AbstrAct
Peripheral primitive neuroectodermal tumors are soft tissue neoplasm’s seen in children and young adults. We are reporting a rare case of peripheral primitive neuroectodermal tumor of ileal mesentry presenting with features suggestive of intestinal obstruction. Abdominopelvic computed tomography revealed 11x8.8x7cm pelvic mass suspicious of ovarian tumor. Following surgical resection, Histopathological examination of the resected specimen showed small round cell tumor. Further testing with Immunohistochemistry and polymerase chain reaction for EWS-FLI1 was suggestive of Peripheral primitive neuroectodermal tumor.
Peripheral Primitive Neuroectodermal Tumor of
Small Bowel Mesentry Presenting as Intestinal
Obstruction: A Case Report.
*Rachan Shetty K S, *Naveen J A, **Premalatha C S, #Lakshmaiah K C.
*Senior Resident - Department of Medical Oncology, **Associate Professor - Department of Pathology, #Professor and HOD - Department of Medical Oncology, Kidwai Memorial Institute of Oncology, M.H Marigowda Road, Bangalore-560029, Karnataka, India.
IntroductIon
Peripheral primitive neuroectodermal tumors (pPnEt) are soft tissue neoplasm’s seen in children and young adults1. Peripheral primitive neuroectodermal tumors are classified as part of Ewing’s family of tumors and are often referred to interchangeably in literature. Ewing’s sarcoma is more common in bone while pPnEts are common in soft tissues. pPnEt-Ewing’s sarcoma tumor family now comprises of extra-osseous Ewing’s sarcoma, peripheral neuroepithelioma, Askin’s tumor of the thoracopulmonary wall, and peripheral neuroblastoma2. pPnEt is a small round cell tumor of neural crest origin known to arise in several sites such as chest in 44%, retroperitoneum and pelvis in 26%, extremities in 20%, head and neck 6% and in other sites 4%3. pPnEt originating from mesentery is rare and there are only five reported cases to the author’s knowledge4-8. We report a rare case presenting as a pelvic mass with small bowel obstruction which has not been reported earlier.
cAsE rEPort
A 24y old woman, who had been previously healthy, was referred to our hospital with a history of abdominal pain, nausea, vomiting, constipation and lower abdominal mass. she had clinical features suggestive of small intestinal obstruction. on preoperative evaluation there was mild elevation of cancer antigen 125 (62u/ml), normal levels of human chorionic gonadotropin, normal carcinoembryonic
the tumor is infiltrating the serosa of the ileum with focal extension up to the submucosa. the mesenteric nodes did not reveal any tumor cells. Margins were negative for tumor. on immunohistochemistry, the cells stained positive for cd-99, FLI-1 and focal positivity for s-100, cd-57. the cells stained negative for cK, EMA, cd-34, HMb-45, inhibin, calretinin, LcA, sMA, PLAP, cd-3, cd-20, desmin, doG-1, cd-117, chromogranin and synaptophysin. reverse transciptase polymerase chain
Fig.2.Erect x-ray abdomen showing distended large bowel loops. Fig.1.A 11.4x8.8 cm sized ,well defined , lobulated moderately enhancing intraperitoneal mass lesion is seen in the pelvis,superior to urinary bladder, Infiltrating the small bowel loops. Fat planes with uterus appears normal. Minimal ascites seen.
A b
antigen levels and computed tomography scan of the abdomen and pelvis showing a pelvic mass measuring 11x8.8x 7 cm (fig. 1) suspicious of ovarian tumor and an erect X-ray abdomen (fig. 2) suggested intestinal obstruction. An emergency exploratory laparotomy was conducted which showed a solid nodular tumor measuring 10x8x6 cm was seen arising from the mesenteric border of the ileum. An intraoperative frozen section of the specimen was suggestive of neuroendocrine tumor. Frozen section Mesenteric Lymph node biopsy was negative for tumor. resection of the tumor along with segmental resection of 15cm ileum with end to end anastomosis was done.
Histopathological examination macroscopically revealed a soft nodular mass with foci of necrosis and hemorrhage.
reaction (rt-Pcr) revealed EWs-FLI1 transcripts hence a diagnosis of mesenteric peripheral primitive neuroectodermal tumor was ascribed.
