Short reports

Dieulafoy's disease associated with early gastriccancer

0 Leone, M Zanelli, D Santini, F Minni, D Marrano

AbstractIn the past different terms have been usedto define the vascular malformations ofDieulafoy's disease-for example, calibrepersistent artery of the stomach, cirsoidaneurysm and gastric atherosclerosis. Acase of Dieulafoy's disease is described ina 41 year old man, who presented withsymptoms of anaemia and melaena, withparticular attention paid to the mor-phological characterisation ofthe vascularhistological lesions. Intimal hyperplasiawith a non-concentric proliferation ofmyointimal cells, areas of muscular de-generation, aspects of vascular neo-formation of the arterial wall, and otherfindings are reported. An association be-tween an early diffuse adenocarcinomaand parietal anomalies of Dieulafoy's dis-ease is illustrated.( Clin Pathol 1995;48:267-270)

Keywords: Dieulafoy's disease, adenocarcinoma.

Department ofPathology,University of Bologna,Bologna,Italy0 LeoneM ZanelliD Santini

Department ofSurgeryF MinniD Marrano

Correspondence to:Dr 0 Leone, Instituto diAnatomia Patologica,Universita di Bologna,Policlinico Sant'Orsola,Via Massarenti 9,40138 Bologna, Italy.Accepted for publication4 August 1994

Dieulafoy's disease is an arterial malformationof the upper stomach which usually occurs inmiddle-aged and elderly men without anyrelevant family history or any previous gas-trointestinal symptomatology. Its typical clini-cal presentation is life threatening, massiveand recurrent gastric bleeding.

In the medical literature there is a lot ofconfusion about the terminology of vascularmalformations and many terms-for example,angiodysplasia, vascular ectasia, arteriovenousmalformation, haemangioma, and angioma,have been used to describe this condition.In 1976 Moore et al2 tried to divide gastro-intestinal arteriovenous malformations intothree types, a classification further modified byLewi et al3 and Fowler et al.4 However, theseclassifications of gastrointestinal vascular mal-formations are not sufficient for a clear defin-ition of the pathology. Different terms havealso been used to describe Dieulafoy's vascularmalformation-for example, calibre persistentartery of the stomach, cirsoid aneurysm, sub-mucosal arterial malformation, gastric ar-

teriosclerosis, and peptic ulcer of peculiarlocation; however, Dieulafoy's vascular mal-formation is the currently accepted term. Thiscondition was first described by Gallard' in

1884 as submucosal miliary aneurysms; thenin 1889 Dieulafoy6 designated it exulceratiosimplex believing that this lesion was an earlystage of peptic ulceration. Recently, it has beeninterpreted as a congenital anomaly char-acterised by a single large, tortuous, and calibrepersistent submucosal artery with no evidenceof vasculitis, atherosclerosis, or aneurysmformation.78 The cause of bleeding is believedto be a mucosal erosion resulting from an arteryprotruding into the overlying mucosa or fromfocal gastritis, leading to exposure of the vessel.The mucosal ulcer, localised along the smallercurvature within 6 cm of the gastro-oeso-phageal junction,9 is usually small and shallow.

Here, we present a report of Dieulafoy'sdisease focusing particularly on the histo-pathological aspects.

MethodsA 41 year old man was admitted to St OrsolaHospital, Bologna with symptoms of anaemia(asthenia, dizziness) and melaena. There wasno relevant family history, or excessive alcoholor aspirin intake. For about seven to eightmonths the patient had been suffering from anepigastric pain, beginning a few hours aftermeals and lasting through the night, but whichdisappeared on ingestion offood. At admission,he was found to have a haemoglobin con-centration of 9 1 g/dl, a red blood cell count of3-01 x 106/ml, a haematocrit of 26%, a meancorpuscular volume of 86m3, a white blood cellcount of 9-76 x 103/ml, and a platelet count of169 x 103ml.An urgent gastroscopy revealed a subcardial

gastric ulcer (diameter 1-5 cm) with irregularedges and profuse bleeding. After transfusionaltherapy and antiulcer treatment (ranitidine), arepeat gastroscopy revealed that the ulcer hadhealed and the presence of chronic gastritiswith no evidence ofactive bleeding. The patientwas discharged and maintained on antiulcertreatment (omeprazole). After further bleedingwith a melaena, the patient was readmittedto the surgical department and a gastroscopyshowed a gastric ulcer in a subcardial locationon the posterior medial wall, with evidence ofrecent bleeding. Analysis of biopsy specimensrevealed atrophic chronic gastritis with diffuseintestinal metaplasia. The patient's ulcer ap-peared to be healing well on gastroscopy but

