Primitive neuroectodermal tumor (PNET) is most commonly encountered in the soft tissue or bone in children and young adults, and its involvement in the intestines is exceedingly rare. To the best of our knowledge, eighteen cases have been reported to date. The present study reports three cases of PNET arising in the mesentery and ileocecum in 59- and 22-year-old males and a 36-year-old female. Computed tomography revealed a solid mass in the lower abdomen, with areas of cystic changes. Microscopically, the tumors were composed of small round cells arranged in sheets and rosettes with scant cytoplasm, hyperchromatic nuclei and a high mitotic rate. The tumor cells were immunopositive for CD99 and FLI1. EWS/FLI1 translocations were detected in all cases. Case 1 and case 2 underwent tumor resection without any preoperative radiotherapy, chemotherapy or biological therapy. Case 3 underwent tumor resection and received eight cycles of IAP chemotherapy (2.0 mg ifosfamide, 80 mg epirubicin, 30 mg cisplatin 30mg). Case 3 was followed up for 34 months until they succumbed to peritoneal recurrence, whereas the other cases were not followed up. The incidence of these small round-cell tumors in the intestinal system, their clinical and pathological features and differential diagnosis are discussed with a review of the literature.
Primitive neuroectodermal tumor (PNET) is a rare aggressive malignant small round cell tumour, which is most common in children and young adults (
The present study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Jingling Hospital (Nanjing, China). Furthermore, informed consent was obtained from the relatives of each participating patient.
In June 2005, a previously healthy 59-year-old male presented to the Department of Pathology, Nanjing Jinling Hospital (Nanjing, China) following 20 days of lower quadrant pain. Computed tomography (CT) scanning revealed a 5×6 cm mass in the lower quadrant. Tumor markers, such as carcinoembryonic antigen and carbohydrate antigen 19–9, were normal. Explorative laparotomy revealed a 6×5×3 cm mass in the mesentery of the terminal ileum, without any macroscopic spread elsewhere in the abdomen. Microscopically, the sections revealed the proliferation of small round cells in nests with a finely distributed chromatin pattern and rosette formation, hyperchromatic nuclei and scant cytoplasm, and the rosettes were diffusely infiltrated with fat. The tumor cells were positive for CD99, FLI1 and EMA, but negative for CD3, CgA, CD20, CKpan, S100 and HMB45. As no other foci were detected in extensive clinical and radiological investigations, the tumor was considered to be primary. Molecular testing demonstrated the expression of EWS/FLI1 fusion transcripts corresponding to the t(11;22)(q24;q12) translocation. Based on the above clinicopathological and genetic findings, a histopathological diagnosis of PNET developing from the mesentery of the terminal ileum was made. The patient was surgically treated for the tumor and administered with adjuvant chemotherapy.
In September 2005, a 22-year-old male presented with abdominal intermittent abdominal pain of 20 days duration. Physical examination revealed the presence in the lower abdomen of a ~10×8 cm mass, with an uneven surface and no tenderness. Abdominal CT showed a mass (10×11 cm) in the lower abdomen and pelvis; it also revealed multiple areas of intrahepatic cystic density. Explorative laparotomy revealed that the mass adhered tightly to the sigmoid colon, rectum and omentum. The left lateral lobe and right lobe of the liver could touch two obvious nodules, 6 and 8 cm in diameter, respectively. Due to massive intraoperative blood loss and hypotension, the patient did not undergo liver tumor resection. Macroscopic examination revealed a grayish-brown, soft tissue mass, with varicose veins on the surface and areas of cystic changes. Microscopically, the tumor featured a uniform, sheet-like proliferation of small round tumor cells with high mitosis. Focally the tumor cells also formed ribbon-like or rosette-like structures, with areas of hemorrhage and necrosis, and infiltration into adipose tissue. The mesenteric lymph nodes were free. Immunohistochemically, the tumor cells showed diffuse membrane positivity for CD99, Syn and FLI1. There was a punctate pattern of positive staining for S100 and negativity for CKpan, CD3, CD34, SMA, HMB45, MelanA and CgA. EWS/FLI1 fusion gene translocation demonstrated the translocation t(11;22)(q24;q12). The final diagnosis was intestinal PNET with liver metastases. Postoperative adjuvant chemotherapy was not administered.
In January 2009, a 36-year-old female was admitted to hospital with abdominal pain and an abdominal mass. On physical examination, a large and firm mass was evident in the right abdomen. Laboratory evaluation showed a CA125 level of 57.41 IU/ml (normal, 35 IU/ml), whereas the CA199 levels were within normal limits. Magnetic resonance imaging confirmed a large mass in the pelvis (
PNET is a rare aggressive malignant small round cell tumor most commonly arising in the central nervous system, soft tissues or bones, which was first recognized by Stout in 1918 (
In the current study, all cases were primary to the mesentery and ileocecum, with no evidence of the PNET arising elsewhere. The maximum tumor diameter was 6–15 cm. The histologic appearance of the tumor typically comprised round-to-ovoid hyperchromatic cells with minimal cytoplasm, arranged in nests with variable rosette formation. Immunohistological examinations usually revealed CD99 and FLI1 positivity. FISH analysis indicated the presence of EWSR1 gene rearrangement in these three patients.
