International Urology and Nephrology 24 (4), pp. 337-- 343 (1992)
Xanthofibroma of the Adrenal Gland T. NAKADA, I. SASAGAWA, T. YAMAGUCHI, H. SUMIYA,* T. OKI,* J. SHIMAZAKI,* 0 . MATSUZAKI** Department of Urology, Yamagata University, School of Medicine, Yamagata; Departments of *Urology and **Pathology, Chiba University School of Medicine, Chiba, Japan (Accepted August 30, 1991) The authors report on a 43-year-old woman who had undergone unilateral adrenalectomy for a right suprarenal mass. The removed specimen was histopathologically defined as xanthofibroma, a hitherto unpublished adrenal tumour. The connective tissue protein of this rare tumour contained great amounts of collagen, noncollagenous protein and elastin. The significance of such abnormal proliferation of fibrous tissue and the conventional sonographic and CT features of this neoplasm are discussed.
Introduction Various disorders are characterized by an anomalous proliferation of fibrous or xanthogranulomatous tissue in different parts of the body, including the retroperitoneal or trunk region [1, 2]. However, there is no report on a xanthofibroma of the adrenal gland. To our knowledge, this report is the first confirmation of such a case, with special reference to the analysis of the connective tissue component of the removed tumour.
Case report A 43-year-old woman bad been in good health until July, 1988, when an acute onset of eruption led to the diagnosis. Her previous medications included aspirin and penicillamine for the treatment for influenza. She had no relevant family history. She also had no history of hypertension, diabetes or spells. Her family physician failed to find any abnormality by laboratory examination. However, subsequent workups of abdominal ultrasound revealed a round mass above the right kidney and she was referred to our clinic. Attempts to localize the tumour consisted of computed tomography of the abdomen (Fig. 1), ultrasound of the abdomen (Fig. 2), and nuclear magnetic resonance (Fig. 3) which demonstrated the right suprarenal mass. Blood pressure was 110/62 mm Hg. Pulse rate was 74/rain. Laboratory findings for blood count, blood chemistry and urinalysis were normal. The erythrocyte sedimentation rates were 54 mm/1 h and 105 ram/2 h, respectively. Plasma renin activity was 1.48 ng/ml/h (normal: 0.2 to 2.7). Plasma aldosterone concentration and urinary aldosterone excretion were 127 pg/ml (normal: VSP, Utrecht Akaddmiai Kiad6, Budapest
338
Nakada et al.. Xanthofibroma of adrenal gland
Fig. 1. Computed tomography of abdomen without contrast enhancement: Large mass (arrow) in right adrenal. There is slight inhomogeneity of the gland
Fig. 2. Longitudinal sonogram: Enlarged right adrenal mass (black arrow) and normal appearance of the ipsilateral kidney (white arrow)
Fig. 3. Tl-weighted magnetic resonance imaging demonstrates right adrenal mass (arrow). Note low intensity of the tumour
l0 to 180) and 6.8/~g/day (normal: 3 to 7), respectively, under regular sodium diet. Urinary excretion of 17-hydroxycorticosterone was 5.2 mg/day (normal: 3 to 7) and that of 17-ketosteroid was 7.6 rag/day (normal: 6 to 10). Plasma cortisol was 8.9 #g/dl (normal: 5 to 14). Intravenous injection of 0.25 mg of adrenocorticotropic hormone for 6 hours increased plasma cortisol concentration from 6.2 to 20 #g/dl (normal response). Plasma pregnenolone concentration was 0.32 ng/ml (normal: 0.2 to 1.5). Plasma dehydroepiandrosterone concentration was 3.1 ng/ml International Urology and Nephrology 24, 1992
Nakada et al. : Xanthofibroma of adrenal gland
339
