TESTICULAR TESTIS PATHOLOGY
TESTES
Numbers
4.5cm
20g
Components
Epididymis: pseudostratified with cilia
Rete testis: flat cuboidal
Seminiferous tubules: atypia, lipofushcin
Vas deferens: columnar + lymphocytes
CONGENITAL ANOMALIES
Cryptorchidism
Aplasia (rare)
Fusion of both testes (synorchism)
Developmental cysts
Splenogonadal fusion
CRYPTORCHIDISM
How common?
1% of newborns
Etiology
1st:
2nd: trisomy 13, hormonal abnormalities
% bilateral?
25%
Which hormone controls phases of descent?*
First phase: mullerian-inhibiting substance
Second phase: androgen-dependent
Where is it located mostly?
-inguinal canal
When start seeing histologic change
From 2 years
Gross of cryptoid testis
Small
Micro of cryptoid testis?
Spermatogenesis arrest or decrease
Thick and hyalinized seminiferous tubular BM
Interstitial fibrosis but spares Leydig cells (looks prominent)
Good picture below
Can it occur in contralateral descended testis?
Yes
Long-term consequences? How high for tumors? What type of cancer?
Inguinal hernia
Sterility
Cancers: RR=5x, mostly seminomas (85%)
When surgery is done?
At 2 years (spontaneous descent in most within first year)
How can orchiopexy help?
Recover sterility, decrease cancer risk to some extent but not entirely (true for both testes)
Any follow-up? % with ITGCN?
Testicular biopsy controversial
3%
How are cryptorchid-associated tumors compared to sporadic?
Earlier and more bilateral
ATROPHY
Etiology
Cryptorchidism
Vascular disease (atherosclerosis, old age)
Inflammatory disorders
Hypopituitarism
Malnutrition or cachexia
Obstruction of semen outflow
High estrogen (prostate cancer treatment, cirrhosis)
High FSH
Exogenous androgenic steroids
Chemoradiation
Klinefelter
Micro
Same as cryptorchidism
INFERTILITY
Etiology of decreased fertility with normal histology***
Any obstruction: vas deferens, hypospadia, past paratesticular surgery
Retrograde ejaculation (TURP)
Varicocele
History of mumps or any orchitis
Idiopathic
Immotile cilia syndrome
Chemoradiation
Indications for testicular biopsy in fertility
Azoospermy to differentiate obstructive vs non-obstructive
Unexplained by other tests
Asymmetric testes
Screening for ITGCN in cryptorchid
Histologic patterns
Normal or hypospermatogenesis (all cells present but reduced numbers)
Germ cell arrest (earlier cellular elements of spermatogenesis present but stops at a certain stage, most often at primary spermatocytes)
Sertoli-cell-only syndrome or germ cell aplasia (the tubules contain Sertoli cells but no germ cells)
Hyalinization (cellular elements disappear, leaving thickened seminiferous tubules as in Klinefelter)
Immature testis (no gonadotropin stimulation, prepubertal appearance).
Micro: what do you see in azoospermia?***
-???
INFLAMMATION
Which infection starts in testis vs which in epididymis?*
Syphilis starts in testis
TB and gonorrhea start in epididymis
Name some epididymitis/orchitis
Nonspecific epididymitis and orchitis
Granulomatous orchitis: aka AI orchitis
Infectious: gonorrhea, mumps, TB, syphilis
NONSPECIFIC EPIDIDYMITIS AND ORCHITIS
Mechanism?
