Table 3.
Previously reported cases of presacral NEN.
| Reference | Age | Sex | Histology | Anomalies | IHC +: positive (+): weak or focal positive −: negative | Metastases synchronous | Metastases metachronous | Treatment (best response, PFS in months) | Follow-up (months) †deceased |
|---|---|---|---|---|---|---|---|---|---|
| (42) Fiandaca 1988 | 35 | F | NET | Teratoma | NR | LYM, HEP, OTH (ovary) | Surgery, PEB (NR) | NR (12 presurgery) | |
| (70) Noshiro 1990 | 48 | F | NET | – | NR | LYM | Surgery (CR, 24 og) | 24 | |
| (60) Addis 1991 | 57 | F | NET | – | CAM5.2+, S100(+), NSE(+), Vimentin-, GFAP- | Surgery (NR, 12 og) | 12 | ||
| (64) Lin 1992 | 18 | F | NET | Tailgut cyst | NR | NR | NR | ||
| (55) Edelstein 1996 | 51 | F | NET | – | NR | Surgery (CR, 18 og) | 18 | ||
| (71) Horenstein 1998 | 19 | F | NET (Ki67 NR) | Tailgut cyst | CgA+, Syn+, NSE+, Cam5.2+, S100−, GFAP− | Surgery (CR, 48 og) | 48 | ||
| (71) Horenstein 1998 | 19 | F | NET (Ki67 NR) | – | CgA+, Syn+, NSE+, Cam5.2+, GFAP−, NeuF−, serotonin−, Somatostatin−, VIP−, Gastrin−, Calcitonin− | 2x Cis/Eto/Ifo, 3x Doxo/DTIC/Cyclo, embolization (SD, 12 og) Surgery (CR, 36 og) |
48 | ||
| (71) Horenstein 1998 | 21 | F | NET (Ki67 NR) | – | CgA+, Syn+, NSE+, Cam5.2+, Ck7−, Ck20−, GFAP−, serotonin−, somatostatin−, VIP−, Gastrin−, Calcitonin− | LR, OTH (Breast) | Surgery (CR, 12) Surgery Breast (CR, 1) |
13 | |
| (68) Gorski 1999 | 42 | F | NR | NR | |||||
| (56) Oyama 2000 | 52 | M | NET G1 (Ki67 NR) | Tailgut cyst | NR | Surgery (CR, 6 og) | 6 | ||
| (43) Prasad 2000 | 69 | F | NEC (Ki67 NR) | Tailgut cyst | Ck+, CgA+ | Surgery(CR, 24og) | 24 | ||
| (58) Theunissen 2001 | 51 | F | NET G2 (“LCNEC”, Ki67 NR) | – | MNF116+, Vimentin(+), CEA−, CA125−, S100−, CgA+, Syn+ | Cis/Eto (SD, 3) | 3 † | ||
| (31) Mourra 2003 | 68 | M | NET/NEC (Ki67 NR) | Tailgut cyst | NSE+, CgA+, Syn+, Ck+, EMA+, PSA−, CD45− | Surgery (CR, 12 og) | 12 | ||
| (26) Jacob 2004 | 42 | F | NR | Tailgut cyst | NR | Surgery (NR) | NR | ||
| (16) Song 2004 | 41 | F | NET (Ki67 NR) | Tailgut cyst | AE1/3+, Syn+, CgA+ | HEP, BRA | Surgery (CR, 12) 5-FU (NR, 3) RT BRA (NR) |
15 | |
| (48) Urioste 2004 | 22 | M | NR | Teratoma, Currarino | NR | NR | |||
| (18) Luong 2005 | 37 | M | NET G1 (Ki67 2.9%) | Teratoma | Ck+, Syn+, NSE+, CgA−, | HEP, LYM, OSS | Lan (PD, 10) Lan (NR, 3) |
18 | |
| (28) Mathieu 2005 | 49 | F | NET (Ki67 NR) | Tailgut cyst | NR | Surgery (CR, 24 og) | 24 | ||
| (34) Kim 2007 | 58 | F | NET (Ki67 NR | Imperforate anus | Syn+, CgA+, NSE+, Ck+, S100− | Surgery (CR, 10 og) | 10 | ||
