The Pathology of Tuberculosis

Item

Title
The Pathology of Tuberculosis
extracted text
the pathology of tuberculosis

4

E.A. Sheffield

4.1 THE MORPHOLOGY OF
CRANULOMATA

I he histological features of tuberculosis are
characteristic and similar in all sites of infec­
tion. The hallmark of active infection is the
necrotizing epithelioid cell granuloma. It is
also important to point out that tuberculous
granulomata are identical morphologically
and immunologically to granulomata due to
other infectious causes such as histoplasmo­
sis and blastomycosis[l]. Before describing
the pathology of tuberculosis, some general
points will be covered.
The predominant cells in all granulomata,
whether organized into epithelioid cell foci or
not, are non-lymphoid mononuclear cells[2,3).
This diverse group, known as the reticulo­
endothelial or mononuclear phagocyte
system[4], includes blood monocytes, tissue
macrophages (or histiocytes), and organ­
specific forms such as the Kupffer cells of the
liver. In epithelioid cell granulomata they are
represented by macrophages, epithelioid
cells and giant cells of predominantly Langer­
hans type[2,5,6]. The nuclei of these giant
ceils are arranged in an arc around central
granular cytoplasm. Tuberculous granulomas
typically show necrosis; as described later
this is due to the inherent toxicity of the
bacilli and the release of cytokines such as
tumour necrosis factor and interleukin-1 [7].
Mononuclear phagocytes arise from im­
mature bone marrow precursors, circulate
briefly as monocytes and then populate the
tissues as macrophages. They are capable of

rapid differentiation and activation. Mackaness[8] used the term 'activation' to describe
increased activity against ingested patho­
gens; such macrophages can be recognized
functionally[9] and morphologically[10].
An epithelioid cell granuloma consists of a
collection of partly or highly specialized
mononuclear phagocytes in response to a
persistent inflammatory agent. Epithelioid
cells appear large with abundant eosinophilic
cytoplasm and show indistinct cell boundaries[l 1 ]. Enzyme histochemistry and immuno­
chemistry support the concept that the cell
population of a granuloma is mixed, with
different activities of cells in varying regions
of the granuloma.
Inclusions, such as asteroid or Schaumann
bodies, may be found in the giant cells in
long-standing granulomatous inflammation.
Asteroid bodies are also seen in giant cells
and are formed from a radial arrangement of
cytoskeletal elements. Schaumann bodies are
laminated calcified bodies 10-100 |xm in
diameter found within epithelioid cells and
giant cells. They may lie free in areas of
fibrosis and indicate previous granulomatous
inflammation. They show a central crystalline
core containing iron and calcium. They are
probably of lysosomal origin[12). They have
been reported as occurring in up to 6% of
tuberculous granulomata.
On electron microscopy, macrophages
have a deeply indented nucleus with fairly
dense chromatin. A nucleolus may be promi­
nent. Mitochondria are relatively numerous.

Clinical Tuberculosis. Edited by P.D.O. Davies. Published in 1994 by Chapman & Hall, London. ISBN 0 412 48630 X

44

The pathology of tuberculosis

Strands of rough endoplasmic reticulum and
lysosomes he in the cytoplasm. Variable areas of the cell i._
membrane where cyto^bers of microfilaments and microtubules skeletal filaments relate
----- ? to the extracellular
matrix[23].
re aIs° present throughout the cytoplasm
The most striking feature is the presence of
These^n”! erS °f cytoPlasm>c vacuoles[13,14], 4—
1>mivi<Ji\OLOGY
-2 THE
IMMUNOLOGY OF
OF