UTIà retrograde propagation via vas deferens or lymphatics of spermatic cord
Etiology: Age dependent
| Kids | GNB |
| Sexually active <35 | Chlamydia, gono |
| Elderly | E coli, Pseudomonas |
Micro
Interstitial congestion, edema, PMN, macrophages, lymphocytesà abscess with necrosis of epididymisà scarringà sterility but still potent sexually (because Leydig cells spared)
GRANULOMATOUS ORCHITIS (AI orchitis)
Classic presentation
Mid-aged men with unilateral large testis of sudden onset
AI vs TB
| AI orchitis | TB |
| -Diffuse granulomas
-Granuloma in seminiferous tubules |
No |
| No | AFB, ZN |
DDx
Seminoma
Lymphoma
INFECTIONS
GONORRHEA
Pathway
Urethraà prostateà seminal vesiclesà epididymis
Micro
Same as nonspecific orchitis
MUMPS
Risk
Sterility (but not common)
Micro: Unilteral, patchy, interstitial inflammation
TB
Pathway of spread in TB
Always starts from epididymis
SYPHILIS
Pathway of spread in syphilis
Always starts from testis
Micro: Diffuse interstitial inflammation (edema, plasma cells, obliterative endarteritis, perivascular cuffing by lymphocytes) or nodular gummas
TORSION
Mechanism
Venous compression
Neonatal: no anatomic defects
Adult: bell-clapper deformity
Micro: Interstitial hemorrhage, hemorrhagic necrosis
LESIONS OF TUNICA VAGINALIS
Name a few and explain causes
Hydrocele: serous fluid in tunica vaginalis, due to generalized edema or incomplete closure of processus vaginalis. May be infected secondarily
Hematocele: secondary to trauma, torsion, bleeding disorders, invasion by malignancy
Chylocele: secondary to lymphatic obstruction (elephantiasis)
Spermatocele: local accumulation of semen in spermatic cord, generally in head of epididymis
Varicocele: blood within dilated vein in spermatic cord
SPERMATOCELE
Micro
Epididymal cyst filled with spermatozoa and lined by epithelium (flat to pseudostratified)
VASITIS NODOSUM
What is vasitis nodosum?
Occurs in vas deferens in the setting of obstruction
This causes azoospermic infertility
Proliferation of duct structures stuffed with spermatozoa (in the muscular layer of vas)
Obstruction is also associated with sperm granulomas in the vas
INFERTILITY
Types of infertility
Pre-testicular: pituitary/adrenal gl.
Testicular
Post-testicular: (obstructive)
3 causes associated with normal histology
Post-obstructive causes secondary to congenital
Post-surgical
Young’s syndrome (obstructive azoospermia + sinopulmonary infections)
Indications for testicular biopsy
Cryptorchidism to confirm ITGCN
Intersex infertility syndromes (gonadal dysgenesis, androgen insensitivity syndrome)
Previous germ cell tumor
TUMOURS
RF for germ cell neoplasia (not for non-GCT tumors)
Cryptorchidism
Intersex syndromes: gonadal dysgenesis, true hermaphroditism, male pseudohermaphroditism, androgen insensitivity syndrome
Previous testicular GCT
Oligospermic infertility
Family history of GCT
IGCNU (intertubular germ cell neoplasia, unclassified)
Name 3 RF (in particular cytogenetics)*
Cryptorchidism
Family history
Testicular dysgenesis: testicular feminization, Klinefelter
Cytogenetics: i(12p) resulting in gain of copy in 90% testicular GCT (including YST) and ITGCNà number of copies corresponds to aggressiveness
Prior GCT
Is GCT tumor of whites or blacks?
Whites
What are 2 genetic features of most germ cell tumours?
Hyperdiploid
12p amplifications, i(12p)
Give 5 IHC for sex cord-stromal tumors
α-inhibin
Calretinin
MelanA
CD99
S100
Chromogranin
Steroidogenic hormones
Incidence for sex cord-stromal tumors in testis?
Leydig> Sertoli> granulose> pure stromal tumors
AFP-producing tumors
YET
HCG-producing tumors
SEC
Ages with each tumour?
Seminoma: 40
Spermatocytic seminoma: 50-60
EC: 30
Choriocarcinoma: 10-20
YST and teratoma: <3 + adults
Leydig cell and Sertoli: kids to adults
Theory behind totipotent cells and germ cells tumours.
Germ cell tumours thought to derive from totipotent cell to become seminoma or non-seminomatous tumour
Metastases of one germ cell tumour may be different from another. (eg. EC can mets to the lung and show up as a teratomatous met)
Common clinical presentation
Painless enlargement
DDx for enlarged testis
Non-neoplastic (including painful masses!)
