Adamantinoma-like Ewing sarcoma of the parotid gland: A case report

INTRODUCTION

Adamantinoma-like Ewing sarcoma (ALES) is a rare histologic variant of Ewing sarcoma that predominantly affects non-osseous tissues such as salivary glands. To date, only 27 cases of parotid gland ALES have been documented in the literature, underscoring its extreme rarity.^[1] Among reported cases, approximately 60% were female and 40% were male, with disease occurring primarily in adults but representing a broad age range from 12 to 79 years. Histologically, ALES exhibits overlapping features with basal cell adenocarcinoma, lymphoma, and poorly differentiated carcinoma, which frequently complicates the diagnostic process. Immunohistochemistry and molecular testing, particularly the detection of Fused in Sarcoma-Fifth Ewing Variant (FUS-FEV) or Ewing Sarcoma Breakpoint Region 1 (EWSR1) gene rearrangements, are critical for establishing an accurate diagnosis. Although prognostic data are limited due to the rarity of this tumor, majority of patients remain free of disease recurrence or progression. In this report, we present a rare case of parotid ALES, highlighting its clinical, radiologic, and histopathologic features, along with a multidisciplinary therapeutic approach.

CASE REPORT

A 57-year-old male presented for further evaluation of a left parotid mass identified on a computed tomography (CT) scan of the neck. The patient had a prior history of an asymptomatic left tonsillar mass noted in 2018 by an oral surgeon, and he was ultimately diagnosed with stage cT2N1M0 p16-positive squamous cell carcinoma. Comorbidities included hypertension, stage III chronic kidney disease, and psoriasis. Significant social history included a 10 pack-years smoking history (quit in February 2022) and two cans of chewing tobacco per day for 8 years. The patient underwent left tonsillectomy with removal of squamous papilloma of the uvula, followed by post-operative chemoradiation with 60Gy in 30 fractions to the left tonsil and left neck along with concurrent weekly cisplatin therapy. Treatment was completed in 2019, but he reportedly did not complete the final 2 weeks of cisplatin due to toxicity. During this time, the patient did not require enteral feeding, but he did report a 70 lbs weight loss. He remained clinically disease-free and denied any associated symptoms for 2 years while in remission. A surveillance CT scan of the neck in February 2021 showed no signs of disease.

In December 2021, the patient reported new symptoms of excess mucus production and neck stiffness. On presentation, physical examination showed the neck was supple and non-tender with fullness of the left parotid tail area but no visible swelling or mass. Follow-up CT scan of the neck demonstrated interval development of a soft tissue mass involving the superficial and deep lobe of the left parotid gland [Figure 1]. Subsequently, a positron emission tomography (PET) scan was performed, which confirmed a 2.8 × 2.5 × 2.0 cm hypermetabolic left parotid mass on both axial [Figure 2a] and coronal [Figure 2b] views. After challenges with patient follow-up and re-establishment of care, 1 year later, left parotid mass biopsy was completed through ultrasound-guided fine needle aspiration (FNA). Results showed highly atypical cells suspicious for carcinoma and consistent with salivary gland neoplasm of unknown malignant potential. Upon collaborative review, recommendations were made for left parotidectomy and left neck dissection with intraoperative nerve monitoring.

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Figure 1:

A 57-year-old man presenting with excess mucus production and neck stiffness. Axial non-contrast neck computed tomography performed on December 17, 2021, demonstrates a new soft tissue mass (blue arrow) involving the superficial and deep lobes of the left parotid gland.

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Figure 2:

A 57-year-old man presenting with excess mucus production and neck stiffness. (a) Axial and (b) coronal positron emission tomography/computed tomography (CT) performed on December 27, 2021 shows an fluorodeoxyglucose-avid soft tissue mass (blue arrows) in the left parotid gland, concordant with neck CT findings performed several days earlier.

