Ewing Sarcoma/Primitive Neuroectodermal Tumor Involving the Duodenum

CASE REPORT

A 66-year-old female initially presented to the emergency department (ED) for evaluation of hypotension, palpitations, and progressive dyspnea with exertion. The patient also reported palpitations and lightheadedness with positional changes for a period of 3 weeks prior to presentation, as well as a 6-month history of loss of appetite. Her medical history was notable for prediabetes, vitamin D deficiency, hyperlipidemia, and hypertension. Her surgical history was notable for cesarean section and tubal ligation. Patient's weight at presentation was 53.9 kg, and her body mass index was 22 kg/m². At the time of initial presentation, the patient's medications included ramipril, metformin, and vitamin D supplement. Physical examination was notable for a small external hemorrhoid but was otherwise normal. Laboratory analysis at the initial ED visit demonstrated profound anemia with hemoglobin of 5.4 g/dL (reference range, 11.6-15 g/dL) and hematocrit of 18.3% (reference range, 35.5%-44.9%). The patient was admitted, managed with 2 blood transfusions (900 mL total), and discharged home in stable condition the next day with a consultation placed for gastroenterology.

The patient returned to the ED 1 week later, presenting with new symptoms of coffee-ground emesis and abdominal pain. During the second ED visit, computed tomography (CT) of the abdomen showed a large heterogeneous mass measuring 10.3 × 8.8 × 12.3 cm (anteroposterior × transverse × craniocaudal dimensions) arising from the third segment of the duodenum (Figures 1A, 1B, and 1C). Evidence of duodenal and gastric outlet obstructions, as well as extrinsic mass effect on the pancreatic head, was also noted. No lymphadenopathy was identified. Evaluation of the mass with positron emission tomography demonstrated a maximum standardized uptake value of 6.8 without additional sites of disease (Figure 1D).

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Figure 1.

(A) Anteroposterior view of the abdomen after administration of oral contrast (Omnipaque, GE Healthcare) demonstrates narrowed third and fourth segments of the duodenum secondary to mass effect (black arrowhead). (B) Coronal and (C) axial computed tomography (CT) images demonstrate a heterogeneous mass arising from the superior and anterior walls of the third segment of the duodenum (white arrowheads). Approximately 90 mL of Visipaque 320 (GE Healthcare) was administered intravenously. (D) Fluorodeoxyglucose (F 18-FDG) positron emission tomography/CT demonstrates the same mass with intense metabolic activity (white arrow). Approximately 7.15 mCi of F 18-FDG was administered intravenously. The patient's blood glucose level just prior to imaging was 90 mg/dL. Time from F 18-FDG injection to scan was 51 minutes.

CT-guided biopsy demonstrated a malignant round cell tumor with positivity for CD99, synaptophysin, CD56, and CD117, with negative expression of CD45, CD43, pancytokeratin, beta-catenin, chromogranin, WT1, desmin, S100, DOG1, and TLE1. Fluorescence in situ hybridization (FISH) analysis performed using DNA probes for EWSR1 demonstrated an unusual variant pattern of rearrangement of EWSR1 locus at 22q12 in 52% of nuclei, with 1 fusion and 1 free 5′ EWSR1 signal among 100 interphase nuclei examined.

The patient's treatment course included palliative external beam radiotherapy (EBRT) to the mass at a dose of 20 Gy in 5 fractions that was initiated 17 days after her initial presentation and completed 23 days after her initial presentation. The EBRT resulted in the cessation of her emesis.

The patient also completed 3 cycles of vincristine (2 mg intravenously [IV]), doxorubicin (113 mg IV), and cyclophosphamide (1,800 mg IV) alternating with ifosfamide (2,880 mg IV) and etoposide (160 mg IV) in alternating 14-day cycles initiated 3 weeks after her first presentation and completed 3½ months after her initial presentation. The patient then received treatment with 5 cycles of vincristine (2 mg IV), doxorubicin (113 mg IV), cyclophosphamide (1,800 mg IV), and denosumab (60 mg subcutaneously) beginning approximately 3½ months after her initial presentation and completed 6 months after her initial presentation.

Surgical course after systemic therapy included radical resection of the duodenal mass, open cholecystectomy, wedge gastrectomy, inferior mesenteric artery ligation, and small bowel resection approximately 7 months from initial presentation. The specimen from the radical resection (Figure 2) consisted of a 5.2-cm retroperitoneal mass that was affixed to the duodenum and encroached on the superior mesenteric artery.

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Figure 2.

Gross examination demonstrated a 5.2-cm tumor posttreatment (arrowhead) in the right retroperitoneum affixed to the duodenum. The long single suture marks the distal surgical margin (asterisk), and the short single suture marks the proximal surgical margin (black arrow). The double suture on the left represents the tumor margin abutting the superior mesenteric artery (white arrows).

Cross-sectional analysis of the specimen showed a multiloculated hemorrhagic mass and multiple white-orange plaques within the duodenal wall. Light microscopy showed solid and sheet-like configurations of densely packed tumor cells with indistinct cell borders, scant cytoplasm, fine chromatin, and inconspicuous nucleoli (Figure 3A). The surgical and mesenteric artery margins were clear of tumor cells. Extraskeletal Ewing sarcomas have a tumor differentiation score of 3.⁶ A tumor differentiation score of 3 along with <50% necrosis and 24 mitoses/10 high power fields observed in this case assigns a grade 3 for the tumor (total score 8/9). A single lymph node was identified and was negative for malignancy (0/1). Immunohistochemistry of the resection was positive for CD99 and negative for vimentin and nuclear WT1 expression (Figures 3B, 3C, and 3D). Pathologic staging of ypT2N0 was assigned.⁷

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Figure 3.

Histologic and immunohistochemistry features of the retroperitoneal tumor. (A) Solid and sheet-like configurations of densely packed tumor cells demonstrate indistinct cell borders, scant cytoplasm, fine chromatin, and inconspicuous nucleoli (hematoxylin and eosin, magnification ×100). The boxed region in the upper left corner shows a tumor cell undergoing mitosis (magnification ×400). The tumor is positive for (B) CD99 and negative for (C) vimentin and (D) WT1 (nonnuclear staining) (magnification ×200).

One year from initial presentation, the patient was being actively managed for chronic abscess formation at the surgical resection site. The patient was symptomatically improved and reported 5 to 6 watery bowel movements per day with no other complaints.