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Ollier disease (enchondromatosis) associated with ovarian juvenile granulosa cell tumor and precocious pseudopuberty
Volume 108 Number 6
Clinical and laboratory observations
4. Takayanagi M, Ohtake A, Ogura N, et al. A female case of ornithine transcarbamylase deficiency with marked computed tomographic abnormalities of the brain. Brain Dev 1984; 6:58. 5. Krieger I, Snodgrass P J, Roskamp J. Atypical clinical course of ornithine transcarbamylase deficiency due to a new mutant. J Clin Endocrinol Metab 1979;48:388. 6. Bruton C J, Corsellis JAN, Russel A. Hereditary hyperammonemia. Brain 1970;93:423. 7. Kornfeld M, Woodfin BM, Papile L, et al. Neuropathology of ornithine earbamyl transferase deficiency. Acta Neuropathol 1985;65:261. 8. Campbell AGM, Rosenberg LE, Snodgrass P J, Nuzum CT. Ornithine transearbamylase deficiency: a cause of lethal neonatal hyperammonemia in males. N Engl J Med 1973;288:1. 9. Janzer RC, Friede RL. Perisulcal infarcts: lesions caused by
10. 11.
12.
13.
14.
945
hypotension during increased intracranial pressure. Ann Neurol 1979;6:399. Martin JJ, Farriaux JP, Jonghe PD. Neuropathology of citrullinemia. Aeta Neuropathol 1982;56:303. Amir J, Alpert G, Statter M, et al. lntracranial hemorrhage in siblings and ornithine transcarbamylase deficiency. Acta Pediatr Scand 1982;71:671. Voorhies TM, Ehrlich ME, Duffy TE, et al. Acute hyperammonemia in the young primate: physiologic and neuropathologic correlates. Pediatr Res 1983;17:970. Tallan HH, Schaffner F, Taffet SL, et al. Ornithine carbamoyltransferase deficiency in an adult male patient: significance of hepatic ultrastructure in clinical diagnosis. Pediatrics 1983;71:224. Finlayson MH, Superville B. Distribution of cerebral lesions in acquired hepatocerebral degeneration. Brain 198l; 104:79.
Oilier disease (enchondromatosis) associated with ovarian juvenile granulosa cell tumor and
precocious pseudopuberty Rosalind M. Vaz, M.D., and Charles Turner, M.D. From the Brenner Center for Adolescent Medicine, Department of Pediatrics, and the Department of Surgery, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina
\
Ollier disease (enchodrorn'atosis) affects the m e t a p h y s e a l ends of t u b u l a r bones, man~ifests itself prepubertally in a wide variety of skeletal deformities, and is considered a n o n h e r e d i t a r y mesodermal dysplasia. 1 It has been distinguished from Maffucci syndrome, a similar disorder including multiple enchondromas, h e m a n g i o m a s , and other m e s e n c h y m a l tumors. 1 A l t h o u g h there have been a few instances of familial Ollier disease, most cases of Ollier disease and of Maffucei syndrome have been sporadieY T h e coexistence of m e s e n e h y m a l ovarian tumors in patients with Oilier disease and Maffueci s y n d r o m e is more frequent t h a n expected by mere chance, 24 a n d juvenile granulosa cell t u m o r has been described in a patient with Oilier disease? W e describe a n o t h e r such patient with precocious pseudopuberty.
Submitted for publication Sept. 19, 1985; accepted Dec. 4, 1985. Reprint requests: Rosalind M. Vaz, M.D., Assistant Professor of Pediatrics, Department of Pediatrics, Bowman Gray School of Medicine, 300 S. Hawthorne Road, Winston-Salem, NC 27103.
