A germ cell tumor (GCT) is a neoplasm derived from primordial germ cells. Germ-cell tumors can be

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

ous or benign. Germ cell tumors typically originate from the gonads (

ovary The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/ oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are end ...

and testis), but can arise in other areas of the body. Extragonadal GCTs are thought to result from abnormal migration of germ cell precursors during development of the embryo.

Classification

Relative incidences of testicular tumors

GCTs are classified by their

histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...

, regardless of location in the body. However, as more information about the genetics of these tumors become available, they may be classified based on specific gene mutations that characterize specific tumors. They are broadly divided in two classes: * The germinomatous or seminomatous germ-cell tumors (GGCT, SGCT) include only germinoma and its synonyms dysgerminoma and

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 ...

. * The nongerminomatous or nonseminomatous germ-cell tumors (NGGCT, NSGCT) include all other germ-cell tumors, pure and mixed. The two classes reflect an important clinical difference. Compared with germinomatous tumors, nongerminomatous tumors tend to grow faster, have an earlier mean age at time of diagnosis (around 25 years versus 35 years, in the case of testicular cancers), and have a lower five-year survival rate. The survival rate for germinomatous tumors is higher in part because these tumors are very sensitive to radiation, and they also respond well to chemotherapy. The prognosis for nongerminomatous tumours has improved dramatically, however, due to the use of platinum-based chemotherapy regimens.

Germinomatous

Nongerminomatous

Mixed

Mixed germ cell tumors occur in many forms. Among these, a common form is teratoma with endodermal sinus tumor. Teratocarcinoma refers to a germ cell tumor that is a mixture of teratoma with embryonal carcinoma, or with choriocarcinoma, or with both. This kind of mixed germ cell tumor may be known simply as a teratoma with elements of embryonal carcinoma or choriocarcinoma, or simply by ignoring the teratoma component and referring only to its malignant component: embryonal carcinoma and/or choriocarcinoma. They can present in the anterior mediastinum.

Cause

Extragonadal GCTs were thought initially to be isolated metastases from an undetected primary tumor in a

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 many germ cell tumors are now known to be congenital and originate outside the gonads. The most notable of these is sacrococcygeal teratoma, the single most common tumor diagnosed in babies at birth. Of all anterior mediastinal tumors, 15–20% are GCTs of which about 50% are benign teratomas. Ovarian teratomas may be associated with anti-NMDA receptor encephalitis.

Location

GCTs most commonly arise in the testis, followed by the

and extragonadal sites. Extragonadal GCTs tend to arise in the midline, most commonly at the following sites: *

Central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

— in the pineal gland or sella turcica * Head and neck — inside the

mouth A mouth also referred to as the oral is the body orifice through which many animals ingest food and animal communication#Auditory, vocalize. The body cavity immediately behind the mouth opening, known as the oral cavity (or in Latin), is also t ...

* Mediastinum * Retroperitoneum * Spine, particularly sacrococcygeal teratoma In females, GCTs account for 20-25% of ovarian tumors, but are predominantly benign mature teratomas. Malignant ovarian GCTs are comparatively rare, and consist of immature teratomas, dysgerminomas, yolk sac tumors, and mixed germ cell tumors. In males, GCTs account of 95% of testicular tumors, and are all considered malignant.

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 ...

is the most common diagnosis (50%), followed by mixed-germ cell tumor (40%), and other pure GCTs. In neonates, infants, and

children A child () is a human being between the stages of childbirth, birth and puberty, or between the Development of the human body, developmental period of infancy and puberty. The term may also refer to an unborn human being. In English-speaking ...

younger than 4 years, most are sacrococcygeal teratomas. Males with Klinefelter syndrome have a 50 times greater risk of GSTs. In these persons, GSTs usually contain nonseminomatous elements, present at an earlier age, and seldom are gonadal in location.

Treatment

Treatment typically involves a combination of surgery and chemotherapy, depending on the subtype and location of the tumor. Surgery is performed upfront for testicular and ovarian tumors, as biopsies are associated with peritoneal and scrotal tumor seeding. Benign GCTs such as mature teratomas (dermoid cysts) are cured by simple excision. Testicular germ cell tumors are treated by orchiectomy, followed by surveillance, lymph node staging, and/or chemotherapy depending on the risk stratification defined by the International Germ Cell Cancer Collaborative Group (IGCCCG). Treatment for ovarian germ cell tumors typically involves at least ovarian cystectomy. Removal of the

ovaries The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...

fallopian tube The fallopian tubes, also known as uterine tubes, oviducts or salpinges (: salpinx), are paired tubular sex organs in the human female body that stretch from the Ovary, ovaries to the uterus. The fallopian tubes are part of the female reproduct ...

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

, and retroperitoneal lymph nodes may be planned depending on patient age, reproductive status, and extent of disease. Patients with advanced or high-risk GCT may need to be treated with combination

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

. The

chemotherapy regimen A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combi ...

most commonly used in GCTs is called PEB (or BEP), and consists of bleomycin, etoposide, and a platinum-based antineoplastic ( cisplatin). Targeted treatments, such as immunotherapy, hormonal therapy and kinase inhibitors, are being evaluated for tumors that do not respond to chemotherapy.

Prognosis

Germ cell tumors are a heterogeneous group with prognosis specific to their subtype and location, but cure rates exceed 80%. Advanced or metastatic germ cell tumors tend to be relatively responsive to chemotherapy compared to other types of cancer. Even for metastatic non-seminomatous germ cell tumors of the testis, 10-year median overall survival is 70-90%. In extragonadal GCTs, 5-year median overall survival ranges from 90% for extragonadal seminoma, to 17-70% for non-seminomatous tumors. The 1997 International Germ Cell Consensus Classification is a prognostic tool for estimating the risk of relapse after treatment of germ-cell tumor. Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with nonseminomatous (nongerminomatous) GCTs diagnosed between 1975 and 1989, five-year survival increased over time and with earlier diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a cancer unit that treated the majority of these men, though the unit treated more men with the worst prognosis.