Table 1.

Characteristic morphologic and immunohistochemical features of histopathologic mimics of primary ovarian large cell neuroendocrine carcinoma [2,3,7,16-18]

Tumor	Gross features	Microscopic features	Immunohistochemistry
Primary large cell neuroendocrine carcinoma	Predominantly solid, lobulated, grey-white mass with areas of necrosis	Prominent nesting/organoid or trabecular pattern of arrangement. Tumor cells are large, round to polygonal with large nuclei, prominent nucleoli and scant to moderate amount of pale to eosinophilic cytoplasm.	Positive for chromogranin, synaptophysin, CD56, neuron specific enolase, dot-like positivity for cytokeratin, high Ki-67 index.
			Negative for inhibin, EMA, WT1, CDX2, S-100, HMB-45, Melan-A, retained nuclear expression for SMARCA4/BRG1 and SMARCB1/INI1.
High-grade serous carcinoma	Large, complex, solid-cystic mass with numerous soft, friable papillary excrescences, with areas of necrosis and calcification	Complex, hierarchical branching papillae, glands, trabeculae and/or sheets of tumor cells, moderate to marked nuclear pleomorphism, with round to irregular nuclei, coarse chromatin, prominent nucleoli and moderate amount of cytoplasm.	Positive for CK7, PAX8, WT1, p16 and show mutant type positivity for p53, 7-20% may show neuroendocrine marker positivity, high Ki-67 index.
			Negative for inhibin, CD10, HMB-45, Melan-A, CD10, retained nuclear expression for SMARCA4/BRG1 and SMARCB1/INI1.
Small cell carcinoma of the ovary, pulmonary type	Large solid-cystic mass with areas of necrosis, no papillary excrescences	Infiltrative tumor with diffuse sheet like arrangement of small hyperchromatic tumor cells with inconspicuous nucleoli and scant cytoplasm. Brisk mitotic activity along with multifocal necrosis is common.	Positive for chromogranin, synaptophysin and CD56 with variable positivity for EMA and TTF1.
			Negative for vimentin, inhibin, CD10 and retained nuclear expression of SMARCA4/BRG1 and SMARCB1/INI1.
Small cell carcinoma of the ovary, hypercalcemic type	Large solid-cystic mass with areas of necrosis, no papillary excrescences	Infiltrative tumor with diffuse sheet like arrangement of small hyperchromatic tumor cells; focal macrofollicle-like arrangement can also be noted. Scattered tumor cells with rhabdoid morphology with eccentric nuclei and prominent nucleoli also seen. Brisk mitosis and multifocal necrosis is common.	Hallmark is the loss of nuclear expression of SMARCA4/BRG1 and/or SMARCB1/INI1.
			Generally positive for vimentin, variable expression of EMA, pancytokeratin, WT1, CD99, CD56.
			Negative for chromogranin, synaptophysin, CD10, inhibin.
Undifferentiated carcinoma	Solid/solid-cystic, large tan-brown mass with necrosis and hemorrhage, mostly showing capsular breach	Infiltrative tumor with pattern less, sheet-like arrangement of tumor cells, no evidence of any particular differentiation, frequent mitosis, apoptosis and vascular invasion.	Tumor cells show focal, strong positivity for AE1/AE3, EMA, CK18, ER and PR, variable staining for vimentin, S-100, CD56, chromogranin, synaptophysin.
			Negative for inhibin, HMB-45, Melan-A, retained nuclear expression of SMARCA4/BRG1 and SMARCB1/INI1.
Sex-cord stromal tumors with neuroendocrine differentiation	Predominantly solid, lobulated, pale-yellowish mass	Varied architectural patterns, including hollow/solid tubules, nodules, trabeculae, retiform and diffuse sheet-like arrangement. Tubules may be filled with hyaline material. Variable amount of cytoplasm. Admixed Leydig cells serve as an important diagnostic clue.	Tumor cells are positive for inhibin, calretinin, WT1, CD99, vimentin, ER, PR, with focal expression of chromogranin, synaptophysin and CD56 in areas with neuroendocrine differentiation, variable expression of pan cytokeratin, CK7 and CK8/18. Leydig cells positive for Melan-A.
			Negative for EMA, HMB45, S-100.
Metastatic neuroendocrine carcinoma	Bilateral small, lobulated/irregular solid/solid-cystic ovarian masses with prominent surface involvement with/without areas of necrosis	Insular/trabecular/cord-like architecture. Round to polygonal, moderately pleomorphic tumour cells with round to oval hyperchromatic nuclei, granular chromatin and moderate amount of granular eosinophilic cytoplasm. Necrosis may be noted.	Tumor cells are positive for chromogranin, synaptophysin, CD56, focally for pan-cytokeratin and TTF1. High Ki-67 index.
			Negative for S-100, WT1, PAX8, EMA, HMB-45, Melan-A.
Metastatic melanoma	Unilateral/bilateral predominantly cystic/solid-cystic ovarian masses with large areas of necrosis and rarely blackish discoloration may be noted	Nodular or diffuse or nested architecture with focal follicle-like arrangement. Tumor cells can exhibit epithelioid or spindled morphology with moderate to marked pleomorphism, prominent nucleoli, nuclear inclusions and cytoplasmic melanin. Multifocal necrosis is common.	Tumor cells are positive for S100, HMB-45, MART-1 and MiTF.
			Negative for EMA, WT1, PAX8, chromogranin and synaptophysin.