report familial giant hypertrophic …analysis, whereas serum total protein (61 g/l) and serum...

Gut, 1987, 28, 1517-1521

Case report

Familial giant hypertrophic gastritis (M6netrier'sdisease)B LARSEN, U TARP, AND E KRISTENSEN

From the Medical Department, The Silkeborg Hospital, Silkeborg, Denmark

SUMMARY Familial giant hypertrophic gastritis involving three generations is reported. A reviewof the literature, where approximately 200 cases are described, showed only few cases of familialoccurrence of this disease, and only in siblings. Our findings suggest dominant heredity, butconsidering the sparsity of familial occurrence reported earlier, heredity seems to be of only minorpathogenetic significance.

Giant hypertrophic gastritis was originally describedas a clinical entity by Menetrier in 1888 (Menetrier'sdisease). This rare condition is characterised byenlargement of the gastric mucosal folds primarilyaffecting the body of the stomach, whereas the gastricantrum is often saved. Histologically, there is pro-liferation of the gastric glands with preservation ofnuclear polarity, and cystic dilatation of the basilarportion of the glands. In extensive cases, the mucoussecreting cells are present in the glands deep in themucosa replacing the normal chief and parietal cells.The number of lymphocytes in the lamina propriamay be increased. 'Some authors diagnose Menetrier's disease on the

basis of histopathological lesions and presence ofhypochlorhydria and hypoproteinemia, while otherauthors do not include these deficiencies in thedefinition.'-' The most frequent clinical features areasthenia, weight loss, upper abdominal pain ordiscomfort, nausea, diarrhoea, oedema andanaemia. The disease is reported in infants, butoccurs most often in adults. Thus, some 200 adultcases and 16 children cases have been published since1888."'

Information of the aetiology of Menetrier's diseaseis inadequate, although a causative role of allergyand various infections and toxicants has beensuggested.7 Hereditary disposition presumablyplays a minor role as familial relationships have beenreported in only a few cases, and only betweensiblings." We here describe natural heredity ofMenetrier's disease in three generations.Addrcss for corrcspondencc: Birgit L.arscn. MD. Medical DIepartmentl TheSilkchorg tiospiti.l. DK - 8601) Silkehorg. Dcrnmark.Rcccivcd for publication 9 April 1987.

Case 1

In July 1974, a 49 years old woman entered thehospital because of asthenia, hunger sensation andepigastric pain from which she had suffered sincechildhood. Physical examination revealed a wellnourished woman in a good general condition.Epigastric palpation was painful. Laboratory testsshowed normal values of haemoglobin, haematocrit,ESR, alkaline phosphatases, aspartate aminotrans-ferases, serum calcium, serum creatinine and urineanalysis, whereas serum total protein (61 g/l) andserum albumin (34.7 g/l) were slightly decreased.Analysis of gastric juice revealed hyposecretion(peak acid output 2-6 meqH+/hour). Barium mealrevealed markedly enlarged gastric rugae of thefundus ventriculi (Fig. 1). Gastroscopy showedhypertrophic gastric rugae of corpus and fundus.Microscopic examination of the gastric biopsy speci-men showed elongated foveolae gastricae and cysticdilatation of the deeper part of some foveolae. Thefindings were compatible with Menetrier's disease.The patient's symptoms have since partially dis-appeared. No re-examination has been carried out.There was no family history of symptoms of gastricdisease.

Case 2

In October 1973 at the age of 16, the son of case 1,was admitted to the hospital because of a prolonged,marked asthenia and epigastric pain. Physical exami-nation revealed a pale, poorly nourished youth,appearing acutely and chronically ill. Laboratoryanalysis showed iron deficiency anaemia (haemo-

1517

on April 25, 2020 by guest. P

rotected by copyright.http://gut.bm

j.com/

Gut: first published as 10.1136/gut.28.11.1517 on 1 N

ovember 1987. D

ownloaded from

http://gut.bmj.com/

Larsen, Tarp, anid Kristenisen

s

o-

s

s

s;>

. ._

* kCe

i z' A,

*QoeS:._

o

-S

s

S

,

Ce:_,

.. N

._on.. v

._

-

eS

_

* z._

s

s

.k;e;

;OJJS

-

.hCs

-

S*_S

-

...

