CASE REPORTS
Vol. 69 • No. 6
References
12
13 14. 15 16.
Malacoplakia of the Endometrium, a Probable Cause of Postmenopausal Bleeding WILLIAM THOMAS, JR., M.D., BAHRAM SADEGHIEH, M.D., RAOUL FRESCO, M.D., PH.D., ALBERT I. RUBENSTONE, M.D., ROBERT C. STEPTO, M.D., PH.D., AND BENJAMIN CARASSO, M.D.
Thomas, William, Jr., Sadeghieh, Bahram, Fresco, Raoul, Rubenstone, Albert I., Stepto, Robert C , and Carasso, Benjamin: Malacoplakia of the endometrium, a probable cause of post menopausal bleeding. A m J Clin Pathol 69: 6 3 7 - 6 4 1 , 1978. A 60-year-old woman, 20 years postmenopausal, who had deforming rheumatoid arthritis of 7 years' duration and Sjogren's syndrome of 1 year's duraReceived April 1, 1977; received revised manuscript May 20, 1977; accepted for publication May 20, 1977. Address reprint requests to Dr. Thomas: Department of Pathology, Mount Sinai Hospital Medical Center, California Ave. at 15th St., Chicago, Illinois 60608.
From the Mount Sinai Hospital Medical Center, and the Rush Medical College, Chicago, Illinois
tion, had had postmenopausal bleeding for a month prior to admission to the hospital. A diagnostic dilatation and curettage was interpreted as showing acute suppurative endometritis. The patient was discharged, only to have recurrent vaginal bleeding. She was readmitted five weeks later, at which time results of another dilatation and curettage were interpreted as showing xanthomatous endometritis. Total hysterectomy with bilateral salpingo-oophorectomy
0002-9173-78-0600—0637S00.75 © American Society of Clinical Pathologists
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10.
Berry CL, Keeling J, Hilton C: Teratoma in infancy and childhood: A review of 91 cases. J Pathol 98:241-252. 1969 Bove KE, Koffler H, McAdams AJ: Nodular renal blastema. Definition and possible significance. Cancer 24:323-332, 1969 Calvani M: Severe combined immune deficiency and trisomy D. Arch Dis Child 51:485, 1976 Clatworthy HW, Schiller M, Grosfeld JL: Primary tumors in infancy and childhood. 41 cases variously treated. Arch Surg 109:143-147, 1974 Froboese C: Kindskopfgrosses echtes Teratoma triphyllium adultum polycysticum der Leber als absolutes Geburtshindernis. Zentralbl Allg Pathol 89:364-379, 1952 Gardner HA, Wood EM, Strecker E: Placental cultures for cytogenetic assessment in saline-aborted fetuses. Am J Obstet Gynecol 126:350-352, 1976 German J: Genes which increase chromosomal instability in somatic cells and predispose to cancer. Prog Med Genet 8:61-101, 1972 Grave GF: Teratoma of the liver. S AfrJSurg 10:121-123. 1972 Grosfeld JL, Ballantine TVN, Lowe D: Benign and malignant teratomas in children. Surgery 80:297-305, 1976 Hajdu SI, Faruque AA, Hajdu EO, et al: Teratoma of the neck in infants. Am J Dis Child 111:412-416, 1966 Hartz PH, Van der Sar A: Teratoma of the liver in an infant. Am J Clin Pathol 15:159-162, 1945 Imai T: Ein Fall von zystischem Teratom der Leber in welchem Plattenepithelkrebs entstand. Trans Soc Pathol Jpn 24:578-580, 1934 Ishak KG: Primary hepatic tumors in childhood. Prog Liver Dis 5:636-667, 1976 Kiryabwire JWN, Mugerwa JW: Teratoma of the liver in an African child. Br J Surg 54:585-587, 1967 Leschke W: Ueber ein Leberteratom des Erwachsenen. Zentralbl Allg Pathol 99:255-258, 1959 Mahour GH, Wooley MM, Trivedi SN, et al: Sacrococcygeal teratoma: A 33-year experience. J Pediatr Surg 10: 183-188, 1975
637
17. Miller RW. Todaro GJ: Viral transformation from persons at high risk for cancer. Lancet 1:81-82, 1969 18. Miller RW: Down's syndrome (mongolism), other congenital malformations and cancers among sibs of leukemic children. N Engl S Med 268:393-401, 1963 19. Misugi K, Reiner CB: A malignant true teratoma of liver in childhood. Arch Pathol 80:409-412, 1965 20. Nikaidoh H, Boggs J, Swenson O: Liver tumors in infants and children. Clinical and pathological analysis of 22 cases. Arch Surg 101:245-257, 1970 21. Pear BL, Boline JE: Teratoma of the liver. Cancer Sem 4: 229-233, 1972 22. Pollice L: Primary hepatic tumors in infancy and childhood. Am J Clin Pathol 60:512-521. 1973 23. Potter EL: Pathology of the Fetus and the Infant. Second edition. Chicago, Year Book Medical Publishers. 1962, p 411 24. Rickham PP: Zervikalteratome. Helv Paediatr Acta 27:549-555, 1972 25. Sasaki MS, Tonomura A, Matsubara S: Chromosome constitution and its bearing on the chromosomal radiosensitivity in man. Mutat Res 101:617-633, 1970 26. Schade H, Schoeller L, Schultze VWD: D-Trisomie (Patau) mit kongenitaler myeloischer Leukaemie. Med Welt 50:26902692, 1962 27. Seabright M: A rapid staining technique for human chromosomes. Lancet 2:971-972, 1971 28. Warkany J: Congenital Malformations. Chicago, Year Book Medical Publishers, 1971 29. Weitzner S: Benign teratoma of the neck in an infant. Am J Dis Child 107:84-87, 1964 30. Yarbrough SSM, Evashwick G: A case of teratoma of the liver with 14 years postoperative survival. Cancer 9:848-850. 1956 31. Zuelzer WW, Thompson RI, Mastrangelo R: Evidence of a genetic factor related to leukemogenesis and congenital anomalies: Chromosomal aberrations in pedigree of an infant with partial Dtrisomy and leukemia. J Pediatr 72:367376, 1968
THOMAS ETAL.
