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Incarcerated Umbilical Hernia of Unexpected Origin: A Primitive Neuroectodermal Tumor With Early Recurrence Introduction Primitive neuroectodermal tumor (PNET)/Ewing sarcoma (ES) is the second most common sarcoma of bone and soft tissue in children.1 PNET/ES usually occurs in adolescence or in early adulthood, with the age at diagnosis ranging from 14 to 22 years.2 An association between ES and hernias has been demonstrated,3 especially in children and young adults. However, the ES found in these patients were not in the umbilical or inguinal hernia region but in various parts of the body.4 Other risk factors such as smoking during pregnancy5 or farming could also be identified.6-9 Most patients with extraskeletal PNET/ES present with a nonpainful mass in the thoracic or paraspinal soft tissues, with the extremities and head and neck as less common sites of involvement.10-12 Apart from these sites, there have been isolated reports of peripheral PNET/ES arising from unusual locations in the body, including the lung, uterus, ovary, testis, pancreas, urinary bladder, parotid gland, skin, and subcutaneous tissue.13-17 Case Report A 35-year-old woman presented at the emergency room with a clinically incarcerated umbilical hernia. The hernia was repaired by an emergency operation with direct fascial closure. In the resected omental fat, malignant cells with neuroendocrine differentiation were found. Fourteen days after initial surgery, the patient felt a strong pain in the right lower abdomen and complained of an umbilical secretion. Blood analysis was unexceptional except for a slight elevation in the leukocyte count with 11.05 ⫻109/L. The patient was afebrile. As a result of the unusual histologic finding and pain in the right lower abdomen, an ultrasound of the abdominal wall was performed. A semisolid infraumbilical mass with a diameter of 5.5 cm was detected and further investigated with a computed tomography (CT) scan of the abdomen. Here the infraumbilical mass was confirmed and any metastatic lesions were excluded. We considered a hematoma as the first differential diagnosis because of the postoperative chronology (Fig 1; red circle indicates the infraumbilical mass). We performed a surgical re-exploration as a matter of caution in regard to the last histologic findings. Consequently, an infraumbilical mass was resected by an open procedure and the definitive histologic workup showed a malignant, small, round, blue-cell tumor of the Ewing type with a high proliferation fraction (MIB1) of 60% (Fig 2C). Immunohistochemically (positivity for CD99 [Fig 2A], synaptophysin, neuron-specific enolase [Fig 2B] and protein gene product 9.5), the diagnosis of a PNET was made. A rearrangement of the EWSR1 gene was found by fluorescent in situ hybridization. The tumor was completely resected. However, during the second operation, the tumor was accidentally opened. Journal of Clinical Oncology, Vol 32, No 5 (February 10), 2014: pp e3-e6
Fig 1.
A postoperative [18F]fluorodeoxyglucose–positron emission tomography/CT scan did not show additional tumor manifestations. On the basis of an interdisciplinary discussion, we decided to treat the patient according to the European Ewing Tumour Working Initiative of National Groups–Ewing Tumour Studies 1999 (EURO-EWING 1999) protocol with six cycles of chemotherapy with VIDE (vincristine, ifosfamide, doxorubicin, and etoposide) followed by eight cycles of VAC (vincristine, dactinomycin, cyclophosphamide). We planned to complete the treatment by local irradiation. The first part of the therapy with VIDE was completed according to plan. The patient tolerated the therapy quite well with hematotoxicity the most relevant adverse effect. After the first cycle of the VAC scheme, the patient presented with a new palpable mass of about 2 centimeters in the abdominal wall. The CT and positron emission tomography/CT scan confirmed the finding of a metabolically active tumor in the abdominal wall and did not show other suspicious lesions (Fig 3). A local recurrence within the scar of the abdominal wall was diagnosed by ultrasonography-guided punch biopsy. Histologically diffuse infiltrates of widely necrotic small, round, and blue cells were described. An interdisciplinary decision was made to start a new induction chemotherapy with cyclophosphamide and topotecan alternating with irinotecan and temozolomide.18,19 After the first cycle, a clinical and radiologic tumor progression was observed. Therefore, a surgical procedure for local tumor control was planned. The patient was treated with abdominal wall resection and reconstruction with a mesh in sublay technique. Intraoperatively, a small mesenteric metastasis was found. Histologically, the diagnosis of PNET/ES was confirmed. Regions of tumor necrosis (approximately 15% of the total tumor volume) were found. Postoperatively, we recommended irradiation of the abdomen and the abdominal wall at the site of tumor © 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Umea university library on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.239.20.174
e3
Droeser et al
A
B Fig 3.
suspicion of an in-field relapse was verified by a core-needle biopsy. Radiographically, lung metastases were diagnosed at that time. The patient started palliative chemotherapy with cyclophosphamide.
