patoloji-ders-notlari

Title

Serdar Balcı

Diseases and Tumors of the Mediastinum and Pleura

Serdar BALCI, MD

Pleural Lesions

Primary intrapleural bacterial infections

Primary neoplasm, malignant mesothelioma

A secondary complication of an underlying pulmonary disease

Pleural Effusion and Pleuritis

• Pleural effusion
• Presence of fluid in the pleural space
• Transudate → hydrothorax
  • CHF most common cause
• Exudate
  • protein content greater than 2.9gm/dL
  • inflammatory cells
  • pleuritis

Causes of pleural exudate

• Microbial invasion through either direct extension of a pulmonary infection or blood-borne seeding
  • suppurative pleuritis or empyema
• **Cancer **
  • lung carcinoma, metastatic neoplasms to the lung or pleural surface, mesothelioma
  • malignant effusion
  • bloody, hemorrhagic pleuritis
• Pulmonary infarction
• Viral pleuritis
• Systemic lupus erythematosus, rheumatoid arthritis, and uremia
• Previous thoracic surgery

Acute serofibrinous pleuritis related to pneumonia

Autopsy Pathology: A Manual and Atlas

Suppurative pleuritis

Empyema

Autopsy Pathology: A Manual and Atlas

Pleural effusions

• Transudates and serous exudates
  • Resorbed without residual effects
• **Fibrinous, hemorrhagic, and suppurative exudates **
  • Organization, adhesions, fibrous pleural thickening, massive calcifications

Pneumothorax

• Presence of air or other gas in the pleural sac
• Simple or spontaneous pneumothorax
  • Young, healthy adults, men without any known pulmonary disease
• Secondary pneumothorax
  • Thoracic or lung disorder, emphysema, fractured rib
  • Inspired air goes to pleural cavity
    • Emphysema, lung abscess, tuberculosis, carcinoma
    • Mechanical ventilatory support with high pressure

Complications of pneumothorax

• Tension pneumothorax
  • Leak- valve
  • Shifts the mediastinum
  • Compromise pulmonary circulation
  • May be fatal
  • Leak seals but lung is not reexpanded within a few weeks
    • Spontaneously or medical or surgical intervention
    • Scarring may occur, never fully reexpand
  • Serous fluid collects → hydropneumothorax
    • Vulnerable to infection
    • Empyema → pyopneumothorax

Hemothorax

Collection of whole blood

Ruptured intrathoracic aortic aneurysm

In contrast with bloody pleural effusions, the blood clots within the pleural cavity

Autopsy Pathology: A Manual and Atlas

Chylothorax

• Milky lymphatic fluid containing microglobules of lipid
• Always significant
• Obstruction of the major lymph ducts
  • intrathoracic cancer

Malignant Mesothelioma

Cancer of mesothelial cells

Usually arising in the parietal or visceral pleura

Less commonly, in the peritoneum and pericardium

Related to occupational exposure to asbestos in the air

50% of persons with this cancer have a history of exposure to asbestos

Shipyard workers, miners, insulators

Living in proximity to an asbestos factory, a relative of an asbestos worker

The latent period for developing malignant mesothelioma is long

25-40 years after initial asbestos exposure

With combination of cigarette smoking, asbestos exposure greatly increases the risk of lung carcinoma

• Preceded by extensive pleural fibrosis and plaque formation
• Begin in a localized area and over time spread widely
  • contiguous growth or by diffusely seeding the pleural surfaces
• Lung typically is ensheathed by a yellow-white, firm, sometimes gelatinous layer of tumor that obliterates the pleural space

Autopsy Pathology: A Manual and Atlas

Malignant mesothelioma

Autopsy Pathology: A Manual and Atlas

Malignant mesothelioma

Thick, firm, white pleural tumor

Ensheathes lung

Robbins Basic Pathology

Distant metastases are rare

Directly invade the thoracic wall or the subpleural lung tissue

Mesothelioma patterns

• Normal mesothelial cells are biphasic
  • Pleural lining cells
  • Underlying fibrous tissue
• Mesothelioma patterns
  • Epithelial
    • Cuboidal cells line tubular and microcystic spaces
    • Small papillary buds project
    • Most common pattern
    • Confused with a pulmonary adenocarcinoma
  • Sarcomatous
    • Spindled and sometimes fibroblastic-appearing cells
    • Nondistinctive sheets
  • Biphasic, having both sarcomatous and epithelial areas