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was done. Examination of Epon-embedded endometrium 1 /xm thick by light microscopy and subsequently by electron microscopy disclosed intracellular bacilliform organisms within phagolysosomes of atypical histiocytes, lamellar bodies, and various developing stages of calcospherites, Michaelis-Gutmann bodies. The curettings were then received and classic MichaelisGutmann bodies were identified in periodic acid-Schiff-stained sections. (Key words: Malacoplakia; Atypical histiocytes; Michaelis-Gutmann bodies; Phagolysosomes; Bacilliform organisms; Endometrium.)
hospital. Vaginal bleeding soon recurred, and she was readmitted September 23, 1974, for further evaluation. The patient had had deforming rheumatoid arthritis for seven years and Sjogren's syndrome for a year. Treatment of arthritis had consisted initially of a total daily dose of 60 mg prednisone, subsequently reduced to a total maintenance dose of 28 mg per day. At one point, the leukocyte count had decreased to 1,900/cu mm. A lupus erythematosus test was positive. The antinuclear antibody and rheumatoid factor titers were each 1:1280.
MALACOPLAKIA, an unusual granulomatous inflammatory disease, was initially reported to occur in the urinary bladder where it is found most often, but it has also occurred in other organs and tissues. We describe what we believe to be the first documented case of malacoplakia of the endometrium, manifesting as postmenopausal bleeding.
Physical
Report of a Case A 60-year-old white woman, multigravida, 20 years postmenopausal, first noticed the onset of vaginal bleeding and discharge in July 1974. She was admitted to Mount Sinai Hospital Medical Center on August 9, 1974, for dilatation and currettage. Histologic examination of the tissue was interpreted as acute suppurative endometritis. The patient was discharged from the
Examination
Temperature was 100 F, blood pressure 148/90 mm Hg, and pulse rate 99/min. The liver was palpable 4 cm below the right costal margin. There were stiffness and severe deformities of the metacarpophalangeal and metatarsophalangeal joints. The knees and elbow joints were markedly enlarged. Pelvic examination disclosed a small uterus and cervix, which drained a meager amount of thick, yellowish-white material. The clinical impressions were: carcinoma of the endometrium or cervix, rheumatoid arthritis, and Sjogren's syndrome. Course in the Hospital A fractional dilatation and curettage was done September 25, 1974, and a diagnosis of benign xanthomatous endometritis was made. Urinary cultures grew Escherichia coli. The plate counts ranged from 75,000 to 4,000.
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FIG. I. Endometrial stroma, showing a histiocytic and neutrophilic infiltrate and numerous Michaelis-Gutmann bodies (arrows), which stain with varying intensity as bull's-eyes. Periodic acid-Schiff stain, x 160.
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639
FIG. 2. Epon-embedded sections 1 ftm thick show foamy histiocytes containing intracytoplasmic Michaelis-Gutmann bodies (m-g) and bacteria (b). Plasma cells are also present. Toluidine blue strain. x2,000. Subsequent to rendering of the diagnosis of benign disease on the basis of uterine scrapings, elective hysterectomy with bilateral salpingo-oophorectomy was performed October 2, 1974. The uterus was small, and the gynecologist reported it to be softer than normal. Both ovaries and tubes were grossly normal. Postoperatively, the patient had a brief episode of abdominal distention and ileus, which abated within three to four days. Cystoscopy and proctoscopy were performed after a definitive diagnosis of malacoplakia was made. Malacoplakic lesions were not found in the bladder or rectosigmoid. The patient was discharged October 15. 1974. She has been doing well since that time.
