Mucormycosis is an angioinvasive opportunistic fungal infection caused by fungi of the order Mucorales. Rhizopus species are the most prevalent Mucorales and account for more than 70% of infections [4]. Its incidence cannot be precisely measured due to limited population studies, but various studies have shown an increase in its occurrence which account for 1.7 cases per 1 million individuals [4, 5]. The most significant predisposing conditions for mucormycosis include diabetes mellitus (DM), with or without ketoacidosis, hematological neoplasms, other malignant neoplasms, transplants, prolonged neutropenia, corticosteroids, trauma, iron overload, illicit intravenous drug use, neonatal prematurity, and malnutrition [4]. Immunocompetent patients can also be affected when fungal spores are directly inoculated into the skin due to trauma or burn, facilitated by the fungus’s cell wall composition and genetic alterations, allowing rapid growth in the host environment and evasion of its defenses [5].

Cases of mucormycosis in HIV + individuals without any additional risk factors such as the case presented have rarely been reported [6], owing to the initial response of neutrophils rather than lymphocytes to fungal infections [2, 7]. The majority of HIV patients who present with mucormycosis have associated conditions (e.g. DM) [2]. In some cases, this may be related to the use of the latest generation of antiretroviral regimens that can predispose patients to diabetes and/or the appearance of malignant neoplasms [2] such as our previously reported case, who was diagnosed with AML [8]. Therefore, mucormycosis may become more common in association with HIV infection in patients with severe neutropenia and in those who lack phagocytic function, increasing their susceptibility to fungal infections [9]. Phagocytes play a critical role in the host defense against Mucorales, as macrophages phagocyte inhaled sporangiospores, preventing their germination, while neutrophiles produce oxidative metabolites and cationic peptides, killing the fungus [10]. For instance, an important prognostic factor in patients with hematological malignancies in the recovery from neutropenia [10].

These pathogens can infect various organs, including the head and neck, nasal cavity, lungs, skin, central nervous system, and gastrointestinal (GI) tract, causing infarction and tissue necrosis. This is mediated through the expression of spore coat protein homologue (CotH) proteins in spores and hyphae, facilitating adhesion to endothelial cell receptors, angioinvasion, and dissemination [11]. The hyphae of Mucorales specifically recognize the host receptor GRP78 on endothelial cells, an interaction mediated by the fungal ligand CotH3 for endocytosis of the fungus [12]. Angioinvasion by Mucorales causes endothelial injury and death leading to thrombosis, dissemination, and tissue necrosis [12]. The toxic metabolites produced by Mucorales (e.g., mucoricin) have shown to induce inflammation, vascular permeability, and tissue necrosis [12]. The production of lytic enzymes and proteases, along with mycotoxins, enhances fungal invasion. Therefore, the main pathological feature in affected organs is angioinvasion, which results in hemorrhage, infarction, and suppurative inflammation [7, 11].

Gastrointestinal mucormycosis is a relatively rare manifestation of infection, with a mortality rate between 40% and 85%. It is most frequently observed in the stomach (57.5%), followed by the small intestine (10.3%) and the colon (32.2%), as observed in this case [13]. Mucorales primarily enter the gastrointestinal tract through nasogastric intubation, infected wooden tongue depressors, and contaminated foods such as fermented milk, dried bread products, and alcoholic beverages derived from infected corn [5, 13]. Due to the nonspecific clinical signs of gastrointestinal mucormycosis, including abdominal pain and distension, rectal bleeding, and fever, the disease is often diagnosed late. The lack of differentiation from other gastrointestinal diseases complicates its diagnosis, which underscores the need for a high index of suspicion [13, 14].

Our patient presented with angioinvasion due to mucormycosis. This complication has been previously reported as potentially fatal due to the fungus’s strong tendency to invade blood vessels, leading to necrosis, thrombosis and tissue infraction, causing intestinal necrosis with visceral perforation, peritonitis and massive gastrointestinal bleeding [2]. Prominent infarcts and angioinvasion characterize invasive disease and are predominant in neutropenic patients, which is consistent with the present case [14].

Histopathology and various clinical cultures are the cornerstones of the diagnosis of mucormycosis [7]. The histopathological characteristics of the affected tissue of our patient revealed the presence of extensive necrosis with numerous large, branched, pale, wide, flat, non-septate hyphae, with common high-angle bifurcations (90°). Staining with hematoxylin-eosin made it possible to evaluate neutrophilic or granulomatous inflammation and the presence of fungal elements, which in some cases could only show the cell wall of the fungus without structures inside or, sometimes, very degenerated hyphae. The dyes used to visualize fungal walls include Grocott’s methenamine silver (GMS) and periodic acid-Schiff (PAS). PAS provided us with better visualization of the surrounding tissue than GMS, allowing for more detailed analysis of the microanatomy of the fungus [5, 14].

Treatment for mucormycosis typically involves surgical debridement of the involved tissues and antifungal therapy, along with a suggested empirical antifungal therapy, considering the adversity of infection and the risk of poor outcomes [15]. Treatment for the present case involved surgical removal of infected tissue and debridement of necrotic tissue to prevent the progression of infection to vital structures or spread to other sites. Adequate surgical debridement of compromised tissues can improve the penetration of antifungal agents into the still viable infected tissue associated with the early initiation of antifungal therapy, when mucormycosis infection is suspected [11, 14]. However, the patient had severe neutropenia, associated with anemia and thrombocytopenia, in addition to a systemic mycosis; despite the initiation of broad-spectrum antifungal and surgical procedures, the patient continued with an unfavorable evolution without response to medical treatment.

Early diagnosis and treatment are crucial for preventing complications and death, such as the case described above, which had a fatal outcome. However, initial diagnosis is challenging due to the non-specificity of signs and symptoms and the lack of a diagnostic tool to confirm the disease. It is important to highlight the role of pathologist and the histopathological studies, which are essential for diagnosis and treatment.