Introduction To Histopathology
Introduction To Histopathology
Introduction
to Histopathology
Bela Szende and Zsuzsanna Suba
Bevezetes a hisztopatol6giiiba
Contents
Degeneration
1 . Vacuolar degen e ratio n of renal t u b u lar epithel i u m
2 . Fatty degenerati o n of the l iver . . . . . . . . . . . . . .
3 . Renal amyl o i dosis . . . . . . . . . . . . . . . . . . . . . . .
Storage D iseases
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4. Liver i n Niel]a n n -pick disease . . . . . . . . . . . . . .
" 5 . B ra i n i n Tay-'S iiCh s-Schaffer disease . . . . . . . . . . .
Pigmentation and Metabolic D iseases.
6. C h ro n i c passive congestion of l u n g . . . . . . . . . .
7. Hepatic hemosiderosis . . . . . . . . . . . . . . . . . . .
8. H epatic cholestasi s . . . . . . . . . . . . . . . . . . . . . .
9. Pigmented nevus . . . . . . . . . . . . . . . . . . . . . . .
Atrophy
1 0. P u l monary e m p hysema . . . . . . . . . . . . . . . . . . .
1 1 . Polycystic k i dn ey disease . . . . . . . . . . . . . . . . . .
1 2 . Testicu lar atrophy . . . . . . . . . . . . . . . . . . . . . . .
Necrosis
1 3 . Anemic i n farct of k i dn ey . . . . . . . . . . . . . . . . . .
1 4. Hemorrhagic i n farct of l u n g . . . . . . . . . . . . . . . .
1 5 . Ischemic i n farct of b ra i n . . . . . . . . . . . . . . . . . .
1 6 . Centrilobular necro s i s of l iver . . . . . . . . . . . . . .
Hyperplasia
17. S i mp l e hyperpl asia of e n do m etri u m . . . . . . . . . .
1 8 . Nodu lar hyperplasia of p rostate . . . . . . . . . . . . .
Hemodynamic Disorders
1 9 . P u l m o n ary edema . . . . . . . . . . . . . . . . . . . . . .
20. T h rombosis . . . . . . . . . . . . . . . . . . . . . . . . . . .
I nflammation
21 . F i b r i n o u s pericarditis . . . . . . . . . . . . . . . . . . . .
22. P u l monary and cerebral abscess . . . . . . . . . . . . .
23. Cervicofacial act i n omycosis . . . . . . . . . . . . . . . .
24. M i l iary t u b e rcu losis i n l u n g . . . . . . . . . . . . . . . .
25. Tubercu l o u s lymphadenitis . . . . . . . . . . . . . . . .
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Neoplasms
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Systemic Pathology
Cardiovascu l a r System
50. F i b ro s i s and fatty i nfi l t ratio n of myocardi u m
51 . Acute myocardial i n fa rct . . . . . . . . . . . . .
52. Rheu mat i c myocarditis . . . . . . . . . . . . . .
5 3. E n docardial f i b roelastosi s . . . . . . . . . . . . .
54. Atherosclerosis of aorta . . . . . . . . . . . . . .
5 5 . Cysti c medial necrosis of the aorta . . . . . .
56. B u e rger's disease . . . . . . . . . . . . . . . . . .
57. Periarteritis n odosa . . . . . . . . . . . . . . . . .
58. Kaposi's sarcoma . . . . . . . . . . . . . . . . .
Resp i ratory System
59. Lobar p n e u m o n i a . . . . . . . . . . . . . . . . . .
60. B ronch p n e u m o n i a . . . . . . . . . . . . . . . . .
61 . P n e u mocystis cari n i i p n e u m o n i a . . . . . . . .
62 . Hyal i n e m e m b rane disease . . . . . . . . . . .
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The fi rst edition of " I ntroduction t o H i stopathology" was wel l received a n d con
t i n u o u s demand for a book of this type has become evident. When Medici n a Pub
l ishers p roposed a new, e n l arged editi o n , the opport u n ity arose fo r a revised and
expanded boo k .
Because o f the great p rogress i n pathology, w e h ave i ntroduced some i m m u nohis
tochemi cal stai ns in an Appendix. These stai ns h ave becom e i n di spensab le today fo r
the p ract i c i n g patho l ogist.
We reco m m e n d this e n l arged edition m ai n ly to medical students and to you n g
pathologi sts i n trai n i n g .
B. S . , Z. S .
10
Translator's Note
Medical texts are rel atively straightforward and can be read i ly tran s l ated .
Nevertheless, d i fferences i n nomenclatu re and sometimes i n c l assifi catio n of d i s
eases have to be taken i nto consideratio n . The H u n garian text (2nd edition) was
translated u s i n g cu rrent American med ical terms. Whereve r feas i b l e , the Lat i n d i ag
noses were retai ned and i n d i cated in parentheses, in o rd e r to h e l p students fam i l i ar
with the classical term i no l ogy. Eponyms and tech n ical terms com mo n l y u sed i n
E u rope also h ave been mento i ned, e . g . , G raves' ( Basedow's) d i sease. The ai m h as
been to p reserve the l ucid ity of the orig i n al text and to avoi d am b i g u ities i n the
translatio n . Hopefu l ly , en deavo u rs of this kind wi l l contri b ute to the real ization of
o u r common goal , better health care in every cou ntry.
11
12
GENERAL PATHOLOGY
14
Fig. 1 . N
n u cleu s ; C
cytoplasm ; V
vacuole
16
L
c
3 . Renal amyloidosis
(AMYLO I DOSIS R E N I S)
H e m atoxyl i n -eos i n , Co n g o red
Amyl o i d i s a generic des i g n ation of a ch aracte ristic p rote i n aceou s deposit i n the
i n terstit i u m of o rgans an d tissues. Various amyl oid p rote i n s exist, their common
components i n c l u de glycosam i noglycans and p roteoglycan s . Several diseases
c h aracterized by necro s i s of tissues or destruction of p rote i n s (e.g. chronic os
teomye l itis, tu bercu losis, cachex i a due to neoplasms, etc . ) can be associated with
system i c amylo i dos i s . Advanced amyl o i dosis of the k i dneys can lead to renal i n suffi
ciency.
Gross Findings. In ren al amy l o i do s i s the ki dneys are l arge, pale, tan to yel low, feel
stiff. The cortex i s con s i de rably swo l l e n , w i dened an d on cut s u rface it appears waxy;
on t h i n sections it h as a g l assy trans l u cency.
Microscopic Findings. Amyl o i d appears as an eos i nop h i l i c homogeneo u s ace l l u l ar
s u bstance, w h i ch affects m ai n ly the glomeruli. Amy l o i d deposits u n der the en
dothel i u m of the loops of the glome r u l u s and causes an i rregu l ar thicke n i ng of the
basement membrane. Becau se of the s i m u ltaneous deposition of amyloid, the
mesangium becomes widened an d homogeneo u s l y eosi noph i l i c . As this process
p rogresses the cap i l l ary wal l s t h i cken an d t h e i r l u men n arrows; eventually the
glomeru l u s is no l o n ge r perfu sed, its cel l u l ar components disappear an d it becomes
rep l aced by b u n dles of homogeneous eos i noph i l i c amyl o i d. I n the cortex an d in the
medu l l a the small arteries and arterioles become thicker due to deposits of amyl oid
wit h i n the i r wal l an d stai n homogeneously eos i n o p h i l i c . In advanced cases deposits
of amyl o i d can also be observed in the basement membrane of the renal tubules an d
i n the interstitium along the co n nective tissue fi bers . Amy l o i d can be demo nstrated
m icroscop ical l y with speci al stai n s . Congo red (bottom , left) metac h romatical ly
stai n s amyl o i d a vivid o range, wh i l e the u n i nvolved areas are pale yel l ow. The pre
sence of amy l o i d can be verified with pol arized l i ght, s i nce amy l o i d deposits stai ned
with Congo red give an apple-green b i refri ngence (bottom , right) .
18
G
M
4.
20
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7. H epatic hemosiderosis
( HAEM OSIDEROSIS H EPAT IS)
Prus s i a n blue reacti o n
H emosiderosis, the acc u m u l ation of hemoside ri n , i s due to destruction of red
b lood cel l s . Excessive hemoside r i n deposits in parenchymal cel l s m ay lead in the
long run to cel l i n j u ry . Generalized hemoside rosis can devel o p in severe chro n i c
passive congest i o n , o r i n protracted hemo lytic conditions ( h em olytic anem i as, seps i s
d u e t o hemolytic streptococcu s , poiso n s) . An i atroge n i c fo rm of hemoside rosis can
occ u r after m u lt i p l e blood transfusions which l ead to the deposition of large
amo u nts of hemoside ri n .
Gross Findings. The l iver i s mode rately e n l arged, ru sty b rown an d feel s firm.
Microscopic Findings. I ro n-contai n i n g pigment i s zonally deposited in the l iver
l o b u l es . As a consequence of severe passive congestion around the central veins, the
adj ace nt s i n u ses are q u ite disten ded with b lood; here an i ncreased dis i n tegration of
eryth rocytes an d deposition of hemosideri n can be see n . I n case of hemolysis the
periphery of the lobulest i . e. the periportal hepatocytes, meet with l arger amou nts
of damaged e ryth rocytes ; co nsequently, it is here t h at sign ificant amou nts of
hemo s i deri n are deposited. I n sections stai ned with hematoxy l i n-eo s i n hemosiderin
appears in its n atu ral , gol den b rown col o r . The i ron contai n i ng pigment stai ns deep
b l u e with the Prussian b l u e reaction . Deep b l u e gran u les i n dicate the accu m u l ated
deposits of hemoside r i n in the cytop l as m of hepatocytes . S i m i l ar pigment gran u les
can also be seen in the ste l l ate Ku pffer cel l s which are p h agocytic an d l i ne the
s i n u so i ds . I n cases of l o n g-stan di n g hemosiderosis one m ay observe coarse gran u l es
of hemosideri n extracel l u l arly, m ai n ly i n the peri portal connective tissue.
26
8. H epatic cholestasis
(CH O L ESTASI S H EPAT I S)
H e m atoxy l i n -eos i n
Cholestas i s co n n otes a distu rbance i n the n o rm al b i l e secretory mechan i s m s ac
companied by acc u m u l ation of b i l e i n the l iver. S i m u ltaneously the serum level of
b i l e p i gments becomes elevated and causes jau n dice (icterus) . Hepatocellular ic
terus (i ntrahepatic cholestas i s) is see n , most often i n vi ral hepatitis or p rovoked by
drugs, alco hol or othe r toxic s u b stan ce s . Obstructive (mechanical) icterus occ u rs
when the extrahepatic b i l e ducts are obstructed by a sto ne, tumor or cicatrical stric
ture.
Gross Findings. The cholestatic l iver i s swo l l e n , i t s free edges are rou n ded, an d it
i s tan to b rown o r yel lowish-gree n . I n prolonged obstructive j au n dice the l ive r i s
dark green and on i t s cut s u rface the di l ated l arger b i l e ducts are p rom i n ently dis
tended.
Microscopic Findings. H e p atoce l l u l ar i cterus ( i ntrah epatic chol estasis) u s u al ly can
be di st i n g u i s hed from obstructive (mechan ical) icterus, which is of great i m portance
in estab l i s h i n g the correct diagnosis i n l iver biopsies. I n hepatocellular icterus the
most m arked c h anges are seen in the center of the lobu les, where the bile flow is
the s l owest . H ere the swo l l e n hepatocytes h ave a f l u ffy cytop l asm which is stai ned
yel low to b rown by cholestas i s . The acc u m u l ated b i l e fo rms yel l ow to green fine
gran u les and c l u mps in the cytop l asm of the hepatocytes . S i m i l ar bile pigment can
be observed i n the cytop l as m of the Kupffer cells. The b i l e canal icu l i are markedly
di l ated by yel lowi s h green cyl i n de rs of b i l e . I n p ro l o n ged icte rus the toxic effect of
b i l e acids and r u pt u re of the disten ded bile canaliculi leads to destruction of some
hepatocytes . I n the peri portal area there i s f i b rosis and b i l e duct u l ar p ro l ife ratio n .