| (24) Liang 2008 | 51 | F | NET G2? (Ki67 > 1%) | Tailgut cyst | ER+, PR(+), Syn+, CgA+, PanCk+, | Surgery (NR) | NR (3 presurgery) | ||
| (20) La Rosa 2010 | 73 | F | NET G1 (Ki67 < 2%) | Tailgut cyst | Syn+, CgB+, VMAT2+, SSTR2A+, PAP+, Ghrelin+, CgA+, Serotonin+, Somatostatin+, Ck20+, CDX2−, VMAT1−, PP−, YY−, GRP−, Gastrin−, glicentin−, encephalin−, GFAP−, ER−, PR−, AR−, Ck7−, TTF1− | Surgery (CR, 5) | 5 (36 presurgery) | ||
| (65) Pendlimari 2010 (32) Liu 2020 |
22 | F | NET G2 (Ki67 5%) | Currarino, teratoma | CgA+, Syn+, CD56(+) | LYM | Surgery (CR, 24 og) | 24 | |
| (59) Ciotti 2011 | 44 | F | NET G1/G2 (Ki67 < 10%) | Currrarino, teratoma | CgA+, Syn+ | LYM | LR, LYM, HEP | Surgery (CR, 16) Surgery LR, LYM (CR, 24) Octreotide, CT (PD) |
40 † |
| (69) Harbeck 2011 | 39 | F | NET G2 (Ki67 5%)/NEC G3 (Ki67 30%) | – | CgA+, Syn+, Ck+, SSTR2+, serotonin−, glucagon−, somatostatin− | LYM, OSS | Surgery (CR, 30) PRRT (PR, 6 og) |
36 | |
| (30) Spada 2011 | 63 | F | NET G1 (Ki67 < 2%) | Tailgut cyst | AE1/3+, Syn+, PP+, AP+, CgA(+) | HEP | Surgery (CR, 25 og) | 25 | |
| (30) Spada 2011 | 41 | F | NET G2 (Ki67 18%) | Tailgut cyst | CgA+, Syn+, AE1/3+, SSTR2+ | HEP | PLE, OSS, OTH (ovary) | Surgery (PR, NR) Carbo/Eto for HEP (NR, 7) PRRT (PR, NR) Surgery for PLE+Ovary (NR, NR) SSA (SD, NR) PRRT (SD, NR) |
79 |
| (62) Wöhlke 2011 | 55 | F | NET G2 (Ki67 20%) | Tailgut cyst | AE1/3+, Syn+, CgA(+), somatostatin+, glucagon−, insulin−, gastrin−, CDX2− | LYM, HEP | OSS | Surgery, PRRT (CR, 22) PRRT (PR, 8) |
30 |
| (66) Zhong 2012 | 48 | F | NET G1 (Ki67 1%) | – | OTH (muscle) | Surgery, cis/eto/doxo/cyclo RT (SD, 36 og) | 36 | ||
| (63) Zoccali 2012 | 64 | M | NEN (Ki67 NR) | Tailgut cyst | AE1/3+, Syn+, CgA−, p63− | Surgery (NR) | NR | ||
| (57) Damato 2013 | 24 | F | NET (Ki67 NR 5%)? | Tailgut cyst | Vimentin+, Ck+, S100−, Syn+, PSAP+ | Surgery (CR, 3 og) | 3 | ||
| (41) Misawa 2013 | 53 | F | NET/NEC (Ki67 20–60/70%) | AE1/3+, CAM5.1+/−, KL1+/−, S100 +/−, NSE+, Ubiquitin+, CD56+, CgA−, Syn+, LCA−, SMA−, Desmin−, CD10−/+, CD34−, HMB45−, GCDFP15− | LR, PER, PUL | Surgery (NR, 4) RTX for LR (NR, 4) |
11 † | ||
| (67) Simpson 2014 | 64 | F | NEN (Ki67 NR) | Teratoma | NR | NR | Surgery (NR) | NR | |
| (39) Abukar 2014 | 61 | M | NET G2 (Ki67 low) | Tailgut cyst | PAP+, CD56(+), Syn+, CgA+, MNF116+, AE1/3+ | Surgery (NR) | NR | ||
| (17) Charalampakis 2014 | 35 | M | NET G1 (Ki67 < 1%)? | Tailgut cyst | PanCk+, CgA+, Syn+ | Surgery (CR, 36 og) | 36 | ||