Fig. 4. Surgical specimen consisting of well-demarcated elastic-hard tumour mass, measuring 8x 7x 8 cm and weighing 84 g (A). Cut section reveals yellow-coloured tumour encapsulated by thin fibrous capsule (B) (normal: 1.2 to 7.5). Plasma A C T H was 35 pg/ml (normal: 30 to 60). Urinary and plasma epinephrine values were 4.4 l~g/day (normal: 2.0 to 30) and 0.01 ng/ml (normal: less than 0.12). Urinary and plasma norepinephrine values were 62.1/tg/day (normal: 25 to 120) and 0.34 ng/ml (normal: 0.1 to 0.4). Urinary excretion of dopamine was 508/zg/day (normal: 190 to 740) and that of vanillylmandelic acid 2.5 mg/day (normal: 1.3 to 5.1). Infusion of 0.2 pg of glucagon produced no discernible effects on blood pressure (before glucagon infusion 106/59 m m Hg, 20 min after glucagon infusion 103/56 m m Hg) and blood sugar level (before treatment
Fig. 5. Low power view of well-demarcated and fibrous adrenal tumour. Remains of adrenocortical tissue are compressed (arrow). H & E stain, original magnification X 10 International Urology and Nephrolooy 24, 1992
340
Nakada et al. : Xanthofibroma o f adrenal gland
Fig. 6. Spindle-shaped turnout cells arranged in storiform pattern and intermingled with foamy histiocytes. H & E stain, original magnification • 50
88 mg/dl, 20 min after glucagon treatment 101 mg/dl). Based on these findings, nonfunctioning adrenal turnout was suspected. A moderately enlarged right adrenal mass was removed by a curving transverse subcostal incision (Fig. 4). Histologic examination revealed that the tumour was composed of spindleshaped fibroblastic ceils intermingled with foamy histiocytes in a collagenous background. The former component was arranged in storiform pattern. Scant adrenocortical tissue remaining beneath the fibrous capsule was compressed by the tumour mass. Foamy histiocytic tumour cells showed fine granular immunoreactivity for desmin, lysozyme, and alpha l-antitrypsin, and spindle-shaped cells were cytoplasmically immunoreactive for S100 and desmin, but not for lysozyme and myosin (Figs 5 and 6). Fresh specimens were removed from the tumour and kept frozen at - 80 ~ until the assay of connective tissue protein. The sample for collagen was determined by a slight modification of the method of Fitch et al. [3]. Elastin was measured by the method of Wolinsky et al. [4]. Detailed description of these Table 1 Concentration of connective tissue proteins in the removed tumour (mg/g tissue) Collagen Non-collagenous protein Elastin
International Uroloyy and Nephrology 24, 1992
145 184 236
N a k a d a et al. : X a n t h o f i b r o m a o f adrenal gland
341
methods can be seen elsewhere [5]. Contents of collagen, non-collagenous protein and elastin are depicted in Table 1. One year later she is asymptomatic, and there is no evidence of recurrence. Discussion
Some uncommon characteristics of this case are worthy of comment. The majority of the fibrous tissues were hyperdense relative to adjoining soft regions on CT and hypoechoic on sonography [2]. On pre- and post-contrast CT scans, histologically verified fibrous lesions appeared as hyperdense or significantly enhanced pictures [2]. The pre-contrast CT hyperdensity may reverberate, in part, the enhanced physical density of the collagen within fibrous tissues [6]. Indeed, contrast enhancement has been noted in retroperitoneal fibrosis during angiography [6, 7]. Another hypothesis of the post-contrast CT hyperdensity of the fibrous lesions may be associated in part with their abundant capillary network [2]. In our case, however, neither pre-contrast nor post-contrast CT hyperdensity could be demonstrated in the adrenal mass. The cause of the regular density of the CT picture in our case is uncertain. However, the content of collagen accounts for up to 14.4% (Table 1) of the removed