Neoplastic: primary vs mets, germ cell vs non,
Why no biopsy?
Will require scrotal skin excision in addition to orchiectomy
Most common spread pathways
LN: retroperitoneal para-aortic (sometimes mediastinal or supraclavicular)
Hemato: lungs, liver, brain, bone (2L2B)
Mets can mature into teratoma
Name tumors with best prognosis
Seminoma (curable for stage 1 and 2)
Teratoma in kids
Which one is bad
Pure choriocarcinoma (not so bad when it’s mixed)
Prognostic difference between histologic types?
Seminomatous better than non-seminomatous
No difference among non-seminomatous
What’s radical orchiectomy?
Testis and tunica vaginalis
Sequence of tumorigenesis. Exceptions?
ITGCNà seminomaà NSGCT
Exceptions: spermatocytic seminoma, pediatric GCT, all teratomas
Value of EM in GCT
Don’t forget this in exam…
Micro for GCT regression
Intratubular hematoxylin-staining bodies (nuclear debris)
Intratubular calcifications
Teratomatous elements
Fibrous scar, macrophages, chronic inflammation
All possible but mostly in choriocarcinoma
Micro for post-chemotherapy effects & relevance
| No more chemotherapy | Additional chemotherapy needed |
| Teratoma | Residual tumor |
| Necrosis | |
| Fibrosis | |
| Repair change: foamy macrophages, hemosiderin, FB proliferation, cholesterol clefts |
Concept of late recurrence
Prognosis***
Staging (serum markers included here)
Histologic type
ITGCN
% in cryptorchid?
3%
Risky for GCT?
50% in 5 years
How often is ITGCN adjacent to invasive GCT?
98%
How should it be called CIS?
Not carcinoma. Seminoma in situ acceptable
Genetics?
i(12p)
In what conditions?
Cryptorchid
Contralateral testis to testis with prior GCT
Infertility
Intersex syndromes
Coexists with most GCT
Micro
Large dark nuclei
Clear cytoplasm
Nucleoli
Mitoses
Sertoli displaced towards lumen
No normal spermatogenesis
Thickened BM
Spread
Pagetoid spread to rete testis common
Variants
Unclassified
Intratubular seminoma
Intratubular embryonal carcinoma
Intratubular YST
What stains (where)? (hint: same as seminoma)*
PAS+: also in normal germ cells
PLAP+: membranous, not in normal germ cells
C-KIT+
OCT3/4+: member of POU transcription factors, “master switch” in differentiation by regulating cells with pluripotent potential
D2-40
Other: ferritin, M2A, 43F
Treatment?
Radiation, orchiectomy
SEMINOMA
Peak age compared to NSGCT? Presentation? Can seminoma have AFP?
Peak 40 (10 years later than NSGCT)
Mass (pain only in 1/10), increased hCG (gynecomastia!)
No unless mixed with non-sampled YST
Equivalent in ovary and brain?
Dysgerminoma, germinoma
Gross. Often necrotic and hemorrhagic?
Lobulated bulging creamy white-yellow mass
Not extensive (only syncytiotrophoblastic foci)
Tunica albuginea often intact
Micro*
Sheets of large polygonal cells with clear to eosinophilic cytoplasm, slightly “squared” cell borders
Large central nuclei with large 1-2 nucleoli
No nuclear overlapping due to abundant cytoplasm
Fibrous septa containing lymphocyte
Granulomas in 50%à DDx granulomatous orchitis!
Syncytial trophoblasts in 20%à DDx choriocarcinoma
Fibrous scar with calcificationà DDx gonadoblastoma
What type of lymphocytes?
T (most lymphomas are B)
IHC*
PAS+ (glycogen)
C-KIT+
PLAP+
HCG+ in syncytiotrophoblast-like cells
CKAE1/3- or weak or focal+: vs strong in NSGCT. Remember seminoma is CK- except CAM5.2 (CK8/18)
EMA-
What’s PLAP?
