The following representative diseases will be presented in each section:

Table 1: Table of contents.

1 - HYPERATTENUATING LINEAR OR RETICULAR OPACITIES

a) Dendriform pulmonary ossification

• Pulmonary ossification can happen in a dendritic pattern.
• Idiopathic or secondary to cardiopulmonary and systemic disorders (fibrosing lung diseases, mitral stenosis, Goodpasture syndrome).

Fig 2: Case 1 – 71-year-old male with idiopathic pulmonary fibrosis.

Fig 3: Case 2 – 27-year-old female with rheumatic fever and mitral valve repair.

• Chronic tissue injury and recurrent alveolar hemorrhage initiate calcium salt and interstitial metallic deposition, causing metaplastic ossification.
• Calcium and phosphate serum levels are normal.
• Mature bone spicules can be seen as branching hyperattenuating reticular opacities, localized or diffuse, mainly peripheral and in the lower zones of the lung.

b) Diffuse parenchymal pulmonary amyloidosis

• Amyloidosis is a rare group of diseases defined by extracellular deposition of insoluble amyloid proteins: can affect every system and present in almost any way.
• Male predilection, around 60 years old.
• Imaging features vary across each organ system, but share some common findings, such as soft-tissue infiltration and calcification.
• Pulmonary amyloidosis can be focal (nodular) or diffuse (alveolar-septal).

Fig 4: Case 3 – 44-year-old male with primary systemic amyloidosis associated with multiple myeloma.

• Diffuse alveolar-septal is the least common type and tends to carry a poor prognosis. Amyloid deposits occur in the interstitial alveolar septa, especially around capillary vessels.
• Can present with abnormal reticular opacities, interlobular septal thickening and confluent consolidations in subpleural regions and be associated with multiple micronodules.
• Mediastinal lymphadenopathy with calcified components is common.
• Pleural effusion may be present.

2 - NON-CALCIFIED HYPERDENSE NODULES

• Mainly occurs due to embolization or inhalation of exogenous hyperdense substances.
• Usually diffuse and peripherally distributed.
• The material is trapped on distal circulation / airways and may acquire a tubular (and sometimes branching) appearance.
• Knowing the clinical scenario and previous procedures is crucial to determine etiology.

a) Mercury vapor inhalation

Fig 5: Case 4 – 39-year-old male, worker in gold mines.

b) Pulmonary cement embolization

Fig 6: Case 5 – 80-year-old female, after vertebroplasty with bone cement.

• Bone cement is widely used in vertebroplasty for compression fractures. It is percutaneously injected through pedicles into the vertebral body, helping it regain height and strength.

c) Cyanoacrilate pulmonary embolization

Fig 7: Case 6 – 65-year-old male with chronic liver disease, submitted to sclerosis of gastric varices with cyanoacrylate.

• Cyanoacrylate glue is commonly used for gastric varices sclerotherapy. They may occur due to pancreatitis-induced splenic vein thrombosis and left-sided portal hypertension.

3 - CALCIFIED PULMONARY NODULES

a) Distrophic calcifications: post-infectious

• Commonly seen as sequelae after healed infections such as disseminated histoplasmosis and rarely after miliary tuberculosis.
• Varicella-zoster virus may also cause pneumonia (almost exclusively in immunocompromised adults) and leave calcified nodules.

Fig 8: Case 7 – 35-year-old female with residual miliary tuberculosis.

• Nodules are usually well-defined and diffuse throughout both lungs, measuring 2 to 5 mm.
• Calcified hilar and mediastinal lymph nodes are often seen (except in varicella pneumonia).

b) Distrophic calcifications: pulmonary hemosiderosis

• Occur due to iron deposition on the lung parenchyma and can be either idiopathic (uncommon, tipically affecting young patients), primary (associated with some syndromes) or secondary to diseases that cause alveolar hemorrhage.
• Rheumatic fever is the most common cause of mitral valve stenosis, which leads to pulmonary hypertension as a common complication and predisposition to chronic alveolar hemorrhage.

Fig 9: Case 8 – 30-year-old female with rheumatic fever.

• Ground glass opacities may be seen if there is current hemorrhage.
• Interstitial septal thickening may be present due to hemosiderin deposition in the interstitium.

c) Distrophic calcifications: occupational diseases / pneumoconioses

• Broad group of diseases caused by the inhalation of dust particles, mainly mineral.
• Dystrophic calcifications are classically seen on fibrotic pneumoconiosis, mainly silicosis (inhalation of crystalline silica; most common) and coal worker's pneumoconiosis (CWP; inhalation of washed coal dust).

Fig 10: Case 9 – 70-year-old male with classic silicosis.

• In its simple form (reticulonodular disease), both present with diffuse small nodules with calcifications and perilymphatic distribution, mainly in the posterior region of the upper lobes.
• Hilar and mediastinal lymphadenopathy may be present and even precede the pulmonary nodules. Lymph nodes may be calcified in an eggshell pattern.
• Both increase risk of tuberculosis.

d) Metastatic calcification

• Metastatic calcification is a metabolic lung disease caused by calcium deposition in the pulmonary parenchyma.
• The calcium and phosphate metabolism abnormalities leading to chronic hypercalcemia predispose calcium salt deposition in the normal lung parenchyma. Differently, dystrophic calcifications require a previously damaged lung, even in the absence of increased serum calcium levels.
• Unlike suggested by its name, the condition does not refer to calcified metastasis and can be caused by benign or malignant conditions (chronic renal disease, hyperparathyroidism, multiple myeloma, lymphoma, osteolysis).
• Usually asymptomatic and likely underdiagnosed: seen in 60 – 75% of autopsies of patients with renal failure.
• Resolution of pulmonary calcifications may occur after treatment of the cause.