I Clin Pathol 1995;48:267-270 267

on May 25, 2022 by guest. P

rotected by copyright.http://jcp.bm

j.com/

J Clin P

athol: first published as 10.1136/jcp.48.3.267 on 1 March 1995. D

ownloaded from

Leone, Zanelli, Santini, Minni, Marrano

Figure I A: Gastric mucosa with a mild ischaemia; B: scattered signet ring cellsdescending from the lower part of the glandular necks.

the examination of the biopsy specimens dis-closed the presence of diffuse carcinoma (mi-croglandular type). The patient subsequentlyunderwent laparotomy, gastrectomy and splen-ectomy.The excised stomach measured 13 cm along

the smaller and 29 cm along the larger cur-

vature with an annexed duodenal tract of 2 cm.

On gross examination, the gastric mucosa was

widely haemorrhagic, especially in the fundusand body regions and a retracting star-shapedarea measuring 1-4 cm in diameter was present4-5 cm from the proximal resection margin. Atsectioning, this area showed focal fibrous tissuelocalised to the mucosa and submucosa. Asecond, slightly depressed area (diameter1-5 cm) was evident 0-2 cm from the proximalresection margin, while the antral mucosa

showed diffuse bulging areas. The star-shapedand slightly depressed areas were sampled.

ox'*

Or

Figure 2 Photomicrograph showing the large artery running through the gastric musclecoat (haematoxylin and eosin x 100). The insert shows focal reduplication of arteriallamina elastica (Van Gieson x 400).

Other samples were obtained from the antralregion, local lymph nodes, spleen, and omen-tum.

All specimens were fixed in 10% bufferedformalin, embedded in paraffin wax and 2,msections were stained using haematoxylin andeosin, Van Gieson and Masson's trichromemethods. Immunohistochemical staining forkeratin (clone MNF 116; Dako, Glostrup,Denmark) was performed using the Strept-avidin-biotin immunoperoxidase method.

ResultsMorphological examination of specimensshowed the following histopathological find-ings. The grossly depressed areas showed re-epithelialisation with residual erosions. The re-maining mucosa was thickened and oed-ematous with diffuse intestinal metaplasia andactive chronic gastritis. In the lamina propriaaspects of ischaemia (fig 1A) such as subacutenecrosis, fibrosis, and granulation tissue closeto the muscularis mucosae were observed. Inthe submucosa, vessels (arteries and veins)close to focal areas of haemorrhagic effusionwere enlarged and filled with serum, eryth-rocytes and granulocytes. The muscularis mu-cosae was focally thickened and dissociated bylymphoid aggregates and penetrating arterioles.The muscle coat also appeared to be disruptedby frail connective tissue and arterial vessels.Another characteristic histological feature wasthe presence of an unusually large artery (fig2), with intimal non-concentric hyperplasia,in the muscularis and submucosa and inclose contact with the mucous membrane. Ar-terial muscle layer fibres were mixed with fib-rous tissue: in these vessels the stained elastictissue had normal internal lamina elastica withfocal areas of thickening and reduplication (fig2 insert).The intima of the arteriolar walls showed

circumscribed thickening (fig 3B) with vacuo-lated cells, focal aspects of vascular neo-formation (fig 3A) and areas of degeneration(muscle fibre vacuolation). Intimal hyperplasiawith a non-concentric proliferation of myo-intimal cells was present in the arterioles pen-etrating through the muscularis mucosae.Some veins had rather thick walls and dis-

sociated elastic fibres (fig 3C). An early intra-mucosal, signet-ring cell, gastric cancer wasnoted: microfoci of scattered signet-ring cells(fig 1B) in close contact with the lower part ofthe glandular necks were detected in the mu-cosa surrounding the re-epithelialised star-shaped area. We think that this aspect cor-responds to the "early gastric cancer signet-ring cell drippings" studied by Grundmann.10

DiscussionDieulafoy's disease, as described in variousreports, is a clinical rather than a pathologicalentity: the unchanging clinical feature is thepresence of massive, recurrent bleeding inmiddle-aged and elderly men with no familyhistory or any previous gastrointestinal symp-tomatology. Vascular abnormalities of the

