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Multiple Unilateral Renal Angiomyolipomas with Regional Lymphangioleiomyomatosis
0022-534 7 /89 /1425-1305$02.00/0 JOURNAL OF UROLOGY Copyright© 1989 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Vol. 142, November
THE
Printed in U.S.A.
Case Reports MULTIPLE UNILATERAL RENAL ANGIOMYOLIPOMAS WITH REGIONAL LYMPHANGIOLEIOMYOMATOSIS G. S. McINTOSH, S. HAMILTON DUTOIT, N. V. CHRONOS AND A. V. KAISARY From the Departments of Urology and Histopathology, Royal Free Hospital and School of Medicine, London, England
ABSTRACT
We present an unusual case of multiple unilateral renal angiomyolipomas occurring together with lymphangioleiomyomatosis of the regional lymph nodes. The association of these 2 hamartomatous lesions has been described only rarely but lends support to the concept that they represent a forme fruste of the tuberous sclerosis disease complex. (J. Ural., 142: 1305-1307, 1989) Renal angiomyolipomas are uncommon and, when multiple and bilateral, often are associated with tuberous sclerosis. In patients without tuberous sclerosis the lesions usually are solitary. We report a case of multiple unilateral renal angiomyolipomas associated with another rare condition, namely lymphangioleiomyomatosis in the regional lymph nodes.
were visible only on microscopy, were all angiomyolipomas variably composed of mature fat, smooth muscle and abnormal vessels (fig. 2, B). Grossly, the hilar lymph nodes were partly replaced by white tissue. Histological study showed the typical changes of lym-
CASE REPORT
A 55-year-old previously well woman presented with severe left loin pain a few hours in duration. The pain resolved rapidly with analgesia and anticholinergic antispasmodics. Examination showed tenderness in the left loin but no mass was palpable. There were no other abnormalities on general examination, and in particular the skin and central nervous system were normal. In addition, urinalysis and microscopy of the urine showed no abnormality. Abdominal ultrasound showed a complex, partly cystic, partly solid mass arising from the upper pole of the left kidney. The spleen, pancreas, liver and right kidney were normal. A computerized tomography scan confirmed these findings and indicated the mass to be either a renal carcinoma or hemorrhage into a cyst. An arteriogram of the kidney demonstrated abnormal circulation in the left upper pole consistent with tumor; the right side was normal. The chest x-ray also was normal and there was no evidence of spread of the disease. The patient was post-menopausal, and was receiving cyclic estrogen and progestogen as hormonal replacement therapy. Radical left nephrectomy was uncomplicated; the hilar and para-aortic lymph nodes were removed en bloc. No intraabdominal spread of disease was detected and convalescence was uneventful. The left kidney weighed 180 gm. and measured 14 X 7.5 x 4 cm. The upper pole was replaced by a 4.5 cm. in diameter, partly cystic, hemorrhagic mass. Elsewhere, the substance of the kidney contained numerous yellow and white nodules up to 1 cm. in diameter (fig. 1). Microscopy revealed the main mass to be a partly necrotic, cystic and extensively degenerate angiomyolipoma that extended into the perirenal fat. The lesion was composed of sheets of large abnormal smooth muscle cells with ample, often vacuolated eosinophilic cytoplasm. Many of the cells showed marked nuclear pleomorphism (fig. 2, A). Mitotic figures were found easily and numerous thick-walled, elasticdeficient, abnormal blood vessels were identified. Elsewhere, more typical spindle-shaped smooth muscle cells were seen with foci of mature fat cells. The smaller lesions, many of which Accepted for publication May 17, 1989.
FIG. 1. Cut surface of kidney shows upper pole tumor and some white nodules (arrow).
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MCINTOSH AND ASSOCIATES
review of her and the family history has revealed no evidence of either tuberous sclerosis or disseminated lymphangioleiomyomatosis. DISCUSSION
Fm. 2. A, section from solid portion of main mass shows angiomyolipoma composed of spindle shaped smooth muscle cells with considerable cytological pleomorphism. Part of abnormal, thick-walled blood vessel can be seen to right of field. H & E, reduced from X56. B, section from 1 of numerous small nodules demonstrates angiomyolipoma composed of mature fat, smooth muscle and many abnormal thick-walled blood vessels. H & E, reduced from X56. C, section of hilar lymph node shows lymphangioleiomyomatosis. There is extensive proliferation of cytologically benign, spindle shaped smooth muscle cells within lymphatic sinuses. Similar changes were present in neighboring lymph nodes. H & E, reduced from X56.
