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Journal of Clinical Oncology, Vol 25, No 30 (October 20), 2007: pp. 4845-4848 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.13.0930
Extraosseous Ewing's SarcomaDepartment of Pathology, University of Utah, School of Medicine, Salt Lake City, UT
Department of Surgery, Division of Otolaryngology Head & Neck Surgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Community Hospital, Springfield, OH
Department of Radiology, University of Utah, School of Medicine, Salt Lake City, UT
Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Department of Internal Medicine, Division of Hematology and Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT A 31-year-old man presented to a senior otolaryngologist with a 1-month history of left-sided neck pain associated with a small mass at the mastoid tip. The computed tomography (CT) scan of the head and neck did not reveal any evidence of disease. The otolaryngologist attributed the pain to muscle strain of the sternocleidomastoid muscle and prescribed physical therapy. The patient presented 4-months later with another left neck mass accompanied by increasing pain. Kenalog injections initially improved the patient's pain, but after a third injection, worsening neck pain, and evidence of external ear canal compression on examination, a contrast-enhanced axial T1-weighted magnetic resonance imaging (MRI) of the skull base was ordered. A centrally necrotic, peripherally enhancing mass (Fig 1; white arrow) inferior to the mastoid tip and lateral to the external auditory canal was seen displacing the parotid gland anteriorly. Infiltrating margins, with a finger-like projection into the trapezius muscle (curved white arrow), are characteristic of sarcoma. The patient was referred to the otolaryngologist's head and neck surgical oncology colleague (B.G.B.), who recommended a fine needle aspiration of the mass.
The fine needle aspirate of the mass revealed necrotic cells and was inadequate for diagnosis. The frozen section of a subsequent excisional biopsy was initially suggestive of lymphoma. The final pathology, however, revealed a monotonous tumor (Fig 2; routine hematoxylin and eosin [H & E]; x10) staining positive only for CD117 (Fig 2 inset), which did not narrow the differential diagnoses between a lymphoma versus a sarcoma. A bone marrow biopsy and aspirate demonstrated no tumor. The polymerase chain reaction of the paraffin-embedded tissue was positive for B-cell clonality, suggestive of a hematopoietic tumor. But despite this, an electron microscopic evaluation revealed gap junctions. Thus, a hematopoietic tumor was ruled out.
A positron emission tomography (PET)/CT scan was ordered in an attempt to determine if another focus of disease could be detected. The PET revealed uptake in level 2 and 5 lymph nodes in addition to uptake at the primary mastoid site. Because sarcomas rarely metastasize to cervical lymph nodes, other epithelial carcinomas had to be ruled out. A thorough endoscopic evaluation of the upper aerodigestive tract did not discover any abnormalities and a modified radical neck dissection was performed.
The final pathology confirmed tumor involvement in six of 83 lymph nodes. The tumor cells showed high nuclear to cytoplasmic ratio with scant cytoplasm. The nuclei were small, round to oval with irregular borders and stippled chromatin with scattered multinucleated pleomorphic giant cells (Fig 3; routine H & E; x100 oil immersion). The cells stained diffusely for neuron specific enolase and dot-like for synaptophysin, vimentin, and chromogranin, supporting neuroendocrine differentiation. Electron microscopy was examined further, and confirmed the presence of multiple small round 100 to 120
Further evaluation included positive immunostaining for CD-99 and Fli-1. Eighty percent of the cells stained for the EWSR-1 break-apart rearrangement for the EWS/Fli-1 fusion gene by fluorescence in situ hybridization confirming the diagnosis of a tumor with neural/neuroectodermal differentiation of the Ewing's sarcoma family of tumors (Fig 5). The break-apart (abnormal) signal configuration is represented by one single orange signal and one single green signal (x60 oil immersion.)The remainder of his diagnostic evaluation including a CBC and lactate dehydrogenase, and blood chemistries were within normal limits.
The patient received off-protocol adjuvant chemotherapy with planned radiation on arm B2 (Children's Oncology Group American Ewings Sarcoma 0031 protocol) dose-dense combination of cyclophosphamide, vincristine, doxorubicin, alternating with ifosfamide and etoposide. A repeat MRI of the base of the skull and a PET/CT after two cycles of adjuvant chemotherapy revealed no evidence of disease. At the time of publication, the patient has received seven of the 13 planned cycles of chemotherapy and is starting adjuvant radiation therapy. This case report is presented to emphasize the importance of establishing a correct diagnosis so that targeted management can be instituted thereby optimizing the potential for curative treatment. In this case, lymphoma was the initial leading diagnosis, although the clinical picture including the non-nodal neck mass and the muscle infiltration by the mass on MRI, was atypical for lymphoma. Furthermore, the extensive necrosis noted in the original neck biopsy is unusual for a low grade-lymphoma, although steroid injections may have altered the pathologic appearance of the mass.1-2 Ewing's sarcomas have been successfully diagnosed by fine needle aspiration.3 PET scan was useful in establishing tumor involvement in the neck. Because a definitive diagnosis could not be made from the initial neck mass and a poorly differentiated carcinoma was still in the differential, a neck dissection was essential for diagnosis and instituting appropriate therapy. The additional pathologic material from the neck dissection allowed for additional immunophenotyping and molecular studies leading ultimately to the correct diagnosis of a tumor with neural/neuroectodermal differentiation consistent either with an extraosseous Ewing's sarcoma or a primitive neuroectodermal tumor. The Ewing's sarcoma family of tumors is the second most common primary bone malignancy in children and adolescents.4 Extraosseous Ewing's sarcoma is less common but has been reported in many sites including skin, kidney, small intestine, pelvis, and CNS.5-10 The more indolent head and neck cutaneous and subcutaneous extraosseous Ewing's sarcomas do not usually involve nodal sites.6 In general, extraosseous Ewing's sarcomas are rarely reported in the soft tissues of the head and neck. Poor prognostic factors have included age at the time of diagnosis, bulk of disease, site, and the presence of metastatic disease.8 The presence of nodal metastasis in Ewing's sarcoma upstages our patient to stage IV with no predicted survivors at 5 years.11 Multimodality management of Ewing's sarcoma family of tumors includes systemic chemotherapy, surgery, and radiation therapy.12 Current chemotherapy regimens include combinations of vincristine, cyclophosphamide, and doxorubicin often combined with ifosfamide and etoposide.13-21 Local control is dependent on the resectability of the primary site. Radiation is often used for local control postoperatively for positive margins or definitively if the primary can not be resected. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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m diameter dense core granules in approximately 3% of the tumor cells resembling neurosecretory granules (
