0016-5107/90/3604-0376$02.00
GASTROINTESTINAL ENDOSCOPY Copyright © 1990 by the American Society for Gastrointestinal Endoscopy
Endoscopic appearance and significance of functional lymphangiectasia of the duodenal mucosa Atulkumar S. Patel, MD Peter H. DeRidder, MD, FACP, FACG Royal Oak, Michigan
Intestinal lymphangiectasia is found in a wide variety of pathologic conditions. Functional lymphangiectasia has not been well characterized. We report 20 patients followed for 9 to 55 months (mean 30 months) after incidental detection at endoscopy of lymphangiectasia. Our study indicates that functional lymphangiectasia is not pathologic and does not warrant repeat endoscopy in the absence of other clinical indications. (Gastrointest Endosc 1990;36:376-378)
Intestinal lymphangiectasia (lL) is characterized by focal dilation of intestinal mucosa and submucosa. The endoscopic appearance is that of tiny whitetipped villi in the duodenum (Fig. 1). A wide body of literature exists (1-9) describing various pathologic types of IL. An idiopathic form is associated with malabsorption and excessive protein loss in the digestive tract. Secondary forms can be seen associated with various neoplastic, infiltrative, or inflammatory disorders involving the intestinal lymphatic system. We describe 20 patients with functional duodenal lymphangiectasia detected incidentally over a 5-year period.
30 months (9 to 55 months). A majority ofthe patients were being evaluated for abdominal pain (Table 1), and the radiology studies performed on most patients were negative, with the exception of one patient (7) with mild thickening of the gastric folds on the upper GI series not confirmed at endoscopy, and another (12) with an antral polyp. In four patients who underwent three endoscopies (Table 1), lymphangiectasia was not demonstrated at each examination. Repeat endoscopy was not performed in the remaining patients due to the lack of clinical indication. In addition, all had normal fasting cholesterol, triglycerides, albumin, and lymphocyte count levels, and none exhibited any stigmata suggestive of malabsorption.
METHODS
The clinical case summaries of consecutive patients with endoscopic and histologic duodenal lymphangiectasia discovered incidentally were reviewed. All patients had fasted for more than 12 hours prior to the procedure. In each case, the diagnosis was confirmed by obtaining a biopsy of the affected area that showed dilated lacteals (Fig. 2). RESULTS
Twenty patients were found to meet the above criteria including 2 men and 18 women. The average age ofthe patients was 57 years (range, 14 to 94 years). The mean duration of follow-up after detection was Received April 1, 1989. For revision October 8, 1989. Accepted February 26, 1990. From the Division of Gastroenterology, William Beaumont Hospital, Royal Oak, Michigan. Reprint address: Peter A. DeRidder, MD, William Beamont Hospital, 3601 W. 13 Mile Rd., Royal Oak, Michigan 48072.
376
DISCUSSION
Fat transport in the small intestine generally involves a series of coordinated chemical reactions. These include hydrolysis, and reconstitution of triglycerides which are then eventually secreted into the intestinallacteals as chylomicrons. Lacteals are usually dilated during active absorption. They measure 20 p.m in diameter, lie beneath the epithelial cells, and eventually joint the submucosal lymphatic plexus, leaving the mesentery in association with blood vessels. Waldmann et al. 7 first described idiopathic hypoproteinemia due to intestinal lymphangiectasia in 15 patients. The majority of these patients had hypoproteinemia, edema, diarrhea, and abnormal fecal fat output: at postmortem examination patients also had dilated serosal lymphatics and villi with whitish tips GASTROINTESTINAL ENDOSCOPY
Figure 1. Endoscopic photograph of the duodenum showing tiny white pebble-like lesions, which histologically showed lymphangiectasia.
