Multiple Cavitary Pulmonary Nodules-Resolution Without Identification A Case Report and Review

Introduction

Multiple cavitary pulmonary nodules can be the manifestation of a diverse group of local and systemic diseases. We report a rare case of remission without an identifiable cause after extensive workup.

Case Report

A 52 Year old African American female with medical history of chronic obstructive pulmonary disease, diabetes mellitus, and hypertension presented with complaints of blood mixed sputum for 3 days. Patient denied any chest pain, shortness of breath, palpitations, fever, night sweats, loss of appetite or any sick contacts. Patient admitted to being a smoker (30 packs a year), and had not travelled outside US recently. She was purified protein derivative (PPD) negative one month prior, and HIV negative 6 months prior to this admission.

On physical examination, she was afebrile with normal vital signs. Examination of the chest, cardiovascular system and abdomen were unremarkable. All the basic labs on admission were within normal limits. Chest x-ray preliminary report was negative. The patient was admitted with impression of bronchitis, rule out community acquired pneumonia, rule out Bronchiectasis and rule out malignancy. Patient was started on antibiotics empirically for bronchitis, Tiotropium metered dose inhaler (MDI) and Beclomethasone MDI for her COPD, and her other home medicines. Sputum was sent for gram stain, culture and sensitivity. Two sets of blood cultures were also sent.

Sputum gram stain showed gram positive cocci in clusters and the chest x- ray official report showed probable right upper lobe nodule. In view of these findings, patient subsequently went for CAT scan of chest which showed several bilateral small irregular cavitating nodules, the largest measuring 1.2×1.0 cm in size at the apex of right upper lobe.

In the light of patient’s symptoms, gram stain result and CT chest findings, she was started on Vancomycin empirically to cover Staphylococcus Aureus.

On day 2 of admission, sputum culture and blood cultures revealed no growth. A PPD was placed again, and sputum for Acid Fast Bacilli (AFB) x3 was sent to rule out pulmonary tuberculosis, and the patient was scheduled for bronchoscopy the next day. Bronchoscopy was performed, and bronchial washings were sent for AFB smear, fungal culture, gram stain and cytology- all of which came back negative. Meanwhile, the patient’s symptoms had improved and her hospital stay had thus far been uneventful. Sputum AFB smear x3 and PPD had also proved negative.

The patient’s serology was also negative for rheumatoid factor, P-ANCA, C-ANCA, and ANA. She was also negative for Toxoplasma antibody, Mycoplasma Pneumoniae antibody, and Cryptococcal antigen. 2D transthoracic echocardiogram with Doppler was also negative. She also had mammography to rule out any breast mass, which too came back as negative. Since most of the blood tests were negative and bronchoscopy was inconclusive, the patient was scheduled for CT guided biopsy on the fifth day of admission. Histopathologic examination of biopsy showed prominent type 2 pneumocytes, patchy neutrophilic infiltrate and patchy fibrosis. There was no tumor, granuloma, or hemosiderin laden macrophage.

The patient was discharged on the 8th day of admission and advised to follow up in 4 weeks for chest CT and instructed to continue all her home medicines which included pioglitazone for diabetes, metoprolol and hydrochlorothiazide for her hypertension, and tiotropium MDI, beclomethasone MDI and albuterol MDI for COPD. By the time of discharge, the patient had completed 7 days of ceftriaxone and Vancomycin, along with 5 days course of Azithromycin.

Four weeks later when the patient followed up in the pulmonary clinic, she was completely asymptomatic and the physical examination was unremarkable.

She had the CT chest done which showed resolution of most of the previous nodules, and near resolution of right apical nodules. The patient was discharged and advised to follow up in 6 months with repeat CT chest.

Conclusion

Although an extensive workup of this patient’s multiple cavitary nodules was performed and the patient’s nodules resolved, no definitive diagnosis was made. One possible explanation is that the patient had staphylococcus Aureus that responded to Vancomycin. However, this explanation is suspect because the patient, who is diabetic, never had a fever, and never had leukocytosis; moreover, the sputum culture was negative, the bronchoscopy was negative and the patient was never very ill clinically. Another possible explanation is the patient had an inflammatory disease that responded to inhaled steroids, as the patient never received intravenous or oral steroids. This too seems unlikely, especially since the patient’s rheumatological work up was also negative.

Discussion

Multiple cavitary pulmonary nodules have a diverse etiology, including infectious and noninfectious causes. Examples of infectious causes are various bacteria, fungi, mycobacterium tuberculosis, Paragonismus westermani, septic emboli, abscesses and aspiration pneumonia. Noninfectious causes include sarcoidosis, arteriovenous malformation, pneumoconiosis, primary malignancy and metastatic disease, rheumatoid arthritis, and Wegener’s granulomatosis.

We shall now discuss each of the causes ¹ briefly, beginning with malignancy.

Malignancy

Metastatic solid organ malignancies (from testis, ovaries, kidneys, breast, anal canal, and melanoma) are the most common cause of multiple pulmonary nodules, and account for 80 percent of such cases. The lesions are variable in size and location, with a proclivity for the better perfused lung bases. The lesions are usually round with sharply demarcated borders, although metastases with a tendency towards hemorrhage, such as choriocarcinoma, can also have indistinct, fuzzy borders. Cavitation of metastatic lesions occurs in less than 5 percent of cases.