Mechanical obstruction of t h e m ajor b i l e ducts also l eads t o acc u m u l ation o f b i l e i n
t h e cytop l as m of hepatocytes an d i n t h e b i l e cap i l l aries, but t h e ch aracte ristic
chan ges are in the portal areas. The epithel i u m of the l arge r bile ducts becomes flat
an d thei r di l ated l u men is chock-f u l l of yel l owish green b i l e . The peri ductal con n ec
tive tissue is edem atou s and p ro l i ferating b i l e duct u l es can be recognized. Beside
the i n c rease i n f i b ro b l asts and co n n ective tissue fi bers o n e can al so observe an i n
f l am m ato ry i nfi ltrate of Iymphocytes, h i stiocytes and neutroph i l ic polymorpho n u c
lear l e u kocytes. I n p ro l onged obstruction the wal l of the disten ded b i l e ducts rup
t u res an d bile escapes i nto the con n ective tissue of the peri portal tract. The extrava
sated b i l e forms b i l e l akes which give rise to a phagocytic react i o n , occasion ally
accompanied by a foreign body giant cel l reaction .
E - bile pigment; C
28
9. Pigmented nevus
( NAEVUS P I G M E N TOSUS)
H e m atoxyl i n -eo s i n
A n ev u s i s a pigmented lesion of the s k i n or a m u co u s membrane an d can be
p resent at b i rth or devel o p l ater in l ife.
Gross Findings. Nevi can be flat, c i rcu mscri bed pigmented lesions with a smooth
s u rface, or p rotruding, wart- l i ke, hairy an d someti mes pedu n c u l ated. Dependi n g on
the content of pigment they m ay vary in col o r from flesh col o r to dark brown o r
b l ac k .
Microscopic Findings. Nevi can be c l assified acco rdi n g t o the l ocation o f the tumor
( nevu s) cel l s , thus we disti n g u i s h intraepidermal, intradermal, and compound (com
plex dermoepidermal) nevi. In intraepidermal nevi the rou n ded, wel l-defined nests
of n ev u s cel l s are seated in the basal l ayers of the epiderm is, pri m arily at the tips of
the p ap i l l ae . The n evu s ce l l s produ c i n g m e l an i n (mel anocytes) are cuboidal or poly
go nal, den sely p acked cel l s . Their n uclei are rou n d an d m itotic figu res are o n ly
occas i o n al ly e ncou ntered. The cytop l asm of the t u m o r cel ls stai n s pale and co ntai ns
a fai ntly b rown i s h cloud of m e l an i n o r m o re coarsely gran u l ar dark b rown pigment.
Intradermal nevi are l i m ited to the der m i s and are composed of i s l an ds of nevus cel l s
s u rrou n ded by del i cate b u n dles of co n n ective tissue. T h e t u m o r p ro l i fe rates i n the
der m i s an d l i fts the overlyi n g atro p h i c epiderm i s above the level of the u n i nvolved
s k i n . The amo u n t of pigment in the den sely arranged u n iform cel l s varies an d
ame l anotic areas can also occ u r . Dark brown, coarse gran u les of pigment are seen
in the cytoplas m of p h agocytic h istiocytes (melanophages) an d also among the fibers
of the i nterce l l u l ar con nective tissu e . Compound (complex dermoepidermal) nevi show
h i stologic ch aracteristics of both of the above types. Prol iferat i n g nevus cel l s can be
observed in the epiderm is as wel l as i n the der m i s .
30
epi derm i s ;
derm i s ; N
nevus cel l s ; F
32
Fig. 10. A
i ntact alveol i ; K
34
Fig. 1 1 . G
1 2 . Testicular atrophy
(ATROPHIA TESTIS)
H e m atoxy l i n-eo s i n
Atrophy of the testes can b e seen i n o l d age, as the en dstage o f orch itis of vario u s
etiologies, i n cryptorch i di s m , a s wel l a s i n e n docri ne ab n o rm al ities, i n mal n utrition,
fol lowing i rradi ati o n o r after treatment with anti neoplastic dru gs . Testicu lar atrophy
is always associated with reduced fert i l ity. I n the study of m al e i nfert i l i ty, beside
cytologic exam i n ation of the ejac u l ate, testic u l ar biopsy is an i mportant sou rce of
informati o n .
Gross Findings. T h e atro p h ic testis is always smal l e r than no rmal . I t s capsu l e, the
t u n ica al b u g i nea, i s g ray to white, somewhat thickened an d wri n k l ed.
Microscopic Findings. The germ cell population in the seminiferous tubules is sig
nificantly reduced in number; spermatogenesis i s m arkedly di m i n i shed. I n m arked
atrophy o n l y a few spermatogo n i a, l arge cel l s with spherical n uclei, and the s u pport
i n g Serto l i cel l s with the base of the i r triangu l ar body on the basement memb rane,
are l i n i n g the sem i n ifero u s t u b u les. D u e to f i b rosis of the t u b u l ar basement mem
brane the wal l of the sem i n ifero u s t u b u les i s thickened, hyal i n ized an d homogene
o u s l y eos i n op h i l ic. The l u men of some t u b u les m ay be completely obl ite rated by
f i b ro u s hyal i n e con nective tissue. The interstitium is markedly increased and i s rich
in co n nective tissue fi bers . Some atrop h i c t u b u l es are s u rro u n ded by rings of co n
n ective tissue fibers (peritubular fibrosis). Concom itant with the i ncrease of connec
tive tissue there is a proliferation of the interstitial Leydig cells. These cel l s form
smal l e r o r l arge r gro u ps in the i nterstiti u m ; the ce l l s have ample, eosinoph i l ic cyto
p l as m and ro u n ded n uclei .
36
Fig. 12. B
t u b u les ; I
i ntersti t i u m .
38
40
42
4)
,.
': .
t
"
,.
'.
.,.
\.
..
... ,
\1
Zs
44
Fig. 16. V
central ve i n ; N
necrotic zone ; H
46
Fig. 17. C
48
Fig. 18. 5
50
Fig. 19. 5
20. Thrombosis
Mal l o ry's trich ro m e , Wei g e rt's fi bri n sta i n
A thrombus fo rms when blood coag u l ates i n the b l ood vessel s o r i n the heart of
a l iv i n g perso n . The changes in the composition of b lood, i n j u ry of the endothe l ial
l i n i n g of b l ood vessel s , as well as s l ower blood flow o r distu rbance in the lami nar
flow patte rn may p l ay a rol e in the format i o n of a thrombus (th rombosis).
Gross Findings. One can distinguish a white, red and lami nated thrombus. White
thrombi develop when they are superi mposed on a damaged i ntima; they usual ly are
parietal throm b i i n large arteries. These thrombi are tightly attached to the arte rial wal l
and are dry, friable, gray-white with a finely rippled su rface. Red or coagulation
thrombi develop when the blood flow slows down o r stagnates. Red thrombi occur
mai n ly in the vei n s , tightly f i l l i n g thei r l u men. Genera l ly, they are loosely attached to
the wal l of the vei n , are succulent, soft, dark and l ivid. Laminated thrombi occur most
frequently in cardiac and aortic aneurysms. The cut su rface of these thrombi shows
gray-wh ite and dark red streaks ( l i nes of Zah n ) .
Microscopic Findings. Developing (freshly formed) white thrombi consist o f platelets,
leu kocytes and fibri n filaments. The aggregated platelets are faintly eosinophi l ic and
form i rregu larly-shaped, branch i n g trabecu lae which are bordered by a zone of leuko
cytes with dark nuclei. A fine network of fibrin fi laments is recogn izable between these
trabecu lae. O n ly a few scattered red blood cells are seen in white th rombi . The entire
col u m n of blood coagulates in red thrombi; therefore they contain all components of
blood. The fresh red thrombus f i l ls the entire l u men of the blood vessel and consists of
concentrically oriented fine fi laments of fibri n ; between these fibrin filaments one sees
all the cel l u lar elements of blood, but mostly red blood cells. The m icroscopic structure
of thrombi can be conven iently studied with Weigert's fibrin stain which renders fibrin
fi laments violet and conspicuous between yel low-stained eryth rocytes. After a few days
the thrombus begins to break down, its disi ntegrating cel l ular component forms granu
lar debris. From the vessel wal l macrophages enter i nto the debris and dispose of it. The
breakdown of erythrocytes leads to the formation and accu m u lation of hemosiderin in
the organizing blood clot which i s tightly attached to the endothelial l i n ing of the blood
vessel. Proliferating buds of capi l laries and fibroblasts enter the blood clot and a
meshwork of connective tissue fibers develops in the throm bus (organization). Later the
newly formed di lated capi l laries in the th rombus wil l transform i nto larger vessels with
a thicker wal l and endothel ial l i ning. These newly formed blood vessels partly reestablish
the blood flow in the completely occluded segment (recanalization) . With time the sub
stance of the thrombus may hyalinize or calcify.
52
Fig. 20. Top : Mallory's trichrome sta i n ; Bottom : Weigert's fibrin sta i n .
V - wal l of vei n ; Th - th rombu s ; E - eryth rocyte; F - fibrin filaments; 0 - orga n izati o n .
' /.
\
't '
, _....
Th
E
E
2 1 . Fibrinous pericarditis
(PE R I CA RD I T I S FIBR I N OSA)
H e m atoxyl i n-eosi n
F i b r i n o u s exu date m ay be seen on the visceral pericardi u m i n several pathologic
con ditions ( u re m i a, r h e u m atic carditis, auto i m m u ne diseases, myocardial i n farc
tion ) . If the p rocess becomes chron ic, the f i b r i n o rgan i zes and it m ay cause del i cate,
stri n gy adhesions between the visce ral and parietal peri cardi u m or more extensive
i n teradhere nce with com p l ete o b l iteration of the pericardial sac. These m assive
adhesions m ay becom e calcified as if the heart was enclosed with i n a p l aster mold
(concretio cordi s ) , thereby sign ificantly i m pedi n g cardiac fu nctio n .
Gross Findings. T h e pericardi u m appears du l l , it i s covered b y friab l e gray t o tan
exu date , which can be e as i ly w i ped off. If the exu date is vol u m i no u s the fibrin de
posits m at together on the visce ral pericardi u m of the vigoro u sly moving heart an d
give it a ch aracteristic s h aggy appearance resem b l i ng a hairy s u rface (cor v i l l os u m ) ,
also k n own a s " b read an d b u tter" pericarditis.
Microscopic Findings. The myocardi u m an d s u bpericardial fat tissue are u n remark
abl e . The mesothe l i al l i n i n g of the pericardi u m h as been partially destroyed an d is
o n ly focal ly p resent. The pericardial s u rface i s covered by a thick l ayer of
eosi no p h i l ic f i b r i n which focal ly can be recognized as a n etwork of f i n e f i l aments,
e l sewhere it forms c l u mps o r homogeneous m asses. In t h i cker deposits coarse b u n
dles of fibrin are arranged i n l ayers paral lel to the s u rface . U n der the mesothe l i al
l i n i n g there are di l ated and congested cap i l l aries an d ven u les with a scattered inflam
m atory i nf i l t rate of Iymphocytes an d some neutrop h i l ic polymorphonuclear l e u ko
cytes .
54
Fig. 2 1 . P
pericard i u m ; F
fibri n ; C
ven u l e ; I
L
p
c
56
2 3 . Cervicofacial actinomycosis
(ACTINOMYCOSIS CE RVICO FACIALlS)
H em atoxy l i n -eos i n , Pe r i o d i c aci d -Sch i ff react i o n
Act i nomycosis i s a c h ro n i c s u pp u rative disease which occ u rs ch iefly i n its cervico
fac i al , thoracic an d abdo m i n al for m s . Its causative agent is Act i n omyces israe l i i , a
G ram-positive bacteri u m . It i s a com mo n constituent of the n o rm al bacterial flora of
the mouth and can become pathogen i c fol lowi n g local trau m a, operation or i m
m u nosu ppress i o n .
