Histopathology 1978, 2, 349-361
Inflammatory fibroid polyp of the gastrointestha1 tract J . M. J O H N ST O N E * & B . C . M O R S O N Departments of Pathology, General Hospital, Grimsby, and St. Mark’s Hospital, London Accepted for publication 7 May 1978 JOHNSTONE J.M.& MORSONB.C. (1978) Histopathology
2,
349361
Inflammatory fibroid polyp of the gastrointestinal tract Details of 1 3 new cases of inflammatory fibroid polyp of the gastrointestinal tract and of 76 patients recorded in the literature (total 89) are described and analysed. The lesion is always benign, may occur at any age but is commonest in the sixth and seventh decades, and involves the stomach most frequently. Abdominal pain, often related to obstruction, is the principal symptom. Eosinophilia of the peripheral blood does not occur. The lesions are sessile or polypoidal, originate in the gut submucosa, vary greatly in cellularity, and have a wide range of tissue eosinophilia. Some are very vascular, many of the larger vessels having a notably broad zone of connective tissue about them. The aetiology of the condition is discussed and reasons for distinguishing it from eosinophilic gastroenteritis, with which it is frequently confused, are given. The precise nature and aetiology of the inflammatory fibroid polyp remains undetermined. Keywords : polyp fibroid, polyp inflammatory, gastrointestinal polyp
Introduction Inflammatory fibroid polyp is a simple, localized lesion which arises in the submucosa of the gastrointestinal tract, principally the stomach, and has, in its connective tissue stroma, a variable degree of eosinophilic infiltration. First described by Vanek (1949) as a gastric submucosal granuloma with eosinophilic infiltration, many other names have been applied subsequently and include such terms as eosinophilic granuloma, inflammatory fibroid polyp, granuloma with eosinophils, ‘hemangiopericytoma’, inflammatory pseudotumour, gastric fibroma with eosinophilic infiltration, eosinophilic gastroenteritis, polyp with eosinophilic granuloma, and others. The lesion has been reported in the United Kingdom, in many European countries, in North and South America, and in Israel (see bibliography). * Address for correspondence : Dr J.M. Johnstone, Department of Pathology, General Hospital, Grimsby, South Humberside DN31 ITZ. 0309-0167/78/090~0349$02.00 01978 Blackwell Scientific Publications
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In this report details of 1 3 further examples of the lesion are given, the literature on the subject is reviewed, and the distinction between inflammatory fibroid polyp and eosinophilic gastroenteritis, a condition with which it is frequently associated and confused, is emphasized.
Materials and methods Material from I 3 previously unreported examples of inflammatory fibroid polyp has been studied by routine histological methods and details of another 76 cases have been obtained from 35 reports in the literature, bringing the total number of patients for study to 89.
Results The essential facts relating to the 13 patients presently reported are set out in Table I.
In the entire series of 89 patients, men were affected rather more frequently than women (5 I :38). The age at onset of symptoms ranged from 2 years to 90 years, the mean being 53 years, with almost half of the patients being in the sixth and seventh decades (Table 2). The lesion occurred most commonly in the stomach (60), generally in the antrum or prepyloric region, less frequently in the ileum (17) and then usually in the distal half, and only occasionally in the colon (five), jejunum (four), duodenum (three) and oesophagus (one). It is almost always a solitary lesion and multiple polypi, in the duodenum and jejunum, have only been recorded in one instance (Balmer, Stucki, Pedrinis & Halter 1974). Although gastric lesions account for some 74% of the polypi in the literature they form only 23% of those personally studied: this rather unexpected proportion is the same both in that part of the series collected from a small geographical area and in that gathered from a very wide field. The incidence of small bowel lesions in the personal series is very high and the total number (10)is almost as great as that recorded in the literature (14). Abdominal pain was the commonest and main symptom and was often associated with pyloric stenosis or small bowel obstruction. Weight loss was quite common, but other gastrointestinal signs and symptoms such as vomiting, diarrhoea or haemorrhage were infrequent. While symptoms occasionally were present for 10 years or more generally the duration was a matter of a few weeks or months, and in almost one fifth of the patients it was an incidental finding at operation or at postmortem examination. Eosinophils in the peripheral blood were recorded in 50 patients and were normal in all but four. In two, both of whom had ova in the stools, there was a slight eosinophilia : in one, who also had a gastric ulcer, eosinophils were recorded as I I % on one
61
8
9
Removedat cholecystectomy
Intussusception
Intussusception Intussusception
M
F
M
F M
37
48
51
44 62
10
I1
12
13
Incidental autopsy finding Intussusception
M Yr
I
wk
5 mth
6 mth
1
4 mth
Intussusception
F
39
7
yr
10
Abdominal pain (‘dyspepsia’)
50
6
F
21
5
4 mth
Intussusception
75
3 4
Ileum (polyp) Distal ileum (polyp)
Distal ileum (polyp)
Antrum (sessile)
Distal ileum (polyp) Proximal duodenum (sessile) Distal ileum (polyp) Antrum (sessile) Ileum (polyp) cm diam
7 x4.5 x 4 cm
6 cm long
8 x 5.5 x 5 cm
2.5 x 2 x I cm
2.5 x 2 x 2 cm
2
5 x 3 x 3 cm
1.25 cm diam
3 x 3 x2.5 cm
Up to 4.5 cm 3 x 1.5 x 1.5 cm
4 cm diam
Prepylorus (sessile) Ileum (polyp) Ileum (polyp)
4 mth
M
Abdominal pain and vomiting
M
37
2
3 cm diam
Size
Mid-ileum (polyp)
Site
6 wk
Intussusception
Intussusception
M
51
I
Duration
F F
Presenting symptoms
Sex
Age at Case onset ( x lo9/])
Blood
No recurrence
-
No recurrence No recurrence
No recurrence
No recurrence
+ +++
+ ++ +
++
N o recurrence
No recurrence
No recurrence
No recurrence (no eosinophilia 6 yrs later) No recurrence
Progress
++t
+ ++
i
+++
+++
lissue
Eosinophils
Table I. Details of 13 patients with inflammatory fibroid polyp
mth
yr
5 Yr
5 mth
10
6 Yr
2
6 wk
6 mth
4 Yr
3 Yr
10 yr
Follow-up
A,G,E normal. M slightly lowered A,GE normal M low
Ig
c1
ul
W
’”0
Fs
k?
