Epidemiology

· 15-35 yrs

— Teratoma 20-30 yrs

— Seminoma 30-40yrs

— Yolk sac younger (90% yolk sac occur <15yrs)

· Incidence

— 3/100000

· Geographical variation

­ NZ, Scandinavia

¯ Africa, Asia

Aetiology

· Maldescended testis – 1:80 inguinal, 1:20 intra-abdominal

— RR20x

· Contralateral testicular tumour

— 2-5% cumulative risk

— risk not­ if Rx with chemo

· Cis, maternal estorgens and prolonged sitting

Pathology

Classification

1°

· Germ cell 85%

— Seminoma 40%

— Non-seminoma

Teratoma 30%

Combined 15%

· Interstitial cell 10%

— Leydig

— Sertoli

· Other

— Lymphoma 5%

2°

Germ cell tumours

· Arise from

— Trophoblasts ß HCG

— Yolk sac cells aFP

· Worse prognosis with presence of yolk-sac or trophoblastic tissue

Classification

WHO Tumours with 1 cell type

Seminoma (have spermatocytic differentiation). 10% have elevated HCG. Any elevation of AFP precludes diagnosis of seminoma.

Typical seminoma -85% seminoma

Spermatocytic seminoma – 10% older age group (55 years). Not associated with Cis

Non-seminomatous germ cell tumour (non-spermatocytic differentiation). 40% have elevated HCG and AFP, 80% have either elevated HCG or AFP

Embryonal carcinoma

Embryonal carcinoma with teratome

Mature termatoma

Choriocarcinoma

Yolk sac tumour

Tumour markers

AFP – produced by foetal liver. High levels in foetal serum. Present in varying degrees in NSGCT.

HCG – Indicates synctiotrophblastic elements.

LDH – correlated with burden of NSGCT

Seminoma

· Grey nodule macroscopically

· Microscopically monotonous sheets of large cells with clear cytoplasm and densely staining nuclei.

· Extrascrotal 1°

— Mediastinum

— Hypothalamus

Teratoma

· Contains >1 germ layer

· Often asymmetrically enlarged

· Cysts of gelatinous or mucinous material with haemorrhagic areas

· Microscopically:

mature teratoma has elements resembling mesoderm, endoderm and ectoderm.

Immature teratoma has sheets of undifferentiated cells

Patterns of metastasis

· Sequential lymphatic

· Right – right aorto-caval nodes at right renal hilum

· Left – left para-aortic nodes at left renal hilum

· Invasion of spermatic cord – external ilac or obturator nodes

· Invasion of scrotum or previous scrotal surgery – inguinal nodes

Staging

TNM

· T

1 Confined to testis & epididymis

2 Confined to testis & epididymis with vascular invasion

o r involvement of tunica vaginalis

3 Invading spermatic cord ± vascular invasion

4 Invading scrotum ± vascular invasion

· N

1 LNM, < 2cm

2 LNM > 2cm,< 5m

3 LNM > 5cm

· S

1 LDH <1.5x & HCG <5000 & AFP <1000

2 LDH 1.5-10x or HCG 500 – 50000 or AFP 1000-10000

3 LDH>10x or HCG > 50000 or AFP > 10000

· M

1a non regional nodal or pulmonary

1b other distant

Stage

· I

A T1

B T2-4

S N0 M0 S1-3

· II

A N1 ± S1

B N2 ± S1

C N3 ± S1

· III

A M1a ±S1

B S2

C S3, M1b

Interstital tumours

· Leydig & Sertoli

· 10% malignant

— Sertoli any age

— Leydig adults only

· Good prognosis

Lymphoma

· More frequent >50yrs

· Diffuse enlargement

· Survival poor if bilateral or other disease

Clinical

· Mass -85%. Mass palpable +/- hydrocele.

— Painless

—    Not separate from testis

—    10% have acute scrotal pain

· Gynaecomastia

— Principally teratoma & sertoli cell tumours – 5%

· Metastatic disease

— Presenting feature in 30% - Lung/Bone/IVC obstruction

Back ache (RPL mets), cough or dysponea, anorexia/nausea/vomiting, bone pain, lower extremity swelling

Ix

· USS

—    Seminoma – well-defined hypo-echoic lesion without cystic areas

—    NSGCT – inhomogenous, calcifications, cystic areas, indistinct margins.

