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741
Amyloidosis Findings
Shuji Tada1 Mitsuo lida1 Toshiyuki Matsui1 Tadahiko Fuchigami2 Akinori Iwashita3 T I
I.
SUflfOSi
V
ul
Masatoshi
,
Fujlshlma
on Double-Contrast
Intestine: Radiographs
The appearance of the small intestinal mucosa on double-contrast barium examinations was studied in 26 patients with proved intestinal amyloidosis. Findings included innumerable fine granular densities 1-3 mm in diameter (16 patients), multiple nodular densities 3-4 mm in diameter (four patients), multiple polypoid protrusions 4-10 mm in diameter (three patients), irregularities of Kercknng folds (12 patients), and multiple 4
ao
of the Small
erosions
(eight
patients). The multiple treated with total
the patients were maineci unchanged
on follow-up
nodular densities and erosions disappeared parenteral nutrition. The other abnormalities
examinations.
after re-
Our results indicate that double-contrast radiographic findings of the small intestine in patients with amyloidosis include mucosal abnormalities that vary according to the pathologic type of amyloid deposition. AJR
156:741-744,
April 1991
Amyloidosis commonly involves the gastrointestinal tract, resulting in a wide variety of clinical and radiologic manifestations [1 -3]. The small intestine is the most frequent site [4, 5]. Radiographs of the small intestine reflect the morphologic changes in this disease [6-8].
Numerous
reports
have
described
the radiologic
findings
of small
intestinal
amyloidosis; emphasis has been given to thickening of the valvulae conniventes and decreased intestinal motility [6-9]. However, these radiologic findings are not
specific and are not useful in the differentiation
of amyloidosis
from other diseases.
In the present study, we analyzed the findings of amyloidosis on double-contrast barium examinations of the small intestine and compared them with clinical symptoms, endoscopy, and biopsy findings. Materials
and
Methods
1978
Between
both double-contrast duodenofiberscope Received July 5, 1990; accepted October 16, 1990. 1 Department of Internal Medicine versity, Japan. 2
Maidashi
3-1-1
,
Higashi-ku,
revision
Department
Fukuoka
of Pathology,
University,
Department of Hospital of Fukuoka pan. 4
0361-803x/91/1564-0741 © American Roentgen
Fukuoka
derxsition. one had
II, Kyushu
Uni-
Crohn
Fukuoka
812,
Higashi
Address reprint requests to S. Tada. Department of Gastroenterology, Matsuyama
Red Cross Hospital, Matsuyama 3
after
790, Japan. Chikushi
Hospital
protein The
Chikushi 812, Ja-
in two,
syndrome
for Congo of
primary amyloidosis, three had myeloma-associated and 1 7 had secondary amyloidosis (rheumatoid
unclassified
in one,
intestinal
ankylosing
red was reduced
was
ulcers
spondylitis
in one
patient
age
patients
was
average
(1
.
patients
) severe
(four
of the
At the time hemorrhage,
were
divided
patients),
of examination,
into
four
and
type
potassium I familial
45 years (range, gastrointestinal and
groups
patients
myositis
pulmonary
amyloidosis, arthritis in 10,
in one, Ch#{233}diak-
tuberculosis
in one).
light chain protein in six patients and amyloid an antecedent or coexisting disease, affinity
with
with
obstruction,
comprising
in one, multiple
in one,
after treatment
demonstrated
ratio was 1 :1 pain, diarrhea, patients. The
Ray Society
disease
patients had amyloidosis,
Principal amyloid proteins consisted of amyloid A piotein in 1 9 patients. In two patients without
812, Japan.
Gastroenterology, University, Fukuoka
Five familial
and 1 990, amyloidosis was diagnosed in 46 patients. Of these, 26 had barium studies of the small intestine and jejunal endoscopy with a long [1 0]. In all patients, endoscopic biopsies of the jejunum revealed amyloid
perrnanganate amyloid
20-71 years). symptoms,
malnutrition,
according
were
to the
with severe
[1 1]. Amyloid
The male-to-female such as abdominal present in 24 of the 26
degree of digestive
abdominal
F
polyneuropathy.
pain, frequent
symptoms: diarrhea
TADA
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742
Fig. 1.-A, B, Jejunal
ET
AL.