Gross Findings. The re i s a board- l i ke i n du ration i n the region of the mandi b l e o r
neck, respectively. The p rocess u s ually l eads to the fo rmation of a n abscess, which
ch aracteristical ly fl u ct u ates o n p al p ati o n . Later the p u s breaks t h rough to the su rface
of the s k i n or m u cosa by creat i n g a fist u l a. Ch aracte ri stical ly the p u s contai ns grossly
v i s i b l e small ( 1 -2 m m ) yel low gran u l es ( " s u l f u r gran u les"), which are the typical col
o n i e s of Act i n omyce s .
Microscopic Findings. O n e sees an abscess cavity, w i t h i t s wal l an d the s u rro u n di ng
gran u l ation tissue with i nf l am m atio n . The pathogen i n the abscess appears as an
oval to rou n d gran u l e and from its periphery fi l am e ntous struct u res are radiating;
these are eos i noph i l ic an d stai n deep red with the PAS reaction . The gran u les are
e nveloped by p u r u lent exu date an d debris of tissue. The abscess cavity is del i neated
by g ran u l ation tissue wh ich contai ns f i b ro b l asts, ro u n d cel l s and h i stiocytes, the
l atter partly with foamy cyto p l asm ( m acrophages) . On fortu ito u s p l anes of sectio n i ng
the ope n i n g of the fist u l o u s tract can be see n ; it is l i n ed by s q u amous epithel i u m
which i s conti n u o u s with t h e s u rro u n di n g epide r m i s . T h rough the fist u l a colon ies
of bacteria an d p u r u l ent exu date is e m ptyi n g o n the s u rface .
58
Fig. 23. Top : H ematoxyli n-eosi n ; Botto m : Periodic acid Schiff reaction.
actinomyces gran u l e ; 0 debris of tissue and cel l s ; E epiderm i s ; F fistu la;
I
i nflam matory infiltrate; L leu kocytes .
-
60
2 5 . Tuberculous lymphadenitis
( LYMPHADENIT I S T U BE RCULOSA)
H e m atoxy l i n -eos i n
As a r u l e , some lymph n odes are also i n volved i n tubercu losis. Specific lym
phade n i t i s is most often seen in the regional (cervical , b ro n c h i al o r mesenteric)
lymph nodes, depe nding on the l ocation of the p r i m ary i n fecti o n .
Gross Findings. The tubercu l o u s lymph n odes are s i g n ificantly e n l arged an d may
be greater than 1 .0 c m . i n diameter. Their congested cut s u rface reveal s gray to
yel l ow, putty- l i ke areas of variable size. These areas of caseat i n g necros i s may u n
dergo l i q u efaction a n d thei r contents can b reak i nto the l u m e n o f adjacent organs
(e. g. b ronch u s ) , o r can drain through a fistu l o u s tract to the s u rface of the s k i n . The
l atter com mo n l y occ u rs in the cervical region (scroph u lo derma) an d heals with dis
f i g u r i n g scars .
Microscopic Findings. The n o rm al arch itectu re of the lymph n ode can not be recog
n i zed, it is rep l aced by tu bercles of vary i n g sizes and n u m bers. The center of a
typ ical t u bercle h as an eosinoph i l ic center of caseat i n g n ecrosis s u rrou nded by a
zone of epithelioid cells and Langhans-type giant cells. The n uclei of the epithelioid
cel l s are oval , pale stai n i n g and t h e i r body i s e l o ngate. The Langhan s-type g i ant cel l s
h ave a diamete r of 1 50-200 ft , are generally rou n d an d thei r n u mero u s smal l n uclei
are at the periphery of the cel l in a wreath-l i ke arrangement. The tu bercle i s s u r
ro u n ded by Iymphocytes an d p l asma cel l s which represent a tran s itional zone to
ward the cel l popu l ation of the lymph node .
62
Ly
;.:.-
_
_
_
_
64
Fig. 26. M
mycobacteria; T
debris o f necrotic ce l l s .
_
_
.-:-
T
____
/M
2 7. Candidal esophagitis
( CA N D I D I ASIS ESOPHAG I )
Pe r i o d i c aci d -Sch i ff react i o n
Can dida al b i cans, a n o rm al i n h abitant o f the mouth, i s the most frequent agent of
fu ngal i nfections in the u pper digestive tract (o ral cavity, esophagus) . Predisposing
factors are long treatment with antib iotics and i m m u nosu p p ression (e. g. acq u i red
i m m u nodeficiency syndrome).
Gross Findings. The lesion o n the m ucosal s u rface appears as a thick, creamy,
pearly wh ite to gray pse u domem b rane wh ich can be wi ped away, leaving a red ooz
i n g s u rface . C l i n ical ly, chron i c can didias i s h as a hyperplastic and an atrophic form .
I n the former, the m u cosa appears thickened, edem ato u s and red; i n the atrophic
fo rm the m ucosa i s e rythematou s , thin and eas i ly rubs off.
Microscopic Findings. The sq u am o u s epithel i u m of the esophagus is u lcerated, the
adj acent stro m a is ede m atou s an d congested. The u lcer is covered by a mass of
f i l amentous structu res (can di da) form i n g a dense tangle of fine th reads which stai n
m agenta with the PAS-reaction .
66
Fig. 27. U
u lcerat i o n ; K
necrotic debri s ; C
28. G ranuloma
(G RAN ULOMA)
H e m atoxy l i n -eo s i n
If fo reign m aterial (e. g. g l ass o r wooden s p l i nters, metal particles, s u rgical s u
t u res, etc . ) gets i nto l iving t i s s u e s o r if deposits of e n dogenous s u bstances which
are i ns o l u b l e i n body f l u i ds (e. g. cho lesterol crystals, u rate crystals, cal c i u m salts)
can not be e l i m i n ated, then they are wal led off by a so-cal led foreign body
gran u loma. L i p i d s u bstances which get i nto the i nterstiti u m by i n j u ry of adipose
tissue ( e . g. b reast) are e l iciting the fo rmation of a so-cal led l i pogran u loma.
Gross Findings. These gran u l o m as are firm, ci rcu m scribed structu res varying from
0.1 to 1 .0 cm . in di ameter. On cut s u rface a fo reign body is someti mes recogn izable.
The center of l i pogran u l om as contai ns yel l ow to tan , poorly c i rcu mscribed fat tissue.
Li pogran u l o m as freq uently are f i rm ly adhe rent to skin scars and can be m i staken for
a tumor.
Microscopic Findings. In the center of the foreign body granuloma there are re
m n ants of s u rgical sutu res cut longitudi n al ly or on cross sectio n . In the i m medi ate
vicin ity of the fo reign body there are i rreg u l arly-sh aped, m u lti n u cleated fo reign
body type g i ant cel l s which have a wide rim of eos i noph i l ic cyto p l as m . These giant
cel l s s u rrou n d the foreign m aterial. In thei r vicin ity there are i nflam m atory cel l s
(Iymphocytes, p l asma cel l s), cap i l l aries a n d p rol iferating yo u n g mesenchymal cel l s
(fibroblasts), t h e l atte r with a n e l ongated cell body a n d oval n u cleus. I f t h e fo reign
body i s not removed, the gran u l o m a wi l l become paucice l l u l ar, f i b rous, wi l l shri n k
and fo rm a scar. T h e lipogranuloma demarcates necrotic fat tissue which, i f l i q u ified,
leaves cavities l i ned by l i p i d- l aden m acro p h ages ( l i pophages, xanthoma cel l s) an d by
the so-cal led To uton-type giant cel l s . The cytoplas m of both cel l types appears foamy
due to the l i p i d which h as been dissolved.
6'8
K - connective tissue,
Fig. 288. Bottom : L i pogran u l oma.
L - necrotic adipose tissue; T - Touton -type giant cel l s ; X - xanthoma cel l s .
70
Fig. 29. E
squamous epithel i u m of gu m ; 0
giant c e l l s ; F
fi b roblasts; C
cap i l l aries.
epiderm i s ; C
l i ne of scar ; A s k i n appendage;
I
i nf l a m m atory i nfiltrate.
normal d e r m i s ; C scar tissue.
-
72
3 1 . Verruca vulgaris
(VE R R U CA VU LGAR I S)
H e m atoxyl i n -eo s i n
This s k i n lesion i s caused by the h u m an papi l l o m a v i r u s . I t mostly occu rs o n the
f i n gers and the back of the h and of c h i l d re n and you n g ad u lts . The benign lesion
freq uently heals ( d isappears) spo ntaneo u s ly.
Gross Findings. The lesion flatly protrudes above the l evel of the s k i n , has an un
even gray-wh ite to tan-brown s u rface and meas u res 0.2 to 0 . 6 cm i n d i amete r.
Microscopic Findings. The e levated lesion i s covered by a thick hyperpl astic epider
m i s wh ich fo rms pointed p ap i l l ae . The epiderm i s shows i ncreased keratin ization
(hyperke ratosis) res u lt i n g in a s i g n ificant amo u n t of l am e l l ated, someti mes frag
m ented eos i noph i l i c ace l l u l ar kerat i n which covers the papi l l ary s u rface . Th i s hyper
ke ratosi s is o rderly, i . e . no n uc l e i are seen in the kerat i n ( hyperorthokeratosis). The
epiderm al cel l s of the gran u l ar l ayer contai n i n tracytop l as m i c eosinoph i l ic gran u l es,
thei r s h ru n ke n n uclei are d eeply basoph i l i c and are s u rro u nded by an em pty appear
i n g space ( ko i l ocyto s i s) . The vac u o l ated cel l s are referred to as koilocytes. With the
l i ght m i c roscope, someti mes i nc l u s i o n bodies can be seen in the n uclei, suggestive
of a vi ral i n fecti o n . The strat u m mal pi g h i i (the basal , s q u amous and gran u l ar cel l
l ayer o f the epiderm i s) i s i n c reased i n thickness, this ch ange i s referred t o as acan
thos i s . The t h i ckened epidermis extends downward f i n ge r-l i ke e l ongations (cal led
rete ridges) i nto the u pper d e r m i s . The lower ends of these rete ridges tend to point
toward the geometric center of the base of the verruca. The rete ridges are separated
by the papi l l ary derm i s which is u pward ly e l o ngated (pap i l lomatosis) . The basement
membrane i s recognizable and s h arply separates the epid erm i s from the derm i s .
Often there i s a c h ro n i c i nflam m ato ry i nfiltrate i n t h e adjacent derm i s .
Fig. 318. H
74
3 2 . Molluscum contagiosum
H e m atoxyl i n -eo s i n
76
Fig. 32. E
i ntact epiderm i s ; K
kerat i n ; I
E
E
78
Fig. 33. 5
stroma; H
hyperke ratos i s ; A
acanthosi s ; M
80
82
84
Fig. 36A. M
stroma.
lumen.
3 7. Cystadenocarcinoma of ovary
( CYSTOCARCI N O MA OVARII)
H e m atoxyl i n -eosi n
T h i s t u m o r freq uently arises i n pre-exi stent benign cystadenoma of the ovary by
malignant t ransfo r m at i o n .
Gross Findings. The ovary c a n be enorm o u s , reach i n g a diameter of 1 5 cm o r more .
O n c u t s u rface the t u m o r i s m u lti cystic con s i st i n g of n u mero u s cham bers of varyi n g
s izes and s h apes. These com partments are partly o r al most completely f i l led with
polypoid o r p ap i l l ary cel l growt h s ; sol i d portions m ay also be seen . The cysts are
f i l led with blood-stai ned f l u i d. The wal l s of the cysts are thick , firm an d gray-white
on c u t s u rface. When the t u m o r extends to the periton eal s u rface, it wi l l spread by
i m p l ants an d metastases, cau s i n g sero u s and hemorrhagic ascites .
