Campbell Neoplasms of the Testis 2021 Flashcards
Chapter 76
Testis cancer is the most common malignancy among men aged ____ to ___ and second most common after leukemia among males aged ___ to ___
20-40
15-19
Four risk factors for testis cancer
- White race
- Cryptorchidism
- Family history of testis cancer
- Personal history of testis cancer and germ cell neoplasia in situ (GCNIS), a.k.a. intratubular germ cell neoplasia (ITGCN)
Cryptorchidism: ___ to ___ times more likely to get testicular CA in affected gonad.
Risk falls to ___ to ___ if ____ is performed before puberty.
Men with cryptorchidism are 4 to 6 times more likely to be diagnosed with testis cancer in the affected gonad, but the relative risk falls to 2 to 3 if ORCHIDOPEXY is performed before puberty.
GCNIS is associated with a ___ risk of GCT within 5 years, and ___ within 7 years.
50%
70%
TRUE or FALSE:
In men with a history of GCT, the finding of testicular microlithiasis on ultrasound of the contralateral testis is associated with an increased risk of GCNIS
TRUE. Only in men with a HISTORY OF GCT.
However, the significance of microlithiasis in the general population is unclear; a study of 1500 army volunteers found a 5.6% prevalence of microlithiasis, yet fewer than 2% of those with microlithiasis developed GCT within 5 years.
___ is a universal finding in postpubertal testicular and extragonadal germ cell tumors except for spermatocytic tumors.
An increased number of copies of genetic material from the short arm of chromosome 12
Most common sites of extragonadal GCTs
Approximately 5% of postpubertal GCTs are extragondal in origin, and most develop in midline anatomic locations (RETROPERITONEUM and MEDIASTINUM are most common).
MEDIASTINAL: less sensitive to chemo, poor 5-year overall survival (45%), likely to have yolk-sac components; elevated AFP
RETROPERITONEAL: indistinguishable biologically from testicular GCTs and carry the same prognosis
Most common type of GCT
Seminoma
GCT that does NOT arise from GCNIS
Spermatocytic tumor
ALSO: not associated with a history of cryptorchidism or bilaterality, does not demonstrate i(12p), and does not occur as part of mixed GCTs
Benign tumor, peak 6th decade of life
Almost always cured with orchiectomy
EXCEPTION: + sarcomatous differentiation = chemo resistant, poor prognosis
Most undifferentiated type of NSGCT
EC is the most undifferentiated cell type of NSGCT, with totipo- tential capacity to differentiate to other NSGCT cell types (including teratoma) within the primary tumor or at metastatic sites.
Aggressive, high rate of metastasis.
___ is a rare and aggressive tumor that typically is seen with extremely highly elevated serum HCG levels and disseminated disease.
Choriocarcinoma
Spreads by hematogenous routes
Common site of metastasis: lung, liver, brain
Prone to hemorrhage - catastrophic when it occurs in lungs or brain
Can cause hyperthyroidism, elevated androgen production
Hyperprolactinemia
___ almost always produce AFP but NOT HCG
Yolk Sac Tumors
Characteristic feature: Schiller-Duval body
Tumors that contain well or incompletely differentiated elements of at least two of the three germ cell layers.
Teratomas
Normal serum tumor markers, or mildly elevated serum AFP
Resistant to chemotherapy: requires consolidative surgical resection
May transform to: rhabdomyosarcoma, adenocarcinoma, or primitive neuroectodermal tumor
Most common presentation of testicular cancer
Painless testis mass
A firm intratesticular mass should be ___ and should be evaluated with ___.
Presumptive epididymoorchitis should be re-evaluated within ___ weeks after completion of antibiotics.
Considered cancer until proven otherwise
Scrotal ultrasound
2-4 weeks
Typical GCT vs NSGCT findings on ultrasound
GCT: Hypoechoic, 2 or more lesions may be identified
NSGCT: Heterogenous
In men with advanced GCT and a normal testicular examination, ___ should be performed to rule out the presence of a small, impalpable scar or calcification, indicating a ___ .
