Acute mediastinitis, mediastinal granuloma, and fibrosing mediastinitis: a narrative review

Introduction

The mediastinum is the central part of the thoracic cavity. Anatomically, it is bound anteriorly by the sternum, posteriorly by the thoracic spinal column, and laterally by the mediastinal parietal pleural surfaces. It is further divided into superior, anterior, middle, and posterior parts (Table 1) and contains the heart, great vessels, trachea and mainstem bronchi, esophagus, thymus gland, and multiple lymph nodes (1). Mediastinitis or inflammation of the mediastinum, can be acute or chronic and has multiple etiologies. Acute mediastinitis is an infection resulting from intrathoracic instrumentation such as median sternotomy, esophageal perforation, odontogenic infection, or lymphatic spread from an extra-thoracic site. The pathogens driving acute mediastinitis are predominantly bacterial, and the causative organism or organisms depend on the inciting pathology (2). To the contrary, chronic fibrosing mediastinitis (FM) has a more insidious onset and involves fibrosis of mediastinal structures. This condition is generally driven by granulomatous diseases (fungal or mycobacterial infection). Mediastinal granulomas (MGs) are mass-like lesions that develop within the mediastinal space and sometimes cause compression of nearby structures. In this review, we will discuss each of these conditions in further detail. We present this article in accordance with the Narrative Review reporting checklist (available at https://med.amegroups.com/article/view/10.21037/med-2026-1-0003/rc).

Methods

We conducted a comprehensive literature review of relevant articles on databases such as PubMed and Google Scholar. Articles were filtered into English only. The literature review was conducted from January 2016 until December 2025 (Table 2). Articles were individually reviewed. Articles felt to be less relevant or superseded by new information were reviewed by a multidisciplinary author panel and determined to be included or excluded.

Acute mediastinitis

Acute mediastinitis has variable etiologies. The most common etiologies of acute mediastinitis include deep sternal wound infection (DSWI) following median sternotomy, esophageal perforation, and descending necrotizing mediastinitis (DNM) from odontogenic infection (3). Other etiologies include seeding via the lymphatic system or spread from other regions such as the lungs or peritoneal cavity. Patients presenting with acute mediastinitis generally have fever, chest pain, and other systemic infectious symptoms. If they have recently undergone median sternotomy, they may have erythematous skin around or frankly purulent drainage from the surgical wound. Patients may be septic-appearing with leukocytosis, elevated procalcitonin, lactic acid levels, and acute-phase reactants such as C-reactive protein on laboratory studies. As plain chest radiography can show nonspecific mediastinal widening, computed tomography (CT) imaging with intravenous contrast (as well as oral contrast if esophageal rupture is suspected) is generally required to confirm the diagnosis (3). It is worth noting that, during the first few weeks after surgery, mediastinal post-operative changes are indistinguishable from acute mediastinitis on imaging (4). Patients are frequently critically ill and require admission to an intensive care unit. Management has multiple facets, including intravenous antibiotics and operative intervention to further assess the underlying cause, drain mediastinal fluid collections, and debride diseased tissue. In this section, we will further examine the major causes of acute mediastinitis.

Specific etiologies of acute mediastinitis

Acute mediastinitis due to esophageal perforation

One of the most common causes of acute mediastinitis is esophageal perforation. Esophageal perforation has a high rate of morbidity and mortality, especially if not promptly recognized and treated. There are multiple etiologies of esophageal perforation including neoplastic disease, trauma, foreign body ingestion, spontaneous (i.e., Boerhaave Syndrome, seizure), as well as iatrogenic related to endoscopic and surgical procedures (5). The most common cause of esophageal perforation is iatrogenic-related injury secondary to therapeutic endoscopic interventions (6). When the esophageal wall is breached, esophageal contents are introduced into the mediastinal space paving the way for chemical inflammation and microbial infection. Acute mediastinitis secondary to esophageal perforation is usually polymicrobial. Predominant organisms include Peptostreptococcus, Fusobacterium, Bacteroides, alpha-hemolytic Streptococcus, Staphylococcus aureus, and Klebsiella (7).

