|Year : 2013 | Volume
| Issue : 4 | Page : 709-711
Primitive neuroectodermal tumor of adrenal: Clinical presentation and outcomes
Deep Dutta1, KS Shivaprasad1, Ram Narayan Das2, Sujoy Ghosh1, Subhankar Chowdhury1
1 Department of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, India
2 Department of Pathology, Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, India
|Date of Web Publication||11-Feb-2014|
Room 9A, 4th Floor Ronald Ross Building, Department of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, 244 AJC Bose Road, Kolkata 700 020
Source of Support: None, Conflict of Interest: None
Primitive neuroectodermal tumor (PNET) of adrenal is an extremely rare tumor of neural crest origin. A nonfunctional left adrenal mass (14.6 × 10.5 × 10.0 cm) on computed tomography (CT) was detected in a 40-year-old lady with abdominal pain, swelling, and left pleural effusion. She underwent left adrenalectomy and left nephrectomy with retroperitoneal resection. Histopathology revealed sheets and nest of oval tumor cells with hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm, brisk mitotic activity, necrosis, lymphovascular invasion, capsular invasion, and extension to the surrounding muscles; staining positive for Mic-2 (CD-99 antigen), vimentin, synaptophysin, and Melan-A. Thoracocentesis, pleural fluid study, and pleural biopsy did not show metastasis. She responded well to vincristine, adriamycin, and cyclophosphamide followed by ifosfamide and etoposide (IE). This is the first report of adrenal peripheral PNET (pPNET) from India. This report intends to highlight that pPNET should be suspected in a patient presenting with huge nonfunctional adrenal mass which may be confused with adrenocortical carcinoma.
Keywords: Adrenal, Ewing′s tumor, incidentaloma, primitive neuroectodermal tumor
|How to cite this article:|
Dutta D, Shivaprasad K S, Das RN, Ghosh S, Chowdhury S. Primitive neuroectodermal tumor of adrenal: Clinical presentation and outcomes. J Can Res Ther 2013;9:709-11
|How to cite this URL:|
Dutta D, Shivaprasad K S, Das RN, Ghosh S, Chowdhury S. Primitive neuroectodermal tumor of adrenal: Clinical presentation and outcomes. J Can Res Ther [serial online] 2013 [cited 2019 Nov 20];9:709-11. Available from: http://www.cancerjournal.net/text.asp?2013/9/4/709/126459
| > Introduction|| |
Primitive neuroectodermal tumor (PNET) is an extremely rare malignant tumor with poor prognosis, of neural crest origin, arising mainly from the central nervous system (cPNET) or rarely from the peripheral tissue (pPNET).  pPNET has been reported most commonly from the soft tissues of extremities, chest wall, paravertebral, or retroperitoneal areas and constitutes 1% of all sarcomas.  Even rarely PNETs have been reported from solid organs, the most common being kidney, ,, others being ovary, vagina, testis, uterus, cervix uteri, urinary bladder, parotid gland, heart, lung, rectum, pancreas, liver, and gall bladder.  pPNET from adrenals is extremely rare with few isolated reports. ,,,, We report a lady presenting with abdominal mass and left pleural effusion diagnosed to have PNET of left adrenal.
| > Case Report|| |
A 40-year-old lady presented with abdominal pain and swelling for 4 weeks and respiratory distress of 2 weeks duration. Examination was significant for tachycardia, tachypnea, left-sided pleural effusion, and an abdominal lump palpable in the left lumbar region. Ultrasonography abdomen revealed left adrenal mass. She did not have any stigmata of Cushing's syndrome. Blood pressure was normal. Computerized tomography (CT) abdomen for better characterization of the abdominal mass revealed 14.6 × 10.5 × 10.0 cm heterogeneous left adrenal mass with areas of necrosis [Figure 1]a and b. Chest X-ray (CXR) confirmed large left-sided pleural effusion. Investigations were significant for normal morning cortisol, normal overnight dexamethasone suppression test, and normal urinary metanephrines [Table 1]. Thoracocentesis with pleural biopsy was done. Biochemistry and cytology of pleural fluid was suggestive of exudative effusion [Table 1]. Study for malignant cells in the pleural fluid was negative. Pleural biospy did not reveal any evidence of tuberculosis or malignancy. Repeat CXR about a month after the initial CXR showed a decrease in pleural effusion with presence of iatrogenic hydropneumothorax. She underwent explorative laprotomy with removal of left adrenal mass (15 × 13 × 10 cm), left kidney (10 × 5 × 4 cm), and a section of the retroperitoneal tissue as the mass was infiltrating the retroperitoneal muscles. Histopathology revealed sheets and nest (rosettes) of oval tumor cells with hyperchromatic nuclei and scanty cytoplasm in a fibrous stroma [Figure 2] with brisk mitotic activity, extensive areas of necrosis [Figure 3], lymphovascular invasion [Figure 4]a and b, capsular invasion and extension to the surrounding muscles. Perineural invasion and invasion into the kidney was not demonstrated. Immunohistochemistry revealed tumor cells expressing Mic-2 (CD-99 antigen), vimentin, synaptophysin, and Melan-A (focally and weakly); but negative for cytokeratin, EMA, CK-8/18 chromogranin A, and calretinin. Hence a diagnosis of primitive neuroectodermal tumor of left adrenal with local extension and lymphovascular invasion was made. Repeat CXRs done 2 weeks and 4 weeks postoperatively showed a resolving small effusion obliterating the left costophrenic angle which disappeared by 12 weeks postoperatively. Ultrasonography of the abdomen done a month after surgery was normal, without any evidence of residual tumor.