Placental alkaline phosphatase
Prognosis
Excellent treat with radiation
Spread
Retroperitoneal LN, mediastinum
Name 3 variants
Seminoma with trophoblast giant cells
Mixed
Rare patterns
Cords
Solid tubules
Reticular, cribriform (edema)
Interstitial
Plasmacytoid (atypical seminoma): CK+, CD30+, no difference in therapy
Most important prognosticator
Staging (no1)
Ddx
Granulomatous reaction: PLAP- (useful for identifying residual seminoma)
EM
Glycogen aggregates
Simple cellular organelles…
Seminoma vs embryonal carcinoma
| Seminoma | Embryonal carcinoma |
| 40 | 30 |
| Often confined to testis on presentation | Often outside of testis on presentationà much more symptomatic |
| Yellow creamy yellow | Hemonecrosis |
| Pure possible | Pure rare |
| -Distinct borders
-No nuclear overlap -Less pleomorphism -Lymphocytes -Fibrous septa -Necrosis less -Sheets mainly -Less mitoses -Clear cytoplasm -Never glandular |
-Indistinct borders
-Nuclear overlapping -Pleomorphism -No lymphocytes -No fibrous septa -Necrosis common -STP patterns -High mitoses -Basophilic cytoplasm -Glandular pattern |
| No | CD30+/CKAE1/3+ |
| OCT3/4+ | |
| Radiation | Chemotherapy |
| -HCG-producing ST (gynecomastia)
-AFP elevation (with mixed with YST) -PLAP+ |
|
Seminoma vs solid YST
| Seminoma | Solid YST |
| Single pattern (solid)à edema may mimic microcysts | Other patterns (especially microcysts) |
| Lymphocytes | Less |
| Fibrous septa | No |
| No | Extracellular BM deposit |
| No | Hyaline globules |
| -OCT3/4+ | -CK+
-AFP+ |
Seminoma vs choriocarcinoma
| Seminoma | Choriocarcinoma |
| No | Biphasic |
| HCG only moderate | HCG very high |
| OCT3/4+ | CK+/EMA+ |
Seminoma vs lymphoma
| Seminoma | Lymphoma |
| Younger | Older |
| Interstitial pattern with tubular preservation | |
| Fibrous septa | No |
| Clear cytoplasm | No |
| Distinct | Border less distinct |
| Uniform rounder nuclei | Irregular nuclei |
| ITGCN | No |
| T | Mostly B |
| PLAP+ | LCA+ |
SPERMATOCYTIC SEMINOMA
How much older compared to seminoma?
50-60yrs, 1/10 bilateral
SSx and prognosis
Painless enlargementà usually larger than seminoma
No mets, excellent prog
Origin: Premeiotic
| Small (6-8µm) | Some
Resembling secondary spermatocytes (hence spermatocytic)à lymphocyte-like but more cytoplasm |
| Medium (15-18µmà 2x) | Many
Round nuclei Filamentous chromatin “spireme” |
| Giants (50-100µmà 10x size) | Scattered
Can be multinucleated Sometimes spireme |
Nodules of sheets of cells, interrupted by edema
Usually pure, no IGCNU
High mitoses and apoptosis
Uniformly round nuclei, spirene chromatin, inconspicuous nucleoli
Numerous apoptoses
No lymphocytes, no fibrous septa
Variants?
Anaplastic: monomorphic population of intermediate cells
Spread
Intratubular often but never metsà therefore orchiectomy alone curative
When does spermatocytic sarcoma kill?
Sarcomatous differentiation
IHC*
Noneà PLAP-, PAS- (no glycogen), AFP-, HCG-, CK-
Does it occur outside of testis? No
| Spermatocytic | Seminoma |
| 60 | 40 |
| Testis only | Testis, ovary, mediastinum, pineal, RP |
| No | Cryptorchid |
| 10% bilateral | 2% |
| Never | Often mixed |
| No | ITGCN |
| Rarely sarcomatous differentiation | Never |
| -3 cell types
-Denser cytoplasm -Round nuclei -Interstitial edema common -Scanty fibrous stroma -No lymphocytes -No granulomas |
-1 cell type
-Clear cytoplasm -Nuclei with squared edges -No edema -Fibrous septa common -Lymphocytes -Granulomas |
| No | Glycogen |
| PLAP+, HCG+ (10%) | |
| Never | Mets |
| Anaplastic SS | Embryonal carcinoma |
| -More rounded
-Foci of typical appearance |
-Uglier |
| No | ITGCN |
| CD30+/CK+/PLAP+/- |
EMBRYONAL CARCINOMA
Age compared to seminoma?
