El papel de la PET/TC con 2-[18F]FDG en la enfermedad de Erdheim-Chester / The role of 2-[18F]FDG PET/CT in Erdheim-Chester disease

Objetivo Analizar la distribución corporal de la enfermedad Erdheim-Chester (ECD) y determinar la utilidad de la 2-[18F]FDG-PET/TC frente a otras técnicas de imagen. Asimismo, evaluar la agresividad y la extensión de la enfermedad según la presencia/ausencia de mutación BRAFV600E. Material y métodos Se revisaron las 2-[18F]FDG-PET/TC de todos los pacientes diagnosticados con ECD entre 2008 y 2021: en total, 19 pacientes. Los territorios afectados se clasificaron como detectables por PET/TC o detectables solamente por otras técnicas de imagen (gammagrafía ósea, TC con contraste yodado o RM). Se realizó análisis descriptivo y correlación de la mutación BRAF con los órganos afectados y SUVmáx mediante la prueba t de Student. Resultados De los 19 pacientes (14 hombres; edad media 60,3años), 11 presentaban la mutación BRAFV600E. Se detectaron un total de 127 territorios (64 órgano-sistemas) afectados utilizando las diferentes modalidades de imagen, de los cuales 112 fueron detectados por la PET/TC y 15 territorios adicionales fueron identificados únicamente por la RM cerebral y cardiaca. La presencia de mutación BRAFV600E se asoció con mayor afectación orgánica (p<0,05), sin diferencias en el SUVmáx (p>0,05). Conclusión La 2-[18F]FDG-PET/TC es una prueba de alto rendimiento diagnóstico en pacientes con ECD, detectando la mayoría de los territorios afectados. La RM fue la única prueba de imagen con hallazgos adicionales en territorios con alta captación fisiológica de 2-[18F]FDG (cerebral y cardíaca). La presencia de mutación del BRAFV600E se correlacionó con mayor extensión de la enfermedad (AU)

Objective To analyze the body distribution of Erdheim-Chester disease (ECD) and determine the utility of 2-[18F]FDG PET/CT compared to other imaging techniques. Additionally, to assess the aggressiveness and extent of the disease based on the presence/absence of the BRAFV600E mutation. Materials and methods The 2-[18F]FDG PET/CT scans of all patients diagnosed with ECD between 2008 and 2021 were reviewed, including 19 patients. The affected territories were classified as detectable by PET/CT or detectable only by other imaging techniques (bone scintigraphy, contrast-enhanced CT, or MRI). Descriptive analysis and correlation of the BRAF mutation with the affected organs and maximum SUV were performed using the Student's t-test. Results Out of the 19 patients (14 males; mean age 60.3years), 11 had the BRAFV600E mutation. A total of 127 territories (64 organ-systems) affected were identified using different imaging modalities, of which 112 were detected by PET/CT, and an additional 15 territories were solely identified by cerebral and cardiac MRI. The presence of BRAFV600E mutation was associated with greater organ involvement (P<.05) without differences in SUVmax (P>.05). Conclusion 2-[18F]FDG PET/CT is a highly effective diagnostic tool in patients with ECD, detecting the majority of affected territories. MRI was the only imaging modality with additional findings in territories showing high physiological uptake of 2-[18F]FDG (cerebral and cardiac). The presence of the BRAFV600E mutation correlated with a higher extent of the disease (AU)

The role of 2-[18F]FDG PET/CT in Erdheim-Chester disease.

OBJECTIVE: To analyze the body distribution of Erdheim-Chester disease (ECD) and determine the utility of 2-[18 F]FDG PET/CT compared to other imaging techniques. Additionally, to assess the aggressiveness and extent of the disease based on the presence/absence of the BRAFV600E mutation. MATERIALS AND METHODS: The 2-[18F]FDG-PET/CT scans of all patients diagnosed with ECD between 2008 and 2021 were reviewed, including 19 patients. The affected territories were classified as detectable by PET/CT or detectable only by other imaging techniques (bone scintigraphy, contrast-enhanced CT, or MRI). Descriptive analysis and correlation of the BRAF mutation with the affected organs and maximum SUV were performed using the Student's t-test. RESULTS: Out of the 19 patients (14 males; mean age 60.3 years), 11 had the BRAFV600E mutation. A total of 127 territories (64 organ-systems) affected were identified using different imaging modalities, of which 112 were detected by PET/CT, and an additional 15 territories were solely identified by cerebral and cardiac MRI. The presence of BRAFV600E mutation was associated with greater organ involvement (p < 0.05) without differences in SUVmax (p > 0.05). CONCLUSION: 2-[18F]FDG PET/CT is a highly effective diagnostic tool in patients with ECD, detecting the majority of affected territories. MRI was the only imaging modality with additional findings in territories showing high physiological uptake of 2-[18F]FDG (cerebral and cardiac). The presence of the BRAFV600E mutation correlated with a higher extent of the disease.