AJR:156,
April 1991
Double-contrast study of upper jejunum shows multiple fine granular densities and irregularities of Kerckring folds caused by amyloidosis. endoscopy performed with a sprayed dye technique reveals innumerable fine granular elevations. Minute elevations are seen on Kerckring
folds. C, Jejunal magnification
specimen x146)
shows
obvious
amyloid
(amyloid
A protein)
deposition
in lamina
propria
mucosae
Fig. 2.-A, Double-contrast study of jejunum reveals markedly thickened folds and multiple polypoid B, Endoscopy of upperjejunum shows multiple yellow white polypoid protrusions (arrows). C, Biopsy specimen from upper jejunum reveals massive amyloid (amyloid light chain protein) magnification xllO)
(six or more dehydration;
movements per day) (2) mild (13 patients),
or obstruction,
malnutrition,
and
patients with occasional diarrhea (three or fewer movements per day) and mild abdominal pain; (3) moderate (seven patients), in which the severity of symptoms was between that of the severe and mild groups; and (4) no digestive symptoms (two patients). Double-contrast
barium
study
comprising
of the small
intestine
was
performed
as follows, modifying the methods reported by Nakamura et al. [12] and Kobayashi et al. [13]: (1) a duodenal tube with a balloon on the tip was inserted as far as the third portion of the duodenum; (2) the balloon was filled with 15-20 ml of air; (3) 250-350 ml of 60% (w/v) barium sulfate was slowly injected via the tube until the terminal ileum was filled and radiographs were obtained; (4) 700-800 ml of air was injected; (5) an anticholinergic agent (scopolamine butylbromide) was administered IV; and (6) double-contrast radiographs of the small intestine were obtained.
(arrows)
and wide,
blunted
villi. (H and E, original
caused by amyloidosis.
protrusions
(arrows)
deposition
in submucosa.
(Congo
red,
original
The upper jejunum was examined in all patients with a long duodenofiberscope [1 0]. Three to five biopsy specimens were taken from the upper jejunum. Endoscopic examinations were performed at almost the same time as the radiologic examinations in all 26 patients. In all cases, formalin-fixed, paraffin-embedded sections were stained with hematoxylin and eosin or Congo red and examined under polarized light for the presence of green birefringence.
Results Double-contrast
examinations
revealed
innumerable
fine
granular densities 1-3 mm in diameter in 16 patients (Fig. 1A). The findings were accompanied by irregularities of Kerckring folds in 12 patients (Fig. 1A). Multiple erosions were observed
trusions
in eight
patients.
In addition,
4-1 0 mm in diameter
multiple
(Fig. 2A) were
polypoid
present
pro-
in three
AJR:156,
AMYLOIDOSIS
April 1991
Fig. 3.-A,
Double-contrast
radiograph
OF
SMALL
INTESTINE
743
of je-
junum shows multiple nodular densities caused by amyloidosis. B, Endoscopy of upper jejunum shows multipIe nodular elevations and shallow ulcers. C, Jejunal specimen shows obvious amyloid (amyloid A protein) deposition in wall of submucosal vessels. (H and E, original magnification
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x230) D, Follow-up
nutrition
radiograph
therapy
shows
after
total parenteral
that nodular
changes
have disappeared. Multiple fine granular radiolucencies and irregularities of Kerckring folds are faint.
patients and multiple nodular densities 3-4 mm in diameter (Fig. 3A) in four. These findings were observed throughout the small intestine, but were found most often in the jejunum. No abnormalities were seen in three patients. On endoscopy, the fine granular appearance reflected innumerable, somewhat whitish granules of varying size (Fig.
