EOSINOPHILIC GRANULOMA OF BLADDER G. WITTERS, M.D. L. BAERT, M.D. M. D'HOEDT, M.D. W. TANGHE, M.D. From the Department of Urology, University Clinic St.-Pieter, Leuven, and the Department of Pathology, Heilig Hart Ziekenhuis, Roeselare, Belgium
ABSTRACT--Eosinophilic granuloma of the bladder, a rare and certainly poorly known disease, simulates bladder neoplasms. Clinical aspects, histology, and therapy in a young boy are described.
Eosinophilic granuloma is an unusual and puzzling condition, first described nearly simultaneously by Brown I and Palubinskas 2 in 1960. Eosinophilic infiltrations involving the gastrointestinal tract and other soft tissues are being recognized with increasing frequency, but those within the lower part of the urinary tract are extremely infrequent. In the present case, an inflammatory mass lesion of the urinary bladder wall could not be satisfactorily distinguished from a neoplastic process by urologic or roentgenographic studies. Biopsy of the bladder wall revealed a massive interstitial infiltration by eosinophilic leukocytes. Case Report A sixteen-year-old boy was admitted to the hospital in January 1984, with a two-month
history of recurrent episodes of dysuria, frequency, and burning and pain in the suprapubic region. He had been treated previously with antibiotics with good subjective result; however, post-micturitional hematuria was ob-: served for which he was hospitalized. No history of allergy to food or drugs was obtainable. Physical examination was unremarkable. Laboratory data included hemoglobin 14 g,~ hematocrit 43, white blood cells 5,200 with 211 percent eosinophilia. There was microscopic i hematuria and pyuria. The urine culture:! showed no growth; cytology findings were neg-! ative. An intravenous urogram showed normal I upper urinary tracts, but a filling defect of 2 crn~i on the left bladder wall, containing multiplei small calcifications (Fig. 1). On cystoscopy a I solid, well-lined exophytic lesion, covered with~i normal mucosa and central ulceration was!
FIGURE 1. Preoperative in-I
travenous pyelogram (IVP)~ showing Jilling deject on Iefi~ bladder wall (A), containing~ multiple small calciJicationd!~ (B).
72
UROLOGY /
JANUARY 1991 /
VOLUME XXXVII, NUMBER 1;~
FICU~E 2. Suburothelium shows moderately dense in/iltration of mixed composition, i.e., lymphocytes, eosinophilic granulocytes, and histiocytes. (B) Some histiocytes have large pale nucleus with briskly indented nuclear membrane, reminiscent of so-called Langerhans histiocyte of skin. These cells were S-lO0-protein positive (peroxidase-antiperoxidase technique). Cells of histiocytic range contained lysozyme positive granules. (Hematoxylin and eosin, original magnifications x 250 and x 1,000, respectively.)
seen. The large lesion was excised with a resectoscope. The histologic diagnosis was eosinophilic granuloma (Fig. 2A). Postoperative treatment consisted of prednisolone in a start dosage of 20 g daily, with progressive regression over two months. Findings on cystoscopy three months later were perfectly normal, and biopsy of the same region showed no specific inflammation. With a follow-up period of thirty-four months the patient remained free of complaints. Comment Eosinophilic granuloma of the bladder has been encountered at all ages with a prevalence in children and young adults. The pathogenesis has not been established. Hypersensitivity to food and drugs has been frequently identified, followed by respiratory infections, 3 parasitic infestation, and warfarin (Coumadin). Apart from 1 case where Toxocara cati infection was found, ~ no etiologic agent could be demonstrated despite the search for ova and parasites. Recently even the more sensitive Elisa technique could not demonstrate evidence of toxocaral or a,scaris infection. Major clinical features have i n c l u d e d symptoms of vesical irritabilit3; hematuria (usually microscopic), and proteinuria (usually slight). Despite the fact that peripheral eosinophilia is considered unnecessary to the diagnosis of eosinophilic granuloma (contrasting with its characteristic in eosinophilic gastroenteritis), 84.6 percent of the patients demonstrated this feature. 5
UBOLOCy
/
JANUARY 1991
/
Most of the reported patients had normal intravenous urograms, but a thick bladder with a small capacity, filling defect, or vesicoureteral reflux may be apparent in some. In our patient we found small intratumoral calcifications, which have never been mentioned before. Eosinophilic granuloma is a baffling rarity impossible to distinguish grossly from bladder t u m o r on endoscopy. It may form tumor masses, proliferative or ulcerative, either single or multiple. Histologic examination reveals infiltration of the submucosa and musculosa by an admixture of eosinophilic granulocytes (eosinophils) and histiocytes. Connective tissue proliferation in the form of sheets of spindly fibroblasts may occur. The histiocytes often vary in size and configuration and may display a degree of nuclear pyknosis and enlargement (Fig. 2B). CharotLeyden crystals may be observed. Diffuse submucosal infiltration with eosinophilic granulocytes only, is described as eosinophilic cystitis. The prognosis of this disorder is favorable in most cases. Eosinophilic granuloma of the bladder appears to be a self-limiting disease. Therefore therapy will be as conservative as possible. Surgery will be limited to transurethral biopsy after which a symptomatic medical treatment will be given. Therapeutic measures have ineluded stibophen (anti-schistosome) local radiotherapy; antibiotics, silver nitrate instillations, and steroids, with only the latter currently given consideration, in analogy with the treatment of eosinophilic gastroenteritis.
