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Morfopatologie Combinat PDF
Morfopatologie Combinat PDF
CUPRINS
I. PARTEA I: MORFOPATOLOGIE GENERALĂ
1. LEZIUNI CELULARE ŞI EXTRACELULARE. REACŢII DE ADAPTARE 1
2. INFLAMAŢIA 35
3. TUMORILE 78
II. PARTEA II: MORFOPATOLOGIA SPECIALĂ
1. PATOLOGIA RINICHIULUI ŞI CĂILOR URINARE 124
2. APARATUL GENITAL FEMININ 154
3. PATOLOGIA GLANDEI MAMARE 179
4. TULBURĂRI HEMODINAMICE 189
5. PATOLOGIA CARDIO‐VASCULARĂ 205
6. PATOLOGIA APARATULUI RESPIRATOR 261
7. PATOLOGIA TRACTULUI GASTRO‐INTESTINAL 285
8. PATOLOGIA FICATULUI, CĂILOR BILIARE ŞI A PANCREASULUI EXOCRINE 311
9. PATOLOGIA SISTEMULUI HEMOPOIETIC ŞI LIMFOID 335
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.1. DEFINIğIE
5.2. TERMINOLOGIE
79
Parenchimul tumoral, atât în tumorile benigne cât úi în cele maligne,
provine dintr-o singură celulă, fiind deci monoclonal. Prin tehnici de biologie
moleculară s-a demonstrate că majoritatea neoplasmelor sunt monoclonale. În
cursul proliferării, celula stem poate prezenta o diferenĠiere divergentă, ceea ce
va duce la apariĠia tumorilor mixte. Un exemplu este tumora mixtă a glandelor
salivare, caracterizată prin componente epiteliale dispersate într-o stromă
fibromixoidă, uneori cu formarea de insule de cartilaj sau os. Aceste elemente
celulare se consideră că ar deriva din celulele epiteliale sau / úi mioepiteliale din
glandele salivare (de aici denumirea de adenom pleomorf). ùi fibroadenomul de
glandă mamară este considerat o tumoră mixtă deoarece conĠine un amestec de
elemente ductale proliferate (adenom) incluse într-un Ġesut fibros lax (fibrom).
Deúi studii recente au demonstrat monoclonalitatea numai pentru componenta
fibroblastică (neoplazică), proliferarea elementelor epiteliale fiind indusă de
aceasta, termenul de fibroadenom este menĠinut. Tumorile mixte cu aspecte
multiple nu trebuie confundate cu un teratom care este alcătuit din celule mature
sau imature sau Ġesuturi reprezentative din mai mult decât un strat germinal,
uneori chiar din toate cele trei foiĠe embrionare. Teratoamele au originea în
celulele totipotente prezente în gonade (ovar, testicul) úi uneori sechestrate în
resturile embrionare la nivelul liniei mediane a corpului. Aceste celule
totipotente au capacitatea de a se diferenĠia în orice tip de celulă prezentă în
corp, astfel că în structura tumorii pot apare concomitent plaje de os, epitelii,
muúchi, Ġesut adipos, nervos, etc. Când toate componentele sunt bine
diferenĠiate, tumora este denumită teratom chistic matur úi are evoluĠie benignă.
Când componentele sunt imature, tumora este denumită teratom imatur, malign.
În tabelul nr. 5.1 sunt prezentate denumirile specifice pentru cele mai
frecvente forme de neoplasme.
Există denumiri mai puĠin raĠionale, ca limfom, mezoteliom, melanom,
seminom, care sunt însă intrate în terminologia curentă medicală. În afara
neoplasmelor există o serie de denumiri care ar putea să determine confuzie.
Astfel, hamartomul este o malformaĠie localizată, constituită din componente
tisulare locale, dar dispuse într-o arhitectură dezorganizată. Hamartomul hepatic
este alcătuit din hepatocite mature, vase sanguine úi posibil canale biliare
dispuse dezordonat. Hamartomul pulmonar este un nodul format din insule de
cartilaj, bronúii úi vase sanguine. Altă denumire confuză este cea de coristom,
care semnifică tot o anomalie congenitală ne-neoplazică. Constă într-un rest
heterotopic de celule mature (ex. noduli de parenchim pancreatic matur incluúi
în submucoasa stomacului, duodenului sau intestinului subĠire).
Terminologia neoplasmelor are o importanĠă deosebită deoarece are
conotaĠii clinice úi histogenetice, încadrând tumora ca evoluĠie, respectiv
origine.
80
Tabel nr. 5.1 : Nomenclatura tumorilor
Tumori formate dintr-un singur
Benigne Maligne
tip celular
1. tumori epiteliale Papilom
Ɣepiteliu scuamos multistratificat Carcinom scuamocelular
81
Tabel nr. 5.1. –continuare
5.3.4. Metastazarea
Termenul „metastază” semnifică dezvoltarea de implante tumorale
secundare, la distanĠă úi în discontinuitate faĠă de tumora primară. Această
capacitate este proprie tumorilor maligne. Invazivitatea permite cancerelor să
penetreze în cavităĠile celomice ale organismului (pleură, peritoneu, pericard),
în vasele sanguine úi limfatice. Cu puĠine excepĠii, toate cancerele dau
metastaze. ExcepĠii majore sunt tumorile sistemului nervos central úi
carcinomul bazocelular al pielii. Ambele au caracter foarte invaziv local, dar
dau foarte rar metastaze. La cealaltă extremă sunt sarcoamele osteogene care în
momentul diagnosticului au deja metastaze pulmonare. Aproximativ 30% din
bolnavii nou diagnosticaĠi prezintă metastaze în momentul diagnosticului, la
care se adaugă 20% care au metastaze oculte. În general, cu cât tumora primară
este mai mare în dimensiuni úi mai anaplazică, cu atât este mai probabilă
prezenĠa metastazelor. Există úi excepĠii. De exemplu, cancere foarte mici
85
(oculte) tiroidiene, pulmonare se pot manifesta iniĠial prin metastaze, în timp ce
unele cancere sunt voluminoase, dar nu au metastaze.
Neoplasmele maligne metastazează pe trei căi principale: prin cavităĠi
seroase sau de-a lungul unor suprafeĠe, pe cale limfatică úi pe cale hematogenă.
1. Diseminarea prin cavităĠile seroase
Carcinomul de colon poate invada úi penetra peretele intestinal úi să se
reimplanteze la distanĠă în cavitatea peritoneală. Similar, cancerele bronho-
pulmonare pot disemina în cavitatea pleurală, iar cancerele ovariene la nivelul
seroasei peritoneale. Uneori mucusul secretat de carcinoamele ovariene sau
intestinale umple cavitatea peritoneală sub forma unei mase gelatinoase numită
„pseudomixoma peritoneii”. Neoplasmele SNC precum meduloblastomul sau
ependimomul pot penetra ventriculii cerebrali, iar celulele neoplazice pot fi
vehiculate prin LCR determinând implante pe suprafeĠele meningeale ale
encefalului sau măduvei rahidiene.
2. Diseminarea limfatică
Este caracteristică pentru carcinoame, sarcoamele preferând calea
hematogenă. Deoarece însă există numeroase conexiuni între sistemul limfatic
úi cel sanguin, în final toate formele de cancer diseminează pe ambele căi.