CASE REPORT
This 8y2-Year-old white girl with Oilier disease was seen at North Carolina Baptist Hospital for evaluation of vaginal bleeding. In the 2 years prior to admission, she had grown 15.2 cm and gained 19.1 kg. Although unsure about the actual progression of pubertal events, the mother had noted the onset of bilateral breast enlargement 9 months before the pubic hair development 6 months before admission. Two and one-half months before admission, the patient had a 3-week episode of vaginal bleeding, causing her hematocrit to decrease to 22%. She was examined by a gynecologist, and began treatment with levonorgestrel-ethinyl estradiol (Triphasil) and ferrous sulfate. The vaginal bleeding stopped, and hematocrit rose to 34.1%. She was midway through the third cycle of levonorgestrel-ethinyl estradiol therapy at the time of admission. Oilier disease bad been diagnosed when the patient was 18 months of age, when a slight leg length discrepancy and "crooked fingers" on the right hand were noted. Two and a half years before admission, her right leg was amputated below the knee, and a right middle finger osteotomy performed. Her weight was 40.9 kg (>95th percentile), height 138.5 cm (90th to 95th percentile), and blood pressure 100/64 mm Hg. Breast development was at Tanner stage Ill, with hyperpigmentation of the areolae. Pubic hair was at Tanner Stage II1, and she had sparse axillary hair. Examination of the external genitalia
9 46
Clinical and laboratory observations
revealed a pink vaginal mucosa with copious mucous discharge. The clitoris was not enlarged. The cervical os was tightly closed. Because of patient discomfort, only a single finger himanual examination and rectal examination could be done. The uterus felt slightly enlarged, the left ovary seemed of normal size, an,d the right ovary was not well defined, although no definite masses were palpable. Laboratory values included hemoglobin 12.7 gm/dl, hematocrit 37.7%, and white blood cell count and differential in the normal range. Routine urinalysis gave normal results. Plasma estradiol concentration was <20 pg/ml (normal prepubertal <10 pg/ml), 17 hydroxyprogesterone 0.6 ng/ml, testosterone 36 ng/dl, and dehydroepiandrosterone sulfate 1505 ng/ml. Human chorionic gonadotropin concentration was <5 mlU/ml, luteinizing hormone <5 mU/ml, follicle-stimulating hormone 3 mU/ml, prolactin 10 ng/ml, and c~-fetoprotein 0 ng/ml. A vaginal smear revealed 0% of the cells to be basal, 92% intermediate, and 8% superficial. Roentgenograms of the chest and skull were normal. Bone age was 11 years. Ultrasonography of the pelvis revealed a slightly enlarged uterus. The right ovary was thought to be solid and markedly enlarged, measuring 5.66 cm. The left ovary was not enlarged, but contained a small follicular cyst. Exploratory laparotomy revealed a 6 • 4 • 3.5 cm right ovarian mass; the left ovary was of normal size. Right salpingo-oophereetomy was performed and a wedge biopsy specimen of the left ovary obtained. The right ovary weighed 56 gm; it was solid and had a smooth capsule. On sect.ioning, the ovarian parenehyma had several ill-defined nodules of tan papillary tissue ranging in size from 0.5 to 2.0 cm in greatest dimension. Between the nodules the tissue was yellow and extended into the surrounding pink-tan soft parenchyma. The fallopian tube had several clear fluid-filled cysts 0.2 to 0.3 cm in diameter. On histologic examination, the cortex was intact, with no evidence of invasion of the capsule nor any vascular involvement. There was some cytologic atypia and mitotic activity. The tubular pattern was consistent with juvenile granulosa cell tumor. The initial vaginal bleeding that started after withdrawal of the hormonal therapy stopped 3 days postoperatively. There has been no farther vaginal bleeding or discharge. On follow-up 7 weeks postoperatively, there was some regression in the size of the breasts and decrease in pigmentation of the areolae. Serum estradiol concentration 19 weeks postoperatively was <10 pg/ ml. DISCUSSION The clinical history and radiologic and histologic findings in our patient support the diagnosis of Ollier disease. Roentgenograms and active enchondromas were submitted to the Armed Forces Institute of Pathology, where the diagnosis was confirmed. In addition, our patient was found to have pseudoprecocious puberty secondary to a juvenile granulosa cell tumor of the ovary. Granulosa cell tumors of the ovary are uncommon in childhood; only 5% of all such tumors occur before the age of normal puberty, and 80% occur in women older than 40 years. 5 The histologic features of granulosa cell tumors in