1 B). On biopsy, mucosal granularity
represented
marked amy-
bid deposition in the lamina propria mucosae and wide, blunted villi (Fig. 1 C). Irregularities of Kerckring folds on radiographs corresponded to multiple fine granules located on Kerckring folds (Fig. 1 B). Multiple polypoid protrusions appeared sessile and yellow white compared with surrounding mucosa (Fig. 2B). On biopsy, polypoid protrusions represented massive amyloid deposits in the mucosa and submu-
cosa (Fig. 2C). Multiple
nodular
elevations
were white,
bled
easily when touched, and often were associated with multiple erosions or shallow ulcers (Fig. 3B). On biopsy, the mucosa and submucosa showed the presence of marked edema with inflammatory cells. Marked amyloid deposition in the wall of the submucosal vessels also was evident (Fig. 3C). According to the biochemical categorization of amyloid disease [1 4], the major amyloid fibril proteins are known to
be amyloid light
chain
loidosis.
A protein
in secondary
protein
in primary
and
Our study
revealed
some
amyloidosis
and amyloid
myeloma-associated
differences
amy-
in the prefer-
ential protein
sites and
of amyloid amyloid
light
deposition chain
between protein
types:
the
amyloid
diffuse
A
paren-
chymal deposition in the lamina propria mucosae was observed mainly in the former type (Fig. 1 C), whereas nodular parenchymal deposition in the muscularis mucosa and submucosa was often revealed in the latter type (Fig. 2C). Radiographs of all patients with severe digestive symptoms showed multiple nodular densities and erosions. Radiographs of all patients with moderate digestive symptoms and of 12 patients with mild symptoms demonstrated fine granular densities and irregularity of Kerckring folds, or multiple polypoid protrusions. In two patients with no digestive symptoms and one patient with mild symptoms, no abnormalities were seen on radiographs. The more severe the clinical symptoms, the more remarkable the radiologic changes tended to be. Four patients with severe digestive symptoms received total parenteral nutrition, which led to improvement of subjective symptoms and laboratory data. Double-contrast study of the small intestine 1 .5-7.0 months after the start of therapy revealed that multiple nodular densities and erosions disappeared, but innumerable fine granular densities and irregularities of Kerckring folds were seen more clearly than before (Fig. 3D). Eight patients with moderate or mild digestive symptoms
were
followed
for an average
of 2.7 years
(range,
13-61
744
changed.
radiologic abnormalities, but biopsy specimens enough to lead to a proper understanding structure.
Discussion
ACKNOWLEDGMENT
months).
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toms
During
the follow-up
and radiographs
Gastrointestinal
amyloidosis,
period,
of the small
symptoms
gastrointestinal
intestine
are common
and the digestive
symp-
remained
un-
in patients
with
We thank
Peter
Flaherty
for critical
readings
were not large of the overall
of the manuscript.
tract is often a site of amyloid
deposition [1 2, 1 5]. Gilat et al. [4] reported that gastrointestinal amyloid deposition was found in 68 of 70 autopsied cases of systemic amyloidosis, and amyloid was found to be deposited more frequently in the mucosa of the small intestine than in the stomach or colon. Clinically, patients with amyloid ,
deposits
in the small
intestine
may present
with
diarrhea,
obstruction [1 6, 1 7], malabsorption [5, 1 8], hemorrhage 20], infarction [21 22], and perforation [23, 24]. Seliger et al. [3] compared radiologic features with
[18-
,
logic findings cluded
in small- and large-bowel
that vascular
changes
amyloid
most strongly.
amyloidosis,
deposition
In patients
affected
patho-
and con-
the radiologic
with intestinal
amyloidosis,
the vessel walls are thickened and the lumen is gradually reduced and eventually occluded, leading to ischemia, ulceration, infarction, and even perforation [21 23]. In our patients ,
with severe symptoms, in the submucosal view that multiple
caused
by ischemic
marked
amyloid deposition
was found
vessels (Fig. 3C). This finding supports the nodular densities and erosions may be
changes
in the submucosa.
