Neuroendocrine carcinoma of the common hepatic duct coexisting with distal cholangiocarcinoma: A case report and review of literature

Table 1 Neuroendocrine carcinoma of the extrahepatic bile duct, review of the literature

Ref.	Age	Sex	Location	Symptom	Pathology	Size (mm)	Ki-67 index (%)	Treatment	Metastasis	Prognosis
van der Wal et al[7], 1990	55	Male	Bm	Jaundice, abdominal pain	SCNEC + AC	40	NA	SR	NA	12 months, alive
Nishihara et al[8], 1993	64	Male	Bh-Bs	Jaundice, weight loss	SCNEC + AC	19	NA	SR	NA	8 months, alive
Oikawa et al[9], 1998	70	Male	Bh-Bs	Jaundice	NEC	25	NA	SR	Liver	6 months, dead
Yamamoto et al[10], 1998	71	Female	Bh	Jaundice, fever	SCNEC + AC	60	NA	SR	Liver, bone	7 months, dead
Kim et al[11], 2000	64	Male	Bm	Abdominal pain	SCNEC + AC	30	NA	SR	NA	1 months, alive
Kuraoka et al[12], 2003	75	Male	Bi	Jaundice	SCNEC	45	90	SR	LN	5 months, alive
Hazama et al[13], 2003	60	Male	Bi	Jaundice	SCNEC	3	NA	SR	Brain, LN	17 months, dead
Park et al[14], 2004	60	Female	Bs-Bm	Jaundice	SCNEC	30	NA	SR	Brain, LN	17 months, dead
Thomas et al[15], 2005	54	Male	Bh-Bm	Jaundice	SCNEC	NA	NA	SR	Brain	6 months, alive
Kaiho et al[16], 2005	66	Female	Bi	Abdominal pain	SCNEC + AC	35	NA	SR + chemo	Liver	8 months, dead
Viana Miguel et al[17], 2006	76	Male	Bm	Jaundice	SCNEC	NA	NA	SR + chemo + radio	NA	5 months, alive
Jeon et al[18], 2006	65	Male	Bs-Bm	Jaundice	SCNEC	20	NA	SR + chemo	Liver	12 months, dead
Sato et al[19], 2006	68	Male	Bi	Jaundice	LCNEC + AC	20	71.4	SR	Liver	3 months, dead
Nakai et al[20], 2008	32	Male	Bs-Bi	Abdominal pain	SCNEC	NA	NA	NA	Liver, lung	18 d, dead
Hosonuma et al[21], 2008	69	Female	Bh-Bs	Jaundice	SCNEC	30	NA	NA	NA	2 months, dead
Arakura et al[22], 2008	75	Male	Bh-Bm	Jaundice	SCNEC	65	NA	Chemo + radio	Peritoneal, pleural, LN	10 months, dead
Okamura et al[23], 2009	62	Male	Bm	Abdominal, pain, fever	SCNEC	30	NA	SR + chemo + radio	Bone, LN	23 months, dead
Kohashi et al[24], 2009	77	Male	Bi	Jaundice	LCNEC	18	67	SR	Liver, lung, local	3 months, dead
Cho et al[25], 2009	59	Female	Bh	Jaundice, abdominal pain	SCNEC	30	NA	SR	NA	6 months, alive
Demoreuil et al[26], 2009	73	Male	Bs	Jaundice, abdominal pain, weight loss	LCNEC + AC	30	50	SR + chemo	Lung, peritoneal	12 months, dead
Masui et al[27], 2011	82	Male	Bm	Jaundice, anorexia	MANEC	25	35	SR	Liver	6 months, dead
Takahashi et al[28], 2012	28	Female	Bm	Pruritus	NEC	30	89.8	SR	None	36 months, alive
