Male genitourinary cancers Notes

NOTES NOTES MALE GENITOURINARY CANCERS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Male reproductive, urinary system cancers CAUSES ▪ Depends on cancer type RISK FACTORS ▪ Depends on cancer type ▫ Tobacco smoking, increased age, positive family history COMPLICATIONS ▪ Metastasis, affected part function loss SIGNS & SYMPTOMS ▪ Depends on cancer type ▫ Dysuria, painful ejaculation, back pain, hematuria/hematospermia, pelvic pain, weight loss, lower back/abdominal pain DIAGNOSIS DIAGNOSTIC IMAGING ▪ CT scan/MRI/ultrasound ▪ Identify lesions LAB RESULTS ▪ Serum tumor markers 766 OSMOSIS.ORG OTHER DIAGNOSTICS ▪ History/physical exam Biopsy ▪ Grading ▫ GX: grade cannot be assessed (undetermined grade) ▫ G1: well differentiated (low grade) ▫ G2: moderately differentiated (intermediate grade) ▫ G3: poorly differentiated (high grade) ▫ G4: undifferentiated (high grade) Staging ▪ Tumor, nodes, metastasis (TNM) system; scored 0–4 ▫ T: size, sites invaded (e.g. only testis/ extratesticular invasion) ▫ N: degree of spread to regional lymph nodes ▫ M: distant metastasis presence ▫ V: Vascular invasion TREATMENT MEDICATIONS ▪ Chemotherapy SURGERY ▪ See individual cancers OTHER INTERVENTIONS ▪ Radiotherapy

Chapter 127 Male Genitourinary Cancers PENILE CANCER osms.it/penile-cancer PATHOLOGY & CAUSES ▪ ▪ ▪ ▪ Malignant penis tumor Rare in high-income countries Initial lesions found on prepuce, glans Can invade corpora, shaft of penis → penile autoamputation TYPES Squamous cell carcinoma (SCC) ▪ Most predominant; melanoma, small-cell carcinoma, Kaposi sarcoma, Meckel cell carcinoma, basal cell carcinoma, etc. ▪ Bowenoid papulosis ▫ SCC form in situ of penis ▪ Erythroplasia of Queyrat ▫ SCC of penis glans, presents as erythroplakia (red patch) Histologic subtypes of SCC ▪ Usual type ▫ Most predominant ▫ Involves corpus spongiosum ▫ Invades perineural, regional lymphovascular system ▪ Papillary carcinoma ▫ Involves superficial erectile tissues ▫ Not associated with human papillomavirus (HPV) ▫ Histology: papillomatosis, hyperkeratosis ▪ Warty tumors ▫ Associated with HPV infection ▫ Histology: irregular stroma with papillary fibrovascular core ▪ Basaloid carcinoma ▫ Associated with HPV ▫ Histology: necrosis, erectile tissue invasion ▪ Verrucous carcinoma ▫ Not aggressive (low metastatic ability) ▫ Histology: straight papillae, surface, interpapillary hyperkeratosis ▪ Sarcomatoid carcinoma ▫ Very rare ▫ Highly aggressive ▫ Histology: SCC, spindle cell carcinoma components RISK FACTORS ▪ Infection ▫ HPV 16/18 infection, HIV, urinary tract infections (UTIs) ▪ Genital warts, poor hygiene, phimosis/ paraphimosis, tobacco smoking, smegma accumulation, increased age COMPLICATIONS ▪ Metastasis ▫ Inguinal/femoral lymph nodes; liver, lung, bone, brain (rare) ▪ Penile autoamputation SIGNS & SYMPTOMS ▪ Painless mass ▪ Ulcer/rash ▪ Penile pain/foul-smelling discharge/ bleeding ▪ Inguinal lymphadenopathy ▪ Penile skin color change (redness) DIAGNOSIS DIAGNOSTIC IMAGING CT scan/MRI/ultrasound ▪ Regional lymph, distant metastasis assessment OSMOSIS.ORG 767