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Before surgery, the patient reported that the mass had nearly doubled in size with mild tenderness to palpation but otherwise denied any new symptoms or signs of infection. In March 2022, he underwent a left radical parotidectomy with resection of the facial nerve and left selective neck dissection (Levels II-IV). Intraoperatively, the patient was found to have a 2.9 cm tumor encasing the facial nerve around the main branch and the pes anserinus, both lower and upper divisions. Frozen sections collected during the surgery were found to be poorly differentiated malignant tumor. There was no significant lymphadenopathy throughout the neck dissection and all nine lymph node specimens were negative for carcinoma.

Histologic evaluation of the resected specimen revealed features characteristic of ALES. Hematoxylin and eosin staining showed sheets of basaloid cells with round nuclei, scant cytoplasm, and minimal pleomorphism [Figure 3a]. Immunohistochemically, the tumor exhibited a profile consistent with conventional Ewing sarcoma, with diffuse membranous positivity for CD99 [Figure 3b] and nuclear expression of NKX2.2 [Figure 3c]. Additional staining demonstrated strong diffuse positivity for cytokeratin [Figure 3d] and P63 [Figure 3e], with variable synaptophysin expression [Figure 3f]. Final pathology showed undifferentiated small round cell sarcoma ALES of the left parotid gland, a G3 tumor positive at the stylomastoid foramen with perineural invasion.

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Figure 3:

A 57-year-old man underwent left radical parotidectomy and was found to have a 2.9 cm tumor. (a) Histological appearance on hematoxylin and eosin of adamantinoma-like Ewing sarcoma (ALES) demonstrates sheets of basaloid cells with round nuclei and scant cytoplasm with minimal pleomorphism. The tumor cells exhibit an immunohistochemical profile of conventional Ewing Sarcoma by positive (b) membranous staining for CD99 and (c) nuclear NKX2.2. In addition, ALES stains strongly positive for (d) cytokeratin, (e) P63 and , (f) variable expression of synaptophysin (a-f: ×20 magnification).

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Status-post resection, the patient was referred for radiation and chemotherapy, and genomic testing was performed which found the specimen to be positive for an FUS-FEV fusion but negative for EWSR 1 and tropomyosin receptor kinase 1/2/3 alterations. After review by the Precision Medicine Clinical Service, the FUS-FEV fusion did not appear to be targetable. An magnetic resonance imaging of the left parotid surgical bed was completed and consultation with the multidisciplinary tumor board and discussion at the multidisciplinary sarcoma conference confirmed the treatment plan. Recommendation was made for the patient to receive adjuvant external beam radiation to the left parotid bed consisting of 6440 cGy with microscopic dosing tracking along the facial nerve of 5040 cGy. Concurrent systemic chemotherapy was initiated as per the Ewing sarcoma treatment paradigm with 4 cycles of ifosfamide and etoposide given inpatient and vincristine, doxorubicin, and cyclophosphamide given as outpatient medications.

The patient’s chemotherapy was complicated by profound fatigue, appetite loss, bone pain, and infections requiring dosing and schedule adjustments and ultimately a treatment break. Restaging PET/CT scans after two complete treatment cycles showed adjacent hypermetabolism of the left-side tongue and hypermetabolic left groin lymphadenopathy (most likely reactive). However, after three treatment cycles restaging demonstrated response to treatment, and once treatment was suspended in March 2023, final scans were negative for metastatic disease and showed no new suspicious activity with persistent heterogeneous activity in the left neck, most consistent with post-treatment changes.

In the following months, the patient presented with new complaints of hoarseness and dysphagia after an episode of choking on food at home which resulted in partial paralysis of the left-sided vocal cord. CT scan of the neck demonstrated stable post-surgical and treatment-related changes to the left oropharynx with no recurrent or residual left parotid mass or recurrent tonsillar squamous cell carcinoma. CT scan of the chest was also unremarkable and without any concerns for metastatic disease. PET/CT of the whole body demonstrated developing fluorodeoxyglucose activity in the nasopharyngeal and left prevertebral soft tissues determined to be non-specific and likely reactive. There was persistent activity in the left neck most compatible with post-treatment changes, and a few small reactive right cervical lymph nodes.

