Histoplasmosis Imaging
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Histoplasmosis is the most common endemic mycosis in North America, Central America, and many areas of South America; it also occurs in China, India, Southeast Asia, Africa, Australia, and Europe. Histoplasmosis is a major cause of morbidity and mortality in patients living in endemic areas. [1]
Histoplasma capsulatum was first described in 1905 by Samuel Darling, a US Army pathologist stationed in Panama. Darling examined visceral tissues and bone marrow from a young man from Martinique whose death originally was attributed to miliary tuberculosis. The organism initially was described as protozoal. Because it lacked a kinetoplast, Darling assumed that it was not a member of Leishmania. He called the microbe H capsulatum. [2, 3, 4] In 1912, after reviewing tissue specimens, da Rocha-Lima suggested that the organism resembled a yeast rather than a protozoan. H capsulatum has since been found worldwide. In the United States, histoplasmosis is highly prevalent in the Ohio and Mississippi River valleys.
Imaging characteristics of histoplasmosis are seen below.
Complications of histoplasmosis infection include the following:
Mediastinal granuloma
Fibrosing mediastinitis
Broncholithiasis
Cavitary pulmonary histoplasmosis
Although chest radiographic findings are normal in most patients, chest radiography is the first radiologic examination performed. Radiographic findings primarily depend on the type of presentations and the immune status of the host.
The abnormality that is most frequently found on radiographs consists of a single or multiple poorly defined areas of airspace consolidation, frequently in the lower lobes. With time, these opacities clear and a nodule forms; the nodule may later calcify.
Radiographic findings depend primarily on the type of presentation and on the immune status of the host. (See the images below). [5]
Chest radiographic findings are normal in most patients. A solitary pulmonary nodule is a frequent finding on chest radiographs of the patient with asymptomatic primary infection. These nodules vary from a few millimeters to several centimeters. Most of these nodules have well-defined margins and central, laminar, or diffuse calcification patterns. Interestingly, some nodules slowly enlarge because of continued elaboration of collagen at the periphery of the lesion; in such cases, histoplasmosis may be difficult to distinguish from malignancy.
As many as 10-25% of patients with asymptomatic infection develop single or multiple poorly defined areas of airspace consolidation and/or nodules, with or without hilar lymph node enlargement. Enlarged lymph nodes often are seen after an asymptomatic infection. Adenopathy is frequently seen with lung parenchymal abnormalities. Calcification is often present with adenopathy; in some cases, such calcification may be seen only on computed tomography (CT) scans. Cases of noncalcified mediastinal adenopathy need to be distinguished from cases of sarcoidosis, lymphoma, and metastases. Enlarged lymph nodes may cause significant bronchial or tracheal compression or obstruction and may cause esophageal obstruction. Atelectasis, collapse, and obstructive pneumonitis may develop as a consequence of airway obstruction.
In acute symptomatic pulmonary histoplasmosis, radiographic findings include areas of airspace parenchymal consolidation that involve more than one segment or lobe, simulating acute bacterial pneumonia.
Pleural effusions are seen in a minority of patients with acute pulmonary histoplasmosis. Organisms rarely are isolated from pleural fluid.
After heavy exposure, radiographs may show widely disseminated, diffuse, fairly discrete nodular shadows throughout the lungs, with individual lesions measuring 1-10 mm in diameter. This form of disease is termed miliary histoplasmosis (see the image below); it is similar to miliary tuberculosis. The infiltrates clear within 2-8 months; however, lesions may fibrose and calcify or persist for many years.
Lung cavitation usually is noted in persons with underlying obstructive lung disease; it is similar to chronic active tuberculosis, with predominantly upper lobe disease characterized by fibrosis, necrosis, cavitation, and granulomatous inflammation.
Failure to consider histoplasmosis because the chest radiograph is normal may delay diagnosis.
CT scanning is helpful in detecting calcification in a lung nodule (histoplasmoma) and in evaluating patients with fibrosing mediastinitis and broncholithiasis. (Soft-tissue masses are not associated with broncholithiasis; if found, consideration should be given to other diseases, such as lung cancer engulfing a calcified node.) See the images below. [6, 7]
The modality is more sensitive in detecting subtle calcification in a nodule and may identify other, smaller nodules that are not seen on chest radiographs.
CT scanning is very useful in the evaluation of patients with suspected fibrosing mediastinitis. The modality may define the extent of the fibrous mass in the mediastinum/hilum and demonstrate its obstructing effect on the superior vena cava (SVC), pulmonary vessels, esophagus, trachea, or bronchi. Venous collaterals may be seen; they indicate long-standing venous occlusion. Stippled or dense calcification within the mass is present in most patients with fibrosing mediastinitis and may easily be seen on CT (see the image below).
Serial CT scans may identify progression of the fibrosis and may be useful in assessing indications for surgery. CT is superior to magnetic resonance imaging (MRI) in demonstrating calcification.
In a retrospective review of the radiographic findings of fibrosing mediastinitis in 33 patients on various imaging studies, including chest radiographs, CT scans, MRI examinations, esophagrams, ventilation perfusion scans, angiograms, and venograms, Sherrick et al reported the following [5] :
Bronchial narrowing in 11 patients (33%)
Pulmonary artery obstruction/narrowing in 6 patients (18%)
Esophageal narrowing in 3 patients (9%)
SVC obstruction/narrowing in 13 patients (39%)
Two distinctly different radiographic patterns were identified in the study: (1) a localized pattern, observed in 27 patients (82%), that often contained calcification, and (2) a diffuse pattern, found in 6 patients (18%), that had no calcification. The localized pattern most likely was a result of histoplasmosis in which there was no radiographic evidence of improvement with steroid therapy. The diffuse pattern was most likely truly idiopathic or had a noninfectious etiology. In several patients with the diffuse pattern, there was radiographic evidence of improvement with steroid therapy. For patients without calcification or with progressive radiographic findings, it is advisable to obtain tissue specimens for definitive diagnosis.
