Tuberculosis is prevalent in underdeveloped and developing nations, including China. Tuberculosis infection occurs primarily in the lung, called pulmonary tuberculosis, but it can also attack other organs or sites outside the lungs causing extrapulmonary tuberculosis (1, 2). A Chinese tuberculosis study reported that extrapulmonary tuberculosis accounts for approximately 24.6% of tuberculosis cases, including the respiratory system (35.5% of extrapulmonary), musculoskeletal system (15.8%), and peripheral lymphatic system (15.8%) (3). Soft tissue tuberculosis is caused by the direct invasion of Mycobacterium tuberculosis or by the spread of tuberculosis lesions from other organs to soft tissues, such as muscles, tendons, and subcutaneous tissues via the bloodstream or lymphatic system. It may occur alone or in association with pulmonary tuberculosis.

Isolated soft tissue tuberculosis is relatively rare, accounting for only 1–2% of all cases of pulmonary and extrapulmonary tuberculosis (4). The clinical presentation of soft tissue tuberculosis is variable and can often be ignored by clinicians (5). Herein, we report a case of soft tissue tuberculosis of the forearm with progressive enlargement of a subcutaneous mass as the first symptom. We also review the relevant literature to discuss its clinical features and prognosis.

The patient was a 40-year-old female admitted to the hospital with a 2 years history of progressive enlargement in the right forearm. The patient had no cough, sputum, hypothermia, night sweats, dyspnea, chest tightness, or fatigue. Physical examination revealed a 6 cm × 3 cm mass was found on the right forearm with a soft texture, no tenderness, and normal skin temperature, mobility, and wrist joint movement. The patient denied any history of local tissue trauma and had no previous history of tuberculosis, immune disorders, tumors, or other systemic diseases.

Superficial ultrasonography of the forearm revealed an irregular mass measuring approximately 56.7 mm × 16.4 mm with unclear borders (Figure 1). CT examination of the chest showed no abnormality (Figure 2). The laboratory blood test revealed a hemoglobin level of 131 g/L, leukocytes of 5.13 × 10⁹/L, neutrophil percentage of 70.6%, lymphocyte percentage of 19.4%, eosinophil percentage of 4.68%, and hematocrit of 20 mm/h. Liver and renal function tests were normal.

The lipoma diagnosis was established according to the examination results, and the mass was resected on August 12, 2022. The mass was observed intraoperatively as a cystic-solid mass with an incomplete covering, and the mass incision revealed grayish-white fluid with small grayish-white particles like fish eggs. Soft tissue tuberculosis of the right forearm was identified by postoperative pathology, which showed fibrocystic tissue with granulation tissue and granuloma formation, inflammatory cell infiltration (Figure 3A), and multinucleated giant cells in some areas (Figure 3B). Staining for acid fast bacilli were positive (Figure 3C) and the IS6110 gene was detected by quantitative real-time PCR (qPCR) using the Mycobacterium tuberculosis Complex kit (Cat.801176, Zeesan Biotech, Xiamen, China), the result showed positive amplification (Figure 4). However, there is no standardized treatment for soft tissue tuberculosis. Considering that the patient lives in a region with a high prevalence of isoniazid resistance (6). The Chinese guideline for diagnosis and treatment of pulmonary tuberculosis suggests that the 2HRZE/4HRE regimen be used in regions where new tuberculosis patients have high prevalence of resistance to isoniazid (7). Finally, we formulated a 2HRZE/4HRE anti-tuberculosis regimen for the patient. It included a 4-drug anti-tuberculosis treatment with isoniazid (H) 300 mg, rifampicin (R) 450 mg, ethambutol (E) 750 mg, and pyrazinamide (Z) 1,500 mg for 2 months, followed by isoniazid (H) 300 mg, rifampicin (R) 450 mg, and ethambutol (E) 750 mg for 4 months. Ten days after the surgery, the patient had good wound healing in the right forearm. After 6 months of anti-tuberculosis treatment follow-up, the patient’s swelling had completely disappeared and the appearance of the right hand was similar to that of the left hand.

The 2019 WHO report estimated a total of 10 million new cases of tuberculosis and 1.5 million tuberculosis-related deaths worldwide (49). Soft tissue tuberculosis is a rare form of extrapulmonary infection caused by Mycobacterium tuberculosis. It is most common in young and middle-aged people and slightly more frequent in males than females (50). According to the literature review, most patients (95.6%) had localized swelling or masses as their primary symptom, and more than half of patients (60.8%) had localized pain or tenderness. Soft tissue tuberculosis had the highest rate of involvement in the extremities (60.8%). However, fewer people (13.0%) developed symptoms of systemic tuberculosis toxicity.