gland which is smaller than regular tendons [2]. In addition, no abundant capillary network was histopathologically observed in the removed tumour. Gospodarowicz et al. [8] reported on the utilization of extracellular matrix (ECM) originated in bovine corneal endothelial cells as a substrate for growing human solid tumours. Though the precise peculiarity of the ECM is not fully known yet, it appears to be composed of a texture ofelastin and collagen embedded in a ground substance of proteoglycans, glycosaminoglycans and glycoproteins including fibronectin and laminin [9]. Previous investigations have shown a much faster and more stable attachment for both turnout and normal cells to ECM than to plastic, or an interaction of endothelial or mesothelial cell monolayers [10, 11]. Depending on the cell type and its surface properties, cells can either interwork straightforwardly with collagen [10] or through large glycoproteins such as fibronectin and laminin. Clinically aggressive tumours were considered to be associated with extensive ECM degradation [12]. In our case, the amount of ECM in the removed tumour was not determined. However, relatively high quantities of collagen, non-collagenous protein and elastin were extracted (Table 1). Although the functional significance of these fibrous components is unclear, it may be attributed to altered endothelial smooth muscle cell interactions [13], continuing degradation or turnover of collagen, noncollagenous protein or elastin in the extracellular component and vessel wall of the neoplasm. The stromal tissues appear to play an important role in tumour growth. To characterize the epithelium and stroma from this neoplasm, proteins in the tumour, in the whole epithelium, and stroma were analyzed by SDS-polyacrylamide gel electrophoresis [14] or by direct determination of connective tissue proteins [3, 4, 5]. We determined 3 connective tissue proteins by the latter direct International Urology and Nephrology 24, 1992
342
Nakada et al. : Xanthofibroma of adrenal gland
analysis method, but other neoplastic proteins were not determined. It will be consequential to scrutinize the biochemical property of progressive stimulation of insoluble collagen and elastin that was partly reverberated by the augmentation in their total accumulation in the neoplasm. There are reports of patients with retroperitoneal fibrosis in whom methysergide, lysergic acid diethylamide, phenacetin, methyldopa, ergotamine, hydralazine, hydrochlorothiazide or ampicillin were excessively administered [15, 16, 17]. In our case, no drugs described above had been given and the real pathogenesis of tumour development remains obscure. Analysis of tumour components and the follow-up of patients with adrenal tumour consisting of fibrous elements may be helpful in future to clarify the pathogenesis.
References 1. Seo, S., Min, K. W., Mirkin, L. D. : Juvenile xanthogranuloma. Arch. Pathol. Lab. Med., 110, 911 (1986). 2. Rubenstein, W. A., Gray, G., Auh, Y. H., Honig, C. L., Thorbjarnarson, B., Williams, J. J., Haimes, A. B., Zirinsky, K., Kazam, E.: CT of fibrous tissues and tumors with sonographic correlation. Am. J. Roentgenol., 147, 1067 (1986). 3. Fitch, S. M., Harkness, M. L. R., Harkness, R. D.: Extraction of collagen from tissues. Nature, 176, 163 (1955). 4. Wolinsky, H. : Response of the rat aortic media to hypertension. Morphological and chemical studies. Circulat. Res., 26, 507 (1970). 5. Nakada, T., Sasagawa, l., Furuta, H., Katayama, T., Shimazaki, J.: Age-related differences in norepinephrine and non-collagenous protein in human vas deferens. J. Urol., 141, 998 (1989). 