McCluggage, Hull, Mayne, Bharucha, Wickramasinghe

ised and karyorrhectic nuclei, differences in theappearance of individual nuclei within thesame erythroblast, and focal loss of nuclearmembrane material. Mitochondrial abnor-malities, autophagic vacuoles, extensive my-elinisation of the nuclear membrane, and thepresence of intracytoplasmic myelin figureshave also been reported.CDA type III has been described in only a

few families and individuals.' 4 6 7 Sand-strom et at in 1994 in an extensive investiga-tion in a known family with CDA type III5observed a high prevalence of monoclonalgammopathy ofundetermined significance andmultiple myeloma. The authors speculatedthat genes for the development of monoclonalgammopathy/myeloma and CDA type III maybe linked. Prior to this, Byrnes et ar' in 1980described an individual who had been treatedby radiotherapy for Hodgkin's disease and wasfound to have abnormalities of erythroblasts ona bone marrow aspirate. The abnormalitieswere initially interpreted as being radiotherapyinduced but review of a bone marrow aspiratetaken 18 years earlier revealed identicalchanges in the red cell series and a diagnosis ofCDA type III was established.

In conclusion, we present bone marrowaspirate findings and ultrastructural features oferythroblasts in a case of CDA type III. Thepatient developed a malignant T cell

lymphoma with cutaneous and widespreadnodal involvement. This case, in conjunctionwith previous studies,' 4 suggests that theremay be an increased risk of development oflymphoproliferative disease in CDA type III.The mechanism of this association is not clearbut it may be that genes for the development ofCDA type III are linked to those which controllymphoid proliferation or development.

1 Wolff JA, Von Hofe FH. Familial erythroid multinuclearity.Blood 1951;6:1274-83.

2 Heimpel H,Wendt F. Congenital dyserythropoietic anaemiawith karyorrhexis and multinuclearity of erythroblasts.Helv MedActa 1968;34:103-15.

3 Sandstrom H, Wahlin A, Eriksson M, Bergstrom I, Wickra-masinghe SN. Intravascular haemolysis and increasedprevalence of myeloma and monoclonal gammopathy incongenital dyserythropoietic anaemia, type III. EurJ Hae-matol 1994;52:42-6.

4 Byrnes RK, Dhru R, Brady AM, Galen WP, Hopper B.Congenital dyserythropoietic anaemia in treated Hodg-kin's disease [letter]. Hum Pathol 1980;5:485-6.

5 Wickramasinghe SN, Wahlin A, Anstee D, Parsons SF,Stopps G, Bergstrom I, et al. Observations on twomembers of the Swedish family with congenital dyseryth-ropoietic anaemia, type III. Eur3rHaematol 1993;50:213-21.

6 Bergstrom I, Jacobsson L. Hereditary benign erythroreticu-losis. Blood 1962;19:296-303.

7 Goudsmit R, Beckers D, DeBruijne JL, Engelfriet CP, JamesJ, Morselt AFW, et al. Congenital dyserythropoieticanaemia, type III. BrJrHaematol 1972;23:97-105.

8 Wickramasinghe SN, Parry TE, Williams C, Bond AN,Hughes M, Crook S. A new case of congenital dyserythro-poietic anaemia, type III: Studies of the cell cycle distribu-tion and ultrastructure of erythroblasts and of nucleic acidsynthesis in marrow cells. J Clin Pathol 1982;35: 1103-9.

9 Choudhry VP, Saraya AK, Kasturi J, Rath PK. Congenitaldyserythropoietic anaemias: splenectomy as a mode oftherapy. Acta Haematol 1981;66:195-201.

Clin Pathol 1996;49:602-604

Duodeno-jejunal adenocarcinoma as a firstpresentation of coeliac disease

D J L MacGowan, D O'B Hourihane,W A Tanner, C O'Morain

Department ofGastroenterology,Meath/Adelaide and StJames's Hospitals,Trinity Coliege,Dublin, IrelandC O'Morain

Department ofSurgeryW A Tanner

Department ofPathologyD J L MacGowanD O'B Hourihane

Correspondence to:Professor Colm O'Morain,Department ofGastroenterology,The Meath Hospital,Heytesbury Street,Dublin 2,Ireland.