352
J.M.Johnstone and B.C.Morson Table 2. Inflammatory fibroid polyp (88 patients): decade in which symptoms first presented Decade Number of patients
1 4
2 2
7
3 9
4 5 1 3 2
6 1
7 2
8 0
9
9 3
occasion: in the fourth the raised eosinophil count (1.7 x 10~11) returned to normal after removal of a mid-ileal lesion. Tissue eosinophils were very variable in number in the 13 new lesions presently reported and were considered to be few in six, moderate numbers in three, and numerous in four instances. There was no relationship between the numbers of eosinophils in the blood and in the lesions. Details of the subsequent history are known in 10 of these patients: the follow-up period varied from 6 weeks to 10 years and in none was there any recurrence of any disorder which might be in any way associated. The macroscopic appearance was that of a sessile (Figure I ) or, more commonly, polypoidal lesion (Figure 2) arising in the submucosal layer of the gut. The lesions
Figure I. Case 8 : sessile, ulcerated lesion of the antrum of the stomach: an incidental finding at autopsy. H & E. x 8.7.
Inflammatory ,fibroid polyp
353
Figure 2. Case 9: polypoidal lesion of the distal ileum. H & E. x 4.3.
varied greatly in size, one being an antral polyp prolapsing into the duodenum and measuring 9.5 x 3.5 x 3.0 cm. Ulceration of the overlying mucosa was common and a few gastric lesions occurred in association with peptic ulceration or with carcinoma of the stomach. Histologically, the lesions consisted essentially of a mass of loose connective tissue developing in the submucosa and projecting into the lumen of the gut where they were usually ulcerated. Cellularity varied considerably (Figure 3 & 4) and the nuclei, ovoid to spindle shaped in the more cellular lesions, were often stellate in looser examples. Collagen fibres were present in slight to moderate degree, there was generally considerable reticulin, and elastic fibres were mainly confined to the larger vessels. Electron microscopic examination of imperfectly fixed tissue from one ileal lesion demonstrated that the predominant cells were fibroblasts, and that the intercellular fibres had the characteristic periodicity of mature collagen and were associated with some amorphous material which was presumably mucin. All of the lesions were very vascular, this vascularity often being quite striking (Figure 5). The vessels ranged from capillaries to large, thick-walled channels : around these large vessels there was often a broad zone of loose connective tissue of low cellularity which formed a distinctive feature of some of the more cellular lesions. At the base of some of the larger polypi there were many very large, thin-walled vascular channels, usually close to the muscle coat or its remnants. The muscle coats of the gut, particularly the inner layer, appeared at first to be hypertrophied, but later the loose connective tissue of the stroma of the polyp
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J .M .Johnstone and B. C.Morson
Inflammatory jbroid polyp
355
Figure 5. Case 4: few eosinophils in a very vascular stroma: about some of the larger vessels there is a broad band of loose connective tissue. H & E. x 42.
insinuated between the muscle bundles, separating and finally destroying them (Figure 6). The stroma then continued to extend in the subserous layer of the gut where it formed a mass which projected well above the level of the adjacent serosa. No encapsulation occurred, the process being one of extension in the submucosa and insinuation between, and destruction of the muscle bundles and coats. About the edges of the lesions the muscularis mucosae was greatly hypertrophied, but it thinned at the sides of the lesions and disappeared at the apex. The gastric lesions were generally smaller, sessile rather than polypoidal, and tended to be more compact and cellular. The muscularis mucosae was hypertrophied at the edges but thinned and lost towards the apex: the muscle coat however was little affected. The stroma extended into the overlying mucosa although this was not a feature of the ileal lesions. In one case a single focus of multinucleated giant cells was observed. Eosinophils were spread evenly throughout the lesions but the degree of this tissue eosinophilia varied enormously (Figure 3 & 4). In some it was minimal and Figure 3. Case 8: cellular strorna with many eosinophils. H & E. x 292. Figure 4. Case I I : loose stroma with stellate cells and only occasional eosinophils. H & E. x 292.
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J.M.Johnstone and B.C.Morson
little more than that seen in loose connective tissue anywhere else, while at the other extreme the eosinophilia was very marked and was a predominant and striking feature. In some lesions there was a small number of plasma cells or lymphocytes, or both, the lymphocytes sometimes being in small aggregates. Mast cells (Barlow 1957) were rare as were mitotic figures, and any adjacent lymph nodes were generally normal or showed some reactive hyperplasia. Treatment when necessary was always by resection and was imperative when obstruction occurred. However a number of smaller, and possibly earlier lesions, were symptomless and were discovered incidentally.
Figure 6. Case I : the stroma of the polyp (above) insinuates between, and destroys the fibres of the circular, muscular layer. Very large vessels occur not only in the main part of the polyp but also in that insinuating between the muscle fibres, and in the subserosa (bottom). H & E. x 50.