The Journal of Pediatrics June 1986
the first three decades of life are sufficiently distinctive from those in older women that they have been called juvenile granulosa cell tumors? The tumor in our patient caused precocious sexual development manifested by breast changes and pubic hair, premature onset of menses, and the presence of a highly estrogenized vaginal mucosa. Because autonomous estrogen secretion is thought to cause pseudoprecoeity, we expected to find a much higher serum level of estradiol. However, tow to normal levels have been reported in patients with juvenile granulosa cell tumor and pseudoprecocity, causing one author to postulate that the quantity of estrogen secreted by the tumor may fluctuate. 6 The decrease in breast size and pigmentation of the areola in our patient postoperatively, together with the cessation of vaginal bleeding and vaginal discharge, support the granulosa cell tumor as the cause of the precocious pseudopuberty. Fortunately, the tumor was confined to one ovary, so the prognosis is excellent. Death resulting from recurrences has been described, however, even in patients with stage I juvenile granulosa cell tumor. 7 Patients with multiple enchondromas are at higher risk for secondary malignant transformation, usually to chondrosarcoma, than are patients with a solitary enchondroma. The association of a mesenchymal ovarian tumor, specifically juvenile granulosa cell tumor, has been previously reported with enchondromatosis. 2 Another patient with Ollier disease with sexual precocity reportedly had a thecoma? Although the microscopic appearance of this tumor was not illustrated, Young and Scully 9 later indicated that its description was suggestive of a juvenile granulosa cell tumor and made mention of a second patient with Ollier disease with co-existent juvenile granulosa cell tumor. The first example of an ovarian tumor of mesodermal origin occurring in a patient with Maffucci syndrome was reported by Kuzma and King? Lewis and Ketcham 4 reviewed the slides from this patient and interpreted them as charae~feristic of juvenile granulosa cell tumor, and subsequently reported a second example of a granulosa cell tumor occurring in a patient with Maffucci syndrome. The association of rare ovarian tumors with precocious pseudopuberty has been previously made in two girls with Peutz-Jeghers syndrome, which like Maffucci syndrome is characterized by hamartomatous changes? ~ The first patient had a granulosa-theca cell tumor, the second a sex cord tumor with annular tubules. ~~ Pediatricians should be alert to the possible development of juvenile granulosa cell tumor of the ovary in patients with Ollier disease. The association of this additional mesenchymal tumor raises the interesting question of whether Ollier disease is in fact distinct from Maffucci syndrome, in which a variety of mesenchymal tumors have been described. Perhaps they are both part of a spectrum
Volume 108 Number 6
of mesodermal dysplasia in which t h e expression of specific m e s o d e r m a l features is modified in the individual patient by the presence of as yet unknown enviromental or genetic factors. REFERENCES
1. Horton WA. Abnormalities of bone structure. In: Emery A, Rimoin D, eds. Principles and practice of medical genetics. New York: Churchill Livingstone, 1983. 2. Tamimi HK, Bolen JW. Enchondromatosis (Ollier's disease) and ovarian juvenile granulosa cell tumor. ~Cancer 1984;53:1605-1608. 3. Kuzma JF, King JM. Dyschondroplasia with hemangiomatosis (Maffucci's syndrome) and teratoid tumor of the ovary. Arch Pathol 1948;46:74-82. 4. Lewis R J, Ketcham AS. Maffucci's syndrome: functional and
Clinical and laboratory observations
5.
6.
7. .8. 9. 10.
