Malacoplakia of the Colon and Rectum: Report of Two Cases and Review of the Literature
1982; King Faisal Specialist Hospital and Research Centre; Volume: 2; Issue: 3 Linguagem: Inglês
10.5144/0256-4947.1982.147
ISSN0975-4466
AutoresMohammed Akhtar, Charles Robinson, Mohamed Ashraf Ali, W Larkworthy, Harb A. Harfi,
Tópico(s)Biliary and Gastrointestinal Fistulas
ResumoOriginal ArticlesMalacoplakia of the Colon and Rectum: Report of Two Cases and Review of the Literature Mohammed Akhtar, MD FCAP Charles R. Robinson, MD FRCP (C) M. Ashraf Ali, MD FRCP (C) William Larkworthy, and MB BS FRCP Harb HarfiMD FAAA Mohammed Akhtar * Director, Electron Microscopy Section, Department of Pathology and Laboratory Medicine; King Faisal Specialist Hospital and Research Centre Search for more papers by this author , Charles R. Robinson † Pathologist, Department of Pathology and Laboratory Medicine; King Faisal Specialist Hospital and Research Centre Search for more papers by this author , M. Ashraf Ali ‡ Pathologist, Department of Pathology and Laboratory Medicine; King Faisal Specialist Hospital and Research Centre Search for more papers by this author , William Larkworthy Gastroenterologist, Department of Medicine; King Faisal Specialist Hospital and Research Centre Search for more papers by this author , and Harb Harfi Allergy/Immunology, Department of Pediatrics, King Faisal Specialist Hospital and Research Centre Search for more papers by this author Published Online:1 Jul 1982https://doi.org/10.5144/0256-4947.1982.147SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutABSTRACTABSTRACTMalacoplakia of the colon and rectum is uncommon with only 30 cases having been reported in the literature. This paper documents two additional cases involving the colon and rectum. The first patient had extensive disease involving virtually the entire rectum and colon and portions of the terminal ileum. The clinical course was marked by several perianal and cutaneous fistulae and repeated abscesses in the retroperitoneum. The second case had more limited disease involving the left and transverse colon. Lesional tissues from both cases were studied by light and electron microscopy. Light microscopic appearance was characterized by the presence of large numbers of histiocytes with typical intracytoplasmic Michaelis–Gutmann bodies. Ultrastructurally, the histiocytes had numerous phagolysosomes and several Michaelis–Gutmann bodies seen as round structures with concentric rings of calcification. These appeared to be derived from large phagolysosomes. In one of our cases, intracytoplasmic clusters of bacillary bodies were also seen within malacoplakic histiocytes.INTRODUCTIONMalacoplakia is a rare disease generally considered to be a chronic inflammatory process. It is characterized, histologically, by the presence of large numbers of histiocytic cells, many of which contain calcified, laminated, or target-shaped intracytoplasmic bodies termed Michaelis–Gutmann bodies. The lesion was first described by Michaelis and Gutmann in 1902 and was subsequently called malacoplakia (Gr. malakos soft + plax plaque) by Von Hanseman in 1903.1, 2Michaelis and Gutmann considered it to be a benign tumor. Subsequently, however, it became apparent that the condition was not neoplastic but represented a chronic inflammatory process associated with infection by a variety of organisms, most notably Escherichia coli.The most common site of malacoplakia is the urinary bladder. Other sites within the urinary tract include kidneys, ureters, urethra, and prostate. The disease also strikes outside the urinary tract in such locations as the gastrointestinal tract, testes, epididymis, skin adrenal glands, brain, vagina, bone, lung, conjunctiva, endometrium, broad ligament, lymph nodes, inguinal region, and tonsils.3, 4After the urinary tract, involvement of the gastrointestinal tract appears to be the most common. A total of 33 cases of gastrointestinal malacoplakia have been reported.3–12 Of these, 29 cases showed large bowel involvement. In one case both the stomach and the colon were the sites of the disease, while in two cases only the stomach and in one case only the appendix were involved.CASE REPORTSCase 1A 13-year-old Saudi Arabian boy was admitted in January 1979 because of diarrhea associated with abdominal pain of six years' duration. The stools contained blood and mucus. Two years prior to admission he developed a vague abdominal mass with several fistulous tracts opening around the anus and anterior abdominal wall. One month prior to admission he underwent exploratory surgery elsewhere and a diagnosis of malacoplakia was made. On admission the boy weighed 22 kg. A fistulous tract