Rheumatic immune-related adverse events in patients on anti-PD-1 inhibitors: Fasciitis with myositis syndrome as a new complication of immunotherapy.

OBJECTIVE: To evaluate the prevalence and type of rheumatic immune-related adverse events (IRAEs) in patients receiving programmed cell death protein-1 (PD-1) inhibitors. METHODS: This is a single-center prospective observational study, including all cancer patients receiving PD-1 inhibitors between January 2016 and January 2018. RESULTS: During the period analyzed, we evaluated a total of 11 patients. No patient had pre-existing rheumatic or autoimmune disease. In this period, a total of 220 patients were treated with PD1 inhibitors in our center; therefore, the estimated minimum prevalence of rheumatic IRAEs related to these therapies in our population was 5%. The rheumatic IRAEs evaluated included 5 cases of oligo- or polyarthritis, 1 with a polymialgia rheumatica-type syndrome, 2 cases of immunotherapy-induced sicca syndrome, 2 patients who presented symptomatic inflammatory myositis with fasciitis in lower extremities, and 1 patient with a paraneoplastic acral vascular syndrome. The median time to IRAE after anti-PD1 exposure was 8 weeks (range: 2-24). In 5 patients, immunotherapy was discontinued (due to the adverse effect in three and cancer progression in two). In general terms the symptoms resolved completely with symptomatic treatment. Disease-modifying antirheumatic drugs were needed for 2 patients. CONCLUSION: Rheumatic IRAEs should be kept in mind during the follow-up and evaluation of patients treated with PD-1 inhibitors. The concomitant development of symptomatic inflammatory myositis with fasciitis in lower extremities appears to be a new adverse effect of anti-PD-1 immunotherapy. Additional studies are needed to determine how to adequately control and manage these complications.

Mapping of methionine-enkephalin-arg6-gly7-leu8 in the human diencephalon.

Using an immunohistochemical technique, we mapped the immunoreactive structures containing methionine-enkephalin-Arg6-Gly7-Leu8 (Met-8) (a marker for the pro-enkephalin system) in the human diencephalon. Compared with previous studies, we observed a more widespread distribution of Met-8 in the human diencephalon. Met-8-immunoreactive cell bodies and fibers exhibited a more widespread distribution in the hypothalamus than in the thalamus. We observed six populations of Met-8-immunoreactive cell bodies. These perikarya were observed in the paratenial thalamic nucleus, ventromedial and dorsomedial hypothalamic nuclei, lateral hypothalamic area, pallidohypothalamic nucleus and in the paraventricular hypothalamic nucleus (posterior part). In the thalamus, Met-8-immunoreactive fibers were primarily observed in the midline region, whereas in the hypothalamus, these fibers were widely distributed. In general, a moderate/low density of Met-8-immunoreactive fibers was observed in the diencephalic nuclei. A moderate density was observed in the paraventricular thalamic nucleus, reuniens thalamic nucleus, lateral and medial geniculate nuclei, dorsomedial hypothalamic nucleus, paraventricular hypothalamic nucleus (posterior part) and ventromedial hypothalamic nucleus. The present study is the first to demonstrate the presence of clusters of Met-8-immunoreactive cell bodies in the human thalamus and hypothalamus, the distribution of fibers containing neuropeptides in the hypothalamus and the presence of these fibers in several thalamic nuclei. This neuroanatomical study will serve to elucidate the physiological roles of Met-8 in future studies of the human diencephalon.

Rheumatic diseases of the spine: imaging diagnosis. / Enfermedades reumatológicas en la columna vertebral: diagnóstico radiológico.

