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Unilateral Ovarian Dermoid Cyst Accompanied by an Ipsilateral Paratubal Cyst in a Girl with Proteus Syndrome Discovered by Laparoscopic Surgery
J Pediatr Adolesc Gynecol (2010) 23:e107ee110
Case Report Unilateral Ovarian Dermoid Cyst Accompanied by an Ipsilateral Paratubal Cyst in a Girl with Proteus Syndrome Discovered by Laparoscopic Surgery Jin Hwa Hong, MD1, Jae Kwan Lee, MD1, Seung Hun Song, MD1, Jong Ha Hwang, MD1, Kyung A. So, MD1, Bong Kyung Shin, MD2, Nak Woo Lee, MD1, and Kyu Wan Lee, MD1 1
Department of Obstetrics and Gynecology; 2Department of Pathology, Guro Hospital, College of Medicine, Korea University, Seoul, Korea
Abstract. Background: Proteus syndrome is a rare hamartomatous disorder characterized by the overgrowth of multiple tissues in a mosaic pattern. Tumors of genitourinary tract in Proteus syndrome are uncommon. Case: We here report a 5-year-old girl with Proteus syndrome who developed a cystic mass in the pelvic cavity. The cyst was discovered by ultrasonographic examination and finally proved to be a unilateral ovarian dermoid cyst accompanied by an ipsilateral paratubal cyst by laparoscopic surgery. Summary and Conclusion: Proteus syndrome accompanied by an ovarian cyst is rare in girls. The possibilities of underlying ovarian cyst required for surgical intervention should be considered in Proteus syndrome.
hamartomatous tumors. Specifically, lymphangioma, hemangiomatosis, and aggressive lipomatosis are remarkable. Only a few of cases ovarian cysts have been reported.4e6 We herein report a 5-year-old girl with Proteus syndrome who developed a unilateral ovarian dermoid cyst accompanied by an ipsilateral paratubal cyst discovered by laparoscopic surgery. Case Report
Address correspondence to: Jae Kwan Lee, MD, Department of Obstetrics and Gynecology, Guro Hospital, College of Medicine, Korea University, 80 Guro-gu Guro-dong, Seoul, 152-703, Korea; E-mail: [email protected]
A 5-year-old girl was referred to the Department of Obstetrics and Gynecology for the evaluation of a pelvic mass. She was the second-born child of a consanguineous marriage of healthy parents. The family history was unremarkable and her mother had an uneventful prenatal period. She was delivered by cesarean section due to her mother’s previous cesarean section and her birth weight was 3.2 kg. Her morphological characteristics at birth were poorly documented. At 7 months of age, a seizure disorder was noted and a brain MRI scan revealed periventricular leukomalacia. Her parents noticed that she had a leg length discrepancy (left longer than right) combined with genu valgum deformity, minor ptosis, and leftsided facial asymmetry with hyperpigmented striae on both cheeks and around the neck that appeared at the age of 21 months. In addition, calvarial asymmetry and thoracolumbar scoliosis were identified. An abdominal sonogram was performed to identify other anomalies, which showed a 5.2 3.4-cm cystic mass on the superior aspect of the urinary bladder, suggestive of a urachal or ovarian cyst. The patient was then referred to the Department of Pediatrics and she was recommended to take an MRI scan to evaluate the nature of the cyst more accurately, but her parents refused. The patient began treatment for her leg at
Ó 2010 North American Society for Pediatric and Adolescent Gynecology Published by Elsevier Inc.