-20-30
What can be elevated?
+/- HCG (“SEC”=seminoma, embryonal, choriocarcinoma), AFP (“YET”=YST, embryonal, teratoma)
Gross
Small like seminoma (≈2.5cm)
Not WC
Gray-white with punctuate hemorrhage and necrosis
Micro*
Usually mixedà found in 90% mixed tumors!
STP patterns (solid[1], tubular, papillary, alveolar), double-layered pattern
Indistinct cell borders
Atypical cells, large vesicular nuclei, large nucleoli
Nuclear overlapping
Extensive necrosis
High mitoses
Vascular invasion (important, mostly at periphery)
Can have HCG+ (syncytiotrophoblasts) or AFP+ (syncytial cells) cells or both!*
Intratubular embryonal carcinoma at periphery often
What’s crucial in reporting for embryonal carcinoma?
LVI
% of embryonal carcinoma component
Tumor size
Therefore, sample thoroughly!
IHC*
CD30+
CK+ but EMA-
Patchy PLAP+
OCT3/4+
Focal AFP+ may represent partial YST transformation
DDx
Seminoma:
Carcinoma: CK+, EMA+, CD30-, PLAP-
Solid YST:
Lymphoma (DLBCL): interstitial growth, no ITGCN, PLAP-
Anaplastic spermatocytic seminoma:
YST
Incidence? Serum marker?
Pure in kids (#1 testicular tumor <3 yo) vs mixed in adults
Increased serum AFP
Association with cryptorchid?
No
Gross
Yellow-gray myxoid, cystic or hemonecrotic
Name 5 patterns (11 in total)
Microcystic (reticular): most common; prominent cytoplasmic vacuolation confers cystic/lacelike appearance, focal myxoid background. Some microcysts coalesce to become macrocysts
Macrocystic
Solid
Parietal: extensive extracellular deposit of BM between tumor cells
Papillary
Glandular
Hepatoid
Myxomatous: resembling pulmonary edema
Sarcomatoid: RMS
Polyvesicular vitelline (not same as endodermal sinus): regular round vesicle lined by intestinel-type epithetium bulging out from cystic space. Rare…
Endodermal sinus: Schiller-Duval bodies (primitive glomeruli: BVà loose clear stromaà cuboidal epitheliumà spaceà cuboidal epithelium), labyrinth pattern (resembling angiosarcoma)
Relative frequency of each pattern?
Microcystic> macrocystic, solid, parietal> hepatoid, endodermal sinus, polyvesicular vitelline
What else in micro?
Hyaline globules (D-PAS, AFP, AAT+) inside and outside cells, variable size (1-50µm).
Where else can you find hyaline globules?
Rarely in seminoma and embryonal carcinoma
IHC
AFP diffuse+: some may be negative
CK+
A1AT+ in 50%
PLAP+: slightly less than other GCT
EMA-: useful vs carcinoma
OCT3/4-
CD30-
Prognosis
Good <3yo
Mostly mixed in adults
DDx: Seminoma
Solid YST vs embryonal carcinoma
| YST | Embryonal carcinoma |
| More patterns | |
| More pleomorphic | |
| Smaller cells | |
| Smaller nuclei, not as crowded | Large nuclei and very crowded |
| Hyaline globules | |
| Extracellular BM deposit | |
| AFP+ | CD30+, OCT3/4+ |
YST vs juvenile granulosa cell tumor
| YST | JGCT |
| Solid, cystic, mitoses, atypia | |
| Older kids | Neonates, infants |
| AFP+ | Inhibin+, CD99+ |
CHORIOCARCINOMA
Age
20-30
Potential sources?
Ovary, placenta, ectopic germ cell nests in mediastinum or abdomen
Is it common?
