Gut, 1986, 27, 873-875

Case report

Extramedullary haemopoiesis in the small bowelB K SHARMA, R E POUNDER, J P CRUSE, S M KNOWLES, AND A A M LEWIS

From the Academic Departments of Medicine, Histopathology, and Haematology, and the Department ofSurgery, Royal Free Hospital School of Medicine, London.

SUMMARY A patient with myelofibrosis developed repeated gastrointestinal haemorrhage fromthe small intestine, which was found to be infiltrated with extramedullary haemopoiesis.Nineteen months later he presented with subacute intestinal obstruction; radiology andlaparotomy documented progressive infiltration of the small bowel. Histological examination ofthe resected terminal ileum showed patchy mucosal ulceration, with underlying submucosal andserosal extramedullary haemopoiesis.

We describe a patient with extramedullary haemo-poiesis involving the small intestine, who presentedinitially with rectal bleeding and later developedsmall bowel obstruction.

Case report

A 43 year old man presented in 1977 with a history 'of recurrent oral ulceration. He was found to haveuncomplicated aphthous ulceration, but a peripheralblood film showed a number of nucleated red bloodcells with marked anisocytosis, poikilocytosis, andspherocytosis. His haemoglobin was 119 g/dl. Atrephine bone biopsy revealed appearances consis-tent with early myelofibrosis. He remained asymp-tomatic until March 1979 when he developedspontaneous bruising over both ankles and oc-casional episodes of epistaxis. In May 1979 heunderwent an elective splenectomy to relieve severethrombocytopaenia. In August 1980 and January1981 the patient reported two episodes of briskbleeding per rectum which settled spontaneously; abarium enema was normal.

In December 1981 he presented with furtherbleeding per rectum. His haemoglobin was 10-9 g/dl,WBC 121 x 109/l and platelets 270x 109/l. Uppergastrointestinal endoscopy and colonoscopy within

Address for correspondence: Dr R E Pounder, Academic Depart-ment of Medicine, Royal Free Hospital, Pond Street, London NW320G. Fig. 1 Barium follow-through in July 1982, showing

displacement of ileal loops, with narrowing of the terminalReceived for publication 26 September 1985. ileum, caused by extramedullary haemopoiesis.

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Sharma, Pounder, Cruse, Knowles, and Lewis

12 hours of the haemorrhage failed to identify asource of bleeding. A barium small bowel follow-through revealed a dilated distal small bowel withthickening and infiltration of the terminal ileum. Atlaparotomy the terminal ileum was noted to bethickened with patches of inflammation. The mesen-tric lymph nodes were large and fleshy, and theperitoneum was thickened. Biopsies taken from theterminal ileum, peritoneum, and mesenteric lymphnodes all revealed histological appearances consis-tent with extramedullary haemopoiesis. He wasstarted on a low residue diet, to avoid bolusobstruction. One month later he suffered a furtherepisode of rectal bleeding; his Hb fell to 9-1 g/dl andhe was transfused two units of packed cells.

In June 1982 he developed further intermittentcramping lower abdominal pain. In July 1982 he wasadmitted with severe lower abdominal pain andvomiting: a plain radiograph of the abdomenshowed several air fluid levels in the right iliac fossa.A barium follow through showed separation of thedistal ileal loops by adjacent masses, and theterminal ileum was narrowed at its junction with thecaecum (Fig. 1). At laparotomy the surgeon

(AAML), who had operated seven months earlier,noted more extensive thickening of the small intes-tinal wall. He resected the most severely affectedbowel, leaving macroscopic disease in the jejunumand the proximal ileum. The resected specimencomprised 60 cm of the terminal ileum and theproximal 3 cm of the caecum. Nine areas of mucosalulceration were identified in the terminal ileum,ranging from 0*5 to 1.0 cm in maximum diameter.The mesentery was normal but the mesentericlymph nodes were slightly enlarged.

Histological sections from the ulcerated areas(Fig. 2) showed well demarcated mucosal ulcers ofvariable depth with acute inflammatory exudate andslough overlying granulation and fibrous tissue. Theintervening non-ulcerated mucosa had a normalvillous architecture. Subjacent to the ulcers wereareas showing striking evidence of extramedullaryhaemopoiesis (see inset, Fig. 2) with large atypicalmegakaryocytes, groups of normoblasts andimmature myeloid precursors. Similar extra-medullary haemopoiesis was present focally in theserosa and the perinodal fat, but the lymph nodesshowed reactive follicular hyperplasia only. There

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Fig. 2 Photomicrograph showing ileal mucosal ulceration with megakaryocytes, normoblasts and myeloid precursors (seeinset) present in the ulcer base.

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Extramedullary haemopoiesis in the small bowel 875

was no evidence of vascular occlusion in any of thesections.