Malignant mesothelioma

**Papillary formations and desmoplastic stromal reaction. **

Rosai and Ackerman’s Surgical Pathology

Asbestos

• Not removed
• Not metabolized
• Fibers remain in the body for life
• Lifetime risk after exposure does not diminish over time
• Asbestos fibers preferentially gather near the mesothelial cell layer
• Generate reactive oxygen species
• DNA damage with potentially oncogenic mutations
  • p16/CDKN2A, 9p21
  • NF2, 22q12

**Metastatic tumor involving the parietal pleura **

Autopsy Pathology: A Manual and Atlas

Rosai and Ackerman’s Surgical Pathology

THYMOMA

Thymoma

Tumors of thymic epithelial cells

Typically also contain benign immature T cells (thymocytes)

Tumors that are cytologically benign and noninvasive

Tumors that are cytologically benign but invasive or metastatic

Tumors that are cytologically malignant (thymic carcinoma)

• >40 years old
• No gender difference
• Localisation:
  • Most arise in the anterior superior mediastinum
  • Sometimes they occur in the neck, thyroid, pulmonary hilus, or elsewhere
  • Uncommon in the posterior mediastinum
  • 20-30% of tumors in the anterosuperior mediastinum, which is also a common location for certain lymphomas

Clinical Presentation of Thymomas

40% mass effect

30-45% myasthenia gravis

Others incidentally during imaging studies or cardiothoracic surgery

Diseases Associated with Thymoma

**Myasthenia gravis **

Hypogammaglobulinemia

Pure red cell aplasia

Graves disease

Pernicious anemia

Dermatomyositis-polymyositis

Cushing syndrome

Autoimmune Diseases Associated with Thymoma

Thymocytes within thymomas give rise to long-lived CD4+ and CD8+ T cells

Cortical thymomas rich in thymocytes are more likely to be associated with autoimmune disease

Abnormalities in the selection or “education” of T cells maturing within the environment of the neoplasm contribute to the development of diverse autoimmune disorders

Thymomas

• Macroscopically
  • Lobulated
  • Firm
  • Gray-white masses
  • 15-20 cm
  • Sometimes cystic necrosis and calcification
  • Most encapsulated
  • 20-25% penetrate the capsule and infiltrate perithymic tissues and structures

**Gross appearance of a thymoma showing distinct multinodularity. There is focal cystic change in the larger nodule. **

Noninvasive thymomas

Composed of medullary-type epithelial cells

Mixture of medullary and cortical type epithelial cells

The medullary type epithelial cells are elongated or spindle-shaped

There is usually a sparse infiltrate of thymocytes, which often recapitulate the phenotype of medullary thymocytes

Benign thymoma (medullary type):

Neoplastic epithelial cells in a swirling pattern and have bland, oval to elongated nuclei with inconspicuous nucleoli. Few small, reactive lymphoid cells are interspersed.

Invasive thymoma

Tumor that is cytologically benign but locally invasive

Much more likely to metastasize

Epithelial cells are most commonly of the cortical variety, with abundant cytoplasm and rounded vesicular nuclei, and are usually mixed with numerous thymocytes

Malignant thymoma, type I. The neoplastic epithelial cells are polygonal and have round to oval, bland nuclei with inconspicuous nucleoli. Numerous small, reactive lymphoid cells are interspersed.

Thymic carcinoma

• 5% of thymomas
• Macroscopically
  • Fleshy
  • obviously invasive masses
  • accompanied by metastases, lungs
• Microscopically
• Most are squamous cell carcinomas
• Lymphoepithelioma-like carcinoma
  • 50% contain monoclonal EBV genomes

**Gross appearance of thymic carcinoma (type C thymoma). The tumor is invasive and shows foci of necrosis. **

thymic carcinoma