Testis Cancer, Anatomy, Embryology Flashcards
Gene that determines gonadal transition to a male
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.
Which cells produce testosterone?
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.
Table of timing of male gonadal development
Normal adult testis size and volume
On average, the normal adult testis measures 4-5cm long, 3cm wide, and 2.5cm deep with volume ranging 12-30ml.
Three types of histologic cells in testis
Seminiferous tubules, Sertoli cells, Leydig cells
Arterial blood supply to testis
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
Left Testicle Lymphatic Drainage
The primary drainage pattern on the left is to the para-aortic and preaortic lymph nodes, followed by the interaortocaval nodes.
Right Testicle Lymphatic Drainage
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!
Layers of the scrotum and spermatic cord encountered during surgical exploration, progressing from superficial to deep
Skin, dartos, external spermatic fascia, cremasteric fascia, cremasteric muscle, internal spermatic fascia, tunica vaginalis (parietal then visceral), tunica albuginea
T staging of testicular tumors
N staging of testicular cancer
M staging of testicular cancer
Serum Tumor Marker Staging
Stage Grouping
Risk Classification for Sem and Non-Sem
Treatment options for stage IA and IB pure seminoma
(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.
AUA Guideline Algorithm for treatment of early testicular cancer
Surveillance for Stage IA and IB Seminoma
Risk factors for predicting relapse
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.
Stage I Seminoma Surveillance NCCN and AUA
Types of testicular cancer
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).
Risk factors for developing testicular cancer
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.
Histologic Subtypes of Testicular Cancer
Germ Cell Tumors:
- Seminoma
- Nonseminomatous Germ Cell Tumors: Embryonal, Choriocarcinoma, Teratoma, Yolk Sac (Endodermal Sinus Tumor)
Does Seminoma produce AFP? bHCG?
NO AFP
5% produce bHCG (because 5% contain syncytiotrophoblasts, which secrete bHCG)
Most common GCT in children/infants?
Yolk Sac (Endodermal Sinus Tumor)
Do Yolk Sac tumors produce AFP? bHCG?
Generally will produce AFP
NEVER bHCG
Classic pathologic finding of Yolk Sac Tumors?
Schiller-Duval bodies
Does choriocarcinoma produce AFP? bCHG?
NEVER AFP
Yes bHCG, usually high
Do pure teratomas produce AFP? bHCG?
Pure teratoma will produce neither, but pure teratoma is very rare in adults
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)
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.
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.
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
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
Staging: Tis
Germ Cell Neoplasia in Situ
Staging: T1
Confined to testis
NO LVI
Can be into epididymis
Can involve tunica albuginea but not vaginalis
Staging: T2
Testis with or without epididymal involvement
+LVI OR into tunica vaginalis
Staging: T3
Into spermatic cord
+/- LVI
Staging: T4
Into scrotum
+/- LVI
Staging: Clinical Nodes
N1
1-5 lymph nodes, all less than 2cm
Staging: Clinical Nodes
N2
> 5 LNs (less than 5 cm)
OR
LN 2-5 cm in size
Staging: Clinical Nodes
N3
LNs >5cm
Staging: M1a
Distant mets
- Nonregional LNs
OR
- Pulmonary nodules/mets
Staging: M1b
Distant mets OUTSIDE of nonregional LNs or lung
Staging: Serum Tumor Markers
S1
AFP - <1k
bHCG - <5k
LDH - <1.5x normal
Staging: Serum Tumor Markers
S2
AFP - 1k-10k
bHCG - 5k - 50k
LDH - 1.5 -10x normal
Staging: Serum Tumor Markers
S3
AFP - >10k
bHCG - >50k
LDH - >10x normal
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