Inflamniatory ,fibroid polyp
357
Discussion The first report of the condition is generally attributed to Vanek (1949) who described six patients with a lesion which he termed ‘gastric submucosal granuloma with eosinophilic infiltration’ : he considered it to be inflammatory rather than neoplastic, and possibly, because of the eosinophilic infiltrate, some form of allergic phenomenon. Although many other terms have been given to the condition, the great majority of subsequent writers have largely agreed with his views. The largest number of reported cases (10) and probably the fullest account of the condition as it occurs in the stomach is that by Helwig & Raiiier (1952, 1953). In their consideration of the pathogenesis the possibility of the lesion having either a neurogenous origin as suggested by Feyrter (1949) and by Lortat-Jacob & Moricheau-Beauchant (1950), and subsequently by Goldman & Friedman (1967), or a vascular origin as put forward by Stout (1949) and by Sawyer & Lubchenco (1951) was discussed and discarded. In none of the 13 examples of the condition described in the present paper was there anything which might suggest either such origin. The eosinophilia observed in many lesions has inevitably been a major subject of discussion by many authors and reference has often been made to a possible allergic association, but the incidence of any known form of allergy in the previous and presently published cases is probably no different from that in any random sample of the population. Helwig & Ranier (1953) thought that any increase in eosinophils should be interpreted with caution in view of the wide range of conditions in which it may be encountered and their statement that ‘there seems to be no justification for interpreting the lesion. . . . as of allergic origin on the basis of the eosinophilia’ still holds true today. A raised IgE value often occurs in various allergic states but, although it could only be measured in four patients, it was normal in each instance (Table I). The main debate on the aetiology of the condition concerns whether it is neoplastic or inflammatory although most writers on the subject favour the latter. The localized nature of the lesion is the principal feature in keeping with a neoplasm but that growth does not occur by local expansion is clear from the manner in which the loose mesenchyme which forms the main stroma insinuates and proliferates between the fibres of the muscle layer with no evidence anywhere of any form of ‘encapsulation’, a feature noted by Helwig & Ranier (1953). Recurrence is claimed to have occurred only once (McGreevy, Doberneck, McLeay & Miller 1967) and malignant change is unknown. Until the true aetiology is determined, of the many names which have been applied, that used by Helwig & Ranier (1952, 1953), inflammatory fibroid polyp, seems to be the most suitable, but, while the lesions are undoubtedly polypoidal, or sessile, and are in general of fibroblastic origin, it is conceded that the grounds for calling them inflammatory are tenuous and debatable. The continued use of the term however avoids any addition to the already overloaded nomenclature and helps to distinguish the condition from eosinophilic gastroenteritis. The polypi originate in the loose connective tissue of the submucosa and the fibrous and collagenous tissue content is slight and very variable in distribution.
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Although the stroma is sometimes described as being vascular granulation tissue it seldom bears any similarity to the healing granulation tissue of trauma or of bacterial infection. Certainly by the time the lesions produce symptoms sufficient to merit their removal evidence of any such relationship has been lost and the dense collagenous tissue which might be expected to result is notably absent. The eosinophils, plasma cells and lymphocytes which are often observed are very variable, and a bacterial causation cannot be inferred simply from their presence. That the ‘inflammatory’ stimulus need not be bacterial but might be chemical, traumatic, or even metabolic was pointed out by Helwig & Ranier (1953). It is tempting to postulate that the condition is an uncontrolled proliferation of the mesenchymal tissue of the submucosa of the gut, possibly as a result of some form of minor trauma, and rather akin to the fibrous tissue overgrowth of a keloid. This, however, is entirely speculative and while it might account for some of the features of the condition it does not explain others such as the loose bands of perivascular fibrous tissue, the large thin-walled vascular channels often present in the base of the polypi, or the inconstant eosinophilia. Largely because of the common eosinophilic infiltration inflammatory fibroid polyp and eosinophilic gastroenteritis have frequently been associated, often as variants of the same entity. Further confusion has arisen from the remarkably varied nomenclature which has been used and by the lack of understanding of the aetiology of the two conditions. A provisional classification, based on the pathological and clinical pictures, was proposed by Ureles, Alschibaja, Lodico & Stabins (1961). They described two main categories, diffuse eosinophilic gastroenteritis and circumscribed eosinophilic-infiltrated granuloma, each with various subgroups, and discussed the possibility of the two categories having a common aetiology. O’Neill (1970) suggested two groups determined by the presence or absence of peripheral eosinophilia, but the failure of such a classification, and the need for one related to an aetiological basis was pointed out by Kumar (1972). Although about this time the term eosinophilic gastroenteritis was still being used for both entities by some authors others, such as Samter, Alstott & Kurlander (1966), Heddle, Parrott, Paloshi, Prentice, Persyko & Beck (1969), Kaplan, Goldstein & Kowlessar (1970) and Klein, Hargrove, Sleisenger & Jeffries (1970), were distinguishing between inflammatory fibroid polyp and eosinophilic gastroenteritis and emphasizing the lack of any inter-relationship. While the aetiology of both conditions is still obscure there seems little doubt that they are quite separate entities. The literature on eosinophilic gastroenteritis has been reviewed recently by Johnstone & Morson (1978) and the main features of the condition are compared with those of inflammatory fibroid polyp in Table 3. Almost the only factor which they have in common, apart from involvement of the gastrointestinal tract, is infiltration by eosinophils, an infiltration which not only varies greatly in intensity but may even be absent, and which occurs in many other gastrointestinal lesions. The presence of the eosinophil in inflammatory fibroid polyp may even be fortuitous and act as a distraction in the consideration of the lesions and their aetiology. In our present state of knowledge concerning the eosinophil and the precise nature of inflammatory fibroid polyp the advice of Pinkus & Mehregan (1969) concerning
Inflammatory fibroid polyp
359
Table 3. Main features of inflammatory fibroid polyp and eosinophilic gastroenteritis Inflammatory fibroid polyp Main age group Sex ratio (M :F) Allergic history Blood eosinophilia Tissue eosinophilia Immunoglobulins Commonest affected organ Gross appearance Microscopic appearance Recurrence Treat men t
6th-7th decades 1.3: 1.0 Absent Absent Present Normal Stomach Localized :solitary Fibroblastic None Surgery
Eosinophilic gastroenteritis 3rd-4th decades 2.0 : I .o
Present in 25 ”/, Present in 80% Present Normal Stomach Diffuse: often multiple Oedematous Common Steroids
granulomata of the skin may be appropriate: ‘If a granulomatous lesion contains a striking number of eosinophils, discount them, and try to ascertain what the diagnosis would be in their absence’.
