TUMORS of the TESTIS
incidence
risk factors
- age peak: 25-35 ys
- geographical distribution: west
classification (2016 WHO classification)
2-10x100.000, increasing
- cryptorchydism
- testicular dysgenesia
- Kleinfelter syndrome
- race (caucasians)
- hereditary predisposition
germ cell (95%):
all malignant
seminomatous
non-germ cell (5%):
more frequently benign
MIXED GERM CELL TUMORS
- 70% of non-seminomatous
- with or without seminoma
- any combination
distant metastases: 10% morphology not similar to primary
a minimum of 10 blocks for larger homogeneous tumors and complete blocking of smaller ones if entire tumor can be submitted in 10 blocks or less
precursor lesion: germ cell neoplasia in situ
- found in cryptorchidism, infertility
- risk of controlateral germ cell tumor in 25-50x
- morphology: large clear/vacuolated cells (PAS+), with large irregular nuclei
no 12p gain
pathological relevance
- to be differentiated from vascular invasion / intratubular spread
- helps distinguish germ cell tumors vs sex chord tumors
- helps to distinguish seminoma from spermatocytic tumor
- may be found in biopsies for infertility
- may be found in cryptorchidism
two pathways
default
SE
reprogramming
EC
it can also undergo the reprogramming path
SEMINOMA
- the most frequent
- 4th decade, pure or mixed
- 94% at 4 ys
- 12p isochromosome
histology
- classic 85%
- anaplastic 10%
- with SCT
pathology
macro:
- white-to-gray
- lobulated
- homogeneous
- without hemorrhage or necrosis
- with no involvement of the tunica albuginea
micro:
- round-to-polygonal cells
- medium size
- aboundant clear cytoplasm (glycogen, PAS+)
- hyperchromic nuclei, large nucleoli
- dyscohesive pattern of growth
- intratumoral lymphoid infiltrate
exception
- seminoma with SCT cells beta-hCG+ variant
- mixed
SPERMATOCYTIC TUMOR
- 5% seminomatous
- for the remaining %, specific tumor entity
- cells generally smaller than in seminoma
- more heterogeneous
- similar to type II spermatocytes
- not associated to GCNIS, no ovarian counterpart, no 12p anomalies, excellent prognosis, age >50
non-seminomatous
EMBRYONAL CARCINOMA
pathology
macro:
- small testicular nodules with necrosis and hemorrhage
- infiltration of the tunica albuginea
micro:
- tubular
- alveolar
- papillary
- chordonal growth of epithelioid cells with high grade atypia
- CD30+ and CEA+
YOLK SAC TUMOR
types:
prebuperal:
- children <3 y,
- pure,
- good prognosis
post-puberal:
- adults <30 y,
- mixed,
- highly malignant
pathology:
micro:
- irregular sheets of cuboidal cells
- papillae
- tubules
- centrifugal pattern
macro:
similar to embryonal carcinoma
PAS+ and AFP+
globules in the cytoplasm
CHORIOCARCINOMA
- pure form <1%
- mixed in 8% of germ cell tumors
- 25-30 y
- highly malignant
pathology
macro:
- small lesions
- marked hemorrhage
- necrosis
micro:
- large cells with cyto-syncytio-trophoblastic differentiation
- pale-to-eosinophilic cytoplasm
TERATOMA
- heterogeneous tumor
- pure in children (pre-pubertal type, benign, desmoid/epidermoid cysts)
- complex forms in adults (post-pubertal type), including mixed with embryonal carcinoma
pathology
macro:
heterogeneous
micro:
mature
mixed histologies: nervous tissue, muscle, thyroid, bronchi, cartilage, intestine, epidermis, connective tissue
immature
same as mature, but embryonal-like with some degree of cytological atypia
malignant transformation
- rhabdomyosarcoma, PNET, wilms, squamous cell carcinoma, adenocarcinoma
- expansile and infiltrative growth of epithelial or mesenchymal component measuring >5mm
- prognostic impact: not completely known in the primary, in metastatic lesions poor response to chemotherapy
serum markers
- alpha fetoprotein
- beta hCG
- PLAP
- CEA
- LDH
role:
- nature of the primary lesion
- staging
- response to therapy
- follow up
- germ cell vs non-germ cell nature
- histological typing
- prognosis
IHC germ cell tumor algorithm
OCT4+
OCT4-
+CD117
-CD30
-CD117
+CD30
embryonal carcinoma
seminoma
+glypican 3
+/-AFP
-hCG
+/-PLAP
