Testicular Cancers Flashcards
Etiology of testicular cancer
Congenital
- 3-14 times more likely in undescended testes
- Abnormal germ cell morphology
- Gonadal dysgenesis
- Elevated temperature
- Hormonal disease
- Interferece with blood supply
Etiology of testicular cancer
Aquired
- Trauma
- Hormonal fluctuation
- Infections→MUMPS induced atrophy
- in addition to non specific infections
Testicular tumors
Risk factors
- Cryptorchidism
- 10% of tumors with the risk increasing the higher up the testes are in the abdomen
- Genetics
- Whites are 5X more succeptible than blacks
- SIblings of patients are 10X more at risk
- Kleinfelter syndrome
- Li-Fraumeni syndrome
- Prior testicular germ cell/intratubular tumor
Genetic marker for all germ cell tumors
Isochrome of the short arm of ch 12 ie i12p
Genetic marker for Intratubular germ cell tumor
66% have alteration in p53 locus
Familial cases are linked to
- Tyrosine kinase receptor→KIT and BAK
- involved in gonadal development
- Transcription factors→OCT3/4 and NANOG
- maintain pluripotent stem cells
Incidence of testicular cancer
AGE
Most common solid tumor 20-30
RACE
Whites are 4-5 times more likely
SIDE
Right>left
SES
High SES are twice as likely
Geographical
Highest in Scan ger and swis
Intermediate in UK and US
Low in africa and asia
Lymphoma common in which age group
>50
Yolk sac tumor common in which age group
Infancy and childhood
Pure teratoma common in which age group
Pediatric
Lymphatic spread of RIGHT tumor
Inter aortocaval at L2 →precaval→preaortic→right common iliac→right external iliac
Left testicular cancer lymphatic spread
paraaortic at renal hilum→preaortic→common iliac→left external iliac
Blood metastatsis
- Lung
- Liver
- Brain
- Bone
- Kidney
- Adrenal
- GIT
- Spleen
Haematological investigatons
- Hb
- Blood urea or serum creatnine
- LFT
Tumor markers
- AFP (elevated in NSGCT ONLY)
- Beta-HCG (elevated in NSGCT and SGCT)
- LDH (elevated in NSGCT and SGCT)
Scrotal ultrasound in testicular cancer
- Homogenous
- Hypoechoic
- Itratesticular mass
Investigations for staging
CXR
CT/MRI of abdomen
Boden and Gibbs
Stage 1(A)
- Confined to testis
- NO spread to capsule nor spermatic cord
Boden and Gibbs
Stage 2 (B)
- Clinical/radiological evidence of spread beyond testis but WITHIN REGIONAL LN
B1 <2cm
B2 2-5cm
B3 >5cm
Boden and Gibbs
Stage 3 (C)
VIsceral disease ie above diaphragm
Incidenc of testicular tumors
- <1% of malignancies in males; hughly curable regardless of stage
- 95% are germ cell tumors
- 5% sex cord stromal cells
- bening mostly
- maybe associated withwith hormonal syndromes
Intratubular germ cell neoplasia
IGCN
- In situ stage of germ cell neoplasia
- Seen in 90-100% of testes adjacent to germ cell tumor
- Less often in childhood yolk sac and teratomas
Germ Cell Tumors
- Seminoma
- Embryonal carcinoma
- Yolk sac tumor
- Choriocarcinoma
Sex cord stroma
- Leydig cell tumor
- Sertoli cell tumor
Mixed germ cell- gonadal stromal tumors
Gonadoblastoma
- rare
- associated with testicular dysgenesis
- cryptorchidism
- hypospadias
- poor sperm quality
Seminoma
Epidemiology
- Most common tumor in 25-29 yrs
- Account for 50% of germ cell tumors
- 1-2% bilateral
- 15% are bilateral if both testes are undescended
NOTE: identical to ovarian dysgerminoma
Seminoma
Origin
Arises from intratubular germ cell neoplasia
EXCEPT
Adult spermatocytic seminoma variant
Seminoma
Genetics
- Isochrome 12p
- Express OCT3/4 and NANOG
- 25% have KIT activating mutations
Seminoma
Gross description
- Bulky
- Homogenous
- Grey-white
- Well circumscribed
- Lobulated, bulging surface
- NO (usuallly)
- hemorrhage
- cystic changes
- extensive necrosis
- INASION
- <10% invade tunica albuginea
- rarely extend to epididymis, spermatic cord, scrotal sac
Seminoma
Microscopic description
- Sheets of uniform tumor cells
- Divided into poorly demarcated lobules
- by delicate fibrous septa
- Lobules contain lymphocytes and plasma cells
- Cells are
- large
- round-polyhedral
- distinct cell membranes
- abundant clear/watery cytoplasm
- large central nuclei