Scrotal ultrasonography
“burned-out” primary testis tumor
*** Radical orchiectomy should be performed in those patients with sonographic evidence of intratesticular lesions (discrete nodule, stellate scar, coarse calcification) because GCNIS and residual teratoma are frequently encountered.
One of the most striking features of GCTs is their sensitivity to ___ chemotherapy.
Cisplatin-based
- Enables cure in the vast majority of patients with widely metastatic disease
- GCTs lack transporters to export cisplatin from the cell and have a reduced ability to repair cisplatin-induced DNA damage
Serum tumor markers for testis cancer
Lactate dehydrogenase (LDH) Alpha fetoprotein (AFP) Human chorionic gonadotropin (HCG)
AFP levels are elevated in ___ % of low-stage ____ and ____ % of ____.
Also: ___ and ___ tumors secrete AFP.
AFP levels are elevated in 50% to 70% of low-stage (CS I, IIA, IIB) NSGCTs and 60% to 80% of advanced (CS IIC, III) NSGCTs.
EC and yolk sac tumors secrete AFP.
These tumors DO NOT secrete AFP:
Choriocarcinomas
Seminomas
Pure seminoma in primary tumor + elevated AFP = ____
Considered to have NSGCT
AFP half-life
5-7 days
HCG levels are elevated in: ___.
__% of seminomas secrete HCG.
HCG levels are elevated in 20% to 40% of low-stage NSGCTs and 40% to 60% of advanced NSGCTs.
15% of seminomas secrete HCG.
___ and ___ also secrete HCG.
Choriocarcinoma
EC
HCG levels above ____ are usually associated with NSGCT.
Above 5,000 IU/L
HCG half-life
24-36 hours
Causes of HCG elevation:
Cancers of the liver, biliary tract, pancreas, stomach, lung, breast, kidney, and bladder.
False-positive:
Primary hypogonadism (normalizes in 48-72 hours after administration of testosterone)
Marijuana
Causes of AFP elevation
Hepatocellular carcinoma, cancers of the stomach, pancreas, biliary tract and lung, non-malignant liver disease (infectious, drug-induced, alcohol-induced, autoimmune), ataxic telangiectasia, and hereditary tyrosinemia.
LDH levels are elevated in ____.
LDH levels are elevated in approximately 20% of low-stage GCT and 20% to 60% of advanced GCT.
LDH is a nonspecific marker for ___ and mainly used for ___.
As a nonspecific marker for GCT, its main use is in the PROGNOSTIC assessment of GCT at diagnosis.
Dr. Lantin answer: Indicator of tumor bulk
LDH half-life
24 hours
Surgical procedure for patients suspected of testicular neoplasm
Radical INGUINAL orchiectomy, removal of tumor-bearing testicle and spermatic cord to the level of the internal inguinal ring.
Why is a transscrotal orchiectomy or biopsy contraindicated in testis CA?
- It leaves the inguinal portion of the spermatic cord intact
- Alters the lymphatic drainage of the testis, increasing the risk of local recurrence and pelvic or inguinal lymph node metastasis.
GCTs grow rapidly. Delays in orchiectomy should not be greater than ____.
1-2 weeks
Testis-sparing surgery (partial orchiectomy) may be considered ONLY in:
Organ-confined tumors < 2-3 cm, <30% testicular volume, with synchronous or bilateral tumors, OR solitary testis with sufficient androgen production
Testis-sparing (partial orchiectomy) has NO ROLE in:
Patients suspected of having a testicular neoplasm with a normal contralateral testis.
Benign histology may be encountered in up to ___ of testicular lesions smaller than ___ and long duration ___
80%
3 cm
> 6 months
Patients with GCNIS who underwent partial orchiectomy should undergo ___ to prevent GCT development.
