TESTICULAR TUMOURS

Dr. Abrar Ahmad

Anatomy of the Scrotum Scrotum: muscular pouch containing testes Testis: a network of tightly coiled

seminiferous tubules that converge and anastamose into efferent tubules

Encapsulated by tunica albuginea Epididymis: a structure formed from merged

efferent tubules, which attaches along the posterior and upper border of the testis

Described as having head, body & tail Vas deferens: tube arising from tail of

epididymis, Passes through inguinal canal and joins seminal vesicle duct to form ejaculatory duct, which passes into prostate gland

Spermatic cord: structure formed by vas deferens, testicular arteries, and veins

Introduction• Although rare, is the most common malignancy

in men in 15-35 yr age group• Delayed diagnosis• Has become one of the most curable solid

tumour– Associated with accurate tumour markers– Origin in germ cells– Capacity to differentiate into histologically more

benign forms– Predictable, systematic pattern of spread– Occurrence in young individuals

Etiology/Risk Factors• Congenital Causes:

Cryptorchidism Klinefelter’s syndrome

• Age: 20-35 years highest risk group• Hormones

Maternal hormone ingestion during pregnancy• History of mumps orchitis, inguinal hernia, hydrocele in childhood -

Atrophy• High socioeconomic status• Testicular cancer contralateral testis• HIV positive.

CRYPTORCHIDISM & TESTICULAR TUMOUR

Risk of Carcinoma developing in undescended testis is

14 to 48 times the normal expected incidence

CRYPTORCHIDISM & TESTICULAR TUMOUR

The cause for malignancy are as follows:• Abnormal Germ Cell Morphology• Elevated temperature in abdomen &

Inguinal region as opposed to scrotum• Endocrinal disturbances

CLASSIFICATIONI. Primary Neoplasma of Testis

A.Germ Cell Tumour (90-95%) B.Non-Germ Cell Tumour

(5-10%)II. Secondary Neoplasms.

III. Paratesticular Tumours.

PRIMARY NEOPLASMS OF TESTIS

Germinal Neoplasms : (90 - 95 %)

Seminomas - 40%(a) Classic Typical Seminoma(b) Anaplastic Seminoma(c) Spermatocytic Seminoma

Teratoma - 25 - 35%(a) Mature(b) Immature

Embryonal Carcinoma - 20 - 25%Choriocarcinoma - 1%Yolk Sac Tumour

PRIMARY NEOPLASMS OF TESTISNongerminal Neoplasms : ( 5 to 10% )

Specialized gonadal stromal tumor(a) Leydig cell tumor(b) Sertoli’s cell tumour(c) Granulosa cell tumour(b) Other gonadal stromal tumor

GonadoblastomaMiscellaneous Neoplasms

(a) Adenocarcinoma of the rete testis(b) Mesenchymal neoplasms(c) Carcinoid

A. AdenomatoidB. Cystadenoma of EpididymisC. Mesenchymal NeoplasmsD. Mesothelioma (Benign & malignant)

SECONDARY NEOPLASMS OF TESTIS

A. Reticuloendothelial NeoplasmsB. Metastases(prostate,lung,colorectal,

renal cell carcinoma,thyroid,breast)PARATESTICULAR NEOPLASMS

SEMINOMA• Typical : 82-85%

ThirtiesSlow growth

• Anaplastic: 5-10%More aggressive, potentially more lethalGreater metastatic potential

• Spermatocytic Seminoma: 2-12 %Cells closely resemble different phases of

maturing spermatogoniaB/L tumours have been reportedExtremely low metastatic potentialFavourable prognosis

NON SEMINOMATOUS GERM CELL TUMOURS• Embryonal carcinoma

Generally discovered as a small, rounded but irregular mass invading the tunica vaginalis

• Choriocarcinoma May occur as palpable nodule or normal testis Central hemorrhage High metastatic potential (blood & lymphatic) Most malignant tumor Produces HCG

NON SEMINOMATOUS GERM CELL TUMOURS• Teratoma

Contains more than one germ cell layers in various stages of maturation and differentiation

Grosssly large, lobulated, nonhomogenous tumours

Microscopically, cystic & solid componenets• Yolk cell tumours

Most common testicular tumour in infants & children

80% confined to testis at time of diagnosis

Pathogenesis & Natural History of Testicular Tumour

Course of Spread of Germ Cell Tumours are predictible once histology of Tumour confirmed

