Ann Thorac Surg 2004;78:277-281
© 2004 The Society of Thoracic Surgeons
Original article: general thoracic
Endobronchial histoplasmosis: a masquerade of primary endobronchial neoplasia—a clinical study of four cases
Patrick Ross, Jr, MD, PhDa*,
Cynthia M. Magro, MDb,
Mark A. King, MDc
a Department of Cardiothoracic Surgery, The Ohio State University, Columbus, Ohio, USA
b Department of Pathology, The Ohio State University, Columbus, Ohio, USA
c Division of Diagnostic Radiology, The Ohio State University, Columbus, Ohio, USA
Accepted for publication December 10, 2003.
* Address reprint requests to Dr Ross, Division of Cardiothoracic Surgery, The Ohio State University, N839 Doan Hall, 410 W 10th Ave, Columbus, OH 43210, USA
e-mail: ross-3{at}medctr.osu.edu
 |
Abstract
|
|---|
BACKGROUND: Histoplasma capsulatum is a dimorphic fungus with both hyphal and microconidial elements and is endemic in certain areas of the central United States. Most clinically recognized syndromes are self-limited, presenting in more than 80% of cases as an influenza-like acute pulmonary illness. We encountered four patients with an endobronchial presentation of histoplasmosis masquerading as a bronchogenic malignancy.
METHODS: The patient files from one of the authors (PR) uncovered four patients diagnosed with, and treated for, endobronchial histoplasmosis; all cases were referred for a presumptive diagnosis of endobronchial neoplasia.
RESULTS: The case study group comprised three women, ages 52, 68, and 81 years, respectively, and one man age 29 years, all presenting with recurrent hemoptysis. An obstructing adherent lesion was apparent on bronchoscopy in three, involving the right upper lobe bronchus in two, and right mainstem bronchus in one. In one patient, blood was observed in the bronchus intermedius; there was no gross lesion. Recurrent hemoptysis necessitated a right upper sleeve lobectomy in one, a right upper lobe lobectomy and right lower wedge resection in one, a right middle lobectomy in one, and wedge resection of the right upper lobe in one.
CONCLUSIONS: Endobronchial histoplasmosis may mimic primary bronchogenic carcinoma, presenting as a fixed obstructing endobronchial lesion associated with hemoptysis; the latter potentially necessitating surgical intervention. Endobronchial histoplasmosis should be considered in the differential diagnosis of obstructing endobronchial lesions associated with hemoptysis, especially when prior and(or) concurrent biopsies fail to disclose malignancy.
|
Introduction
|
|---|
Endobronchial lesions comprise a heterogeneous group of pathologic entities. Regardless of the cause, the clinical symptomatology and signs are similar including those of hemoptysis, stricture, and obstruction. These lesions often represent a malignancy, specifically in the context of bronchogenic small cell carcinoma, well-differentiated neuroendocrine carcinomas-carcinoid and(or) bronchogenic squamous cell carcinoma. Over the years, however, there have been a number of reports of bronchial lesions manifesting an imitable clinical presentation to primary bronchogenic carcinoma. These comprise a myriad of conditions including endobronchial infection, lymphoma, endobronchial hamartomatous lesions, other, rare forms of primary endobronchial neoplasia, broncholithiasis, and finally metastatic disease [1–6]. Perhaps the least frequently reported are those cases representing endobronchial fungal disease. The recognition of this cause of endobronchial obstruction is imperative as the treatment must include, and(or) may potentially be confined to, antifungal therapy. Nevertheless it is also recognized that in some cases surgical intervention may be necessary to control the complications associated with endobronchial fungal disease [7, 8]. Although rare, a very distinctive form of endobronchial fungal disease, frequently resulting in surgical intervention, is that caused by Histoplasma capsulatum. We encountered four patients with endobronchial histoplasmosis, masquerading as primary endobronchial neoplasia. The clinical features, bronchoscopic and radiographic findings, surgical approach, and pathogenetic basis of endobronchial histoplasmosis are reviewed. In addition, a novel therapeutic option regarding photodynamic therapy (PDT) is discussed.
|
Material and methods
|
|---|
Four cases of culture and biopsy proven endobronchial histoplasmosis were uncovered from the patient records of one of the authors (PR). In each case the patient referral was made for a presumptive diagnosis of primary bronchogenic carcinoma.
|
Results
|
|---|
Patient 1
One patient was an
82-year-old woman who presented with a several month history of recurrent hemoptysis (Table 1). Bronchoscopic evaluation revealed a friable endobronchial mass involving the right upper lobe bronchial segments with attendant mucosal induration, erythema and luminal attenuation (Fig 1).