opening into the left lower quadrant of the anterior abdominal wall and at least two fistulae opening on the left side of the anus were noted. There was a diffuse, slightly tender mass in the umbilical region. Barium enema study revealed an abnormal mucosal pattern in the entire colon. An upper gastrointestinal series revealed a gastrocolic fistula and fistulae involving the transverse colon and lower one-third of the duodenum.In February 1979, the patient underwent exploratory laparotomy during which segments of the transverse and descending colon were removed because of gross disease and the gastrocolic and duodenocolic fistulae were resected. In July 1979 the patient underwent total colectomy and resection of ileocolic fistulae. A terminal ileostomy was performed. The patient continued to have disease, however, with retroperitoneal abscess formation. Prolonged treatment with a variety of antibiotics failed to control the disease.Pathologic FindingsNumerous biopsies and bowel resection specimens from this patient revealed disease involvement. The lesions were characterized by the presence of large numbers of closely packed histiocytes with abundant eosinophilic and granular cytoplasm. Figures 1 and 2. Within the cytoplasm of these cells, characteristic calciferrugenous bodies measuring two to eight microns were present. The inclusion bodies as well as the cytoplasm of these cells stained positive with PAS stains. Occasionally, multinucleated giant cells containing similar cytoplasmic inclusions were also seen.Figure 1. Case 1. Photomicrograph showing an area from the rectosigmoid. The mucosa is ulcerated and is covered by an exudate composed mostly of histiocytic cells. Similar cells are also present in the lamina propria. Hematoxylin and eosin stain. Magnified 150 times.Download FigureFigure 2. Case 1. Higher magnification of another lesion of the left colon featuring closely packed histiocytic cells. Many of the cells contain intracytoplasmic dense, round inclusions (Michaelis–Gutmann bodies). Hematoxylin and eosin stain. Magnified 250 times.Download FigureHistological proven disease was present in all parts of the colon, rectum, terminal ileum, gastrocolic, enterocolic fistulae, several cutaneous fistulae, retroperitoneal and pelvic abscesses, and paracolic lymph nodes. Figures 3, 4, and 5.Figure 3. Case 1. Photomicrograph of a cutaneous fistulae tract lined by granulation tissue and large numbers of inflammatory cells. Hematoxylin and eosin stain. Magnified 100 times.Download FigureFigure 4. Case 1. Higher magnification of the inflammatory infiltrates in Figure 3 featuring large numbers of histiocytes, many containing Michaelis–Gutmann bodies (arrows). Hematoxylin and eosin stain. Magnified 400 times.Download FigureFigure 5. Case 1. Photomicrograph showing a lymph node and adjacent tissue. There is extensive infiltration by malacoplakic cells. Hematoxylin and eosin stain. Magnified 100 times.Download FigureCase 2A 13-year-old Saudi Arabian boy was admitted because of recurrent, intermittent abdominal pain of three years' duration. Stool examination done one year prior to admission revealed the presence of Schistosoma and Trichuris trichiura for which he was treated with ambilhar. During the two months prior to admission, he developed diarrhea with streaks of blood and mucus. There was no fever nor weight loss.On examination, the boy was of average build, height 145 cm, weight 35 kg. There was mild pallor and clubbing of the fingernails. No organomegaly nor abdominal masses were noted. There was slight tenderness in the periumbilical area.InvestigationsThe patient’s hemoglobin was 8.5 g/dl. Barium enema studies revealed loss of haustral markings in the transverse colon and the upper one-half of the descending colon. Figure 6. The colon appeared stiff. The sigmoid colon mucosa was suggestive of pseudopolypoid lesions. A colonoscopic examination revealed markedly inflamed, friable, and focally ulcerated mucosa alternating with patches of normal mucosa. Figure 7. In some areas, the mucosa appeared polypoid. The ulcers involved the entire descending colon and extended up to the hepatic flexure. Multiple biopsies from various parts of the colon and rectum were taken.Figure 6. Case 2. Barium enema study featuring loss of haustration of the transverse colon. The colon appears somewhat shortened and stiffened.Download FigureFigure 7. Case 2. Endoscopic appearance of an area in the left colon. A patch of normal mucosa is noted in the lower part of the photograph. The remaining mucosa is markedly congested and somewhat polypoid.Download FigurePathologic FindingsThe rectal biopsy results revealed a slight, chronic, nonspecific