Microscopic Findings. The t u m o r contai n s cystic spaces which are l i ned by atypical
cyl i n drical epithe l i u m . These t u m o r cel l s can appear i rregu l arly pseudostratified o r
m u lt i l ayered. N u merous m itoses are seen amo n g the darkly stai ned mal i g n ant
epithe l i al cel l s . S i m i l ar epithel i u m covers the pap i l l ary and polypoid growths which
are s u p po rted by bran c h i n g cords of f i b rovascu l ar stroma. The tumor cel l s i nfi ltrate
the stro m a an d also the wal l of the cysts where they form n ests of p ro l i ferating
epithe l i u m an d abortive g l an ds .
86
Fig. 37. C
cyst wal l ; L
l u men o f cysts; 5
H
c
5
E
L
88
Fig. 38. T
t u m o r' cel l s ; 5
stroma; N
necrosis.
90
Mal ignant tu mors grow i n g i n body cavities freq u e ntly shed cel l s which can be
fou n d i n the b loody p l e u ral fl u i d, ascites, u ri ne, sputu m , etc. Ben ign and mal i g n ant
cel l s exfo l i ated from the uteri n e cerv i x can be exam i ned in vag i n al smears with the
Papan i co l ao u tech n i q u e . More recently fine n eedle asp i rates from suspicious lesions
of vario u s o rgan s (thyro i d, b reast, lymph nodes, l iver, pancreas, etc . ) are exam i ned
for cyto logic diagnos i s . Cytologic mate rial can be studied on s mears o r on sections
of cel l b locks (after centrifu gation and paraff i n e m beddi ng) . The preparations can
be stai ned with hematoxyl i n -eosi n , G i e msa's or Papan ico l ao u ' s stai n, but can also
be studied with i m m u n o h i stochemical methods o r with the e lectron m i croscope.
A cytologic diagnosis i s often difficult because the exfo l i ated cel l s are eas i ly damaged
before or du ring p reparation of the m i c roscopic specimen . The res u lts of cytologic
exam i n ation always h ave to be corre l ated with the c l i n i cal f i n di n gs an d often a biopsy
is needed to confirm them .
Microscopic Findings. Mal ignant t u m o r cel l s and cel l gro u ps can be seen em bedded
i n fibrin and b loody cel l deb ris. The t u m o r cel l s are of variab l e size and shape
(pleomorphism) and stai n vari ab ly. The n u cleus to cyto p l as m ratio i s i n creased, the
n uclei are l arger an d h ave darkly stai n i n g c h romat i n ( hyperch romasia) . Mitotic fi
gu res m ay be seen, some abnorm al ( e . g . tripolar) m i toses are also p resent. Bes ide
the t u m o r cel l s there are also exfo l i ated mesothe l i al cel l s , polymorphonuclear l e u ko
cytes, Iypmhocytes an d red blood cel l s .
92
Fig. 40. F
fibri n ; T
t u m o r ce l l s ; G
4 1 . Myxoma
H e m atoxyl i n -eo s i n
94
, Fig. 4 1 . A
g ro u n d su bstance ; T
t u m o r cel l s ,
96
98
K
H
44. Rhabdomyosarcoma
H e m atoxyl i n -eos i n , i ro n h e m atoxyl i n
1 00
E
o
R
a
1 02
1 04
Fig. 46. E
epithelial i s l a n d s ; M E
myoepith e l i u m ; M
P
myxomatous tissue;
cart i l agi nous tissue.
1 06
1 1).
Microscopic Findings. T u m o r cells can b e seen i n al l l ayers o f the ski n . The tumor
i nfiltrates the epiderm i s , overflows the de rmis and exten ds i nto the su bcutaneous
fat tiss u e . Conseq u ently the overlyi n g s k i n u lcerates. The size an d p igment content
of the t u m o r cel l s show great variation ; in some cases the t u m o r cel l s have am ple
cytop l as m (epithe l i o i d cel l type) ; in others they are e l o ngate and form streams (spi n
dle-s haped cel l type) . T h e cyto p l asm contai n s varying amo u nts of brown pigment
( m e l an i n ) . In some cel l s there i s no pigment o r only a few small pigment gran ules;
however, i n the same t u m o r heavily pigmented cel l s with a homogeneously dark
b rown cytop l as m can also be observed. A lymphocytic i nfiltrate s u rro u n ds the
tumor.
epiderm i s ; U
u lcer; T - t u m o r cel l s ; Ly - lymp hocytic i n f i ltrate.
Fig. 488. E epithelioid melanoma cel l s ; M - melan i n pigment.
Fig. 48C. 0 - s p i n d le-shaped melanoma cel l s ; M mela n i n pigment.
Fig. 48A . H
1 08
49. Choriocarcinoma
( CH O R I O N EPIT H ELI OMA)
H e m atoxyl i n -eo s i n
This rare m al i gn ant t u m o r i s composed of trophoblast arranged i n a dimorph ic
p attern and l ac k i n g chorionic vi l l i . I t develops i n the uterus fol lowi n g del ivery o r an
abo rt i o n , l ess fre q ue ntly it is anteceded by m o l ar p regn ancy. Ectopic choriocar
c i n o m as m ay occ u r in the ovary and testi s as a component of a malignant germ cel l
t u m o r o r very rarely as a p u re neoplas m . The t u m o r i s fatal without ade q u ate medical
treatment. Choriocarci n o m as , part i c u l arly those of the uteru s , respond wel l to
cytotoxic chemothe rapy an d can be c u red i n a l arge percentage of cases. Choriocar
c i n o m as p roduce h u m an chorion ic gon adotro p i n (hCG) which is also present in the
u ri n e ; t h u s , a positive p regn ancy test m ay be helpful i n the c l i n ical diagnosis.
Gross Findings. The tumor i s soft, spongy, dark red, s i m i l ar to p l acental tissue.
There are p ale, friab l e , necrotic focuses and hemorrhages o n cut s u rface .
Microscopic Findings. Atyp ical p ro l iferation of trophoblastic cel l s is seen without
stro m a. The t u m o r i nfiltrates the myometri u m an d is com posed of two cel l types,
those of the cytotrophoblast ( Langhans cel l) an d those of the syncytiotrophoblast. The
cytotrophoblastic cel l s are prim itive po lygon al m o n o n u cleate smaller cel l s with pale,
eos i n o p h i l i c , s l ightly gran u l ar cytop l asm an d distinct cel l bo rders. The i r n uclei are
rou n d or oval with f i n e ly dispe rsed c h ro m at i n ; m itotic activity i s evident. The syn
cytiotrophoblastic cel l s are l arge, differentiated, m u lt i n ucleated. I n the i r atypi cal ,
neoplastic form they show n u merous hyperchromatic rou n d n uclei which are i rregu
l arly di stributed in the dense eos i noph i l ic cytop l asm. The tumor is vascu l ar, num erous
di l ated b lood vessels are see n . Some b lood vessels have bee n i nvaded by tumor cel l s
which expl ains t h e p ropensity o f t h e t u m o r f o r early hematogenous metastases.
110
SYSTEM I C PATHOLOGY
114
Fig. 50. M
116
5 2 . Rheumatic myocarditis
(MYOCA RDIT I S R H E U MATI CA)
H e m atoxyl i n -eos i n
Rheu m atic myocarditis i s a m an i festation of acute rheumatic fever, a systemic i l l
ness which i s princi p al l y a disease of c h i l dhood. I n the majo rity of cases there is a
h i story of an u pper ai rway i n fection caused by gro u p A, beta-hemo lytic Streptococ
c u s . Rhe u m atic fever is con s i dered to be an i m m u nologic phenomenon i n which
some anti bodies agai n st streptococcal antigens cross- react with heart antige n s .
Gross Findings. T h e myocardi u m i s p a l e b rown to red, flabby, somewhat brittle.
O n the left s i de of the heart, s u be n docardi al ly an d al ong the smal l b ranches of the
co ron ary arteries, small n odu les appear. These nodu l es are barely visible with the
n aked eye an d are gray-tan , rou n d o r oval o n cut s u rface. In l ater stages of the
disease, when the gran u lo m as h ave healed with fibros i s , they appear as small foci
of gray-wh ite fi rm scar tiss u e .
Microscopic Findings. I n t h e interstiti um o f the myocardi u m , there are ch aracteristic
oval nodules (Aschoff bodies), primarily in the perivascu l ar con nective tissue. The
microscopic appearance of Aschoff bodies changes with progression of the di sease :
we di stinguish an exudative, a prol iferative and a heal ing phase of rheumatic myocar
ditis. I n the early, exudative phase, the interstitial co nnective tissue of the myocardi um
i s loose, edem atou s . Homogeneous eosi noph i l i c foci appear in it; these represent fib
rinoid necrosis. Here the col l agen fi bers are swollen, fragmented and proteinaceous
material precipitates on their su rface . Aro u n d these foci of fibrinoid necrosis there is
an infi ltrate of i nflam m atory cel l s , predomi n antly of neutroph i l ic polymorphonuclear
leu kocytes. I n the proliferative phase the characte ristic m icroscopic picture of an
Aschoff body i s see n , its cyto logic featu res are di agnostic. The center of an Aschoff
body is acel l u lar, eos i noph i l ic and necrotic; it is su rrounded by a zone of rou nd cel ls
(lymphocytes , plasma cel ls) elongate fi broblasts an d large, modified mesenchymal cel l s
(Anitchkov cells). T h e l atter have elongate n uclei with a central band o f chromatin
which on longitudi n al sections resembles a caterpi l l ar. O n cross section the chromatin
bar is s u rrounded by a halo- l i ke space so that the nucleus looks l i ke an owl-eye. The
Anitch kov cell has i rreg u l ar ragged cytoplasm ic borders, sometimes shows
pseudopodia. The origi n of these cel l s i n u n clear, acco rdi ng to some authors these are
modified fibroblasts . Ch aracteristic components of the proliferative phase are the
Aschoff-type giant cells (or Aschoff myocytes) . They have basoph i l i c cytoplasm and
lobu l ated, often mu ltiple n uclei with conspicuous nucleo l i . They also appear to be of
mesenchymal origi n by the i r histochemical an d electron microscopic profi le. In thei r
healing phase the earlier cel l u l ar gran u lomas show fibrosis and hyal i n ization.
118
m u scle fibers; N
f i b r i n o i d necrosi s ; An - A n i tchkov ce l l ;
As - Aschoff cel l ; Ly - Iymphocytes.
5 3. Endocardial fibroelastosis
( FI BRO ELASTOSI S E N DOCA RD I AL l S)
Van G i eso n 's e lasti n
Fibroe l astosi s of the endocard i u m is a rare d isease of u n k nown etiology. Thicken
i n g of the e ndocard i u m of the l eft ventricle i m pedes card i ac fu nction early i n l ife .
Gross Findings. The heart i s e n l arged and its cham bers are d i l ated . The m u ral en
docard i u m i s s mooth and d iffusely, o r i n a c i rc u m scri bed area, opal escent pearl
wh ite and feel s rubbe ry. On cut s u rface the e ndocard i u m is conside rably th ickened,
sometimes several m m t h i c k ; it fo rms a rigid l i n i n g of the left ventricle, less com
m o n ly of the left au ricu l ar appendage, right ventricle and l eft au ricu l ar appen d age.