The etiology of soft tissue tuberculosis remains unclear. Nonetheless, two main mechanisms of infection have been described: endogenous and exogenous. Endogenous tuberculosis results from the spread of infection through the lymphatic and blood circulation from tuberculous lesions in other body organs. Indeed, Mycobacterium tuberculosis can easily spread from distant organs via blood or lymph when the body is immunocompromised, such as in HIV infection, diabetes mellitus, renal failure, and long-term use of glucocorticoids (51). On the other hand, exogenous infection is the result of direct invasion of Mycobacterium tuberculosis. About a decade ago, there were case reports in China of tuberculosis bacteria multiplying around the injection site after Bacille Calmette-Guerin (BCG) vaccination, resulting in soft tissue tuberculosis (4). However, no comparable cases have been reported in recent years as a consequence of advances in vaccine preparation techniques in China. Similarly, in an early case report, a patient with tuberculosis suffered a traumatic injury to the buttocks, which resulted in the formation of a cold abscess and a diagnosis of tuberculosis. Thus, the hypothesis was proposed that latent Mycobacterium tuberculosis in the lung spreads to the gluteal muscles via the bloodstream (52). Obviously, the hypothesis has yet to be proven. Only 2 of the 46 patients reported in the literature had a history of trauma.

Of the 46 case studies analyzed in this study, 29 (63%) were diagnosed by surgical debridement or excisional tissue biopsy, and 17 (37%) were diagnosed by ultrasound or CT-guided puncture biopsy. Microscopic examination of pathological sections from 20 patients (43.5%) showed a significant lymphocytic, neutrophilic, or monocytic infiltration with caseous necrosis or granuloma formation and some multinucleated giant cells. All patients had Mycobacterium tuberculosis infection detected by one or more tests, including Gram staining, acid-fast bacilli smear, polymerase chain reaction (PCR), Xpert MTB/RIF test, T-SPOT test, next-generation sequencing (NGS), Mycobacterium tuberculosis tissue or puncture fluid culture, and direct Mycobacterium tuberculosis test (53). The qPCR or gene detection of Mycobacterium tuberculosis is essential for the diagnosis of soft tissue tuberculosis. On the other hand, the acid-fast bacilli smear is less sensitive for detecting Mycobacterium tuberculosis, usually 40% sensitive in extrapulmonary tuberculosis (54). This was also demonstrated in our analysis, where the positive rate of the acid-fast bacilli smear was only 33.3%. Due to the insidious nature of soft tissue tuberculosis symptoms and the low positive predictive value of associated tests, a combination of tests is often used for diagnosis in clinical practice (55). The diagnosis of soft tissue tuberculosis in the analyzed patients was based on pathological examination showing inflammatory cell infiltration, granuloma formation, multinucleated giant cells, positive staining for acid fast bacilli, and positive PCR for Mycobacterium tuberculosis.

Treatment of extrapulmonary tuberculosis consists mainly of lesion debridement and standardized anti-tuberculous drug therapy. Soft tissue tuberculosis with single-site involvement can be surgically excised. However, in patients with multi-site infections and abscess formation, surgical debridement, puncture, and drainage are often used to reduce the lesions and treat them with a sequential standardized anti-tuberculosis regimen (42). Anti-tuberculosis drug therapy is divided into an intensive and a consolidation phase, with emphasis on early treatment, appropriate dosage, regular and complete course, and combination therapy (56). A combination of at least 2 drugs is used to reduce drug resistance. The latest WHO guidelines recommend a 6 months 2HRZE/4HR regimen as the first-line treatment option for pulmonary tuberculosis without arbitrary extension of intensive therapy. Meanwhile, in areas with a high prevalence of isoniazid resistance, the WHO 2022 guideline recommends a 2HRZE/4HR regimen for newly diagnosed patients with extrapulmonary tuberculosis other than central nervous system, bone or joint tuberculosis (57). However, the 2018 edition of the Chinese guideline and the WHO 2010 guideline recommend a 2HRZE/4HRE regimen (7, 58). The literature review shown that 36.9% of patients on the standard 2HRZE/4HR regimen significantly improved. Considering that the patient lives in a region with a high prevalence of isoniazid resistance and the Chinese guideline, we formulated a 2HRZE/4HRE regimen for the patient. Although 2HRZE/4HRE is recommended for new patients with high levels of isoniazid resistance in both the WHO 2010 guideline and the Chinese guideline, the Chinese guideline does not emphasise that 10.3% of previously treated patients are resistant to ethambutol (compared with 2.5% of new patients), which would reduce the effectiveness of this therapy. This is probably why 2HRZE/4HRE remains the usual regimen in China. Regardless of the chosen optimization strategy, it should be noted that long-term use of anti-tuberculosis drugs can cause serious side effects in the internal organs, such as intestinal necrosis (46), hepatic and renal insufficiency (40). The case report and literature review advances our understanding of soft tissue tuberculosis and treatment methods and perform aggressive anti-tuberculosis treatment against drug-resistant Mycobacterium tuberculosis.

In conclusion, comprehensive treatment with surgical excision combined with anti-tuberculosis therapy should be provided for soft tissue tuberculosis. Tuberculosis drug resistance should be taken into account when developing a regimen. Moreover, the regimen should be based on the results of drug susceptibility testing whenever possible.

The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding authors.

The manuscript is a case report with a literature review. No human studies were carried out in preparing the manuscript. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

JL and XC were involved in the conception and design of the work. JL revised the manuscript. JC, YZ, and QW collected the data. KW analyzed the histopathological figures. BC and YB prepared the manuscript. All authors contributed to the article and approved the submitted version.