TESTICULAR TUMORS

NORMAL TESTIS
TESTICULAR TUMORS are
divided on:
GERM CELL TUMORS(90%) and
NONGERMINAL TUMORS
GERM CELL TUMORS

About 8000 new cases per year in

USA, 400 deaths per year, with
worldwide increase in incidence
Most common tumor of men in the 15-
34 year age group
GERM CELL TUMORS

:May be divided into two categories

Tumors with single histological
.(pattern(40%
.(Mixture of two or more patterns (60%
Clinically most important distinction is
between seminoma and
nonseminomatous tumors
INTRATUBULAR GERM CELL NEOPLASIA

Precusor lesion of most ADULT germ cell.1

tumors(except spermatocytic seminoma). Untreated
ITGCN progresses to invasive germ tumor in 50%
over 5 years of follow up(similar to carcinoma in
.(situ in other organs
High frequency of ITGCN seen in cryptorchidism, .2
strong family history of GCT(germ cell Tu),
androgen insensitivity syndrome,gonadal
.dysgenesis syndrome
 Cryptorchidism cause atrophy of
seminipherous tubules with preservation of
only Sertoli cells. Relatively increased
.proportion of Leydig cells
Up to 10% of GCT associated with
cryptorchidism
The higher the location of undescendent
testis(intraabdominal vs. inguinal) the
greater is the risk of developing cancer.
Other important risk factors – testicular
dysgenesis(testicular feminization and
Klinefelter syndrome) and genetic factors
(racial differences).
(KLINEFELTER SYMDROME(47 XXY
CRYPTORCHIDISM
ITGCN IN KLINEFELTER SYNDROME
PLAP positivity in ITGCN
 GENOMIC CHANGES IN GCT

An isochromosome of the short arm of

chromosome 12, i(12p) is found in
virtually all GCT
In 10% of cases i(12p) is not
detected,but extra genetic material
derived from 12p is found on other
chromosomes
12p is critical for pathogenesis of GCT
(in women ovarian tumors also)
 IMMUNOHISTOCHEMICAL MARKERS IN
DIAGNOSIS OF GCT
 Germ cell tumors often secrete polypeptide hormones or
enzymes that can be detected in blood and used in
diagnosis and monitoring
 Such biologic markers include α-fetoprotein(AFP), human
chorionic gonadotropin(HCG),placental alkaline
phosphatase and more
 Some molecular markers may be very helpful –
transcription factor,encoded by OCT3/4 is expressed in
premordial germ cells and also in seminomas and
embryonal carcinomas.
 The same markers may be used in pathological diagnosis
as immunohistochemical antibodies
 SEMINOMA

Most common type (50%) of GCT

Peak incidence in 30-ties
The same tumor in ovary is called dysgerminoma
GROSS PICTURE
MICROSCOPIC PICTURE
SYNCYTIOTROPHOBLAST CELLS IN
SEMINOMA
 ANAPLASTIC SEMINOMA

Seminoma with greater pleomorphism and

numerous mitoses
Have the same prognosis(stage by stage) as
usual seminoma and is treated the same
way, so it is not recognized as a distinct
entity
 IMMUNOPROFILE OF CLASSIC
SEMINOMA

 PLAP(placental alkaline
phosphotase)+
 c-Kit(CD117)+
 OCT3/4+
 CD30-
 AFP-
 hCG-
 SPERMATOCYTIC SEMINOMA

 It is not arising from ITGCN

 Represents 1-2% of GCT
 Patients are usually over 65 years old
 Very rarely metastasize, exellent
prognosis
 The name is related to resemblence
of some cells to spermatocytes
IMMUNOPROFILE OF SPERMATOCYTIC
SEMINOMA

 PLAP –
 OCT3/4 –
 hCG –
 AFP –
 CD30 -
 EMBRYONAL CARCINOMA

 Occurs mostly in the age 20-30 years

 Are much more aggressive than
seminomas
 Grossly smaller than seminoma,poorly
demarkated margins,hemorrhage,necrosis
 Extension to epididymis and spermatic
cord is not rare
 Microscopically may be
tubular,alveolar,papillary or
undifferentiated
SYNCYTIOTROPHOBLAST IN EMBRYONAL
CARCINOMA
 IMMUNOPROFILE OF EMBRYONAL
CARCINOMA

 PLAP+
 OCT3/4+
 CD30+
 CYTOKERATIN+
 AFP ±
 hCG –
 c-Kit (CD117) -
 YOLK SAC TUMOR(infantile embryonal
(carcinoma,endodermal sinus tumor

