Sorry for missing the train on this one. February 4th is the World Cancer Day and is one of the public health days that could do with some more propaganda in the public eye. I was so caught up with work and studies it just passed me by and I could not even get the chance to post about it. But it seems to have been an opportune miss, since, right now the newspaper headlines are abuzz with one of India’s most beloved celebrities being diagnosed with cancer, that too a rather rare and exotic one:

Yuvrai Singh is suffering from a very rare form of cancer, the extragonadal (mediastinal, in his case) Germ Cell Tumor (seminoma). Although less than 7% of germ cell tumors occur outside the gonads, the mediastinum is the most common location for the extragonadal seminoma. These tumors comprise about 10% of all malignant mediastinal lesions. They are seen almost exclusively in males in the second to fourth decade of their lives (1). Thankfully, the patients are symptomatic early on and hence can be diagnosed and treated in quick succession. Interestingly enough, men with Klinefelter’s Syndrome are known to develop these tumors earlier than the usual demography.

The etiology of this tumor is not clearly known and there is considerable debate in the medical world about how the germ cells find their ways into the mediastinum. Some authorities are of the opinion that the germ cells migrate into the mediastinum during embryogenesis from the developing genital ridge due to some error in signaling pathways (2). Another school of thought states that germ cells are widely distributed during embryogenesis and play a critical role in conveying genetic information or maintaining homeostasis. And remnants of these controlling germ cells may lead to formation of extragonadal germ cell tumors. (3)

Funnily enough, there seems to be evidence that this disease is amenable to spontaneous regression (4). Another tumor that has commonly been associated with spontaneous regression is Neuroblastoma, but more about that some other time. For now, back to Yuvi’s mystery illness that was purportedly misdiagnosed in India, causing a delay in the institution of appropriate therapy.

The radiologic findings are typical for mediastinal masses in case the tumor is sufficiently large enough:

Plain chest X-ray showing enlarged mediastinum due to tumor mass (5).

Now, coming to the two most important aspects of mediastinal germ cell tumors – treatment and prognosis.

The consensus (6) for treating mediastinal germ cell tumors seems to be intense chemotherapy followed by surgical resection if needed. Surgical resection alone is not advocated due to high recurrence rates. Also, surgery without tissue diagnosis is discouraged owing to the possibility of a mediastinal lymphoma, which is more common in this age group and is amenable to cure using non-surgical means.

It has been shown that primary chemotherapy is more effective in instituting progression free survival than radiotherapy alone and hence it is now the standard of treatment (7). Though the recommended regimen is three cycles of BEP (Bleomycin, Etoposide and Cisplatin) (8) there is poor evidence on the nature of the optimal therapy. The ideal way to find this out would be to conduct a randomized controlled trial but given how rare this disease is, it is unlikely that the numbers for such a research design can ever be drawn up.

The prognosis for seminomatous tumors of the mediastinum is pretty good. Though the sample size numbers are fairly low in the post-multi-agent chemotherapy period, still, a 5 year survival is pegged at over 90% (9). As far as Yuvraj is concerned, an even better outcome is predicted by the fact that he is less than 37 years old. Other factors which may lead to a good outcome is absence of extrapulmonary metastases and early initiation of multi-agent chemotherapy (10).

I realize that a lot of this post is in “medic speak” but owing to the fact that the disease itself is rare, I could not resist the temptation of going into more details about it. However, if there is something I have missed or something you would like a clarification about, feel free to drop in a comment or if you prefer to initiate a personal conversation, do write in to my email:

References:

1. Weidner N. Germ-cell tumors of the mediastinum. Semin Diagn Pathol. Feb 1999;16(1):42-50.

2.  Fine G, Smith RW, Pachter MR. Primary extragenital choriocarcinoma in male subject: Case report and review of the literature. Am J Med. 1962;32:776–94.

3.  Friedman NB. The function of primordial germ cell in extragonadal tissues. Int J Androl 10: 43-49, 1987.

4. Hachiya T, Koizumi T, Hayasaka M, Kubo K, Sekiguchi M, Hanyuuda M, Honda T. Spontaneous regression of primary mediastinal germ cell tumor. Jpn J Clin Oncol. 1998 Apr;28(4):281-3. PubMed PMID: 9657016.

5. Khan FY, Al Ani A, Allaithy MS, Al-Bozom IA. A young male with shortness of
breath. Ann Thorac Med. 2008 Jan;3(1):28-30. PubMed PMID: 19561881; PubMed
Central PMCID: PMC2700432

6. Takeda S, Miyoshi S, Ohta M, Minami M, Masaoka A, Matsuda H. Primary germ cell tumors in the mediastinum: A 50-year experience at a single Japanese institution. Cancer. 2003;97:367–76.

7. Bokemeyer C, Droz JP, Horwich A, Gerl A, Fossa SD, Beyer J, Pont J, Schmoll HJ, Kanz L, Einhorn L, Nichols CR, & Hartmann JT (2001). Extragonadal seminoma: an international multicenter analysis of prognostic factors and long term treatment outcome. Cancer, 91 (7), 1394-401 PMID: 11283942

8. Schmoll HJ. Extragonadal germ cell tumors. Ann Oncol 13: 265-272, 2002.

9. Bokemeyer C, Nichols CR, Droz JP, Schmoll HJ, Horwich A, Gerl A, et al. Extragonadal germ cell tumors of the mediastinum and retroperitoneum: Results from an international analysis. J Clin Oncol. 2002;20:1864–73.

10. International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 15: 594-603, 1997.