Pathologic Findings Uterine curettings and tissue sections from the uterus, cervix, tubes and ovaries were fixed in 10% formalin, cut at 5 /xm and stained with hematoxylin and eosin, periodic acid-Schiff reaction with and without diastase digestion, Brown-Brenn stain for bacteria, Prussian blue for iron, and von Kossa's technic for calcium. Some of the fragments of endometrial tissue were retrieved from the formalin-fixed tissues and postfixed in osmium tetroxide for electron microscopic examination. Comparison of the gross uterine scrapings obtained September 25, 1974, with the specimen obtained August 9, 1974, disclosed that both specimens con-
tained a moderate amount of brown, soft material mixed with blood. The later specimen measured approximately 3.5 x 2 x 1.5 cm. Microscopically, both specimens were infiltrated by large numbers of foamy histiocytes admixed with moderate numbers of plasma cells that extensively replaced endometrial stroma, which contained a paucity of small atrophic endometrial glands. There was a moderate, dense, focal neutrophilic infiltrate. The impression was xanthomatous endometritis, and the material was sent for consultation. The consultant's diagnosis was xanthogranulomatous endometritis also. The hysterectomy specimen revealed the uterus to measure 5 x 4 x 2.5 cm and to weigh 58 g. The endometrium was thick, soft, nodular, and gray-white, with foci of hemorrhage. The mucosa measured 0.6 cm. There was a single intramural leiomyoma 0.8 cm in diameter in the anterior uterine wall. The cervix measured 3 x 2 . 5 x 1 . 8 cm. The mucosa of the exocervix was smooth and unremarkable. The endocervical canal was ragged and hemorrhagic due to the recent curettage. Both tubes and ovaries were grossly unremarkable. Microscopic examination of the cervix, tubes and ovaries disclosed no significant alteration. The endo-
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THOMAS ETAL.
metrium was thick because the stroma was composed of large, foamy macrophages [von Hansemann histiocytes (H)], many plasma cells, and a very few atrophic endometrial glands. In the hematoxylin and eosinstained sections, small bull's-eye-like structures of varying staining intensities were seen in the cytoplasm of some of the foamy macrophages and in the intercellular spaces. Periodic acid-Schiff post-diastasetreated sections delineated the lamellar arrangement of many of the calcified bodies (Fig. 1.) Numerous intraand extracytoplasmic Michaelis-Gutmann bodies stained black for calcium by the von Kossa technic. Only rare bodies were Prussian blue-positive for iron. The Brown-Brenn stain revealed intra- and extracytoplasmic gram-negative rods.
der the light microscope in Epon-embedded tissue I /xm thick, and numerous plasma cells were also seen (Fig. 2). Some of the Michaelis-Gutmann bodies showed concentric laminations (Fig. 3), giving them a characteristic target appearance. Ultrathin sections of the same material (Fig. 4) revealed Michaelis-Gutmann bodies to have a dense crystalline core and a lighter outer zone. Phagosomes resembling the light outer zone of the Michaelis-Gutmann bodies but lacking the calcific electron-dense core, which suggested that they represented an intermediary stage in the formation of the Michaelis-Gutmann bodies, could also be seen. The cytoplasm of some of the malacoplakic histiocytes contained, in addition to the Michaelis-Gutmann bodies and phagosomes, several bacilliform organisms, some of which appeared to be undergoing binary fission. Also present were several concentric lamellar bodies, better recognized at higher magnification (Fig. 5).
jv*"^.*^ ;* X
./ ».
. *t~jfr*ipf
• fcFIG. 3 {upper, left). Intracytoplasmic calcospherule (Michaelis-Gutmann body) showing concentric lamination, x 1,600. FIG. 4 (right). Portion of the cytoplasm of a malacoplakic histiocyte containing a Michaelis-Gutmann body (m-g) with an electron-dense core and a lighter outer zone, a phagosome (ph) probably representing an early M-G body without the central core, and two bacteria (b). Numerous small concentric lamellar bodies (arrow) are also present. x9,300. FIG. 5 (lower, left). Portion of an adjacent plasma cell (p) is also visible. High magnification of a concentric lamellar body, x 150,000.
