The patient arrived with a palpable, tender mass in the right anterior chest wall. Imaging with color Doppler ultrasound revealed a predominantly cystic lesion situated between the right pectoralis major muscle and the adjacent costal cartilage, an anatomical location where infectious masses are uncommon and neoplastic ones draw immediate attention. Faced with a lesion of uncertain nature, the clinical team proceeded to a core-needle biopsy, the standard approach for obtaining tissue when imaging alone cannot distinguish between a tumor, an abscess, or something rarer still.

What the pathologists saw under the microscope was suggestive but not conclusive. The biopsy showed a reactive spindle-cell proliferation accompanied by prominent inflammatory infiltrates, a pattern indicating that the tissue was responding to some kind of insult, but it did not identify the cause. Reactive spindle-cell lesions can accompany infection, trauma, or neoplasia, and without an etiological agent in view, histopathology alone could not deliver a diagnosis. This is a familiar frustration in infectious disease practice: tissue shows inflammation, but the organism responsible remains invisible, either because it is present in very low numbers, because it is difficult to stain, or because it simply is not on the laboratory’s radar.

That is where the sequencing came in. The team sent the biopsy specimen for metagenomic next-generation sequencing, an unbiased technique that extracts all genetic material from a sample and reads it without needing to guess in advance which pathogen might be present. Unlike targeted PCR tests, which hunt for one organism at a time, mNGS surveys everything, comparing the sequences obtained against reference databases such as those maintained by the National Center for Biotechnology Information. In this case, the analysis detected Encephalitozoon cuniculi, and no other pathogen reached the reporting threshold, giving the clinicians a single, coherent answer to a question that microscopy had left open.

Encephalitozoon cuniculi belongs to the microsporidia, a group of obligate intracellular parasites that are now classified as fungi. They are among the smallest eukaryotic cells known, and their biology is strikingly streamlined: they carry severely reduced genomes and rely on the host cell for much of their metabolism, including energy generation, which they extract through a unique plasma membrane transporter called a polar tube injection machinery that physically injects the sporoplasm, the infectious contents of the spore, directly into a host cell. Spores shed by infected individuals are environmentally resistant and can survive for extended periods outside a host, making transmission through contaminated water, food, or direct contact a persistent concern, particularly in settings involving animals, since E. cuniculi infects rabbits and other mammals and is considered zoonotic.

In immunocompetent people, exposure to microsporidia is thought to be relatively common and usually either asymptomatic or self-limited, particularly when it involves the gastrointestinal tract. Clinically apparent disease, however, has historically been concentrated in people living with HIV, transplant recipients on immunosuppressive drugs, and others with compromised cellular immunity. Symptomatic infection in a person without recognized immunodeficiency is uncommon, and a deep tissue infection presenting as a chest wall mass is rarer still. The authors of the report note that this case underscores an unusual presentation of tissue microsporidiosis, one that could easily have been misclassified as a tumor or an nonspecific inflammatory lesion had the workup stopped at conventional histology.

Importantly, the sequencing result did not stand alone. Once mNGS had pointed to microsporidia, the team revisited the biopsy tissue with specialized stains. Periodic acid–Schiff staining and Grocott’s methenamine silver staining, both of which highlight carbohydrate-rich structures in fungal and fungal-like organisms, revealed small spore-like structures compatible with microsporidia. This convergence of independent lines of evidence, molecular detection on one hand and morphological visualization on the other, is exactly how modern diagnostic workflows are meant to function: sequencing generates a hypothesis rapidly, and targeted classical techniques then confirm it on the original material. Based on the combined findings, the clinicians considered tissue microsporidiosis associated with E. cuniculi the most likely diagnosis.

Treatment followed promptly. Albendazole, a benzimidazole anthelmintic that disrupts microtubule polymerization and is the mainstay of therapy for microsporidial infections, was initiated and administered for three months. At telephone follow-up after completion of the treatment course, the patient reported that the palpable mass and the tenderness had resolved. A follow-up contrast-enhanced chest CT scan performed on August 13, 2026 showed no residual lesion in the right anterior chest wall, a satisfying radiological confirmation of what the patient had already reported clinically. The authors discontinued albendazole after the three-month course, and the case stands as an example of a complete diagnostic and therapeutic arc, from an undifferentiated mass to a confirmed rare infection and a documented cure.

The case carries several broader lessons for clinical practice. First, it demonstrates the diagnostic value of mNGS as an adjunct when conventional histopathology is inconclusive, a scenario that arises constantly in hospitals worldwide. The technology is not a replacement for pathologists; the reactive spindle-cell proliferation seen on biopsy was itself meaningful information, and the confirmatory special stains required a human expert to interpret them. Rather, mNGS functions as a wide-net complement, particularly for organisms like microsporidia that are small, easily overlooked, and absent from most routine laboratory panels. Second, the case is a reminder that rare opportunistic pathogens can occasionally cause disease in hosts who appear immunologically normal, and that a patient’s immune status should not be the sole gatekeeper determining which infections clinicians consider.

There are also open questions that a single case report cannot answer. The route of exposure in this patient remains unclear, as does the reason why an apparently immunocompetent individual developed a localized deep tissue infection. The report notes that the patient had no known major immunodeficiency, but subtle immune defects, whether genetic, medication-related, or transient, can sometimes underlie infections that seem surprising at first glance. As mNGS becomes more widely available and more affordable, cases like this one are likely to surface with greater frequency, gradually refining the map of where microsporidia infect humans and under what circumstances. For now, the Guangzhou case offers a concrete demonstration of how unbiased sequencing, classical staining, and attentive clinical follow-up can together resolve an infection that would otherwise have remained nameless, and it adds a rare etiology to the differential diagnosis of chest wall masses, a list that clinicians may now consult with slightly wider eyes.

Subject of Research: Tissue microsporidiosis caused by Encephalitozoon cuniculi diagnosed by metagenomic next-generation sequencing in an immunocompetent patient

Article Title: Chest wall tissue microsporidiosis associated with metagenomic next-generation sequencing detection of Encephalitozoon cuniculi: a case report

Article References: Zhang, W., Guan, J., Yi, H., & Zhang, J. (2026). Chest wall tissue microsporidiosis associated with metagenomic next-generation sequencing detection of Encephalitozoon cuniculi: a case report. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14555-1

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14555-1

Keywords: Encephalitozoon cuniculi, microsporidiosis, metagenomic next-generation sequencing, chest wall mass, case report, albendazole, histopathology, infectious diseases, immunocompetent host, diagnostic sequencing, Chest, wall