germ cell tumors of the testis - pathology...(siegel et al. ca cancer j clin 68:7, 2018) ... tumor...
TRANSCRIPT
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TESTICULAR GERM CELL TUMORS TUMORS: UNCOMMON BUT
OFTEN CHALLENGING
Alaskan Rocky Mountains
TESTICULAR TUMORS
CLASSIFICATION
• GERM CELL TUMORS
• GONADAL STROMAL TUMORS
• MIXED GERM CELL – GONADAL
STROMAL TUMORS
• MESENCHYMAL TUMORS
• LYMPHORETICULAR NEOPLASMS
• METASTATIC TUMORS
TESTICULAR GERM CELL TUMORS
INTRODUCTION
• Estimated 9,310 new cases and 400 related deaths
in USA in 2017 (Siegel et al. CA Cancer J Clin 68:7, 2018)
• Incidence (5 per 100,000) has been steadily
increasing over last few decades
• Major risk factors are cryptorchidism and low
birth weight
• Higher incidence in infertile men
• More common in Caucasians vs African Americans
• A disease of young adults (late teens to early 40’s)
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TESTICULAR GERM CELL TUMORS
CLASSIFICATION (WHO 2016)
Germ Cell Tumors Related to GCNIS
• Germ cell neoplasia in situ– Specific forms of intratubular germ cell neoplasia
• Seminoma– With syncytiotrophoblastic giant cells
• Embryonal carcinoma
• Yolk sac tumor
• Trophoblastic tumors– Choriocarcinoma
– Non-choriocarcinomatous trophoblastic tumors• Placental site trophoblastic tumor
• Epithelioid trophoblastic tumor
• Cystic trophoblastic tumor
• Teratoma, postpubertal-type
• Teratoma, with somatic-type malignancy
• Germ cell tumors of unknown type (regressed GCT)
TESTICULAR GERM CELL TUMORS
CLASSIFICATION (WHO 2016)
Germ Cell Tumors Unrelated to GCNIS• Spermatocytic tumor
• Teratoma, prepubertal type– Dermoid cyst
– Epidermoid cyst
– Well differentiated neuroendocrine tumor (monodermal teratoma)
• Mixed teratoma and yolk sac tumor, prepubertal type
• Yolk sac tumor, prepubertal type
GERM CELL NEOPLASIA IN SITU
• Most frequent adjacent to GCTs (up to 100%)
• Also seen in association with:
• cryptorchid testis (2% - 8%)
• biopsies of infertile men (1% - 2%)
• contralateral testis in GCT patients (5% - 8%)
• adjacent to regressed GCTs
• Infrequent in pediatric age group
• Progresses to invasive GCT in ~ 50% at 5 years
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GERM CELL NEOPLASIA IN SITU
• Large cells (approx. 3x size of normal germ
cells) with abundant clear cytoplasm (glycogen)
• Large nuclei with single macro nucleolus
• Hug the tubule basement membrane
• Tubules are usually but not always atrophic
• IHC: PLAP +, OCT4 +, CD117 +, CD30-
• If fill the tubules: seminoma or embryonal ca in
situ
• Watch for microinvasive disease
GERM CELL NEOPLASIA IN SITU
GERM CELL NEOPLASIA IN SITU
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GERM CELL NEOPLASIA IN SITU
Rete testis involvement
GERM CELL NEOPLASIA IN SITU
OCT4
CD117 PLAP
GERM CELL NEOPLASIA IN SITU
OCT4
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IT Seminoma IT Embryonal Ca
MICROINVASIVE SEMINOMA
INFERTILITY BIOPSY: 29 yo with a history of varicocele
OCT 3/4
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SEMINOMA• Young to middle aged adults
• Circumscribed, lobulated, homogeneous, pale tan
• Can see necrosis and hemorrhage
• Pale to clear cytoplasm, arranged in nests separated
by fibrous septae with lymphocytic infiltrate
• Granulomatous inflammation
• Syncytiotrophoblastic giant cells
• Problems with fibrosis or necrosis, amphophilic
cytoplasm, pseudotubular or pseudoglandular
architecture
• IHC: PLAP +, OCT4 +, CD117 +, CK +/-, CD30 -
SEMINOMA
SEMINOMA
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SEMINOMA
SEMINOMA – LYMPHOCYTE POOR
SEMINOMA WITH AMPHOPHILIA
CD117
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SEMINOMA WITH CORDS
SEMINOMA WITH CORDS
SEMINOMA WITH CORDS
OCT 3/4
CD 117 D2-40
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SEMINOMA WITH TUBULES
SEMINOMA WITH PSEUDOGLANDS
OCT4
CD117
SEMINOMA WITH PSEUDOPAPILLAE
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SEMINOMA WITH GRANULOMATA