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Electron Microscopy The numerous macrophages containing the MichaelisGutmann bodies and bacteria were easily identified un-
A.J.C.P. . J u n e 1978
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Vol. 69 • No. 6
Discussion
A year after the lesion was first described by Michaelis and Gutmann in 1902," von Hansemann 5 observed the large atypical histiocytes later known as von Hansemann's cells in malacoplakia. As previously mentioned, the disease was initially found in the urinary bladder, and later in other organs and tissues such as the appendix, 1 testicle, 6 prostate, 2 epididymis, 3 renal pelvis,14 stomach, 17 colon and retroperitoneum, 16 skin, 13 lung and bone. 4 Price and co-workers 1 '' in studying a biopsy specimen of malacoplakia of the skin with the electron microscope, found both intracellular and extracellular Michaelis-Gutmann bodies. The intracellular bodies were formed within a single membrane-lined structure resembling a cytosome. Three stages were evident in the development of the characteristic structure. Very early in the first stage of development of the characteristic structure, prior to calcification, the lesion contained a homogenous, finely granular matrix and concentric membranous fragments, which were likened to the counterpart of small basophilic PAS-positive granules observed by light microscopy, described by McKeil and colleagues 7 as the probable precursor of Michaelis-Gutmann bodies. The next stage in the development of the calcospherule was the formation of randomly scattered, small, dense particles within the matrix of the cytosomes. The final stage of development was manifested by the calcification of the concentrically laminated Michaelis-Gutmann bodies. The
References 1. Blackshear W Jr: Malakoplakia of the appendix. A case report. Am J Clin Pathol 53:284-287, 1970 2. Goldman RL: A case of malakoplakia with involvement by the prostate gland. J Urol 83:407-410, 1965 3. Green WUJ: Malakoplakia of the epididymis (without testicular involvement). The first reported case. Arch Pathol 86: 438-441, 1968 4. Gupta RK. Schuster RA, Christian WD: Autopsy findings in a unique case of malakoplakia. Arch Pathol 93:42-48, 1972 5. von Hansemann D: Ueger Malakoplakia der Hornblase. Arch Pathol Anat 173:302-308, 1903 6. Haukohl RS, Chinchincan H: Malakoplakia of the testicles. Am J Clin Pathol 29:473-478, 1958 7. McKeil CR Jr, Eisenstein R, McDonald JH: Morphological and microbiological studies in malacoplakia. J Urol 88:236242, 1962 8. Michaelis L, Gutmann C: Ueger Einschlusse in blasen tumoren. Z K Lin Med 47:208-215, 1902 9. Nashashib B: Pyometria with massive foam cell reaction. A case report. Am J Obstet Gynecol 112:126-129, 1972 10. Novak ER: Post menopausal endometrial hyperplasia. Am J Obstet Gynecol 71:1312-1321, 1956 11. Novak ER, Woodruff JP: Novak's Gynecologic and Obstetric Pathology. Seventh edition. Philadelphia, London, and Toronto, W. B. Saunders, 1974, p 226 12. Peterson WF, Novak ER: Endometrial polyps. Obstet Gynecol 8:40-49, 1956 13. Price HM, Hanrahan JB, Florida RG: Morphogenesis of calcium laden cytoplasmic bodies in malakoplakia of the skin. Hum Pathol 4:380-394, 1973 14. Purpan L, Perez-Tamago RS: Malakoplakia, renal pelvis. J Urol 84:231-235, 1960 15. Rao NR: Malacoplakia of broad ligament, inguinal region and Endometrium. Arch Pathol 88, 85-88, 1969 16. Terner JY, Lattes A: Malakoplakia of colon and retroperitoneum: Report of a case with histochemical study of Michaelis-Gutmann inclusion bodies. Am J Clin Pathol 44: 20-31, 1965 17. Unis EJ, Estevez JM, Pinzon GJ, et al: Malakoplakia: Discussion of pathogenesis and reports of three cases including one fatal gastric and colonic involvement. Arch Pathol 83: 180-187, 1967
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Causes of postmenopausal bleeding include carcinoma of the endometrium," senile endometritis," endometrial polyps, 12 postmenopausal hyperplasia, 10 and pyometria. 9 In this case, malacoplakia, not having been known to occur in the endometrium, was not considered in the differential diagnosis. Rao15 mentioned the presence of scattered histiocytes in scanty fragments of endometrial stroma and glands of a 40year-old woman who had malacoplakic lesions of the broad ligament and inguinal region. Rao's diagnosis of the disorder was based upon the demonstration of Michaelis-Gutmann bodies (calcospherites) in the inguinal soft tissues and broad ligament. Rao concluded the endometrium was probably involved, but because there was insufficient endometrial tissue, he was unable to confirm his impression histologically. A search of the literature leads us to conclude that this is the first case in which histologic and electron microscopic study unequivocally demonstrated Michaelis-Gutmann bodies and gram-negative bacilliform organisms in the endometrial lesion. To our knowledge, it is also the first case in which the disorder precipitated postmenopausal bleeding.
calcification was composed of needle-shaped hydroxyapatite crystals. Price and associates did not see ferritin deposits within the Michaelis-Gutmann body, but speculated that the ferritin might have been masked by dispersion among the more dense hydroxyapatite crystals. Except for spotty degenerative changes observed in the mitochondria, none of the cellular organelles was affected. Microorganisms were not observed but some of the cytosegresomes contained dense material that could have represented partially degenerated bacterial components. The authors reasoned 13 that the finely granular matrix was, in part, composed of polysaccharides and lipoprotein material, which others suggested was derived from bacterial membranes that were incompletely digested by the macrophages. Terner and Lattes 16 demonstrated non-human glycolipids in von Hansemann's macrophages of malacoplakia and concluded that the glycolipid was probably of bacterial origin.