Microscopic Findings. The endocard i u m appears markedly th ickened due to an i n
creased n u mber o f both collagen and elastic fibers. The col l agen fibers are coarse
and appear b l u e with Mal l o ry's trichro m e stai n . E l astic fibers are t h i n ner, wavy and
appear d ark b rown with van G i eson ' s stai n . These con n ective tissue fi bers are ar
ranged in b u n d l es paral l e l to the s u rface of the endocard i u m . There is also an i n
crease of cel l s i n t h e e ndocard i u m : s p i n d l e-sh aped f i b ro b l asts and elongate, ribbon
l i ke s mooth m u scle cel l s are scattered in the thickened l i n i ng. Co l l ections of a few
Iymphocytes are also occas i o n al ly see n . S m al l e r or thicker b u nd les of the co n n ective
tissue fibers are reach i n g i nto the adjacent myocard i u m . S i nce the abnormally thic
kened e ndocard i u m i m pedes an ade q u ate oxygen s u pply of the card i ac m uscle,
small foci of necrosis can be seen in the myocard i u m .
1 20
Fig. 53. M
myocard i u m ; E
endocardi u m ; R
elastic f i bers.
1 22
Fig. 54. I
intima; M
media; L
lipids; C
1 24
1 26
5 7. Periarteritis nodosa
(PO lYART E RI I T I S N ODOSA)
Aza n , Mal l o ry's trich ro m e
Peri arte ritis ( o r polyarte riitis) nodosa i s a severe disease characterized by necrotiz
i n g i nf l am m ation of the blood vesse l s . The p rocess m ai n ly affects small and medi u m
sized arte ries, and presu m ably i m m u nopatho l ogic mechan i sms are respo nsible for
it. The disease l eads to n ecrosis of the areas s u p p l ied by the affected arte ries i n
vario u s o rgans ( e . g . heart, ki dneys, i ntesti nes) .
Gross Findings. Small f i rm nodules are fou n d on the affected arte ries, primarily at
the site of their bran c h i ng. I n typ ical cases the disease i s segmental , alte rnati ng
wel l-demarcated sections of i nvolved an d n ormal wal l . The damaged arterial wal l is
weakened and con seq u e ntly m ay form an aneurysm o r rupture. Often the l u men is
occ l u ded by a t h ro m b u s .
Microscopic Findings. T h e changes vary acco rdi n g t o t h e phase o f t h e disease. I n
t h e acute phase al l l ayers of t h e arte rial wal l show a dense inflammatory infiltrate of
m o n o n u c l ear ce l l s (lymphocytes, mon ocytes) and neutroph i l ic polymorphon uclear
l e u kocytes. The m edia of the severely affected arte ries shows segmental o r c i rcumfe
rential fibrinoid necrosis which sometimes extends to al l l ayers of the vessel wal l .
The necrotic areas appear homogeneous, strongly eos i noph i l ic and l ack n uclear
stai n i ng. Li ke f i b r i n , the necrotic areas appear b ri ght red with the Azan stai n . The
wal l of the arteries weakened by i nf l am m ation and n ecrosis becomes t h i n ner, may
b u l ge and rupt u re, t h u s vary i n g amo u nts of hemorrhage m ay be seen in its vicin ity.
Acute arteritis is often assoc i ated with thrombosis, which occl udes the l u me n . In a
l ater, proliferative phase of the disease the p ro l i ferat i n g f i b ro b l asts and newly formed
con nective tissue fi bers repai r the n ecrotic port i o n s . The arte rial wal l becomes thic
kened an d defo rmed, the l u men n arrow. The i n flammatory i nfi ltrate is no longer
dom i n ant, although m acrop h ages an d p l asma cel l s are see n . In the healing phase the
arteries appear deformed, have thick, scarred wal l s in which the regu l ar l ayers no
longer can be recogn ized; no i nflammation i s see n .
1 28
1 30
1 32
Fig. 59. 5
alveolar septa; L
fibri n .
60. B ronchopneumonia
H e m atoxyl i n -eo s i n
1 34
P - plasma cel l s ; E
1 36
1 38
1 40
Fig. 63. P
d u st particles; G
gra n u loma; 5
i n teralveolar septa.
G
5
1 42
1 44
Fig. 65. T
l u ng parenchyma; 5
alveolar septa; L
l u me n ; 0
tumor cel l s .
1 46
Fig. 66. C
s i n uses.
Fig. 67. Top and Bottom, left : M L i nfiltrate o f chronic myeloge nous leukemia;
V central ve i n ; M trabeculae of h epatocytes .
Bottom, right : LL
i nfiltrate of c h ro n i c lymp hocyt i c leukemia.
-
1 48
1 50
Figs. 68A and 8. S R - Reed-Sternberg giant cel l ; H o - Hodgki n 's (or lacunar) cel l s ;
H i - neoplastic h i sti ocyte; L y - Iymphocyte ; K - f i b r o u s stroma ( i n m i xed c e l l u l a rity type) .
Fig. 68C. S - septa of con n ective tissue; T nodu les of tumor ( i n nodu lar sclerosis type).
-
1 52
1 54
fat vacuole.
1 56
Fig. 71. A
72 . Chronic sialadenitis
(SIALOADENIT I S CH RO NICA)
H e m atoxyl i n -eo s i n
I n flam mation o f the maj o r sal ivary glands i s freq u ently of bacterial origi n . The
most i m portant pred i spos i n g factor is d i m i n i s hed secretion of sal i va which can be
d u e to d ehyd ratio n , med ication , rad iation or tra u m a . An i m portant eti ologic factor
i s stagnation of sal iva d u e to obstruction by sialolithiasis. I n n eglected cases the
i n fection penetrates the caps u l e of the gland and i n vo lves adjacent tissues .
Gross Findings. The i n vo lved sal ivary gland is swo l l e n , f i r m , sensitive to touch and
its secretion of sal iva i s d i m i n ished. Pu r u l e nt exu date may e m pty from the main d u ct
on gentle massage of the gland. O n cut s u rface gray, fi rm tissue can be seen with
o bs c u re l o b u l a r struct u re .
Microscopic Findings. T h e destruction of aci n i i s n oted and with i n t h e i nvolved
l o b u l e they are replaced by fibrous tiss u e . Some resi d u a l aci n i are l i ned by cubo i dal
epithe l i u m . A lymphocytic and plasma cel l u lar i nfi ltrate of variable i ntensity i s seen
in the i n te rstiti u m . The d u cts are d i lated and there is a peri d u ctal rou n d cel l i nfi ltrate.
The con nective tissue of the i nterlobular se pta is also i ncreased and may be foca l ly
homogeneo u s , eos i noph i l i c d u e to hyal i n e degeneratio n .
1 58
Fig. 72. A
aci n i ; D
d ucts ; L
lymphocytic i n f i ltrate.
1 60
1 62
1 64
Fig. 75. K
kerati n ; G
strat u m g ra n u losu m ; 5
Ly
- .
,
..
' V..'
\ .
"
..
...
:
.
.... .
.. ,
...."
Ly
The origi n o f t h i s t u m o r has n ot been com p l etely clari fied , because the normal
co u nterparts of the characteristic gran u lar cel l s have not been identified as yet.
These t u m o r cel l s were thought to be of myoblast origi n , but recent i m m u nohis
tochem ical stu d i es s uggest a n e u roge n i c t u m o r . S i n ce m o rphologica l ly s i m i lar
gran u l a r cel l s can occu r i n othe r t u m o rs as wel l (e.g. i n ameloblastomas) , it i s as
s u med that the gra n u lar cells develop as a res u lt of a degenerative p rocess. The
t u m o r can occ u r anywhere in the oral cavity o r at othe r sites, but it i s most common
in the ton g u e .
Gross Findings. T h e t u m o r appears a s a 0.5 t o 1 .5 c m . firm, asymptomatic mass ; it
can be m i staken for a f i b ro m a . The overlying m ucosa i s i n tact. O n cut s u rface the
gray to white lesion stands out in contrast to the m u scle of the to ngue.
Microscopic Findings. The t u m o r cel l s fo rm i rregu l a r b u n d l es, nests o r gro u ps
which extend without sharp del i n eati o n i nto the adjacent m u scle fi bers . The gran u lar
cel l s are po lygonal o r ro u n d , the i r abu ndant cyto plasm i s pale and conta i n s charac
teristic s m a l l eos i noph i l ic gran u le s . The n uclei of the gra n u lar cel l s are sma l l ,
rou nded and d a r k stai n i ng . T h e cel l s are not pleomorphic, m i toses are very rare. The
overlying stratified squamous epithel i u m can be u n u s u a l ly hyperplastic and may ex
tend i rreg u l a r elongate p rojections i nto the tu mor. This growth pattern is cal led
pseudoepithel i o mato u s hyperp las i a which can be m istaken fo r squamous cell car
cinoma.
1 66
Fig. 76. M
t u m o r cel l s .
77. Ameloblastoma
H e m atoxyl i n -eos i n
1 68
1 70
Fig. 78. P
1 72
Fig. 79. 5
stroma; T
1 74
1 76
Fig. 81. U
u lcer; N
m ucosa; M
m u scularis propr i a ; H
S granu lation tissue;
-
scar tissue;
detritus.
1 78
1 80
Fig. 84. M
1 82
1 84
1 86
F
N
F
1 88
Fig. 87. M
m u cosa; F
u lcer; L
blood vessels;
hemor rhage.
1 90
Fig. BB. K
1 92
Fig. 90A . a n d B . L
1 94
T
L
.
. ,
a
I..
I
-.
..
.- \.
...
N
L
L
D
9 1 . Alcoholic hepatitis
( H EPAT I T I S ALCO H O LlCA)
H e m atoxy l i n -eos i n , Mal l o ry's trich ro m e
C l i n ical a n d experi m ental data have p roven t h e potentially hepatotoxic effect of
ethyl alcohol which p r i ma r i ly damages the l i p i d metabolism of l iver cel l s .
Gross Findings. T h e l iver i s en larged , yel l ow , has a greasy sheen a n d fee l s fi rm d u e
t o f i b rosis.
Microscopic Findings. The characteristic features of alcoholic hepatitis are damage
and necrosis of hepatocytes, focal collections of neutrophilic leukocytes, and in
creased collagen (fi b ros i s ) . The changes are most p ro m i n ent i n the center of the
l o b u l es . In the cytop lasm of many hepatocytes large vacuoles may be seen which
correspond to the fat glob u l es d i ssolved d u ri n g tissue em bedd i n g . The centri lobu lar
hepatocytes are swo l l e n , have abu ndant pale-sta i n i ng cytoplasm, their outli nes are
i n d i st i n ct. I n the cytoplasm of some hepatocytes Mallory bodies (also cal led al
coh o l i c hya l i n ) can be see n , which are horseshoe-shaped strands o r peri n uclear
r i n gs of eos i noph i l i c , homoge n o u s , dense material . Less frequently Mallory bod ies
can be seen as rou n d ed structu res eccentrically located in the peri n uclear cyto
p lasm . Electron m icroscopica l l y Mal l o ry bodies are com posed largely of b u n d les of
1 4-15 n m t h i ck i ntermed iate fi l am e nts of the cytoskeleton . These bod i es can be
fou n d i n cel l s which appear i n tact, and also i n dyi n g cel ls with pyknotic n u clei . After
d i s i ntegration of the h epatocytes the Mallory bodies can be observed i n the extracel
l u lar space. The damaged hepatocytes and M a l l o ry bod ies are feq uently s u rrou nded
by small col l ecti o n s of i nflammatory cel l s , mai n ly neutrophilic leukocytes. The
changes in the parenchyma are acco m pa n i ed by a mesenchymal reaction. There i s an
i n crease in Ku pffer cel l s and grad u a l l y col l agen fi bers are laid down aro u n d the
central vei n s . Characteristically in the centri l o b u l a r zone i n d ividual hepatocytes are
s u rro u n ded and separated by co l lagen fibers (pericellular fibrosis), which can be
wel l demon strated with co n n ective tissue sta i n s .