C
Fig 2.
recurrence. Treatment with 30 Gy to the abdominal cavity and a boost up to 50 Gy to the site of tumor resection with 25 fractions in 5 weeks was administered using helical tomotherapy. During the final visit to the radiation oncology department, the patient complained about a new mass in the abdominal wall. The clinical e4
© 2014 by American Society of Clinical Oncology
Discussion Fourteen percent of all hernia operations are umbilical hernia repairs. Slightly more women than men are treated for umbilical hernias, with a ratio of 1.7 to 1. Usually small umbilical hernias (⬍ 3 cm) in young adults are repaired by direct closure of the fascia. Ewing’s family of sarcomas consists of Ewing’s tumor of the bone (87%), extraosseous Ewing’s (8%), and PNETs (5%). PNETs are believed to arise from migrating embryonal cells of the neural crest. These tumors have in common a poorly differentiated small roundcell morphology with hyperchromatic nuclei, scant cytoplasm, and characteristic chromosomal translocation, which involves the ES gene (11:22;q24;q12). Distinguishing between PNET/ES and other small round-cell tumors is sometimes difficult by conventional morphologic methods, especially if the tumor arises in an unusual region. The distinction between ES and PNET is based primarily on the presence of neural differentiation, usually detected immunohistochemically (neuron-specific enolase, synaptophysin, S-100 protein, protein gene product 9.5, secretogranin II, vimentin, and keratin), in the latter tumor.20,21 Approximately 7% of PNET/ES occur in extraosseous soft tissue.22 These tumors are usually localized in the paravertebral region, lower extremities, chest wall (Askin tumor), or retroperitoneum.23 They are extremely rare in the abdomen.24,25 An association of ES and umblical or inguinal hernias is known and epidemiologically well studied.3,4,26 However, to our knowledge, no reports have been made of a PNET/ES arising in the omental fat in relation to an umbilical hernia. The present case is unique in terms of the tumor’s primary site and its relation to an incarcerated umbilical hernia, making a preoperative diagnosis difficult. Microscopic examinations of the tumor tissue obtained during surgery contributed to the diagnosis of a small round-cell tumor. By immunohistochemistry and reverse transcription polymerase chain reaction the definitive diagnosis of a PNET was JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Umea university library on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.239.20.174
Diagnosis in Oncology
made. Recently, a proposal has been made to redefine the Ewing family of tumors according to the unambiguous identification of fused transcripts involving the EWS/FLI1 or EWS/ERG genes. The presence of fused transcripts should allow accurate and reproducible diagnosis of PNET/ES to be made and enable their differentiation from phenotypically similar tumors.27 Current standard treatment consists of five drug chemotherapy and local control via surgical resection, irradiation, or both.28 Distant metastases are identified in 20% to 25% of patients with newly diagnosed disease and are negative prognostic factors.29,30 PNET is generally considered to have an unfavorable prognosis. In a recent study, the overall 5-year survival for localized and metastatic tumors ranged from 65% to 74% and 25% to 45%, respectively.31 It has been found that tumors arising from the paraspinal region respond better to treatment, whereas abdominal and pelvic PNET respond poorly.32 Helical tomotherapy is a volumetric image-guided, fully dynamic, intensity-modulated radiation therapy delivery system. It has been developed at the University of Wisconsin and is now commercially manufactured as the Tomotherapy Hi䡠Art System (Accuray, Madison, WI).33 Tomotherapy allows highly conformal dose distributions to be delivered to patients in a helical fashion. Advantages are accurate target and organ at-risk definition leading to a better distribution of the cumulative dose distribution to the target while observing the constraints on dosage to adjacent normal tissues. Helical tomotherapy has been used clinically to treat a wide variety of malignancies.34 In this case, the aim of using tomotherapy was bowel sparing, which could be achieved by using tomotherapy.35 Use of tomotherapy for whole abdominal irradiation was investigated in patients with advanced ovarian cancer.36 In general, malignant tumors within umbilical hernias are rare. In a PubMed search limited to case reports only and based on the medical subject heading (MESH) terms “umbilical hernia” and “neoplasms,” there were 108 results. However, no article documented a PNET that clinically presented as an umbilical hernia. Most of them were in the context of an omphalocele,37-40 hamartoma,41 teratoma,42,43 squamous cell carcinoma,44 endometrial,45 or ovarian carcinoma.46 In conclusion, we have reported a patient with a PNET/ES with unique localization in the omental fat within an incarcerated umbilical hernia. Therefore, PNET/ES should be considered in the differential diagnosis in this clinical situation.