Spinal involvement is common both in the spondyloarthritides and in rheumatoid arthritis, in which the cervical segment is selectively affected. Rheumatoid involvement of the cervical spine has characteristic radiologic manifestations, fundamentally different patterns of atlantoaxial instability. Magnetic resonance imaging (MRI) is the technique of choice for evaluating the possible repercussions of atlantoaxial instability on the spinal cord and/or nerve roots in patients with rheumatoid arthritis as well as for evaluating parameters indicative of active inflammation, such as bone edema and synovitis. Axial involvement is characteristic in the spondyloarthritides and has distinctive manifestations on plain-film X-rays, which reflect destructive and reparative phenomena. The use of MRI has changed the conception of spondyloarthritis because it is able to directly detect the inflammatory changes that form part of the disease, making it possible to establish the diagnosis early in the disease process, when plain-film X-ray findings are normal (non-radiographic axial spondyloarthritis), to assess the prognosis of the disease, and to contribute to treatment planning.

Guidelines for magnetic resonance imaging in axial spondyloarthritis: A Delphi study.

OBJECTIVE: The term axial spondyloarthritis refers to a group of chronic inflammatory rheumatic diseases with a common genetic basis that course with axial and peripheral involvement and enthesitis. Recently, the Assessment of SpondyloArthritis international Society (ASAS) established some diagnostic criteria, including for the first time magnetic resonance imaging (MRI) findings. Given the difficulties of obtaining MRI in some environments and the lack of experience with axial spondyloarthritis, a group of radiologists and rheumatologists sought to establish some practical guidelines to ensure the correct use of MRI in this disease. MATERIAL AND METHODS: Using the Delphi method, we used a questionnaire with 49 items stratified into 4 blocks to survey 46 experts in the MRI diagnosis of axial spondyloarthritis. RESULTS: The experts agreed on 82% of the items. The degree of agreement was 100% in the block "Importance of early diagnosis of axial spondyloarthritis", 69% in the block "Optimization of the use of MRI in the diagnosis of axial spondyloarthritis", 93% in the block "Use of MRI in axial spondyloarthritis: Technical aspects", and 57% in the block "Usefulness of MRI in the prognosis, follow-up, and evaluation of the response to treatment in axial spondyloarthritis". CONCLUSIONS: Despite the importance of MRI in the early diagnosis of axial spondyloarthritis, this study shows the need for standardization and points to relative disagreement about how to use MRI in the follow-up of the disease and evaluation of the response to treatment. The results of this study can help improve the use of MRI in axial spondyloarthritis.

Immunohistochemical mapping of pro-opiomelanocortin- and pro-dynorphin-derived peptides in the alpaca (Lama pacos) diencephalon.

Using an indirect immunoperoxidase technique, we studied the distribution of cell bodies and fibres containing non-opioid peptides (adrenocorticotropin hormone (ACTH), alpha-melanocyte-stimulating hormone) and opioid peptides (beta-endorphin (1-27), alpha-neo-endorphin, leucine-enkephalin) in the alpaca diencephalon. No immunoreactive cell bodies containing ACTH were found. Perikarya containing the other four peptides were observed exclusively in the hypothalamus and their distribution was restricted. Perikarya containing alpha-melanocyte-stimulating hormone or alpha-neo-endorphin showed a more widespread distribution than those containing leucine-enkephalin or beta-endorphin (1-27). Cell bodies containing pro-opiomelanocortin-derived peptides were observed in the arcuate nucleus, anterior and lateral hypothalamic areas and in the ventromedial and supraoptic hypothalamic nuclei, whereas perikarya containing alpha-neo-endorphin (a pro-dynorphin-derived peptide) were found in the arcuate nucleus, dorsal and lateral hypothalamic areas, and in the paraventricular, ventromedial and supraoptic hypothalamic nuclei. Immunoreactive cell bodies containing leucine-enkephalin were found in the lateral hypothalamic area and in the paraventricular hypothalamic nucleus. Immunoreactive fibres expressing pro-opiomelanocortin-derived peptides were more numerous than those expressing pro-dynorphin-derived peptides. A close anatomical relationship was observed: in all the diencephalic nuclei in which beta-endorphin (1-27)-immunoreactive fibres were found, fibres containing alpha-melanocyte-stimulating hormone or alpha-neo-endorphin were also observed. Fibres containing beta-endorphin (1-27), alpha-melanocyte-stimulating hormone or alpha-neo-endorphin were widely distributed throughout the diencephalon, but fibres containing ACTH or leucine-enkephalin showed a moderate distribution. The distribution of the five peptides studied here is also compared with that reported previously in other mammalian species. The widespread distribution observed indicates that both the pro-dynorphin and the pro-opiomelanocortin systems are involved in multiple physiological actions (e.g., food intake, thermoregulation, neuroendocrine and reproductive mechanisms) in the alpaca diencephalon.

