Download
1 / 49
500 likes | 660 Vues
بسم الله الرحمن الرحيم. Iman Loay Hussein Lecturer of pathology, NCI, Cairo University 5-12-2011. Germ cell tumors. Embryology. WHO classification. Tumours of one histological type (pure forms) Seminoma / Dysgerminoma Embryonal carcinoma Yolk sac tumour Trophoblastic tumours
E N D
Iman Loay Hussein Lecturer of pathology, NCI, Cairo University 5-12-2011 Germ cell tumors
WHO classification • Tumours of one histological type (pure forms) • Seminoma /Dysgerminoma • Embryonal carcinoma • Yolk sac tumour • Trophoblastictumours • Choriocarcinoma • Trophoblasticneoplasms other than choriocarcinoma • Monophasicchoriocarcinoma • Placental site trophoblastictumour • Teratoma • Dermoid cyst • Monodermalteratoma • Teratoma with somatic type malignancies • Tumours of more than one histological type (mixed forms) • Mixed embryonal carcinoma and teratoma • Mixed teratoma and seminoma • Choriocarcinoma and teratoma/embryonal carcinoma
overview Germ cell tumors (GCTs) occur most frequently in the gonads and are relatively rare in other sites, such as the pineal gland, mediastinum, and retroperitoneum The testes and ovaries are the most common sites where GCTs occur; however, the prevalence of GCTs is different at each of these sites. Ninety-five percent of testicular tumors are GCTs; on the other hand, only 30% of ovarian tumors are GCTs. The mediastinum is the second most common site affected by GCTs, with GCTs accounting for 15% of anterior mediastinal tumors in adults and 24% in children. GCTs also occur in the central nervous system, such as the pineal gland, and sacrococcygeal region. However, GCTs in these sites are rare.
Extra gonadal germ cell tumors During embryonic development, germ cells are first seen outside of the embryo in the yolk sac. At about 4 to 6 weeks of development, these cells migrate into the embryo where they populate the developing testes or ovaries. If these cells miss their destination, they are likely to come to rest in one of a number of midline sites in the body. Extragonadal tumors arise when these cells become cancerous. In some cases, however, an apparent extragonadal tumor turns out to be a metastatic testicular tumor where the primary tumor has "burnt out" or died on its own.
Extra Gonadal Germ cell Tumors They are thought to be developed from primordial germ cells, which can be misplaced during the long trip to the gonads The migration error of the primordial germ cells would inhibit the apoptosis of ectopic primordial germ cells, which are considered the origin of GCTs some researchers consider that all extragonadal GCTs are metastases from the testes or ovaries
How to improve diagnostic accuracy of germ cell tumors Interaction between pathologist, radiologist and clinician
GCTs consist of histologically varying tumors Imaging studies indicate that the histologic features of each tumor variety are similar wherever it occurs. Seminomas, which are known as germinomas in the pineal gland and dysgerminomas in the ovary, usually appear as grossly large, bulky, solid masses with fibrovascular septa. On the other hand, nonseminomatous malignant GCTs, such as embryonal carcinomas, yolk sac tumors, or choriocarcinomas, tend to have a more heterogeneous appearance caused by coexistent hemorrhage and necrosis. Teratomas usually contain sebaceous fat with calcification, and immature teratomas tend to have a large solid component.
The essential role of the pathologist is thorough gross dissection of the specimen knowing that different gross morphology actually reflects different microscopic pathology.
Germinoma Immature teratoma
Mixed Germ Cell Tumors (Seminoma & Choriocarcinoma
In over 90%, the histology of the metastasis is identical to that of the primary tumour knowing that every cell type in the primary tumour, irrespective of its histological appearance or volumeis capable of invasion and metastasis. In 10% of cases, the histological features of the metastases may be different from those of the initial sections of the primary tumour. Further sectioning may identify an additional element in the primary tumour or a scar referred to as a regressed or burned out tumour Thus, the information provided by the pathologist guides the surgeon and the oncologist toward the best mode of therapy.
Therefore, it is essential that the specimen be examined adequately with extensive slicing and macroscopic description, including the major dimensions. Tissue available for microscopic examination must include the tumour (at least one block for each 1 cm maximum tumourdiameter and more if the tissue is heterogeneous).