| (37) Kim 2014 | 49 | M | NET G2 (Ki67 5%) | Tailgut cyst | CgA+, Syn+, CD56+ | Surgery, w&w for residual tumor (SD, 14 og) | 24 | ||
| (61) Menter 2014 | 69 | M | NET G2 (Ki67 10%), PLE: Ki67 15% | – | PSAP+, TTF1−, PSA−, Ck20(+), CD56+, CgA+, Syn+, SSTR2+, Ck22+, Ck7−, EMA−, ERG−, S100−, | OSS, HEP, PUL, LYM, OTH, heart, duodenum, mesenterium | Surgery, RT (PR, 36) | 72† | |
| (22) Mitsuyama 2015 | 53 | M | NET G2 (Ki67 12.5%) | Tailgut cyst | Vimentin+, panCk(+), EMA−, S100−, CD99−, CgA+, Syn+, SSTR2+ | Surgery (CR, 10) Octreotide (NR) Irradiation (NR, 10) Everolimus (NR, 8 og) |
28 | ||
| (52) Sable 2014 | 35 | F | NET G1 (Ki67 2%) | Teratoma | Ck+, Syn+ | Surgery, CT | NR | ||
| (35) Falkmer 2015 | 57 | M | NET G2 (Ki67 5–10%) | – | AE1/3+, Syn+, CgA+, CgB+, Ghrelin+, PYY(+), Motilin(+), VMAT2−, Serotonin−, Gastrin−, GIP−, CGRP−, CART−, Calcitonin−, ACTH−, Secretin−, VIP−, NRK−, Insulin−, IAPP−, glucagon−, GLP1−, GRP−, neurotensin− | LYM, OSS | LR, SKI, BRA, OTH (soft tissue, kidney, heart) | Watch&wait (NR, 27) Surgery (8) RTX (4) STZ/5-FU (PD, NR) PRRT (NR,19) Octreotide (NR, NR) Octreotide-HD (NR, NR) RTX (NR, 13) PRRT (NR, 25) PRRT (PR, 9) |
135 † |
| (38) Jehangir 2016 | 74 | M | NET (Ki67 NR) | Tailgut cyst | Syn+, NSE+, CgA− | Surgery (CR, 60 og) | 60 | ||
| (40) Ferrer-Márquez 2017 | NR | NR | NET (Ki67 NR) | NR | NR | Surgery (CR, 24 og) | 24 | ||
| (40) Ferrer-Márquez 2017 | NR | NR | NET (Ki67 NR) | NR | Surgery (CR, 24 og) | 24 | |||
| (40) Ferrer-Márquez 2017 | NR | NR | NET (Ki67 NR) | NR | Surgery (CR, 6 og) | 6 | |||
| (45) Mora-Guzmán 2017 | 56 | F | NET G1 (Ki67 < 2%) | Tailgut cyst | AE1/3+, CD56+, Syn+, CgA+ | Surgery (CR) | 7 | ||
| (29) Al Khaldi 2018 | 53 | F | NET G2 (Ki67 5-10%) | Tailgut cyst | CgA+, Syn+, Cam5.2+, AE1/3(+), CD56(+) | LYM, PUL, HEP | Surgery (CR, 24) SSA for LYM+PUL (NR, 6) SZT/5-FU (SD, 12) Everolimus (PD, 4) |
46 | |
| (19) Erdrich 2018 | 77 | M | NET G2 (Ki67 8.6%) HEP: NET G2 (Ki67 6.4%) |
Tailgut cyst | CgA(+), Syn+ | HEP | Surgery primary + HEP | NR | |
| (14) Iwata 2019 | 25 | F | NET G2, (Ki67 20%) | Tailgut cyst | Ck+, Syn+, CgA+, ER−, PR− | Surgery (NR) | NR (8 presurgery) | ||
| (51) Soyer 2018 | 14 | M | Tailgut cyst | NR | |||||
| (72) Yang 2018 | 39 | F | NET G2 (Ki67 5–10%) | Tailgut cyst | CgA+, Syn+, Serotonin−, TTF1−, CDX2−, PAX8−, PP− | LR, HEP, PUL, PER, OTH (ovaries) | Surgery (CR, 12) Surgery + SSA for LR (CR,12) Surgery LR + PER, ablation (NR, 41) Surgery + RT for LR + PER + OTH (NR, 36) SIRT + SSA (NR, NR) |
120 | |
