Case #1 Community Acquired Pneumonia

CLINICAL HISTORY-1

• A 45-year-old man was found wandering in downtown Orange with alcohol on his breath and coughing up thin, rusty sputum. He was brought to the emergency room where, although a poor historian, he said he had been fine the day before but that morning he had begun to shake uncontrollably and felt alternately cold then hot and sweaty. He said his chest hurt when he breathed and he felt nauseated..

CLINICAL HISTORY-2

• Information from the old hospital chart indicated that significant past history included a hospital admission for tuberculosis 10 years previously. Physical examination revealed a thin white male who was anxious and mildly cyanotic. Other abnormal physical findings included tachypnea and chest splinting, accompanied by fine rales and decreased breath sounds by auscultation over the right lower lobe. His temperature was 100.2o F, but his pulse was normal.

CLINICAL HISTORY-3

• WBC count was 16 × 103/μL (ref. range 4.1-10.9 x 103/μL) with 70% polys, 18% bands, and 12% lymphocytes. Blood gases demonstrated hypoxia and respiratory alkalosis. A chest x-ray is shown in Image 1 (next slide).

• Sputum was collected for smear and culture, and blood was drawn over the next hour for two sets of blood cultures. A Gram stain of the sputum showed lancet-shaped, Gram-positive diplococci.

• 1 - Chest, lobar pneumonia - Radiograph   Note that the usual angle between the right heart border and the right diaphragm has been lost, and a diffuse infiltrate extends to the fissure between the right middle and right lower lobes. This is a lobar

pneumonic infiltrate.  

CLINICAL HISTORY-4

• The patient was admitted and promptly begun on antibiotics and oxygen therapy. However, he became progressively more hypoxic, was placed in the intensive care unit on increasing concentrations of oxygen, and expired 24 hours after admission. During this time, both of the blood cultures were positive for Streptococcus pneumoniae. An autopsy was done; the pulmonary findings are shown in Images 2 and 3.

• 2 - Lungs, lobar pneumonia, gray and red hepatization - Gross, cut surfaces   Lobar pneumonia differs from bronchopneumonia in that bronchopneumonia is patchy and lobar pneumonia is diffuse. These demonstrate the contrast between the stages of red hepatization (right) and gray hepatization (left). The lower lobe is expanded in both photographs; in the stage of red hepatization, the gross appearance reflects the microscopic features of congestion and hemorrhage along with a fibrinosuppurative exudate in the alveoli. The pneumonia takes on the appearance of gray hepatization when the congestion becomes less prominent and red blood cells have exited into the alveoli lyse, leaving behind the fibrinosuppurative exudate.

• 3 - Lung, lobar pneumonia - High power   The alveolar spaces are filled with neutrophils (PMNs) and a fibrinous exudate. The alveolar septa are easily demarcated because of congestion with red cells. Because of the alveolar exudate, the lung becomes airless (solid). This is called consolidation. Interstitial pneumonitis, the typical inflammatory response to viruses and mycoplasma, is very different from acute bacterial pneumonia. The clinical presentation of interstitial pneumonitis is that of nonproductive cough, fever, and malaise. Pathologically, there is a lymphoplasmacytic infiltrate in the alveolar septa, shown in the second feature above. Note the absence of inflammatory cells in the alveolar spaces.

QUESTION #1

• Q: What would bronchopneumonia look like radiographically?

• A. Bronchopneumonia tends to be patchy, although, if severe, even bronchopneumonia may become confluent and involve an entire lobe of lung.

QUESTION #2

• Q: What is the most common pathogen causing lobar pneumonia?

• A. Streptococcus pneumoniae.

QUESTION #3

• Q: What predisposed this patient to get pneumonia?

• A. This patient appears to be a chronic alcoholic who is probably malnourished and somewhat immunosuppressed. Alcoholics are also prone to aspirate bacteria-laden secretions from the upper respiratory tract during an alcoholic bout. In all likelihood, impaired mucociliary clearance and defective phagocytic functions of alveolar macrophages also contributed to lung infection.

QUESTION #4

• Q: What are the components of the inflammatory reaction to bacteria?

• A: Bacteria typically cause acute inflammation, characterized by congestion, formation of an exudate, and a polymorphonuclear infiltrate

QUESTION #5

• Q: While viral pneumonitis is usually self-limited, some patients develop pulmonary complications secondary to viral pneumonitis. What are these?