Prompt recognition of esophageal perforation and resultant mediastinitis is essential as its mortality rate is up to 40% (8). Most patients with intrathoracic esophageal perforation are ill-appearing on presentation, although some patients may appear more stable and with vague symptoms. In about 50% of cases, patients have accompanying subcutaneous emphysema and dyspnea, which, when combined with chest pain, compose the Mackler Triad (8,9). Common CT findings include esophageal wall thickening, extra-luminal air, mediastinal fluid collection, pneumothorax, pleural effusion, and mediastinal extravasation of water-soluble contrast. Extraluminal air is seen in over 90% of cases (10). Pleural effusion related to esophageal perforation generally occurs in the left hemothorax. The effusion may be sympathetic if the mediastinal parietal pleura remains intact, or it could be exudative if the pleura is perforated, allowing gastric contents to travel into the pleural space (6). Pleural effusion in the setting of esophageal perforation warrants thoracentesis at a minimum, which may show the presence of salivary amylase, food, or a pleural fluid pH of less than 6.0 (11). There should be a low threshold for chest tube placement.

Initial management of esophageal perforation and resultant mediastinitis includes prompt initiation of broad-spectrum antibiotics, including coverage for anaerobic organisms. There should be a low threshold for empiric antifungal coverage, as well. The patient should be kept nil per os (NPO), and thoracic surgical consultation should be promptly obtained. Management depends on the etiology and size of the esophageal perforation as well as the degree of mediastinal contamination and the stability of the patient. If the perforation is small and the result of an endoscopic procedure, then endoscopic closure techniques may be successful (12). For stable patients with contained perforation and no evidence of mediastinitis, conservative management with close monitoring of hemodynamics and serial imaging is a viable option (13). For unstable patients or those with extensive contamination, surgical management with debridement and primary repair of the perforation site is the mainstay. Esophageal stent placement may be an option for patients with multiple comorbidities, large esophageal tears, or who cannot tolerate thoracic surgery. Postoperatively, patients are kept NPO for 7 days and require enteric access, usually with a nasojejunostomy tube, for nutrition. Broad-spectrum antibiotics are continued for a minimum of 7 days, and contrast esophagram is repeated on post-operative day seven to assess for persistent leak. Patients without evidence of esophageal leakage may have enteral access removed and resume oral feeding.

Acute mediastinitis secondary to DSWI and median sternotomy

Another common cause of acute mediastinitis is DSWI and median sternotomy. The incidence of post-sternotomy mediastinitis varies, but the rate of this complication is estimated to be 1–3% (14). Patients undergoing cardiac transplantation or requiring mechanical circulatory support devices are at higher risk (15,16). There are multiple risk factors for post-sternotomy mediastinitis including nasal colonization with Staphylococcus aureus, diabetes mellitus, heart failure, obesity, tobacco use, end-stage renal disease on dialysis, urgent or emergent surgical procedure, and prolonged intensive care unit stays. Obesity and diabetes mellitus are thought to be the most important risk factors for predicting mediastinitis (17). The predominant causative organism for post-sternotomy mediastinitis is methicillin-sensitive Staphylococcus aureus. Other implicated organisms include Gram-negative rods, methicillin-resistant Staphylococcus aureus, and coagulase-negative Staphylococcus species (18).

Time from sternotomy to development of acute mediastinitis is variable, with one study finding a median time from surgery to disease development of 7 days (19). The mediastinum can become contaminated directly during surgery. Following median sternotomy, DSWI may also develop that can lead to mediastinal infection. DSWI is defined by the Centers for Disease Control and Prevention (CDC) as the following (20):

Fever and chest pain or sternal instability and any of the following:

• Purulent drainage from the sternal wound;
• Mediastinal widening on imaging studies;
• Positive culture from mediastinal fluid or tissue sample;
• Histopathological evidence of mediastinitis.