Modul de afectare a ganglionului limfatic depinde de localizarea neoplasmului
primar úi de căile limfatice de drenaj ale sale. Astfel, carcinomul de glandă
mamară localizat în cadranul supero-extern, va afecta iniĠial ganglionii axilari,
în timp ce în carcinomul localizat în cadranul intern, vor fi afectaĠi ganglionii
toracici de-a lungul arterelor mamare interne. Ulterior vor fi afectaĠi ganglionii
subclaviculari úi supraclaviculari. Carcinoamele bronhogene din căile aeriene
principale metastazează iniĠial în ganglionii limfatici bronúici regionali, apoi
perihilari, traheobronúici úi mediastinali. În unele cazuri, celulele maligne pot
doar traversa canalele limfatice dintr-un grup ganglionar trecând la ganglionii
din staĠia următoare (metastaze prin „omisiune” sau „pe sărite”). În final
celulele canceroase din vasele limfatice vor ajunge în compartimentul vascular
pe calea ductului toracic.
În general, limfadenopatia din vecinătatea unui neoplasm primar malign
este suspectată de metastază, dar nu întotdeauna este astfel. Deoarece produsele
necrotice ale tumorii úi antigenele tumorale pot iniĠia modificări reactive în
ganglionii limfatici, precum hiperplazia foliculilor limfoizi úi acumularea
histiocitelor în sinusurile subcapsulare sau medulare (histiocitoză sinusală), o
limfadenopatie în raport cu o tumoră malignă primară poate fi de mai multe
cauze:
- diseminarea úi proliferarea metastatică a celulelor neoplazice;
- hiperplazia foliculară;
- hiperplazia ariei paracorticale T;
- histiocitoza sinusală.
3. Diseminarea hematogenă
Diseminarea hematogenă este cea mai gravă consecinĠă a unui
86
cancer. Celulele canceroase invadează frecvent capilarele úi venulele, în timp ce
arteriolele úi arterele, având perete mai gros, sunt mai rezistente. Odată cu
invazia venoasă, celulele neoplazice vor urma sensul fluxului venos care
drenează Ġesutul în care este localizată tumora. Vena portă drenează fluxul
venos de la organele abdominale (stomac, intestin, splină) în ficat. Venele cave
drenează sângele în pulmon. Astfel, neoplasmele maligne primare gastro-
intestinale vor metastaza în ficat, iar prin intermediul sistemului venos cav,
tumorile localizate în aria de drenaj vor metastaza în pulmon. Prin poziĠia sa în
circulaĠia sanguină, pulmonul poate trimite în circulaĠia arterială celulele
canceroase, determinând metastaze în orice organ sau Ġesut care acceptă
proliferarea lor (ficat, os, creier, piele, etc.). Cancerele care apar în vecinătatea
coloanei vertebrale pot să embolizeze prin plexul paravertebral, producând
frecvent metastaze vertebrale în carcinoamele de tiroidă úi de prostată. Unele
carcinoame au tendinĠa de a invada venele. Carcinomul renal invadează vena
renală unde creúte ca o masă tumorală ce se poate extinde până în vena cavă
inferioară úi chiar la nivelul cordului drept. Carcinoamele hepatice, prin venele
suprahepatice se pot extinde până în vena cavă inferioară. Trebuie remarcat că
proliferările intravenoase nu sunt însoĠite de diseminare hematogenă.
Metastazele viscerale au aspect nodular multiplu, sunt alb-slăninoase,
fără nici o reacĠie din partea Ġesutului în care se dezvoltă. Pulmonul, ficatul úi
osul sunt cele mai frecvente localizări ale metastazelor produse pe cale
hematogenă, urmând creierul, tegumentele úi glanda suprarenală. Apar rar
metastaze în rinichi, organele cavitare úi în Ġesuturile moi.
Histologic, metastaza poate fi similară tumorii primare, poate avea un
grad de diferenĠiere mai redus sau, în cazul glandei tiroide, poate fi identică cu
parenchimul normal.
În sinteză, caracterele generale ale tumorilor benigne úi maligne sunt
prezentate în tabelul nr. 5.2.
5.4. CARCINOGENEZA
88
Studiul modificărilor genetice din celulele tumorale a arătat o bază
moleculară fermă pentru conceptul de carcinogeneză, care se desfăúoară în mai
multe etape (multisecvenĠial):
Celula normală
reparare
Lezarea ADN
expansiune clonală
heterogenitate citogenetică
neoplasm malign
91
- celulele transformate sunt perene. Celulele normale se pot multiplica
printr-un număr limitat de diviziuni celulare, apoi mor. Celulele
transformate sunt capabile de a fi menĠinute în cultură perioade
îndelungate, chiar decenii;
92
Fig. 5.2. Progresia tumorală úi heterogenitatea celulară (după Stevens 1995)
97
- Sindroame paraneoplazice. Aceste sindroame reprezintă un complex
de simptome care apar la bolnavi cu tumori maligne úi care nu pot fi
explicate prin extinderea locală sau la distanĠă a neoplasmului sau prin
producerea de hormoni. În tabelul nr. 5.3 sunt prezentate aceste
sindroame).
Tabel nr. 5.3.: Sindroame paraneoplazice (după Cotran úi col. 1999)
Sindrom clinic Tip de cancer Mecanism cauzal
Sindroame endocrinectopice
Ɣ sdr. Cushing
c. bronho-pulmonar cu ACTH sau substanĠe
celule mici, c. de pancreas, similare
tumori neurale
Ɣ hipersecreĠie de ADH c. bronho-pulmonar cu hormon antidiuretic
celule mici, tumori sau natriuretic atrial
intracraniene
Ɣ hipercalcemie c. scuamo-celular bronho-
pulmonar, c. glandă
mamară, c. renal,
leucemie/limfom cu celule
T adulte, c. ovarian,
fibrosarcom, alte sarcoame
Ɣ hipoglicemie c. hepatocelular. insulină sau substanĠe
carcinoid bronúic, similare
c. pancreas, c. gastric.
Ɣsdr. Carcinoid c. renal, hemangiom serotonină,
cerebelos,c.hepatocelular bradikinină, histamină
Ɣ policitemie eritropoietină
Sindroame cu tulburări
nervoase úi musculare
Ɣ miastenie c. bronhogenic imunologic
Ɣ tulburări SNC úi periferic c. glandă mamară
Tulburări osteo-articulare úi
ale Ġesuturilor moi
Ɣ osteoartropatie hipertrofică c. bronhogenic necunoscut
cu mărirea degetelor (beĠe de
toboúar)
Tulburări vasculare úi
hemoragice
Ɣ tromboză venoasă (fenomen c. pancreas produúi tumorali
Trousseau, tromboflebita c. bronhogenic (mucină) care
migratorie) alte tipuri de cancere activează coagularea
Ɣ endocardită trombotică ne- cancer în stadii avansate hipercoagulabilitate
bacteriană
Ɣ anemie c. tiroidiene necunoscut
Tulburări dermatologice
Ɣ acantozis nigricans c. gastric, c. bronho- Imunologic? SecreĠie
pulmonar, c. endometrial de factor de creútere
epidermală?