SEMINOMA with SyncytiotrophoblastsSEMINOMA with Syncytiotrophoblasts
SEMINOMA with SyncytiotrophoblastsSEMINOMA with Syncytiotrophoblasts
ßHCG
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SALL4 CD20
Large B-Cell Lymphoma with
MYC rearrangement
EMBRYONAL CARCINOMA
• Young adults (~ 10 years younger than seminoma)
• No typical gross – often with hemorrhage and necrosis
• Solid, papillary and glandular growth
• Pleomorphic cells with amphophilic to basophilic cytoplasm, poorly defined cell borders
• Problems with clear cytoplasm
• IHC: PLAP +, OCT4 +, CD117 -, CK +, CD30 +
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EMBRYONAL CARCINOMA
EMBRYONAL CARCINOMA
EMBRYONAL CARCINOMA
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EMBRYONAL CARCINOMA
POLYEMBRYOMA
EMBRYOID BODIES
EMBRYONAL CA & SEMINOMA
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EMBRYONAL CA & SEMINOMA
CD 30
EMBRYONAL CA & SEMINOMA
CD117
YOLK SAC TUMOR
• Most common GCT in pediatric age group
• Rarely pure in adults
• Associated with alphafetoprotein production
• In children typically circumscribed and
yellow; no typical features in adults
• Wide range of histologic patterns – one of the
more frequent causes of disagreement
• IHC: AFP + (+/-), PLAP +, Glypican-3 +,
OCT4 -, CD117 -, CK +, CD30 -
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YOLK SAC TUMOR
Yolk Sac Tumor- Histologic Patterns
• Endodermal sinus (most distinctive)
• Reticular or microcystic (most common)
• Macrocystic
• Solid
• Glandular / alveolar
• Papillary
• Myxomatous (magma reticulare)
• Spindle cell
• Polyvesicular vitelline
• Hepatoid
• Enteric (primitive intestinal)
• Parietal
YOLK SAC TUMOR
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YOLK SAC TUMOR
Schiller Duval bodies
YOLK SAC TUMOR
HYALINE GLOBULES
YOLK SAC TUMOR
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YOLK SAC TUMOR
YOLK SAC TUMOR
YOLK SAC TUMOR
AFP
Glypican-3
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YOLK SAC TUMOR
CK (AE1/AE3)
YOLK SAC TUMOR – LATE RECURRENCE
YOLK SAC TUMOR –LATE RECURRENCE
AFPGLYPICAN-3
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CHORIOCARCINOMA
• Pure form very rare
• Associated with production of βHCG
• Metastases can be associated with
hemorrhage
• Grossly are hemorrhagic
• Made up of syncytiotrophoblasts and
cytotrophoblasts
• IHC: HCG +, PLAP +, OCT4 -, CD117 -,
CK +, GATA3 +, CD30 -
CHORIOCARCINOMA
CHORIOCARCINOMA
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CHORIOCARCINOMA
S
SS
C
CHORIOCARCINOMA
S
SS
C
βHCG
CHORIOCARCINOMA EPITHELIOID TYPE
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CHORIOCARCINOMA EPITHELIOID TYPE
ßHCG GATA3
p63 OCT4
CYSTIC TROPHOBLASTIC TUMOR
• Most commonly seen in post-chemotherapy
RPLND specimens with teratoma
• Can be found in primary germ cell tumors
• Serum ßHCG not or minimally elevated
• Considered to be “benign” in RPLND (not an
indication for additional chemotherapy)
CYSTIC TROPHOBLASTIC TUMOR
GATA3
ßHCG
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TERATOMA, POSTPUBERTAL-TYPE
• Can be pure or mixed
• Postpubertal are malignant; prepubertal are benign
• Cystic areas almost always are teratoma
• Combination of ectodermal, endodermal and mesodermally derived tissues
• No longer separated into mature and immature elements (overgrowth of PNET)
• Development of somatic malignancies
• Not responsive to chemotherapy/radiation therapy
• IHC: SALL4 +, OCT4 -, AFP +/- (depending on elements)
TERATOMA, POSTPUBERTAL-TYPE
TERATOMA, POSTPUBERTAL-TYPE
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TERATOMA, POSTPUBERTAL-TYPE
TERATOMA, WITH SOMATIC MALIGNANCY
• Defined as “a teratoma that develops a distinct secondary component that resembles a somatic-type malignant neoplasm, as seen in other organs and tissues”
• Most often present in RP lymph nodes but also in primary site
• Reported in 3% - 6% of germ cell tumors
• Sarcomas most common
• Requires at least one 4x field
• Distinguish from sarcomatoid YST