1 96
Fig. 9 1 . L
1 98
93 . Hepatocellular carcinoma
(CARCI N O MA H EPATO CELLULARE)
H e m atoxyl i n -eos i n , o rce i n
H e patoce l l u l a r carci noma i s by far the most com m o n pri mary mal ignant tumor of
the l iver. D i etary components (aflatoxi n B ) , besides ci rrhos i s and chronic hepatitis B
and C v i ral i nfection play an i m portant role i n its pathogenesis.
Gross Findings. There may be a s i ngle, large, 5 .0 to 20 cm in diamete r, c i r
cu mscribed mass, o r scattered nod u l es s u ggestive of m u lticentric orig i n . The l atter
i s com mo n l y seen in ci rrhotic l ivers . More seldom the tumor i s vol u m i nous and
i nfi ltrates the l iver parenchyma without sharp borders. On cut s u rface the tumor is
soft, gray to yel low o r gree n i s h , depe n d i n g o n its capabi l ity to p roduce b i le .
Microscopic Findings. Hepatoce l l u lar carc i n omas may be wel l-d ifferentiated or u n
d i fferentiated (anapl astic) . T h e cel l s o f well-differentiated tumors resem b l e hepato
cytes , are po lygon a l , t h e i r abu ndant cytoplasm is b ri ghtly eosi noph i l ic . The cyto
p lasm may conta i n b i l e pigment, l i pid vacuoles and occasional Mallory bod ies. The
t u m o r cel l n uclei are ro u nded, variable in size, shape and ti nctorial properties. Dif
ferentiated hepatoce l l u lar carc i n omas most often have a trabecular arch itect u re . The
t u m o r cel l s are o rgan ized in i rreg u l ar plates, one cel l o r m u lt i p l e cel l s thick, however
they do not fo rm l o b u l es . Between the plates of t u m o r cel l s there are s i n u soids l i ned
by flat e ndothel ial cel ls . The stroma is sparse, portal spaces o r b i l e d ucts are not
see n . I n freq uently a pseudoglandular patte rn can be encou ntered, when the tumor
cel ls are form i n g struct u res rem i n i scent of i rreg u l ar glands. A rare type of hepatocel
l u l a r carci noma i s com p osed of cel l s with a clear cytoplasm, also cal led hyperneph
roid carcinoma. The cytop lasm of these cel l s is swo l l e n and water-clear because of
the i r abu n dant glycogen and l i p i d content. The cel l s of undifferentiated hepatomas
are h ighly variable i n size and shape; thei r n uclei are large, hyperc h romatic, have
scant basoph i l ic cytoplasm, b izarre, gigantic m u lti n u cl eated tumor cel l s and abnor
mal mitoses are freq uent. The t u m o r cel l s fo rm gro u ps of variable shape and size.
The cel ls of some h epatoce l l u lar carci n omas are positive for the S h i kata reaction
(orce i n sta i n for hepatitis B s u rface antige n ) .
200
202
204
Fig. 95. G
glomeru l u s ; T
tubule; I
i ntersti t i u m .
206
208
210
212
214
Fig. 100. G
t u b u l e s ; A artery; V vei n ;
L y - lymphocytic i nf i ltrate.
-
21 6
Fig. 101A. T
tumor; P
Fig. 102A. K
218
1 0 3 . Seminoma
H e m atoxyl i n -eos i n
S e m i n oma i s a mal ignant t u m o r that ari ses from germ cel l s . The tumor i s very
rarely seen before p u be rty, it occu rs most often i n you n g ad u lts and midd le-aged
men .
Gross Findings. The size of the t u m o r varies between 0 . 5 to 1 0 cm i n d i amete r. Cut
s u rface s hows a l o b u l ated, b u l g i n g , tan to wh ite soft mass. Larger tumors freq u ently
have gray to yel low areas of necrosis and p u rp l e foci of hemo rrhage.
Microscopic Findings. S e m i'nomas characte ristically have large, ro u n d o r polyhedral
cel l s loosely arranged in sheets and cords. The t u m o r cel l s resem b l e spermatocytes
and are fai rly u n i fo r m . Their n u clei are large, rou n d , vesicular and have a fine
c h romati n network with one o r two conspicuous, dark n ucleo l i . M itoses are in
freq uent. The tumor cel ls have a fi nely foamy cytoplasm which conta i n s m i n ute vac
u o l e s . Best's carm i n e sta i n for glycogen reveals b ri ght red i ntracytoplasmic gran u les
at the s ite of the vacuoles. G lycogen has been d issolved d u ri n g fixation of the tissue.
The n ests of tumor cel l s are enclosed by th i n wal l s of stroma, from which delicate
septa of co n n ective tissue s u bd i v i de the tumor i nto s m a l l e r o r larger lobules. The
stroma i s vascu lar and shows a characteristic lymphocytic i nf i ltrate, p resu mably as
an i m m u n e response of t he host to the tu mor. An abu ndant lymp hocytic i nfi lt rate is
generally s u ggestive of a m o re favo rab l e p rognosi s . Someti mes the sem i noma is
accompan i ed by an e m b ryonal carcinoma, wh ich i n d icates a poor prognosis.
220
Fig. 103. T
tumor c e l l s ; 5
Ly
222
224
Fig. 1058. L
1 06. Pregnancy
(G RAV I D I TAS)
H e m atoxyl i n -eo s i n
D u r i n g the m en strual cycle the endometri u m i s i n a state of special preparation
for the reception of the fert i l ized egg. After i m pl antation f u rther changes s u pport
the n utrition and p rotection of the grow i n g e m b ryo . If the fal lopian tube i s narrowed
or obstructed by chron i c i nflammation or scarring, the fe rt i l ized ovu m can not reach
the uteri n e cavity. I n such i n stances the e m b ryo wi l l attach and grow o utside the
ute r u s , most often in the fal lopian tube (tu bal p regnancy) . I n such a case the ex
trauterine p regnancy may l ead to tubal r u pt u re and l i fe-th reate n i n g hemo rrhage .
Microscopic Findings. The age of early gestation can be estab l i s hed by the charac
teri stics of the endometri u m . I n the first month of p regnancy the endometri u m be
comes the decid ua, in which a m o re s u perficial compact layer with narrower glands
and a deeper spongy layer with e n larged and saccu l ated endometrial glands is noted.
The glan d u lar epithel i u m i s vacu o l ated , i n d icat i n g i ncreased secretory activity. The
stromal cel l s of the decidua are en larged , polyhed ral , tightly packed resem b l i n g a
pavement. The decid ual cel l s have spherical n u clei and ample fai ntly eosi noph i l ic
cytop lasm which i s rich i n glycoge n . The stroma is vascular and n u m erou s d i lated
b lood vessels can be see n . Afte r the second month of p regnancy the glands grad u a l ly
d i sappear and by the end of the third month the placenta has developed . At this
stage chorionic vi l l i are p resent which have a loose stroma and are rich in cap i l laries.
The chorionic v i l l i are covered by two cel l laye rs. Basally i s a row of cuboidal Lan
ghans cells, and on the s u rface are the m u lt i n u c leated giant cel l s (syncytial cells)
which have a b rightly eos i n o p h i l i c cytoplasm. The chori o n i c vi l l i a re bathed i n a sea
of maternal e ryth rocytes.
I n tubal p regnancy the fal lopian tube is d i stended , its t h i n wal l s a re stretched and
its l u men is f i l led with b lood and chorionic vi l l i .
226
Ny
1 0 7. Hydatidiform mole
(MOlA H YDAT I DOSA)
H e m atoxyl i n -eo s i n
The hydatid iform mole is characterized by edemato u s , ves i c u l a r chorionic vi l l i .
The fetu s d ies i n early p regnancy and the abno rmal vi l l i grow faster than a normal
p regnancy, thus rapi d ly en larg i n g the ute r u s . This p rocess i s accom panied by a pro
l iferative trophoblast from w h i c h , in a small percentage of cases, cho riocarci noma
may arise.
Gross Findings. The uterine cavity conta i n s characte ristic grape- l i ke cystic struc
t u res which range from a few mm to as large as 3.0 cm in diameter.
Microscopic Findings. The key features are marked stromal edema of vi l l i and
trophoblastic p ro l i fe ratio n . The chorionic vi l l i are markedly e n l a rged and swo l l e n ,
the i r stroma is extraord i na r i ly l oose, d u e t o edema a n d central l i q uefactio n . I n the
v i l l i the b lood vessels are ten u ou s , do not conta i n blood; many vi l l i are avascular.
There i s a c i rcu mferential proliferation of trophoblast o n the s u rface of the vi l l i . I n
the p ro l i fe rat i n g cel l popu lation the cuboidal cytotrophoblast and m u lt i n u cleated
syncytiotrophoblast can be see n . The trophoblast is i rregu larly p ro l iferati ng, some
times fo r m i n g buds or cel l col u m n s without s u pportive co n nective tissue. Due to
the rapid swe l l i ng of the stroma d egen e rative changes (vac u o l ization) can be seen
in the trophob last. On the giant v i l l i the trophoblast i s atten u ated and may be foca l ly
n ecroti c. Based on morphologic and cytogenetic evidence many consider a
hydati d iform mole to be a true neoplasm s i nce the shape, size and ti ncto rial charac
teristics of the trophoblast are q u ite variable and DNA ploidy analysis reveals its
a n e u p l o idy.
228
Fig. 107. 5
squamous epithel i u m ; E
eros i o n ; I
230
232
234
cyst space ; P
H
s
236
238
Fig. 1 12. C
cysts; M
apoc ri n e metaplasia; E
gland u lar t i s s u e ; I
fibrous stroma.
1 1 3. Fibroadenoma of breast
( FI BROADEN OMA MAMMAE)
H e m atoxyl i n-eos i n
Fib roadenoma i s the most com mo n ben ign t u m o r of the female b reast and occurs
in you n g women between 20 and 30 years of age . Its pathogenesis i s related to
hormonal alterations.
Gross Findings. The t u m o r is 0.4 to 3 .0 cm i n d i ameter, f i r m , encaps u l ated , sharply
demarcated and freely movab l e i n the b reast . On cut s u rface the tumor is bu lging,
pearl-wh ite and has a whorled appearance with tiny tan to yel low foci .
Microscopic Findings. S i m u ltaneous prolife ration of connective tissue and glandu
lar epithelium is seen i n the t u m o r . The gro u n d s u bstance consists of loose fibrous
tissue with s p i n d l e-s haped f i b roblasts. With i n this con n ective tissue there are gro u ps
of d ucts of variable shape and l ength . These d ucts are l i ned by a s i ngle or double
row of regu lar cuboidal o r polygonal cel l s which have spherical n uclei ; no mitotic
activity i s see n . A wel l-deve loped basement m e m b rane separates the epithel i u m
from t h e f i b ro u s stro m a . Some d ucts have a ro u n d o r oval l u men s u rrou nded by
concentrically arrange d , densely packed col lagen fibers (pericanalicular fibroadeno
maY. I n other i n stances the p ro l iferati n g stroma b u l ges i nto the d u ct, p u s h i n g its
epithelial l i n i n g i nto the l u me n . T h i s way the l u men becomes d i storted , s l it-l i ke,
sickle o r star-shaped . Some l u m i na co m p l etely d i sappear and are i nd i cated o n ly by
two closely apposed rows of epithel ial cel ls (intracanalicular fibroadenoma). Both his
tologic types of f i b roadenoma may be p resent i n vario u s p roportions wit h i n one
tumor.
240
242
Fig. 1 14. L
The d i sease occ u rs primarily i n older men ; its eti o logy i s u n ce rtai n . The changes
may affect a s i ngle bone (monostotic form) or may i nvolve several bones {polyostotic
form}. Osteosarcoma develops i n about 1 -2 % of widespread Paget's d i sease .
Gross Findings. The affected bones are stri ki ngly thickened; they are bent, de
formed and the i r s u rface i s rou g h , u neven . The bones are soft, sometimes they can
be cut with a k n ife . On cut s u rface the marrow cavity is narrowed , the bone marrow
is f i b ro u s , fi rm ; it s h ows red to b rown patches and small cavities of variable size.