phangioleiomyomatosis with proliferation of well differentiated smooth muscle cells within the nodal sinuses and adjacent lymphatic channels (fig. 2, C). The patient remained well 12 months postoperatively and a
Renal angiomyolipomas are benign lesions, generally regarded as hamartomas, that are composed of variable amounts of smooth muscle, blood vessels and mature fat. While the association with tuberous sclerosis is well recognized, they also occur in patients without evidence of this disease. 1 The abnormal blood vessels are deficient in elasticity, thus, predisposing to hemorrhage and accounting for the common presentation with intrarenal or perirenal bleeding. We presume that the initial presentation of our patient was at a time of such bleeding. Multiple small angiomyolipomas, such as those seen in our case, have been described before in patients without tuberous sclerosis but this is unusual. Such patients usually have large solitary tumors. 1 In addition to the presence of multiple unilateral lesions, our case is noteworthy because of its association with lymphangioleiomyomatosis. This rare disease is characterized by a proliferation of smooth muscle within the lymphatics and lymph nodes in various parts of the body, including the lungs, mediastinum and retroperitoneum. 2 It may be localized to 1 area, as in our case, or it may occur in a more extensive form involving large segments of the lymphatic system. It generally is asymptomatic unless there is pulmonary involvement, when the disease may prove fatal. Generally considered a multifocal malformation or hamartoma, the disease is seen exclusively in female patients, usually during the reproductive years. The relationship between lymphangioleiomyomatosis and the tuberous sclerosis complex remains controversial. Some investigator:; regard the former condition as a forme fruste of the latter. 2• 11 Evidence in support of this theory comes from 2 sources: 1) a small number of patients with tuberous sclerosis have pulmonary changes that are indistinguishable histologically from those of lymphangioleiomyomatosis3 and 2) there have been rare case reports describing the occurrence of renal angiomyolipomas with lymphangioleiomyomatosis, although the latter generally has been of the disseminated form with pulmonary involvement. 4 - 6 Our case, in which multiple angiomyolipomas were found together with localized, regional lymph nodal lymphangioleiomyomatosis, lends further support to the close association of these 2 lesions. There was no evidence of tuberous sclerosis in our patient. Recognition of cases with lymphangioleiomyomatosis and angiomyolipomas is important, even if it occurs only rarely, since it should prompt a careful search for evidence of pulmonary involvement. As mentioned previously, this complication potentially is fatal but in the early stages it may possibly be amenable to hormonal therapy. 7 However, the frequency with which lymph nodes will be available for examination in cases of angiomyolipoma is likely to decrease as these lesions are managed increasingly by more conservative means. 8 Our case demonstrates the propensity of angiomyolipomas to mimic malignant tumors clinically and histologically. Cellular atypia, easily identifiable mitotic figures and extracapsular extension, as found in our case, are not uncommon in these lesions and can lead easily to a mistaken diagnosis of carcinoma. REFERENCES 1. Bissada, N. K., White, H.J., Sun, C. N., Smith, P. L., Barbour, G.
L. and Redman, J. F.: Tuberous sclerosis complex and renal angiomyolipoma. Collective review. Urology, 6: 105, 1975. 2. Wolff, M.: Lymphangiomyoma: clinicopathologic study and ultrastructural confirmation of its histogeneis. Cancer, 31: 988, 1973. 3. Valensi, Q. J.: Pulmonary lymphangiomyoma, a probable forme fruste of tuberous sclerosis: a case report and survey of the literature. Amer. Rev. Respir. Dis., 108: 1411, 1973. 4. Vadas, G., Pare, J. A. and Thurlbeck, W. M.: Pulmonary and lymph
MULTIPLE UNILATERAL RENAL ANGIOMYOLIPOMAS WITH LYMPHANGIOLEIOMYOMATOSIS node myomatosis: review of the literature and report of a case. Canad. Med. Ass. J., 96: 420, 1967. 5. Monteforte, W. J., Jr. and Kohnen, P. W.: Angiomyolipomas in a case of lymphangiomyomatosis syndrome: relationships to tuberous sclerosis. Cancer, 34: 317, 1974. 6. Lack, E. E., Dolan, M. F., Finisio, J., Grover, G., Singh, M. and Triche, T. J.: Pulmonary and extrapulmonary lymphangioleiomyomatosis. Report of a case with bilateral renal angiomyoli-
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pomas, multifocal lymphangioleiomyomatosis, and a glial polyp of the endocervix. Amer. J. Surg. Path., 10: 650, 1986. 7. McCarty, K. S., Jr., Mossler, J. A., McLelland, R. and Sieker, H. 0.: Pulmonary lymphangiomyomatosis responsive to progesterone. New Engl. J. Med., 303: 1461, 1980. 8. Oesterling, J.E., Fishman, E. K., Goldman, S. M. and Marshall, F. F.: The management of renal angiomyolipoma. J. Urol., 135: 1121, 1986.