Follow up: Post operative ct scan of the abdomen and pelvis did not reveal any tumor and cancer antigen 125 levels were normal. since the tumor was completely resected adjuvant chemotherapy was planned with courses of vincristine 2mg IV on day 1, doxorubicin 75mg/ m2 on day 1, cyclophospamide 1.2g/m2 with mesna on day1 alternating with courses of ifosfamide with mesna 1.8g/m2/day from day 1 to 5 and etoposide 100mg/m2/day from day 1 to 5 with both cycles repeated alternating every 3 weeks for a total of 17 cycles. Patient has completed treatment with a disease free survival of 15 months
dIscussIon
PnEt is a soft tissue sarcoma of neural crest origin that was first recognized by A.P stout in 1918. It belongs to the Ewing family of tumors, which include Ewing’s tumor of bone, extra-osseous Ewing’s, and Askin’s tumor (pPnEt of the chest wall). over 90% of cases occur within the first and second decades of life1. Peripheral primitive
neuroectodermal tumor can occur anywhere in the body. A study at memorial sloan Kettering cancer center by Kushner et al who reviewed 54 cases over 20 years found that the primary sites where thoracopulmonary (25cases), pelvis (12cases), retroperitoneum or abdomen (10cases), limb (5cases) neck (one case) with only 25% of cases with tumors greater than 5cm survive to 24months3. pPnEt of mesentry has been reported earlier4-8, with one case presenting as an ovarian tumor as in our report, however none has presented with small intestinal obstruction. Preoperative imaging by ct scan and MrI is not specific for differentiating pPnEts from other soft tissue sarcomas. on MrI PnEts appear isointense to muscle on t1 weighted images, heterogeneously hyperintense on t2 weighted images and demonstrate variable enhancement with intravenous contrast medium. on ct scan imaging they were of low attenuation or contained cystic areas9. since Ewing’s family of tumors have propensity for distant metastases to lung and bone chest imaging by x-ray or ct scan and bone scan should be done.
Histopathologically pPnEt appears as round-to ovoid hyper chromatic cells with minimal cytoplasm. the tumor cells are typically arranged in nests and trabeculae with variable (Flexner-wintersteiner) rosette
Fig.3. (A)FLI-1 immunoperoxidase stain showing nuclear positivity in neoplastic cells,[x400].(b)Immunostain for MIc-2/cd-99 shows membranous positivity,[X400].(c)H&E stain shows sheets of neoplastic cells with rosette formation focally,[x400].(d) H&E stain shows sheets of uniform neoplastic cells seperated by thin fibrovascular septa.
c A
formation. the rosettes may have a central lumen, but are often ill-defined, and are composed of tumor cells arranged around an empty space1. Histopathological diagnosis is by excluding other small round cell tumors, such as neuroblastoma, rhabdomyosarcoma, lymphoma, and small cell osteosarcoma should be excluded by immunocytochemistry. Intraoperative lymph node biopsy was carried out in our patient and was negative for tumor.
there is uniform consensus among authors that demonstration of cd-99 (MIc-2) which is seen in 90% of cases immunohistochemically is diagnostic of pPnEt10.
cd-99 expression may also be seen in malignant lymphoma, leukemia, gastrointestinal stromal tumor and small cell carcinoma. Malignant lymphoma and leukemia were excluded because tumor cell were negative for lymphoid markers (cd45, cd20, cd3), Gastrointestinal stromal tumors and leiomyosarcoma were ruled out because the cells were negative for cd117, desmin, smooth muscle actin. the most diagnostic tool for the diagnosis is karyotypic analysis demonstrating t11;22 (q24; q12) translocation which is seen in 87% of cases 11-12. Alternatively demonstration of the chimeric mrnA EWs-FLI1 is also diagnostic of pPnEt12. We
Table 1. Clinical characteristicts and outcomes of patients with Ewings sarcoma of mesentry
no sex/age Location size* distant
meta surgery chemotx duration#F/u survival 1 F/57y (3) M e s e n t r y o f
terminal ileum 12cm no Ileocaecal resection and anastomosis yes 8 yes 2 M/40y(4) M e s e n t r y o f
jejunum 11cm no resection of bowel with anastomosis yes 6 no 3 F/24y(5) M e s e n t r y o f
transverse colon 12cm no En bloc resection with end to end anastomosis
no 20 yes
4 F/53(6) M e s e n t r y o f
terminal ileum 25cm no Ileal resection with anastomosis na na na 5 M/23y(7) M e s e n t r y o f
jejunum 11cm no segmental resection o f j e j u n u m w i t h omentectomy
yes 12 yes
6 F/24y## M e s e n t r y o f
ileum 10cm no Ileal resection with anastomosis yes 10 yes
chemo tx = chemotherapy; F/u = follow up; M = male; F = female ;cm= centimetre;Y=years.