1083-3188/$36.00 doi:10.1016/j.jpag.2009.08.010
Key Words. Proteus syndrome—Dermoid cyst—Para tubal cyst—Laparoscopic surgery
Introduction Proteus syndrome is a rare, sporadic and progressive overgrowth disorder that is probably caused by a somatic mosaicism that is lethal in the non-mosaic state. The disease was described by Cohen and Hayden in 1979,1 named by Wiedemann et al in 1983,2 and further defined by Happle in 1987.3 The responsible genetic defect has not been identified. The clinical features of Proteus syndrome are highly variable, and include hemi-hypertrophy, macrodactyly, exostoses, pigmented nevi, and subcutaneous and visceral
e108
Hong et al: Cysts in Proteus Syndrome
Table 1. Diagnostic Criteria for Proteus Syndrome General criteria (mandatory for diagnosis), plus specific criteria (see below) Mosaic distribution Progressive course Sporadic occurrence Specific criteria (category signs): either one from category A or two from B or three from C Category A Connective tissue nevus Category B Epidermal nevus Disproportionate overgrowth (one or more) Limbs (arms/legs/hands/feet/digits) Skull (hyperostoses) External auditory meatus (hyperostoses) Vertebrae (megaspondylodysplasia) Viscera (spleen/thymus) Specific tumors before end of second decade of life (either one) Bilateral ovarian cystadenoma Parotid monomorphic adenoma Category C Dysregulated adipose tissue (either one) Lipomas Regional absence of fat Vascular malformations (O1) Capillary malformation Lymphatic malformation Facial phenotype Dolichocephaly Long face Minor downslanting of palpebral fissures and/or minor ptosis Low nasal bridge Wide or anteverted nares Open mouth at rest
the Department of Orthopedics at Guro Hospital, College of Medicine, Korea University, which culminated in a left proximal tibia and distal fibula osteotomy 2 years later. During rehabilitation she underwent 2 additional surgeries, one for strabismus of the left eye and one for narrowing of the external auditory canal.
As listed in Table 1, the patient’s problems are sporadic, mosaic, and progressive, satisfying all 3 ‘‘general’’ criteria for the diagnosis of Proteus syndrome.7e10 Further diagnostic criteria are met as 2 category B features: epidermal nevus (both cheeks and around the neck) and disproportionate limb overgrowth (left leg longer than right). Regarding category C features, she possessed a characteristic facial phenotype that involved dolichocephaly, a long face, downslanted palpebral fissures, a low nasal bridge, and an open mouth at rest (Fig. 1A, B). Following consultation with a pediatric geneticist, a diagnosis of Proteus syndrome was established. At 5 years of age, the patient was referred to the Department of Obstetrics and Gynecology for reevaluation of the pelvic mass initially found 3 years prior. She also complained of low abdominal pain, but further specification of the pain was not possible due to her linguistic difficulties. Transabdominal ultrasonography showed a bilobed cystic mass (lobes measured 4.7 3.1 cm and 3.3 3.1 cm) with no solid portion in the left pelvic cavity. We subsequently performed a pelvic MRI, which showed a bilobed cystic mass (lobes measured 5.5 3.0 cm and 4.4 2.9 cm) containing small amount of fat. Serum CA 125 and AFP were 32.9 U/mL and 1.53 ng/mL, respectively, which were in the normal range. Complete blood count and chemistries were all within normal limits. At laparoscopy, the uterus was small and smooth surfaced. The left ovary contained a 5-cm whitish, well-encapsulated cyst and a second 4-cm elongated cyst originating from the ipsilateral fallopian tube (Fig. 2). The right ovary and the fallopian tube were normal in shape and size. Laparoscopic left ovarian cystectomy and paratubal cystectomy were performed. The left ovarian cyst was unilocular and contained serous fluid with a small amount of fat, while the paratubal cyst contained purely serous fluid. No other abnormalities were identified during laparoscopic surgery.
Fig. 1. Patient with Proteus syndrome. A. Hyperpigmented striae on her cheek and neck. B. Left facial asymmetry, downslanted palpebral fissure, and open mouth at rest are shown.
Hong et al: Cysts in Proteus Syndrome
Fig. 2. Left ovarian dermoid cyst accompanied by an ipsilateral paratubal cyst discovered during laparoscopic surgery.
