Essential thrombocythemia

We report a case of gastric myeloid metaplasia in an 89-year-old woman with agnogenic myeloid metaplasia. The lesions were fortuitously discovered on upper endoscopy. The antral mucosa was thickened and polypoid, and on histologic examination contained immature granulocytes, megakaryocytes, and a few erythroblasts without desmoplastic stromal reaction. The granulocytes were positive for CD15, CD68, and myeloperoxidase on immunohistochemistry, and the megakaryocytes showed positive reactivity for factor VIII. Gastric myeloid metaplasia is a very rare event, and to our knowledge only 6 cases have been reported in the literature to date. It usually occurs in patients with advanced myeloproliferative syndrome. Gastric myeloid metaplasia often has a pseudotumoral appearance, leading to digestive symptoms. Histologic diagnosis is straightforward when trilinear hematopoietic elements are identified in gastric biopsies. Immunohistochemistry with anti-factor VIII antibody can be useful to confirm the presence of megakaryocytes.

(Arch Pathol Lab Med. 2004;128:568-570)

Myeloid metaplasia of the stomach is a very rare event.1-6 It usually occurs in patients with myeloproliferative disorder, and it is characterized histologically by the presence of trilinear hematopoietic elements in the gastric wall.1-6 We report a case of gastric myeloid metaplasia in an 89-year-old woman with myelofibrosis and myeloid metaplasia and review the literature on this topic.

REPORT OF A CASE

An 89-year-old woman with a past history of hip arthroplasty, chronic renal failure, atrial tachyarrhythmia, and amiodarone-induced hypothyroidism presented with asthenia. She had been diagnosed 2 years previously with agnogenic myeloid metaplasia and had been treated with hydroxyurea for several months. On physical examination, the patient had cutaneous pallor and a firm and markedly enlarged spleen. Laboratory findings included the following: hemoglobin, 8 g/dL; hematocrit, 26%; red blood cell count, 3.25 × 10^sup 6^/µL with dacryocytes and marked anisopoikilocytosis; leukocyte count, 32 × 10^sup 3^/µL with 5% myelocytes, 5% metamyelocytes, and 5% myeloblasts; and platelet count, 31 × 10^sup 3^/µL. The patient did not complain of digestive symptoms, but to rule out occult digestive bleeding, a gastroduodenal endoscopy was performed. It showed an unusual appearance of thickened and polypoid antral mucosa.

PATHOLOGIC FINDINGS

Microscopic examination of the gastric biopsies revealed the presence of cellular infiltrate in the mucosa and submucosa. This infiltrate was composed of numerous granular cells in all stages of differentiation, and a few atypical multinucleated megakaryocytes (Figures 1 and 2). Erythroid elements were rare. Blasts were not identified. No desmoplastic stromal reaction was evident. On immunohistochemistry, the granulocytes were positive for myeloperoxidase (Dako, Glostrup, Denmark; 1:150) (Figure 3) and CD15 antibodies (Immunotech, Marseille, France; 1: 50), and some were positive for CD68 (Dako, 1:100). Megakaryocytes were immunoreactive for factor VIII (Dako, 1:100) (Figure 4). No hematopoietic cell was positive for CD34 (Immunotech, prediluted).

COMMENT

Primary myelofibrosis with myeloid metaplasia, also called agnogenic myeloid metaplasia, is a rare chronic myeloproliferative disorder of adults and elderly people.7 It is caused by the clonal proliferation of a multipotent hematopoietic progenitor cell.7 It leads to an abnormal population of hematopoietic cells, notably clonal megakaryocytes that release fibrogenic cytokines in the bone marrow and colonize extramedullary sites.7 Patients manifest splenomegaly, bone marrow myelofibrosis, and immature myeloid and erythroid cells with marked poikilocytosis and anisocytosis in the peripheral blood.7

Extramedullary hematopoiesis in myelofibrosis with myeloid metaplasia was originally believed to arise from the reactivation of fetal hematopoietic elements, occurring in compensation for a progressively failing fibrotic bone marrow. Current evidence suggests that extramedullary hematopoiesis could result from filtration of circulating myeloid precursors.7 The altered marrow stroma could provide hematopoietic cells access to the circulation, from which they are filtered by the spleen and other organs.7 The most common sites of extramedullary hematopoiesis are the spleen, liver, and lymph nodes.2 Other organs, such as the kidney, adrenal glands, lung, thymus, breast, serosal surfaces (pleura, pericardium, peritoneum), ovary, central nervous system, epidural space, skin, pancreas, epididymis, and retroperitoneal fat, may also be involved.1,2,5 Development of extramedullary hematopoiesis in the gastrointestinal tract is extremely rare.1-9 It can involve the small intestine,8 large intestine,2 and the esophagus.9

Gastric myeloid metaplasia is a rare event, and to our knowledge, only 6 cases have been reported in the literature to date (Table).1-6 It always occurs in patients with a myeloproliferative disorder, such as chronic myeloid leukemia,3 polycythemia vera,5 essential thrombocythemia,4 and primary myelofibrosis with myeloid metaplasia (Table).1,2,6 Patients often complain of abdominal pain, vomiting, or digestive bleeding (Table). On endoscopy or gross examination, gastric extramedullary hematopoiesis resembles a polyp, a mass, or a thickened gastric wall, sometimes with giant gastric folds (Table). The lesions result from the sequestration, accumulation, and proliferation of circulating myeloid progenitors in the gastric wall. Histologic examination reveals the presence of immature myeloid cells in all stages of differentiation, erythroid nests, and atypical megakaryocytes. Endothelial markers, such as anti-factor VIII antibody, can be useful in identifying atypical multinucleated cells as megakaryocytes on immunohistochemistry.10 Myeloid metaplasia can sometimes be accompanied by an intense desmoplastic stromal reaction,5 and these lesions have been referred to as fibrous hematopoietic tumors,11 extramedullary myeloid tumors, or sclerosing extramedullary hematopoietic tumors.12 The diagnosis of gastric extramedullary hematopoiesis can be made using gastric biopsies, as in the present case,6 but also has been made using gastric specimens taken during postmortem examination in 5 of the 6 reported cases.1-5 Gastric extramedullary hematopoiesis is often accompanied by extramedullary hematopoiesis in other organs (Table).1-5