inflammation. Biopsy results from the descending and transverse colon revealed infiltration of lamina propria by large numbers of histiocytes with abundant, slightly eosinophilic and somewhat granular cytoplasm. Figure 8. In addition, clusters of plasma cells and lymphocytes were present. Within some of the histiocytes, one or more well-defined, calcified, concentrically laminated, intracytoplasmic inclusions measuring two to five microns in diameter were seen. Focal ulceration of the mucosa was also seen; however, no crypt abscesses were apparent.Figure 8. Case 2. Photomicrograph of a polypoid lesion in the left colon. The lamina propria is extensively infiltrated by malacoplakic cells. Hematoxylin and eosin stain. Magnified 200 times.Download FigureELECTRON MICROSCOPIC FINDINGSTissue for electron microscopy from both patients was fixed in three percent gluteraldehyde, rinsed in Millonig buffer (pH 7.3), postfixed in one percent osmium tetroxide, dehydrated in graded acetones, and embedded in araldite epon mixture. One micron section was stained with toluidine blue for orientation. Ultra-thin sections were stained with uranyl acetate and lead citrate.Ultrastructure findings in both cases were essentially the same. The lesions were characterized by the presence of large numbers of histiocytes with abundant cytoplasm, rich in organelles. The most dominant components of the cytoplasm were large numbers of membrane-bound phagolysosomes. These contained a variety of structures showing varying degrees of degeneration. Many of the macrophages contained large, rounded bodies with several concentric rings of calcification. Figures 9 to 12. These calcified bodies (Michaelis–Gutmann bodies) appeared to be derived from some of the large phagolysosomes. In the second case, only occasional clusters of bacillary bodies were present within some of the cells. Figure 13. In addition to the macrophages, large numbers of plasma cells with numerous profiles of rough endoplasmic reticulum were present.Figure 9. Case 1. Electron micrograph featuring a malacoplakic histiocyte. The cytoplasm is full of phagolysosomes (P). The nucleus (N) has been pushed to one side. Two calcified Michaelis–Gutmann bodies are also present. Another similar inclusion body is present in another cell in the lower right corner. Uranyl acetate and lead citrate stain. Magnified 8000 times.Download FigureFigure 10. Case 1. Electron micrograph depicting cytoplasm of another malacoplakic histiocyte. Large numbers of the phagolysosomes are present. Within the phagolysosomes, several structures are present. Some of the rounded structures might represent portions of bacteria, however, no bacteria are clearly identifiable. Uranyl acetate and lead citrate stain. Magnified 12,000 times.Download FigureFigure 11. Case 1. Electron micrograph featuring a Michaelis-Gutmann body with concentric rings of calcification. Uranyl acetate and lead citrate stain. Magnified 15,000 times.Download FigureFigure 12. Case 2. Electron micrograph of a typical histiocyte in the malacoplakic lesion. The cytoplasm is full of large phagolysosomes. A single calcified Michaelis–Gutmann body is also present. Uranyl acetate and lead citrate stain. Magnified 12,000 times.Download FigureFigure 13. Case 2. Electron micrograph of a malacoplakic lesion. There is a cluster of well-preserved bacillary bodies within the cytoplasm of a cell. Uranyl acetate and lead citrate stain. Magnified 10,000 times.Download FigureDISCUSSIONTo date, including the present patients, a total of 32 cases of malacoplakia of the colon and rectum have been documented in the world literature.3, 5, 11, 12In a review of gastrointestinal malacoplakia, Nakabayashi, et al. suggested that malacoplakia of the gastrointestinal tract has three, different gross morphologic patterns.4 The first and most common is the unifocal, mucosal pattern. The second is the multinodular or polypoid mucosal pattern; our Case 2 shows the gross features of this pattern. Finally, the least common are the large mass lesions involving multiple organs such as loops of small bowel, adrenal gland, abdominal wall, pancreas, and retroperitoneum. Case 1 seems to conform to this pattern.The etiology and pathogenesis of malacoplakia has been a subject for considerable speculation and controversy. Michaelis and Gutmann suggested that malacoplakia had a neoplastic origin.1 Later, an etiologic relationship with a variety of other conditions such as sarcoidosis, tuberculosis, viral infections and parasitic infestations were also suggested. These concepts, however, were not substantiated by subsequent experience. More recently, several ultrastructural studies have demonstrated the presence of