Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website https://www.gastrores.org

Original Article

Volume 13, Number 4, August 2020, pages 129-137

Primary Localized Amyloidosis of the Intestine: A Pathologist Viewpoint

Figure 1. Flow chart of literature search and study selection for cases of localized intestinal amyloidosis. The inclusion criteria included patients who had amyloid deposition in the intestine without evidence of systemic involvement or an associated condition leading to secondary amyloidosis [42]. The exclusion criteria included patients with one or more of the followings: 1) Evidence of chronic diseases such as collagen vascular disease, that may have led to secondary amyloidosis [42]; 2) Additional organ involvement by amyloidosis; 3) Intestinal symptoms suggestive of amyloidosis but without confirmatory diagnostic tissue biopsy; 4) Plasma cell dyscrasia, myeloma, lymphoplasmacytic disorders or other B-cell malignancies such as Waldenstrom’s macroglobulinemia [5]; 5) Systemic AL type [43]; 6) Laboratory findings revealing positive detection of monoclonal light chains in serum and/or urine [15].

Figure 2. Isolated primary amyloidosis of the intestine (case report): (a - e) Colonic mucosa with deposition of pale eosinophilic amorphous material (star) in the submucosa with abundant deposits of pink amorphous materials with some cracking artifacts, characteristic of amyloid. Focal surface mucosal ulceration is noted. The background mucosa shows focal active inflammation, including cryptitis (arrow), and there is patchy crypt distortion. No granulomas are seen (hematoxylin and eosin: (a) × 20, (b) × 40, (c, d) × 200, and (e) × 400). (f, g) Congo red stain which reveals the characteristic salmon-pink color, confirming the presence of amyloid deposits (Congo red, (f) × 200 and (g) × 400). (h, i) The deposits exhibit characteristic apple-green birefringence under polarized light (Congo red under polarized light ((h) × 200 and (i) × 400).

**Table 1.** Data From Individual Studies of Primary Localized Amyloidosis of the Small Intestine
Case	Sex	Age (years)	Sites	Clinical manifestations	Colonoscopic findings	Studies
1	F	44	Ileum	Acute abdominal pain, diarrhea, and vomiting	Thickening of the wall of the ileum and ascending colon	[28]
2	M	47	Jejunum	Pseudo-intestinal obstruction	Thickening of the mucosal folds and multiple polypoid protrusions	[29]
3	F	81	Jejunum	Melena, and anemia	Diffuse thickening of the mucosa with friability, nodularity, erosions, and polypoid protrusions	[30]
4	M	71	Small intestine	Intestinal obstruction	Diffuse thickening of the wall of the small intestine	[31]
5	F	51	Jejunum and ileum	Chronic diarrhea and malabsorption	Thickening of the jejunal and proximal ileal mucosal folds	[32]
6	M	Middle age	Small intestine	Acute abdomen	Perforation of the wall	[33]
7	M	62	Duodenum and jejunum	Abdominal pain, nausea, and constipation	Multiple shallow ulcers and several erosions	[34]
8	M	62	Small intestine	Small bowel obstruction	Band of amyloid and connective tissue surrounding the small intestine	[35]
9	M	Aged	Small intestine	Abdominal pains and hematemesis	Mucosal ulcerations with discrete nodules	[36]
10	M	60	Small intestine	Nonspecific digestive symptoms	Multiple mucosal polyps	[37]
11	M	74	Jejunum	Nonspecific digestive symptoms	Polypoid, pseudo-tumoral mucosal formations.	[38]
12	F	68	Small intestine	Nonspecific digestive symptoms	Thickening of the wall with rough, and polypoid intestinal mucosal folds	[39]
13	F, M	59	Small intestine (three cases)	Heartburn and constipation	-	[6]
14	M	55	Duodenum	Screening for cancer stomach	A localized depressed lesion	[40]

Table 1. Data From Individual Studies of Primary Localized Amyloidosis of the Small Intestine

Case

Sex

Age (years)

Sites

Clinical manifestations

Colonoscopic findings

Studies

Ileum

Acute abdominal pain, diarrhea, and vomiting

Thickening of the wall of the ileum and ascending colon

[28]

Jejunum

Pseudo-intestinal obstruction

Thickening of the mucosal folds and multiple polypoid protrusions

[29]