Pathological examination of the two cysts revealed a mature cystic teratoma of the left ovary and a paratubal cyst on the left fallopian tube (Fig. 3A, B). The patient’s postoperative course was uneventful. Summary and Conclusion Proteus syndrome is a complex disorder of unknown etiology. The name of the condition comes from the Greek god Proteus, ‘the polymorphous,’ who could change his shape at will to avoid capture.3 It is hypothesized that an unknown sporadic postzygotic gene mutation gives rise to chimeric tissues.11 The clinical features of Proteus syndrome are highly variable and include disproportionate tissue overgrowth, vascular malformations, lipomatosis, and epidermal nevi. People with Proteus syndrome may exhibit one or many characteristics of the syndrome. Currently, there is no specific molecular marker or diagnostic test
e109
to aid in diagnosis. To further complicate the clinical picture, a patient’s clinical manifestations may overlap with other overgrowth or hamartomatous disorders. In describing certain features of Proteus syndrome, the term ‘hamartomatous’ refers to a non-neoplastic overgrowth of tissue growing in its native site but in a disorganized manner.10 The differential diagnosis includes several other syndromes such as Klipper-Trenaunay, Parkes Weber, epidermal nevus, Maffucci, neurofibromatosis, Bannayan-Riley-Ruvalcaba and lipomatosis. The diagnostic criteria for Proteus syndrome have recently been revised.8,9,12 Various neoplasms may complicate Proteus syndrome, which several reports have divided into common (subcutaneous hemangiomas, lymphangiomas and lipomas) and uncommon neoplasms.11 Approximately 30 uncommon neoplasms have been reported, most often in the genital tract, parotid gland and central nervous system.11 Reported neoplasms of the genital tract include serous cystadenoma with nuclear atypia,11 papillary adenocarcinoma of the testes,13 and mesothelioma of the testicular tunica vaginalis.14 A total of 3 female patients with Proteus syndrome have been reported to have ovarian cysts.4e6 Kousseff reported a patient with a 5.3 4.2-cm cyst that was not accompanied by sexual precocity.4 A second case occurred in a 30-year-old woman who underwent a hysterectomy for uterine leiomyoma with ovarian cysts of unknown size.5 The third case of bilateral ovarian cysts of unknown size occurred in a girl with multiple meningiomas.6 The authors of these reports did not specify the specific histologic types of the cysts. In this report, we presented a case of a unilateral ovarian dermoid cyst accompanied by an ipsilateral paratubal cyst in a 5-year-old girl. This is most likely the first case of simultaneous ovarian and paratubal cysts in a patient with Proteus syndrome. In the revised diagnostic criteria for Proteus syndrome, ‘‘bilateral
Fig. 3. A. Ovarian mature cystic teratoma (H&E 40); B. Paratubal cyst (H&E 40).
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Hong et al: Cysts in Proteus Syndrome
ovarian cystadenomas’’ is currently included as part of category B. Although our case does not meet this criterion, the patient possessed other characteristic morphologic features that led to a firm diagnosis of Proteus syndrome. In this case, the presence of ipsilateral ovarian and paratubal cysts deserves special mention. These manifestations may prove to be more common components of the wide variety of manifestations in Proteus syndrome. In addition, the possibilities of underlying ovarian cyst required for surgical treatment should be considered in Proteus syndrome.
References 1. Cohen MM Jr, Hayden PW: A newly recognized hamartomatous syndrome. Birth Defects Orig Artic Ser 1979; 15:291 2. Wiedemann HR, Burgio GR, Aldenhoff P, et al: The proteus syndrome. Partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections. Eur J Pediatr 1983; 140:5 3. Happle R: Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J Am Acad Dermatol 1987; 16:899