Acknowledgements The authors wish to thank Dr J.C.E. Underwood for the electron microscopy, Dr A. Milford Ward for the immunoglobulin estimations, and the Cancer Research Campaign for support of this study.
References BALMER F., STUCKI P., PEDRINIS E. & HALTERF. (1974) Tumoren und Eosinophile Granulome des Diinndarms bei Malabsorption. Schweizerische medizinische Wochenschrijt 104,78-83 BARLOW R.M. (1957) A tribasic stain for the granules of mast cells. Journalof’Pathology and Bacteriolou 73, 2-1-274 FEYRTER F. (1949) Veber die Vasculaere Neurofibromatose, nach Untersuchungen Am Menschlichen Magen-Darmschlauch. Virchows Archiv fur parhologische Anatomie und Physiologie undfur ltlinische Medizin 317, 221-265. Quoted by Helwig E.B. & Ranier A. (1953) N.B. (1967) Neurogenic nature of the so-called inflammatory fibroid GOLDMAN R.L. & FRIEDMAN polyps of the stomach. Cancer 20, 134-143 G.P.G., PRENTICE R.S.A., PERSYKO L. & BECKI.T. (1969) HEDDLE S.B., PARROTT K.B., PALOSCHI Diffuse eosinophilic gastroenteritis. Canadian Medical Association Journal 100, 554-559 HELWIGE.B. & RANIER A. (1952) Inflammatory fibroid polyps of the stomach. American Journalof Pathology 28, 535-536 HELWIGE.B. & RANIER A. (1953) lnflamatory fibroid polyps of the stomach. Surgery, Obsretrics and Gynecology 96,355-367 JOHNSTONE J.M. & MORSONB.C. (1978) Eosinophilic gastroenteritis. Histopathology 2 , 335-348 F. & KOWLESSAR O.D. (1970) Eosinophilic gastroenteritis. GastroenterKAPLAN S.M., GOLDSTEIN OlOgY 58,540-545
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KLEINN.C., HARGROVE L., SLEISENGER M.H. & JEFFRIES G.H. (1970)Eosinophilic gastroenteritis. Medicine 49,299-3 I 9 KUMAR P. (1972) Eosinophilic infiltration of the gastrointestinal tract. Proceedings sf the Royal Society of Medicine 65, 287 LORTAT-JACOB J.L. & MORICHEAU-BEAUCHANT J. (1950) Schwannome atypique de I'estomac. Socikti National Frangaise de Gastro-enteroiogie. Sdance du, November 12, p. I r7-122. Quoted by Helwig E.B. & Ranier A. (1953) MCGREEVY P., DOBERNECK R.C., MCLEAYJ.M. & MILLERF.A. (1967) Recurrent eosinophilic infiltrate (granuloma) of the ileum causing intussusception in a 2-year-old child. Surgery 61, 280-284 O'NEILLT. (1970)Eosinophilic granuloma of the gastro-intestinal tract. British Journal of Surgery 579704-708 PINKUS H. & MEHREGAN A.W. (1969)A Guide to Dermatohistopathology,p. 244.Appleton-CenturyCrofts, New York SAMTER T.G.,ALSTOTT D.F. & KURLANDER G.J. (1966)Inflammatory fibroid polyps of the gastrointestinal tract. American Journal of Clinical Pathology 45, 420-435 SAWYER K.C. & LUBCHENCO A.E. (1951)Hemangio-endothelioma of the stomach. Surgery 30,383387 STOUTA.P. (1949)Hemangiopericytoma, a study of 25 new cases. Cancer 2, 1027-1054 URELES A.L., ALSCHIBAJA T., LODICO D. & STABINS S.J. (1961)Idiopathic eosinophilic infiltration of the gastrointestinal tract, diffuse and circumscribed. American Journal of Medicine 30,899-909 VANEKJ. (1949)Gastric submucosal granuloma with eosinophilic infiltration. American Journal of Pathology 25, 397-41 I
Bibliography BEDRNA J. (1973)Eozinofilni Granulom Zaludku. Rozhiedy v chirurgli 52, 53-58 BOOHER R.J. & GRANTR.N. (1951) Eosinophilic granuloma of the stomach and small intestine. surgery 30, 388-397 BULLOCK W.K.& MORANE.T. (1953)Inflammatory fibroid polyps of the stomach. Cancer 6,488493. BURKHART C.R. & WILKINSON R.H. (1965)Inflammatory pseudoturnours of the stomach. Cancer 18, 1310-1316 BURKHART C.R. & WILKINSON R.H. (1968)Inflammatory pseudotumours of the stomach. Cancer 21, 1052-1054 CARLSON E. & WARDJ.G. (1960)Inflammatory gastric polyps (eosinophilic granulomas of the stomach). American Journal of Surgery 9,352-357 COHEN N. & YESNER R. (1959)Inflammatory fibroid polyp (hemangiopericytoma) of the stomach. American Journal of Digestive Diseases 4, 549-555 Cox J.S.T. (1960)Submucosal ileal granuloma with eosinophilic infiltration and intussusception. British Journal of Surgery 48, 149-150 DABROWSKI w., LIPNICKI T., ZACHWIEJ Z. & DABROWSKI K.(1974)Eosinophilic granuloma of large bowel. Polski Przeglad Chirurgiczny 46, 1007-1009 ESHCHAR J., KIMERLING J.J. & GILBOA Y. (1973)Eosinophilic granuloma of the stomach simulating leiomyoma. Gastrointestinal Endoscopy 20, 72 FILIMON C., VEXLERL. & CORDUN-TARABIJTA G. (1973)On a case of inflammatory pseudotumour of the small intestine. Chirurgia (Bucur) 22, 73-78 GREENE E.I., KAVKA S.J. & GREENE J.M. (1962)Gastric carcinoma associated with an inflammatory fibroid polyp of the stomach. Journal of the International College of Surgeons 38, I I 1-1 15 KLEINN.C., HARGROVE R.L., SLEISENGER M.H. & JEFFRIES G.H. (1970)Eosinophilic gastroenteritis. Medicine 49, 299-3 I 9
Inflammatory jibroid polyp