Jejunum

Melena, and anemia

Diffuse thickening of the mucosa with friability, nodularity, erosions, and polypoid protrusions

[30]

Small intestine

Intestinal obstruction

Diffuse thickening of the wall of the small intestine

[31]

Jejunum and ileum

Chronic diarrhea and malabsorption

Thickening of the jejunal and proximal ileal mucosal folds

[32]

Middle age

Small intestine

Acute abdomen

Perforation of the wall

[33]

Duodenum and jejunum

Abdominal pain, nausea, and constipation

Multiple shallow ulcers and several erosions

[34]

Small intestine

Small bowel obstruction

Band of amyloid and connective tissue surrounding the small intestine

[35]

Aged

Small intestine

Abdominal pains and hematemesis

Mucosal ulcerations with discrete nodules

[36]

Small intestine

Nonspecific digestive symptoms

Multiple mucosal polyps

[37]

Jejunum

Nonspecific digestive symptoms

Polypoid, pseudo-tumoral mucosal formations.

[38]

Small intestine

Nonspecific digestive symptoms

Thickening of the wall with rough, and polypoid intestinal mucosal folds

[39]

F, M

Small intestine (three cases)

Heartburn and constipation

[6]

Duodenum

Screening for cancer stomach

A localized depressed lesion

[40]

**Table 2.** Data From Individual Studies of Primary Localized Amyloidosis of the Colon
Case	Sex	Age (years)	Sites	Clinical presentation	Colonoscopic findings	Studies
1	M	52	Transverse colon	A periumbilical pain, rectal bleeding, and weight loss	Ulcerations and luminal narrowing by multiple polypoid lesions	[15]
2	M	Elderly	Transverse colon	Intestinal obstruction	A stenosing mass	[16]
3	M	Middle age	Transverse colon	Nonspecific digestive symptoms	Submucosal mass	[17]
4	M	74	Descending colon	Anemia	Ulcerative lesions	[18]
5	M	88	Sigmoid colon	Acute abdominal pain, rectal bleeding, and fecal peritonitis	Mucosal ulceration, perforation, and thickening of the bowel wall	[20]
6	F	64	Sigmoid colon	Hematochezia	A submucosal tumor-like mass	[21]
7	M	51	Sigmoid colon	Heme-positive stools	Mucosal ulcer	[22]
8	M	58	Sigmoid colon	Rectal bleeding	A single friable, rounded mucosal lesion	[23]
9	M	73	Sigmoid colon	Routine colonoscopy	A 1.5-cm shallow depressed mucosal lesion	[24]
10	F	79	Sigmoid	Nonspecific digestive symptoms	Several irregularly-shaped discrete ulcerations	[25]
11	M	46	Descending colon	Abdominal pain, bloating, flatulence and hematochezia	Hemorrhagic mucosa and amass lesion	[12]
12	F	59	Ascending and descending colons	Rectal bleeding	Diffuse nodular friable lesions (ascending colon) and several irregular large ulcers with nodularity (descending colon)	[26]
13	F, M	Middle age	Colon	Rectal bleeding (two cases)	Thickening of the wall and mucosal ulcerations	[27]
14	F, M	59	Colon (seven cases)	Heartburn and constipation	-	[6]
15	F	44	Ascending colon	Acute abdominal pain, diarrhea, and vomiting	Thickening of the wall of the ileum and ascending colon	[28]

Table 2. Data From Individual Studies of Primary Localized Amyloidosis of the Colon

Case

Sex

Age (years)

Sites

Clinical presentation

Colonoscopic findings

Studies

Transverse colon

A periumbilical pain, rectal bleeding, and weight loss

Ulcerations and luminal narrowing by multiple polypoid lesions

[15]

Elderly

Transverse colon

Intestinal obstruction

A stenosing mass

[16]

Middle age

Transverse colon

Nonspecific digestive symptoms

Submucosal mass

[17]

Descending colon

Anemia

Ulcerative lesions

[18]

Sigmoid colon

Acute abdominal pain, rectal bleeding, and fecal peritonitis

Mucosal ulceration, perforation, and thickening of the bowel wall

[20]

Sigmoid colon

Hematochezia

A submucosal tumor-like mass

[21]

Sigmoid colon

Heme-positive stools

Mucosal ulcer

[22]

Sigmoid colon

Rectal bleeding

A single friable, rounded mucosal lesion

[23]

