PART TWO
Diagnostic Cytology
Im p o rta n t prognostic m arkers in neurob lastom a are D N A
ploidy, N -m yc a m p lific atio n, TRK A levels, and chrom osom al
ab norm alities. N euroblasts are im m un ore ac tive fo r C H R, NSE,
and synaptophysin, am ong others, b u t unreactive fo r v im e n tin .
S trom a is im m un ore ac tive fo r v im e n tin and S-100 protein. Elec-
tro n m icroscopy shows neurosecretory granules, neural tubules,
and neu ro fila m en ts in the cytoplasm o f neoplastic cells. C yto-
genetics and m olec ular b io lo g y play an im p o rta n t ro le in the
d iffe re n tia l diagnosis in d o u b tfu l cases.
Key features of neuroblastoma
• N u m e ro u s s m a ll ro u n d n on co he sive cells;
• S om e cells fo rm in g th re e -d im e n s io n a l cong lom erates;
and
• S o m e tim e s H o m e r-W rig h t rosettes.
Tumors of the Retroperitoneum
In children, the retroperitoneum can be affected by num erous
benign and m alig nant tum ors and pseudotum oral lesions that
vary in frequency depending on the patient's age. They produce
diverse clinical m anifestations, such as anorexia, w eight loss, fever,
malaise, vom iting , abdom inal pain a nd /or distention, compres-
sion o f abdom inal structures, collateral venous, intestinal obstruc-
tion , and hem aturia o r u rina ry tract infection. These tum ors can
also produce Cushing's disease, precocious puberty, hypertension,
hypercalcemia, and hirsutism secondary to endocrine dysfunction
and systemic syndromes such as the tu m o ral lysis syndrome, Cush-
ing's syndrome, and choriocarcinom a syndrome. In newborns, the
m ost frequent tum ors o f the retroperitoneum are those o f renal
origin: polycystic o r m ulticystic kidneys and hydronephrosis, b u t
neuroblastom as, teratomas, and W ilm s ' tum ors can also be found.
The m ost frequent tum ors in infants are teratomas, ganglioneuro-
mas, mesoblastic nephrom as, and adrenal cortex adenomas, b u t
there are also neuroblastomas, W ilm s ' tum ors, and rhabdoid
tum ors. The m ost frequent tum ors in preschool children are ter-
atomas and lym phangiom as, b u t W ilm s ' tum ors, neuroblastomas,
adrenal carcinomas, and soft tissue sarcomas can also be observed.
In children older than 5 years, the m ost frequent tum ors are renal
angiom yolipom a, m alig nant teratom a, soft tissue sarcoma, W ilm s'
tum or, and lym p h om a.46,47 FN A guided under imageneology,
especially ultrasound, is an excellent diagnostic m ethod fo r retro-
peritoneal lesions; it reaches a sensitivity and specificity o f > 90%
and produces few com plications, b u t it is s till underused in chil-
dren. FN A o f these tum ors is described in each organ section.48
Differential Diagnosis
Round Cell Tumors
M ost pediatric m alignancies belong to this category. R ound cell
tu m o rs are m o rp h o lo g ic a lly very s im ila r to each o the r and are the
group presenting greater d ifficulties in d eterm ining the d ifferen-
tia l diagnosis in cytology and histopathology. C om p lem entary
techniques are essential fo r d e term in in g the precise diagno-
sis. C lin ica l appearances and lab o rato ry exam inations are also
very im p o rta n t. Som e im p o rta n t c lin ic a l-p a th o lo g ic features
include age group, gender preference, loc atio n, and biochem ical
a n d /o r hem atolog ic alterations. This u su ally helps determ ine a
p retty accurate diagnosis. The m a in ro u n d cell tu m o rs in c h il-
dren are neuroblastom as, em b ryonary rhabdom yosarcom as,
P N E T-E W S , n on -H od g kin's lym p h o m a , and W ilm s ' tum or.
