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Renal Angiomyolipoma in a Case of Tuberous Sclerosis, an Electron Microscopy Study
Beitr. Path. Bd. 156,401-410 (1975)
Case Reports
Veterans Administration Hospital and University of Arkansas School of Medicine, Little Rock, Arkansas 72206, USA
Renal Angiomyolipoma in a Case of Tuberous Sclerosis, an Electron Microscopy Study Renales Angiomyolipom im FaIle einer tuberosen Sklerose (Eine ultrastrukturelle Studie) C. N. SUN, H.
J. WHITE, and N. K. BISSADA
With 4 Figures' Received January 5, 1975 . Accepted in revised form September 3, 1975
Key words: Angiomyolipoma - Kidney tumors - Renal tumors - Tuberous sclerosis
Summary Electron microscopic study of bilateral renal angiomyolipoma in a case of tuberous sclerosis showed two cell types: smooth muscle cells and fibroblasts. There were no tubular or glomerular elements within the tumor mass. To our knowledge this study represents the first ultrastructural demonstration of smooth muscle cells occurring in the renal lesions of this complex.
Numerous cases of renal angiomyolipoma with or without tuberous sclerosis have been reported (Fischer, 1911; Morgan, et al., 1951). Different terminology has been used to describe the disease, such as: lipomyohemangioma (Heckel and Penick, 1948); angiolipoleiomyoma (Tweeddale, et al., 1955); benign arterioleiomyoma (Gordon et al., 1939); benign mesenchymoma (Lucke and Schlumberger, 1957); angiolipomyosarcoma (Berg, 1955); and myoangiolipoma (Deming and Harvard, 1970). There have
402 .
C. N. Sun, H. J. White, and N. K. Bissada
been few previous reports of electron microscopic studies of this disease (Mori et aI., 1971). The purpose of this report is to present a case of this unusual renal tumor, angiomyolipoma with tuberous sclerosis, its cellular fine structures and propose possible origins of the tumor cells.
Case Report L. B. (LRVAH # 96-5251), a 23-year old white male, was admitted to the Veterans Administration Hospital on January 7, 1974. Two weeks prior to admission he had an acute onset of right colicky flank pain and gross hematuria. An excretory urogram showed a space-occupying lesion in the mid portion of the right kidney distorting the collecting system. A single instance of right flank pain lasting several hours occurred three months prior to admission. Multiple papules were present on the patient's face. By history they had been present since age 10 and had persisted with little change over the years. The patient's mother remembered that he had "little, white birthmarks" on his abdomen and back since birth. In his early teens he had a pedunculated mass removed from the border of a fingernail. There was no history of seizures or mental deficiency. He had completed two years of college. There was no family history of seizures, mental deficiency or renal disease. Physical examination revealed a well-developed, intelligent, white male. Pertinent findings were limited to the skin. Adenoma sebaceum was present along the nasolabial furrows and extending onto the medial portion of the cheeks. Several fibrous nodules on the forehead, and four hypopigmented maculae on the chest and back were present. Multiple periungual fibromata were present on the feet. Several small soft pedunculated skin tags were present in the axillary region bilaterally. Fundoscopic examination did not reveal phacomata. EKG was normal. Renal arteriography demonstrated bilateral vascular renal tumors. It was believed that the lesions were angiomyolipomas. However, it was elected to confirm the diagnosis by open biopsy. The left kidney was explored transperitoneally on January 22, 1974. Multiple solid tumors involving the lower pole and a large cystic mass in the upper pole were found. Biopsies were obtained and frozen section examination was compatible with a diagnosis of renal angiomyolipoma. The postoperative course was uneventful, and the patient was discharged on February 13, 1974·
Renal Angiomyolipoma . 4 0 3
Fig. 1. Smooth muscle cells in the tumor mass are surrounded by portions of basement membrane or connective tissue. (B). basement membrane; (C). connective tissue; (ER), endoplasmic reticulum; (D). dense granules; (S), elongated dense spots; X 30,000; (G), glycogen granules; (M), mitochondrion; (Mf), myofilaments; X 12,000.