yolk sac tumor
-glypican 3
-AFP
-hCG
-PLAP
spermatocytic seminoma
+/-glypican 3
-AFP
+hCG
+/-PLAP
choriocarcinoma
LEYDIG CELL TUMOR
- yellowish
- <5 cm
- Leydig cells with Reinke crystals
- lipofuscins
- mostly benign
- rare
in children: precocious puberty
in adults: gynecomastia and feminization
IHC markers: alpha inhibitin, SF1, melan A
SERTOLI CELL TUMOR
- aka androblastoma
- yellow-to-white
- very rare
- chords or trabeculae or tubules
- prominent stroma in some cases
- broad spectrum of DD: SF1+, CD99+, melan A+, chromogranin A+, cytokeratins
- asymptomatic / gynecomastia
- malignant in 5% of cases
other tumors:
- theca-/granulosa cell tumors
- mixed sex chord/germ cell tumors
- unclassified
- lymphoma: 2% of testicular tumors, 40-60% primary,
age 60-80 y, usually diffuse large B cell type - carcinoid
- mesothelial tumors: paratesticular; adenomatoid
tumor and mesothelioma - soft tissue tumors: lipoma, leyomyoma,
rhabdomyosarcoma - metastases
staging 2017
- rete testis invasion
- size of tumor
- epididymal invasion
- tunica vaginalis invasion
- vascular invasion
- soft tissue invasion
- cord invasion
NEVER CONSIDER INGUINAL LYMPH NODES INVOLVEMENT IN THE CASE OF TESTICULAR METASTASES!!!!!
non-neoplastic pathology
developmental anomalies
pseudohermaphroditism
primary hypogonadism
- isolated LH deficit
- Klinefelter syndrome (testicular atrophy, azoospermia, gynecomastia)
cryptorchidism
- 5% males at birth
- trans-abdominal and inguino-scrotal phases
- unknown causes (hormones, trisomy 13?)
- 25-30% bilateral
- isolated or associated with other anomalies
decreased volume and increase consistency of the testis
micro: maturation arrest of germ cells (atypia), decrease in Sertoli cell number, tubular hyalinization and basal membrane thickening
- 2-10% pure, usually mixed
- age 20-30 y
- EARLY DEVELOPMENT OF DISTANT METASTASES (lung)
- Leydig cell agenesis
- deficit in testosterone synthesis
- insensitivity to androgens --> Morris syndrome, undifferentiated tubules, Leydig cell hyperplasia
risk of malignant transformation: 3-5 (7-11) x
atrophy
- focal
- diffuse
causes:
- ischemia
- post-inflammatory
- cryptorchidism
- hypopituitarism
- iatrogenic
- peritumoral
torsion
- twisting of the spermatic chord, leading to blockade of venous blood flow
- swelling, edema, hemorrhage, necrosis
newborns or adults: increased mobility of the testis for bilateral laxity of the gubernaculum testis
inflammatory disorders
acute specific: granulocytes and macrophafes / interstitial and then intratubular --> abscess
specific forms:
gonococcus from urethritis
mumps --> rare complication in children, 20% in adults, 70% monolateral, with lymphocytes and plasma cells
testicular TBC
- post-primary
- uni-/bilateral
- granulomatous, productive caseous process
- fistulae
- primary of the epididymis, late testicular lesions
- hematogenous spread or canalicular from the urinary tract
syphilis
epididymitis:
- congenital
- acquired
obliterative endoarteritis with perivascular infiltrate of lymphocytes and plasma cells
granulomatous lesions: scar --> gumma
autoimmune diseases
- granulomatous orchitis
- middle-aged men
- sudden unilateral enlargement of the testis
- fever and pain
intra- and inter-tubular granulomatous inflammation with localized fibrosis and atrophy
no epididymitis (important for TBC DD)
male infertility
pre-testicular causes
- hypopituitarism
- estrogen and androgen excess
- glucocorticoid excess
- hypothyroidism
- diabetes
post-testicular causes
- congenital or acquired stenosis of the deferens ductus
- impaired sperm cell motility
testicular causes
- maturation arrest
- hypospermatogenesis
- "sertoli cell only" syndrome
- Klinefelter syndrome
- cryptorchidism
- radiation exposure
- post-inflammatory diffuse sclerosis
testicular biopsy
adequate material, clinical information and hormonal tests
- normal parenchyma
- hypospermatogenesis
- maturation arrest
- germ cell loss (Sertoli cell only vs. end-stage testis)
- fibrosis / atrophy
- GCNIS