Pyelonephrtis

Conception
pyelonephritis is an purulent inflammation of
the renal pelvis, intesitium and tubules.

2
 Ages and Sex
all ages ( diabetes mellitus,
catheterization,cystocopy)
Femal is more frequently than male (trauma
and pregnancy, shorter urethra)
Boy ( anatomical abnormalities –obstructive-
ureteric reflex)
Man ( prostatic diseases)
3
 Infective routes
heamatogenous routes by septicaemia
Retrograd routes

4
 Infective organisma
Bacteria
Fungi
Richettsia
Viruse

5
 Classification
• Acute pyelonephritis
• Chronic pyelonephritis

6
 Acute pyelonephritis
• Acute pyelonephritis is due to infection of
the kidney by pyogenic organisms.
• It presents with malaise ,fever, pain and
tenderness in the loin.dysuria ,urgency of
micturition
• Pyuria(pus cells in the urine) ,white cell
caste

7
 Pathogenesis
• heamatogenous spread can occur in a
patient with infective endocaditis or
bacteraemia
• Retrograd routes: reflex of urine
（ Bacteria e.g. E. coli)

8
 Morphology
• Abscesses :infection is blood -throghout the
cortex and medulla, wedge-at the upper and
lower poles. But retrograde- at pelvic
,calyceal mucosa
• Intratubular polymorph with intersitial
edema ,fibrosis; inflammatory infiltrate by
lymphocytes and plasma cells,white cell
granular casts.
9
 Complication
• Renal papillary necrosis-the medullary
blood supply is compromised
• Pyonephrosis :the kidney becomes grossly
distended with pus
• Perinephric absces: the infection breaches
the renal capasule and perirenal tissues

10
11
12
13
14
15
 Chronic pyelonephritis
• Chronic pyelonephritis occurs in association
with vesicoureteric reflex( congenital lesion
or obstruction)

16
 pathogenesis
• Reflex of urine into the kidney during
micturition raises the intrapelvic and
intracalyceal pressure

17
 morphology
• Deep irregular scar are seen towards the
poles of the kidney.-unilateral or bilateral
but asymmetrical,dilated calyces
• Interstitial fibrosis with atrophic and dilated
tubules containing eosinophilic cell casts

18
19
20
21
 Renal cell carcinoma
• Adults-most frequently over the age of 50
years
• Male preponderance
• Haematuria , lion pain and a mass
• Poor prognosis-without metastasis 5 year
survival may be as high as 70%,15-20%
with metastasis
22
 etiology
• Smoke tabacco ,hereditary condition

23
 morphology
• The kidney is distorted by a largy
bossellated tumor which most often occurs
in the upper pole,the cut surface reveals a
solid yellowish-grey with areas of
haemorrhage and necrosis,some times
cystic
the margins of the tumor are usually well
demarcated
24
• Histologically; renal cell carcinoms are
compoed of either clear or granular cells the
small nuclei

25
 Malignant renal tumors

• Classification:
1.renal cell carcinoma.(hypernephroma)
2.Wilms’ tumor( nephroblastoma)
3.Transitional cell carcinoma of the renal
pelvis
4.Tumor of the bladder

26
 Ages and sex
• Adults- 50 years
• Male preponderance

27
 Clinical pathologic correlation
• Haematuria, lion pain and a mass
• Hypercalcaemia,
hypertension,polycythaemia,amyloidosis

28
 prognosis
• Poor- 5 year survival may be as high as 70
% without metastasis ,but with metastasis
fall to 15-20%

29
 Etiology
• Smoke tobacco
• A genetic predisposition- von Hippel-
Lindau disease
• Hypercalcaemia
• Hypertension
• polycythemia

30
 Morphology
• The kidney is distorted by a large
bossellated tumor which most often occurs
in the upper pole. The cut surface reveals a
solid yellowish-grey tumor with areas of
haemorrhage and necrosis ,sometimes
cystic,the margins of the tumor are usually
well demarcated, some breach the ranal
capsule and invade the perinephric fat.
31
• Extension into the renal vein or the inferior
vena cava, or the right atrium

32
33
 histologically
• Renal cell carcinoma are composed of
either clear or granular cells .
• The small nuclei

34
35
 图注：肾细胞癌
36
肾脏下极巨大肿物，界限较清，黄白色，中央有坏死。
 图注：肾细胞癌
癌细胞排列成腺泡状。癌细胞大，多角形，轮郭清楚，胞浆清亮透明
或含有伊红色细颗粒。核小，深染，圆形，位于细胞中央，可见核仁
37
。
38
 Wilms’ tumor
• Children under 10 years –peak incidence is
between the age 1 to 4 years
• Sexs are equally involved
• The most common presentation is an
abdomonl mass.haematuria, hypertension,
abdominal pain ,intestinal obstruction
Metastasis to lung
39
 Morphology
1.The tumor is large ,frequently extends into
perinephric fat .the cut surface is variegated,
Haemorrhagye, necrosis, white, cartilaginous,
mucinous.
2. Both epithelial( glomeruli and tubules) and
mesenchymal tissues( spindle cell)
Striated muscle, fibrous tissue, cartilage , bone
and fat.

40
41
　　　图注：肾母细胞瘤
图示分化较成熟的横纹肌组织。 HE×200
42
　　图注：肾母细胞瘤
图示肾小球样结构。 HE×400 43
44
45
　　　　　　　图注：肾母细胞瘤
瘤组织主要由 2 种成分组成，一是肉瘤样梭形细胞呈弥漫性或团块状
排列，核明显异型，二是肾小管样结构，表面被覆 1-2 层细 46
 Tumor of the bladder
• Common – epithelial tumor
• Rare- sarcomas
• Transitional cell carcinoma- majority
• Sqamous carcinoma-a small proportion
• Adenocarcinoma-uncommon

47
 Etiology
• Chemical-dyes (textiles and printing),
reagents( rubber ,cable, plastic)
• Heavy smoker
• Analgesic abuser
• schistosomiasis

48
 Transitional cell carcinoma
• Arise from the urothelium
• Frequently multiple
• Dysplsia
• Painless haematuria, dysuria ,obsrtruction
• papillary

49
 Morphology
• Papillare
• Urothelium are abnormally thick
• Atypia cytologic feature

50
 Staging and grading
• I grade: papillary growths –cytological
atypia
• III grade: invasive-non papillary, flat
ulcerated

