This document discusses the pathology of tuberculosis and leprosy lesions. It describes the types and morphology of granulomatous lesions caused by each disease. For tuberculosis, it covers primary and secondary pulmonary TB as well as extrapulmonary TB. It discusses non-caseating and caseating granulomas and the role of host immunity. For leprosy, it describes the clinical classifications and pathophysiology of tuberculoid and lepromatous forms. It also notes complications that can arise from delayed diagnosis or treatment of each disease.

1. Pathological Lesion in Tuberculosis and Leprosy
Lecture- 42

2. Learning Objectives
Identify the morphology of granulomatous lesions produced by tuberculosis
and leprosy

3. Part ATuberculosis

4. Types of Tuberculosis
A- Pulmonary Tuberculosis
Primary Pulmonary Tuberculosis
Secondary Pulmonary Tuberculosis
B- Extrapulmonary or Isolated organ Tuberculosis
Involves ; intestine, lymph node, bone, skin, vertebrae (Pott disease )
meninges, kidney , adrenals, testis, ovaries, fallopian tubes and
epididymis
C- Miliary Tuberculosis
Pulmonary miliary tuberculosis
Systemic miliary tuberculosis

5. Primary Pulmonary Tuberculosis
Primary/Ghon Complex
Initial focus of infection a small subpleural
granuloma about 10 mm in diameter with caseous
granulomas in draining hilar lymph nodes
Fibrocalcific nodule
Primary lesion get organized, leaving a
fibrocalcific nodule, however, TB bacilli may persist
as viable organism for years
Miliary TB
In immunocomprised patient primary pulmonary
TB would leads to miliary TB
5

6. Secondary Pulmonary Tuberculosis
Reactivation of old primary infection or by
reinfection
Lesions nearly always located in the lung apices,
sometimes bilaterally, and are about 30 mm in
diameter, cavitation can occur at clinical
presentation.
Histologically
Chronic caseous granulomatous inflammation
Progression of disease
Depends on the balance between host sensitivity
and organism virulence
Most lesions, converted to fibrocalcific scars

7. Extrapulmonary or Isolated Organ Secondary Tuberculosis
Dissemination of TB outside of lungs can lead to TB of tonsils, intestine,
CNS, Kidney, bone , skin and genital organs
Miliary Tuberculosis:
May be a consequence of either primary or secondary TB when resistance
to infection is particularly poor, a "miliary" pattern of spread can occur in
which small millet seed (1-3 mm) sized granulomas develops either in lung
or in other organs
Mantoux test is frequently negative

8. Pathogenesis of Tuberculosis

9. Pathogenesis of Granuloma Formation
• Type IV hypersensitivity or delayed type hypersensitivity as the
reaction takes several days to develop. Unlike the other types, it is
not antibody-mediated but rather is a type of cell-mediated response.
• The term delayed is used to differentiate a secondary cellular response,
which appears 48-72 hours after antigen exposure, from an immediate
hypersensitivity response, which generally appears within 12 minutes of
an antigen challenge. These reactions are mediated by T cells and
monocytes/macrophages rather than by antibodies. They are also
termed type IV hypersensitivity reactions.
• CD4+ Th1 helper T cells recognize antigen in a complex with the MHC
class II major histocompatibility complex on the surface of antigen-
presenting cells. These can be macrophages that secrete IL-12, which
stimulates the proliferation of further CD4+ Th1 cells. CD4+ T cells
secrete IL-2 and interferon gamma, inducing the further release of other
Th1 cytokines, thus mediating the immune response. Activated CD8+ T
cells destroy target cells on contact, whereas activated macrophages
produce hydrolytic enzymes and, on presentation with certain
intracellular pathogens, transform into multinucleated giant cells.
Delayed hypersensitivity reactions are inflammatory reactions initiated
by mononuclear leukocytes.
9

10. Morphology of TB Granulomas
Active Lesions; granulomatous reaction which comprises of:
Nodular collection of epithelioid cells
With or without central caseation necrosis
Langhans type of giant cells (multiple nuclei arranged in a
horse-shoe pattern)
Circumferential collar of lymphocytes
Old Lesions;
Granulomas enclosed by rim of fibroblasts
When healed, get fibrocalcifed

11. Non Caseating and Caseating Granulomas

12. Tuberculosis and HIV infection
In the absence of appropriate
T cell-mediated immunity
granulomatous host response
does not occur
The intracellular bacteria
persist and even proliferate
within the macrophages
Mycobacterium avium infection
in a patient with AIDS, showing
clumps of acid-fast organisms