R ound cell desm oplastic tu m o rs are less frequent. M an y m alig -
n an t neoplasm s, especially those affecting fetuses, newborns,
and infants, can show up to ta lly o r p a rtia lly as ro u n d cell tum ors,
w h ic h is explained b y the presence o f p rim itiv e blastem a, such as
in the hepatoblastom a, pancreatoblastom a, adrenal carcinom a,
and osteosarcom a, am ong others (Table 2 9.2).1,4,23,24,25
Fusocellular Tumors
Fusocellular tu m o rs represent a freq uent pediatric tu m o r cat-
egory, especially those o f soft tissues, and the m a jo rity o f them
are reactive processes o r benign neoplasm s (> 95% ). C ytologic
d iffe re n tia l diagnosis between reactive o r reparative fusocellular
lesions o f soft tissues, benign neoplasm s such as fib rom atosis
and neural neoplasm s, and low-grade sarcomas is often very d if-
ficult. C lin ica lly, the loc atio n, physical exa m in ation , and ages
o f patients are very im p o rta n t fo r m aking a good presum ptive
diagnosis. For example, fib rom atosis c o lli is typ ica lly observed
in the sternocleid om astoid area and in new borns, the anteced-
ent o f tra um a suggests a reparative o r inflam m atory-reactive
lesion. Fusocellular tu m o rs o f diverse nature fre q u e n tly show
a m yxo id strom a, w h ic h is o f little help in the d iffe re n tia l diag-
nosis. Typical benign ro u n d cell neoplasm s can show m ore o r
less extended areas o f fu s ifo rm cells such as the neuroblastom a,
e m b ryonary rhabdom yosarcom a, W ilm s ' tu m o r, and hepato-
blastom a. O n the o th e r hand, diverse m a lig n a n t neoplasm s
can show m uscular, cartilaginous, o r osseous m etaplasia, w h ic h
can lead to the erroneous diagnosis o f rhabdom yosarcom a,
chondrosarcom a, o r osteosarcom a, respectively, as occurs w ith
W ilm s ' tu m o r o r hepatoblastom a. T he clinical h is to ry and the
tu m o r lo c a tio n are o f p a ra m ou nt im p ortance in these cases.
H em ang iom a, w h ic h is one o f the m ost freq uent soft tissue
tu m o rs in children, is also am ong freq uent pediatric fusocel-
lu la r tum ors. C linically, hem angiom as occur at d iffe re n t loca-
tio n s and o fte n grow rapidly. A large n um b er o f hem angiom as
are fo rm e d by great b lo o d vessels fille d w ith b lood . FN A sam -
ples often show o n ly b lo o d and som etim es macrophages w ith
hem osiderine, fibroblasts, and fib rin w h e n th ey have suffered
hem orrhage and throm b osis.
M ore cellular hem angiom as,
w h ic h are also fre q ue nt in children, show FN A samples w ith
variable cellularity, som etim es significant, w ith isolated n o rm o -
typic spindle cells o r in sm all bundles w ith hem atic background.
S p indle cells are im m un ore ac tive fo r factor V III.35-37,40
Epithelia l/Epithelioid Tumors
E p ith e lia l/e p ith e lio id tu m o rs are an im p o rta n t group o f relatively
freq uent benign e p ith elial tu m o rs in children, such as c o llo id
fo llic u la r hyperplasia nodules o f the th y ro id gland, developm en-
tal cervical cysts such as branchial o r thyroglossal cyst, fib roa d -
enom a o f the breast, and cutaneous p ilo m a trixo m a . M a lig n a n t
e p ith elial tu m o rs are infre q u e n t in children. T he m ost freq uent
is p a p illa ry carcinom a o f th e th y ro id gland (15% o f m alig n an t
head and neck tu m o rs), o fte n expressed b y cervical lym p h node
metastasis and n o t b y the p rim a ry tu m o r. P ilo m a trix o m a is a fre-
quent cutaneous benign tu m o r in child ren th a t has characteris-
tic cytologic and histo lo g ic features and is m ore freq uent in boys
and in the head and neck. T he m ost freq uent ab d om in al m alig -
n an t e p ith elial tu m o rs is hepatoblastom a, w h ic h often shows
a variable cytom orp holog ic appearance th a t includes p rim itiv e
blastom atous hepatic epithelial, round , fu sifo rm , and m etaplastic
946
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