404 . C. N. Sun, H.
J. White, and N. K. Bissada
Materials and Methods Biopsy specimens of the renal lesion were studied by light and electron microscopy. For light microscopic studies, tissues were fixed in 10010 buffered formalin. Paraffin embedded tissues were sectioned and stained with Hematoxylin and Eosin. For electron microscopy, tissues were cut into small pieces about I mm 3 and immediately fixed in 4010 glutaraldehyde in phosphate buffer for two hours, then postfixed in 1010 buffered osmium tetroxide for one hour. After dehydration, tissues were embedded in Epon 812. Thin sections were stained with uranyl acetate and lead citrate (Reynolds, 1963). Light microscopy showed an array of spindle cells arranged about vessels. Stains with Schiff's periodic acid showed granules in the cytoplasm of these cells. Foci of fatty tissue were also noted within the rumor.
Observations Electron microscopy: Within the tumor mass, no tubular or glomerular elements were present. There were two types of cells that could be distinguished in the tumorous mass: smooth muscle cells and what appeared to be fibroblastic or parenchymal cells. The smooth muscle cells were loosely arranged, contain myofilaments, large indented nuclei, rough endoplasmic reticulum, mitochondria, dense granules, fat vacuoles, and an unusual amount of glycogen granules (Fig. I). In many of the smooth muscle cells showing degenerated myofilaments and microtubules, there appeared to be an increased amount of glycogen granules. Goigi fields were identified (Fig. 2). In the fibroblastic or parenchymal cells, the nuclei were frequently lobed and showed nuclear or cytoplasmic inclusions. In the cytoplasm, the endoplasmic reticulum occasionally took on a whorl-like arrangement, or in the form of parallel arrays. There were abundant small lysosomal granules and large amount of glycogen granules. Golgi fields were also present (Fig. 3). In some small areas, the smooth muscle cells had plasma membranes about 75 A in thickness and exhibited the typical triplelawered unit membrane. However, in many locations, these were separated by a considerable amount of extracellular substances. Each cell had its own basement membrane. In some locations, the intercellular spaces
Fig. n. A portion of degenerated smooth muscle cells in the tumor; basement membrane (B), glycogen granules (G), microtubules (MT), vesicles (V). X 25,000. Fig.2b. In a portion of the rumor cells, basement membrane (B), dense granules (D), endoplasmic reticulum (ER), glycogen granules (G), Mitochondria (M), and nucleus (N) are shown. X 27,500.
Renal Angiomyolipoma . 4 0 5
4 06 . C. N. Sun, H . J. White, and N . K. Bissada
Fig. 3. In the fibroblastic cells, Lobe nucleus (N), whorl-like or parallel array endoplasmic reticulum (ER) are seen. (D), dense granule; (G), glycogen; (Go), Golgi field; (M), mitochondrion. X 10,000.
Renal Angiomyolipoma . 4 0 7
Fig. 4. In the tumor mass, small capillary is surrounded by the connective tissue. (B), basement membrane; (Co), collagen fibrils; (Ds), desomosome; (En), endothelial cell; (G), glycogen granules; (L), lipid deposits. X 25,000.
408 . C. N. Sun, H.
J. White,
and N. K. Bissada
were considerably widened and filled with collagen fibrils as well as occasional glycogen granules and lipid deposits (Fig. 4). Many small capillaries were present in the connective tissue.