Mapping of neurotensin in the alpaca (Lama pacos) brainstem.

We studied the distribution of cell bodies and fibres containing neurotensin (NT) in the brainstem of the alpaca using an indirect immunoperoxidase technique. Immunoreactive fibres were widely distributed throughout the brainstem, whereas the distribution of cell bodies was less widespread. Immunoreactive perikarya were only found in the mesencephalic and bulbar reticular formation, periaqueductal grey, nucleus of the solitary tract, laminar spinal trigeminal nucleus and in the inferior colliculus. A high density of fibres containing NT was found in the dorsal nucleus of the raphe, marginal nucleus of the brachium conjunctivum, locus coeruleus, inferior colliculus, inter-peduncular nucleus, substantia nigra, periaqueductal grey, reticular formation of the mesencephalon, pons and medulla oblongata, nucleus of the solitary tract, laminar spinal trigeminal nucleus, hypoglossal nucleus, inferior central nucleus and in the tegmental reticular nucleus. The widespread distribution indicates that NT might be involved in multiple physiological actions in the alpaca brainstem; this must be investigated in the future as alpacas lives from 0 m above sea level to altitudes of up 5000 m and hence the involvement of this neuropeptide in special and unique regulatory physiological mechanisms could be suggested.

[Calcific myonecrosis of the leg]. / Mionecrosis calcificante de la pierna.

Calcific myonecrosis is a rare post-traumatic sequela almost exclusively located in the lower extremity, which can be mistaken for an aggressive primary neoplasm. This lesion, initially described by Gallei and Thompson in 1960, is characterized by the formation of a calcified mass that appears decades after trauma. The pathophysiologic mechanism is not fully understood, although the lesion most likely results from post-traumatic ischemia and it may be associated with a common peroneal nerve injury. The typical radiographic image is a fusiform soft tissue mass with linear calcifications. The treatment of choice is conservative in asymptomatic patients because the surgical treatment has a high complication rate. We report four cases of calcific myonecrosis treated surgically in our hospital. Three of the cases had an infection as a complication that required subsequent debridement and special therapies to achieve the resolution of the cases.

[Analysis of cost-effectiveness in the diagnosis of fever of unknown origin and the role of (18)F-FDG PET-CT: a proposal of diagnostic algorithm]. / Análisis de costo-efectividad en el diagnóstico de fiebre de origen desconocido y el papel de la (18)F-FDG PET-TC: propuesta de algoritmo diagnóstico.

AIM: To analyze the costs of Fever of Unknown Origin (FUO) prior to the PET-CT study. To determine the effectiveness of PET-CT in the diagnosis of FUO. A proposal of diagnostic algorithm. MATERIAL AND METHODS: A retrospective study was performed that included 20 patients who had been studied between January 2007 and January 2011, with a mean age of 57.75 years and FUO diagnosis. All underwent a PET-CT study with (18)F-FDG. Individual and mean costs of FUO in these patients were assessed, including hospitalization days and complementary tests prior to the PET-CT study. The effectiveness of the PET-CT study in the diagnosis of FUO was analyzed. Costs of the FUO process were determined, including those of the PET-CT study, and if it had been done earlier in the diagnostic process. RESULTS: Mean hospital stay per patient until the PET-CT study was 28 days. The cost per hospitalization day was 342 €. Average cost per patient in complementary tests was 1395 €. Total cost of the FUO process until the PET-CT study was around 11167 € per patient. The PET-CT study showed a 78% sensitivity, 83% specificity, 92% PPV and 62% NPV. If PET-CT had been performed earlier in the FUO process, assuming the same effectiveness, 5471 € per patient would have been saved. CONCLUSION: The PET-CT study could be cost-effective in the FUO process if used at an early stage, helping to establish an early diagnosis, reducing hospitalization days due to diagnostic purposes and the repetition of unnecessary tests.

Mapping of CGRP in the alpaca diencephalon.