947
neoplastic significance. Case report and review of the literature. J Bone Joint Surg 1973;55-A:1465-79. Scully RE. Sex cord-stromal tumors. In: Blaustein A, ed. Pathology of the female genital tract. New York: SpringerVerlag, 1977. Eberlein WR, Bongiovanni AM, Jones IT, Yakovac WC. Ovarian tumors and cysts associated with sexual precocity. J P~DIATR 1960;57:484-497. Young RH, Dickersin GR, Scully RE. Juvenile granulosa cell tumor of the ovary. Am J Surg Pathol 1984;8:575-596. Grenet P, Badoual J, Gallet J-P, Lange C. Dyschondroplasie et tumeur de l'ovaire. Ann Pediatr (Paris) 1972;19:759-64. Young RH, Scully RE, Ovarian sex cord-stromal tumors: recent progress, lnt J Gynecol Pathol 1982;1:101-23. Solh HM, Azoury RS, Najjar SS. Peutz-Jeghers syndrome associated with precocious puberty, J PEDIATR 1983;103:593597.
Pheochromocytoma and multiple intracerebral aneurysms Trevor G. DeSouza, M.B., Ch.B., Lee Berlad, M.D., Kenneth Shapiro, M.D., Christine Walsh, M.D., Paul Saenger, M.D., and Shlomo Shinnar, M.D., Ph.D. From the Departments of Neurology, Neurosurgery, and Pediatrics Montefiore Medical Center-Albert Einstein College of Medicine, Bronx, New York
A n e u r y s m s in children are u n c o m m o n , and approximately 50% are associated with other anomalies. ~ T h e y usually form as a result of the interplay between h e m o d y n a m i c factors and structural weaknesses at apexes of arterial bifurcations. 2 W e describe a child who had a s u b a r a c h n o i d h e m o r r h a g e a n d evidence of long-standing hypertension caused by a pheochromocytoma. CASE REPORT A 13-year-old black male, while swimming, had the acute onset of severe frontal headache, neck pain, and photophobia, and later of nausea. He subsequently became lethargic and febrile, and sought medical attention 1 week after the initial episode. Past medical history was unremarkable except for three episodes of epistaxis and intermittent frontal headaches during the past year. General physical examination showed a thin, lethargic black
Supported in part by a Teacher-lnvestigator Development Award (1 K07 NS00930) from the National Institute of Neurological and Communicative Disorders and Stroke (S.S.). Submitted for publication Nov. 1, 1985; accepted Jan. 2, 1986. Reprint requests: Shlomo Shinnar, M.D., Ph.D., Division of Pediatric Neurology, VCP-207, Montefiore Medical Center, 111 E. 210th St., Bronx, NY 10467.
male arousable to verbal stimuli. Blood pressure was 180/110 mm Hg, pulse 120 beats per minute, and temperature 39.5 ~ C. Marked nuchal rigidity was observed. No cranial or abdominal bruits were heard. Cardiac examination revealed a grade 2 to 6 systolic ejection murmur at the left sternal border. The cardiac impulse and first and second heart sounds were normal. No abdominal masses were palpable. He was lethargic, and had bilateral papilledema with hard exudates and a left lateral rectus palsy. Computed tomographic scan of the head demonstrated blood in the anterior interhemispheric fissure and hydrocephalus, but no focal parenchymal lesions. At lumbar puncture the opening pressure was 34 cm water. The fluid was xanthochromic with RBC count 5000//zl and WBC count 2/uJ; the protein concentration was 25 mg/dl, and glucose concentration was 84 mg/dl. A diagnosis of subarachnoid hemorrhage was made, and aminocaproic acid was administered. Hypertension was initially treated with hydralazine. The patient's hospital course was complicated by fluctuating mental status and recurrent transient neurologic deficits. Although normally alert, he would experience periods of lethargy and diaphoresis lasting 10 to 30 minutes. During these episodes a right hemiparesis and either left or right facial weakness were also present. The transient motor deficits persisted for several hours after the resolution of the lethargy. These symptoms were attributed to vasospasm and hydrocephalus, both of which were radiologically confirmed. They were treated with hydration and a temporary ventriculostomy to relieve the
Clinical and laboratory observations
4. Takayanagi M, Ohtake A, Ogura N, et al. A female case of ornithine transcarbamylase deficiency with marked computed tomographic abnormalities of the brain. Brain Dev 1984; 6:58. 5. Krieger I, Snodgrass P J, Roskamp J. Atypical clinical course of ornithine transcarbamylase deficiency due to a new mutant. J Clin Endocrinol Metab 1979;48:388. 6. Bruton C J, Corsellis JAN, Russel A. Hereditary hyperammonemia. Brain 1970;93:423. 7. Kornfeld M, Woodfin BM, Papile L, et al. Neuropathology of ornithine earbamyl transferase deficiency. Acta Neuropathol 1985;65:261. 8. Campbell AGM, Rosenberg LE, Snodgrass P J, Nuzum CT. Ornithine transearbamylase deficiency: a cause of lethal neonatal hyperammonemia in males. N Engl J Med 1973;288:1. 9. Janzer RC, Friede RL. Perisulcal infarcts: lesions caused by
10. 11.
