Primitive neuroectodermal tumor of the pancreas

Abstract

Primitive neuroectodermal tumors (PNETs) are rare small round cell malignancies closely related to Ewing’s sarcoma. Involvement of the abdominal cavity, specifically the pancreas, is extremely rare. PNETs affect predominantly children and young adults. The clinical presentation is mostly vague, with a short history of symptoms even in metastatic disease. Findings on imaging studies are nonspecific. The diagnosis can be suggested by the microscopic appearance of the tumor cells, but should be confirmed by histology, immunohistochemistry, fluorescence in situ hybridization, immunoreactivity evaluation of MIC2-protein (CD99) expression, and when possible testing for the chromosome translocation t(11;22) (q24,q12). In adults, the prognosis is poor with no standard treatment. Here, we present a case of pancreatic PNET in a 61-year-old man who presented with persistent abdominal pain and weight loss.

Primitive neuroectodermal tumor (PNET), a term coined by Hart and Earle, comprises a group of malignant neoplasms derived from multipotent progenitor cells of neuroectodermal origin.¹ Since 1973, when it was first described, <100 cases have been documented.² PNETs are rapidly growing soft tissue masses, highly malignant and invasive, with a high rate of relapse and a poor prognosis. They are characterized by undifferentiated small round cells that exhibit a neural phenotype. Often these cells resemble other small round cell tumors, so the diagnosis should be confirmed by immunohistochemistry. CD99, a product of the MIC2 gene, is expressed in >95% of Ewing’s sarcoma/PNETs.^1,2 Although PNETs can occur in numerous solid organs such as the kidney, ovary, testis, uterus, urinary bladder, parotid gland, heart, lung, rectum, and pancreas, they are extremely rare, and <15 cases of PNET originating from the pancreas have been reported.³ PNETs primarily occur in children and young adults; however, they may present at any age, in any population. Our study reports the case of an otherwise healthy 61-year-old man diagnosed with advanced PNET of the pancreas.

CASE REPORT

A 61-year-old man with known alcohol and tobacco abuse presented to an outside hospital with complaints of vague abdominal pain, loss of appetite, and weight loss. He was noted to have a pancreatic head mass with a pseudocyst causing gastric outlet obstruction with widespread tumor burden. Initial esophageal ultrasound with fine-needle aspiration showed no evidence of malignancy, with only inflammatory cells present. He underwent initial surgery to remove large areas of the tumor and the associated pancreatic pseudocyst. A subsequent surgery was performed 3 days later with subtotal excision of a large pancreatic pseudocyst, cholecystectomy, distal gastrectomy, and Roux-en-Y gastrojejunostomy. Pathology from the surgical procedure was consistent with a PNET tumor that was widely disseminated in the abdomen with peritoneal carcinomatosis, large liver metastasis, and frank omental caking.

The patient’s clinical course was complicated by peritonitis, with yeast cultured from peritoneal fluid. He was treated with linezolid, piperacillin/tazobactam, and micafungin and discharged on empiric ertapenem with close follow-up. During a follow-up clinic visit, laboratory results were significant for elevated white blood cells (17.0 × 10⁹/L) and C-reactive protein (25.0 mg/L), and the patient was readmitted for further evaluation. Computed tomography (CT) of the abdomen showed extensive spread of malignancy throughout the abdomen along with free peritoneal fluid (Figure 1). Given the concern for active abdominal infection, the patient was not a candidate for palliative chemotherapy. Due to poor performance status and guarded prognosis, he opted for comfort care measures and was discharged following a 10-day hospital stay. He died shortly after discharge.

Figure 1.

Contrast-enhanced CT of the abdomen revealing extensive metastatic disease involving the liver.

DISCUSSION

PNETs comprise only 1% of all sarcomas. Literature describing these tumors is extremely limited, and most published reports describe involvement of solid organs, mostly soft tissues of the pelvis and lower limbs of young adults. Pancreatic involvement is extremely rare, accounting for 0.3% of primary tumors. Ewing’s sarcoma and PNET belong to the same family of tumors, which result from fusion of the Ewing’s sarcoma gene to transcription factor genes forming a chimeric protein. PNETs are considered extremely aggressive, with 25% to 30% of patients presenting with metastatic disease at the time of diagnosis. Frequent sites of metastasis include lung, bone, and bone marrow.¹ Because of the high metastatic potential, chemotherapy with adequate local control is prioritized. Immunohistochemistry is particularly helpful in diagnosing PNETs, as they express a cell surface glycoprotein that is rarely found on other forms of tumors. The glycoprotein is a product of the MIC2 gene, also called CD99 or p30/p32_MIC2, which is important in cell adhesion.^1,2 Histologically, PNETs are made of small monomorphic round cells with scant cytoplasm and small nuclei. This pattern can also be found in other forms of tumors, further solidifying immunohistochemistry as a necessary diagnostic tool.

Commonly employed diagnostic imaging methods include CT and magnetic resonance imaging (MRI) of the abdomen. Diagnosis can be challenging, as no particular radiological findings separate these tumors from other pancreatic malignancies. The most frequent findings include masses with clear margins at the head of the pancreas.³ Compared to CT, MRI is considered superior due to its ability to distinguish various structures based on different signal intensity. Drawbacks are the limited availability and prolonged image acquisition time compared to CT. Different approaches to ultrasound are available, including conventional abdominal ultrasound, endoscopic ultrasound, and intraoperative ultrasound. The biggest advantage of ultrasound is guidance of the biopsy needle during fine-needle aspiration for cytology and core biopsy.⁴

Despite the extreme rarity of the disease, pancreatic PNETs should be considered in the differential diagnosis among those presenting with findings concerning for pancreatic malignancy. The clinical presentation has an insidious onset and often an asymptomatic or poorly symptomatic course, even in advanced stages.^2,3 Most pancreatic PNETs are identified during childhood; however, diagnosis during adulthood remains a possibility. The combination of clinical symptoms, immunohistochemical features, and pathological features, combined with cytogenetic analysis, is required for correct diagnosis of pancreatic PNET. The 5-year survival rate of 30% to 40% has not changed significantly over the last 30 years. In spite of the meager prognosis, surgical resection followed by chemoradiotherapy is the most widely accepted option,^2,3 but there is currently no consensus on the best therapeutic strategy.