After the ileocaecal resection, the patient had astormy postoperative period with several severewound and skin infections.The patient suffered no further episode of gas-

trointestinal haemorrhage until April 1983 when hewas admitted to another hospital having passed 'alarge quanitity' of fresh blood per rectum. Whenreviewed in outpatients in September 1983 hementioned that he had suffered two further episodesof rectal bleeding during the preceding three weeksbut he did not seek medical advice. Investigationsrevealed a haemoglobin of 8-1 g/dl, WBC 8 5x 109/1with 60% myeloblasts, platelets 82x 109/l. He hadtransformed to acute myeloblastic leukaemia. Thepatient refused aggressive chemotherapy; he wasgiven transfusions of blood and platelets as suppor-tive measures. He died at home in February 1984.An autopsy was not performed.

DiscussionExtramedullary erythropoiesis occurs in conditionsaccompanied by increased numbers of circulatingmyeloid progenitor cells'-2. The commonest sites ofextramedullary haemopoiesis are the spleen, liver,kidneys and the adrenal glands. Other organs areoccasionally involved, however, these include theposterior mediastinum, the Vericardium, skin,joints, and the epidural space.-= The haemopoieticmass can cause symptoms resulting from com-pression of adjacent structures. For example, pro-gressive paraplegia may develop when extra-medullary haemopoiesis occurs in the epiduralspace.5A search of the medical literature failed to reveal

any report of extramedullary haemopoiesis occur-ring within the wall of the small intestine. Thisabsence is surprising as lymphoid tissue is present inabundance throughout the small intestine, particu-larly in the terminal ileum. The pathogenesis of thispatient's mucosal ulceration seen in the resectedileum is unclear; it is possible that pressure fromsubmucosal extramedullary haemopoiesis causedlocalised ischaemic ulceration. There was no histo-logical evidence of Crohn's disease, tuberculosis or aprimary lymphoma. In addition there was no evi-dence of a vasculitis, or features of an ulcerative

6enteritis.Gastrointestinal haemorrhage caused by ruptured

oesophageal varices, although uncommon inpatients with myelofibrosis, has been reported byseveral authors. - It is aggravated by the presenceof either a low platelet count or platelet dysfunction.Portal hypertension is due to two main mechanisms:firstly, an increased blood flow through the mass-

ively enlarged spleen; secondly, functional intra-hepatic obstruction caused by extramedullaryhaemopoiesis or periportal fibrosis in the liver.This patient did not have portal hypertension, asassessed by oesophagoscopy or laparotomy.

In a series of 138 patients with myelofibrosis, overa five year period, 12 patients died from acutemyeloid leukaemia, six died from gastrointestinalhaemorrhage (three of whom had ulcerative lesionsof the duodenal mucosa) and seven died frominfections.'2 This patient died from acute myeloidleukaemia, having survived not only subacute intes-tinal obstruction and gastrointestinal haemorrhagesdue to infiltration of the small bowel wall byextramedullary haemopoiesis, but also severe post-operative sepsis.

The authors thank Dr A P O'Reilly who initiallyexamined the resected specimen, Mr P Bates whoprepared the photomicrographs, and Miss JuliaSemus who processed the manuscript.

References1 Ersler AJ. Medullary and extramedullary blood forma-

tion. Clin Orthop 1967; 52: 25.2 Laszlo J. Myeloproliferative disorders (MDP): myelo-

fibrosis, meylosclerosis, extramedullary haemato-poiesis, undifferentiated MPD, and hamorrhagicthrombocythaemia. Sem Hematol 1975; 12: 409-32.

3 Ward HP, Block MH. The natural history of agnogenicmyeloid metaplasia (AMM) and a critical evaluationwith the myeloproliferative syndrome. Medicine 1971;50: 357-420.

4 Silverstein NM, Wollaeger EE, Baggenstoss AH.Gastrointestinal and abdominal manifestations ofagnogenic myeloid metaplasia. Arch Intern Med 1973;131: 532-7.

5 Close AS, Taira Y, Cleveland DA. Spinal cordcompression due to extramedullary haemopoiesis. AnnIntern Med 1958; 48: 421-7.

6 Jewell DP. Ulcerative enteritis. Br Med J 1983; 287:1740-1.

7 Hickling RA. Chronic non-leukaemic myelosis. Q JMed 1937; 6: 253-75.

8 Wyatt JP, Sommers SC. Chronic marrow failure,myelosclerosis and extramedullary haemopoiesis.Blood 1950; 5: 329-47.

9 Oishi N, Swisher SN, Stormont JM et al. Portalhypertension in myeloid metaplasia: report of a casewithout apparent portal obstruction. Arch Surg 1960;81: 80-6.

10 Shaldon S. Sherlock S. Portal hypertension in themyeloproliferative syndrome and the reticuloses. Am JMed 1962; 32: 758-64.

11 Dagradi AE, Siemsen J. Brook et al. Bleedingoesophageal varices in myelofibrosis. Am J Gastroen-terol 1965; 44: 536-44.

12 Silverstein NM, Linman JW. Causes of death inagnogenic myeloid metaplasia. Mayo Clin Proc 1969;44: 36-9.

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