Figure 2. Section of the duodenal mucosa showing dilated lacteals (long arrows) within the villous stroma. Traumatic artifacts resembling dilated lacteals (short arrows) are also present (hematoxylin and eosin; original magnification X16).
which were variable in size. The protein loss was attributed to either rupture of the lymphatics and subsequent luminal loss, or extravasation from an intact, but more distally obstructed vessel. A congenital malformation was postulated to be the most likely etiology. Mistilis et al. 4 in addition, also demonstrated dilated lymphatics with retrograde lymph flow in a patient with idiopathic lymphangiectasia. The present study involved only mucosal biopsies obtained at endoscopy, and we were unable to ascertain whether the serosal lymphatics were affected. However, no radioVOLUME 36, NO.4, 1990
logic or clinical evidence suggested serosal involvement. Secondary forms of intestinal lymphangiectasia are due to various inflammatory, neoplastic, or infectious etiologies. Lymphangiectasia occurs in these instances predominantly due to obstruction of the lymphatic flow. Typical laboratory values in these patients include hypoproteinemia and lymphocytopenia. Severe gastrointestinal protein loss and associated decreased survival time for albumin is described. 5 Lymphangiograms may show significant hypoplasia of the peripherallymphatics with dermal backflow. 5 The concept of functional lymphangiectasia was first put forward by Fempell et al. lO who described diffuse transient lymphangiectasia in the duodenal biopsies of normal volunteers who had nasogastric instillation of olive oil. They showed that at 4 hours, and there was marked basal intercellular dilation with extensive lymphedema. The villi became prominent with a whitish subepithelial engorgement. These findings were no longer visible 14 hours later. They concluded that the finding was probably due to a functional disturbance of fat transport. A similar method has been used since to diagnose suspected primary IL. 2 The significance of functional duodenal lymphangiectasia detected at endoscopy is not clear. Unlike its demonstration by Fempell et al. lO in healthy individuals after olive oil instillation, the finding of lymphangiectasia in fasting patients, as in our study, remains unexplained. One possible etiology may be transient disturbance of fat transport. Other as yet undefined factors such as vascular, hormonal, or other chemical mediators are also possible. Interestingly, none of our patients have exhibited any of the pathologic conditions associated with primary or secondary IL and all continue to do well clinically. This finding may be transient and reversible as demonstrated in one patient who underwent three endoscopies and had lymphangiectasia detected at the first and third examinations but not the second. IL should be distinguished from lymphangiectatic cysts, a benign condition which can be found in the small intestine of up to 20% of the population. l l In an extensive review, Shilkin et al. l l describe the major characteristics of this entity: occurrence in older individuals (>50 years), submucosal location, variation in size, and unilocular architecture. The inner endothelial lining resembles lymphatic vascular endothelium, and a collagen fibrous capsule may be present. Functional lymphangiectasia of the duodenum is very likely a benign finding which may be present in the fasting state and also after fat ingestion. Its presence does not necessarily indicate a pathologic diagnosis and does not warrant repeat endoscopy in the absence of other clinical indications. 377
Table 1. Patients with functional duodenal lymphangiectasia Patient
Sex
Age
Reason for EGD
1
M
58
Surveillance
UGI- b US-
2
M
42
Abdominal pain
3
F
60
Abdominal pain
4 5 6
F F F
92 14 64
Anemia Abdominal pain Dyspepsia
7
F
80
Abdominal pain
8
F
79
Abdominal pain
USBEUSUGIUSUGIUGIUSBEUGI+ USUS-
9
F
32
Abdominal pain
10 12 13
F F F F
28 57 89 42
Abdominal pain Abdominal pain Anemia Dysphagia
14
F
54
Dyspepsia
15
F
25
Surveillance
UGIUSBEUGIUGI+ UGIUSERCP UGICTNone
16
F
76
Dysphagia
None
17
F
68
Surveillance
18
F
39
Abdominal pain
19
F
81
Abdominal pain
20
F
61
Dyspepsia
USCTUGIUSUSBEUGI-
11
Radiologya
Year EGD performed
Follow-up (mo) after detection
83 84 86' 85 e
35
46
86'
39
86' 84' 85'
33 54 37
88'
9
84 e 86 88 e 86'
55
86' 86' 85' 86'
31 27 31 33
87'
27
85 87 88' 86 86 88' 87'
11
27
86'
9
86'
35
87'
13
33
9
UGI, upper gastrointestinal; US, ultrasound; BE, barium enema. b _, normal study; +, abnormal study. , Detection of lymphangiectasia.
