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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2021  |  Volume : 32  |  Issue : 2  |  Page : 568-573
The therapeutic dilemma in pre-transplant asymptomatic aspergilloma: A case report and review of literature

1 Department of Nephrology, Command Hospital Air Force, Bengaluru, Karnataka, India
2 Department of Internal Medicine, Command Hospital Air Force, Bengaluru, Karnataka, India
3 Department of Pathology, Command Hospital Air Force, Bengaluru, Karnataka, India

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Date of Web Publication11-Jan-2022


Aspergillus species are ubiquitous, and inhalation of infectious conidia is not so uncommon. With immunosuppression, it can invade adjacent structures and lead to widespread invasive disease. There is no randomized, prospective trial for optimized treatment including the antifungal and surgical approach for aspergilloma. The available literature related to the management of asymptomatic aspergilloma in pre-renal transplant setting is scarce and debatable. Opinion favoring surgery is that it is necessary to eliminate the fungus reservoir before transplantation because of the inadequacy of pharmacological fungus control measures in immunocompromised patients. We present a case of end-stage renal disease that was planned for renal transplantation and during the workup, was detected to have asymptomatic right upper lobe aspergilloma. He underwent surgical resection of the aspergilloma before undergoing successful renal transplantation. In this case report, we will discuss this case and controversies related to its management before undergoing successful renal transplantation.

How to cite this article:
Jha VK, Mahapatra D, Ghana P, Jairam A, Sharma P. The therapeutic dilemma in pre-transplant asymptomatic aspergilloma: A case report and review of literature. Saudi J Kidney Dis Transpl 2021;32:568-73

How to cite this URL:
Jha VK, Mahapatra D, Ghana P, Jairam A, Sharma P. The therapeutic dilemma in pre-transplant asymptomatic aspergilloma: A case report and review of literature. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Jul 2];32:568-73. Available from: https://www.sjkdt.org/text.asp?2021/32/2/568/335473

   Introduction Top

Chronic pulmonary aspergillosis refers to a spectrum of disease entities which include aspergilloma, aspergillus nodule, chronic cavitary pulmonary aspergillosis, and chronic fibrosing pulmonary aspergillosis. An aspergilloma is a fungus ball which arises in preexisting pulmonary cavities and is composed of aspergillus hyphae, fibrin, mucus, and cellular debris.[1] The management of asymptomatic aspergillomas in the pre-renal-transplant setting is debatable. We present such a case that underwent surgical resection of the aspergilloma before undergoing successful renal transplantation/putting on immunosuppressive agents.

   Case Report Top

A 40-year-old male was detected to have raised blood pressure eight years back. Evaluation revealed proteinuria (urine protein 3+), mild renal dysfunction (serum creatinine 1.6 mg/dL) and normal-sized kidney. He had a history of pulmonary tuberculosis- treated 25 years back. Subsequently, he underwent a renal biopsy which was suggestive of focal segmental glomerulosclerosis with moderate chronicity (interstitial fibrosis and tubular atrophy 30%–40%). In view of subnephrotic range proteinuria (24-h urinary protein - 1845 mg), he was managed conservatively and put on angiotensin-converting enzyme inhibitor only. He gradually progressed to end-stage renal disease 1½ year back and was put on maintenance hemodialysis since then. He was immunized for hepatitis B, pneumococcus and influenza infections. He was willing for live related renal transplant with sister as a prospective renal donor.

