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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 5  |  Issue : 2  |  Page : 83-87

Cavitating lung cancer with underlying lung fibrosis treated as case of post-COVID-19 lung fibrosis with invasive mucormycosis


1 Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra, India
2 Department of Internal Medicine, MIMSR Medical College, Latur, Maharashtra, India

Date of Submission17-Aug-2022
Date of Decision12-Oct-2022
Date of Acceptance15-Nov-2022
Date of Web Publication23-Dec-2022

Correspondence Address:
Dr. Shital Patil
Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/japt.japt_26_22

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  Abstract 


The pulmonary cavity is caused by infective, inflammatory, and malignant lung pathologies. In the currently ongoing COVID-19 pandemic, the most common cause for pulmonary cavities would be tuberculosis and fungal infections in the presence of exposure of high-dose steroids given during the course of hospitalization for COVID-19 pneumonia. In the present case report, an 86-year-old male presented with cavitating lung mass with hemoptysis who had received high-dose steroids for acute hypoxic respiratory failure due to COVID-19 pneumonia. He was treated with high-dose steroids during and after hospitalization for post-COVID-19 lung fibrosis with oxygen dependency and continuous oxygen supplementation. The right upper lobe mass was underevaluated, and developed cavitating consolidation in 3 months. He was evaluated and treated as a case of right upper lobe invasive aspergillosis and mucormycosis infection documented on sputum culture. He was treated with amphotericin B and higher antibiotics and discharged with oral voriconazole. Intermittent hemoptysis was a clinical clue to workup further with bronchoscopy for protocolized diagnosis of cavitating lung mass. Bronchoscopy documented moderately to poorly differentiated squamous cell carcinoma as a cause for cavitating consolidation. A high index of suspicion is must while dealing with pulmonary cavities. The currently ongoing COVID-19 pandemic may result in an underestimation of malignancy as a cause for cavitating lung pathology due to the rampant use of steroids during treatment of these cases and more documentation of fungal lung infections in post-COVID-19 care settings. We recommend bronchoscopy in cavitating lung disease for exact 'etiopathology documentation' of tropical and or malignant lung disease.

Keywords: Bronchoscopy, cavitating lung cancer, lung fibrosis, mucormycosis, post-COVID-19 lung fibrosis


How to cite this article:
Patil S, Patil D, Gondhali G. Cavitating lung cancer with underlying lung fibrosis treated as case of post-COVID-19 lung fibrosis with invasive mucormycosis. J Assoc Pulmonologist Tamilnadu 2022;5:83-7

How to cite this URL:
Patil S, Patil D, Gondhali G. Cavitating lung cancer with underlying lung fibrosis treated as case of post-COVID-19 lung fibrosis with invasive mucormycosis. J Assoc Pulmonologist Tamilnadu [serial online] 2022 [cited 2023 Jan 27];5:83-7. Available from: http://www.japt.com/text.asp?2022/5/2/83/365082




  Introduction Top


Lung cavitation due to COVID-19 pneumonia is uncommon. Although the exact mechanism of cavitation in COVID-19 pneumonia is unknown, it may be related to diffuse alveolar damage, intra-alveolar hemorrhage, and necrosis of parenchymal cells based on prior autopsy reports.[1] Pulmonary sequelae of COVID-19 are currently little understood; hence, information in this regard can help us in identifying the risk groups that need close follow-up. The development of pulmonary fibrosis is considered one of the key concerns regarding COVID-19 pulmonary sequelae as it is associated with architectural distortion of the lung parenchyma and overall impairment of lung function resulting in decreased quality of life.[2] The pathogenic progression of pulmonary fibrosis post-COVID-19 is yet to be fully illuminated; however, it is thought to be multifactorial. Whatever the cause, fibrosis is considered to be due to the abnormal healing of the injured lung parenchyma.[3] Overall evaluation, including a combination of symptoms, laboratory results, past clinical history, and imaging findings, leads to recognition of the correct diagnosis as, in our case, presented with thick-walled cavitary lung disease encasing the right main pulmonary artery finally diagnosed as squamous cell lung cancer.