a
REFERENCES 1. Riemann JF, Schmidt H. Synopsis of endoscopic and other morphological finding in intestinal lymphangiectasia. Endoscopy 1981;13:60-3. 2. Veldhuyzen Van Zanten SJO, Bartelsman JFWM, Tytgat GNJ. Endoscopic diagnosis of primary intestinal lymphangiectasia using a high fat meal. Endoscopy 1986;18:108-10. 3. Whitehead R. Intestinal lymphangiectasia. In: Bennington JL, ed. Mucosa biopsy ofthe GI tract. 3rd ed. Vol 3. Philadelphia: WB Saunders, 1985:181-3. 4. Mistilis SP, Skyring AP, Stephen DD. Intestinallymphangiectasia. Mechanism of enteric loss of plasma protein and fat. Lancet 1965;1:77-80. 5. Waldmann TA. Protein losing enteropathy. Gastroenterology 1966;50:422-43.
378
6. Pomerantz M, Waldmann TA. Systemic lymphatic abnormalities associated with gastrointestinal protein loss secondary to intestinal lymphangiectasia. Gastroenterology 1963;45:703-11. 7. Waldmann TA, Steinfeld JL, Dutcher TF, Davidson JD, Gordon RS. The role of the gastrointestinal system in idiopathic hypoproteinemia. Gastroenterology 1961;41:197-207. 8. Roberts SH, Douglas AP. Intestinal lymphangiectasia: the variability of presentation. A study of five cases. Q J Med 1976;177:39-48. 9. Olmsted WW, Madewell JE. Lymphangiectasia of the small intestine. Description and pathophysiology of the roentgenographic signs. Gastrointest RadioI1976;1:241-3. 10. Fempell J, Lux G, Kaduk B, Roesch W. Functionallymphangiectasia of the duodenal mucosa. Endoscopy 1978;10:44-6. 11. Shilkin KB, Zerman BJ, Blackwell JB. Lymphangiectatic cysts of the small bowel. J Pathol Bacterol 1968;96:353-8.
GASTROINTESTINAL ENDOSCOPY
GASTROINTESTINAL ENDOSCOPY Copyright © 1990 by the American Society for Gastrointestinal Endoscopy
Endoscopic appearance and significance of functional lymphangiectasia of the duodenal mucosa Atulkumar S. Patel, MD Peter H. DeRidder, MD, FACP, FACG Royal Oak, Michigan
Intestinal lymphangiectasia is found in a wide variety of pathologic conditions. Functional lymphangiectasia has not been well characterized. We report 20 patients followed for 9 to 55 months (mean 30 months) after incidental detection at endoscopy of lymphangiectasia. Our study indicates that functional lymphangiectasia is not pathologic and does not warrant repeat endoscopy in the absence of other clinical indications. (Gastrointest Endosc 1990;36:376-378)
Intestinal lymphangiectasia (lL) is characterized by focal dilation of intestinal mucosa and submucosa. The endoscopic appearance is that of tiny whitetipped villi in the duodenum (Fig. 1). A wide body of literature exists (1-9) describing various pathologic types of IL. An idiopathic form is associated with malabsorption and excessive protein loss in the digestive tract. Secondary forms can be seen associated with various neoplastic, infiltrative, or inflammatory disorders involving the intestinal lymphatic system. We describe 20 patients with functional duodenal lymphangiectasia detected incidentally over a 5-year period.
30 months (9 to 55 months). A majority ofthe patients were being evaluated for abdominal pain (Table 1), and the radiology studies performed on most patients were negative, with the exception of one patient (7) with mild thickening of the gastric folds on the upper GI series not confirmed at endoscopy, and another (12) with an antral polyp. In four patients who underwent three endoscopies (Table 1), lymphangiectasia was not demonstrated at each examination. Repeat endoscopy was not performed in the remaining patients due to the lack of clinical indication. In addition, all had normal fasting cholesterol, triglycerides, albumin, and lymphocyte count levels, and none exhibited any stigmata suggestive of malabsorption.