OTHER DIAGNOSTICS ▪ Obvious suspicious penile lesions ▪ Biopsy ▫ Diagnosis, tumor grading ▪ Staging ▫ TNM TREATMENT MEDICATIONS ▪ Chemotherapy SURGERY ▪ Local excision in early stage ▪ Partial/total penectomy if glans/shaft invaded Figure 127.1 The clinical appearance of a fungating penile tumor, likely a squamous-cell carcinoma. There is visible lymphadenopathy of the left superficial inguinal chain which almost certainly represents metastatic disease. OTHER INTERVENTIONS ▪ Radiotherapy PROSTATE CANCER osms.it/prostate-cancer PATHOLOGY & CAUSES ▪ Very common male cancer ▫ Arises in prostate gland ▪ Second leading cancer death cause in biologically-male individuals ▪ Usually associated with BRCA1/BRCA2 gene mutations ▪ Early cancer cells require androgens to survive ▪ Can later become androgen-independent ▪ Usually arise in prostate’s peripheral zone TYPES Adenocarcinomas ▪ Most common ▪ Arise from glandular tissues; from luminal/ basal cells 768 OSMOSIS.ORG Transitional cell cancer ▪ Arises from prostatic urethra transitional epithelium cells Small cell prostate cancer ▪ Arise from neuroendocrine cells RISK FACTORS ▪ ▪ ▪ ▪ ▪ ▪ > 40 years old Black people of African descent ↑ risk Positive family history Smoking Obesity Animal-fat rich diet COMPLICATIONS ▪ Bone osteolysis → hypercalcemia (rare) ▪ Metastasis ▫ Lymph nodes → more metastasis to distant organs (e.g. lungs)

Chapter 127 Male Genitourinary Cancers ▫ Bones (thoracic/lumbar spine, pelvis) → lower back pain, pathologic fractures → spinal cord compression (if spine involved) → neurological deficits (e.g. lower limb pain/weakness, bowel/ urinary bladder control loss, etc.) ▪ Nearby structure compression/invasion ▫ Urinary bladder/prostatic urethra (later stages) → difficulty urinating; bleeding; urination, ejaculation pain SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ ▪ ▪ Urinary frequency/hesitancy/incontinence Dysuria Painful ejaculation Lower-back/bone pain Hematuria/hematospermia (rare) Neurological deficits (e.g. weakness/lack of lower limb sensation) DIAGNOSIS Gleason score ▪ 2–4: low grade ▪ 5–7: moderate grade ▪ 8–10: high grade Figure 127.2 The histological appearance of prostate adenocarcinoma. On the left the tumor forms vague gland like structures (Gleason 4) and on the right is composed of infiltrating single cells (Gleason 5). DIAGNOSTIC IMAGING Ultrasound ▪ Hypoechoic areas in prostate → suggestive of cancer X-ray/CT scan/MRI ▪ Lesions in prostate, pelvic lymph nodes, bones ▫ Staging: TNM ▪ Bone scan ▫ Bone metastases presence LAB RESULTS ▪ ↑ prostate specific antigen (PSA) serum levels ▪ ↑ alkaline phosphatase serum levels ▫ Suggestive of bone metastasis ▪ Biopsy used for Gleason scoring OTHER DIAGNOSTICS ▪ Digital rectal exam (DRE) ▫ Asymmetric prostate enlargement Figure 127.3 The histological appearance of prostate adenocarcinoma, Gleason grade 3. The tumor is composed of small, compressed glands with only a tiny amount of intervening stroma. TREATMENT MEDICATIONS ▪ Anti-androgen therapy ▫ ↓ testosterone levels → ↓ cancer cell growth OSMOSIS.ORG 769