Discussion The three types of neurocutaneous syndromes most often encountered, are Recklinghausen's neurofibromatosis, Bourneville's tuberous sclerosis, and Lindau's type of von Hippel's disease. Each show congenital malformations occurring in the brain, skin, heart, eyes, kidneys, bones, and occasionally other viscera (Mertz, 1943). The basic lesion of tuberous sclerosis is a hamartomatous tumor which can involve multiple organ systems (Moolten, 1942; Chonko et aI., 1974). The abnormalities involve tissues of ectodermal origin particularly the brain, retina, skin and skin appendages (Deming and Harvard, 1970; Golgi, 1961; Charlot-Charles and Jones, 1974; Bissada et aI., 1975). The only previous report of electron microscopic study of the renal lesions of tuberous sclerosis which came to our attention was that of Mori et al. (1971). However, they did not find myofilamentous structures in the tumor cell cytoplasm. They claimed that the tumor cells were not myogenic in ultrastructure but quite similar to a blastic form of Schwann cell. By contrast, in our study although we found a few fibroblastic cells, however, we consider the majority of the tumor cells to be either smooth muscle type or a degenerated form thereof. Smooth muscle cells occurring in renal tumors has been rarely reported. The only previous reports were by Wigger (1969) on fetal hamartoma and by Tannenbaum (197 I) of leimyosarcoma. These cases of leimyosarcomas have many ultrastructural features similar to the present study of angiomyolipoma, such as smooth cells with myofilaments, glycogen granules and basement membranes. Although glycogen stores may be present in the liver, in the skeletal muscle, or small amount in a great many cell types, large amounts of glycogen granules were not found in the typical nontumorous smooth muscle cells (Ishikawa, 1962; Rhodin, 1962). The accumulation of the large amount of glycogen may indicate that the metabolic activity of the smooth muscle was in an abnormal state.
Zusammenfassung Die ultrastrukturelle Untersuchung eines beidseitigen renalen Angiomyolipoms im Falle einer tuberosen Sklerose laJh zwar die Zelltypen unterscheiden: glatte Muskelzellen und
Renal Angiomyolipoma . 4 0 9 Fibroblasten. 1m Tumorgewebe sind weder tubulare noch glomeruHire Strukturelemente zu erkennen. Nach Meinung der Autoren scheint diese Untersuchung zum ersten Mal glatte Muskelzellen bei solchen Nierenaffektionen zu zeigen. Acknowledgment This project supported by VA Research funds, Project No. 8221-011. Technical assistance of Joe Meador and Bettye Stallings is greatly appreciated.
References 1. Berg, ]. W.: Angiolipomyosarcoma of Kidney (Malignant hamartomatous angiolipomyoma) in a case with solitary metastasis from bronchogenic carcinoma. Cancer 8,759-7 63 (1955) 2. Bissada, N. K., White, H. ]., Sun, C. N., Smith, P. L., Barbour, G. L., and Redman, ]. F.: Tuberous sclerosis complex and renal angiomyolipoma. Urology 6, I05-II 3 (1975 ) 3. Charlot-Charles, ]., and Jones, G. W.: Renal angiomyolipoma associated with tuberous sclerosis: Review of the literature. Urology 3, 465-469 (1974) 4. Chonko, A. M., Weiss, S. M., Stein, ]. H., and Ferris, T. F.: Renal involvement in tuberous sclerosis. Amer. ]. Med. 56, I24-132 (1974) 5. Deming, C. L., and Harvard, B. M.: Tuberous sclerosis. In: Campbell, M. F., and Harrison, ]. H. (eds.) Urology, 3rd ed., Vol. 2, p. 943, 952. W. B. Saunders Co., Philadelphia 1970 6. Fischer, W.: Die Nierentumoren bei der tuberosen Hirnsklerose. Beitr. path. Anat. 50,235-282 (19 11 ) 7. Golji, H.: Tuberous sclerosis and renal neoplasms.]