VOLUME XXXVII, NUMBER 1
73
These drugs seem to have a favorable influence on the evolution of the disease 1,6 (own observation). Aggressive surgery to prevent damage to the upper urinary tract has been mandatory only on very rare occasions. ~ Knowledge of this disorder is of great importance while it is presenting as a malignant tumor, though the spontaneous evolution is often self-limited. Department of Urology University of Stellenboseh EO. Box 63 Tygerberg 7505 Republic of South Africa (DR. WITTERS)
74
References 1. Brown EW: Eosinophilic granuloma of bladder~ J tyrol 83:: 665 (1960). 2. Palubinskas AJ: Eosinophilic cystitis: case report ofl cosinophilic infiltration of urinary bladder, Radiology 75:589 (1960). 3. Frensilli FJ, Sacher EC, and Kergan GT: Eosinophilic eys, titis: observations on etiology, J Urol 107:595 0972). 4. Perlmutter AD, Edlow JB, and Kcvy SV: ]bxocara antibodies in eosinophflic cystitis, J Pcdiatr 73:340 (1968). ':¢ 5. Tauscher JW: Eosinophilic cystitis, Clin Pcdiatr 11: "~41,.:
(1967). 6. Madersbacher H, and Bartsch G'. Eosinophile Infiltrate deri Harnblase. Ein Beitrag zur granulomat6sen Zystitis, Urol Int 27:! 149 (1972). ~: 7. Sidh SM, Smith SR Si]ber SB, and Young JD: Eosinophilic! cystitis: advanced disease requiring surgical intervention, Urology~ 15:'23 (1980).
UROLOGY
/ JANUARY 1991 /
VOLUME XXXVII, NUMBER I
ABSTRACT--Eosinophilic granuloma of the bladder, a rare and certainly poorly known disease, simulates bladder neoplasms. Clinical aspects, histology, and therapy in a young boy are described.
Eosinophilic granuloma is an unusual and puzzling condition, first described nearly simultaneously by Brown I and Palubinskas 2 in 1960. Eosinophilic infiltrations involving the gastrointestinal tract and other soft tissues are being recognized with increasing frequency, but those within the lower part of the urinary tract are extremely infrequent. In the present case, an inflammatory mass lesion of the urinary bladder wall could not be satisfactorily distinguished from a neoplastic process by urologic or roentgenographic studies. Biopsy of the bladder wall revealed a massive interstitial infiltration by eosinophilic leukocytes. Case Report A sixteen-year-old boy was admitted to the hospital in January 1984, with a two-month
history of recurrent episodes of dysuria, frequency, and burning and pain in the suprapubic region. He had been treated previously with antibiotics with good subjective result; however, post-micturitional hematuria was ob-: served for which he was hospitalized. No history of allergy to food or drugs was obtainable. Physical examination was unremarkable. Laboratory data included hemoglobin 14 g,~ hematocrit 43, white blood cells 5,200 with 211 percent eosinophilia. There was microscopic i hematuria and pyuria. The urine culture:! showed no growth; cytology findings were neg-! ative. An intravenous urogram showed normal I upper urinary tracts, but a filling defect of 2 crn~i on the left bladder wall, containing multiplei small calcifications (Fig. 1). On cystoscopy a I solid, well-lined exophytic lesion, covered with~i normal mucosa and central ulceration was!
FIGURE 1. Preoperative in-I
travenous pyelogram (IVP)~ showing Jilling deject on Iefi~ bladder wall (A), containing~ multiple small calciJicationd!~ (B).
