Jpn J Radiol (2013) 31:766–769 DOI 10.1007/s11604-013-0250-4
CASE REPORT
Pulmonary alveolar microlithiasis: imaging characteristics of planar and SPECT/CT bone scan versus 18F-FDG and 18F-sodium fluoride PET/CT scanning Manas Kumar Sahoo • Sellam Karunanithi Chandra Shekhar Bal
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Received: 25 August 2013 / Accepted: 17 September 2013 / Published online: 2 October 2013 Ó Japan Radiological Society 2013
Abstract Pulmonary alveolar microlithiasis (PAM) is a very rare disease in which multiple microscopic calcium phosphate microliths are deposited within the alveoli of both lungs. A lung biopsy is considered to be definitive for final diagnosis; however, non-invasive imaging modalities such as chest X-ray, HRCT scan and 99mTc-MDP bone scan suggest the diagnosis in the vast majority of patients. Although 18F-FDG PET/CT has been tried to characterize the disease, 18F-sodium fluoride PET/CT as a ‘proof-ofprinciple’ was tried for the first time in a known case of PAM in order to characterize the lung lesions. Interestingly, we noted that 18F-sodium fluoride PET/CT is a superior modality in characterization and assessment of the extent of disease in PAM compared to all other non-invasive imaging modalities. Thus, we recommend that 18Fsodium fluoride PET/CT should be the investigation of choice in PAM. Keywords Pulmonary alveolar microlithiasis Sodium fluoride PET/CT FDG PET/CT 99m Tc-MDP bone scintigraphy
M. K. Sahoo S. Karunanithi C. S. Bal (&) Department of Nuclear Medicine, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, India e-mail:
[email protected] M. K. Sahoo e-mail:
[email protected] S. Karunanithi e-mail:
[email protected]
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Introduction Pulmonary alveolar microlithiasis (PAM) is a rare disease in which multiple microscopic calcium phosphate microliths are deposited within the alveoli of both lungs, probably due to mutation in the type IIb sodium-phosphate co-transporter gene (SCL34A2 gene) [1]. PAM is also associated with similar calcification in extra-pulmonary sites like the sympathetic nervous system, testes and seminal vesicles [2, 3]. In the workup of the patient, chest radiography and high resolution computed tomography (HRCT) play important roles that obviate the need for a lung biopsy. 99mTc-methylene diphosphonate (MDP) bone scintigraphy has been shown to be useful in the management of PAM [4]. Recently, some studies have shown the variable pattern of abnormal accumulation of 18F-fluoro-2deoxyglucose (FDG) in the lungs [5, 6]. No head-to-head comparative study has been published in the literature using 99mTc-MDP planar scintigraphy, single photon emission computed tomography (SPECT)/CT, and 18FFDG positron emission tomography (PET)/CT. Moreover, there has not yet been a comparison of 18F-sodium fluoride PET/CT with 18F-FDG PET/CT. We report the first case of a 54-year-old male with PAM presenting without any significant increase in 18F-FDG uptake in bilateral lungs but showing intensely increased 18F-sodium fluoride uptake involving bilateral lungs resembling ‘‘hot furnace lungs’’ in 18F-sodium fluoride PET/CT.
Case report A 54-year-old male patient presented with a 9-year history of exertional dyspnea. He was a non-smoker. No significant medical and family history was obtained except a 7-year
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history of histopathologically proven PAM. Physical examination revealed presence of the chest wall deformity (pectus excavatum). Other systemic examinations, including cardiac, were unremarkable. Routine laboratory tests, namely complete blood count, liver function tests and kidney function tests, C-reactive protein, erythrocyte sedimentation rate, and serum electrolytes including calcium level, were within normal limits. Immunological workups were within normal limits (normal IgG and subclasses, IgM, IgA, normal WBC differentiation and immune phenotyping, normal complement, normal lymphocyte stimulation tests, no auto antibodies). An ultrasonogram of the abdomen revealed no gross abnormality except for mild fatty changes in the liver. The pulmonary function test demonstrated a restrictive pattern of lung disease with parameters as follows: forced vital capacity (FVC) was 40 % of predicted value, forced expiratory volume in 1st second (FEV1) was 48 % of predicted value, FEV1/FVC was found to be 92 %, diffusion capacity of the lung for carbon monoxide (DLCO): 42 mmol/kPa min and DLCO/ alveolar volume (VA) was 78 mmol/kPa min/l. The whole-body planar scintigraphy showed diffuse 99m Tc-MDP uptake in both lungs with classical ‘sandstorm’ appearance (Fig. 1a). SPECT/CT at the same time confirmed the calcified micro-nodules as having a bilateral diffuse interstitial pattern and bilateral apical fibrotic changes (Fig. 2a, b). 18F-FDG PET/CT which was performed after 3 days to evaluate the inflammatory status in the lungs did not show any significantly increased 18F-FDG uptake in both lungs (Fig. 1b, c). 18 F-sodium fluoride PET/CT was done after 7 days of bone scan, and revealed intensely increased radiotracer uptake in both the lungs which was termed by the authors
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as an appearance of ‘hot furnace lung’ (Figs. 1c, 2d). A maximum intensity projection (MIP) view of 18F-sodium fluoride PET/CT showed the absence of any extra-pulmonary sites of calcification in PAM. Unlike 18F-FDG PET/CT, which is based on inflammatory pathology in PAM, 18F-sodium fluoride PET/CT is based on increased avidity of fluoride for the microliths (hydroxyl-apatite crystals).
