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Year : 2012  |  Volume : 55  |  Issue : 2  |  Page : 253-255
Nested stromal epithelial tumor of liver presenting with Cushing syndrome: A Rare case Report

1 Department of Pathology; Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Pediatric Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of Pediatric Oncology, Shiraz University of Medical Sciences, Shiraz, Iran

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Date of Web Publication3-Jul-2012


Nested stromal and epithelial tumor of the liver is an extremely rare pediatric hepatic tumor. To the best of our knowledge, about 25 cases have been reported in the English literature so far, few of which accompanied with Cushing syndrome. Herein we report our experience with an 8-year-old boy presented with Cushing's syndrome because of ectopic ACTH production by this tumor.

Keywords: Cushing syndrome, liver, nested stromal epithelial tumor

How to cite this article:
Geramizadeh B, Foroutan H, Foroutan A, Bordbar M. Nested stromal epithelial tumor of liver presenting with Cushing syndrome: A Rare case Report. Indian J Pathol Microbiol 2012;55:253-5

How to cite this URL:
Geramizadeh B, Foroutan H, Foroutan A, Bordbar M. Nested stromal epithelial tumor of liver presenting with Cushing syndrome: A Rare case Report. Indian J Pathol Microbiol [serial online] 2012 [cited 2022 Jul 1];55:253-5. Available from: https://www.ijpmonline.org/text.asp?2012/55/2/253/97898

   Introduction Top

Nested stromal epithelial tumor (NSET) of liver is a recently described, extremely rare hepatic tumor occurring most commonly in the pediatric age group. [1],[2] Ishak et al. [3] have first described this tumor in 2001, and since then only 25 cases has been described in the English literature, a few of which presented with Cushing syndrome. Herein we report our experience with an 8-year-old boy presented with Cushing syndrome and high adrenocorticotrophic hormone (ACTH), who was found to have a large hepatic tumor diagnosed as NSET of liver after surgery and resection of the tumor.

   Case Report Top

An 8-year-old boy presented with weight gain, increased appetite and bilateral flank pain since 3 months prior to admission. Physical examination showed high blood pressure (140/80 mm of Hg), moon face, central obesity, extremity edema, buffalo hump, and purple striae as well as hepatomegaly.

Laboratory analysis showed metabolic alkalosis, normal renal, and thyroid function tests, but liver function tests showed high alanine aminotransferase level (ALT = 85 IU/L, normal <40). Random blood sugar was 256 mg/dl. At 8:00 AM Serum cortisol = 1750 nmol/L (normal = 138-635) and ACTH = 208 Pmol/L (normal = 4.4-22). Urine cortisol in 24 h was 1101 nmol (normal = 5-75). The standard high dose dexamethasone suppression test revealed a partial decrease in 24-h urine-free cortisol (876 nmol).

Imaging studies showed a large heterogeneous mass (10 ΄ 9 cm) in the right lobe of the liver by spiral CT scan [Figure 1]. Both the adrenal glands were unremarkable except for mild bilateral hyperplasia. There was no evidence of any other mass in the abdomen. Magnetic resonance imaging (MRI) of brain and pituitary gland was normal. There was no mass in the computed tomography (CT) scan of the thorax. Serum alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) were in normal range. Tru-cut biopsy of the liver mass showed nests of epithelial cell separated by spindle cell stroma. Because of the reactivity of the epithelial nests with neuroendocrine markers, it was reported as neuroendocrine tumor and complete excision was suggested for definite diagnosis. Decision was made to excise the tumor, so the patient scheduled for tumor resection. During surgery, the peritoneal cavity was entered by right subcostal incision extending to the subxyphoid area. Right extended hepatectomy was performed after evaluation of the whole peritoneum and intra-abdominal organs for the possibility of any primary source of metastasis to the liver.
Figure 1: CT scan of the abdomen shows a large liver mass (10.6 ΄ 9.3 cm) in right lobe of liver

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The liver specimen was sent to the department of pathology. It showed a huge liver mass measuring 10 ΄ 9 ΄ 8 cm [Figure 2] with well-defined but irregular border and no capsule. Cut section was multilobated and whitish creamy. There was no necrosis or calcification. Surgical margins were free.