 The most common tumors in infants

and children up to 3 years of age
 In this age has a very good prognosis
 In adults is usually the component of
mixed tumor(with embryonal
carcinoma)
YOLK SAC
MICROCYSTIC PATTERN
SHILLER-DUVAL BODIES(resembling endodermal
(sinus
HEPATOID PATTERN((with hyaline globules
SOLID AND MICROCYSTIC PATTERN
IMMUNOPROFILE OF YOLK SAC TUMOR

 AFP+
 CYTOKERATIN+
 PLAP+
 hCG –
 OCT3/4 –
 CD30 -
 CHORIOCARCINOMA
 Highly malignant tumor,composed of
cytotrophoblastic and
syncytiotrophoblastic cells
 In “pure” form choriocarcinoma is rare (less
1% of GCT)
 Mostly present as foci in mixed tumors
 Usually are small lesions
 Early metastases (and sometimes with
regression of primary tumor)
 IMMUNOPROFILE OF
CHORIOCARCINOMA

 hCG +
 CYTOKERATIN +
 PLAP +(50%)
 AFP –
 CD30 -
 TERATOMA

 Complex tumors,composed of cellular and organoid

components,reminiscent of normal derivatives from more
than one germ layer
 In “pure” form common in infants and children and rare in
adults (2-3%); in adults mostly present in mixed tumors
 Microscopically are composed of collection of tissues an
organoid structures(thyroid,bronchial wall, brain
tissue,intestinal structures etc.)
 Tissue elements may be mature (like in adult ) or
immature(like fetal or embryonic tissues)
 May show malignant transformation with the appearance of
non-germ cell tumors – carcinoma(adeno-,squamous) or
sarcoma
 MATURE AND IMMATURE TERATOMA
((CLINICAL IMPLICATIONS

 In childen mature teratomas have

very good prognosis and behave as
benign tumors
 In adults all teratomas are regarded
as malignant and capable of
metastatic behavior (whenever
mature or immature)
 MIXED GERM CELL TUMORS

 About 60% of GCT are composed of more

than one pattern.
 Common mixtures are:
teratoma+emb.carcinoma+yolk sac
tumor; seminoma+emb.carcinoma;
teratoma+emb.carcinoma
 Prognosis depends on presence of more
aggressive elements
 PROGNOSIS and SPREAD

 Most important clinical classification:seminoma

and nonseminomatous germ cell tumors
 GCT spread through lymphatics to retroperitoneal
para-aortic LN and father – to mediastinum and
subclavicular LN
 Hematogenous metastases – to the lungs,liver,
brain and bones
 Histology of metastases may be different from
primary tumor(emb.carcinoma>teratoma in
metastases)
 STAGING

 pT0 – no tumor present

 pTis – intratubular germ cell neoplasia
 pT1 – tumor limited to testis and
epididymis,no vascular/lymphatic invasion
 pT2 – tumor limited to testis and
epididymis with invasion to tunica
vaginalis and vascular/lymphatic invasion
 pT3 – tumor invades spermatic cord
 pT4 – tumor invades scrotum
 LYMPHATIC SPREAD

 pN0 – no metastases to lymph nodes

 pN1 – no more than 5 positive LN,no
larger than 2 cm mass
 pN2 – 2-5 cm mass,more than 5
nodes involved no more than 5 cm
 pN3 – nodal mass more than 5 cm
 DISTANT METASTASES

 pM0 – no distant metastases

 pM1a – non-regional lympn nodes or
pulmonary metastases
 pM1b – distant metastases other
than non-regional LN or lungs
 PROGNOSIS

 Seminomas tend to remain localized to the

testis for a long time(70% -stage I)
 More than 60% of nonseminomatous GCT
present with advanced stages(II or III).
 Seminomas spread predominantly through
lymphatics,nonseminomatous GCT – both
lymphogenous and hematogenous spread
 Generally, nonsemonomatous GCT are
more aggressive and have a poorer
prognosis
(SAINT-BENEZET BRIDGE(AVIGNON
PATHOLOGY OF PROSTATA
ANATOMY AND HISTOLOGY
NORMAL PROSTATIC GLAND
NODULAR HYPERPLASIA(BENIGN
(PROSTATIC HYPERPLASIA - BPH

 BPH – extremely common after 50

 Hyperplasia of epithelial cells and stroma
 Formation of nodules in periurethral
region, may cause narrowing or occlusion
of urethral canal
 BPH