Adjuvant RT to residual testis at least 20 Gy to prevent GCT development and preserve Leydig cell function (androgen production).
Open inguinal biopsy of the contralateral testis considered in patients with:
Atrophic testis
History of cryptorchidism
< 40 years
Suspicious lesions on preop ultrasound
**5-9% of patients with GCT have GCNIS in the contralateral testis.
** With risk factors (above): up to 36%
TRUE or FALSE: Preorchiectomy serum tumor marker levels should not be used in management decisions.
TRUE.
Serum tumor marker levels should be obtained at diagnosis, after orchiectomy, to monitor for response to chemotherapy, and to monitor for relapse in patients on surveillance and after completion of therapy.
Most common route of disease dissemination in testicular CA: ___
Exception: ___ which spreads ___
Lymphatic channels to RPLNs —> distant sites.
70-80% of patients with GCT –> initial site of spread is the retroperitoneum.
Except: CHORIOCARCINOMA, which spreads hematogenously.
Primary drainage site/landing zone:
RIGHT testis tumors: ___
LEFT testis tumors:
___
Pattern of drainage:
___
RIGHT: Interaortocaval LNs, then paracaval and para-aortic LNs.
LEFT: Para-aortic LNs, then interaortocaval LNs.
Pattern: RIGHT to LEFT (contralateral spread from the primary “landing zone” is common with right-sided tumors but is rarely seen with left-sided tumors)
Retroperitoneal LNs ____ in size = suspicious for regional LN metastasis, especially if they are located ___
5-9 mm in size
ANTERIOR to the great vessels
TRUE or FALSE:
FDG-PET is useful in the routine evaluation of NSGCT and seminoma at the time of diagnosis.
FALSE.
There is currently NO role for FDG-PET in the routine evaluation of NSGCT and seminoma at the time of diagnosis.
IGCCG Risk Classification for Advanced GCT
International Germ Cell Collaborative Group risk stratification:
Used to guide choice of chemotherapy for metastatic GCT
NOT applicable to patients with relapsed GCT
IGCCG NSGCT
Good Prognosis
NSGCT GOOD PROGNOSIS Testicular/retroperitoneal primary and No nonpulmonary visceral metastases and Good markers—all of: AFP <1000 ng/mL and HCG <5000 IU/L (1000 ng/mL) and LDH <1.5 × upper limit of normal (N) 56% of nonseminomas 5-year PFS 89% 5-year survival 92%
IGCCG NSGCT
Intermediate Prognosis
NSGCT Intermediate Prognosis Testicular/retroperitoneal primary AND No nonpulmonary visceral metastases Intermediate markers—any of: AFP ≥1000–10,000 ng/mL and ≤10,000 ng/mL or HCG ≥5000–50,000 IU/L and ≤50,000 IU/L or LDH ≥1.5 × N and ≤10 × N 28% of nonseminomas 5-year PFS 75% 5-year survival 80%
IGCCG NSGCT
Poor Prognosis
IGCCG NSGCT
Poor Prognosis
Mediastinal primary OR Nonpulmonary visceral metastases OR Poor serum markers—any of: AFP >10,000 ng/mL or HCG >50,000 IU/L (10,000 ng/mL) or LDH >10 × upper limit of normal 16% of nonseminomas 5-year PFS 41% 5-year survival 48%
IGCCG Seminoma
Good Prognosis
IGCCG Seminoma Good Prognosis Any primary site AND No nonpulmonary visceral metastases AND Normal AFP, any HCG, any LDH 90% of seminomas 5-year PFS 82% 5-year survival 86%
IGCCG Seminoma
Intermediate Prognosis
IGCCG Seminoma Intermediate Prognosis Any primary site AND Nonpulmonary visceral metastases AND Normal AFP, any HCG, any LDH 10% of seminomas 5-year PFS 67% 5-year survival 72%
IGCCG Seminoma
Poor Prognosis
IGCCG Seminoma
Poor Prognosis
NO patients classified as poor prognosis!!