12.
13.
14.
945
hypotension during increased intracranial pressure. Ann Neurol 1979;6:399. Martin JJ, Farriaux JP, Jonghe PD. Neuropathology of citrullinemia. Aeta Neuropathol 1982;56:303. Amir J, Alpert G, Statter M, et al. lntracranial hemorrhage in siblings and ornithine transcarbamylase deficiency. Acta Pediatr Scand 1982;71:671. Voorhies TM, Ehrlich ME, Duffy TE, et al. Acute hyperammonemia in the young primate: physiologic and neuropathologic correlates. Pediatr Res 1983;17:970. Tallan HH, Schaffner F, Taffet SL, et al. Ornithine carbamoyltransferase deficiency in an adult male patient: significance of hepatic ultrastructure in clinical diagnosis. Pediatrics 1983;71:224. Finlayson MH, Superville B. Distribution of cerebral lesions in acquired hepatocerebral degeneration. Brain 198l; 104:79.
Oilier disease (enchondromatosis) associated with ovarian juvenile granulosa cell tumor and
precocious pseudopuberty Rosalind M. Vaz, M.D., and Charles Turner, M.D. From the Brenner Center for Adolescent Medicine, Department of Pediatrics, and the Department of Surgery, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina
\
Ollier disease (enchodrorn'atosis) affects the m e t a p h y s e a l ends of t u b u l a r bones, man~ifests itself prepubertally in a wide variety of skeletal deformities, and is considered a n o n h e r e d i t a r y mesodermal dysplasia. 1 It has been distinguished from Maffucci syndrome, a similar disorder including multiple enchondromas, h e m a n g i o m a s , and other m e s e n c h y m a l tumors. 1 A l t h o u g h there have been a few instances of familial Ollier disease, most cases of Ollier disease and of Maffucei syndrome have been sporadieY T h e coexistence of m e s e n e h y m a l ovarian tumors in patients with Oilier disease and Maffueci s y n d r o m e is more frequent t h a n expected by mere chance, 24 a n d juvenile granulosa cell t u m o r has been described in a patient with Oilier disease? W e describe a n o t h e r such patient with precocious pseudopuberty.
Submitted for publication Sept. 19, 1985; accepted Dec. 4, 1985. Reprint requests: Rosalind M. Vaz, M.D., Assistant Professor of Pediatrics, Department of Pediatrics, Bowman Gray School of Medicine, 300 S. Hawthorne Road, Winston-Salem, NC 27103.
