Germ cell tumor

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Germ Cell Tumors Microchapters
Patient Information
Overview
Classification Dysgerminoma Seminoma Embryonal carcinoma Teratoma Choriocarcinoma Yolk sac tumor
Causes
Risk Factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Huda A. Karman, M.D.

Synonyms and keywords: Polyembryoma;

Overview

A germ-cell tumor (GCT) is a neoplasm derived from germ cells and it can be cancerous or benign. Based on their location, germ cell tumors can be classified into intragonadal (ovary and testis) or extragonadal (mediastinum, brain, retroperitoneum, coccyx). Histologically, Germ cell tumors can be classified as germinomatous/undifferentiated germ cell tumors which include, dysgerminoma and seminoma. and nongermminomatous/differentiated which include embryonic and extra-embryonic germ cell tumors. Embryonic germ cell tumors include teratoma, and extraembryonic germ cell tumors include Choriocarcinoma and Yolk sac tumor. The name of a germ cell tumor came from the word (germinate), which means to begin to grow. During fetus development, germ cells migrate to become the eggs in the ovary or the sperms in the testicles. Germ cell tumors develop due to the abnormal growth of the germ cells in the ovary, testis, brain, mediastinum, coccyx, or pelvis. World health organization (WHO) classified germ cell tumors into 7 types based on histology. The cause of germ cell tumors development is not fully understood but some causes include, genetic mutations, cryptorchidism, undescended testes, trauma, mumps, maternal estrogen exposure. Common risk factors include Caucasian race,Family history or personal history of germ cell tumor, Klinefelter syndrome. Less common risk factors include,Infections such as HIV, orchitis, or history of trauma. Symptoms and signs of germ cell tumors depend on the type and location of the tumor. Symptoms of dysgerminoma can include, abdominal distention, acute/ subacute abdominal pain, menstrual irregularities, and precocious puberty. Symptoms of seminoma include painless testicular mass with discomfort, back pain, abdominal discomfort, or abdominal mass. Common complications of germ cell tumors include recurrence, lymph node metastasis, distant metastasis, and secondary malignancies. Lab findings include abnormal serum tumor marker levels such as LDH, HCG (seminoma), lactate dehydrogenase (LDH), human chorionic gonadotropin (HCG), CA-125, and alpha-fetoprotein (AFP) (ovarian germ cell tumors), alpha fetoprotein (AFP) greater than 100 ng/ml (Endodermal sinus tumor). CT, MRI, and ultrasound are used in combination with biopsy to distinguish between the types and subtypes of germ cell tumors and for diagnosis confirmation. Surgery along with chemotherapy are the mainstay of treatment depending on the staging of the tumor. Depending on the type, location, and the extent of the tumor at the time of diagnosis, the prognosis may vary.

Classification

Germ cell tumors can be classified as follows:

Histologic-based classification

Germ cell tumors

Germinomatous/Undifferentiated/Immature

Nongerminomatous/Differentiated/Mature

Dysgerminoma(Ovary)

Seminoma(Testis)

Embryonal carcinoma

Embryonic tissue

Extraembryonic tissue

Teratoma

Yolk sac tumor

Choriocarcinoma

Location-based classification, regardless to the histologic findings:

Germ cell tumors

Gonadal

Extragonadal

Located in the gonads Ovary Testis

Located in the midline of the body including: CNS Mediastinum Retroperitoneum Coccyx