During workup for renal transplant, his chest X-ray [Figure 1] revealed multiple varying sized calcific density nodular opacities in both upper and mid-zone. There was a well-defined round soft tissue opacity measuring approximately 1 cm. Noncontrast computerized tomography (NCCT) chest [Figure 2] revealed fibrocalcific opacities both upper lobes with a cavity in the right upper lobe. A well-defined nodule 20 mm × 15 mm abutting and projectting into this cavity on its anteroinferior aspect with minimal wall thickening (maximum: 6 mm). Whole-body positron emission tomography CT scan done subsequently revealed low-grade fluorodeoxyglucose (FDG) uptake in the speculated lesion in the upper lobe of right lung measuring 1.5 cm × 1.4 cm. Few low-grade FDG avid centrilobular nodules were adjacent to this. A large no-FDG avid cavitating lesion was present with eccentric thick wall and intracavitary mobile foreign body. This was seen to communicate with a bronchus. The pulmonologist consultation was taken and he underwent fiberoptic bronchoscopy. Broncho-alveolarlavage (BAL) for cytology, AFB, gram stain, fungal stain, MTB PCR, Gene Xpertwere negative. BAL galactomannan and serum galactomannan were within normal limits. Serum Aspergillus IgG was negative. QuantiFERON®–TB Gold, (Draw Site Incubated) was negative. Lung perfusion scan revealed normal perfusion in the left lung with abnormal perfusion with segmental defects in apical and anterior segments of the right lung. In view of findings suggestive of right upper lobe aspergilloma with post tubercular changes in both lung field, it was planned for right upper lobectomy to remove the focus of fungal infection and the case was referred to a cardiothoracic surgeon for the same. He underwent successful right upper lobectomy (right upper lobe bronchus transacted, stump closed. Right upper lobe pulmonary artery and vein ligated and clamped). Histopathological examination of the resected lung [Figure 3] and [Figure 4] revealed on gross examination on cut opening, multiple dilated airways were seen. On sectioning, an ill-defined greyish white solid to cystic areas seen measuring 4 cm × 2 cm × 2 cm. 2 cavities were noted larger measuring 2 cm × 1.5 cm × 2 cm and smaller measuring 0.6 cm × 0.5 cm × 0.5 cm. On microscopic examination; section from the upper lobe mass lesion shows a dilated respiratory bronchiole lined by ciliated columnar epithelium. Proliferating mass of fungal hyphae were seen within the respiratory bronchioles comprising of acute branching septate hyphae, surrounded by dense mixed inflammatory infiltrate comprising predominantly eosinophils and neutrophils, lymphocytes and histiocytes where the bronchiolar wall was ulcerated. There was extensive fibrosis in adjacent parenchyma. Another section from the adjacent parenchyma showed a patchwork pattern of interstitial fibrosis with intervening areas of emphysematous changes in the alveoli. Mild to moderate chronic inflammatory infiltrate, exudation, accumulation of alveolar macrophages, and intra-alveolar edema were seen at places in the interstitial space. No granuloma/atypia/dysplasia was seen. These findings were suggestive of colonization by fungi with histomorphological features suggestive of aspergillus and post tubercular changes in lung. He was put on eight weeks of oral voriconazole post right upper lobectomy. Repeat NCCT chest [Figure 5] revealed post right upper lobectomy status with 4 cm sized loculated collection in the right apex suggestive of postoperative sequelae. His other investigations done as a workup for renal transplant were normal. HIV, HBsAg, anti-HCV were negative. HBV DNA PCR and HCV RNA PCR were negative. Cardiac evaluation (ECG, 2D Echo) – was normal. Post right upper lobectomy pulmonary function test was normal suggestive of adequate respiratory reserve. He was 6/6 match with his sister in HLA typing and the CDC crossmatch was negative. Repeat serum Aspergillus IgG and serum galactomannan were negative. He underwent successful transplantation after eight weeks of last dose of voriconazole with basiliximab induction and was put on tacrolimus/ mycophenolatemofetil/prednisolone post-renal transplant. He attained serum creatinine 1.2 mg/dL on post-operative day 5 and is doing well at present with nil complications six months post-transplant. He is clinically asymptomatic with stable graft function. Repeat serum aspergillus IgG/serum galactomannan done six months posttransplant was negative.
Figure 1: Radiograph Chest PA view showing multiple varying sized calcific nodular opacities in both upper and mid-zone. A well-defined round soft tissue opacity approximately 1 cm in the right mid-zone.

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Figure 2: Noncontrast computerized tomography chest showing well defined thin-walled cavity measuring 24 mm × 25 mm × 32 mm (APXTRXCC) noted in the junction of the anterior and posterior segment of the right upper lobe. A well-defined nodule 20 mm × 15 mm abutting and projecting into the cavity. Multiple small centrilobular nodules in right upper lobe.

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Figure 3: Right upper lobe lung. On the right side are fungal hyphae showing acute angle branching and focal septations. On the left is host tissue showing no inflammatory reaction suggestive of colonization (H and E, ×40).