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KOCHW., STOCKMEYER E. & APABLAZA H. (1958)Eosinophilic granulomaofthestomach. American Journal of Roentgenology, Radium Therapy and Nuclear Medicine 80, 54-56 KONEMAN E.W., SAWYER K.C. & LUBCHENCO A.E. (1959) Eosinophilic granuloma of the ileum. Archives of Surgery 78, 923-927 KORTASJ . & CHOJNACKI J . (1974) Gastric eosinophilic granuloma. Wiadomosci Lekarskie 27, 269272
LEANDP.M., MURRAY G.F., ZUIDEMA G.D. & SHELLEY W.M. (1968) Obstructing esophageal polyp with eosinophilic infiltration. American Journul of’Surgery 116, 93-96 MAKARUK Z. ( 1973) Eosinophilic granuloma of caecum. Wiadomosci Lekarskie 26, 263-264 MCGEEH.J. (1960) Inflammatory fibroid polyps of the ileum and cecum. Archices ofPathology 70, 203-207 NEIBLING H.A. (1974) Eosinophilic granuloma of stomach. American Surgeon 40, 305-308 PERSOFF M.M. & ARTEREURN J.G. (1972) Eosinophilic granuloma causing intussusception in a three year old child. American Journal of Surgery 124, 676678 POLAYES S.H. & KRIEGER J.L. (1950)Eosinophilic granuloma of the jejunum. Journalof the American Medical Association 143, 549-55 I RENDLVON K.-H. (1976)Eosinophilic granuloma of the gastrointestinal tract. Wiener Medizinische Wocheschrift 126, 370-373 RIGLERL.G., BLANKL. & HEEEER R. (1956) Granuloma with eosinophils. Radiology 66, 169-176 RUTGEERTS L., DE COWERM., TYTGATG. & TANGHE W. (1975) Eosinophilic granuloma (inflammatory fibrinoid polyp) of the gastrointestinal tract. Tiidschrifr Voor Gustroenterol. 18, 2 1-30 SALMR. (1965) Gastric fibroma with eosinophilic infiltration. Gut 6, 85-91 SCHREIBER M.H. (1962) Granuloma of the esophagogastric junction with eosinophilic infiltration. Gastroenterology 43, 2 0 6 2 I I SCHWINGER A. (1965) Eosinophilic granuloma of the upper GI tract. American Journal of’igestice Diseases 10, 58-62 SMITHM.J. ( 1956) Gastric granuloma with eosinophilic infiltration. Radiology 66, 177-180 TOOLEH.J. & MCISCHOPOULCS A.N. f I 959) Eosinophilic granuloma of the gastro-intestinal tract. British Journal of Surgery 46, 445-448 TURDIU F.. KROPEC I. & DUBRAVCIC D. (1971) Eosinophilic granuloma of the stomach. Loecnicki Vjesnik 93, 1219-1225
D
Inflammatory fibroid polyp of the gastrointestha1 tract J . M. J O H N ST O N E * & B . C . M O R S O N Departments of Pathology, General Hospital, Grimsby, and St. Mark’s Hospital, London Accepted for publication 7 May 1978 JOHNSTONE J.M.& MORSONB.C. (1978) Histopathology
2,
349361
Inflammatory fibroid polyp of the gastrointestinal tract Details of 1 3 new cases of inflammatory fibroid polyp of the gastrointestinal tract and of 76 patients recorded in the literature (total 89) are described and analysed. The lesion is always benign, may occur at any age but is commonest in the sixth and seventh decades, and involves the stomach most frequently. Abdominal pain, often related to obstruction, is the principal symptom. Eosinophilia of the peripheral blood does not occur. The lesions are sessile or polypoidal, originate in the gut submucosa, vary greatly in cellularity, and have a wide range of tissue eosinophilia. Some are very vascular, many of the larger vessels having a notably broad zone of connective tissue about them. The aetiology of the condition is discussed and reasons for distinguishing it from eosinophilic gastroenteritis, with which it is frequently confused, are given. The precise nature and aetiology of the inflammatory fibroid polyp remains undetermined. Keywords : polyp fibroid, polyp inflammatory, gastrointestinal polyp
Introduction Inflammatory fibroid polyp is a simple, localized lesion which arises in the submucosa of the gastrointestinal tract, principally the stomach, and has, in its connective tissue stroma, a variable degree of eosinophilic infiltration. First described by Vanek (1949) as a gastric submucosal granuloma with eosinophilic infiltration, many other names have been applied subsequently and include such terms as eosinophilic granuloma, inflammatory fibroid polyp, granuloma with eosinophils, ‘hemangiopericytoma’, inflammatory pseudotumour, gastric fibroma with eosinophilic infiltration, eosinophilic gastroenteritis, polyp with eosinophilic granuloma, and others. The lesion has been reported in the United Kingdom, in many European countries, in North and South America, and in Israel (see bibliography). * Address for correspondence : Dr J.M. Johnstone, Department of Pathology, General Hospital, Grimsby, South Humberside DN31 ITZ. 0309-0167/78/090~0349$02.00 01978 Blackwell Scientific Publications
349
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J.M.Johnstone and B.C.Morson
In this report details of 1 3 further examples of the lesion are given, the literature on the subject is reviewed, and the distinction between inflammatory fibroid polyp and eosinophilic gastroenteritis, a condition with which it is frequently associated and confused, is emphasized.