In our patients with severe symptoms, follow-up radiographs of the small intestine after total parenteral nutrition revealed the disappearance of multiple nodular densities and erosions. However, there was no difference in the amount of amyloid deposits in the biopsy specimens before and after the therapy, thereby suggesting that these findings were secondary and probably resulted from ischemic change as-
sociated
with amyloid
deposition
in the vascular
walls [3, 5,
21]. In contrast, multiple polypoid protrusions, fine granular densities, and irregularities of Kerckring folds remained unchanged during the follow-up period. As elevated lesions on radiographs became more prominent, histologic studies of the biopsy specimens tended to show more remarkable amybid deposits in the mucosa and submucosa of the jejunum.
Therefore, these three radiologic findings may directly amyloid deposition in the mucosa and submucosa.
reflect
Diffuse mucosal granularity in the small intestine was reported by Glick and Teplick [25] in 39 patients with. smallbowel Crohn disease. They described a granular pattern consisting of a diffuse reticular network of round or occasionally angular radiolucent filling defects 0.5-1 .0 mm in diameter.
Recently, lanty
Jones et al. [26] reported
was also demonstrated
other than Crohn disease, glucagonoma,
ischemia.
demonstrated
namely,
protein-losing
Most recently,
a granular tive small
in four
mucosal intestinal
that small-bowel patients
radiation
enteropathy,
Matsumoto
with
granu-
conditions
ileitis, pancreatic and
small-bowel
et al. [27] have reported
pattern in patients with immunoproliferadisease. We found the fine granules
in patients
with small-bowel
amyloidosis
to be
slightly larger and more variable in size than those reported by these authors. Finally, our histologic study showed villous abnormalities such as widening or blunting together with amyloid deposition in the lamina propna mucosae and massive amyloid deposition
in the
submucosa.
These
findings
seem
to affect
the
REFERENCES 1 . Cohen AS. Amyloidosis (concluded). N EngI J Med 1967;277:628-638 2. Kyle RA, Bayrd ED. Amyloidosis: review of 236 cases. Medicine (Baltimore) 1975;54:271-299 3. Seliger G, Krassner RL, Beranbaum ER, Miller F. The spectrum of roentgen appearance in amyloidosis of the small and large bowel: radiologic-pathologic correlation. Radiology 1971;100:63-70 4. Gilat T, Revach M, Sohar E. Deposition of amyloid in the gastrointestinal tract. Gut 1969:10:98-104 5. Pettersson T, Wegelius 0. Biopsy diagnosis of amyloidosis in rheumatoid arthritis: malabsorption caused by intestinal amyloid deposits. Gastroenterology 1972;62:22-27 6. Golden A. Amyloidosis of the small intestine. AJR 1954;72:401-408 7. Pear BL. Radiographic studies of amyloidosis. Crlf Rev Diagn Imaging 1972;3:425-452 8. Legge DA, Carison HC, Wollaeger EE. Roentgenologic appearance of systemic amyloidosis involving gastrointestinal tract. AJR 1970:110: 406-412 9. Marshak RH, Lindner AE. Radiology of the small intestine, 2nd ed. Philadelphia: Saunders, 1976:62-68 1 0. lida M, Yamamoto T, Yao T, Fuchigami T, Fujishima M. Jejunal endoscopy using a long duodenofiberscope. Gastrointest Endosc 1986;32:233-236 1 1 . Wright JR, Calkins E, Humphrey RL. Potassium permanganate reaction in amyloidosis: a histologic method to assist in differentiating forms of this disease. Lab Invest 1977;36:274-281 12. Nakamura U, Tani K, Nakamura T, Yao T, Fuyuno 5, Koga S. X-ray examination of the small intestine by means of duodenal intubation. Stomach Intestine 1974;9: 1461 -1 469 13. Kobayashi 5, Nishizawa M, Mizuno K, et al. Roentgenographic examinations of the small intestine. Rinsho Hoshasen 1974:19:619-625 14. Glenner GG. Amyloid deposits and amyloidosis. The f-fibrilloses. N EngI J Med 1980;302:1283-1292, 1333-1343 15. Tada 5, ida M, Iwashita A, et al. Endoscopic and biopsy findings of the upper digestive tract in patients with amyloidosis. Gastrointest Endosc 1990;36: 10-14 16. Yoshida T, Kanbe H, Haraguchi Y, Sakamoto A, Iwashita T, Tanaka K. Significance of abnormal gastrointestinal gas in systemic amyloidosis. Am J Gastroenterol 1982;77:917-921 17. Wald A, Kickler J, Mendelow H. Amyloidosis and chronic intestinal pseudoobstruction. Dig Dis Sci 1981:26:462-465 1 8. Jamum S. Gastrointestinal haemorrhage and protein loss in primary amyloidosis. Gut 1965;6:14-18 1 9. Long L, Mahony TO, Jewell WA. Selective amyloidosis of the jejunum: case report of a rare cause for gastrointestinal bleeding. Am J Surg 1965;109:217-220