I,:_J

*- L

'M.: L k

1518



j.com/


ovember 1987. D

ownloaded from

http://gut.bmj.com/

Familial giant hypertrophic gastritis (Menetrier's disease)

Fig. 3 C'ase 2. Marked thickening ofthe gastric mucosa with elongated and Fig. 4 Case 2. Transition from Menetrier-tvpetortuous pits and cystic dilatations covered by surface type mucous cells mucosa (left) to adenoma with slight dysplasia(H+ E). (right). (H+ E).

globin 6-4 mmol/l, serum iron 2 [tmol/l, serumtransferrin 38 tmol/l) and hypoproteinaemia (serumtotal protein 58 g/l). Other tests showed normal whiteblood cell count, thrombocyte count, and serumcalcium and creatinine concentrations.

Analysis of gastric juice was not done. Bariummeal showed enlargement of the gastric rugae (Fig.2). Gastroscopy revealed marked rugae hypertrophyof the fundus and corpus ventriculi, whereas thechanges in antrum were minimal. The mucosaappeared oedematous and very vulnerable. Thefindings were compatible with Menetrier's disease.The patient received iron substitution, whichbalanced the disease until April 1986, when he wasreadmitted, now 29 years old, presenting severeanaemia and hypoalbuminaemia. Laboratory datashowed haemoglobin 1*7 mmol/l, haematocrit 0- 12,erythrocytes 1-5- 1071/, reticulocytes 155* 10)/1, serumiron 4 smol/l, serum transferrin 65 tmol/l, whiteblood cell count 8-1 -(10/I, serum albumin 27 g/l andserum gastrin 120 pmol/l. Gastric Juice analysis wasnot done. Bone marrow aspirate showed pronouncedmyelopoiesis and no other abnormalities.

Gastroscopy revealed significant hypertrophy ofthe gastric rugae in the corpus ventriculi, mostprominent at the great curvature. Besides, a 1 cmpolypoid projection in the corpus was removed byendoscopic polypectomy. Microscopic examinationof the gastric biopsy specimens showed elongation ofthe gastric pits with cystic dilatation (Fig. 3). Thepolyp was a tubulo-villous adenoma with slight atypia(Fig. 4). There were no signs of invasive malignancy.The patient was given blood transfusion and ironsubstitution. The patient has no siblings, and hisfather is reported to be healthy.

Case 3

In April 1986 at the age of 5, the eldest daughter ofcase 2, the grandchild of case 1, was admitted becauseof severe anaemia. Two months before admission shedeveloped abdominal pain, and at one occasion blackstools were observed. Physical examination revealeda pale, but well nourished girl. Height and weightwere normal for her age. Epigastric palpation pro-duced slight pain. Laboratory values showed severeanaemia, haemoglobin 4-0 mmol/l, haematocrit 0(23,erythrocytes 3-7 10' /7, reticulocytes 70 10/1, serumiron 4 [tmol/l, serum transferrin 124 !tmol/l, whiteblood cell count 105 1079/1. Serum albumin wasnormal (40 gIl). Bone marrow aspirate showedhyperplastic bone marrow with strong erythropoiesisand signs of iron deficiency. Barium meal revealedmarked enlargement of the gastric mucosal folds,especially in the fundic zone compatible withMenetrier's disease (Fig. 5). Gastroscopy and gastricjuice analysis were not done. The findings werecompatible with Menetrier's disease. The patient wasgiven blood transfusions and iron substitution. Thepatient has a younger sister age 21/2 year reported tobe healthy as well as their mother.

Discussion

To establish a certain proof for the diagnosis ofMenetrier's disease, full thickness mucosal biopsy isnecessary. The biopsies obtained with a conventionalbiopsy forceps are often inadequate, as the character-istic histological feature of cysts with replacement ofthe fundic glands are placed in the deep part of thethickened mucosa. Hiowever, the endoscopic biop-

1519



j.com/


ovember 1987. D

ownloaded from

http://gut.bmj.com/

Larsen, Tarp, atnd Krislensen

Fig. 5 Case 3. Barium meal showing large gastric rugae especially in thefundic zone (dorsalview).

sies might be suggestive for the diagnosis. Fullthickness mucosal biopsies can often be obtained bymeans of a diathermic snare. This procedure ismeanwhile not possible in all hospital units andlaparotomy for diagnostic purposes is in most casesnot acceptable. Therefore, the diagnosis may bebased on radiography, endoscopy and endoscopicbiopsies perhaps combined with hypoproteinaemiaand hypochlorhydria. This practice has also beenadopted in the vast majority of cases published inliterature. I'll

