Unraveling the enigma: A comprehensive review of solid pseudopapillary tumor of the pancreas

Table 1 Pancreatic cyst fluid analysis based on endoscopic ultrasound-fine needle aspiration

Type	SCN	MCN	IPMN	SPTP	Pseudocyst
Viscosity	Low	High	High	NA	Low
Mucin	Low	High	High	NA	Low
Amylase	< 250 U/L	< 250 U/L	High	Low	High
Cytology	Negative or Glyogen containing cuboid cells	Mucin containing column cells	Papillary clusters of mucin column cells, atypia	Branching papillae cuboid or cylindric cells, high cellularity, myxoid stroma	Dirty material, macrophages, inflammatory cell
NGS	VHL; chr3 LOH	CEA	KRAS; GNAS; TP53; PTEN; CEA	CTNNB1	NA

SCN: Serous cystadenoma; MCN: Mucinous cystadenoma; IPMN: Intraductal papillary mucinous neoplasm; SPTP: Solid pseudopapillary tumor of the pancreas; NGS: Next-generation sequencing; LOH: Loss of heterozygosity; CEA: Carcinoembryonic antigen; NA: Not available.

Table 2 Markers for diagnosing solid pseudopapillary tumor of the pancreas on immunohistochemistry analysis

Markers	Positive rate	Mechanisms/implications
β-catenin[26,65]	Almost 100% (nuclear)	Activating the Wnt-signaling pathway
CD200[73]	100% (focal)	Marker of stem cell status
CD10[65,66,74]	100%	Marker of SPTP; expressed in immature lymphocyte
CD56[66]	100%	Marker of SPTP
AMACR[75]	96.2%	Marker of SPTP
LEF1[18]	94.7%	Regulating the Wnt-signaling pathway
TFE3[76]	94.7%	Activating and regulating the Wnt-signaling pathway
CD99[77]	78.4% (paranuclear dot-like)	Differentiating from PNET
E-cadherin[65,78]	0%	Differentiating from PNET
CgA[26]	0%	Differentiating from PNET
Trypsin[26,79]	0%	Differentiating from ACC
BCL10[26,79]	0%	Differentiating from ACC
Ki-67[31,80]	Mostly 1-2%	Predicting prognosis

CD: Cluster of differentiation; PNET: Pancreatic neuroendocrine tumor; SPTP: Solid pseudopapillary tumor of the pancreas; LEF1: Lymphoid enhancer-binding factor 1; TFE3: Transcription factor E3; AMACR: α-methylacyl-CoA racemase; CgA: Chromogranin A; ACC: Acinar cell carcinoma; BCL10: B-cell lymphoma-10.

Table 3 Differential diagnosis of solid pseudopapillary tumor of the pancreas

Disease	Female	Age (yr)	Marker	Clinicopathological features
SPTP	90%	20-40	β-catenin	Well-circumscribed; < 3 cm: Mainly solid; > 3 cm: Solid-cystic; myxoid stroma enveloping fibrovascular cores; discohesive epithelioid cells
Non-functional PNET	50%	50-60	CgA	Solid: Obviously enhanced with capsule ring-like enhancement; solid-cystic: Mural nodule, uneven wall; high rate of G2 and G3
ACC	< 50%	60	AFP	Enhanced solid with large mass having hypodense areas; heterogeneous enhancement; full of large polygonal cells with background necrosis, zymogen-rich and granular cytoplasm, cherry-red nucleoli
SCN	75%	55-70	NA	Honeycomb appearance, central scar; stellate scar in the center of the cyst cavity; clear serous fluid
MCN	> 95%	40-60	NA	Mucin secretion; disconnection from pancreatic duct; ovarian-like stroma; intracellular mucin
IPMN	50%	60-80	NA	Communication with pancreatic duct; absence of ovarian-like stroma; mucin
Pseudocyst	≤ 25%	Any	NA	History of pancreatitis or pancreatic trauma; high amylase in pancreatic juice
PBL	NA	< 10	AFP	Hypodense mass; central mass; squamous nest; well-defined margin; heterogeneous; enhanced; circumscribed, plump spindly cell whorls with squamous morules

SPTP: Solid pseudopapillary tumor of the pancreas; PNET: Pancreatic neuroendocrine tumor; CgA: Chromogranin A; ACC: Acinar cell carcinoma; AFP: Alpha-fetoprotein; SCN: Serous cystic neoplasms; MCN: Mucinous cystic neoplasms; IPMN: Intraductal papillary mucinous neoplasms; PBL: Pancreatoblastoma; NA: Not available.

Table 4 Reported parenchyma-preserving pancreatectomy for solid pseudopapillary tumor of the pancreas

Ref.	Country	F/M	Median/mean age (year)	Surgery type	Median/mean follow-up (month, range)	R/M
Li et al[100]	China	129/37	32.5 (10-68)	11 EN, 22 CP	49 (24-102)	2
Wang et al[103]	China	84/17	31.7 (10-65)	31 EN	46.1 (12-101)	0
Tjaden et al[101]	Germany	44/8	29 (8-71)	4 EN, 5 CP	54 (2-230)	2
Cho et al[102]	Korea	56/10	14.5 ± 5.8	15 EN, 4 CP	24.9 (10-76)	1
Gao et al[99]	China	49/13	31.76 ± 10.19	15 EN, 47 CP	31 (3-69)	0
Chen et al[104]	China	8/2	44.6 (32-57)	10 CP	22.9 (3-48)	0
Guo et al[11]	China	71/16	31.3 ± 13.1	6 EN, 4 CP	46 (13-97)	0
Wang et al[13]	China	85/12	31.6 ± 13.92	15 EN, 20 CP, 2 DPPHR	54 (7-121)	0

F: Female; M: Male; EN: Enucleation; CP: Central pancreatectomy; R/M: Recurrence/metastasis; LR: Local resection; DPPHR: Duodenal-preserving pancreatic head resection.

Table 5 Current models to predict the risk of recurrence of solid pseudopapillary tumor of the pancreas

	Tumor size	Ki-67 index	LVI (extratumoral)	Classification
Fudan Prognostic Index[8]	≤ 10 cm	< 3%	-	Low risk
	> 10 cm	< 3%	-	Intermediate risk
	Any	3-20%	-
	Any	> 20%	-	High risk
PUMCH risk model[9]	≤ 9 cm	≤ 1%	Negative	Low risk
	> 9 cm	Any	Any	High risk
	Any	> 1%	Any
	Any	Any	Positive

LVI: Lymphovascular invasion; PUMCH: Peking Union Medical College Hospital.