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Inicio Cirugía Española (English Edition) Calcifying nested stromal-epithelial tumor: A rare hepatic neoplasm
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Vol. 99. Issue 7.
Pages 543-547 (August - September 2021)
Vol. 99. Issue 7.
Pages 543-547 (August - September 2021)
Scientific letter
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Calcifying nested stromal-epithelial tumor: A rare hepatic neoplasm
Tumor calcificante en nidos epitelial-estromal: neoplasia hepática excepcional
María Pérez Reyes
Corresponding author

Corresponding author.
, Belinda Sánchez Pérez, Francisco Javier León Díaz, Julio Santoyo Villalba, Julio Santoyo Santoyo
Hospital Regional Universitario, Málaga, Spain
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Tables (1)
Table 1. Clinical and pathlogical characterístics of 44 cases of calcifying nested stromal-epithelial tumor.
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Calcifying nested stromal-epithelial tumors (CNSET) are rare primary liver tumors1–6 that were first described by Ishak in 20011,3,4,6. Only 43 cases have been published in the literature2–9 (Table 1). These neoplasms present an apparently benign and indolent clinical course, attributable to their low malignant potential10. Surgical treatment with free margins usually provides high long-term survival rates.

Table 1.

Clinical and pathlogical characterístics of 44 cases of calcifying nested stromal-epithelial tumor.

Journal  Age  Sex  Síntoms  Surgical treatment  Chemotherapy  Follow-up 
Heywook, Cancer 2002  28  Female  Incidental  Right trisegmentectomy  No  Recurrence 72 months → RF 
Hill, Am J Surg Pathol 2005  Male  Incidental  Right partial hepatectomy  post-op CTx  Living, 84 months 
  Female  Incidental  Liver resection in right lobe  No  Living, 58 months 
  Female  Incidental  Liver resection in right lobe  No  Living, 8 months 
  14  Female  Incidental  Liver resection in right lobe  post-op CTx  Recurrence 11 years 
Herema Mc Kenney, Am J Surg Pathol 2005  Male  Incidental  Hepatic excision  No  Living, 8 months 
  Female  Incidental  Liver resection  Pre-op and post-op CTx  Living, 6 months 
  Male  Incidental  Enucleation  post-op CTx  Living, 36 months 
  11  Female  Characteristics of Cushing + abdominal mass  Left lobectomy  No  Living, 24 months 
  12  Female  Característics of Cushing + abdominal mass  Right hepatectomy  No  Living, 168 months 
  14  Female  Íleo  Liver resection  post-op CTx  Recurrence 12 months (Local) →CTx 
Brodsky, Pediatr Dev Pathol 2008  17,5  Female  Características of Cushing + abdominal pain  Left lobectomy + partia hepatectomy  No  Recurrence 12 months (local and lymph nodes) → liver trasplant 
Wirojanan, J Pediatr Hematol Oncol 2008  Female  Not determined  Liver resection  post-op CTx  Living, 84 months 
Meir, Pediatr Dev Pathol 2009  2,5  Female  Incidental  Lobectomía derecha  No  Living, 8 months 
Makhlouf, Am J Surg Pathol 2009  Female  Incidental  Right partial hepatectomy  No  Living, 6 months 
  14  Female  Incidental  Right partial hepatectomy  post-op CTx  Living, 264 months 
  15  Female  Incidental  Right partial hepatectomy  No  Living, 151 months 
  16  Male  Características Cushing  Right partial hepatectomy  No  Living, 56 months 
  18  Female  Incidental  Liver transplant  No  Éxitus 50 months→ complicaciones postoperatorias. No Recurrence 
  19  Male  Incidental  Needle biopsy (right lobe lesion)  post-op CTx (after recurrence)  Local recurrence 168 months→ RF ablation and CTx 
  32  Female  Incidental  Right partial hepatectomy  No  Living, 13 months 
  33  Female  Incidental  Right partial hepatectomy  No  Living, 14 months 
Rod, Eur J Endocrinol 2009  17  Female  Características of Cushing + abdominal mass  Left resection  No  Living, 30 months 
Grazi, Pathol Res Pract 2010  25  Female  Diarrhea + recurrent abdominal pain  Right lobectomy extended to caudate and segment IV  No  Living, 6 months 
Oviedo Ramírez, Ann Diagn Pathol 2010  33  Male  Nonsoecific abdominal pain + dyspepsia  Left lobectomy  No  Living, 15 months 
Marin, Am Surg 2010  33  Male  Epigastralgia + pirosis + regurgitación  Unknown  Unknown  Unknown 
Wang, Int J Surg Pathol 2011  34  Female  Incidental  Left lobectomy  No  Living, 42 months 
Homman, J Gastrointest Cancer 201116FemaleIncidentalLiver transplantPost-op CTxRecurrence after 28 months with lung metástases 
Éxitus, 37 months 
Assmann, Hum Pathol 2012  16  Male  Palpable abdominal mass  Liver transplant (right/left liver lobe lesion)  Pre-op CTx  Living, 24 months 
  Female  Constipation  Partial left hepatectomy  Post-op CTx  Living, 5 years 
Geramizadeh, Indian J Pathol Microbiol 2012  Male  Características of Cushing + weight gain + abdominal pain  Extended right hepatectomy  No  Éxitus, 10 days (due to postoperative complications) 
Ghodke, J Postgrad Med, 2012  Male  Abdominal pain + fever + jaundice + weight loss  Liver segmentectomy  Not determined  Living, 12 months 
Malowany, Pediatr Dev Pathol 2013  Female  Incidental  Right resection  Not determined  No Recurrence 
Procopio, World J Hepatol 2014  23  Female  Abdominal distension + dispepsia  Extended left hepatectomy  No  Living, 21 months 
Samarghandi, Clin Nucl Med 2015  11  Female  Weight gain + increased apetito + abdominal pain  Right lobe  Not determined  Not determined 
Schaffer et al.6, Clin Imaging 201614FemaleAbdominal distension + hinchazón mejillas  Liver transplant (left liver lobe lesion)Pre-op CTxLiving, 10 months
Síndrome Cushing 
Weeda et al.5, J Med Case Rep 2016  16  Male  Características Cushing + weight gain + abdominal distension  Right and left trisegmentectomy  No  Living, 13 years 
Khoshnam et al.2, Eur J Med Genet 2017  14  Female  Características Cushing+ Hinchazón y dolor abdominal  Liver transplant (Lesión lóbulo hepático derecho)  Pre-op CTx  Living, 
Tehseen et al.7, Pediatr Transplant 201713FemaleDolor abdominal + abdominal distension  Liver transplant (Lesión lóbulo hepático derecho)Pre-op CTxLiving, 28 months
Cushing syndrome 
Garg et al.8, Indian J Nucl Med 2017  Female  Pancitopenia  Liver resection; liver transplant  Post-op CTx in recurrence  2 months lymoh node and bone recurrence →CTx + Bone RT 
Meletani et al.9, World J Gastroenterol 201731MaleAbdominal pain + weight lossRight triseccionectomy + caudate resection + RF segment IIpost-op CTxLocal recurrence after 6 months + p presacral nodule → chemoembolización + 
CTx after (×4) 
Éxitus: 15 months after surgery 
Tsuruta et al.4, World J Surg Oncol 2018  20  Male  Incidental  Right hepatectomy  post-op CTx  Éxitus: 2 months due to local recurrence and metástases in extrahepátic lymph nodes→ chemoembolización and RF 
Olin et al.3, Int J Surg Case Rep 2020  15  Female  Dolor abdominal  Right trisegmentectomy  No  Living, 12 months, sin Recurrence 
Pérez, 2020  21  Female  Asintomátic  Right triseccionectomy  No  Living, 6 months, sin Recurrence 

