Viktor Migunov¹

¹Vilnius University, Faculty of Medicine

Abstract

Background. Invasive pulmonary aspergillosis is a life-threatening fungal disease and usually affects immunocompromised patients. Clinical symptoms and radiological findings are nonspecific and may be indistinguishable from other pulmonary conditions such as  pneumonia or pulmonary tuberculosis. Invasive pulmonary aspergillosis is a rare condition in patients with solid tumours and is usually  not considered.

Case report. In this case a 58-year-old man was misdiagnosed with pneumonia. After he failed to respond to  antibiotic treatment, pulmonary tuberculosis was suspected. Final diagnosis was invasive pulmonary aspergillosis and lung adenocarcinoma. This case illustrates the challenges of recognizing invasive pulmonary aspergillosis.

Discussion. Diagnosis of invasive pulmonary aspergillosis is challenging and requires a combination of clinical, radiological and microbiological features. Diagnostic methods and  accuracy in recognizing invasive pulmonary aspergillosis can differ and depend on patients clinical features.

Keywords. Aspergillus, invasive pulmonary aspergillosis, tuberculosis, lung adenocarcinoma.

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Medical Sciences 2021 Vol. 10 (1), p. 150-156, https://doi.org/10.53453/ms.2022.03.17

Pneumonia mimicking invasive pulmonary aspergillosis in

patient with lung adenocarcinoma: a case report

Viktor Migunov

1

1

Vilnius University, Faculty of Medicine

Abstract

Background. Invasive pulmonary aspergillosis is a life-threatening fungal disease and usually affects

immunocompromised patients. Clinical symptoms and radiological findings are nonspecific and may be

indistinguishable from other pulmonary conditions such as pneumonia or pulmonary tuberculosis.

Invasive pulmonary aspergillosis is a rare condition in patients with solid tumours and is usually not

considered.

Case report. In this case a 58-year-old man was misdiagnosed with pneumonia. After he failed to respond

to antibiotic treatment, pulmonary tuberculosis was suspected. Final diagnosis was invasive pulmonary

aspergillosis and lung adenocarcinoma. This case illustrates the challenges of recognizing invasive

pulmonary aspergillosis.

Discussion. Diagnosis of invasive pulmonary aspergillosis is challenging and requires a combination of

clinical, radiological and microbiological features. Diagnostic methods and accuracy in recognizing

invasive pulmonary aspergillosis can differ and depend on patients clinical features.

Keywords. Aspergillus, invasive pulmonary aspergillosis, tuberculosis, lung adenocarcinoma.

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Introduction

Invasive aspergillosis is a life-threatening fungal

disease which usually affects

immunocompromised patients. It’s mostly

reported in patients with hematologic

malignancies, stem cell and solid organ

transplant recipients, other risk factors include

prolonged therapy with high-dose

corticosteroids, cytotoxic therapy, advanced

AIDS, chronic granulomatous disease (1-3).

Clinical symptoms of invasive pulmonary

aspergillosis (IPA) and radiological findings are

nonspecific and may be indistinguishable from

pneumonia which can lead to delay in diagnosis

and potentially worse outcomes (4). IPA is often

not considered in patients with solid tumours (5)

and this clinical case illustrates that IPA should

be considered in oncological patients,

particularly those with lung cancer and having

pneumonia symptoms.

Case report

A 58-year-old man went to the primary care

physician with complaints of cough, fever, left

side chest pain and arthralgias lasting for one

week. Patient has about thirty pack-year

smoking history and is without any underlying

diseases. On physical examination the patient

presented with fever 38,5 °C, auscultation of the

chest revealed left-sided coarse crackles in the

upper zone, other vital signs were normal. White

blood cell count (WBC) was 19 ´ 10

9

/L (4 - 10

´ 10

9

/L), C-reactive protein (CRP) 90 mg/l (<

5mg/l). Chest X-ray revealed infiltrative

changes in the left upper lobe pulling left lung

root upward (Fig.1). Patient was diagnosed with

pneumonia and discharged home with prescribed

oral antibiotic treatment (amoxiclav

875/125mg). Ten days later with no clinical

improvement the patient was referred to a

pulmonologist for consultation suspecting a

pulmonary tuberculosis (PTB). On examination

the patient presented with fever (38.5 °C),

fatigue and worsening left side chest pain. WBC

34 ´ 10

9

/L (4 - 10 ´ 10

9

/L), CRP 90mg/l (<

5mg/l). Chest X-ray without essential dynamics.

