04/04/2016
1
The Most Common, Clinically
Significant Misdiagnoses in
Testicular Tumor Pathology
Thomas M. Ulbright, M.D.
Indiana University School of Medicine
Indianapolis, Indiana
Seminoma or Embryonal
Carcinoma?
(It’s usually seminoma)
Seminoma
04/04/2016
2
Seminoma
Seminoma
Seminoma
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3
Seminoma
Germ
Cell
Prepub
Teratoma
Prepub
Mixed GCT
Prepub
YST
Epiderm
Cyst
Dermoid
Cyst
Spermatocytic
Tumor
GCNIS
Seminoma
Seminoma
+
SynT
Postpub
YST
Postpub
Teratoma
Chorio-
carcinoma Embryonal
Carcinoma
Mixed GCT
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4
Mixed GCT
Mixed GCT
Seminoma
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5
Immunostains for Seminoma vs. Embryonal
Carcinoma (EC)
Stain Sem. EC
AE1/AE3 ± ++
*CD30 ++
SOX2 ++
*Podoplanin ++ ±
CD117 ++ ±
SOX17 ++
Seminoma & EC
AE1/AE3
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6
CD30
CD117
Podoplanin
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Embryonal Carcinoma & Seminoma – SOX2 Stain (Courtesy of Dr. Jason Hornick)
Seminoma or Yolk Sac
Tumor?
YST
04/04/2016
8
YST
YST
YST
04/04/2016
9
Morphologic feature % positive
Associated yolk sac
tumor patterns
Microcystic/Reticular
75%
Glandular 35%
Myxoid 25%
Endodermal sinus 19%
Macrocystic 14%
Hepatoid 14%
None (Pure solid) 4%
Papillary 4%
PVV 2%
Cytoplasm- pale/clear 85%
Intercellular basement
membrane
75%
Microcysts within solid
area
67%
Hyaline globules 65%
Sinusoidal vascularity 58%
Myxoid background 39%
Fibrovascular septa 17%
Lymphocytic infiltrate 17%
Features of Solid YSTs
Seminoma
Seminoma
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10
YST
YST
Immunostains for Seminoma vs Yolk Sac
Tumor (YST)
Stain Sem. YST
AFP ±
GPC3 +
AE1/AE3 ± +
*OCT3/4 +
Podoplanin +
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IHC stains Number of
cases
stained
% cases
positive
Overall
Staining
Score (E x I) +
SD
AE1/AE3 30 100 6.5 ± 2.3
Glypican 3 36 97 4.6 ± 2.5
AFP 29 62 2.3 ± 2.3
CD117 32 59 1.7 ± 1.9
Podoplanin 33 3 0.1 ± 0.5
OCT 3/4 36 0 0
Immunoreactivity of Solid YST
AFP
AFP GPC3
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12
OCT 3/4
OCT 3/4
Mixed GCT
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13
OCT 3/4
Seminoma or Sertoli Cell Tumor?
SCT
04/04/2016
14
SCT
SCT Seminoma
Normal IGCNU
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15
Aberrant Clinical History for Seminoma
• Recurrence within a radiated field
• Recurrence 3 or more years after
treatment
Immunostains for Seminoma vs Sertoli
Cell Tumor (SCT)
Stain Sem. SCT
*OCT3/4 +
SALL4 +
PLAP +
*SF1 +
Inhibin +
Nuc β-cat +
Seminoma with
Syncytiotrophoblast Cells or
Choriocarcinoma?
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16
Seminoma+SynT
Chorio.
Seminoma+SynT
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Monophasic Chorio.
Seminoma+SynT
OCT 3/4
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Sem.+Chorio.
Seminoma with a Prominent
Granulomatous Reaction or
Granulomatous Orchitis?
Seminoma
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Seminoma
OCT 3/4
IGCNU
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20
IGO
IT Grans.
Real or Pseudo Vascular
Invasion?
04/04/2016
21
Primary Tumor Staging
pT1 -Testis and epididymis only; no
vascular invasion or penetration of
tunica vaginalis
pT2 - Testis and epididymis with vascular
invasion or penetration of tunica
vaginalis
Pseudo Invasion
“Buttered On” Tumor
04/04/2016
22
Real Invasion
Intratubular
Embryonal
Carcinoma
Intratubular
Embryonal
Carcinoma
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23
Intratubular
Embryonal
Carcinoma
Intravascular
Embryonal
Carcinoma
Intravascular
Embryonal
Carcinoma
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24
Intravascular
Histiocytes
Scar or a Regressed GCT?
Regressed GCT
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Regressed GCT
Regressed GCT
Atrophy, Microlith
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Atrophy, LCs
IGCNU
Distribution of Features in Regressed
Testicular GCTs
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Features of Regressed GCTs
Diagnostic
• Scar + GCNIS
• Scar + coarse
intratubular
calcifications
Suspicious • Scar with
hypervascularity, siderophages &/or lymphoplasmacytic infiltrates
• Scar with peripheral seminiferous tubule atrophy, intratubular granulomas, microlithiasis, and/or Leydig cell hyperplasia
N.B. – Tubular “ghosts” in the scar do not R/O a
regressed GCT
Problems with Metastases
• No prior history of cancer – 62%
• Unilateral involvement – 92%
• Occasional prominent intrarete growth,
especially prostate carcinoma
• Occasional prominent intratubular growth
Prost. Ca
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Prost. Ca
Prost. Ca
PSA
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29
RCC
RCC
Prost. Ca
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30
Prost. Ca
PAP
TCC
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