Testicular tumors

• Germ cell (90-95%)
  • Seminoma - most common testis tumor (65% of germ cell tumors) (age 30-40)
  • Non-seminoma
    • Yolk sac (infants/children) = most common malignant testicular tumor in boys
    • Embryonal, choriocarcinoma (worst prognosis), teratoma (age 20-30), mixed with seminoma
      • Mature teratoma = benign in children, mostly benign in adults
    • Gonadoblastoma - rare, a/w intersex (DSD with Y chromosome). Invasive = dysgerminoma
• Non-germ cell (stromal) (5-10%)
  • Leydig (most common non-germ cell) - can present with precocious puberty (usually benign, but 10% malignant behavior/metastasize - treat with RPLND as resistant to chemo/radiation)
  • Sertoli - a/w genetic syndromes (usually benign)
  • However if Leydig/Sertoli do metastasize, prognosis is poor. Still monitor these patients
  • Granulosa (neonate)
• Lymphoma - most common cause of bilateral testis tumors (age > 50, or a/w ALL relapse in peds)
• Microlithiasis - no increased risk factors for cancer; ignore/manage with self exams only
• Germ cell neoplasia in situ (GCNIS) - risk of developing invasive GCT is 50% within 5 years. Increased but low risk for contralateral tumor
  • Discuss surveillance vs XRT (18-20 Gy) vs orchiectomy (if found on testis sparing surgery)

Risk factors

• Cryptorchidism - testis location (height) correlates with cancer risk; more common on right. Unilateral crypto causes increased cancer risk in contralateral testis too.

Metastasis

• Most commonly to retroperitoneal lymph nodes
  • L-sided: left para-aortic nodes
  • R-sided: R interaortocaval nodes
  • **hide**Altered lymphatic flow (previous surgery, invasion) can → inguinal nodes (from scrotum) or pelvic nodes (from spermatic cord)
• Distant metastasis: lung, liver, brain, bone
• Choriocarcinoma spreads hematogenously
• Spermatocytic seminoma (1-4% of seminoma) has very low metastatic potential

Staging: pathologic staging after radical orchiectomy.

S stage: determined by nadir of post-orchiectomy tumor markers

• Useful for staging, risk stratification, relapse monitoring
• Mnemonic for S1 threshold: "1, 5, 1.5" for AFP < 1k, HCG < 5k, LDH < 1.5 ULN
• Normal AFP: < 10 , or < 20 and stable
• Normal hCG: < 10 ish

IGCCCG risk stratification

• Good - S1 and no nonpulmonary visceral mets (90% 'cure' rate)
• Intermediate - S2 and no nonpulmonary visceral mets (70% 'cure' rate)
• Poor - S3 or mediastinal primary or nonpulmonary visceral mets (50% 'cure' rate)
• Chemo based on IGCCCG risk - 3 vs 4 cycles of BEP

Stage grouping: used for treatment

• **hide**8th edition (2017)

Presentation

• Painless mass or swelling in testes; some with hydrocele.
  • More common on right (cryptorchidism ismore common on right)
  • Bilateral in 1-3% (lymphoma is most common cause)
• Gynecomastia in 30-50% with Sertoli/Leydig tumors (testosterone → estrogen)
• Back pain, abdominal mass with large retroperitoneal metastases
  • Sometimes supraclavicular node/mass
  • If hx surgery for undescended testicle, may alter lymphatic planes and could have inguinal lymphadenopathy

Diagnosis

If normal markers but equivocal exam/imaging (e.g. marginally enlarged lymph nodes 0.8 - 1.5 cm) - re-image in 6-8 weeks.

