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 A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they unde ...

rest remnants in the

mediastinum The mediastinum (from ;: mediastina) is the central compartment of the thoracic cavity. Surrounded by loose connective tissue, it is a region that contains vital organs and structures within the thorax, mainly the heart and its vessels, the eso ...

. Germ cell tumors most commonly occur in the

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

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 di ...

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 m ...

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 tot ...

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 abnormalities in the developing ...

, and an extra

X chromosome The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...

. 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 the initial stage of development for 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 ...

. 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 ...

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 di ...

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 (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

and

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 th ...

. 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 , C=55 , H=84 , N=17 , O=21 , S=3 , SMI ...

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 chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...

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 that involves cutting open the chest wall to gain access into the pleural cavity, It is mostly performed by specialist cardiothoracic surgeons, although emergency physicians or paramedics occasionally also ...

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 c ...

. 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 ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone. The ...

, 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 a chromosome anomaly where a male has an extra X chromosome. These complications commonly include infertility and small, poorly functioning testicles (if present). These symptoms are often not ...

History

Malignant Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

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

Mediastinal The mediastinum (from ;: mediastina) is the central compartment of the thoracic cavity. Surrounded by loose connective tissue, it is a region that contains vital organs and structures within the thorax, mainly the heart and its vessels, the eso ...

and other extragonadal

germ cell tumors A germ cell tumor (GCT) is a neoplasm derived from primordial germ cells. Germ-cell tumors can be cancerous or benign. Germ cell tumors typically originate from the gonads (ovary and testis), but can arise in other areas of the body. Extragonadal ...

were initially thought to represent isolated

metastases Metastasis is a pathogenic agent's spreading 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, ...

from an inapparent

gonadal A gonad, sex gland, or reproductive gland is a mixed gland and sex organ 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, ...

primary site.

References

External links

* {{Germ cell tumors Germ cell neoplasia