Pulmonary Hyalinizing Granuloma Mimicking Primary Lung Cancer.

We herein report a case of pulmonary hyalinizing granuloma (PHG), which is a rare pulmonary mass. A 69-year-old man with no symptoms presented to our hospital because of the appearance of an abnormal shadow on chest X-ray. Computed tomography revealed a right middle-lobe mass with spicula and infiltration into the upper lobe. Since a bronchofiberscopic examination showed no malignant cells in the specimen, the patient underwent thoracoscopic surgery, which revealed PHG. Spiculation and interlobar infiltration, which comprise the characteristic features of primary lung cancer, are uncommon presentations of this rare entity.

Introduction

Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by hyalinized lamellar collagen bundles, usually surrounded by plasma cells, lymphocytes, and histiocytes (1). Although an immune response to the antigenic stimulation by bacterial infection or autoimmune response has been suggested as a cause of this disease, its etiology remains unknown. Most of its lesions are reported as single or multiple pulmonary round nodules (2). Furthermore, its radiological findings indicate the possibility of metastatic lung cancer. However, the presence of a single nodular lesion with parenchymal and interlobar infiltration, indicating the possibility of primary lung cancer, is very rare in this disease.

We herein report an interesting case of PHG mimicking primary lung cancer.

Case Report

A 69-year-old man was referred to our hospital for the further evaluation of an abnormal shadow on chest X-ray. He had no symptoms. His medical history included hypertension, hyperlipidemia, diabetes mellitus, hyperuricemia, nephrotic syndrome, and renal failure. He also had a history of smoking 5 cigarettes per day for 29 years and had quit smoking 20 years ago. He was a maintenance worker of a building management company.

On presentation, his blood pressure was 174/92 mmHg, pulse rate 80 beats per minute, and respiratory rate 16 breaths per minute with an O2 saturation of 99% on room air. The cardiovascular examination findings were normal, his lungs were clear on auscultation, and no subcutaneous edema was observed. Laboratory examinations revealed elevated levels of blood urea nitrogen (27.9 mg/dL) and creatinine (2.93 mg/dL). Although carcinoembryonic antigen (2.8 ng/mL) and cytokeratin 19 fragment (1.6 ng/mL) levels were not elevated, an increased level of progastrin-releasing peptide (83.5 pg/mL) was found because of renal failure. The results of the pulmonary function tests were within normal limits.

A chest radiograph revealed a tumorous shadow on the right middle-lobe field (Fig. 1). Computed tomography (CT) revealed an abnormal mass with spicula on the right middle lobe that had infiltrated the right upper lobe (Fig. 2A-C). Fluorodeoxyglucose positron emission tomography (FDG-PET) indicated a low uptake of FDG (maximum standardized uptake value, 1.9) in this lesion (Fig. 2D).

Figure 1.

Chest radiograph showing nodular opacity in the right middle field.

Figure 2.

(A-C) Chest CT without contrast showing a nodular lesion with spicula and infiltration into the upper lobe. (D) PET-CT showing the slight uptake of FDG (SUVmax 1.9).

In light of these findings, bronchofiberscopy was performed. A transbronchial biopsy from the right B4b using radial endobronchial ultrasonography with a guide sheath revealed no malignant cells in the specimen. A second attempt of bronchofiberscopy revealed the same result. To establish a definite diagnosis, the patient underwent video-assisted thoracoscopic surgery. An elastic hard tumor in the right middle lobe and its infiltration and adhesion into the right upper lobe was identified. Therefore, resection of the right middle lobe and part of the right upper lobe was performed.

The postoperative course was uneventful, and the patient was discharged. A histological analysis demonstrated complicated proliferation of thick collagen fibers surrounded by lymphoplasmacytic infiltrate (Fig. 3). No atypical epithelial cells were found. Amyloid was not detected with Congo red stain. These histopathological findings led to the diagnosis of PHG. The patient received no specific subsequent treatment and remained asymptomatic.

Figure 3.

(A, B) Histopathology of the resected tumor in the right middle lobe with part of the upper lobe (Hematoxylin and Eosin staining, A: × 40, B: × 400). Complicated proliferations of thick collagen fibers were found in association with surrounded lymphocyte infiltration. No atypical epithelial cells were found.

Discussion

First reported by Benfield et al. in 1964 (3) and characterized by Engleman et al. in 1977 (1), PHG is a rare benign condition. The etiology and pathogenesis of this tumor remain unknown. PHG has been previously reported to be associated with immune disorders, such as sclerosing mediastinitis, rheumatoid arthritis, multiple sclerosis, Sjögren syndrome, granulomatosis with polyangiitis, primary biliary cirrhosis, and membranous glomerulonephritis (4, 5). Although our patient developed renal failure, the findings for antinuclear antibody, antineutrophil cytoplasmic antibody, and other autoantibodies were negative. Furthermore, no evidence of arthralgia, erythema, or other signs of collagen vascular diseases was noted. The differential diagnosis of PHG includes infectious diseases, such as tuberculosis, histoplasmosis, and fungal infections (2, 4). In this case, bronchial wash fluid for bacterial infection, including Mycobacterium tuberculosis, was negative.

PHG tumors often exist in the subpleural pulmonary parenchyma. Histopathologically, hyalinized lamellar collagen bundles are found in the central area surrounded by lymphocyte and plasma cell infiltrates. Bronchoalveolar lavage and a transbronchial biopsy reportedly do not permit the diagnosis of PHG (2). A bronchoscopic biopsy might fail to make an accurate diagnosis because this tumor comprises a central hard and peripheral soft lesion. Therefore, a CT-guided percutaneous biopsy or surgical resection should be considered to confirm the diagnosis.

In the literature review, isolated or multiple nodular lesions were the most frequent findings, sometimes with excavation and/or calcification (2, 5-8), and parenchymal infiltration and condensation were rare conditions. In this case, the tumor was initially suspected to be primary lung cancer. It was radiologically observed to be spiculated and to have infiltrated into another pulmonary lobe, and this feature was quite similar to those of primary lung neoplasm. To our knowledge, there have been no reports of PHG cases with infiltration into the adjacent lobe. It is difficult to distinguish between PHG and lung cancer by radiological findings alone. Both PHG and lung cancer radiologically appear to be solitary or multiple nodules with well-defined or irregular borders. A histopathological evaluation is therefore very important for making an accurate diagnosis. A 3-mm-diameter hyalinizing nodule with anthracosis near the resected tumor was noted, and silicate crystals were found using polarized light microscopy. Although the resected tumor showed no silicotic nodules, silicosis may have affected the development of PHG in this case.

The prognosis of PHG is generally favorable. A single nodule can be cured by surgical resection, whereas multiple nodules cannot. Some publications recommend glucocorticoid treatment for PHG (2, 9); however, the efficacy of this approach remains unclear. No effective treatment has yet been established for multiple nodules of PHG.

In conclusion, this case should remind clinicians to consider PHG as a possible cause of pulmonary tumor found on imaging. Furthermore, histological examinations with proper specimens are required to make an accurate diagnosis of PHG.

The authors state that they have no Conflict of Interest (COI).