Testicular Tumours

-Dr. Shubham Lavania21/10/2016

Introduction Testicular tumors are rare.

1 – 2 % of all malignant tumors.

Most common malignancy in men in the 15 to 35 year age group.

Benign lesions represent a greater percentage of cases in children than in adults.

Most curable solid neoplasm

• Age - 3 peaks 2 – 4 yrs 20 – 40 yrs above 60 yrs

• Testicular cancer is one of the few neoplasms associated with accurate serum markers.

• Most curable solid neoplasms and serves as a paradigm for the multimodal treatment of malignancies.

Improvement in Survival

Effective diagnostic techniques

Improved tumor markers

Multi-model treatment

Surgical

Radiotherapy

Multi-drug chemotherapy regimens

Mortality

before 1970 – 50 %

1997 – 5 %

AETIOLOGY OF TESTICULAR TUMOUR

• Cryptorchidism • Intersex disorder – Klinefelter’s syndrome• Testicular atrophy• Trauma- prompts medical evaluation • Chromosomal abnormalities - loss of chromosome 11, 13, 18, abnormal

chromosome 12p.

• Sex hormone fluctuations, estrogen administration during pregnancy

• Race • Carcinoma in situ• Previous testicular cancer

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

2. Embryonal Carcinoma - 20 - 25%

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

4. Choriocarcinoma - 1%

5. Yolk Sac Tumour

Germ cell tumors

Non Germ Cell Tumors1. Specialized gonadal stromal tumor

(a) Leydig cell tumor(b) sertoli cell tumor

2. Gonadoblastoma

3. Miscellaneous Neoplasms(a) Carcinoid tumor

(b) Tumors of ovarian epithelial sub types

Age wise incidence of testicular tumour

Tumour Type Age group (years)1. Seminoma 35-402. Pure Teratoma Pediatric age group3. Embryonal CA 25-304. Chorio CA 25-355. Yolk sac Tumour infancy & child hood6. Mixed terato CA 25-30 7. Lymphoma > 50

Germ cell tumors

Favourable outcome - GCT

Sensitive to both

Radiotherapy

Chemotherapy

Differentiation

Rapid rate of growth

Young – no co-morbid

Extra Gonadal Germ Cell Tumors (EGCT)

Prognosis is ½ GCT

Seminoma

The commonest variety of testicular tumourAdults are the usual target (4th and 5th decade);

never seen in infancyRight > Left TestisStarts in the mediastinum: compresses the

surrounding structure.Patients present with painless testicular mass 30 % have metastases at presentation, but only

3% have symptoms related to metastases

• Serum alpha fetoprotein is normal• Beta HCG is elevated in 30% of patients with

Seminoma• Classification

a) Typicalb) Anaplasticc) Spermatocytic

Anaplastic

5% - 10

Middle age

Aggressive - lethal

Greater mitotic activity

Higher local invasion

Higher metastatic potential

Higher rate of β

-HCG production

Inguinal orchidectomy +

Radiation

Spermatocytic

2% - 12% of seminomas

Old age > 50 yr

Extremely low metastatic potential

Good prognosis

Typical/ Classical

82% - 85%

Middle age

PLAP – 90%

Syncytiotrophoblsts – ↑Beta HCG (10%)

Very slow growth

Inguinal orchidectomy + Radiation

Macroscopically:Characterized by a

circumscribed lobular gray white fleshy tumor that have areas of necrosis & hemorrhage

Cut surface in homogenous and greyish white or pinkish in colour

• Microscopically:Typical seminoma Cells have

round to oval nuclei with one to several nucleoli & clear to eosinophillic cytoplasm.

Cell borders are well defined arranged in solid nests separated by fibrous septa.

Active lymphocytic infiltration in 80% cases.

Strongly positive for placental Alkaline phosphatase (PLAP)

Embryonal Carcinoma

2nd most common germ cell tumorPresent in majority of mixed germ cell tumors Most men present in their 20s to 30s with a

testicular mass Highly malignant tumours; may invade the cord

stucturesHigh degree of metastasisSerum AFP is normal , & beta HCG is elevated in

60 % of cases

Macroscopically:Tan to yellow neoplasms

(fleshy tumor) that exhibit large areas of hemorrhage and necrosis.