Menetrier's disease has been considered as aprecancerous condition.' The finding of a tubulo-

villous adenoma with slight atypia in case 2 is inagreement with this point of view.Among the earlier published cases of giant hyper-

trophic gastritis, only three cases of familial occur-rence have been described, and all in siblings."-"Catanzaro et al reported two cases in a 43 year old manand his 31 year old sister.9 Maimon et al found that afamilial occurrence was pertinent because a sister to apatient with Menetrier's disease had been operatedfor benign gastric polyposis 27 years earlier."' Lamet al reported pachydermoperiostosis, an autosomaldominant syndrome, and Men6trier's disease in twoChinese brothers aged 27 and 29 years.'"

1520



j.com/


ovember 1987. D

ownloaded from

http://gut.bmj.com/

Familialgiant hypertrophic gastritis (Menetrier's disease) 1521

The cases presented here involve three genera-tions, which indicates a dominant pattern of heredityrather than coincidence. The few published reportstaken into consideration genetic transmission seemsto play only a minor role. Mild symptoms may resultin subclinical cases, however, and the frequency ofMWn6trier's disease may therefore be underesti-mated.7 '3 This possibility further hampers an evalua-tion of the genetic impact based on the cases in theliterature.

Peter K A Jensen, MD, Institute of Human Genetics,University of Aarhus, is acknowledged for valuablediscussions, and N 0 Jacobsen, MD, Institute ofPathology, The Aarhus Kommunehospital forevaluation of the biopsies.

References

1 Scharschmidt BF. The natural history of hypertrophicgastropathy (Menetrier's disease). Am J Med 1977; 63:644-52.

2 Searcy RM, Malagelada J-R. Menetrier's disease andidiopathic hypertrophic gastropathy. Ann Intern Med1984; 100: 565-70.

3 Citrin Y, Sterling K, Halsted JA. The mechanisms ofhypoproteinemia associated with giant hypertrophy ofthe gastric mucosa. N EnglJ Med 1957; 257: 906-12.

4 Chokas WV, Connor DH, Innes RC. Giant hypertrophyof the gastric mucosa, hypoproteinemia and edema(Menetrier's disease). Am J Med 1959; 27: 125-31.

5 Tan DTD, Stempien SJ, Dagradi AE. The clinicalspectrum of hypertrophic hypersecretory gastropathy.Gastrointest Endosc 1971; 18: 69-73.

6 Chouraqui JP, Roy CC, Brochu P, Gregoire H, MorinCL, Weber AM. Menetrier's disease in children: reportof a patient and review of sixteen other cases. Gastro-enterology 1981; 80: 1042-7.

7 Lesser PB, Falchuk KR, Singer M, Isselbacher KJ.Menetrier's Disease: report of a case with transient andreversible findings. Gastroenterology 1975; 68:1598-601.

8 Lachman RS, Martin DJ, Vawter GF. Thick gastricfolds in childhood. A J R 1971; 112: 83-92.

9 Catanzaro C, Weeks CB, Kafka RM. Chronic hyper-trophic gastritis: report of two cases in siblings. Am JGastroenterol 1962; 37: 525-36.

10 Maimon SN, Bartlett JP, Humphreys EM, Palmer WL.Giant hypertrophic gastritis. Gastroenterology 1947; 8:397-428.

11 Lam SK, Hui WKK, Ho J, Wong KP, Rotter JI, SamloffIM. Pachydermoperiostosis. Hypertrophic gastropathyand peptic ulcer. Gastroenterology 1983; 84: 834-9.

12 Kraut JR, Powell R, Hruby MA, Lloyd-Still JD.Menetrier's disease in childhood: report of two casesand a review of the literature. J Pediatr Surg 1981; 16:707-11.

13 Morson BC, Sobin LH, Grundmann E, Johansen A,Nagayo T, Serck-Hanssen, A. Precancerous conditionsand epithelial dysplasia in the stomach. J Clin Pathol1980; 33:711-21.



j.com/


ovember 1987. D

ownloaded from

http://gut.bmj.com/

report familial giant hypertrophic …analysis, whereas serum total protein (61 g/l) and serum...

Documents