Testis Cancer, Anatomy, Embryology Flashcards

1
Q

Gene that determines gonadal transition to a male

A

SRY

Under the influence of the SRY gene (sex-determining region of the Y chromosome), in the 7th to 8th week, cells in the genital ridge differentiate into seminiferous tubules containing spermatogonia and Sertoli cells. Without the SRY protein, ovarian follicles form.

The Sertoli cells begin to secrete Müllerian-inhibiting substance (MIS), acting locally and causing the Müllerian ducts to regress between 8-10 weeks, thus contributing to normal male phenotypic development.

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2
Q

Which cells produce testosterone?

A

Leydig cells

In the 9th-10th weeks, Leydig cells differentiate from genital ridge cells in response to SRY protein and are located between the seminiferous tubules. These cells begin to produce testosterone. There is a rise in both serum and testicular testosterone that peaks at 13 weeks before beginning to decline.

Between the 8th and 12th week, testosterone secretion stimulates the virilization of the wolffian ducts into the vas deferens, seminal vesicles, and ejaculatory ducts.

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3
Q

Table of timing of male gonadal development

A
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4
Q

Normal adult testis size and volume

A

On average, the normal adult testis measures 4-5cm long, 3cm wide, and 2.5cm deep with volume ranging 12-30ml.

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5
Q

Three types of histologic cells in testis

A

Seminiferous tubules, Sertoli cells, Leydig cells

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6
Q

Arterial blood supply to testis

A

Three:
1. Gonadal/Testicular
- Arises inferior to SMA, directly off of aorta
2. Cremasteric
- Arises from inferior epigastric artery
- Anastomoses with testicular artery within testis
3. Vasal

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7
Q

Left Testicle Lymphatic Drainage

A

The primary drainage pattern on the left is to the para-aortic and preaortic lymph nodes, followed by the interaortocaval nodes.

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8
Q

Right Testicle Lymphatic Drainage

A

On the right side, primary drainage is to the interaortocaval nodes, followed by the precaval and preaortic nodes.

It is more common for the lymphatic drainage of the right testis, and rare with left-sided tumors, to cross the midline and exhibit bilateral lymph node metastases

Drainage is right to left!

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9
Q

Layers of the scrotum and spermatic cord encountered during surgical exploration, progressing from superficial to deep

A

Skin, dartos, external spermatic fascia, cremasteric fascia, cremasteric muscle, internal spermatic fascia, tunica vaginalis (parietal then visceral), tunica albuginea

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10
Q

T staging of testicular tumors

A
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11
Q

N staging of testicular cancer

A
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12
Q

M staging of testicular cancer

A
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13
Q

Serum Tumor Marker Staging

A
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14
Q

Stage Grouping

A
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15
Q

Risk Classification for Sem and Non-Sem

A
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16
Q

Treatment options for stage IA and IB pure seminoma

A

(i) Surveillance (preferred)
(ii) Retroperitoneal Radiotherapy
(iii) Chemotherapy with carboplatin (1 or 2 cycles)

More than 80% of patients with stage I seminoma are cured with orchiectomy alone, therefore surveillance is the preferred approach, and the disease specific survival for stage I disease is 99% irrespective of the management strategy used.

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17
Q

AUA Guideline Algorithm for treatment of early testicular cancer

A
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18
Q

Surveillance for Stage IA and IB Seminoma

A
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19
Q

Risk factors for predicting relapse

A

In an analysis of over 600 patients, rete testis invasion and tumors ≥ 4 cm were identified as risk factors for predicting relapse.

For patients with 0, 1, or 2 of these risk factors the recurrence rates were 12%, 16%, and 32%, respectively.

NCCN recommends against a risk-adapted approach and supporting surveillance as the preferred strategy for all stage I patients.

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20
Q

Stage I Seminoma Surveillance NCCN and AUA

21
Q

Types of testicular cancer

A

The vast majority are classified as germ cell tumors (95%), while the remaining are predominately sex cord/stromal tumors (mainly Leydig cell and Sertoli cell tumors). Germ cell tumors (GCT) are further designated as seminoma or non-seminoma germ cell tumors (NSGCT).

22
Q

Risk factors for developing testicular cancer

A

Cryptorchidism, personal or family history, intra-tubular germ cell neoplasia (ITGCN).

It is felt that most GCTs arise from ITGCN and its presence is a major risk factor as 50% of men with ITGCN will develop a GCT within 5 years.