Making an accurate diagnosis is critical for optimal patient management and prognostication. Physical examination often reveals an abdominal or pelvic mass with recurrent abdominal pain. Imaging examination such as CT scanning is able to provide important information regarding the size of the mass, the involvement of adjacent structures and the presence of metastasis. There are no suggestive blood markers that can be used to diagnose PNET. Mhawech-Fauceglia
It is difficult to differentiate PNET from other small round-cell tumors. However, immunohistochemical examinations with myogenic, neurogenic, and lymphoid cell markers can rule out many of these tumors. In gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), histological examination reveals a trabecular or solid arrangement and immunohistochemical analysis reveals the expression of neuroendocrine markers (Syn and CgA) (
There is no established treatment modality for intestinal PNET. Surgical excision when complete offers the best chance for survival and adjuvant radiotherapy may reduce local recurrence (
In conclusion, the present study reviewed 18 known cases of PNET arising from the intestine and mesentery and reported three additional cases. Immunohistochemical examination and molecular characterization are beneficial for differentiating PNET from other small round-cell tumors.
This study was supported in part by the National Natural Science Foundation of China (81371611, 81171391, 81372743) and the National Basic Research Priorities Program 973 Project (2014CB744504) from the Ministry of Science and Technology of China.
Case 3. MRI scan of the abdomen and pelvis showing a large, heterogeneous and enhanced right lower quadrant mass. (A) Parietal image. (B) Horizontal image. MRI, magnetic resonance imaging.
Case 3. (A) Tumor infiltrating the bowel wall starting from the deep layer of the mucosa. (B) High power view of the tumor cells showing uniform small round blue cells with scant cytoplasm, uniform nuclei and stippled chromatin, with areas of hemorrhage and necrosis. (C) CD99 was diffusely expressed with strong membranous staining. (D) Strong nuclear immunoreactivity was demonstrated for FLI1. Hematoxylin-eosin; magnification, ×200.
Case 3. Nuclei exhibited positive signals for EWS gene translocations (one integrated, one red and one green signal; fluorescence in situ hybridization method). Magnification, ×1,000).
Clinical features of previously reported cases with PNET arising from the intestine and mesentery.
Authors (ref.) | Age (years)/gender | Location | Tumor size and/or weight | Positive immunomarker | Follow-up |
---|---|---|---|---|---|
1 Balasubramanian |
53/F | Small bowel mesentery | 25×26×17.5 cm; 2.6 kg | MIC-2 and PGP9.5 strongly | NM |
2 Sethi and Smith ( |
44/M | Small bowel | 120 mm diameter | MIC-2 strongly and NSE weakly | Succumbed with recurrence, 13 mo |
3 Bala |
57/F | Small bowel mesentery | 12 cm diameter | Vimentin, NSE, O-13, c-Kit, FLI | NED, 8 mo |
4 Horie and Kato ( |
40/M | Small bowel mesentery | 11×8 cm | CD99, NSE, syn and vimentin. | Succumbed with recurrence, 5 mo |
5 Tokudome |
24/F | Transverse colonic mesentery | 12×10×7 cm, 590 g | NSE and Mic-2 | NED, 20 mo |
6 Maisonnette |
56/F | Mesocolon | 12×14×12 cm | CD99 and FLI1 | Succumbed to acute respiratory failure, 13 mo |
7 Adair |
21/F | Duodenum | NM | CD99 and CK | 10 mo DFS |
8 Rodarte-Shade |
32/M | Small bowel | 12×8 cm | CD99 and FLI1 | 6 mo DFS |
9 Sarangarajan |
13/M | Jejunum | NM | CD99 and CK | 12 mo DFS |
10 Graham |
14/M | Small bowel and mesentery | 6×3.5×3 cm | CD99 and CK | 10 mo DFS |
11 Vignali |
15/F | Ileum | 12×9×8 cm | NM | NM |
12 Kim |
63/M | Small bowel | NM | CD99 and CD117 | NM |
13 Shek |
9/F | Small bowel and mesentery | NM | CD99 | 18 mo DFS |
14 Boehm |
18/M | Ileum | NM | NM | NM |
15 Kie |
20/F | Duodenum | NM | CD99 | 18 mo DFS |
16 Prasertvit and Stoikes ( |
28/F | Small intestine | NM | NM | NM |
17 Turkyilmaz |
15/F | Mesocolon | 10×10×12 cm | Vimentin and CD99 | NM |
18 Kim |
23/M | Mesentery of jejunum | 12×8×7.5 cm | CD99, CD57 and NSE | NM |
PNET, primitive neuroectodermal tumor; NM, not mentioned; DFS, disease-free survival; NED, no evidence of disease; Mo, months; ref, reference.