CASE REPORT
This 8y2-Year-old white girl with Oilier disease was seen at North Carolina Baptist Hospital for evaluation of vaginal bleeding. In the 2 years prior to admission, she had grown 15.2 cm and gained 19.1 kg. Although unsure about the actual progression of pubertal events, the mother had noted the onset of bilateral breast enlargement 9 months before the pubic hair development 6 months before admission. Two and one-half months before admission, the patient had a 3-week episode of vaginal bleeding, causing her hematocrit to decrease to 22%. She was examined by a gynecologist, and began treatment with levonorgestrel-ethinyl estradiol (Triphasil) and ferrous sulfate. The vaginal bleeding stopped, and hematocrit rose to 34.1%. She was midway through the third cycle of levonorgestrel-ethinyl estradiol therapy at the time of admission. Oilier disease bad been diagnosed when the patient was 18 months of age, when a slight leg length discrepancy and "crooked fingers" on the right hand were noted. Two and a half years before admission, her right leg was amputated below the knee, and a right middle finger osteotomy performed. Her weight was 40.9 kg (>95th percentile), height 138.5 cm (90th to 95th percentile), and blood pressure 100/64 mm Hg. Breast development was at Tanner stage Ill, with hyperpigmentation of the areolae. Pubic hair was at Tanner Stage II1, and she had sparse axillary hair. Examination of the external genitalia
9 46
Clinical and laboratory observations
revealed a pink vaginal mucosa with copious mucous discharge. The clitoris was not enlarged. The cervical os was tightly closed. Because of patient discomfort, only a single finger himanual examination and rectal examination could be done. The uterus felt slightly enlarged, the left ovary seemed of normal size, an,d the right ovary was not well defined, although no definite masses were palpable. Laboratory values included hemoglobin 12.7 gm/dl, hematocrit 37.7%, and white blood cell count and differential in the normal range. Routine urinalysis gave normal results. Plasma estradiol concentration was <20 pg/ml (normal prepubertal <10 pg/ml), 17 hydroxyprogesterone 0.6 ng/ml, testosterone 36 ng/dl, and dehydroepiandrosterone sulfate 1505 ng/ml. Human chorionic gonadotropin concentration was <5 mlU/ml, luteinizing hormone <5 mU/ml, follicle-stimulating hormone 3 mU/ml, prolactin 10 ng/ml, and c~-fetoprotein 0 ng/ml. A vaginal smear revealed 0% of the cells to be basal, 92% intermediate, and 8% superficial. Roentgenograms of the chest and skull were normal. Bone age was 11 years. Ultrasonography of the pelvis revealed a slightly enlarged uterus. The right ovary was thought to be solid and markedly enlarged, measuring 5.66 cm. The left ovary was not enlarged, but contained a small follicular cyst. Exploratory laparotomy revealed a 6 • 4 • 3.5 cm right ovarian mass; the left ovary was of normal size. Right salpingo-oophereetomy was performed and a wedge biopsy specimen of the left ovary obtained. The right ovary weighed 56 gm; it was solid and had a smooth capsule. On sect.ioning, the ovarian parenehyma had several ill-defined nodules of tan papillary tissue ranging in size from 0.5 to 2.0 cm in greatest dimension. Between the nodules the tissue was yellow and extended into the surrounding pink-tan soft parenchyma. The fallopian tube had several clear fluid-filled cysts 0.2 to 0.3 cm in diameter. On histologic examination, the cortex was intact, with no evidence of invasion of the capsule nor any vascular involvement. There was some cytologic atypia and mitotic activity. The tubular pattern was consistent with juvenile granulosa cell tumor. The initial vaginal bleeding that started after withdrawal of the hormonal therapy stopped 3 days postoperatively. There has been no farther vaginal bleeding or discharge. On follow-up 7 weeks postoperatively, there was some regression in the size of the breasts and decrease in pigmentation of the areolae. Serum estradiol concentration 19 weeks postoperatively was <10 pg/ ml. DISCUSSION The clinical history and radiologic and histologic findings in our patient support the diagnosis of Ollier disease. Roentgenograms and active enchondromas were submitted to the Armed Forces Institute of Pathology, where the diagnosis was confirmed. In addition, our patient was found to have pseudoprecocious puberty secondary to a juvenile granulosa cell tumor of the ovary. Granulosa cell tumors of the ovary are uncommon in childhood; only 5% of all such tumors occur before the age of normal puberty, and 80% occur in women older than 40 years. 5 The histologic features of granulosa cell tumors in
