Evaluation of the detection of melanin by the Fontana-Masson silver stain in tissue with a wide range of organisms including Cryptococcus

It is not uncommon for surgical pathologists to encounter yeast and yeast-like organisms in tissue sections, and correct identification is imperative for guiding therapy. The Fontana-Masson silver stain for detecting melanin has been accepted as a relatively specific stain for diagnosing cryptococcosis in tissue based on few studies with limited numbers of organisms. This study was designed to test the value of the Fontana-Masson silver by investigating a large collection of tissues with infections that may mimic cryptococcosis. Cases of cryptococcosis and other infections that can morphologically mimic it were identified in the pathology archives of The Johns Hopkins Hospital and The Armed Forces Institute of Pathology. Overall, Fontana-Masson silver was positive in 25 (56%) of 45 cases, including infections caused by Cryptococcus neoformans (9/9), Coccidioides immitis (7/7), Blastomyces dermatitidis (4/10), Paracoccidioides brasiliensis (2/2), Lacazia loboi (1/1), and Rhinosporidium seeberi (1/1). The percentage of organisms staining varied widely, from less than 1% to 100%. Fontana-Masson silver was negative in all infections caused by Histoplasma capsulatum (n = 10), Histoplasma duboisii (n = 1), Sporothrix schenckii (n = 1), and the alga genus Prototheca (n = 2). Fontana-Masson silver was 100% sensitive for cryptococcosis. The specificity was low, however, with 5 of 9 noncryptococcal species being positive in some cases. These results need to be confirmed and extended to other isolates and species but it is clear that many organisms in the morphological differential diagnosis of cryptococcosis can be Fontana-Masson silver stain positive. Accordingly, results of the Fontana-Masson silver stain, especially a positive, should be interpreted cautiously and only in the context of the organism's morphological features and host factors.