Pure very rare (young/prepubertal boys)
Mostly mixed
Ssx (hint=HCG, mets)
Gynecomastia, thyrotoxicosis (HCG mimics TSH), GI bleed, lumbar pain, hemoptysis, neural symptoms
Lab
HCG
Spread
Hematogenous spread to brain
What’s special about size?*
Small even in disseminated cases (so no testicular enlargement or sometimes even atrophic due to HCG), sometimes involuted to scar
Friable, hemorrhagic, solid, necrotic
Micro
| Cytotrophoblast
Intermediate trophoblast |
Syncytiotrophoblast |
| Uniform nuclei | Pleomorphic, multinucleated |
| Clear cytoplasm | Amphophilic |
| Intracytoplasmic lacunae containing RBC | |
| Smudged chromatin | |
| “Caps” CT/IT | |
| Sheets, cords | |
| Remains after chemotherapy (monophasic variant) | Rare after chemotherapy |
Extensive hemonecrosisà extensive sampling required
Vascular invasion common
ITGCN
IHC
PLAP+ in 50%
HCG+ and inhibin+ in ST only
HPL+ in IT only
CK+
EMA+ (unique) in STà negative in other GCT!
Prognosis
Worse than any other GCT
DDx
Embryonal carcinoma (vs monophasic choriocarcinoma): use IHC
Solid YST: AFP+, HCG-
Seminoma with syncytiotrophoblasts: CK-, HPL-
Choriocarcinoma vs torsion-induced hemonecrosis
| Choriocarcinoma | Torsion |
| Small painless | Painful |
| HGG elevation | No |
| ITGCN | No |
IS HE A MAN?
Inhibin
Small
Hemorrhagic, hCG
Extra sections
Angioinvasion, Aggressive
Mononuclear (CT: polygonal cells with clear cytoplasm in cords/nests) and Multinuclear (ST: group of cells with smudged chromatin)
Necrotic Nodule
TERATOMA
Kids vs adults
| Infants/kids | Adults |
| <4yo | Young |
| Pure | Mixed (present in 50% of GCT); pure form rare |
| Always mature | Mature or immature |
| Always benign | Malignant regardess of maturity* |
| No | ITGCN??? |
| Derives from invasive GCT |
Locations
Midlineà brain, neck, mediastinum, retroperitoneal
Gross
Nodular, cystic, cartilage
Lab
Can have AFP elevation in pure teratoma (without YST)
Micro
Mature (differentiated) 3 germ cell layers
| Endoderm | Gut, bronchial epithelium |
| Mesoderm | Muscle, cartilage, fat |
| Ectoderm | Skin, neural |
Immature: immature neuroepithelium, foci resembling Wilms’, immature skeletal muscle
With a malignant component: SCC, neuroblastoma, LMS, chondrosarcoma
Genetics
i(12p)
How to grade?
No need to grade because mets even in mature teratomas (unlike in ovary)
Malignant transformation
Sarcoma (no1 in contrast to ovaries): mostly UPS
Carcinoma: IHC useful (CK+, EMA+, +/-CEA+, PLAP-, AFP-, HCG-)
Wilms
PNET
Treatment for malignant transformation
Surgical as nearly all are chemoresistant
How to differentiate PNET from immature teratomatous focus? How to diagnose epithelial malignancy?
Diagnose as PNET if >1LPF (4x)à concept of GCT overgrowth
Stromal invasion
Peculiar behavior
Pure teratoma can metastasize as non-teratomatous GCT
Prognosis? Tell when it’s critical to find immature component?
Childs: all mature teratomas are benignà critical to find immature elements
Adults: all teratomas (regardless maturity) are considered malignantà not important to find immature elements
Malignant transformation once outside of testis does not respond to chemotherapyà therefore must resect before it spreads
DDx
Epidermoid cyst: squamous epithelium lining cyst with no sebaceous glands, no ITGCN
Dermoid cyst: squamous epithelium lining a cyst with sebaceous glands in the wall, no ITGCNà just like in ovary but very rare in testis, completely benign
Why important to differentiate epidermoid and dermoid cysts from teratomas?