Post-op: postoperative; Pre-op: preoerative; CTx: chemotherapy; RF: radiofrecuency.

We present a 21-year-old patient with no relevant history. Follow-up lab work showed an altered liver profile (gamma glutamyl transpeptidase [GGT] 122 IU/L). Physical examination revealed hepatomegaly. Abdominal ultrasound identified a hyper-isoechoic focal lesion, apparently calcified, with a lobulated shape and limited vascularization. Magnetic resonance imaging (MRI) and computed tomography (CT) scan (Fig. 1A–B) showed a large, irregular, heterogeneous mass with multiple calcifications, with irregular enhancement in the arterial phase and washout in the portal phase. The initial diagnosis was fibrolamellar hepatocellular carcinoma (FHCC) in segments IV, V, VI, VII and VIII. Tumor marker levels (Alpha-fetoprotein, carcinoembryonic antigen and CA 19.9) were normal. Total liver volume was 1172.83 cc. The calculated residual volume percentages were: 42.2% for segments II-III (495.59 cc) and 48% for segments I-II-III (562 cc). Due to the suspicion of FHCC, surgery was indicated, and we performed right trisectionectomy by laparotomy as well as lymphadenectomy of the hepatic hilum and celiac trunk. The postoperative period transpired without incident, and the patient was discharged on the 7th postoperative day.

Fig. 1.

A) MRI of the liver: large, heterogeneous, polylobulated mass measuring 11.5 × 10 × 19 cm in segments IV, V, VI, VII and VIII with hypervascular uptake, with no clear washout in the portal and late phases, maintaining foci with no uptake at the central level, which coincided with the calcification on the CT scan; diffusion was slightly restricted; characteristics were compatible with fibrolamellar carcinoma; B) abdominal computed tomography: a large heterogeneous hepatic mass with irregular contour and heterogeneous density occupied segments IV, V, VI, VII and VIII, with multiple calcifications; irregular enhancement in arterial phase, and contrast washout in portal phase; C) macroscopic image: hepatectomy specimen measuring 24 × 17 × 19 cm and weighing 1500 g. It is almost entirely occupied by a 21 × 13 × 8 cm nodular whitish tumor that is in contact with the hepatic capsule and is away from the parenchymal resection margin; D) microscopic image with hematoxylin-eosin (10× magnification): proliferation of epithelioid and spindle-shaped cells with formation of osteoid; nests are observed with a central epithelial appearance, surrounded by spindle-shaped cells; calcified area.