Raoul A. Droeser and Sacha I. Rothschild University Hospital of Basel, Basel, Switzerland
Luigi Tornillo and Gernot Jundt Institute of Pathology, University Hospital of Basel, Basel, Switzerland
Christoph Kettelhack, Daniel Oertli, and Philipp Kirchhoff University Hospital of Basel, Basel, Switzerland
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Ushigome S, Machinami R, Sorensen PH: Ewing sarcoma/primitve neuroectodermal tumor, in Fletcher CDM, Unni K, Mertens F, et al (eds): Tumors of Soft Tissue and Bone: Pathology and Genetics. Lyon, France, IARC Press, 2002, pp 298-300 2. Coffin CM, Dehner LP: Neurogenic tumors of soft tissue, in Coffin CM, Dehner LP, O’Shea PA (eds): Pediatric Soft Tissue Tumors: A Clinical Pathological and Therapeutic Approach. Baltimore, MD, Lippincott, William and Wilkins, 1997, pp 80-132 www.jco.org
3. Valery PC, Holly EA, Sleigh AC, et al: Hernias and Ewing’s sarcoma family of tumours: A pooled analysis and meta-analysis. Lancet Oncol 6:485-490, 2005 4. Valery PC, McWhirter W, Sleigh A, et al: A national case-control study of Ewing’s sarcoma family of tumours in Australia. Int J Cancer 105:825-830, 2003 5. Winn DM, Li FP, Robison LL, et al: A case-control study of the etiology of Ewing’s sarcoma. Cancer Epidemiol Biomarkers Prev 1:525-532, 1992 6. Holly EA, Aston DA, Ahn DK, et al: Ewing’s bone sarcoma, paternal occupational exposure, and other factors. Am J Epidemiol 135:122-129, 1992 7. Hum L, Kreiger N, Finkelstein MM: The relationship between parental occupation and bone cancer risk in offspring. Int J Epidemiol 27:766-771, 1998 8. Holman CD, Reynolds PM, Byrne MJ, et al: Possible infectious etiology of six cases of Ewing’s sarcoma in Western Australia. Cancer 52:1974-1976, 1983 9. Valery PC, McWhirter W, Sleigh A, et al: Farm exposures, parental occupation, and risk of Ewing’s sarcoma in Australia: A national case-control study. Cancer Causes Control 13:263-270, 2002 10. Coffin CM, Dehner LP: Peripheral neurogenic tumors of the soft tissues in children and adolescents: A clinicopathologic study of 139 cases. Pediatr Pathol 9:387-407, 1989 11. Hashimoto H, Enjoji M, Nakajima T, et al: Malignant neuroepithelioma (peripheral neuroblastoma): A clinicopathologic study of 15 cases. Am J Surg Pathol 7:309-318, 1983 12. Schmidt D, Harms D, Burdach S: Malignant peripheral neuroectodermal tumours of childhood and adolescence. Virchows Arch A Pathol Anat Histopathol 406:351-365, 1985 13. Catalan RL, Murphy T: Primary primitive neuroectodermal tumor of the lung. AJR Am J Roentgenol 169:1201-1202, 1997 14. Taı¨eb S, Cabaret V, Bonodeau F, et al: MRI of primitive neuroectodermal tumor of the uterus. J Comput Assist Tomogr 22:896-898, 1998 15. Deb RA, Desai SB, Amonkar PP, et al: Primary primitive neuroectodermal tumour of the parotid gland. Histopathology 33:375-378, 1998 16. Banerjee SS, Agbamu DA, Eyden BP, et al: Clinicopathological characteristics of peripheral primitive neuroectodermal tumour of skin and subcutaneous tissue. Histopathology 31:355-366, 1997 17. Somers GR, Shago M, Zielenska M, et al: Primary subcutaneous primitive neuroectodermal tumor with aggressive behavior and an unusual karyotype: Case report. Pediatr Dev Pathol 7:538-545, 2004 18. Bernstein ML, Devidas M, Lafreniere D, et al: Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children’s Cancer Group Phase II Study 9457—A report from the Children’s Oncology Group. J Clin Oncol 24:152-159, 2006 19. Casey DA, Wexler LH, Merchant MS, et al: Irinotecan and temozolomide for Ewing sarcoma: The Memorial Sloan-Kettering experience. Pediatr Blood Cancer 53:1029-1034, 2009 20. Rosai J: Rosai and Ackerman’s Surgical Pathology (ed 10). London, United Kingdom, Mosby, 2004, pp 2237-2373 21. Khong PL, Chan GC, Shek TW, et al: Imaging of peripheral PNET: Common and uncommon locations. Clin Radiol 57:272-277, 2002 22. Dehner LP: Primitive neuroectodermal tumor and Ewing’s sarcoma. Am J Surg Pathol 17:1-13, 1993 23. Angervall L, Enzinger FM: Extraskeletal neoplasm resembling Ewing’s sarcoma. Cancer 36:240-251, 1975 24. Kushner BH, Hajdu SI, Gulati SC, et al: Extracranial primitive neuroectodermal tumors: The Memorial Sloan-Kettering Cancer Center experience. Cancer 67:1825-1829, 1991 25. Parham DM, Dias P, Kelly DR, et al: Desmin positivity in primitive neuroectodermal tumors of childhood. Am J Surg Pathol 16:483-492, 1992 26. Cope JU, Tsokos M, Helman LJ, et al: Inguinal hernia in patients with Ewing sarcoma: