Paracoccidioidomycosis (PCM), formerly known as South American blastomycosis, was first described in 1908 by Adolpho Lutz. It is a systemic mycosis caused by thermally dimorphic fungi of the Paracoccidioides brasiliensis complex or by P. lutzii.1 Importantly, PCM has not been included in the World Health Organization’s portfolio of neglected tropical diseases. Estimates suggest that nearly 10 million individuals in Latin America are infected, with PCM representing the leading cause of mortality among systemic mycoses.2 Its burden is likely underestimated, as compulsory reporting was only recently implemented in Brazil. Infection occurs through inhalation of conidia from soil, predominantly affecting rural populations.1,3 The clinical spectrum ranges from acute to chronic forms, often involving multiple organs, including the oral cavity.1,3,4 This report describes a rare case of oral PCM in a young patient from a non-endemic region of northeastern Brazil.

A 37-year-old male farmer from Rio Formoso, Pernambuco, Brazil (latitude − 8.66146, longitude − 35.1516), presented with a painless oral lesion that had progressed over 12-months. The patient was a chronic smoker and alcohol user, with no significant personal or family medical history. Extraoral examination revealed no submandibular or cervical lymphadenopathy. He denied weight loss, cough, dyspnea, and fever. Intraoral examination revealed an ulcerated, moriform lesion with infiltrative borders on the right buccal mucosa, extending toward the labial commissure and measuring approximately 3 × 3 cm (Fig. 1). The differential diagnosis included oral leukoplakia and oral squamous cell carcinoma. Computed tomography of the thorax demonstrated subtle interstitial changes consistent with chronic disease in both lungs. Cranial and sinus imaging revealed no abnormalities. Laboratory tests showed normal biochemical parameters, with negative VDRL and HIV results.

Fig. 1.

Clinical features of oral paracoccidioidomycosis.

(A) Intraoral view showing an ulcerated, moriform lesion with infiltrative borders on the right buccal mucosa contiguous to the labial commissure, measuring approximately 3 × 3 cm. (B) Clinical follow-up image after 24-months demonstrating cicatricial fibrosis and no evidence of recurrence.

An incisional biopsy was performed. Histopathological examination revealed chronic inflammation with multinucleated giant cells, lymphocytes, and plasma cells within the connective tissue stroma. Round fungal structures consistent with Paracoccidioides spp. were identified. Grocott-Gomori Methenamine Silver (GMS) and Periodic Acid-Schiff (PAS) stains confirmed multiple budding yeasts in the characteristic “pilot wheel” arrangement (Fig. 2). A diagnosis of PCM was established. The patient was treated with oral itraconazole 200 mg/day for 12-months. No adverse effects were reported. At the 24-month follow-up, there was no clinical evidence of recurrence.

Fig. 2.

Histopathological features of oral paracoccidioidomycosis.

(A) Low-power view showing pseudoepitheliomatous hyperplasia with underlying chronic inflammatory infiltrate. (B) Higher magnification demonstrating multinucleated giant cells, lymphocytes, and plasma cells. (C) Periodic acid-Schiff (PAS) and (D) Grocott-Gomori Methenamine Silver (GMS) staining illustrating multiple budding yeasts of the Paracoccidioides spp. in the profile of the “pilot wheel” arrangement (yellow arrows; inset) or round structures (red arrows) (hematoxylin and eosin staining: 40× and 200× magnification; PAS and GMS: 200× magnification).

Data from a literature review indicate that only eight cases of oral PCM in northeastern Brazil have been documented hitherto (Table 1).5–8 Previous literature of autochthonous cases in Ceará and the high number of cases reported in specific regions of Maranhão suggest that humid areas of northeastern Brazil may also be considered endemic.1 Nonetheless, both the present case and the other patients with oral PCM from northeastern Brazil had no history of travel to recognized endemic zones.5–8

We previously reported that oral PCM lesions accounted for 0.3% of specimens submitted for histopathological evaluation.4 Oral mucosal lesions may represent the first clinical manifestation of PCM, with approximately 60% of patients presenting with oral and/or oropharyngeal involvement,9 most frequently affecting the gingiva/alveolar ridge.4 Middle-aged and older men are disproportionately affected,4,7 reflecting both agricultural exposure and the possible protective effect of β-estradiol in women; the latter inhibits the transition of the fungus to the pathogenic yeast form.10 Although the armadillo is acknowledged as a natural reservoir, neither zoonotic nor human-to-human transmission has been demonstrated.3

The diagnosis of PCM based on oral lesions is challenging, as they often emulate other infectious diseases and malignancies.4 Oral manifestations are typically ulcerative or erosive, multiple, erythematous, with granular surfaces and hemorrhagic petechiae, termed “moriform stomatitis”. The mechanism by which the fungus compromises oral tissues remains elusive.4 Diagnostic approaches include direct microscopy, culture, histopathology, and molecular methods.1,3 Histopathology shows chronic inflammation with macrophages and multinucleated giant cells containing yeast cells. The fungi, larger than those observed in histoplasmosis, are demonstrable with GMS or PAS stains. A hallmark feature is the presence of multiple budding daughter cells radiating from the parent yeast, forming a “pilot wheel” appearance.4 Current Brazilian guidelines recommend itraconazole (200 mg daily for 9–12 months) as first-line therapy for mild-to-moderate disease.3

Awareness of the clinicopathological spectrum of PCM is therefore crucial for timely diagnosis, as its evolving ecoepidemiology and the probable expansion of autochthonous foci pose significant public health concerns.