Types	Subtypes	Signs and Symptoms	Histopathology	Lab finding	Prognosis
Germinomatous /Undifferentiated	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.	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 (Ovary)	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.
Germinomatous/ Differentiated	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.
Extraembryonic
Choriocarcinoma(Gestational Trophoblastic Neoplasia)	Early Symptoms: Vaginal bleeding Nausea and vomiting Passing of tissue resembling a “bunch of grapes” from the vagina Absent fetal movement during pregnancy Abdominal distension Rare Symptoms: Headache Edema of the hands and feet Abdominal or pelvic pain Vaginal discharge Overactive thyroid gland (hyperthyroidism) that causes: Tachycardia Sweating Shaking Heat intolerance Fever Late Symptoms Hemoptysis Dry cough Chest pain Trouble breathing Headache Dizziness Jaundice Paralysis Seizure Dysarthria and dysphasia Vision problems Lump in the vagina	Gross pathological: Bulky, destructive mass with hemorrhage and necrosis Can be associated with deep myometrial invasion Microscopic histopathological: Columns and sheets of trophoblastic tissue invading uterine muscle and blood vessels Syncytiotrophoblasts (large eosinophilic smudgy multinucleated cells with large hyperchromatic nuclei) are intermixed with cytotrophoblasts (polygonal cells with distinct borders, and single irregular nuclei)	Human chorionic gonadotropin (HCG or b-HCG) is the most common tumor marker test used to diagnose GTD HCG is markedly elevated (usu. >10,000 IU Human placental lactogen (hPL) is a tumor marker that may be used to follow women with placental site trophoblastic tumors Elevated hPL levels are found in women with some types of GTD Complete blood count can check for anemia from long-term (chronic) vaginal bleeding	Poor prognosis of gestational trophoblastic neoplasia (GTN) can be determined by the following factors: Age over 35 years (P = 0.025) Interval since the last pregnancy of over 2 years (P = 0.014) Deep myometrial invasion (P = 0.006) Stage III or IV (P < 0.0005) Maximum βhCG level > 1000 mIU/ml (P = 0.034) Extensive coagulative necrosis (P = 0.024) High mitotic rate (P = 0.005) Presence of cells with clear cytoplasm (P < 0.0005)
Yolk sac tumor (Endodermal sinus tumor)	Symptoms: Abdominal distention Acute/sub acute abdominal pain Signs: Abdomen: Abdominal distention Abdominal tenderness Pelvis: Adnexal mass	On gross pathology: Encaptulated, firm, smooth, round, globular, solid gray-white with a gelatinous, myxoid, or mucoid appearance, necrosis, cystic changes, and hemorrhage are characteristic findings of endodermal sinus tumor. On microscopic histopathological analysis: Schiller-Duval bodies (invaginated papillary structures with central vessel) is a characteristic finding of endodermal sinus tumor. The tumors are composed of irregular space lined by flattened to cuboidal cells and recticular stroma	An elevated concentration of serum alpha feto-protein is diagnostic of endodermal sinus tumor. AFP is very important for diagnosis, disease monitoring and early metastasis Endodermal sinus tumor may also be diagnosed using biopsy and measurement of GATA-4, a transcription factor	Endodermal sinus tumor has a poor prognosis in adult. Endodermal sinus tumor has a favorable prognosis in children. Endodermal sinus tumor is the most common malignant germ cell tumor in children. If left untreated, endodermal sinus tumor quickly metastasizes in other parts of the body such as the brain. Endodermal sinus tumor can be found in the ovaries or testicles including the chest, abdomen, and the brain. Ovarian germ cell tumor (endodermal sinus tumor) is surgically staged using the FIGO cancer staging system:

Causes

• The cause of germ cell tumor is not understood fully but there are many risk factors that believed to play a role in the development of germ cell tumors.

The etiology of yolk sac tumors (YSTs) is essentially unknown. It is speculated that hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor that regulates differentiation and function of yolk sac endoderm, may play important roles in the pathogenesis of yolk sac tumors (YSTs)

Germ cell tumor	causes
General Causes
Dysgerminoma
Seminoma	Common causes Cryptorchidism Undescended testis Abdominal testis Trauma Mumps Maternal estrogen exposure Genetic Causes Seminoma is caused by a mutation in the KIT gene. 12p11.2-p12.1 chromosomal amplifications and deletions observed in majority of cases.
Embryonal cell carcinoma
Choriocarcinoma	Abnormal trophoblastic population undergoing hyperplasia and anaplasia can give rise to choriocarcinoma. Gestational type arises following a hydatidiform mole, normal pregnancy, or most commonly, abortion. Non-gestational type arises from pluripotent germ cells.
Yolk sac tumor

Risk Factors

Germ cell tumor	Risk factors
Ovarian germ cell tumor	gonadal dysgenesis Maternal hormonal factors: Maternal high body mass index Maternal use of exogenous hormones Other reproductive factors: Parity Oral contraceptive use Age at first and last births Dysgerminoma: gonadal dysgenesis, androgen insensitivity syndrome gonadoblastoma. Mature teratoma: Common risk factors in the malignant transformation of mature teratoma include: Old age (> 50 years old) Large tumor size (> 10 cm) Presence of a solid portion
Seminoma	Common Risk Factors Caucasian race Undescended testicle Family history of testicular cancer Personal history of testicular cancer (previous tumor in contralateral testis) Klinefelter syndrome Impaired spermatogenesis Hypospadias Testicular microlithiasis Testicular dysgenesis Testicular feminization Klinefelter syndrome Less Common Risk Factors Infections such as HIV, orchitis History of trauma Organ transplant immunosuppression Canabis exposure
Embryonal carcinoma
Teratoma
Choriocarcinoma	Maternal The risk of choriocarcinoma increases progressively in women older than 25 years The risk increases more rapidly in women older than 39 years The risk is higher for women younger than 20 compared with women aged 20 – 24 years History of Gestational Trophoblastic Disease Reproductive Factors
Yolk sac tumor

Related chapters

• Embryonic stem cells

External Links

• Childhood Extracranial Germ Cell Tumors
• Extragonadal Germ Cell Tumors
• Ovarian Germ Cell Tumors

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References