268

:....r................g 4.Y'

on May 25, 2022 by guest. P

rotected by copyright.http://jcp.bm

j.com/

J Clin P

athol: first published as 10.1136/jcp.48.3.267 on 1 March 1995. D

ownloaded from

Dieulafoy' disease associated with early gastric cancer

:n7

Figure 3 A: Thickened intima of an arteriole with aspects of vascular neoformation (Masson trichrome x 250);B: focal circumscribed thickening of the arteriolar wall with corresponding fragmentation of the lamina elastica (x 100);C: segment of a thick venous wall with dissociated elastic fibres (Van Gieson x 400).

gastric wall and a small and shallow mucosalulcer, localised to the upper stomach are thepathological features invariably observed. Inthe literature vascular malformations include atypical single large artery as well as thin-walledvenous vessels, but a common morphologicalaspect does not exist. Therefore, different typesof vascular anomalies have been reported andhistopathological lesions range from venous toarterial alterations, as noted by Geoffrey et al.1However, in our report, in accordance withother studies'12 we noted that somepathological features occur more frequently.The architecture of the wall of the large arteryis mainly normal, except for focal areas ofintimal hyperplasia and duplication of the in-ternal elastic lamina. The enlarged and tortuoussubmucosal vessels also show intimal non-con-centric hyperplasia caused by focal myointimalcell proliferation.

Originally, Dieulafoy's disease was thoughtto be related to an acquired aneurysm of anatherosclerotic submucosal vessel,5 but mi-croscopic examination does not support thisview because the vessels do not show any signsof aneurysm formation, such as an arterial wallmade up of fibrous tissue with no evidence ofa normal arterial structure. In the same wayvascular anomalies seem to be different fromthe telangiectasies characteristic of Osler-Rendu-Weber syndrome because of the ab-sence of enlarged and thin-walled venules andcapillaries. Moreover, microscopic examinationdid not disclose any evidence of atherosclerosis,as no typical lesions-for example, muscularcells plunging into a dense collagenous weft

with several elastic fibres and/or rare foamycells filled with fat, were observed. Vasculitiswas excluded because of the lack of necrosisand lymphoid penetration of the vessel walls;the identification of active inflammatorychanges in the vessel wall is considered ob-ligatory for a histological diagnosis of arteritis.Fragmentation of the internal elastic lamina issuch a constant feature of aging in all arteriesthat its presence alone is not suggestive ofactiveor healed arteritis."3

In conclusion, in our opinion this study isimportant as we attempted to examine thehistological lesions in detail. As attention hasbeen mainly focused on the clinico-endo-scopic aspects of Dieulafoy's disease in theliterature, we feel we have provided furtherinformation on the morphological char-acteristics of this disease. We would like tounderline three other points: (1) the absenceof signs of atherosclerosis, aneurysm formationor vasculitis; (2) the mixture of arterial andvenous anomalies as a distinctive histo-pathological characteristic of Dieulafoy'sdisease in addition to the calibre persistentsubmucosal arteries; and (3) gastric wall an-omalies such as oedema, thickening of the sub-mucosa, dissociation of the muscularismucosae and muscle coat, which occur as aconsequence ofthe vascular malformations andwhich could upset the trophism of the gastricwall. Finally, we would like to point out that,in the context of regenerating mucosa withaspects of ischaemic injury related to the vas-cular malformations, "early gastric cancer sig-net ring cell drippings" should be considered.

269

on May 25, 2022 by guest. P

rotected by copyright.http://jcp.bm

j.com/

J Clin P

athol: first published as 10.1136/jcp.48.3.267 on 1 March 1995. D

ownloaded from

Leone, Zanelli, Santini, Minni, Marrano

The authors are greatly indebted to Professor AM Mancini forhis helpful suggestions and criticism. Thanks also to A Busi forthe photographic work.

1 Scully R, Mark EJ, McNeely WF. Case records of theMassachussets General Hospital. N EnglJ Med 1991;10:1086-96.

2 Moore JD, Thompson NW, Appelman JD, Foley D. Ar-teriovenous malformations of the gastrointestinal tract.Arch Surg 1976;111:381-9.

3 Lewi HJE, Gledhill T, Gilmour HM, Buist TAS. Ar-teriovenous malformations of the intestine. Surg GynecolObstet 1979;149:712-16.

4 Fowler DL, Fortin D, Wood WG, Pinkerton JA Jr, KoontzPG Jr. Intestinal vascular malformations. Surgery 1979;86:377-85.

5 Gallard T. Aneurysmes miliaires de l'estomac, donnant lieua des hematemeses mortelles. Bull Soc Med Hop Paris1884;1:84-91.

6 Dieulafoy G. Exulceratio simplex: l'intervention chirurgicaledans les hematemeses foudroyantes consecutives a l'ex-

ulceration simplex de l'estomac. Bull Acad Med 1989;39:49-84.