A clue to etiology. Med Pediatr Oncol 34:195-199, 2000 27. Delattre O, Zucman J, Melot T, et al: The Ewing family of tumors: A subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 331:294-299, 1994 28. Ludwig JA: Ewing sarcoma: Historical perspectives, current state-of-theart, and opportunities for targeted therapy in the future. Curr Opin Oncol 20:412-418, 2008 29. Kolb EA, Kushner BH, Gorlick R, et al: Long-term event-free survival after intensive chemotherapy for Ewing’s family of tumors in children and young adults. J Clin Oncol 21:3423-3430, 2003 30. Kushner BH, Meyers PA: How effective is dose-intensive/myeloablative therapy against Ewing’s sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review. J Clin Oncol 19:870-880, 2001 31. Parham DM, Hijazi Y, Steinberg SM, et al: Neuroectodermal differentiation in Ewing’s sarcoma family of tumors does not predict tumor behavior. Hum Pathol 30:911-918, 1999
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Umea university library on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.239.20.174
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32. Kimber C, Michalski A, Spitz L, et al: Primitive neuroectodermal tumours: Anatomic location, extent of surgery, and outcome. J Pediatr Surg 33:39-41, 1998 33. Mackie TR, Olivera GH, Kapatoes JM, et al: Helical tomotherapy, in Palta J, Mackie TR (eds): Intensity-Modulated Radiation Therapy: The State of the Art. Madison, WI, Medical Physics Publishing, 2003, pp 247-284 34. Sterzing F, Schubert K, Sroka-Perez G, et al: Helical tomotherapy. Experiences of the first 150 patients in Heidelberg. Strahlenther Onkol 184:8-14, 2008 35. Harron E, Lewis J: Bowel sparing in pediatric cranio-spinal radiotherapy: A comparison of combined electron and photon and helical TomoTherapy techniques to a standard photon method. Med Dosim 37:140-144, 2012 36. Rochet N, Sterzing F, Jensen A, et al: Helical tomotherapy as a new treatment technique for whole abdominal irradiation. Strahlenther Onkol 184: 145-149, 2008 37. Ben Achour D, Daghfous MH, Rachdi R, et al: Early echographic diagnosis of omphalocele: 2 case reports and review of the literature [in French]. Rev Fr Gynecol Obstet 87:45-48, 1992 38. Jauniaux E, Jurkovic D, Campbell S: Sonographic features of an umbilical cord abnormality combining a cord pseudocyst and a small omphalocele: A case report. Eur J Obstet Gynecol Reprod Biol 40:245-248, 1991
39. Kiris¸tiog˘lu I, Gu¨rpinar A, Dog˘ruyol H: Giant omphalocele filled by a duplication cyst. Eur J Pediatr Surg 8:315-316, 1998 40. Stella A, Babbo GL: Omphalocele and umbilical cord cyst: Prenatal diagnosis. Minerva Ginecol 52:213-216, 2000 41. Scobie WG, Eckstein HB: Umbilical hernia with associated hamartoma in a neonate. J Pediatr Surg 6:73, 1971 42. Satge´ DC, Laumond MA, Desfarges F, et al: An umbilical cord teratoma in a 17-week-old fetus. Prenat Diagn 21:284-288, 2001 43. Kreczy A, Alge A, Menardi G, et al: Teratoma of the umbilical cord: Case report with review of the literature. Arch Pathol Lab Med 118:934-937, 1994 44. Christofi T, Jonas-Obichere M, mo-Takyi BK: An unusual finding in an umbilical hernia. J Obstet Gynaecol 27:740, 2007 45. Bukovsky I, Lifshitz Y, Langer R, et al: Umbilical mass as a presenting symptom of endometrial adenocarcinoma. Int J Gynaecol Obstet 17:229-230, 1979 46. Millar RC, Geelhoed GW, Ketcham AS: Ovarian cancer presenting as umbilical hernia. J Surg Oncol 7:493-496, 1975
DOI: 10.1200/JCO.2012.45.3092; published online ahead of print at www.jco.org on January 6, 2014
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Incarcerated Umbilical Hernia of Unexpected Origin: A Primitive Neuroectodermal Tumor With Early Recurrence Introduction Primitive neuroectodermal tumor (PNET)/Ewing sarcoma (ES) is the second most common sarcoma of bone and soft tissue in children.1 PNET/ES usually occurs in adolescence or in early adulthood, with the age at diagnosis ranging from 14 to 22 years.2 An association between ES and hernias has been demonstrated,3 especially in children and young adults. However, the ES found in these patients were not in the umbilical or inguinal hernia region but in various parts of the body.4 Other risk factors such as smoking during pregnancy5 or farming could also be identified.6-9 Most patients with extraskeletal PNET/ES present with a nonpainful mass in the thoracic or paraspinal soft tissues, with the extremities and head and neck as less common sites