Local invasion of epidydimis or spermatic cord is hindered by tunica albugenia

Lymphatic Spread has a set pattern depending on site of tumour

Seminoma may have non-seminomatous metastasis

High Grade Tumours spread by both Vascular invasion & via Lymphatics

Pattern of Spread of Germ Cell Tumour

Right sided tumours- intraaortocaval Left sided tumours – left paraaortic &

preaortic nodes Then cephalad to cisterna chyli, thoracic duct

and supraclavicular (usually left) Epidydimis- External iliac chain

CLINICAL FEATURES

• Nodule/Painless Swelling of One Gonad

• Dull Ache or Heaviness in Lower Abdomen

• 10% - Acute Scrotal Pain

• 10% - Present with Metatstasis

- Neck Mass / Cough / Anorexia / Back Ache

• 5% - Gynecomastia

• Infertility

PHYSICAL EXAMINATION

• Bimanual Palpation of testis and paratesticular structures

• Abdominal examination

• Lymph nodes

• Chest

All patients with a solid, Firm Intratesticular Mass that cannot be

Transilluminated should be regarded as Malignant unless otherwise proved

WAKE UP

Differential Diagnosis

• Metastasis from prostate, lung, or melanoma.

• Epididymitis• Lymphoma

• Spermatocele• TB, gumma• Leukemia

Clinical Staging of Testicular Tumour

Staging A or I - Tumour confined to testis.

Staging B or II - Spread to Regional nodes.

IIA - Nodes <2 cm in size or < 6 Positive NodesIIB - 2 to 5 cm in size or > 6 Positive Nodes IIC - Large, Bulky, abd.mass usually > 5 to 10 cm

Staging C or III - Spread beyond retroperitoneal Nodes or Above Diaphragm or visceral disease

To properly Stage Testicular Tumours following are pre-requisites:

(a) Pathology of Tumour Specimen

(b) History

(c) Clinical Examination

(d) Radiological procedure - USG / CT / MRI / Bone Scan

(e) Tumour Markers - HCG, AFP

Requirements for staging

TNM Staging of Testicular Tumour

T0 = No evidence of TumourT1s = Intratubular, pre invasiveT1 = Confined to TestisT2 = Limited to testis and epididymis with vascular/ lymphatic invasion or tumour extending through Tunica Albuginea with involvement of tunica vaginalisT3 = Invades Spermatic Cord with/without vascular/ lymphatic invasionT4 = Invades Scrotum with/without vascular/ lymphatic invasion

N1 = Single or multiple < 2 cmN2 = Multiple < 5 cm / Single 2-5 cmN3 = Any node > 5 cm

Epididymis or Scrotal skin – Lymph drainage to Inguinal Nodes

Investigation

1. Ultrasound - Hypoechoic area2. Chest X-Ray - PA and lateral views3. CT Scan4. MRI4. Tumour Markers

- AFP- HCG- LDH- PLAP(placental alkaline phosphatase)

Left RightAxial CT Section demonstarating - Left Hydronephrosis, due to large Para-Aortic Nodal Mass from a Germ cell tumour

Tumour Markers

TWO MAIN CLASSES• Onco-fetal Substances : AFP & HCG• Cellular Enzymes : LDH & PLAP

( AFP - Trophoblastic Cells

HCG - Syncytiotrophoblastic Cells )

AFP –( Alfafetoprotein )

NORMAL VALUE: Below 16 ngm / mlHALF LIFE OF AFP – 5 and 7 days

Raised AFP : • Pure embryonal carcinoma• Teratocarcinoma • Yolk sac Tumour • Combined Tumour

REMEMBER: AFP Not raised is Pure Choriocarcinoma or Pure Seminoma

HCG – ( Human Chorionic Gonadotropin )

Has and polypeptide chain

NORMAL VALUE: < 1 ng / ml HALF LIFE of HCG: 24 to 36 hours

RAISED HCG - 100 % - Choriocarcinoma 60% - Embryonal carcinoma 55% - Teratocarcinoma25% - Yolk Cell Tumour7% - Seminomas

Lactate Dehydrogenase (LDH)• Nonspecific tumor marker but is a useful prognostic

indicator• Indicator of tumor burden

ROLE OF TUMOUR MARKERS

• Helps in Diagnosis - 80 to 85% of Testicular Tumours have Positive Markers

• Most of Non-Seminomas have raised markers• Only 10 to 15% Non-Seminomas have normal marker

level • After Orchidectomy if Markers Elevated means

Residual Disease or Stage II or III Disease

• Elevation of Markers after Lymphadenectomy means

a STAGE III Disease

ROLE OF TUMOUR MARKERS cont...