Microscopic examination of the liver mass showed nests of epithelioid and spindle bland looking cells with oval-shaped nuclei [Figure 3]a-c which were surrounded by a delicate myofibrolastic collar. Mitotic numbers were low (<2/10 HPF). There was no calcification or osteoid formation despite of thorough sectioning. The NSET stroma was variably cellular, i.e. in some areas the stromal cells were similar to myofibroblasts, and in some areas the stroma was paucicellular containing occasional blood vessels and bile ducts.
Figure 2: Section from the resected liver tumor shows a large well-defined and nonencapsulated tumor with a small rim of normal liver around it

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Figure 3: (a) Microscopic section of the liver tumor show nests of epithelial cell which are separated by fibrous stroma (Hematoxylin and eosin, ×100). (b) High power view of the same section shows bland looking cells with low mitosis. (Hematoxylin and eosin, ×250). (c) Details of tumor cells show nests of bland looking epithelial cells (Hematoxylin and eosin, ×400)

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Immunohistochemistry showed: positive cytokeratin, vimentin, CD 56, and neuron specific enolase (NSE), but negative chromogranin, CD99, HepPar1, desmin, WT1, estrogen receptor (ER) and progestron receptor (PR) [Figure 4]a and b ACTH was focally positive.
Figure 4: Immunohistochemistry of the tumor shows reactive cytokeratin (a) and CD56 (b)

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The diagnosis of nested stromal epithelial tumor was made. After excision, the ACTH and cortisol began to gradually decrease (ACTH from 100-120 Pmol/L and cortisol 850-1000 nmol/L), but the patient developed low grade fever and left subcostal pain. Blood culture turned positive for  Staphylococcus epidermidis Scientific Name Search pulmonary secretion for Acinetobacter. Despite of antibiotic therapy his condition deteriorated with decreased level of consciousness. Unfortunately 10 days after surgery, he expired with the clinical picture of sepsis.

   Discussion Top

Nested stromal epithelial tumor (NSET) of liver was first described in 2001 by Ishak et al. [4] as ossifying stromal epithelial tumor.

After that about 24 other cases have been reported under different names of "desmoplastic nested spindle cell tumor of liver" "desmoplastic nested spindle cell tumor of liver," and "calcifying nested stroma-epithelial tumor of the liver". [3],[4],[5] This tumor is an extremely rare hepatic tumor with unique clinicopathologic features. [6]

Most of the reported cases have been in children between 2 and 17 years of age but there are also rare reports in adults. [3],[5] This tumor is more common in girls and until now less than five cases have been reported in boys. [5],[7]

Most of the previously reported patients presented with different clinical pictures such as abdominal pain, dyspepsia, and intestinal obstruction. [4],[5] However, some of these tumors can produce ACTH and the patient presents with Cushing syndrome. [4],[5],[6],[8]

Our patient was an 8-year-old boy presented with Cushing syndrome. During investigation for finding the cause of this syndrome, high ACTH was detected with normal brain MRI and no evidence of pituitary tumor. Abdominal CT scan showed normal adrenal glands and a large heterogeneous mass in the liver. After surgery and excision of the mass was diagnosed as nested stromal and epithelial tumor of the liver and the level of ACTH and cortisol significantly decreased. The previous cases had variable size from 2.5 to 30 cm. [4],[5]

This tumor has characteristic pathologic features with typical mixture of spindle and epithelioid tumor cells arranged in a nesting pattern. [6]

Some of the cases showed calcification and ossification. [3],[6],[8]

The most consistent positive immunohistochemical markers in the previously reported cases have been cytokeratin, vimentin, SMA (in the stroma), c-kit, CD 56, NSE, and WT-1. All the previous cases have been negative with HepPar-1, AEP, CK7, CK20, desmin, chromogranin, synaptophysin, and CD99. [4],[6]

The histologic picture of this tumor is somehow reminiscent of desmoplastic small round cell tumor (DSRCT), which is most common in adolescent males and shows highly aggressive behavior and is also reactive with CD99. [6] Other histologic differential diagnoses are synovial sarcoma, metastatic Wilms tumor, and mixed epithelial and stromal hepatoblastoma which can be excluded by Immunohistochemical studies. [6]