Non-Hodgkin’s lymphoma can also cause multiple pulmonary nodules; these are more common in the lower lobes. Intrapulmonary lymphoma nodules usually originate from the bronchial-associated lymphoid tissue (BALT). Cavitation occurs in less than 4 percent of cases. ²   Enlarged mediastinal and/or hilar lymph nodes need not be present, particularly in cases where lymphoma has recurred outside of a previously irradiated field. ³

In patients with HIV, Kaposi’s sarcoma can present with multiple pulmonary nodules in a peribronchovascular distribution. The size of these nodules tends to exceed 1 cm at the time of diagnosis. ⁴

Infections

A number of infectious processes characteristically produce multiple pulmonary nodules. These include: Multiple abscesses — bacteremic patients may develop multiple lung abscesses, which are more common in dependent areas of the lungs. Recurrent aspiration can yield multiple abscesses as well. Typically the lesions are between 0.5 and 3 cm in diameter, round, and well-defined. Formation of thick-walled cavities is common once the central necrotic debris has been expectorated through a bronchiolar communication.

Septic emboli — Septic thrombophlebitis may generate septic emboli which produce multiple 0.5 to 3 cm round or wedge-shaped nodules with a predilection for peripheral areas of the lower lobes. ⁵   Cavitation is common, usually producing thin-walled lesions.

Fungi — multiple pulmonary nodules can arise from a number of fungal infections, like histoplasmosis, coccidioidomycosis, or invasive Aspergillosis in immunocompromised hosts. In these cases, the lesions tend to range from 0.5 to 3 cm in diameter without a clear predilection for a specific area of the lungs. Patients with invasive Aspergillosis commonly display a surrounding halo of ground glass attenuation due to local hemorrhage (the halo sign), followed by cavitation and “crescent-sign” formation, while these findings are rare in histoplasmosis. ^{6 7 8 9}  Multiple pulmonary nodules from histoplasmosis may remain unchanged in size for many years, and may display calcification. ¹⁰   In patients with HIV, cryptococcus can produce multiple sub centimeter nodules which generally lack specific radiographic findings. ⁴

PARASITE: Paragonismus westermani — Paragonismus westermani is a fluke that is endemic in parts of China, Korea, Japan, the Philippines, and Taiwan. Humans acquire the infection by ingesting uncooked fresh water crabs or crayfish that harbor the metacercarial stage of the parasite. ¹¹  After human ingestion, the metacercariae excyst in the duodenum, penetrate the gastrointestinal wall, and migrate within the peritoneal cavity. Although some young flukes may migrate to extra pulmonary sites, most of the developing flukes penetrate the diaphragm to migrate within the pulmonary parenchyma. Radiographic appearance includes multiple cavities with surrounding thin areas of opacity, although noncavitary nodules can also be present. ¹²   The lower and middle lung zones are most commonly affected.

Noninfectious Inflammatory Conditions

A number of infectious processes characteristically produce multiple pulmonary nodules. These include: Multiple abscesses — bacteremic patients may develop multiple lung abscesses, which are more common in dependent areas of the lungs. Recurrent aspiration can yield multiple abscesses as well. Typically the lesions are between 0.5 and 3 cm in diameter, round, and well-defined. Formation of thick-walled cavities is common once the central necrotic debris has been expectorated through a bronchiolar communication.

Septic emboli — Septic thrombophlebitis may generate septic emboli which produce multiple 0.5 to 3 cm round or wedge-shaped nodules with a predilection for peripheral areas of the lower lobes. ⁵   Cavitation is common, usually producing thin-walled lesions.

Fungi — multiple pulmonary nodules can arise from a number of fungal infections, like histoplasmosis, coccidioidomycosis, or invasive Aspergillosis in immunocompromised hosts. In these cases, the lesions tend to range from 0.5 to 3 cm in diameter without a clear predilection for a specific area of the lungs. Patients with invasive Aspergillosis commonly display a surrounding halo of ground glass attenuation due to local hemorrhage (the halo sign), followed by cavitation and “crescent-sign” formation, while these findings are rare in histoplasmosis. ^{6 7 8 9}  Multiple pulmonary nodules from histoplasmosis may remain unchanged in size for many years, and may display calcification. ¹⁰   In patients with HIV, cryptococcus can produce multiple sub centimeter nodules which generally lack specific radiographic findings. ⁴

PARASITE: Paragonismus westermani — Paragonismus westermani is a fluke that is endemic in parts of China, Korea, Japan, the Philippines, and Taiwan. Humans acquire the infection by ingesting uncooked fresh water crabs or crayfish that harbor the metacercarial stage of the parasite. ¹¹   After human ingestion, the metacercariae excyst in the duodenum, penetrate the gastrointestinal wall, and migrate within the peritoneal cavity. Although some young flukes may migrate to extra pulmonary sites, most of the developing flukes penetrate the diaphragm to migrate within the pulmonary parenchyma. Radiographic appearance includes multiple cavities with surrounding thin areas of opacity, although noncavitary nodules can also be present. ¹²   The lower and middle lung zones are most commonly affected.

Pulmonary Arteriovenous Malformations

Pulmonary arteriovenous malformations consist of abnormal communications between pulmonary veins and arteries and may present radiographically as either solitary or, in 30 percent of cases, multiple pulmonary nodules. ¹⁴   Lesions are usually well-defined, round or oval opacities ranging from 1 to 5 cm in diameter. The presence of a shunt fraction of >5 percent when breathing 100 percent oxygen in the absence of an intracardiac shunt strongly favors the diagnosis of pulmonary arteriovenous malformations.

Pneumoconioses

Both coal workers’ pneumoconiosis and silicosis may evolve to progressive massive fibrosis or conglomerate masses, yielding a radiographic appearance of multiple pulmonary nodules; these may range in size from 1 to 10 cm and usually are located in the upper lobes. ^{15 16}  Calcification and cavitation are unusual, but can occur and raise the possibility of superimposed tuberculosis.