6. Kees, C. J.: Angiographic staining and vascularity in a case of fibrous retroperitonitis. Radiology, 113, 329 (1974). 7. Dalla-Palma, I., Rocca-Rosseni, S., Pozzi-Muceli, R. S., Rizzatto, G.: Computed tomography in the diagnosis of retroperitoneal fibrosis. Urol. Radiol., 3, 77 (1981). 8. Gospodarowicz, D., Mescher, A. L., Birdwell, C. R. : Stimulation of corneal endothelial cell proliferation in vitro by fibroblast and epidermal growth factors. Exp. Eye Res., 25, 75 (1977). 9. Bulbul, M. A., Pavelic, K., Slocum, H. K., Frankfurt, O. S., Rustum, Y. M., Huben, R. P., Bernacki, R. J.: Growth of human urologic tumors on extracellular matrix. J. Urol., 136, 512 (1986). 10. Murray, C. J., Liotta, L., Rennards, S. l., Martin, G. R.: Adhesion characteristics of murine metastatic and nonmetastatic tumor cells in vitro. Cancer Res., 40, 347 (1980). 11. Vlodavsky, I., Fuks, Z., Bar-Ner, M., Araiv, Y., Schirrmacher, V.: Lymphoma cell mediated degradation of surfated proteoglycans in the subendothelial extracellular matrix. Relationship to tumor cell metastasis. Cancer Res., 43, 2704 (1983). 12. Pavelic, K., Bulbul, M. A., Slocum, H. K., Pavelic, Z. P., Rustum, Y. M., Niedbala, M. J., Bernacki, R. J.: Growth of human urological tumors on extraeellular matrix as a model for the in vitro cultivation of primary human tumor explants. Cancer Res., 46, 3653 (1986). 13. Todorovich-Hunter, L., Johnson, D. J., Ranger, P., Keeley, F. W., Rabinovitch, M.: Altered elastin and collagen synthesis associated with progressive pulmonary hypertension induced by monocrotaline. A biochemical and ultrastruetural study. Lab. Invest., 58, 184 (1988). International Urology and Nephrology 24, 1992
Nakada et aL : Xanthofibroma o f adrenal gland
343
14. Mizutani, M., Nakamoto, T., Nishi, N., Matsuo, Y., Kadohama, N., Sandberg, A. A., Nihira, H., Wada, F.: Protein profiles of benign hypertrophic prostate. Stromaabundant distribution of BPH-associated nonhistone proteins. Arch. AndroL, 19, 43 (1987). 15. Graham, J. R., Suby, H. I., Le Compte, P. R., Sadowsky, N. L.: Fibrotic disorders associated with methysergide therapy for headache. N. Engl. J. Med., 274, 359 (1966). 16. Damstrup, L., Jensen, T. T.: Retroperitoneal fibrosis after long-term daily use of ergotamine. Int. Urol. Nephrol., 18, 299 (1986). 17. Waters, V. V. : Hydralazine, hydrochlorothiazide and ampicillin associated with retroperitoneal fibrosis. Case report. J. UroL, 141,936 (1989).
International Urology and Nephrology 24, 1992
Xanthofibroma of the Adrenal Gland T. NAKADA, I. SASAGAWA, T. YAMAGUCHI, H. SUMIYA,* T. OKI,* J. SHIMAZAKI,* 0 . MATSUZAKI** Department of Urology, Yamagata University, School of Medicine, Yamagata; Departments of *Urology and **Pathology, Chiba University School of Medicine, Chiba, Japan (Accepted August 30, 1991) The authors report on a 43-year-old woman who had undergone unilateral adrenalectomy for a right suprarenal mass. The removed specimen was histopathologically defined as xanthofibroma, a hitherto unpublished adrenal tumour. The connective tissue protein of this rare tumour contained great amounts of collagen, noncollagenous protein and elastin. The significance of such abnormal proliferation of fibrous tissue and the conventional sonographic and CT features of this neoplasm are discussed.
Introduction Various disorders are characterized by an anomalous proliferation of fibrous or xanthogranulomatous tissue in different parts of the body, including the retroperitoneal or trunk region [1, 2]. However, there is no report on a xanthofibroma of the adrenal gland. To our knowledge, this report is the first confirmation of such a case, with special reference to the analysis of the connective tissue component of the removed tumour.