7 Mik6 TL, Thomazy VA. The caliber persistent artery ofthe stomach: an unifying approach to gastric aneurysm,Dieulafoy's lesion, and submucosal arterial malformation.Hum Pathol 1988;19:914-21.

8 Mortesen NJMcC, Mountford RA, Davies JD, Jeans WD.Dieulafoy's disease: a distinctive arteriovenous mal-formation causing massive gastric haemorrhage. BrJ Surg1983;70:76-8.

9 Veldhuyzen van Zanten SJO, Bartelsman JFWM, ShipperMEI, Tytgat GNJ. Recurrent massive haematemesis fromDieulafoy's vascular malformations-a review of 101 cases.Gut 1986;27:213-22.

10 Grundmann E. Histologic types and possible initial stagesin early gastric carcinoma. Beitrage zur Pathologie 1975;154:256-80.

11 Mower GA, Whitehead R. Gastric hemorrhage due to iup-tured arteriovenous malformation (Dieulafoy's disease).Pathology 1986;18:54-7.

12 Jaspersen D, Gaster CB, Koemer TH, Hammar CH. Dop-pler-controlled injection treatment of Dielafoy's disease.J Gastroenterol Hepatol 1993;8:267-9.

13 HamrinB. Polymialgiaarteritica.ActaMedScand 1972;7:533.

_7 Clin Pathol 1995;48:270-272

Importance of hepatic artery node involvementin patients with colorectal liver metastases

M J Dworkin, S Earlam, C Fordy, T G Allen-Mersh

Departmentof Surgery,Charing Cross andWestminster MedicalSchool, LondonM J DworkinS EarlamC FordyT G Alllen-Mersh

Correspondence to:Mr T G Allen-Mersh,Department of AcademicSurgery,Chelsea and WestminsterHospital,369 Fulham Road,London SW1O 9NH.

Accepted for publication25 August 1994

AbstractHepatic artery lymph node (HALN) in-volvement is an adverse prognostic factorin patients treated for colorectal livermetastases. The prevalence of HALN po-sitivity for mid-gut and hind-gut derivedcolonic tumours, for differing amounts ofliver involvement, and for Dukes' A andB versus Dukes' C primary tumours wascompared in 75 patients with colorectalliver metastases. All patients whose prim-ary tumours did not invade lymph nodes(Dukes' A or B) had liver metastases thatdid not involve local hepatic nodes, re-gardless ofthe extent ofthe disease withinthe liver. This suggests that factors con-trolling metastasis are not identical withthose which control lymphatic invasion incolorectal cancer. HALN positive patientsmay benefit less from treatment becausethey are significantly more likely to haveboth a greater burden ofdisease within theliver and a tumour with greater lymphinvasive potential than patients withHALN negative liver metastases.(J Clin Pathol 1995;48:270-272)

Keywords: Liver metastases, colorectal cancer, hepaticartery lymph node.

Hepatic artery lymph node (HALN) in-volvement is an adverse prognostic factor inpatients being treated by resection' or chemo-therapy2 for colorectal liver metastases. How-

ever, the route and mechanism of HALNinvolvement is uncertain.There are two possible routes ofinvolvement.

Firstly, by direct extension of disease alongthe para-aortic lymph nodes from local lymphnodes draining the primary colonic tumour. Ifthis were the case, then the prevalence ofHALN positivity would be greater where theprimary tumour and associated local nodeswere closer to the hepatic artery-that is, prim-ary tumours arising in mid-gut derived colonsupplied by the superior mesenteric artery, thanif the primary tumour and associated nodesarose more caudally in the hind-gut, whichis supplied by the inferior mesenteric artery.'Secondly, HALN involvement could occur asa result of lymphatic spread directly from thehaematogenously derived liver metastases intothe local lymph nodes draining the liver.4We have examined this by measuring the

prevalence ofHALN positivity in patients withcolorectal liver metastases and correlating thiswith primary tumour location in the colon andwith the extent of liver metastases.

MethodsPatients with primary colorectal carcinoma andeither synchronous or metachronous livermetastases undergoing hepatic artery infusionalchemotherapy were prospectively studied. Atthe time oflaparotomy for insertion ofa hepaticartery catheter, hepatic artery lymph nodes ad-jacent to the junction between the common

270

on May 25, 2022 by guest. P

rotected by copyright.http://jcp.bm

j.com/

J Clin P

athol: first published as 10.1136/jcp.48.3.267 on 1 March 1995. D

ownloaded from