51
 Carcinoma in situ
• Carcinoma in situ of the urothelium
• Precursor of invasive carcinoma

52
53
54
55
。膀 　
胱 　
后 　
壁 图
见 注
隆 ：
起 膀
的 胱
菜 移
花 行
状 上
肿 皮
物 癌
，
基
底
较
宽

56
润膀 　
肌胱 　
层壁 　
。增 图
厚 注
， ：
粘 膀
膜 胱
面 移
多 行
数 上
乳 皮
头 癌
状
肿
物
，
并
浸
57
58
59
　　　　　　　　图注：移行上皮癌Ⅰ级
　　移行上皮细胞增生成乳头结构，细胞复层化，细胞有异形性。
60
　　图注：移行上皮乳头状瘤／移行细胞乳头状癌０级
　　　移行上皮细胞增生成乳头状，细胞层次少，异形性不明显 。61
62
63
64
胞 增 　
异 生 　
形 细
性 胞 　
明 与 　
显 其 图
， 间 注
分 质 ：
裂 构
象 成 移
多 乳 行
。 头 上
状 皮
。 癌
细

Ⅱ
胞 级
层
次
明
显
增
多
，
细
65
66
 图注：移行上皮癌 III 级
肿瘤细胞增生无乳头形成，以实性条索状浸润于肌层。
67
68
Diseases of the reproductive system
and breasts
• Commnoly
• Inflammations, tumors, hormonal
disturbances, complications of pregnancy

69
 Vulva
• The vulva is less frequently a site of disease
than is the cervix, uterus, or ovary. The
major pathologic changes of the vulva can
be conveniently divided into the following
categories: inflammatory, disorders
(vulvitis), epidermal hyperplasias or
atrophy (dystrophy), cysts, and tumors
(benign and malignant).
70
 Diseases of the cervix
• The cervix is both a sentinal for potential
serious genital tract infection and a target
for viral and other carcinogens.

71
 Chronic cervicitis
• Common
• Multiparous and nulliparousadult women
• Nicroorganisms( streptococci,
enterococci,E.coli, staphylococci;
chlamydiae, gonococci, mycoplasmas,
herpes simplex , human papilloma), injury,
disorders of hormone,local hemodynamics,
leukorrhea

72
 Morphology
• Grossly, chronic, cervicitis appears as a
reddening, swelling and granularity around
the margins of the external cervical as.
Histologically, the infiltration is largely
mononuclear cells. Inflammatory
stensclosis of the cervical glands may yield
cystic dilatations dasignated as nabothian
cysts
73
• The cervical, epithelium may show
hyperplasia and reactive atypia,
characterized by epithelial disorganization
and nuclear atterations not to be confused
with the changes of dysplasia. In the course
of these changes, the epithelial cells are
depleted of their normal content of
glycogen

74
• squarnous metaplasia of endocervical
glands

75
 TUMORS OF THE CERVIX
• Although a wide variety of tumors may
develop in the cervix uteri, all are rare
except the relatively unimportant polyp and
squamous 'cell neoplasia and its sometimes
accompanying condylomas.

76
 POLYPS
• Although polyps occur in 2 to 5% of adult
females they are innocuous, occasionally
being important as a cause of abnormal
bleeding that must be differentiated from
that due to more ominous causes.

77
 Morphology
• These lesions typically are within the
endocervical canal. They may be sessile,
hemispheric masses or pedunculated,
spherical lesions up to 3 cm in diameter.
Those with long stalks may be seen on
clinical examination, hanging down through
the exocervical os and causing dilatation of
the cervix. Characteristically, cervical
polyps are soft, almost mucoid.
78
• Their histologic nature is that of a loose
fibromyxomatous stroma containing
cystically dilated endocervical glands.
Although the coveting epithelium is usually
columnar and secretes mucus,
superimposed chronic inflammation may
lead to squamous metaplasia and
ulcerations.
79
 Carcinoma oF THE cervix
• The decline in the number of deaths caused
by cancer of the cervix in the United States
and in other developed nations is a dramatic
and grafifying testament to the benefits of
early diagnosis.

80
• Once one of the leading causes of cancer
death, cervical cancer now ranks seventh or
eighth among the Killer cancers of females
in the United States. causing about 4000
deaths yearly, according to a 199! estimate.
In sharp contrast, there are still more than
13,000 new cases of invasive cancer and
50,000 of carcinoma in similar every, year.
81
• It is evident that well over half of invasive cancers
are curetted by effective therapy and. even more
important. most lesions are discovered while still
in situ and amenable to eradication by timely and
appropriate treatment. These dramatic gains in
discovery and treatment are owed largely to the
effectiveness of the Papanicolaou cytologic test in
detecting cervical carcinoma during its incipiency
and by the fortuitous accessibility of the cervix to
colposcopy and biopsy.
82
• The widespread application of the "Pap
smear" in mass screening programs and in
routine physical examinations, followed by
biopsy to evaluate and confi,rrn abnormal
cytoiogic findings, has documented that
carcinoma of the ce,wix arises in a series of
incremental epithelial changes ranging from
progressively more
83
• severe dysplasia (also called cervical
intraepitheiiai neoplasia CIN) to invasive
carcinoma.

84
 INCIDENCE AND
EPIDEMIOLOGY
• Both in situ and invasive carcinomas are
diagnosed now at younger ages than in past
decades. Indeed. CIN is now being
discovered in teenagers and young adults.

85
• The peak incidence is at about 30 years of
age. Similarly. invasire carcinoma is now
appearing as early as the third decade of life
with. a peak incidence at about age 40 (i.e.
about 10 to 15 years later).

86
• Deaths begin in the fourth decade, and the
mortality rate rises throughout life. Only a
few decades ago, all of these unfortunate
events were delayed at least 10 years,
strongly suggesting that oncogenic
influences (as will be noted later) are now at
work earlier in life.

87
 risk factors
• Early age at first intercourse
• Multiple sexual partners
• High-risk male sexual partners--i.e., those
who are promiscuous; who have a former
wife with cervical cancer, or who have a
history of penile condylomas.

88
• All other risk factors can be related to these
three influences, such as the higher
incidence of cervical carcinoma in lower
socioeconomic groups, the higher incidence
among married women (increasing with the
number of marriages and children), the
rarity of cervical carcinoma in virgins, and
the high incidence in prostitutes.
89
• No longer considered significant risk
factors are cigarette smoking, birth control
pills, vague agents in semen, and lack of
circumcision in the male sexual partner
(implicating some putative carcinogen in
smegma).

