Campbell Neoplasms of the Testis 2021

Question 1

Testis cancer is the most common malignancy among men aged ____ to ___ and second most common after leukemia among males aged ___ to ___

Answer 1

20-40

15-19

Question 2

Four risk factors for testis cancer

Answer 2

1. White race
2. Cryptorchidism
3. Family history of testis cancer
4. Personal history of testis cancer and germ cell neoplasia in situ (GCNIS), a.k.a. intratubular germ cell neoplasia (ITGCN)

Question 3

Cryptorchidism: ___ to ___ times more likely to get testicular CA in affected gonad.

Risk falls to ___ to ___ if ____ is performed before puberty.

Answer 3

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.

Question 4

GCNIS is associated with a ___ risk of GCT within 5 years, and ___ within 7 years.

Answer 4

50%

70%

Question 5

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

Answer 5

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.

Question 6

___ is a universal finding in postpubertal testicular and extragonadal germ cell tumors except for spermatocytic tumors.

Answer 6

An increased number of copies of genetic material from the short arm of chromosome 12

Question 7

Most common sites of extragonadal GCTs

Answer 7

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

Question 8

Most common type of GCT

Answer 8

Seminoma

Question 9

GCT that does NOT arise from GCNIS

Answer 9

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

Question 10

Most undifferentiated type of NSGCT

Answer 10

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.

Question 11

___ is a rare and aggressive tumor that typically is seen with extremely highly elevated serum HCG levels and disseminated disease.

Answer 11

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

Question 12

___ almost always produce AFP but NOT HCG

Answer 12

Yolk Sac Tumors

Characteristic feature: Schiller-Duval body

Question 13

Tumors that contain well or incompletely differentiated elements of at least two of the three germ cell layers.

Answer 13

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

Question 14

Most common presentation of testicular cancer

Answer 14

Painless testis mass

Question 15

A firm intratesticular mass should be ___ and should be evaluated with ___.

Presumptive epididymoorchitis should be re-evaluated within ___ weeks after completion of antibiotics.

Answer 15

Considered cancer until proven otherwise
Scrotal ultrasound

2-4 weeks

Question 16

Typical GCT vs NSGCT findings on ultrasound

Answer 16

GCT: Hypoechoic, 2 or more lesions may be identified

NSGCT: Heterogenous

Question 17

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 ___ .

Answer 17

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.

Question 18

One of the most striking features of GCTs is their sensitivity to ___ chemotherapy.

Answer 18

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

Question 19

Serum tumor markers for testis cancer

Answer 19

Lactate dehydrogenase (LDH)
Alpha fetoprotein (AFP)
Human chorionic gonadotropin (HCG)

Question 20

AFP levels are elevated in ___ % of low-stage ____ and ____ % of ____.

Also: ___ and ___ tumors secrete AFP.

Answer 20

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.

Question 21

These tumors DO NOT secrete AFP:

Answer 21

Choriocarcinomas

Seminomas

Question 22

Pure seminoma in primary tumor + elevated AFP = ____

Answer 22

Considered to have NSGCT

Question 23

AFP half-life

Answer 23

5-7 days

Question 24

HCG levels are elevated in: ___.

__% of seminomas secrete HCG.

Answer 24

HCG levels are elevated in 20% to 40% of low-stage NSGCTs and 40% to 60% of advanced NSGCTs.

15% of seminomas secrete HCG.

Question 25

___ and ___ also secrete HCG.

Answer 25

Choriocarcinoma | EC

Question 26

HCG levels above ____ are usually associated with NSGCT.

Answer 26

Above 5,000 IU/L

Question 27

HCG half-life

Answer 27

24-36 hours

Question 28

Causes of HCG elevation:

Answer 28

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

Question 29

Causes of AFP elevation

Answer 29

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.

Question 30

LDH levels are elevated in ____.

Answer 30

LDH levels are elevated in approximately 20% of low-stage GCT and 20% to 60% of advanced GCT.

Question 31

LDH is a nonspecific marker for ___ and mainly used for ___.

Answer 31

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

Question 32

LDH half-life

Answer 32

24 hours

Question 33

Surgical procedure for patients suspected of testicular neoplasm

Answer 33

Radical INGUINAL orchiectomy, removal of tumor-bearing testicle and spermatic cord to the level of the internal inguinal ring.