20. Levy DJ, Franklin GO, Rosenthal WS. Gastrointestinal loidosis.
bleeding and amy-
Am J Gastroenterol
1982;77:422-426 21. Mallory A, Struthers JE Jr, Kern F Jr. Persistent hypotension and intestinal infarction in a patient with primary amyloidosis. Gastroenterology 1975:68:1587-1592 22. Choi HH, Heller D, Picken MM, Sidhu GS, Kahn T. Infarction of intestine with massive amyloid deposition in two patients on long-term hemodialysis. Gastroenterology 1989;96:230-234 23. Gilat T, Spiro H. Amyloidosis and the gut. Dig Dis Sci 1968;13:619-633 24. Griffel B, Man B, Kraus L. Selective massive amyloidosis of small intestine. 25.
Arch Surg 1978;1 10:215-217 Glick SN, Teplick 5K. Crohn disease of the small intestine: granularity. Radiology 1985;154:313-317
diffuse
mucosal
26. Jones B, Hamilton SR, Rubesin SE, Bayless TM, Ravich WJ, Hendnx TR. Granular small bowel mucosa: test Radiol 1987;12:219-225
27. Matsumoto
a reflection
of villous
abnormality.
T, lida M, Matsui T, Tanaka H, Fujishima
Gastroin-
M. The value of
double-contrast study of the small intestine in immunoproliferative intestinal disease. Gastrointest Radiol 1990:15: 159-1 63
small
741
Amyloidosis Findings
Shuji Tada1 Mitsuo lida1 Toshiyuki Matsui1 Tadahiko Fuchigami2 Akinori Iwashita3 T I
I.
SUflfOSi
V
ul
Masatoshi
,
Fujlshlma
on Double-Contrast
Intestine: Radiographs
The appearance of the small intestinal mucosa on double-contrast barium examinations was studied in 26 patients with proved intestinal amyloidosis. Findings included innumerable fine granular densities 1-3 mm in diameter (16 patients), multiple nodular densities 3-4 mm in diameter (four patients), multiple polypoid protrusions 4-10 mm in diameter (three patients), irregularities of Kercknng folds (12 patients), and multiple 4
ao
of the Small
erosions
(eight
patients). The multiple treated with total
the patients were maineci unchanged
on follow-up
nodular densities and erosions disappeared parenteral nutrition. The other abnormalities
examinations.
after re-
Our results indicate that double-contrast radiographic findings of the small intestine in patients with amyloidosis include mucosal abnormalities that vary according to the pathologic type of amyloid deposition. AJR
156:741-744,
April 1991
Amyloidosis commonly involves the gastrointestinal tract, resulting in a wide variety of clinical and radiologic manifestations [1 -3]. The small intestine is the most frequent site [4, 5]. Radiographs of the small intestine reflect the morphologic changes in this disease [6-8].
Numerous
reports
have
described
the radiologic
findings
of small
intestinal
amyloidosis; emphasis has been given to thickening of the valvulae conniventes and decreased intestinal motility [6-9]. However, these radiologic findings are not
specific and are not useful in the differentiation
of amyloidosis
from other diseases.
