Germ cell tumor classification

Germ cell tumors can be classified based on their histologic features into:

Germ cell tumors

Germinomatous/Undifferentiated/Immature

Nongerminomatous/Differentiated/Embryonal

Dysgerminoma(Ovary)

Seminoma(Testis)

Embryonal carcinoma

embryonic tissue

Extraembryonic tissue

Teratoma

Yolk sac tumor

Choriocarcinoma

Germ cell tumors

Germinomatous/Undifferentiated/Immature

Nongerminomatous/Differentiated/Embryonal

Dysgerminoma(Ovary)

Seminoma(Testis)

Embryonal carcinoma

embryonic tissue

Extraembryonic tissue

Yolk sac tumor

Choriocarcinoma

Germ cell

Pathogenesis

Malignant transformation

Mature teratoma

Tumors esxpressing transcription factors of pluripotency

Tumors with primitive embryonic ectoderm, mesoderm, and/or endoderm differentiation

Tumors with extraembroyonic differentiation

Dysgerminoma/Embryonal carcinoma

Immature teratoma

Yolk sac tumor/Choriocarcinoma

Germ cell tumors classification is based on the histologic features and whether they are differentiated or not into:

• Germinomatous tumors: (non-differentiated): Gonadal and Extra-gonadal
  • Germinoma ( Gonadal: dysgerminoma and seminoma), (Extra-gonadal: mediastinum, or pineal region)
  • Dysgerminoma (Ovary)
  • Seminoma (testes)
• Nongerminomatous tumors: all other germ-cell tumors, pure and mixed
  • Embryonal carcinoma
  • Endodermal sinus tumor, also known as yolk sac tumor (EST, YST)
  • Choriocarcinoma
  • Teratoma including mature teratoma, dermoid cyst, immature teratoma, teratoma with malignant transformation
  • Polyembryoma
  • Gonadoblastoma
• Mixed germ cell tumors:

Germ cell tumors can also be classified based on their location into:

• Gonadal (ovary and testes)
• Extra-gonadal (MC:mediastinum, retroperitoneal. Less common: Pineal gland, sacrococcigeal)

• Ovarian germ cell tumors (OGCTs ): The histologic types that arise from the ovary are similar to those arising from the testes of men
  • Embryo-like neoplasms
    • Teratomas and their subtypes
    • Dysgerminomas: The female version of the male seminoma (comprised of immature germ cells)
  • Extraembryonic fetal-derived (placenta-like) cell populations
    • Yolk sac/primitive placenta forms (epithelial neoplasms differentiate into yolk sac tumors)
  • Rare OGCTs
    • Pure embryonal carcinomas
    • Nongestational choriocarcinomas
    • Pure polyembryoma.
  • Mixed germ cell tumors (teratoma with yolk sac, dysgerminoma, and/or embryonal carcinoma)
• Extragonadal germ cell tumors (GCTs): no evidence of a primary tumor in the testes or ovaries
  • Typically arise in midline locations,
  • Specific sites vary with age
  • The most common sites in order of frequency
  • In adults:
    • Anterior mediastinum
      • Mature teratomas
      • Immature teratoma
      • Mediastinal seminoma
      • Mediastinal non-seminomatous GCT:
        • Yolk sac tumor (most common, pure or mixed)
        • Choriocarcinoma (less common)
        • Embryonal carcinoma (infrequent)
        • Mixed GCTs (a mixture of teratoma, seminoma, and other cell types)
    • Retroperitoneum
      • Retroperitoneal seminoma
      • Retroperitoneal non-seminomatous GCTs (Embryonal carcinoma is common)
      • Retroperitoneal teratomas (rare)
    • Pineal and suprasellar regions
  • In infants and young children:
    • Sacrococcygeal
    • Intracranial GCTs

