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Pathology – Research and Practice 202 (2006) 517–522

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ORIGINAL ARTICLE

Focal myointimal hyperplasia of mesenteric veins is associated

with previous trauma in surgical specimens

Jessica Shermana, Patricia C. Kaob, A. Brian Westc, Hagen Blaszyka,�

aDepartment of Pathology, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USAbInternal Medicine, University of Vermont College of Medicine, Burlington, VT, USAcDepartment of Pathology, New York University Medical Center, New York, NY, USA

Received 2 August 2005; accepted 8 March 2006

Abstract

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood disease thatoccurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. This disease is oftenconfused with chronic idiopathic inflammatory bowel disease clinically, and pathologists may miss the diagnosis unlesselastin stains are performed because diseased veins may readily be mistaken for arteries. The etiology of IMHMV isunclear, but a traumatic pathomechanism resulting in arterialization of the veins has been proposed. Review of bowelresection specimens (n ¼ 68) for non-neoplastic disease within a 1-year period in patients younger than 50 years of agerevealed 10 cases with focal mesenteric vein myointimal hyperplasia. Significantly more cases with focal myointimalhyperplasia of mesenteric veins (MHMV) were associated with pre-resection trauma to the involved bowel segment(5/11 vs. 5/57; p ¼ 0:0016). A significant association of MHMV with pre-resection trauma supports the hypothesis thatidiopathic myointimal hyperplasia of the mesenteric veins may be the result of trauma through torsion/stretching ofthe sigmoid colon and, subsequently, increased mesenteric venous pressure through arterialization.r 2006 Elsevier GmbH. All rights reserved.

Keywords: Colon; Ischemia; Mesenteric veins; Inflammatory bowel disease

Introduction

Mesenteric ischemia is a condition most commonlycaused by arterial thromboembolic disease and isassociated with the elderly population [5]. Venousocclusion is an uncommon cause of ischemic boweldisease, and the majority of such cases are caused byvenous thrombosis [6,8]. Non-thrombotic occlusion ofthe mesenteric veins is rare and has been previouslydescribed to occur in vasculitis associated with systemiclupus erythematosus, Behcet’s disease, and enterocolic

e front matter r 2006 Elsevier GmbH. All rights reserved.

p.2006.03.003

ng author. Tel.: 802 847 2469; fax: 802 847 9644.

ss: hagen.blaszyk@vtmednet.org (H. Blaszyk).

lymphocytic phlebitis, also known as mesenteric inflam-matory veno-occlusive disease (MIVOD) [1,5]. Idio-pathic myointimal hyperplasia of mesenteric veins(IMHMV) is a rare and poorly understood conditionthat has been described to occur in the rectosigmoidcolon of predominantly young, previously healthy, malepatients [1,5] who ultimately require segmental resectiondue to complications after a relatively protracted clinicalcourse. IMHMV is frequently confused with IBDclinically and may be underdiagnosed in routinegastroenterology and pathology practice [2].

The etiology of IMHMV remains obscure. Abu-Alfaet al. [1] hypothesized that the venous myointimalhyperplasia is caused by an acquired traumatic

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segmental arteriovenous fistulization secondary to tor-sion or stretching injury to the sigmoid mesocolon,which is far more mobile than other colon segments.Herein, we studied whether (1) IMHMV may not havebeen recognized in the surgical pathology practice of alarge tertiary care center; (2) focal IMHMV-like changescan be seen in bowel specimens resected for non-neoplastic conditions other than IMHMV; and (3) focalIMHMV-like changes are associated with previoustraumatic injury to the affected bowel segment.

Table 1. Distribution of the 68 study cases according to

possible traumatic injury to the involved bowel segment and

presence or absence of IMHMV-like changes

n IMHMV-like

changes

Cases not associated with prior trauma:

IBD 24 2

Diverticular disease 17 3

Ischemia 4 0

Materials and methods

A SNOMED search was performed for all small andlarge bowel resections received in the Department ofPathology at Fletcher Allen Hospital in Burlington,Vermont for a 1-year period (2003). The InstitutionalReview Board approved this study. Since IMHMVoccurs typically at a younger age and in patients with nohistory of malignancy, further selection criteria refinedour search excluding patients 450 years of age andpatients undergoing bowel resection for malignancy.This search strategy revealed 68 cases of non-neoplasticbowel resections, which were further studied histologi-cally. The original hematoxylin-eosin-stained slides werereviewed, and the surgical pathology diagnosis wasconfirmed in the context of the clinical history.Particular attention was paid to mesenteric vessels,which were evaluated for myointimal smooth musclehyperplasia, narrowing, and thromboembolic lesions.Cases that showed any mesenteric vessel abnormalitywere stained (Elastic van Gieson) to definitively identifyveins and arteries. Frequencies of at least focalmyointimal hyperplasia of mesenteric veins in caseswith and without previous trauma to the affected bowelsegment were compared using the Chi-square test.

Hemorrhage 2 0

Perforation 2 0

Intramural duplication cyst 1 0

Hemorrhagic colitis 1 0

Serositis 1 0

Meckel’s diverticulum 1 0

Mesenteric venous

thrombosis

1 0

Constipation 1 0

Endometriosis 1 0

Abscess 1 0

Total non-traumatic: 57 5

Cases associated with prior trauma:

Volvulus/intusussception 4 1

Stoma takedown 4 2

Incarcerated hernia 2 1

Revision of surgical

anastomosis IBD

1 1

Total traumatic 11 5

Results

The 68 resection specimens included left ðn ¼ 21Þ andright ðn ¼ 24Þ segmental colon resections, total colec-tomies ðn ¼ 9Þ, segmental resections of small bowelðn ¼ 10Þ, and stomal takedowns ðn ¼ 4Þ. Clinicopatho-logic diagnoses included diverticular disease ðn ¼ 17Þ,inflammatory bowel disease ðn ¼ 24Þ, ischemiaðn ¼ 4Þ, stoma takedown procedure ðn ¼ 4Þ, perforationðn ¼ 2Þ, volvulus/intussusception ðn ¼ 4Þ, hemorrhageðn ¼ 2Þ, incarcerated hernia ðn ¼ 2Þ, and other ðn ¼ 9Þ.In each case, 1–5 sections (median ¼ 3) containingsections of mesenteric vessels were available for review.The distribution of cases according to prior trauma tothe involved bowel segment and the presence or absenceof focal myointimal hyperplasia of mesenteric veins

(MHMV) is detailed in Table 1. The category of ‘‘other’’included one of each of the following: intramuralduplication cyst, hemorrhagic colitis, serositis, Meckel’sdiverticulum, fistula, mesenteric vein thrombosis, con-stipation, interstitial endometriosis, and abscess. Noexample of diffuse or extensive MHMV was found.However, 10 cases (14.7%) demonstrated convincingfocal myointimal hyperplasia of mesenteric veins withluminal narrowing involving 41 vascular cross sectionin 1–4 sections per case (average 1.5). This includedspecimens resected for stoma takedown ðn ¼ 2Þ, diverti-cular disease ðn ¼ 3Þ, inflammatory bowel diseaseðn ¼ 2Þ, incarcerated hernia ðn ¼ 1Þ, volvulus/intussus-ception ðn ¼ 1Þ, and fistula ðn ¼ 1Þ. Patient character-istics, including site and history of previous trauma, isdetailed in Table 2. The myointimal changes presentin the veins often obliterates the vessel lumen (Fig. 1).Four cases showed mild changes of the accompanyingarteries that were much less severe and may representhypertensive atherosclerotic changes. In most cases,the Elastic van Gieson stain was helpful in demonstrat-ing a histologically normal artery immediatelyadjacent to the affected vein (Fig. 2). Histologicfeatures in areas adjacent to these vessels includesubmucosal fibrosis, hemosiderin-laden macrophages,

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Table 2. Characteristics of ten cases with focal myointimal hyperplasia of the mesenteric vein

Patient Sex Age Site History Prior trauma Time elapsed

1 F 20 Left colon Pancreatitis/fistula N

2 F 48 Small bowel incarcerated Incarcerated o1 montha

Hernia Bowel

3 M 45 Sigmoid colon Quadraplegic Ostomy 36 months

4 M 47 Sigmoid colon Diverticulitis Ileostomy 12 months

5 F 47 Transverse colon Crohn’s disease Ileectomy 108 months

6 M 47 Small intestine Intusseption Intusseption o1 montha

7 M 47 Sigmoid colon Diverticulosis N

8 F 39 Sigmoid colon Diverticulitis N

9 M 27 Cecum Crohn’s disease N

10 M 43 Sigmoid colon Diverticulitis N

aIntermittent/chronic trauma to bowel and mesenteric vessels.