2 cysts are benign
Monodermal variants
Carcinoid: considered to be monodermal teratomas
PNET: considered to be monodermal teratomas
CARCINOID
Can they have carcinoid syndrome?
Yes, 10%
Most important ddx?
Metastatic carcinoid
| Primary | Metastatic |
| Teratomatous component | Bilateral, multifocal |
| LVI |
PNET
Diagnosis
->1LPF of immature neuroepithelium
IHC
-CD99+
-NE markers+
MIXED TUMORS* (more common than pure)
Name a few common combos
YET (YST, embryonal, teratoma): with HCG-containing giantsà YST confers slightly better prognosis
ET (embryonal, teratoma): aka teratocarcinoma, lower metastatic rate than embryonal carcinoma alone (remember embryonal carcinoma tends to differentiate into teratoma)
Less common for seminomas, never for spermatocytic seminoma
Why grossing important?
To get all components!
Significance of having YST, EC, CC?
YST associated with decreased relapses when confined to testis whereas EC and CC correlated with aggressiveness. However, YST less sensitive to chemotherapy than EC
POLYEMBRYOMA
Embryoid bodies (resembling developing yolk sacs)
LEYDIG CELL TUMOURS (interstitial)
Demo and presentation
-Peak 20-40
-Can elaborate androgen, estrogens or CTSDà sexual precocity in kids, gynecomastia in adults
Gross
-WC, homogeneous gold brown, with fibrous bands, buldging
Micro
-Sheets and cords
-Polygonal, central nuclei, nucleoli, abundant granular eosinophilic cytoplasm, indistinct cell bordersà hepatocyte-like
-Inclusions: lipofuscin, lipid vacuoles, Renke crystalloids and eosinophilic globoid inclusions (Renke precursors)
-Mitoses present but rare
Benign? What are malignant criteria?
No, 10% mets. How to tell?
>5 cm, >3 MF/10 HPF, atypical mitoses, nuclear pleomorphism, necrosis, vascular invasion, infiltrative margins, metastasis
IHC (hint: “MIC”)
CK ?
Calretinin+
Inhibin+
MelanA+
EM
SER
Intracytoplasmic droplets
SERTOLI CELL TUMOURS
Demo and presentation
Anyone under 40
Can elaborate androgens and estrogens but often insufficient to masculinize or feminize
Gross
WC, white homogeneous
Micro
Numerous hollow tubules (trying to recapitulate seminiferous tubules), lined by tall columnar cells
Benign? What are malignant features?
10% mets
Size>5cm, necrosis, moderate-severe atypia, vascular invasion, >5/10 mitoses
IHC
Calretinin
Inhibin
EM
SER
Intracytoplasmic droplets
Variants (2)
Sclerosing: abundant dense stromal tissue distorting sertoli tubules
Large cell calcifying: focal ossification + sertoli tubulesà Carney’s complex (acromegaly, pituitary gigantism, hypercortisolemia, sexual precocity, spotty skin pigmentation, sudden death) (pituitary GH adenomas, bilateral black adrenals, testicular LCCSCT, cardiac myxomas, skin lentigines and psammomatous melanotic schwannoma)
Name 3 syndromic associations
Androgen insensitivity
Carney’s: LCCSCT (50 cases reported…)
Peutz-Jeghers: LCCSCT
GRANULOSA CELL TUMOR
Incidence
Very rare
| Adult | Juvenile |
| No1 tumor for infants <6m | |
| Gynecomastic in 20% | Often cystic |
| 10% malignant | All benign |
LYMPHOMA
Demo
>60yo*, can be bilateral
Gross
Diffuse tan involvement (looks like seminoma)
Commonest type
DLBCL
CLASSIFY TESTICULAR TUMOURS
GCT (95%)
Precursor
Intratubular Germ Cell Neoplasia ITGCN
Seminomatous GCTà more pure
Seminoma: 40
With syncytiotrophoblast cells
Spermatocytic seminoma: 50-60
With sarcomatous component
NSGCTà often mixed
Embryonal carcinoma: 30
Yolk sac tumour: <3 and adults
Teratoma: <3 and adults?