90
• ETIOLOGY AND PATHOGENESIS. The
epidemiology of cervical cancer, strongly
suggests sexual transmission of an oncogen,
and particularly incriminated is HPV

91
• This virus is known to cause the venereally
transmitted vulvar condyloma acuminamm
and is suspected to be an oncogenic agent in
squamous cell tumors of skin and mucous
membranes. DNA sequences of HPV are
detected in 75 to 100% of patients with
cervical condylomas, precancerous cervical
dysplasia, and invasive carcinoma.
92
93
• The cervical condylomas can be verrucous,
like those of the vulva, but much more often
they are flat lesions (flat condylomas).
Although there is overlap in the HPV types
present in various lesion, HPVs 6 and
• Il (low-risk HPVs) are found most
frequently in condylomas associated with
the typical viral changes of koilocytosis
94
• In contrast, lesions exhibiting epithelial
atypia (carcinoma and high-grade
dysplasia) contain HPVs 76. 18, and 31
(high-risk HPVs).

95
• The precise reasons for the difference in
oncogenicity between low- and high-risk
HPVs are still unclear. Currently it is
thought that the low-risk HPVs lead to
productive infection associated with
unintegrated episomal viral DNA,
characterized by cell proliferation, cell
maturation, koitocytosis, and other features
distinctive of condylomas.
96
• High-risk HPVs are associated with a
greater proportion of viral DNA becoming
integrated into the host genome, but it is not
clear that this property correlates with
malignant transformation. Current interest
is in the interaction of the proteins encoded
by the E6 and E7 open reading frames of
these high-risk HPV types with p53 and the
retinoblastoma gene product, respectively.
97
• The p53 gene and the retinoblastoma gene,
as you recall are tumor suppressor genes
involved in oncogenesis.

98
• Although the cause of cervical carcinoma is
still uncertain, there is agreement that this
form of cancer is derived from dysplastic
epithelial changes or CIN.

99
• These changes begin with mild dysplasia
(grade I CIN) either in the usual cervical
epithelium or in a fiat condytoma marked
by koilocytotic changes. The dysplasia
becomes more disorderly and may be
associated with some variation in cell and
nuclear size and with normal-looking
mitoses above the basal layer of either the
usual cervical mucosa or flat condytoma;
100
• this stage is designated moderate dysptasia
(grade fi CIN). The superficial layer of cells
is still well-differentiated but in some cases
shows koilocytotic changes. The next step
in the sequence is severe d.vsplasia (grade
[II CIN].

101
• marked by greater variation in ceil and
nuclear size, disorderly orientation,
hyperchromasia, and mitoses, normal or
abnormal, sometimes near the surface layer

102
• Differentiation of surface cells and koilo-
cytotic changes have usually disappeared or
are fbund very uncommonly. In grade III
CIN the atypical ePithelium has not invaded
the underlying stroma but may extend into
endocervical glands: this stage represents
carcinoma in sittt. The next stage is invasive

103
• the a grading system, based on the degree of
cellular differentiation, and a staging
system, based on rumor spread, have been
devised. Grades I through III refer to
progressively less differentiated lesions.
The details of the currently used staging
system are beyond our needs.

104
• In brief, it recognizes stage 0—carcinoma
in situ--and then stages I to 4. based on
whether the carcinoma is strictly confined
to the cervix (stage l) or has extended
beyond the cervix ultimately to reach stage
4, marked by extension beyond the uterus
into the pelvis and by involvement of
adjacent organs or metastatic dissemination.
105
 CLINICAL COURSE.
• Results of a Pap smear may first become
abnormal with mild dysplasia in
asymptomatic teenagers or young adults.
Even frank carcinoma in situ is usually
asymptomatic except possibly for the
presence of some leukorrhea,

106
• which is more often related to concurrent
cervicitis or vaginitis. The cervix may still appear
normal to the naked eye, but colposcopy and the
Schiller or acetic acid test may disclose an
abnormal area. When invasive carcinoma appears,
usually in the fourth or fifth decade of fife or
sometimes later, it is often associated with
irregular vaginal bleeding, leukorrhea, painful
coitus, and dysuria.
107
• Biopsy is always necessary, to confirm the
cytologic findings and to evaluate the depth
of penetration of the lesion.

108
• The mortality from this form of cancer is
more often related to its local effects (i.e..
obstruction of the ureters or penetration into
the bladder or rectum) than to distant
metastases. Death from this disease is a
particularly lamentable tragedy because at
least a decade elapses between the in situ
and invasive stages providing ample
opportunity, for early diagnosis.
109
• Neither is there any need for hasty ill-
considered treatment. If the interpretation of
a biopsy is in doubt, there is time to permit
the lesion to declare itself.

110
• Survival with this disease, assuming
appropriate management (usually surge,'5,',
radiotherapy, or both). depends largely on
the stage when first discovered, as the
following damon five-year survival
indicate: stage 0. 100%; stage 1. 85-95%:
stage 2. 70-75%; stage 3, 35%: stage 4.
10%
111
Gestational trophoblastic diseases
• the gestational trophoblastic tumors haye
been divided mainly into three overlapping
morphotogic categories--hydatidiform
mole, invasive mole and choriocarcinoma.

112
• They range in level of aggressiveness from
the hydatidiform moles, most of which are
benign, to the highly malignant
choriocarcinomas.

113
• All elaborate human chorionic
gonadotropin (HCG), which can be detected
in the circulating blood and urine at titers
considerably higher than those found during
normal pregnancy, the titers progressively
rising from hydatidiform mole. to invasive
mole. to choriocarcinoma.

114
 HYDATIDIFORM MOLE
• The typical hydatidiform mole is a
voluminous mass of swollen, sometimes
cystically dilated, chorionic villi covered by
varying amounts of banal to highly atypical
chorionic epithelium and appearing grossly
as grape-like structures.

115
• Two distinctive subtypes of moles have
been segregated, complete and partial
moles. The complete hydatidiform mole
never contains fetal parts.

116
• The incidence of complete hydatidiform
moles is about 1 to 1.5 per 2000
pregnancies in the United States and other
Western countries. For unknown' reasons,
there is a much higher incidence in Asian
countries.

117
• They are much more common before age 20
and after age 40.

118
• They usually present clinically with
painless vaginal bleeding, on average 16 to
17 weeks after conception. The uterus is
"too large for dates." and no fetal parts or
heart sounds are present. Elevated levels of
HCG are present in maternal blood and
urine, and ultrasonography provides a
positive diagnosis.
119
• When discovered, usually in the fourth or
fifth month of gestation, the uterus is larger
than antidpated for the duration of the
pregnancy, The uterine cavity is filled with
a delicate friable mass of thin-walled,
translucent

120
121
• All the chorionic villi are abnormal, and the
chorionic epithelial cells are diploid (46XX
or uncommonly.46XY).

