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!!