of involvement.10-12 Apart from these sites, there have been isolated reports of peripheral PNET/ES arising from unusual locations in the body, including the lung, uterus, ovary, testis, pancreas, urinary bladder, parotid gland, skin, and subcutaneous tissue.13-17 Case Report A 35-year-old woman presented at the emergency room with a clinically incarcerated umbilical hernia. The hernia was repaired by an emergency operation with direct fascial closure. In the resected omental fat, malignant cells with neuroendocrine differentiation were found. Fourteen days after initial surgery, the patient felt a strong pain in the right lower abdomen and complained of an umbilical secretion. Blood analysis was unexceptional except for a slight elevation in the leukocyte count with 11.05 ⫻109/L. The patient was afebrile. As a result of the unusual histologic finding and pain in the right lower abdomen, an ultrasound of the abdominal wall was performed. A semisolid infraumbilical mass with a diameter of 5.5 cm was detected and further investigated with a computed tomography (CT) scan of the abdomen. Here the infraumbilical mass was confirmed and any metastatic lesions were excluded. We considered a hematoma as the first differential diagnosis because of the postoperative chronology (Fig 1; red circle indicates the infraumbilical mass). We performed a surgical re-exploration as a matter of caution in regard to the last histologic findings. Consequently, an infraumbilical mass was resected by an open procedure and the definitive histologic workup showed a malignant, small, round, blue-cell tumor of the Ewing type with a high proliferation fraction (MIB1) of 60% (Fig 2C). Immunohistochemically (positivity for CD99 [Fig 2A], synaptophysin, neuron-specific enolase [Fig 2B] and protein gene product 9.5), the diagnosis of a PNET was made. A rearrangement of the EWSR1 gene was found by fluorescent in situ hybridization. The tumor was completely resected. However, during the second operation, the tumor was accidentally opened. Journal of Clinical Oncology, Vol 32, No 5 (February 10), 2014: pp e3-e6
Fig 1.
A postoperative [18F]fluorodeoxyglucose–positron emission tomography/CT scan did not show additional tumor manifestations. On the basis of an interdisciplinary discussion, we decided to treat the patient according to the European Ewing Tumour Working Initiative of National Groups–Ewing Tumour Studies 1999 (EURO-EWING 1999) protocol with six cycles of chemotherapy with VIDE (vincristine, ifosfamide, doxorubicin, and etoposide) followed by eight cycles of VAC (vincristine, dactinomycin, cyclophosphamide). We planned to complete the treatment by local irradiation. The first part of the therapy with VIDE was completed according to plan. The patient tolerated the therapy quite well with hematotoxicity the most relevant adverse effect. After the first cycle of the VAC scheme, the patient presented with a new palpable mass of about 2 centimeters in the abdominal wall. The CT and positron emission tomography/CT scan confirmed the finding of a metabolically active tumor in the abdominal wall and did not show other suspicious lesions (Fig 3). A local recurrence within the scar of the abdominal wall was diagnosed by ultrasonography-guided punch biopsy. Histologically diffuse infiltrates of widely necrotic small, round, and blue cells were described. An interdisciplinary decision was made to start a new induction chemotherapy with cyclophosphamide and topotecan alternating with irinotecan and temozolomide.18,19 After the first cycle, a clinical and radiologic tumor progression was observed. Therefore, a surgical procedure for local tumor control was planned. The patient was treated with abdominal wall resection and reconstruction with a mesh in sublay technique. Intraoperatively, a small mesenteric metastasis was found. Histologically, the diagnosis of PNET/ES was confirmed. Regions of tumor necrosis (approximately 15% of the total tumor volume) were found. Postoperatively, we recommended irradiation of the abdomen and the abdominal wall at the site of tumor © 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Umea university library on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.239.20.174
e3
Droeser et al
A
B Fig 3.
suspicion of an in-field relapse was verified by a core-needle biopsy. Radiographically, lung metastases were diagnosed at that time. The patient started palliative chemotherapy with cyclophosphamide.