• A: The most common complications of viral pneumonitis are secondary bacterial pneumonia and diffuse alveolar damage

QUESTION #6

• Q: What accounts for the rusty sputum in this case?

• A: The sputum is composed of the exudate in the alveoli; it is rusty because of the red cells in the exudate.

• 4 - Lung, bronchopneumonia - Gross, cut surface   This photograph of part of the lower lobe of a lung shows extensive involvement of the anterior aspect of the lung by bronchopneumonia. Bronchopneumonia is different from lobar pneumonia in that, in bronchopneumonia, the consolidation in the lung is patchy and follows the distribution of the bronchi and bronchioles. The light tan peribronchiolar areas represent acute inflammatory cells and fibrin. In addition, an abscess has formed in the basal section of the lung

QUESTION #7

• Q: What organisms are particularly associated with abscess formation?

• A. Staphylococcus aureus, Klebsiella pneumoniae, and type 3 Pneumococcus

• 5 - Lung, bronchopneumonia - Low power   This image highlights the focal distribution of the inflammatory process in bronchopneumonia. The inflammation is in a bronchiolar distribution, that is, there is abundant inflammation within and surrounding the bronchioles. Some normal areas can also be seen.  

QUESTION #8

• What are the complications of pneumonia?

• Abscess formation, empyema, organization with subsequent fibrosis, bacteremic dissemination.

• 6 - Lung, fungal pneumonia (immunosuppressed patient) - Gross, cut surface   There is diffuse consolidation and vascular thrombosis with infarction of surrounding parenchyma of the right middle lobe of the lung, secondary to fungal infection. The picture on the left is before fixation in formalin, and the picture on the right is a closer view after fixation.  

QUESTION #9

• Q: What are the mechanisms of pulmonary damage in immunocompromised patients with fungal infection?

• A: Patients with fungal pneumonia may have pulmonary damage from vascular occlusion by the fungus, resulting in ischemic necrosis, or from direct invasion by and host reaction to the organism.

• 7 - Lung, fungal pneumonia (immunosuppressed patient) - High power   This fungus is causing pulmonary damage by occluding a major arterial branch, resulting in a surrounding infarct. Aspergillus and fungi of the Mucorales group are the most likely to produce this type of damage. In this case, the fungus was a dematiaceous fungus acquired through a sinus infection. The PAS stain highlights the fungi, which are seen occluding and penetrating through the wall of a large pulmonary vessel.    

QUESTION #10

• Q: Aside from the lungs, what are the other two sites in the body frequently infected by Mucor?

• A. Sites frequently infected by Mucor are the paranasal sinuses with extension to the brain (rhinocerebral Mucor).

Case 2: Neonatal Respiratory Distress Syndrome

CLINICAL HISTORY- 1

• A newborn girl was delivered at 28 weeks’ gestation (calculated by mother's last menstrual period) to a 25-year-old woman with a history of pregnancy-induced hypertension and continued heavy tobacco use. The mother came to the clinic complaining of cramping. She had a fever of 39°C. The fetal heartbeat was irregular, indicative of fetal distress. Because of concerns about fetal well-being, the delivery was induced.

CLINICAL HISTORY- 2

• The infant was delivered 4 hours later and weighed 600 gm; the Apgar scores were 4 at 1 minute and 7 at 5 minutes. The infant appeared long and thin with a relatively enlarged head size. By measurements, the body weight and crown-heel length were consistent with 25 weeks’ gestational age, and the head circumference was consistent with 28 weeks’ gestation. The gestation was estimated by clinical maturity studies to be 28 weeks.

CLINICAL HISTORY -3

• Sternal retractions were noted, indicating respiratory difficulties, and artificial surfactant was given. The respiratory status did not improve, and the infant was placed on a ventilator. Blood for cultures was drawn, and the infant was begun on antibiotics. Over the course of the next day, increasing ventilatory support was required. The chest radiograph is shown in Image 1.

• 1 - Chest, hyaline membrane disease - Radiograph   This chest radiograph of a newborn premature infant shows hazy lung fields indicating fluid or an infiltrate in the airspaces. This is often called ground-glass opacification, and is characteristic of hyaline membrane disease. Similar changes are seen with group B streptococcal pneumonia.