  Case Report Top


A 86-year-old male, retired teacher, ex-smoker, hypertensive, nondiabetic, known case of ischemic heart disease underwent coronary angioplasty 10 years back. He was referred to our center by a family physician for increased shortness of breath in a recently diagnosed case of post-COVID-19 lung fibrosis with mucormycosis, as narrated by accompanying family members.

Clinical details are documented as:

  1. Cough for 12 months dry, intermittent, with minimal white sputum production
  2. Shortness of breath on exertion in the past 12 months, initially grade I and progressed to grade IV and associated with drastic change in the quality of life leading to inability to perform routine activities due to shortness of breath
  3. Loss of appetite and weight loss over a period of 6 months
  4. Weakness and myalgia with fatigability for 6 months.


Clinical examination documented as:

  • Restless, dry oral mucosa, cyanosis
  • Heart rate: 130/min, respiratory rate: 46/bpm, blood pressure: 160/90 mmhg
  • PsO2: [email protected] room air resting and 89%–91% @ 14 l/min oxygen with reservoir bag
  • Respiratory system examination revealed bilateral vesicular breath sounds. Adventitious breath sounds documented as crepitations heard over both lung fields
  • Nervous system examination-higher functions normal, no neurological abnormality
  • Cardiovascular and gastrointestinal systems were normal.


His son disclosed that he was diagnosed with a case of COVID-19 pneumonia diagnosed 12 months back. He required intensive care unit hospitalization in another hospital with ventilatory support (noninvasive ventilation) for 10 days. He recovered of acute COVID-19 pneumonia, and due to persistent oxygen requirement, he was undergone high-resolution computed tomography (HRCT) thorax for assessment of lung parenchymal status.

His HRCT thorax documented [Figure 1] and [Figure 2]:
Figure 1: HRCT thorax showing right paratracheal heterogeneous mass with interlobular septal thickenings. HRCT: High-resolution computed tomography

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Figure 2: HRCT thorax showing bilateral peripheral subpleural interlobular septal thickening in craniocaudal distribution with honeycombing and tractional bronchiectasis. HRCT: High-resolution computed tomography

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  1. Right paratracheal upper lobe heterogeneous mass
  2. Mass with sunray sign positive
  3. Bilateral peripheral subpleural interlobular septal thickening in craniocaudal distribution
  4. Bilateral peripheral and subpleural honeycombing predominantly posterior aspect
  5. Bilateral peripheral subpleural tractional bronchiectasis predominantly posterior aspect.


Primary care physicians called our center and requested for expert opinion and possible bronchoscopy for diagnosis of lung mass in their center as portable nonvideo bronchoscopy. As patients' general health was unstable and required oxygen supplementation with comorbidities and with advanced age, we performed nonvideo bronchoscopy in the intensive care unit. During bronchoscopy, we have documented mucosal abnormalities without any endobronchial, submucosal or peribronchial abnormalities or growth in the right upper lobe bronchus and intermediate bronchus, and other bronchial tree on the right lower lobe and left-sided bronchial tree were normal. We have collected bronchoalveolar lavage from the right upper lobe and performed 5–6 bronchoscopic biopsies blindly passing bronchial forceps in the right upper lobe anterior segment, and specimens were sent for histopathology analysis.

Bronchoalveolar lavage documented doubtful cytology for malignancy and mentioned as few atypical cells. Histopathology analysis reported as chronic nonspecific inflammation.

The patient had received a high dose methylprednisolone during the course of hospitalization in primary care physicians' settings during hospitalization for 2 weeks for COVID-19 pneumonia with acute hypoxic respiratory failure. He was discharged to home with home oxygen therapy and lung antifibrotics as nintedanib and oral methylprednisolone for 2 weeks. His symptoms of breathlessness improved significantly, and his oxygen requirement was decreased. He was advised for the continuation of oxygen supplementation with oral methylprednisolone and Nintedanib for post-COVID-19 lung fibrosis for additional eight weeks. After 10 weeks of discharge from the hospital, he started to cough with intermittent hemoptysis, and increased breathlessness. Relatives brought the patient to the primary care physician center and admitted for acute hypoxic respiratory failure in the intensive care unit. Due to intermittent hemoptysis and worsened dyspnea, they repeated HRCT thorax.