C
Fig 2.
recurrence. Treatment with 30 Gy to the abdominal cavity and a boost up to 50 Gy to the site of tumor resection with 25 fractions in 5 weeks was administered using helical tomotherapy. During the final visit to the radiation oncology department, the patient complained about a new mass in the abdominal wall. The clinical e4
© 2014 by American Society of Clinical Oncology
Discussion Fourteen percent of all hernia operations are umbilical hernia repairs. Slightly more women than men are treated for umbilical hernias, with a ratio of 1.7 to 1. Usually small umbilical hernias (⬍ 3 cm) in young adults are repaired by direct closure of the fascia. Ewing’s family of sarcomas consists of Ewing’s tumor of the bone (87%), extraosseous Ewing’s (8%), and PNETs (5%). PNETs are believed to arise from migrating embryonal cells of the neural crest. These tumors have in common a poorly differentiated small roundcell morphology with hyperchromatic nuclei, scant cytoplasm, and characteristic chromosomal translocation, which involves the ES gene (11:22;q24;q12). Distinguishing between PNET/ES and other small round-cell tumors is sometimes difficult by conventional morphologic methods, especially if the tumor arises in an unusual region. The distinction between ES and PNET is based primarily on the presence of neural differentiation, usually detected immunohistochemically (neuron-specific enolase, synaptophysin, S-100 protein, protein gene product 9.5, secretogranin II, vimentin, and keratin), in the latter tumor.20,21 Approximately 7% of PNET/ES occur in extraosseous soft tissue.22 These tumors are usually localized in the paravertebral region, lower extremities, chest wall (Askin tumor), or retroperitoneum.23 They are extremely rare in the abdomen.24,25 An association of ES and umblical or inguinal hernias is known and epidemiologically well studied.3,4,26 However, to our knowledge, no reports have been made of a PNET/ES arising in the omental fat in relation to an umbilical hernia. The present case is unique in terms of the tumor’s primary site and its relation to an incarcerated umbilical hernia, making a preoperative diagnosis difficult. Microscopic examinations of the tumor tissue obtained during surgery contributed to the diagnosis of a small round-cell tumor. By immunohistochemistry and reverse transcription polymerase chain reaction the definitive diagnosis of a PNET was JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Umea university library on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.239.20.174
Diagnosis in Oncology
made. Recently, a proposal has been made to redefine the Ewing family of tumors according to the unambiguous identification of fused transcripts involving the EWS/FLI1 or EWS/ERG genes. The presence of fused transcripts should allow accurate and reproducible diagnosis of PNET/ES to be made and enable their differentiation from phenotypically similar tumors.27 Current standard treatment consists of five drug chemotherapy and local control via surgical resection, irradiation, or both.28 Distant metastases are identified in 20% to 25% of patients with newly diagnosed disease and are negative prognostic factors.29,30 PNET is generally considered to have an unfavorable prognosis. In a recent study, the overall 5-year survival for localized and metastatic tumors ranged from 65% to 74% and 25% to 45%, respectively.31 It has been found that tumors arising from the paraspinal region respond better to treatment, whereas abdominal and pelvic PNET respond poorly.32 Helical tomotherapy is a volumetric image-guided, fully dynamic, intensity-modulated radiation therapy delivery system. It has been developed at the University of Wisconsin and is now commercially manufactured as the Tomotherapy Hi䡠Art System (Accuray, Madison, WI).33 Tomotherapy allows highly conformal dose distributions to be delivered to patients in a helical fashion. Advantages are accurate target and organ at-risk definition leading to a better distribution of the cumulative dose distribution to the target while observing the constraints on dosage to adjacent normal tissues. Helical tomotherapy has been used clinically to treat a wide variety of malignancies.34 In this case, the aim of using tomotherapy was bowel sparing, which could be achieved by using tomotherapy.35 Use of tomotherapy for whole abdominal irradiation was investigated in patients with advanced ovarian cancer.36 In general, malignant tumors within umbilical hernias are rare. In a PubMed search limited to case reports only and based on the medical subject heading (MESH) terms “umbilical hernia” and “neoplasms,” there were 108 results. However, no article documented a PNET that clinically presented as an umbilical hernia. Most of them were in the context of an omphalocele,37-40 hamartoma,41 teratoma,42,43 squamous cell carcinoma,44 endometrial,45 or ovarian carcinoma.46 In conclusion, we have reported a patient with a PNET/ES with unique localization in the omental fat within an incarcerated umbilical hernia. Therefore, PNET/ES should be considered in the differential diagnosis in this clinical situation.
