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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, and account for only 1 to 5% of all germ cell neoplasms.
Syndromes associated with mediastinal germ cell tumors include Hematologic Neoplasia and Klinefelter's syndrome.
Giant-cell lung cancers have long been considered to be exceptionally aggressive malignancies that grow very rapidly and have a very poor prognosis.
Many small series have suggested that the prognosis of lung tumors with giant cells is worse than that of most other forms of non-small-cell lung cancer (NSCLC), including squamous cell carcinoma, and spindle cell carcinoma.
The overall five-year survival rate in GCCL varies between studies but is generally considered to be very low. The (US) Armed Forces Institute of Pathology has reported a figure of 10%, and in a study examining over 150,000 lung cancer cases, a figure of 11.8% was given. However, in the latter report the 11.8% figure was based on data that included spindle cell carcinoma, a variant which is generally considered to have a less dismal prognosis than GCCL. Therefore, the likely survival of "pure" GCCL is probably lower than the stated figure.
In the large 1995 database review by Travis and colleagues, giant-cell carcinoma has the third-worst prognosis among 18 histological forms of lung cancer. (Only small-cell carcinoma and large-cell carcinoma had shorter average survival.)
Most GCCL have already grown and invaded locally and/or regionally, and/or have already metastasized distantly, and are inoperable, at the time of diagnosis.
While cancer is generally considered a disease of old age, children can also develop cancer. In contrast to adults, carcinomas are exceptionally rare in children..
The two biggest risk factors for ovarian carcinoma are age and family history.
A prospective study of ovarian sex cord–stromal tumours in children and adolescents began enrolling participants in 2005.
Some investigators suggest that this distribution arises as a consequence of abnormal migration of germ cells during embryogenesis. 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.
The true incidence, prevalence, and mortality of GCCL is generally unknown due to a lack of accurate cancer data on a national level. It is known to be a very rare tumor variant in all populations examined, however. In an American study of a database of over 60,000 lung cancers, GCCL comprised between 0.3% and 0.4% of primary pulmonary malignancies, with an age-adjusted incidence rate of about 3 new cases per million persons per year. With approximately 220,000 total lung cancers diagnosed in the US each year, the proportion suggests that approximately 660 and 880 new cases are diagnosed in Americans annually.
However, in a more recent series of 4,212 consecutive lung cancer cases, only one (0.024%) lesion was determined to be a "pure" giant-cell carcinoma after complete sectioning of all available tumor tissue. While some evidence suggests GCCL may have been considerably more common several decades ago, with one series identifying 3.4% of all lung carcinomas as giant-cell malignancies, it is possible that this number reflect
Most published case series and reports on giant cell-containing lung cancers show that they are diagnosed much more frequently in men than they are in women, with some studies showing extremely high male-to-female ratios (12:1 or more). In a study of over 150,000 lung cancer victims in the US, however, the gender ratio was just over 2:1, with women actually having a higher relative proportion of giant-cell cancers (0.4%) than men (0.3%).
Giant-cell carcinomas have been reported to be diagnosed in a significantly younger population than all non-small-cell carcinomas considered as a group. Like nearly all lung carcinomas, however, GCCs are exceedingly rare in very young people: in the US SEER program, only 2 cases were recorded to occur in persons younger than 30 years of age between 1983 and 1987. The average age at diagnosis of these tumors has been estimated at 60 years.
The vast majority of individuals with GCCL are heavy smokers.
Although the definitions of "central" and "peripheral" can vary between studies, GCCL are consistently diagnosed much more frequently in the lung periphery. In a review of literature compiled by Kallenburg and co-workers, less than 30% of GCCLs arose in the hilum or other parts of the "central" pulmonary tree.
A significant predilection for genesis of GCCL in the upper lobes of victims has also been postulated.
A dysgerminoma is a type of germ cell tumor; it usually is malignant and usually occurs in the ovary.
A tumor of the identical histology but not occurring in the ovary may be described by an alternate name: seminoma in the testis or germinoma in the central nervous system or other parts of the body.
Dysgerminoma accounts for less than 1% of ovarian tumors overall. Dysgerminoma usually occurs in adolescence and early adult life; about 5% occur in pre-pubertal children. Dysgerminoma is extremely rare after age 50. Dysgerminoma occurs in both ovaries in 10% of patients and, in a further 10%, there is microscopic tumor in the other ovary.
Abnormal gonads (due to gonadal dysgenesis and androgen insensitivity syndrome) have a high risk of developing a dysgerminoma. Most dysgerminomas are associated with elevated serum lactic dehydrogenase (LDH), which is sometimes used as a tumor marker.