Types	Subtypes	Signs and Symptoms	Histopathology	Lab finding	Treatment	Prognosis
Gonadal	Seminoma (Testis)	Painless testicular mass with discomfort Back pain Abdominal discomfort Abdominal mass.	Gross: pale gray to yellow nodules that are uniform or slightly lobulated and often bulge from the cut surface	Complete blood count and blood chemistry tests. Abnormal serum tumor marker levels (LDH, HCG). CT: Metastases to the para-aortic, inguinal, or iliac lymph nodes. Visceral metastasis may also be seen. Pelvic MRI: may be diagnostic. multinodular tumors of uniform signal intensity Hypo- to isointense on T2-weighted images and inhomogenous enhancement on contrast enhanced T1-weighted images. Other diagnostic studies for seminoma include biopsy, FDG-PET scan, and bone scan.	Radical inguinal orchiectomy is the first treatment for any stage of testicular seminoma. Usually done as diagnostic and therapeutic.	Prognosis of seminoma is good for all stages with greater than 90% cure rate. The International Germ Cell Cancer Consensus Group divides seminoma into two prognosis groups: good and intermediate. Common complications of seminoma include recurrence, lymph node metastasis, distant metastasis, and secondary malignancies.
Dysgerminoma (Ovarian germ cell tumor)	Depend on the type of the tumor and its potential to produce hormonalmaterials Abdominal pain or distention Menstrual irregularities Symptoms of virilization Rapidly growing abdominal/pelvic mass Acute abdominal pain from complications such as: * Necrosis * Capsular distention * Rupture or torsion and or simply they can be asymptomatic.	The majority of ovarian germ celltumors have a solid and cystic appearance with areas of hemorrhageand necrosis A uniform “fried egg” appearance (dysgerminoma)	Beta-hCG to rule out pregnancy in women with abdominopelvic symptoms Cultures for gonorrhea and chlamydia and a wet mount in reproductive and sexually active women to role out and treat before surgery if positive. Lactate dehydrogenase (LDH), alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-hCG) levels. If any levels are elevated, they may assist in diagnosis and/ or follow-up of women diagnosed with malignant ovarian GCTs. Inhibin A and B Cancer antigen 125 (CA-125) - For epithelial tumors Ultrasound: Dysgerminoma often appears as a hypoechoic mass	Chemotherapy: except those with stage 1a, stage 1a, 1b dysgerminoma Radiotherapy: ** Dysgerminoma is radiosensitive. ** Radiotherapy is not anymore the first option of treatment for dysgerminoma considering its association with ovarian failuredevelopment. Surgery: for diagnostic grading and therapy depending on if the patient prefers to preserve the ovary or not.	The 5-year survival rate of the patient even with disseminateddysgerminoma at the time of diagnosis is above 90%.
Germinoma (Brain)
Extragonadal	Embryonic
Teratoma	Chest pain Cough Shortness of breath Abdominal pain Lump, Abdominal(ovarian teratoma) Abnormal bleeding from the vagina Fatigue, weight loss Limited ability to tolerate exercise	Teratomas belong to a class of tumors known as nonseminomatous germ cell tumor (NSGCT). All tumors of this class are the result of abnormal development of pluripotent cells: germ cells and embryonal cells. Teratomas of embryonal origin are congenital; teratomas of germ cell origin may or may not be congenital (this is not known). Embryonal teratomas most commonly occur in the sacrococcygeal region: sacrococcygeal teratoma is the single most common tumor found in newborn babies.	AFP MSAFP CT scans are often used to diagnose teratoma.	For malignant teratomas, usually, surgery is followed by chemotherapy. Teratomas that are in surgically inaccessible locations, or are very complex, or are likely to be malignant (due to late discovery and/or treatment) sometimes are treated first with chemotherapy.	The prognosis of teratoma depends on the following: Whether or not the tumor can be removed by surgery. The size and location of the tumor The patient’s general health Teratomas are not dangerous for the fetus unless there is either a mass effect or a large amount of blood flow through the tumor (known as vascular steal). The mass effect frequently consists of obstruction of normal passage of fluids from surrounding organs. The vascular steal can place a strain on the growing heart of the fetus, even resulting in heart failure, and thus must be monitored by fetal echocardiography. After surgery, there is a risk of regrowth in place, or in nearby organs [1]
Extraembryonic
Coriocarcinoma
Yolk sac tumor		On microscopic pathology Presence of Schiller-Duval bodies (yolk sac tumor)