TABLE 3:

Differential Diagnoses of Pancreatic Sclerosing Epithelioid Mesenchymal Neoplasm

	Sclerosing Epithelioid Mesenchymal Neoplasm	Solid Pseudopapillary Neoplasms	Sarcomatoid Carcinomas of the Pancreas	Sclerosing Epithelioid Fibrosarcomas	Myoepithelial Neoplasms of Soft Tissue	Angiomatoid Fibrous Histiocytoma	Solitary Fibrous Tumor	Perivascular Epithelioid Cell Neoplasm (PEComa)	Leiomyosarcoma	Gastrointestinal Stromal Tumor
Median Age	40s	20–30s	50–60s	50s	40s	10s-20s	50s	30s-40s	60s	60s
Gender	Female predominance	Female predominance	Female predominance	No gender predilection	No gender predilection	Slight female predominance	Female predominance	Female predominance	No gender predilection	Slight male predominance
Microscopic Features	Geographic apparence of hypo and hypercellular areas with collagenous stroma ("ropey collagen"); epithelioid to spindle cells with scant cytoplasm,round-oval nuclei and open chromatin; mild to moderate nuclear atypia	Variety of patterns (solid, pseudopapillary, cystic, trabecular, etc); small to medium-sized and polygonal to elongated cells with clear to eosinophilic cytoplasm and ovoid nuclei (often have grooves)	Sheets of spindle cells, sometimes with pleomorphic giant cells and/or heterologous elements	Hypo or hypercellular with large areas of hyalinized fibrous stroma; small to medium sized, uniform epithelioid cells with clear to scant eosinophilic cytoplasm and bland nuclei with vesicular or finely stipple chromatin	Often infiltrative with heterogenous morphology and myxoid or hyalinized stroma; epithelioid, spindled or plasmacytoid cells arranged in small nests, strands or file	Often highly cellular with sheets, short fascicles or whorls of bland spindle to ovoid eosinophilic cells	Spindle cells in a collagenous stroma ("ropey collagen") with irregularly distributed thick walled "staghorn" vessels	Nested, trabecular, or sheet-like architecture, sometime with a dense collagenous stroma; epithelioid and/or spindle cells with granular eosinophilic to clear cytoplasm	Interlacing spindle cells with varying degree of pleomorphism and atypia, necrosis; mitotic figures are common	Spindle cell, epithelioid or mixed morphology; extracellular collagen globules ("skeinoid fibres") may be seen; variable mitotic activity
Immunohistochemical Features	Vimentin, CD99 and cytokeratins (weak)	PR and abnormal B-catenin	Vimentin and cytokeratin (weak)	MUC4	S100, cytokeratins, EMA	Desmin, SMA, CD68, CD99, EMA	CD34, Bcl2, nuclear STAT6	Smooth muscle (SMA, desmin - less common) and melanocytic (HMB-45, Melan-A) markers	HHF35, SMA and desmin	CD117, DOG1, CD34
Molecular Features	No recurrent somatic mutations, amplifications or deletions in any known oncogenes or suppressor genes; distinct methylation pattern	Somatic activating mutation in exon 3 of CTNNB1	Oncogenic mutations of KRAS, and loss of function mutations and/or deletions of the tumor suppressor genes TP53, SMAD4/DPC4, CDKN2A/p16	EWSR1-CREB3L1 or FUS-CREB3L21, FUS-CREB3L2 fusions	EWSR1-PBX1, EWSR1-POU5F1, EWSR1-ZNF44, FUS-KLF17 or EWSR1-KLF17 fusions	EWSR1-CREB1, EWSR1-ATF1, or FUS-ATF1 fusions	NAB2-STAT6 fusion	TSC1/ TSC2 mutations, SFPQ-TFE3, RAD51B-OPHN1, RAD51B -BRAGB fusions	Complex genotype; TP53 mutations common	Mutually exclusive activating mutations of KIT or PDGFRA receptor tyrosine kinases