LUNG PATHOLOGY

Review Of Anatomy & physiology

• Cartilage is present to level of proximal bronchioles

• Beyond terminal bronchiole gas exchange occurs

• The distal airspaces are kept open by elastic tension in alveolar walls

Pulmonary Atelectasis

Pulmonary Atelectasis

• Lung Collapse

• loss of lung volume caused by inadequate expansion of airspaces

• May involve the entire lung, a lobe or a segment

PE

PE with Hemosiderin laden macrophages

ARDS (Diffuse alveolar damage

DAD hyaline membrane

Asthma

Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or in the early morning. These symptoms are usually associated with widespread but variable bronchoconstriction and airflow limitation that is at least partly reversible, either spontaneously or with treatment.

• These lungs appear essentially normal, but are normal-appearing because they are the hyperinflated lungs of a patient who died with status asthmaticus.

• The cut section of the hyperinflated lung of a patient dying in status asthmaticus appears essentially normal.

What are the 4 classical histologic findings in bronchial asthma?

• This cast of the bronchial tree is formed of inspissated mucus and was coughed up by a patient during an asthmatic attack. The outpouring of mucus from hypertrophied bronchial submucosal glands, the bronchoconstriction, and dehydration all contribute to the formation of mucus plugs that can block airways in asthmatic patients.

• Between the bronchial cartilage at the right and the bronchial lumen filled with mucus at the left is a submucosa widened by smooth muscle hypertrophy and inflammation (mainly eosinophils). These are changes of bronchial asthma. The peripheral eosinophil count or the sputum eosinophils can be increased during an asthmatic attack.

• At high magnification, the numerous eosinophils are prominent from their bright red cytoplasmic granules in this case of bronchial asthma.

Bronchiectasis

• Is the permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic supporting tissue

BRONCHIECTASIS

• This is another form of obstructive lung disease known as bronchiectasis. Bronchiectasis occurs when there is obstruction or infection with inflammation and destruction of bronchi so that there is permanent dilation. Once the dilated bronchi are present, as seen here grossly in the mid lower portion of the lung, the patient has recurrent infections because of the stasis in these airways. Copius purulent sputum production with cough is typical.

• A closer view demonstrates the focal area of dilated bronchi with bronchiectasis. Bronchiectasis tends to be localized with disease processes such as neoplasms and aspirated foreign bodies that block a portion of the airways. Widespread bronchiectasis is typical for patients with cystic fibrosis who have recurrent infections and obstruction of airways by mucus throughout the lungs.

• Bronchiectasis is seen here. The repeated episodes of inflammation can result in scarring, which has resulted in fibrous adhesions between the lobes. Fibrous pleural adhesions are common in persons who have had past episodes of inflammation of the lung that involve the pleura. With extensive involvement, the pleural space may be obliterated.

• The mid lower portion of this photomicrograph demonstrates a dilated bronchus in which the mucosa and wall is not clearly seen because of the necrotizing inflammation with destruction. This is the microscopic appearance of bronchiectasis. Bronchiectasis is not a specific disease, but a consequence of another disease process that destroys airways.

Chronic BronchitisChronic productive cough on most days of 3 consecutive months in 2 consecutive years Providing other causes have been excluded..The pathological hallmarks of chronic bronchitis are congestion of the bronchial mucosa and a prominent increase in the number and size of the bronchial mucus glands.

• Chronic bronchitis does not have characteristic pathologic findings, but is defined clinically as a persistent productive cough for at least three consecutive months in at least two consecutive years. Most patients are smokers. Often, there are features of emphysema as well.

Emphysema

Abnormal and permanent dilatation of air spaces associated with destruction of their walls .

• The chest cavity is opened at autopsy to reveal numerous large bullae apparent on the surface of the lungs in a patient dying with emphysema. Bullae are large dilated airspaces that bulge out from beneath the pleura. Emphysema is characterized by a loss of lung parenchyma by destruction of alveoli so that there is permanent dilation of airspaces.

• On cut section of the lung, the dilated airspaces with emphysema are seen. Although there tends to be some scarring with time because of superimposed infections, the emphysematous process is one of loss of lung parenchyma, not fibrosis.

CENTRI-acinar PAN-acinar

• Microscopically at high magnification, the loss of alveolar walls with emphysema is demonstrated. Remaining airspaces are dilated.

Granulomatous disease

Here is the gross appearance of a lung with tuberculosis. Scattered tan granulomas are present, mostly in the upper lung fields. Some of the larger granulomas have central caseation. Granulomatous disease of the lung grossly appears as irregularly sized rounded nodules that are firm and tan. Larger nodules may have central necrosis known as caseation

This is another example of granulomatous disease of the lung. The pattern of smaller nodules which have a propensity for upper lobe involvement suggests a granulomatous process rather than metastatic disease .