Materials and methods Material from I 3 previously unreported examples of inflammatory fibroid polyp has been studied by routine histological methods and details of another 76 cases have been obtained from 35 reports in the literature, bringing the total number of patients for study to 89.
Results The essential facts relating to the 13 patients presently reported are set out in Table I.
In the entire series of 89 patients, men were affected rather more frequently than women (5 I :38). The age at onset of symptoms ranged from 2 years to 90 years, the mean being 53 years, with almost half of the patients being in the sixth and seventh decades (Table 2). The lesion occurred most commonly in the stomach (60), generally in the antrum or prepyloric region, less frequently in the ileum (17) and then usually in the distal half, and only occasionally in the colon (five), jejunum (four), duodenum (three) and oesophagus (one). It is almost always a solitary lesion and multiple polypi, in the duodenum and jejunum, have only been recorded in one instance (Balmer, Stucki, Pedrinis & Halter 1974). Although gastric lesions account for some 74% of the polypi in the literature they form only 23% of those personally studied: this rather unexpected proportion is the same both in that part of the series collected from a small geographical area and in that gathered from a very wide field. The incidence of small bowel lesions in the personal series is very high and the total number (10)is almost as great as that recorded in the literature (14). Abdominal pain was the commonest and main symptom and was often associated with pyloric stenosis or small bowel obstruction. Weight loss was quite common, but other gastrointestinal signs and symptoms such as vomiting, diarrhoea or haemorrhage were infrequent. While symptoms occasionally were present for 10 years or more generally the duration was a matter of a few weeks or months, and in almost one fifth of the patients it was an incidental finding at operation or at postmortem examination. Eosinophils in the peripheral blood were recorded in 50 patients and were normal in all but four. In two, both of whom had ova in the stools, there was a slight eosinophilia : in one, who also had a gastric ulcer, eosinophils were recorded as I I % on one
61
8
9
Removedat cholecystectomy
Intussusception
Intussusception Intussusception
M
F
M
F M
37
48
51
44 62
10
I1
12
13
Incidental autopsy finding Intussusception
M Yr
I
wk
5 mth
6 mth
1
4 mth
Intussusception
F
39
7
yr
10
Abdominal pain (‘dyspepsia’)
50
6
F
21
5
4 mth
Intussusception
75
3 4
Ileum (polyp) Distal ileum (polyp)
Distal ileum (polyp)
Antrum (sessile)
Distal ileum (polyp) Proximal duodenum (sessile) Distal ileum (polyp) Antrum (sessile) Ileum (polyp) cm diam
7 x4.5 x 4 cm
6 cm long
8 x 5.5 x 5 cm
2.5 x 2 x I cm
2.5 x 2 x 2 cm
2
5 x 3 x 3 cm
1.25 cm diam
3 x 3 x2.5 cm
Up to 4.5 cm 3 x 1.5 x 1.5 cm
4 cm diam
Prepylorus (sessile) Ileum (polyp) Ileum (polyp)
4 mth
M
Abdominal pain and vomiting
M
37
2
3 cm diam
Size
Mid-ileum (polyp)
Site
6 wk
Intussusception
Intussusception
M
51
I
Duration
F F
Presenting symptoms
Sex
Age at Case onset ( x lo9/])
Blood
No recurrence
-
No recurrence No recurrence
No recurrence
No recurrence
+ +++
+ ++ +
++
N o recurrence
No recurrence
No recurrence
No recurrence (no eosinophilia 6 yrs later) No recurrence
Progress
++t
+ ++
i
+++
+++
lissue
Eosinophils
Table I. Details of 13 patients with inflammatory fibroid polyp
mth
yr
5 Yr
5 mth
10
6 Yr
2
6 wk
6 mth
4 Yr
3 Yr
10 yr
Follow-up
A,G,E normal. M slightly lowered A,GE normal M low
Ig
c1
ul
W
’”0
Fs
k?
352
J.M.Johnstone and B.C.Morson Table 2. Inflammatory fibroid polyp (88 patients): decade in which symptoms first presented Decade Number of patients
1 4
2 2
7
3 9
4 5 1 3 2
6 1
7 2
8 0
9
9 3
occasion: in the fourth the raised eosinophil count (1.7 x 10~11) returned to normal after removal of a mid-ileal lesion. Tissue eosinophils were very variable in number in the 13 new lesions presently reported and were considered to be few in six, moderate numbers in three, and numerous in four instances. There was no relationship between the numbers of eosinophils in the blood and in the lesions. Details of the subsequent history are known in 10 of these patients: the follow-up period varied from 6 weeks to 10 years and in none was there any recurrence of any disorder which might be in any way associated. The macroscopic appearance was that of a sessile (Figure I ) or, more commonly, polypoidal lesion (Figure 2) arising in the submucosal layer of the gut. The lesions
Figure I. Case 8 : sessile, ulcerated lesion of the antrum of the stomach: an incidental finding at autopsy. H & E. x 8.7.