Vol. 69 • No. 6
References
12
13 14. 15 16.
Malacoplakia of the Endometrium, a Probable Cause of Postmenopausal Bleeding WILLIAM THOMAS, JR., M.D., BAHRAM SADEGHIEH, M.D., RAOUL FRESCO, M.D., PH.D., ALBERT I. RUBENSTONE, M.D., ROBERT C. STEPTO, M.D., PH.D., AND BENJAMIN CARASSO, M.D.
Thomas, William, Jr., Sadeghieh, Bahram, Fresco, Raoul, Rubenstone, Albert I., Stepto, Robert C , and Carasso, Benjamin: Malacoplakia of the endometrium, a probable cause of post menopausal bleeding. A m J Clin Pathol 69: 6 3 7 - 6 4 1 , 1978. A 60-year-old woman, 20 years postmenopausal, who had deforming rheumatoid arthritis of 7 years' duration and Sjogren's syndrome of 1 year's duraReceived April 1, 1977; received revised manuscript May 20, 1977; accepted for publication May 20, 1977. Address reprint requests to Dr. Thomas: Department of Pathology, Mount Sinai Hospital Medical Center, California Ave. at 15th St., Chicago, Illinois 60608.
From the Mount Sinai Hospital Medical Center, and the Rush Medical College, Chicago, Illinois
tion, had had postmenopausal bleeding for a month prior to admission to the hospital. A diagnostic dilatation and curettage was interpreted as showing acute suppurative endometritis. The patient was discharged, only to have recurrent vaginal bleeding. She was readmitted five weeks later, at which time results of another dilatation and curettage were interpreted as showing xanthomatous endometritis. Total hysterectomy with bilateral salpingo-oophorectomy
0002-9173-78-0600—0637S00.75 © American Society of Clinical Pathologists
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
10.
Berry CL, Keeling J, Hilton C: Teratoma in infancy and childhood: A review of 91 cases. J Pathol 98:241-252. 1969 Bove KE, Koffler H, McAdams AJ: Nodular renal blastema. Definition and possible significance. Cancer 24:323-332, 1969 Calvani M: Severe combined immune deficiency and trisomy D. Arch Dis Child 51:485, 1976 Clatworthy HW, Schiller M, Grosfeld JL: Primary tumors in infancy and childhood. 41 cases variously treated. Arch Surg 109:143-147, 1974 Froboese C: Kindskopfgrosses echtes Teratoma triphyllium adultum polycysticum der Leber als absolutes Geburtshindernis. Zentralbl Allg Pathol 89:364-379, 1952 Gardner HA, Wood EM, Strecker E: Placental cultures for cytogenetic assessment in saline-aborted fetuses. Am J Obstet Gynecol 126:350-352, 1976 German J: Genes which increase chromosomal instability in somatic cells and predispose to cancer. Prog Med Genet 8:61-101, 1972 Grave GF: Teratoma of the liver. S AfrJSurg 10:121-123. 1972 Grosfeld JL, Ballantine TVN, Lowe D: Benign and malignant teratomas in children. Surgery 80:297-305, 1976 Hajdu SI, Faruque AA, Hajdu EO, et al: Teratoma of the neck in infants. Am J Dis Child 111:412-416, 1966 Hartz PH, Van der Sar A: Teratoma of the liver in an infant. Am J Clin Pathol 15:159-162, 1945 Imai T: Ein Fall von zystischem Teratom der Leber in welchem Plattenepithelkrebs entstand. Trans Soc Pathol Jpn 24:578-580, 1934 Ishak KG: Primary hepatic tumors in childhood. Prog Liver Dis 5:636-667, 1976 Kiryabwire JWN, Mugerwa JW: Teratoma of the liver in an African child. Br J Surg 54:585-587, 1967 Leschke W: Ueber ein Leberteratom des Erwachsenen. Zentralbl Allg Pathol 99:255-258, 1959 Mahour GH, Wooley MM, Trivedi SN, et al: Sacrococcygeal teratoma: A 33-year experience. J Pediatr Surg 10: 183-188, 1975
637
17. Miller RW. Todaro GJ: Viral transformation from persons at high risk for cancer. Lancet 1:81-82, 1969 18. Miller RW: Down's syndrome (mongolism), other congenital malformations and cancers among sibs of leukemic children. N Engl S Med 268:393-401, 1963 19. Misugi K, Reiner CB: A malignant true teratoma of liver in childhood. Arch Pathol 80:409-412, 1965 20. Nikaidoh H, Boggs J, Swenson O: Liver tumors in infants and children. Clinical and pathological analysis of 22 cases. Arch Surg 101:245-257, 1970 21. Pear BL, Boline JE: Teratoma of the liver. Cancer Sem 4: 229-233, 1972 22. Pollice L: Primary hepatic tumors in infancy and childhood. Am J Clin Pathol 60:512-521. 1973 23. Potter EL: Pathology of the Fetus and the Infant. Second edition. Chicago, Year Book Medical Publishers. 1962, p 411 24. Rickham PP: Zervikalteratome. Helv Paediatr Acta 27:549-555, 1972 25. Sasaki MS, Tonomura A, Matsubara S: Chromosome constitution and its bearing on the chromosomal radiosensitivity in man. Mutat Res 101:617-633, 1970 26. Schade H, Schoeller L, Schultze VWD: D-Trisomie (Patau) mit kongenitaler myeloischer Leukaemie. Med Welt 50:26902692, 1962 27. Seabright M: A rapid staining technique for human chromosomes. Lancet 2:971-972, 1971 28. Warkany J: Congenital Malformations. Chicago, Year Book Medical Publishers, 1971 29. Weitzner S: Benign teratoma of the neck in an infant. Am J Dis Child 107:84-87, 1964 30. Yarbrough SSM, Evashwick G: A case of teratoma of the liver with 14 years postoperative survival. Cancer 9:848-850. 1956 31. Zuelzer WW, Thompson RI, Mastrangelo R: Evidence of a genetic factor related to leukemogenesis and congenital anomalies: Chromosomal aberrations in pedigree of an infant with partial Dtrisomy and leukemia. J Pediatr 72:367376, 1968
THOMAS ETAL.