On closer inspection, the granulomas have areas of caseous necrosis. This is very extensive granulomatous disease. This pattern of multiple caseating granulomas primarily in the upper lobes is most characteristic of secondary (reactivation)

tuberculosis.

When there is extensive caseation and the granulomas involve a larger bronchus, it is possible for much of the soft, necrotic center to drain out and leave behind a cavity. Cavitation is typical for large granulomas with

tuberculosis .

There is a small tan-yellow subpleural granuloma in the mid-lung field on the right. In the hilum is a small yellow tan granuloma in a hilar lymph node next to a bronchus.

This is the "Ghon complex" that is the characteristic gross appearance with

primary tuberculosis .

The Ghon complex is seen here at closer range .

Primary tuberculosis is the pattern seen with initial infection with tuberculosis in children .

Reactivation, or secondary tuberculosis, is more typically seen in adults.

Well-defined granulomas are seen here. They have rounded outlines. The one toward the center of the photograph contains Langhans giant cells. Granulomas are composed of transformed macrophages called epithelioid cells along with lymphocytes, occasional PMN's, plasma cells, and fibroblasts. The localized, small appearance of these granulomas suggests that the immune response is fairly good .

At low magnification, this photomicrograph reveals multiple granulomas. Granulomatous disease by chest radiograph

can appear as reticulonodular densities .

The edge of a granuloma is shown here at high magnification. At the upper right is amorphous pink caseous material composed of the necrotic elements of the granuloma as well as the infectious organisms. This area is ringed by the inflammatory component with epithelioid cells, lymphocytes, and fibroblasts .

At high magnification, the granuloma demonstrates that the epithelioid macrophages are elongated with long, pale nuclei and pink cytoplasm. The macrophages organize into committees called giant cells. The typical giant cell for infectious granulomas is called a

Langhans giant cell and has the nuclei lined up along one edge of the cell .

In order to find the mycobacteria in a tissue section, a stain for acid fast bacilli is done (AFB stain). The mycobacteria stain as red rods.

When the immune response is poor or is overwhelmed by an extensive infection, then it is possible to see the gross pattern of granulomatous disease seen here. This is a "miliary" pattern of granulomas because there are a multitude of small tan granulomas, about 2 to 4 mm in size, scattered throughout the lung parenchyma. The miliary pattern gets its name from the resemblence of the granulomas to

millet seeds .

At closer range, the miliary pattern is seen throughout the lung. Dissemination of the infectious agent (M. tuberculosis, fungi) may produce a similar pattern in other organs

Pneumonias

• The cut surface of this lung demonstrates the typical appearance of a bronchopneumonia with areas of tan-yellow consolidation. Remaining lung is dark red because of marked pulmonary congestion. Bronchopneumonia is characterized by patchy areas of pulmonary consolidation. These areas become almost confluent in the left lower lobe on the bottom left of the photograph. The areas of consolidation are firmer than the surrounding lung.

• Here is another example of a bronchopneumonia. The lighter areas that appear to be raised on cut surface from the surrounding lung are the areas of consolidation of the lung.

• At higher magnification, the pattern of patchy distribution of a bronchopneumonia is seen. The consolidated areas here very closely match the pattern of lung lobules (hence the term "lobular" pneumonia).A bronchopneumonia is classically a "hospital acquired" pneumonia seen in persons already ill from another disease process. Typical bacterial organisms include: Staphylococcus aureus, Klebsiella, E. coli, Pseudomonas.

• This is a lobar pneumonia in which consolidation of the entire left upper lobe has occurred. This pattern is much less common than the bronchopneumonia pattern. In part, this is due to the fact that most lobar pneumonias are due to Streptococcus pneumoniae (pneumococcus) and for decades, these have responded well to penicillin therapy so that advanced, severe cases are not seen as frequently. However, pneumoccoci, like most other bacteria, are developing more resistance to antibiotics. Severe pneumococcal pneumonia still occurs, even in young to middle aged persons (not just the very young and the very old) and has a mortality rate of 20%!

• A closer view of the lobar pneumonia demonstrates the distinct difference between the upper lobe and the consolidated lower lobe. Radiographically, areas of consolidation appear as infiltrates.

• The pleural surface at the lower left demonstrates areas of yellow-tan purulent exudate. Pneumonia may be complicated by a pleuritis. Initially, there may just be an effusion into the pleural space. There may also be a fibrinous pleuritis. However, bacterial infections of lung can spread to the pleura to produce a purulent pleuritis. A collection of pus in the pleural space is known as empyema.

• Seen here are two lung abscesses, one in the upper lobe and one in the lower lobe of this left lung. An abscess is a complication of severe pneumonia, most typically from virulent organisms such as S. aureus. Abscesses are complications of aspiration, where they appear more frequently in the right posterior lung.