• Degree of Marker Elevation Appears to be Directly Proportional to Tumour Burden

• Markers indicate Histology of Tumour: If AFP elevated in Seminoma - Means Tumour has Non-Seminomatous elements

• Negative Tumour Markers becoming positive on follow up usually indicates -Recurrence of Tumour

• Markers become Positive earlier than X-Ray studies

PRINCIPLES OF TREATMENT

• Treatment should be aimed at one stage above the clinical stage

• Seminomas- Radio-Sensitive. Treat with Radiotherapy.• Non-Seminomas are Radio-Resistant and best treated by

Surgery

• Advanced Disease or Metastasis - Responds well to

Chemotherapy

PRINCIPLES OF TREATMENT

• Radical INGUINAL ORCHIDECTOMY is Standard first line of therapy

• Lymphatic spread initially goes to RETRO-PERITONEAL NODES

• Early hematogenous spread RARE• Bulky Retroperitoneal Tumours or Metastatic Tumors

Initially “DOWN-STAGED” with CHEMOTHERAPY

Treatment of Seminomas

Stage I, IIA, IIB –

Radical Inguinal Orichidectomy followed by radiotherapy to Ipsilateral Retroperitonium & Ipsilateral Iliac group Lymph nodes

Bulky stage II and III Seminomas - Radical Inguinal Orchidectomy is followed by Chemotherapy

Treatment of Non-Seminoma

Stage I and IIA: RADICAL ORCHIDECTOMYfollowed by RETROPERITONEAL LYMPH NODES DISSECTION

Stage IIB: RPLND with possible ADJUVANT CHEMOTHERAPY

Stage IIC and Stage III Disease:Initial CHEMOTHERAPY followed by SURGERY for Residual Disease

Radical Orchiectomy

• Inguinal approach• Testicle and spermatic

cord are excised then sent for pathologic staging.

Retroperitoneal Lymph Node Dissection

• RPLND primary treatment (NSGCTs)

• Remove abdominal lymph nodes

Limits of Lymph Nodes Dissection For Right & Left Sided Testicular Tumours

Chemotherapy

BEP: (Bleomycin, Etoposide, Cisplatin)

2-4 cycles 21d intervals (4 most common)

EP: (Etoposide, Platinol)

4 cycles 21d intervals

Salvage Thearpy

• No initial complete response• VIP: (Etoposide, Ifosamide,Mesna, Platinol)

3-4 cycles 21d intervals

• High-dose chemotherapy with autologous bone marrow transplantation in selected patients with bulky disease

Complications

• Pulmonary toxicity: Bleomycin keep total dose under 400 units.

• Nephrotoxicity: Cisplatin- decreased CrCl: Dosed based on CrCl

• Neurologic: Cisplatin- Ototoxicity• Cardiovascular: HTN, MI, Angina• Secondary Malignancies: Etoposide

Follow up– physical examinations, chest radiographs and

serum tumor markers– CT scans detect recurrence in the

retroperitoneum and chest – Follow-up protocols vary by institution, type,

stage and treatment

Recommended Exams

• Every 2-3 months 1st yr.• Every 3-6 month 2nd yr.• Every 6 month remainder 5 yrs.• CTscans: 3-6 months 1st yr. then annually• Men at high risk: Annually with self-exam

monthly

Prognosis

Seminoma (at 5 years)• I: 98% • IIA: 92-94%• IIB-III: 33-75%

NSGT (at 5 years)• I: 96-100%• IIA: >90%• IIB-III: 55-80%

CONCLUSION

• Improved Overall Survival of Testicular Tumour due to Better Understanding of the Disease, Tumour Markers and Cis-platinum based Chemotherapy

Thanks