J Korean Med Sci.  2023 Mar;38(11):e85. 10.3346/jkms.2023.38.e85.

Comparison of Metastatic Patterns Among Neuroendocrine Tumors, Neuroendocrine Carcinomas, and Nonneuroendocrine Carcinomas of Various Primary Organs

• Park HK
• Kwon GY

• KMID: 2540651
• DOI: http://doi.org/10.3346/jkms.2023.38.e85

Abstract

Background
Both neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) exhibit neuroendocrine differentiation and are classified as neuroendocrine neoplasms (NENs). NECs and nonneuroendocrine neoplasms (non-NENs), such as adenocarcinoma, have similar mutational profiles. The purpose of this study was to identify differences in metastatic patterns and to identify the key factor causing these differences by simultaneously comparing the metastatic patterns of NETs, NECs and non-NENs from various primary organs.
Methods
We retrieved data for 4,223 patients with NENs and 41,637 patients with non-NENs arising at various primary sites from an institutional database and then compared NET, NEC, and non-NEN metastatic patterns.
Results
NETs and NECs showed generally similar metastatic patterns. Most NEN patients had a higher liver organotrophic metastasis rate, lower lung organotrophic metastasis rate, and lower pleural/peritoneal organotrophic metastasis rate than non-NEN patients. Some differences were characteristics of specific organs. Some of these site-specific differences were not caused by NENs but by non-NENs, including a higher bone organotrophic metastasis rate for medullary thyroid carcinoma and a lower bone organotrophic metastasis rate for pulmonary NEN. Other differences were probably caused by NENs, including a higher bone organotrophic metastasis rate for colorectal NETs. Uterine cervical NEC showed unique patterns of metastasis compared to NEN from other sites.
Conclusion
Significant differences between the metastatic patterns of NENs and non-NENs were detected. The multigene program that causes neuroendocrine differentiation might be associated with organotropic metastasis.

Keyword

Neuroendocrine Tumor; Neuroendocrine Carcinoma; Metastasis; Carcinoid; Medullary Carcinoma

Figure

• 

  Fig. 1 Comparison of the patients’ median age at diagnosis (years), proportion of male patients (%) and metastasis rate (%).MTC = medullary thyroid carcinoma, PTC = papillary thyroid carcinoma, NET = neuroendocrine tumor, NEC = neuroendocrine carcinoma, ADC = adenocarcinoma, GB = gallbladder, Ut. cervix = uterine cervix.Only statistically significant comparisons are marked with asterisks: *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001.

• 

  Fig. 2 Comparison of metastatic patterns between patients with NENs and patients with non-NENs in various primary sites. Each percentage indicates the percentage of patients with metastasis to the indicated organ divided by the total number of patients with metastasis. For thyroid cancer, patients with LN metastasis alone were excluded from the total number of patients with metastasis.NEN = neuroendocrine neoplasm, MTC = medullary thyroid carcinoma, PTC = papillary thyroid carcinoma, NET = neuroendocrine tumor, NEC = neuroendocrine carcinoma, ADC = adenocarcinoma, GB = gallbladder, Ut. cervix = uterine cervix, LN = lymph node, CNS = central nervous system.Only statistically significant comparisons are marked with asterisks: *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001.

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