Accepted for publication20 July 1995

AbstractLong standing coeliac disease is associatedwith an increased risk of malignancy, notonly of intestinal lymphoma but also smallintestinal adenocarcinoma. Two patientswhose initial presentation was adenocarci-noma ofthe small bowel, but who were sub-sequently found to have coeliac disease afterWhipple's resection, are described. Thediagnosis was made early in the postopera-tive period in the first patient after closehistological examination ofthe tumour-freemucosal margins. This patient was placedon a gluten-free diet and had an uncompli-cated postoperative recovery with rapidweight gain. Diagnosis and dietary inter-vention in the second patient was verydelayed and resulted in the development ofsevere malabsorption and weight loss. Thisillustrates the importance ofruling out coe-liac disease prior to surgery in patients withsmall intestinal malignancies.(7 Clin Pathol 1996;49:602-604)Keywords: small bowel, adenocarcinoma, coeliac disease.

Small intestinal adenocarcinoma is 82 timesmore common in patients with coeliac diseasethan in the normal population, making it as com-mon a tumour as colon cancer in these patients.'This relation has been reported in a total of 40patients."- In the 19 patients for whom adequateinformation is available,2 ' '8 the presentation ofmalignancy was preceded by symptoms ofmalabsorption and usually a longstanding historyof coeliac disease. This is therefore the first reportdescribing two patients in whom the diagnosis ofsmall bowel adenocarcinoma was not precededby a history of malabsorption. Both patientsdeveloped symptoms of malabsorption after sur-gery, raising a possible mechanism of latent coe-liac disease being unmasked by surgery. Latentcoeliac disease (high intraepithelial lymphocytecount with positive a-gliadin antibodies) is anincreasingly recognised entity,9 but a second fac-tor seems to drive this minimal enteropathy fromlatent to clinically overt disease. Followinggastrectomy or upper gastrointestinal surgery, thebowel may be transiently hyperpermeable onreintroduction of oral intake and the intraluminal

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digestion of gluten may be impaired. Conse-quently, there may be an acute surge in glutenchallenge resulting in overt disease.9

Case reportsPATIENT 1A 59 year old woman presented with a sixmonth history of projectile vomiting, postpran-dial fullness and 20 kg weight loss. Bariummeal and follow through revealed retained gas-tric fluid and dilated loops of small bowel in theupper abdomen, suggestive of a partiallyobstructive lesion. She proceeded to lap-arotomy, where a 5 x 3 cm jejunal tumour was

seen close to the duodeno-jejunal flexure withenlarged mesenteric nodes. A Whipple's resec-

tion was performed. Histopathology confirmeda stricturing adenocarcinoma with clear resec-

tion margins, but a small focus of metastaticdeposit in one of three regional lymph nodes.The mucosa not involved by tumour demon-strated severe villous blunting with a promi-nent mononuclear infiltrate in the lamina pro-

pria (fig 1A). Alpha-gliadin antibodies were

also elevated at 2.6 IU/l (normal = 1.27-1.43IU/1) and folate levels reduced to 0.5 ng/l.

Aw ;

51mtVsS

Figure 1 Mucosafrom the distal surgical specimen in (A) shows increased intraepitheliallymphocytes with inflammatory cells in the lamina propria and short, blunted villi. (B) Thejejunal mucosa reverses to a normal pattern after the introduction of a strict gluten-free diet.

Postoperatively, the patient was commencedon a gluten-free diet and recovered rapidly. Herweight increased steadily by over 20 kg. Repeatendoscopic small bowel biopsy two monthslater showed reversal of the duodenal mucosato a normal pattern (fig 1 B). A gluten challengeresulted in abdominal pain and diarrhoeawithin 10 days and repeat duodenal biopsyconfirmed coeliac disease. She remained wellfor five years until local and distal recurrencedeveloped and she died from intestinal ob-struction and perforation.