The Journal of Pediatrics June 1986
the first three decades of life are sufficiently distinctive from those in older women that they have been called juvenile granulosa cell tumors? The tumor in our patient caused precocious sexual development manifested by breast changes and pubic hair, premature onset of menses, and the presence of a highly estrogenized vaginal mucosa. Because autonomous estrogen secretion is thought to cause pseudoprecoeity, we expected to find a much higher serum level of estradiol. However, tow to normal levels have been reported in patients with juvenile granulosa cell tumor and pseudoprecocity, causing one author to postulate that the quantity of estrogen secreted by the tumor may fluctuate. 6 The decrease in breast size and pigmentation of the areola in our patient postoperatively, together with the cessation of vaginal bleeding and vaginal discharge, support the granulosa cell tumor as the cause of the precocious pseudopuberty. Fortunately, the tumor was confined to one ovary, so the prognosis is excellent. Death resulting from recurrences has been described, however, even in patients with stage I juvenile granulosa cell tumor. 7 Patients with multiple enchondromas are at higher risk for secondary malignant transformation, usually to chondrosarcoma, than are patients with a solitary enchondroma. The association of a mesenchymal ovarian tumor, specifically juvenile granulosa cell tumor, has been previously reported with enchondromatosis. 2 Another patient with Ollier disease with sexual precocity reportedly had a thecoma? Although the microscopic appearance of this tumor was not illustrated, Young and Scully 9 later indicated that its description was suggestive of a juvenile granulosa cell tumor and made mention of a second patient with Ollier disease with co-existent juvenile granulosa cell tumor. The first example of an ovarian tumor of mesodermal origin occurring in a patient with Maffucci syndrome was reported by Kuzma and King? Lewis and Ketcham 4 reviewed the slides from this patient and interpreted them as charae~feristic of juvenile granulosa cell tumor, and subsequently reported a second example of a granulosa cell tumor occurring in a patient with Maffucci syndrome. The association of rare ovarian tumors with precocious pseudopuberty has been previously made in two girls with Peutz-Jeghers syndrome, which like Maffucci syndrome is characterized by hamartomatous changes? ~ The first patient had a granulosa-theca cell tumor, the second a sex cord tumor with annular tubules. ~~ Pediatricians should be alert to the possible development of juvenile granulosa cell tumor of the ovary in patients with Ollier disease. The association of this additional mesenchymal tumor raises the interesting question of whether Ollier disease is in fact distinct from Maffucci syndrome, in which a variety of mesenchymal tumors have been described. Perhaps they are both part of a spectrum
Volume 108 Number 6
of mesodermal dysplasia in which t h e expression of specific m e s o d e r m a l features is modified in the individual patient by the presence of as yet unknown enviromental or genetic factors. REFERENCES
1. Horton WA. Abnormalities of bone structure. In: Emery A, Rimoin D, eds. Principles and practice of medical genetics. New York: Churchill Livingstone, 1983. 2. Tamimi HK, Bolen JW. Enchondromatosis (Ollier's disease) and ovarian juvenile granulosa cell tumor. ~Cancer 1984;53:1605-1608. 3. Kuzma JF, King JM. Dyschondroplasia with hemangiomatosis (Maffucci's syndrome) and teratoid tumor of the ovary. Arch Pathol 1948;46:74-82. 4. Lewis R J, Ketcham AS. Maffucci's syndrome: functional and
Clinical and laboratory observations
5.
6.
7. .8. 9. 10.