CT imaging shows mediastinal edema, complex-appearing fluid collections, and pneumomediastinum (21). These imaging findings can be normal up to 21 days after surgery, which makes acute mediastinitis difficult to diagnose in the early stages. If serial post-operative CT images are available for comparison, then new or persistent fluid collections should raise suspicion for mediastinitis. Management for post-sternotomy mediastinitis includes surgical debridement of affected tissues and drainage of fluid collections. Greater omental flaps are an option for bone loss management (22). There is growing evidence that negative pressure wound therapy is helpful for wound healing.

DNM

DNM is a potentially life-threatening infection arising from odontogenic, cervicofacial, or most commonly pharyngeal and retropharyngeal foci (23). Ludwig’s Angina, a well-described infection of the submandibular space predominantly driven by odontogenic infection of the second mandibular molar, can also lead to DNM if the infection spreads through cervical fascial planes into the neck (24,25). Patients of any age or gender may be affected, and risk factors include diabetes mellitus, alcohol use, intravenous drug use, poor dentition, and immunosuppression (26). Common organisms include Staphylococcus aureus, coagulase-negative Staphylococcus, viridans-group Streptococcus, and Pseudomonas. Patients usually present with sore throat, dysphagia, dysphonia, and trismus. They may appear septic. Examination may demonstrate a bulge-like lesion in the pharynx or, in the case of Ludwig’s Angina, a double chin-like lesion that may be warm, erythematous, and tender to palpation. Official diagnostic criteria for DNM were coined initially by Estrera et al. in 1983 (27) and further refined by Wheatley et al. in 1990 (28,29). They include:

• Clinical manifestations of severe cervical infection;
• Demonstration of characteristic imaging features of mediastinitis;
• Documentation of necrotizing infection during surgery or on autopsy;
• Establishment of a relationship between development of the mediastinal process and head and neck infection (29).

Radiography is helpful in making the diagnosis of DNM, especially CT imaging (Figure 1A-1C) of the neck and chest with intravenous contrast (30). Assessment of imaging should include evaluation of head and neck soft tissues as well as investigation for the presence of mediastinitis in the thoracic cavity. If a continuous process is identified extending from the neck into the mediastinum, a diagnosis of DNM can be made radiographically (31).

Figure 1 Lemierre’s syndrome in a 64-year-old man with extensive parapharyngeal abscess and DNM. (A) Contrast-enhanced CT of the neck in axial view showing a hypodense collection along the internal jugular vein (arrow) consistent with Lemierre’s syndrome and presence of gas highlighting the anaerobic infection. (B) CT scan in axial view showing DNM and gas consistent with anaerobic infection (blue arrow) and hypodense collections (arrow) around the internal jugular vein. (C) CT scan in coronal view, parapharyngeal infection, infectious thrombi along the internal jugular vein (arrow), which is extending into the mediastinum. CT, computed tomography; DNM, descending necrotizing mediastinitis.

Intravenous antibiotics are essential in the management of DNM. Surgical management, including incision and drainage of fluid collections in the head or neck or open thoracotomy for management of mediastinitis, is often required. The mortality rate is very high with DNM, with some figures as high as 40%. Some patients suffer chronic dysphagia afterwards.

MG

MGs are mass-like lesions that develop from enlarged mediastinal and hilar lymph nodes. MGs have a variety of infectious and inflammatory etiologies. The most common infectious causes are Histoplasma capsulatum and Mycobacterium tuberculosis. There are also rare cases of bacterial and parasitic infections leading to the formation of MG (32). Sarcoidosis is the most common inflammatory cause, but there are also reports of lesions secondary to granulomatosis with polyangiitis (GPA) (33) as well as post-operative cholesterol granuloma formation (34). Robust epidemiologic data on MG is lacking, likely due in part to its indolent course and sometimes spontaneous resolution (35). MG lesions generally tend to largely be asymptomatic regardless of the etiology. However, if they progress in size, there is potential for mass effect on and damage to critical mediastinal structures. There is at least one report of an MG lesion leading to fistula formation with the esophagus (36). Plain radiography can detect larger lesions, though CT imaging is the preferred imaging modality for identifying and characterizing MG. Biopsy is still often needed for diagnostic confirmation. Bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the preferred diagnostic modality (37). Treatment varies on etiology with immunosuppressive therapy for inflammatory conditions and antimicrobial therapy for infectious etiologies. Thoracic surgery referral or evaluation for endobronchial therapies may be required in cases with compression of adjacent mediastinal structures. In this section, we will further explore the different etiologies and treatments for MG.