• Worse prognosis when present in post chemotherapy RP lymph nodes (or elsewhere)
SOMATIC MALIGNANCY - RHABDOMYOSARCOMASOMATIC MALIGNANCY - RHABDOMYOSARCOMA
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SOMATIC MALIGNANCY - RHABDOMYOSARCOMASOMATIC MALIGNANCY - RHABDOMYOSARCOMA
Myo D1
Myogenin
SOMATIC MALIGNANCY - PNET
Synaptophysin
GERM CELL TUMOR OF UNKNOWN TYPE
(REGRESSED “BURNED OUT” GCT)
• Patients presenting with metastatic GCT
without testicular mass
• US shows scar or microcalcifications
• Morphologic features include:
– Fibrosis with ghost tubules at periphery
– Lymphoplasmacytic infiltrate
– Angiomatous foci +/- hemosiderin
– Coarse calcifications (+/- intratubular)
• GCNIS +/- microinvasive GCT
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REGRESSED “BURNED OUT” GCT
REGRESSED “BURNED OUT” GCT
REGRESSED “BURNED OUT” GCT
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Burned out GCT with GCNIS
Burned out GCT with GCNIS
OCT4
SPERMATOCYTIC TUMOR
• Older age group
• Benign unless an associated sarcoma
• Circumscribed with mucoid surface
• Sheets of cells with fibrous septae and lymphocytic infiltrate of seminoma
• Discohesive with mucinous background
• Admixture of 3 sizes of cells: small, lymphocyte like; intermediate seminoma-like; and large cells
• IHC: PLAP -, OCT4 -, SALL4+, CD117 +/-, CK +/, CD30 -,
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SPERMATOCYTIC TUMOR
SPERMATOCYTIC TUMOR
SPERMATOCYTIC TUMOR
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SPERMATOCYTIC TUMOR
SPERMATOCYTIC TUMOR
SALL4
OCT4 PLAP
TERATOMA, PREPUBERTAL-TYPE
• Tumor unrelated to GCNIS
• Can occur in post-pubertal males
• Stringent criteria required for diagnosis
– No immature elements
– No GCNIS
– No scar
– No evidence of dysgenetic gonad
• Impaired spermatogenesis, tubular atrophy,
microlithiasis, Sertoli cell nodule
• Clinically these are benign
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TERATOMA, PREPUBERTAL-TYPE
TERATOMA, PRE-PUBERTAL TYPE
GCNIS Sertoli cell nodule
Impaired spermatogenesis Microlithiasis
EPIDERMOID CYST
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WELL DIFFERENTIATED NEUROENDOCRINE
TUMOR (MONODERMAL TERATOMA)
GERM CELL TUMORS:
IMMUNOHISTOCHEMISTRY
Ulbright TA, et al. Am J Surg Pathol 38:e50-e59, 2014
TESTICULAR TUMORSPATHOLOGY FEATURES IMPACTING
TREATMENT
• Type of tumor
– Germ cell tumors
• Seminoma
• Non-seminomatous
– Other tumor types
• Tumor stage (TNMS)
– Primary tumor
– Nodal status
– Metastases
– Serum markers
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TESTIS – DEFINITION OF TNM (2018)
Primary Tumor (T)
pTX Primary tumor cannot be assessed
pT0 No evidence of primary tumor (eg. histologic scar)
pTis Germ cell neoplasia in situ
pT1
pT1a
pT1b
Tumor limited to testis without lymphovascular invasion
Seminoma smaller than 3 cm in size
Seminoma 3 cm or larger in size
pT2 Tumor limited to the testis but with vascular/lymphatic
invasion or tumor invading hilar soft tissue or epididymis
or penetrating visceral mesothelial surface of tunica
albuginea with or without lymphovascular invasion
pT3 Tumor invades the spermatic cord with or without
lymphovascular invasion
pT4 Tumor invades the scrotum with or without
lymphovascular invasion
TESTIS – pT1 (2018)
TESTIS – pT1-Seminoma (2018)
pT1a pT1b
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TESTIS – pT2 (2018)
LYMPHVASCULAR INVASION HHILAR/EPIDIDYMAL INVASION
TESTIS – pT2 (2018)
“penetrating visceral mesothelial surface of tunica albuginea”
TA
TV
TESTIS – T AND THE SPERMATIC CORD
pT2 – intravascular tumor pM1 – discontinuous spread
pT3 – direct invasion to level of vas
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Orchiectomy – external surface
Orchiectomy – the first section
X
Orchiectomy – the first section
Spermatic cord margin
Xadditional cord sections
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Spermatic cord margin
Carry over “buttering” Positive margin
“Southern Alps” South Island, NZ