Microscopic Findings. Paget's d i sease of bone i s characerized by ab normal bone
formation o n and off at i rreg u l a r i nterva l s . I n the active phase of the d i sease both
osteoclasts and osteoblasts show an i n c reased activity, i . e . i ntensive reso rption of
bone is associated with new bone format i o n . Osteoclasts are m u lt i n u cl eated large
cel l s with a m p l e acidop h i l ic cytoplas m and up to 1 00 n uclei . Osteoclasts break down
the bone i n deep grooves ( H owshi p's lac u n ae) on the trabec u l a r s u rface, and i n
newly fo rmed perforat i n g canal s . Osteoblasts l i ne the s u rface o f cortical and
trabecu l a r bone, they are oval o r elo ngate monon uclear cel l s . The cytoplasm of the
osteoblasts is i ntensely basoph i l i c and has a perin uclear clear zone (fo rmed by the
Golgi apparatus) . Osteoblasts p roduce osteoi d ( n o n - m i neral ized gro u nd s u bstance
of bone) which is deposited on the s u rface of the bone and adds to the th ickness of
the bone trabecu lae . I n Paget's d isease the lamellar bone shows a characteristic,
mosaic patte rn . The trabecu l ae are abnormally thick and com posed of chaoti cal ly
j u xtaposed , i rregu l a rly-shaped p i eces of lamellar bone demarcated by i rregular
cement l i ne s . The i ntert rabecu lar spaces a re f i l led with vascu lar, loose fi brou s con
nective tissue. The i nvolved bones b reak eas i ly becau se their hap hazard architecture
i s n ot capable of adeq uately f u l fi l l i n g the physical req u i rements.
244
1 1 6. Chondroma
H e m atoxy l i n -eos i n
246
Fig. 1 16. M
1 1 7. Osteosarcoma
H e m atoxyl i n -eo s i n
248
Fig. 1 17A. T
1 1 8. Nodular goiter
(ST R U MA N O DOSA COLLOI DES)
H e m atoxyl i n -eos i n
E n l a rgement of the thyroi d gland, fo r whatever reason, i s cal l ed a goite r. A goiter
may be n od u lar of d iffu se. The so-cal l ed co l lo i d goiter may be endemic (due to
iod i n e deficiency) or sporad ic, when the defect of one enzyme b l ocks hormone
synthesis. In either case, there i s an i n c reased p roduction of thyrotropin (thyroid
sti m u lati n g hormone, TS H ) d u e to negative feedback, cau s i n g hype rplasia of the
glan d u l a r parenchyma without effective thyroi d hormone p roduct i o n .
Gross Findings. T h e thyro i d gland shows d iffuse o r nod u la r e n largement. The
nod u l es are separated from each other by septa of co n nective tissue. The thyroid
gland i s f i rm and has a tan to b rown gelat i n o u s cut s u rface which sometimes is
mottled with f l u i d-fi l l ed cysts and b rown-red foci of hemo rrhage.
Microscopic Findings. Fol l icles (ac i n i ) of vary i n g sizes, but mostly greatly e n larged
ones, are see n . The aci n i are l i n ed by a s i ngle l ayer of flattened cuboidal epithelial
cel l s . N o cytologic atypi a i s see n . The l u men of the fo l l icles i s f i l l ed with a
homogeneo u s fai ntly eosi noph i l ic s u bstance (co l l o i d ) . The aci n i are separated by
t h i n septa of con nective tissue. Evidence of degenerative changes, such as recent
and o l d hemorrhage, hya l i n ized con n ective tissue or basoph i l ic foci of calcification
can be sporadically obse rved .
250
252
R
F
v
c
R
F
E
R
v
254
Fig. 120. F
Fig. 121A . M
normal thyroid gland ; C papi l lary carci noma.
Fig. 1218. A aci n i of tumor; P psammoma body.
-
256
258
1 2 3 . Postvaccinal encephalomyelitis
H e m atoxyl i n -eo s i n
Acute d i ssemi nated e ncep halomyelitis u s u al ly fol l ows v i ral i n fectio n s o r vacci na
tio n . It has been observed as a com p l i cation of measles, chicken pox, rubella or
m u mps, and after s m a l l pox vacci natio n , respectively. Pres umably the vi rus promotes
an auto i m m u n e p rocess which is d i rected agai n st the mye l i n sheath of nerves.
Gross Findings. The re i s a m i ld con gestion of the lepto m e n i n x and swe l l i n g of the
b ra i n d u e to edema.
Microscopic Findings. The lepto m en i nx i s i nfiltrated by Iymphocytes and plasma
ce l l s . In the gray and wh ite matter of the b ra i n the small b lood vessels are conspicu
o u sly d i l ated . Pri mari ly in the wh ite matter aro u n d the small vei n s there are small
foci of edema a n d inflammatory infiltrates of lymp hocytes and plasma cel l s . In these
i n flam mato ry foci the myelin sheaths have been d i s i ntegrat i n g and the l i p i d contai n
ing debris i s removed by macrop hages which have a foamy cytoplasm (gitter cel ls) .
I n the demye l i n ized areas the axo ns s u rvive for a t i m e , m icrogl ial cel l s and o l i goden
d rocytes cl u ster aro u n d them (reactive gl iosis) . With Woelcke's sta i n the mye l i n ated
wh ite m atter appears b l u e to b l ac k whereas the demye l i nated areas appear as
perivasc u l a r pale gray r i n gs with i n d i sti nct borders.
260
Fig. 123. V
s m a l l vei n s ; I
b ra i n tissue.
262
Fig. 124. L
leptomen i nx ; A
b ra i n tissue; E
L
A
E
1 25 . Meni ngioma
( M E N I N G EO MA)
H e m atoxyl i n-eosi n
M e n i ngioma i s a benign t u m o r of the arac h n o i d cove r i n g the b ra i n and spi nal
co rd . The tumor a ri ses from the m e n i ngothe l i a l cel l s of the arach noid vi l l i which are
mesenchymal cel l s capable of p rod u c i n g col lagen fi bers. Meni ngiomas occ u r in m id
d le-aged and elderly person s , more often in wom e n . About 1 5 % of i ntracranial
t u m o rs are m e n i ngiomas.
Gross Findings. The encaps u l ated t u m o rs measu re 0 . 5 to 5 . 0 cm are spherica l , occa
s i o n a l ly l o b u l ated or nod u lar; they cause a dep ressi o n on the adjacent b rai n tissue.
Men i ngiomas are q u ite f i rm and con ta i n calcifications which on cutt i n g with a kn ife
feel gritty and crac k l e .
Microscopic Findings. T h e tu mors p resent a wide spect r u m depe n d i n g on t h e i r
cytological and a rchitect u ral characteristics. Where t h e m e n i ngothelial cel l s pre
d o m i nate (meningotheliomatous meningioma), the t u m o r cells are densely packed and
form cel l n ests separated by trabec u lae of co n n ective tissue. The m e n i ngothelial
cel l s are oval o r s p i n d l e shaped, thei r n uclei are spheroidal and have a delicate
c h romat i n n etwo rk. The cytoplasm i s s l ightly eos i noph i l i c , the cel l borders are o ften
poorly defi ned. Freq uently the t u m o r cel l s are concentrica l l y a rranged and form
crescent-s haped nests or whorls. I n the center of these cel l conglomerates occasion
ally there are small concentrical ly l a m i n ated calcosphe rites, psammoma bodies,
which are strongly basop h i l i c . Psam moma bodies are the calcified remnants of de
generated t u m o r cel l s . Tu mors particu larly rich in psam moma bodies are cal led
psammomatous meningiomas. I n some t u m o rs the cel l s are elongate, s p i n d l e-shaped ,
para l l e l a rranged and form wavy bands ( fibroblastic or fibrous meningiomas) . A rare
type of t u m o r is markedly vascu la r and shows prolife ration of e ndothelial cel l s (an
giomatous meningioma).
264
Fig. 125. 5
stroma; T
nests of t u mor ce l l s ; P
1 26. Astrocytoma
H e m atoxy l i n-eosi n , g l i a stai n
Astrocytoma i s a g l i o ma com posed of wel l-d i ffe rentiated astrocytes and is a rela
tively freq uent b rai n t u m o r . It occu rs mai n ly in the cerebral hemispheres of ad u lts.
Gross Findings. The t u m o r is poorly defi ned and i nfiltrates the neighboring brain
tiss u e . On cut s u rface it i s firm, gray to wh ite and s hows smaller o r larger foci of
cystic dege n e ratio n .
Microscopic Findings. The n o rmal b ra i n tissue i s repl aced b y ste l l ate cel l s resembl
ing astrocyte s . The tumor cel l s have spherical , dark n u clei . Various types of as
trocytoma a re recogn ized : the cel l s of fibrillary astrocytomas are characterized by
abu ndant n e u roglial f i b r i l s . The tumor cel l s have spider-leg- l i ke cytoplasmic proces
ses wh ich form an i ntricate f i b r i l l a ry n etwo rk that can be visual ized with glial stai n s .
T h e cel l s of protoplasmic astrocytomas a r e p l u m per, polygo nal and do n o t have
n e u roglial f i b r i l s . These cel l s a re attached to each other by shorte r cytoplasm ic p ro
cesses. Microscopic foci of pseudocystic degen e ratio n can also be seen ( m i crocysts) .
266
Fig. 126. A
ast rocytes ; C
m i c rocyst; G
neu roglial fi b r i l s ; E
blood vessels.
1 2 7. Neuroblastoma
H e m atoxy l i n-eos i n
268
Fig. 127. N
n e u roblasts ; M
m i toses ; R
rosettes.
1 2 8. G l ioblastoma m ultiforme
H e m atoxyl i n-eosi n
This i s one of the most aggressive malignant t u m o rs of the central nervou s system .
It most freq uently occu rs i n 40 to 50-year-ol d men . I n typical cases it affects the
frontal lobe of the cereb ral h e m i sp heres.
Gross Findings. The t u m o r appears as a ci rcu mscri bed soft mass situated i m
mediately u n der the cereb ral co rtex. The t u m o r shows an extraord i narily vari egated
cut s u rface. The moist, fleshy white t u m o r tissue is mottled with geographic areas
of tan , clay-l i ke d ry n ecros i s , p u rp l e or rust-col o red foci of hemorrhage, and smaller
o r larger cystic space s .
Microscopic Findings. The t u m o r is conspicuously cel l u lar, i t s cel l s a r e u n u s ually
variable in s hape, size and sta i n i ng p ro pe rties. The ce l l s can be spherical , polygonal ,
oval and elongated , s p i n d l e-s haped (pleomorphism). Li kewise the ce l l n u clei sig
n ificantly vary in shape and i n thei r c h romat i n content. B izarre, m u ltin ucl eated
t u m o r giant cel l s with a wide seam of eosi noph i l ic cytoplasm are freq uently see n .
Abnormal m u ltipolar m i toses can a l s o b e observed . I n some areas t h e t u m o r cel l s
rese m b l e matu re astrocytes . T h e cel l u lar neoplasm contai ns foci o f hemorrhage and
necrosis, with t u m o r cel l s fo r m i n g pal i sades aro u n d necrotic centers . The stroma is
h i gh ly vascu lar. A characteristic fi n d i n g wit h i n and adjacent to the tumor is the pro
liferation of en dothel ial cel l s i n the capi l l aries which significantly na rrows their
l u me n . Some bl ood vessels are occl uded by t h ro m b i .
270
Fig. 128A . N
1 2 9. Schwannoma
( N E U RO LEMM OMA)
H e m atoxyl i n -eos i n
N e u rolemmoma i s a benign t u m o r of peripheral nerves and nerve roots which
originates from the Schwa n n cel l s . Most freq uently it ari ses from b ranches of sen
sory n e rves o n the flexor s u rface of extrem ities, the n eck or the med i asti n u m .