In the present study, we analyzed the findings of amyloidosis on double-contrast barium examinations of the small intestine and compared them with clinical symptoms, endoscopy, and biopsy findings. Materials
and
Methods
1978
Between
both double-contrast duodenofiberscope Received July 5, 1990; accepted October 16, 1990. 1 Department of Internal Medicine versity, Japan. 2
Maidashi
3-1-1
,
Higashi-ku,
revision
Department
Fukuoka
of Pathology,
University,
Department of Hospital of Fukuoka pan. 4
0361-803x/91/1564-0741 © American Roentgen
Fukuoka
derxsition. one had
II, Kyushu
Uni-
Crohn
Fukuoka
812,
Higashi
Address reprint requests to S. Tada. Department of Gastroenterology, Matsuyama
Red Cross Hospital, Matsuyama 3
after
790, Japan. Chikushi
Hospital
protein The
Chikushi 812, Ja-
in two,
syndrome
for Congo of
primary amyloidosis, three had myeloma-associated and 1 7 had secondary amyloidosis (rheumatoid
unclassified
in one,
intestinal
ankylosing
red was reduced
was
ulcers
spondylitis
in one
patient
age
patients
was
average
(1
.
patients
) severe
(four
of the
At the time hemorrhage,
were
divided
patients),
of examination,
into
four
and
type
potassium I familial
45 years (range, gastrointestinal and
groups
patients
myositis
pulmonary
amyloidosis, arthritis in 10,
in one, Ch#{233}diak-
tuberculosis
in one).
light chain protein in six patients and amyloid an antecedent or coexisting disease, affinity
with
with
obstruction,
comprising
in one, multiple
in one,
after treatment
demonstrated
ratio was 1 :1 pain, diarrhea, patients. The
Ray Society
disease
patients had amyloidosis,
Principal amyloid proteins consisted of amyloid A piotein in 1 9 patients. In two patients without
812, Japan.
Gastroenterology, University, Fukuoka
Five familial
and 1 990, amyloidosis was diagnosed in 46 patients. Of these, 26 had barium studies of the small intestine and jejunal endoscopy with a long [1 0]. In all patients, endoscopic biopsies of the jejunum revealed amyloid
perrnanganate amyloid
20-71 years). symptoms,
malnutrition,
according
were
to the
with severe
[1 1]. Amyloid
The male-to-female such as abdominal present in 24 of the 26
degree of digestive
abdominal
F
polyneuropathy.
pain, frequent
symptoms: diarrhea
TADA
Downloaded from www.ajronline.org by 49.0.110.102 on 11/12/15 from IP address 49.0.110.102. Copyright ARRS. For personal use only; all rights reserved
742
Fig. 1.-A, B, Jejunal
ET
AL.
AJR:156,
April 1991
Double-contrast study of upper jejunum shows multiple fine granular densities and irregularities of Kerckring folds caused by amyloidosis. endoscopy performed with a sprayed dye technique reveals innumerable fine granular elevations. Minute elevations are seen on Kerckring
folds. C, Jejunal magnification
specimen x146)
shows
obvious
amyloid
(amyloid
A protein)
deposition
in lamina
propria
mucosae
Fig. 2.-A, Double-contrast study of jejunum reveals markedly thickened folds and multiple polypoid B, Endoscopy of upperjejunum shows multiple yellow white polypoid protrusions (arrows). C, Biopsy specimen from upper jejunum reveals massive amyloid (amyloid light chain protein) magnification xllO)
(six or more dehydration;
movements per day) (2) mild (13 patients),
or obstruction,
malnutrition,
and
patients with occasional diarrhea (three or fewer movements per day) and mild abdominal pain; (3) moderate (seven patients), in which the severity of symptoms was between that of the severe and mild groups; and (4) no digestive symptoms (two patients). Double-contrast
barium
study
comprising
of the small
intestine
was
performed
as follows, modifying the methods reported by Nakamura et al. [12] and Kobayashi et al. [13]: (1) a duodenal tube with a balloon on the tip was inserted as far as the third portion of the duodenum; (2) the balloon was filled with 15-20 ml of air; (3) 250-350 ml of 60% (w/v) barium sulfate was slowly injected via the tube until the terminal ileum was filled and radiographs were obtained; (4) 700-800 ml of air was injected; (5) an anticholinergic agent (scopolamine butylbromide) was administered IV; and (6) double-contrast radiographs of the small intestine were obtained.