Mature
Immature
With malignant transformation
Monodermal variants: (struma ovarii, struma carcinoid, PNET)
Dermoid cyst
Epidermoid cyst
Choriocarcinoma: 10-20
Mixed
Mixed (60% of GCT)
Polyembryoma
NON-GCT
Sex-cord stromal tumours
Sertoli cell
Typical
Sclerosing
Large cell calcifying
Peutz-Jeghers syndrome associated
Carney Complex associated
Leydig
Sertoli-Leydig
Granulosa
Juvenile
Adult
Mixed germ cell/sex cord
Gonadoblastoma
Possible cell types in sex cord-stromal tumors
Sertoli
Leydig
Granulosa
Theca
FB
Name 6 major categories of sex cord-stromal tumors
Leydig
Sertoli
SLCT
Granulosa
Fibroma of gonadal stromal origin
Sex cord-stromal tumors of mixed type or indeterminate origin
TESTIS STAGING
Tis ICGNU
T1[2] Testis or epdydimis or TA (but not TV!)
T2 Testis or epdydimis+LVI or TV invasion
T3 Spermatic cord
T4 Scrotum
N0
N1 <2cm in up to 5 nodes
N2 2-5cm, or greater than 5 nodes or extranodal
N3 >5cm in any
M0
M1 Distant
M1a Non-regional nodes or lung “L”
M1b Other than above
S0 Normal markers
S1-3 LDH, HCG, AFP
When to upstage? Is epididymis considered part of testis?
LVI, TV invasionà T2
Spermatic cordà T3
Scrotumà T4
Size and number of LNà N2-3
LDH, HCG, AFP are parts of staging!
Epididymis and TA are parts of testisà therefore T1
Clinical stages
1: Confined to testis
2: Mets limited to retroperitoneal LN below diaphragm
3: Mets outside retroperitoneal LN or above diaphragm
Name 4 uses of serum markers (LDH, AFP, HCG)
Evaluate testicular mass as workup
Stage germ cell tumor
Asses tumor burden
Monitor response
SGCT more likely to met. via lymphatics
NSCGT mets via blood
TESTIS GROSSING
Submit cord margin prior to opening testisà need margin, mid section and peri-testicular
Sample necrotic areas and tumourà bisect testis in long axis across head of epididymisà take photos, sample for EM or othersà serial sections at 3mmà record relationship with TA and hilumà cut epididymis longitudinally (not cross-sections)
Vessels
Normal testis
RPLND GROSSING
-Sample thoroughly
-Done when persistently elevated serum markers after radical orchiectomy and chemotherapy
-Can be done for advanced stage tumors (III)
-May include other organs (vertebra)
ORCHIECTOMY REPORTING
Size
% of different tumor types
LVI
Tunica invasion
Spermatic cord
ITGCN
DIFFERENTIALS
What are the tumours of the rete testes?
Cystic dysplasia
Adenomatous HP
Adenocarcinoma
MESOTHELIUM
PARATESTICULAR TUMOURS
Classification
Primary
Mesothelial origin
Surface epithelial tumors of ovary
Metastatic extension from testes
ADENOMATOID TUMOUR
Clin: 35yrs
Gross: well-circ tan nodule
Micro
Angulated glands
Large signet ring vacuoles
Fibrous stroma
May look infiltrative microscopically
Why important?
Urologist may order FS and this diagnosis can spare patient from orchiectomy!
IHC
Calretinin
Hale’s colloid iron
DSRCT
t(11;22) but CD99-
DIFFERENTIALS
Paratesticular masses
Lipoma: often just herniated retroperitoneal fat
Mesothelioma
Adenomatoid tumor: upper pole of epididymis
Mesothelial HP
DSRCT
Sarcoma
4 mesothelial derived tumours in testes?
Adenomatoidà paratesticular
2. DSRCTà paratesticular (???)
3. Mesothelial HP
4. Mesotheliomaà tunica vaginalis
Most common benign and malignant paratesticular tumors
Benign: adenomatoid tumor
Malignant: RMS in kids, LPS in adults