Inflammatory ,fibroid polyp
353
Figure 2. Case 9: polypoidal lesion of the distal ileum. H & E. x 4.3.
varied greatly in size, one being an antral polyp prolapsing into the duodenum and measuring 9.5 x 3.5 x 3.0 cm. Ulceration of the overlying mucosa was common and a few gastric lesions occurred in association with peptic ulceration or with carcinoma of the stomach. Histologically, the lesions consisted essentially of a mass of loose connective tissue developing in the submucosa and projecting into the lumen of the gut where they were usually ulcerated. Cellularity varied considerably (Figure 3 & 4) and the nuclei, ovoid to spindle shaped in the more cellular lesions, were often stellate in looser examples. Collagen fibres were present in slight to moderate degree, there was generally considerable reticulin, and elastic fibres were mainly confined to the larger vessels. Electron microscopic examination of imperfectly fixed tissue from one ileal lesion demonstrated that the predominant cells were fibroblasts, and that the intercellular fibres had the characteristic periodicity of mature collagen and were associated with some amorphous material which was presumably mucin. All of the lesions were very vascular, this vascularity often being quite striking (Figure 5). The vessels ranged from capillaries to large, thick-walled channels : around these large vessels there was often a broad zone of loose connective tissue of low cellularity which formed a distinctive feature of some of the more cellular lesions. At the base of some of the larger polypi there were many very large, thin-walled vascular channels, usually close to the muscle coat or its remnants. The muscle coats of the gut, particularly the inner layer, appeared at first to be hypertrophied, but later the loose connective tissue of the stroma of the polyp
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J .M .Johnstone and B. C.Morson
Inflammatory jbroid polyp
355
Figure 5. Case 4: few eosinophils in a very vascular stroma: about some of the larger vessels there is a broad band of loose connective tissue. H & E. x 42.
insinuated between the muscle bundles, separating and finally destroying them (Figure 6). The stroma then continued to extend in the subserous layer of the gut where it formed a mass which projected well above the level of the adjacent serosa. No encapsulation occurred, the process being one of extension in the submucosa and insinuation between, and destruction of the muscle bundles and coats. About the edges of the lesions the muscularis mucosae was greatly hypertrophied, but it thinned at the sides of the lesions and disappeared at the apex. The gastric lesions were generally smaller, sessile rather than polypoidal, and tended to be more compact and cellular. The muscularis mucosae was hypertrophied at the edges but thinned and lost towards the apex: the muscle coat however was little affected. The stroma extended into the overlying mucosa although this was not a feature of the ileal lesions. In one case a single focus of multinucleated giant cells was observed. Eosinophils were spread evenly throughout the lesions but the degree of this tissue eosinophilia varied enormously (Figure 3 & 4). In some it was minimal and Figure 3. Case 8: cellular strorna with many eosinophils. H & E. x 292. Figure 4. Case I I : loose stroma with stellate cells and only occasional eosinophils. H & E. x 292.
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J.M.Johnstone and B.C.Morson
little more than that seen in loose connective tissue anywhere else, while at the other extreme the eosinophilia was very marked and was a predominant and striking feature. In some lesions there was a small number of plasma cells or lymphocytes, or both, the lymphocytes sometimes being in small aggregates. Mast cells (Barlow 1957) were rare as were mitotic figures, and any adjacent lymph nodes were generally normal or showed some reactive hyperplasia. Treatment when necessary was always by resection and was imperative when obstruction occurred. However a number of smaller, and possibly earlier lesions, were symptomless and were discovered incidentally.
Figure 6. Case I : the stroma of the polyp (above) insinuates between, and destroys the fibres of the circular, muscular layer. Very large vessels occur not only in the main part of the polyp but also in that insinuating between the muscle fibres, and in the subserosa (bottom). H & E. x 50.
Inflamniatory ,fibroid polyp
357
Discussion The first report of the condition is generally attributed to Vanek (1949) who described six patients with a lesion which he termed ‘gastric submucosal granuloma with eosinophilic infiltration’ : he considered it to be inflammatory rather than neoplastic, and possibly, because of the eosinophilic infiltrate, some form of allergic phenomenon. Although many other terms have been given to the condition, the great majority of subsequent writers have largely agreed with his views. The largest number of reported cases (10) and probably the fullest account of the condition as it occurs in the stomach is that by Helwig & Raiiier (1952, 1953). In their consideration of the pathogenesis the possibility of the lesion having either a neurogenous origin as suggested by Feyrter (1949) and by Lortat-Jacob & Moricheau-Beauchant (1950), and subsequently by Goldman & Friedman (1967), or a vascular origin as put forward by Stout (1949) and by Sawyer & Lubchenco (1951) was discussed and discarded. In none of the 13 examples of the condition described in the present paper was there anything which might suggest either such origin. The eosinophilia observed in many lesions has inevitably been a major subject of discussion by many authors and reference has often been made to a possible allergic association, but the incidence of any known form of allergy in the previous and presently published cases is probably no different from that in any random sample of the population. Helwig & Ranier (1953) thought that any increase in eosinophils should be interpreted with caution in view of the wide range of conditions in which it may be encountered and their statement that ‘there seems to be no justification for interpreting the lesion. . . . as of allergic origin on the basis of the eosinophilia’ still holds true today. A raised IgE value often occurs in various allergic states but, although it could only be measured in four patients, it was normal in each instance (Table I). The main debate on the aetiology of the condition concerns whether it is neoplastic or inflammatory although most writers on the subject favour the latter. The localized nature of the lesion is the principal feature in keeping with a neoplasm but that growth does not occur by local expansion is clear from the manner in which the loose mesenchyme which forms the main stroma insinuates and proliferates between the fibres of the muscle layer with no evidence anywhere of any form of ‘encapsulation’, a feature noted by Helwig & Ranier (1953). Recurrence is claimed to have occurred only once (McGreevy, Doberneck, McLeay & Miller 1967) and malignant change is unknown. Until the true aetiology is determined, of the many names which have been applied, that used by Helwig & Ranier (1952, 1953), inflammatory fibroid polyp, seems to be the most suitable, but, while the lesions are undoubtedly polypoidal, or sessile, and are in general of fibroblastic origin, it is conceded that the grounds for calling them inflammatory are tenuous and debatable. The continued use of the term however avoids any addition to the already overloaded nomenclature and helps to distinguish the condition from eosinophilic gastroenteritis. The polypi originate in the loose connective tissue of the submucosa and the fibrous and collagenous tissue content is slight and very variable in distribution.