|Figure 1: (a) Computerized tomography (CT) of the abdomen showing heterogeneous left adrenal mass with areas of necrosis (black arrow), (b) Scannogram of the abdomen showing huge left adrenal mass (black arrow) compressing the spleen superior to it along with left pleural effusion|
Click here to view
|Figure 2: Hematoxylin and eosin staining of the tumor showing small round blue tumor cells with prominent nuclei and nucleoli, scant cytoplasm, arranged in nests (rosettes) in the background of fibrous stroma|
Click here to view
|Figure 3: Small round blue tumor cells seen with adjacent area of necrosis (black arrow)|
Click here to view
|Figure 4: (a) Tumor cells seen infiltrating into the blood vessel. (b) Tumor cells seen in the blood vessel distant from the primary tumor (low magnification)|
Click here to view
On day-28 postoperatively, she received the first cycle of chemotherapy (VAC; vincristine 2 mg/m 2 , adriamycin 75 mg/m 2 and cyclophosphamide 1,200 mg/m 2 ). VAC was alternated with IE (ifosfamide (1,800 mg/m 2 /day) given along with mesna over 5 days with etoposide (100 mg/m 2 /day)) and the cycles were given after every 2 weeks. In total, she received six cycles each of VAC and IE over a period of 29 weeks. Blood component transfusions were given as and when required. Last evaluated, 2 weeks after the completion of chemotherapy, she was doing well without any evidence of tumor recurrence on ultrasonography.
| > Discussion|| |
PNET, first recognized by Arthur Purdy Stout in 1918, a member of the family of 'small round blue cell tumor (SRBCT)' occurs predominantly in males less than 35 years age.  pPNET shares a lot of features with Ewing's sarcoma and both are believed to be due to an unique translocation (t (11;22)(q24q12): Fusion gene designated EWS/FLI-1).  The most common presenting feature of pPNET including adrenal pPNET is painful swelling with compressive symptoms.  Adrenal pPNET tumors are usually large, non-functioning, and frequently have evidence of metastasis. , Rapidly progressive symptoms, with large size on imaging often lead to initial suspicion of adrenocortical carcinoma, , including in our patient. However, pPNET of adrenals are almost always nonfunctional in contrast to adrenocortical carcinoma.  Our patient presented with pain in the abdomen and left pleural effusion. The cause of the effusion could not be determined. It may be secondary to compressive effects of the tumor impairing pleural fluid drainage or due to pleural metastasis. Lack of evidence of malignant cells in the pleural fluid study and pleural biopsy, lack of recurrence of effusion after thoracocentesis and surgery makes metastasis less likely as the cause of effusion. The size of the tumor was large in our patient (15 × 13 × 10 cm), which is consistent with previous reports. , PNET was diagnosed on the basis of classic histologic features of small round blue tumor cells arranged in nests/rosettes with immunohistochemistry positivity for Mic-2 (CD-99 antigen), vimentin, synaptophysin, and Melan-A. Mic-2 (CD-99), a cell surface glycoprotein coded by gene located on X and Y chromosomes, is the most sensitive and specific marker (nearly 100%) for the diagnosis of PNET.  Visualization of adrenal tissue compressed between tumor cells on either sides confirmed the adrenal origin of the tumor [Figure 5].