PATIENT 2A 51 year old woman presented with a fourmonth history of epigastric pain and 6 kgweight loss. Her bowel habit was normal andshe was not anaemic. A polyp of 7 cm was seenin the second part of the duodenum at endos-copy. Biopsy revealed an invasive adenocarci-noma. A computed tomography (CT) scan ofthe abdomen showed no evidence of metas-tases. An uncomplicated Whipple's procedurefollowed and histopathology showed that all ofthe operative margins and accompanying locallymph nodes were free of tumour. Postopera-tively, the patient initially did well until sherecommenced oral intake when she developedabdominal cramps and loose, watery diar-rhoea. This pattern persisted over the nextthree months and her weight fell by 25 kg, withprofound resulting cachexia despite docu-mented daily caloric intakes of over 2000 kcal.Repeated CT scans of the abdomen showed noabnormalities apart from notable fatty infiltra-tion of the liver. Jejunal biopsy was thenperformed endoscopically and this showedtotal villous atrophy with marked plasma cellinfiltration. The tumour-free mucosal marginsof the original were then re-inspected forevidence of coeliac disease. There was subtotalvillous atrophy along with an intense mononu-clear inflammatory infiltrate in the lamina pro-pria. The original diagnosis of coeliac diseasewas also supported by elevated measurementsof both the serum a-gliadin and anti-endomysial antibodies. On introduction of agluten-free diet, her bowel habit returned tonormal within one month and her weight hadincreased by 10 kg. Although she remains well,she has not been strictly adhering to her diet.This is reflected in her most current jejunalbiopsy which is improved but not completelyreturned to normal and her persistentlyelevated anti-endomysial antibodies.

DiscussionSmall intestinal adenocarcinomas are raretumours. The largest series is of 209 cases over30 years in Saskatchewan, giving an annualincidence rate of 0.7 and 0.6 per 100 000 formen and women, respectively. Swinson et al'documented an 82-fold increase in incidencein the coeliac population when they found 19invasive small intestinal adenocarcinomas outof 259 histologically confirmed malignancies in235 patients with histologically confirmed coe-liac disease. Lymphoma was a much more fre-quently complicating neoplasm and it has beenshown that over the age of 50 years, there is a 1

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in 10 risk of intestinal lymphoma in a newlydiagnosed patient with coeliac disease.'0 Ex-actly how and why coeliac disease is associatedwith an increased risk of lymphomatous andcarcinomatous change remains unknown. Sev-eral explanations have been put forward. Themucosal damage in coeliac disease may makethe small intestine more permeable to environ-mental carcinogens which, with associatedmalabsorptive vitamin A deficiency and in-creased vulnerability to oxidative injury, wouldenhance carcinogenic change. Known predis-posing factors for the development of smallintestinal adenocarcinoma include Crohn'sdisease, adenomatous polyps and Peutz-Jeugher's syndrome.4 Perzin et al" reportedthat 23 of 51 cases of small intestinal adeno-carcinoma had evidence of adenoma and carci-noma in the same lesion. Survival is dependenton the presence or absence of nodal involve-ment at presentation. Five year survival withnode negative disease is 68%, while the overallfigure varies from 15 to 20%.12 Thus, as theprognosis is not uniformly poor and somepatients are potentially curable by total resec-tion (as in patient 2 in the present paper), lim-iting postoperative morbidity and recognisingpotential complications becomes very impor-tant. Clinically unmasked coeliac disease com-plicating Whipple's resection has not beendescribed before and these two cases illustratethe importance of early diagnosis and dietary

intervention prior to surgery. Previous cases offailure to thrive and weight loss followingWhipple's resection may be simply put down tothe effects of small bowel resection, pancreaticinsufficiency, tumour progression, or earlyrecurrence. Underlying coeliac disease shouldalso be considered and the tumour-free mu-cosal margins carefully inspected.

