23. Tuberculosis - Pathogenesis

24. Tuberculosis - Pathogenesis

27. Tuberculosis – Natural History & Spectrum Majority

33. Primary Tuberculosis – Gross Morphology Primary tuberculosis is the pattern seen with initial infection with tuberculosis, most often in children. Reactivation or reinfection to produce secondary tuberculosis is more typically seen in adult

35. Primary Tuberculosis – Microscopic Morphology Well-defined non-caseating granulomas . Granulomas are composed of transformed macrophages called epithelioid cells along with lymphocytes, occasional PMN's, plasma cells, and fibroblasts.

36. Primary Tuberculosis – Microscopic Morphology

37. Primary Tuberculosis – Microscopic Morphology Caseous necrosis is characterized by acellular pink areas of necrosis that is surrounded by a granulomatous inflammatory process

38. Primary Tuberculosis – Microscopic Morphology At high magnification, the granuloma demonstrates epithelioid macrophages that are elongated with long, pale nuclei and pink cytoplasm. The macrophages fuse to form 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.

39. Primary Tuberculosis – Microscopic Morphology This is the acid fast stain of Mycobacterium tuberculosis (MTB). Note the red rods

49. Secondary Tuberculosis – Gross Morphology This is an 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

50. Secondary Tuberculosis – Gross Morphology 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. However, fungal granulomas (histoplasmosis, cryptococcosis, coccidioidomycosis) can mimic this pattern as well

51. Secondary Tuberculosis – Gross Morphology 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. Cavitation is more common in the upper lobes

52. Secondary Tuberculosis – Gross Morphology This is more extensive caseous necrosis, with confluent cheesy tan granulomas in the upper portion of this lung in a patient with tuberculosis. The tissue destruction is so extensive that there are areas of cavitation (cystic spaces) being formed as the necrotic (mainly liquefied) debris drains out via the bronchi

57. Miliary Tuberculosis – Gross Morphology 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

58. Adrenal Gland Tuberculosis This is a caseating granuloma of tuberculosis in the adrenal gland. Tuberculosis used to be the most common cause of chronic adrenal insufficiency. Now, idiopathic (presumably autoimmune) Addison's disease is much more often the cause for chronic adrenal insufficiency

59. Miliary Tuberculosis in Spleen This spleen shows a miliary pattern of granulomatous inflammation, with numerous small tan granulomas. This suggests a poor immune response. This patient had AIDS. The infection turned out to be Mycobacterium avium-intracellulare (MAI), also known as Mycobacterium avium-complex (MAC)

66. Atypical Mycobacterial Infection – Gross Morphology The lymph nodes in this mesentery, best seen at the left, are enlarged and have cut surfaces that appear yellow-tan. These nodes are filled with sheets of Mycobacterium avium-complex (MAC) organisms, and the immune response is so poor in this AIDS patient that there is no focal granuloma formation

67. Atypical Mycobacterial Infection – Microscopic Morphology Microscopically, Mycobacterium avium-intracellulare infection is marked by numerous acid fast organisms growing within macrophages . Lots of bright red rods are seen, particularly in macrophages, in this acid fast stain of lymph node

68. PRIMARY SECONDARY Affect: * Previously unexposed, unsensitized persons * Non immune children * Elderly & immuncomprised * Very young Source: * Exogenous * 5% develop significant disease Morphology & Site: * Primary T.B. mostly in lung rarely in intestine, pharynx, larynx & skin * Involve lower part of upper lobe or upper part of lower lobe close to pleura * Ghon-focus A 1-1.5 cm gray white inflammatory consolidation with involvement of hilar lymph node * In 95% of cases the development of cell- mediated immunity control the infection & no lesion develops Affect: * Previously sensitized persons Sources: * Develop from: - Reactivation of dormant lesion - Primary lesion if immunity of host is lowered “exogenous reinfection” - 5% of primary T.B. develop secondary T.B Morphology & Site: * Localized at the apex of both or one upper lobes because of better 0 2 tension * Less lymph node involvement than the primary * Cavitation is more common with dissemination along air ways - Cavitation is a source of infection by sputum * Typically consolidating lesion 1-2 cm, firm gray-yellow at apical pleura with central caseation & peripheral fibrosis