Hepatic disseminated mycobacterium infection: a case report and a literature review

Introduction

Non-tuberculous mycobacteria (NTM) is an acid-resistant bacterium widely present in the natural environment, with more than 190 species and 14 subspecies classified (http://www.bacterio.net/mycobacterium.html). Its virulence is much lower than that of Mycobacterium tuberculosis, and it is a conditional pathogen, with only a small proportion of it pathogenic to humans—the sites of infection mainly include the skin, lungs, and soft tissues (1,2). However, systemic disseminated infections that spread to the abdominal tissues and organs such as the liver rarely occur with NTM (3). The occurrence of NTM infection in the liver and other abdominal organs and abdominal lymph nodes in patients without significant immunodeficiency is even rarer. A patient with the main manifestation of prolonged fever was admitted to the 900th Hospital of People’s Liberation Army Joint Logistic Support Force and was ultimately diagnosed with disseminated Mycobacterium fortuitum infection in the liver and abdominal lymph nodes. A detailed case report is provided below. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-25-48/rc).

Case presentation

A 44-year-old female chef presented with a 6-month history of fever, chest discomfort, and right upper abdominal distension, accompanied by jaundice of the skin and mucosa for the past 4 days. The patient developed a fever 6 months ago, with body temperature fluctuating between 37.8 and 39.3 ℃. Laboratory tests indicated a white blood cell count of 29.3×10⁹/L and a neutrophil proportion of 79%. Acid-fast staining of sputum smears, T-cell detection for tuberculosis infection (T-SPOT TB), sputum culture, and blood culture were all negative. Chest computed tomography (CT) revealed bilateral pneumonia, left lower lung inflammatory changes with atelectasis, and pleural thickening with adhesions. The patient received a 4-week treatment regimen of moxifloxacin, rifamycin, and fluconazole, but intermittent fever persisted. Follow-up chest and upper abdominal CT showed left lower lung inflammation with atelectasis, pleural thickening, hepatosplenomegaly, and gallbladder sludge with cholecystitis (Figure 1). To confirm the diagnosis, the patient underwent thoracoscopic left pleurectomy and left lower lobectomy. Postoperative pathology confirmed an inflammatory pseudotumor. Acid-fast staining of resected lung and pleural tissues was negative, and no fungiere observed on periodic acid-Schiff (PAS) and periodic acid-methenamine silver with Masson’s trichrome (PAM-Masson) staining. Postoperatively, the patient’s chest pain was alleviated, but fever and right upper abdominal pain remained uncontrolled. Four days prior, the patient’s fever and upper abdominal pain worsened, accompanied by skin and mucosal jaundice, necessitating readmission. Suspecting an acute exacerbation of cholecystitis, the patient underwent cholecystectomy, portal lymphadenectomy, and liver biopsy.

Figure 1 Chest CT revealed pulmonary inflammation (A), mediastinal lymphadenopathy (B), pleural thickening and pleural effusion (C), cholecystitis with cholelithiasis (D), lymphadenopathy in the hepatic hilum and retroperitoneum (E), as well as hepatomegaly accompanied by cholecystitis and cholelithiasis (F). These findings are indicated by red arrows. CT, computed tomography.

During surgery, the liver appeared enlarged, with multiple irregularly shaped white nodules resembling millet grains on its surface, which were firm upon palpation. Several enlarged lymph nodes of varying sizes were observed in the hepatic hilum, with the largest measuring approximately 2 cm in diameter and exhibiting a rubbery texture (Figure 2). Biopsies were obtained from the liver nodules and the enlarged lymph nodes in the hepatic hilum, and a cholecystectomy was performed.

Figure 2 Exploratory laparotomy revealed an enlarged liver with multiple irregular, white, millet-like nodules on its surface, firm to the touch (yellow arrows). Enlarged hepatic hilar lymph nodes were noted, with the largest measuring 2 cm and exhibiting a rubbery texture (blue arrow).