122
• The partial hydatidiform mole contains fetal
pans, has some normal chorionic villi, and
is almost always triploid (e.g. 69XXY).

123
 FEATURES OF COMPLETE
VERSUS PARTIAL HYDATIDIFORM
MOLE
• Feature Complete Mole Partial Mole
• Karype 46,XX (46,XY) Triploid
• Villous All villi Some villi
• edema
• Trophoblast Diffuse: cirumfluent Focal; diffuse
• proliferation ential
• Atypia Often present Absent
• Serum HCG Elevated Less elevated
• HCG in tissue ++++ +
• Behavior 2% choriocarcinoma Rare choriocarcinoma
124
• cystic, grape-like strucfures

125
• absence of vascularization of villi ,The
centrat substance of the villi is a loose,
myxomatous, edematous stroma.The
chorionic epithelium, almost always shows
some degree- of proliferation of both
cytotrophoblast and
syncytiotrophoblast,intermediatephoblast.

126
 INVASIVE MOLE
• Biologically, an invasive mote is
intermediate between a benign mole and
choriocarcinoma. It is more invasive
locally, but it does not have the aggressive
metastatic potential of a choriocarcinoma.

127
• An invasive mole retains hydropic villi,
which penetrate the utrerine wall deeply.
possibly causing rupture and sometimes
life-threatening hemorrhage. Local spread
to the broad ligament and vagina may also
occur. Microscopically, the epithelium of
the villi is markedly hyperplastic and
atypical, with proliferation of both cuboidal
and syncytial components.
128
• metastases do not occur.

129
 CHORICCARCINOMA
• This very, aggressive malignant tumor
arises either from gestational chorionic
epithelium or, less the quently, from
totipotential cells within the gonads or
elsewhere.

130
• Choriocarcinomas are rare in most Western
cultures and in the United States occur in
about one in 30,000 pregnancies. They are
much more common in Asian and African
countries, reaching a frequency of one in
2000 pregnancies.

131
• The risk is somewhat greater before age 20
and is significantlv elevated after age 40.

132
• In about 50% of cases, it follows a complete
hydatidiform mole but only rarely a partial
mole. About 25% arise after an abortion,
and most of the remainder occur in a
previously normal pregnancy. Stated in
another way, the more abnormal the
conception, the greater the hazard of
developing gestafional choriocarcinoma.
133
• Most cases are discovered by the
appearance of a bloody brownish discharge
accompanied by a rising liter of HCG,
particularly the beta subunit, in blood and
urine and by the absence of marked uterine
enlargement such as would be anticipated
with a mole. In general, the liters are much
higher than those associated with a mole.
134
• hemorrhagic, necrotic masses within the
uterus.

135
• the tumor is- purely epithelial, composed of
anaplastic cuboidal cytotrophoblast and
infiltrating into the myometrium and into
vessels.

136
• Nearly 100% cures have been obtained with
neoplasms that have not spread beyond the pelvis,
vagina, and lungs. Almost a 75% remission rate
has been achieved with even widely disseminated
neoplasms. Equally remarkable are the many
reports of healthy infants borne by these survivors.
By contrast, there is relatively poor response to
chemotherapy in choriocarcinomas that arise in
the gonads (ovary or testis).
137
 Breast
• Lesions of the female breast are much more
common than lesions of the male breast,
which is remarkably seldom affected. These
lesions usually take the form of palpable,
sometimes painful, nodules or masses.

138
 BREAST CARCINOMA
• Minimal or no increased risk of breast
carcinoma: Fibrosis cystic changes (micro-
or macroscopic), apocrine metaplasia,
sclerosing adenosis, mild hyperplasia

139
• Slightly increased risk (1.5 to 2 times): Moderate
to florid hyperplasia, ductal papillomatosis
• Significantly increased risk (5 times): Atypical
hyperptasia. ductular or lobular with duct
involvement
• A family history of breast cancer increases the risk
in all categories (e.g.. to about 10-fold with
atypical hyperplasia).

140
 EPIDEMIOLOGY.
• Geographic influences: Five times more common
in the United States than in Japan and Taiwan.
• Genetic predisposition: Well-defined: the risk is
proporfional to the number of close relatives with
breast cancer and inversely proportional to the age
at which their cancers developed. Bilateral cancers
are also associated with greater genetic
predisposition. There are uncommon high-risk
families in which there is apparent autosomal
dominant transmission and familial association of
breast and ovarian carcinomas.
141
• Increasing age: Breast carcinoma is uncommon be fore age
20, but then a steady rise to the time of menopause is
followed by a slower rise throughout later life.
• Length of reproductive life. Risk increases with early
menarche and late menopause.
• Parity: More frequent in nulliparous than in multiparous
women.
• Age at first child. Increased risk when over 30 at time of
first child.
• Obesity: Increased risk attributed to synthesis of estrogens
in fat depots.
142
• Exogenous estrogens: Still controversial,
but some data show moderately increased
risk with high-dose therapy for menopausal
symptoms.
• Oral contraceptives: No clearly increased
risk with present use: this is attributed to
balanced content of estrogens and
progestins in currently used formulations
143
• Fibrocystic changes with atypical epithelial
hyperplasia. Increased risk, as noted in
earlier discussion of this condition.
• Carcinoma of the contralateral breast or the
endometrium: Increased risk.

144
 classification
• A. Noninfiltrating
• 1. Intraductal carcinoma
(comedocaminoma)
• 2. Intraductal papillary carcinoma
• 3. Lobular carcinoma in situ

145
• B. Infiltrating (invasive) ductal carcinoma
• 1. Nototherwfse specified {NOS)-scirrhous
• 2. Invasive lobular carcinoma
• 3. Medullary carcinoma
• 4. Colloid (mucinous) carcinoma
• 5. Paget's disease
• 6. Tubular carcinoma

146
 GRADING AND STAGING
• Nonmetastasizing: Intraductal carcinoma without
strornal invasion: in situ lobular carcinoma
• Uncommonly metastasizing. Colloid carcinoma;
medullary, carcinoma w4th lymphocytic
infiltration; inffitrating papillary carcinoma
• Moderately to aggressively metastasizing: All
other types

147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
 Infectious Diseases
• conception: infectious disease is s group of
diseases caused by pathogenic
microorganism, which invade the
susceptible population through a
transmission route and can cause popularity
in crowd.