Fig 11: Case 10 – 40-year-old male with chronic renal disease and parathyroid tumor.

• Usually appears as ill-defined and diffuse calcified nodules or patchy airspace opacities with calcified components.
• More prominent in the upper lobes, due to a more alkaline environment that accelerates tissue calcification.
• Relative stability of findings and resistance to treatment in the clinical context of hypercalcemia are of diagnostic value.
• Calcifications in chest wall vessels are frequent.

e) Pulmonary alveolar microlithiasis

Fig 12: Case 11 – CT and chest radiograph findings of pulmonary alveolar microlithiasis in a 40-year-old female.

• Rare disease caused by intra-alveolar accumulation of round calcified micronodules.
• It is believed that a mutation in the SLC34A2 gene inactives a cotransporter in the type II pneumocytes that clears phosphate from degraded surfactant, predisposing formation of calcium phosphate microliths.
• Usually there is no abnormal calcium metabolism – normal serum calcium.
• Clinical-radiological dissociation: patients may be asymptomatic even with exuberant imaging findings.
• There is no specific treatment; lung transplantation may be required in end-stage fibrosing disease.

4 - LARGE CALCIFIED NODULES OR MASSES

a) Calcified metastasis

• Calcified metastasis from a primary pulmonary tumor are rare and can result either from sarcomas or carcinomas.
• There may be solitary or multiple calcified nodules with well-defined margins.
• Distribution is usually random and peripheral.
• Mechanisms: bone formation, calcification and ossification of tumor cartilage, dystrophic and mucoid calcification.

Fig 13: Cases 12 and 13 – 32-year-old male, medullary thyroid carcinoma, and 18-year-old male staging an osteosarcoma, respectively.

Fig 14: Case 14 – 47-year-old male with pulmonary metastasis from pelvic chondrosarcoma.

• Main primary tumors: osteo- and chondrosarcoma, mucinous carcinoma (colon, ovary, breast), thyroid carcinoma (medullary or papillary) and giant cell tumor.
• Patient’s oncologic history may increase suspicion if a calcified lung lesion is detected.

b) Progressive massive fibrosis

Fig 15: Case 15 – 60-year-old male, miner.

• Characterized by the development of mass-like conglomerates, mainly in upper pulmonary lobes.
• Caused by complicated pneumoconioses, classically silicosis and CWP.
• Usually takes several years of exposure to develop.
• Coalescence of nodules in mass-like areas may have a "sausage shape" and be associated with fibrotic parenchymal bands. Calcification is common.

c) Talcosis

• Talc-induced lung diseases are caused by talc (magnesium silicate) inhalation or embolism (intravenous drug users that inject dissolved tablets intended for oral use).
• The least common type is associated with inhalation of pure talc (powder), often due to abundant use of talc-based cosmetics.

Fig 16: Case 16 – Male patient after 28 years of exposure working in talc-based cosmetics industry.

• Typically presents as small and intrinsically hyperdense non-calcified micronodules, but slowly progresses to large areas of increased opacity and complicates with progressive massive fibrosis.
• Lymphadenopathy is uncommon.

d) Granulomas

• Granulomas caused by healed infections represent around 80% of benign pulmonary nodules.
• Primarily due to endemic fungal and mycobacterial infections.

Fig 17: Case 17 – 50-year-old male, asymptomatic.

• Classically appear as well-defined and total or centrally calcified nodules.
• Can be non-calcified and indistinguishable from other pulmonary nodules, therefore may require biopsy.

e) Nodular parenchymal amyloidosis

Fig 18: Case 18 – Non-enhanced chest CT on mediastinal window from a patient with pulmonary nodular amyloidosis.

• Nodular form presents as solitary or multiple nodules of different sizes that have a predilection for peripheral distribution in the middle and lower zones of the lungs. Around 50% of them calcify or ossify.
• Amyloidosis in the chest can affect the airways (circumferential and extensive tracheobronchial thickening with calcified areas), mediastinum (amyloidoma with calcified lymphadenopathy), heart or pulmonary parenchyma, focal or diffusely.
• Amyloid deposition retains the Congo red stain and shows a pathognomonic apple-green birefringence under polarized light microscopy.

5 - HIGH-ATTENUATION CONSOLIDATIONS

a) Amiodarone lung

• Amiodarone is an iodinated benzofuran derivative (therefore hyperdense) used as and antiarrhythmic drug.
• One of the most commonly used drugs in atrial fibrillation; its toxicity is related to cumulative dose.
• Pulmonary involvement happens in around 10% of patients.
• Pneumonitis is the most common pathologic pattern and the high-attenuation opacities occur due to amiodarone accumulation in type II pneumocytes.

Fig 19: Case 19 – 77-year-old female with heart disease.

• Hyperattenuating atelectasis are seen on dependent regions of the lungs, associated with pleural thickening of effusion. Septal thickening and interstitial fibrosis may occur, with basal predominance.
• Prognosis is good if therapy is discontinued.

b) Pulmonary lipiodol embolism

• Lipiodol-based emulsions contain ethyl acids of iodized fatty-acids from poppy seed oil and are used in lymphography, dacryocystography, hysterosalpingography and interventional procedures, such as transarterial catheter chemoembolization.
• The oil microemboli creates a high concentration of free fatty acids, which may cause pulmonary capillary leakage and non-cardiogenic edema.

Fig 20: Case 20 – Pulmonary embolism after lymphography with Lipiodol.

• Bilateral areas of hyperdense consolidations, peripheral and prominent in the lung bases.
• There is a correlation between the amount of lipiodol injected and the clinical severity of lung injury.