Multiple biopsies were performed. Due to the very high index of suspicion with respect to having primary bronchogenic carcinoma, she received PDT for a presumptive diagnosis of malignancy; three sequential treatments were given at 48-hour intervals, respectively. The PDT therapy was effective in relieving the endobronchial obstruction. However, due to persistent hemoptysis over the ensuing 3 months, she subsequently underwent an uneventful upper lobe sleeve lobectomy. Histologic examination revealed bronchocentric granulomatous inflammation in association with histoplasma fungal forms.
Patient 2
The patient was a 52-year-old woman who presented with a 10-day history of hemoptysis. Radiographic studies revealed an infiltrative process within the right middle lobe. Bronchoscopic evaluation demonstrated old blood within the bronchus intermedius. Due to intractable hemoptysis confounded by the high index of suspicion of malignancy, she subsequently underwent a bronchoscopy, right thoracotomy, and right middle lobectomy. Histologic examination revealed bronchocentric granulomatosis and necrotizing granulomatous lymphadenitis in association with fungal forms compatible with Histoplasma capsulatum.
Patient 3
The patient was a 29-year-old white male nonsmoker with a history of smokeless tobacco use. He was in his usual state of health until he developed cough and hemoptysis. At this time he was admitted to the emergency room and was found to be hypoxic on room air. A computerized tomographic study at the level of the carina showed effacement of the medial wall of the right main bronchus and irregularity of the medial wall of the bronchus, suggesting an endobronchial mass (Fig 2).
He was referred for bronchoscopy, which revealed a right main stem lesion; a biopsy was performed and was held to be suspicious for squamous cell carcinoma at the time of frozen section. He subsequently underwent a right video assisted thoracoscopy with wedge resection of the right upper lobe performed to exclude a diagnosis of carcinoma. Resection of the main stem lesion was not performed. Pathologic examination was compatible with a diagnosis of intraparenchymal and intranodal histoplasmosis with extensive concomitant fibrosis (Figs 3 and 4);
no evidence of malignancy was found. He was placed on Diflucan (Pfizer Inc, New York, NY) 200 mg a day for one month. He has no respiratory complaints although, due to the persistence of extensive mediastinal fibrosis with associated esophageal diverticulum, he continues to have solid food dysphagia.
View larger version (140K):
[in this window]
[in a new window]
|
Fig 2. Computed tomographic image at the level of the carina shows effacement of the medial wall of the right main bronchus and irregularity of the medial wall of the bronchus, suggesting an endobronchial mass.
|
|
View larger version (179K):
[in this window]
[in a new window]
|
Fig 3. A lymph node shows extensive hyalinizing granular necrosis with a demarcating peripheral rim of mononuclear cell histiocytic forms. (Periodic Acid Schiff; x20).
|
|
Patient 4
The patient was a 68-year-old female who had a history of persistent hemoptysis whereby bronchoscopy performed on two separate occasions demonstrated an obliterated right upper lobe orifice, although with no evidence of malignancy. The right lobe of the lung appeared fibrotic and scarred and corresponded to the mass discernible on radiographic assessment. Nodular induration was apparent in the right lower lobe as well. The adjacent lymph nodes were heavily calcified. The patient underwent a right upper lobectomy and wedge resection of the right lower lobe. Histologic examination revealed multiple intrapulmonary and intranodal foci of hyalinizing granular necrosis with concomitant granulomatous inflammation. Yeast forms compatible with Histoplasma capsulatum were discernible on special stains.
|
Comment
|
|---|
We have presented four patients who had clinical and radiographic findings clinically suspicious for primary bronchogenic carcinoma and in which subsequent pathologic evaluation revealed endobronchial histoplasmosis. Histoplasma capsulatum is an ascomycete of the family Arthrodermataceae. It grows as a dimorphic mold found in soil, comprising both hyphal elements and small microconidia, although above 35 degrees celsius it is found primarily as a small form yeast [9]. In some areas of the central United States and Latin American Histoplasma capsulatum is endemic. After low inoculum exposure, approximately 1 in 100 exposed individuals will develop symptomatic histoplasmosis. The most well-recognized clinical syndrome is an influenza-like illness with acute pulmonary symptoms accompanied by pleuritic chest pain, fever, chills, headache, myalgia, and a nonproductive cough, lasting about nine weeks [10]. In 1 of 200 cases of acute infection, multiorgan dissemination may occur, typically occurring in immunocompromised hosts [11].