Hepatocellular edema accompanied by focal necrosis was observed, along with lymphocytic infiltration in the portal areas and hepatic lobules. Scattered focal granulomatous inflammatory lesions were identified. The hepatic hilar lymph nodes exhibited structural disruption, with reduced or absent lymphoid follicles. Diffuse granulomatous lesions of varying sizes were observed, characterized by an onion-skin-like appearance. Clusters of activated lymphoid-like cells were observed in the sinuses. These cells were relatively large, containing abundant eosinophilic cytoplasm, centrally located nuclei, and coarse chromatin. No evidence of caseous necrosis was detected. Auramine O fluorescence and acid-fast staining revealed varying numbers of acid-fast bacilli. These were rod-shaped or curved, measuring approximately 6–13 µm in length and 0.5–0.9 µm in width, larger than Mycobacterium tuberculosis and Mycobacterium leprae. Their morphology was consistent with NTM characteristics (Figure 3). Immunohistochemical findings for the liver and lymph nodes were consistent. Pathological examination confirmed the diagnosis of NTM. Fluorescence polymerase chain reaction (PCR) melting curve analysis detected NTM in the liver tissue, abdominal lymph nodes, and resected liver samples. The patient was ultimately diagnosed with Mycobacterium fortuitum.

Figure 3 Pathological findings of liver and hepatic hilar lymph nodes. (A) Low magnification of liver tissue: enlarged portal areas with inflammatory cell infiltration and granuloma formation (HE staining, 200×). (B) High magnification of liver tissue: markedly enlarged portal areas with lymphocytic and mononuclear cell infiltration and granuloma formation; bile ducts remain intact (HE staining, 400×). (C) Medium magnification of hepatic hilar lymph nodes: loss of lymph node structure with preserved subcapsular sinuses; scattered microgranulomas observed (HE staining, 200×). (D) High magnification of hepatic hilar lymph nodes: complete loss of lymph node structure with focal epithelioid granulomas (HE staining, 400×). (E) Acid-fast bacilli observed in lymph nodes, appearing red, rod-shaped, or curved (indicated by black arrow) (acid-fast staining, 400×). (F) Fluorescence microscopy showed green fluorescent rod-shaped or curved bacilli in lymph nodes (auramine O staining, 1,000×). HE, hematoxylin and eosin.

Following diagnosis, the patient was treated with rifampin, isoniazid, pyrazinamide, ethambutol, and clarithromycin. The fever subsided, abdominal pain resolved, and liver function improved, enabling the patient to be discharged. However, 3 months into continued oral administration of these medications, the symptoms recurred. Suspected drug resistance to Mycobacterium fortuitum prompted adjustment of the treatment regimen to alternative antimycobacterial agents. Despite these efforts, the therapeutic response was suboptimal, and the patient ultimately succumbed to multi-organ failure.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s family for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

As noted, NTM is a widespread environmental acid-resistant microorganism which are far less virulent than Mycobacterium tuberculosis but can cause a wide range of diseases, including skin, lung, and soft tissue infections (1,2). However, systemic disseminated infections that spread to the abdominal tissues and to organs such as the liver rarely occur with NTM (3). The final diagnosis was confirmed mainly on the basis of biopsies of the patient’s liver and lymph nodes in the liver region, while the lymphatic histology revealed lymphocytic infiltration with granuloma formation in the portal area of the liver. Both the gold amine O and the antacid staining revealed a large amount of acid-resistant bacilli, and the morphology of the bacterium was in accordance with NTM. The fluorescent PCR melting curve method was adopted to further identify the strain (4,5), and the final diagnosis was confirmed as Mycobacterium fortuitum. In the early stage of the disease, fever, coughing, and chest pain were the main manifestations, with the CT chest scan indicating left lower lung atelectasis and left pleural hypertrophy. On reviewing the histological features of the lung and pleural tissue sections, the histological changes were essentially consistent with the pathological features of Mycobacterium infection. Therefore, the patient was diagnosed with systemic disseminated Mycobacterium fortuitum infection with multi-organ infection of the liver, lung, and abdominal lymph nodes.

The main pathological features of the patient’s lesions included enlargement of the liver with multiple white diffuse hyperplastic nodules on the surface, hepatocellular edema with punctate necrosis, lymphocytic infiltration with granuloma formation in the portal area, and no caseous necrosis. The pathology of the lymph nodes was characterized by diffusely proliferating granulomatous lesions of variable size, with onion-skin-like changes and activated lymphoid blasts observed within the sinusoids. Meanwhile, the light microscopy analysis revealed that the Mycobacterium fortuitum was rod-shaped or curved and was thicker than both Mycobacterium tuberculosis and Mycobacterium leprae. Finally, histocytes expressing CD68⁺, CD163⁺, CD20⁺, CD21, and CD3⁺ indicated inflammatory cell infiltration by macrophages, lymphocytes, and dendritic cells. The above histopathology and mycobacterial morphology were similar to those described in the existing literature (6,7).