HRCT Thorax documented abnormalities as [Figure 3], [Figure 4], [Figure 5]:
Figure 3: HRCT thorax showing right paratracheal well-defined cavitating mass with bilateral interlobular septal thickenings and honeycombing (increase as compared to the previous scan). HRCT: High-resolution computed tomography

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Figure 4: HRCT thorax showing right paratracheal heterogeneous cavitating mass with irregular inner margins and thick wall with bilateral interlobular septal thickenings. HRCT: High-resolution computed tomography

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Figure 5: HRCT thorax showing right paratracheal heterogeneous cavitating mass with irregular inner margins and thick wall with encasement of the right main pulmonary artery. HRCT: High-resolution computed tomography

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  1. Right para-tracheal upper lobe heterogeneous “Cavitating Mass”
  2. Large cavity with irregular inner margins and peri-cavitary consolidation
  3. Thick-walled cavity with no air-fluid level
  4. Cavitating mass is encasing the right main pulmonary artery
  5. Bilateral peripheral subpleural interlobular septal thickening in craniocaudal distribution (increased in comparison with the previous scan)
  6. Bilateral peripheral and subpleural honeycombing predominantly posterior aspect (increased in comparison with the previous scan)
  7. Bilateral peripheral subpleural tractional bronchiectasis predominantly posterior aspect


(Increased in comparison with the previous scan)

The primary care physician sent induced sputum for tropical workup, including fungal culture for possible secondary fungal due to high-dose steroids in the recent past.

  • Sputum Gram stain – Gram-positive cocci in chains, pairs, and clusters
  • Zn stain – no acid-fast bacilli
  • Sputum CBNAAT-negative for mycobacterium tuberculosis (MTB)
  • Sputum fungal stain – nonseptal hyphae with branching at right or obtuse angles
  • Fungal culture: mixed fungal culture positive for Aspergillus species and Mucormycosis.


Primary care physician started liposomal amphotericin B as per the weight band and higher antibiotics as per their Intensive care unit protocol. His general health stabilized with 2 weeks of amphotericin B and higher antibiotics in the intensive care unit. He was discharged to home on oral voriconazole and oral antibiotics with advice for home oxygen supplementation due to chronic respiratory failure because of underlying lung fibrosis. His health remained stable for 2 weeks and had one episode of massive hemoptysis. This time relatives brought the patient to our center as per guidance by the primary care physician for further workup.

We have admitted the patient to the intensive care unit and stabilized his general health. We have started higher antibiotics and intravenous hemostatics for the control of hemoptysis. The complete case was reassessed for the possibility of alternative diagnosis, and decided to perform nonvideo bronchoscopy in the intensive care unit.

Nonvideo bronchoscopy was performed in the intensive care unit and observed hemorrhagic secretions were coming out from the right bronchial tree. After the instillation of 40 normal salines, an ulcerated growth visualized in the right upper lobe bronchus. Bronchoscopic biopsy specimens were collected, and BAL was collected before and after biopsy specimens. Local minor bleeding was documented after the biopsy, which can be controlled with cold saline. We have monitored vital parameters for 1 h after the procedure and continued supplementation of oxygen as preprocedure.

BAL AFB (Bronchoalveolar lavage Acid fast bacilli)– Negative, BAL Gene Xpert MTB/RIF– Negative

BAL bacterial culture – no growth,

BAL cytology – Malignant cells positive and possibility of the non-small cell type of lung cancer.

Histopathological examination revealed moderately to poorly differentiated squamous cell carcinoma [Figure 6]
Figure 6: Histopathology image showing moderate to poorly differentiated squamous cell carcinoma

Click here to view


The oncology opinion suggested palliative care due to limited performance status and poor general health. As the patient was on oxygen supplementation for underlying advanced lung fibrosis, we have decided to continue only antifibrotics and supplementation of oxygen at home after a discussion with our team of pulmonologists and oncologists.


