Liver & intrahepatic bile ducts
Other malignancies
Calcifying nested stromal epithelial tumor
Editorial Board Members: Raul S. Gonzalez, M.D., Monika Vyas, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 20 February 2023
Last staff update: 20 February 2023
Copyright: 2019-2023, PathologyOutlines.com, Inc.
PubMed Search: Calcifying nested stromal epithelial tumor
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Xia R, Neto AG, Zhang X. Calcifying nested stromal epithelial tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livertumorCNSET.html. Accessed June 2nd, 2023.
Definition / general
- Rare primary tumor of the liver
- Nonhepatocytic and nonbiliary origin (Arch Pathol Lab Med 2019;143:264)
- Nests of epithelioid and spindle cells with an associated desmoplastic, myofibroblastic stroma and variable calcification or ossification
- Can occur in children of all ages with a female predominance
Essential features
- Often presents as a solitary, well demarcated and lobulated mass with a variable degree of calcification
- Characterized by a nested morphologic growth pattern composed of epithelioid and spindle cells with variable degrees of calcification or ossification
Terminology
- Calcifying nested stromal epithelial tumor (CNSET) of the liver
- Ossifying malignant mixed epithelial and stromal tumor
- Ossifying stromal epithelial tumor
- Desmoplastic nested spindle cell tumor of the liver
ICD coding
Epidemiology
- Age: 2 - 34 years (Arch Pathol Lab Med 2019;143:264)
- M:F = 1:2.5
- Association: Beckwith-Wiedemann syndrome, Cushing type syndrome, Klinefelter syndrome (World J Surg Oncol 2018;16:227, Eur J Med Genet 2017;60:136, Am J Surg Pathol 2005;29:10)
Sites
- Predilection to arise within the right lobe of the liver (Arch Pathol Lab Med 2019;143:264, Mod Pathol 2021;34:1696)
Pathophysiology
- Histogenesis is uncertain
- Several postulations have been raised regarding the origin of the tumor cells (Arch Pathol Lab Med 2019;143:264)
- Epithelial origin with differentiation toward a mesenchymal phenotype
- Mesenchymal origin with the expression of WT1, which reflects a mesenchymal to epithelial phenotype
- Impaired mesenchymal epithelial transition supported by increased expression of mesenchymal epithelial transition factors SNAIL, SLUG, TWIST, c-Met, vimentin and beta catenin
Etiology
- Unknown
- History of oral contraceptive use has been proposed (Int J Surg Pathol 2011;19:268)
Clinical features
- No specific clinical features
- Can present with abdominal pain / distention
- May be associated with Beckwith-Wiedemann syndrome, Cushing type syndrome or Klinefelter syndrome
- Symptoms typically resolve after resection of the liver tumor; however, up to 57% of cases metastasize and recur (Mod Pathol 2021;34:1696)
Diagnosis
- Nests of epithelioid and spindle cells with an associated desmoplastic myofibroblastic stroma
- Variable amount of calcification or ossification
- Expression of cytokeratin, WT1 and beta catenin
Laboratory
- Normal liver function tests and serum tumor markers (AFP and CEA)
Radiology description
- CT:
- Large, well circumscribed, macrolobulated masses, with enhancement and calcification
- Areas of calcification appear hyperdense, whereas cystic or myxoid components within the tumor appear hypodense (Clin Imaging 2016;40:137, Clin Nucl Med 2015;40:131)
- MRI:
- Predominant T1 hypointensity and T2 hyperintensity (Clin Imaging 2016;40:137, Clin Nucl Med 2015;40:131)
- Main differential diagnosis on radiology includes hepatoblastoma, fibrolamellar hepatocellular carcinoma or a calcified hemangioma
Radiology images
Images hosted on other servers:
Large liver mass
Prognostic factors
- Indolent behavior but may recur and metastasize
- Large size, infiltrative growth, vascular invasion, necrosis and increased mitotic activity are risk factors associated with recurrence or metastasis (Am J Surg Pathol 2009;33:976, Mod Pathol 2021;34:1696)
Case reports
- 2 year old girl presented with an incidentally detected calcified liver lesion on a chest radiograph (Radiol Case Rep 2021;16:2337)
- 14 year old girl with Beckwith-Wiedemann syndrome (Eur J Med Genet 2017;60:136)
- 20 year old man with Klinefelter syndrome (World J Surg Oncol 2018;16:227)
- 23 year old woman underwent liver resection for a large hepatic lesion (World J Hepatol 2014;6:155)
- 28 year old woman presented with mild abdominal pain and normal laboratory values (Front Surg 2022;9:875782)
Treatment
- Wedge resections for smaller tumors and partial hepatectomy or liver transplant for larger tumors (Pediatr Transplant 2017;21:e13000)
- Complete resection is curative in more than half of the reported cases
- Uncertain whether chemotherapy holds any benefit with the current available data
Gross description
- Solitary or multiple, mean of 12.6 cm (range 2.1 - 30 cm), well demarcated and lobulated mass with variable calcifications (Arch Pathol Lab Med 2019;143:264)
- Homogenous, tan, granular appearing texture
- May have cystic changes
- May display irregular borders or satellite tumor nodules (Arch Pathol Lab Med 2019;143:264, Mod Pathol 2021;34:1696)
Gross images
Images hosted on other servers:
Well demarcated liver mass
Microscopic (histologic) description
- Well defined nests of relatively bland appearing cells surrounded by variably cellular bands of desmoplastic stroma
- Cells are small, uniformly spindled to large eosinophilic epithelioid cells
- Spindle cells within the nests are arranged in short fascicles at the periphery of the nest, while the epithelioid cells are more apparent in the central portion of the nests
- Stroma surrounding the nests is comprised of spindled cells with long, tapered, cytoplasmic processes, tapered nuclei, bland nuclear chromatin and a small pinpoint nucleolus typical of myofibroblasts
- Foci of psammoma-like calcifications, osteoid material (ossification) and areas of cystic degeneration, necrosis and myxoid change may be present
- In most cases, mitotic activity is < 1 per 10 high power fields (HPFs); increased mitotic activity with up to 22 mitoses per 10 HPFs has been reported (Mod Pathol 2021;34:1696)
- Entrapped, normally formed, mature appearing bile ducts as well as cords of hepatocytes may be seen within the tumor
- Vascular invasion is rare (and is likely related to tumor recurrence or metastasis) (Int J Surg Pathol 2011;19:268, Mod Pathol 2021;34:1696)
Microscopic (histologic) images
Contributed by Xuchen Zhang, M.D., Ph.D.