- 1-2 irregular elongated nucleoli
- minimal mitotic figures
Seminoma
Positive for
- KIT
- OCT4
- Placental alkaline phosphatase (PLAP)
Embryonal Carcinoma
Epidemiology
- Pure tumors: 2% of germ cell tumors
- 85% mixed with seminoma
- 65% already met at time of diagnosis
- frequent extension though tunica albuginea to epidiymis and cord
Embryonal Carcinoma
Gross appearance
- Replace only small portion of testes
- Variegated or pale gray
- Poorly demaracted
- Hemorrhage
- Necrosis
Embryological Carcinoma
Markers
OCT3/4
PLAP
CD30
CK
NEGATIVE FOR KIT
Embyological Carcimoma
Histological appearance
- Solid
- Pseudoglandular, alveolar, tubular or papillary
- Primitive epithelial type
- HIgh grade features
- prominent nucleoli
- indistinct cell borders
- nuclear overlapping
- Pleomorphism
- Frequent mitoses
Yolk sac Tumor
Epidemiology
- Most common testicular tumor at age _<_3
- oftern pure→good prognosis
- In adults→ part of mixed tumor→prognosis of embryonal carcinoma
Yolk sac tumor
Marker
>95% positive for alpha feto protein
Yolk sac tumor
Gross
- Non-encapsulated
- Homogenous
- Yello-white
- Mucinous
- Soft
- Multicystic
Yolk sac tumor
Microscopic features
- Lace like→reticular
- Papillary
- Cord like pattern of cuboidal/elongated cells
-
Schiller Duval Bodies
- 50%
- central capillay
- visceral and parietal layer of cells resembling primitive glomeruli
- Eosinophilic hyaline globules
- AFP
- a1 antitrypsin
NOTE: Intratubular germ cel neoplasia may be seen after puberty
Teratoma
Epidemiology
- 2-3% of germ cell tumors of adults
- 2nd to yolk sac in children
- 45% mixed with other GCTs
- Benign in prepubertile
- Malignant postpubertile
Teratoma
Gross appearance
- Contain cellular components derived from 2-3 germ cell layers
- If contains all three→mature
- Large
- Multinodular
- Heterogeous
- solid
- cartilaginous
- cystic
- May have hair, bone, teeth
Immatrure teratoma
Histo
- Neuroepithelium
- foci resembeling embryo/fetal structures
- cytological atypia
- includes primitive neuroectoderm
- poorly formed cartilage
- neuroblast
- loose mesenchyme
- primitive glandular structures
- High vs low grade
- based on cellularity and mitotic activity
Choriocarcinoma
Epidemiology
- 0.3% to 1% of GCTs
- pure→FATAL
- gestational CC→curable with chemo
- mixed→98%
*
Choriocarcinoma
Metastasis
- Present with metastasis from get go
- liver
- lung
- brain
- mediastinum
- retroperitoneum
NORMAL TESTIS or small tumor
HIGH SERUM HCG
Choriocarcinoma
Gross
- hemorrhagic
- necrotic mass
Choriocarcinoma
Micro
- Hemorrhage
- Necrosis
- Cytotrophoblast
- polygonal/round cell
- distict cell border
- clear cytoplasm
- single bland nucleus
- Syncytiotrophoblast
- Large
- multinucleated
- eosinophilic cytoplasm
- INTRATUBULAR GERM CELL N. common in adj testis
Clinical aspect of Sex cord-stromal tumors
- Non germinative stromal cells
- Leydig mosty common
- Some in context of AIS
- tumor like lesion as part of syndrome
- Uncommon in adults
- 30% of tumors of infants, cjildren
- Wide range and clinically distinct
- Biologically distinct
Leydig cell tumor
- 1-3%
- 10% malignant
- Produce T, DHT, Androstendione and estrogen
- Present with precocious puberty or gynecomastia
- Most often present with testicular swelling
- Well circumscribed
- encapsulated
- homogenous yellow or mahogany
Leydig cell tumor histo
Reinke crystalloids
- Solid nests of uniform cells
- Vesicular round nuclei
- Prominent nucleoli
- Well developed eosiniphilic cytoplasm
Sertoli cell tumor
- 1% in all age groups
- Occurs in children 15% of cases and middle age adults
- 10% malignnat
- Part of AIS, Carney’s Complex, Peutz-Jegher’s syndrome
- Present with feminization and gynecomastia
- 25%
-
Gross
- spherical
- lobulated
- well circumsribed
- tan yellow or grey
Sertoli cell tumor
Micro
- Arranged in solid or hollow tubules separated by basement membrane
- Cytoplasm
- eosinophilic to vacuolated due to lipid
- Bland and uniformly round
- oval or elongated nucle
- NO
- prominent nucleoli
- nuclea grooves
- inclusions
- RARE mild nuclear atypia and pleomorphism