Case report A 43-year-old woman bad been in good health until July, 1988, when an acute onset of eruption led to the diagnosis. Her previous medications included aspirin and penicillamine for the treatment for influenza. She had no relevant family history. She also had no history of hypertension, diabetes or spells. Her family physician failed to find any abnormality by laboratory examination. However, subsequent workups of abdominal ultrasound revealed a round mass above the right kidney and she was referred to our clinic. Attempts to localize the tumour consisted of computed tomography of the abdomen (Fig. 1), ultrasound of the abdomen (Fig. 2), and nuclear magnetic resonance (Fig. 3) which demonstrated the right suprarenal mass. Blood pressure was 110/62 mm Hg. Pulse rate was 74/rain. Laboratory findings for blood count, blood chemistry and urinalysis were normal. The erythrocyte sedimentation rates were 54 mm/1 h and 105 ram/2 h, respectively. Plasma renin activity was 1.48 ng/ml/h (normal: 0.2 to 2.7). Plasma aldosterone concentration and urinary aldosterone excretion were 127 pg/ml (normal: VSP, Utrecht Akaddmiai Kiad6, Budapest
338
Nakada et al.. Xanthofibroma of adrenal gland
Fig. 1. Computed tomography of abdomen without contrast enhancement: Large mass (arrow) in right adrenal. There is slight inhomogeneity of the gland
Fig. 2. Longitudinal sonogram: Enlarged right adrenal mass (black arrow) and normal appearance of the ipsilateral kidney (white arrow)
Fig. 3. Tl-weighted magnetic resonance imaging demonstrates right adrenal mass (arrow). Note low intensity of the tumour
l0 to 180) and 6.8/~g/day (normal: 3 to 7), respectively, under regular sodium diet. Urinary excretion of 17-hydroxycorticosterone was 5.2 mg/day (normal: 3 to 7) and that of 17-ketosteroid was 7.6 rag/day (normal: 6 to 10). Plasma cortisol was 8.9 #g/dl (normal: 5 to 14). Intravenous injection of 0.25 mg of adrenocorticotropic hormone for 6 hours increased plasma cortisol concentration from 6.2 to 20 #g/dl (normal response). Plasma pregnenolone concentration was 0.32 ng/ml (normal: 0.2 to 1.5). Plasma dehydroepiandrosterone concentration was 3.1 ng/ml International Urology and Nephrology 24, 1992
Nakada et al. : Xanthofibroma of adrenal gland
339
Fig. 4. Surgical specimen consisting of well-demarcated elastic-hard tumour mass, measuring 8x 7x 8 cm and weighing 84 g (A). Cut section reveals yellow-coloured tumour encapsulated by thin fibrous capsule (B) (normal: 1.2 to 7.5). Plasma A C T H was 35 pg/ml (normal: 30 to 60). Urinary and plasma epinephrine values were 4.4 l~g/day (normal: 2.0 to 30) and 0.01 ng/ml (normal: less than 0.12). Urinary and plasma norepinephrine values were 62.1/tg/day (normal: 25 to 120) and 0.34 ng/ml (normal: 0.1 to 0.4). Urinary excretion of dopamine was 508/zg/day (normal: 190 to 740) and that of vanillylmandelic acid 2.5 mg/day (normal: 1.3 to 5.1). Infusion of 0.2 pg of glucagon produced no discernible effects on blood pressure (before glucagon infusion 106/59 m m Hg, 20 min after glucagon infusion 103/56 m m Hg) and blood sugar level (before treatment
Fig. 5. Low power view of well-demarcated and fibrous adrenal tumour. Remains of adrenocortical tissue are compressed (arrow). H & E stain, original magnification X 10 International Urology and Nephrolooy 24, 1992
340
Nakada et al. : Xanthofibroma o f adrenal gland
Fig. 6. Spindle-shaped turnout cells arranged in storiform pattern and intermingled with foamy histiocytes. H & E stain, original magnification • 50
88 mg/dl, 20 min after glucagon treatment 101 mg/dl). Based on these findings, nonfunctioning adrenal turnout was suspected. A moderately enlarged right adrenal mass was removed by a curving transverse subcostal incision (Fig. 4). Histologic examination revealed that the tumour was composed of spindleshaped fibroblastic ceils intermingled with foamy histiocytes in a collagenous background. The former component was arranged in storiform pattern. Scant adrenocortical tissue remaining beneath the fibrous capsule was compressed by the tumour mass. Foamy histiocytic tumour cells showed fine granular immunoreactivity for desmin, lysozyme, and alpha l-antitrypsin, and spindle-shaped cells were cytoplasmically immunoreactive for S100 and desmin, but not for lysozyme and myosin (Figs 5 and 6). Fresh specimens were removed from the tumour and kept frozen at - 80 ~ until the assay of connective tissue protein. The sample for collagen was determined by a slight modification of the method of Fitch et al. [3]. Elastin was measured by the method of Wolinsky et al. [4]. Detailed description of these Table 1 Concentration of connective tissue proteins in the removed tumour (mg/g tissue) Collagen Non-collagenous protein Elastin