meaSu:toS^S,rdrCUlar0rel0nSatedand GRANULOMATA

sure 0.05-0.25 jim in diameter. Some are Th •
m6 °r InSe and resemble lysosomes. The Ph lmmunolo8ical response to tuberculosis
majority, however, contain fluffy material
ajm0St entlrely cell-mediated, the epithe
vacLXPearS homo8enous- This latter type of
Ce" bein8 the effector cell. Macrophages
cellsflS 1MPFarS tO be UniqUe tO ePithelioid
assoclatl™ Wlth a delayed hypersensih 4ty
ma k '
’ Fra8ments of micro-organisms
eactl0n show increased phagocytic an 4
thehnid
WJtHin theSe vacuoIes[lS7]. Epi- IntraceI'tilar killing ability[24]. There is sub

cells show prominent rough endo-

stantiaJ evidence that the mononnH

£=====

SSSSS sgS- ~

stimuli
•
,
of environmer'tai factors
hate in a^ TF8 m°n0C^S to diff—
tiate m a particular way,
£
ar Way'.or the ^ence of
different j
macrophage subsets[26]. Different
subsets
of‘ jmacroPhages are seen in B and T
The intercellular junctions that form ^11
a
ell-dependent areas of peripheral human
between epithelioid cells resemble desm™
somes. Subplasmalemmal densities present lympho.d tissuespzj. Further evidence that
on the opposing cells closely relate to a epithelioid cells are derived from monocytes
by the retention
of the monoclep aque of electron-dense extracellular mater- IS provided
,
---------lack Ft 6 F in 8ranulomata generally macroPha8c marker RFD-2 by
ack such membrane interconnecting pIp
ce ,s thr
ouehnm
----- -- epithelioid
jirou
Shout granulomata[28].
Epithenients. Isolated subplasmalemmal VeaJ
densrhes of the type seen in relation to
UKM1(29,3O]. However, mononuclear phago­
quemfo see ,UnChO1?,S
gra™lomas
cytes m the centre and periphery of granuquently seen m cells of the mononuclear- ,omata differ in the
their immunological
junchTnsebetttem[211' THe Iar8e number of Phenotype[31]. Activated
J^cbons between epithehoid cells suggests
" ‘
cell-to-cell communication is promtaem
IS prominent.
strongly express HLA-DR and show
Adhesion molecules are
nith ma ! aCid PhosPhat^e activity. In the
these junction complexes, Cel’S
ally form junctions[19,201. This featnrp
accounts for the indistinct and^Xt “c
cytoplasmic
mteroscopy
epithelioid cel,s scen on light
seen on light

to these molecules has
immunocytochemistry, in
VLA-3[22]. This integrin
is strongly associated with intercellular
contact sites. Subplasmalemmal densities
are associated with

TTFI ”

r.,„:

™

degree of acid phosphatase actMty. These
ce&F"
rnCti°n an«8-P-sent"g
cells[32], Epthehoid giant cells also strongly

w-

I

I

. --mi 1 io
Immunology of granulomata

re cytoacellular

express HLA-DR, and may also function as
.mtigen-presenting cells[30].
,l ? I m |. ROLE OFT CELLS

rculosis
epithe•phages
isitivity
ic and
is sub■ar and
iata are
? circugocytic
} show
differreflect
factors
fferennce of
fferent
and T
uman
e that
□cytes
)cyteelioid
pithelarker
hagoranuJgical
; and
nuloshow
the
addiVDR
;mall
hese
iting
ngly

I he feature that distinguishes hypersensitivitv granulomata from non-specific foreignIhhIv type granulomata is the presence of
lymphocytes (Plate 3). In hypersensitivity
type epithelioid cell granulomata, lymphocytes are seen in close association with the
.H tiyated macrophage-monocyte cells. These
I cell-macrophage interactions are important
in the immunology of tuberculosis[33]. The
majority of lymphocytes seen in epithelioid
cell granulomata are T cells[34]. These cells
show features of activation[35]. A higher
proportion of CD4 helper cells are present in
the centre of granulomata than at the periphery|36]. CDS suppressor and B cells tend
to be associated with epithelioid cells at the
periphery, particularly in tuberculosis[37],
where occasionally they form a mantle separating the granuloma from the surrounding
tih.sue|30]. Paradoxically, some CD4 helper
cells can show suppressor functional activity.
I hese features support the concept that a
lunction of a granuloma is the formation
of an isolated microenvironment[38] with
immunoregulation occurring at the periphery.
Some workers have emphasized the role of T
lymphocytes in granulomatous inflamma­
tion, hypothesizing that these cells may
initiate epithelioid cell granulomata[39,40]. In
tuberculous granulomata, T lymphocytes
produce interferon-1 [41]. There are reports,
however, of epithelioid cell granulomata
being induced in the absence of T cell
function[42]. The importance of cytokine
activity in granulomata is shown by the
suppressive role of corticosteroids. The
macrophages in granulomata show de­
creased activation and number in the
presence of steroids in experimental situa­
tions. There is also decreased tissue necrosis,
with steroids showing an anti-inflammatory
effect[43). The release from granulomata of