Well demarcated border
Cell nests and stroma
Epithelioid nests with osteoid
Spindle nests with osteoid
Beta catenin
WT1
Cytology description
- Spindle cells have oval nuclei with stippled chromatin
- Epithelioid cell nuclei are bland and round with finely stippled chromatin and variably conspicuous nucleoli
Positive stains
- AE1 / AE3, vimentin, cytoplasmic and nuclear beta catenin
- Variable CK7, CK8, CK18 and CK19
- Nuclear WT1 with cases of cytoplasmic dot-like paranuclear pattern positivity
- Patchy positivity with CD117, S100, CD99, neuron specific enolase, CD57, CD56 and progesterone receptor
Negative stains
- CK20, synaptophysin, chromogranin A, desmin, CD34, arginase1, INSM1, KIT, HepPar1, polyclonal CEA (canalicular pattern), AFP, HMB45, inhibin A, estrogen receptor, albumin ISH and thyroid transcription factor
Electron microscopy description
- Abundance of rough cytoplasmic reticulum and mitochondria with no evidence of neuroendocrine differentiation (Pediatr Dev Pathol 2008;11:469)
Molecular / cytogenetics description
- Large deletions in exon 3 (155 and 228 base pairs) or other mutations of the beta catenin gene (Hum Pathol 2012;43:1815, Mod Pathol 2021;34:1696)
- TERT promoter alterations (Mod Pathol 2021;34:1696)
Sample pathology report
- Liver, segment 6, partial hepatectomy:
- Calcifying nested stromal epithelial tumor, 11.0 cm (see comment)
- Surgical margins negative for tumor
- Comment: This well demarcated and lobulated mass is present in a background liver without cirrhosis. Microscopically, the tumor is composed of epithelioid and spindle cell nests surrounded by band of desmoplastic stroma. Foci of psammoma-like calcifications and osteoid material (ossification) are present. No mitosis, necrosis or lymphovascular invasion is seen. Immunohistochemically, the tumor cells are positive for cytokeratin AE1 / AE3, vimentin, beta catenin (cytoplasmic and nuclear) and WT1 (nuclear and dot-like perinuclear), whereas negative for HepPar1, CK20, synaptophysin and HMB45. Albumin ISH is negative. The tumor morphology along with immunoprofile is consistent with calcifying nested stromal epithelial tumor. The tumor is completely excised and is 2.2 cm from the closest resection margin.
Differential diagnosis
- Synovial sarcoma:
- SYT::SSX1 and SYT::SSX2 are characteristic translocations
- Hepatoblastoma:
- Desmoplastic small round cell tumor:
- Typically is both positive for WT1 stain and t(11;22) WT1::EWS translocation
- Metastatic gastrointestinal stromal tumor:
Board review style question #1
Which of the following is true about the liver tumor shown above?
- Grossly characterized by large, poorly defined or infiltrative masses, with variable degrees of calcification
- Histopathologically characterized by nests of spindled and epithelioid cells surrounded by a desmoplastic stroma with occasional psammomatous calcification and ossification
- Most commonly seen in adults and with a male predominance
- Positive for AE1 / AE3, vimentin, HepPar1 and AFP
- The tumor is of hepatocellular origin and positive for albumin by in situ hybridization
Board review style answer #1
B. This tumor is histopathologically characterized by nests of spindled and epithelioid cells surrounded by a desmoplastic stroma with occasional psammomatous calcification and ossification
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Board review style question #2
Which of the following is true about calcifying nested stromal epithelial tumor of the liver?
- Liver function tests (aspartate aminotransferase and alanine aminotransferase) and serum tumor markers (alpha fetoprotein [AFP] and carcinoembryonic antigen) are typically abnormal
- May be associated with cortisol related syndrome or Beckwith-Wiedemann syndrome
- Most commonly seen in adults and with a male predominance
- Regarded to be of hepatocellular origin with nests of epithelioid and spindle cells and variable calcification, even ossification
- Similar to desmoplastic small round cell tumor, typically positive for WT1 and t(11;22) WT1::EWS
Board review style answer #2
B. May be associated with cortisol related syndrome or Beckwith-Wiedemann syndrome
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