  Discussion Top


A cavity is defined in the Fleischner glossary as “a gas-filled space, seen as a lucency or low-attenuation area, within pulmonary consolidation, a mass, or a nodule.”[4] The cavity wall thickness may vary considerably. The wall thickness of the cavitary lung lesions in solitary disease can be useful in differentiating between benign and malignant disorders. A recent study found that a wall thickness of less than 7 mm was highly specific for benign disease, and a thickness of greater than 24 mm was highly specific for malignant disease. However, these thresholds are not absolute, as thin-walled carcinomas are also reported.[5] The content of the cavities is of little help in differentiating benign and malignant lesions. A benign bronchogenic cyst may contain fluid levels, as may a bronchoalveolar carcinoma. The degree of contrast enhancement in the content of nodules (<10 HU) is shown to indicate benign lesions and may be used to distinguish aspergillomas from lung cancer.[6] Rim enhancement of the walls on contrast-enhanced computed tomography (CT) is common in abscesses.[7] A connecting pulmonary artery may be seen in smaller metastases but not in larger ones, as the larger nodules tend to compress the vessels, so a lack of a feeding artery cannot be used to imply benign nodules.[8] The acute onset of symptoms is sometimes helpful to distinguish malignant and nonmalignant diseases. Benign diseases may also cause fatigue and weight loss, similar to malignancies. Acute onset of fever is usually helpful to distinguish benign disorders from malignancies, but a pulmonary cancer may present with a superinfection secondary to the tumor.[9] Cavitary lung lesions are usually related to mycobacterial, parasitic, fungal, autoimmune, or neoplastic etiologies. Typical CT imaging features of COVID-19 mainly include ground-glass and consolidative pulmonary opacities, primarily in the lower lobes. Notably, there is also the absence of cavitation, lymphadenopathy, and pleural effusion.[10],[11] Lung cavitation following pulmonary embolism and infarction has been described previously in non-COVID-19 patients. In COVID-19 patients, possible sources of injury include cytokine storm due to improper inflammatory response, bacterial co-infections, and thromboembolic events causing microvascular damage and endothelial dysfunction.[12] Recovered COVID-19 patients who have developed pulmonary fibrosis, suffer more frequently from persistent symptoms, including dyspnoea, cough, chest pain, fatigue, and myalgia compared to nonfibrotic patients. In the present case report, symptoms of shortness of breath were there before COVID-19 pneumonia, which will give a clue that underlying fibrosis might have started before it. In a 2019 nationwide multi-center study of 388 confirmed or suspected cases of mucormycosis in India before COVID-19, Prakash et al. found that 18% had diabetic ketoacidosis and 57% of patients had uncontrolled diabetes mellitus (DM).[13] Sputum cultures are not reliable indicators of invasive mucormycosis, as some Zygomycetes species often colonize the respiratory tract, and as in our case, sputum culture was considered reliable technique and received antifungals Amphotericin B, which is costly and nephrotoxic.

Issues that need to be considered during the evaluation of such cases are-

  1. Is bilateral lung fibrosis and right upper lobe mass there before the diagnosis of COVID-19 pneumonia?
  2. Lung parenchymal opacities were never “typical” for COVID-19 pneumonia, but rather “typical” for usual interstitial pneumonia (UIP) or idiopathic pulmonary fibrosis (IPF)
  3. Chances of malignant lung process and lymphangitis carcinomatosis or lymphangitic spread of malignant lung pathology should be considered than infective tropical or pandemic etiology
  4. Does the cavitating lung process with underlying lung fibrosis be of fungal etiology whenever there is a history of high-dose steroids for 2 weeks or more in intensive care units in the absence of hyperglycemia or known DM cases?
  5. Cavitating lung process with irregular margins and underlying lung fibrosis warrants bronchoscopy to rule out tropical causes from malignant lung pathology.



  Conclusion Top


In our case, we thought initially as it was post-COVID-19 mucormycosis due history of steroids and initial response to antifungals. As patients' clinical courses were deteriorating and they presented with recurrent hemoptysis, we performed bronchoscopy in the intensive care unit. Finally, we confirmed diagnosis as cavitating squamous cell lung cancer with underlying UIP-IPF which was misdiagnosed as pulmonary mucormycosis with COVID-19 pneumonia due to overlapping clinical and radiological picture in currently ongoing pandemic.