Ninomiya et al[29], 2013	74	Female	Bm	Jaundice	SCNEC	30	NA	SR	NA	14 months, alive
Sasatomi et al[30], 2013	76	Male	Bh	Jaundice	LCNEC	50	75	SR	LN	21 d, dead
Linder et al[31], 2013	82	Male	Bi	Jaundice, abdominal pain, weight loss	MANEC	19	NA	SR	None	6 months, alive
Park et al[32], 2014	75	Female	Bm	Nausea, jaundice	LCNEC	27	NA	SR + chemo	Local	12 months, dead
Lee et al[33], 2014	75	Male	Bs	Jaundice	SCNEC + AC	20	NA	SR	None	11 months, alive
Wysocki et al[34], 2014	65	Male	Bm	Jaundice, vomit, weight loss	LCNEC + AC	36	80	SR	NA	5 months, dead
Aigner et al[35], 2015	61	Male	Bm	Abdominal pain, jaundice, nausea, pruritus	SCNEC	27	90	SR + chemo	Liver, LN, bone	3 months, alive
Kihara et al[36], 2015	70	Female	Bh	Jaundice	SCNEC	30	70	SR + chemo	None	10 months, alive
Nakamaru et al[37], 2015	75	Male	Bh-Bm	Jaundice	SCNEC	40	NA	SR + chemo	NA	16 months, alive
Oshiro et al[38], 2016	72	Male	Bs	Jaundice	LCNEC	30	56.2	SR + chemo	Liver	7 months, alive
Katada et al[39], 2016	78	Male	Bh	Jaundice	SCNEC	30	NA	SR + chemo	NA	5 months, alive
Murakami et al[40], 2016	80	Male	Bm	Jaundice, anorexia	LCNEC + AC	24	72	SR	Liver, lung, peritoneal	3 months, dead
Priyanka Akhilesh et al[41], 2016	76	Male	Bh	Jaundice, weight loss	MANEC	14	90	SR	NA	NA
Izumo et al[42], 2017	66	Male	Bi	Jaundice, anorexia, fatigue	LCNEC + AC	10	30	SR	None	30 months, alive
Komo et al[43], 2017	82	Male	Bi	Liver dysfunction	MANEC	18	37	SR	None	7 months, alive
Park and Jeon[44], 2018	59	Male	Bh	Jaundice	LCNEC	62	20	SR + chemo	None	10 months, alive
Zhang et al[45], 2018	62	Male	Bh	Jaundice	SCNEC	20	80	SR	Liver	6 months, dead
Koo et al[46], 2019	77	Female	Bh	Jaundice, abdominal pain	LCNEC	10	60	Radio	Liver	1.5 months, alive
Zhang et al[47], 2019	60	Male	Bh-Bs	Abdominal pain	LCNEC + AC	17	70	SR	NA	NA
Zhang et al[48], 2019	64	Female	Bi	Jaundice, abdominal pain	MANEC	45	50	SR	Liver, lung	12 months, dead
Kamiya et al[49], 2020	84	Male	Bm	Jaundice, abdominal pain	MANEC	25	80	SR	Liver	3 months, dead
Kiya et al[50], 2021	29	Female	Bm	Abdominal pain	LCNEC	50	90	SR + chemo	NA	16 months, alive
Sugita et al[51], 2022	62	Female	Bi	Jaundice	SCNEC + AC	19	80	SR	NA	4 months, alive
Han et al[52], 2023	84	Female	Bs	Abdominal pain	SCNEC	17	85	NA	NA	NA
Jevdokimov et al[1], 2023	42	Female	Bs	Jaundice	NEC	30	75	SR + chemo	NA	4 months, alive
This study	62	Female	Bh	Abdominal pain	LCNEC	5	50	SR	Liver, LN, bone	24 months, dead