Fig. 1. Mesenteric vein pathology of two representative cases with histories of trauma from the current study, including a revision of

an anastomotic site in a patient with Crohn’s disease (A,B; � 100) and a resection of a subacute hernia incarceration with secondary

vascular involvement by diffuse chronic inflammation (C,D; � 40). Focal mesenteric vein changes resembling IMHMV are evident

both on H&E stain (A,C) and Elastica-van-Gieson stain (B,D).

J. Sherman et al. / Pathology – Research and Practice 202 (2006) 517–522 519

and mucosal architectural disarray. No arterial-venousanastomoses were identified. A significantly greaterproportion of cases with myointimal hyperplasia ofmesenteric veins was associated with pre-resectiontrauma to the involved bowel segment (5/11 vs. 5/57;p ¼ 0:0016). Two cases were associated with chronicinflammation of the bowel wall with secondaryinvolvement of the vessels. (Fig. 1) This inflammationhad a diffuse interstitial and perivascular distributionwithout definitive vasculitis or fibrinoid necrosis. No

specific drug history was available at the time of thisstudy.

Discussion

There have been few reports of IMHMV [5] since theoriginal description of this disease by Genta and Haggittin 1991 [5]. Idiopathic myointimal hyperplasia of themesenteric veins usually effects young, previously

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Fig. 2. Endoscopic appearance, biopsy findings, and mesenteric vein pathology of a typical case of IMHMV. (A) At an early clinical

stage, the mucosa appears endoscopically edematous, erythematous (arrow), and focally friable (double arrow). Ulcerations and an

inflammatory exudate may not be present until a later stage. (B) Endoscopic biopsies show patchy mild stromal changes, congestion,

mostly intact surface epithelium, and regenerative mucosal changes but no chronicity. Numerous prominent dilated vessels are

evident. They are distributed diffusely throughout the lamina propria in the affected areas and display gaping luminal profiles,

thickened walls, and prominent endothelial cells. (C–D) Histopathologic findings of a rectosigmoid resection specimen in IMHMV.

A mesenteric vein with corresponding artery is stained with H&E (C) and Elastica-van-Gieson (D). The special stain clearly

distinguishes the normal artery from the vein, which shows near-total occlusion, prominent myointimal proliferation, perivenous

fibrosis, and focal areas of recanalization.

J. Sherman et al. / Pathology – Research and Practice 202 (2006) 517–522520

healthy, male patients with a relatively protractedclinical course. Clinical presentation, including a historyof weight loss, the duration of disease, negative stoolcultures, and initial endoscopic appearance are clearlyconsistent with IBD. The appearance is that of anedematous, erythematous, and friable colonic mucosa inthe sigmoid colon. Ulceration and inflammatory exu-dates may be seen later in the disease process [9]. This iscontrasted by subtle and less specific endoscopic biopsyfindings that are incompatible with IBD and are eitherreported as nonspecific or suggestive of an ischemicetiology. Thus, IMHMV may elude the pathologist sothat prior to resection, the entity may not even beconsidered in the differential diagnosis. The recentreport of a case of IMHMV as ‘‘isolated visceral smallartery fibromuscular hyperplasia-induced ischemic coli-tis mimicking inflammatory bowel disease’’ [4] highlightsanother potential diagnostic pitfall. While the quitespectacular pathognomonic venous lesions are obviousin resection specimens, they may readily be mistaken forabnormal arteries, especially if an elastin stain is not

performed. The discrepancy between clinical impressionand endoscopic biopsy findings in IMHMV has led tothe clinical management of most reported cases ofIMHMV as IBD [9]. While the fairly prolonged clinicalcourse of IMHMV usually cumulates in emergencysurgical resection, follow-up data indicate an uneventfulrecovery of affected patients without recurrence. Histo-logic features of vascular changes secondary to activechronic colitis are associated with generalized inflam-mation, ulceration, neutrophilic infiltrate, and fibrinoidnecrosis, features which are not associated withIMHMV.