1 Swinson CM, Slavin G, Coles EC, Booth CC. Coeliac dis-ease and malignancy. Lancet 1983-i: 111-15.

2 Holmes GKT, Dunn GI, Cockel R, Brookes VS. Adenocar-cinoma of the upper small bowel complicating coeliac dis-ease. Gut 1980;21:1010-16.

3 Selby WS, Gallagher ND. Malignancy in a 19 yearexperience of adult Coeliac disease. Dig Dis Sci 1979;24:684-8.

4 Lioe TF, Biggart JD. Primary adenocarcinoma of thejejunum and ileum: Clincopathological review of 25 cases.J Clin Pathol 1990;43:533-6.

5 Farrell DJ, Shrimankar J, Griffin SM. Duodenal adenocarci-noma complicating coeliac disease. Histopathology 1991;19:285-7.

6 Straker RJ, Gunasekaran S, Brady PG. Adenocarcinoma ofthe jejunum in association with Coeliac sprue. J Clin Gas-troenterol 1989;11:320-3.

7 Marignani M, Levin MF, Bach DB, Sinha R. Coeliacdisease complicated by adenocarcinoma. Resident's caseof the month. Can Assoc RadiolJ 1993;44:481-4.

8 Pelli MA, Cavalletti ML, Bassotti G, Ribacchi F, Morelli A.Adenocarcinoma of the duodenal bulb in a young Coeliacwoman. ItalJ3 Gastroenterol 1993;25:121-2.

9 Ferguson A, Arranz E, O'Mahony S. Clinical and pathologi-cal spectrum of Coeliac disease -active, silent, latent,potential. Gut 1993;34:150-1.

10 Cooper BT, Holmes GK, Cooke WT. Lymphoma risk inCoeliac disease of later life. Digestion 1982;23:89-92.

11 Perzin KH, Bridge MF. Adenomas of the small intestine: Aclinicopathological review of 51 cases and a study of theirrelationship to carcinoma. Cancer 1981;48:799-819.

12 Barclay THC, Schapira DV. Malignant tumours of the smallintestine. Cancer 1983;51:878-81.

J Clin Pathol 1996;49:604-607

Mixed low grade and high grade endometrialstromal sarcoma of uterus: differences onimmunohistochemistry and chromosome in situhybridisation

A N-Y Cheung,W-F Ng, L-P Chung, U-S Khoo

Department ofPathology,University ofHongKong,Hong Kong

Correspondence to:Dr Annie Cheung,Department of Pathology,University of Hong Kong,Queen Mary Hospital,Pokfulam Road,Hong Kong.

Accepted for publication18 October 1995

AbstractA case of a 64 year old woman with a

tumour of the uterus is reported. Thepatient presented with postmenopausalbleeding and subsequently underwenttotal hysterectomy and bilateral salpingo-oophorectomy. Sections of the tumourshowed a low grade endometrial stromalsarcoma coexisting with areas consistentwith high grade sarcoma. The sarcoma

cells, in both the low and high grade areas,were positive for vimentin and negativefor desmin and cytokeratin on immuno-histochemistry. While the sarcoma cells inthe low grade region showed immunore-activity for oestrogen and progestogenreceptors, those in the high grade region

did not. Using chromosome in situ hy-bridisation, the low grade portion of thesarcoma was diploid for chromosomes X,11, 12, and 17, whereas the more anaplas-tic areas were aneuploid for these chro-mosomes. This case may represent anexample of high grade endometrial stro-mal sarcoma arising by dedifferentiationfrom a low grade stromal sarcoma. Ad-equate sampling is important in identify-ing such anaplastic changes as the originof the tumour will affect patient manage-ment.(7 Clin Pathol 1996;49:604-607)

Keywords: endometrial stromal sarcoma, dedifferentia-tion.

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