Vol. 142, November
THE
Printed in U.S.A.
Case Reports MULTIPLE UNILATERAL RENAL ANGIOMYOLIPOMAS WITH REGIONAL LYMPHANGIOLEIOMYOMATOSIS G. S. McINTOSH, S. HAMILTON DUTOIT, N. V. CHRONOS AND A. V. KAISARY From the Departments of Urology and Histopathology, Royal Free Hospital and School of Medicine, London, England
ABSTRACT
We present an unusual case of multiple unilateral renal angiomyolipomas occurring together with lymphangioleiomyomatosis of the regional lymph nodes. The association of these 2 hamartomatous lesions has been described only rarely but lends support to the concept that they represent a forme fruste of the tuberous sclerosis disease complex. (J. Ural., 142: 1305-1307, 1989) Renal angiomyolipomas are uncommon and, when multiple and bilateral, often are associated with tuberous sclerosis. In patients without tuberous sclerosis the lesions usually are solitary. We report a case of multiple unilateral renal angiomyolipomas associated with another rare condition, namely lymphangioleiomyomatosis in the regional lymph nodes.
were visible only on microscopy, were all angiomyolipomas variably composed of mature fat, smooth muscle and abnormal vessels (fig. 2, B). Grossly, the hilar lymph nodes were partly replaced by white tissue. Histological study showed the typical changes of lym-
CASE REPORT
A 55-year-old previously well woman presented with severe left loin pain a few hours in duration. The pain resolved rapidly with analgesia and anticholinergic antispasmodics. Examination showed tenderness in the left loin but no mass was palpable. There were no other abnormalities on general examination, and in particular the skin and central nervous system were normal. In addition, urinalysis and microscopy of the urine showed no abnormality. Abdominal ultrasound showed a complex, partly cystic, partly solid mass arising from the upper pole of the left kidney. The spleen, pancreas, liver and right kidney were normal. A computerized tomography scan confirmed these findings and indicated the mass to be either a renal carcinoma or hemorrhage into a cyst. An arteriogram of the kidney demonstrated abnormal circulation in the left upper pole consistent with tumor; the right side was normal. The chest x-ray also was normal and there was no evidence of spread of the disease. The patient was post-menopausal, and was receiving cyclic estrogen and progestogen as hormonal replacement therapy. Radical left nephrectomy was uncomplicated; the hilar and para-aortic lymph nodes were removed en bloc. No intraabdominal spread of disease was detected and convalescence was uneventful. The left kidney weighed 180 gm. and measured 14 X 7.5 x 4 cm. The upper pole was replaced by a 4.5 cm. in diameter, partly cystic, hemorrhagic mass. Elsewhere, the substance of the kidney contained numerous yellow and white nodules up to 1 cm. in diameter (fig. 1). Microscopy revealed the main mass to be a partly necrotic, cystic and extensively degenerate angiomyolipoma that extended into the perirenal fat. The lesion was composed of sheets of large abnormal smooth muscle cells with ample, often vacuolated eosinophilic cytoplasm. Many of the cells showed marked nuclear pleomorphism (fig. 2, A). Mitotic figures were found easily and numerous thick-walled, elasticdeficient, abnormal blood vessels were identified. Elsewhere, more typical spindle-shaped smooth muscle cells were seen with foci of mature fat cells. The smaller lesions, many of which Accepted for publication May 17, 1989.
FIG. 1. Cut surface of kidney shows upper pole tumor and some white nodules (arrow).
1305
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MCINTOSH AND ASSOCIATES
review of her and the family history has revealed no evidence of either tuberous sclerosis or disseminated lymphangioleiomyomatosis. DISCUSSION
Fm. 2. A, section from solid portion of main mass shows angiomyolipoma composed of spindle shaped smooth muscle cells with considerable cytological pleomorphism. Part of abnormal, thick-walled blood vessel can be seen to right of field. H & E, reduced from X56. B, section from 1 of numerous small nodules demonstrates angiomyolipoma composed of mature fat, smooth muscle and many abnormal thick-walled blood vessels. H & E, reduced from X56. C, section of hilar lymph node shows lymphangioleiomyomatosis. There is extensive proliferation of cytologically benign, spindle shaped smooth muscle cells within lymphatic sinuses. Similar changes were present in neighboring lymph nodes. H & E, reduced from X56.