Some investigators suggest that this distribution arises as a consequence of abnormal migration of germ cells during embryogenesis. 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.
Extragonadal germ cell tumors were thought initially to be isolated metastases from an undetected primary tumor in a gonad, but it is now known that many germ cell tumors are 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 germ cell tumors of which approximately 50% are benign teratomas.
Spermatocytic seminoma is not considered a subtype of seminoma and, unlike seminoma and most other germ cell tumours, it does not arise from "intratubular germ cell neoplasia". It has not been described as arising in locations outside the testis, and does not occur in association with other germ cell tumours.
The new WHO classification, due to be published in 2016, will rename the condition spermatocytic tumour to avoid confusion with classical seminoma as the biology and treatment are different.
Dysgerminomas, like other seminomatous germ cell tumors, are very sensitive to both chemotherapy and radiotherapy. For this reason, with treatment patients' chances of long-term survival, even cure, is excellent.
Spermatocytic seminoma is a neoplasm of the testis ("i.e." a tumour of the testis), and classified as a germ cell tumour.
The name of the tumour comes from the similarity (under the microscope) between the small cells of the tumour and secondary spermatocytes.
The 1997 International Germ Cell Consensus Classification is a tool for estimating the risk of relapse after treatment of malignant germ cell tumor.
A small study of ovarian tumors in girls reports a correlation between cystic and benign tumors and, conversely, solid and malignant tumors. Because the cystic extent of a tumor can be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most appropriate surgical plan to minimize risk of spillage of a malignant tumor.
Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with non-seminomatous (non-germinomatous) germ cell tumors diagnosed between 1975 and 1989, 5-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, even though the unit treated more men with the worst prognosis.
Choriocarcinoma of the testicles has the worst prognosis of all germ cell cancers
Spermatocytic seminomas are not considered a subtype of seminoma and unlike other germ cell tumours do not arise from intratubular germ cell neoplasia.
Most people with cancer of unknown primary origin have widely disseminated and incurable disease, although a few can be cured through treatment. With treatment, typical survival with CUP ranges from 6 to 16 months. Survival rates are lower in cases with visceral metastatic disease, ranging from 6 to 9 months. Survival rates are higher when the cancer is more limited to lymph nodes, pleura, or peritoneal metastasis, which ranges from 14 to 16 months. Long-term prognosis is somewhat better if a particular source of cancer is strongly suggested by clinical evidence.
CUP sometimes runs in families. It has been associated with familial lung, kidney, and colorectal cancers, which suggests that these sites may often be the origin of unidentifiable CUP cancers.
Seminoma (also known as "pure seminoma" or "classical seminoma") is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if discovered in early stages.
Testicular seminoma originates in the germinal epithelium of the seminiferous tubules. About half of germ cell tumors of the testicles are seminomas. Treatment usually requires removal of one testicle. However, fertility usually isn't affected. All other sexual functions will remain intact.
Embryonal carcinoma is a relatively uncommon type of germ cell tumour that occurs in the ovaries and testes.
There are no known risk factors that have been identified specific to the disease. The tumor appears to arise from the primitive cells of childhood, and is considered a childhood cancer.
Research has indicated that there is a chimeric relationship between desmoplastic small-round-cell tumor (DSRCT) and Wilms' tumor and Ewing's sarcoma. Together with neuroblastoma and non-Hodgkin's lymphoma, they form the small cell tumors.
DSRCT is associated with a unique chromosomal translocation t(11;22)(p13:q12) resulting in an EWS/WT1 transcript that is diagnostic of this tumor. This transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth.
The EWS/WT1 translocation product targets ENT4. ENT4 is also known as PMAT.
An estimated 3% of pediatric brain tumors are AT/RTs, although this percentage may increase with better differentiation between PNET/medulloblastoma tumors and AT/RTs.
As with other CNS tumors, more males are affected than females (ratio 1.6:1). The ASCO study showed a 1.4:1 male to female ratio.
The prognosis for AT/RT has been very poor, although some indications exist that an IRSIII-based therapy can produce long-term survival (60 to 72 months). Two-year survival is less than 20%, average survival postoperatively is 11 months, and doctors often recommend palliative care, especially with younger children because of the poor outcomes. Recently, a protocol used by a multicenter trial reported in the "Journal of Clinical Oncology" resulted in a 70% survival rate at 2–3 years, with most relapses occurring within months, leading to hope that a point exists beyond which patients can be considered cured.