• Scrotal ultrasound (testis tumor is benign in 1% of adults, 20% of children)
  • Heterogeneous, vascular 
  • Other benign lesions
    • Epidermoid cyst = "onion skin" appearance, alternating hypo/hyperechoic layers. Single cell type mature teratoma. Remove with partial orchiectomy
• Solid intratesticular mass (suspicion for malignancy)
  • Tumor markers (AFP, β-HCG, LDH)
  • LFTs (check for liver metastasis; other causes of ↑ AFP)
    • AFP very high in infants (10,000s) - does not normalize until 8 mo - 12 year 
  • CBC, Cr (RPLN metastases may obstruct ureter), CXR (lung metastasis)
• No biopsy - risk of scrotal seeding, causing inguinal lymphatic spread
  • If biopsy was done, will require upstaging of disease
• CT A/P, chest imaging
  • Can wait til after orchiectomy path back - could be benign
  • Seminoma - can get CXR only (less aggressive spread/does not skip)
  • Get CT chest for NSGCT, or seminoma with abdominal disease
  • Technically if clean orch, don't need to monitor the pelvis
  • If borderline lymphadenopathy, can repeat scan 4 weeks before chemo to see if chemo really needed
• If neuro symptoms and concern for chorio (bHCG > 5000), brain MRI (hematogenous spread)

Tumor markers:

• *seminoma on orchiectomy histology but ↑ AFP → treat as mixed germ cell tumor (assume unidentified non-seminoma element)

Initial management of testicular mass

• Radical inguinal orchiectomy
  • Offer sperm banking, testicular prosthesis to adults
    • 1-3 deposits 3-5 days apart (doesn't need to happen before orch, just before chemo). ~$500/year
    • Can refer to REI clinic, California Cryobank, www.meetfellow.com/
    • Reasons against prosthesis - infection risk, delay to chemo if infected, asymmetric appearance, easy to do later if he wants
  • Inguinal approach to remove entire spermatic cord and testicle - avoid trans-scrotal approaches.
    • Make sure to tag remnant spermatic cord with permanent suture in case the abdominal portion needs to be removed in future surgery
• If there was scrotal violation
  • 2.9% risk of local recurrence but no difference in survival (e.g. only rarely consider adjuvant treatment such as scar excision or XRT)
  • If RPLND - excision of spermatic cord remnant and scrotal scar, with no additional treatment
  • If post-chemo, spermatic cord remnant excision alone at time of RPLND (no need for scar excision)
• Mature teratoma in pediatrics
  • Partial orchiectomy OK if diagnosis confirmed on frozen
  • If excision complete pre-puberty, no need for further onc followup

Overall survival 95% (all-comers)

Post-orchiectomy management of germ cell tumors

• Orchiectomy reveals primary malignancy → staging
  • Stage with histopathology
  • S-stage with nadir of post-orchiectomy serum markers (wait ≥ 5 half-lives after surgery, see above).
  • CT A/P → chest CT for lung metastasis if abnormality found on CT A/P or CXR
    • Can omit CXR in pure seminoma if CT A/P normal - does not 'skip' RP to go to lungs
    • If borderline IIA nodes (e.g. 1-2 cm) - repeat imaging in 6-8 wks

• Surveillance schedules - see NCCN guidelines PDF at bottom, page 27-31
  • Stage I GCT - < 1% risk of late relapse after 5 years
    • Seminoma - Chest and tumor markers PRN. TRISST trial - less frequent surveillance with MRI (e.g. 3 scans vs 7 scans over 72 mo) is OK
    • NSGCT - include CXR + tumor markers and surveil more frequently than seminoma
• Chemo: cisplatin is most effective against germ cell tumors.
  • Give EP x 4 (etoposide + cisplatin) or BEP x 3 (bleomycin + EP). Each cycle is ~ 3 weeks
    • VIP = replace bleomycin with ifosfamide if bleomycin is contraindicated. V = etoposide (VePesid).
    • Bleomycin a/w pulmonary toxicity; relatively contraindicated for > 40 yo (although has minimal myelosuppression compared to other agents)
  • Teratoma will not respond to chemo; will need RPLND
  • Toxicity: hearing loss, peripheral neuropathy, CVD, pulmonary fibrosis, renal impairment, secondary malignancy
  • Post chemo - tumor markers ~ 1 wk, repeat scan ~ 1 mo to see if needs post chemo RPLND
  • Lung masses only have 75% pathology concordance with RP masses post-chemo - still have to resect even if RP mass is fibrosis
• Relapse
  • Late relapse (> 5 years) - consider RPLND, more likely to be teratoma (unresponsive to chemo)

Non-germ cell (Sertoli/Leydig): surveillance if no metastases

Lymphoma: Med-onc referral for systemic chemo