Liver & intrahepatic bile ducts
Other malignancies
Calcifying nested stromal epithelial tumor
Editorial Board Member: Raul S. Gonzalez, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 11 June 2019
Minor changes: 6 May 2021
Copyright: 2019-2021, 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 | 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, Zhang X. Calcifying nested stromal epithelial tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livertumorCNSET.html. Accessed May 16th, 2021.
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 variable calcifications
- 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
- ICD-10: D37.6 - neoplasm of uncertain behavior of liver, gallbladder and bile ducts
Epidemiology
- Age: 2 to 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)
Pathophysiology
- Histogenesis uncertain
- Several postulations have been raised for 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, though about 12% of cases recur
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 if not completely excised
- Large size, infiltrative growth, vascular invasion, necrosis and increased mitotic activity are risk factors associated with recurrence (Am J Surg Pathol 2009;33:976)
Case reports
- 2.5 year old girl (Pediatr Dev Pathol 2009;12:233)
- 14 year old girl with Beckwith-Wiedemann syndrome (Eur J Med Genet 2017;60:136)
- 16 year old boy with Cushing syndrome (J Med Case Rep 2016;10:160)
- 20 year old man with Klinefelter syndrome (World J Surg Oncol 2018;16:227)
- 23 year old woman (World J Hepatol 2014;6:155)
- 34 year old woman (Int J Surg Pathol 2011;19:268)
Treatment
- Wedge resections for smaller tumors and partial hepatectomy or liver transplant for larger tumors (Pediatr Transplant 2017;21)
- 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 12.6 cm (range 2.1 to 30 cm) well demarcated and lobulated mass with variable calcifications
- Homogenous, tan, granular appearing texture
- May have cystic changes
- May display irregular borders
Gross images
Contributed by Rong Xia, M.D., Ph. D.
Large well demarcated mass
Microscopic (histologic) description
- Well defined nests of relatively bland appearing cells surrounded by a 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 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, myxoid change and necrosis may be present
- In most cases, mitotic activity is < 1 per 10 high power fields (HPFs); increased mitotic activity with up to 5 to 7 mitoses per 10 HPFs has been reported (Int J Surg Pathol 2011;19:268)
- 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) (Int J Surg Pathol 2011;19:268)
Microscopic (histologic) images
Contributed by Rong Xia, 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 show bland round nuclei 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 dotlike 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, HepPar1, polyclonal CEA (canalicular pattern), AFP, HMB45, inhibin A, estrogen receptor 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 of the beta catenin gene (155 and 228 base pairs) (Hum Pathol 2012;43:1815)
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 dotlike paranuclear); whereas negative for HepPar1, CK20, synaptophysin and HMB45. 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 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 this liver tumor?
- Most commonly seen in adults with a male predominance
- Grossly characterized by large, poorly defined or infiltrative masses, with variable calcifications
- Histologically characterized by nests of spindled and epithelioid cells surrounded by a desmoplastic stroma with occasional psammomatous calcification and ossification
- Often shows vascular invasion with high tumoral recurrence rate
- Positive for AE1/AE3, vimentin, HepPar1 and AFP
Board review style answer #1
C. This tumor is histopathologically characterized by nests of spindled and epithelioid cells surrounded by a desmoplastic stroma with occasional psammomatous calcification and ossification
Comment Here
Reference: Calcifying nested stromal epithelial tumor (CNSET)
Comment Here
Reference: Calcifying nested stromal epithelial tumor (CNSET)
Board review style question #2
- Which of the following is true about calcifying nested stromal epithelial tumor of the liver?
- Most commonly seen in adults with a male predominance
- May be associated with cortisol related syndrome or Beckwith-Wiedemann syndrome
- Liver function tests (aspartate aminotransferase and alanine aminotransferase) and serum tumor markers (α-fetoprotein (AFP) and carcinoembryonic antigen) are typically abnormal
- Regarded as 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
Comment Here
Reference: Calcifying nested stromal epithelial tumor (CNSET)
Comment Here
Reference: Calcifying nested stromal epithelial tumor (CNSET)