. Urol. 85, 919-923 (1961) 8. Gordon jr., M. P., Kimmelstiel, P., and Cabell, C. L.: Leiomyoma of the kidney: Report of a case with review of the literature. ]. Urol. 42, 507-519 (1939) 9. Heckel, N. ]., and Penick, G. D.: A mixed tumor of the kidney: Lipomyohemangioma. ]. Urol. 59, 572-576 (1948) 10. Ishikawa, T.: Fine structure of the human ciliary muscle. Invest. Ophthalmol. I, 587-608 (1962) 11. Lucke, B., and Schlumberger, H. G.: Tumors of the kidney, renal pelvis and ureter. In: Atlas of Tumor Path. Sect. VIII, Fascicle 30, p. 133. Armed Forces Institute of Pathology, Washington D.C. (1957) 12. Mertz, H. 0.: Tuberous sclerosis and renal tumor. Trans. Amer. Ass. Genitourin. Surg. 35,73- 85 (1943) 13. Moolten, S. E.: Hamartial nature of the tuberous sclerosis complex and its bearing on the tumor problem. Arch. Intern. Med. 69, 589-623 (1942) 14. Morgan, G. S., Straumfjord, ]. V., and Hall, E. ].: Angiomyolipoma of the kidney. ]. Urol. 65,525-527 (1951) 15. Mori, M., Ikeda, T., and Onoe, T.: Blastic schwann cells in renal tumor of tuberous sclerosis complex. An electron microscopic study. Acta Path. Jap. 2I, 121-129 (1971) 16. Reynolds, E. S.: The use of lead citrate at high pH as an electronopaque stain in electron microscopy. ]. Cell BioI. I7, 208-212 (1963) 17. Rhodin, ]. A. G.: Fince structure of vascular walls in mammals with special reference to smooth muscle component. Physio!. Rev. 42, Supp!. 5, 48-81 (1962)
410 .
C. N. Sun, H. ]. White, and N. K. Bissada
18. Tannenbaum, M.: Ultrastructural pathology of human renal cell tumors. Path. Annu. 6,249-277 (1971) 19. Tweeddale, D. N., Dawe, C. ]., McDonald, ]. R., and Culp, O. S.: Angiolipoleiomyoma of the kidney; Report of a case with observations on histogenesis. Cancer 8,7 64-77 0 (1955) 20. Wigger, H. ].; Fetal Hamartoma of kidney. A benign, symptomatic, congenital tumor, not a form of Wilms' tumor. Amer.]. Clin. Path. jI, 323-337 (1969) C. N. Sun, Ph.D., Veterans Administration Hospital and University of Arkansas School of Medicine, Little Rock, Arkansas 72206, USA
Case Reports
Veterans Administration Hospital and University of Arkansas School of Medicine, Little Rock, Arkansas 72206, USA
Renal Angiomyolipoma in a Case of Tuberous Sclerosis, an Electron Microscopy Study Renales Angiomyolipom im FaIle einer tuberosen Sklerose (Eine ultrastrukturelle Studie) C. N. SUN, H.
J. WHITE, and N. K. BISSADA
With 4 Figures' Received January 5, 1975 . Accepted in revised form September 3, 1975
Key words: Angiomyolipoma - Kidney tumors - Renal tumors - Tuberous sclerosis
Summary Electron microscopic study of bilateral renal angiomyolipoma in a case of tuberous sclerosis showed two cell types: smooth muscle cells and fibroblasts. There were no tubular or glomerular elements within the tumor mass. To our knowledge this study represents the first ultrastructural demonstration of smooth muscle cells occurring in the renal lesions of this complex.
Numerous cases of renal angiomyolipoma with or without tuberous sclerosis have been reported (Fischer, 1911; Morgan, et al., 1951). Different terminology has been used to describe the disease, such as: lipomyohemangioma (Heckel and Penick, 1948); angiolipoleiomyoma (Tweeddale, et al., 1955); benign arterioleiomyoma (Gordon et al., 1939); benign mesenchymoma (Lucke and Schlumberger, 1957); angiolipomyosarcoma (Berg, 1955); and myoangiolipoma (Deming and Harvard, 1970). There have
402 .
C. N. Sun, H. J. White, and N. K. Bissada
been few previous reports of electron microscopic studies of this disease (Mori et aI., 1971). The purpose of this report is to present a case of this unusual renal tumor, angiomyolipoma with tuberous sclerosis, its cellular fine structures and propose possible origins of the tumor cells.
