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Ewing’s sarcoma/primitive neuroectodermal tumor arising from the adrenal gland: a case report and literature review
Takeshi Sasaki1, Takehisa Onishi1, Tadashi Yabana2, and Akira Hoshina1
1Department of Urology, and 2Department of Pathology, Ise Red Cross Hospital, Ise, Mie, Japan
ABSTRACT
We report a rare case of Ewing’s sarcoma (ES)/primitive neuroectodermal tumor (PNET) arising from the adrenal gland. A 17-year-old Japanese woman presented with left upper abdominal pain and high fever. Computed tomography and magnet- ic resonance imaging revealed a 15×10 cm tumor replacing the adrenal gland. Preop- erative diagnosis was an adrenocortical carcinoma. Resection of the tumor was per- formed. We obtained the final diagnosis of ES/PNET by immunohistochemical mo- lecular study with positive staining for the MIC2 gene product (CD99) and a Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement. Local recurrence was ob- served one month after the surgery. The patient was then treated with systemic chemotherapy and localized radiotherapy.
Introduction
Ewing’s sarcoma (ES)/primitive neuroectodermal tumor (PNET) is a malignant tu- mor of bone or soft tissue in children, adolescents and young adults. According to im- munohistochemical molecular studies, it belongs to the phenotypic spectrum of a single entity1. Only 10 cases of ES/PNET arising from the adrenal gland have been re- ported in the literature2-8, which were difficult to differentiate from adrenocortical carcinoma. We herein report the 11th case of a primary ES/PNET of the adrenal gland. An exact diagnosis is crucial for deciding the treatment strategy for these rare adrenal tumors.
Case report
A 17-year-old Japanese woman presented to our hospital with left upper abdominal pain and high fever. Physical examination showed no palpable mass in the abdomen. Enhanced computed tomography (CT) and magnetic resonance imaging (MRI) re- vealed a 15×10 cm tumor in the region of the left adrenal gland, which appeared mul- tilobulated with intratumoral heterogeneity (Figure 1A, 1B). No obvious metastasis was apparent on systemic radiological investigation. The serum tumor markers carci- noembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) and all hor- monal examinations were within normal limits. We diagnosed the tumor as a non- functional adrenocortical carcinoma. After obtaining the patient’s informed consent, we performed a left adrenalectomy by the transperitoneal approach. The large tumor (450 mL) originated from the left adrenal gland. Histopathological examination showed bare nucleus round atypical cells with a scarce cytoplasm in sheets like a seat and nest. Some of the cells formed a rosette-like structure. The tumor cells were pos- itive for the MIC2 gene product (CD99) and vimentin but negative for desmin, lead- ing to the diagnosis of a primary ES/PNET arising from the adrenal gland. In addition, fluorescence in situ hybridization (FISH) confirmed a Ewing sarcoma breakpoint re- gion 1 (EWSR1) gene rearrangement at chromosome 22q12.
Key words: Ewing’s sarcoma, primi- tive neuroectodermal tumor, adrenal gland.
Correspondence to: Takehisa Onishi, MD, 471-2 Hunae 1-chome, Ise, Mie 516-8512, Japan.
Tel +81-596-282171; fax +81-596-282965; email takehisa@ise.jrc.or.jp
Received May 26, 2012; accepted October 10, 2012.
A
B
Adjuvant chemotherapy with etoposide, vincristine, doxorubicin, ifosfamide and actinomycin D (EVAIA) based on the European Intergroup Cooperative Ewing’s Sarcoma Study (EICESS)-929 was given soon after the surgery because she was a high-risk patient with a tu- mor volume >100 mL. When local recurrence was ob- served 1 month after the surgery, localized radiation (54.4 Gy) was given after the fourth course of chemotherapy, and an additional tenth course of chemotherapy was administered. She has no evidence of disease progression 24 months after surgery.
Discussion
ES/PNET commonly develops in the second decade of life and is the second most frequent primary bone cancer. It can also occur in soft tissue, namely in the
chest wall, paravertebral extradural locations, extremi- ties and retroperitoneum. These tumors are highly ag- gressive and progress rapidly, with metastases mostly to lung, bone and bone marrow10.
