and had been resected for cure. One adenocarcinoma (case 9) was
diagnosed by wedge biopsy, and another (case 10) had been initially
diagnosed by needle biopsy of pleura to be an epithelial mesothelioma,
but on post-mortem examination was shown to be a pseudomesotheliomatous
adenocarcinoma, similar to that described by Harwood, et al.,
Koss, et al. and Robb, et al.