Extrapulmonary tuberculosis and NTM infections are clinically uncommon and are frequently subject to misdiagnosis and missed diagnosis. Hepatic mycobacterial disease, in particular, can present with variable features at different stages, ranging from nonspecific hepatomegaly to low-density nodular lesions and eventually to high-density calcified nodules. Despite these imaging findings, the lack of specificity in hepatitis tuberculosis imaging can complicate diagnosis. Patients often exhibit systemic symptoms such as fever, weight loss, and fatigue, which may be mistaken for hepatic or hematological malignancies (8). Therefore, timely liver biopsy and pathological examination are crucial. The identification of granulomatous inflammation and/or caseous necrosis highly suggests infection with Mycobacterium tuberculosis complex or NTM. Definitive diagnosis can be achieved by combining acid-fast staining and auramine O-rhodamine fluorescent staining with molecular diagnostic techniques (9).

The clinical manifestations of NTM and tuberculosis are highly similar, but the sensitivity to drugs differs between NTM and Mycobacterium tuberculosis complex, with most NTMs being naturally resistant to anti-tuberculosis drugs (1,10). Following diagnosis, the patient was treated with rifampin, isoniazid, pyrazinamide, ethambutol, and clarithromycin. The fever subsided, abdominal pain resolved, and liver function improved, enabling the patient to be discharged. However, 3 months into continued oral administration of these medications, the symptoms recurred. Suspected drug resistance to Mycobacterium fortuitum prompted adjustment of the treatment regimen to alternative antimycobacterial agents. Despite these efforts, the therapeutic response was suboptimal, and the patient ultimately succumbed to multi-organ failure.

While NTM is traditionally considered to be weakly pathogenic, a combination of multiple antimicrobial drugs and appropriate control of the source of infection can achieve a good clinical outcome and a high cure rate. For patients with multi-organ disseminated infection involving the liver, conventional anti-tuberculosis drugs are less effective and the infection will continue to pose a serious risk and should be regarded as high priority.

Conclusions

For patients with multi-organ disseminated infection involving the liver, conventional anti-tuberculosis drugs are often ineffective, and the infection continues to pose a serious risk; therefore, it should be given heightened attention.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-25-48/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-25-48/prf

Funding: This study was supported by the Guiding Projects of Social Development of Fujian Province (No. 2021Y0062).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-25-48/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s family for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J 2020;56:2000535. [Crossref] [PubMed]
2. Haworth CS, Banks J, Capstick T, et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax 2017;72:ii1-ii64. [Crossref] [PubMed]
3. Wallace RJ Jr, Brown BA, Griffith DE. Nosocomial outbreaks/pseudo-outbreaks caused by nontuberculous mycobacteria. Annu Rev Microbiol 1998;52:453-90. [Crossref] [PubMed]
4. Kim YN, Kim KM, Choi HN, et al. Clinical Usefulness of PCR for Differential Diagnosis of Tuberculosis and Nontuberculous Mycobacterial Infection in Paraffin-Embedded Lung Tissues. J Mol Diagn 2015;17:597-604. [Crossref] [PubMed]
5. Li AF, Tan XW, Cui XL, et al. Application value of fluorescence PCR melting curve method in the identification of non-tuberculous mycobacteria. Chinese Journal of Antituberculosis 2021;43:664-9.
6. Jain D, Ghosh S, Teixeira L, et al. Pathology of pulmonary tuberculosis and non-tuberculous mycobacterial lung disease: Facts, misconceptions, and practical tips for pathologists. Semin Diagn Pathol 2017;34:518-29. [Crossref] [PubMed]
7. Mu J, Liu ZC, Zhang C, et al. Pathological characteristics and molecular diagnosis of non-tuberculosis Mycobacterium lung disease. Zhonghua Bing Li Xue Za Zhi 2020;49:562-7. [Crossref] [PubMed]
8. Forgione A, Tovoli F, Ravaioli M, et al. Contrast-enhanced ultrasound LI-RADS LR-5 in hepatic tuberculosis: case report and literature review of imaging features. Gastroenterology Insights 2021;12:1-9.
9. Cheng M, Chen Y. Disseminated lymph node tuberculosis after splenectomy: an unusual case report in an adolescent. BMC Infect Dis 2021;21:1181. [Crossref] [PubMed]
10. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367-416. [Crossref] [PubMed]