Testicular Pathology

John Higgins, MD
Professor of Pathology
Stanford University School of Medicine
 Medical Testicular Problems
Cryptorchidism Torsion
Associated with
Neonatal
Infertility
No anatomic defect
Tumors
Treated by orchiopexy Adult
Inflammatory disorders Due to increased
mobility bilaterally
Epididymis TB,
gonorrhea Miscellaneous
Testis syphilis Hydrocele
Granulomatous orchititis
Spermatocele
Mumps orchitis
varicocele
Testicular Tumor Objectives

Subtypes
Prognosis
Age
Stage
General principles of
treatment
 Testicular Tumors
Surface Epithelial
(malignant)

Germ Cell Sex Cord-Stromal

(usually benign)
95%
(Malignant)
 Germ Cell Tumors

Age:
Most common in 15-34 year-olds
Presentation:
Testicular mass
Consequences of metastatic disease
Prognosis:
Excellent with cisplatin based chemotherapy
 Germ Cell Tumors

Risk factors:
Cryptorchidism
Undescended testes
10% of all germ cell tumors
Related to position vs
development
Testicular Dysgenesis Syndrome
(TDS)
Testicular feminization
Klinefelter syndrome
Genetic factors?
Familial clustering
 Germ Cell Tumors

Genetic changes
i(12p) is found in almost all germ cell tumors
of adults, regardless of subtype
 Germ Cell Tumor Classification
Pure Seminoma (Dysgerminoma)
Non-Seminoma
Embryonal carcinoma
Yolk sac tumor (Endodermal sinus tumor)
Choriocarcinoma
Teratoma
Any mixture including admixed
seminoma
Spermatocytic Seminoma
Germ Cell Tumors: Patterns of Mets

Lymphatic spread most common

1st
Para-aortic retroperitoneal nodes
2nd
Mediastinal and supraclavicular nodes
Hematogenous spread
Lungs (most common)
Brain
Liver
Bone
 Germ Cell Tumors

Staging
Stage I
Testis, epididymis, and spermatic cord confined
Stage II
Retroperitoneal nodes below diaphragm
Stage III
Metastases outside retroperitoneal nodes or above
the diaphragm
Mets may not remain true to type seen in
the testis, e.g. embryonal carcinoma may
produce teratoma mets
Germ Cell Treatment

Work-up
Testicular ultrasound
Serum markers
AFP
-hCG
CT staging
Germ Cell Treatment

Treatment
Radical orchiectomy for solid
mass
Adjuvant therapy?
None (Surveillance)
Cisplatin based chemo
Radiation
Retroperitoneal lymph node
dissection (RPLND)
 Germ Cell Treatment

Broad classification: treatment based

Pure Seminoma
Least aggressive (many Stage I)
Very radiation sensitive
95% CURE RATE
Non-Seminoma
Extra-testicular spread more common
Cisplatin based chemo or RPLND
High cure rate, but less than seminoma
 Germ Cell Treatment

Spermatocytic Seminoma
No need for adjuvant therapy
Almost 100% CURE RATE
 Classification

Pure histology
Immunohistochemistry
 Germ cell
immunohistochemistry
Marker IGCNU Usual Spermat Embryo Yolk Teratoma Chorio-
Seminoma ocytic nal Sac carcinoma
semino carcino
ma ma

PLAP - + - +/- +/- - +

c-kit + + +/- -- - - -

AFP - - - +/- + +/- -

-HCG - - - - - - +

CD30 - - - + - - -

OCT3/4 + + - + - - -
 Intratubular Germ Cell Neoplasia

Precursor lesion to germ cell tumors in

adults
Not in childhood teratoma or YST
Not in spermatocytic seminoma
50% invasive GCT over 5 year period
Intratubular Germ Cell Neoplasia
Normal
(ITGCN)

Neoplastic germ cells

with abundant clear cytoplasm
and no sperm Leydig cells

Seminiferous
tubules

Sperm

Germ cells and Sertoli cells

 Seminoma

Frequency
Most common subtype (50% of all GCT)
Serum Markers
-hCG (admixed syncytiotrophoblasts 15%)
Alpha fetoprotein not elevated
Almost never in infants
 Seminoma

Delicate fibrovascular septa

Uniform tumor cell population

 Seminoma

Tumor cells that resemble ITGCN

Lymphocytes that follow the fibrovascular septa

Seminoma
Seminoma with syncytiotrophoblasts

Syncytiotrophoblast

Serum -hCG
Yolk Sac Tumor/Endodermal Sinus Tumor

Most common subtype in infants and

children up to 3 years of age
Pure yolk sac
Excellent prognosis in kids
In adults, often admixed with embryonal
carcinoma
Serum Markers
Alpha-fetoprotein
Yolk Sac Tumor