Question 34

Why is a transscrotal orchiectomy or biopsy contraindicated in testis CA?

Answer 34

- 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.

Question 35

GCTs grow rapidly. Delays in orchiectomy should not be greater than ____.

Answer 35

1-2 weeks

Question 36

Testis-sparing surgery (partial orchiectomy) may be considered ONLY in:

Answer 36

Organ-confined tumors < 2-3 cm, <30% testicular volume, with synchronous or bilateral tumors, OR solitary testis with sufficient androgen production

Question 37

Testis-sparing (partial orchiectomy) has NO ROLE in:

Answer 37

Patients suspected of having a testicular neoplasm with a normal contralateral testis.

Question 38

Benign histology may be encountered in up to ___ of testicular lesions smaller than ___ and long duration ___

Answer 38

80% 3 cm > 6 months

Question 39

Patients with GCNIS who underwent partial orchiectomy should undergo ___ to prevent GCT development.

Answer 39

Adjuvant RT to residual testis at least 20 Gy to prevent GCT development and preserve Leydig cell function (androgen production).

Question 40

Open inguinal biopsy of the contralateral testis considered in patients with:

Answer 40

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%

Question 41

TRUE or FALSE: Preorchiectomy serum tumor marker levels should not be used in management decisions.

Answer 41

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.

Question 42

Most common route of disease dissemination in testicular CA: ___ Exception: ___ which spreads ___

Answer 42

Lymphatic channels to RPLNs ---> distant sites. 70-80% of patients with GCT --> initial site of spread is the retroperitoneum. Except: CHORIOCARCINOMA, which spreads hematogenously.

Question 43

Primary drainage site/landing zone: RIGHT testis tumors: ___ LEFT testis tumors: ___ Pattern of drainage: ___

Answer 43

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)

Question 44

Retroperitoneal LNs ____ in size = suspicious for regional LN metastasis, especially if they are located ___

Answer 44

5-9 mm in size | ANTERIOR to the great vessels

Question 45

TRUE or FALSE: | FDG-PET is useful in the routine evaluation of NSGCT and seminoma at the time of diagnosis.

Answer 45

FALSE. | There is currently NO role for FDG-PET in the routine evaluation of NSGCT and seminoma at the time of diagnosis.

Question 46

IGCCG Risk Classification for Advanced GCT

Answer 46

International Germ Cell Collaborative Group risk stratification: Used to guide choice of chemotherapy for metastatic GCT NOT applicable to patients with relapsed GCT

Question 47

IGCCG NSGCT | Good Prognosis

Answer 47

``` 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% ```

Question 48

IGCCG NSGCT | Intermediate Prognosis

Answer 48

``` 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% ```

Question 49

IGCCG NSGCT | Poor Prognosis

Answer 49

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% ```

Question 50

IGCCG Seminoma | Good Prognosis

Answer 50

``` 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% ```

Question 51

IGCCG Seminoma | Intermediate Prognosis

Answer 51

``` 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% ```

Question 52

IGCCG Seminoma | Poor Prognosis

Answer 52

IGCCG Seminoma Poor Prognosis NO patients classified as poor prognosis!!

Question 53

TRUE or FALSE Seminoma is associated with decreased sensitivity to radiation therapy and platin-based chemotherapy compared with NSGCT.

Answer 53

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.

Question 54

Sex Cord-Stromal Tumors

Answer 54

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 ```

Question 55

Leydig Cell Tumors

Answer 55

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

Question 56

Sertoli Cell Tumor

Answer 56

< 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

Question 57

Granulosa Cell Tumors

Answer 57

Rare Juvenile type: benign, most frequent congenital testis tumor (< 6mos) Adult type: granulosa cell tumors of the ovary Treatment: Testis-sparing if < 3 cm

Question 58

Gonadoblastoma

Answer 58

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

Question 59

Dermoid & Epidermoid Cyst

Answer 59

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

Question 60

Adenocarcinoma of the Rete Testis

Answer 60

``` 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 ```

Question 61

Lymphoma

Answer 61

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

Question 62

Leukemic infiltration

Answer 62

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

Question 63

Paratesticular tumors: Adenomatoid

Answer 63

Mesothelial origin MOST COMMON paratesticular tumor, 75% involves the epididymios Small (0.5-5cm) painless mass Benign Managed by inguinal exploration + Surgical excision

Question 64

Sarcoma

Answer 64

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)