Patients with metastasis (disseminated tumor), larger tumors, tumors that could not be fully removed, or tumor recurrence, and who were younger than 36 months had the worst outcomes (i.e., shorter survival times).
A retrospective survey from 36 AT/RT cases at St. Jude Children's Hospital from 1984 to 2003 showed that the two-year event-free survival (EFS) for children under three was 11%, and the overall survival (OS) rate was 17%. For children aged 3 years or older, the EFS was 78% and the OS 89%. A retrospective register at the Cleveland Children's hospital on 42 AT/RT patients found median survival time is 16.25 months and a survival rate around 33%. One-quarter of these cases did not show the mutation in the "INI1/hSNF5" gene.
The longest-term survivals reported in the literature are:
- (a) Hilden and associates reported a child who was still free from disease at 46 months from diagnosis.
- (b) Olson and associates reported a child who was disease free at five years from diagnosis based on the IRS III protocol.
- (c) In 2003, Hirth reported a patient who had been disease-free over six years.
- (d) Zimmerman in 2005 reported 50-to-72 month survival rates on four patients using an IRS III-based protocol. Two of these long-term survivors had been treated after an AT/RT recurrence.
- (e) A NYU study (Gardner 2004) has four of 12 longer-term AT/RT survivors; the oldest was alive at 46 months after diagnosis.
- (f) Aurélie Fabre, 2004, reported a 16-year survivor of a soft-tissue rhabdoid tumor.
- (g) Medical University of Vienna, 2013, reported a 16-year survivor, among other long-term survivors
Cancer treatments in long-term survivors who are children usually cause a series of negative effects on physical well being, fertility, cognition, and learning.
The prognosis for DSRCT remains poor. Prognosis depends upon the stage of the cancer. Because the disease can be misdiagnosed or remain undetected, tumors frequently grow large within the abdomen and metastasize or seed to other parts of the body.
There is no known organ or area of origin. DSRCT can metastasize through lymph nodes or the blood stream. Sites of metastasis include the spleen, diaphragm, liver, large and small intestine, lungs, central nervous system, bones, uterus, bladder, genitals, abdominal cavity, and the brain.
A multi-modality approach of high-dose chemotherapy, aggressive surgical resection, radiation, and stem cell rescue improves survival for some patients. Reports have indicated that patients will initially respond to first line chemotherapy and treatment but that relapse is common.
Some patients in remission or with inoperable tumor seem to benefit from long term low dose chemotherapy, turning DSRCT into a chronic disease.
A retrospective study of 83 women with sex cord–stromal tumours (73 with granulosa cell tumour and 10 with Sertoli-Leydig cell tumour), all diagnosed between 1975 and 2003, reported that survival was higher with age under 50, smaller tumour size, and absence of residual disease. The study found no effect of chemotherapy. A retrospective study of 67 children and adolescents reported some benefit of cisplatin-based chemotherapy.
In the ovary, embryonal carcinoma is quite rare, amounting to approximately three percent of ovarian germ cell tumours. The median age at diagnosis is 15 years. Symptoms and signs are varied, and may include sexual precocity and abnormal (increased, reduced or absent) uterine bleeding.
There may be elevations in serum human chorionic gonadotropin (hCG) and alpha fetoprotein (AFP) levels but it would be in association with other tumors, (e.g. yolk sac tumor) because they themselves do not produce the serum markers. At surgery, there is extension of the tumour beyond the ovary in forty percent of cases. They are generally large, unilateral tumours, with a median diameter of 17 centimetres. Long-term survival has improved following the advent of chemotherapy. The gross and histologic features of this tumour are similar to that seen in the testis.
Dysgerminoma is the most common type of malignant germ cell ovarian cancer. Dysgerminoma usually occurs in adolescence and early adult life; about 5% occur in pre-pubertal children. Dysgerminoma is extremely rare after age 50. Dysgerminoma occurs in both ovaries in 10% of patients and, in a further 10%, there is microscopic tumor in the other ovary.
Seminoma is the second most common testicular cancer; the most common is mixed, which may contain seminoma.
Abnormal gonads (due to gonadal dysgenesis and androgen insensitivity syndrome) have a high risk of developing a dysgerminoma. Most dysgerminomas are associated with elevated serum lactic dehydrogenase (LDH), which is sometimes used as a tumor marker.
Metastases are most often present in the lymph nodes.
A germinoma is a type of germ cell tumor, which is not differentiated upon examination. It may be benign or malignant.