Mixed Germ Cell Tumors

Steven S. Shen, MD, PhD

Jae Y. Ro, MD, PhD

Key Facts

Terminology

Germ cell tumor composed of > 1 histologic type of germ cell tumor, including seminoma

Clinical Issues

Accounts for 30-40% of all testicular germ cell tumors
Depends on clinical stage, proportion of embryonal carcinoma component, and lymphovascular invasion

Macroscopic Features

Variegated cystic and solid mass with hemorrhage and necrosis

Microscopic Pathology

Variable combination and percentage of all germ cell tumor components
Embryonal carcinoma (EC) and teratoma (T) are most common (26%)
Other combinations include teratoma and EC, teratoma with EC and yolk sac tumor (YST)
Areas of necrosis and hemorrhage are common
Rare special variants include polyembryoma and diffuse embryoma

Ancillary Tests

Immunoprofile reflects histologic component of different germ cell tumors
1st-line germ cell markers: Oct3/4, CD30(BerH2), PLAP, cytokeratin

Top Differential Diagnoses

Pure germ cell tumor, such as EC, YST, or teratoma, and metastatic carcinoma

Large MGCT with a variegated cut surface replaces the testicular parenchyma. The tumor is predominantly teratoma

; other areas are solid, hemorrhagic, and necrotic EC and YST components

A MGCT composed of variable germ cell tumor components includes mature teratoma (including cartilage, bone, and squamous nest

), immature teratoma

, EC

, and YST

TERMINOLOGY

Abbreviations

Mixed germ cell tumor (MGCT), mixed nonseminomatous germ cell tumor (MNSGCT)

Synonyms

Mixed nonseminomatous germ cell tumor

Definitions

Germ cell tumor composed of > 1 histologic type of germ cell tumor, including seminoma

CLINICAL ISSUES

Epidemiology

Incidence
- 2nd most common germ cell tumor after seminoma
- Accounts for 30-40% of all testicular germ cell tumors
Age
- Range: 20-40 years (10 years younger than seminoma)
- Rarely seen in prepubertal children and older adults (> 50 years)

Presentation

Testicular mass or swelling ± pain

Treatment

Similar to pure nonseminomatous germ cell tumor and depends on clinical stage
Radical inguinal orchiectomy ± retroperitoneal lymph node dissection or adjuvant therapy

Prognosis

Depends on clinical stage, proportion of embryonal carcinoma (unfavorable) and mature teratoma (favorable) component, and lymphovascular invasion
Cure rate > 95% for stage I and stage II disease
Cure rate approximately 70-85% for stage III disease

IMAGE FINDINGS

Radiographic Findings

Heterogeneous testicular mass on ultrasound examination
May be accompanied by retroperitoneal lymph node enlargement

MACROSCOPIC FEATURES

General Features

Variegated cystic and solid mass with hemorrhage and necrosis
Seminomatous germ cell component with solid white and gray areas
Nonseminomatous component with granular and firm areas with hemorrhage, necrosis, and cystic areas
Teratoma with bone, cartilage, and skin elements

Sections to Be Submitted

Multiple sections of different areas of tumor and at least 1 section per cm tumor
Should include necrotic and hemorrhagic areas

Size

Variable, often large bulky mass

MICROSCOPIC PATHOLOGY

Histologic Features

Variable combination and percentage of all germ cell tumor components
Embryonal carcinoma (EC) and teratoma (T) are most common (26%)
Other combinations include
- EC and seminoma (S) (16%)
- EC, yolk sac tumor (YST), and T (11%)
- EC, T, and choriocarcinoma (CC) (7%)
- EC, T, and S (6%)
- T and S (6%)
- EC and YST (4%)
- EC and CC (4%)
- Other combinations may occur (16%)
Areas of necrosis and hemorrhage are common
Rare variants include polyembryoma and diffuse embryoma
- Polyembryoma is composed of entirely or predominantly embryoid bodies with embryonic disc, yolk sac, and surrounded by myxoid stroma
- Diffuse embryoma is characterized by intimately admixture of EC and YST with YST wrapping around EC component

Cytologic Features

Reflects histologic composition of each component

Predominant Pattern/Injury Type

Neoplastic

Predominant Cell/Compartment Type

> 1 type of germ cell tumor component

ANCILLARY TESTS

Immunohistochemistry

Immunoprofile reflects histologic component of different germ cell tumors
1st-line germ cell markers: Oct3/4, PLAP, Podoplanin(D2-40), CD30(BerH2), α-fetoprotein, HCG, cytokeratin
Other germ cell markers: CD117, glypican-3, SALL4, NANOG

DIFFERENTIAL DIAGNOSIS

Pure Germ Cell Tumor

Such as embryonal carcinoma, yolk sac tumor, or teratoma
Multiple sections are required to demonstrate different germ cell tumor components

Metastatic Carcinoma

Old age, history, and bilaterality
Interstitial pattern is frequently seen in metastatic carcinoma
Positive for EMA/MUC1; negative for germ cell tumor markers

DIAGNOSTIC CHECKLIST

Pathologic Interpretation Pearls

Mixture of different histologic components of germ cell neoplasm

REPORTING CONSIDERATIONS

Key Elements to Report

Specific histologic types and percentage of each component
Lymphovascular invasion
Involvement of rete testis, epididymis, spermatic cord, and tunica
Pathology of uninvolved testicular parenchyma

SELECTED REFERENCES

1. Berney DM et al: Malignant germ cell tumours in the elderly: a histopathological review of 50 cases in men aged 60 years or over. Mod Pathol. 21(1):54-9, 2008

2. Mosharafa AA et al: Histology in mixed germ cell tumors. Is there a favorite pairing? J Urol. 171(4):1471-3, 2004

3. Sesterhenn IA et al: Pathology of germ cell tumors of the testis. Cancer Control. 11(6):374-87, 2004

4. Ayala AG et al: Testicular tumors: clinically relevant histological findings. Semin Urol Oncol. 16(2):72-81, 1998

Image Gallery

Gross and Microscopic Features

(Left) MGCT usually shows an irregular mass with variegated cut surface. Creamy gray lobulated areas suggest seminoma

, mucoid areas suggest teratoma

, and hemorrhagic brown areas suggest EC

. Gross appearances are not absolutely specific for histologic subtype. (Right) MGCT with typical variegated cut surface is shown. The cystic mucoid areas represent mature teratoma