170
 Primary factors
• Infection sources
• Route of infection
• Susceptible population

171
• Organisms affect human bodies in certain
organs or tissues via a certain route

172
 Tuberculosis(TB)
• Conception:TB is a chronic granulomatous
disease caused by bacteria called
mycobactrium tuberculosis

173
"It is nice to have money and the
things that money can buy, but
it's important to make sure you
haven't lost the things money
can't buy."
George Lorimer
1867-1937, Editor of "Saturday Evening Post"

174
 Pathology of
Tuberculosis

Chenrenyin 68062837
 Introduction:
• Infects one third of world population..!
• 3 million deaths due to TB every year
• Under privileged population -
– Crowding, Poverty, malnutrition, single
male..! – economic burden.
• Since 1985 incidence is increasing in west
– AIDS, Diabetes, Immunosuppressed patients,
Diabetes, Drug resistance.
176
 Microbiology of TB:
• Mycobacteria – ‘fungus like..
• Bacilli, Aerobic, non motile, no toxins, no spore.
• Mycolic acid wax in cell wall
• Carbol dye - Acid & alcohol fast (AFB)
• M. tuberculosis & M. bovis
• M. avium, M.intracellulare in AIDS - Atypical TB

177
AFB - Ziehl-Nielson stain

178
Colony Morphology – LJ Slant

179
180
 Pathogenesis of TB:
• Type IV ? hypersensitivity – T cells –
Macrophages  Granuloma
• Activated macrophages – epithelioid cells.
• Remain viable inside macrophages (Mycolic
acid wax coat)
• Cord Factor - surface glycolipid Antigenic.
• Self destruction by lysosomal enzymes.
• Gandhi Principle ….!
181
TB Pathogenesis
• Bacterial entry
• T Lymphocytes.
• Macrophages.
• Epitheloid cells.
• Proliferation.
• Central Necrosis.
• Giant cell
formation.
• Fibrosis.

182
Lung TB - Cavitation

183
 Pathogenesis of TB:

Infection - Immunity

184
 Morphology of Granuloma
1. Rounded tight collection of chronic
inflammatory cells.
2. Central Caseous necrosis.
3. Active macrophages - epithelioid cells.
4. Outer layer of lymphocytes, plasma cells
& fibroblasts.
5. Langhans giant cells – joined epithelioid
cells.
185
Tuberculous Granuloma

186
 Primary tuberculosis
• In a non immunized individual – children* adult*
• Lesion in subpleural zone of lung – can be at
other sites*
• Brief acute inflammation – neutrophils.
• 5-6 days invoke granuloma formation.
• 2 to 8 weeks – healing – Ghon focus (+ lymph
node  Ghon complex)
• Develop immunity – Mantoux positive

187
 Primary or Ghon’s Complex

• Primary tuberculosis is the

pattern seen with initial
infection with tuberculosis
in children.
• Reactivation, or secondary
tuberculosis, is more
typically seen in adults.

188
 Primary Tuberculosis
In Non Immunized individuals (Children)
• Primary Tuberculosis:
– Self Limited disease
– Ghons focus, complex or Primary complex.
• Primary Progressive TB
– Miliary TB and TB Meningitis.
– Common in malnourished children
– 10% of adults, Immuno-suppressed individuals
189
 Secondary Tuberculosis:
• Post Primary in immunized individuals.
• Cavitary Granulomatous response.
• Reactivation or Reinfection
• Apical lobes or upper part of lower lobes – O2
• Caseation, cavity - soft granuloma
• Pulmonary or extra-pulmonary
• Local or systemic spread / Miliary
– Vein – via left ventricle to whole body
– Artery – miliary spread within the lung

190
 Secondary Tuberculosis:

• Reactivation occurs in 10-15% of patients.

• Most commonly males 30-50 y
• Slowly Progressive (several months)
• Cough, sputum, Low grade fever, night sweats,
fatigue and weight loss.
• Hemoptysis or pleuritic pain = severe disease

191
192
Ghon Complex

193
Typical cavitating granuloma

194
 Miliary TB
• Millet like – grain.
• Extensive micro spread.
• Through blood or
bronchial spread
• Low immunity
• Pulmonary or Systemic
types.

195
Miliary TB

196
Miliary
spread
TB

197
Miliary TB Lung

198
 Cavitary Tuberculosis

• When necrotic tissue is

coughed up  cavity.
• Cavitation is typical for
large granulomas.
• Cavitation is more
common in the secondary
reactivation tuberculosis -
upper lobes.

199
200
201
202
Tuberculous Granulomas

203
Caseation Necrosis

204
Epitheloid cells in Granuloma

205
Cells in Granuloma

206
Cavitary Secondary TB

207
Systemic Miliary TB

208
Adrenal TB - Addison Disease

209
Testes TB Orchitis.

210
TB Peritonitis + liver Miliary TB

211
TB Brain – Caudate n.

212
TB Intestine

213
Prostate TB

214
Spinal TB - Potts Disease

215
216
217
 Diagnosis of TB
• Clinical features are not confirmatory.
• Zeil Nielson Stain - 1x104/ml, 60% sensitivity
• Release of acid-fast bacilli from cavities intermittent.
• 3 negative smears to assure low infectivity*
• Culture most sensitive and specific test.
– Conventional Lowenstein Jensen media 3-6 wks.
– Automated techniques within 9-16 days
• PCR is available, but should only be performed by
experienced laboratories
• PPD for clinical activity / exposure sometime in life.
218
•
PPD
Sub cutaneous
Tuberculin Testing
• Weal formation
• Itching – no scratch.
• Read after 72 hours.
• Induration size.
• 5-10-15mm (non-ende)
• < 72 hour is not diag*
• +ve after 2-4 weeks.
• BCG gives + result.

219
PPD result after – 72 hours.

220
 Granuloma or LH giant cell is not
pathagnomonic
• Foreign body granuloma. of TB…!
• Fat necrosis.
• Fungal infections.
• Sarcoidosis.
• Crohns disease.

221
•
Conclusions:
Chronic, Mycobacterial, infection - Weight loss,
fever, night sweats, lung damage.
• Commonest fatal infection in the world.
• CXR - apical lesions (CXR atypical AIDS)
• AIDS, Diabetes, malnutrition & crowding.
• Two forms Primary, Secondary
• Pulmonary, extrapulmonary, miliary.
• AFB positivity - infectiousness - isolation
• Multi drug to prevent selection of resistance
• Prevention depends on PPD & INH prophylaxis
222
•
What is New…?
14-30% of TB patients also HIV infected.
• New drugs - Rifapentine, Interferons,
Thalidomide.
• Immune therapy : Killed M. vaccine stimulates
CD8 cells (increased INF and IL-12).
• The genome of TB has been identified (~4000
genes) potential to develop new vaccines and
tests.