98
Ɣ dermatomiozită b. bronhogenic, Imunologic?
c. glandă mamară
Alte sindroame Antigene tumorale,
Ɣ sdr. nefrotic Cancere variate complexe imune
c. – carcinom
5.6. GRADAREA ùI STADIALIZAREA TUMORILOR
99
5.7.1. Papilomul
Papilomul este o tumoră epitelială benignă care formează, macroscopic
úi microscopic, proiecĠii digitiforme de epiteliu susĠinut de axe conjunctive. Are
originea în epiteliile multistratificate sau unistratificate, denumirea completă
fiind de papilom scuamocelular sau intraductal. Proliferarea epitelială este
însoĠită de o dezvoltare corespunzătoare a Ġesutului conjunctiv de susĠinere úi a
vaselor sanguine care formează proiecĠiile digitiforme.
Exemple tipice sunt papiloamele de la nivel cutanat, ale esofagului,
laringelui, exocolului, numite papiloame scuamocelulare. În canalele
galactofore se pot dezvolta papiloame intraductale, constituite din proiecĠii
papilare acoperite de epiteliu unistratificat.
Ɣ Veruca vulgaris (denumită popular, neg) este o formaĠiune exofitică, fermă,
cu bază largă de implantare. Poate fi observată la orice vârstă, dar este mai
frecventă la copii úi adolescenĠi. Cauza este virusul papilomului uman (HPV)
care se transmite prin contact între persoane sau prin autoinoculare. EvoluĠia lor
este autolimitată, cu regresie spontană în 6 luni – 2 ani.
Ɣ Condiloma acuminatum (veruci venerice) se dezvoltă la nivelul penisului,
organelor genitale externe feminine, perineului úi rectului. Sunt tumori exofitice
de câĠiva centimetri în diametru, cu aspect conopidiform úi bază largă de
implantare. Histologic constă în epiteliu pluristratificat identic cu cel al pielii,
dispus pe axe conjunctivo-vasculare, cu aspect papilar. Astfel, se identifică
stratul bazal, separat de axul conjunctivo-vascular prin membrana bazală. Acest
strat este acoperit de mai multe rânduri de celule poligonale cu numeroase
tonofibrile (stratul spinos). Când acesta este foarte bine dezvoltat, se utilizează
termenul de acantoză. Urmează straturile granulos úi keratinizat, care dacă sunt
mai groase decât normal, papilomul este considerat hipergranulos úi
hiperkeratinizat. Unele celule din stratul spinos pot prezenta un halou clar
perinuclear cu o condensare periferică a citoplasmei úi nuclei mai mari,
neregulaĠi. Acestea sunt celule infectate viral, denumite koilocite. Uneori aceste
celule conĠin în citoplasmă granule de keratohialin condensat úi agregate
eozinofile de keratină ca rezultat al efectului citopatic viral.
Papilomul se poate dezvolta în canalele galactofore, epiteliul proliferat
fiind dispus pe axe conjunctivo-vasculare subĠiri, cu caracter digitiform care se
dezvoltă în lumenul ductului (papilom intraductal).
O altă localizare relativ frecventă este tractul urinar, unde tumora este
denumită papilom urotelial sau tranziĠional.
5.7.2. Adenomul
Adenoamele derivă din epiteliul ductelor (canale), al glandelor acinoase
úi al mucoaselor. Astfel, ele apar din proliferarea epiteliului unor glande
exocrine, endocrine sau a parenchimului unor organe ca ficatul sau rinichiul. În
general, adenomul nu prezintă comunicarea iniĠială cu ductul sau acinul de
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origine. Adenoamele au forme diferite în raport cu forma anatomică a organului
în care s-au dezvoltat.
Adenoamele dezvoltate în glande endocrine, exocrine sau organe
parenchimatoase au o formă nodulară, cu capsulă úi sunt incluse în parenchimul
respectiv.
Microscopic, au o structură asemănătoare cu a glandelor de origine,
deci sunt bine diferenĠiate, păstrând úi activitatea funcĠională secretorie.
Exemplul este al adenoamelor glandelor endocrine care au o importanĠă
particulară deoarece sunt capabile de a genera sindroame de hipersecreĠie
endocrină: hipertiroidism dacă se dezvoltă în glanda tiroidă, hiperparatiroidism
primar (glande paratiroide), sindrom Cushing sau sindrom Conn când se
dezvoltă în corticosuprarenală, feocromocitom când sunt localizate în
medulosuprarenală.
Adenoamele glandelor endocrine alcătuite din mai multe tipuri celulare
(ex. adenohipofiza úi insulele pancreatice) pot fi constituite dintr-un tip celular
predominat care secretă un hormon particular produs în mod normal de acel tip
de celulă. De exemplu, adenoamele insulelor pancreatice pot fi alcătuite
predominant din celule ȕ úi secretă insulină, din celule Į úi secretă glucagon,
din celule į cu secreĠie de somatostatin, celule G care secretă gastrină (sindrom
Zollinger-Ellison).
În toate aceste localizări, adenoamele apar ca noduli rotunzi sau
lobulaĠi, solizi, înconjuraĠi de o capsulă fibroasă rezultată prin atrofia de
compresiune a Ġesutului glandular din jur úi din condensarea stromei lor.
Adenoamele variază în dimensiuni de la cele microscopice, la cele cu peste 10
centimetri diametru.
Similar, adenoamele glandelor exocrine sunt frecvente úi apar mai ales
în glandele salivare, glanda mamară, glanda prostată.
Unul din cele mai frecvente adenoame este fibroadenomul glandei
mamare care este considerat o tumoră mixtă alcătuită din componentă epitelială
úi conjunctivă. Prin tehnici moleculare s-a demonstrat că numai componenta
conjunctivă (stroma) este monoclonală, deci neoplazică. Fibroadenomul are
două varietăĠi structurale:
- peri-canalicular, atunci când Ġesutul conjunctiv este dispus în jurul
elementelor epiteliale care rămân deschise;
- intra-canalicular, când componenta conjunctivă proliferează mai mult úi
comprimă lumenul canalelor dând impresia generală de prezenĠă a
Ġesutului conjunctiv în interiorul elementelor epiteliale. Uneori ambele
forme histologice se găsesc în acelaúi fibroadenom.
Când celulele adenomului au capacitate de secreĠie exocrină, apare o
cavitate plină cu secreĠie seroasă sau mucoasă úi tapetată de celulele proliferate,
tumora fiind denumită chistadenom. Localizarea cea mai frecventă este ovarul,
unde după proliferarea epiteliului celomic de înveliú, celulele produc o secreĠie
abundentă mucoasă sau seroasă cu formarea unui spaĠiu chistic mare –
chistadenom simplu. Când epiteliul care delimitează spaĠiul chistic formează
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proiecĠii intrachistice, tumora este denumită chistadenom papilifer. Aceste
tumori au evoluĠie benignă, dar pentru forma papilară există un risc de
transformare malignă în chistadenocarcinom papilar. Chistadenoame papilare
pot apare, dar rar, în pancreas, rinichi.
