Desmoplastic Nested Spindle Cell Tumor of Liver: Report of Four Cases of a Proposed New Entity Hill,D Ashley MD; Swanson, Paul E MD; Anderson, Keith MD; Covinsky, Michael H MD, Phd; Finn, Laura S MD; Ruchelli, Eduardo D MD; Nascimento, Antonio G MD; Langer, Jacob C MD; Minkes, Robert K MD; McAlister, William MD; Dehner, Louis P MD ~AJSP 2005 January

Background • Pediatric hepatic tumor: a unique age specific neoplasm • Hepatoblastoma, infantile hemangioendothelioma, undifferentiated embryonal sarcoma, • Nosologically unique enitity

Material and method • Washington University’s Institutional Review Board • IHC: 0-+++ • EM • Cytogenetic and molecular analysis: fresh tissue of case-1 and paraffin-embedded tissue of case-2

Age/sex S/s CT other A-FP Case-1 Case-2 Case-3 Case-4 6/F Intermittent, self-limited epigastric pain Well-defined, densely calcified tumor in the right lobe No contrast enhancement 2.9 ng/mL 6/F RUQ pain Well-defined lobulated mass in right lobe, not calcified or enhancement Mass in right lobe with focal calcification Peripheral enhancement, necrosis 3.9 ng/mL 2/M RUQ mass LUQ mass Lung benign nodule normal 14/F Mass in left lobe Past hx: calcified mass in left lobe D/D Teratoma, granuloma, cacified hemagnioma hepatoblastom a hepatoblastoma hepatoblastoma

Case-1 Case-2 Case-3 Case-4 Operation method Wedge resection lymph node sampling Adjuvant theraphy F/u Dx free 4 years resection Dx free 8 months Partial hepatectomy C/T Dx fee 7 years Gross Tumor size (cm) Left lobectomy C/T Dx free 7.5 years Soft, myxoid, gray tumor with fine granular calcification 2.8 x 1.5 x 1.5

Homogenenous firm and white 7.5 x 6.3 x 4.0

Dense white-tan with multiple small spicules of calcification 5.5 x 5.0 x 4.0

Multilobulated tan-white, focal myxoid area 15 x 13 x 8.5

Light Microscopy • Well demarcated nests with ovoid, plump to fusiform spindle cells • With or without intermixed rounded epithelioid cells • Invested by prominent desmoplastic stroma • Well-defined membrane, chromatin fine • Necrosis and cystic degeneration focally • Psammomatous calcification, ossification

Light microscopy • Desmoplastic stroma: variable celluar, with morphologic feature of myofibroblasts • Surrounding liver parenchyma: unremarkable, no ductal plate abnormality

Cytogenetics and Molecular Anaylsis • Normal karyotype, 46xx in case-1 • RT-PCR for

SYT-SSX

and

EWS-WT1

were negative in case-1 and case-2

Nested Stromal Epithelial Tumor of the Liver: Six Cases of a Distinctive Pediatric Neoplasm With Frequent Calcification and Association With Cushing Syndrome Heerema-McKenney, Amy MD; Leuschner, Ivo MD; Smith, Nicholas FRCPath; Sennesh, Joel MD; Finegold, Milton J MD ~AJSP 2005 January

• Nonhepatocytic, nonbiliary liver tumor with nests of epithelial and spindle cells, myofibroblastic stroma, variable calcification and ossification • Ishak et al: ossifying stromal-epithelial tumor • All cases were received by one of the author

Result • Gross: confined to the liver, not encapsulated • Irregular, multinodular borders • Homogeneous, tan, granular-appearing cut surface • Focal softening or cyst formation • Ranged 4-30 cm greatest diameter

Discussion identical hepatic tumor, resembled several other pathological entities including some that are not native to the liver • Fletman et al: mixed cell type • Ossifying malignant mixed epithelial and stromal tumor • Ishak et al: ossifying stromal-epithelial tumors(OSET)

D/D • ? Hepatoblastoma: lack fetal or embrynoic hepatoid component, OCH1E5(-) • ? Synovial sarcoma, thyroid medullary ca, meta spindle cell carcinoid, SETTLE, spindle neuroendocrine carcinoma

Discussion • ? SETTLE • ? DSRCT: no malignant round cell, desmin(-), WT-1 protein N-terminal(+)

Discussion • Origin in AFIP: young adult, calcified mass since children • Our case: all in children, localized, common histological appearance, at least focal nuclear WT-1 expression was detected in the nests, no significant nuclear pleomorphism, hyperchromasia, no atypical mitosis or vascular invasion

Discussion • Ectopic ACTH is most commonly observed in neuroendocrine tumors of the lung( carcinoid, small cell carcinoma) and other site • Hepatoblastoma, cholestatic hepatic adenoma, hepatic adrenocortical tumor • Our case: 11-14 female

Discussion • The two categories of tumor may ultimately prove to be related showing a spectrum of morphologic feature • Calcification difference: maturation changes with the tumor( dystrophic calcification and ossification), decreased activity at the tumor-liver interface • Prefer descriptive name DNSTL over OSET • D/D: calcified liver mass in childhood

Discussion • Unique clinicopathologic entity • Histogenesis and pathogenesis are uncertain • Speculate arising from a primitive mesenchymal cell with the expression of WT-1 protein reflecting some mesenchymal to epithelial transition abnormlity • Slowly growing but with unknown malignant potential