Dear editor, A 71-year-old male patient with a history of Type 2 diabetes mellitus and non-alcoholic fatty liver disease presented in February 2018 with suspected hepatocellular carcinoma (HCC), portal hypertension, hematemesis, ascites, and a 12-kg weight loss over 4 months. An abdominal magnetic resonance imaging (MRI) was performed. He was diagnosed with cirrhosis and HCC based on imaging studies and tumor marker evaluation, notably with an elevated alpha-fetoprotein (AFP) level, which supported the diagnosis. Prompting initiation of tumor radioablation sessions and medical therapy with spironolactone–furosemide plus propranolol for portal hypertension. Although the patient fulfilled the medical criteria for liver transplantation, the procedure was not carried out because the patient expressed a personal decision not to proceed with transplantation after being informed of the potential outcomes and implications, for that reason the patient remained under surveillance, undergoing two transarterial chemoembolization (TACE) procedures aimed at reducing tumor marker levels (AFP 1200 ng/mL) and progressive deterioration of hepatic function led to a reassessment of the indication, and the procedure was ultimately performed. Orthotopic liver transplantation from a cadaveric donor was performed, including splenectomy due to low portal flow without incidents induction was done with 500mg of methylprednisolone and normal taper. The explanted liver revealed carcinosarcoma as the final diagnosis. Two months after transplantation, while receiving baseline immunosuppression with tacrolimus (1 mg twice daily), methylprednisolone (5 mg daily), and mycophenolate mofetil (500 mg daily), the patient presented with generalized malaise, non-productive cough, and an oppressive holocranial headache partially relieved by analgesics, without fever or focal neurological deficits. Upon admission, he presented a general urine examination with abundant yeasts, C-reactive protein at 134, serum glucose of 357, and creatinine of 1.5. A computed tomography (CT) scan of the skull showed no abnormalities. Thoracoabdominal CT demonstrated focal pulmonary opacities with a ground-glass pattern suggestive of viral or fungal infection, as well as an image compatible with a hepatic abscess (Figure 1). Empirical management with isavuconazole and meropenem was initiated for the collection and pulmonary infiltrates. A bronchoscopy was performed; greenish, thick secretions were observed originating from the right lower lobe, extending to the anterior segment, with edematous mucosa in the basal segments. The hepatic collection was drained under ultrasound guidance, obtaining biliary content rather than purulent material, leading to the reclassification of the collection as a bilioma. Following this finding, the patient was scheduled for an endoscopic retrograde cholangiopancreatography (ERCP) for following day. The patient was admitted to the intensive care unit due to sepsis, acute kidney injury, and persistent hyponatremia. Aexpl video-assisted thoracoscopic surgery (VATS) was performed, carrying out a segmentectomy plus left pulmonary decortication and sample collection in an attempt to close the communication defect and determine pneumonia etiology. The viral panel for pneumonia was negative, as were specific stains for Mycobacterium tuberculosis and atypical mycobacteria, as well as the GeneXpert for tuberculosis. The only positive test was the Fungitell 1-3 β-D-glucan. The lung parenchyma biopsy revealed fungal structures consistent with Mucor species. Antifungal therapy with amphotericin B and isavuconazole was initiated, and a complementary surgical intervention for resection and debridement of infected tissue was required. During the procedure, a ganglionic conglomerate was biopsied. A bilobectomy via thoracotomy and a transdiaphragmatic segmental hepatectomy of hepatic Segment 8 were performed. The explanted liver graft demonstrated extensive necrosis and purulent collections (Figure 2). Histopathological examination of the inferior and middle pulmonary lobes revealed three microscopic parenchymal foci, each measuring 2–3 mm. Within these areas, microorganisms morphologically compatible with Zygomycetes were identified and confirmed with Grocott–Gomori's methenamine-silver (GMS) and periodic acid–Schiff (PAS) staining. Examination of liver tissue from Segment VIII demonstrated positivity with fungal elements, also highlighted by Grocott and PAS stains. Lymph node dissection at Level 7 revealed eight nodes with carcinosarcoma involvement, consistent with metastasis from the primary hepatic carcinosarcoma. Surgical margins were free of areas of necrosis. During hospitalization, a multidisciplinary approach was required with the participation of several medical and surgical specialties. Despite combined antifungal therapy and surgical debridement of necrotic tissue, the patient's general condition continued to deteriorate, necessitating vasopressors, mechanical ventilation, and kidney replacement therapy. The clinical course proved unfavorable, ultimately resulting