Mediastinal germ cell tumors are

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s that derive from

germ cell Germ or germs may refer to: Science * Germ (microorganism), an informal word for a pathogen * Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually * Germ layer, a primary layer of cells that forms during embry ...

rest remnants in the

mediastinum The mediastinum (from ) is the central compartment of the thoracic cavity. Surrounded by loose connective tissue, it is an undelineated region that contains a group of structures within the thorax, namely the heart and its vessels, the esophagu ...

. They most commonly occur in the

gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...

but occasionally elsewhere.

Signs and symptoms

Unlike benign germ cell tumors of the mediastinum, malignant mediastinal tumors are usually symptomatic at the time of diagnosis. Most mediastinal malignant tumors are large and cause symptoms by compressing or invading adjacent structures, including the lungs, pleura, pericardium, and chest wall.

Seminoma A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a Malignancy, malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if dis ...

s grow relatively slowly and can become very large before causing symptoms. Tumors 20 to 30 cm in diameter can exist with minimal symptomatology. Rare cases of adult onset

acute megakaryoblastic leukemia Acute megakaryoblastic leukemia (AMKL) is life-threatening leukemia in which malignant megakaryoblasts proliferate abnormally and injure various tissues. Megakaryoblasts are the most immature precursor cells in a platelet-forming lineage; they matu ...

are associated with malignant mediastinal germ cell tumor. In these cases, the mediastinal germ cell tumor develops before or concomitantly with but not after acute megakaryoblastic leukemia. The three most common genetic aberrations in the bone marrow cells of these individuals (representing ~65% of all cases) are inversions in the long arm of

chromosome 12 Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the to ...

trisomy 8 Trisomy 8 causes Warkany syndrome 2, a human chromosomal disorder caused by having three copies (trisomy) of chromosome 8. It can appear with or without mosaicism. Characteristics Complete trisomy 8 causes severe effects on the developing fetus ...

, and an extra

X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...

. In several of these cases, the genetic aberrations in the malignant megakaryoblasts were similar to those in the malignant mediastinal germ cells. These results and those of other analyses suggest that the two malignancies derive from a common founding clone of cells (i.e. a set of genetically identical cells).

Cause

Some investigators suggest that this distribution arises as a consequence of abnormal migration of germ cells during

embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

. Others hypothesize a widespread distribution of germ cells to multiple sites during normal embryogenesis, with these cells conveying genetic information or providing regulatory functions at somatic sites.

Diagnosis

The diagnosis of a mediastinal germ cell tumor should be considered in all young males with a mediastinal mass. In addition to physical examination and routine laboratory studies, initial evaluation should include CT of the chest and abdomen, and determination of serum levels of HCG and

alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...

Treatment

Pure mediastinal

seminoma A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a Malignancy, malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if dis ...

s are curable in the large majority of patients, even when metastatic at the time of diagnosis. These tumors are highly sensitive to

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...

and to

combination chemotherapy The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by the ...

. However, the cardiotoxicity of mediastinal radiation is substantial and the standard treatment of mediastinal seminomas is with chemotherapy using

bleomycin -13- (1''H''-imidazol-5-yl)methyl9-hydroxy-5- 1''R'')-1-hydroxyethyl8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,4'-bi-1,3-thiazol-4-yl)carbonyl]amino}propyl)(dimethyl)sulfonium , chemical_formula = , C=55 , H=84 , N=1 ...

etoposide Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...

and

cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...

for either three or four 21-day treatment cycles depending on the location of any metastatic disease. Patients with small tumors (usually asymptomatic) that appear resectable usually undergo

thoracotomy A thoracotomy is a surgical procedure to gain access into the pleural space of the chest. It is performed by surgeons (emergency physicians or paramedics under certain circumstances) to gain access to the thoracic organs, most commonly the hea ...

and attempted complete resection followed by chemotherapy. The treatment for mediastinal nonseminomatous germ cell tumors should follow guidelines for poor-prognosis

testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an u ...

. Initial treatment with four courses of bleomycin, etoposide, and cisplatin, followed by surgical resection of any residual disease, is considered standard therapy.

Epidemiology

Malignant germ cell tumors of the mediastinum are uncommon, representing only 3 to 10% of tumors originating in the mediastinum. They are much less common than germ cell tumors arising in the

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...

, and account for only 1 to 5% of all germ cell

neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s. Syndromes associated with mediastinal germ cell tumors include Hematologic Neoplasia and

Klinefelter's syndrome Klinefelter syndrome (KS), also known as 47,XXY, is an aneuploid genetic condition where a male has an additional copy of the X chromosome. The primary features are infertility and small, poorly functioning testicles. Usually, symptoms are subt ...

History

Malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

mediastinal germ cell tumors of various histologies were first described as a clinical entity approximately 50 years ago.

Mediastinal The mediastinum (from ) is the central compartment of the thoracic cavity. Surrounded by loose connective tissue, it is an undelineated region that contains a group of structures within the thorax, namely the heart and its vessels, the esophagu ...

and other extragonadal

germ cell tumors Germ cell tumor (GCT) is a neoplasm derived from germ cells. Germ-cell tumors can be cancerous or benign. Germ cells normally occur inside the gonads (ovary and testis). GCTs that originate outside the gonads may be birth defects resulting from er ...

were initially thought to represent isolated

metastases Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

from an inapparent

gonadal A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...

primary site.

References

External links

* {{Germ cell tumors Germ cell neoplasia