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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 51  |  Issue : 3  |  Page : 342-345
Pathology of pulmonary aspergillomas


Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College, Mumbai, Maharashtra, India

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   Abstract 

Aspergilloma refers to a fungal ball formed by saprophytic overgrowth of Aspergillus species and is seen secondary to cavitatory/cystic respiratory diseases. Paucity of clinical and pathological data of aspergilloma in India prompted us to analyze cases of aspergilloma over 15 years. The clinical features were recorded in all and correlated with detailed pathological examination. Aspergillomas were identified in 41 surgical excisions or at autopsy. There was male predominance; half the patients were in their fourth decade. Episodic hemoptysis was the commonest mode of presentation (85.4%). Forty aspergillomas were complex, occurring in cavitatory lesions (82.9%) or in bronchiectasis (14.6%). Simple aspergilloma was seen as an incidental finding in only one. Tuberculosis was the etiological factor in 31 patients, producing cavitatory or bronchiectatic lesions; other causes were chronic lung abscess and bronchiectasis (unrelated to tuberculosis). Surgical resections are endorsed in view of high risk of unpredictable, life-threatening hemoptysis.

Keywords: Aspergilloma, bronchiectasis, cavitatory lesion, lung

How to cite this article:
Shah R, Vaideeswar P, Pandit SP. Pathology of pulmonary aspergillomas. Indian J Pathol Microbiol 2008;51:342-5

How to cite this URL:
Shah R, Vaideeswar P, Pandit SP. Pathology of pulmonary aspergillomas. Indian J Pathol Microbiol [serial online] 2008 [cited 2014 Oct 22];51:342-5. Available from: http://www.ijpmonline.org/text.asp?2008/51/3/342/42507



   Introduction Top


A fungal ball is a term that describes a spatial configuration of saprophytic fungal overgrowth that occurs most frequently in the upper respiratory passages or the lungs. As the fungus Aspergillus has a ubiquitous distribution in nature, aspergillous fungal balls are more common and are referred to as aspergillomas. Damage to the bronchial tree and cavitatory/cystic parenchymal disease predisposes to aspergilloma in some patients. [1] However, despite the saprophytic nature, aspergilloma can produce significant morbidity, which may require surgical intervention, a stand advocated even in the earlier years. [2] There is a paucity of data on both clinical and pathological studies of aspergilloma in India, which prompted us to analyze cases of aspergilloma in surgical and autopsy material.


   Materials and Methods Top


This is a retrospective analysis of 41 cases of pulmonary aspergillomas retrieved in the past 15 years, 1992-2006. The age and gender of the patients, mode and duration of clinical presentation, relevant past history, hematological and radiological investigations and the type of surgery were gathered from the clinical records for the surgical and autopsied cases.

The lesions harboring the aspergilloma were classified as cavitatory and non-cavitatory lesions. The cavities were further assessed with respect to their number, location, site, shape, nature of the inner lining and thickness of the wall, communication with the bronchial tree or vasculature and surrounding parenchyma. On histology, the inflammatory reaction, metaplastic epithelial changes and presence of fungal invasion on routine and special satins was observed. After this detailed examination, the etiologic setting was assigned to each case. An attempt was also made to classify the cavitatory lesions into simple and complex aspergillomas.[3] Simple aspergilloma occurs in a thin-walled cavity with minimal surrounding diseased parenchyma, whereas complex type has a cavity with thick wall of more than 0.3 cm with extensive pulmonary infiltrate. [3]


   Results Top


Among the 41 cases, there were 16 females and 25 males, with an age range of 16-65 years. Twenty-one patients were in their fourth decade. Six cases were encountered at autopsy. Episodic hemoptysis was the commonest mode of presentation, seen in 35 patients (85.4%) [Table 1]. The duration of hemoptysis ranged from 4 days to almost 10 years. It was mainly streaky in most cases, but cupsful in four and massive in three which necessitated bronchial arterial embolization. Six patients had no history of hemoptysis. Mild to moderate neutrophilia and eosinophilia were seen in 23 and three cases, respectively. Pulmonary cavitation with aspergilloma was diagnosed on chest radiography and/or computed tomography in 22 patients, two of whom had a past intracavitatory instillation of amphotericin B. Other diagnoses offered on radiological investigations were radio-opaque mass (one), cavitatory lesion (three), bronchiectasis (three) and destroyed lung (three). The radiological findings were not available in seven and not performed in two patients. Past history of tuberculosis was available in 26 patients (63.4%) with complete, incomplete, or repeated regimens of therapy. Four patients were also found to have diabetes mellitus.