bacteria such as E. coli, Klebsiella, S. aureus, and Mycobacterium intracellularis in various stages of degradation within the phagolysosomes of the malacoplakia.7, 9, 13–15 This suggests that in malacoplakia, the histiocytes can phagocytose the bacteria normally, but somehow their capability to kill and digest bacteria is defective. Because the bactericidal action of the macrophages is usually carried out in the phagolysosomes, a defect in their function has been postulated.13In a detailed study of macrophage function in malacoplakia, Abou, et al. demonstrated that the blood monocytes in patients with malacoplakia had decreased levels of cyclic guanosine monophosphate (GMP).11 Cyclic GMP is essential for normal fusion of lysosomes with phagocytic vacuoles with subsequent release of lysosomal enzymes in the resulting phagolysosomes. These authors suggested that the bactericidal dysfunction of the macrophages in malacoplakia is due to decreased levels of cyclic GMP in these cells. Presumably, due to low levels of cyclic GMP, fusion of the phagocytic vacuoles with the lysosomes is ineffective. This, in turn, results in the poor bactericidal function of these cells.In another, similar study, Schreiber and Maderazo demonstrated a significant monocytic bactericidal dysfunction.16 However, studies on the lysosomal enzymes failed to reveal any deficiency. The reasons for this apparent discrepancy as compared to the findings of Abdou were not clear. It may well be due to the different methodologies employed in the two studies, or it may be a reflection of a heterogenous nature of the basic defect in malacoplakia.Thus, the available data strongly indicate that the basic defect in malacoplakia is an abnormality of the bacteriocidal function of tissue macrophages. The exact biochemical basis for this defect, however, still remains to be fully elucidated.It is well recognized that malacoplakia is an infectious process. The infectious agent in an overwhelming majority of cases is E. coli. Occasionally, Klebsiella pneumonae, S. aureus, and Mycobacterium intercellularis have also been implicated. As a result, various antibiotics have been employed in an attempt to control this disease. The results, however, have not been reassuring. The reason for this apparent lack of success, in spite of the use of seemingly appropriate antibiotic therapy, is not clear. It has been postulated that viable intracellular organisms within the malacoplakic histiocytes are protected from the antibiotics which do not penetrate into the cells. Moreover, these viable intracellular organisms could provide a ready source for reinfection.17Thus, it is apparent that for successful therapy of malacoplakia, it is necessary that the antibiotic used should be not only effective against the offending organism, as demonstrated by antimicrobial testing, but also be able to penetrate the cells and reach the organisms phagocytosed by the histiocytes. This is, however, difficult to accomplish.Another possible therapeutic avenue would be to correct macrophage dysfunction in these patients and thus enhance the bactericidal action of the macrophage cells. Abdou and his colleagues used bethanechol chloride, a cholinergic agonist and demonstrated a successful reversal of the bactericidal dysfunction of the blood monocytes in their patient.11 These authors had demonstrated that the basic defect in their patient was low level of cyclic GMP which was corrected by bethanechol chloride both in vitro and in vivo. Following this therapy, their patient’s disease was successfully controlled. This treatment has now been tried in three other patients with urinary bladder malacoplakia with apparently good results.18 Our second patient is currently being treated with bethanechol chloride, but the follow-up period is too short to make any evaluation with regard to its effectiveness.Maderazo, et al. successfully used a combination of trimethoprim-sulfamethoxazole for one patient with malacoplakia involving the urinary tract and the retroperitoneum.17 Both trimethoprim and sulfamethoxazole had been shown in experimental studies to enhance the bactericidal function of the macrophages. The exact mechanism of action for these agents, however, is not clear. It has been postulated that these drugs bind to the cell membrane and, subsequently, when the membrane becomes internalized during phagocystosis, the drug is released into the phagolysosome thus facilitating the bactericidal actions of the cell. Further experience with these agents is needed before their usefulness in the treatment of malacoplakia can be fully evaluated.Ultrastructural studies in our cases are essentially the same as those described in previous