Table 4.

Differential Diagnosis of Pancreatic Poorly Differentiated Neuroendocrine Carcinoma

	Poorly Differentiated Neuroendocrine Carcinoma	Well Differentiated Neuroendocrine Tumor	Acinar Cell Carcinoma*	Primitive Neuroectodermal Tumor
Histology	• Markedly cellular • Solid and nesting growth patterns • Acinar (glandular) units or pseudorosettes may be present. • Substantial necrosis	• Less cellular • Various organoid growth patterns • Limited or no necrosis	• Markedly cellular • Solid and acinar growth patterns • Necrosis may be extensive. • Eosinophilic granular cytoplasm	• Markedly cellular • Diffuse growth pattern • Pseudorosettes may be present.
Nuclei	• Hyperchromatic nuclei and inconspicuous nucleoli (small cell) • Vesicular chromatin or prominent nucleoli (large cell)	• Monotonous, round nuclei with vesicular chromatin • Nucleoli may be seen.	• Monotonous nuclei • Solitary large nucleoli	• Small, round monotonous nuclei • Inconspicuous nucleoli
Mitoses/10 HPF**	High (by definition > 20 [1]; usually > 30)	Low to intermediate (by definition ≤ 20 [1])	Variable but usually high (> 20)	Variable but usually high (> 20)
Ki67 Labeling Index	High (by definition > 20%; usually > 40%)	High (by definition ≤ 20%)	Variable but usually high (> 20%)	Variable but usually high (> 20%)
Immunohistochemistry
Keratins	Positive	Positive	Positive	Usually positive [33]
Trypsin/Chymotrypsin	Rare, scattered cells may be positive.	Rare, scattered cells may be positive.	Positive	Negative
Chromogranin	Positive, may be weak or focal	Positive, usually strongly	Rare, scattered cells may be positive.	Usually negative [33]
Synaptophysin	Positive, may be weak or focal	Positive, usually strongly	Rare, scattered cells may be positive.	Usually negative [33]
CD99	Negative	May be positive (45% of cases) [38].	Negative	Positive (diffuse, membranous)

^*Mixed acinar-neuroendocrine carcinomas exhibit both acinar and neuroendocrine features.

^**HPF High power field