In one case, an intertwine of aspergillous hyphae was identified microscopically in mildly dilated bronchiole (simple aspergilloma) as an incidental finding at autopsy. Death was related to bronchial asthma-induced cor pulmonale. In all the remaining patients, the aspergillomas appeared as a soft, easily detachable, dirty muddy-brown material seen on histology as a tangle of septate, sometimes bloated hyphae intermingled with fibrin, mucus, cellular debris and other blood products [Figure 1]. The aspergillomas occurred in 34 cavitatory lesions (82.9%). A tuberculous cavity with aspergilloma was seen at autopsy in a fatal case of acute coronary insufficiency. Remaining 33 patients had undergone surgical excisions. Lobectomies were performed in 21 patients and pneumonectomies were in 10 patients. One patient with initial right upper lobectomy, subsequently underwent right pneumonectomy due to infection and bronchopleural fistula. One other patient died due to massive hemoptysis not salvaged by bronchial arterial embolization and was autopsied. Twenty-seven had a solitary cavity, located commonly in the right upper lobe (14 patients [Figure 2]), while the rest had more than one cavitatory lesions (two to five). Thus, among the 44 cavities encountered, 24 had a shaggy inner lining whereas in others it was smooth with or without trabeculations or corrugations. But, all had thick walls (more than 0.3 cm) with surrounding lung lesions, fulfilling the criteria for complex aspergillomas [Figure 2]. The cavities often showed mixed lining of pseudo-stratified columnar or metaplastic squamous epithelium. Areas of ulceration lined by granulation were also noted and were seen in some cavities with smooth linings. Their walls invariably showed inflammation and fibrosis, with endarteritis, lymphoid follicles or at times a granulomatous reaction.

Multiple fungal balls occurred in the dilated and fusiform bronchial tree in six patients (14.6%) as the non-cavitatory forms [Figure 3]. Three had undergone lobectomies (right and left upper and left lower, lobes) for bronchiectasis and three were autopsied cases of bilateral extensive bronchiectasis. The causes of death in two autopsied cases were cor pulmonale and superadded extensive bacterial bronchopneumonia, respectively. The third patient had a cardiac arrest during bronchial arterial embolization; at autopsy, renal and splenic infarcts due to gel-foam emboli were seen [Figure 4]. Three also had cavitatory lesions containing the aspergillomas. These bronchi were lined by ulcerated pseudo-stratified columnar epithelium with focal squamous metaplasia. This was associated with either mixed inflammatory infiltrate or foreign body granulomatous reaction.

Apart from the one incidental aspergillomas, tuberculosis was the etiological factor in 31 patients, producing fibrocavitatory lesions, bronchiectatic cavities, or both. Fibrocaseous lesions were seen in 14 specimens. The other etiologies were chronic lung abscess (three cases) and bronchiectasis (six cases).


   Discussion Top


Saprophytic opportunistic colonization by Aspergillus species occurs in diseased respiratory tract. But, despite the widespread distribution of the fungal spores, it is difficult to predict the incidence of predisposition in patients. We identified only 41 patients in a span of 15 years in both surgical and autopsy materials, that too despite the presence of tuberculosis which is not only rampant in our country, but also the commonest cause of aspergilloma. However, it must be remembered that a fungal ball can be formed in the course of invasive aspergillosis [4] and chronic necrotizing aspergillosis. [5] We did not encounter such mycetomas in our material presented here or published earlier. [1]

Most of the current literature on aspergillomas has been surgical series, [6],[7],[8],[9],[10] showing a slight male preponderance; there were no children. In many, tuberculosis formed the underlying basis for aspergilloma, seen in 59-89%. In our experience too, tuberculosis was the etiology in 79.6%. Other causes included non-tuberculous bronchiectasis and chronic lung abscess, with an incidental microscopic aspergilloma. Among them, 26 patients had received anti-tuberculous therapy, but morphologic lesions of tuberculosis were identified in only 14 lung specimens. Besides, in this background of in tuberculosis, the aspergillomas occurred in fibrocavitatory lesions, bronchiectatic cavities as well as diffuse bronchiectasis, a fact not at all brought out by the clinical studies. The fungal elements in the cavities induce smoldering inflammation as evidenced by multifocal ulceration, inflammation (including granulomatous response) and proliferation of capillaries. None of our cases demonstrated invasion of the lung parenchyma by the fungal hyphae, even in patients with diabetes mellitus.

Another perplexing fact is the presence of aspergilloma without lung disease, seen in the range of 1-18%, [6],[8],[10] even though in these studies, a pathologist had reviewed the specimens. It is difficult to envisage the formation of a radiologically visible fungal ball in an air-filled pulmonary space formed without a diseased state. These cases have been designated as simple aspergilloma occurring in epithelial-lined cysts. [6] One wonders whether all of these are examples of intrapulmonary bronchogenic cysts, which are infrequent occurrences [11] or emphysematous spaces. We found only one case of simple aspergilloma discovered histologically at autopsy in a dilated bronchiole of an asthmatic.

