Lesson 27

Tuberculosis. Syphilis

Key points:
1. Morphology of tissue reactions at tuberculosis. Modern morphological classification oftuberculosis. Primary tuberculosis complex: morphological characteristics. Progression ofprimary tuberculosis with process generalization: morphological characteristics. Chroniccourse of primary tuberculosis: morphological characteristics. Hematogenous tuberculosis(generalized, pulmonary, with predominant internal organ lesions): morphological characteristics.
2. Secondary tuberculosis. Morphological characteristics, complications, consequences,causes of death. Pathomorphosis of tuberculosis.
3. Primary and secondary syphilis. Pathomorphology of visceral syphilis. Pathomorphologyof congenital syphilis: syphilis of stillbirths, early congenital syphilis of newborns and infants,late congenital syphilis of children of preschool and school age.

Sources:
1. Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015. P.266-339, 1196-1207, 1218-1225, paragraph “Tumors”in chapters 15-25.
2. Kumar, Vinay, Abul K Abbas, Jon C Aster, and Stanley L. 1915-2003 Robbins. RobbinsBasic Pathology. Tenth edition. Philadelphia, PA: Elsevier/Saunders, 2018. P.190-238, paragraph “Tumors”in chapters of systemic pathology.
3. Klatt, Edward C. Robbins and Cotran Atlas of Pathology. Third edition. Philadelphia, PA: Elsevier Saunders, 2015.
4. Klatt, Edward C., and Vinay Kumar. Robbins and Cotran Review of Pathology. Fourth edition. Philadelphia, PA: Elsevier Saunders, 2015.
5. Harsh Mohan. Essential Pathology for Dental Students.Fourth edition. Jaypee Brothers,Medical Publishers Pvt. Limited, 2011. P.221-301

Acid-fast bacilli

To identify the mycobacteria in a tissue section, a stain for acid-fast bacilli (AFB) is performed. The mycobacteria stain as red rods, seen here at high magnification. The large amount of lipid in the form of mycolic acid imparts this acid-fast property to the mycobacteria and accounts for their resistance to immune cell destruction. Their destruction depends on a TH1 immune response with CD4 cell elaboration of interferon-γ that recruits monocytes and transforms them into epithelioid macrophages, then stimulates upregulation of nitric oxide synthase within epithelioid cell and giant cell phagosomes. Microscopic identification of AFB in sputum aids in diagnosis; use of PCR amplification of mycobacterial DNA is a more sensitive diagnostic technique.

Primary tuberculosis

There is a small, tan-yellow subpleural granuloma in the mid lung field. In the hilum is a small yellow-tan granuloma in a hilar lymph node next to a large bronchus. This is the Ghon complex, which is the characteristic gross appearance with primary tuberculosis. In most individuals, this granulomatous disease is subclinical and does not progress further. Over time, the granulomas decrease in size and can calcify, leaving a focal bright spot on a chest radiograph that suggests remote granulomatous disease. Primary tuberculosis is seen with initial infection, most often in children. Diagnosis of tuberculosis can be aided by a positive interferon-gamma release assay, positive tuberculin skin test, and findings on chest radiograph.

Secondary tuberculosis

These scattered tan granulomas are present mostly in upper lung fields. Granulomatous lung disease grossly appears as irregularly sized, rounded nodules. Larger nodules may have central caseous necrosis that includes elements of liquefactive and coagulative necrosis. This upper lobe pattern of involvement is most characteristic of secondary (reactivation or reinfection) tuberculosis, typically seen in adults. Fungal granulomas (histoplasmosis, cryptococcosis, coccidioidomycosis, blastomycosis) can mimic this pattern as well. This propensity of granulomas to involve upper lobes is typical and helps distinguish this infection from metastatic disease with radiographic imaging studies.

Miliary tuberculosis

When the immune response is poor or is overwhelmed by an extensive infection, it is possible to see the gross pattern of granulomatous disease known as a miliary pattern because there are a multitude of small, pale tan granulomas, averaging 2 to 4 mm in size, scattered throughout the lung parenchyma. This pattern gets its name from the resemblance of the granulomas to millet seeds. Dissemination of the causative infectious agent (Mycobacterium tuberculosis or fungi) may produce a similar miliary pattern in other organs.

Pulmonary tuberculosis

Well-defined granulomas have rounded outlines with discrete borders. Granulomas are composed of transformed macrophages called epithelioid cells, along with lymphocytes, occasional polymorphonuclear leukocytes, plasma cells, and fibroblasts. The macrophages stimulated by cytokines, such as interferon-γ secreted from nearby T lymphocytes, may group together to form Langhans giant cells. The localized, small appearance of these granulomas suggests that the immune response is good, and the infection is being contained. This would produce a reticulonodular radiographic pattern in the lungs.

Tuberculous granuloma

A granulomatous inflammatory response to tuberculosis includes mainly epithelioid cells, lymphocytes, and fibroblasts. This granuloma shows 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. The process of granulomatous inflammation occurs over months to years (did you ever hear of a committee action that was completed in a short time?).