Adenoamele dezvoltate la nivelul mucoaselor, în organe cavitare, sunt
denumite polipi adenomatoúi. Aceútia trebuie diferenĠiaĠi de pseudopolipi,
proliferări cu caracter reactiv, ne-neoplazic, care se pot prezenta macroscopic cu
aspect similar (ex. polipii inflamatori). Polipii pot fi unici sau multipli
(polipoză), sesili (cu bază de implantare scurtă úi largă) sau pediculaĠi (cu bază
de implantare lungă úi subĠire). Din punct de vedere histologic, polipii
adenomatoúi pot fi de trei tipuri:
1. Polipul de tip tubular este constituit dintr-o proliferare de tubi
glandulari, deseori ramificaĠi. Epiteliul glandular poate prezenta
diferite grade de displazie. Macroscopic are aspect rotund, neted,
pedunculat, cu un diametru de sub 1 cm.
2. Polipul vilos este denumit astfel datorită proiecĠiilor digitiforme
constituite din axe conjunctivo-vasculare acoperite de epiteliu de
suprafaĠă. Macroscopic are un aspect vegetant, este sesil, cu un
diametru de peste 2 cm.
3. Polipul adeno-vilos (tubulo-vilos) reuneúte aspectele descrise la
primele două entităĠi.
Localizarea cea mai importantă a polipilor adenomatoúi este tractul
gastro-intestinal. La acest nivel, leziunile displazice ale epiteliului glandular pot
reprezenta un teren favorizant pentru dezvoltarea carcinomului. Când sunt
multipli, riscul de transformare malignă creúte. Astfel, în polipoza familială,
care se caracterizează printr-un număr foarte mare de polipi, riscul este de
100%, indicaĠia chirurgicală de extirpare a segmentului de colon afectat fiind
absolută.
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5.9.3. Tumori úi leziuni tumor-like ale Ġesutului fibros
Proliferările Ġesutului fibros sunt heterogene. Există leziuni reactive, ne-
tumorale precum fasciita nodulară, în timp ce fibromatozele se caracterizează
printr-o proliferare locală persistentă difuză. Acestea pot fi rezolvate
chirurgical.
Proliferările pseudosarcomatoase reactive nu sunt leziuni neoplazice.
Ele se constituie ca răspuns la anumiĠi factori locali, ca factorii fizici sau
ischemia.
Clinic, evoluează rapid, iar histologic sunt constituite din celule
mezenchimale care pot mima sarcoamele datorită hipercelularităĠii, numărului
de mitoze úi aspectului primitiv al celulelor. Reprezentativ pentru această
categorie de leziuni este fasciita nodulară.
Fasciita nodulară are ca sinonime fasciita infiltrativă sau
pseudosarcomatoasă, care e cea mai frecventă formă dintre pseudosarcoamele
reactive. Apare la persoanele adulte, în ordinea frecvenĠei pe antebraĠ sau pe
torace úi spate. Bolnavii prezintă tipic, în câteva săptămâni, o masă rapid
proliferativă, solitară úi dureroasă, care în 10-15% din cazuri, apare după un
traumatism local.
Leziunile de fasciită nodulară apar în dermul profund, subcutanat sau în
muúchi. Macroscopic, fasciita nodulară are câĠiva centimetri în diametrul cel
mai mare, cu o configuraĠie nodulară, cu marginile puĠin definite. Histologic,
este bogat celularizată, alcătuită din fibroblaste cu aspect imatur, dispuse la
întâmplare (simulând proliferarea celulară din cultură) sau fascicule scurte
neregulate. Celulele variază ca dimensiuni úi forme (fuziforme úi stelate), au
nucleoli evidenĠi úi numeroase mitoze. Frecvent, stroma este mixoidă úi conĠine
limfocite úi eritrocite extravazate. Tratamentul de elecĠie este excizia
chirurgicală, după care nu recidivează.
Ɣ Tumori fibrohistiocitare
Tumorile fibrohistiocitare sunt alcătuite dintr-un amestec de fibroblaste
úi celule cu aspect de histiocit încărcat cu lipide. Ca úi tumorile fibroblastice,
grupul de tumori fibrohistiocitare prezintă o mare variaĠie a tablourilor
histologice úi a evoluĠiei biologice, de la leziuni benigne, la sarcoame de grad
mare. Alte leziuni au o poziĠie intermediară, cu recidivă locală, dar fără a
determina metastaze.
Ɣ Histiocitomul fibros (dermatofibrom)
Histiocitomul fibros este o tumoră benignă care se prezintă ca un nodul
mobil, bine definit în derm sau în Ġesutul subcutanat. Majoritatea cazurilor apare
la adulĠi. Tabloul histologic poate fi variabil, dar este format din celule
fuziforme amestecate cu celule histiocitare cu citoplasma spumoasă, bogată în
lipide. Marginile leziunii sunt infiltrative, dar nu are caracter invaziv. Nu
recidivează după excizia locală.
Ɣ Dermatofibromul protuberans
Acest neoplasm ocupă o poziĠie intermediară între tumorile
fibrohistiocitare benigne úi histiocitomul fibros malign. Macroscopic, se
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prezintă ca o masă nodulară cu dezvoltare lentă în derm úi Ġesutul celular
subcutanat. Majoritatea bolnavilor sunt adulĠi, cu tumori cu caracter infiltrativ
ce recidivează frecvent după excizia locală. În cazuri excepĠionale, pot să se
producă metastaze. Microscopic, dermatofibromul protuberans este alcătuit din
fibroblaste dispuse într-un tablou „storiform”, constituit din fascicule scurte ce
pleacă úi se termină în vecinătatea vaselor. Mitozele sunt rare, iar fibroblastele
prezintă o atipie redusă.
Ɣ Histiocitomul fibros malign
Histiocitomul fibros malign (HFM) constituie un grup heterogen de
tumori agresive ale Ġesuturilor moi, caracterizate printr-un pleomorfism
citologic cu celule bizare multinucleate, cu arhitectură „storiformă” úi un fond
alcătuit din stromă colagenă, cu elemente celulare inflamatorii úi macrofage
spumoase. Apar în musculatura extremităĠilor úi retroperitoneal.
Macroscopic, se prezintă ca mase alb-cenuúii, neîncapsulate, de 5-20
cm diametru. Microscopic, pot prezenta mai multe variante ca: „storiform”,
pleomorf, mixoid, inflamator, cu celule gigante úi angiomatoid.
Majoritatea variantelor de HFM sunt agresive úi dau metastaze cu o rată
de 30-50%.
Ɣ Fibromatozele
Fibromatozele sunt un grup de proliferări fibroblastice care se distinge
prin tendinĠa de dezvoltare infiltrativă asociată cu recidivă după excizia
chirurgicală. Astfel, aceste proliferări au o creútere invazivă locală dar, spre
deosebire de fibrosarcoame, nu metastazează.
Fibromatozele sunt divizate în două grupuri clinico-patologice majore:
fibromatozele superficiale úi profunde. Fibromatozele superficiale cuprind
entităĠi ca fibromatoza palmară (contractura Dupuytren), fibromatoza plantară
úi fibromatoza penisului (boala Peyronie), care apar în fascia superficială.