(arrows)
and wide,
blunted
villi. (H and E, original
caused by amyloidosis.
protrusions
(arrows)
deposition
in submucosa.
(Congo
red,
original
The upper jejunum was examined in all patients with a long duodenofiberscope [1 0]. Three to five biopsy specimens were taken from the upper jejunum. Endoscopic examinations were performed at almost the same time as the radiologic examinations in all 26 patients. In all cases, formalin-fixed, paraffin-embedded sections were stained with hematoxylin and eosin or Congo red and examined under polarized light for the presence of green birefringence.
Results Double-contrast
examinations
revealed
innumerable
fine
granular densities 1-3 mm in diameter in 16 patients (Fig. 1A). The findings were accompanied by irregularities of Kerckring folds in 12 patients (Fig. 1A). Multiple erosions were observed
trusions
in eight
patients.
In addition,
4-1 0 mm in diameter
multiple
(Fig. 2A) were
polypoid
present
pro-
in three
AJR:156,
AMYLOIDOSIS
April 1991
Fig. 3.-A,
Double-contrast
radiograph
OF
SMALL
INTESTINE
743
of je-
junum shows multiple nodular densities caused by amyloidosis. B, Endoscopy of upper jejunum shows multipIe nodular elevations and shallow ulcers. C, Jejunal specimen shows obvious amyloid (amyloid A protein) deposition in wall of submucosal vessels. (H and E, original magnification
Downloaded from www.ajronline.org by 49.0.110.102 on 11/12/15 from IP address 49.0.110.102. Copyright ARRS. For personal use only; all rights reserved
x230) D, Follow-up
nutrition
radiograph
therapy
shows
after
total parenteral
that nodular
changes
have disappeared. Multiple fine granular radiolucencies and irregularities of Kerckring folds are faint.
patients and multiple nodular densities 3-4 mm in diameter (Fig. 3A) in four. These findings were observed throughout the small intestine, but were found most often in the jejunum. No abnormalities were seen in three patients. On endoscopy, the fine granular appearance reflected innumerable, somewhat whitish granules of varying size (Fig.
1 B). On biopsy, mucosal granularity
represented
marked amy-
bid deposition in the lamina propria mucosae and wide, blunted villi (Fig. 1 C). Irregularities of Kerckring folds on radiographs corresponded to multiple fine granules located on Kerckring folds (Fig. 1 B). Multiple polypoid protrusions appeared sessile and yellow white compared with surrounding mucosa (Fig. 2B). On biopsy, polypoid protrusions represented massive amyloid deposits in the mucosa and submu-
cosa (Fig. 2C). Multiple
nodular
elevations
were white,
bled
easily when touched, and often were associated with multiple erosions or shallow ulcers (Fig. 3B). On biopsy, the mucosa and submucosa showed the presence of marked edema with inflammatory cells. Marked amyloid deposition in the wall of the submucosal vessels also was evident (Fig. 3C). According to the biochemical categorization of amyloid disease [1 4], the major amyloid fibril proteins are known to
be amyloid light
chain
loidosis.
A protein
in secondary
protein
in primary
and
Our study
revealed
some
amyloidosis
and amyloid
myeloma-associated
differences
amy-
in the prefer-
ential protein
sites and
of amyloid amyloid
light
deposition chain
between protein
types:
the
amyloid
diffuse
A
paren-
chymal deposition in the lamina propria mucosae was observed mainly in the former type (Fig. 1 C), whereas nodular parenchymal deposition in the muscularis mucosa and submucosa was often revealed in the latter type (Fig. 2C). Radiographs of all patients with severe digestive symptoms showed multiple nodular densities and erosions. Radiographs of all patients with moderate digestive symptoms and of 12 patients with mild symptoms demonstrated fine granular densities and irregularity of Kerckring folds, or multiple polypoid protrusions. In two patients with no digestive symptoms and one patient with mild symptoms, no abnormalities were seen on radiographs. The more severe the clinical symptoms, the more remarkable the radiologic changes tended to be. Four patients with severe digestive symptoms received total parenteral nutrition, which led to improvement of subjective symptoms and laboratory data. Double-contrast study of the small intestine 1 .5-7.0 months after the start of therapy revealed that multiple nodular densities and erosions disappeared, but innumerable fine granular densities and irregularities of Kerckring folds were seen more clearly than before (Fig. 3D). Eight patients with moderate or mild digestive symptoms
were
followed
for an average
of 2.7 years
(range,
13-61
744
changed.