· CT

—    Chest, abdo & pelvis

—    Although CT is the staging Ix of choice the false negative rate is high in terms of assessing retroperitoneal nodal metastasis. The false negative and positive rate depends on the size cut-off for pathological node (usual 10mm). PET is not significantly superior to CT with a similar false negative rate for retroperitoneal disease.

· aFP , ßHCG, LDH

— pre & post op

v Do not do FNA

Rx

v Rx as seminoma & non-seminoma

— Seminoma with ­aFP should be Rx as non-seminoma

Seminoma

· Inguinal orchidectomy

— Clamp cord prior to mobilisation

— If ?D Inguinal exploration & frozen section

— Inguinal vs scrotal approach: ­ LR 0.4%vs 2.9%

· Systemic treatment

—    Stage I – 20% have subclinical mets in retroperitoneum. Receive adjuvant DXT (30Gy in 15; T10-L5)

—    Stage II – A DXT to para-aortic and ipsilateral pelvic nodes or chemo; B Chemo; P Chemo

—    Chemo is 3-4 cycles of BEP

Non seminoma

· Inguinal orchidectomy

For low stage disese (Stage I)

—    Intensive surveilence  (every month for 1 year and then 2 months for second year).

—    30% replapse but if detected early does not affect prognosis

—    Primary adjuvant chemo (2 cycles BEP) if high risk: vascular invasion, embryonal elements, lack of yolk sac elements, lymphatic invasion

—    RLND used in USA a primary adjuvant treatment reduces the risk of relapse to 10%. This requires less intensive follow-up and can be used for poorly compliant patient.

For High stage seminoma (II and III):

BEP chemo: B (Bleomycin- pulmonary fibrosis, raynauds), E (Etoposide – haematological toxicity) P (Cisplatin – 25% loss renal function)

How do you perform inguinal orchidectomy

—    GA. Supine. IV abx. Heparin. TEDS. SCD. Time out. Prepare scrotum, penis and upper thigh.

—    Incision make in skin crease over medial 2/3 of inguinal ligament 2cm above pubic tubercle

—    Open external oblique in the line of fibers

—    Ilioingional nerve is identified and preserved if possible

—    Spermatic cord freed from inguinal canal and clamped with two artery forceps near deep ring. Suture ligate with 0 Vicryl.

—    Using one hand from below and with gentle traction from above, manipulate testis into inguinal canal.

—    Testis is freed from scrotum by blunt dissection outside of the plane of tunica vaginalis.

—    Great care is taken with dividing the last connection (Gubernaculum)

—    Place testicular prosthesis if desired.

—    Haemostais and washout

—    Close external oblique and skin.

Complications

· Oligospermia – sperm storage should be offered to all men having chemo or XRT.

— 2° to chemo

— Many recover

· 2° leukaemias

— assoc with XRT and chemo

· Renal & hearing impairments with chemo, generally recoverable

Prognosis

v Patients with large numbers of mets @ presentation may still be curable

· 15% relapse rate following ingunal orchidectomy alone

Poor prognostic factors

· Liver bone, brain mets

· ­ serum markers

· 1° mediastinal non-seminoma

· large number lung mets

Survival

Good prognosis

· Non-seminoma

— Testis / retroperitoneal 1°, ° non-pulmonary mets, good markers

— 60% non seminoma

— 90% 5yrs

· Seminoma

— Any 1°, ° non-pulmonary mets, normal aFP, any LDH, ßHCG

— 90% seminomas

— 86% 5yrs

Intermediate prognosis

· Non-seminoma

— Testis / retroperitoneal 1°, ° non-pulmonary mets, intermediate markers

— 30% non seminoma

— 80% 5yrs

· Seminoma

— Any 1°, non-pulmonary mets, normal aFP, any LDH, ßHCG

— 10% seminomas

— 72% 5yrs

Poor prognosis

· Non-seminoma

— Mediastinal 1°, o r non-pulmonary mets, o r poor markers

— 10% non seminoma

— 50% 5yrs