223
 "Troubles are often
the tools by which God
fashions us for better
things." Exams…!
- Henry Ward Beecher
• The bacteria can attack any part of the
body,
but they usually attack the lungs. Typically ,
the centers of tubercular granulomas
undergo caseous necrosis.

225
 Etiology
• Mycobacterium tuberculosis
the common species are Mycobacterium
bovine and Mycobacterium hominid.
M. tuberculosis hominis is responsible for
most cases of tuberculosis..

226
• Most infection is aquired by direct person- to-
person transmission of airborne droplets of
organisms.
• Oropharyngeal and intestinal tuberculosis are
caused by eating food or drinking milk
cintaminated with bacteria.
• Infection through wound is rare Dissemination
during respiratory passage is now the
commonest and most important pathway of
infection.

227
• It is usually direct by inhalation of airborne
organisms in aerosols generated by
expectoration or by exposure to
contaminated patient secretions, especially
form patients who have cavities in their
lungs.

228
• The droplets with bacteria which is less
than 5um in diameter can achieve the
pulmonary alveoli- chemotactic- attract
macrophage-effect cell mediated immunity
– the tuberculosis propagates in cells-
causes local inflammation and systemic
hematogenous dissemination and develops
ulterior extrapulmonary tuberculosis
• 30-50 days to develop specific cell
mediated immunity- a positive tuberculin
test results
229
Morphology of TB and immune state
of the host
Pathologic-changes state of host M tuberculosis pathological features
immunity allergy quantity virulence
Exudation weak stronger many strong serous or fibrinous inflamm
Hyperplasia stronger weaker weak tubercle
Necrosis weak strongest strong caseous necrosis

230
Basic morphology of tuberculosis
• 1. Lesion of exudation: earlier period of TB
or when people are in weakened immune
state or when the quantity of bacterium is
great and its virulence is strong.

231
232
• 1.lesion of exudation: earlier period, weakened
immune state,the quantity of bacterium is
great, ,its virulence is strong.
serous inflammation, fibrinous inflammation
neutrophil cells infiltrated locally in earlier
period –macrophages
mycobacterium tuberculosis in exudate and
macrophages
233
these changes usually occur in lung ,chorion,
synovial membrane and menings
Exudate may be absorbed or develop to
hyperplasia or necrotic lesion.

234
 2.Lesion of hyperplasia
• Virulence of infected bacterium strain is
weak or the host has strong immuninty
• Tubercle with diagnostic value is formed

235
 microscopically
• The tubercle or tuberculostic granulomtous
is composed of epithelioid cells, langhans
giant cells, lymphocytes,fibroblasts,
collagen, and characteristic caseous
necrosis presents in the center of the
granuloma
• epithelioid cells derived from macrophages

236
 histologically
• epithelioid cells are fusiform or polygon in
shape and have abundant light eosiphilic
cytoplasma ith indistinct cell boundary
• Their nuclei are spherical or oval containing
1 or 2 nucleoli.
• Chromosomes are less and even present as
vacuolus

237
• Epitherlioid cells have increased activity of
phagocytosing and killing M. tuberculosis

238
 Langhans cells
• Formed by fusion of epitheliod cells and
have an abundant cytoplasma.
• Multipl nuclei arrange at the periphery of
the langhans giant cells in either a circle or
more commonly, a horseshoe configuration
• Conglomeration of epithelioid cells so they
have the similar cytoplasm and nuclei

239
 tubercle
• The single tubercle is usually 0.1mm in
diamenter
• Too small to bevisible by the naked eye or in x-
ray
• A bigger nodule fused by 3 or 4 tubercles is
visible and has distinct boundary
• Grey, semiopaque
• As big as millet.
• Caseous necrosis is yellow
240
 3. Lesion of necrosis
• The quantity of infected bacterium is much
and the strain with strong virulence or the
host has weakened immunity and intensed
hypersensitivity
• Exudative and hyperplasia lesions may
develop to caseous necrosis

241
 Necrotic lesion
• Caseous necrosis
• Typical streamineous cheesy substance
• Delicate and uniform
• Microcopically: red granular and
structureless appearance
• Contain a number of M.tuberculosis that
causes aggravation and progression of TB
242
• Exudation, necrosis and hyperlasia often
develop simultaneously, but one of them is
the prime. They can transform each other

243
 The transition rule of basic
morphology of tuberculosis
• The development and result of tuberculosis
depend on the relation between resistance
of human bodies and virulence of M
tuberculosis,when resistance strengthen,
bacterium are inhibied or killed, the lesion
are healed. On the contrary, they will
aggravate

244
• Healing
1.absorption and dissipation: exudative lesion-
effusion is absorbed by lymphatic vessel-the
lesion diminish or disappear
chest x-ray shows the changes of lesion
,which are ill-defined inhomogenous
cloudlike, minimize gradually or divide into
flap and vanish at last-the period of
absorption-improvement clinically
245
2.Fibrosis and calfication: the lesion of
hyperplasia or small caseous necrosis can
fibrose and be healing by scaring.
difficult to fibrose a bigger lesion with
caseous necrosis totally, but can be enclosed
by peripheral fibrous tissue- the caseous
centre condense to a hard calcified nodule

246
 M.tuberculosis may remain in the calcified
lesion
It can relapse when the host resistance
decreased
Chest x-ray show high –density and clear
boundary fibrotic lesion-calcified induration
stage clinically

247
 aggravation
• 1. progression with infiltration: the lesions
expand and are exudative,followed by
caseous necrosis, x-ray shows pathy
shadow with indistinct boundary around the
prime lesion- infiltration induration stage .

248
 2.Solvation and dissemination
Caseous material undergo liquefaction and
become semifliud which may be discharged
through the natural passegeway(e.g.
bronchi,ureter etc)
The cavities resulting from discharge of
caseous materials contain a number of
M.tuberculosis, which are transmited
through these passegeway and result in
some new lesion in other sites
249
X-ray the density and size of lesion are
different. The lucent area and new lesion
can be observed-solvation and
dissemination stage clinically.
M. Tuberculosis may also be lymphatic and
hematogenous dissemination to other parts
of the body

250
 TB Information

TB (Tuberculosis) is a chronic,
communicable disease
caused by the TB bacterium:
“Mycobacterium
tuberculosis”

251
TB Information

• TB is primarily spread by
airborne droplets from an
infected person ( by a
cough or sneeze) and
inhaled by another person.
• TB infects the upper lungs

252
 Active TB Disease
Symptoms

• Prolonged cough
(>3weeks)
• Chest pain, coughing up
blood
• Systemic Systems: fever,
chills, night sweats, easy
fatigability, loss of
appetite, weight loss

