Primitive neuroectodermal tumor with lung metastases and an unknown primary: a unicorn?

“When one hears hoofbeats, think of horses, not zebras,” is a common line taught to medical students and residents throughout the world. Rarely however those hoofbeats belong not to horses or zebras, rather to unicorns.

In the journal Current Challenges in Thoracic Surgery, Mizelle and colleagues present a case report which describes the first documented case of metastatic Ewing sarcoma (or peripheral primitive neuroectodermal tumor) to the lung with an unknown primary (1). The case described is very atypical for presentation of a Ewing sarcoma. While overall rare, Ewing sarcoma is most commonly identified in the pediatric patient population; adult cases are exceedingly rare (2). Furthermore, in instances of metastatic disease there is typically an easily identifiable primary lesion. Most commonly this is an osseous primary within the pelvis or the lower extremities, but sometimes within the chest wall (3). Ewing sarcoma typically possesses an aggressive phenotype with at least ¼ of patients presenting with metastatic disease. It follows that patients presenting with locally aggressive disease generally outlive their counterparts who present with synchronous metastases. Multimodality treatment, including system chemotherapy, has been associated with improved overall survival (4).

Despite overlap between the treatment algorithms of some soft tissue sarcoma subtypes (i.e., type of chemotherapy used), there are subtle differences and nuances associated with the treatment of rare sarcoma subtypes. The authors demonstrate a key principle in sarcoma management: a thorough histopathologic evaluation to confirm the sarcoma subtype and initiate proper systemic therapy. Accurate diagnosis of Ewing sarcoma is crucial as treatment for this disease carries with it both short- and long-term toxicities (3). Unfortunately, despite early initiation of systemic therapy, cure rates are fairly poor among patients that present with metastatic Ewing sarcoma (4).

Mizelle and colleagues are to be commended for this contribution to the thoracic surgical literature as it highlights several key points in the diagnosis and management of Ewing sarcoma:

• correct diagnosis is paramount as proper systemic treatment may depend on the sarcoma subtype;
• outside consultation with a sarcoma specialist should be pursued if any uncertainty of diagnosis;
• multidrug chemotherapy is the foundation of therapy for metastatic Ewing sarcoma.

While this is the first report of metastatic Ewing sarcoma to the lungs without identification of a primary lesion, thoracic surgeons should be aware of the potential for lung metastases from an identifiable Ewing sarcoma primary. With more standardization of the pathologic evaluation of Ewing sarcoma, namely by immunohistochemistry and fluorescence in situ hybridisation (FISH) to identify EWSR1 rearrangements, there may be increasing identification of this sarcoma subtype in the adult population. As such, thoracic surgeons should be aware of Ewing sarcoma, its diagnosis, prognosis, and treatment, as they may encounter this disease in some fashion during their careers.

Acknowledgments

Funding: None

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Current Challenges in Thoracic Surgery. The article did not undergo external peer review.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts.2019.12.08/coif). The author has no conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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References

1. Mizelle J, Yang J, Burks E, et al. Case report of primitive neuroectodermal tumor with an unknown primary presenting with multiple lung metastasis. Curr Chall Thorac Surg 2019;1:15. [Crossref]
2. Esiashvili N, Goodman M, Marcus RB Jr. Changes in incidence and survival of Ewing sarcoma patients over the past 3 decades: Surveillance Epidemiology and End Results data. J Pediatr Hematol Oncol 2008;30:425-30. [Crossref] [PubMed]
3. Balamuth NJ, Womer RB. Ewing's sarcoma. Lancet Oncol 2010;11:184-92. [Crossref] [PubMed]
4. Martin RC 2nd, Brennan MF. Adult soft tissue Ewing sarcoma or primitive neuroectodermal tumors: predictors of survival? Arch Surg 2003;138:281-5. [Crossref] [PubMed]