Case Report L. B. (LRVAH # 96-5251), a 23-year old white male, was admitted to the Veterans Administration Hospital on January 7, 1974. Two weeks prior to admission he had an acute onset of right colicky flank pain and gross hematuria. An excretory urogram showed a space-occupying lesion in the mid portion of the right kidney distorting the collecting system. A single instance of right flank pain lasting several hours occurred three months prior to admission. Multiple papules were present on the patient's face. By history they had been present since age 10 and had persisted with little change over the years. The patient's mother remembered that he had "little, white birthmarks" on his abdomen and back since birth. In his early teens he had a pedunculated mass removed from the border of a fingernail. There was no history of seizures or mental deficiency. He had completed two years of college. There was no family history of seizures, mental deficiency or renal disease. Physical examination revealed a well-developed, intelligent, white male. Pertinent findings were limited to the skin. Adenoma sebaceum was present along the nasolabial furrows and extending onto the medial portion of the cheeks. Several fibrous nodules on the forehead, and four hypopigmented maculae on the chest and back were present. Multiple periungual fibromata were present on the feet. Several small soft pedunculated skin tags were present in the axillary region bilaterally. Fundoscopic examination did not reveal phacomata. EKG was normal. Renal arteriography demonstrated bilateral vascular renal tumors. It was believed that the lesions were angiomyolipomas. However, it was elected to confirm the diagnosis by open biopsy. The left kidney was explored transperitoneally on January 22, 1974. Multiple solid tumors involving the lower pole and a large cystic mass in the upper pole were found. Biopsies were obtained and frozen section examination was compatible with a diagnosis of renal angiomyolipoma. The postoperative course was uneventful, and the patient was discharged on February 13, 1974·
Renal Angiomyolipoma . 4 0 3
Fig. 1. Smooth muscle cells in the tumor mass are surrounded by portions of basement membrane or connective tissue. (B). basement membrane; (C). connective tissue; (ER), endoplasmic reticulum; (D). dense granules; (S), elongated dense spots; X 30,000; (G), glycogen granules; (M), mitochondrion; (Mf), myofilaments; X 12,000.
404 . C. N. Sun, H.
J. White, and N. K. Bissada
Materials and Methods Biopsy specimens of the renal lesion were studied by light and electron microscopy. For light microscopic studies, tissues were fixed in 10010 buffered formalin. Paraffin embedded tissues were sectioned and stained with Hematoxylin and Eosin. For electron microscopy, tissues were cut into small pieces about I mm 3 and immediately fixed in 4010 glutaraldehyde in phosphate buffer for two hours, then postfixed in 1010 buffered osmium tetroxide for one hour. After dehydration, tissues were embedded in Epon 812. Thin sections were stained with uranyl acetate and lead citrate (Reynolds, 1963). Light microscopy showed an array of spindle cells arranged about vessels. Stains with Schiff's periodic acid showed granules in the cytoplasm of these cells. Foci of fatty tissue were also noted within the rumor.
Observations Electron microscopy: Within the tumor mass, no tubular or glomerular elements were present. There were two types of cells that could be distinguished in the tumorous mass: smooth muscle cells and what appeared to be fibroblastic or parenchymal cells. The smooth muscle cells were loosely arranged, contain myofilaments, large indented nuclei, rough endoplasmic reticulum, mitochondria, dense granules, fat vacuoles, and an unusual amount of glycogen granules (Fig. I). In many of the smooth muscle cells showing degenerated myofilaments and microtubules, there appeared to be an increased amount of glycogen granules. Goigi fields were identified (Fig. 2). In the fibroblastic or parenchymal cells, the nuclei were frequently lobed and showed nuclear or cytoplasmic inclusions. In the cytoplasm, the endoplasmic reticulum occasionally took on a whorl-like arrangement, or in the form of parallel arrays. There were abundant small lysosomal granules and large amount of glycogen granules. Golgi fields were also present (Fig. 3). In some small areas, the smooth muscle cells had plasma membranes about 75 A in thickness and exhibited the typical triplelawered unit membrane. However, in many locations, these were separated by a considerable amount of extracellular substances. Each cell had its own basement membrane. In some locations, the intercellular spaces
Fig. n. A portion of degenerated smooth muscle cells in the tumor; basement membrane (B), glycogen granules (G), microtubules (MT), vesicles (V). X 25,000. Fig.2b. In a portion of the rumor cells, basement membrane (B), dense granules (D), endoplasmic reticulum (ER), glycogen granules (G), Mitochondria (M), and nucleus (N) are shown. X 27,500.