hi
45

cytokines such as tumour necrosis factor and
gamma interferon may be responsible for
systemic effects such as fever in tuberculous
infection [44].
Studies have shown that there is T cell
receptor gene restriction in individuals with
tuberculosis[45]. It is of interest that gamma­
delta T cells are increased in the peripheral
blood; this is a feature seen in mycobacterial
infections[46]. Gamma-delta lymphocytes
react to mycobacterial antigens[47J. They
appear not to be increased in number in the
granulomata themselves[48]. Some mono­
nuclear cells in granulomata stain for S100
antigen, a marker of certain members of the
mononuclear macrophage system, in particu­
lar Langerhans cells and so-called T-zone
histiocytes. These are believed to function as
antigen-presenting cells. Epithelioid cells and
the monocytes in granulomata strongly ex­
press leucocyte function associated antigen-1
(LFA-1) and its ligand intercellular adhesion
molecule-1 (ICAM-1). This supports the view
that the monocyte-macrophage cells in gra­
nulomata are involved in antigen presen­
tation.
The concept of high- and low-turnover
granulomas was introduced by Spector
[49-51]. 'High' turnover granulomata are
dependent on continued recruitment from
the bone marrow. Most foreign-body type
granulomata are of 'low'-turnover type.
These differ in being very long lived with a
low level of monocyte recruitment and mini­
mal fibrosis. The lack of fibrosis in foreignbody granulomata may be due to the low
level of macrophage turnover with subse­
quent small amounts of free lysosomal
enzymes and other fibrogenic substances[52].
In the case of high-turnover granulomata it
appears that activated macrophages stimu­
late the proliferation of fibroblasts[53]. For
example, by secreting fibronectin, activated
macrophages attract fibroblasts and by secret­
ing a growth factor the absolute number of
fibroblasts is increased[54]. Granulomas have
therefore been classified by the presence or

I
I,

46

The pathology of tuberculosis

absence of an associated immunological response[55). 1 hey fall into two main groups:
immunological or hypersensitive type[56]
and the non-immunological foreign-body
type.