|Figure 5: Adrenal tissue seen compressed between sheets of tumor cells on either side confirming the adrenal origin of the tumor|
Click here to view
Surgery for PNET is usually accompanied by chemotherapy and/or radiotherapy due to the high risk of local recurrence as well as distant metastasis.  The most frequently used chemotherapy for PNET is VAC followed by ifosfamide and etoposide (IE) developed originally for treatment of Ewing's sarcoma.  In general, the 5-year survival of a patient with PNET is 58-61% with a median survival of 120 months.  Local or distant metastasis at the time of diagnosis is associated with poor outcomes.  Our patient responded well to surgery and chemotherapy, was asymptomatic and doing well 9 months after the initial diagnosis. However, presence of lymphovascular and muscular invasion makes long-term prognosis guarded necessitating keen watchout for disease recurrence during further follow-up.
To conclude, pPNET of adrenals is an extremely rare tumor with a handful of reported cases in the literature. This is the first report of adrenal pPNET from India. This report intends to highlight that PNET should be suspected whenever a patient presents with huge nonfunctional adrenal mass and may often be confused with adrenocortical carcinoma. Early diagnosis is important to ensure timely surgical resection followed by appropriate chemotherapy and/or radiotherapy.
| > References|| |
|1.||Demir A, Gunluoglu MZ, Dagoglu N, Turna A, Dizdar Y, Kaynak K, et al. Surgical treatment and prognosis of primitive neuroectodermal tumors of the thorax. J Thorac Oncol 2009;4:185-92. |
|2.||Movahedi-Lankarani S, Hruban RH, Westra WH, Klimstra DS. Primitive neuroectodermal tumors of the pancreas: A report of seven cases of a rare neoplasm. Am J Surg Pathol 2002;26:1040-7 |
|3.||Karnes RJ, Gettman MT, Anderson PM, Lager DJ, Blute ML. Primitive neuroectodermal tumor (extraskeletal Ewing′s sarcoma) of the kidney with vena caval tumor thrombus. J Urol 2000;164:772. |
|4.||Marley DF, Liapis H, Humphrey DA, Nadler RB, Siegel CL, Zhu X, et al. Primitive neuroectodermal tumor of the kidney: Another enigma: A pathologic, immunohistochemical, and molecular diagnostic study. Am J Surg Pathol 1997;21:354-9. |
|5.||Sheaff M, McManus A, Scheimberg I, Paris A, Shipley J, Baithun S. Primitive neuroectodermal tumor of the kidney confirmed by fluorescence in situ hybridization. Am J Surg Pathol 1997;21:461-8. |
|6.||Mani S, Dutta D, De BK. Primitive neuroectodermal tumor of the liver: A case report. Jpn J Clin Oncol 2010;40:258-62. |
|7.||Zhang Y, Li H. Primitive neuroectodermal tumors of adrenal gland. Jpn J Clin Oncol 2010;40:800-4. |
|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 2011;57:691-2. |
|9.||Komatsu S, Watanabe R, Naito M, Mizusawa T, Obara K, Nishiyama T, et al. Primitive neuroectodermal tumor of the adrenal gland. Int J Urol 2006;13:606-7. |
|10.||Mohsin R, Hashmi A, Mubarak M, Sultan G, Shehzad A, Qayum A, et al. Primitive neuroectodermal tumor/Ewing′s sarcoma in adult uro-oncology: A case series from a developing country. Urol Ann 2011;3:103-7. |
|11.||Khong PL, Chan GC, Shek TW, Tam PK, Chan FL. Imaging of peripheral PNET: Common and uncommon locations. Clin Radiol 2002;57:272-7. |
|12.||Ambros IM, Ambros PF, Strehl S, Kovar H, Gadner H, Salzer-Kuntschik M. MIC2 is a specific marker for Ewing′s sarcoma and peripheral primitive neuroectodermal tumors. Cancer 1991;67:1886-93. |
|13.||Smorenburg CH, van Groeningen CJ, Meijer OW, Visser M, Boven E. Ewing′s sarcoma and primitive neuroectodermal tumour in adults: Single-centre experience in The Netherlands. Neth J Med 2007;65:132-6. |
|14.||Eralp Y, Bavbek S, Basaran M, Kaytan E, Yaman F, Bilgic B, et al. Prognostic factors and survival in late adolescent and adult patients with small round cell tumors. Am J Clin Oncol 2002;25:418-24. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]