Tumori Epiteliali della Cute

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1 Tumori Epiteliali della Cute

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3 Cheratosi Seborroica v Lesioni molto comuni, spesso multiple, età adulto-avanzata, prevalentemente al tronco, estremità, testa/collo v Patogenesi: Mutazioni attivanti un recettore tirosinchinasico, il recettore del fattore di crescita fibroblastico di tipo 3 (Fibroblast Growth Factor Receptor-3, FGFR3) v Insorgenza improvvisa di un numero elevato può essere correlata a sindrome paraneoplastica (segno di Leser- Trélat), probabilmente dovuta alla stimolazione dei cheratinociti da parte del fattore di crescita TGFa prodotto dalle cellule tumorali, più comunemente carcinomi del tratto gastrointestinale.

4 Istopatologia Ipercheratosi, acantosi, papillomatosi Cisti cornee Proliferazione di elementi basaloidi Melanina (cheratinociti, melanociti, melanofagi) Se irritate o infiammate, presenza di foci vorticoidi di differenziazione squamosa

5 Cheratoacantoma Insorge su cute fotoesposta in età adulto-avanzata Crescita rapida (1-2 mesi) seguita da regressione spontanea (3-6 mesi) Nodulo cupoliforme con invaginazione centrale repleta di materiale corneo Diagnosi differenziale: CACS

6 Istopatologia Cratere centrale con materiale corneo Proliferazione di cheratinociti con atipia citologica Ascessi eosinofili intraepidermici alla periferia Fronte di crescita espansivo Infiltrato infiammatorio

7 Lesioni Precancerose dei Cheratinociti Cheratosi solare/attinica Cheilite solare/attinica Cheratosi da radiazioni Cheratosi arsenicale

8 Cheratosi solare /attinica v Si sviluppa in aree fotoesposte (volto, orecchie, cuoio capelluto, dorso mano, avambracci). Lesioni analoghe a livello delle labbra (cheilite attinica) v Lesioni spesso multiple eritemato-squamose, su cute secca, atrofica, soggetti con pelle chiara v Lesioni piane, rotonde o irregolari, o talora rilevate, ipercheratosiche, tipo corno cutaneo o verruciformi, diametro <1 cm

9 Cheratosi solare /attinica v Possono rimanere stabili per molti anni. v Nel 10-20% dei casi, se non trattate, evolvono verso un CACS v Eziopatogenesi: Esposizione cumulativa alle radiazioni ultraviolette induce progressive alterazioni nel DNA dei cheratinociti

10 Istopatologia v Atipia cellulare degli strati inferiori dell epidermide associata a iperplasia delle cellule basali o atrofia dell epidermide. v Cellule basali atipiche con citoplasma rosa o rosso (discheratosi) v Elastosi solare, anomala sintesi di fibre elastiche da parte dei fibroblasti danneggiati dall esposizione al sole. v Lo strato corneo è ispessito e le cellule dello strato corneo conservano il loro nucleo (aspetto noto con il nome di paracheratosi). v Varianti istopatologiche: ipertrofica, bowenoide, atrofica, acantolitica, pigmentata

11 Carcinomi in situ Malattia di Bowen Eritroplasia di Queyrat Cheratosi arsenicale

12 Malattia di Bowen Età adulto avanzata, cute fotoesposta e non (volto, arti inferiori, tronco) Placca eritemato-squamosa, a lenta crescita, o lesioni nodulari Se non trattata, nel 10% dei casi evolve in CACS

13 Acantosi ed iperorto-paracheratosi Perdita completa del processo di maturazione dei cheratinociti Cheratinociti atipici a tutto spessore, con aspetto chiaro (Carcinoma in situ) Coinvolgimento delle strutture annessiali

14 Premalignant Lesions Bowenoid papulosis Bowen disease Erythroplasia of Queyrat Penile intraepithelial neoplasia (PeIN)

15 Erythroplasia of Queyrat vs. Bowen s disease?- + Features Erythroplasia of Queyrat Bowen s disease Site Glans, prepuce Shaft Age 5-6 decade 4-5 decade Lesion Erythematous plaque Scaly plaque Hyperkeratosis - + Maturation - - Progression to carcinoma 10% 5-10% Association with internal cancer Bostwick DG & Cheng L. Urologic Surgical Pathology 2008 (modified)