Deoarece aceste leziuni sunt constituite din mult colagen, ele produc deformări
sub formă de contractură a palmelor úi plantelor. Fibromatozele profunde
cuprind aúa-numitele tumori desmoide, ce apar în abdomen úi muúchii
trunchiului úi extremităĠilor. Comparate cu fibromatozele superficiale, cele
profunde sunt caracterizate printr-o tendinĠă mai mare de recidivă úi de
dezvoltare într-o manieră agresivă.
Aspectul fibromatozelor variază după localizare. Leziunile sunt
macroscopic constituite din structuri nodulare úi bandelete cu caracter infiltrativ,
fără margini evidente. Microscopic, fibromatozele sunt alcătuite din fibroblaste
cu caracter uniform úi cu producerea unei cantităĠi mari de fibre de colagen.
Ɣ Fibrosarcoamele
Fibrosarcoamele sunt neoplasme maligne, alcătuite din fibroblaste.
Majoritatea cazurilor apar la adulĠi în anumite localizări ca Ġesuturile profunde
ale coapsei, genunchiului úi trunchiului. Fibrosarcoamele nu prezintă aspecte
clinice specifice, care să permită diferenĠierea lor de celelalte tumori ale
Ġesuturilor moi. În general, fibrosarcoamele se dezvoltă lent, chiar pe o perioadă
de ani înainte de a fi diagnosticate. Ca úi celelalte sarcoame, fibrosarcoamele
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recidivează după excizie úi pot metastaza, mai ales pe cale hematogenă, în
pulmon.
Macroscopic, fibrosarcoamele sunt leziuni solitare, neîncapsulate, cu
caracter infiltrativ, cu margini slab definite, cu arii de hemoragii úi necroză.
Histologic, fibrosarcomul diferenĠiat este alcătuit din fascicule de fibroblaste cu
dispoziĠie variată. Fibroblastele din fascicule sunt dispuse într-un tablou ce
aminteúte „osul de hering”. Atipia nucleară úi indicele mitotic constituie
elemente de gradiere histologică a fibrosarcoamelor. Astfel, în fibrosarcoamele
de grad I, atipia nucleară úi indicele mitotic sunt reduse, în timp ce în gradul III
există un pleomorfism nuclear úi un număr mare de mitoze.
5.9.4. Tumori cu diferenĠiere musculară scheletică
Neoplasmele Ġesutului muscular sunt aproape toate maligne. Varianta
benignă, rabdomiom, este foarte rară úi apare la nivelul cordului.
Ɣ Rabdomiosarcomul
Rabdomiosarcoamele sunt cele mai frecvente sarcoame la copil úi
adolescent. Apar înainte de vârsta de 20 de ani. Aceste tumori se pot dezvolta în
orice regiune anatomică, dar cel mai frecvent se localizează la nivelul capului úi
gâtului sau tractului genitourinar, regiune cu o componentă musculară redusă în
mod normal. Aceste tumori apar în legătură cu muúchiul scheletic, numai la
extremităĠi.
Rabdomiosarcomul este subclasificat în următoarele variante:
embrionar, alveolar úi pleomorf. Rabdomioblastul apare în toate tipurile, fiind
elementul de diagnostic histologic. Rabdomioblastele pot fi rotunde sau
alungite, cu o citoplasmă abundentă, eozinofilă, granulară, bogată în filamente
groase úi subĠiri. Ultrastructural, rabdomioblastele conĠin sarcomere iar
imunohistochimic se colorează cu anticorpi la vimentină, actină, desmină úi
mioglobină.
Rabdomiosarcomul embrionar este cel mai frecvent tip, constituind
66% din rabdomiosarcoame. Acest tip cuprinde sarcomul botrioid úi variantele
cu celule fuziforme. Tumorile apar la copii sub vârsta de 10 ani, în cavitatea
nazală, orbită, urechea medie, prostată úi regiunea paratesticulară. Subtipul
sarcom botrioid se dezvoltă în organele cavitare, delimitate de mucoasă, precum
nazofaringele, canalul biliar comun, vezica urinară úi vaginul. Macroscopic,
sarcomul botrioid are un aspect de ciorchine de strugure care proemină în
cavitatea organului (ex. vezica urinară, vaginul). Microscopic, celulele tumorale
mimează celulele musculare scheletice în variate stadii ale embriogenezei.
Tumorile sunt alcătuite din mase de celule rotunde úi fuziforme maligne, într-o
stromă mixoidă. Rabdomioblastele pot prezenta striaĠii transversale la coloraĠii
speciale.
Rabdomiosarcomul alveolar apare cel mai frecvent la adolescent în
musculatura profundă a extremităĠilor. Microscopic, tumora prezintă o reĠea de
septuri fibroase ce delimitează celulele tumorale dispuse în cuiburi sau agregate.
Celulele tumorale din centrul acestor agregate degenerează astfel că formează
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un spaĠiu liber asemănător cu alveolele pulmonare (de aici denumirea de
rabdomiosarcom alveolar). Studiile citogenetice au arătat că această variantă are
aberaĠia cromozomială t(2;13) sau t(1;13).
Rabdomiosarcomul pleomorf este caracterizat prin numeroase celule
mari, uneori multinucleate, cu nuclei bizari úi citoplasma eozinofilă. Această
variantă este rară úi apare în Ġesuturile moi profunde la adulĠi.
Rabdomiosarcoamele sunt neoplasme agresive, totuúi variantele
histologice influenĠează supravieĠuirea. Subtipul botrioid are prognosticul cel
mai bun, urmat de varianta embrionar, pleomorf úi alveolar.
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angiomatoză. Majoritatea leziunilor sunt superficiale în regiunile capului úi
gâtului, dar pot să se dezvolte în viscere, mai ales în ficat.
Hemangioamele sunt foarte frecvente mai ales la copil, constituind 7%
din toate tumorile benigne. Majoritatea hemangioamelor la copil - fie capilare,
fie cavernoase - sunt prezente la naútere úi se măresc odată cu dezvoltarea
copilului. Totuúi, multe din leziunile capilare regresează spontan, înainte de
pubertate. Există mai multe variante histologice úi clinice.
Ɣ Hemangiomul capilar, grupul cel mai mare, este alcătuit din vase
sanguine înguste, ce seamănă cu capilarele cu pereĠi subĠiri, delimitaĠi de
endoteliu. Localizările frecvente sunt cutanate, subcutanate, la nivelul
mucoaselor cavităĠii orale úi buze úi la nivelul viscerelor astfel ca ficatul, splina
úi rinichii. Hemangiomul capilar tip „căpúună” (hemangioame juvenile), la
nivelul pielii la nou născut, este extrem de frecvent (1 la 200 de naúteri) úi poate
fi multiplu. Acest tip de hemangiom se dezvoltă rapid în primele luni, apoi
începe să scadă, astfel că regresează până la vârsta de 7 ani în 90% din cazuri.
Hemangioamele au dimensiuni variate, de la câĠiva milimetri până la
câĠiva centimetri, leziunile fiind roúii strălucitoare până la albastru, plane sau
uúor reliefate, acoperite de epiteliu intact. Uneori pot fi leziuni pediculate,
ataúate printr-un pedicul subĠire.
