Probe-based Confocal Laser Endomicroscopy in Metastatic Pulmonary Calcification

Abstract

We report a case of metastatic pulmonary calcification in a patient with chronic renal failure on hemodialysis and secondary hyperparathyroidism. The diagnosis was made by using a probe-based confocal endomicroscopy which showed specific structures in the lung tissue and was proven by a transbronchial lung biopsy. To the best of our knowledge, this is the first reported case of the confocal endomicroscopy findings in a patient with metastatic pulmonary calcification.

Metastatic pulmonary calcification (MPC) is one of the types of pulmonary calcification in which calcium salts accumulate in lung tissue (metabolic lung diseases). In contrast to dystrophic calcification, it develops in healthy tissue without prior injuries.^1,2 It is known that MPC is found in 60% to 75% of hemodialyzed patients with renal failure at autopsy.³ Some authors have described a rapidly progressive disease that leads to acute respiratory insufficiency and death.^4,5 MPC is characterized by centrilobular ground-glass nodular opacities on computed tomographic scans, with many poorly defined nodules measuring 3 to 10 mm in diameter predominantly in upper lung lobes.⁶ However, calcific nature of these nodules is identified on standard computed tomographic scans in approximately 60% of cases.⁷ Transbronchial or surgical lung biopsy can prove the diagnosis of MPC.

We report a case of using a probe-based confocal laser endomicroscopy (pCLE) in the diagnosis of MPC.

CASE REPORT

A nonsmoking 50-year-old man suffered with chronic glomerulonephritis in a stage of renal failure. He required hemodialysis since 2011. He underwent subtotal parathyroidectomy for adenoma of parathyroid glands in 2014.

The radiographic changes in lungs were revealed during the routine examination in October 2016. Radiographs suggested the diagnosis of tuberculosis.

The patient was admitted to the Center of Thoracic Surgery on November 9, 2016. Physical examination showed no abnormalities. Blood analysis revealed an increased level of creatinine 852 U/L (range: 53 to 115 U/L). Tuberculin skin test was negative. Level of parathyroid hormone was 257 pg/mL (56 pg/mL).

High-resolution computed tomography (HRCT) was performed on November 10. There were revealed multiple diffuse calcified nodules, centrilobular ground-glass opacities, diffuse or patchy areas of ground-glass opacity or consolidation, and confluent high-attenuation parenchymal consolidation (Fig. 1).

FIGURE 1: Axial computed tomographic scan shows multiple calcified nodules and centrilobular ground-glass nodular opacities in left upper lobe.

Bronchoscopy was performed on November 17 which did not reveal any abnormalities in the bronchial tree. Confocal laser probe was introduced through the working channel of the bronchoscope to obtain pCLE images. Bronchial wall structure showed no abnormalities. During alveoloscopy, we revealed some round structures of different sizes in the alveolar tissue with increased autofluorescent signals mostly involving the upper lobes (Fig. 2).

FIGURE 2: Probe-based confocal laser endomicroscopy of the right upper lobe. Some round structures with different sizes visualized in alveolar tissue.

Bronchoalveolar lavage (BAL) was obtained from this location and the pCLE was repeated. The pCLE image showed no difference before and after the BAL procedure (Figs. 3A, B)

FIGURE 3: Probe-based confocal laser endomicroscopy after bronchial lavage imaging of lung alveoli showed round-shaped structures with increased autofluorescent signal in lung interstitium (A, B).

Transbronchial lung biopsy was obtained from the same subsegmental bronchus. Histologic examination revealed accumulation of calcium salts in lung interstitium, which is unique to MPC (Figs. 4A, B).

FIGURE 4: Histologic examination of a transbronchial lung biopsy specimen (hematoxylin and eosin staining, ×100) showed small spherical homogenous basophil calcispherities in sclerotic intraalveolar septies (A) and bronchial walls (B) with a few foreign body giant cells.

DISCUSSION

The chest x-ray had a reduced sensitivity of identification of MPC.^6,7 X-ray findings in our patient were not sufficient to exclude the diagnosis of tuberculosis. An HRCT is more useful to diagnose the condition of MPC. The condition has been described in 3 different patterns: multiple diffuse calcified nodules, diffuse or patchy areas of ground-glass opacity or consolidation, and confluent high-attenuation parenchymal consolidation with a predominantly lobar distribution. The upper zones of the lungs are mostly affected by calcification due to increased alkalinity at the apices, which encourages the deposition of calcium salts.^5,7 In our patient, HRCT picture was also suggestive of other diagnoses including alveolar proteinosis and amyloidosis. Specificity of confocal endomicroscopy for this diagnosis was published recently.^8,9 We decided to use pCLE for the verification and control of alveolar proteinosis treatment effectiveness. According to pCLE, the images were not suggestive of the diagnosis of alveolar proteinosis. Hence we performed a BAL. Incidentally we did not find any changes in the pCLE images following the BAL. Therefore we decided to perform a transbronchial biopsy.

We used pCLE in this patient with the disseminated pulmonary disease who had a long-standing history of chronic renal insufficiency, prolonged hemodialysis and secondary hyperparathyroidism. We observed round structures of different sizes with increased autofluorescent signals throughout the interstitium and the perivascular spaces of the lung. Histologic examination of the material obtained by transbronchial lung biopsy proves the diagnosis of MPC. In 2013 Yserbyt et al⁸ described images of pulmonary alveolar microlithiasis (PAM) using a pCLE. Pulmonary alveolar microlitiasis is an autosomal recessive heritable disease which is associated with SLC34A2 gene mutation.^6,8 The primary distinction of the histopathologic image of PAM from MPC is a location of calcispherites. In PAM it filled the alveolar spaces with either a normal or thickened fibrotic interstitium while in MPC the calcification is only seen in the interstitium and the perivascular spaces.^1,8

Transbronchial lung biopsy is the method of choice for verification of numerous pulmonary conditions. However the procedure can be dangerous in patients with uremia.¹⁰

We performed a confirmatory pCLE after performing the BAL which showed stability of the observed abnormality. We believe that this approach can be used for confirmation of the diagnosis of MPC without transbronchial lung biopsy in patients with chronic renal failure.