Discussion Chemical analysis and energy dispersion X-ray microanalysis of the microliths have demonstrated calcium phosphate to be the main constituent. The mean diameter of the microliths varies in size from 0.01 to 3 mm [7]. The chest radiography in PAM in adults reveals ground-glass or fine sand-like and sometimes a nodular pattern of opacities. Classic ground-glass opacities are most often seen in X-rays of children suffering from PAM. HRCT is useful in the identification of minimal structural changes in the lung parenchyma along with calcified microliths even smaller than 1 mm [8]. Conventional CT scans demonstrate these micronodular calcifications mostly in the sub-pleural parenchyma location and along the bronchovascular bundles. Long-standing PAM is also associated with similar calcification in extra-pulmonary sites like the sympathetic nervous system, testes and seminal vesicles [2, 3]. Though chest X-ray and HRCT have a role in diagnosis, they have limitations in detecting extra-pulmonary calcium depositions. 99m Tc-MDP bone scintigraphy traces the pulmonary uptake of 99mTc-MDP in a diffuse ‘‘sandstorm’’-like
Fig. 1 a 99mTc-MDP wholebody skeletal scintigraphy showing ‘sandstorm’ appearance of increased radiotracer uptake involving bilateral lungs. b MIP image of 18 F-FDG PET showing physiological uptake and without any significant increase in radiotracer uptake in lungs. c MIP image of 18F-sodium fluoride PET showing intensely increased radiotracer uptake involving bilateral lungs to a greater extent than seen in 99m Tc-MDP skeletal scintigraphy. Besides physiological bladder uptake, there is no other abnormal site of radiotracer uptake which rules out extra-pulmonary calcification
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Fig. 2 a Transaxial view of SPECT image showing increased radiotracer uptake suggestive of calcification in bilateral lungs. b Transaxial view of CT image of the patient showing microcalcification in bilateral lungs c Transaxial view of 18F-FDG PET showing physiological cardiac uptake and without any significantly increased
radiotracer uptake in lungs. d Transaxial view of 18F-sodium fluoride PET showing intensely increased bilateral pulmonary radiotracer uptake defining a larger extent of pathological involvement than noted by all other modalities
pattern in PAM [4]. Whole body assessment is an advantage of bone scan over chest X-ray and CT scan. The role of 18F-FDG PET/CT in PAM has been suggested by few authors showing variable pattern of uptake involving bilateral lungs which has been explained to be an evidence of inflammatory status of the lungs [5, 6]. As there is a possibility of extra-pulmonary calcium deposition in long-standing cases of PAM, a better diagnostic modality with higher spatial resolution for whole body assessment is required for accurate diagnosis. With this hypothesis in mind, we tried to compare the planar bone scan with SPECT/CT, 18F-FDG PET/CT and 18Fsodium fluoride PET/CT in PAM. We tested the hypothesis that 18F-sodium fluoride PET/ CT should have better imaging characteristics than 99mTcMDP bone scintigraphy, due to the superior image quality of 18F-sodium fluoride as a bone-seeking radiopharmaceutical, and the better resolution of PET/CT over planar scintigraphy and SPECT/CT. SPECT/CT was found superior over planar scintigraphy as it could demonstrate well
the MDP uptake in a three-dimensional manner along with the CT correlation, slice by slice (Fig. 1c). Interestingly, we did not observe any significant increase in 18F-FDG uptake in the bilateral lungs in our patient (Figs. 1b, 2c), indicating that in long-standing PAM the inflammatory process might have been burnt out. Hence, in our patient 18 F-FDG PET/CT was not very informative; supporting an earlier study by Shah et al. [9]. Our hypothesis was found correct, as we observed that pulmonary involvement in PAM clearly showed up with a ‘hot furnace’ appearance on 18F-sodium fluoride PET/CT in our patient. The better appreciation of the microliths in 18 F-sodium fluoride PET/CT is attributed to the increased avidity of 18F-sodium fluoride for calcification than 99mTcMDP, and the increased spatial resolution of PET over planar scintigraphy and SPECT. Besides, the soft-tissue half-value layers for the 511-keV photons from 18F and 140-keV photons in case of 99m Tc are 7.3 and 4.6 cm, respectively, so that 511-keV photons can deliver their energy to organs distant from the source organ, whereas the
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140-keV photons will deliver more of their energy to organs near the source organ [10]. Additionally, 18Fsodium fluoride PET/CT also confirmed the absence of any extra-pulmonary involvement in the same setting. Although 18F-sodium fluoride PET/CT imaging is superior to 99mTc-MDP bone scintigraphy, it suffers from several logistic limitations; namely poor availability, high examination cost, and no reimbursement by insurance companies in most countries. However, we feel that with an increasing number of cyclotron facilities available, and 18 F-sodium fluoride being a by-product of 18F-FDG synthesis (18F-FDG being widely distributed), the availability of 18F-sodium fluoride should not be an issue. Interestingly, 18 F-sodium fluoride was FDA approved way back in the 1980&s. Reimbursement remains an issue that needs to be sorted out by the nuclear medicine community. On the basis of our observation, we recommend that whenever there is clinical suspicion of PAM, or in a proven case of long-standing PAM, 18F-sodium fluoride PET/CT should be the preferred modality for confirmation of diagnosis and better delineation of disease extent. Conflict of interest
None.
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