Histologic, hemangioamele sunt neîncapsulate, lobulate, ca agregate de
capilare cu pereĠi subĠiri, cu endoteliu turtit úi lumenul plin cu eritrocite; vasele
sunt legate între ele prin Ġesut conjunctiv. Lumenele pot fi nedesfăúurate, parĠial
sau complet trombozate cu trombi recenĠi sau în curs de organizare conjunctivă.
Ruperea vaselor determină microhemoragii, iar eritrocitele extravazate
determină apariĠia macrofagelor cu pigment de hemosiderină.
Ɣ Hemangiomul cavernos. Mai puĠin frecvent decât varietatea
capilară, hemangiomul cavernos este marcat de formarea de canale vasculare
largi, de forme variate, cu pereĠi subĠiri, delimitaĠi de un endoteliu turtit, pline
cu sânge. Aceste tumori sunt difuze, neîncapsulate úi frecvent afectează
structurile profunde.
Macroscopic, hemangiomul cavernos are un aspect buretos, roúu închis,
albăstrui, cu un diametru de 1-2 cm. Relativ rar apar forme gigante, ce afectează
arii subcutanate mari ale feĠei, extremităĠilor sau altor regiuni ale corpului.
Histologic, masa este net definită, neîncapsulată, iar spaĠii vasculare cavernoase
mari sunt parĠial sau complet pline cu sânge, separate prin stromă conjunctivă
subĠire. Pot să se producă tromboze intravasculare ce se pot calcifica.
În majoritatea cazurilor, hemangioamele au o semnificaĠie clinică
redusă, dar în localizare cerebrală pot produce simptoame de compresiune sau
ruptură. In boala von Hippel-Lindau, hemangioamele cavernoase apar în cerebel
sau trunchiul cerebral úi ochi, asociate cu leziuni angiomatoase similare în alte
localizări sau cu neoplasme chistice în pancreas úi ficat sau cu alte neoplasme
viscerale.
Ɣ Limfangiomul
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Limfangioamele sunt tumori benigne ale vaselor limfatice. Se observă
mai multe varietăĠi.
Limfangioamele (capilare) simple sunt mase alcătuite din vase limfatice
mici, care apar subcutanat în regiunea capului úi gâtului úi în axilă. Rar se
constată pe trunchi, în organele interne sau în Ġesutul conjunctiv din cavităĠile
abdominală sau toracică. Pe suprafeĠe ele sunt uúor reliefate sau uneori
pedunculate, de 1- cm diametru. Histologic, sunt alcătuite dintr-o reĠea de spaĠii
limfatice delimitate de endoteliu, conĠin limfă iar în stroma limfoidă se observă
aglomerări limfatice.
Limfagiom cavernos (higroma chistică). Sunt tumori benigne, alcătuite
din spaĠii limfatice, fiind similare cu hemangiomul cavernos. Frecvent apare la
copii laterocervical úi în axilă, mai rar retroperitoneal, ajungând la dimensiuni
de 15 cm diametru. Tumorile sunt constituite din spaĠii chistice foarte mari,
delimitate de celule endoteliale úi separate prin Ġesut conjunctiv, ce conĠin
agregate limfoide. Tumora nu prezintă capsulă úi de aceea îndepărtarea
chirurgicală poate fi dificilă.
Ɣ Tumora glomică (glomangiomul)
Tumora glomică este un neoplasm benign, frecvent manifestat clinic
prin durere. Este alcătuită din fibre musculare netede modificate din corpul
glomusului, o anastomoză arterio-venoasă specializată cu funcĠie în
termoreglare. Tumora glomică poate fi localizată oriunde în piele (sau Ġesuturile
moi úi uneori în tractul gastrointestinal), dar cel mai frecvent apare în porĠiunea
distală a degetelor, mai ales sub unghie. Excizia este tratamentul curativ.
Macroscopic, tumora glomică are dimensiuni mici (sub 1 cm), este
rotundă, roúu albastră, fermă, uneori cu focare de hemoragie recentă sub
unghie.
Histologic, tumora este alcătuită din două componente: canale vasculare
ramificate separate prin stromă de Ġesut conjunctiv ce conĠine al doilea
component – agregate, cuiburi úi insule de celule glomice specializate, dispuse
tipic în jurul vaselor. Celulele glomice sunt mici, uniforme, rotunde sau cubice,
cu citoplasmă puĠină, iar la ME au aspecte similare cu fibrele musculare netede.
Ɣ Tumori vasculare cu grad intermediar (grad scăzut de
malignitate)
Sarcomul Kaposi
Sarcomul Kaposi este o tumoră considerată rară până când a devenit o
problemă medicală la pacienĠii cu SIDA.
Patru forme clinice sunt astăzi considerate:
Sarcomul Kaposi cronic, aúa-numit clasic sau european, descris de
Kaposi în 1872, apare la bărbaĠii în vârstă din Europa de est sau Ġările din
vecinătatea Mării Mediterane. Această formă se manifestă úi în asociere cu
apariĠia unei a doua tumori maligne sau cu stări imune alterate, dar nu cu SIDA.
Clinic, sarcomul Kaposi debutează ca plăci cutanate roúii purpurii, apoi ca
noduli la nivelul extremităĠilor inferioare. Aceste formaĠiuni cresc lent, se extind
114
spre localizări proximale ale membrilor inferioare úi sunt persistente, cu o
evoluĠie cu recăderi úi remisiuni.
Sarcomul Kaposi limfadenopatic, aúa-numit african sau endemic, apare
mai ales la copii din tribul Bantu (aceeaúi distribuĠie geografică cu limfomul
Burkitt). Clinic, se manifestă cu limfadenopatie localizată sau generalizată, cu o
evoluĠie foarte agresivă. Leziunile cutanate sunt puĠine úi rare. AfecĠiunea are o
evoluĠie agresivă, cu implicarea ganglionilor limfatici úi a viscerelor.
Sarcomul Kaposi asociat cu transplantul apare post-operator după un
interval de câteva luni, până la câĠiva ani, la primitori de transplant care au fost
supuúi la imunoterapie în doze mari. Leziunile cutanate sunt localizate úi pot
regresa după întreruperea tratamentului imunosupresiv. Dacă leziunile au
afectat organele interne, pot constitui cauze de deces pentru bolnavii respectivi.
Sarcomul Kaposi asociat cu SIDA (epidemic) apare la aproximativ 25%
din bolnavii de SIDA sau chiar într-un procent mai mare, frecvent la bărbaĠi
homosexuali. Aproximativ 40% din bolnavii acestui grup de risc au dezvoltat
Sarcom Kaposi comparat cu numai 5% din toĠi bolnavii cu SIDA. Sarcomul
Kapsi asociat cu SIDA începe prin leziuni cutanate care se extind precoce la
ganglionii limfatici, intestin úi alte viscere. Majoritatea bolnavilor decedează
prin complicaĠii cu infecĠii oportuniste. Aproximativ o treime din bolnavii cu
sarcom Kaposi úi SIDA dezvoltă ulterior o a doua tumoră malignă, frecvent
limfom.
Macroscopic, leziunile cutanate au trei stadii de evoluĠie, fiind
identificate ca pete, plăci úi noduli.