Renal Angiomyolipoma . 4 0 5
4 06 . C. N. Sun, H . J. White, and N . K. Bissada
Fig. 3. In the fibroblastic cells, Lobe nucleus (N), whorl-like or parallel array endoplasmic reticulum (ER) are seen. (D), dense granule; (G), glycogen; (Go), Golgi field; (M), mitochondrion. X 10,000.
Renal Angiomyolipoma . 4 0 7
Fig. 4. In the tumor mass, small capillary is surrounded by the connective tissue. (B), basement membrane; (Co), collagen fibrils; (Ds), desomosome; (En), endothelial cell; (G), glycogen granules; (L), lipid deposits. X 25,000.
408 . C. N. Sun, H.
J. White,
and N. K. Bissada
were considerably widened and filled with collagen fibrils as well as occasional glycogen granules and lipid deposits (Fig. 4). Many small capillaries were present in the connective tissue.
Discussion The three types of neurocutaneous syndromes most often encountered, are Recklinghausen's neurofibromatosis, Bourneville's tuberous sclerosis, and Lindau's type of von Hippel's disease. Each show congenital malformations occurring in the brain, skin, heart, eyes, kidneys, bones, and occasionally other viscera (Mertz, 1943). The basic lesion of tuberous sclerosis is a hamartomatous tumor which can involve multiple organ systems (Moolten, 1942; Chonko et aI., 1974). The abnormalities involve tissues of ectodermal origin particularly the brain, retina, skin and skin appendages (Deming and Harvard, 1970; Golgi, 1961; Charlot-Charles and Jones, 1974; Bissada et aI., 1975). The only previous report of electron microscopic study of the renal lesions of tuberous sclerosis which came to our attention was that of Mori et al. (1971). However, they did not find myofilamentous structures in the tumor cell cytoplasm. They claimed that the tumor cells were not myogenic in ultrastructure but quite similar to a blastic form of Schwann cell. By contrast, in our study although we found a few fibroblastic cells, however, we consider the majority of the tumor cells to be either smooth muscle type or a degenerated form thereof. Smooth muscle cells occurring in renal tumors has been rarely reported. The only previous reports were by Wigger (1969) on fetal hamartoma and by Tannenbaum (197 I) of leimyosarcoma. These cases of leimyosarcomas have many ultrastructural features similar to the present study of angiomyolipoma, such as smooth cells with myofilaments, glycogen granules and basement membranes. Although glycogen stores may be present in the liver, in the skeletal muscle, or small amount in a great many cell types, large amounts of glycogen granules were not found in the typical nontumorous smooth muscle cells (Ishikawa, 1962; Rhodin, 1962). The accumulation of the large amount of glycogen may indicate that the metabolic activity of the smooth muscle was in an abnormal state.
Zusammenfassung Die ultrastrukturelle Untersuchung eines beidseitigen renalen Angiomyolipoms im Falle einer tuberosen Sklerose laJh zwar die Zelltypen unterscheiden: glatte Muskelzellen und
Renal Angiomyolipoma . 4 0 9 Fibroblasten. 1m Tumorgewebe sind weder tubulare noch glomeruHire Strukturelemente zu erkennen. Nach Meinung der Autoren scheint diese Untersuchung zum ersten Mal glatte Muskelzellen bei solchen Nierenaffektionen zu zeigen. Acknowledgment This project supported by VA Research funds, Project No. 8221-011. Technical assistance of Joe Meador and Bettye Stallings is greatly appreciated.
