Multiple Crusted Swellings on the Chin

The Diagnosis: Cutaneous Cryptococcosis

Histologic examination revealed infiltration of the dermis and subcutaneous tissue with rounded basophilic cells on low magnification (Figure 1A). On higher magnification, encapsulated yeast cells (cryptococci) of varying size accompanied by chronic granulomatous inflammatory infiltration with occasional giant cells were seen (Figure 1B). Alcian blue stain showed mucinous capsular material (Figure 1C). There was no history of diabetes mellitus, tuberculosis, steroid therapy, or immunosuppression. Moreover, systemic involvement or systemic focus of infection was ruled out after computed tomography of the head, chest, and abdomen. Therefore, the diagnosis of primary cutaneous cryptococcosis (PCC) was established. The patient was started on oral itraconazole 100 mg twice daily along with 5 drops of a saturated solution of potassium iodide 3 times daily that later was increased to 20 drops 3 times daily at a weekly interval. The lesions started improving after 1 month and healed completely after 9 months of treatment (Figure 2).

Figure 1. A, The dermis and subcutaneous tissue showed infiltration by basophilic cells (H&E, original magnification ×10). B, The dermis and subcutaneous tissue were heavily colonized with encapsulated yeast cells of various sizes, accompanied by chronic granulomatous inflammatory infiltration with occasional giant cells (H&E, original magnification ×40). C, Mucinous capsular material stained blue with Alcian blue (original magnification ×40).

Figure 2. Lesions healed with slight postinflammatory hypopigmentation after 9 months of treatment with itraconazole.

Primary cutaneous cryptococcosis is the identification of Cryptococcus neoformans in a skin lesion without evidence of simultaneous disseminated disease. Neuville et al¹ observed that skin lesions resemble cellulitis, ulcerations, or whitlows and were located on unclothed areas. In contrast, lesions from disseminated disease presented as scattered umbilicated papules resembling molluscum contagiosum. Diagnosis of PCC is based on the observation of encapsulated yeasts by direct microscopic examination, isolation of C neoformans or Cryptococcus gattii in culture, and by the demonstration of capsular antigen in various fluids, including serum and cerebrospinal fluid by latex particle agglutination or enzyme-linked immunosorbent assay. Histologically, Cryptococcus species produce a proliferative inflammatory reaction in immunocompetent hosts with the formation of compact epithelioid granulomas, with giant cells and a peripheral layer of lymphocytes. Treatment options for PCC infection range from antifungal medications and surgical debridement to observation.

The differential diagnosis may include cutaneous leishmaniasis, cutaneous tuberculosis, cutaneous histoplasmosis, and basal cell carcinoma. These entities may have similar presentations and can only be confidently differentiated on direct microscopy and histopathologic examination. The characteristic Leishmania donovani bodies on microscopy in cutaneous leishmaniasis and tubercular granuloma with central necrosis on histology in cutaneous tuberculosis can differentiate these conditions from cryptococcosis. In some patients with cryptococcosis, the yeast may produce a less characteristic polysaccharide capsule and thus may be confused with histoplasmosis. Fontana-Masson staining may show melanin-producing yeast, which is characteristic of cryptococci.² Ulcerated basal cell carcinoma may present similar clinically; however, histopathology will rule it out.

Cutaneous cryptococcal infection should be presumed to be disseminated until proven otherwise, and a search for other sites of involvement must immediately be undertaken. Cutaneous signs may be the first indication of infection, preceding the diagnosis of disseminated disease by 2 to 8 months, making its recognition crucial to early treatment. It is not possible to diagnose PCC on a specific clinical manifestation because a diverse range of skin lesions may be present. Therefore, culture and histology are the gold standards for diagnosis of cryptococcosis.