In October 2023, after the patient’s progression of severe dysphonia and new development of shortness of breath, CT scan of the thorax demonstrated pleural effusions and interstitial/peribronchial thickening with cardiac enlargement suggestive of pulmonary edema. Restaging PET/ CT imaging was without evidence for recurrent or metastatic disease. With comorbidities including atrial fibrillation with renal vein reflux and supplemental nutritional support through G-tube due to recurrent aspiration pneumonia, ultimately, the patient passed away in January 2024 from complications of acute left lower extremity deep vein thrombosis and bilateral pulmonary embolisms.

DISCUSSION

ALES is a rare tumor, particularly in the parotid gland, which presents significant diagnostic and therapeutic challenges due to its unusual location and histologic overlap with other small round cell tumors, such as basal cell adenocarcinoma, lymphoma, or sialoblastoma.^[2,3] Accurate diagnosis often requires advanced molecular techniques, such as the identification of the FUS-FEV fusion gene, which is a critical and defining genetic hallmark of ALES, helping to distinguish it from other histologic mimics.^[4] Misdiagnosis is common, as ALES can resemble poorly differentiated carcinoma, highlighting the importance of early and accurate recognition.^[5]

Preoperative diagnosis can benefit from cytomorphologic features, including rosettes, cytoplasmic vacuoles, and a tigroid background, which, when combined with ancillary techniques, improve diagnostic accuracy and patient outcomes.^[6] Sampling of parotid gland lesions is typically done using FNA for initial minimally invasive assessment. However, when faced with atypical imaging, indeterminate cytology, or the need for tissue-based diagnostics, core needle biopsy can be useful in providing superior diagnostic clarity, reducing the need for repeat procedures, and supporting tailored treatment plans.

The treatment approach for ALES is largely extrapolated from protocols for Ewing sarcoma due to its rarity and the absence of dedicated treatment guidelines. The combination of radical surgical resection, adjuvant radiation, and multi-agent chemotherapy underlines the aggressive strategy required for both local and systemic control. However, this aggressive regimen is often associated with significant complications. In this case, the patient experienced chemotherapy-related toxicities, infections, and other adverse effects, highlighting the delicate balance between maximizing efficacy and minimizing treatment-related morbidity.

While multimodal therapy has demonstrated potential for initial disease control, this case illustrates an example of the potentially poor prognosis of ALES despite regression of disease. The patient’s treatment course, marked by recurrent infections and systemic complications, and long-term postsurgical morbidities such as vocal cord paralysis, aspiration pneumonia, and thromboembolic events, further exemplify the burdens imposed by both the disease and its treatment.

Our case confirms reported histopathologic and molecular features of parotid ALES while emphasizing the importance of recognizing FUS-based rearrangements and acknowledging that some cases may display more aggressive clinical behavior than historically suggested. While most patients with salivary ALES remain disease-free at short-term follow-up, our patient’s course was complicated by treatment morbidity and eventual demise. This diverges from the generally favorable prognosis seen in several prior parotid ALES cases. As overall survival rate and prognosis remain unclear in parotid ALES, early evaluation and consistent follow-up can help establish more reliable outcomes.

Through this rare case of parotid ALES, the indispensable role of multidisciplinary care in managing complex malignancies is recognized. Collaboration among oncologists, surgeons, radiologists, and pathologists was vital in guiding both diagnosis and treatment. Regular tumor board discussions enabled a coordinated approach tailored to the patient’s evolving clinical condition, demonstrating the value of teamwork in tackling rare and challenging tumors.

CONCLUSION

This case highlights the rarity and complexity of ALES of the parotid gland. Accurate diagnosis requires a combination of advanced histologic and molecular techniques, while effective treatment necessitates a multidisciplinary approach. Although multimodal therapy can achieve initial disease control, the long-term prognosis remains unpredictable due to the rarity of this malignancy and the potential for significant treatment-related morbidities. Continued research is essential to better understand ALES and to develop targeted therapies that may improve outcomes for patients with this rare and challenging tumor.