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A.J.C.P. • June 1978
was done. Examination of Epon-embedded endometrium 1 /xm thick by light microscopy and subsequently by electron microscopy disclosed intracellular bacilliform organisms within phagolysosomes of atypical histiocytes, lamellar bodies, and various developing stages of calcospherites, Michaelis-Gutmann bodies. The curettings were then received and classic MichaelisGutmann bodies were identified in periodic acid-Schiff-stained sections. (Key words: Malacoplakia; Atypical histiocytes; Michaelis-Gutmann bodies; Phagolysosomes; Bacilliform organisms; Endometrium.)
hospital. Vaginal bleeding soon recurred, and she was readmitted September 23, 1974, for further evaluation. The patient had had deforming rheumatoid arthritis for seven years and Sjogren's syndrome for a year. Treatment of arthritis had consisted initially of a total daily dose of 60 mg prednisone, subsequently reduced to a total maintenance dose of 28 mg per day. At one point, the leukocyte count had decreased to 1,900/cu mm. A lupus erythematosus test was positive. The antinuclear antibody and rheumatoid factor titers were each 1:1280.
MALACOPLAKIA, an unusual granulomatous inflammatory disease, was initially reported to occur in the urinary bladder where it is found most often, but it has also occurred in other organs and tissues. We describe what we believe to be the first documented case of malacoplakia of the endometrium, manifesting as postmenopausal bleeding.
Physical
Report of a Case A 60-year-old white woman, multigravida, 20 years postmenopausal, first noticed the onset of vaginal bleeding and discharge in July 1974. She was admitted to Mount Sinai Hospital Medical Center on August 9, 1974, for dilatation and currettage. Histologic examination of the tissue was interpreted as acute suppurative endometritis. The patient was discharged from the
Examination
Temperature was 100 F, blood pressure 148/90 mm Hg, and pulse rate 99/min. The liver was palpable 4 cm below the right costal margin. There were stiffness and severe deformities of the metacarpophalangeal and metatarsophalangeal joints. The knees and elbow joints were markedly enlarged. Pelvic examination disclosed a small uterus and cervix, which drained a meager amount of thick, yellowish-white material. The clinical impressions were: carcinoma of the endometrium or cervix, rheumatoid arthritis, and Sjogren's syndrome. Course in the Hospital A fractional dilatation and curettage was done September 25, 1974, and a diagnosis of benign xanthomatous endometritis was made. Urinary cultures grew Escherichia coli. The plate counts ranged from 75,000 to 4,000.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
FIG. I. Endometrial stroma, showing a histiocytic and neutrophilic infiltrate and numerous Michaelis-Gutmann bodies (arrows), which stain with varying intensity as bull's-eyes. Periodic acid-Schiff stain, x 160.
CASE REPORTS
Vol. 69 • No. 6
639
FIG. 2. Epon-embedded sections 1 ftm thick show foamy histiocytes containing intracytoplasmic Michaelis-Gutmann bodies (m-g) and bacteria (b). Plasma cells are also present. Toluidine blue strain. x2,000. Subsequent to rendering of the diagnosis of benign disease on the basis of uterine scrapings, elective hysterectomy with bilateral salpingo-oophorectomy was performed October 2, 1974. The uterus was small, and the gynecologist reported it to be softer than normal. Both ovaries and tubes were grossly normal. Postoperatively, the patient had a brief episode of abdominal distention and ileus, which abated within three to four days. Cystoscopy and proctoscopy were performed after a definitive diagnosis of malacoplakia was made. Malacoplakic lesions were not found in the bladder or rectosigmoid. The patient was discharged October 15. 1974. She has been doing well since that time.
