Mesenchymal tumors unique to the liver

2024-09-10   Paola Dal Cin, PhD , Rita Alaggio, MD 

1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2.IRCCS Ospedale Bambino Gesu', Roma (Italy)

Keywords
mesenchymal hamartoma, C19MC, MALAT1,embryonal sarcoma ,hemangioma, WWTR1::CAMTA1,YAP1::TFE3

Classification

Definition

Primary mesenchymal neoplasms that are specific to the liver are uncommon and include mesenchymal hamartoma (MA) of the liver, (undifferentiated) embryonal sarcoma of the liver and calcifying nested stromal-epithelial tumor. 1,2  Both mesenchymal hamartoma and embryonal sarcoma of the liver are related tumor types since  both harbor 19q microRNA cluster (C19MC) rearrangements at 19q13.4, mainly involving MALAT1 by t(11;19)(q13;q13.4). MA may rarely undergo malignant transformation into undifferentiated embryonal sarcoma by acquiring additional mutations/loss including on TP53. 3
Hemangiomas (infantile and congenital) are the most common vascular tumors of the liver. Rare cases of hepatic hemangiomas with malignant evolution have been reported. 4,5
While WWTR1::CAMTA1 and YAP1::TFE3 fusions have been associated with epithelioid hemangioendothelioma, there are currently no known signature genetic alterations seen in pediatric hepatic angiosarcoma. 6

Pediatric digestive system tumors
Pediatric mesenchymal tumors unique to the liverGenetic marker(s)
Hepatic mesenchymal hamartoma (HMH) It is lesion predominantly seen in the first 2 years of life. Sporadic HMH lesions are frequently associated with a chromosomal 19q13.4 rearrangements which results in activation of chromosome 19q microRNA cluster (C19MC), mainly by rearrangement with MALAT1 at 11q13, by t(11;19)(q13;q13.4) . 7 While in placental mesenchymal dysplasia and Beckwith-Wiedemann syndrome, androgenetic-biparental mosaicism (ABM) activate 19 microRNA cluster (C19MC) by paternal uniparental disomy . 3
Calcifying nested stromal-epithelial tumor CNSETCo-occurence of CTNNB1 alterations, including exon 3 deletions and acyivating points mutations, and TERT promotor mutations were detected, suggesting that CNSET might perhaps be more aggressive than previously reported. 8 An association between CNSET and Beckwith–Wiedemann syndrome has been also reported.9
Hepatic embryonal sarcoma (HES) It is malignant lesion, usually identified in patients between 6 and 10 years of age. Comparative genomic hybridization (CGH) studies reveales copy number alterations include gains of 1q, 5p, 6q region and losses 14q, 9p and 11p regions. However, rearrangements of 19q13.4)(C19MC) and 11q13 MALAT1 seen mesenchymal hamartoma(HMH) are also observed in the malignant (or more undifferentiated) areas of embryonal sarcoma,combined with TP53 mutation or loss, suggesting that some cases of HMH may indeed undergo malignant transformation into HES. 3,10
Hepatic congenital hemangioma (HCH) Recurrent mutations GNA11, GNAQ and/or PIK3CA were detected. 11,12
Hepatic infantile hemangioma (HIH) The pathogenesis of IHH is not fully understood, but a possible role of GLUT1, marker that distinguishes IHH from congenital hepatic hemangioma, which is GLUT1 negative. 13
Hepatic angiosarcomaThere are currently no known signature genetic alterations seen in pediatric hepatic angiosarcoma. 6
Hepatic malignant vascular tumors Pediatric hepatic epithelioid hemangioendothelioma shows a female predominance .14 Rare reports , so far, with WWTR1::CAMTA1 and YAP1::TFE3 fusions 6,14

Article Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
1375368922023Mesenchymal Neoplasms of the Liver.Papke DJ Jr et al
2380667662023Update on the Pathology of Pediatric Liver Tumors: A Pictorial Review.Bhagat P et al
3326475642020Hepatic mesenchymal hamartoma and undifferentiated embryonal sarcoma of the liver: a pathologic review.Martins-Filho SN et al
4218329532011Widening spectrum of liver angiosarcoma in children.Ackermann O et al
5285210772017Clinical case series of pediatric hepatic angiosarcoma.Grassia KL et al
6338892742021Primary malignant vascular tumors of the liver in children: Angiosarcoma and epithelioid hemangioendothelioma.Bannoura S et al
7241207022013Characterization of translocations in mesenchymal hamartoma and undifferentiated embryonal sarcoma of the liver.Mathews J et al
8339945392021Calcifying nested stromal-epithelial tumor: a clinicopathologic and molecular genetic study of eight cases highlighting metastatic potential and recurrent CTNNB1 and TERT promoter alterations.Papke DJ Jr et al
9279650012017Calcifying nested stromal-epithelial tumor (CNSET) of the liver in Beckwith-Wiedemann syndrome.Khoshnam N et al
10323109402020The genomic landscape of undifferentiated embryonal sarcoma of the liver is typified by C19MC structural rearrangement and overexpression combined with TP53 mutation or loss.Setty BA et al
11272590572016Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma.Ayturk UM et al
12321152272020Congenital hepatic hemangiomas: Clinical, histologic, and genetic correlation.Triana P et al
13317583132020Infantile hepatic hemangioma: current state of the art, controversies, and perspectives.Zavras N et al
14285985852017Epithelioid hemangioendotheliomas of the liver and lung in children and adolescents.Hettmer S et al

Citation

Paola Dal Cin, PhD ; Rita Alaggio, MD

Mesenchymal tumors unique to the liver

Atlas Genet Cytogenet Oncol Haematol. 2024-09-10

Online version: http://atlasgeneticsoncology.org/solid-tumor/209262/mesenchymal-tumors-unique-to-the-liver