• Most undifferentiated; capacity to differentiate to other NSGCT within primary or mets

Microscopically:Undifferentiated malignant cells

with crowded pleomorphic nuclei

Solid sheets,PapillaryGlandularTubular arrangement of cells

ChoriocarcinomaA rare and aggressive tumour (5yrs survival is 5%)Typically elevated hCGPresents with disseminated diseaseMetastasis to lungs and brainPrimary is very small and often exhibit NO TESTICULAR

ENLARGEMENTSmall palpable nodule may be present.Prone to hemorrhage, sometimes spontaneous (lungs and

brain)Catastrophic hemorrhage immediately after chemotherapy;

Macroscopically:Primary lesion may be a

hemorrhagic or a clotted mass in which bits of grey tumor can be seen

Presents as nodules• Microscopically:

Consists of both syncitiotrophoblast and cytotrophoblast

Prominent areas of hemorrhage and necrosis.

Yolk Sac Tumour

Most common germ cell tumor ( & most common testicular tumor ) in children, where it occurs in its pure form.

In adults, it is unusual in pure form, but is found approx. 50 % of mixed germ cell tumors.

Testicular mass the most usual presentation.Always produce AFP, never hCGEasily detectable, lower relapse

Macroscopically:White to tan masses, with myxoid & cystic changes

• Microscopically:Reticular network of medium sized cuboidal

cellswith cytoplasmic and extracytoplasmic eosinophil, hyaline like goblets (84%)

Glandular, papillary or microcystic patternSchiller-Duval bodies are characteristic

TERATOMA

Teratoma in greek means “monster tumor”Occurs in its pure form with a mean age of

diagnosis at 20 monthsIn adults, occur as a component of mixed germ

cell tumor & is identified in > 47 % of mixed tumors.

Pure teratomas are uncommon.Normal serum markers.

◦Mildly elevated AFP levels

Macroscopically:Largely depends on elements within it with solid & cystic areas

Microscopically:Contain more than one germ cell layers(ectoderm, endodermand

mesoderm).Range from “mature” with well differentiated tissue to “immature” with

undifferentiated primitive tisuue.Composed of somatic type of tissues that include enteric type glands,

respiratory epithelium, cartilage, muscles, hair etc.Immature Teratomas contain immature neuroepithelium, blastema or

cellular stroma.Can give rise to carcinoma, such as adenocarcinoma , or sarcoma, such

as rhabdomyosarcoma.

• Growing Teratoma Syndrome:May grow uncontrollably, invade the surrunding

tissueand become unresectable• Teratoma with malignant transformation

Rarely teratoma may transform into a somatic malignancy such as rhabdomyosarcoma, adenocarnoma or primitive neuroectodermal tumour

Cut surfaceVariably sized cysts

Gelatinous, mucinous,

hyalinized material

Intersposed solid islands –

cartilage/ bone/pancreatic/

liver/ intesttinal/ muscle/

neural/ connective tissue

Secondary Tumors of Testis• Lymphoma – most common secondary tumor - most common testicular tumor in patients above 50

years - most common variety is histiocytic • Leukamic Infilteration of testis -primary site of relapse after ALL remission -occurs mainly in the interstitial space -biopsy for diagnosis - no orchidectomy - testicular irradiation for treatment• Metastases to testis - rare cases reported

Tumors of adnexa / Paratesticular tissue

• Adenomatoid tumor -most common paratesticular tumor -benign in nature• Mesothelioma -metastatic in 15% cases to inguinal lymph nodes• Cystadenoma - bilateral cases are associated with Von Hippel Lindau

syndrome• Rhabdomyosarcoma - most commonly seen in second decade of life

Intratubular Germ Cell Neoplasia (ITGCN)