Gross Findings. T h e t u m o r i s 0 . 5 t o 6 . 0 c m , encaps u l ated a n d has a lobu lated ar
ch itectu re . I ts soft s u b stance i s tan to gray, someti mes glassy and transparent. On
cut s u rface it is friable with scattered smaller cysts.
Microscopic Findings. Two types of t u m o rs can be d i st i n g u i shed . Antony type A
schwan n omas have a fascic u l a r arch itect u re , thei r elongated , s p i n d l e cel l s fo rm com
pact b u nd le s . The long, ci gar-shaped n u clei have rou n ded ends and show a loose
ch romatin n etwo rk. The n uc l e i of the t u m o r cel l s are l i ned up in rows paral l e l l i n g
t h e l o n g axis of t h e cel l s , creat i n g a pattern o f a picket fence. T h e rows o f dark b l u e
n uclei are periodically alternat i n g w i t h b a n d s o f eosi noph i l i c fibri l lar cytoplasmic
p rocesses . The fascicles of cel ls are occasionally i nterlacing and fo rm bands of wavy
and whorl i n g con f i g u rati o n . There are also homogeneous eosi noph i l ic hya l i n ized
areas i n the t u m o r . Antoni type B schwa n nomas have a n etwo rk- l i ke ( reti cu lar) his
tologic arch itecture; they have a loose, myxoi d gro u nd s u bstance in which cel l s of
varia b l e (spherica l , polygo n a l , ste l l ate) shape are scattered o r arranged i n a s p i ral
pattern . Macrophages with a foamy cytoplas m can be seen in small gro u p s . I n the
stroma there are small cysts f i l l ed with ace l l u lar eos i n o p h i l i c f l u i d .
272
APPEN D I X
I MM U N O H I STOCH EM I STRY
276
Fig. I(a) F i b rosarcoma. Strongly positive reaction ( b rown precipitate) for vimentin
i n cytoplasm of t u m o r cells (Vp) .
Fig. I(b) Leiomyosarcoma. Positive reaction ( b rown preci pitate) for smooth m u scle act i n
i n cytoplasm of t u m o r cells (Ap) .
Vp
Vp
Ap
278
, '"
.,
'" -.
..
s
.. ,
280
Fig. /l1(a) Positive reacti o n ( b rown precipitate) with anti bodies to keratin i n
cytoplasm o f tumor cel l s (C) .
Fig. /l1(b) Postive reaction (brown p recipitate) for prostate-specific antigen (PSA) i n cytop lasm
of tumor ce l l s (P) .
'.
. .'
.*
.
i'
.'-'
- .
"
0
c
282
Fig. IV(a) Positive reaction ( b rown precip itate) w i t h pan-B cel l marker
in the cytoplasm of the majority of tumor cel ls (B).
Fig. I V(b) Positive reaction (dark b l u e precip itate) with pan-T cell marker on the su rface
of the majo rity of tumor cel l s (T).
284
Fig. V(a) Positive reaction ( b rown p reci pitate) for estrogen receptor prote i n
i n n uclei of majority o f t u m o r cel l s (Oe) .
Fig. V(b) Positive reaction ( b rown precipitate) for progesterone receptor prote i n in n uclei
of majority of tumor cel l s (Pr).
Oe
Pr
B i bl iography
I ndex
Abscess,
cerebral 56
p u l monary 56
Actinomycos i s ,
cervicofacial 58
Adenocarci noma,
of b reast 88
of colon 84
of prostate 224, 280,
of thyro i d , pap i l lary 256
Adenoid cystic carci noma 1 72
Adenoma
of ad renal co rtex 258
of sal ivary glands,
pleomorph i c 1 04
Ad renal cortex,
adenoma of 258
Alco h o l i c hepatitis 1 96
Amelob lastoma, of jaw 1 68
Amyloidosis
of k i d ney 18
Aorta
atherosclerosis of 1 22
cystic med ial necrosis 1 24
Appendicitis
acute 1 84
Astrocytoma 266
Atherosclerosi s ,
aortic 1 22
Atrophy
of testis 36
Bone
chondroma of 246
Paget's d isease of 244
B ra i n
abscess 5 6
encephalomye l itis, postvacci nal 260
i n farct 42
l i q uefactive n ecrosi s of 42
neoplasia of,
astrocytoma 266
g l i o bl astoma m u ltiforme 270
Tay-Sachs-Schaffer d i sease 22
B reast
adenocarc i noma of 88, 284
estrogen and p rogesterone
receptors 284
fi broadenoma of 240
fib rocystic d i sease of 238
B ronchoge n i c carc i n oma, small cell 1 42
B roncho p n e u m o n i a 1 34
B u e rger's d i s ease 1 26
c
Can d i d iasis
of esophagus 66
Carc i noma
adenocarc i noma of p rostate 224, 280
b ro n c h io loalveolar, of l u n g 1 44
e m b ryonal cel l , of testi s 1 22
smal l cel l , of l u n g 1 42
squamous cel l
o f l u n g 80
of uteri n e cervix 232
of p rostate 224, 280
renal cell 2 1 6
o f s k i n , basal cell 82
transitional cel l ,
of u ri nary bladder 2 1 8
287
Degen e ratio n ,
fatty, o f l iver 1 6
vac u o lar, o f kid ney 1 4
D iabetes m e l l itus,
glomeru loscl e rosis i n 2 1 0
288
Edema, l u ngs 50
E m b ryonal carci noma
of testis 222
Emp hysema, l u ngs 32
Encephalomye l it i s
postvacc i n al 260
Endocard i u m
f i b roelastosis o f 120
Endometri u m
hyperplasia 46
1 86
E p u l i s 70
Eso p hagitis
cand idal 66
F
Fat necrosis 68
Fatty
degeneration of l iver 1 6
i nfi ltration o f myocard i u m 1 1 4
Fibrinous
pericard itis 54
p n e u m o n i a 1 32
F i b roadenoma of b reast 240
F i b rocystic di sease i n b reast 238
F i b roel astosis, endocard ial 1 20
Fi b rosarcoma 276
Foreign body g ra n u loma 68
G
Gastritis
c h ro n i c 1 74
G i ant cel l g ra n u loma of o ral cavity,
peri pheral 70
G l ioblastoma m u ltiforme 270
Glomeru loneph ritis
acute poststreptococcal 204
membranopro l i ferative 206
G lomeru losclerosis
d iabetic 21 0
Goiter
n o d u l a r 250
G ra n u lar cel l tumor 1 66
G ra n u loma
foreign body type 68
G ran u l omato u s thyroiditis 254
G ran u l osa cel l tu mor, of
ovary 236
Hemangioma,
cap i l lary 96
cave rnous 96
Hemosiderosis 26
Hepatiti s ,
acute viral 1 92
alcoholic 1 96
chro n i c 1 94
Hepatocel l u lar ca rci noma 200
H i stiocytosis
sinus, lymph node 1 46
Hodgki n ' s d i sease
lymph nodes i n 1 50
Hya l i n e membrane d i sease 1 38
Hydatidiform mole 228
Hyperplasia,
endometri u m 46
prostate 48
Hyperthyroidism 252
Hypokalemic n e p h ropathy 1 4
I n farct
of bra i n 42
of kid ney, anemic 38
of l u ng, hemorrhagic 40
of myocard i u m 1 1 6
Jaund ice
cholestatic 28
Kaposi's sarcoma 1 30
Keratosis
of o ral m ucosa 1 64
Kid n ey
i n amyloidosis 1 8
carci noma,
renal cel l 21 6
degeneration, vacuolar 1 4
en d-stage d i sease 214
i n farct of 38
polycystic d i sease 34
Wi l m s ' tumor 1 06
289
290
e m p hysema 32
i n farct, hemorrhagic 40
in resp i ratory d i stress synd rome
1 38
s i l i cosis 1 40
squamous cel l carci noma 80
tubercu losis 60
Lym phadenitis
tuberc u l o u s 62
Lym ph n ode
metastas i s to 96
s i n u s h i stiocytos i s 1 46
tubercu l o u s 62
Lym phoma
B cel l 282
Hodg k i n ' s 150
n o n - H odgki n ' s 1 52
T cel l 282
Necros i s
caseo u s
i n tubercu losis 6 0 , 62
fat 68
kid ney, anemic 38
l iver, cent rilobular 44
l i q u efactive b ra i n 42
l u ng, h emo rrhagic 40
Neph rosclerosis
benign 202
N e u ri lemmoma 275
N e u rob lasto ma 268
Nevu s , pigmented 30
N i e mann-Pick d i sease 20
N i pple
Paget d i sease of 242
Medial
cystic n ecrosis of ao rta 1 24
Melanocyte, nevus 30
Melanoma
mal ignant 1 08, 278
Meni ngioma 264
M e n i ngitis
s u p p u rative 262
Metastasis
lymphatic 90
M i k u l i cz d i sease 1 62
M ixed tu m o r , paroti d gland 1 04
Mole, hydati d ifo rm 228
M o l l uscum contagios u m 76
Mycobacte ri u m tu bercu losis 64
Myeloma
m u lt i p l e 1 54
Myocard itis
i n rheu matic h eart d isease 1 1 8
Myocard i u m
fatty i nfi ltration 1 1 4
fibros i s 1 1 4
i n farction o f 1 1 6
Myxo ma 94
Odontoge n i c cyst 1 60
Osteosarcoma 248
Ovary
cystadenocarcinoma of 86
cystad enoma
m uc i n o u s 234
sero u s 234
gra n u losa cel l tumor of 236
thecoma 236
Paget d i sease
of bone 244
of n i pple 242
Pap i l lary carci noma
of bladder 21 8
of thyro i d 256
Papi l loma
of l arynx, squamous cel l 78
Parotid gland
cytomegalovi ral i n fection 1 56
pleomorp h i c adenoma 1 04
Sarcoma
Kapos i 's 1 30
osteogen i c 248
Schwan noma 272
Sem i n oma 220
S i al adenitis, chronic 1 58
Signet ring cel l carci noma of stomach 1 78
S i l i cosi s , p u l monary 1 40
S i n u s h i stiocytosis of lymph node 1 46
Skin
basal cel l carci noma of 82
hemangioma 96
mol l u scum contagiosu m 76
verruca vu l garis 74
Squamous cell carc i noma
of l u n g 80
of uterine cervix 232
Squamous cell papi l loma,
of l a rynx 78
Stomach
adenocarci noma, m u c i n o u s of 1 80
early 1 78
s ignet r i n g cell type 1 78
peptic u lcer, c h ro n i c of 1 76
Salivary gland
adenoid cysti c carci noma 1 72
chronic i nflammation 1 58
cytomegalovi ral i n fection 1 56
Iymphoepith elial lesion of, benign 1 62
in M i k u l icz's d i sease 1 62
pleomorp h i c adenoma ( m ixed tu mor)
of 1 04
in Sjogren's synd rome 1 62
Warthi n's t u m o r of 1 70
Tay-Sachs-Schaffer d i sease 22
Testis
atrophy 36
e m b ryonal carci noma of 222
sem i noma of 220
Theco ma, of ovary 236
Th ro m boangitis o b l iterans 1 26
Thro m bosis 52
Thyroid gland
carc i noma, pap i l lary 256
hyperfu n ction of 252
n od u lar goiter 250
Thyroiditis
DeQu e rva i n ' s gra n u l omatou s 254
Transitional cell carci noma
of u ri nary b ladder 2 1 8
Tuberc u l osis
kid ney 212
291
lymphad e n i t i s 62
m i l iary 60
of lymph n odes 62
Tumor
markers i n 276, 278, 280, 282
T u m o r cel l s
i n pleu ral f l u i d 92
U l ce rative colitis 1 88
U ri nary bladder
tran sitional cel l carci noma of
papi l l a ry 21 8
Ute r i n e cervix
carc i noma of 232
erosion 230
l eiomyoma of 98
292