nodes, in which epithelioid cell granulomata
develop. Granulomata develop typical
central necrosis as delayed hypersensitivity
to the bacilli develops (stage III). This takes
about 2-4 weeks, as measured by the tuber­
culin test. The necrosis in the granulomata is
4.3 THE PATHOLOGY OF TUBERCULOSIS
most probably due to local toxic lysosomal or
Tuberculosis can cause lesions in any tissue cytokine effect rather than ischaemia. Tuber­
or organ of the body, but most frequently culous bacilli are also directly cytotoxic. The
involves the lung. In view of this, the follow­ epithelioid cells that result are much more
ing account will focus mainly on this organ. efficient at killing the intracellular bacilli. The
Other organ sytems will be then be described. majority of the bacilli are now extracellular
and have a reduced ability to multiply and
are
more difficult to find at microscopy. A
4.3.1 PULMONARY TUBERCULOSIS
spectrum of reactivity to the tubercle bacilli
appears to exist(60J. There may be a florid
(a) Primary tuberculosis
granulomatous reaction with few identifiable
The pathology of tuberculosis takes into bacilli comparable with tuberculous leprosy.
account the inherent virulence of the organ­ The other end of the spectrum is the presence
ism, the immunity of the person infected, the of quiescent macrophages with abundant
development of hypersensitivity and the
necrosis and large numbers of bacilli[60-62]
formation of epithelioid cell granulomata. (Plate 4).
Primary tuberculosis is the first infection of
This initial focus of caseous bronchopneu­
an unsensitized host. Tubercle bacilli usually monia together with the lymphadenopathy is
enter the lung via the airways, and when in known as a Ghon complex. This type of
small groups of one to three can reach the infection is seen mainly in early childhood in
alveolar spaces[57] in droplets smaller than endemic areas with a maximum incidence at
5 jim in diameter. The 1vejT jady cellular 1-3 years[63j. The lymph nodes on the same
reaction in tuberculosis is not known,- but
it is
------.3 side as the Ghon focus form a mass usually
probable that neutrophils are responsible
i
for larger than the Ghon focus. Histologically
phagocytosis initially, and macrophages
. _ > are there is marked fibrinous exudate and
recruited later. They are t'then phagocytosed
numerous acid-fast bacilli surrounded by
and the majority of the organisms
w
- will
_ _ be granulation tissue. Connective tissue stains
killed. This has been termed stage I of the will show that initially the underlying lung
disease[57,58J. However, a proportion of architecture is preserved. Features corres­
the bacilli will survive and replicate within
pond to the grey hepatizadon phase of lobar
the macrophages and cause cell death (stage
pneumonia. Infection may be centred on
II). Further monocytes are recruited from the blood vessels[64J. The primary pulmonary
circulation and transform into macrophages, focus is usually unilateral and found in a
but unless they are activated they are in­ subpleural position above or below the lobar
efficient at destroying the tubercle bacilli. fissure between the upper and lower lobes, or
Chemotactic factors such as <complement less commonly the basal part of the lower
component C5a and various cytokines such lobes. Grossly it appears as a yellow-while
as monocytic chemotactic protein 1 (MCP-1) area of softening 10-20 mm in diameter
recruit macrophages[59). Acid-fast bacilli are surrounded by a grey capsule. The soft area
easily seen at this stage. Tubercle bacilli are
represents the 'caseous' necrosis. There may
transported via lymphatics to regional lymph be an associated pleural effusion.

i

Pathology of tuberculosis
lata
ical
zity
kes
>era is
lor
>erChe
ore
'he
dar
nd
A
:illi
rid
ble
syice
mt
62]
?u' is
of
in
at
ne
lly
lly
ad
by
ns
ng
?s>ar
an
ry
a
■ar
or
er
te
er
ea