13. Clinical Manifestations of TB
Clinical Features
Systemic manifestations are produced by TNF- alpha and IL -1 released
from activated macrophages
• Fever (low grade, remittent, appear late each afternoon and then subside)
• Night sweats
• Malaise
• Anorexia
• Cough, first mucoid, later purulent and bloody sputum
• Pleuritic chest pain

14. Role of Pathologist in Diagnosis of TB
Sputum Examination: Smears stained
with Z-N examined, under oil immersion
lens, bacilli appear as red rods
FNA – enlarged lymph node
Biopsies - Pleura, Lymph nodes, Lung and
other tissues
14

15. Part B
Leprosy

16. Leprosy
Primarily a granulomatous disease of the peripheral nerves and mucosa of upper
respiratory tract
Etiology: Causative agent: Mycobacterium leprae
In 2009 WHO classify leprosy simply based on the number of (M. leprae bacilli) in
skin lesions;
Paucibacillary leprosy: skin smear from skin lesions shows no leprae bacilli
Multibacillary leprosy: skin smear from skin lesions shows M. leprae bacilli
Clinically classified on the basis of increasing severity of symptoms:
1. Tuberculoid leprosy (host with high resistance)
2. Borderline tuberculoid leprosy
3. Borderline leprosy
4. Borderline lepromatous leprosy
5. Lepromatous leprosy (host with low resistance)
* Indeterminate when not sure

17. Pathophysiology
Lepromatous form
In affected individual with defective T cell immunity,
in contrast excessive B cell response, increase
gamma globulin
Histiocytes in deep dermis and shedding epithelium
shows large numbers of bacilli
Skeletal changes frequent; like claw-hand or flat foot
In advanced leprosy, destruction of sensory nerves
with loss of sensations and circulatory alterations
lead to slowly progressive atrophy of terminal
phalanges and degenerative arthritis

18. Pathophysiology
Tuberculoid form
In affected individual with a relatively high state of natural immunity
Disease is confined to the nerves and the skeletal changes less frequent
Neurotrophic changes may regress but may progress

19. Tuberculoid leprosy
Hypopigmented macules, some become anesthetic
due to early neural involvement
Cell mediated immunity well developed, granulomatous
inflammation, scanty bacilli
Spontaneous resolution in a few years or persists and
progress to other forms
Lepromin test: positive
Borderline Tuberculoid Leprosy
Smaller and more numerous lesions with less nerve
enlargement
May persist, revert to tuberculoid leprosy, or advance to
other forms

20. Borderline Leprosy
Many asymmetrically distributed, reddish plaques, moderately anesthetic,
with regional lymphadenopathy
May persist or regress, often progress to lepromatous type
Borderline Lepromatous Leprosy
Many skin lesions with macules (flat lesions) papules (raised bumps),
plaques, and nodules, sometimes with or without anesthesia
May persist, regress or progress to lepromatous leprosy
2/17/2019

21. Lepromatous Leprosy
Early; hypopigmented macules with no sensory loss, lesions
diffuse and symmetric, with loss of hair, eyebrows or eyelashes
and disfiguring nodularity (Lepromas) of the skin
Late; nerve involvement leads to anesthetic areas and
limb weakness, advance cases aseptic necrosis occurs
Does not regress to less severe forms
Cell mediated immunity is markedly diminished no granulomas
Sheets of foamy macrophages loaded with Z-N positive Lepra
bacilli, lymphoplasmacytic infiltrate
Lepromin test: negative
2/17/2019

22. Clinical Manifestations of Leprosy
Runny nose
Dry scalp
Eye problems
Skin lesions; hypopigmented lesions with decreased sensation, do not heal
after several weeks to months
Thickening of peripheral nerves and loss of sensation in fingers and toes
Muscle weakness
Flat nose due to destruction of nasal cartilage
Skin smears or Nerve biopsy: show acid-fast bacilli with the Ziehl-Neelsen
stain or the Fite stain

23. Complications of Leprosy
Following complications can occur when
diagnosis/treatment is either delayed or started late:
Sensory loss (usually begins in extremities), injured
body parts without awareness ; can lead to additional
infections and poor wound healing
Permanent nerve damage (usually in extremities)
Muscle weakness
Progressive disfigurement (e.g; eyebrows lost,
disfigurement of the toes, fingers, and nose)
Circulatory disturbances leads to aseptic gangrene

24. Assignment
Q1. Draw a diagram of caseous and non-caseous granulomas.
Q2. Why Montoux test is negative in miliary TB?
Q3.Why wound healing is delayed in Leprosy?
Q4. Why Lepromin test is positive in Tuberculoid and negative in
Lepromatous leprosy?
2/17/2019

25. References
• Reading : Robbins Basic Pathology, 10th Edition (2017), By:
Kumar, Abbas, Aster
• Web Path