CLINICAL HISTORY -4

• Blood cultures were positive for group B Streptococcus. On the second day of life, seizures developed. A head ultrasound examination diagnosed a severe intraventricular hemorrhage. After a discussion with the parents, it was decided that heroic measures would not be instituted, and the infant died at 32 hours of age. An autopsy was done.

QUESTION #1

• What other pathologic processes may produce a similar picture?

• Adult (acute) respiratory distress syndrome and pulmonary edema may produce a similar picture.

• 2 - Lungs, hyaline membrane disease - Gross   This image compares the external appearance of a portion of the liver (lower specimen) with the lungs. The lungs appear solid, red, and airless. These are the characteristic findings in hyaline membrane disease. The lungs have an appearance similar to liver

because of extensive collapse and consolidation.

QUESTION #2

• Q: What are the risk factors for hyaline membrane disease?

• A: Hyaline membrane disease is basically a disease of premature infants. Approximately 20% of infants born between 32-36 weeks and 60% of infants born before 28 weeks develop this disease. Other risk factors are diabetes in the mother, prenatal asphyxia, and brain injury.

QUESTION #3

• Q: Would this infant be considered appropriate for gestational age?

• A: This infant is small for gestational age, because her birth weight is below < 10th percentile for her estimated age of 28 weeks' gestation. Her intrauterine growth retardation may have resulted from diminished placental blood flow from the maternal pregnancy-induced hypertension coupled with maternal cigarette smoking. This infant shows asymmetric growth retardation with relative sparing of the growth of the brain and head relative to the rest of the body. This asymmetric growth retardation is seen in cases of growth retardation secondary to maternal or placental factors or both. Many fetal causes of IUGR, such as chromosomal abnormalities and congenital infections, lead to a proportionately small infant.

• 3 - Lung, hyaline membrane disease - Low power   Photomicrograph of hyaline membrane disease of the lung with pneumonia. Note the pink acellular membranes in some airspaces. Neutrophils are also present in the airspaces.

QUESTION #4

• Q: What is the pathogenesis of these changes?

• A: The fundamental defect is the inability of the immature lung to produce surfactant. Surfactant is essential to reduce surface tension within the alveoli, facilitating their expansion. If surfactant is inadequate, the alveoli collapse. Atelectasis leads to hypoxia, causing epithelial and endothelial injury, resulting in leakage of a protein-rich and fibrin-rich exudates into the alveolar spaces, which together with necrotic cellular debris forms hyaline membranes.

QUESTION #5

• Q: Are neutrophils prevalent in all cases of hyaline membrane disease?

• A: Neutrophils are usually inconspicuous in hyaline membrane disease without concurrent pneumonia

• 4 - Lung, hyaline membrane disease - High power   Higher power view of hyaline membrane disease and pneumonia in lung. The hyaline membrane is composed of fibrin and cellular debris.  

QUESTION #6

• Q: How do hyaline membranes form?

• A: Hyaline membranes form from proteinaceous debris, necrotic epithelial cells, and fibrin accumulating in alveolar spaces.

• 5 - Placenta, chorioamnionitis - Gross   A placenta with chorioamnionitis. The fetal membranes, which have flipped over to cover half of the maternal surface, are thickened and gray-tan instead of thin and translucent.

QUESTION #7

• Q: In this case, what pathogenetic sequence of events resulted in fetal infection?

• A. The pathogenetic sequence likely began with an ascending infection by group B Streptococcus, which had presumably colonized the mother's genital tract. The organisms gained access to the amniotic fluid after passing through the placental membranes. The fetus swallowed or aspirated bacteria, resulting in pneumonia and, eventually, sepsis. The infant's difficulty breathing was related to prematurity complicated by pneumonia. Hypoxia secondary to pulmonary disease contributed to the intraventricular hemorrhage.

• Placenta, fetal membranes, chorioamnionitis - Medium power   Chorioamnionitis microscopically is characterized by a dense infiltrate of maternal neutrophils into the fetal membranes. Note the thin cuboidal cell layer of amnion along one edge of the membranes

QUESTION #8

• Q: Where does the inflammatory infiltrate originate?

• A: Neutrophils from the maternal circulation pass through the endometrium and fetal membranes to enter the amniotic fluid

• 7 - Brain, intraventricular hemorrhage - Gross, ventral surface   This brain from a premature infant shows absence of the normal gyral pattern seen later in life. Normal gyration is present by 40 weeks’ gestation. This brain shows external evidence of intraventricular hemorrhage. There is subarachnoid extension of blood from the ventricles through the foramina of Luschka and Magendie.