4. Kousseff BG: Pleiotropy versus heterogeneity in Proteus syndrome. Pediatrics 1986; 78:544 5. Maassen D, Voigtla¨nder V: Proteus syndrome. Hautarzt 1991; 42:186 6. Bouzas EA, Krasnewich D, Koutroumanidis M, et al: Ophthalmologic examination in the diagnosis of proteus syndrome. Ophthalmology 1993; 100:334 7. Cohen MM Jr: Overgrowth syndromes: an update. Adv Pediatr 1999; 46:441 8. Biesecker LG, Happle R, Mulliken JB, et al: Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet 1999; 84:389 9. Turner JT, Cohen MM Jr, Biesecker LG: Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases. Am J Med Genet A 2004; 130:111 10. Hoey SE, Eastwood D, Monsell F, et al: Histopathological features of Proteus syndrome. Clin Exp Dermatol 2008; 33:234 11. Gordon PL, Wilroy RS, Lasater OE, et al: Neoplasms in proteus syndrome. Am J Med Genet 1995; 57:74 12. Cohen MM Jr: Proteus syndrome: an update. Am J Med Genet C Semin Med Genet 2005; 137:38 13. Hornstein L, Bove KE, Towbin RB: Linear nevi, hemihypertrophy, connective tissue hamartomas, and unusual neoplasms in children. J Pediatr 1987; 110:404 14. Malamitsi-Puchner A, Dimitriadis D, Bartsocas C, et al: Proteus syndrome: course of a severe case. Am J Med Genet 1990; 35:283
Case Report Unilateral Ovarian Dermoid Cyst Accompanied by an Ipsilateral Paratubal Cyst in a Girl with Proteus Syndrome Discovered by Laparoscopic Surgery Jin Hwa Hong, MD1, Jae Kwan Lee, MD1, Seung Hun Song, MD1, Jong Ha Hwang, MD1, Kyung A. So, MD1, Bong Kyung Shin, MD2, Nak Woo Lee, MD1, and Kyu Wan Lee, MD1 1
Department of Obstetrics and Gynecology; 2Department of Pathology, Guro Hospital, College of Medicine, Korea University, Seoul, Korea
Abstract. Background: Proteus syndrome is a rare hamartomatous disorder characterized by the overgrowth of multiple tissues in a mosaic pattern. Tumors of genitourinary tract in Proteus syndrome are uncommon. Case: We here report a 5-year-old girl with Proteus syndrome who developed a cystic mass in the pelvic cavity. The cyst was discovered by ultrasonographic examination and finally proved to be a unilateral ovarian dermoid cyst accompanied by an ipsilateral paratubal cyst by laparoscopic surgery. Summary and Conclusion: Proteus syndrome accompanied by an ovarian cyst is rare in girls. The possibilities of underlying ovarian cyst required for surgical intervention should be considered in Proteus syndrome.
hamartomatous tumors. Specifically, lymphangioma, hemangiomatosis, and aggressive lipomatosis are remarkable. Only a few of cases ovarian cysts have been reported.4e6 We herein report a 5-year-old girl with Proteus syndrome who developed a unilateral ovarian dermoid cyst accompanied by an ipsilateral paratubal cyst discovered by laparoscopic surgery. Case Report
Address correspondence to: Jae Kwan Lee, MD, Department of Obstetrics and Gynecology, Guro Hospital, College of Medicine, Korea University, 80 Guro-gu Guro-dong, Seoul, 152-703, Korea; E-mail: [email protected]
A 5-year-old girl was referred to the Department of Obstetrics and Gynecology for the evaluation of a pelvic mass. She was the second-born child of a consanguineous marriage of healthy parents. The family history was unremarkable and her mother had an uneventful prenatal period. She was delivered by cesarean section due to her mother’s previous cesarean section and her birth weight was 3.2 kg. Her morphological characteristics at birth were poorly documented. At 7 months of age, a seizure disorder was noted and a brain MRI scan revealed periventricular leukomalacia. Her parents noticed that she had a leg length discrepancy (left longer than right) combined with genu valgum deformity, minor ptosis, and leftsided facial asymmetry with hyperpigmented striae on both cheeks and around the neck that appeared at the age of 21 months. In addition, calvarial asymmetry and thoracolumbar scoliosis were identified. An abdominal sonogram was performed to identify other anomalies, which showed a 5.2 3.4-cm cystic mass on the superior aspect of the urinary bladder, suggestive of a urachal or ovarian cyst. The patient was then referred to the Department of Pediatrics and she was recommended to take an MRI scan to evaluate the nature of the cyst more accurately, but her parents refused. The patient began treatment for her leg at
Ó 2010 North American Society for Pediatric and Adolescent Gynecology Published by Elsevier Inc.