Pathologic Findings Uterine curettings and tissue sections from the uterus, cervix, tubes and ovaries were fixed in 10% formalin, cut at 5 /xm and stained with hematoxylin and eosin, periodic acid-Schiff reaction with and without diastase digestion, Brown-Brenn stain for bacteria, Prussian blue for iron, and von Kossa's technic for calcium. Some of the fragments of endometrial tissue were retrieved from the formalin-fixed tissues and postfixed in osmium tetroxide for electron microscopic examination. Comparison of the gross uterine scrapings obtained September 25, 1974, with the specimen obtained August 9, 1974, disclosed that both specimens con-
tained a moderate amount of brown, soft material mixed with blood. The later specimen measured approximately 3.5 x 2 x 1.5 cm. Microscopically, both specimens were infiltrated by large numbers of foamy histiocytes admixed with moderate numbers of plasma cells that extensively replaced endometrial stroma, which contained a paucity of small atrophic endometrial glands. There was a moderate, dense, focal neutrophilic infiltrate. The impression was xanthomatous endometritis, and the material was sent for consultation. The consultant's diagnosis was xanthogranulomatous endometritis also. The hysterectomy specimen revealed the uterus to measure 5 x 4 x 2.5 cm and to weigh 58 g. The endometrium was thick, soft, nodular, and gray-white, with foci of hemorrhage. The mucosa measured 0.6 cm. There was a single intramural leiomyoma 0.8 cm in diameter in the anterior uterine wall. The cervix measured 3 x 2 . 5 x 1 . 8 cm. The mucosa of the exocervix was smooth and unremarkable. The endocervical canal was ragged and hemorrhagic due to the recent curettage. Both tubes and ovaries were grossly unremarkable. Microscopic examination of the cervix, tubes and ovaries disclosed no significant alteration. The endo-
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THOMAS ETAL.
metrium was thick because the stroma was composed of large, foamy macrophages [von Hansemann histiocytes (H)], many plasma cells, and a very few atrophic endometrial glands. In the hematoxylin and eosinstained sections, small bull's-eye-like structures of varying staining intensities were seen in the cytoplasm of some of the foamy macrophages and in the intercellular spaces. Periodic acid-Schiff post-diastasetreated sections delineated the lamellar arrangement of many of the calcified bodies (Fig. 1.) Numerous intraand extracytoplasmic Michaelis-Gutmann bodies stained black for calcium by the von Kossa technic. Only rare bodies were Prussian blue-positive for iron. The Brown-Brenn stain revealed intra- and extracytoplasmic gram-negative rods.
der the light microscope in Epon-embedded tissue I /xm thick, and numerous plasma cells were also seen (Fig. 2). Some of the Michaelis-Gutmann bodies showed concentric laminations (Fig. 3), giving them a characteristic target appearance. Ultrathin sections of the same material (Fig. 4) revealed Michaelis-Gutmann bodies to have a dense crystalline core and a lighter outer zone. Phagosomes resembling the light outer zone of the Michaelis-Gutmann bodies but lacking the calcific electron-dense core, which suggested that they represented an intermediary stage in the formation of the Michaelis-Gutmann bodies, could also be seen. The cytoplasm of some of the malacoplakic histiocytes contained, in addition to the Michaelis-Gutmann bodies and phagosomes, several bacilliform organisms, some of which appeared to be undergoing binary fission. Also present were several concentric lamellar bodies, better recognized at higher magnification (Fig. 5).
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• fcFIG. 3 {upper, left). Intracytoplasmic calcospherule (Michaelis-Gutmann body) showing concentric lamination, x 1,600. FIG. 4 (right). Portion of the cytoplasm of a malacoplakic histiocyte containing a Michaelis-Gutmann body (m-g) with an electron-dense core and a lighter outer zone, a phagosome (ph) probably representing an early M-G body without the central core, and two bacteria (b). Numerous small concentric lamellar bodies (arrow) are also present. x9,300. FIG. 5 (lower, left). Portion of an adjacent plasma cell (p) is also visible. High magnification of a concentric lamellar body, x 150,000.
