Embryonal Carcinoma of the Testis

Background

The embryonal carcinoma of the testis is a germ cell neoplasm. Clinically, these tumors present much like other testicular tumors, 80% with a testicular mass associated with pain or discomfort.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/
Other Diagnostic Testing

Gross Appearance
and Clinical Variants

Histopathological Features
and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERISTICS

INCIDENCE 2.3% of testicular germ cell tumors
40% of all germ cell tumors have some embryonal component
87% of non-seminomatous germ cell tumors

AGE-RANGE AND MEDIAN 25-35 yrs Median 32 yrs

SEX (MALE:FEMALE) Male

GEOGRAPHIC DISTRIBUTION Worlwide

DISEASE ASSOCIATIONS CHARACTERIZATION

HLA B-13 Increased risk

PATHOGENESIS CHARACTERIZATION

Possible that they arise from seminomas that have lost cancer suppressor genes Formation of isochromosome i(12p)

Oncogenes K-ras mutations

LABORATORY/
RADIOLOGIC CHARACTERIZATION

Serum AFP Elevated but may be secondary to a yolk sac tumor component

Serum LDH Elevated

Serum PLAP (placental-like alkaline phosphatase) Elevated

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

Soft, pale gray with bulging cut surface with hemorrhage and necrosis Average about 2.5 cm

Local extension Occurs in 25% of cases

HISTOLOGICAL TYPES CHARACTERIZATION

General There is a controversy whether tumors with a minor component of teratoma should be included or excluded-most choose to include it as embryonal if the teratomatous component is primitive mesenchyme

Classic Groups of large cells arranged in solid sheets, papillary, glandular
Occasionally, a pseudo-endodermal sinus pattern and double layered pattern may be present mimicking a yolk sac tumor or choriocarcinoma

SPECIAL STAINS/
IMMUNOPEROXIDASE CHARACTERIZATION

Cytokeratin Positive

OCT4

OCT4 Staining in Testicular Tumors: A Sensitive and Specific Marker for Seminoma and Embryonal Carcinoma.

Jones TD, Ulbright TM, Eble JN, Baldridge LA, Cheng L.

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN.

Am J Surg Pathol. 2004 Jul;28(7):935-40. Abstract quote

OCT4 (POU5F1) is a transcription factor expressed in embryonic stem and germ cells and is involved in the regulation and maintenance of pluripotency. It has been detected in primary testicular germ cell tumors with pluripotent potential, seminoma, and embryonal carcinoma.

We undertook immunohistochemical staining of OCT4 in a wide variety of primary testicular neoplasms (germ cell tumors and other tumors) to assess the specificity and usefulness of this marker as a diagnostic tool.

We examined histologic sections from 91 primary testicular neoplasms, including 64 cases of mixed germ cell tumors containing embryonal carcinoma (54), seminoma (51), yolk sac tumor (38), mature teratoma (31), immature teratoma (20), and choriocarcinoma (15). In addition, we examined sections from spermatocytic seminomas (5), Leydig cell tumors (8), Sertoli cell tumors (6), unclassified sex-cord stromal tumors (4), adenomatoid tumors (2), testicular tumor of adrenogenital syndrome (1), and granulosa cell tumor (1). Each tumor was examined with hematoxylin and eosin staining and with antibodies to OCT4. In all cases of mixed germ cell tumor with components of embryonal carcinoma (54) and seminoma (51), there was greater than 90% nuclear staining of the embryonal carcinoma and seminoma tumor cells with little to no background staining. In all but 1 of these cases (embryonal carcinoma), there was strong (3+) staining intensity. The other germ cell tumor components (yolk sac tumor, mature teratoma, immature teratoma, and choriocarcinoma) showed no staining.

Syncytiotrophoblast cells, which were present in 15 of the cases, were also completely negative, as were all 5 of the spermatocytic seminomas. The 22 cases of non-germ cell tumors were all immunohistochemically negative for OCT4. Fifteen of the 54 germ cell tumors containing embryonal carcinoma were also examined with antibodies to CD30. These embryonal carcinoma components were all positive for CD30 with staining of greater than 90% of the tumor cells but with variable staining intensity.