International Uroloyy and Nephrology 24, 1992
145 184 236
N a k a d a et al. : X a n t h o f i b r o m a o f adrenal gland
341
methods can be seen elsewhere [5]. Contents of collagen, non-collagenous protein and elastin are depicted in Table 1. One year later she is asymptomatic, and there is no evidence of recurrence. Discussion
Some uncommon characteristics of this case are worthy of comment. The majority of the fibrous tissues were hyperdense relative to adjoining soft regions on CT and hypoechoic on sonography [2]. On pre- and post-contrast CT scans, histologically verified fibrous lesions appeared as hyperdense or significantly enhanced pictures [2]. The pre-contrast CT hyperdensity may reverberate, in part, the enhanced physical density of the collagen within fibrous tissues [6]. Indeed, contrast enhancement has been noted in retroperitoneal fibrosis during angiography [6, 7]. Another hypothesis of the post-contrast CT hyperdensity of the fibrous lesions may be associated in part with their abundant capillary network [2]. In our case, however, neither pre-contrast nor post-contrast CT hyperdensity could be demonstrated in the adrenal mass. The cause of the regular density of the CT picture in our case is uncertain. However, the content of collagen accounts for up to 14.4% (Table 1) of the removed gland which is smaller than regular tendons [2]. In addition, no abundant capillary network was histopathologically observed in the removed tumour. Gospodarowicz et al. [8] reported on the utilization of extracellular matrix (ECM) originated in bovine corneal endothelial cells as a substrate for growing human solid tumours. Though the precise peculiarity of the ECM is not fully known yet, it appears to be composed of a texture ofelastin and collagen embedded in a ground substance of proteoglycans, glycosaminoglycans and glycoproteins including fibronectin and laminin [9]. Previous investigations have shown a much faster and more stable attachment for both turnout and normal cells to ECM than to plastic, or an interaction of endothelial or mesothelial cell monolayers [10, 11]. Depending on the cell type and its surface properties, cells can either interwork straightforwardly with collagen [10] or through large glycoproteins such as fibronectin and laminin. Clinically aggressive tumours were considered to be associated with extensive ECM degradation [12]. In our case, the amount of ECM in the removed tumour was not determined. However, relatively high quantities of collagen, non-collagenous protein and elastin were extracted (Table 1). Although the functional significance of these fibrous components is unclear, it may be attributed to altered endothelial smooth muscle cell interactions [13], continuing degradation or turnover of collagen, noncollagenous protein or elastin in the extracellular component and vessel wall of the neoplasm. The stromal tissues appear to play an important role in tumour growth. To characterize the epithelium and stroma from this neoplasm, proteins in the tumour, in the whole epithelium, and stroma were analyzed by SDS-polyacrylamide gel electrophoresis [14] or by direct determination of connective tissue proteins [3, 4, 5]. We determined 3 connective tissue proteins by the latter direct International Urology and Nephrology 24, 1992
342
Nakada et al. : Xanthofibroma of adrenal gland
analysis method, but other neoplastic proteins were not determined. It will be consequential to scrutinize the biochemical property of progressive stimulation of insoluble collagen and elastin that was partly reverberated by the augmentation in their total accumulation in the neoplasm. There are reports of patients with retroperitoneal fibrosis in whom methysergide, lysergic acid diethylamide, phenacetin, methyldopa, ergotamine, hydralazine, hydrochlorothiazide or ampicillin were excessively administered [15, 16, 17]. In our case, no drugs described above had been given and the real pathogenesis of tumour development remains obscure. Analysis of tumour components and the follow-up of patients with adrenal tumour consisting of fibrous elements may be helpful in future to clarify the pathogenesis.