Tuberculous pericarditis

Pericarditis from Mycobacterium tuberculosis infection can produce extensive granulomatous inflammation with resultant calcification that can encircle the heart and severely restrict cardiac motion (so-called constrictive pericarditis). Granulomatous inflammation over the surface of the heart with Langhans giant cells is shown, with myocardial cells at the right. This is a chronic process developing over weeks to months.

Tuberculous enteritis

These circumferential ulcerations, one larger and one smaller ulcer, are characteristic of infection with Mycobacterium bovis (rare now because of pasteurization of milk). Swallowed pulmonary secretions with Mycobacterium tuberculosis may also produce this finding, as well as hematogenous spread of mycobacteria. It may mimic inflammatory bowel disease. Affected persons may have abdominal pain, weight loss, anemia, and fever with night sweats. The circumferential ulcerations may heal with stricture, producing bowel obstruction.

Tuberculous salpingitis

Granulomatous salpingitis is uncommon and is related to rates of tuberculosis. Note the two pale granulomas here, including a large Langhans giant cell at the upper right. Disseminated Mycobacterium tuberculosis infections may involve the female genital tract, including the fallopian tube. Some cases may be related to actinomycosis, schistosomiasis, and sarcoidosis. The result may be infertility.

Tuberculous adrenalitis

Although most cases of Addison disease are now idiopathic (presumably autoimmune in cause), there are still cases resulting from disseminated Mycobacterium tuberculosis infection. Shown here is a granuloma with central pink areas of caseous necrosis and surrounding inflammation with lymphocytes, epithelioid cells, and Langhans giant cells. Residual adrenal is present on the right. This infection proceeds over months to years, and adrenocortical destruction leads to chronic adrenal insufficiency. The decreased plasma cortisol leads to increased ACTH and precursors that can stimulate melanocytes, leading to skin hyperpigmentation.

Tuberculous osteomyelitis

Extensive bone destruction is shown involving the T8 and T9 mid-thoracic vertebrae in a patient with disseminated Mycobacterium tuberculosis infection. Hematogenous spread is most likely, although there may be direct extension from the lung. This is Pott disease of the spine. The vertebral body destruction here has resulted in impingement on the spinal cord. The infection may spread into adjacent paraspinal or psoas muscles to form a cold abscess

Tuberculous meningitis

This is the typical basilar meningitis that occurs with tuberculous meningitis. Note the thickening of the meninges over the pons. Mycobacterium tuberculosis infection involving the brain most often produces a meningoencephalitis, or chronic meningitis, which can lead to headache, malaise, mental confusion, and emesis. Examination of CSF obtained by lumbar puncture may show a pleocytosis marked by mononuclear cells with or without neutrophils, an elevated protein, and normal to reduced glucose. The inflammation can lead to scarring that blocks the flow of CSF through foramina of Luschka and Magendie, resulting in obstructive hydrocephalus. An obliterative endarteritis can lead to focal infarction.

Spirochetes

These corkscrew-shaped organisms seen with Warthin-Starry stain are Treponema pallidum organisms, which cause syphilis. They are usually few in number in the tissue lesions of tertiary syphilis.

Hepar lobatum, tertiary syphilis

The odd clefting that divides the liver into large irregular nodules with smooth surfaces is called hepar lobatum. The use of serologic tests for syphilis coupled with widespread antibiotic therapy for Treponema pallidum infections has greatly reduced the cases of tertiary syphilis.

Neurosyphilis (Craniotabes)

Note the ventricular surface studded with many ependymal granulations secondary to chronic Treponema pallidum infection. This nonspecific finding occurs in other infections or can be caused by chronic pressure hydrocephalus. The perivascular inflammation with abundant plasma cells and lymphocytes can cause focal ischemia with infarction. This granular ependymitis can lead to obstructive hydrocephalus. Gummatous necrosis may be seen. Affected patients may have progressive dementia (general paresis). Involvement of dorsal sensory spinal roots leads to tabes dorsalis with loss of position and pain sense, leading to ataxia and increased risk for trauma (Charcot joint).

Syphilitic (luetic) aortitis

This aortic root is widened, and the commissures of the aortic valve cusps are pulled apart. The arch of the aorta shows peculiar irregular intimal wrinkling (“tree bark” pattern) that is typical of syphilitic aortitis. The widening of the root can cause aortic insufficiency and aneurysmal dilation of the ascending aorta. Such dilation may also be seen with Marfan syndrome, but the intima would not show this wrinkling. Given the rarity of tertiary syphilis, atherosclerosis is now the most common cause of proximal aortic aneurysmal dilation.

Syphilitic aortitis

The intimal surface of the aorta shows wrinkling or “tree-barking” that is typical of syphilitic aortitis. This aortitis is caused by infection with the spirochete Treponema pallidum, which involves the vasa vasorum (an end aortitis) and leads to focal medial loss that produces the wrinkling. This is a complication of tertiary syphilis that manifests decades after the initial infection, and primary syphilis typically is diagnosed with the appearance of a firm chancre on the genitalia.

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