However, there are distinctive atypical clinical presentations which may be a source of diagnostic confusion such as one which closely mimics autoimmune disease presenting with arthritis, pericarditis, and arthralgia [12, 13], the basis being an Arthus type III immune complex reaction. Perhaps the least common presentation is one masquerading as primary bronchogenic neoplasia, where symptomatic endobronchial obstruction presenting as hemoptysis and dyspnea may be the defining presentation of histoplasmosis [14]. There are only a few papers exclusively addressing an endobronchial presentation of histoplasmosis, representing isolated case reports [15–21]. The age range of the reported patients is 7 years to 51 years. In our own series, three of the four affected patients were middle-aged and(or) elderly women. In our cases, and in all of the other reported cases, an endobronchial presentation of histoplasmosis was defined by hemoptysis. The erosive effect of petrified histoplasmosis-broncholithiasis on the bronchial mucosa is the most common proposed basis for the hemoptysis. Calcified hilar and peribronchial lymph nodes and centrally placed pulmonary calcific nodules are the presumptive sources of broncholiths in this circumstance [16–21]. The characteristic involvement of the bronchus intermedius likely reflects the high concentration of lymph nodes in the area. In our series, in addition to the bronchus intermedius, the other sites of involvement were the right upper lobe bronchus and right main stem bronchus. Other features of chronic pulmonary histoplasmosis, such as fibrotic apical lung infiltrates with cavitation, mediastinal and pulmonary calcifications, and pleural thickening may be seen radiographically [22, 23].
In three of our cases there was a visible obstructing endobronchial lesion. One could surmise that the lesion represented a calculus, which in one case was no longer detectable, possibly reflecting expectoration and(or) aspiration in smaller caliber distal bronchi. However, in our series, in no case was the diagnosis of broncholithiasis made on gross inspection. It is possible that upon contact with the mucosal surface, an exuberant inflammatory response with secondary fibrosis and neovascularization may result in adherence to the endobronchial surface. Hence, a fixed endobronchial mass lesion eventuates, where the broncholith quality of the lesion may no longer be discernible even to the experienced bronchoscopist.
Other conditions can mimic histoplasma broncholithiasis including other mediastinal nodal infections such as those due to Coccidioidomycosis and Mycobacterium Tuberculosis, calcified cartilage plates, calcified carcinoid, enlarged bronchial arteries due to various pulmonary disorders such as chronic obstructive lung disease, a calcified carcinoid, tracheobronchial amyloidosis, a bronchial hamartoma, and calcified aspergilloma [24].
The radiographic features are also worthy of note as in each case the radiographic impression was indeed one of malignancy and(or) at least a malignant diagnosis could not be excluded. An endobronchial mass detected on a chest radiograph or on a computed tomographic (CT) scan of the chest is generally considered to be malignant, unless the lesion is calcified. A calcified endobronchial lesion is almost always benign. A CT is the radiologic exam of choice for diagnosing an endobronchial mass [24]. Volumetric data sets acquired with helical CT, and in particular multislice CT, allow for high resolution reconstructions in coronal and sagittal planes, and allow surface rendering techniques for "virtual bronchoscopy" imaging of the lesion [25, 26]. An advantage of virtual bronchoscopy over bronchoscopy is the ability to image the airway beyond the lesion, something not possible at bronchoscopy when an obstructing lesion is present [27].
