Letter to the Editor: Ileocecal basidiobolomycosis resembling malignancy - histopathological insights and a justification for nonsurgical therapy

Abstract

Basidiobolomycosis usually manifests as persistent subcutaneous swelling and hardly infects the gastrointestinal tract. Due to infrequent gastrointestinal involvement along with nonspecific clinical signs, it frequently leads to misdiagnosed cases and treatment delays. Gastrointestinal basidiobolomycosis (GIB) should be recognized as a differential diagnosis in patients with abdominal pain, weight loss, eosinophilia, and an inflammatory mass refractory to non-antifungal therapy, especially if the patient hails from Iran, Saudi Arabia, Kuwait, or desert regions of the United States (primarily Arizona). Histopathological findings, including mixed inflammatory cells, especially eosinophilic infiltration, granulomatous reactions, broad, thin-walled, and aseptate hyphae, and Splendore-Hoeppli phenomenon (radiating intensely eosinophilic material) around fungal hyphae, are highly characteristic of GIB. In this editorial, we comment on the article published by Alsulaimi et al in the World Journal of Clinical Cases, showing a case of 32-year Saudi male with an ileocecal mass. It was confirmed to be GIB on histopathology and was treated by antifungal therapy alone. In this article, we emphasized the importance of histopathology in making the diagnosis of GIB and suggested that more polymerase chain reaction-based methods be used for early identification.

Key Words: Gastrointestinal basidiobolomycosis; Splendore-Hoeppli phenomenon; Ileocecal mass; Antifungal; Histopathology

Core Tip: Gastrointestinal basidiobolomycosis is a rare fungal infection most seen in Iran, Saudi Arabia, and the desert areas of the United States. Unlike other fungal infections, it commonly occurs in immunocompetent individuals. Histopathological findings like the Splendore-Hoeppli phenomenon remains cornerstone of this infection diagnosis. While itraconazole is first line medication in most cases, posaconazole is utilized in treatment-refractory cases. Awareness should be raised in clinicians of endemic regions to consider gastrointestinal basidiobolomycosis as a differential diagnosis in patients presenting with an inflammatory ileocecal mass with eosinophilia.

TO THE EDITOR

Ileocecal basidiobolomycosis resembling malignancy: Histopathological insights and a justification for nonsurgical therapy

Gastrointestinal basidiobolomycosis (GIB) is a unique fungal infection caused by Basidiobolus ranarum, a saprophytic fungus prevalent mostly in soil and decomposing vegetables[1]. The first human case of infection caused by Basidiobolus ranarum was documented in Indonesia in 1956[2]. The unique feature of this fungal infection is that it is relatively uncommon in immunocompromised hosts, such as diabetics and renal transplant patients[3]. The first documented incidence of GIB came to light in a 4-year-old kid in 1964[4,5]. Although the exact mechanism by which the fungus enters the digestive system is unknown, it most likely occurs through ingestion of infected food, animal excrement, or soil. The use of contaminated toilet leaves for cleansing the skin after defecation has also been explored as a potential channel of entry for this[6,7].

GIB prevalence is seen primarily in tropical and subtropical regions of the world, with most cases documented in the United States, Saudi Arabia, and Iran. In Saudi Arabia and Iran, exposure to geckos and insect bites has been identified as a potential source of infection[8]. The colon or cecum is the most common site of gastrointestinal involvement in GIB (84.2%), with liver and gall bladder involvement identified in 21.8% of cases[9,10]. The pathogenesis of primary GIB is still unclear. Local injuries to the colonic mucosa can lead to a breakdown in the mucosal defense barrier and immunity. Several host defense systems resist this infection, including sequestration of iron molecules, the generation of reactive oxygen species, and the production of molecules that damage fungal structures. Furthermore, polymorphonuclear leukocytes and histiocytes can kill fungal bodies by producing defensins, potent cationic peptides. The progression of GIB depends on the scavenging of iron molecules required for fungal growth from the host-affected tissues[11,12].

In an interesting case report, Alsulaimi et al[13] in the World Journal of Clinical Cases described a 32-year-old immunocompetent Saudi male who experienced lower abdomen pain in the right lower quadrant. On computed tomography and colonoscopy, it became apparent that he had a fungating ileocecal mass that was highly suspected of cancer. However, the histopathology of the colonoscopy biopsy confirmed the diagnosis of GIB. The patient was initially treated with voriconazole, but eventually switched to posaconazole because of hepatotoxicity, and after four months of therapy, he had complete resolution without having to opt for surgery. This case emphasizes the crucial concerns about non-surgical GIB care and evaluation techniques.

