Table 2.

Summary of the mimics of PEM.

	Clinical Features	Histologic Features	Immunohistochemical Features	Molecular Alterations
Dendritic blue nevus	Well-demarcated papule	Dermal sclerosisDiffuse rather than nested dermal componentNo nuclear pleomorphism	(+) S100, elan-A, HMB-45 (diffuse), SOX10 Low Ki- 67Retained BAP1, p16	GNAQ or GNA11
Cellular blue nevus	Can also involve subcutaneous and soft tissue (muscle, bone)	Nuclei are not epithelioidNo pigmented and clear epithelioid cellsDermal sclerosis	(+) Melan-A, HMB-45 (diffuse), SOX10(+/−) S100, CD34 Low Ki- 67Retained BAP1, p16	GNAQ or GNA11
Deep penetrating nevus	Rarely involves lymph nodes	No dendritic cellsNo mitotic activity	(+) Melan-A, HMB-45 (diffuse), SOX10, Cyclin D1(+) LEF1, $\beta$-catenin (nuclear)(+/−) S100, BRAF V600E(−) PRAMELow Ki- 67	BRAF, MAP2K1, CTNNB1
Pigmented epithelioid melanocytoma (PEM)	Sporadic or Carney ComplexCommonly involves lymph nodesNo distant metastasis	Abundant melanophagesEpidermal hyperplasiaInfiltrative bordersUlceration or necrosis rare	(+) Melan-A, HMB-45 (diffuse), SOX10(+/−) S100, BRAF V600E, PRKAR1ARetained p16Low Ki-67	PRKCA, PRKAR1A, GNAQ, MAP2K1
Combined nevus	Combination of variants of acquired nevus, blue nevus, Spitz nevus or PEM	The cellular features of two components need to be architecturally distinct	As per components	As per components
Cutaneous and pilar neurocristic hamartoma	Recurs, can metastasize and be lethal	Nevomelanoctyic, neural and pigmented dendritic cell elements	(+) S100, HMB-45, Melan-A, CD34
Atypical cellular blue nevus	Similar to blue nevusCan involve lymph nodesCan be large (>10 cm)	Abundant melanophagesFocal cytologic atypiaOccasional mitoses (<2/mm2)No atypical mitotic figures or tumor necrosis	(+) Melan-A, HMB-45 (diffuse or patchy), SOX10(+/−) S100, p16 (variable)Intermediate Ki-67	GNAQ, CYSLTR2, PLCB4
Melanoma arising within cellular blue nevus	Similar to blue nevusCommonly involves lymph nodesDistant metastasisPoor prognosis	Abundant melanophagesWidespread necrosisHigh mitotic rate (>2/mm2)Atypical mitotic figuresVascular invasionUlceration or necrosis possible	(+) Melan-A, HMB-45 (patchy), SOX10 (+/−) S100, p16 (variable), BAP1High Ki-67	GNAQ, GNA11, PLCB4, CYSLTR2, BAP1, SF3B1, EIF1AX, TERT promoter, chromosomal gains/losses
Melanomas that arise from deep penetrating melanocytoma or DPN	Similar to DPN or deep penetrating melanocytomaCommonly involves lymph nodesDistant metastasis	Abundant pigmentationEpithelioid and spindled cellsSimilar to melanoma	Predicted to be similar to deep penetrating nevus	BRAF, MAP2K1, CTNNB1, TERT promoter, chromosomal gains/losses
Melanoma metastasizing to the skin	Single or multiple nodules	Abundant melanophagesAtypical melanocytesHigh mitotic rate (>2/mm2)Stromal reaction	(+) Melan-A, HMB-45 (patchy), SOX10 (+/−) S100, p16 (variable), BAP1, PRAMEHigh Ki-67	TERT promoter, chromosomal gains/losses