Specific etiologies of MGs

MGs due to infection

MG can be caused by fungal, bacterial, and rarely parasitic infections. Although many infections feature a predisposition to MG formation, only a fraction of patients with these conditions develop lesions. Diagnosis may be delayed as MGs often do not cause symptoms. Histoplasma capsulatum is the predominant infectious cause of MG, particularly in the United States where the fungus is endemic to the Midwest and southeastern regions in the Ohio River Valley distribution. MGs due to Histoplasma infection has been shown to increase morbidity and mortality according to reported cases between 1938 and 2013 (38). Another common cause of MG development is infection with Mycobacterium tuberculosis. Tuberculosis is still a prevalent disease with a global incidence of tuberculosis was 133 cases per 100,000 in 2022 (39). Infections with Treponema pallidum and Actinomyces have also been reported to cause MG formation. Even a case of schistosomiasis with MG has been reported (32).

General infectious laboratory evaluation with complete blood count and cultures is required. Fungal studies can be helpful, especially Histoplasma urine antigen testing if histoplasmosis is suspected. Interferon gamma release assay (IGRA) and purified protein derivative can inform prior exposure to and infection with tuberculosis, although IGRA alone cannot differentiate between active and latent tuberculosis. If there is concern for active tuberculosis disease, then serial acid-fast bacteria sputum stain, culture, and Mycobacterium tuberculosis polymerase chain reaction (PCR) are indicated. Chest imaging, especially CT, can show characteristic imaging patterns of distinct infectious etiologies. Bronchoscopy with bronchial alveolar lavage, which allows for sampling of the more distal airways and alveoli, can provide high-quality cultures as well as cell count and cytology. EBUS-TBNA biopsy of MG lesions is often required to exclude malignancy. Biopsy is also helpful in differentiating between inflammatory and infectious etiologies in non-malignant lesions, especially in regions where tuberculosis is endemic (40).

Treatment varies by etiology, but it is worth noting that many infectious granulomas may resolve spontaneously. For mild to moderate histoplasmosis-related pulmonary nodules, no treatment is recommended per the 2025 Infectious Diseases Society of America (IDSA) guidelines (41). An azole, mainly itraconazole, may be considered for symptomatic MGs and lymphadenitis caused by histoplasmosis (42). In contrast, granulomas due to active pulmonary tuberculosis should be promptly treated. The primary recommended treatment regimen for drug-sensitive pulmonary tuberculosis is 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol followed by 4 months of isoniazid and rifampin, though there are many permutations based on based on culture sensitivities and patient comorbidities (43).

MGs due to inflammation

Inflammatory conditions represent a large portion of MGs reported in the literature with sarcoidosis and immunoglobulin G4 (IgG4)-related disease being the most common causes. GPA is another well-described cause, and there are a series of case reports on cholesterol granulomas. It is worth noting that there is likely an element of reporting bias in these numbers as asymptomatic granulomas may not be further evaluated and, thus, the etiology not ascertained. The prevalence of sarcoidosis in the United States has been reported at 60 individuals per 100,000 with an incidence of 8.3 per 100,000 per year, though this number accounts for both intra- and extra-pulmonary manifestations of the disease (44). IgG4-related disease occurs less frequently at 1 per 100,000 per year, and approximately 30% of cases are thoracic manifestations of the disease (45). GPA has a reported prevalence of 2.4 to 15.7 per 100,000 amongst European populations, though this includes all manifestations of the disease (46). Cholesterol granulomas are rare and are largely described in case reports with less than 25 cases described in the last 5 years (34,47-51).