• 8 - Brain, intraventricular hemorrhage - Gross, coronal section   This image shows subependymal (germinal matrix) hemorrhage with rupture and extension into ventricles.  

QUESTION #9

• Q: What are the predisposing factors for intraventricular hemorrhage?

• A: Predisposing factors include prematurity, hypoxia, and breech delivery.

•

QUESTION #10

• Q: What clinical symptoms may result from this?

•

• A: Clinical symptoms include apnea, lethargy, poor muscle tone, and seizures.

• 9 - Chest, bronchopulmonary dysplasia (BPD) - Radiograph   This chest radiograph shows areas of haziness and lucency in the lung fields. The haziness results from zones of interstitial fibrosis. The lucency reflects areas of hyperinflation.

QUESTION #11

• Q: What is the pathogenesis of BPD?

• A: BPD results from prolonged assisted ventilation at high oxygen concentrations. Oxygen toxicity and mechanical ventilation damage the developing lung, leading to poor alveolar development

QUESTION #12

• Q: How have the histologic findings in BPD changed in recent years?

• A: The major histologic finding in new BPD cases is a decreased number of alveoli, also called alveolar hypoplasia, which is thought to result from arrested lung development at the saccular stage.

• 10 - Lung, bronchopulmonary dysplasia - Gross   This is a lateral view of the external surface of the right lung from a patient who died with bronchopulmonary dysplasia typical of the severe glucocorticoid therapy and surfactant therapy. Note the cobblestone exterior surface of the lung owing to scarring and alternating hyperinflation and collapse of the underlying parenchyma. Compare this with the radiographic appearance of bronchopulmonary dysplasia in the previous image.  

QUESTION #13

• Q: What are the clinical sequelae of this disorder?

• A: The clinical sequelae include reactive airway disease, exercise intolerance, risk of recurrent infection, and cor pulmonale.

• 11 - Lung, bronchopulmonary dysplasia - Medium power   This microscopic view of bronchopulmonary dysplasia shows resolving hyaline membranes, hyperplasia of alveolar type II cells, and developing interstitial fibrosis, the typical features of severe bronchopulmonary dysplasia as it was seen before to the surfactant therapy era. Most cases now show diminished alveolar development, but lack the prominent alveolar epithelial hyperplasia and fibrosis depicted.

Case 3: Adult ARDS

CLINICAL HISTORY #1

• A 30-year-old white woman presented to the emergency department with fever, chills, and shortness of breath for 24 hours. She was well until 4 days earlier, when she noted pain on urination, followed shortly thereafter by pain in her left flank. She had diabetes treated with insulin.

CLINICAL HISTORY #2

• On arrival, the patient's blood pressure was 70/40 mm Hg, pulse was 120 beats/min, respiratory rate was 24/breaths, and temperature was 39 °C. On examination, wet rales were present in both lungs, and there was tenderness in the left flank. Chest x-ray revealed bilateral diffuse pulmonary infiltrates.

CLINICAL HISTORY #3

• Laboratory results were as follows: WBC 14,000, 82% PMNs, 7% bands; hematocrit 26% with fragmented red blood cells on peripheral blood smear; platelets 25,000; prothrombin time 18 sec (reference range 9.8-11.9 sec), partial thromboplastin time 80 sec (reference range 23-32.5 sec); arterial blood gases pH 7.25, PCO2 36 mm Hg, PO2 28 mm Hg; creatinine 4.8 mg/dL, glucose 600 mg/dL; urine cloudy with protein and PMNs.

CLINICAL HISTORY #4

• The patient was intubated and placed on dopamine, 100% O2, and intravenous antibiotics. She experienced progressive hypotension, an upper gastrointestinal hemorrhage, and intractable acidosis; blood cultures grew gram-negative rods. She died on the second hospital day. At autopsy, her lungs were heavy, firm, red, and boggy.

• 1 - Lungs, acute respiratory distress syndrome (ARDS) - Chest radiograph   Radiograph shows extensive, diffuse, bilateral pulmonary infiltrates.

QUESTION #1

• Q: What is the morphologic basis for these radiographic findings?

• A: Protein-rich edema fluid is present in the alveoli. Superimposed infection may be present.