METHODS
The clinical case summaries of consecutive patients with endoscopic and histologic duodenal lymphangiectasia discovered incidentally were reviewed. All patients had fasted for more than 12 hours prior to the procedure. In each case, the diagnosis was confirmed by obtaining a biopsy of the affected area that showed dilated lacteals (Fig. 2). RESULTS
Twenty patients were found to meet the above criteria including 2 men and 18 women. The average age ofthe patients was 57 years (range, 14 to 94 years). The mean duration of follow-up after detection was Received April 1, 1989. For revision October 8, 1989. Accepted February 26, 1990. From the Division of Gastroenterology, William Beaumont Hospital, Royal Oak, Michigan. Reprint address: Peter A. DeRidder, MD, William Beamont Hospital, 3601 W. 13 Mile Rd., Royal Oak, Michigan 48072.
376
DISCUSSION
Fat transport in the small intestine generally involves a series of coordinated chemical reactions. These include hydrolysis, and reconstitution of triglycerides which are then eventually secreted into the intestinallacteals as chylomicrons. Lacteals are usually dilated during active absorption. They measure 20 p.m in diameter, lie beneath the epithelial cells, and eventually joint the submucosal lymphatic plexus, leaving the mesentery in association with blood vessels. Waldmann et al. 7 first described idiopathic hypoproteinemia due to intestinal lymphangiectasia in 15 patients. The majority of these patients had hypoproteinemia, edema, diarrhea, and abnormal fecal fat output: at postmortem examination patients also had dilated serosal lymphatics and villi with whitish tips GASTROINTESTINAL ENDOSCOPY
Figure 1. Endoscopic photograph of the duodenum showing tiny white pebble-like lesions, which histologically showed lymphangiectasia.
Figure 2. Section of the duodenal mucosa showing dilated lacteals (long arrows) within the villous stroma. Traumatic artifacts resembling dilated lacteals (short arrows) are also present (hematoxylin and eosin; original magnification X16).
which were variable in size. The protein loss was attributed to either rupture of the lymphatics and subsequent luminal loss, or extravasation from an intact, but more distally obstructed vessel. A congenital malformation was postulated to be the most likely etiology. Mistilis et al. 4 in addition, also demonstrated dilated lymphatics with retrograde lymph flow in a patient with idiopathic lymphangiectasia. The present study involved only mucosal biopsies obtained at endoscopy, and we were unable to ascertain whether the serosal lymphatics were affected. However, no radioVOLUME 36, NO.4, 1990
logic or clinical evidence suggested serosal involvement. Secondary forms of intestinal lymphangiectasia are due to various inflammatory, neoplastic, or infectious etiologies. Lymphangiectasia occurs in these instances predominantly due to obstruction of the lymphatic flow. Typical laboratory values in these patients include hypoproteinemia and lymphocytopenia. Severe gastrointestinal protein loss and associated decreased survival time for albumin is described. 5 Lymphangiograms may show significant hypoplasia of the peripherallymphatics with dermal backflow. 5 The concept of functional lymphangiectasia was first put forward by Fempell et al. lO who described diffuse transient lymphangiectasia in the duodenal biopsies of normal volunteers who had nasogastric instillation of olive oil. They showed that at 4 hours, and there was marked basal intercellular dilation with extensive lymphedema. The villi became prominent with a whitish subepithelial engorgement. These findings were no longer visible 14 hours later. They concluded that the finding was probably due to a functional disturbance of fat transport. A similar method has been used since to diagnose suspected primary IL. 2 The significance of functional duodenal lymphangiectasia detected at endoscopy is not clear. Unlike its demonstration by Fempell et al. lO in healthy individuals