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Electron Microscopy The numerous macrophages containing the MichaelisGutmann bodies and bacteria were easily identified un-
A.J.C.P. . J u n e 1978
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CASE REPORTS
Vol. 69 • No. 6
Discussion
A year after the lesion was first described by Michaelis and Gutmann in 1902," von Hansemann 5 observed the large atypical histiocytes later known as von Hansemann's cells in malacoplakia. As previously mentioned, the disease was initially found in the urinary bladder, and later in other organs and tissues such as the appendix, 1 testicle, 6 prostate, 2 epididymis, 3 renal pelvis,14 stomach, 17 colon and retroperitoneum, 16 skin, 13 lung and bone. 4 Price and co-workers 1 '' in studying a biopsy specimen of malacoplakia of the skin with the electron microscope, found both intracellular and extracellular Michaelis-Gutmann bodies. The intracellular bodies were formed within a single membrane-lined structure resembling a cytosome. Three stages were evident in the development of the characteristic structure. Very early in the first stage of development of the characteristic structure, prior to calcification, the lesion contained a homogenous, finely granular matrix and concentric membranous fragments, which were likened to the counterpart of small basophilic PAS-positive granules observed by light microscopy, described by McKeil and colleagues 7 as the probable precursor of Michaelis-Gutmann bodies. The next stage in the development of the calcospherule was the formation of randomly scattered, small, dense particles within the matrix of the cytosomes. The final stage of development was manifested by the calcification of the concentrically laminated Michaelis-Gutmann bodies. The
References 1. Blackshear W Jr: Malakoplakia of the appendix. A case report. Am J Clin Pathol 53:284-287, 1970 2. Goldman RL: A case of malakoplakia with involvement by the prostate gland. J Urol 83:407-410, 1965 3. Green WUJ: Malakoplakia of the epididymis (without testicular involvement). The first reported case. Arch Pathol 86: 438-441, 1968 4. Gupta RK. Schuster RA, Christian WD: Autopsy findings in a unique case of malakoplakia. Arch Pathol 93:42-48, 1972 5. von Hansemann D: Ueger Malakoplakia der Hornblase. Arch Pathol Anat 173:302-308, 1903 6. Haukohl RS, Chinchincan H: Malakoplakia of the testicles. Am J Clin Pathol 29:473-478, 1958 7. McKeil CR Jr, Eisenstein R, McDonald JH: Morphological and microbiological studies in malacoplakia. J Urol 88:236242, 1962 8. Michaelis L, Gutmann C: Ueger Einschlusse in blasen tumoren. Z K Lin Med 47:208-215, 1902 9. Nashashib B: Pyometria with massive foam cell reaction. A case report. Am J Obstet Gynecol 112:126-129, 1972 10. Novak ER: Post menopausal endometrial hyperplasia. Am J Obstet Gynecol 71:1312-1321, 1956 11. Novak ER, Woodruff JP: Novak's Gynecologic and Obstetric Pathology. Seventh edition. Philadelphia, London, and Toronto, W. B. Saunders, 1974, p 226 12. Peterson WF, Novak ER: Endometrial polyps. Obstet Gynecol 8:40-49, 1956 13. Price HM, Hanrahan JB, Florida RG: Morphogenesis of calcium laden cytoplasmic bodies in malakoplakia of the skin. Hum Pathol 4:380-394, 1973 14. Purpan L, Perez-Tamago RS: Malakoplakia, renal pelvis. J Urol 84:231-235, 1960 15. Rao NR: Malacoplakia of broad ligament, inguinal region and Endometrium. Arch Pathol 88, 85-88, 1969 16. Terner JY, Lattes A: Malakoplakia of colon and retroperitoneum: Report of a case with histochemical study of Michaelis-Gutmann inclusion bodies. Am J Clin Pathol 44: 20-31, 1965 17. Unis EJ, Estevez JM, Pinzon GJ, et al: Malakoplakia: Discussion of pathogenesis and reports of three cases including one fatal gastric and colonic involvement. Arch Pathol 83: 180-187, 1967
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Causes of postmenopausal bleeding include carcinoma of the endometrium," senile endometritis," endometrial polyps, 12 postmenopausal hyperplasia, 10 and pyometria. 9 In this case, malacoplakia, not having been known to occur in the endometrium, was not considered in the differential diagnosis. Rao15 mentioned the presence of scattered histiocytes in scanty fragments of endometrial stroma and glands of a 40year-old woman who had malacoplakic lesions of the broad ligament and inguinal region. Rao's diagnosis of the disorder was based upon the demonstration of Michaelis-Gutmann bodies (calcospherites) in the inguinal soft tissues and broad ligament. Rao concluded the endometrium was probably involved, but because there was insufficient endometrial tissue, he was unable to confirm his impression histologically. A search of the literature leads us to conclude that this is the first case in which histologic and electron microscopic study unequivocally demonstrated Michaelis-Gutmann bodies and gram-negative bacilliform organisms in the endometrial lesion. To our knowledge, it is also the first case in which the disorder precipitated postmenopausal bleeding.
calcification was composed of needle-shaped hydroxyapatite crystals. Price and associates did not see ferritin deposits within the Michaelis-Gutmann body, but speculated that the ferritin might have been masked by dispersion among the more dense hydroxyapatite crystals. Except for spotty degenerative changes observed in the mitochondria, none of the cellular organelles was affected. Microorganisms were not observed but some of the cytosegresomes contained dense material that could have represented partially degenerated bacterial components. The authors reasoned 13 that the finely granular matrix was, in part, composed of polysaccharides and lipoprotein material, which others suggested was derived from bacterial membranes that were incompletely digested by the macrophages. Terner and Lattes 16 demonstrated non-human glycolipids in von Hansemann's macrophages of malacoplakia and concluded that the glycolipid was probably of bacterial origin.