• Seen here are lung abscesses grossly in which the purulent exudate has drained following sectioning to reveal the abscess cavities. Abscesses can be a source for septicemia and are difficult to treat.

• At higher magnification can be seen a patchy area of alveoli that are filled with inflammatory cells. The alveolar structure is still maintained, which is why a pneumonia often resolves with minimal residual destruction or damage to the lung.

• At high magnification, the alveolar exudate of mainly neutrophils is seen. The surrounding alveolar walls have capillaries that are dilated and filled with RBC's. Such an exudative process is typical for bacterial infection. This exudate gives rise to the productive cough of purulent yellow sputum seen with bacterial pneumonias.

• More virulent bacteria and/or more severe pneumonias can be associated with destruction of lung tissue and hemorrhage. Here, alveolar walls are no longer visible because there is early abscess formation. There is also hemorrhage.

• At higher magnification, early abscessing pneumonia is shown. Alveolar walls are not clearly seen, only sheets of neutrophils.

Lung Tumors

This is a squamous cell carcinoma of the lung that is arising centrally in the lung (as most squamous cell carcinomas do). It is obstructing the right main bronchus. The neoplasm is very firm and has a pale white to tan cut surface .

This is a larger squamous cell carcinoma in which a portion of the tumor demonstrates central cavitation, probably because the tumor outgrew its blood supply. Squamous cell carcinomas are one of the more common primary malignancies of lung and are most often seen in smokers

• The pink cytoplasm with distinct cell borders and intercellular bridges characteristic for a squamous cell carcinoma are seen here at high magnification. Such features are seen in well-differentiated tumors (those that more closely mimic the cell of origin(.

• In this squamous cell carcinoma at the upper left is a squamous eddy with a keratin pearl. At the right, the tumor is less differentiated and several dark mitotic figures are seen.

This chest radiograph demonstrates a large 5 cm diameter squamous cell carcinoma of the right lower lobe. The 1.5 cm bright opacity in the middle of the mass is a calcified granuloma that was seen on lateral view to be behind the neoplasm. Additional calcified granulomatous areas are medial to the mass. The sternal wire loops are from a previous coronary artery bypass

procedure.

This is a peripheral adenocarcinoma of the lung .

Adenocarcinomas and large cell anaplastic carcinomas tend to occur more peripherally in lung. Adenocarcinoma is the one cell type of primary lung tumor that occurs more often in non-smokers and in smokers who have quit. If this neoplasm were confined to the lung (a lower stage), then resection would have a greater chance for cure. The solitary appearance of this neoplasm suggests that the tumor is primary rather than metastatic

This is another type of adenocarcinoma of lung known as bronchioloalveolar carcinoma. Seen here is the multifocal variant that appears grossly as a pneumonic consolidation. Most of the upper lobe toward the right has a pale tan to grey appearance

Microscopically, the bronchioloalveolar carcinoma is composed of columnar cells that proliferate along the framework of alveolar septae. The cells are well-differentiated. These neoplasms in general have a better prognosis than most other primary lung cancers

Arising centrally in this lung and spreading extensively is a small cell anaplastic (oat cell) carcinoma. The cut surface of this tumor has a soft, lobulated, white to tan appearance. The tumor seen here has caused obstruction of the main bronchus to left lung so that the distal lung is collapsed. Oat cell carcinomas are very aggressive and often metastasize widely before the primary tumor mass in the lung reaches a large size

Here is an oat cell carcinoma which is spreading along the bronchi. The speckled black rounded areas represent hilar lymph nodes with metastatic carcinoma. These neoplasms are more amenable to chemotherapy than radiation therapy or surgery, but the prognosis is still poor. Oat cell carcinomas occur almost exclusively

in smokers .

This is the microscopic pattern of a small cell anaplastic (oat cell) carcinoma in which small dark blue cells with minimal cytoplasm are packed together in sheets

The dense white encircling tumor mass is arising from the visceral pleura and is a mesothelioma. These are big bulky tumors that can fill the chest cavity.The risk factor for mesothelioma is asbestos exposure. However, mesothelioma is rare even in persons with asbestos exposure. Asbestosis more commonly predisposes to bronchogenic carcinomas, increasing the risk by a factor of five. Smoking increases the risk for lung cancer by a factor of ten. Thus, smokers with a history of asbestos exposure have a risk 50 fold greater likelihood of for

developing lung cancer .

Here are larger but still variably-sized nodules of metastatic carcinoma in lung

Multiple variably-sized masses are seen in all lung fields. These tan-white nodules are characteristic for metastatic carcinoma. Metastases to the lungs are more common even than primary lung neoplasms simply because so many other primary tumors can metastasize to the lungs. Even the hilar nodes in this photograph demonstrate nodules of metastatic carcinoma. The nodules are usually in the periphery and do not

cause major obstruction .

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