| (72) Yang 2018 | 41 | F | NET (Ki67 NR) | Teratoma | Syn+, CgA+, Ck+, AE1/3+, S100+ | OTH (ovaries, retroperitoneal) | Surgery, SSA (CR, 48) Surgery (ovaries, retroperitoneal) (NR, NR) |
48 | |
| (72) Yang 2018 | 45 | F | NET (Ki67 NR), BRA: NET G2, Ki67 18% | Anterior sacral meningocele, tailgut cyst | CAM5.2+, CgA+, Syn+, CDX2+ | BRA, LYM, HEP, OSS | Surgery (CR, 9) Surgery brain (CR, 3) Octreotide, PRRT LR, LYM, HEP (SD, 36) PRRT for HEP, OSS (PR, NR) |
46 (156 presurgery | |
| (72) Yang 2018 | 46 | M | NET G2 (Ki67 15%) BRA: NET G2 (Ki67 12%) |
Tailgut cyst | Syn+, CgA+, AE1/3+, TTF1−, CDX2− | HEP, OSS | FOLFOX + Bev (SD?, 14 og) Everolimus + Oct, Irradiation (NR, 12) Surgery (BRA) |
28 | |
| (72) Yang 2018 | 75 | M | NET G1, Ki67 < 1% | – | LYM, OSS, PUL | HEP | Surgery, RTX, Oct (NR, 47) SIRT, Oct (PR, 27 og) |
78 | |
| (72) Yang 2018 | 42 | F | NET G2 (Ki67 6%) | – | Syn+, CD56+, NSE+, WT1+, | HEP | Surgery (CR, 12) Oct (NR, 25) Oct + CC-223 (NR, 9) SIRT (PR, 11) Surgery pancreas (NR, NR) Tem (PD, NR) Sunitinib (NR, NR) PRRT (SD, NR) |
68 | |
| (72) Yang 2018 | 41 | F | NET G2 (Ki67 13%) | – | PUL, HEP, OSS | BRA | Lan + IFN (NR, 9) Pazopanib (NR, 16) RT OSS BRA (SD, 6 og) |
36 | |
| (72) Yang 2018 | 44 | F | NEC G3 (Ki67 80–90%) | – | Ck+, Syn+, CD56+ | LYM | Cis/Eto, RTX (PR, 5 og) | 5 | |
| (72) Yang 2018 | 77 | F | Large-cell NET/NEC (Ki67 50%) | – | Syn+, CD56+, Villin+ | Carbo/Eto (SD, 3 og) Oct (PD, 4) |
7 | ||
| (72) Yang 2018 | 50 | F | NET (Ki67 NR) | – | LYM, HEP, OTH (pancreas) | Tem/Cap (NR), Oct (NR) | NR | ||
| (21) Chatani 2019 | 59 | F | NET G2 (Ki67 NR), Adenocarcinoma | Teratoma, Currarino | Syn+, CgA+ | Resection, RT (CR, 8 og) |
8 | ||
| (49) Coetzee 2019 | 60 | F | NET G2 (Ki67 14%) | Teratoma, Currarino | CgA+, Syn+ | Surgery (CR, 18 og) | 18 | ||
| (53) Colombo 2019 | 46 | M | NET (Ki67 NR) | Currarino, dermoid cyst | NR | NR | |||
| (36) Kim 2019 | 78 | M | NET G2 (Ki67 6.6%) | – | CgA+, Syn+, CD56+, Ck7-, TTF1-, CDX2- | HEP | PER | Surgery HEP (CR, 48) Octreotide + everolimus (SD, 14) Pazopanib (NR, 14) PRRT (SD, 2 og) |
96 |
| (15) Lee 2019 | 33 | F | NET G1 (Ki67 1-2%) | Tailgut cyst | AE1/3+, Syn+, CgA+, CDX2(+), ER(+), Ck7(+), Ck20- | Surgery (NR, NR) | NR (96 presurgery) | ||
| (46) Olczak 2019 | 49 | M | |||||||
| (50) Rod 2019 | 51 | M | NET (Ki67 NR) | Currarino | NR | Surgery (NR, NR) | 60 | ||
| (27) Sakr 2019 | M | NET (Ki67 NR) | Tailgut cyst | NR | Surgery (NR, NR), RT (NR, NR) | NR | |||
| (33) Singh 2019 | 63 | M | NET G1 (Ki67 < 1%) | Tailgut cyst | Syn+, Ck+, CgA−, GFAP−, SMHC−, p63−, CD56− | Surgery (NR, NR) | NR | ||