Prominent myointimal hyperplasia of mesentericveins is seen in another rare entity that has been termedenterocolic lymphocytic phlebitis [7] or mesentericinflammatory veno-occlusive disease [11]. Distinct de-mographic patient characteristics, different enterocolicdisease distribution patterns, and diverse histologicfindings suggest that enterocolic lymphocytic phlebitisand IMHMV are separate entities [1]. Histologicfeatures of enterocolic lymphocytic phlebitis and

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mesenteric inflammatory veno-occlusive disease includea prominent lymphocytic infiltrate in all three layers ofthe vessel wall involving the mesenteric veins andintramucosal tributaries while sparing the arteries andarterioles. Venous thrombi are seen in various stages oforganization, and myointimal hyperplasia may bepresent in presumably older resolving lesions [7,11].This pattern was not identified in any of our cases andcan be excluded in our differential diagnosis. However,potential overlap between disorders is highlighted by acase reported as mesenteric inflammatory veno-occlu-sive disease, which would fit the diagnostic criteria forIMHMV much better [3]. It might be best to separatethese entities for the time being based on diseasedistribution characteristic, in that IMHMV seems tooccur exclusively in the rectosigmoid colon. The controlcases with vascular changes included one case of IBD,one fistula, and three cases of diverticulitis. In thesecases, the myointimal hyperplasia may represent latechanges of a resolved acute inflammatory process.Although definitive vasculitis was not identified, thepresence of inflammation in the cases with MHMV inour study warrants further investigation.

The true incidence of IMHMV is unknown, but it maybe underdiagnosed. Our review of 68 large and smallbowel resection specimens performed for non-neoplasticdisease received over a 1-year period at a large tertiarycare center did not reveal any ‘‘classic’’ cases of IMHMVthat were misdiagnosed. A larger study involving multi-ple institutions would be necessary to define the trueincidence of this disease. It is conceivable that the fewreported cases may represent only cases that resulted insurgical intervention, and where the diagnostic histologicfeatures have been recognized.

The etiology of IMHMV remains obscure. Mostpatients with IMHMV are reported to have nosignificant drug history. Histologically, the mesentericveins in IMHMV closely resemble those seen in failedcardiac saphenous vein bypass grafts, consistent with asecondary ‘‘arterialization’’ effect caused by greatlyincreased pressure within affected veins [10]. Thehistologic findings are also consistent with stenosis ofarterio-venous fistulas in dialysis patients [12]. Abu-Alfaet al. [1] hypothesized that the venous myointimalhyperplasia in IMHMV is caused by an acquiredsegmental arteriovenous fistulization. This appears tobe possible, since the sigmoid colon is far more mobilethan other parts of the colon. Traumatic injury to thesigmoid mesocolon secondary to torsion, volvulus, orstretching may occur more readily than in other colonsegments and lead to the formation of a traumaticarteriovenous fistulization within the mesentery. Thiswould explain why such cases are exclusively seen in thesigmoid colon of young, healthy, and physically fitadults. No arteriovenous malformation has been identi-fied in any of the reported cases, but the diagnosis of

IMHMV did not become evident until post-surgery.Arteriovenous malformations can be difficult to identifyin pathology specimens, and specific angiographicstudies have not been performed preoperatively. A casereported by Lavu and Minocha [11] detailed someconspicuous findings that were seen on retrospectiveanalysis of an angiogram performed in their patient.There was an enlarged and tortuous marginal artery atthe rectosigmoid colon, but no early draining veins thatare characteristic of arterio-venous anastomoses. Therewere also large vessels draping around about therectosigmoid colon, which were noted to feed ectaticmucosal vessels of the involved colon segment.

In this study, we showed a significant association ofprior trauma to the resected bowel segment and focalmyointimal hyperplasia of mesenteric veins. However,several sources of bias exist. This is a retrospective studyexamining varying amounts of mesenteric tissue thathad been processed at the time of surgery. Thedistribution of these lesions could not be assessed, andthe frequency is likely underestimated in this studydesign. Moreover, the time interval between traumaticinjury to the resected bowel segments has obviously beenvariable. Our findings, nonetheless, support the traumahypothesis suggested as a plausible pathomechanism forIMHMV [1]. Future prospective studies will help todefinitively answer this question.

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