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Figure 4: Right upper lobe lung. Hematoxylin and Eosin stain showing fungal hyphae in acute angle branching and septations.

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Figure 5: Noncontrast computerized tomography chest showing right upper lobectomy status. 4 cm sized loculated collection in the right apex. Multiple fibrocalcific opacities in the left lung and calcified nodular opacities in the right middle lobe.

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The authors obtained all appropriate consent forms from the patient for the publication of the case report.

   Discussion Top

On searching the available literature and personal communications with the nephrologists, opinions regarding the management of pre-renal transplant asymptomatic aspergilloma were divided. Questions arose-should it be surgically excised, considering the poor outcome of aspergillosis following renal transplantation or should we go ahead with transplant with a close watch as BAL was normal? However, judging quiescence of a walled-off cavity with negative BAL would be inviting catastrophe especially when the patient is to be given immunosuppression – maximum in the immediate post-transplant period.

Secondary aspergilloma tends to occur in immunocompetent patients with underlying lung pathology such as tuberculosis, sarcoidosis, lung abscess, bronchogenic cysts, or lung tumor who are exposed to aspergillus spores in dry or very dusty environments, hay barns, or compost sites.[2] The time interval between the diagnosis of tuberculosis ranges from <1 year to 30 years.[2] This patient has a history of pulmonary Koch’s disease 25 years back. The natural history of aspergilloma is unknown.[3],[4] Most cases are asymptomatic and spontaneous resolution may be observed in 10% of cases.[4],[5] Repetitive hemosputum or massive hemoptysis is thought to occur as a result of mechanical or endotoxic irritation of vessels or direct invasion by the fungal ball. Many asymptomatic patients have stable radiographic findings over many months and require no therapy. However, continued observation is required as progression to chronic cavitary pulmonary aspergillosis with extensive fibrosis can occur silently. The development of the invasive disease is also a recognized complication.[6] In the index case, the patient was detected to have aspergilloma during the workup for renal transplantation otherwise he was asymptomatic. The risk of conversion into florid invasive aspergillosis after putting on immunosuppression could not be ruled out.

Surgical resection of aspergilloma is the only option for curative treatment. It is generally well tolerated with a mortality rate of less than 1% in multiple studies.[7],[8] Surgical removal of aspergillomas is very difficult in patients with chronic cavitary pulmonary aspergilloma because of increased vascularity, adherent pleura and infected residual pleural space, leading to Aspergillus empyema and/or a bronchopleural fistula.[9] Pleural based aspergilloma removal, in particular, is prone to many complications. Many patients with underlying respiratory insufficiency would leave them with inadequate pulmonary reserve after removal of a lobe of the lung. In our case, the patient has a normal pulmonary function test after surgical resection. Recurrent infection, inability to take azole therapy, azole resistance, and concurrent infection or tumor represent additional indications for surgical resection but carry greater risk. In a few studies, antifungal therapy is also administered before and immediately after surgery.[6],[10] The disease relapse/progression of the disease is more frequent in those patients not given antifungal therapy, irrespective of manifestation of aspergillosis. The preferred anti-fungal is voriconazole. It should be given orally as 400 mg twice daily for the 1st day followed by 200 mg twice daily one or two weeks before surgery, if possible. If the aspergilloma is fully resected without spillage of the contents of the cavity into the pleura, then a four-week course of voriconazole postoperatively is reasonable. If there is a spillage, then a minimum of 12 weeks therapy is recommended to prevent pleural aspergillosis/empyema.[6] The Infectious Diseases Society of America guidelines recommend that patients with chronic cavitary pulmonary aspergillosis and either pulmonary or generalized symptoms or progressive loss of lung function or radiographic progression receive a minimum of six months of antifungal therapy.[11] The present case was planned for renal transplantation and so would be on over immunosuppression immediate post-transplant. The risk of dissemination of the disease or coinfection should be considered very high. He underwent right upper lobectomy and was given eight weeks of oral voriconazole post-resection just to avoid even a minor risk of the disease from a possible spillage post lobectomy and risk of spreading of the disease post immunosuppression.