We conclude that immunostaining with antibodies to OCT4 is a useful diagnostic tool in the identification of primary testicular embryonal carcinomas and "usual," but not spermatocytic, seminomas. OCT4 immunostaining has comparable sensitivity but greater consistency compared with CD30 in the diagnosis of embryonal carcinoma.

PLAP Positive in 86-97%

CD30 (Ber-H2, Ki-1) Positive in 80%

p53 Positive in 5-50%

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

Yolk sac tumor Lack CD30 positivity

Large cell lymphoma Cytokeratin negative
LCA positive

PROGNOSIS AND TREATMENT CHARACTERIZATION

Prognostic Factors
Stage is most important

40% have tumors limited to testis at presentation
40% have retroperitoneal involvement
20% have supradiaphragmatic involvement or visceral organ spread

5 Year Survival >90% overall

Metastasis Retroperitoneal lymph nodes

TREATMENT
If tumor is limited to testis, some advocate retroperitoneal lymph node dissection (RPLND)

If there is relapse after initial negative nodes, cisplatin-based chemotherapy may be started, with 98-100% survival

If nodes are positive (6 cm or less of total nodal involvement) with chemotherapy, 98% survival

Advanced stage bulky disease
Defined as:
Mediastinal mass >50% intrathoracic diameter
>10 pulmonary metastases per lung field, largest >3cm
Palpable abdominal mass with lung, liver, bone, or brain metastases

Chemotherapy achieves clinical remission in 57%

Atlas of Tumor Pathology-Tumors of the Testis, Adnexa, Spermatic Cord, and Scrotum. AFIP 1997.

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Last Updated 7/19/2004

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERISTICS
INCIDENCE	2.3% of testicular germ cell tumors 40% of all germ cell tumors have some embryonal component 87% of non-seminomatous germ cell tumors
AGE-RANGE AND MEDIAN	25-35 yrs Median 32 yrs
SEX (MALE:FEMALE)	Male
GEOGRAPHIC DISTRIBUTION	Worlwide

DISEASE ASSOCIATIONS	CHARACTERIZATION
HLA B-13	Increased risk

PATHOGENESIS	CHARACTERIZATION
Possible that they arise from seminomas that have lost cancer suppressor genes	Formation of isochromosome i(12p)
Oncogenes	K-ras mutations

LABORATORY/ RADIOLOGIC	CHARACTERIZATION
Serum AFP	Elevated but may be secondary to a yolk sac tumor component
Serum LDH	Elevated
Serum PLAP (placental-like alkaline phosphatase)	Elevated

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
Soft, pale gray with bulging cut surface with hemorrhage and necrosis	Average about 2.5 cm
Local extension	Occurs in 25% of cases

HISTOLOGICAL TYPES	CHARACTERIZATION
General	There is a controversy whether tumors with a minor component of teratoma should be included or excluded-most choose to include it as embryonal if the teratomatous component is primitive mesenchyme
Classic	Groups of large cells arranged in solid sheets, papillary, glandular Occasionally, a pseudo-endodermal sinus pattern and double layered pattern may be present mimicking a yolk sac tumor or choriocarcinoma

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Yolk sac tumor	Lack CD30 positivity
Large cell lymphoma	Cytokeratin negative LCA positive

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors	Stage is most important 40% have tumors limited to testis at presentation 40% have retroperitoneal involvement 20% have supradiaphragmatic involvement or visceral organ spread
5 Year Survival	>90% overall
Metastasis	Retroperitoneal lymph nodes
TREATMENT	If tumor is limited to testis, some advocate retroperitoneal lymph node dissection (RPLND) If there is relapse after initial negative nodes, cisplatin-based chemotherapy may be started, with 98-100% survival If nodes are positive (6 cm or less of total nodal involvement) with chemotherapy, 98% survival
Advanced stage bulky disease	Defined as: Mediastinal mass >50% intrathoracic diameter >10 pulmonary metastases per lung field, largest >3cm Palpable abdominal mass with lung, liver, bone, or brain metastases Chemotherapy achieves clinical remission in 57%