While antifungal therapy is part of the treatment regimen, there are select circumstances that necessitate surgical intervention such as massive and(or) recurrent hemoptysis, bronchoesophageal fistula formation, and severe symptomatic endobronchial obstruction resulting in airway compromise [28, 29]. If the basis of the endobronchial presentation of histoplasmosis is a broncholith, the calcified mass can be removed through rigid bronchoscopy; however, only those lesions which are visible, clearly intraluminal, and apparently mobile are those which should be attempted to be removed through this less intrusive technique. Complications include massive hemoptysis reflecting the close proximity of the pulmonary arteries to the bronchus and bronchoesophageal fistula. In the largest series to date on symptomatic histoplasma associated mediastinal fibrosis, surgical procedures were done in 18 of the 20 patients, where in 6 of the cases hemoptysis was reported although was not specifically attributed to histoplasma broncholithiasis. Among the operations were subcarinal mass resection, right middle and lower lobectomy, carinal pneumonectomy, esophagoplasty, sleeve resection involving the right main bronchus, right lower and middle lobe and carina and right upper lobectomy, middle lobectomy, and bronchoplasty of the left main bronchus. There were 3 deaths following carinal pneumonectomy [8]. Mathisen and Grillo [8] attributed the tremendous surgical challenges to the intense fibrosis characteristic of histoplasmosis related mediastinitis. In another series on histoplasmosis, of 115 cases, 65% of the patients were symptomatic, presenting with chest pain, wheezing, weight loss, hemoptysis, and shortness of breath. Sixty-five patients had various operative procedures such as lung biopsy, wedge resection, lobectomy, pneumonectomy, and bypass of the superior vena cava for diagnosis and treatment [6]. In our series massive and(or) recurrent hemoptysis necessitated surgical intervention in at least 3 of the patients. Patient 3 could potentially have been managed medically at least initially, however, the suspicion for malignancy was high and intraoperative frozen section was suggestive of carcinoma.
Of interest was the response to PDT in relieving the endobronchial obstruction in patient 1. Photodynamic therapy has been proven to be an effective modality for treating endoluminal bronchogenic carcinoma, esophageal carcinoma, skin, head, neck, and oral lesions, age-related macular degeneration, and certain metastatic carcinomas including renal cell carcinoma and breast carcinoma. Photodynamic therapy involves the selective retention of a porphyrin by tumor cells. When activated by laser light at the proper wavelength (630 nm), this agent generates toxic oxygen free radicals, eliciting tumor necrosis. In our experience, photodynamic therapy has been effective in more than 70% of patients who present with symptoms related to endobronchial obstruction, similar to previous studies. We have used it primarily for the treatment of malignancies including endobronchial lymphoma [30–35]. Whether or not PDT, in concert with antifungal therapy, could potentially avoid more invasive surgical approaches for treating endobronchial histoplasmosis is at least worthy of further pursuit [36, 37].
|
References
|
|---|
- Kim J.S., Rhee Y., Kang S.M., et al. A case of endobronchial aspergilloma. Yonsei Med J 2000;41:422-425.[Medline]
- Shepherd M.P. Endobronchial metastatic disease. Thorax 1982;37:362-365.[Abstract/Free Full Text]
- Kern W.H., Crepeau A.G., Jones J.C. Primary Hodgkin's disease of the lung. Cancer 1961;14:1151-1165.
- Cooley J.C., McDonald J.R., Clagett O.T. Primary lymphoma of lung. Ann Surg 1956;143:18-28.
- Wang SC. Lung hamartoma: a report of 30 cases and review of 477 cases. Zhonghua Wai Ke Za Zhi 1992;30:540–2, 571–2
- Saha S.P., Mayo P., Long G.A., Myers J.E. Histoplasmosis: clinical manifestations and surgical management. South Med J 1979;72:1123-1126.[Medline]
- Cole F.H., Cole F.H., Jr, Khandekar A., Watson D.C. Management of broncholithiasis: is thoracotomy necessary?. Ann Thorac Surg 1986;42:155-157.
- Mathisen D.J., Grillo H.C. Clinical manifestations of mediastinal fibrosis and histoplasmosis. Ann Thorac Surg 1992;54:1053-1057.[Abstract]
- Bowman B.H., Taylor J.W., White T.J. Molecular evolution of the fungi. Human pathogens. Mol Biol Evol 1992;9:893-904.[Abstract]
- Wheat L.J., Slama T.G., Eitzen H.E. A large urban outbreak of histoplasmosis: clinical features. Ann Intern Med 1981;94:331-337.