3y

47

Similar primary complexes occur in organs infections, at least 90%, do not progress any
mlected by less frequent routes of infection, further. Reactivation of the disease (post­
such as the gastrointestinal tract, oropharyn­ primary or secondary tuberculosis) occurs
geal lymphoid tissue and the skin. Regional when host resistance is impaired. This may
lvnlnh nodes are involved by lymphatic be due to immunosuppression from any
transport of bacilli from the initial site of cause, including malnutrition, alcoholism,
malignant disease, silicosis, diabetes[67] and
infection.
1^001 the lymphatics, the bacilli enter veins acquired immune deficiency syndrome
and spread to other parts of the body, (AIDS). Post-primary pulmonary tuberculo­
including the lungs, the brain, kidney and sis
si may also be the result of further infection
bone. If bacilli enter a pulmonary artery, from an exogenous source. This disease is
spread to other parts of the lung will result. mainly a disease of the elderly[68], who were
Die systemic haematogenous stage is fre­ infected at a young age when tuberculosis
quently marked by acid-fast bacilli in the was more common. It is usually seen in the
urine. Despite this wide distribution, in the apical1 or posterior segments of the upper
majority of cases the infection is controlled lobes (Simon's foci) 10-20 mm from the
and lesions resolve without clinical features. pleura and apical segments of the lower
Areas of infection smaller than a millimetre in lobes. Clinically the disease presents as an
si/e resolve with no fibrosis. Larger areas of acute necrotizing pneumonia (Plate 5). Hilar
‘
’ - is not a prominent
infection, greater than 5 mm across show lymphadenopathy
feature.
In
view
of the sensitivity of the host
fibrosis and dystrophic calcification and occa­
there
is
a
very
florid
response to the bacilli,
sionally ossification. They have the appear­
ance of friable white material surrounded by with marked caseous and liquefactive! necro­
a grey capsule with fibrosis in the adjacent sis. The liquefaction and cavitation is due to
lung. These larger lesions appear to be a the hydrolysis of protein, lipid and nucleic
source of reactivation. Hilar lymph nodes acids by
, the enzyme products of large
----- view of
typically"show dense hyaline fibrosis. In the numbers of macrophages
recruited
infant, however, there may be uncontrolled the hypersensitivity of the host[69^. ^The
proliferation of the tubercle bacilli; the Ghon organisms> are able to multiply extracellularly
________
locus may penetrate
a blood vessel or bron- iin large numbers. This is stage IV of the
bronchopneumonia
and other disease as described by Lurie. The lesion
ch us to cause 1
" ­ often ruptures into a bronchus and may
satellite lesions or 'miliary' disseminated' dis
ease such as meningitis, or renal disease. result in progressive pulmonary tuberculosis
Infected organs show numerous small, white localized to one area of the lung. Endobron­
nodules resembling millet seed. Oesophageal chial and endotracheal infection may result.
perforation has also been rarely described Large numbers of bacilli are usually present
in the sputum. There may be a dominant
165].
Congenital tuberculosis is rare and gener­ florid hypersensitivity reaction to this lique­
ally lethal. Infection appears to be by a fied material in the distal lung, particularly in
haematogenous route or 1from aspiration of children. Diffuse bronchopneumonia can
occur. A tuberculous empyema may result if
infected amniotic fluid[66].
the secondary lesion ruptures into the pleural
cavity. Organisms may be coughed up and
(b) Secondary tuberculosis
infect the larynx or be swallowed and infect
After resolution of the primary infection, the lymphoid tissue of the gastrointestinal
small numbers of bacilli survive within the tract. Other paths of spread within the lung
scarred foci for many years. The majority of are via arteries, with miliary spread to all

r

48

The pathology of tuberculosis

parts of the lung, or via a pulmonary vein
with dissemination to all areas of the body i
Common sites of spread are the bone•
’
marrow, eye, lymph nodes, liver, spleen
kidneys, adrenal, prostate, seminal vesicles,'
uterine tubes, endometrium and the men­
imnnrtanf
r
inges. The eye is another iimportant
----- ----------------site of
involvement. The disease may then progress
in any one of these organs to dominate the
clinical picture. Common sites of isolated
infection are cervical lymph nodes (scrofula),
meninges, kidney, adrenals, bones, uterine
tubes and the epididymis. Diagnosis of such
extrapulmonary sites often requires biopsy

The liquified cavity becomes surrounded by
dense fibrous tissue. It is lined by caseous
material with soft nodules and may contain
remnants of pulmonary vessels. Cavities
usually measure from 3-10 cm across. If they
T develoPing they have thin walls; more
chronic cavities are surrounded by fibrosis
Pulmonary artery aneurysm[75] and broncho­
pleural fistula[76] are complications that may
result. A late problem with a chronic cavity is
co Ionization by a fungus such as aspergillus
with the development of a mycetoma.