*Any family members/close contacts suspected with TB should be seen at the

Pima County Health Department (PCHD) TB Control 520-740-8613 253
Screening for TB
Skin Test
PPD
(Purified Protein Derivative)
• “Reaction” is induration
(palpable swelling), not
color (erythema)
• Swelling will go away
• Is safe during pregnancy
• Is not harmful or infectious
• Once positive, will always
remain positive

254
PreventiveTreatment for Latent
TB
• With INH (Isoniazid) treatment, risk of
latentactive TB decreased:
• 90% with 12 months of treatment
• 69% with 6 months of treatment
• 9 months is optimal, minimal treatment period
• Lifetime risk of latentactive TB disease:
• 1/10 (10%) with no treatment
• 3-4/100 (3-4%) with 6 months of treatment
• 1/100 (1%) with 12 months of treatment
• INH treatment daily for a minimum of 9 months, clinic
appointment is necessary

255
 Difference between Latent and
Active TB
Latent TB Infection Active TB Infection

Have no symptoms Symptoms: bad cough>2 weeks,

pain in the chest, weight loss, fever, chills, cough up
sputum or blood, no appetite, weakness or fatigue,
sweating at night
Do not feel ill Feel ill, see above

Cannot spread TB to others May spread TB to others

Usually have positive ppd skin test Usually have a positive ppd skin test

Chest Xray is normal Chest Xray and/or culture often positive

256
 TB Definitions
ACTIVE TB DISEASE LATENT TB DISEASE
• Infection multiplies, over- • Infected with TB
whelming the immune
bacteria but contained
system, this can occur slowly
or quickly by host immune system
(+ PPD, + CXR*) (+PPD, - CXR*)
• There is a 10% lifetime risk
of converting from latent TB
infection to active TB
disease, without treatment

257
* PPD = skin test (Purified Protein Derivative), CXR= Chest XRay (radiograph)
 TB Information
People who are at the highest risk of infection:
– Close contacts (family, roommates, friends,
coworkers) of a person with infectious (active) TB
– Immunocompromised (HIV, transplants)
– Health care workers
– Foreign born persons from areas where TB is
common (Asia, Africa, Latin America, Eastern
Block Countries)

258
259
Secodary tuberculosis

260
Primary tuberculosis

261
Solvation and dissemination

262
Tuberculosis granuloma

263
Kidney tuberculosis

264
M.tuberculosis

265
• 1.lesion of exudation: earlier period, weakened
immune state,the quantity of bacterium is
great, ,its virulence is strong.
serous inflammation, fibrinous inflammation
neutrophil cells infiltrated locally in earlier
period –macrophages
mycobacterium tuberculosis in exudate and
macrophages
266
these changes usually occur in lung ,chorion,
synovial membrane and menings
Exudate may be absorbed or develop to
hyperplasia or necrotic lesion.

267
 2.Lesion of hyperplasia
• Virulence of infected bacterium strain is
weak or the host has strong immuninty
• Tubercle with diagnostic value is formed

268
 microscopically
• The tubercle or tuberculostic granulomtous
is composed of epithelioid cells, langhans
giant cells, lymphocytes,fibroblasts,
collagen, and characteristic caseous
necrosis presents in the center of the
granuloma
• epithelioid cells derived from macrophages

269
 histologically
• epithelioid cells are fusiform or polygon in
shape and have abundant light eosiphilic
cytoplasma ith indistinct cell boundary
• Their nuclei are spherical or oval containing
1 or 2 nucleoli.
• Chromosomes are less and even present as
vacuolus

270
• Epitherlioid cells have increased activity of
phagocytosing and killing M. tuberculosis

271
 Langhans cells
• Formed by fusion of epitheliod cells and
have an abundant cytoplasma.
• Multipl nuclei arrange at the periphery of
the langhans giant cells in either a circle or
more commonly, a horseshoe configuration
• Conglomeration of epithelioid cells so they
have the similar cytoplasm and nuclei

272
• The single tubercle is usually 0.1mm in
diamenter
• Too small to bevisible by the naked eye or in x-
ray
• A bigger nodule fused by 3 or 4 tubercles is
visible and has distinct boundary
• Grey, semiopaque
• As big as millet.
• Caseous necrosis is yellow
273
 3. Lesion of necrosis
• The quantity of infected bacterium is much
and the strain with srong virulence or the
host has weakened immunity and intensed
hypersensitivity
• Exudative and hyperplasia lesions may
develop to caseous necrosis

274
 Necrotic lesion
• Caseous necrosis
• Typical streamineous cheesy substance
• Delicate and uniform
• Microcopically: red granular and
structureless appearance
• Contain a number of M.tuberculosis that
causes aggravation and progression of TB
275
• Exudation, necrosis and hyperlasia often
develop simultaneously, but one of them is
the prime. They can transform each other

276
 The transition rule of bsic
morphology of tuberculosis
• The development and result of tuberculosis
depend on the relation between resistance
of human bodies and virulence of M
tuberculosis,when resistance strengthen,
bacterium are inhibied or killed, the lesion
are healed. On the contrary, they will
aggravate

277
• Healing
1.absorption and dissipation: exudative lesion-
effusion is absorbed by lymphatic vessel-the
lesion diminish or disappear
chest x-ray shows the changes of lesion
,which are ill-defined inhomogenous
cloudlike, minimize gradually or divide into
flap and vanish at last-the period of
absorption-improvement clinically
278
2.Fibrosis and calfication: the lesion of
hyperplasia or small caseous necrosis can
fibrose and be healing by scaring.
difficult to fibrose a bigger lesion with
caseous necrosis totally, but can be enclosed
by peripheral fibrous tissue- the caseous
centre condense to a hard calcified nodule

279
 M.tuberculosis may remain in the calcified
lesion
It can relapse when the host resistance
decreased
Chest x-ray show high –density and clear
boundary fibrotic lesion-calcified induration
stage clinically

280
 aggravation
• 1. progression with infiltration: the lesions
expand and are exudative,followed by
caseous necrosis, x-ray shows pathy
shadow with indistinct boundary around the
prime lesion- infiltration induration stage .