- Goodwin R.A., Shapiro J.L., Thurman G.H., Thurman S.S., DezPrez R.M. Disseminated histoplasmosis: clinical and pathologic correlations. Medicine 1980;59:1-33.[Medline]
- Davies S.F., Khan M., Sarosi G.A. Disseminated histoplasmosis in immunologically suppresssed patients. Am J Med 1978;64:94-100.[Medline]
- Rosenthal J., Brandt K.D., Wheat L.J., Slama T.G. Rheumatologic manifestations of histoplasmosis in the recent Indianapolis epidemic. Arthritis Rheum 1983;26:1065-1070.[Medline]
- Goodwin R.A., Jr, Owens F.T., Snell J.D., et al. Chronic pulmonary histoplasmosis. Medicine (Baltimore) 1976;55:413-452.[Medline]
- ACCP-seek. A woman with episodic hemoptysis. Chest 1996; 110:271-2
- Bhagavan B.S., Rao D.R., Weinberg T. Histoplasmosis producing broncolithiasis. Arch Pathol 1971;91:577-579.[Medline]
- Shaffer J.P., Barson W., Luquette M., et al. Massive hemoptysis as the presenting manifestation in a child with histoplasmosis. Pediatr Pulmonol 1997;24:57-60.[Medline]
- Daly J.S., Mark E.J. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 14–2002. A 51-year-old woman with recurrent hemoptysis. N Engl J Med 2002;346:1475-1482.[Free Full Text]
- Wu L.A., Thomas C.F. 35 year old man with fever, hemoptysis and lymphadenopathy. Mayo Clin Proc 2000;75:651-654.[Medline]
- Zeiss J., Morgan R., Davis T.J. Pulmonary histoplasmoma presenting as massive hemoptysis. Pediatr Infect Dis J 1987;6:689-692.[Medline]
- Coss K.C., Wheat L.J., Conces D.J., Jr, Brashear R.E., Hull M.T. Esophageal fistula complicating mediastinal histoplasmosis. Response to amphotericin B. Am J Med 1987;83:343-346.[Medline]
- Goodwin R.A., Loyd J.E., Dezprez R.M. Histoplasmosis in normal hosts. Medicine 1981;60:231-266.[Medline]
- Goodwin R.A., Desprez R.M. Histoplasmosis. Am Rev Respir Dis 1978;117:929-965.[Medline]
- Seo J.B., Song K.S., Lee J.S., et al. Broncholithiasis. Review of the causes with radiologic-pathologic correlation. Radiographics 2002;22:S199-213.
- Naidich D.P. CT/MR correlation in the evaluation of tracheobronchial neoplasia. Radiol Clin North Amer 1990;28:555-571.
- Lee K.S., Yoon T.K., Kim J.S., Chung M.P., Kwon O.J. Evaluation of tracheobronchial disease with multiplanar and three dimensional reconstruction: correlation with bronchoscopy. Radiographics 1997;17:555-567.[Abstract]
- Boiselle P.M., Reynolds K.F., Ernst A. Multiplanar and three-dimensional imaging of the central airways with multidetector CT. AJR Am J Roentgenol 2002;179:301-308.[Free Full Text]
- Garet H.E., Jr, Roper C.L. Surgical intervention in histoplasmosis. Ann Thorac Surg 1986;42:711-722.[Abstract]
- Arrigoni M.G., Bernatz P.E., Donoghue F.E. Broncholithiasis. J Thorac Cardiovasc Surg 1971;62:231-237.[Medline]
- Moghissi K., Dixon K., Stringer M., Freeman T., Thorpe A., Brown S. The place of bronchoscopic photodynamic therapy in advanced unresectable lung cancer: experience of 100 cases. Eur J Cardiothorac Surg 1999;15:1-6.[Abstract/Free Full Text]
- Kato H., Okunaka T., Shimatani H. Photodynamic therapy for early stage bronchogenic carcinoma. J Clin Laser Med Surg 1996;14:235-238.[Medline]
- Metz J.M., Friedberg J.S. Endobronchial photodynamic therapy for the treatment of lung cancer. Chest Surg Clin N Am 2001;11:829-839.[Medline]
- Hopper C. Photodynamic therapy: a clinical reality in the treatment of cancer. Lancet Oncol 2000;1:212-219.[Medline]
- Dougherty T.J. An update on photodynamic therapy applications. J Clin Laser Med Surg 2002;20:3-7.[Medline]
- Dima V.F., Vasilu V., Dima S.V. Photodynamic therapy: an update. Roum Arch Microbiol Immunol 1998;57:207-230.[Medline]
- Nollet A.S., Vansteenkiste J.F., Demedts M.G. Broncholithiasis: rare but still present. Respir Med 1998;92:953-955.
- Snyder R.W., Unger M., Sawicki R.W. Bilateral partial bronchial obstruction due to broncholithiasis treated with laser therapy. Chest 1998;113:240-242.[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
H. Youness, R. G. Michel, J. V. Pitha, K. R. Jones, and G. T. Kinasewitz
Tracheal and Endobronchial Involvement in Disseminated Histoplasmosis: A Case Report
Chest,
December 1, 2009;
136(6):
1650 - 1653.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
