Histoplasmosis of the Head and Neck Region Mimicking Malignancy: A Clinic-Pathological Predicament

Abstract

Objective: Histoplasmosis is a systemic, deep mycotic infection caused by Histoplasma capsulatum. Disseminated histoplasmosis (DH) is synonymous with HIV seropositive immunocompromised individuals; however, isolated histoplasmosis involving the head and neck mucosal sites mimicking malignancy is a clinical predicament. The result, in a superficial biopsy with marked pseudoepitheliomatous hyperplasia (PEH), in a tertiary care cancer center where the number of squamous carcinomas far outnumber the infectious diseases, could be catastrophic.

Material and method: The archives of a tertiary care cancer hospital were searched (2010-2019) for cases of histoplasmosis involving the head and neck mucosal sites in HIV non-reactive patients.

Results: Six cases of isolated head and neck histoplasmosis were seen in biopsies from 4 men and 2 women, with an age range of 46-72 years. Three of these patients suffered from chronic illnesses. The most common site involved was the larynx (vocal cords) in three cases, two cases were involving lips, and one involving the tongue. The biopsies were reviewed in-house with a clinical diagnoses of malignancy in all and an outside biopsy diagnosis of "squamous cell carcinoma" in 2 cases. The important histological findings in the biopsy were PEH (3 cases), granulomas (2 cases), lymphoplasmacytic inflammation (all cases). Eosinophils were conspicuous by their absence. Intracellular histoplasma was seen in all cases, albeit to varying density, which was confirmed with GMS stain.

Conclusion: A high index of suspicion, meticulous history taking by oncologists, and appropriate distinction of PEH from neoplastic squamous proliferation by pathologists in superficial biopsies and an apropos deeper wedge biopsy are essential to clinch the correct diagnosis.

Figure 1

Clinical picture of Case 5. Ulcerated and indurated lesion on the left lateral border of tongue mimicking a malignant lesion on clinical examination.

Figure 2

Histopathological findings of histoplasmosis (usual, non-granulomatous type). A case of oral histoplasmosis (Case 5) with prominent pseudoepitheliomatous hyperplasia. A) Prominent pseudoepitheliomatous hyperplasia of the squamous mucosa with small groups and tongues of squamous epithelium appear to infiltrate into the underlying submucosa, which closely resembles squamous cell carcinoma on low power (x100). B,C) Many foamy macrophages scattered in between the squamous islands (B) and in the submucosa (C), which are teeming with intracellular organisms of 2-4 microns (x200). These organisms are strongly positive for GMS (D) and PAS (E, conforming to the morphology of Histoplasma).

Figure 3

Histopathological findings of histoplasmosis with a granulomatous host response. A case of the less common type of histoplasmosis with a granulomatous host response (Case 2) and only a few yeast forms; a potential pitfall. A) Low power view to show relatively less prominent pseudoepitheliomatous hyperplasia with only mildly hyperplastic squamous mucosa(x100). B) Submucosal region showing an ill-formed epithelioid cell granuloma with giant cells, and epithelioid histiocytes (x200). C) Another area in the same biopsy with an admixture of epithelioid and foamy histiocytes; the foamy histiocytes show few intracellular organisms, which are highlighted by GMS (D, x200).