The patient was suspected of having PTB,

though microscopical, cytological and molecular

(Xpert MTB/RIF) test of sputum smear for TB

was negative. Chest computed tomography

revealed a thick walled cavity (66 ´ 45 mm) in

the left upper lobe and mediastinal

lymphadenopathy (Fig.2). Fibrobronchoscopy

was performed and showed bloody-purulent

secretion in the left upper lobe. Bronchial

aspirate sample was taken for Tuberculosis

mycobacterium exclusion and all tests were

negative. Diagnostic biochemical test revealed a

positive galactomannan (GM) test (index >3.5)

from broncho-alveolar lavage (BAL) also

microbiological culture for Aspergillus

fumigatus was positive. Patient was diagnosed

with invasive pulmonary aspergillosis (IPA) and

treated with Voriconazole 200mg twice a day for

two weeks and then underwent surgical

treatment - left lung upper lobe S1 - S2 resection.

Histological examination of resected tissues was

classified as a poorly differentiated G3 lung

adenocarcinoma pT1b pN1.

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Figure 1. Linear chest X-ray. Infiltrative changes

in the left upper lobe.

Figure 2. Axial and coronary chest CT. A thick walled cavity in the left upper lobe.

Discussion

The incidence of Aspergillus growth in patients

with lung carcinoma has been reported as being

14.2 %, but only a few cases of combined

aspergilloma and lung cancer have been reported

in the literature (6). The incidence and severity

of invasive aspergillosis are strongly related to a

patient’s immunosuppression. Individuals with

prolonged neutropenia are particularly at risk,

with reports of an incidence up to 70% in

patients with neutropenia lasting more than 30

days (7). In this discussion I want to emphasize

the most important diagnostic features of IPA as

diagnosis still remains challenging and requires

a combination of clinical, radiological and

microbiological features (5, 8, 9). Because of

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atypical clinical and radiographic characteristics

of infection, a significant part of IPA cases are

still undetectable using current criteria (10, 11).

The clinical and radiographic characteristics of

IPA are nonspecific and appear late in the

dissease’s progression (12). Low-grade fever

may accompany IPA, which may be followed by

a mild, non-productive cough. As a clinical

symptom of angioinvasion and tissue necrosis

caused by invasive fungal growth, pleuritic chest

pain and pneumonia develop. Cavitation, which

is caused by a substantial necrosis of the lung

parenchyma, is more likely to develop in non-

immunocompromised patients (5, 13). During

the early stages of the disease, cough and

sputum production are non-existent or minor and

in patients with respiratory disease who have

failed to respond to broad-spectrum antibiotics,

IPA should be seriously considered (14). While

chest X-rays are not sensitive enough to detect

early stages of disease, CT chest scans are

recommended for IPA detection. A halo sign,

which can be seen on CT scans is a highly

indicative of acute IPA (9, 17). Later after

neutrophils recovery these lesions, which

indicate a halo sign cavitates and creates a “air

crescent” sign, a characteristic indication of a

late filamentous invasive mold disease (18).

Microbiological diagnosis of IPA remains a

challenge as respiratory cultures of Aspergillus

has less than 30% diagnostic sensitivity but more

than 60% predictive value in

immunocompromised patients (9). Serological

tests can be used only for immunocompetent

patients as immunocompromised patients do not

produce anti-Aspergillus antibodies. High

concentration of antibodies indicates the

presence of noninvasive form of Aspergillus

infection and radiographical evaluation should

be considered (14). Galactomannan (GM) is one

of the most important antigen for IPA diagnosis

and this test is most often used in clinics (5, 8,

9). GM values can also be used to monitor

treatment efficacy (19). GM serum assay has a

high sensitivity 67% − 100% and high specificity

86% − 99% in neutropenic patients, though low

sensitivity rates – 30% can be seen in patients

receiving antifungal therapy, pediatric patients

and nonneutropenic patients (20, 21, 23). Other

studies showed that in most cases lesions on CT

scans almost matched with the detection of the

GM antigen in the serum and in other cases CT

scans even preceded it (20). Studies showed that

in high-rsik patiens with IPA, including

nonneutropenic individuals, BAL fluid GM has

a higher sensitivity than serum GM (24).

Obtaining specimens for histopathologic

diagnosis is difficult in many patients. Although

histopathologic evidence of fungus is critical for

determining the importance of Aspergillus

growing in culture, its diagnostic accuracy is low

and these techniques are also time-consuming

and insensitive. (25– 27).

Conclusion

• IPA is a life-threatening condition

and early diagnosis is the cornerstone for

preventing serious complications.

• IPA has a high potential to be

overlooked due to it’s nonspecific clinical

symptoms and radiological findings.

• Clinicians should suspect IPA not

only in immunocompromised patients but also

in oncological patients presenting with

pneumonia symptoms, especially those with

lung cancer.

• Diagnostic methods and accuracy

depend on patients clinical features.

• Diagnosis of IPA requires a

combination of diagnostic features. CT chest

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scans combined with BAL fluid GM assay

should be considered as having the highest

predictive value in patients with lung cancer,

though results should be considered in

conjuction with other diagnostic tests and the

clinical context.

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