phangioleiomyomatosis with proliferation of well differentiated smooth muscle cells within the nodal sinuses and adjacent lymphatic channels (fig. 2, C). The patient remained well 12 months postoperatively and a
Renal angiomyolipomas are benign lesions, generally regarded as hamartomas, that are composed of variable amounts of smooth muscle, blood vessels and mature fat. While the association with tuberous sclerosis is well recognized, they also occur in patients without evidence of this disease. 1 The abnormal blood vessels are deficient in elasticity, thus, predisposing to hemorrhage and accounting for the common presentation with intrarenal or perirenal bleeding. We presume that the initial presentation of our patient was at a time of such bleeding. Multiple small angiomyolipomas, such as those seen in our case, have been described before in patients without tuberous sclerosis but this is unusual. Such patients usually have large solitary tumors. 1 In addition to the presence of multiple unilateral lesions, our case is noteworthy because of its association with lymphangioleiomyomatosis. This rare disease is characterized by a proliferation of smooth muscle within the lymphatics and lymph nodes in various parts of the body, including the lungs, mediastinum and retroperitoneum. 2 It may be localized to 1 area, as in our case, or it may occur in a more extensive form involving large segments of the lymphatic system. It generally is asymptomatic unless there is pulmonary involvement, when the disease may prove fatal. Generally considered a multifocal malformation or hamartoma, the disease is seen exclusively in female patients, usually during the reproductive years. The relationship between lymphangioleiomyomatosis and the tuberous sclerosis complex remains controversial. Some investigator:; regard the former condition as a forme fruste of the latter. 2• 11 Evidence in support of this theory comes from 2 sources: 1) a small number of patients with tuberous sclerosis have pulmonary changes that are indistinguishable histologically from those of lymphangioleiomyomatosis3 and 2) there have been rare case reports describing the occurrence of renal angiomyolipomas with lymphangioleiomyomatosis, although the latter generally has been of the disseminated form with pulmonary involvement. 4 - 6 Our case, in which multiple angiomyolipomas were found together with localized, regional lymph nodal lymphangioleiomyomatosis, lends further support to the close association of these 2 lesions. There was no evidence of tuberous sclerosis in our patient. Recognition of cases with lymphangioleiomyomatosis and angiomyolipomas is important, even if it occurs only rarely, since it should prompt a careful search for evidence of pulmonary involvement. As mentioned previously, this complication potentially is fatal but in the early stages it may possibly be amenable to hormonal therapy. 7 However, the frequency with which lymph nodes will be available for examination in cases of angiomyolipoma is likely to decrease as these lesions are managed increasingly by more conservative means. 8 Our case demonstrates the propensity of angiomyolipomas to mimic malignant tumors clinically and histologically. Cellular atypia, easily identifiable mitotic figures and extracapsular extension, as found in our case, are not uncommon in these lesions and can lead easily to a mistaken diagnosis of carcinoma. REFERENCES 1. Bissada, N. K., White, H.J., Sun, C. N., Smith, P. L., Barbour, G.
L. and Redman, J. F.: Tuberous sclerosis complex and renal angiomyolipoma. Collective review. Urology, 6: 105, 1975. 2. Wolff, M.: Lymphangiomyoma: clinicopathologic study and ultrastructural confirmation of its histogeneis. Cancer, 31: 988, 1973. 3. Valensi, Q. J.: Pulmonary lymphangiomyoma, a probable forme fruste of tuberous sclerosis: a case report and survey of the literature. Amer. Rev. Respir. Dis., 108: 1411, 1973. 4. Vadas, G., Pare, J. A. and Thurlbeck, W. M.: Pulmonary and lymph
MULTIPLE UNILATERAL RENAL ANGIOMYOLIPOMAS WITH LYMPHANGIOLEIOMYOMATOSIS node myomatosis: review of the literature and report of a case. Canad. Med. Ass. J., 96: 420, 1967. 5. Monteforte, W. J., Jr. and Kohnen, P. W.: Angiomyolipomas in a case of lymphangiomyomatosis syndrome: relationships to tuberous sclerosis. Cancer, 34: 317, 1974. 6. Lack, E. E., Dolan, M. F., Finisio, J., Grover, G., Singh, M. and Triche, T. J.: Pulmonary and extrapulmonary lymphangioleiomyomatosis. Report of a case with bilateral renal angiomyoli-
1307
pomas, multifocal lymphangioleiomyomatosis, and a glial polyp of the endocervix. Amer. J. Surg. Path., 10: 650, 1986. 7. McCarty, K. S., Jr., Mossler, J. A., McLelland, R. and Sieker, H. 0.: Pulmonary lymphangiomyomatosis responsive to progesterone. New Engl. J. Med., 303: 1461, 1980. 8. Oesterling, J.E., Fishman, E. K., Goldman, S. M. and Marshall, F. F.: The management of renal angiomyolipoma. J. Urol., 135: 1121, 1986.