16 Premalignant Lesions Bowenoid papulosis Bowen disease Erythroplasia of Queyrat Penile intraepithelial neoplasia (PeIN)

17 Bowenoid Papulosis Definition: Multifocal HPV-related papular condition affecting anogenital region in young adults. Lesions exhibit spectrum of changes from dysplasia to in situ carcinoma; usually associated with favorable prognosis Etiology/Pathogenesis: Related to high-risk types of HPV, especially type 16; usually transmitted via sexual contact

18 Bowenoid Papulosis Clinical issues: Immunosuppression, including HIV infection, greatly increases the risk for bowenoid papulosis; mean age 30 yrs Presentation: Young, sexually active adults with solitary or more often multiple soft papules or macules with flat/verruciform surface Lesions are often small, red, brown, or flesh-colored Usually affects skin or shaft, may also affect glans, coronal sulcus or foreskin May be pruritic or painful but usually asymptomatic Lesions in IS tend to be more widespread

19 Bowenoid Papulosis Histopathology: Proliferation of atypical (basaloid) cells with high nuclar/cytoplasmic ratio Koilocytic-like changes are also seen in most cases Range of atypia from scattered atypical cells to low-grade dysplasia to full thickness atypia of the squamous epithelium Morphologically similar to HPV-related PeIN, clinical correlation is crucial Variable pigmentation of the basal layer

20 Bowenoid Papulosis Differential diagnosis: Squamous cell carcinoma, in situ Clinical correlation Treated flat condyloma Changes secondary to podophyllin application Atypical mitoses should not be seen Pallor of the epithelium, nuclear enlargement, necrotic keratinocytes

21 Penile Intraepithelial Neoplasia (PeIN) Synonims: Erythroplasia of Queyrat, Bowen disease, SCC in situ Definition: PeIN is considered intraepithelial (in situ) precursor lesion of invasive SCC Pathogenesis: Basaloid, warty and warty/basaloid (undifferentiated) PeIN are HPV-related (especially HPV-16) cell carcinoma, usual type Differentiated (simplex) PeIN is unrelated to HPV Lichen sclerosus may be implicated in pathogenesis of differentiated PeIN

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23 Penile Intraepithelial Neoplasia Clinical issues: 5th-6th decades (PeIN) 2/3 associated with invasive SCC When invasive SCC is associated with PeIN, 65% are differentiated PeIN and 35% are undifferentiated PeIN Presentation: Differentiated PeIN - Older patients, frequently affects foreskin, usually arises in the setting of chronic scarring, inflammatory conditions, especially LSA Warty/basaloid PeIN - Younger patients, usually affects glans, perimeatal region, usually not associated with LSA, possible previous history of condyloma

24 Penile Intraepithelial Neoplasia (PeIN) Macroscopic Features: Gross appearance does not allow distinction between different types Uni- or multifocal Sharp or ill-defined borders Flat to slightly elevated hyperkeratotic or even papillary lesions Pearly white, moist, eryrthematous, dark/brown/black Macules, papules, or plaques Differentiated PeIN usually arises in the background of LSA

25 Penile Intraepithelial Neoplasia Histopathology: (PeIN) Differentiated (simplex) PeIN (HPV-unrelated) - thickened epithelium with atypical basal cells, subtle abnormal maturation, keratin pearl formation in deep rete ridges, absence of koilocitosis, association with LSA Warty PeIN (HPV-related) - pleomorphic cells with koilocytic changes replacing most to full thickness epithelium, undulated/spiky surface, numerous mitoses Basaloid PeIN (HPV-related) - basaloid cells replacing most to full thickness of the epithelium, prominent apoptosis and mitoses Mixed PeIN (HPV-related) - pleomorphic cells with koilocytic changes seen on upper epidermis, basaloid cells replace lower epidermis, usually undulated/spiky surface

26 Penile Intraepithelial Neoplasia (PeIN) Differential diagnosis: Differentiated PeIN vs squamous hyperplasia/lichen simplex chronicus Warty/basaloid PeIN vs condyloma (koilocytosis confined to upper epithelium, absence of nuclear pleomorphism, scant mitoses confined to lower epithelium) vs bowenoid papulosis (indistinguishable on histology, clinical correlation necessary)