Liver & intrahepatic bile ducts

Other malignancies

Calcifying nested stromal epithelial tumor

Authors: Rong Xia, M.D., Ph.D., Xuchen Zhang, M.D., Ph.D.

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

Page views in 2020: 1,320

Page views in 2021 to date: 2,703

Table of Contents

Cite this page: Xia R, Zhang X. Calcifying nested stromal epithelial tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livertumorCNSET.html. Accessed November 29th, 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:
- Presence of fetal or embryonal hepatocytes and the positivity of IHC for AFP or HepPar1
- Extramedullary hematopoiesis is common in fetal and embryonal subtypes
Desmoplastic small round cell tumor:
- Typically both positive for WT1 stain and t(11;22) WT1-EWS translocation
Metastatic gastrointestinal stromal tumor:
- Perinuclear vacuolization and often distinct nuclear palisading without desmoplastic stroma
- CD34, CD117 and DOG1 are positive

Board review style question #1

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)

Board review style question #2

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)