| (25) Zhang 2019 | 36 | F | NET G3 (Ki67 30%) | – | Syn+, CD56+, Ck+ | Surgery (CR, 1 og) | 1 | ||
| (23) Kodera 2020 | 68 | F | NET G1 (Ki67 < 2%) | Tailgut cyst | CD56+, SSTR2A+, PP+, PR(+), CgA−, p53−, ER−, gastrin−, serotonin−, somatostatin−, CDX2−, TTF1− | Surgery (CR, 12 og) | 12 | ||
| (32) Liu 2020 | 75 | F | NET G2 (Ki67 3%), HEP: NET G2 (Ki67 6.8%) | Tailgut cyst, Currarino | NR | HEP | Octreotide (PD, 11) PRRT (NR, NR) |
11 | |
| (32) Liu 2020 (54) Scott 2021 |
35 | F | NET G2 (Ki67 4%) | Currarino, tailgut cyst | Syn+, SSTR2A+, Islet-1+, CgA−, Ck20−, TTF1−, CDX2−, PAX8−, GATA3−, Inhibin−Desmin−, S100− | LYM, OSS | Surgery, Octreotide (SD, 22 og) PRRT (NR, NR) Oct high dose (SD, NR) |
36 | |
| (47) Rebelo 2020 | 48 | M | NET G2 (Ki67 6%) | Tailgut cyst, Currarino | CD56+, Syn+, CgA− | HEP, OSS, OTH (spleen) | Surgery (CR, 18) CT |
18 | |
| (54) Scott 2021 | 38 | M | NET G2 (Ki67 7.5%), LYM: NET G2 (Ki67 9%) | Currarino, tailgut cyst | Syn+, CgA+, SSTR2A+, Islet−1+, PAX6+, CDX2−, TTF1− | LYM | Surgery (CR, 24) Surgery LYM (CR, NR) |
24 | |
| (54) Scott 2021 | 62 | F | NET G1 (Ki67 < 1%) | Currarino, teratoma | AE1/3+, CAM 5.2+, Syn+, CD56(+), Ck5/6−, p63−, S100−, desmin−, CD34−, CD45−, CgA− | Surgery (CR, 12 og) | 12 |
Histopathology was adapted to the most current WHO 2019 classification according to the description in the report.
AP, acid phosphatase; AR, androgen receptor; BRA, brain; CAM, cell adhesion molecule; Cap, capecitabine; Cis, cisplatin; Ck, cytokeratin; CT, chemotherapy; CgA, chromogranin A; CgB, chromogranin B; CR, complete remission; cyclo, cyclophosphamide; doxo, doxorubicin; DTIC, dacarbazin; EMA, epithelial membrane antigen, ER, estrogen receptor; eto, etoposide; F, female, GCDFP, gross cystic disease fluid protein; GFAP, glial fibrillary acidic protein; GIP, gastric inhibitory peptide; GRP, gastrin releasing peptide; HEP, liver; Lan, lanreotide, LR, local recurrence; LYM, lymph nodes; M, male; NF, neurofilament; NR, not reported; NSE, neuron-specific enolase; Oct, octreotide; og, ongoing; OSS, bone; OTH, other, PD, progressive disease; PER, peritoneum; PgR, progesterone receptor; PLE, pleura; PP, pancreatic polypeptide; PR, partial remission; PRRT, peptide receptor radionuclide therapy; PSAP, prostatic specific acidic phosphatase; PUL, lung; PYY, peptide YY; RT, radiotherapy; SD, stable disease; SKI, skin; SSA, somatostatin analogue; SSTR, somatostatin receptor; syn, synaptophysin; Tem, temozolomide; VIP, vasoactive intestinal peptide; VMAT, vesicular monoamine transporter; w&w: watch & wait.