Laboratory evaluation with complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, and C-reactive protein should be obtained. The soluble interleukin-2 receptor (IL-2R) study can be a helpful tool in making a diagnosis of sarcoidosis as it has fair sensitivity and specificity (52). ¹⁸F fluorodeoxyglucose positron emission therapy (FDG-PET)/CT can show areas of heightened metabolic activity throughout the body that, in concert with history and laboratory evaluation, can support the diagnosis of sarcoidosis. Of course, biopsy is often required for confirmation with pathology demonstrating non-caseating granulomas (53). Serum IgG4, IgG, IgE, and complement levels are the initial laboratory tests to evaluate for IgG4-related disease (54). It is important to note that, in many cases of IgG4-related disease, the IgG4 level is normal. Cross-sectional imaging is helpful in determining the extent of organ involvement and identifying targets for biopsy. Biopsy is essential for the diagnosis of IgG4-related disease, with pathology showing dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis (55). Laboratory evaluation for GPA includes antineutrophil cytoplasmic antibodies (ANCA), particularly myeloperoxidase (MPO) and proteinase 3 (PR3). Cross-sectional imaging is helpful to determine organ involvement as well as identify potential targets for biopsy when GPA is suspected. When feasible, biopsy is helpful to establish the diagnosis. Pathology findings in GPA generally include necrotizing granulomatous inflammation, vasculitis of small- and medium-sized vessels, and tissue necrosis (56). Cholesterol granulomas are diagnosed on histopathology evaluation of lesions (34).

Systemic corticosteroids are the primary treatment for inflammatory conditions with responsiveness to steroids being the main treatment for IgG4-related disease (54). For GPA, treatment includes glucocorticoids combined with disease-modifying anti-rheumatic drugs. For severe cases of GPA, rituximab may be employed (46). Similarly, oral glucocorticoids are first-line in pulmonary sarcoidosis and a significant proportion of patients with advanced disease may require treatment for pulmonary hypertension (57). Cholesterol granulomas are both diagnosed by and treated with excision, though there is a risk of recurrence if the underlying inflammatory state is not addressed (49).

MG vs. early FM

MG and early FM may be difficult to delineate at times. Essentially MG is abnormal enlargement of the mediastinal lymph nodes due to granulomatous involvement and is usually asymptomatic or minimally symptomatic. On the other hand, FM is a continuous fibro-inflammatory state within the middle mediastinum frequently causing compression of the vital structures including vasculature and airways, and hence symptomatic in most cases (58). On CT imaging, MG lesions typically appear as mass-like lesions with rim-enhancing and scattered calcifications (59). Imaging in early FM will possibly show a more invasive mass-like lesion that obliterates fat planes, but this is not always the case (60). Should diagnosis be uncertain, biopsy may be performed to determine the pathology. If an MG lesion is biopsied, histopathology typically demonstrates a large mass with a gelatinous center surrounded by a fibrous capsule. In early FM, there is generally some degree of acellular collagen deposition and fibrous tissue. Follow-up imaging may also be performed to evaluate the process at hand (61).

FM

FM, also called sclerosing mediastinitis, is a rare condition characterized by extensive fibrosis within the mediastinum. The fibrosis is thought to be triggered by an inciting event, which can vary based on geography. In North America, idiosyncratic response to Histoplasma infection may account for up to 78% of cases (35,62). FM is difficult to classify into subgroups given its rarity and the geographic variation in provoking elements, though two primary groups have been proposed: granulomatous FM and non-granulomatous FM. Granulomatous FM is more common, representing 80 to 90% of all cases of FM. The etiology of granulomatous FM can be further divided into infectious and non-infectious causes (63). Of the infectious causes, histoplasmosis and tuberculosis are the most common. Other infectious diseases leading to the granulomatous form of FM include blastomycosis, mucormycosis, and cryptococcosis. Rarely, schistosomiasis has also been reported. The non-infectious etiologies include inflammatory conditions like sarcoidosis, IgG4-related disease, and ANCA vasculitis (62). Non-granulomatous FM comprises about 10% to 20% of all FM cases (63). There is disagreement in the classification of FM as some studies equate idiopathic FM to non-granulomatous FM while others do not exclude idiopathic FM when granulomas are present. There is an overall consensus, though, that granulomas are absent in idiopathic FM (62).