Histologic, se observă o proliferare vasculară neregulată, cu lumene
similare unor fante delimitate de celule endoteliale ce se regăsesc úi între vase
sub forma unor fascicule amestecate în infiltratul inflamator format din
limfocite, plasmocite úi macrofage. In stadiul de placă úi nodul, predomină
fasciculele de celule fuziforme în care se pot identifica vasele similare cu
fantele. Aspectul caracteristic este fondul ce conĠine úiruri de eritrocite úi
picături de hialin, amestecate cu infiltratul inflamator. Mitozele sunt frecvente
ca úi globulele citoplasmatice rotunde, roz.
Patogenie
Fără o deplină certitudine, în prezent se consideră că tumora este
alcătuită din celule mezenchimale primitive sau endoteliale iar evoluĠia sa este
influenĠată de starea de imunitate a bolnavului. Se pare că există o asociere
virală, astfel că produsele HIV úi ale virusului herpetic tip 8 joacă un rol în
inducerea acestei tumori prin elaborarea locală de factori de creútere sau
citokine. Aceste substanĠe acĠionează prin mecanism paracrin sau autocrin,
producând proliferarea necontrolată a celulelor tumorale.
Ɣ Hemangioendoteliom
Termenul de hemangioendoteliom este utilizat pentru a desemna
neoplasme vasculare ce prezintă aspecte histologice úi evolutive intermediare
între hemangioamele benigne úi angiosarcomul anaplazic.
Ɣ Tumori maligne vasculare
115
Angiosarcoamele sunt neoplasme endoteliale maligne, cu structură
variată, de la tumori foarte diferenĠiate ce se aseamănă cu hemangioamele
(hemangiosarcom), la tumori a căror anaplazie le face dificil de diferenĠiat de
carcinoame sau melanoame.
Aceste tumori apar la ambele sexe, la adult, cu localizare în special la
nivelul pielii, Ġesuturilor moi, glandei mamară úi ficatului.
Angiosarcoamele hepatice sunt rare, dar constituie un aspect important
deoarece se asociază cu carcinogene distincte ca pesticidele arsenicale,
thorotrast (mediu de contrast radioactiv utilizat în radiologie) úi clorura de
polivinil (utilizată în industria maselor plastice).
Angiosarcoamele pot apare în ariile de limfedem cu durată de peste 10
ani, ca în cazurile de mastectomie pentru cancer de glandă mamară.
Macroscopic, angiosarcoamele cutanate pot apare iniĠial ca mici noduli
multipli, roúii, cu progresie la mase cărnoase mari de culoare palidă, alb-
cenuúiu. Marginile se opresc imperceptibil în structurile înconjurătoare. Centrul
tumorii este moale, cu prezenĠa de arii de necroză úi hemoragii.
Microscopic, în raport cu gradul de diferenĠiere ale acestei tumori pot fi
observate arii vasculare de dimensiuni variate, delimitate de celule endoteliale
anaplazice sau arii nediferenĠiate, cu celule atipice, fără formarea de vase.
Clinic, angiosarcoamele prezintă o evoluĠie malignă, cu invazie locală
úi metastaze la distanĠă.
Hemangiopericitomul
Derivat din pericite, celule normale dispuse la periferia capilarelor úi
venulelor, hemangiopericitomul este o tumoră rară, ce se localizează în orice
regiune anatomică, dar apare cel mai frecvent la nivelul extremităĠilor (mai ales
coapsă) úi în aria retroperitoneală.
Macroscopic, se prezintă ca o masă de 4 - 8 cm, nedureroasă, care se
măreúte lent. Microscopic, tumora este alcătuită din numeroase capilare
ramificate, înconjurate de mase úi cuiburi de celule fuziforme sau ovoide sau
chiar rotunde. In urma impregnaĠiei argentice se evidenĠiază că pericitele
proliferate sunt separate prin membrana bazală de celulele endoteliale.
După excizie, tumorile pot recidiva úi aproximativ 50% dau metastaze
în pulmon, ficat úi os.
Ɣ Sarcomul sinovial
Sarcomul sinovial reprezintă 10% din sarcoamele Ġesuturilor moi úi
apare la grupul de vârstă 20-40 de ani. Majoritatea se dezvoltă în vecinătatea
articulaĠiilor mari ale extremităĠilor, mai ales ale membrelor inferioare.
Deúi este denumit sarcom sinovial, totuúi nu apare din celulele
sinoviale, ci mai curând, derivă din celulele mezenchimale din jurul cavităĠilor
articulare uneori putând fi identificat în localizări fără articulaĠii. Rar, aceste
tumori apar în regiunea parafaringiană sau în peretele abdominal.
Microscopic, markerul histologic al sarcomului sinovial este morfologia
bifazică a celulelor tumorale, adică celule similare celulelor epiteliale, care
formează glande úi celule fuziforme. Celulele epiteliale sunt cubice sau
116
cilindrice úi formează glande sau cordoane solide. Celulele fuziforme sunt
dispuse în fascicule dens celularizate care înconjoară celulele epiteliale.
Majoritatea sarcoamelor sinoviale sunt monofazice, fie că sunt compuse numai
din celule fuziforme, fie din celule epiteliale. Leziunile alcătuite numai din
celule fuziforme sunt uúor confundate cu fibrosarcoamele.
Imunohistochimia este utilă în identificarea acestor tumori deoarece
celulele epitelioide úi fuziforme sunt pozitive pentru keratină úi antigenul de
membrană epitelială, diferenĠiind aceste tumori de alte sarcoame. În plus,
majoritatea sarcoamelor sinoviale prezintă o translocaĠie cromozomială
caracteristică t(x;18) úi gena fuzată (syT-ssx).
În sarcoamele sinoviale rata de supravieĠuire la 5 ani variază de la 25-
62% úi numai 11-30% supravieĠuiesc 10 ani. Locurile frecvente de metastazare
sunt ganglionii limfatici regionali, pulmonul úi scheletul.
Aceste tumori sunt localizate cel mai frecvent în sistemul osos, dar pot
apare úi în Ġesuturi moi extrascheletice. Diagnosticul tumorilor în general úi al
tumorilor osoase în special necesită o integrare a datelor clinice cu aspectul
radiologic, cu morfologia macroscopică úi microscopică pentru fiecare caz în
parte. În tabelul nr. 5.5 sunt prezentate cele mai frecvente tumori osoase.
118
5.11. TUMORILE MELANOCITELOR
Ɣ Lentigo
Termenul de lentigo se referă la o hiperplazie localizată (benignă) a
melanocitelor, care poate apare la orice vârstă.
Macroscopic, se prezintă ca macule ovale sau rotunde, brune, de 5-10
mm, dispuse la nivelul pielii úi mucoasei. Microscopic, aspectul histologic
esenĠial este hiperplazia melanocitară liniară din stratul bazal al epidermului,
care apare hiperpigmentat.
Ɣ Nevul nevocelular (nev pigmentat, molă)
Nevusul nevocelular se referă la orice neoplasm benign al
melanocitelor, fie congenital fie dobândit.
Aspectul clinic frecvent al nevilor nevocelulari dobândiĠi este de
macule sau papule, rotunde, brune, uniform pigmentate, sub 6 mm diametru, cu
margini bine definite. In tabelul de mai jos (Tabel nr. 5.6) se prezintă aspectele
clinico-histologice ale nevilor melanocitari mai frecvent întâlniĠi.