 Microscopic evidence of hyperplasia can

be seen in 20% of men 40 years of age,
70% by age 60 and 90% by age 70
 Only 50% of those who have microscopic
evidence of BPH have clinical symptoms
 BPH– ETIOLOGY AND
PATHOGENESIS
 Dihydritestosterone(DHT),a metabolite of
testosterone, is the ultimate mediator of prostatic
growth
 Stromal cells are the main site of DHT production
 DHT binds to androgen receptors of stromal and
glandular cells and signals the transcription of
growth factors
 DHT is 10 times more potent than testosterone
because it dissociates from androgen receptors
more slowly
 MICROSCOPIC FEATURES OF BPH

 Nodularity due to stromal and glandular

proliferation
 Varies from purely fibromuscular nodules
to predominantly epithelial nodules with
custic and papillary structures
 Diagnosis of BPH cannot be made on
needle biopsy
 Basal layer preserved
 ADENOCARCINOMA OF PROSTATE

 The most common cancer in men,

second leading cause of cancer
death
 Age-adjusted frequency – 69 per
100000
 Latent(clinically silent) cancer – 20%
in men in their 50, 70% - between 70
and 80 years
 Puzzling racial differences
 GENETICS AND MOLECULAR PATHOLOGY

 In 10% of Americans with PCa there are germ line

inheritance of PCa suscepribility genes, in 30% of
this cases mapped on chromosome 1q24-25
 Men with family history of PCa have much higher
incidence of this cancer(two- to five-
fold)compared to men with no history
 Putative tumor supressor genes, that are lost
early in prostatic carcinogenesis were localized to
chromosomes 8p,10q/13q and 16q
 P53 is not involved in early stages of
carcinogenesis
 MOLECULAR PATHOLOGY

 No overexpression of oncogene Her2/neu was

found
 Gene microarray studies reveal cohorts of genes,
overexpressed in PCa: hepsin, transmembrane
serine protease,alfa-metilacyl CoA racemase
 90% of PCa show hypermetilation of GSTP1 gene
promoter(glutathione S-transferase) which turns
off its expression. These gene is a part of
pathway, preventing damage from a wide range
of oncogenes
 ADENOCARCINOMA OF PROSTATE

 In 70% of cases arises in peripheral zone of the

gland
 Grossly may be difficult to visualize in the
specimen
 Histologically – adenocarcinoma, composed of
small glands, lined by single layer of cuboidal or
columnar epithelial cells
 Nuclei of tumor cells are large, often contain one
or more nucleoli
 Pleomorphism is not marked, no mitoses seen
 Pathological diagnosis on needle biopsy may be
difficult
ADENOCARCINOMA OF PROSTATE

 In difficult cases only constellation of

architectural,cytological and ancillary findings can
help

Very important feature – the
absence of
basal cells in carcinoma glands
 Special immunostains for basal cells (34βE12
keratin and p63) are very helpful
 Recently “positive” marker for prostatic
carcinoma enter routine work-up – p504(alfa-
metylacil CoA-racemase)
 GRADING OF PROSTATIC
(CANCER(Gleason system
 GLEASON SYSTEM

 Grade I is most well differentiated, grade 5

– less differentiated
 Most tumors contain more than one
pattern,in this case two patterns(dominant
and secondary) are added to obtain
Gleason score or combined grade(2+3=5;
3+3=6; 4+3=7 etc.)
 Majority of cancers in needle biopsies are
of Gleason scores 5-7
Gleason pattern(grade) 2
Gleason grade 3
Gleason grade 4
Gleason grade 5
Gleason score– 10-years probability of local
progression

 4 and less – 25%

 5-7 – 50%
 >7 – 75%
 Tumors with Gleason score 8-10 are
mostly clinically advanced
cancers,unlikely to be curable
 PROSTATIC INTRAEPITHELIAL
(NEOPLASIA(PIN
 Presumtive precursor lesion – high grade
prostatic intraepithelial neoplasia(PIN)
 Benign glands lined by cells, cytologically
identical to prostatic carcinoma
 Basal cell layer is preserved
 Present in ~80% of prostatic tissue, removed for
carcinoma
 Pathological and molecular data support the link
between PIN and prostatic cancer
PRESERVED BASAL CELLS IN HIGH
GRADE PIN
 SPREAD OF PROSTATIC CANCER

 Direct local invasion, through blood stream

or lymph
 Lymphatic spread – to obturator lymph
nodes,followed by
perivesicular,iliac,presacral and paraaortic
 Hematogenous spread – most commonly
to bones – lumbar spine,proximal
femur,pelvis,thoracic spine,ribs
 Bone metastases are usually osteoblastic