A primary ES/PNET of the adrenal gland is extreme- ly rare: only 10 cases have been reported to date2-8 (Table 1). The median age of patients with adrenal ES/PNET was 24 years old (range 11-57 years). Three patients had metastases at the time of initial presenta- tion. Six of these 10 patients presented with abdominal pain and the adrenal gland turned out to be replaced by a large-sized tumor (>100 mL). The most common CT or MRI finding was a heterogeneously enhanced mass. A central, non-enhancing, low-density area is occasionally seen, which may be due to the presence of hemorrhage and/or necrosis1. ES/PNET of the adre- nal gland is difficult to diagnose preoperatively by im- aging and can only be accurately diagnosed by patho- logical examination.
Neoadjuvant chemotherapy is commonly effective in ES/PNET patients, and wide-margin resection is recom- mended after the neoadjuvant chemotherapy9. A patho- logical diagnosis would therefore be essential for ES/PNET. In our patient, we should have performed a biopsy of the tumor prior to surgery, followed by neoad- juvant chemotherapy for mass reduction. The surgical margin was negative for tumor in our case, but inade- quate wide-margin resection might contribute to early local recurrence. Only 1 patient with adrenal ES/PNET was reported to have received neoadjuvant chemother- apy, but he had progression of metastasis and died with- in 2 years of the initial presentation4.
Immunohistochemistry has proved valuable in the differential diagnosis of ES/PNET. The MIC2 gene prod- uct (CD99) was detected in all cases of ES/PNET arising from the adrenal gland. However, CD99 was also posi- tive in a few other tumors, including rhabdomyosarco- ma and lymphoblastic lymphoma10,11. Therefore, in ad- dition to immunohistochemistry, we investigated an EWSR1 gene rearrangement in our patient.
Recently, EICESS-92 demonstrated that EVAIA chemotherapy seemed to be beneficial for event-free survival in high-risk ES/PNET patients with large local- ized tumors (>100 mL) or metastatic disease9. However, only 6 patients underwent systemic chemotherapy and 3 underwent radiotherapy for adrenal ES/PNET2-8; the long-term prognosis of ES/PNET of the adrenal gland is still a poor outcome (Table 1). We postulate that the rea- son for the poor outcome may be related to inadequate systemic therapy. In our case, both the EVAIA regimen and localized radiotherapy were performed, and our pa- tient is well controlled without disease progression. This case suggests that appropriate systemic therapy is nec- essary for ES/PNET of the adrenal gland.
In conclusion, primary ES/PNET arising from the ad- renal gland is an extremely rare tumor that should be considered in the differential diagnosis of an adrenal
| Ref no. | Sex | Age | Chief complaint | Site | Size (cm) | Direct extension | Initial metastasis | Treatment | Prognosis |
|---|---|---|---|---|---|---|---|---|---|
| 1 | F | 32 | Abdominal pain | Left | 10 | None | Liver | Surg+adjuvant chemo | 5 Mo - Dead |
| 2 | M | 57 | Leg pain, leg edema | Right | 15 | IVC thrombus | None | Surg | Unknown |
| 3 | M | 11 | Abdominal distension | Right | Child's head | None | Douglas' | Surg+ | 2 Mo - Dead |
| size | pouch | neoadjuvant chemo+RTx | |||||||
| 4 | F | 53 | None | Right | 2×3 | None | None | Surg | 10 Mo - Alive |
| 5 | F | 28 | Unknown | Right | 10×9×5 | None | None | Surg+adjuvant | 12 Mo - Lung |
| chemo | metastasis | ||||||||
| 6 | M | 30 | Abdominal pain | Right | 12×9×10 | IVC thrombus | None | Surg+RTx | 8 Mo - Dead |
| 6 | F | 21 | Abdominal pain | Left | 10×8×10 | None | Liver | None | 6 Mo - Dead |
| 6 | F | 24 | Abdominal pain | Left | 9×8×6 | None | None | Surg+adjuvant | 1 Mo - LN |
| chemo | metastasis | ||||||||
| 6 | M | 22 | Abdominal pain | Left | 17×13×13 | IVC thrombus | None | Surg+adjuvant | 1 Mo - Local |
| chemo | recurrence | ||||||||
| 7 | F | 17 | Abdominal pain | Right | 5 | None | None | Surg+adjuvant chemo+RTx | 14 Mo - Alive |
| Present case | F | 17 | Abdominal pain, fever | Left | 10×15 | None | None | Surg+adjuvant chemo+RTx | 1 Mo - Local recurrence |
F, female; M, male; IVC, inferior vena cava; Surg, surgery; Chemo, chemotherapy; RTx, radiotherapy; LN, lymph node; Mo, month(s).