We report the distribution of immunoreactive cell bodies and fibers containing calcitonin gene-related peptide in the alpaca diencephalon. This study was carried out in alpacas that lived from birth to death at 0 m above sea level. Immunoreactive fibers were widely distributed throughout the thalamus and hypothalamus. A moderate density of these fibers was found in the zona incerta, the central medial, subparafascicular, reuniens and rhomboid thalamic nuclei, in the preoptic, anterior, lateral and dorsal hypothalamic areas, around the fornix, in the posterior, ventromedial and paraventricular hypothalamic nuclei and in the lateral mammillary nucleus. Cell bodies were only found in the hypothalamus: a high density in the paraventricular and supraoptic hypothalamic nuclei and a low density in the anterior, lateral and dorsal hypothalamic areas, around the fornix, and in the posterior and ventromedial hypothalamic nuclei. The widespread distribution of calcitonin gene-related peptide in the alpaca diencephalon suggests that it is involved in many physiological actions that must be investigated in-depth in the future, since alpacas lives from 0 m above sea level to altitudes of up to 5000 m altitude and hence the involvement of neuropeptides in special and unique regulatory physiological mechanisms could be suggested.

Mapping of somatostatin-28 (1-12) in the alpaca diencephalon.

Using an immunocytochemical technique, we report for the first time the distribution of immunoreactive cell bodies and fibers containing somatostatin-28 (1-12) in the alpaca diencephalon. Somatostatin-28 (1-12)-immunoreactive cell bodies were only observed in the hypothalamus (lateral hypothalamic area, arcuate nucleus and ventromedial hypothalamic nucleus). However, immunoreactive fibers were widely distributed throughout the thalamus and hypothalamus. A high density of such fibers was observed in the central medial thalamic nucleus, laterodorsal thalamic nucleus, lateral habenular nucleus, mediodorsal thalamic nucleus, paraventricular thalamic nucleus, reuniens thalamic nucleus, rhomboid thalamic nucleus, subparafascicular thalamic nucleus, anterior hypothalamic area, arcuate nucleus, dorsal hypothalamic area, around the fornix, lateral hypothalamic area, lateral mammilary nucleus, posterior hypothalamic nucleus, paraventricular hypothalamic nucleus, suprachiasmatic nucleus, supraoptic hypothalamic nucleus, and in the ventromedial hypothalamic nucleus. The widespread distribution of somatostatin-28 (1-12) in the thalamus and hypothalamus of the alpaca suggests that the neuropeptide could be involved in many physiological actions.

Involvement of oxytocin in the nucleus tractus solitarii on central cardiovascular control: interactions with glutamate.

Oxytocin (OT) is a peptide involved in several physiological functions in the central nervous system including central cardiovascular regulation. To clarify the role of endogenous OT in cardiovascular control, one group of anesthetized rats received unilateral microinjections of the OT receptor antagonist [d(CH(2))(5),Tyr(Me)(2),Orn(8)]-vasotocin (OTA) in the nucleus tractus solitarii (NTS) and a second group was injected with specific OT antiserum (Anti-OT). Moreover, the modulation of the cardiovascular effect of L-glutamate (GLU) by OT was also evaluated by cardiovascular analysis using effective and threshold doses of GLU. Mean arterial pressure (MAP) and heart rate (HR) were measured from a femoral catheter. OTA significantly (p<0.01) decreased the vasopressor and tachycardiac long-lasting response elicited by an effective dose of OT. Microinjections of Anti-OT antibody did not modify the values of MAP and HR compared with the control group. With regard to the OT/GLU coinjections, a subthreshold dose of OT significantly (p<0.001) counteracted the vasodepressor and bradycardiac responses induced by GLU. The coinjection of subthreshold doses of OT and GLU did not produce a change in MAP or in HR. These findings seem to exclude an endogenous tonic action of OT on central regulation of MAP and HR, although they confirm the significant role of OT on central cardiovascular control within the NTS. In fact, the modulation of GLU responses by OT supports the importance of OT on the central cardiovascular adjustments likely acting on the baroreceptor reflex sensitivity.

18F-FDG PET/CT in the evaluation of POEMS syndrome.