Raoul A. Droeser and Sacha I. Rothschild University Hospital of Basel, Basel, Switzerland
Luigi Tornillo and Gernot Jundt Institute of Pathology, University Hospital of Basel, Basel, Switzerland
Christoph Kettelhack, Daniel Oertli, and Philipp Kirchhoff University Hospital of Basel, Basel, Switzerland
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Ushigome S, Machinami R, Sorensen PH: Ewing sarcoma/primitve neuroectodermal tumor, in Fletcher CDM, Unni K, Mertens F, et al (eds): Tumors of Soft Tissue and Bone: Pathology and Genetics. Lyon, France, IARC Press, 2002, pp 298-300 2. Coffin CM, Dehner LP: Neurogenic tumors of soft tissue, in Coffin CM, Dehner LP, O’Shea PA (eds): Pediatric Soft Tissue Tumors: A Clinical Pathological and Therapeutic Approach. Baltimore, MD, Lippincott, William and Wilkins, 1997, pp 80-132 www.jco.org
3. Valery PC, Holly EA, Sleigh AC, et al: Hernias and Ewing’s sarcoma family of tumours: A pooled analysis and meta-analysis. Lancet Oncol 6:485-490, 2005 4. Valery PC, McWhirter W, Sleigh A, et al: A national case-control study of Ewing’s sarcoma family of tumours in Australia. Int J Cancer 105:825-830, 2003 5. Winn DM, Li FP, Robison LL, et al: A case-control study of the etiology of Ewing’s sarcoma. Cancer Epidemiol Biomarkers Prev 1:525-532, 1992 6. Holly EA, Aston DA, Ahn DK, et al: Ewing’s bone sarcoma, paternal occupational exposure, and other factors. Am J Epidemiol 135:122-129, 1992 7. Hum L, Kreiger N, Finkelstein MM: The relationship between parental occupation and bone cancer risk in offspring. Int J Epidemiol 27:766-771, 1998 8. Holman CD, Reynolds PM, Byrne MJ, et al: Possible infectious etiology of six cases of Ewing’s sarcoma in Western Australia. Cancer 52:1974-1976, 1983 9. Valery PC, McWhirter W, Sleigh A, et al: Farm exposures, parental occupation, and risk of Ewing’s sarcoma in Australia: A national case-control study. Cancer Causes Control 13:263-270, 2002 10. Coffin CM, Dehner LP: Peripheral neurogenic tumors of the soft tissues in children and adolescents: A clinicopathologic study of 139 cases. Pediatr Pathol 9:387-407, 1989 11. Hashimoto H, Enjoji M, Nakajima T, et al: Malignant neuroepithelioma (peripheral neuroblastoma): A clinicopathologic study of 15 cases. Am J Surg Pathol 7:309-318, 1983 12. Schmidt D, Harms D, Burdach S: Malignant peripheral neuroectodermal tumours of childhood and adolescence. Virchows Arch A Pathol Anat Histopathol 406:351-365, 1985 13. Catalan RL, Murphy T: Primary primitive neuroectodermal tumor of the lung. AJR Am J Roentgenol 169:1201-1202, 1997 14. Taı¨eb S, Cabaret V, Bonodeau F, et al: MRI of primitive neuroectodermal tumor of the uterus. J Comput Assist Tomogr 22:896-898, 1998 15. Deb RA, Desai SB, Amonkar PP, et al: Primary primitive neuroectodermal tumour of the parotid gland. Histopathology 33:375-378, 1998 16. Banerjee SS, Agbamu DA, Eyden BP, et al: Clinicopathological characteristics of peripheral primitive neuroectodermal tumour of skin and subcutaneous tissue. Histopathology 31:355-366, 1997 17. Somers GR, Shago M, Zielenska M, et al: Primary subcutaneous primitive neuroectodermal tumor with aggressive behavior and an unusual karyotype: Case report. Pediatr Dev Pathol 7:538-545, 2004 18. Bernstein ML, Devidas M, Lafreniere D, et al: Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children’s Cancer Group Phase II Study 9457—A report from the Children’s Oncology Group. J Clin Oncol 24:152-159, 2006 19. Casey DA, Wexler LH, Merchant MS, et al: Irinotecan and temozolomide for Ewing sarcoma: The Memorial Sloan-Kettering experience. Pediatr Blood Cancer 53:1029-1034, 2009 20. Rosai J: Rosai and Ackerman’s Surgical Pathology (ed 10). London, United Kingdom, Mosby, 2004, pp 2237-2373 21. Khong PL, Chan GC, Shek TW, et al: Imaging of peripheral PNET: Common and uncommon locations. Clin Radiol 57:272-277, 2002 22. Dehner LP: Primitive neuroectodermal tumor and Ewing’s sarcoma. Am J Surg Pathol 17:1-13, 1993 23. Angervall L, Enzinger FM: Extraskeletal neoplasm resembling Ewing’s sarcoma. Cancer 