4.4 SYSTEMIC INVOLVEMENT IN
In renal disease, infection of the renal tuberculosis
pelvis and the bladder may result. Tuberculo­
The more common sites of involvement are
sis of the uterine tubes may spread to the
described.
endometrium and the adjacent pelvic struc­
tures. In infection of the spine (Pott's dis­
ease), the disease may spread along the psoas 4-4’1 LYMPH NODES

m

I

dLymph nodes may bc™me - “

of
in secondary tuberculosis; involve­
known cause of reactive «
ment of cervical nodes is termed 'scrofula'. A
(secondary, AA type).
sinus
may develop, connecting with the skin.
In severely immunosuppressed indivi­
Cervical
lymphadenopathy may occur in
duals, particularly in AIDS, in view of the
primary
tuberculosis
where the site of infec­
reduced T lymphocyte population there is
tion
is
the
oropharynx,
including the tonsil,
almost a total absence of granulomata and
_______
cl
he
nodes
may
become
adherent
and form
large numbers of mycobacteria proliferate
multinodular
mass
that
uncontrolled
- ‘ within
-... 1 i
s^tircaXmT55
may imit3te meta‘
patients show ioss of skin se^t^'and lo2
Lymph nodes infected with tuberculosis
of
Of cell-mediated immunity to the mycomay enlarge when antituberculosis chemoth­
bacteria[71J.
7
Another rare form of disseminated spread erapy is started. It is suggested that the
of infection is cryptic disseminated tuberculo­ breakdown of degenerating bacilli stimulates
sis. This occurs in immunodeficient indivi­ cell-mediated immunity[77].
duals and the elderly. Very small lesions are
present with large numbers of bacilli[72J. The 4.4.2 SKIN
cause of such reduced response to the infec­
Primary tuberculosis of the skin
skin is
is very
very raie
rare
tion is not known but may be due to
and is usually the result of direct inoculation.
ducr^]1 eXpreSSion of HLA-DR gene pro­ The lesion develops withini 22-4 weeks after
Secondary lesions are associated with a the inoculation. The earliest response is a
great deal of lung destruction. Much of the neutrophilic reaction with necrosis and
destruction may be due to overproduction of ulceration. Macrophages are recruited and
necrotizing epithelioid cell granulomata
cytokines such as tumour necrosis factor[74J. develop'

't

i

I

Systemic involvement

aded by
caseous
contain
Cavities
If they
s; more
ibrosis.
ronchoat may
avity is
argillus

•nt are

site of
volvetla'. A
■ skin,
ur in
infeconsil.
arm a
neta-

ilosis
ioththe
lates

rare
tion.
after
is a
and
and
nata

Miliary tuberculosis of the skin can occur in
primary pulmonary tuberculosis and is char­
acterized by numerous micro-abscesses sur­
rounded by macrophages containing acid­
last bacilli.
Involvement of the skin in secondary
tuberculosis is manifested by lupus vulgaris.
These chronic lesions are found on the head
and neck as red-brown patches with nodules.
Well-formed epithelioid cell granulomata with
Langerhans giant cells are seen histologically,
although necrosis is minimal. Acid-fast bacilli
are rarely seen.
Occasionally disseminated skin lesions are

seen in active tuberculous infection. They
show well-formed granulomata without acid­
fast baciili. Regression occurs on treatment
and they probably represent a local response
to fragments of tuberculous <antigenic
material[78]. They are known as tuberculids
(papulonecrotic, lichen scrofulosorum and
erythema induratum). Necrosis and vasculitis
may be seen.
4.4.3 CENTRAL NERVOUS SYSTEM

Tuberculous meningitis may occur after the
escape into the subarachnoid space of bacilli
from a focus of infection
in the meninges or
------- —
cortex. There is a <""
diffuse meningitis with
severe inflammation and fibrin exudation and
eventual fibrosis. Nerves and blood vessels
may be compromised; obliterative endarteri­
tis develops. A rare form of tuberculosis in an
epidural site may result from spread of
tuberculous infection from the middle ear.
Subdural tuberculosis manifests as large con­
fluent plaques of exudate.
Tuberculomas
are
localized
space­
occupying masses within the brain tissue
with central necrosis and surrounding granu­
lomatous inflammation. In adults they are
supratentorial while in children they tend to
occur in the posterior fossa. Old lesions
may calcify. In only half the cases is there a
previous history of tuberculosis[79].
A hypersensitivity phenomenon manifest­