FM has an insidious onset with slow progression. It is not until the fibrosis compromises important mediastinal structures such as the airway, vasculature, or gastrointestinal tract that symptoms occur (3). Common symptoms include dysphagia from esophageal constriction, cough from airway obstruction, hemoptysis, superior vena cava (SVC) syndrome, and pulmonary hypertension from vascular narrowing (35).

Laboratory testing can be helpful in elucidating the etiology behind the diagnosis. Infectious studies, particularly those for tuberculosis, histoplasmosis, and other endemic fungal organisms, may be considered. Inflammatory markers, particularly those for sarcoidosis, may additionally be helpful. In many cases, oncologic markers may be obtained to rule out malignancy or help determine the need for biopsy. Testing for IgG4-related disease with IgG4, IgG, IgE, complement, and inflammatory markers can be done, but these studies are often normal in the subset of IgG4-related disease that presents with FM (54).

Chest plain radiography may suggest FM, but the findings are often nonspecific with mediastinal widening and lymphadenopathy (64). CT is the preferred imaging modality for diagnosis. On CT imaging, the granulomatous subtype can present with paratracheal, subcarinal, or hilar calcified masses (4) (Figure 2A-2D). The IgG4-related disease subtype can present with periaortic, perivascular, and paravertebral masses (54). The non-granulomatous subtype can present as diffuse soft tissue infiltration of multiple mediastinal compartments without calcification, and more often requires surgical biopsy for confirmation (4). Fibroblast activation protein inhibitor (FAPI)-PET/CT and ¹⁸F FDG-PET/CT are being explored as alternative modalities for diagnosis, but this has only been evaluated in animal models and in one case report (65,66). History, laboratory, and imaging are sufficient for diagnosis in the right clinical context, but biopsy may be required for atypical presentations. Endobronchial ultrasound-guided cryobiopsy is also being explored as an alternative to surgical biopsy with promising results in a handful of case reports (66-68).

Figure 2 FM in a 44-year-old woman. (A) Contrast-enhanced CT scan of the chest in axial view showing the large, calcified conglomerate of mediastinal lymph nodes (arrow). (B) CT chest in coronal view showing the calcified conglomerate of mediastinal lymph nodes and dilated azygos vein (arrow) due to superior vena cava occlusion. (C) CT chest in axial view showing the compression of the Right Pulmonary artery (arrow) by the calcified conglomeration of lymph nodes consistent with FM. (D) Notice the right pulmonary venous compression (arrow) in the same patient on CT chest axial view. CT, computed tomography; FM, fibrosing mediastinitis.

As mentioned previously, FM can lead to significant chest pathology depending on which structures are affected. Compression of the SVC by FM may lead to the SVC syndrome, the most common complication of FM (69,70). Symptoms at presentation may include facial swelling, neck swelling, upper extremity swelling, dyspnea, and hoarseness. CT imaging of the chest is generally required to visualize compression of the SVC by FM, and it can also assist with visualization of thrombi caused by venous stasis. Stent placement in the SVC may improve venous return and relieve venous stasis-related symptoms (71).

Encasement of the pulmonary arterial circulation may lead to pulmonary vascular pathology (72,73). Presenting symptoms may include dyspnea on exertion, lightheadedness and pre-syncope, as well as hemoptysis. Patients may develop pre-capillary pulmonary hypertension on right heart catheterization, and perfusion defects may be visible on V/Q lung scan similar to those seen in chronic thromboembolic pulmonary hypertension (CTEPH) (74,75). If encasement of the pulmonary arterial circulation leads to vascular occlusion, pulmonary infarction may occur in the territory supplied by the encased vessel (76,77). Computed tomography angiography (CTA) of the pulmonary vasculature may be helpful as imaging may show normal peripheral branching of pulmonary arterial circulation or focal occlusion which is more indicative of FM than CTEPH. Additionally, CT imaging may show the diffuse fibrosis characteristic of FM as well as pulmonary infarction. In certain cases, stenting of the pulmonary artery may improve lung perfusion, reduce pulmonary hypertension, and abate symptoms. Pulmonary vasodilators have also been shown to have excellent responses; and may be considered in select cases (78).