Computed tomography was used in one study to observe a calcified primary complex pulmonary histoplasmosis and predict which patients with N2 disease would benefit from surgery. The data obtained showed a predictable pattern of segmental and lobar lymphatic drainage to the mediastinum and suggested that skip involvement could represent the initial mediastinal node involvement via direct lymphatic drainage. [8]
MRI is comparable to CT scanning in its ability to define the extent of hilar or mediastinal lymphadenopathy. The primary advantage of MRI is its ability to diagnose vascular obstruction without the need for intravenous contrast material, especially for patients with renal failure. However, CT is superior to MRI in demonstrating calcification. The adenopathy associated with fibrosing mediastinitis demonstrates relatively low signal intensity on T2-weighted images.
Ultrasonography has a limited role in diagnosing histoplasmosis; however, the modality helps to define hepatomegaly or splenomegaly. Ultrasonography also is useful in assessing pleural and pericardial effusions, cardiac tamponade, calcification of the pericardium, and constrictive pericarditis.
Endobronchial ultrasound (EBUS) has been demonstrated to be useful in the diagnosis of subacute pulmonary histoplasmosis (SPH) with mediastinal lymphadenopathy. EBUS transbronchial needle aspiration (EBUS-TBNA) was found in one study to support a diagnosis of SPH in patients with a degree of clinical suspicion, along with clinical presentation, fungal serologies, and antigen testing. [9]
Angiography may be helpful in demonstrating some conditions associated with histoplasmosis (eg, SVC obstruction) and in determining whether great vessels are involved with fibrosing mediastinitis.
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Conces DJ. Histoplasmosis. Semin Roentgenol. 1996 Jan. 31(1):14-27. [Medline].
Kennedy CC, Limper AH. Redefining the clinical spectrum of chronic pulmonary histoplasmosis: a retrospective case series of 46 patients. Medicine (Baltimore). 2007 Jul. 86(4):252-8. [Medline].
Wheat LJ. Improvements in diagnosis of histoplasmosis. Expert Opin Biol Ther. 2006 Nov. 6(11):1207-21. [Medline].
Sherrick AD, Brown LR, Harms GF, Myers JL. The radiographic findings of fibrosing mediastinitis. Chest. 1994 Aug. 106(2):484-9. [Medline].
McGuinness G, Naidich DP, Jagirdar J, et al. High resolution CT findings in miliary lung disease. J Comput Assist Tomogr. 1992 May-Jun. 16(3):384-90. [Medline].
Takahashi K, Stanford W, Van Beek E, Thompson B, Mullan B, Sato Y. Mediastinal lymphatic drainage from pulmonary lobe based on CT observations of histoplasmosis: implications for minimal N2 disease of non-small-cell lung cancer. Radiat Med. 2007 Oct. 25(8):393-401. [Medline].
Takahashi K, Sasaki T, Nabaa B, van Beek EJ, Stanford W, Aburano T. Pulmonary lymphatic drainage to the mediastinum based on computed tomographic observations of the primary complex of pulmonary histoplasmosis. Acta Radiol. 2012 Mar 1. 53 (2):161-7. [Medline].
Egressy Kv, Mohammed M, Ferguson JS. The Use of Endobronchial Ultrasound in the Diagnosis of Subacute Pulmonary Histoplasmosis. Diagn Ther Endosc. 2015. 2015:510863. [Medline].
Fahad M Al-Hameed, MD, AmBIM, FCCP, FRCPC Chairman, Intensive Care Department, Director, Ambulatory Care Center (Services), Professor Associate of Medicine/Critical Care, College of Medicine, King Saud Ben Abdulaziz University for Health Sciences; Consultant in Critical Care and Pulmonary Medicine, King Khalid National Guard Hospital, King Abdulaziz Medical City, Saudi Arabia
Fahad M Al-Hameed, MD, AmBIM, FCCP, FRCPC is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Saudi Association for Venous Thrombo-Embolism
Disclosure: Nothing to disclose.
Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba Faculty of Medicine; Site Director, Respiratory Medicine, St Boniface General Hospital, Canada
Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, World Medical Association
Disclosure: Nothing to disclose.
Bruce Maycher, MD
Bruce Maycher, MD is a member of the following medical societies: American Roentgen Ray Society, Canadian Medical Association, Radiological Society of North America, Society of Thoracic Radiology
Disclosure: Nothing to disclose.
Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.
Eugene C Lin, MD Attending Radiologist, Teaching Coordinator for Cardiac Imaging, Radiology Residency Program, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, Society of Nuclear Medicine and Molecular Imaging
Disclosure: Nothing to disclose.
Satinder P Singh, MD, FCCP Professor of Radiology and Medicine, Chief of Cardiopulmonary Radiology, Director of Cardiac CT, Director of Combined Cardiopulmonary and Abdominal Radiology, Department of Radiology, University of Alabama at Birmingham School of Medicine
Disclosure: Nothing to disclose.
We thank Sean Tsuyuki, MD, for his contributions to this article.
Histoplasmosis Imaging
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