Penile and Testicular Tumors.pdf

Penile and Testicular Tumors Penile Intraepithelial Neoplasia (PeIN) Intraepithelial squamous cell atypia Initially precancerous Associated with HPV Whitish changes with erythema and ulcer Common in HIV+ men with anal dysplasia Four variants o Differentiated: Most common o Warty: Papillary growth o...

Penile and Testicular Tumors Penile Intraepithelial Neoplasia (PeIN) Intraepithelial squamous cell atypia Initially precancerous Associated with HPV Whitish changes with erythema and ulcer Common in HIV+ men with anal dysplasia Four variants o Differentiated: Most common o Warty: Papillary growth o Basaloid o Warty basaloid Squamous Cell Carcinoma Most common penile neoplasms Low education, high poverty areas Risk factors: o Long inner foreskin o HPV o Lichen sclerosis Pathogenesis o Degradation and Inactivation of p53, pRb, E6, E7 o Tumor Suppressor Gene Retinoblastoma (pRb) Pathological findings o Exophytic or ulcerated lesion o Atypical squamous cells o Large hyperchromatic irregular nuclei o Prominent nucleoli o Abnormal keratinization Treatment o Excision (partial / total penectomy), with or without inguinal lymph node dissection o Poor prognostic factors: § High stage § High histologic grade § Deeper invasion § Angiolymphatic invasion (vessel and node infiltration) § Perineural invasion (increases metastasis risk) Types: Bowen’s Dz (in situ), Verrucous Carcinoma Bowen’s Dz In situ Sharply marginated, erythematous, scaly patch or plaque Epithelial dysplasia with mitosis in upper third layer HPV postive P16 overexpression Verrucous Carcinoma Well-differentiated Slow growing verruciform tumor HPV negative NO P16 overexpression (Bowman’s overexpresses P16) Penetrates through lamina propria with broad base and pushing borders Excellent prognosis, may recur Anatomy of Testes Tunica vaginalis: extension of peritoneal cavity Tunica albuginea: fibrous capsule extending into testis, separates into lobules Tunica vasculosa: Vascular layer Histology of Testes Major cells o Spermatogenic cells: initiate spermatogenesis o Sertoli cells: Located in seminiferous tubules o Leydig cells: In interstitial tissue, endocrine in nature Testicular Tumors Most common solid tumor in males age 15-35 Predominantly germ cell tumors in young patients Usually presents as a painless mass 2 Types of Spread: o Lymphatic spread: periaortic, iliac, mediastinal and supraclavicular nodes, NOT inguinal nodes o Hematogenous spread: to Liver, Lungs, brain, bones Germ Cell Tumors Most common tumor in men 25-29 years Usually highly curable even if advanced Commonly mixed histologic types Arises from seminiferous epithelium Bilateral is classical seminoma In elderly, usually spermatocytic seminoma p53 mutations are common Risk factors: o Cryptorchidism o Family history o Testicular dysgenesis o Li-Fraumeni syndrome o Prior testicular germ cell tumor o Prior intratubular germ cell neoplasia (in situ) Prognosis: Depending on histologic type AND tumor stage Teratoma Tumors contain cellular components Derived from 2 or 3 germ layers Malignant in adults Mixed Germ Cell Tumor Elevated AFP suggestive of yolk sac tumor components Intratubular Germ Cell Neoplasia (ITGCN) AKA germ cell neoplasia in situ (GCNIS) Occur adjacent to germ cell tumor Less often in childhood yolk sac tumors and teratoma Management: serum measurement of o hCG o AFP o Human placental lactogen (HPL) Seminoma 30-50% of testicular germ cell tumors Also present in mediastinum, pineal gland (germinoma), retroperitoneum 3 elevations in serum: o PLAP (placental alkaline phosphatase) o LDH (Lactate dehydrogenase): Less-specific marker, but levels correlate with overall tumor burden o hCG (Human chorionic gonadotropin) Overrepresentation of 12p chromosome sequences, probably KRAS, CCND2, and NANOG Seminoma Pathologic Findings o Homogenous well demarcated gray-white with lobulated and bulging cut surface o Uniform tumor cells w clear cytoplasm (glycogen contents) o Prominent cell border o Large nuclei o Prominent nucleoli o PLAP (+) o Cytokeratin (–) o AFP (normal) Seral Markers for GCT (Germ Cell Tumor) Beta subunit of (hCG): Germ cell tumor with trophoblast differentiation Alpha-fetoprotein (AFP): Germ cell tumor with yolk sac differentiation Lactate dehydrogenase (LDH): Germ cell tumor, the only abnormal seral marker for some seminomas Spermatocytic Tumor NOT related to classic seminoma Does NOT arise from intratubular germ cell neoplasia Treatment: Orchiectomy Poor prognostic factor: Sarcomatous components PLAP (–) hCG (–) AFP (–) Pathologic findings o Pale gray, mucoid, edematous o Contains 3 cell types o Varying from lymphocyte size to giant cells, o Most commonly composed of intermediate sized cells Choriocarcinoma Cytotrophoblast and Syncytiotrophoblast PLAP (+) hCG (+) Cytokeratin (+) Intratubular GC neoplasia hCG AFP HPL Seminoma PLAP hCG AFP (normal) Cytokertain (–) LDH Spermatocytic tumor PLAP (–) hCG (–) AFP (–) Choriocarcinoma PLAP (+) hCG (+) Cytokeratin (+)