mass occurring in children, adolescents and young adults in order to choose the best treatment strategy for this rare tumor.
References
1. Funahashi Y, Yoshino Y, Hattori R: Ewing’s sarcoma/primi- tive neuroectodermal tumor of the prostate. Int J Urol, 16: 769, 2009.
2. Matsuoka Y, Fujii Y, Akashi T, Gosehi N, Kihara K: Primitive neuroectodermal tumor of the adrenal gland. BJU Int, 83: 515-516, 1999.
3. Pirani JF, Woolums CS, Dishop MK, Herman JR: Primitive neuroectodermal tumor of the adrenal gland. J Urol, 163: 1855-1856, 2000.
4. Kato K, Kato Y, Ijiri R, Misugi K, Nanba I, Nagai J, Nagahara N, Kigasawa H, Toyoda Y, Nishi T, Tanaka Y: Ewing’s sarco- ma family of tumor arising in the adrenal gland-possible diagnostic pitfall in pediatric pathology: histologic, im- munohistochemical, ultrastructural, and molecular study. Hum Pathol, 32: 1012-1016, 2001.
5. Komatsu S, Watanabe R, Naito M, Mizusawa T, Obara K, Nishiyama T, Takahashi K: Primitive neuroectodermal tu- mor of the adrenal gland. Int J Urol, 13: 606-607, 2006.
6. Ahmed AA, Nava VE, Pham T, Taubenberger JK, Lichy JH,
Sorbara L, Raffeld M, Mackall CL, Tsokos M: Ewing sarco- ma family of tumors in unusual sites: confirmation by rt- PCR. Pediatr Dev Pathol, 9: 488-495, 2006.
7. Zhang Y, Li H: Primitive neuroectodermal tumors of adre- nal gland. Jpn J Clin Oncol, 40: 800-804, 2010.
8. Stephenson J, Gow KW, Meehan J, Hawkins DS, Avansino J: Ewing sarcoma/primitive neuroectodermal tumor arising from the adrenal gland in an adolescent. Pediatr Blood Cancer, 57: 691-692, 2011.
9. Paulussen M, Craft AW, Lewis I, Hackshaw A, Douglas C, Dunst J, Schuck A, Winkelmann W, Köhler G, Poremba C, Zoubek A, Ladenstein R, van den Berg H, Hunold A, Cas- soni A, Spooner D, Grimer R, Whelan J, McTiernan A, Jür- gens H; European Intergroup Cooperative Ewing’s Sarco- ma Study-92: Results of the EICESS-92 study: two random- ized trials of Ewing’s sarcoma treatment-cyclophos- phamide compared with ifosfamide in standard-risk pa- tients and assessment of benefit of etoposide added to standard treatment in high-risk patients. J Clin Oncol, 26: 4385-4393, 2008.
10. Okada Y, Kamata S, Akashi T, Kurata M, Nakamura T, Kihara K: Primitive neuroectodermal tumor/Ewing’s sarcoma of the urinary bladder: a case report and its molecular diag- nosis. Int J Clin Oncol, 16: 435-438, 2011.
11. Bernstein M, Kovar H, Paulussen M, Randall RL, Schuck A, Teot LA, Juergens H: Ewing’s sarcoma family of tumors: current management. Oncologist, 11: 503-519, 2006.