In POEMS syndrome the identification and biopsy of an osteosclerotic lesion or a lymph node typical of Castleman's disease (CD) is essential to establish the diagnosis and plan appropriate treatment. We report four patients in whom the localisation and identification of diagnostic bone lesions or lymphadenopathies were guided by fluorodeoxyglucose positron emission tomography integrated with computerised tomography (FDG PET/CT). FDG PET/CT identified bone lesions not detected with other techniques in one patient, and revealed hypermetabolic characteristics in bone lesions or adenopathies in the others, thus guiding the diagnostic biopsy in those with hypermetabolism. In conclusion, FDG PET/CT may be useful in detecting and selecting bone lesions and lymph nodes for biopsy in patients with suspected POEMS syndrome.

Reliability of ultrasonography in detecting shoulder disease in patients with rheumatoid arthritis.

OBJECTIVE: To assess the intra and interobserver reproducibility of musculoskeletal ultrasonography (US) among rheumatologists in detecting destructive and inflammatory shoulder abnormalities in patients with rheumatoid arthritis (RA) and to determine the overall agreement between US and MRI. METHODS: A total of 14 observers examined 5 patients in 2 rounds independently and blindly of each other. US results were compared with MRI. Overall agreement of all findings, of positive findings on MRI, as well as intra and interobserver reliabilities, were calculated. RESULTS: Overall agreement between US and MRI was seen in 79% with regard to humeral head erosions (HHE), in 64% with regard to posterior recess synovitis (PRS), in 31% with regard to axillary recess synovitis (ARS), in 64% with regard to bursitis, in 50% with regard to biceps tenosynovitis (BT), and in 84% for complete cuff tear (CCT). Intraobserver and interobserver kappa was 0.69 and 0.43 for HHE, 0.29 and 0.49 for PRS, 0.57 and 1.00 for ARS, -0.17 and 0.51 for bursitis, 0.17 and 0.46 for BT and 0.52 and 0.6 for CCT, respectively. The intraobserver and interobserver kappa for power Doppler (PD) was 0.90 and 0.70 for glenohumeral signals and 0.60 and 0.51 for bursal signals, respectively. CONCLUSIONS: US is a reliable imaging technique for most shoulder pathology in RA especially with regard to PD. Standardisation of scanning technique and definitions of particular lesions may further enhance the reliability of US investigation of the shoulder.

Cervical spine involvement in rheumatoid arthritis: correlation between neurological manifestations and magnetic resonance imaging findings.

OBJECTIVE: To evaluate the correlation between neurological deficits indicative of compressive myelopathy and MRI findings in a series of patients with RA and symptomatic involvement of the cervical spine. METHODS: Forty-one consecutive patients with RA were studied using cervical spine MRI. Unconditional logistic regression analysis was used to identify MRI parameters of cervical spine involvement associated with the development of neurological dysfunction. RESULTS: The mean age of the 41 patients (33 women and 8 men) was 59 yrs (range 23-82 yrs), while the median disease duration was 18 +/- 9 yrs (range 4-40 yrs). According to Ranawat's classification, 17 (42%) patients were in Class I, 21 (51%) in Class II and 3 (7%) in Class III. Thus, patients with clinical manifestations of compressive myelopathy (Ranawat's Class II + III) represented 58% (24/41) of all cases. Among the different MRI parameters of cervical spine involvement analysed, only the presence of atlantoaxial spinal canal stenosis [odds ratio (OR) 4.55; 95% CI 1.14-18.15], atlantoaxial cervical cord compression (OR 9.6; 95% CI 1.08-85.16) and subaxial myelopathy changes (OR 11.43; 95% CI 1.3-100.81) were associated with a significantly increased risk for neurological dysfunction (Ranawat's Class II or III). CONCLUSION: In RA patients with symptomatic cervical spine involvement, there is a strong correlation between the development of neurological dysfunction and MRI identification of atlantoaxial spinal canal stenosis, especially in those cases with evidence of upper cervical cord or brainstem compression and subaxial myelopathy changes.

[Alveolar microlithiasis: an uncommon cause of the crazy paving pattern]. / Microlitiasis alveolar: presentación infrecuente del "patrón en empedrado"

Alveolar microlithiasis is an uncommon disease of unknown etiology characterized by the presence of multiple, predominantly subpleural, intra-alveolar microcalcifications. We present a case in which the high-resolution CT images show diffuse pulmonary microcalcifications together with patchy areas of ground glass attenuation associated to marked thickening of the interlobular septa, all of which taken together constitute the crazy paving pattern. This pattern is not specific for alveolar microlithiasis; it has also been reported in other entities, including alveolar proteinosis, lipoid pneumonia, and bronchial alveolar carcinoma.