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germ cell tumor with sarcomatous components

Tuesday 15 December 2009

Development of somatic malignancies in GCTs is a rare but well-known phenomenon that can occur in neoplasms of gonadal, mediastinal, and intracranial origin.

Malignancies derived from the 3 germinal layers have been reported. The somatic neoplasia may be a carcinoma of any type, or more frequently a sarcoma.

The sarcomatous components may appear in the primary tumor or manifest subsequently in the recurrences or in the metastases.

Most tumors were associated with mature or immature teratomatous elements supporting origin of the sarcomatous components from malignant transformation of mesenchymal elements within the teratoma.

Some cases contained pure embryonal rhabdomyosarcoma in association with intratubular germ cell neoplasia, and or a pure seminoma in the testis and rhabdomyosarcoma in the metastasis, suggesting that the emergence of sarcomatous elements in these tumors may obey several different mechanisms.

The association of pure seminoma with sarcoma has not been reported to date (with the exception of sarcomas arising in spermatocytic seminomas of the testis).

Finally, the presence of sarcomatous components in the recurrence or in the metastases after chemotherapy would support the concept of a selection phenomenon with further development of chemotherapy-resistant clones.

The most frequent sarcomatous components is RMS followed by well-differentiated angiosarcoma and leiomyosarcoma.

In teratomas developing somatic malignancies, the malignant component corresponded to a sarcoma in 63% of patients, with rhabdomyosarcoma representing the most common subtype. Most cases of rhabdomyosarcoma correspond to the embryonal variant but cases of pleomorphic rhabdomyosarcoma have also been described. (17721191)

Several other types of sarcomas such as malignant peripheral nerve sheath tumor (MPNST), malignant triton tumor, myxoid liposarcoma, undifferentiated carcinoma, osteosarcoma, and epithelioid hemangioendothelioma (EHE) can also be observed. Although these sarcomas are less frequently observed in association with GCTs, GCTs have the potential to develop almost any type of sarcoma. (17721191)

The sarcomatous components may be present in the primary tumor, in the recurrences or in the metastases, either in combination with GCT or as an independent tumor.

Differential diagnosis

In fact, many of the pure testicular sarcomas reported in the literature may represent an overgrowth of the SC originating in a GCT. A pitfall to be avoided in the evaluation of these cases is misinterpreting focal areas of atypical stromal overgrowth within otherwise conventional GCTs (a virtually universal finding in testicular GCTs with a teratomatous or yolk sac tumor component) for true sarcomatous elements. (17721191)

True sarcomatous elements are distinguished from microscopic foci of atypical immature teratoma or florid stromal overgrowth by their expansile growth with infiltration of the surrounding elements, and by displaying the characteristic morphologic features of the various distinctive types of sarcomas.

Ulbright et al. have previously emphasized the importance of not diagnosing sarcoma in GCTs with foci of stromal overgrowth until the stromal elements manifest independent growth by virtue of replacing teratomatous glands or other germ cell elements and thus forming an area of pure sarcoma. This should be taken into consideration to avoid an overdiagnosis of sarcoma and unnecessarily aggressive treatment. (17721191)

Pathogenesis

The pathogenesis of the development of sarcomatous components in this setting is unclear. Theories proposed by several authors in the past include a dedifferentiation phenomenon; malignant transformation of certain mesenchymal elements within teratomas; origin from primitive germ cells; and transformation of the blastematous stroma in yolk sac tumor. (17721191)

Prognosis (17721191)

Although the prognosis of GCT depends on the site and clinical stage, the emergence of SC in a GCT portends a worse prognosis.

Most cases of GCTSC are admitted in advanced stages, and the overall progression and mortality was worse than for age and stage-matched GCT without SC (80% vs. 32%; P@<@0.001).

In the majority of published studies, the patients died or had progressive disease at the time of last follow-up.

In all studies, the SC appears to have been resistant to cisplatinum-based combination chemotherapy and to other agents used for GCT.

Comparison of mediastinal cases with testicular cases showed that mediastinal cases tended overall to behave more aggressively that the testicular primaries.

Only 17.6% of patients with mediastinal cases were alive and well or alive with disease, whereas 82.4% of patients died with disease within an average of 14 months; in comparison with the testicular GCTSC in whom 56% were alive and well or alive with disease and 44% died of tumor over an average of 20 months. These differences may be accounted for on the basis of location, size of the lesion, and status of resectability.

The majority of the extragonadal tumors were larger and bulkier that the gonadal lesions, and were excised with positive margins, as opposed to the testicular tumors that were smaller and often excised with clear margins.

The mediastinal location also allows tumors to attain a much larger size before becoming symptomatic; therefore, increasing the potential for the emergence of foci of malignant transformation.

Owing to their large size, the majority of such tumors are extensively infiltrative at the time of surgery making complete resection with clear margins very difficult. It is also of interest that the mediastinal tumors rarely gave rise to metastases and instead killed the patients owing to the local compromise of vital structures, unlike the testicular tumors which gave rise to distant metastases in almost all the patients who died of their tumors.

The fact that testicular tumors tended to be discovered when they were of smaller size and were amenable to complete resection with clear margins may thus partly explain their more favorable behavior.

The presence of sarcomatous components in GCT is a factor that portends a more aggressive behavior. The sarcomatous components may behave as an independent tumor that can metastasize autonomously, and appears to be highly resistant to the standard combination chemotherapy commonly employed for the treatment of GCT. Addition of sarcoma-specific treatment modalities should be explored in such patients to increase the chances for survival.

Sarcomatous components

- embryonal rhabdomyosarcoma (17023832)
- pleomorphic rhabdomyosarcoma (18287801)
- angiosarcoma
- leiomyosarcoma
- myxoid liposarcoma
- malignant peripheral nerve sheath tumor
- primitive neuroectodermal tumor (PNET)
- malignant "triton" tumor
- epithelioid hemangioendothelioma
- chondrosarcoma (15590027)
- poorly differentiated sarcoma (15590027)
- undifferentiated sarcoma
- anaplastic small-cell tumor

See also

- germ cell tumor with malignant transformation

  • germ cell tumor with carcinomatous component
    • germ cell tumor with adenocarcinoma (15590027)

Credits

- Malagon HD, Valdez AM, Moran CA, Suster S. Germ cell tumors with sarcomatous components: a clinicopathologic and immunohistochemical study of 46 cases. Am J Surg Pathol. 2007 Sep;31(9):1356-62. PMID: 17721191

References

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