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Although the stroma is sometimes described as being vascular granulation tissue it seldom bears any similarity to the healing granulation tissue of trauma or of bacterial infection. Certainly by the time the lesions produce symptoms sufficient to merit their removal evidence of any such relationship has been lost and the dense collagenous tissue which might be expected to result is notably absent. The eosinophils, plasma cells and lymphocytes which are often observed are very variable, and a bacterial causation cannot be inferred simply from their presence. That the ‘inflammatory’ stimulus need not be bacterial but might be chemical, traumatic, or even metabolic was pointed out by Helwig & Ranier (1953). It is tempting to postulate that the condition is an uncontrolled proliferation of the mesenchymal tissue of the submucosa of the gut, possibly as a result of some form of minor trauma, and rather akin to the fibrous tissue overgrowth of a keloid. This, however, is entirely speculative and while it might account for some of the features of the condition it does not explain others such as the loose bands of perivascular fibrous tissue, the large thin-walled vascular channels often present in the base of the polypi, or the inconstant eosinophilia. Largely because of the common eosinophilic infiltration inflammatory fibroid polyp and eosinophilic gastroenteritis have frequently been associated, often as variants of the same entity. Further confusion has arisen from the remarkably varied nomenclature which has been used and by the lack of understanding of the aetiology of the two conditions. A provisional classification, based on the pathological and clinical pictures, was proposed by Ureles, Alschibaja, Lodico & Stabins (1961). They described two main categories, diffuse eosinophilic gastroenteritis and circumscribed eosinophilic-infiltrated granuloma, each with various subgroups, and discussed the possibility of the two categories having a common aetiology. O’Neill (1970) suggested two groups determined by the presence or absence of peripheral eosinophilia, but the failure of such a classification, and the need for one related to an aetiological basis was pointed out by Kumar (1972). Although about this time the term eosinophilic gastroenteritis was still being used for both entities by some authors others, such as Samter, Alstott & Kurlander (1966), Heddle, Parrott, Paloshi, Prentice, Persyko & Beck (1969), Kaplan, Goldstein & Kowlessar (1970) and Klein, Hargrove, Sleisenger & Jeffries (1970), were distinguishing between inflammatory fibroid polyp and eosinophilic gastroenteritis and emphasizing the lack of any inter-relationship. While the aetiology of both conditions is still obscure there seems little doubt that they are quite separate entities. The literature on eosinophilic gastroenteritis has been reviewed recently by Johnstone & Morson (1978) and the main features of the condition are compared with those of inflammatory fibroid polyp in Table 3. Almost the only factor which they have in common, apart from involvement of the gastrointestinal tract, is infiltration by eosinophils, an infiltration which not only varies greatly in intensity but may even be absent, and which occurs in many other gastrointestinal lesions. The presence of the eosinophil in inflammatory fibroid polyp may even be fortuitous and act as a distraction in the consideration of the lesions and their aetiology. In our present state of knowledge concerning the eosinophil and the precise nature of inflammatory fibroid polyp the advice of Pinkus & Mehregan (1969) concerning
Inflammatory fibroid polyp
359
Table 3. Main features of inflammatory fibroid polyp and eosinophilic gastroenteritis Inflammatory fibroid polyp Main age group Sex ratio (M :F) Allergic history Blood eosinophilia Tissue eosinophilia Immunoglobulins Commonest affected organ Gross appearance Microscopic appearance Recurrence Treat men t
6th-7th decades 1.3: 1.0 Absent Absent Present Normal Stomach Localized :solitary Fibroblastic None Surgery
Eosinophilic gastroenteritis 3rd-4th decades 2.0 : I .o
Present in 25 ”/, Present in 80% Present Normal Stomach Diffuse: often multiple Oedematous Common Steroids
granulomata of the skin may be appropriate: ‘If a granulomatous lesion contains a striking number of eosinophils, discount them, and try to ascertain what the diagnosis would be in their absence’.
Acknowledgements The authors wish to thank Dr J.C.E. Underwood for the electron microscopy, Dr A. Milford Ward for the immunoglobulin estimations, and the Cancer Research Campaign for support of this study.
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KLEINN.C., HARGROVE L., SLEISENGER M.H. & JEFFRIES G.H. (1970)Eosinophilic gastroenteritis. Medicine 49,299-3 I 9 KUMAR P. (1972) Eosinophilic infiltration of the gastrointestinal tract. Proceedings sf the Royal Society of Medicine 65, 287 LORTAT-JACOB J.L. & MORICHEAU-BEAUCHANT J. (1950) Schwannome atypique de I'estomac. Socikti National Frangaise de Gastro-enteroiogie. Sdance du, November 12, p. I r7-122. Quoted by Helwig E.B. & Ranier A. (1953) MCGREEVY P., DOBERNECK R.C., MCLEAYJ.M. & MILLERF.A. (1967) Recurrent eosinophilic infiltrate (granuloma) of the ileum causing intussusception in a 2-year-old child. Surgery 61, 280-284 O'NEILLT. (1970)Eosinophilic granuloma of the gastro-intestinal tract. British Journal of Surgery 579704-708 PINKUS H. & MEHREGAN A.W. (1969)A Guide to Dermatohistopathology,p. 244.Appleton-CenturyCrofts, New York SAMTER T.G.,ALSTOTT D.F. & KURLANDER G.J. (1966)Inflammatory fibroid polyps of the gastrointestinal tract. American Journal of Clinical Pathology 45, 420-435 SAWYER K.C. & LUBCHENCO A.E. (1951)Hemangio-endothelioma of the stomach. Surgery 30,383387 STOUTA.P. (1949)Hemangiopericytoma, a study of 25 new cases. Cancer 2, 1027-1054 URELES A.L., ALSCHIBAJA T., LODICO D. & STABINS S.J. (1961)Idiopathic eosinophilic infiltration of the gastrointestinal tract, diffuse and circumscribed. American Journal of Medicine 30,899-909 VANEKJ. (1949)Gastric submucosal granuloma with eosinophilic infiltration. American Journal of Pathology 25, 397-41 I
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D
