Germ Cell Tumor (GCT), Isochromosome 12p, FISH, Tissue
Supporting the diagnosis of germ cell tumors when used in conjunction with an anatomic pathology consultation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Germ cell tumors (GCT) comprise a heterogeneous group of solid neoplasms that arise in midline locations including the gonads, retroperitoneum, mediastinum, and central nervous system. GCT are categorized based upon their histologic differentiation and can be separated into 2 classes. Seminomatous GCT include seminoma of the testis, dysgerminoma of the ovaries, and germinoma of the brain. Nonseminomatous GCT include yolk sac tumor, embryonal carcinoma, choriocarcinoma, immature teratoma, and mixed forms. Due to the wide spectrum of histologic features observed in these tumors, distinction from non-GCT can be difficult. GCT are often very responsive to chemotherapy and have a better outcome relative to histologically similar malignancies. Thus, distinguishing GCT from non-GCT is critical to provide the appropriate treatment for the patient. Gain of the short arm of chromosome 12, most commonly as an isochromosome 12p: i(12p), is a highly nonrandom chromosomal marker seen in a significant percentage of GCT. While i(12p) is not 100% specific for GCT, the literature indicates it has diagnostic and possible therapeutic relevance for patients with these tumors. Testing of i(12p) should be concomitant with histologic evaluation, and positive results may support the diagnosis of GCT.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for the i(12p) probe set.
A positive result is consistent with the diagnosis of a germ cell tumors (GCT).
A negative result suggests that the i(12p) marker is not present, but does not exclude the diagnosis of a GCT.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not approved by the FDA and it is best used as an adjunct to existing clinical and pathologic information.
Fixatives other than formalin (eg, Prefer, Bouin's) may not be successful for FISH assays. Although FISH testing will not be rejected due to nonformalin fixation, results may be compromised.
Paraffin embedded tissues that have been decalcified are generally unsuccessful for FISH analysis. The pathologist reviewing the hematoxylin and eosin-stained slide may find it necessary to cancel testing.
FISH analysis was performed on 171 formalin-fixed, paraffin-embedded tissue samples from the testis, ovary, and brain. These included 22 dysgerminomas, 20 seminomas, 10 mixed germ cell tumors (GCT), 18 germinoma, 4 embryonal carcinoma, 22 GCT histological mimics, and 75 noncancerous control specimens. The normal controls were used to generate a normal cutoff for this assay. The presence of i(12p) was identified in 29% of brain, 55% of testis, and 56% of ovarian GCT.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Woodward PJ, Heidenreich A, Looijenga LHJ, et al: Germ cell tumors. WHO classification of tumors: Pathology and Genetics of Tumors of the Urinary System and Male Genital Organs. 2004
2. Wehle D, Yonescu R, Long PP, et al: Fluorescence in situ hybridization of 12p in germ cell tumors using a bacterial artificial chromosome clone 12p probe on paraffin-embedded tissue: clinical test validation. Cancer Genet Cytogenet 2008;June;183(2):99-104
3. Poulos C, Cheng L, Zhang S, et al: Analysis of ovarian teratomas for Isochromosome 12p: evidence supporting a dual histogenetic pathway for teratomatous elements. Mod Pathology 2006;19:766-771