after olive oil instillation, the finding of lymphangiectasia in fasting patients, as in our study, remains unexplained. One possible etiology may be transient disturbance of fat transport. Other as yet undefined factors such as vascular, hormonal, or other chemical mediators are also possible. Interestingly, none of our patients have exhibited any of the pathologic conditions associated with primary or secondary IL and all continue to do well clinically. This finding may be transient and reversible as demonstrated in one patient who underwent three endoscopies and had lymphangiectasia detected at the first and third examinations but not the second. IL should be distinguished from lymphangiectatic cysts, a benign condition which can be found in the small intestine of up to 20% of the population. l l In an extensive review, Shilkin et al. l l describe the major characteristics of this entity: occurrence in older individuals (>50 years), submucosal location, variation in size, and unilocular architecture. The inner endothelial lining resembles lymphatic vascular endothelium, and a collagen fibrous capsule may be present. Functional lymphangiectasia of the duodenum is very likely a benign finding which may be present in the fasting state and also after fat ingestion. Its presence does not necessarily indicate a pathologic diagnosis and does not warrant repeat endoscopy in the absence of other clinical indications. 377
Table 1. Patients with functional duodenal lymphangiectasia Patient
Sex
Age
Reason for EGD
1
M
58
Surveillance
UGI- b US-
2
M
42
Abdominal pain
3
F
60
Abdominal pain
4 5 6
F F F
92 14 64
Anemia Abdominal pain Dyspepsia
7
F
80
Abdominal pain
8
F
79
Abdominal pain
USBEUSUGIUSUGIUGIUSBEUGI+ USUS-
9
F
32
Abdominal pain
10 12 13
F F F F
28 57 89 42
Abdominal pain Abdominal pain Anemia Dysphagia
14
F
54
Dyspepsia
15
F
25
Surveillance
UGIUSBEUGIUGI+ UGIUSERCP UGICTNone
16
F
76
Dysphagia
None
17
F
68
Surveillance
18
F
39
Abdominal pain
19
F
81
Abdominal pain
20
F
61
Dyspepsia
USCTUGIUSUSBEUGI-
11
Radiologya
Year EGD performed
Follow-up (mo) after detection
83 84 86' 85 e
35
46
86'
39
86' 84' 85'
33 54 37
88'
9
84 e 86 88 e 86'
55
86' 86' 85' 86'
31 27 31 33
87'
27
85 87 88' 86 86 88' 87'
11
27
86'
9
86'
35
87'
13
33
9
UGI, upper gastrointestinal; US, ultrasound; BE, barium enema. b _, normal study; +, abnormal study. , Detection of lymphangiectasia.
a
REFERENCES 1. Riemann JF, Schmidt H. Synopsis of endoscopic and other morphological finding in intestinal lymphangiectasia. Endoscopy 1981;13:60-3. 2. Veldhuyzen Van Zanten SJO, Bartelsman JFWM, Tytgat GNJ. Endoscopic diagnosis of primary intestinal lymphangiectasia using a high fat meal. Endoscopy 1986;18:108-10. 3. Whitehead R. Intestinal lymphangiectasia. In: Bennington JL, ed. Mucosa biopsy ofthe GI tract. 3rd ed. Vol 3. Philadelphia: WB Saunders, 1985:181-3. 4. Mistilis SP, Skyring AP, Stephen DD. Intestinallymphangiectasia. Mechanism of enteric loss of plasma protein and fat. Lancet 1965;1:77-80. 5. Waldmann TA. Protein losing enteropathy. Gastroenterology 1966;50:422-43.
378
6. Pomerantz M, Waldmann TA. Systemic lymphatic abnormalities associated with gastrointestinal protein loss secondary to intestinal lymphangiectasia. Gastroenterology 1963;45:703-11. 7. Waldmann TA, Steinfeld JL, Dutcher TF, Davidson JD, Gordon RS. The role of the gastrointestinal system in idiopathic hypoproteinemia. Gastroenterology 1961;41:197-207. 8. Roberts SH, Douglas AP. Intestinal lymphangiectasia: the variability of presentation. A study of five cases. Q J Med 1976;177:39-48. 9. Olmsted WW, Madewell JE. Lymphangiectasia of the small intestine. Description and pathophysiology of the roentgenographic signs. Gastrointest RadioI1976;1:241-3. 10. Fempell J, Lux G, Kaduk B, Roesch W. Functionallymphangiectasia of the duodenal mucosa. Endoscopy 1978;10:44-6. 11. Shilkin KB, Zerman BJ, Blackwell JB. Lymphangiectatic cysts of the small bowel. J Pathol Bacterol 1968;96:353-8.
GASTROINTESTINAL ENDOSCOPY