References 1. Berg, ]. W.: Angiolipomyosarcoma of Kidney (Malignant hamartomatous angiolipomyoma) in a case with solitary metastasis from bronchogenic carcinoma. Cancer 8,759-7 63 (1955) 2. Bissada, N. K., White, H. ]., Sun, C. N., Smith, P. L., Barbour, G. L., and Redman, ]. F.: Tuberous sclerosis complex and renal angiomyolipoma. Urology 6, I05-II 3 (1975 ) 3. Charlot-Charles, ]., and Jones, G. W.: Renal angiomyolipoma associated with tuberous sclerosis: Review of the literature. Urology 3, 465-469 (1974) 4. Chonko, A. M., Weiss, S. M., Stein, ]. H., and Ferris, T. F.: Renal involvement in tuberous sclerosis. Amer. ]. Med. 56, I24-132 (1974) 5. Deming, C. L., and Harvard, B. M.: Tuberous sclerosis. In: Campbell, M. F., and Harrison, ]. H. (eds.) Urology, 3rd ed., Vol. 2, p. 943, 952. W. B. Saunders Co., Philadelphia 1970 6. Fischer, W.: Die Nierentumoren bei der tuberosen Hirnsklerose. Beitr. path. Anat. 50,235-282 (19 11 ) 7. Golji, H.: Tuberous sclerosis and renal neoplasms.]. Urol. 85, 919-923 (1961) 8. Gordon jr., M. P., Kimmelstiel, P., and Cabell, C. L.: Leiomyoma of the kidney: Report of a case with review of the literature. ]. Urol. 42, 507-519 (1939) 9. Heckel, N. ]., and Penick, G. D.: A mixed tumor of the kidney: Lipomyohemangioma. ]. Urol. 59, 572-576 (1948) 10. Ishikawa, T.: Fine structure of the human ciliary muscle. Invest. Ophthalmol. I, 587-608 (1962) 11. Lucke, B., and Schlumberger, H. G.: Tumors of the kidney, renal pelvis and ureter. In: Atlas of Tumor Path. Sect. VIII, Fascicle 30, p. 133. Armed Forces Institute of Pathology, Washington D.C. (1957) 12. Mertz, H. 0.: Tuberous sclerosis and renal tumor. Trans. Amer. Ass. Genitourin. Surg. 35,73- 85 (1943) 13. Moolten, S. E.: Hamartial nature of the tuberous sclerosis complex and its bearing on the tumor problem. Arch. Intern. Med. 69, 589-623 (1942) 14. Morgan, G. S., Straumfjord, ]. V., and Hall, E. ].: Angiomyolipoma of the kidney. ]. Urol. 65,525-527 (1951) 15. Mori, M., Ikeda, T., and Onoe, T.: Blastic schwann cells in renal tumor of tuberous sclerosis complex. An electron microscopic study. Acta Path. Jap. 2I, 121-129 (1971) 16. Reynolds, E. S.: The use of lead citrate at high pH as an electronopaque stain in electron microscopy. ]. Cell BioI. I7, 208-212 (1963) 17. Rhodin, ]. A. G.: Fince structure of vascular walls in mammals with special reference to smooth muscle component. Physio!. Rev. 42, Supp!. 5, 48-81 (1962)
410 .
C. N. Sun, H. ]. White, and N. K. Bissada
18. Tannenbaum, M.: Ultrastructural pathology of human renal cell tumors. Path. Annu. 6,249-277 (1971) 19. Tweeddale, D. N., Dawe, C. ]., McDonald, ]. R., and Culp, O. S.: Angiolipoleiomyoma of the kidney; Report of a case with observations on histogenesis. Cancer 8,7 64-77 0 (1955) 20. Wigger, H. ].; Fetal Hamartoma of kidney. A benign, symptomatic, congenital tumor, not a form of Wilms' tumor. Amer.]. Clin. Path. jI, 323-337 (1969) C. N. Sun, Ph.D., Veterans Administration Hospital and University of Arkansas School of Medicine, Little Rock, Arkansas 72206, USA