Differential diagnoses include gastric involvement of Hodgkin disease,13 gastric granulocytic sarcoma,14 linitis plastica, and gastric myelolipoma.15 Primary Hodgkin disease of the stomach is very rare13 and is histologically characterized by the presence of Reed-Sternberg cells and immunoreactivity for CD15 and CD30 in a background of reactive inflammatory cells accompanied by fibrosis of a variable degree. Gastric granulocytic sarcoma is a rare tumor composed of immature myeloid cells.14 The tumor is histologically composed of a diffuse infiltrate of large cells with round nuclei containing cytoplasmic azurophilic granules that can be detected by Giemsa stain. The infiltrate often contains immature eosinophils, but contains neither erythroblasts nor megakaryocytes. Poorly differentiated diffuse gastric adenocarcinoma (linitis plastica) is composed of round cells that are immunoreactive for cytokeratin and are isolated or organized in a diffuse or single-file pattern in a dense fibroblastic stroma. Only 1 case of gastric myelolipoma has been reported in the literature in a patient without myeloproliferative disorder.14 The lesion contains mature adipose tissue with no sclerotic background and trilinear hematopoietic elements with no atypical cytologic features.

In conclusion, gastric myeloid metaplasia is a rare event that usually occurs in patients with advanced myeloproliferative syndrome. It can be asymptomatic, as in our case, but often has a pseudotumoral appearance, leading to digestive symptoms. Histologic diagnosis can be straight-forward when trilinear hematopoietic elements are identified on gastric biopsies, but immunohistochemistry with anti-factor VIII antibody can also be useful to confirm the presence of megakaryocytes.

References

1. Rutman JY, Meidinger R, Keith JI. Unusual radiologic and neurologic findings in a case of myelofibrosis with extramedullary hematopoiesis. Neurology. 1972;22:567-570.

2. Glew RH, Haese WH, McIntyre PA. Myeloid metaplasia with myelofibrosis: the clinical spectrum of extramedullary hematopoiesis and tumor formation. Johns Hopkins Mod J. 1973;132:253-270.

3. Gomes AS, Harell GS. Tumefactive extramedullary hemalopoiesis of the stomach. Gastrointest Radiol. 1976;1:163-165.

4. Ismail SM, Myers K. Infiltrative myeloid metaplasia: an unusual cause of gastric outlet obstruction. J Clin Pathol. 1989;42:1112-1113.

5. Bureau N, Ethier S, Bourdon F, Schurch W. Myeloid metaplasia complicating polycythemia vera: ultrasonographic findings in the stomach. J Cln Ultrasound. 1993;21:631-635.

6. Palmer GM, Shortsleeve MJ. Gastric polyps due to extramedullary hematopoiesis. AJR Am J Roentgenol. 1998;171:531.

7. Barosi G. Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines. J Clin Oncol. 1999;17:2954-2970.

8. Sharma BK, Pounder RE, Cruse JP, Knowles SM, Lewis AAM. Extramedullary haemopoiesis in the small bowel. Gut. 1986;27:873-875.

9. Fedeli G, Certo M, Cannizzaro O, et al. Extramedullary hematopoiesis involving the esophagus in myelofibrosis. Am J Gaslrocnterol. 1990;85:1512-1514.

10. Calapso P, Vitarelli E, Crisafulli C, Tuccari G. Immunocytochemical detection of megacaryoeytes by endothelial markers: a comparative study. Pathologica. 1992;84:215-223.

11. Beckman EN, Oehrle JS. Fibrous hematopoietic tumors arising in agnogenic myeloid metaplasia. Hum Pathol. 1982;13:804-810.

12. Remstein ED, Kurtin PJ, Nascimento AG. Sclerosing extramedullary hematopoietic tumor in chronic myeloproliferative disorders. Am J Surg Pathol. 2000;24:51-55.

13. Mori N, Yatabe Y, Narita M, et al. Primary gastric Hodgkin's disease: morphologic, immunohistochemical, and immunogenetic analyses. Arch Pathol Lab Med. 1995;119:163-166.

14. Chennareddy SB, Chcnnaredy SP, Polidori G, Eisenberg E, Saleh HA, Bergsman KL. Gastric granulocytic sarcoma as a cause of acute upper gastrointestinal bleeding. Am J Gastroenterol. 1996;91:609-611.

15. Le Bodic MF, Mussini-Montpellier J, Magois JY, Lepère J. Myélolipome à localisation gastrique. Arch Anat Pathol. 1974;22:119-122.

Denis Chatelain, MD; Agnès Devendeville, MD; Alain Rudelli, MD; Alexis Bruniau, MD; Guillaume Geslin, MD; Henri Sevestre, PhD

Accepted for publication January 2, 2004.

From the Departments of Pathology (Drs Chatelain, Bruniau, and Sevestre), Geriatrics (Dr Devendeville), and Castroenterology (Drs Rudelli and Geslin), Centre Hospitalo-Universitaire Amiens, Amiens, France.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Denis Chatelain, MD, Service d'Anatomie Pathologique, Centre Hospitalo-Universitaire Amiens, Place Victor Pauchet, 80054 Amiens Cedex 01, France (e-mail: Chatelain.denis@chu-amiens.fr).

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