Key learning points from this case report are:

  1. Cavitating lung disease in this currently ongoing COVID-19 pandemic would be infective first and malignant lung process second
  2. The possibility of underlying lung fibrosis as ongoing primary pathology would be more in geriatric cases in the absence of “typical” COVID opacities. COVID-19 lung disease will have more ground glass opacities and consolidations in peripheral lung fields bilaterally than the classical “UIP-IPF” pattern
  3. UIP-IPF pattern classically described as bilateral, peripheral, subpleural intralobular, and interlobular septal thickenings with or without traction bronchiectasis with honeycombing is very rarely described in ongoing acute COVID-19 pneumonia. These types of opacities have been described in the literature in post-COVID-19 care settings with a history of very severe COVID-19 pneumonia with high CT severity and longer ventilatory support requirement
  4. Cavitating lung mass with irregular margins and underlying lung fibrosis favors lung mass more than typical infective cause for the same radiological pattern
  5. Bronchoscopy training in an intensive care unit with expertise in biopsy procedure is the crucial step in workup of advanced cases with poor performance status and oxygen dependency in suspected lung cancer cases
  6. Although high-dose steroids use has been documented with concurrent opportunistic infections such as tuberculosis and fungal infections, sputum samples are the least specific sample for assessment and treatment of post-COVID-19 care setting due to high false-positive results
  7. Treatment of invasive pulmonary fungal infections is very costly, and antifungals are highly nephrotoxic. Liposomal amphotericin B with higher antibiotics in intensive care units will make caretakers financially weak and have a significant impact on further care of these cases with intensive care unit treatments
  8. We have documented the “crucial” role of bronchoscopy during the evaluation of this case and diagnosing squamous cell carcinoma as a cause for cavitating lung disease. Lung cancer is suspected in the presence of underlying UIP-IPF patterns due to the more mitotic nature of the fibrosis process resulting in the development of lung cancer
  9. We recommend bronchoscopy in all cases with cavitary lung disease with underlying lung fibrosis. Special training is required for ICU or critical care setup bronchoscopy as this case is usually performed with on-video bronchoscopy. We also recommend protocolized and timely clinical-radiological-pathological collaboration is must while managing cavitating lung disease.


Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Haseli S, Khalili N, Bakhshayeshkaram M, Sanei Taheri M, Moharramzad Y. Lobar distribution of COVID-19 pneumonia based on chest computed tomography findings; a retrospective study. Arch Acad Emerg Med 2020;8:e55.  Back to cited text no. 3
    
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Ahmed OF, Kakamad FH, Hama Amin BJ, Abdullah BA, Hassan MN, Salih RQ, et al. Post COVID-19 pulmonary complications; a single center experience. Ann Med Surg (Lond) 2021;72:103052.  Back to cited text no. 5
    
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Fernandez IE, Eickelberg O. New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis. Lancet 2012;380:680-8.  Back to cited text no. 6
    
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Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: Glossary of terms for thoracic imaging. Radiology 2008;246:697-722.  Back to cited text no. 7
    
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Guo J, Liang C, Sun Y, Zhou N, Liu Y, Chu X. Lung cancer presenting as thin-walled cysts: An analysis of 15 cases and review of literature. Asia Pac J Clin Oncol 2016;12:e105-12.  Back to cited text no. 8
    
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Park Y, Kim TS, Yi CA, Cho EY, Kim H, Choi YS. Pulmonary cavitary mass containing a mural nodule: Differential diagnosis between intracavitary aspergilloma and cavitating lung cancer on contrast-enhanced computed tomography. Clin Radiol 2007;62:227-32.  Back to cited text no. 9
    
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Walker CM, Abbott GF, Greene RE, Shepard JA, Vummidi D, Digumarthy SR. Imaging pulmonary infection: Classic signs and patterns. AJR Am J Roentgenol 2014;202:479-92.  Back to cited text no. 10
    
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Phua J, Weng L, Ling L, Egi M, Lim CM, Divatia JV, et al. Intensive care management of coronavirus disease 2019 (COVID-19): Challenges and recommendations. Lancet Respir Med 2020;8:506-17.  Back to cited text no. 12
    
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Prakash H, Ghosh AK, Rudramurthy SM, Singh P, Xess I, Savio J, et al. A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment. Med Mycol 2019;57:395-402.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

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