49

ing as acute haemorrhagic leucoencephalopathy may occur in tuberculous patients.
This may also be associated with upper
respiratory tract infections due to organisms
other than tuberculosis and in septicaemia.
There is diffuse oedema, focal demyelination
and a perivascular macrophage reaction.
Spinal cord involvement has been des­
cribed [80].
4.4.4 FEMALE GENITAL TRACT
3 Uterine tubes and ovary
Primary tuberculosis is rare; secondary infec­
tion is almost always by the haematogenous
route. The uterine tubes are the most
common site of infection. Although a pulmonary lesion may not be evident, involve­
ment of the peritoneum or kidneys may be
present. Lymphatic spread from primary
intestinal infection may occur or there may be
direct spread from the bladder or gastrointes­
tinal tract.
As the disease becomes chronic, there is
thickening and nodularity of the tube. Dense
fibrous adhesions between the ovary and
tube develop, and the fimbriae and ostium
may obliterate. The ovary can be involved by
direct spread from the uterine tube, but this
is less common than tube involvement
itself[81]. It is rare to see necrotizing granulo­
mata within the ovarian stroma. The uterine
tube can dilate and form a hydrosalpinx.
Mucosal granulomata are seen, which extend
into the muscle wall and to the serosa. They
can become confluent and cause obstruction.
The granulomata ulcerate and infectious
material is released into the tube lumen.
Tubal obstruction is almost always the end
result of this process[82]. Calcification is
common in old lesions.

(b) Endometrium

Involvement of the endometrium follows
infection of the uterine tubes. The resulting

50

r/ie pathology of tuberculosis

granulomatous inflammation may be focal
and! pQDrly formed in view of the monthly
shedding of the endometrium. The inflam

T
Poncet's
disease jmay
----- occur in association
with
tu'be’tc^fe
tuberaiI
“-«- Hypertrophic osteoarthro­
-------pathy may also occur where pulmonary dis­
ease is long-standing or extensive. Organisms
are not found at the involved sites and the
conditions probably have an immunological
basis. Tuberculous arthritis may originate in
the synovium itself or develop from direct
spread from tuberculous arthrihs. The knee
and hip joints are the most commonly involved
sites The end result is joint restriction or
ankylosis.

mation can, however, be diffuse with numerOUS necrotizing granulomata. The only
manifestation of the disease may be a chronic
endometritis with plasma cells. The inflam­
mation is normally superficial: deep granulo­
matous inflammation is rare[83j. Reactive
changes may be seen in the adjacent endomenal glands. Placental tuberculous infection is
rare[84J. Infection of the cervix and vulva
may follow tuberculous endometritis. Tuber­
culous cervicitis may resemble carcinoma
macroscopically.
4.4.7 GASTROINTESTINAL