23
Q

Histologic Subtypes of Testicular Cancer

A

Germ Cell Tumors:
- Seminoma
- Nonseminomatous Germ Cell Tumors: Embryonal, Choriocarcinoma, Teratoma, Yolk Sac (Endodermal Sinus Tumor)

24
Q

Does Seminoma produce AFP? bHCG?

A

NO AFP
5% produce bHCG (because 5% contain syncytiotrophoblasts, which secrete bHCG)

25
Most common GCT in children/infants?
Yolk Sac (Endodermal Sinus Tumor)
26
Do Yolk Sac tumors produce AFP? bHCG?
Generally will produce AFP NEVER bHCG
27
Classic pathologic finding of Yolk Sac Tumors?
Schiller-Duval bodies
28
Does choriocarcinoma produce AFP? bCHG?
NEVER AFP Yes bHCG, usually high
29
Do pure teratomas produce AFP? bHCG?
Pure teratoma will produce neither, but pure teratoma is very rare in adults
30
What to do for evaluation of initial presentation of testicular mass?
Testicular US - Homogeneous mass more likely to be seminoma - Heterogeneous mass more likely to be NSGCT No role for further imaging OF THE TESTIS at time of presentation Microlithiasis: just recommend routine self-exam Obtain tumor markers at time of diagnosis, prior to any intervention (AFP, LDH, bHCG)
31
AFP: - Half life? - Which testicular cancers produce? - Why else elevated? - What is a true elevation?
5-7 days NOT PRODUCED by seminoma Normal <10 Elevated in 50-80% of NSGCT Embryonal carcinoma and yolk sac tumors produce AFP, seminoma and choriocarcinoma do not. AFP may also be elevated in patients with liver disease, hepatocellular carcinoma, and stomach/pancreas/biliary duct/lung cancers. Mildly elevated AFP may not represent germ cell tumor, thus the decision to treat a patient should not be made for an AFP level < 20.
32
bHCG: - Half life? - Which testicular cancers produce? - Why else elevated? - What is a true elevation?
Half life 24-36 hours Elevated in 20-60% of NSGCT and 15% of seminomas bHCG is elevated in embryonal carcinoma/choriocarcinoma/seminoma. Elevations may also be observed in liver, biliary, pancreas, stomach, lung, breast, kidney, and bladder cancers as well as secondary to marijuana use. Significant hypogonadism may also cause low level elevation of HCG and these patients can be challenged with testosterone injections which normalize their HCG levels.
33
LDH: - Half life? - Which testicular cancers produce? - Why else elevated? - What is a true elevation?
Half life is 24 hours Non-specific marker of GCT Patients should not be treated due to elevated LDH alone
34
Role of miRNA in testicular cancer?
miR-371a-3p is the promising blood-based biomarker Reliably detects all macroscopic GCT histologies, except for teratoma miR-371a-3p holds promise in the following clinical scenarios: 1) patients with inconclusive testicular masses 2) surveillance after orchiectomy for early detection of relapse 3) response monitoring during chemotherapy 4) management of post-chemotherapy residual masses 5) surveillance after curative intent short half-life of <24 hours
35
Staging: Tis
Germ Cell Neoplasia in Situ
36
Staging: T1
Confined to testis NO LVI Can be into epididymis Can involve tunica albuginea but not vaginalis
37
Staging: T2
Testis with or without epididymal involvement +LVI OR into tunica vaginalis
38
Staging: T3
Into spermatic cord +/- LVI
39
Staging: T4
Into scrotum +/- LVI
40
Staging: Clinical Nodes N1
1-5 lymph nodes, all less than 2cm
41
Staging: Clinical Nodes N2
>5 LNs (less than 5 cm) OR LN 2-5 cm in size
42
Staging: Clinical Nodes N3
LNs >5cm
43
Staging: M1a
Distant mets - Nonregional LNs OR - Pulmonary nodules/mets
44
Staging: M1b
Distant mets OUTSIDE of nonregional LNs or lung
45
Staging: Serum Tumor Markers S1
AFP - <1k bHCG - <5k LDH - <1.5x normal
46
Staging: Serum Tumor Markers S2
AFP - 1k-10k bHCG - 5k - 50k LDH - 1.5 -10x normal
47
Staging: Serum Tumor Markers S3
AFP - >10k bHCG - >50k LDH - >10x normal
48
Role of PET CT in testicular cancer
ONLY in seminoma to assess response to chemotherapy/determine if residual masses are active cancer 6-8 weeks after treatment