The histogenesis of NSET of the liver is uncertain, but the possible origin is hepatic mesenchymal precursor cells. [4]

This tumor is extremely rare and newly described, so it is very difficult to accurately predict its outcome, but according to previous experiences, it seems that it is a low grade malignant tumor with indolent course. [8] However, there have been tumors with local recurrences and lymph node metastasis and a report of extrahepatic lung metastasis. [2],[5],[9]

There is no consensus about the treatment protocol, but in most of the previous cases complete excision has been curative, but for unresectable ones there are reports of preoperative chemotherapy with different regimens for hepatoblastoma with no necrosis and soft tissue sarcoma, with mild tumor shrinkage. [1],[4] There is also report of liver transplantation for a non-resectable tumor, which one of them finally developed pulmonary metastasis and died after 37 months. [2],[9] The clinicopathologic and immunohistochemical features of NSET of the liver suggest treatment for neuroendocrine tumors. [6] Unfortunately we lost our patient after a successful surgery because of infection and sepsis, but our experience with this case shows that in a child presenting with liver mass specially accompanied with Cushing syndrome and high ACTH and also no other primary tumor source, NSET should be considered as an important differential diagnosis.

   References Top

1.Grazi GL, Vetrone G, d'Errico A, Caprara G, Ercolani G, Cescon M, et al. Nested stromal-epitelial tumor(NSET) of the liver: A case report of an extremely rare tumor. Pathol Res Pract 2010;206:282-6.  Back to cited text no. 1
2.Hommann M, Kaemmerer D, Daffner W, Prasad V, Baum RP, Petrovitch A, et al. Nested stromal epithelial tumor of the liver-liver transplantation and follow up. J Gastrointest Cancer 2011;42:292-5.  Back to cited text no. 2
3.Wang Y, Zhou J, Huang WB, Rao Q, HH M, Zhou XJ. Calcifying nested stroma-epithelial tumor of the liver: A case report and review of literature. Int J Surg Pathol 2011;19:268-72.  Back to cited text no. 3
4.Heerema-McKenney A, Leuschner I, Smith N, Sennesh J, Finegold MJ. Nested stromal stromal epithelial tumor of the liver. Six cases of a distinctive pediatric neoplasm with frequent calcifications and association with Cushing syndrome. Am J Surg Pathol 2005;29:10-20.  Back to cited text no. 4
5.Ramirez MI, Bernal AB, Ruiz EO, Bermejo J, Alava ED, Hernandez T. Desmoplastic nested spindle cell tumor of the liver in an adult. Ann Diagn Pathol 2010;14:44-9.  Back to cited text no. 5
6.Makhlouf HR, Abdul-Al HM, Wang G, Goodman ZD. Calcifying nested stromal epithelial tumors of the liver. A clinicopathologic, immunohistochemical, and molecular genetic study of 9 cases with a long term follow up. Am J Surg Pathol 2009;33:976-83.  Back to cited text no. 6
7.Rod A, Voicu M, Chiche L, Bazille C, Mittre H, Louiset E, et al. Cushing's syndrome associated with a nested stromal epithelial tumor of the liver: Hormonal, immunohistochemical, and molecular studies. Eur J Endocrinol 2009;16:805-10.  Back to cited text no. 7
8.More J, Young J, Reznik Y, Raverot G, Borson-Chazot F, Rohmer V, et al. Ectopic ACTH syndrome in children and adolescents. J Clin Endocrinol Metab 2011;96:1213-22.  Back to cited text no. 8
9.Brodsky SV, Sandoval C, Sharma N, Yusuf Y, Facciuto ME, Humphrey M, et al. Recurrent nested stromal epithelial tum,or of the liver with extrahepatic metastasis: Case report and review of literature. Pediatr Dev Pathol 2008;11:469-73.  Back to cited text no. 9

Correspondence Address:
Bita Geramizadeh
Department of Pathology, Shiraz University of Medical Sciences, Shiraz, , 71345-1864
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.97898

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