The specimen should not be discarded until the clinician and the pathologist have agreed that the pathology report and diagnosis correlate with the clinical features. • The presence of discordant findings (e.g. elevated AFP in a seminoma) indicates a need for further sectioning of the gross specimen. • In addition to histological typing of the tumour, the estimated quantity of cell types, determination of vascular/lymphatic invasion and the pathological stage of the tumour should be reported
Tumor markers • There are two principal serum tumour markers, alpha fetoprotein (AFP) and the beta subunit of human chorionic gonadotropin(ßhCG). • AFP is normally synthesized by fetal yolk sac and also the liver and intestine. It is elevated in 50-70% of germ cell tumours • AFP is detected in patients with yolk sac tumours and teratomas. • ßhCG is secreted by placental trophoblastic cells, is elevated in 50% of patients with germ cell tumours • ßhCGmay be seen in any patients whose tumours include syncytiotrophoblastic cells. • Patients with seminoma or dysgerminoma may have an elevation of this tumour marker in 10-25% of cases, and all those with choriocarcinoma have elevated levels. • If postoperative levels do not decline as predicted to appropriate levels residual disease should be suspected. • Lactate dehydrogenase (LDH) may also be elevated, and there is a direct relationship between LDH and tumour burden. • However, this test is nonspecific • although its degree of elevation correlates with bulk of disease.
Tumor markers Positive staining for AFP is helpful in diagnosis but the reaction is variable and sometimes weak. Negative staining does not exclude a diagnosis of YST The presence of hCG positive cells is frequently associated with elevated serum hCG (100 mIU/ml) . Higher levels may indicate bulky disease but possibly choriocarcinoma. Note: hCG could be produced by mononuclear cells. Seminomas and dysgeminomas with STCs or elevated serum hCG do not have a poorer prognosis in comparison to tumors of similar stage.
To improve the diagnostic accuracy of Germ Cell Tumors Clinician should supply adequate data concerning clinical history and data about tumor markers. Radiologist could offer preliminary data suggesting type of germ cell tumor and if possible perform guided biopsies representative of different imaging features within the tumor
Pathologist Adequate gross sectioning Detailed microscopic findings Provide pathology report
Pathology report The report of the pathologist can explain the relationship of the histology of the tumour to tumour markers And the response of the metastasis to the specific postoperative treatment Can explain why the metastases do not respond to the treatment as they may consist of some form of teratoma for which surgical intervention is the method of treatment.
Germ Cell Tumors in Pediatric Sahar Ahmed Khalil Lecturer of pediatric oncology 5-12-2011
Germ cell tumors account for 2-4 % of all pediatric cancers. They occur in two peak periods during childhood: Early infancy - in which benign and malignant teratomas (usually extragonadal) are frequent. Adolescence - in which gonadal tumors are more common. They are either Malignant or non-malignant. Germ cell tumors can metastasize to other parts of the body. The most common sites for metastasis are the lungs, liver, lymph nodes, and central nervous system. Rarely, germ cell tumors can spread to the bone, bone marrow, and other organs.
Origin • Youlk sac endoderm => Primordial germ cells • Primordial germ cells migrate in midline behind gut to reach the genital ridge.
Neoplastic cells Not differentiated Differentiated Germinoma (Seminoma) (Dysgerminoma) Embryonic Extra-embryonic Embryonal carcinoma Teratomas *** (Mature / immature) Choriocarcinoma Yolk sac tumor (EST)
Genetics and molecular biology Famelial tumors accounts for 1.5 to 2% of adolescent and adult GCT The association between sex – chromosomal abnormalities and GCT is well established - Klienfeltre syndrome and extragonadal (mediastinal) GCT -Turner syndrome and ovarian GCT Isochromosome 12p-i(12p)- can be demonestrated in 80% of adolescent , adult testicular GCT and ovarian MGCT Deletion of 1p36 can be demonestrated in 80-100% of infantile testicular and extragonadal MGCT
Ovary 24 % Dysgerminoma Teratomas EST (2nd decade ) Pineal region 6% Germinomas Mediastinum 7% Teratomas (child female) Germinoma(adolescent male) Sacrococcygeal 42% Teratomas (1st m) EST (1st y ) Testis 9% EST Teratoma Embryonal carcinoma (Before 4 y) Retroperitoneal 4 % Presacral Teratomas EST Other sites 8%
Workup • H&P • CBC • Chem 7 • AFP / HCG • Local radiology evaluation CT/MRI • Radiographic evaluation for distant metastasis CT chest,abdomen and pelvis , bone scan and brainCT/MRI if clinically indicated .
Low risk : Stage I Gonadal Intermediate risk : Stage II- IV Testicular Stage II- III Ovarian Stage I-II Extragonadal High risk : Stage IV Ovarian Stage III- IV Extragonadal
Required Observations for Induction and Post Surgical Consolidation Therapy