TRUE or FALSE
Seminoma is associated with decreased sensitivity to radiation therapy and platin-based chemotherapy compared with NSGCT.
FALSE
Compared with NSGCT, seminoma is exquisitely sensitive to radiation therapy and platin-based chemotherapy.
Radiation therapy is a standard treatment option for CS I and IIA-B seminoma but has no role in NSGCT, with the exception of treatment for brain metastases.
Sex Cord-Stromal Tumors
90% benign, 10% malignant
Most malignant cases have at least 2 features:
Size larger than 5 cm, necrosis, vascular invasion, nuclear atypia, high mitotic index, increased MIB-1 expression, infiltrative margins, extension beyond the testicular parenchyma, and DNA ploidy.
PRESENCE OF METASTASIS: only reliable criteria
Types: Leydig Cell Sertoli Cell Granulosa Cell Gonadoblastoma
Leydig Cell Tumors
75-80% of sex-cord stromal tumors
No association with cryptorchidism
Ultrasound indistinguishable from GCT
Children: testis mass + isosexual precocious puberty
Treatment:
Radical orchiectomy
OR
Testis-sparing if < 3 cm then completion orchiectomy if GCT histology seen on frozen section or if malignant features
Frequent mets:
RP
Lungs
Metastatic Leydig cell:
Chemo and RT resistant
Sertoli Cell Tumor
< 1% of testis neoplasms
Rare: associated with Peutz-Jeghers syndrome
No association with cryptorchidism
Treatment:
Testis-sparing if < 3 cm (high incidence of benign histology)
If > 3 cm: intraop frozen section –> radical orchiectomy
Granulosa Cell Tumors
Rare
Juvenile type: benign, most frequent congenital testis tumor (< 6mos)
Adult type: granulosa cell tumors of the ovary
Treatment:
Testis-sparing if < 3 cm
Gonadoblastoma
Mixed germ-cell cord-stromal tumor, with seminoma-like germ cells and sex cord cells with Sertoli differentiation.
80% affected are phenotypic females, with primary amenorrhea
Considered in situ form of malignant GCT, 50% will develop invasive GCT
BILATERAL ORCHIECTOMY required: 40% RISK OF BILATERAL TUMORS
Dermoid & Epidermoid Cyst
Rare benign neoplasms from germ cells with retained embryonic properties
Usually smaller than 3 cm, no flow or enhancement on Doppler
TX:
Enucleation or partial orchiectomy;
Histopath to rule out GCT or GCNIS
Adenocarcinoma of the Rete Testis
Rare, but HIGHLY malignant Painless testis mass + hydrocele 50% have metastatic disease Overall median survival: 1 year RPLND may be curative if limited RPLN disease
Lymphoma
Primary NHL: rare tumor, 1-2% of all cases are lymphoma
Most common testicular neoplasm in men over 50
Bilateral involvement in 35% of cases
Painless testicular mass
CNS involvement in 10% of men
Poor overall prognosis
Leukemic infiltration
Frequent site of relapse in acute lymphocytic leukemia
Diagnosis by biopsy
Orchiectomy unnecessary
Local control with low dose RT (20Gy)
Include contralateral testis: frequent risk of bilateral involvement
Paratesticular tumors: Adenomatoid
Mesothelial origin
MOST COMMON paratesticular tumor, 75% involves the epididymios
Small (0.5-5cm) painless mass
Benign
Managed by inguinal exploration + Surgical excision
Sarcoma
MOST COMMON SUBTYPE in adults: Liposarcoma
Embryonal rhabdomyosarcoma: most common histologic subtype in men under age 30
Most commonly arise from the spermatic cord
Painless, palpable mass
Large > 5 cm
If ultrasound: extension to tunica albuginea – inguinal exploration and biopsy
Systemic chemo if with RPLN metastasis (postop)