The pathological study reported a whitish nodular tumor measuring 21 × 13 × 8 cm with multiple calcifications, areas of ossification and lymphadenopathies without neoplasm. Immunohistochemistry showed the cells were positive for Vimentin, Actin, WT-1, CD56, CD99, CD117 with Ki67:1% (Fig. 1C–D). These results were compatible with CNSET with free surgical margin, no perineural invasion or lymphovascular permeation.

The case was presented to the Oncology Committee, who decided to monitor the patient in an outpatient clinic without adjuvant chemotherapy because there is no clear benefit to justify adjuvant therapy. Six months after surgery, the patient remains asymptomatic and disease free. Follow-up studies included laboratory testing with liver panel and CT scan.

CNSET have been described in the literature with various terminologies: ossifying malignant mixed epithelial and stromal tumor, ossifying stromal epithelial tumor, and desmoplastic nested spindle-cell tumor of the liver1. It was Markhouf who proposed the term CNSET because it incorporates all the characteristics of the tumor.

Despite their exceptional nature, we know that they present more frequently in young (≤20 years) or pediatric patients (77%) and females (70%) (Table 1). They are usually located in the right hepatic lobe (64%), and in 40% of cases their diagnosis is incidental (Table 1). The association of CNSET with hormonal alterations is notable (36%): Cushing syndrome or cushingoid symptoms (25%)5,7, Klinefelter syndrome4 and oral contraceptives. Some authors have tried to link the development of these tumors with hormonal alterations, but this has not been proven. In four patients, it was associated with Beckwith-Wiedemann syndrome (overgrowth syndrome with increased risk of developing cancer)2,8. Our case did not present an association with these pathologies.

In terms of diagnosis, the lab analysis highlights normal liver function as well as the usual tumor markers1,3, although elevated GGT has been described in some cases5, including ours. On CT and MRI, it is characteristic to observe a large, well circumscribed, heterogeneous mass with dense calcification and macrolobulated margin1,3,4,6. The most common radiological differential diagnosis is hepatoblastoma, followed by FHCC. Confirmation of the diagnosis by preoperative biopsy has been described3. Geramizadeh published low profitability in a cohort of 12 patients with CNSET, where the diagnosis was reached in only three cases (25%). At our hospital, the use of liver biopsy is unusual and only reserved for uncertain diagnoses.

The standard treatment of CNSET is surgical resection, obtaining free margins1,3–5. The technique used has varied from partial resections to liver transplantation, which occurred in eight cases, depending on the extension and location of the tumor (Table 1).

Chemotherapy (CTx) was used in 38% of the cases of the series analyzed. Five cases received preoperative CTx, showing no effects of reduction or necrosis in the imaging tests or in the surgical specimens. Twelve patients received postoperative CTx, 50% as treatment for postoperative recurrence (Table 1). The regimens administered were similar to those for sarcoma or hepatoblastoma4–6. Today, its role in the prevention or treatment of recurrence is unclear1,4,5. Three were treated with radiofrequency (RF)4, and only Makhlouf describes a successful result with this therapy.

80% (35/44) of the patients did not experience disease recurrence. This occurred in nine patients with an interval from two months to 11 years4,8,9. Most recurrences were local, but they were found in several locations: lymph nodes, lungs or bone (Table 1). The follow-up described in the literature varies from two months to 22 years. In total, 7% of patients died from the disease, and 14% are living with recurrence (Table 1).

The prognosis is uncertain, but growth is usually slow, with low malignant potential1,4,5. Most cases have long-term survival after resection4 and often remain recurrence-free if the resection margins are negative3. A close and sustained follow-up is necessary, with lab work and imaging studies due to the risk of long-term recurrence2–5.

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Calcifying nested stromal-epithelial tumor of the liver. An uptodate and literature review.
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N. Khoshnam, H. Robinson, M.R. Clay, L.R. Schaffer, S.E. Gillespie, B.M. Shehata.
Calcifying nested stromal-epithelial tumor (CNSET) of the liver in Beckwith-Wiedemann syndrome.
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Please cite this article as: Pérez Reyes M, Sánchez Pérez B, León Díaz FJ, Santoyo Villalba J, Santoyo Santoyo J. Tumor calcificante en nidos epitelial-estromal: neoplasia hepática excepcional. Cir Esp. 2021;99:543–547.

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