72
UROLOGY /
JANUARY 1991 /
VOLUME XXXVII, NUMBER 1;~
FICU~E 2. Suburothelium shows moderately dense in/iltration of mixed composition, i.e., lymphocytes, eosinophilic granulocytes, and histiocytes. (B) Some histiocytes have large pale nucleus with briskly indented nuclear membrane, reminiscent of so-called Langerhans histiocyte of skin. These cells were S-lO0-protein positive (peroxidase-antiperoxidase technique). Cells of histiocytic range contained lysozyme positive granules. (Hematoxylin and eosin, original magnifications x 250 and x 1,000, respectively.)
seen. The large lesion was excised with a resectoscope. The histologic diagnosis was eosinophilic granuloma (Fig. 2A). Postoperative treatment consisted of prednisolone in a start dosage of 20 g daily, with progressive regression over two months. Findings on cystoscopy three months later were perfectly normal, and biopsy of the same region showed no specific inflammation. With a follow-up period of thirty-four months the patient remained free of complaints. Comment Eosinophilic granuloma of the bladder has been encountered at all ages with a prevalence in children and young adults. The pathogenesis has not been established. Hypersensitivity to food and drugs has been frequently identified, followed by respiratory infections, 3 parasitic infestation, and warfarin (Coumadin). Apart from 1 case where Toxocara cati infection was found, ~ no etiologic agent could be demonstrated despite the search for ova and parasites. Recently even the more sensitive Elisa technique could not demonstrate evidence of toxocaral or a,scaris infection. Major clinical features have i n c l u d e d symptoms of vesical irritabilit3; hematuria (usually microscopic), and proteinuria (usually slight). Despite the fact that peripheral eosinophilia is considered unnecessary to the diagnosis of eosinophilic granuloma (contrasting with its characteristic in eosinophilic gastroenteritis), 84.6 percent of the patients demonstrated this feature. 5
UBOLOCy
/
JANUARY 1991
/
Most of the reported patients had normal intravenous urograms, but a thick bladder with a small capacity, filling defect, or vesicoureteral reflux may be apparent in some. In our patient we found small intratumoral calcifications, which have never been mentioned before. Eosinophilic granuloma is a baffling rarity impossible to distinguish grossly from bladder t u m o r on endoscopy. It may form tumor masses, proliferative or ulcerative, either single or multiple. Histologic examination reveals infiltration of the submucosa and musculosa by an admixture of eosinophilic granulocytes (eosinophils) and histiocytes. Connective tissue proliferation in the form of sheets of spindly fibroblasts may occur. The histiocytes often vary in size and configuration and may display a degree of nuclear pyknosis and enlargement (Fig. 2B). CharotLeyden crystals may be observed. Diffuse submucosal infiltration with eosinophilic granulocytes only, is described as eosinophilic cystitis. The prognosis of this disorder is favorable in most cases. Eosinophilic granuloma of the bladder appears to be a self-limiting disease. Therefore therapy will be as conservative as possible. Surgery will be limited to transurethral biopsy after which a symptomatic medical treatment will be given. Therapeutic measures have ineluded stibophen (anti-schistosome) local radiotherapy; antibiotics, silver nitrate instillations, and steroids, with only the latter currently given consideration, in analogy with the treatment of eosinophilic gastroenteritis.
VOLUME XXXVII, NUMBER 1
73
These drugs seem to have a favorable influence on the evolution of the disease 1,6 (own observation). Aggressive surgery to prevent damage to the upper urinary tract has been mandatory only on very rare occasions. ~ Knowledge of this disorder is of great importance while it is presenting as a malignant tumor, though the spontaneous evolution is often self-limited. Department of Urology University of Stellenboseh EO. Box 63 Tygerberg 7505 Republic of South Africa (DR. WITTERS)
74
References 1. Brown EW: Eosinophilic granuloma of bladder~ J tyrol 83:: 665 (1960). 2. Palubinskas AJ: Eosinophilic cystitis: case report ofl cosinophilic infiltration of urinary bladder, Radiology 75:589 (1960). 3. Frensilli FJ, Sacher EC, and Kergan GT: Eosinophilic eys, titis: observations on etiology, J Urol 107:595 0972). 4. Perlmutter AD, Edlow JB, and Kcvy SV: ]bxocara antibodies in eosinophflic cystitis, J Pcdiatr 73:340 (1968). ':¢ 5. Tauscher JW: Eosinophilic cystitis, Clin Pcdiatr 11: "~41,.:
(1967). 6. Madersbacher H, and Bartsch G'. Eosinophile Infiltrate deri Harnblase. Ein Beitrag zur granulomat6sen Zystitis, Urol Int 27:! 149 (1972). ~: 7. Sidh SM, Smith SR Si]ber SB, and Young JD: Eosinophilic! cystitis: advanced disease requiring surgical intervention, Urology~ 15:'23 (1980).
UROLOGY
/ JANUARY 1991 /
VOLUME XXXVII, NUMBER I