studies.13–15, 19–22 Our findings are also consonant with the concept that the abundant eosinophilic and granular cytoplasm of the mala-coplakic histiocytes is due to the presence of large numbers of phagolysosomes. The Michaellis-Gutmann bodies are derived from calcification within some of the larger phagolysosomes. The factors responsible for this calcification are not clear. Intracellular bacillary bodies are noted in Case 2 but these were absent in Case 1. Similar bacillary bodies have been seen in some but not all of the previous ultrastructural studies.13–15, 19–22 It is now generally agreed that these represent bacteria phagocytosed by the histiocytes. It is not clear, however, why these bacteria can be easily demonstrated in some cases but not in others.Table 1. Malacoplakia of the colon and rectum. Cases reported since last review in 1977Table 1. Malacoplakia of the colon and rectum. Cases reported since last review in 1977ARTICLE REFERENCES:1. Michaelis L, Gutmann C: "Ueber Einschulusse in Blasentumoren" . A Klin Med 47: 2081902. Google Scholar2. Von Hansemann D: "Ueber Malacoplakia der Harnblase" . Virchows Arch (Pathol Anat) 173: 3021903. Google Scholar3. Joyeuse , Lott JV, Michaelis M, et al.: "Malacoplakia of the colon and rectum: report of a case and review of the literature" . Surgery 81(2): 1891977. Google Scholar4. Nakabayashi H, Ito T, Izutsu K, et al.: "Malacoplakia of the stomach. Report of a case and review of the literature" . Arch Pathol Lab Med 102(3): 1361978. Google Scholar5. Taghinia MA, Amiri H: "Colonic malakoplakia in a child: report of a case and review of the literature" . Pahlavi Med J 7(3): 3711976. Google Scholar6. Costero C, Loredo A, Ramos S: "Malacoplasias de ciego y recto. Informe de dos casos" . Rev Invest Clin 30(2): 1551978. Google Scholar7. Mackay EH: "Malakoplakia in ulcerative colitis" . Arch Pathol Lab Med 102(3): 1401978. Google Scholar8. Miranda D, Vuletin JC, Kauffman SL: "Disseminated histiocytes and intestinal malakoplakia. Occurrence due to Mycobacterium intercellulare infection" . Arch Pathol Lab Med 103(6): 3021979. Google Scholar9. Bhusnurmath SR, Joshi VV, Bhagwat AG: "Malakoplakia of rectum presenting as fistulae in ano—diagnosed by proctoscopic biopsy" . Indian J Pathol Microbiol 22(3): 2241979. Google Scholar10. Chaudry AP, Saigal KP, Intengan M: "Malakoplakia of the large intestine found incidentally at necropsy: light and electron microscopy features" . Dis Colon Rectum 22(2): 731979. Google Scholar11. Abdou NI, NaPombejara C, Sagawa A, et al.: "Malacoplakia: evidence for monocyte lysosomal abnormability correctable by cholinergic agonist in vitro and in vivo" . N Eng J Med 297(26): 14131977. Google Scholar12. Birkentstock W, Louw JH: "Malakoplakia of the colon" . Br J Surg 59: 6621972. Google Scholar13. Lou TY, Tepliz C: "Malakoplakia: pathogenesis and ultrastructural morphogenesis. A problem of altered macrophage (phagolysosomal) response" . Hum Pathol 5: 1911974. Google Scholar14. McClurg FV, D'Agostino AN, Martin JH, et al.: "Ultrastructural demonstration of intracellular bacteria in three cases of malakoplakia of the bladder" . Am J Clin Pathol 60: 7801973. Google Scholar15. Lewin KJ, Harell GS, Lee AS, et al.: "Malacoplakia: an electron-microscopic study: demonstration of bacilliform organisms in malacoplakic macrophages" . Gastroenterology 66: 281974. Google Scholar16. Schreiber AG, Maderazo EG: "Leukocytic function studies in malakoplakia" . Arch Pathol Lab Med 102(10): 5341978. Google Scholar17. Maderazo EG, Berlin BB, Morhardt C: "Treatment of malakoplakia with trimethoprim-sulfamethoxazole" . Urology 13(1):701979. Google Scholar18. Zornow DH, Landes RR, Morganstern SL, et al.: "Malacoplakia of the bladder: efficacy of bethanechol chloride therapy" . J Urol 122(5): 7031979. Google Scholar19. Sencer O, Sencer H, Uluoğlu O, et al.: "Malakoplakia of the skin: ultrastructure and quantitative x-ray microanalysis of Michaelis–Gutmann bodies" . Arch Pathol 103: 4461979. Google Scholar20. Finlay-Jones LR, Blackwell JB, Papadimitriou JM: "Malacoplakia of the colon" . Am J Clin Pathol 50: 3201968. Google Scholar21. Kerr JFR, Gaffney TJ, McGeary HM, et al.: "Malakoplakia: an electron-microscope and chemical study" . J Pathol 107: 2891972. Google Scholar22. Price HM, Hanrahan JB, Florida RG: "Morphogenesis of calcium laden cytoplasmic bodies in malakoplakia of skin. An electron microscopic study" . Hum Pathol 4(3): 3811973. Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 2, Issue 3July 1982 Metrics History Published online1 July 1982 KeywordsRectal diseasesMalacoplakia Colonic diseasesInformationCopyright © 1982, Annals of Saudi MedicinePDF download
Referência(s)