Tuberculosis
Mycobacterium tuberculosis is the organism that is the causative agent for
tuberculosis (TB). There are other "atypical" mycobacteria such as M. kansasii that
may produced a similar clincal and pathologic appearance of disease. M. avium-
intracellulare (MAI) seen in immunocompromised hosts (particularly in persons with
AIDS) is not primarily a pulmonary infection in terms of its organ distribution (mostly
in organs of the mononuclear phagocyte system).
Tuberculosis is becoming a world-wide problem. War, famine, homelessness, and a
lack of medical care all contribute to the increasing incidence of tuberculosis among
disadvantaged persons. Since TB is easily transmissible between persons, then the
increase in TB in any segment of the population represents a threat to all segments
of the population. This means that it is important to institute and maintain appropriate
public health measures, including screening, vaccination (where deemed of value),
and treatment. A laxity of public health measures will contribute to an increase in
cases. Failure of adequate treatment promotes the development of resistant strains
of tuberculosis.
Patterns of Infection
There are two major patterns of disease with TB:
Primary tuberculosis: seen as an initial infection, usually in children. The initial
focus of infection is a small subpleural granuloma accompanied by
granulomatous hilar lymph node infection. Together, these make up the Ghon
complex. In nearly all cases, these granulomas resolve and there is no further
spread of the infection.
Secondary tuberculosis: seen mostly in adults as a reactivation of previous
infection (or reinfection), particularly when health status declines. The
granulomatous inflammation is much more florid and widespread. Typically,
the upper lung lobes are most affected, and cavitation can occur.
When resistance to infection is particularly poor, a "miliary" pattern of spread can
occur in which there are a myriad of small millet seed (1-3 mm) sized granulomas,
either in lung or in other organs.
Dissemination of tuberculosis outside of lungs can lead to the appearance of a
number of uncommon findings with characteristic patterns:
Skeletal Tuberculosis: Tuberculous osteomyelitis involves mainly the
thoracic and lumbar vertebrae (known as Pott's disease) followed by knee and
hip. There is extensive necrosis and bony destruction with compressed
fractures (with kyphosis) and extension to soft tissues, including psoas "cold"
abscess.
Genital Tract Tuberculosis: Tuberculous salpingitis and endometritis result
from dissemination of tuberculosis to the fallopian tube that leads to
granulomatous salpingitis, which can drain into the endometrial cavity and
cause a granulomatous endometritis with irregular menstrual bleeding and
infertility. In the male, tuberculosis involves prostate and epididymis most
often with non-tender induration and infertility.
Urinary Tract Tuberculosis: A "sterile pyuria" with WBC's present in urine
but a negative routine bacterial culture may suggest the diagnosis of renal
tuberculosis. Progressive destruction of renal parenchyma occurs if not
treated. Drainage to the ureters can lead to inflammation with ureteral
stricture.
CNS Tuberculosis: A meningeal pattern of spread can occur, and the
cerebrospinal fluid typically shows a high protein, low glucose, and
lymphocytosis. The base of the brain is often involved, so that various cranial
nerve signs may be present. Rarely, a solitary granuloma, or "tuberculoma",
may form and manifest with seizures.
Gastrointestinal Tuberculosis: This is uncommon today because routine
pasteurization of milk has eliminated Mycobacterium bovis infections.
However, M. tuberculosis organisms coughed up in sputum may be
swallowed into the GI tract. The classic lesions are circumferential ulcerations
with stricture of the small intestine. There is a predilection for ileocecal
involvement because of the abundant lymphoid tissue and slower rate of
passage of lumenal contents.
Adrenal Tuberculosis: Spread of tuberculosis to adrenals is usually bilateral,
so that both adrenals are markedly enlarged. Destruction of cortex leads to
Addison's disease.
Scrofula: Tuberculous lymphadenitis of the cervical nodes may produce a
mass of firm, matted nodes just under the mandible. There can be chronic
draining fistulous tracts to overlying skin. This complication may appear in
children, and Mycobacterium scrofulaceum may be cultured.
Cardiac Tuberculosis: The pericardium is the usual site for tuberculous
infection of heart. The result is a granulomatous pericarditis that can be
hemorrhagic. If extensive and chronic, there can be fibrosis with calcification,
leading to a constrictive pericarditis.
The following images illustrate gross pathologic findings with tuberculosis:
1. Ghon complex in lung, gross.
2. Ghon complex in lung, closer view, gross.
3. Cavitary tuberculosis in lung, gross.
4. Cavitary tuberculosis in lung, closer view, gross.
5. Cavitary tuberculosis in lung, florid, gross.
6. Miliary tuberculosis in lung, gross.
7. Miliary tuberculosis in lung, closer view, gross.
Microscopic Findings
Microscopically, the inflammation produced with TB infection is granulomatous, with
epithelioid macrophages and Langhans giant cells along with lymphocytes, plasma
cells, maybe a few PMN's, fibroblasts with collagen, and characteristic caseous
necrosis in the center. The inflammatory response is mediated by a type IV
hypersensitivity reaction. This can be utilized as a basis for diagnosis by a TB skin
test. An acid fast stain (Ziehl-Neelsen or Kinyoun's acid fast stains) will show the
organisms as slender red rods. An auramine stain of the organisms as viewed under
fluorescence microscopy will be easier to screen and more organisms will be
apparent. The most common specimen screened is sputum, but the histologic stains
can also be performed on tissues or other body fluids. Culture of sputum or tissues
or other body fluids can be done to determine drug sensitivities.
1. Granulomas in lung, low power microscopic.
2. Granuloma with caseous necrosis, high power microscopic.
3. Granuloma with epithelioid macrophages and a Langhans giant cell,
high power microscopic.
4. Granulomatous endometritis, high power microscopic.
5. Ziehl-Neelsen acid fast stain, microscopic, AFB stain.
6. Auramine stain, M. tuberculosis, fluorescence microscopy.
Tuberculin Skin Testing
Skin testing for tuberculosis is useful in countries where the incidence of tuberculosis
is low, and the health care system works well to detect and treat new cases. In
countries where BCG vaccination has been widely used, the TB skin test is not
useful, because persons vaccinated with BCG will have a positive skin test.
The TB skin test is based upon the type 4 hypersensitivity reaction. If a previous TB
infection has occurred, then there are sensitized lymphocytes that can react to
another encounter with antigens from TB organisms. For the TB skin test, a
measured amount (the intermediate strength of 5 tuberculin units, used in North
America) of tuberculin purified protein derivative (PPD) is injected intracutaneously to
form a small wheal, typically on the forearm. In 48 to 72 hours, a positive reaction is
marked by an area of red induration that can be measured by gentle palpation
(redness from itching and scratching doesn't count). Reactions over 10 mm in size
are considered positive in non-immunocompromised persons.
Repeated testing may increase the size of the reaction (induration), but repeated TB
skin testing will not lead to a positive test in a person not infected by TB. Anergy, or
absence of PPD reactivity in persons infected with TB, can occur in
immunocompromised persons, or it may even occur in persons newly infected with
TB, or in persons with miliary TB.
1. Injecting PPD intracutaneously, gross.
2. A properly placed TB skin test, gross.
3. A positive TB skin test, gross.