Schiller-Duval Body
Yolk Sac Tumor
Yolk Sac Tumor
 Embryonal

Occurs commonly in 20-30 year old age

group
In adults, often admixed with yolk sac
tumor
Serum Markers
-hCG
Although said to be more aggressive
than seminoma, still has excellent
response to therapy
 Embryonal

Sheet like growth of cells with larger, uglier nuclei than seminoma
Lack of cytoplasmic clearing
Embryonal
Embryonal

Angiolymphatic space invasion

 Choriocarcinoma

Intimate admixture of syncytiotrophoblasts

and cytotrophoblasts
Identical to those arising in gestational setting
Very rare in pure form
Infrequent in mixed tumors as well
Widespread metastases common
Serum marker
Markedly elevated -hCG
Poor prognosis in pure form
 Choriocarcinoma

Syncytiotrophoblasts
Cytotrophoblasts
 Choriocarcinoma

Cytotrophoblasts

Syncytiotrophoblasts
 Teratoma

Mixture of tissue from more than one

germ layer
Endoderm, ectoderm, mesoderm
Gut epithelium, skin, cartilage and fat
Gross cysts
Serum markers
Negative
 Teratoma

Testicular teratoma is biologically

distinct from ovarian teratoma
Pre-pubertal: Benign
No risk of mets
Post-pubertal (~12): Malignant
Risk of mets
In the ovary, immature versus mature is
based on histology
In the testis, no histologic subtyping of
teratoma
 Teratoma

Skin and sebaceous glands

Cartilage
 Teratoma

Intestinal-type glands
 Teratoma with Secondary
Somatic Malignancy

Sarcoma
Carcinoma
Retain isochromosome 12p
Mets do not respond to germ cell
tumor chemotherapy
Teratoma with Rhabdomyosarcoma
Teratoma with Rhabdomyosarcoma
Teratoma with Carcinoma
 Mixed Germ Cell Tumors

More than half of all testicular germ cell

tumors are mixed
Most common elements
Teratoma
Embryonal
Yolk sac
Seminoma
 Spermatocytic Seminoma
Unique tumor distinct from typical
seminoma
Age:
Usually >65 years
Serum Markers:
Negative
Prognosis
Excellent after orchiectomy
Practically no metastatic risk
No adjuvant therapy
 Spermatocytic Seminoma

Lymphocyte-like cell
Intermediate cell

Giant cell
Testis: Sex Cord Stromal Tumors

Most Common Types

Leydig cell
Sertoli cell
Age
Wide range (Commonly 20-60 years)
Testis: Sex Cord Stromal Tumors

Presentation
Mass lesion
Hormonal symptoms
Gynecomastia
Prognosis
Most are benign
10% in adults behave malignant
Leydig Cell Tumor
 Leydig Cell Tumor

Crystals of Reinke
Sertoli Cell Tumor
Sertoli Cell Tumor
Sertoli Cell Tumor
 Testis: Lymphoma

Most common testicular tumor in men

over 60 years of age
Presentation
Testicular mass
May be bilateral ~ 15%
Prognosis
Poor
 Seminiferous tubules

Interstitial lymphoma

Seminiferous tubules
Seminiferous tubules

Seminiferous tubules

Seminiferous tubules

Interstitial lymphoma
Interstitial lymphoma
 Paratesticular
Hydrocele
Serous fluid accumulation in the tunica vaginalis
Spermatocele
Cystic accumulation of semen in efferent ducts or rete testis
Varicocele
Dilated veins in the spermatic cord
Lipoma (Adult)
Benign fatty tumor
Adenomatoid tumor (Adult)
Benign mesothelial tumor
Rhabdomyosarcoma (Children)
Malignant tumor of skeletal muscle
Well-differentiated liposarcoma/atypical lipomatous tumor (Adult)
Fatty tumor with high risk of local recurrence
Adenomatoid Tumor
Adenomatoid Tumor
Testicular Tumor Objectives

Subtypes
Prognosis
Age
Stage
General principles of
treatment
Germ Cell Treatment

Treatment
Radical orchiectomy
Adjuvant therapy?
None (Surveillance)
Cisplatin based chemo
Radiation
Retroperitoneal lymph node
dissection (RPLND)