• 2 - Shock lung - Gross, cut surface   If the patient dies during the acute stage of ARDS (as in this case), the lungs are heavy (owing to accumulation of fluid), firm, red, and boggy. The cut surface bulges and oozes fluid.

QUESTION #2• Q: List some of the major causes of ARDS.

• A: Major causes of ARDS include • (1.) sepsis; • (2.) diffuse pulmonary infections; • (3) aspiration - (gastric contents, drowning); • (4) mechanical trauma - (head injury); • (5) inhalation of toxins and irritants - (high O2, chlorine, smoke); • (6) chemical/drug injury - (heroin, methadone, nitrofurantoin); • (7) hematologic conditions - (disseminated intravascular coagulation); • (8) systemic processes - (pancreatitis, uremia, diabetic ketoacidosis,

other metabolic disorders); • (9) hemodialysis,;• (10) cardiopulmonary bypass;• (11) hypersensitivity reactions.

QUESTION #3

• Q: How did the patient develop ARDS?

• A: This diabetic woman presented with a history suggestive of urinary tract infection. From this infection, she developed gram-negative septicemia and septic shock. This condition gave rise to diffuse alveolar damage and ARDS. Other complications resulting from septic shock in this patient are disseminated intravascular coagulation (prolonged PT, PTT, thrombocytopenia, and hemolytic anemia with fragmented red blood cells) and acute renal failure (high creatinine).

• 3 - Lung, ARDS, exudative stage - Medium power   Within the first 5 days, alveolar septa show interstitial inflammation with mononuclear infiltrates and develop hyaline membranes that line alveolar ducts. Alveoli tend to collapse. These findings are present in this image

QUESTION #4

• Q: What is the pathogenesis of hyaline membrane formation?

• A: Alveolar hyaline membranes consist of fibrin-rich edema fluid mixed with the cytoplasmic and lipid remnants of necrotic epithelial cells

QUESTION #5

• Q: How does the pathogenesis differ in hyaline membrane disease in newborns?

• A: The mechanism of the respiratory distress syndrome of newborns is a deficiency of surfactant, whereas in ARDS, the mechanism is damage to the alveolar epithelium (diffuse alveolar damage)

• 4 - Lung, ARDS, proliferative stage - Medium power   About 5 days after the onset of ARDS, the fibroblasts in the interstitium begin to proliferate and lay down collagen. Hyaline membranes begin to organize. Greatly thickened alveolar septa suggest that in this lung, the process may have developed over a few weeks. Lymphocytes and a few PMNs are in the interstitium. Residual hyaline membranes lie in patches in alveolar ducts and alveoli.

QUESTION #6

• Q: With continued proliferation, what type of lung disease develops in these patients?

• A: Although complete resolution may occur, hyperplasia of type II alveolar pneumocytes plus intra-alveolar fibrosis are common sequelae. Marked thickening of the alveolar walls and interstitial fibrosis may persist, giving rise to restrictive lung disease.

• 5 - Lung, ARDS secondary to measles infection - High power   Several acute infectious agents may result in ARDS. The measles virus propagates in epithelial cells of the respiratory tract and causes diffuse alveolar damage. Type II alveolar cells may fuse to form the characteristic multinucleated giant cells containing viral inclusion bodies. A marked interstitial infiltrate is present, accompanied by extravasation of red blood cells.

QUESTION #7

• Q: What other pulmonary diseases are associated with giant cells?

• A:Multinucleated giant cells are frequent in numerous granulomatous diseases (eg, tuberculosis, sarcoidosis, histoplasmosis).

• 6 - Lung, massive pulmonary hemorrhage and infarct - Gross   The lower lobe of this lung has a dark, wedge-shaped discoloration. This is most likely due to hemorrhage in an area of infarction.

QUESTION #8

• Q: What are the usual causes of pulmonary infarction?

• A: Infarcts are caused by thromboembolism, the source of emboli being deep vein thrombosis in the leg. Infarcts tend to occur, however, only when pre-existing lung or heart disease compromises the oxygenation of the lung.

• 7 - Lung, hemorrhagic infarct - Gross, cut surface   Pulmonary hemorrhage, with or without infarction, may follow embolism. The lower lobes are more frequently involved. Triangular subpleural lesions are characteristic.

QUESTION #9

• Q: Why do only a few emboli result in infarction?

• A: Because of the dual arterial circulation (pulmonary and bronchial arteries), which have independent origins, pulmonary infarcts are uncommon.