Adjacent to germ cell tumor: 98% •Cryptorchidism: 2-8% •Prior germ cell tumor (contralateral testis): 5% •50% risk of developing GCT in 5y •Treat with observation, XRT (20 Gy) or orchiectomy •Chemo reduces risk but still 25% - 45% risk of GCT at 10y

(Christensen et al. Ann. Oncol. 1998) •Can be precursor to all types of GCT except spermatocytic

seminoma

Metastasis

1. Direct Spread: This spread occurs by invasion. Whole of testis in involved and restricted Tunica albuginea is rarely penetrated May be crossed by “blunder biopsy” Scrotal skin involvement Fungation on the anterior aspect Spread to spermatic cord and epidedymis may

occur : points towards bad prognosis

2. Lymphatic spread:Seminoma metastasize exclusively

through lymphaticsThey drain primarily to para-aortic

lymph nodes in the region of origin of tetsticular arteries

Left supraclavicular fossa through the thoracic duct

Lymph from medial side of testes run along the artery to the vas to drain to nodes at the bifurcation of common iliac

No inguinal nodes until scrotal skin involvement

3. Blood Spread NSGCT spread through blood route Lungs, liver, bones and brain are the usual sites

usually involved

Chemo and radiation sensitive Capacity to differentiate Consistent pattern of metastasis Ability to produce marker substances (AFP/HCG) NSGCT: unique potential for teratomatous differentiation High growth rates 10-30 days

Retroperitoneum is usually the first and only site of metastatic disease

Landing zones for right-sided tumors: Interaortocaval, precaval lymph nodes

Landing zones for left-sided tumors: Para-aortic, left hilar lymph nodes

Right to Left Crossover extremely common

GCT – Unique Features

Clinical Features / Presentaion

1. Due to primary tumora) Painless testicular lumpb) Sensation of heaviness if size > than 2-3 timesc) Rarely dragging pain is complained of (1/3rd

cases)d) May mimic epidedymo-orchitise) Sudden pain and enlargement due to

hemorrhage mimicking torsionf) History of trauma (co-incidental

2. Due to metastasis Abdominal or lumbar pain (lymphatic spread) Mass in epigastrium Dyspnoea, hemoptysis and chest pain with lung mets Jaundice with liver mets Hydronephrosis by para-aortic lymph nodes

enlargement Pedal oedema by IVC obstruction Troiser’s sign

Differential Diagnosis • Testicular torsion

• Epididymitis, or epididymo-orchitis

• Hydrocele, • Hernia, • Hematoma, • Spermatocele, • Syphilitic gumma .

Investigations

1. USG testes: gold standard2. Tumor markers/ hormones

a) AFPb) Beta hCG

3. Chest radiography4. USG abdomen5. CT abdomen6. MRI: intra-abdominal and intra-thoracic secondaries7. IVP and RFT : obstruction on ureters

Radiological work up

Plain X-Ray

chest:

Metastasis

USG : Hypoechoic relative to the surrounding parenchyma

Seminoma

• Seminomas are well defined within the tunica

albuginea and homogeneously hypoechoic

Embryonal cell cancers

• Embryonal cell cancers are

heterogeneous.

• The borders of the tumor are

less distinct.

• More aggressive in behavior.

• The tunica albuginea may be

invaded

Yolk Sac Tumor

• Imaging findings are

nonspecific,especially in

children, in whom the only

finding may be testicular

enlargement without a defined

mass.

Teratoma

• Well-circumscribed complex

masses. a common feature and

may be a

• Cysts are anechoic or complex,

depending on the cyst

contents (ie, serous, mucoid,

or keratinous fluid)

• Choriocarcinomas are often

heterogeneous with multiple

internal calcifications present.

• Leydig and Sertoli

cell, are generally

well defined and

hypoechoic.

• Calcifications are

frequently

described.

Testicular lymphoma generally appears as discrete hypoechoic lesions, which may completely infiltrate the testicle & epididymis

“Burned-out" Germ Cell Tumor

• The patient may present with

widespread metastases even though the

primary tumor has involuted.

• These tumors are clinically occult, with

the testis being normal to small upon

palpation.