According to the European Society for Clinical Microbiology and Infectious Diseases/ European Respiratory Society, the diagnosis of aspergilloma requires radiological imaging consistent with aspergilloma, direct serological or microbiological evidence of Aspergillus spp. and exclusion of other diagnoses. Symptoms also need to have been present for three months before the criteria are met.[12] A fungal ball within a pulmonary cavity is highly suggestive and a CT scan is preferential for diagnostic purposes like in the present case. Air crescent sign-crescent-shaped air space separating the fungal ball within the cavity wall and Monod sign- a change in position of the fungal ball with movement may aid in diagnosis.[13] The sensitivity for galactomannan in BAL is much greater than serum galactomannan. The serological test and BAL galactomannan in our case were normal. The diagnosis of aspergilloma was confirmed on histopathological examination of resected lobe in this case.

In solid organ transplant recipients, the intensity of immunosuppression, colonization, and coinfection drive the risk of invasive aspergillosis. Polymorphisms in specific host defense genes in solid organ transplant recipients can also influence the risk of aspergillosis.[14]It was, therefore, wise to undergo excision of aspergilloma to avoid the risk of invasive aspergillosis and to prevent any colonization or coinfection.

   Conclusion Top

In asymptomatic aspergilloma, we propose to go for the surgical excision as any chances of transformation to invasive aspergillosis in post-renal transplant setting on immuno-suppression portend very high mortality. The aspergilloma may erupt at any time especially in immunocompromised patients and also, in these patients who may be on follow up, there is no agreed-upon frequency of repeat imaging. It is, therefore, in a disease with the need for further immunosuppression and lack of dissemination, surgical resection may be curative and useful. Any wrong move in a transplant setting may put the transplant physician under a lot of stress and in rare situations like this, even a single patient experience counts.

Conflict of interest: None declared.

   References Top

Denning DW, Riniotis K, Dobrashian R, Sambatakou H. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: Case series, proposed nomenclature change, and review. Clin Infect Dis 2003;37 Suppl 3:S265-80.  Back to cited text no. 1
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. 2
Hassan MY, BaldanM. Aspergillus of the lung with hemoptysis: A surgical emergency. East Cent Afr J Surg 2004;9:72-3.  Back to cited text no. 3
Moodley L, Pillay J, Dheda K. Aspergilloma and the surgeon. J Thorac Dis 2014;6:202-9.  Back to cited text no. 4
Hammerman KJ, Christianson CS, Huntington I, Hurst GA, Zelman M, Tosh FE. Spontaneous lysis of aspergillomata. Chest 1973;64:679-9.  Back to cited text no. 5
Campbell JH, Winter JH, Richardson MD, Shankland GS, Banham SW. Treatment of pulmonary aspergilloma with itraconazole. Thorax 1991;46:839-41.  Back to cited text no. 6
Farid S, Mohamed S, Devbhandari M, et al. Results of surgery for chronic pulmonary aspergillosis, optimal antifungal therapy and proposed high-risk factors for recurrence – A National Centres experience. J Cardiothorac Surg 2013;8:180.  Back to cited text no. 7
Regnard JF, Icard 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. 8
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. 9
He B, Wan C, Zhou W, Rui Y, Shi Y, Su X. Clinical profile and surgical outcome for different types of chronic pulmonary aspergillosis. Am J Transl Res 2019;11:3671-9.  Back to cited text no. 10
Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016;63: e1-e60.  Back to cited text no. 11
Denning DW, Cadranel J, Aubry CB, et al. Chronic pulmonary aspergillosis: Rationale and clinical guidelines for diagnosis and management. Eur Respir J 2016;47:45-68.  Back to cited text no. 12
Sharma S, Dubey SK, Kumar N. ‘Monad’ and ‘air crescent’ sign in aspergilloma. BMJ Case Rep 2013;2013:bcr 2013200936.  Back to cited text no. 13
Wójtowicz A, Lecompte TD, Bibert S, et al. PTX3 polymorphisms and invasive mold infections after solid organ transplant. Clin Infect Dis 2015;61:619-22.  Back to cited text no. 14

Correspondence Address:
Vijoy Kumar Jha
Department of Nephrology, Command Hospital Air Force, Bengaluru - 560 007, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.335473

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