Sigmoid colon

Routine colonoscopy

A 1.5-cm shallow depressed mucosal lesion

[24]

Sigmoid

Nonspecific digestive symptoms

Several irregularly-shaped discrete ulcerations

[25]

Descending colon

Abdominal pain, bloating, flatulence and hematochezia

Hemorrhagic mucosa and amass lesion

[12]

Ascending and descending colons

Rectal bleeding

Diffuse nodular friable lesions (ascending colon) and several irregular large ulcers with nodularity (descending colon)

[26]

F, M

Middle age

Colon

Rectal bleeding (two cases)

Thickening of the wall and mucosal ulcerations

[27]

F, M

Colon (seven cases)

Heartburn and constipation

[6]

Ascending colon

Acute abdominal pain, diarrhea, and vomiting

Thickening of the wall of the ileum and ascending colon

[28]

**Table 3.** Clinical, Colonoscopic and Histological Findings in the Primary Localized Amyloidosis of the Intestine
Aspects	Small intestine (duodenum, jejunum, and ilium)	Colorectum
Age (mean ± SEM)	62 ± 3.7 years [6, 28-39]	65.1 ± 3.9 years [6, 12, 15-27]
Male to female ratio	8/4	12/3
Site of involvement
	Jejunum (40%)	The left colon (44%)
	Ileum (7%)	Transverse colon (11%)
Clinical presentations
	Abdominal pain and intestinal obstruction (33%) [6, 28, 29, 31, 33-36]	Rectal bleeding (37%) [15, 20-23], followed by abdominal pain (11%) [15, 20] and anemia [18]
Colonoscopic findings
	Thickening of the wall (18%) [28-32, 39]; polyps and polypoid mucosal protrusions (11%) [37-39]; ulcerations (7%) [34, 36]; friability and nodularity of the mucosa (7%) [30, 36], and perforation (3%) [33].	Mass lesions (tumor-like lesion, polypoid protrusions, and polyps) with narrowing were the most common (29%) [12, 15-18, 21]. Ulcerations with solitary or multiple ulcers (14%) [20, 22, 25-27], thickening of the wall (7%) [20, 27], nodularity and friability of the mucosa (2%) [23, 24, 26], and perforation (3%) [20].
Histological features
	Amyloid deposits; increased density of mixed inflammatory cells in the lamina propria; light chain protein [21, 34].	Amyloid deposits; increased density of mixed inflammatory cells in the lamina propria; foreign body giant cell reaction; amyloid angiopathy; necrotizing angiitis; focal active colitis; and immunoglobulin light-chain (AL) [16, 23, 24].

Table 3. Clinical, Colonoscopic and Histological Findings in the Primary Localized Amyloidosis of the Intestine

Aspects

Small intestine (duodenum, jejunum, and ilium)

Colorectum

Age (mean ± SEM)

62 ± 3.7 years [6, 28-39]

65.1 ± 3.9 years [6, 12, 15-27]

Male to female ratio

8/4

12/3

Site of involvement

Jejunum (40%)

The left colon (44%)

Ileum (7%)

Transverse colon (11%)

Clinical presentations

Abdominal pain and intestinal obstruction (33%) [6, 28, 29, 31, 33-36]

Rectal bleeding (37%) [15, 20-23], followed by abdominal pain (11%) [15, 20] and anemia [18]

Colonoscopic findings

Thickening of the wall (18%) [28-32, 39]; polyps and polypoid mucosal protrusions (11%) [37-39]; ulcerations (7%) [34, 36]; friability and nodularity of the mucosa (7%) [30, 36], and perforation (3%) [33].

Mass lesions (tumor-like lesion, polypoid protrusions, and polyps) with narrowing were the most common (29%) [12, 15-18, 21]. Ulcerations with solitary or multiple ulcers (14%) [20, 22, 25-27], thickening of the wall (7%) [20, 27], nodularity and friability of the mucosa (2%) [23, 24, 26], and perforation (3%) [20].

Histological features

Amyloid deposits; increased density of mixed inflammatory cells in the lamina propria; light chain protein [21, 34].

Amyloid deposits; increased density of mixed inflammatory cells in the lamina propria; foreign body giant cell reaction; amyloid angiopathy; necrotizing angiitis; focal active colitis; and immunoglobulin light-chain (AL) [16, 23, 24].