in the patient's death. Liver transplantation is currently considered a curative therapy for various hepatic pathologies. However, the transplanted liver is susceptible to multiple complications that can jeopardize both graft viability and patient survival. Infectious complications in liver transplant patients are closely associated with the use of immunosuppressants. The most common opportunistic infections include cytomegalovirus (CMV) and Aspergillus spp., as well as candidiasis and recurrent viral hepatitis 1. Mucormycosis is a rare but highly lethal opportunistic fungal infection in liver transplant recipients, with a reported incidence of approximately 2% among solid organ transplant patients and a particularly high mortality rate 2. Caused by fungi of the Mucorales order (mainly Rhizopus), with a varied clinical presentation. Cases may occur early posttransplant, especially in the context of graft-transmitted infection or profound immunosuppression, but late presentations are also described. A systematic search was conducted, which yielded a total of 24 case reports published between 1995 and 2025, of which four case report articles were selected for including pulmonary mucormycosis infection in post-liver transplant patients 3-7. Transplant recipients, patients with hematological malignancies, and those with poorly controlled diabetes are particularly susceptible to mucormycosis infection. Although the classic rhino-orbital presentation has been well described, increasing reports highlight involvement of multiple anatomical sites with variable clinical manifestations. Diabetes mellitus is the most common comorbidity and is considered an independent risk factor in rhino-orbital mucormycosis. Hematological malignancies are strongly associated with invasive disease, while solid organ transplantation is most frequently linked to pulmonary and gastrointestinal involvement 8. In patients with solid organ transplants, evidence regarding mucormycosis is limited. Palomba et al. reported only 183 cases of mucormycosis in solid organ transplant recipients, with 16% corresponding to liver transplants. Surgical debridement was performed in approximately half of the cases, with a mortality rate at 90 days of 36.3% and at 1 year of 63.4% 9. The diagnosis of mucormycosis relies on the direct histopathological identification of fungal hyphae. Non-pigmented hyphae demonstrating tissue invasion must be visualized in tissue sections using hematoxylin–eosin, PAS, or GMS staining 10. In our case, most of the molecular tests were negative, and the test commonly used to detect fungal infections (Fungitell and Aspergillus galactomann) are not reliable for mucor species, delaying the diagnosis until de direct sample recollection. Renal failure, diabetes mellitus, and prior use of voriconazole or caspofungin are associated with a higher risk of mucormycosis. In contrast, the use of calcineurin inhibitors is associated with a reduction of up to four times in the risk of developing mucormycosis in solid organ transplant recipients 8. Liver transplant recipients have earlier rates of infection in comparison with other solid organ transplants 11. Although the patient had a good response to the prior downstage therapy, and had no history of transplant infection of the graft. Likely factors such as the final diagnosis of liver carcinosarcoma, poorly controlled history of diabetes mellitus, and early access to the intensive care unit contributed to the enhancement of his immunosuppression. Most recommendations for mucormycosis are based on consensus or limited evidence. In the pulmonary form, surgery combined with antifungal therapy improves survival compared to exclusive medical treatment 12. In liver transplant recipients, it is an anecdotal event, with barely a dozen cases reported in the literature, although the true incidence could be higher given the rarity of the infection. Julio Alfonso Lagarda Ramos: conceptualization, investigation, writing – original draft, visualization. Dolores Edith Lopez Garnica: methodology, supervision, writing – review and editing. Cesar E. Escareno: resources, supervision, validation, writing – review and editing. The authors thank the Departments of Pathology and Interventional Radiology for their technical support, and the intensive care team for their contribution to patient management, as well as the transplant coordination team for their clinical support. Michel Fernando Martínez Reséndez, Juan Francisco Moreno Hoyos Abril, and Marani Zacatenco Carreño as part of the multidisciplinary team. Portions of this manuscript were assisted by the use of an AI-based language model for language refinement and structural editing, “OpenAI,” specifically the discussion section. All scientific content, interpretation, and conclusions were generated and critically reviewed by the authors. The authors take full responsibility for the integrity and accuracy of the manuscript. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest.
Ramos et al. (Thu,) studied this question.
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