Sunday, October 3, 2010

Germ cell tumor common precancer: itgcn

In yesterday's blog , we discussed the terminology problem with the germ cell tumors. Basically, if you have a sub-class of germ cell tumors that are called "non-germinomatous germ cell tumors," isn't that a contradiction in terms? Isn't it like saying that dehydrated water is a subclass of water?

The answer is simple: the classic germ cell tumor of the testes (seminoma), as well as most of the malignant non-germinomatous germ cell tumors of the testes, arise from the same precancer: intratubular germ cell neoplasia (itgcn). Because itgcn is composed of dysplastic (early neoplastic) germ cells, both the germinomatous and non-germinomatous tumors have a germ cell origin.

You can easily appreciate the morphologic similarity between itgcn and seminoma by looking at a histologic preparation of each.


Image of Intratubular Germ Cell neoplasia
Distributed by Wikimedia
under a Creative Commons License


The germ cell precancer, itgcn, is a collection of atypical gonocytic cells lining seminiferous tubules in the testis.



Image of Seminoma
Distributed by Wikimedia
under a GNU License


Seminoma cells closely resemble the cells of itgcn, from which they derive (with the rare exception of the so-called spermatocytic seminoma, which behaves unlike the other types of seminomas).

The same precancer (itgcn) precedes the development of most of the invasive non-germinomatous germ cell tumors of the testis.

So, the terminologic mystery is solved. The germinomatous and the non-germinomatous germ cell tumors are classified together because most of them are derived from neoplastic intratubular germ cells (i.e., intratubular germ cell neoplasia).

But solving the terminologic mystery does not help us understand the biology of what's happening. Why does itgcn give rise to tumors of germ cells (e.g., seminomas) and to tumors of primimitive non-germ cells (e.g., embryonal carcinoma, choriocarcinoma)? How can a tumor be derived from cells that have a committed lineage (i.e., sperm cells in the case of males) that is completely unrelated to the lineages found in the tumor?

There's an answer. It has a lot to do with a phenomenon unique to germ cells called epigenomic erasure. This will be the topic of the next blog in our series on germ cell tumors.

Jump to Tomorrow's Blog

- © 2010 Jules Berman

key words: carcinogenesis, neoplasia, neoplasms, tumor development, tumour development, germ cell tumor, germ cell tumour, tumor epidemiology, increasing germ cell cancer rates, germ cell cancer, seminomas, seminomatous, non-seminomatous, non-germinomatous, embryonal carcinoma, choriocarcinoma, testis, testes, itgcn, intratubular germ cell neoplasm
In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.



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