As with the lung, tuberculosis can be divided
into primary and secondary types. TubercuTuberculosis of the kidney results from losis can affect any part of the gastrointestinal
secondary spread from a pulmonary site and
ract, but it is most commonly found in the
it may be either unilateral or bilateral The terminal ileum and ileocaecal region. It is rare
resulting
granulomata
involve to see tuberculosis in the colon and rectum
.
- necrotizing a
----------- U.vu.vt
cortex and medulla and eventually rup- Acute obstruction and perforahon are freure into the renal pelvis.
quent complications. The differential diagnouberculous cystitis, epididymitis and
of tuberculosis always includes Crohn's
orchitis may result from this. Tuberculous dlsease- Tuberculosis can cause single or
epi lymihs may also originate from the pro- ff o^ple strictures with mucosal ulceration
u baemat°genous spread, the head of
^cers tend to be annular in distribuhon
e epididymis is most frequently involved, tbe base being raised. The submucosa is
the yas being spared. In spread from the characteristically obliterated in tuberculosis
prostate, both the vas and tail are involved. Wlth severe associated fibrosis. This fibrosis
eshcular involvement may simulate a neo- ^esults in hypertrophic or ulceroconstrictive
Plasmforms of tbe disease. Fissures and fistulae are
rare. Granulomata are well formed, found in
4.4.6 BONE AND JOINT
eyer s patches and lymphoid follicles, and
almost
always are found in regional lymph
Tuberculosis at these sites is i
normally nodes.
Enterocolitis
. .
------- 3 may result from acute
secondary by the haematogenous <
i spread infection and perforation
.
-I with the develop­
rom the lung. The most common site
involved is the spine, in the area of the tenth ment of peritonitis, and ascities may occur,
In peritonitis
i ■' ’ ‘ the
1______
.J is studded with
-i
surface
thoracic vertebra, although any bone j
may be myriads of tubercles, which
involved. There is
can fuse to form
is bone
cone destruction
destruction with
caseous masses. Involvement of
replacement by <caseous
—
-- the
-.e greater
inflammation. A omentum predominates.
paravertebral abscess
—J may result. Spinal cord
•^nOreu a,itubercu,osis is common in areas
compression is a recognized complication.
with a high incidence of pulmonary and
The infection can track■ along anatomical ___
_
intestinal
tuberculosis[85]. One clinical type
planes to discharge a distance from the is
in
- -i patients presenting with active tuber­
involved bone.
culosis with anal ulceration in which acid-fast

4.4.5 KIDNEY AND MALE GENITAL TRACT

I

I

References
bacilli are numerous. The second clinical type
is more chronic with marked fibrosis and
listulae in which bacilli are sparse; differentiation from Crohn's disease is difficult.
Gastric tuberculosis is almost always
secondary and presents with chronic ulcera­
tion associated with destruction but minimal
hbrosis. A tuberculous mass may develop at
the pylorus. Regional lymph nodes are nor­
mally involved[86].

sociation
eoarthronary disrganisms
and the
nological
^inate in
n direct
he knee
nvolved
ction or

.1,.1.8 CARDIOVASCULAR

divided
ubercutestinal
in the
t is rare
ectum.
ire freliagno2rohn's
gle or
ration.
?ution,
osa is
ulosis,
ibrosis
rictive
lae are
ind in
5, and
ymph
acute
velopaccur.
with
form
neater

areas
and
type
uberi-fast

lubcrculous pericarditis is associated with
generalized infection; myocarditis is less fre­
quent. Constrictive pericarditis with heart
failure may result. Although involvement of
small vessels is common in tuberculosis,
large vessel involvement is rare. The aorta is
most commonly involved.
4.4.9 ENDOCRINE

I

The adrenal is the most frequently involved
endocrine gland and tuberculosis is a typical
cause of Addison's disease. In extensive
multi-system disease, the adrenals are
spared. In contrast to this, when the adrenals
are involved and destroyed by necrotizing
granulomatous inflammation, extra-adrenal
tuberculosis is rare[87]. Involvement of the
pituitary, in particular the hypophysis,
follows pulmonary infection.
REFERENCES

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2. Adams, D.O. (1976) The granulomatous
inflammatory response. A review. Am. J.
Pathol., 84, 164-91.
3. Williams, G.T. and Jones Williams, W. (1983)
Granulomatous inflammation - a review. /.
Clin Pathol., 36, 723-33.
4. van Furth, R., Langevoort, M.L. and Schaberg,
A. (1975) Mononuclear phagocytes in human
pathology - proposal for an approach to im­
proved classification. In Mononuclear Phagocytes
in Immunity, Infection and Pathology (ed. R. van
Furth), Blackwell Scientific, London, pp. 1-15.

51

5. Dannenberg, A.M. (1975) Macrophages in
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In Mononuclear Phagocytes in Immunity, Infection
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Immunology, 62, 229-34.
8. Mackaness, G.B. (1971) Delayed hypersensiti­
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]. Pathol., 12, 229-33.
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