281
 2.Solvation and dissemination
Caseous material undergo liquefaction and
become semifliud which may be discharged
through the natural passegeway(e.g.
bronchi,ureter etc)
The cavities resulting from discharge of
caseous materials contain a number of
M.tuberculosis, which are transmited
through these passegeway and result in
some new lesion in other sites
282
X-ray the density and size of lesion are
different. The lucent area and new lesion
can be observed-solvation and
dissemination stage clinically.
M. Tuberculosis may also be lymphatic and
hematogenous dissemination to other parts
of the body

283
Pulmonary tuberculosis

284
 Case Presentation
• A 68-year old man presented with:
– Weight loss over a 4-month period
– Recent onset of fever/chills at night
– Chest x-ray upon admission revealed irregular opacity of
right lung with pleural effusion
– Thoracocentesis of pleural fluid revealed
adenocarcinoma
– Hepatomegaly with diffuse lymphadenopathy
– Hyperkalemia and hypocalcemia (ion imbalance)
– Fever did not respond to antibiotics and the patient dies
four days after admission.

285
 Left lung, caseous necrosis
• Histological stain
shows hallmarks of
TB infection:
– Granulomas
– Caseous necrosis
(most frequently
the lung)
– Giant cells

286
Tuberculosis-Acid fast stain
of M. tuberculosis
• Direct person-to-person
contact via transmission
of airborne droplets
containing Mycobacterium
tuberculosis (high content
of complex lipids)
• More prevalent in
developing countries
• Seen in US amongst the
elderly and
immunosuppressed
individuals
(*adenocarcinoma)

287
 Tuberculosis-Pathology
• M. tuberculosis infects host alveolar macrophage
endosome and inhibits microbicidal response allowing
for uninhibited proliferation  bacteremia  seeding
of multiple sites (patients are asymptomatic)
• ~ 3 weeks post-exposure  cell-mediated immunity
when processed M. tuberculosis antigens reach draining
lymph nodes and are presented my macrophages to CD4
T cells  TH1 sub-type cytotoxic T cells that kill
infected macrophages Chronic inflammation
• End result: Granulomas with hypersensitivity and host
resistance with caseous necrosis of destroyed tissues

288
 Characteristics of Chronic
Inflammation
• Nature of response
– Mononuclear cell infiltrate:
• Macrophages, once activated, secrete acid/neutral proteases,
complement components, coagulation factors, ROS, NO,
eicosanoids and cytokines (IL-1/TNF)
– Systemic response of patient presented as weight loss and
fever/chills at night
• Lymphocytes activate additional macrophages which secrete
IL-1/TNF which activate additional lymphocytes…vicious cycle
• Plasma cells produce antibodies

289
 Characteristics of
Inflammation
• Nature of response
– Angiogenesis: repair of damaged tissues
initiated by the release of angiogenesis
factors FGF from macrophages
– Fibrosis: non functional tissue initiated
by release of growth factors and
fibrogenic cytokines from macrophages

290
 Characteristics of Chronic
Inflammation
• Tissue changes
– Regeneration with return to normal
function
– Scarring with loss of function
– Granulomatous inflammation: TB

291
Granulomatous Inflammation
• Aggregate of activated macrophages assuming a
squamous cell-like appearance with pink granular
cytoplasm epitheliod cells
• Indistinct cell boundaries with a collar of lymphocytes
secreting cytokines for ongoing macrophage activation
• Giant cells generally found: multinucleate fusion of >20
macrophages
• Resulting in hypoxia and free radical injury causing a
central zone of necrosis: caseous necrosis (total loss
of tissue structure with a cheese-like appearance)

292
 Granulomatous
Inflammation-Lung
• Histochemical stain Caseous necrosis

of patient’s right
lung with caseous
necrosis
• Pulmonary Giant
cell
radiograph
confirmation with
irregular opacity Epitheliod cells

293
 Tuberculosis-Other
potential problems
• In immunosuppressed individuals (AIDS,
cancer) or in the elderly, progressive
primary tuberculosis or secondary
(reactivation) tuberculosis may occur.
• Reactivation of viable bacilli that had been
contained in foci of scarring.
• Due to patient’s previously acquired
hypersensitivity, a prompt response occurs
resulting in cavitations of airways, a large
source of infectivity because now patient is
raises sputum containing bacilli.
294
 Tuberculosis-Other
potential problems cont.
• Organisms can drain
through lympatics 
ducts  venous return to
right heart  pulmonary
arteries  pleural
effusions  seeds
pulmonary return to the
heart  systemic
arterial system 
seeding of multiple
organs (Miliary TB)
Testis granulomatous
inflammation
295
Granulomatous inflammation of
multiple organs- Disseminated
TB
• Disseminated TB
caused
hepatomegaly/lymphad
enopathy in my patient
• Destruction of the
adrenal cortex
accounts for patient’s
ion imbalance and
resulting
hyperkalemia/hypocalc
emia Adrenal gland

296
 Patient’s symptoms
• Adenocarcinoma: immunosuppression 
Reactivation TB
• Opacity of right lung: Caseous necrosis
• Lymphadenopathy/hepatomegaly: disseminated TB
(Systemic miliary tuberculosis)
• Granulomatous inflammation of adrenal gland and
testis: disseminated TB

297
 Patient’s symptoms
• Hyperkalemia/hypocalcemia: destruction of
adrenal cortex  ion imbalance
• Pleural effusion: disseminated TB into
pulmonary arteries
• Weight loss, fever and chills at night:
systemic response to cytokines released by
activated macrophages
• No response to antibiotic: MDR-TB or too
severely immunocompromised to fight off
infection
298
 Tuberculosis- Diagnostic
Tools
• Pulmonary examination
• Pulmonary radiographs
• Skin test
• Fine-needle aspiration (FNA) cytological
examination: Ziehl-Neelsen coloration for
acid-fast bacilli
• Blood cultures using modified Lowenstein-
Jenson medium (for patients also infected
with HIV)
• Biopsy specimens from lung, liver or bone
marrow
299
 Treatment of Tuberculosis
• Currently includes multiple drugs to be
taken for 6-9 months that include:
– 2 months with Rifater (isoniazid, rifampin, and
pyrazinamide)
4 months of isoniazid and rifampin (Rifamate,
Rimactane).
Ethambutol (Myambutol) or streptomycin will be
added until your drug sensitivity is known.
– Directly Observed Therapy is strongly
recommended by the CDC to ensure drug
regimen completion.

300
 Today in Tuberculosis-Multi-
drug Resistant Strains
• Guidelines for use of
second-line anti-TB
drugs:
– Creating evidence-based
clinical guidelines for
MDR-TB treatment
– Start treatment early and
use high-end dosing due to
lower potency
– DOT
– Improper management 
increased drug resistance
• Fighting MDR-TB in
developing countries:
– Price reduction in second-
line drugs
– Global Fund to Fight
AIDS, TB and Malaria
– Green Light Committee
for Access to Second-line
anti-TB Drugs
301