The Most Common, Clinically Significant Misdiagnoses in ......The Most Common, Clinically Significant Misdiagnoses in Testicular Tumor Pathology Thomas M. Ulbright, M.D. Indiana University

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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

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Seminoma

Seminoma

Seminoma

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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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Mixed GCT

Mixed GCT

Seminoma

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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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CD30

CD117

Podoplanin

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Embryonal Carcinoma & Seminoma – SOX2 Stain (Courtesy of Dr. Jason Hornick)

Seminoma or Yolk Sac

Tumor?

YST

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YST

YST

YST

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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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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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OCT 3/4

OCT 3/4

Mixed GCT

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OCT 3/4

Seminoma or Sertoli Cell Tumor?

SCT

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SCT

SCT Seminoma

Normal IGCNU

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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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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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IGO

IT Grans.

Real or Pseudo Vascular

Invasion?

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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

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Real Invasion

Intratubular

Embryonal

Carcinoma

Intratubular

Embryonal

Carcinoma

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Intratubular

Embryonal

Carcinoma

Intravascular

Embryonal

Carcinoma

Intravascular

Embryonal

Carcinoma

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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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RCC

RCC

Prost. Ca

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Prost. Ca

PAP

TCC

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