Nevii nevocelulari sunt iniĠial formaĠi din melanocite care s-au
transformat de la celule unice dendritice normale, amestecate printre
keratinocitele bazale, in celule ovale sau rotunde ce proliferează în agregate sau
“cuiburi” de-a lungul joncĠiunii dermo-epidermice. Nucleii celulelor nevice sunt
uniformi, cu contur rotund, cu nucleoli puĠin evidenĠiaĠi sau absenĠi, fără
activitate mitotică (nev joncĠional). Celulele nevice cu aceste caractere
proliferează în derm úi formează nevus compus. Uneori celulele nevice
joncĠionale regresează, astfel că nevul este constituit numai din componenta
dermică - nevus dermic.
Proliferarea progresivă a celulelor nevice de la joncĠiunea dermo-
epidermică în dermul subiacent este însoĠită de un proces de maturare al
celulelor. Astfel, celulele nevice superficiale, mai puĠin mature, sunt mai mari,
produc melanină, formează cuiburi, ajungând în părĠile profunde ca celule mai
mici, fără pigment sau cu pigment mai puĠin úi formând astfel cordoane
asemănătoare Ġesutului neuronal. Această metamorfoză se corelează cu
transformările enzimatice; astfel, celulele dendritice melanocitare din stratul
superficial conĠin tirozinază pentru fotosinteza melaninei, iar celulele profunde,
mai mici, dobândesc capacitatea de a dezvolta o activitate colinesterazică,
similară celor din Ġesutul neuronal. Această secvenĠă de maturare a celulelor
nevice are importanĠă în diagnostic, deoarece nevii fără maturare prezintă un
potenĠial de transformare în melanom malign.
119
Tabel nr. 5.6.: Forme de nevi melanocitari
Aspectele
SemnificaĠia
Tipul de nev Aspectele histopatologice citologice de
clinică
diagnostic
1. Nevus congenital Localizat în dermul Melanocite Prezente la naú-
profund úi subcutanat, în identice cu tere, variantele
jurul anexelor, a cele ale nevi- gigante au un risc
structurilor nervoase úi a lor dobândiĠi mare de
vaselor sanguine transformare în
melanom
2. Nevi dobândiĠi
Nevus joncĠional Cuiburi mici de Melanocite Risc de transfor-
melanocite la nivelul fără atipii mare
stratului bazal
Nevus intradermic Cuiburi mici de Fără risc de
melanocite numai în derm, transformare
în jurul anexelor úi vaselor -s -
120
Ɣ Nevii displazici
Clark úi col. (1978) au descris în detaliu caracteristicile leziunilor
denumite mole BK (abreviere după primele litere ale numelui familiilor
studiate) sau nevi displazici.
Macroscopic, nevii displazici apar ca macule cu centru uúor ridicat, mai
brun úi periferia plată, neregulată.
Histologic, nevii displazici sunt nevi compuúi cu arhitectură úi citologie
atipică Cuiburile de celule nevice din epiderm sunt alungite, cu fuzionări sau
coalescenĠe anormale intre cuiburi adiacente. Ca parte a acestui proces, celulele
nevice încep să înlocuiască stratul bazal normal de-a lungul joncĠiunii dermo-
epidermice, producând aúa numita hiperplazie lentiginoasă. Atipia citologică a
melanocitelor proliferate din nevul displazic constă din nuclei neregulaĠi,
angulari, úi hipercromatici. Aceste aspecte se asociază cu un infiltrat limfocitar
úi o fibroză particulară, liniară, ce înconjoară crestele epidermice afectate de
cuiburile nevice.
Date recente sugerează că unii nevi displazici sunt precursori ai
melanomului malign. Nevi displazici au fost identificaĠi la mulĠi membri ai
familiilor care dezvoltă melanom malign (sindrom melanotic ereditar). În aceste
cazuri, analizele genetice au demonstrat o transmitere automat dominantă a
defectelor genelor localizate pe 1p36, 9p21, 12g14. În privinĠa probabilităĠii
reale de a dezvolta melanom malign a persoanelor cu sindrom de nev displazic,
concluziile trase în urma cercetărilor, menĠionează o probabilitate de 56% la
vârsta de 59 de ani.
Nevii displazici au prezentat expresia unor antigene anormale pe
suprafaĠa celulelor, anomalii cariotipice úi o vulnerabilitate in vitro la efectele
mutagene ale luminii ultraviolete.
Ɣ Melanomul malign
Melanomul malign este un neoplasm malign relativ frecvent, cu
prognostic sever, evoluând spre deces.
Deúi cea mai mare parte a melanoamelor apare în piele, totuúi există úi
alte localizări precum mucoasele orale úi anogenitale, esofagul, meningele úi
mai ales globul ocular.
Aspectele clinice cele mai importante se identifică pe baza modificării
culorii unei leziuni pigmentate. Spre deosebire de nevii benigni (ne-displazici),
melanoamele prezintă o pigmentare variabilă: negru, brun, roúu, albastru închis
úi cenuúiu, iar marginile sunt neregulate. Se consideră semne clinice relevante
ale unui melanom următoarele aspecte:
R o mărire a unui nev existent anterior;
R prurit sau durere localizate la nivelul unui nev;
R apariĠia de noi leziuni pigmentare la adult;
R conturul neregulat al leziunilor pigmentate;
R variaĠia pigmentării;
R ulcerarea unui nev pre-existent.
121
Melanomul malign are posibilitatea dezvoltării în două modalităĠi:
radială (orizontală) úi verticală. IniĠial, proliferarea radială indică dezvoltarea
melanomului pe linie orizontală în epiderm úi straturile dermice superficiale
pentru o perioadă lungă de timp. Pe parcursul acestui stadiu, celulele tumorale
nu au capacitatea de a genera metastaze. Tipurile specifice fazei de dezvoltare
orizontală a melanomului sunt lentigo malign, melanomul cu extindere
superficială úi melanomul lentiginos acral / al mucoaselor.
În timp, tabloul de dezvoltare se modifică, aceasta devenind verticală.
Melanomul proliferează úi invadează straturile dermice mai profunde ca o masă
de celule atipice fără semn de maturare, ajungând în dermul reticular. Această
etapă este marcată clinic prin apariĠia unui nodul într-o maculă relativ plată
rezultată din proliferarea radială. Formarea nodului se corelează cu momentul
apariĠiei unei clone de celule tumorale cu potenĠial metastatic.
Celulele tumorale ale melanomului sunt considerabil mai mari decât
celulele nevice, au nuclei mari cu contur neregulat úi nucleoli mari, eozinofili.
Aceste celule nu formează cuiburi. Prognosticul úi răspunsul la tratament poate
fi apreciat printr-o serie de parametri ce sunt incluúi în buletinul de analiză
anatomo-patologică al piesei de exereză chirurgicală.
În evoluĠie, melanomul malign poate genera metastaze atât pe calea
limfatică, cat úi hematogenă, cu metastaze viscerale în ficat, pulmon, tract
digestiv, pancreas, creier.
5.12. TERATOAMELE
123
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