*Longest length of the mass in centimetre; # Follow up duration after treatment at the time of publishing(months); ## our case; na= not available.
mimic as ovarian tumor and may cause bowel obstruction and should be kept in differential diagnosis.
concLusIon
In conclusion, we have reported the first case of pPnEt of abdomen presenting as intestinal obstruction. Intraabdominal pPnEt is a rare occurrence however it may present as acute abdomen hence it is imperative that surgeons and pathologist consider this.
rEFErEncEs
1. Enzinger FM,Weiss sW. Primitive neuroectodermal tumors and related lesions. In: soft tissue tumors; 3rd edn Mosby, new York 1995;925-964.
2. Kawauchi s, Fukuda t, Miyamoto s, et al. Peripheral primitive neuroectodermal tumor of the ovary confirmed by cd99 immunostaining, karyotypic analysis, and rt-Pcr for EWS/FLI-1 chimeric mrnA. Am J surg Pathol 1998; 22: 1417-22. 3. Kushner bH, Hajdu sI, Gulati sc , et al. Extracranial primitive
neuroectodermal tumors; the Memorial sloan Kettering cancer center experience. cancer 1991;67:1825-1829.
4. bala M, Maly A, remo n, Gimmon Z, Almogy G. Peripheral primitive neuroectodermal tumor of bowel mesentery in adults. Isr Med Assoc J 2006; 8: 515-6.
5. Horie Y, Kato M. Peripheral primitive neuroectodermal tumor of the small bowel mesentery: a case showing perforation at onset.
Pathol Int 2000; 50: 398-403.
6. tokudome n, tanaka K, Kai MH, sueyoshi K, Matsukita s, setoguchi t. Primitive neuroectodermal tumor of the transverse colonic mesentery defined by the presence of EWS-FLI1 chimeric mrnA in a Japanese woman. J Gastroenterol 2002; 37: 543-9. 7. balasubramanian b, dinakarababu E, Molyneux AJ. Primary
primitive neuroectodermal tumour of the small bowel mesentery: case report. Eur J surg oncol 2002; 28: 197-8.
8. Joon Mee kim, Young cc, chang Hc. Peripheral primitive neuroectodermal tumor with osseous component of the small bowel mesentry: A case study. the Korean J of pathol 2013;47:77-81.
9. Khong et al.Imaging of Peripheral PnEt: common and uncommon locations. clinical radiology 2002;57:272-277.
10. scotlandi K, serra M, Manara Mc, et al. Immunostaining of the p30/32MIc2 antigen and molecular detection of EWS rearrangements for the diagnosis of Ewing’s sarcoma and peripheral neuroectodermal tumor. Hum Pathol 1996; 27: 408-16. 11. Kawauchi s, Fukuda t, Miyamoto s, et al. Peripheral primitive
neuroectodermal tumor of the ovary confirmed by cd99 immunostaining, karyotypic analysis, and rt-Pcr for EWS/FLI-1 chimeric mrnA. Am J surg Pathol 1998; 22: 1417-2
12. Ida K, Kobayashi s, taki t, Hanada r, bessho F, Yamamori s,et al. EWs-FLI-1 and EWs-ErG chimeric mrnAs in Ewing’s sarcoma and primitive neuroectodermal tumor. Int J cancer 1995;63:500–4.
13. carvajal r, Meyers P. Ewing’s sarcoma and primitive neuroectodermal family of tumors . Hematol oncol clin north am. Jun2005;19(3):501-25.