The coronary circulation can be affected by FM, particularly at the ostia. Patients may present with classic angina symptoms as well as ST-segment elevations on electrocardiogram. Angiography may show narrowing of the arterial lumen like what is visualized in cases of atherosclerotic coronary artery disease. In one case report, a patient was noted to have ostial narrowing of her ostial left main coronary artery and ostial right coronary artery necessitating placement of an intra-aortic balloon pump and coronary artery bypass grafting (79).

Compromise of the airways is known to occur in FM. Patients may initially present with dyspnea, chest discomfort, and hemoptysis. CT imaging may show luminal narrowing of the trachea, mainstem bronchi, bronchus intermedius, and other airways due to extrinsic compression from FM lesions. Additionally, it has been noted that patients with airway compression due to FM have significant mucosal friability with easy bleeding that is likely secondary to compression of pulmonary vascular structures. Placement of airway stents, specifically silicon stents, may mitigate airway compression and allow for airway remodeling.

Nervous structures such as the phrenic and recurrent laryngeal nerves may be affected by FM when lesions exert mass effect. Patients may present with dyspnea, difficulty speaking loudly, and hoarseness. In cases where the phrenic nerve is involved, chest radiography may show an elevated hemidiaphragm. Vocal cord endoscopy may show a paretic vocal cord in cases of phrenic nerve involvement. In one case report of vocal cord paralysis related to recurrent laryngeal nerve involvement, the vocal cord paralysis resolved with treatment (80).

There is no single approved treatment for FM. One retrospective study showed a cessation in progression with use of rituximab in patients with symptomatic and progressive disease (81). Glucocorticoid treatment is commonly used and has shown some promise with the IgG4-related disease subtype, but otherwise it has not been shown to be effective (82). The 2025 update to the IDSA guidelines for management of asymptomatic-to-mild Histoplasma pulmonary nodules advises against antifungal treatment for immunocompetent individuals. However, the guidelines note that, for those with symptoms lasting more than a month, treatment may be considered to theoretically decrease the change of progression to FM. Indeed, it is worth noting that there is no data at present to verify this assumption (41). Interventional treatments, including airway and vascular stents for compression of the bronchi and mediastinal great vessels respectively, have been employed as previously mentioned. The intent of these procedures is palliative and not curative (83-85). There currently remains no clinical trials to show whether endovascular interventions alone or in combination with medical therapy improves survival. The decision for invasive interventions in addition to medical therapy should be undertaken after careful evaluation of the risk- benefit analysis and a multi-disciplinary evaluation involving interventional pulmonology (in cases of airway interventions), interventional radiology and thoracic surgery. The use of stents whether endovascular or airway are fraught with downstream complications and short durability, all of which should be put into consideration before decisions to place them are undertaken (86).

Conclusions

Acute mediastinitis, MG, and chronic FM are disease processes that have different causes, clinical courses, and outcomes. Acute mediastinitis generally follows thoracic surgery, esophageal perforation, or metastatic spread from odontogenic infection. Swift diagnosis and aggressive management are paramount given high morbidity and mortality, and management frequently requires invasive intervention. MG is also usually driven by a granulomatous or fungal disease and only requires treatment in some cases where the lesions cause mass effect. On occasion, these lesions will spontaneously resolve. For chronic FM, the onset is usually more insidious with either an inflammatory or fungal disease as the nidus. Treatment options for chronic FM usually involve palliative intervention to ameliorate mass-effect from lesions, and the prognosis is poor. There is currently, no clinical trials to show whether the addition of invasive interventions in addition to systemic therapy would be of more benefit. Future prospective studies are necessary to clearly identify the best approach in patients with FM.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://med.amegroups.com/article/view/10.21037/med-2026-1-0003/rc

Peer Review File: Available at https://med.amegroups.com/article/view/10.21037/med-2026-1-0003/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-2026-1-0003/coif). S.V.C. reports receiving royalties from Taylor and Francis Publishers for co-editing the book Rare Lung Diseases: A Comprehensive Clinical Guide to Diagnosis and Management. The other 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 clinical procedures described in this study were performed 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. Given that no patient identifying information was obtained, written consent was waived for the publication of this article and the accompanying images.

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/.

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