radiologic abnormalities, but biopsy specimens enough to lead to a proper understanding structure.
Discussion
ACKNOWLEDGMENT
months).
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toms
During
the follow-up
and radiographs
Gastrointestinal
amyloidosis,
period,
of the small
symptoms
gastrointestinal
intestine
are common
and the digestive
symp-
remained
un-
in patients
with
We thank
Peter
Flaherty
for critical
readings
were not large of the overall
of the manuscript.
tract is often a site of amyloid
deposition [1 2, 1 5]. Gilat et al. [4] reported that gastrointestinal amyloid deposition was found in 68 of 70 autopsied cases of systemic amyloidosis, and amyloid was found to be deposited more frequently in the mucosa of the small intestine than in the stomach or colon. Clinically, patients with amyloid ,
deposits
in the small
intestine
may present
with
diarrhea,
obstruction [1 6, 1 7], malabsorption [5, 1 8], hemorrhage 20], infarction [21 22], and perforation [23, 24]. Seliger et al. [3] compared radiologic features with
[18-
,
logic findings cluded
in small- and large-bowel
that vascular
changes
amyloid
most strongly.
amyloidosis,
deposition
In patients
affected
patho-
and con-
the radiologic
with intestinal
amyloidosis,
the vessel walls are thickened and the lumen is gradually reduced and eventually occluded, leading to ischemia, ulceration, infarction, and even perforation [21 23]. In our patients ,
with severe symptoms, in the submucosal view that multiple
caused
by ischemic
marked
amyloid deposition
was found
vessels (Fig. 3C). This finding supports the nodular densities and erosions may be
changes
in the submucosa.
In our patients with severe symptoms, follow-up radiographs of the small intestine after total parenteral nutrition revealed the disappearance of multiple nodular densities and erosions. However, there was no difference in the amount of amyloid deposits in the biopsy specimens before and after the therapy, thereby suggesting that these findings were secondary and probably resulted from ischemic change as-
sociated
with amyloid
deposition
in the vascular
walls [3, 5,
21]. In contrast, multiple polypoid protrusions, fine granular densities, and irregularities of Kerckring folds remained unchanged during the follow-up period. As elevated lesions on radiographs became more prominent, histologic studies of the biopsy specimens tended to show more remarkable amybid deposits in the mucosa and submucosa of the jejunum.
Therefore, these three radiologic findings may directly amyloid deposition in the mucosa and submucosa.
reflect
Diffuse mucosal granularity in the small intestine was reported by Glick and Teplick [25] in 39 patients with. smallbowel Crohn disease. They described a granular pattern consisting of a diffuse reticular network of round or occasionally angular radiolucent filling defects 0.5-1 .0 mm in diameter.
Recently, lanty
Jones et al. [26] reported
was also demonstrated
other than Crohn disease, glucagonoma,
ischemia.
demonstrated
namely,
protein-losing
Most recently,
a granular tive small
in four
mucosal intestinal
that small-bowel patients
radiation
enteropathy,
Matsumoto
with
granu-
conditions
ileitis, pancreatic and
small-bowel
et al. [27] have reported
pattern in patients with immunoproliferadisease. We found the fine granules
in patients
with small-bowel
amyloidosis
to be
slightly larger and more variable in size than those reported by these authors. Finally, our histologic study showed villous abnormalities such as widening or blunting together with amyloid deposition in the lamina propna mucosae and massive amyloid deposition
in the
submucosa.
These
findings
seem
to affect
the
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small
