Important of case-reports/series, in rare diseases: Using neuroendocrine tumors as an example

Table 1 Sentinel case reports/series defining syndromes of disease aspects in patients with gastrointestinal neuroendocrine tumors

Year	Author	Pt#	Type of report	Syndrome	Importance	Ref.
1890	Ranson	1	Case report	Carcinoid	First description of ileal carcinoid	[50]
1902	Nichols	1	Case report	Insulinoma	First islet tumor	[49]
1922	Banting et al	7	Case report	Insulin treatment diabetes	Extracted insulin and effectiveness of insulin therapy in diabetes mellitus demonstrated.	[51]
1924	Harris et al	3	Case report	Insulinoma	1st postulate the possibility of insulinoma in his patients	[37]
1927	Wilder et al	1	Case report	Insulinoma	1st pNET syndrome (insulinoma). Extracting insulin from malignant pNET operated by WJ Mayo	[62]
1938	Whipple	Case review	Case review	Insulinoma	Diagnostic triad for insulinoma proposed	[52]
1942	Becker et al	2	Case report	Glucagonoma	First description of Glucagonoma in a patient with skin rash later found to have pNET	[38]
1950	Del Castillo et al	1	Case report	Cushing syndrome	First pNET associated with Cushing syndrome	[39]
1954	Thorson et al	16	Case series review	Carcinoid syndrome	First described a series of patients with small intestinal carcinoids, establishing the clinical entity “carcinoid syndrome”	[48]
1955	Zollinger et al	2	Case report	ZES	First description of ZES (gastrinoma)	[40]
1957	Priest et al	1	Case report	VIPoma	Recognition of WDHA syndrome (VIPoma) with pNET	[41]
1958	Verner et al	2	Case report	VIPoma	First complete description of all features WDHA from review/2 personal cases and 7 literature cases	[63]
1966	McGavran et al	1	Case report	Glucagonoma	Reported case of pNET with hyperglucagonemia and glucose elevation	[54]
1971,3	Wilkinson	1	Case report	Glucagonoma	Proposed term “NME” to describe rash in glucagonoma.	[55,56]
1974	Mallinson et al	9	Case series review	Glucagonoma	Reviewed pNET secreting glucagon and called attention to their association with necrotic migratory erythema (NME)	[57]
1977	Larsson et al	2	Case report	Somatostatinoma	Initial case of pNET producing somatostatin with symptoms	[42]
1977	Ganda et al	1	Case report	Somatostatinoma	Initial case of pNET producing somatostatin with diabetes	[43]
1978	Caplan et al	1	Case report	GRFoma	1st case of pNET secreting growth hormone-like substance with acromegaly	[46]
1979	Krejs et al	1	Case report	Somatostatinoma	Clinical features of somatostatinoma syndrome described and full endocrine characterization	[44]
1982	Guillemin et al	1	Biochemistry	GRFoma	Isolation of growth-hormone releasing factor (GRF) from patient with acromegaly with pNET	[45]
1982	Rivier et al	1	Case report	GRFoma		[64]
1982	Ruddy et al	1	Case report	Reninoma	First description of renin secreting pancreatic tumor causing symptoms	[31]
2004	Samyn et al	1	Case report	EPOma	Description of pNET secreting erythropoietin with syndrome	[30]
2004	Brignardello et al	1	Case report	LHoma	Description of pNET secreting luteinizing hormone with syndrome	[35]
2008	Chung et al	1	Case report	IGF-2oma	First report of pNET secreting IGF-2 with symptoms	[33]
2012	Roberts et al	1	Case report	GLP-1oma	First description of pNET secreting GLP-1 causing symptoms	[32]
2013	Rehfeld et al	1	Case report	CCKoma	First description of CCK secreting pNET with syndrome	[47]

CCKoma: pNET secreting cholecystokinin; EPoma: pNET secreting erythropoietin; GRFoma: pNET secreting Growth Hormone Releasing Factor; IGF-1oma/IGF-2oma: pNET secreting insulin-like growth factor 1 or 2; LHoma: pNET secreting luteinizing hormone; NET: Neuroendocrine tumor: NME: Necrolytic migratory erythema (skin rash) seen in glucagonoma cases; pNET: Pancreatic neuroendocrine tumor; Reninoma: pNET secreting renin; Somatostatinoma: pNET secreting somatostatin; VIPoma: pNET secreting vasoactive intestinal peptide; WDHA: Watery diarrhea, hypokalemia and achlorhydria which are features seen in VIPoma patients; ZES: Zollinger-Ellison syndrome due to ectopic secretion of gastrin by a gastrinoma causing acid hypersecretion.