36:240-251, 1975 24. Kushner BH, Hajdu SI, Gulati SC, et al: Extracranial primitive neuroectodermal tumors: The Memorial Sloan-Kettering Cancer Center experience. Cancer 67:1825-1829, 1991 25. Parham DM, Dias P, Kelly DR, et al: Desmin positivity in primitive neuroectodermal tumors of childhood. Am J Surg Pathol 16:483-492, 1992 26. Cope JU, Tsokos M, Helman LJ, et al: Inguinal hernia in patients with Ewing sarcoma: A clue to etiology. Med Pediatr Oncol 34:195-199, 2000 27. Delattre O, Zucman J, Melot T, et al: The Ewing family of tumors: A subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 331:294-299, 1994 28. Ludwig JA: Ewing sarcoma: Historical perspectives, current state-of-theart, and opportunities for targeted therapy in the future. Curr Opin Oncol 20:412-418, 2008 29. Kolb EA, Kushner BH, Gorlick R, et al: Long-term event-free survival after intensive chemotherapy for Ewing’s family of tumors in children and young adults. J Clin Oncol 21:3423-3430, 2003 30. Kushner BH, Meyers PA: How effective is dose-intensive/myeloablative therapy against Ewing’s sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review. J Clin Oncol 19:870-880, 2001 31. Parham DM, Hijazi Y, Steinberg SM, et al: Neuroectodermal differentiation in Ewing’s sarcoma family of tumors does not predict tumor behavior. Hum Pathol 30:911-918, 1999
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Umea university library on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 130.239.20.174
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Droeser et al
32. Kimber C, Michalski A, Spitz L, et al: Primitive neuroectodermal tumours: Anatomic location, extent of surgery, and outcome. J Pediatr Surg 33:39-41, 1998 33. Mackie TR, Olivera GH, Kapatoes JM, et al: Helical tomotherapy, in Palta J, Mackie TR (eds): Intensity-Modulated Radiation Therapy: The State of the Art. Madison, WI, Medical Physics Publishing, 2003, pp 247-284 34. Sterzing F, Schubert K, Sroka-Perez G, et al: Helical tomotherapy. Experiences of the first 150 patients in Heidelberg. Strahlenther Onkol 184:8-14, 2008 35. Harron E, Lewis J: Bowel sparing in pediatric cranio-spinal radiotherapy: A comparison of combined electron and photon and helical TomoTherapy techniques to a standard photon method. Med Dosim 37:140-144, 2012 36. Rochet N, Sterzing F, Jensen A, et al: Helical tomotherapy as a new treatment technique for whole abdominal irradiation. Strahlenther Onkol 184: 145-149, 2008 37. Ben Achour D, Daghfous MH, Rachdi R, et al: Early echographic diagnosis of omphalocele: 2 case reports and review of the literature [in French]. Rev Fr Gynecol Obstet 87:45-48, 1992 38. Jauniaux E, Jurkovic D, Campbell S: Sonographic features of an umbilical cord abnormality combining a cord pseudocyst and a small omphalocele: A case report. Eur J Obstet Gynecol Reprod Biol 40:245-248, 1991
39. Kiris¸tiog˘lu I, Gu¨rpinar A, Dog˘ruyol H: Giant omphalocele filled by a duplication cyst. Eur J Pediatr Surg 8:315-316, 1998 40. Stella A, Babbo GL: Omphalocele and umbilical cord cyst: Prenatal diagnosis. Minerva Ginecol 52:213-216, 2000 41. Scobie WG, Eckstein HB: Umbilical hernia with associated hamartoma in a neonate. J Pediatr Surg 6:73, 1971 42. Satge´ DC, Laumond MA, Desfarges F, et al: An umbilical cord teratoma in a 17-week-old fetus. Prenat Diagn 21:284-288, 2001 43. Kreczy A, Alge A, Menardi G, et al: Teratoma of the umbilical cord: Case report with review of the literature. Arch Pathol Lab Med 118:934-937, 1994 44. Christofi T, Jonas-Obichere M, mo-Takyi BK: An unusual finding in an umbilical hernia. J Obstet Gynaecol 27:740, 2007 45. Bukovsky I, Lifshitz Y, Langer R, et al: Umbilical mass as a presenting symptom of endometrial adenocarcinoma. Int J Gynaecol Obstet 17:229-230, 1979 46. Millar RC, Geelhoed GW, Ketcham AS: Ovarian cancer presenting as umbilical hernia. J Surg Oncol 7:493-496, 1975
DOI: 10.1200/JCO.2012.45.3092; published online ahead of print at www.jco.org on January 6, 2014
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