Hemoptysis is the commonest mode of presentation in patients with aspergilloma, with an incidence of around 80%, which is life threatening in 30%. [12]

Thirty-five of our patients had history of hemoptysis of short or prolonged duration, though in a few it may have been related to the presence of tuberculosis itself. Traditionally, the hemoptysis, streaky or otherwise, has been ascribed to erosion of the bronchial arteries. [13] This occurs regardless of the presence of endarteritis obliterans as observed in 63% of the lesions examined in this study. However, ramifications of the pulmonary arteries are much more and these would have a greater exposure during the destructive processes in the lungs. Inflammation may further lead to opening up of the low pressure pulmonary arterial and high pressure bronchial arterial anastomotic plexus, which we feel is the source of bleeding rather than the radicles of the bronchial arteries. Massive hemoptysis occurred in three patients (7.3%), requiring bronchial arterial embolization, which in all probability abolishes the feeders to pulmonary-bronchial vascular anastomosis. In one of them, unfortunately, there was systemic embolism, with acute renal failure. There are no clinical markers or sophisticated radiological investigations that anticipate cataclysmic hemoptysis. Inoue et al. advocate use of endothelial growth factor as a serum marker to determine the extent of hemoptysis. [14]

The natural history of patients affected is variable. Some aspergillomas are known to undergo spontaneous lyses. [12] Many endorse surgical resections in view of high risk of unpredictable, life-threatening hemoptysis, which at times is recalcitrant to embolization procedures. [6],[7],[8],[9],[10] Besides, the success after oral, intravenous therapy or trans-cavitatory instillation of anti-fungal drugs has not been consistent. [13] Simple aspergilloma is mostly bereft of postoperative complications, but complex aspergillomas may not always be amenable to surgery [15] and are associated with complications and even death. [16] Hence, it is mandatory to assess the pulmonary functions to expect good outcomes after surgery as well as after long-term follow-up.

 
   References Top

1.Vaideeswar P, Prasad S, Deshpande JR, Pandit SP. Invasive pulmonary aspergillosis: A study of 39 cases at autopsy. J Postgrad Med 2004;50:21-6.  Back to cited text no. 1    
2.Belcher J, Plummer N. Surgery in broncho-pulmonary aspergillosis. Br J Dis Chest 1960;54:335-41.  Back to cited text no. 2    
3.Daly RC, Pairolero PC, Piehler JM, Trastek VF, Payne WS, Bernatz PE. Pulmonary aspergilloma: Results of surgical treatment. J Thorac Cardiovasc Surg 1986;92;981-8.  Back to cited text no. 3    
4.Kibbler CC, Milkins SR, Bhamra A, Spiteri MA, Noone P, Prentice HG. Apparent pulmonary mycetoma following invasive aspergillosis in neutropenic patients. Thorax 1988;43:102-12.  Back to cited text no. 4    
5.Binder RE, Faling LJ, Pugatch RD, Mahasen C, Snider GL. Chronic necrotizing pulmonary aspergillosis: A distinct entity. Medicine 1982;61:109-24.  Back to cited text no. 5    
6.Kim YT, Kang MC, Sung SW, Kim JH. Good long-term outcomes after surgical treatment of simple and complex pulmonary aspergilloma. Ann Thorac Surg 2005;79:294-8.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Lee SH, Lee BJ, Jung do Y, Kim JH, Sohn DS, Shin JW, et al . Clinical manifestations and treatment outcomes of pulmonary aspergilloma. Korean J Intern Med 2004;19:38-42.  Back to cited text no. 7    
8.Park CK, Theon S. Results of surgical treatment for pulmonary aspergilloma. Eur J Cardiothorac Surg 2002;21:918-23.  Back to cited text no. 8    
9.Babatasi G, Massetti M, Chapelier A, Fadel E, Macchiarini P, Khayat A, et al . Surgical treatment of pulmonary aspergilloma: Current outcome. J Thorac Cardiovasc Surg 2000;119:906-12.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Regnard JF, Sacrd P, Nicolosi M, Spagiarri L, Magdeleinat P, Jauffret B, et al . Aspergilloma: A series of 89 surgical cases. Ann Thorac Surg 2000;69:898-903.  Back to cited text no. 10    
11.Chang YC, Chang YL, Chen SY, Wang TC, Yang PC, Liu HM, et al . Intrapulmonary bronchogenic cysts: Computed tomography, clinical and histopathologic correlations. J Formos Med Assoc 2007;106:8-15.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.el Oakley R, Petrou M, Goldstraw P. Indications and outcome of surgery for aspergilloma. Thorax 1997;52:813-5.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Kay PH. Surgical management of pulmonary aspergilloma. Thorax 1997;52:753-4.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Inoue K, Matsuyama W, Hashiguchi T, Wakimoto J, Hirotsu Y, Kawabata M, et al . Expression of vascular endothelial growth factor in pulmonary aspergilloma. Intern Med 2001;40:1195-9.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Judson MA, Stevens DA. The treatment of pulmonary aspergillomas. Curr Opin Investig Drugs 2001;2:1375-7.  Back to cited text no. 15  [PUBMED]  
16.Chen JC, Chang YL, Luh SP, Lee JM, Lee YC. Surgical treatment for pulmonary aspergilloma: A 28 year experience. Thorax 1997;52:810-3.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Pradeep Vaideeswar
Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College, Parel, Mumbai - 400 012, Maharashtra
India
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DOI: 10.4103/0377-4929.42507

PMID: 18723954

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