References 1. Seo, S., Min, K. W., Mirkin, L. D. : Juvenile xanthogranuloma. Arch. Pathol. Lab. Med., 110, 911 (1986). 2. Rubenstein, W. A., Gray, G., Auh, Y. H., Honig, C. L., Thorbjarnarson, B., Williams, J. J., Haimes, A. B., Zirinsky, K., Kazam, E.: CT of fibrous tissues and tumors with sonographic correlation. Am. J. Roentgenol., 147, 1067 (1986). 3. Fitch, S. M., Harkness, M. L. R., Harkness, R. D.: Extraction of collagen from tissues. Nature, 176, 163 (1955). 4. Wolinsky, H. : Response of the rat aortic media to hypertension. Morphological and chemical studies. Circulat. Res., 26, 507 (1970). 5. Nakada, T., Sasagawa, l., Furuta, H., Katayama, T., Shimazaki, J.: Age-related differences in norepinephrine and non-collagenous protein in human vas deferens. J. Urol., 141, 998 (1989). 6. Kees, C. J.: Angiographic staining and vascularity in a case of fibrous retroperitonitis. Radiology, 113, 329 (1974). 7. Dalla-Palma, I., Rocca-Rosseni, S., Pozzi-Muceli, R. S., Rizzatto, G.: Computed tomography in the diagnosis of retroperitoneal fibrosis. Urol. Radiol., 3, 77 (1981). 8. Gospodarowicz, D., Mescher, A. L., Birdwell, C. R. : Stimulation of corneal endothelial cell proliferation in vitro by fibroblast and epidermal growth factors. Exp. Eye Res., 25, 75 (1977). 9. Bulbul, M. A., Pavelic, K., Slocum, H. K., Frankfurt, O. S., Rustum, Y. M., Huben, R. P., Bernacki, R. J.: Growth of human urologic tumors on extracellular matrix. J. Urol., 136, 512 (1986). 10. Murray, C. J., Liotta, L., Rennards, S. l., Martin, G. R.: Adhesion characteristics of murine metastatic and nonmetastatic tumor cells in vitro. Cancer Res., 40, 347 (1980). 11. Vlodavsky, I., Fuks, Z., Bar-Ner, M., Araiv, Y., Schirrmacher, V.: Lymphoma cell mediated degradation of surfated proteoglycans in the subendothelial extracellular matrix. Relationship to tumor cell metastasis. Cancer Res., 43, 2704 (1983). 12. Pavelic, K., Bulbul, M. A., Slocum, H. K., Pavelic, Z. P., Rustum, Y. M., Niedbala, M. J., Bernacki, R. J.: Growth of human urological tumors on extraeellular matrix as a model for the in vitro cultivation of primary human tumor explants. Cancer Res., 46, 3653 (1986). 13. Todorovich-Hunter, L., Johnson, D. J., Ranger, P., Keeley, F. W., Rabinovitch, M.: Altered elastin and collagen synthesis associated with progressive pulmonary hypertension induced by monocrotaline. A biochemical and ultrastruetural study. Lab. Invest., 58, 184 (1988). International Urology and Nephrology 24, 1992
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14. Mizutani, M., Nakamoto, T., Nishi, N., Matsuo, Y., Kadohama, N., Sandberg, A. A., Nihira, H., Wada, F.: Protein profiles of benign hypertrophic prostate. Stromaabundant distribution of BPH-associated nonhistone proteins. Arch. AndroL, 19, 43 (1987). 15. Graham, J. R., Suby, H. I., Le Compte, P. R., Sadowsky, N. L.: Fibrotic disorders associated with methysergide therapy for headache. N. Engl. J. Med., 274, 359 (1966). 16. Damstrup, L., Jensen, T. T.: Retroperitoneal fibrosis after long-term daily use of ergotamine. Int. Urol. Nephrol., 18, 299 (1986). 17. Waters, V. V. : Hydralazine, hydrochlorothiazide and ampicillin associated with retroperitoneal fibrosis. Case report. J. UroL, 141,936 (1989).
International Urology and Nephrology 24, 1992