AC: Adenocarcinoma; NEC: Neuroendocrine carcinoma; SCNEC: Small cell neuroendocrine carcinoma; LCNEC: Large cell neuroendocrine carcinoma; MANEC: Mixed adenoneuroendocrine carcinoma; SR: Surgical resection; Chemo: Chemotherapy; Radio: Radiotherapy; Bh: Hilar bile duct; Bs: Superior portion of common bile duct; Bm: Mid-portion of common bile duct; Bi: Inferior portion of common bile duct; LN: lymph node(s); NA: not available.

Table 2 Comparison of neuroendocrine-non-neuroendocrine neoplasm and pure neuroendocrine carcinoma in the extrahepatic biliary tract

	MiNEN	Pure NEC
Number of cases	19	29
Age, yr	70.47 ± 8.67	64.07 ± 14.88
Sex
Male	15	17
Female	4	12
Location
CHD	2	8
CBD	15	5
CHD + CBD	2	16
Symptom
Jaundice/pruritus	15	24
Abdominal pain	8	8
Anorexia/nauseas/vomit/fatigue/weight loss/ fever	9	3
Size, mm	26.63 ± 12.22	30.15 ± 15.08
Ki-67 index, %	62.12 ± 20.61	69.42 ± 20.75
Treatment
SR	17	12
SR + chemo/radio	2	12
Chemo/radio	0	2
Metastasis
Liver	7	9
Lymph node	0	8
Lung	3	2
Bone	1	3
Brain	0	3
Peritoneal/pleural/local	2	3

MiNEN: Mixed neuroendocrine-non-neuroendocrine neoplasm; NEC: Neuroendocrine carcinoma; CHD: Common hepatic duct; CBD: Common bile duct; SR: Surgical resection; Chemo: Chemotherapy; Radio: Radiotherapy.

Table 3 Comparison of gene mutations in the two primary bile duct tumours

Gene	LCNEC	dCCA
ERBB2	14.10%, exon17, c.2033G>A, p.R678Q	3.70%, exon17, c.2033G>A, p.R678Q
	10.80%, exon17, c.1970C>T, p.A657V
ERBB3	20.10%, exon3, c.310G>A, p.V104M	3.60%, exon3, c.310G>A, p.V104M
LCE1F	43.40%, exon2, c.244C>T, p.R82W	41.70%, exon2, c.244C>T, p.R82W
MSH6	47.80%, exon5, c.3173-3C>G	47.30%, exon5, c.3173-3C>G
	18.00%, exon6, c.3514dup, p.R1172fs
FCAMR	47.00%, exon4, c.250C>T, p.R84W	47.90%, exon4, c.250C>T, p.R84W
BRAF	No	1.30%, exon11, c.1391G>T, p.G464V
CREBBP	45.10%, exon28, c.4711G>A, p.A1571T	52.90%, exon28, c.4711G>A, p.A1571T
ARID1A	17.20%, exon5, c.2077C>T, p.R693*	No
	17.20%, exon20, c.5842_5843del, p.S 1948fs
KMT2C	13.30%, exon46, c.11878C>T, p.R3960	No
	19.80%, exon36, c.5668C>T, p.R1890
KMT2D	21.30%, exon12, c.3318del, p.S1107fs	No
KRAS	18.50%, exon2, c.38G>A, p.G13D	No
CDKN2A	22.20%, exon2, c.238C>T, p.R80	No
ATR	19.30%, exon7, c.1544G>A, p.R515H	No
NTRK1	15.30%, exon11, c.1330C>T, p.R444W	No
CDC73	12.40%, exon6, c.439C>T, p.R147C	No
FOXP1	29.40%, exon12, c.952G>A, p.E318K	No
FBXW7	30.10%, exon10, c.1514G>A, p.R505H	No
MAP3K1	25.10%, exon3, c.746G>A, p.R249H	No
CTNNA1	13.50%, exon7, c.943G>A, p.G315R	No
PRKDC	15.30%, exon73, c.10241C>T, p.T3414M	No
RUNX1T1	23.10%, exon8, c.1084G>A, p.A362T	No
RIC8A	21.30%, exon3, c.568C>T, p.R190C	No
CBL	8.90%, exon14, c.2222C>T, p.A741V	No
KDM5A	15.60%, exon26, c.4400G>A, p.R1467Q	No
	19.80%, exon23, c.3470G>A, p.R1157H
RB1	15.10%, exon8, c.763C>T, p.R255*	No
	15.30%, exon18, c.1735C>T, p.R579*
TP53	2.20%, exon5, c.473G>A, p.R158H	No
BCOR	15.10%, exon4, c.1754G>T, p.R585M	No
STAG2	19.60%, exon9, c.775C>T, p.R259*	No
BCORL1	21.80%, exon4, c.1279G>A, p.A427T	No
	18.10%, exon8, c.4258C>T, p.R1420*

LCNEC: Large cell neuroendocrine carcinoma; dCCA: Distal cholangiocarcinoma.