Germ cell tumor

Germ cell tumor
Micrograph of a seminoma, a common germ cell tumor.
Classification and external resources
Specialty Oncology
ICD-10 C56, C62, D27, D29.2
ICD-9-CM 183, 186, 220, 222.0
ICD-O 9060-9100
eMedicine med/863
MeSH D009373

A germ cell tumor (GCT) is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads (ovary and testis). Germ cell tumors that originate outside the gonads may be birth defects resulting from errors during development of the embryo.

Etiology

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.[1]

Classification

Germ cell tumors are classified by their histology,[2] regardless of location in the body.

Germ cell tumors are broadly divided in two classes:[3]

The two classes reflect an important clinical difference. Compared to germinomatous tumors, nongerminomatous tumors tend to grow faster, have an earlier mean age at time of diagnosis (~25 years versus ~35 years, in the case of testicular cancers), and have a lower 5 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.[4]

Germinomatous

Tumor ICD-O Peak Age (yr) Benign or malignant Histology Tumor marker
Germinoma (including dysgerminoma and seminoma) 40–50 Malignant Sheets of uniform polygonal cells with cleared cytoplasm; lymphocytes in the stroma 10% have elevated hCG
Dysgerminoma M9060/3
Seminoma M9061/3 Placental alkaline phosphate (PLAP)[5]

Nongerminomatous

Tumor ICD-O Peak Age (yr) Benign or malignant Histology Tumor marker
Embryonal carcinoma 9070/3 20–30 Malignant Poorly differentiated, pleomorphic cells in cords, sheets, or papillary formation secrete hCG, AFP
Endodermal sinus tumor, also known as yolk sac tumor (EST, YST) 9071/3 3 Malignant Poorly differentiated endothelium-like, cuboidal, or columnar cells 100% secrete AFP
Choriocarcinoma 9100/3 20–30 Malignant Cytotrophoblast and syncytiotrophoblast without villus formation 100% secrete hCG
Teratoma including mature teratoma, dermoid cyst, immature teratoma, teratoma with malignant transformation 9080/0-9080/3 0–3, 15–30 Mature teratoma, dermoid cyst usually benign (but follow-up required); others usually malignant Very variable, but "normal" tissues are common Pure tumors do not secrete hCG, AFP
Polyembryoma 9072/3 15–25 ? ? ?
Gonadoblastoma 9073/1 ? ? ? ?

Mixed

Tumor ICD-O Peak Age (yr) Benign or malignant Histology Tumor marker
Mixed 15–30 Malignant Depends on elements present Depends on elements present

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.[6] 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.

Location

Despite their name, germ cell tumors occur both within and outside the ovary and testis.

In females, germ cell tumors account for 30% of ovarian tumors, but only 1 to 3% of ovarian cancers in North America. In younger women germ cell tumors are more common, thus in patients under the age of 21, 60% of ovarian tumors are of the germ cell type, and up to one-third are malignant. In males, germ cell tumors of the testis occur typically after puberty and are malignant (testicular cancer). In neonates, infants, and children younger than 4 years, the majority of germ cell tumors are sacrococcygeal teratomas.

Males with Klinefelter syndrome have a 50 times greater risk of germ cell tumors (GSTs).[7] In these persons, GSTs usually contain nonseminomatous elements, present at an earlier age, and seldom are gonadal in location.

Treatment

Women with benign germ cell tumors such as mature teratomas (dermoid cysts) are cured by ovarian cystectomy or oophorectomy.[8] In general, all patients with malignant germ cell tumors will have the same staging surgery that is done for epithelial ovarian cancer. If the patient is still interested in having children, an alternative is unilateral salpingoophorectomy, while the uterus, the ovary, and the fallopian tube on the opposite side can be left behind. This isn't an option when the cancer is in both ovaries. If the patient has finished having children, the surgery involves complete staging including salpingoophorectomy on both sides as well as hysterectomy.[8]

Most patients with germ cell cancer will need to be treated with combination chemotherapy for at least 3 cycles. The chemotherapy regimen most commonly used in germ cell tumors is called PEB (or BEP), and consists of bleomycin, etoposide, a platinum-based antineoplastic (cisplatin).[8]

Prognosis

The 1997 International Germ Cell Consensus Classification[9] is a tool for estimating the risk of relapse after treatment of malignant germ cell tumor.

A small study of ovarian tumors in girls[10] 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.[11]

Choriocarcinoma of the testicles has the worst prognosis of all germ cell cancers[12]

Research

Further information: Cancer research

Germ cell tumors of children are the subject of clinical research by the worldwide Children's Oncology Group (COG), in a number of studies coordinated by Dr. John Cullen, MD.[13]

Intracranial Germ Cell Tumors have been studied through the International CNS GCT Study Group. Under the direction of Jonathan Finlay, the program director, three international treatment studies have been initiated since 1990 with the goal to maintain a high rate of cure while minimizing the late effects of treatment.

See also

References

  1. ↑ Clinical Image: Mediastinal Teratoma
  2. ↑ Ulbright TM (2005). "Germ cell tumors of the gonads: review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues". Mod. Pathol. 18 (Suppl 2): S61–79. doi:10.1038/modpathol.3800310. PMID 15761467.
  3. ↑ Germinoma, Central Nervous System at eMedicine
  4. ↑ Robbins, Stanley L.; Kumar, Vinay; Cotran, Ramzi S. (2003). Robbins basic pathology (7th ed.). Philadelphia: Saunders. p. 664. ISBN 0-7216-9274-5.
  5. ↑ Nielsen OS, Munro AJ, Duncan W, Sturgeon J, Gospodarowicz MK, Jewett MA, Malkin A, Thomas GM (1990). "Is placental alkaline phosphatase (PLAP) a useful marker for seminoma?". Eur J Cancer. 26 (10): 1049–54. doi:10.1016/0277-5379(90)90049-y. PMID 2148879.
  6. ↑ MESH 2008: Teratocarcinoma
  7. ↑ Bebb GG, Grannis FW, Paz IB, Slovak ML, Chilcote R (August 1998). "Mediastinal germ cell tumor in a child with precocious puberty and Klinefelter syndrome". Ann. Thorac. Surg. 66 (2): 547–8. doi:10.1016/S0003-4975(98)00504-9. PMID 9725401.
  8. 1 2 3 Treatment for germ cell tumors of the ovary at American Cancer Society. Last Medical Review: 12/05/2011. Last Revised: 01/11/2012
  9. ↑ "International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group". J. Clin. Oncol. 15 (2): 594–603. February 1997. PMID 9053482.
  10. ↑ Stankovic ZB, Djukic MK, Savic D, Lukac BJ, Djuricic S, Sedlecki K, Zdravkovic D (2006). "Pre-operative differentiation of pediatric ovarian tumors: morphological scoring system and tumor markers". J. Pediatr. Endocrinol. Metab. 19 (10): 1231–8. doi:10.1515/JPEM.2006.19.10.1231. PMID 17172084.
  11. ↑ Harding MJ, Paul J, Gillis CR, Kaye SB (April 1993). "Management of malignant teratoma: does referral to a specialist unit matter?". Lancet. 341 (8851): 999–1002. doi:10.1016/0140-6736(93)91082-W. PMID 8096954.
  12. ↑ Verville, Kathleen M. (2009). Testicular Cancer. Infobase Publishing. p. 76. ISBN 9781604131666.
  13. ↑ CureSearch.org press release re Germ Cell Cancer
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