QUESTION #10

• Q: What are the likely outcomes of pulmonary thromboembolism?

• A: Outcomes include sudden death, pulmonary infarction, pulmonary hypertension, or complete resolution.

QUESTION #11

• Q: What are the typical symptoms and signs in a patient who has nonlethal pulmonary infarction?

• A: Symptoms may resemble an acute myocardial infarction. Small emboli cause pleuritic pain and cough. Many emboli, even large ones, may be asymptomatic.

• 8 - Lung, hemorrhage and infarct - Low power   There is a line of demarcation between normal-appearing lung (right) and an area of hemorrhagice infarction (left). In the hemorrhagic region, faint outlines of alveolar septa can be seen. These have undergone coagulative necrosis.

QUESTION #12

• Q: As this infarct heals, what morphologic evidence remains?

• A: Subpleural fibrosis and scar formation with puckering of the overlying pleura remain.

• 9 - Lung, fat embolism   Not all pulmonary emboli are thromboembolic in origin. This fat embolus contains cellular marrow elements; a more accurate term would be bone marrow embolus.

QUESTION #13

• Q: How did the fat embolus arise, and from where?

• A: Fat embolism arises from fracture, usually of the long bones, but a fat embolism (without marrow) may follow severe soft tissue trauma.

QUESTION #14

• Q: What other types of emboli may reach the lungs?

• A: Other types of emboli that may reach the lungs include air emboli, amniotic fluid emboli, and vegetative or infectious endocarditis.

• 10 - Lung, acute passive congestion - Gross, cut surfaces   Acute pulmonary edema and congestion. Typically, it follows left ventricular failure.

QUESTION #15

• Q: What is the appearance of the lung and its cut surface?

• A: Lungs are heavy, two to three times their normal weight. Frothy, blood-tinged fluid oozes from the cut surface.

QUESTION #15

• Q: Name some other causes of acute pulmonary congestion.

• A: Mitral stenosis, fluid overload, pulmonary vein obstruction, liver failure, and renal failure are other causes of acute pulmonary congestion.

• 11 - Lung, pulmonary edema and congestion - High power   Pulmonary edema and congestion, characterized by heavy, wet lungs, usually result from hemodynamic causes (cardiogenic edema) or from increased capillary permeability owing to microvascular injuries. In cardiogenic edema (see image), the capillaries are engorged and prominent, and there is an intra-alveolar granular pink transudate.

QUESTION #16

• Q: What would the histologic finding be in edema secondary to microvascular injury?

• A: The histologic finding would be hyaline membrane formation.

QUESTION #17

• Q: What parts of the lung are likely to be more severely involved by congestion and edema?

• A: The basal regions of the lower lobes are likely to be more severely involved, since because hydrostatic pressure is greater in these sites.

QUESTION #18

• Q: What is the most common cause of cardiogenic edema?

• A: Increased hydrostatic pressure from left-sided heart failure is the most common cause of cardiogenic edema.

• 12 - Lung, chronic passive congestion - Gross, cut surface   In chronic passive congestion, the lungs are heavy, firm, and relatively airless, and they have a patchy brown discoloration. The microscopic basis for this brown induration is discussed with the following image.

QUESTION #19

• Q: What is the nature of this pigment?

• A: The brown pigment is the result of hemosiderin.

• 13 - Lung, chronic passive congestion - Medium power   In long-standing pulmonary congestion, the engorged capillaries may rupture, causing intra-alveolar hemorrhages. Phagocytosis and breakdown of the extravasated red blood cells leads to the appearance of pigmented macrophages ("heart failure cells"). Chronically edematous alveolar septa may undergo fibrosis. This feature, combined with the presence of brown pigment, results in a gross finding termed brown induration.

QUESTION #20

• Q: Name some other conditions in which abundant iron pigment is present in the lungs.

• A: When there is a local or systemic excess of iron, ferritin forms hemosiderin granules. Any form of pulmonary hemorrhage, including thromboembolism, acute left-sided heart failure, Goodpasture syndrome, and idiopathic pulmonary hemosiderosis, may result in accumulation of iron in the lung.

• 14 - Lung, pigmented macrophages in chronic passive congestion - Low power   In more advanced cases of passive congestion, large focal aggregates of pigmented macrophages are present. The pigment has been stained blue in a cytochemical reaction for detection of iron (Prussian Blue Stain).