DIAGNOSTIC AND THERAPEUTIC CHALLENGES

Diagnosing GIB is challenging due to its nonspecific clinical presentation and rarity. Patients mostly present with abdominal discomfort (86.3%), followed by fever (40.2%), weight loss (33.3%), abdominal mass (30.4%), vomiting (15.7%), and diarrhea (13.7%)[10]. However, these features frequently coexist with Crohn’s disease, intestinal tuberculosis, colorectal cancer, lymphoma, and parasitic infections such as amoebiasis. Microbiologic cultivation of the fungus extracted from tissues is necessary for the definitive diagnosis. It should be isolated promptly after resection, given that it does not survive at 4 °C. Sabouraud agar is an adequate medium for this fungus, and growth is typically seen 2 days to 3 days after incubation at 25 degrees to 30 degrees Celsius. Fungal stains (Grocott-Gomori methenamine-silver, periodic acid-Schiff) weakly stain the broad, pleomorphic, sparsely septate hyphae that make up the fungal elements. Colonies resemble white or pale grey, with radial folds[14]. Histopathology of GIB typically shows prominent folds, isolated bleeding, or ulceration in the gut and surrounding fat. With granulomatous inflammation situated in the muscularis propria and extending into the submucosa, subserosa, and adipose tissue, the mucosal surface shows prominent folds, isolated bleeding, or ulceration. Granulomas have palisading histiocytes and numerous multinucleated giant cells around central necrosis[15]. Abscess formation in the afflicted area can occasionally be observed as a localized accumulation of fluid or pus. At times, GIB manifests as ulcerated polypoidal or nodular mucosa with necrosis and exudates[16]. Splendore-Hoeppli phenomenon is typically seen on histopathology, demonstrating an eosinophilic cuff encircling the hyphae with a radius of up to 20 mm. It happens because of the accumulation of antigen-antibody complexes and debris from the host’s inflammatory cells[17]. Recent reports have also documented the use of enzyme-linked immunosorbent assay and polymerase chain reaction for the diagnosis of GIB[18].

For this rare infection, an ideal standardized treatment plan has not yet been established. Most patients have received both pharmaceutical and surgical interventions. Itraconazole is the most used antifungal agent (73%), followed by amphotericin (22%), ketoconazole (8%), and voriconazole (5%). When antifungal medication is administered for eight months, the average overall survival rate is expected to be 80%. Posaconazole is the preferred drug in treatment-resistant cases[19,20]. Alsulaimi et al[13] illustrated in their report effectively this point by using posaconazole after voriconazole resistance. The absence of surgical intervention in this case further supports the growing evidence that non-operative care is a viable first-line option in immunocompetent patients with GIB.

FUTURE RECOMMENDATIONS

Alsulaimi et al[13] shed light on numerous critical challenges for future study on GIB management. Firstly, there is no standardized diagnostic and therapeutic protocol for GIB. Regarding its treatment plan, length of treatment, and follow-up tests, an international consensus guideline needs to be developed. Prospective multicenter trials should be conducted to establish the most efficient therapy for this illness[21]. Secondly, Future research should concentrate more on how polymerase chain reaction-based diagnostic methods might be used in situations lacking fungal culture. More attention should be paid to ultra-deep sequencing methods to enhance identification and the therapeutic strategy[22]. Implementing molecular diagnostics like next generation sequencing may improve the diagnosis of GIB while reducing the amount of secondary invasive procedures, particularly in cases of negative culture or when Splendore-Hoeppli phenomenon is absent. As it has high sensitivity, it can confirm a diagnosis even with low fungal burden[23]. Thirdly, while non-surgical is a viable first-line option, surgery remains necessary in cases of perforation or obstruction, which are common complications of GIB. Prospective cohort studies should be undertaken on surgical vs non-surgical outcomes for GIB. These studies may offer proof necessary for making confident clinical judgments. Finally, clinicians in endemic areas should be trained to consider GIB as a differential, which will lead to earlier detection and better management.

CONCLUSION

Considering a wide range of clinical and radiological differentials, GIB has remained challenging to diagnose. GIB can persuasively mimic colonic cancer, highlighting the critical significance of histopathological investigation, which includes identifying the Splendore-Hoeppli phenomenon for an appropriate diagnosis. Future studies should focus on the creation of a standardized diagnostic approach through multidisciplinary cooperation and the incorporation of polymerase chain reaction and ultra-deep sequencing techniques for early detection. GIB awareness should be raised among clinicians in the endemic region to avoid unnecessary delays and improve care.