SURGERY ▪ Prostatectomy ▪ Cryosurgery ▪ Orchidectomy ▫ ↓ testosterone levels → ↓ cancer cell growth OTHER INTERVENTIONS ▪ Active surveillance (early stage) ▫ Regular biopsy, PSA monitoring ▪ Radiotherapy Figure 127.4 An MRI scan of the pelvis in the axial plane demonstrating prostate adenocarcinoma invading the bladder and the rectum. TESTICULAR CANCER osms.it/testicular-cancer PATHOLOGY & CAUSES ▪ Cancer develops in testicular cells ▫ Unilateral/bilateral ▫ Common in biologically-male individuals (15–35 years old) ▪ High cure rate (very high five year survival rate) TYPES Germ cell tumors (GCT) ▪ Most common ▪ Seminomas ▫ Very poor prognosis ▫ Syncytiotrophoblastic/spermatocytic seminoma ▫ Histology: “fried egg”-like cells (clear cytoplasm, central nucleus) ▪ Non-seminomas germ cell tumors (NSGCT) ▫ Produce beta human chorionic gonadotropin (β-hCG) 770 OSMOSIS.ORG ▫ Yolk sac tumor (AKA endodermal sinus tumor) ▫ Histology: Schiller–Duval bodies (germ cells encircle blood vessel, resemble glomerulus) ▪ Embryonal carcinoma ▫ Histology: prominent nucleoli; necrotic areas; clear, empty-appearing nuclei ▪ Choriocarcinoma ▫ Histology: cytotrophoblasts, syncytiotrophoblasts, hemorrhagic areas ▪ Teratoma ▫ Histology: contains many tissue types (hair, teeth, neurons, etc.) Sex cord/gonadal stromal tumors ▪ Sertoli cells tumor ▫ Histology: dense fibrous stroma, abundant eosinophilic cytoplasm, cells have tubular arrangement ▪ Leydig cells tumors ▫ Histology: Reinke crystals (eosinophilic cytoplasmic inclusion bodies)

Chapter 127 Male Genitourinary Cancers SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ ▪ Painless/painful testis mass Lower abdominal pain, heaviness Previously atrophied testis → ↑ size Gynecomastia Metastasis evidence (e.g. dyspnea, hemoptysis, palpable lymph nodes, bone pain) DIAGNOSIS DIAGNOSTIC IMAGING ▪ Tumor identification, TNM staging ▪ Orchidectomy ▫ Biopsy: diagnosis, tumor grading Chest X-ray ▪ Evaluate pulmonary metastasis CT scan ▪ Asses abdominal, pelvic metastasis Figure 127.5 The gross pathological appearance of a testicular seminoma. The tumor has entirely replaced the normal testicular parenchyma. ▪ Granulosa cell tumor ▫ Histology: Call–Exner bodies (fluid-filled eosinophilic spaces granulosa cells) MRI ▪ If brain involvement is suspected Ultrasound ▪ Seminoma: smooth echogenic mass ▪ NSGCT: no defined borders, calcified cystic masses CAUSES ▪ Unknown; chromosome 12p gene mutations usually present RISK FACTORS Cryptorchidism (undescended testis) Previous testicular malignancy Family history White individuals Congenital abnormality (hypospadias, inguinal hernias) ▪ Infection (mumps virus → orchitis) ▪ ▪ ▪ ▪ ▪ COMPLICATIONS ▪ Infertility ▪ Lungs, liver, bones, brain metastases Figure 127.6 A scrotal MRI scan in the coronal plane demonstrating a tumor of the left testicle. OSMOSIS.ORG 771

LAB RESULTS ▪ Serum tumor markers ▫ ↑ alpha fetoprotein (AFP): NSGCT ▫ Normal AFP: pure seminoma, choriocarcinoma ▫ β-hCG: NSGCT ▫ ↑ lactate dehydrogenase (LDH): GCT TREATMENT MEDICATIONS ▪ Chemotherapy ▪ High-dose chemotherapy + stem cell transplantation SURGERY ▪ Surgery ▫ Orchidectomy, affected lymph node removal OTHER INTERVENTIONS ▪ Follow up/surveillance ▫ Regular AFP/β-hCG serum-level monitoring ▪ Radiotherapy for seminomas 772 OSMOSIS.ORG Figure 127.7 The histological appearance of a testicular seminoma, the most common form of testicular cancer. The cells have a fried egg appearance with clear cytoplasm, well-defined nuclei with open chromatin and a well-defined cell border.