Multinodular lung infiltrate in a patient with lymphoma: metastasis, tuberculosis or other?

The differential diagnosis of multinodular lung disease includes miliary tuberculosis, pneumoconiosis, sarcoidosis and metastases. In many cases, high-resolution computed tomography can help the diagnosis, but sometimes, tissue diagnosis may be necessary. We report a case of malignant lymphoma on a background of pre-existing silicosis, distinguished from miliary tuberculosis by percutaneous needle lung biopsy.

INTRODUCTION

Common causes of miliary lung disease include tuberculosis, pneumoconiosis, sarcoidosis and metastases. In many cases, a careful history combined with high-resolution computed tomography (HRCT) will be diagnostic, but in some cases differentiation is more difficult. We report a case of malignant lymphoma concomitant with a silicotic multinodular lung infiltrate that was quickly distinguished from miliary tuberculosis (TB) by lung biopsy, which allowed the patient to begin chemotherapy without delay.

CASE REPORT

A 78-year-old man was admitted to our hospital with dyspnea. He had never been a smoker and had no family history of lung disease. His past medical history was notable for atrial fibrillation and congestive heart failure, and he was taking warfarin, famotidine and furosemide. He had been a mine worker for 30 years. Vital signs at admission were blood pressure 190/118 mmHg, pulse 102/min, temperature 36.0°C and respiratory rate 28/min. The oxygen saturation was 96% on 3 L supplemental oxygen via nasal cannulae. On physical examination, the breath sounds were decreased bilaterally and the heart sounds were muffled. Notable laboratory abnormalities included a white blood cell count of 13 900/mm3 with a left shift, a serum lactate dehydrogenase level of 942 U/L (normal 112–213 U/L), serum aspartate and alanine aminotransferase levels of 1072 and 1561 U/L (normal 13–34 and 7–37 U/L), serum albumin level of 3.1 g/dL (normal 4.1–5.1 g/dL), serum C-reactive protein level of 6.8 mg/dL (normal < 0.3 mg/dL), and serum soluble interleukin-2 receptor (sIL-2 R) level of 2760 U/mL (normal 145–519 U/mL). Serum T-SPOT, TB, and human T-cell lymphotropic virus-1 tests were all negative. Echocardiography showed a moderate pericardial effusion with a normal ejection fraction, and 12-lead electrocardiogram showed atrial fibrillation. Chest x-ray showed bilateral pleural effusions with multiple tiny lung nodules (Fig. 1A) and computed tomography (CT) showed moderate bilateral pleural effusion, pericardial effusion and diffuse bilateral micronodular lung infiltration (Fig. 1B). Pericardiocentesis and pleurocentesis were performed on hospital Day 2, and the cytology showed malignant lymphoma (Fig. 2A). It became more urgent to rule out miliary TB so the patient could quickly start chemotherapy. Bone marrow biopsy and percutaneous lung biopsy were performed, and no granuloma or malignancy was detected (Fig. 2B). Acid-fast stain, culture and polymerase chain reaction for mycobacteria in biopsy specimens (bone marrow and lung), sputum, gastric aspirate, urine and pericardial and pleural fluid were all negative. The lymphoma was classified as T-cell type by CD45 gating (CD3+, 4+, 8+, 19−, 20−), and since miliary TB had been definitively excluded by hospital Day 4, we were able to initiate low dose THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) therapy on hospital Day 5. Repeat CT on Day 7 of chemotherapy showed no change in the diffuse micronodular lung infiltrate. The patient developed a neutropenic fever on Day 13 of chemotherapy and was treated with antibiotics until the neutrophil count recovered. He was moved to another hospital on hospital Day 23 and was to continue chemotherapy.

Figure 1:

chest radiograph at admission showing bilateral pleural effusions and multiple tiny lung nodules (A). Contrast-enhanced computed tomography at admission showing moderate, bilateral pleural effusion, pericardial effusion (B) and diffuse micronodules (C).

Figure 2:

cytologic examination of pericardial and pleural effusion revealed malignant lymphoma (A). The percutaneous lung biopsy results were negative for granuloma and malignancy (B).

DISCUSSION

CT or HRCT can help to narrow the differential diagnosis of multinodular lung infiltrates [1]. In particular, the distribution (centrilobular, perilymphatic or random) of the micronodules can provide valuable diagnostic clues [2]. Centrilobular distribution, in which nodules are seen in the airway and far from the pleural space, is commonly associated with hypersensitivity pneumonia and certain infectious diseases. Perilymphatic distribution is commonly seen in association with sarcoidosis and pneumoconiosis, and the nodules are mainly seen in the in the peribronchovascular interstitium, the interlobular septa, the subpleural regions, and the centrilobular interstitium. Random distribution of nodules is associated with miliary TB, miliary fungal infections and hematogenous metastases. Our patient had a large number of micronodules that seemed to be located in the airway and in the subpleural region, and it was difficult to narrow the diagnosis. Based on the history, we considered miliary TB, metastatic lymphoma and silicosis. Given his occupational history, we thought silicosis was the most likely diagnosis, but it was important to rule out infectious disease and metastases before starting chemotherapy. Silicosis is caused by inhalation of free crystalline silica dust, and silicotic patients are at high risk of developing pulmonary and extrapulmonary TB [3].

Acid-fast stain and culture are often negative in patients with miliary TB, which may delay diagnosis. Biopsy may be necessary for more rapid diagnosis [4]. The Fleischner Society guideline [5] recommends an invasive approach to diagnosis and management only after a follow-up CT examination at 3 months after the initial study. However, because we needed to rule out infectious diseases before initiating chemotherapy, we performed a percutaneous lung biopsy promptly after the initial CT. We chose percutaneous lung biopsy rather than transbronchial biopsy because of our patient's decreased performance status. In terms of the diagnostic value of percutaneous lung biopsy for military lung diseases, Peng et al. [6] have reported that CT-guided percutaneous cutting needle lung biopsy of diffuse parenchymal lung disease has a high diagnostic yield in patients with infectious or neoplastic diseases, and Gupta et al. [7] reported that percutaneous CT-guided needle biopsy had high diagnostic yield for pulmonary lesions of various etiologies in patients with hematologic malignancies. In the present case, an early percutaneous lung biopsy allowed us to definitively exclude miliary TB and metastatic disease in a patient with lymphoma and diffuse micronodular lung infiltration.