• These primary tumors have a variable

appearance. They are generally small

and can be hypoechoic, hyperechoic, or

merely an area of focal calcification.

Clinical Staging TNMS

• Findings at Inguinal Orchiectomy Histology, size, extent of invasion, LVI

• •Imaging Chest and Retroperitoneum • CT scan with IV contrast • PET CT more accurate for seminoma rather than NSCGT

• •Serum Tumor Markers AFP, bHCG , LDH

Serum Markers

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

HCG - Syncytiotrophoblastic Cells ( PLAP- placental alkaline phosphatase, & LDH lactic acid

dehydrogenase)

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

Raised AFP : • Pure embryonal carcinoma• Teratocarcinoma • Yolk sac Tumor • Combined tumors,• AFP not raised in pure choriocarcinoma , & in 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

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

• 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

LDH HCGMiu/ml

AFPNg/ml

S0 _< N <N <N

S1 <1.5 x N < 5000 < 1000

S2 1.5-10x N 5000 to 50000

1000 to 10000

S3 >10x N > 50000 >10000

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

• Transscrotal biopsy is to be condemned.

• The inguinal approach permits early control of the vascular and lymphatic supply as well as en-bloc removal of the testis with all its tunicae.

• Frozen section in case of dilemma

Treatment of SeminomasStage I, IIA, ?IIB – Radical Inguinal Orchidectomy followed by radiotherapy to Ipsilateral Retroperitonium & Ipsilateral Iliac group Lymph nodes (2500-3500 rads)

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

Testes sparing surgery •Controversial •Mass <2cm •Simultaneous bilateral tumors •Solitary testicle with normal testosterone •Biopsy adjacent parenchyma (80% ITGCN) •Can treat remaining testicle with 20Gy of XRT

Scrotal violation

• Local recurrence higher (2.9% vs 0.4%) (Capelouto et al. J. Urol. 1995)

• •Seminoma – extend radiation portal to include groin and scrotum area

• •NSCGT – excise scar and cord remnant • •Extensive groin resection or hemiscrotectomy

not required especially after chemo

Treatment of Non-SeminomaStage 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

Lymph Nodes Dissection For Right & Left Sided Testicular Tumours

Lymphatic drainage

• The primary drainage of the right testis is within the interaortocaval region.

• Left testis drainage , the para-aortic region in the compartment bounded by the left ureter, the left renal vein, the aorta, and the origin of the inferior mesenteric artery.

• Cross over from right to left is possible.

Retroperitoneal lymph node dissection

Rationale for RPLND:The retroperitoneum is the most common site of occult metastasis15-25% of retroperitoneal teratoma, resistant to cheotherapyLow risk of Abdomino-pelvic recurrence no need for long term

surveillance after bilateral RPLNDOffers high cure ratesThe long term survival approaches 100% with RPLND + adjuvant

chemotherapyDisadvantage:

Experienced surgeonMajor surgical procedure

STANDARD CHEMOTHERAPY FOR NON-SEMINOMATOUS GERM CELL TUMOURS

Chemotherapy Toxicity

BEP -Bleomycin Pulmonary fibrosis

Etoposide (VP-16) MyelosuppressionAlopeciaRenal insufficiency (mild)Secondary leukemia

Cis-platin Renal insufficiencyNausea, vomitingNeuropathy

PROGNOSIS

Seminoma Nonseminoma

Stage I 99% 95% to 99%

Stage II 70% to 92% 90%

Stage III 80% to 85% 70% to 80%

SurveillanceRationale for surveillance:

70-80% patients of stage I are cured by orchidectomy alone

No need of chemotherapy in majority of the patientsThe disadvantages being:

Higher risk of relapseNeed for long term surveillance (>5yrs)Potential for secondary malignancies by surveillance CTMore intensive therapy required in cases of relapse than

primary chemotherapy

“I always had the size difference there, but I didn’t know…I would’ve still been waiting

if it hadn’t started hurting, it just got so painful I couldn’t sit on my bike anymore.”

-Lance Armstrong

Yuvraj Singh –extra gonadal seminoma

THANK YOU!!