947
neoplastic significance. Case report and review of the literature. J Bone Joint Surg 1973;55-A:1465-79. Scully RE. Sex cord-stromal tumors. In: Blaustein A, ed. Pathology of the female genital tract. New York: SpringerVerlag, 1977. Eberlein WR, Bongiovanni AM, Jones IT, Yakovac WC. Ovarian tumors and cysts associated with sexual precocity. J P~DIATR 1960;57:484-497. Young RH, Dickersin GR, Scully RE. Juvenile granulosa cell tumor of the ovary. Am J Surg Pathol 1984;8:575-596. Grenet P, Badoual J, Gallet J-P, Lange C. Dyschondroplasie et tumeur de l'ovaire. Ann Pediatr (Paris) 1972;19:759-64. Young RH, Scully RE, Ovarian sex cord-stromal tumors: recent progress, lnt J Gynecol Pathol 1982;1:101-23. Solh HM, Azoury RS, Najjar SS. Peutz-Jeghers syndrome associated with precocious puberty, J PEDIATR 1983;103:593597.
Pheochromocytoma and multiple intracerebral aneurysms Trevor G. DeSouza, M.B., Ch.B., Lee Berlad, M.D., Kenneth Shapiro, M.D., Christine Walsh, M.D., Paul Saenger, M.D., and Shlomo Shinnar, M.D., Ph.D. From the Departments of Neurology, Neurosurgery, and Pediatrics Montefiore Medical Center-Albert Einstein College of Medicine, Bronx, New York
A n e u r y s m s in children are u n c o m m o n , and approximately 50% are associated with other anomalies. ~ T h e y usually form as a result of the interplay between h e m o d y n a m i c factors and structural weaknesses at apexes of arterial bifurcations. 2 W e describe a child who had a s u b a r a c h n o i d h e m o r r h a g e a n d evidence of long-standing hypertension caused by a pheochromocytoma. CASE REPORT A 13-year-old black male, while swimming, had the acute onset of severe frontal headache, neck pain, and photophobia, and later of nausea. He subsequently became lethargic and febrile, and sought medical attention 1 week after the initial episode. Past medical history was unremarkable except for three episodes of epistaxis and intermittent frontal headaches during the past year. General physical examination showed a thin, lethargic black
Supported in part by a Teacher-lnvestigator Development Award (1 K07 NS00930) from the National Institute of Neurological and Communicative Disorders and Stroke (S.S.). Submitted for publication Nov. 1, 1985; accepted Jan. 2, 1986. Reprint requests: Shlomo Shinnar, M.D., Ph.D., Division of Pediatric Neurology, VCP-207, Montefiore Medical Center, 111 E. 210th St., Bronx, NY 10467.
male arousable to verbal stimuli. Blood pressure was 180/110 mm Hg, pulse 120 beats per minute, and temperature 39.5 ~ C. Marked nuchal rigidity was observed. No cranial or abdominal bruits were heard. Cardiac examination revealed a grade 2 to 6 systolic ejection murmur at the left sternal border. The cardiac impulse and first and second heart sounds were normal. No abdominal masses were palpable. He was lethargic, and had bilateral papilledema with hard exudates and a left lateral rectus palsy. Computed tomographic scan of the head demonstrated blood in the anterior interhemispheric fissure and hydrocephalus, but no focal parenchymal lesions. At lumbar puncture the opening pressure was 34 cm water. The fluid was xanthochromic with RBC count 5000//zl and WBC count 2/uJ; the protein concentration was 25 mg/dl, and glucose concentration was 84 mg/dl. A diagnosis of subarachnoid hemorrhage was made, and aminocaproic acid was administered. Hypertension was initially treated with hydralazine. The patient's hospital course was complicated by fluctuating mental status and recurrent transient neurologic deficits. Although normally alert, he would experience periods of lethargy and diaphoresis lasting 10 to 30 minutes. During these episodes a right hemiparesis and either left or right facial weakness were also present. The transient motor deficits persisted for several hours after the resolution of the lethargy. These symptoms were attributed to vasospasm and hydrocephalus, both of which were radiologically confirmed. They were treated with hydration and a temporary ventriculostomy to relieve the