1083-3188/$36.00 doi:10.1016/j.jpag.2009.08.010
Key Words. Proteus syndrome—Dermoid cyst—Para tubal cyst—Laparoscopic surgery
Introduction Proteus syndrome is a rare, sporadic and progressive overgrowth disorder that is probably caused by a somatic mosaicism that is lethal in the non-mosaic state. The disease was described by Cohen and Hayden in 1979,1 named by Wiedemann et al in 1983,2 and further defined by Happle in 1987.3 The responsible genetic defect has not been identified. The clinical features of Proteus syndrome are highly variable, and include hemi-hypertrophy, macrodactyly, exostoses, pigmented nevi, and subcutaneous and visceral
e108
Hong et al: Cysts in Proteus Syndrome
Table 1. Diagnostic Criteria for Proteus Syndrome General criteria (mandatory for diagnosis), plus specific criteria (see below) Mosaic distribution Progressive course Sporadic occurrence Specific criteria (category signs): either one from category A or two from B or three from C Category A Connective tissue nevus Category B Epidermal nevus Disproportionate overgrowth (one or more) Limbs (arms/legs/hands/feet/digits) Skull (hyperostoses) External auditory meatus (hyperostoses) Vertebrae (megaspondylodysplasia) Viscera (spleen/thymus) Specific tumors before end of second decade of life (either one) Bilateral ovarian cystadenoma Parotid monomorphic adenoma Category C Dysregulated adipose tissue (either one) Lipomas Regional absence of fat Vascular malformations (O1) Capillary malformation Lymphatic malformation Facial phenotype Dolichocephaly Long face Minor downslanting of palpebral fissures and/or minor ptosis Low nasal bridge Wide or anteverted nares Open mouth at rest
the Department of Orthopedics at Guro Hospital, College of Medicine, Korea University, which culminated in a left proximal tibia and distal fibula osteotomy 2 years later. During rehabilitation she underwent 2 additional surgeries, one for strabismus of the left eye and one for narrowing of the external auditory canal.
As listed in Table 1, the patient’s problems are sporadic, mosaic, and progressive, satisfying all 3 ‘‘general’’ criteria for the diagnosis of Proteus syndrome.7e10 Further diagnostic criteria are met as 2 category B features: epidermal nevus (both cheeks and around the neck) and disproportionate limb overgrowth (left leg longer than right). Regarding category C features, she possessed a characteristic facial phenotype that involved dolichocephaly, a long face, downslanted palpebral fissures, a low nasal bridge, and an open mouth at rest (Fig. 1A, B). Following consultation with a pediatric geneticist, a diagnosis of Proteus syndrome was established. At 5 years of age, the patient was referred to the Department of Obstetrics and Gynecology for reevaluation of the pelvic mass initially found 3 years prior. She also complained of low abdominal pain, but further specification of the pain was not possible due to her linguistic difficulties. Transabdominal ultrasonography showed a bilobed cystic mass (lobes measured 4.7 3.1 cm and 3.3 3.1 cm) with no solid portion in the left pelvic cavity. We subsequently performed a pelvic MRI, which showed a bilobed cystic mass (lobes measured 5.5 3.0 cm and 4.4 2.9 cm) containing small amount of fat. Serum CA 125 and AFP were 32.9 U/mL and 1.53 ng/mL, respectively, which were in the normal range. Complete blood count and chemistries were all within normal limits. At laparoscopy, the uterus was small and smooth surfaced. The left ovary contained a 5-cm whitish, well-encapsulated cyst and a second 4-cm elongated cyst originating from the ipsilateral fallopian tube (Fig. 2). The right ovary and the fallopian tube were normal in shape and size. Laparoscopic left ovarian cystectomy and paratubal cystectomy were performed. The left ovarian cyst was unilocular and contained serous fluid with a small amount of fat, while the paratubal cyst contained purely serous fluid. No other abnormalities were identified during laparoscopic surgery.
Fig. 1. Patient with Proteus syndrome. A. Hyperpigmented striae on her cheek and neck. B. Left facial asymmetry, downslanted palpebral fissure, and open mouth at rest are shown.
Hong et al: Cysts in Proteus Syndrome
Fig. 2. Left ovarian dermoid cyst accompanied by an ipsilateral paratubal cyst discovered during laparoscopic surgery.
Pathological examination of the two cysts revealed a mature cystic teratoma of the left ovary and a paratubal cyst on the left fallopian tube (Fig. 3A, B). The patient’s postoperative course was uneventful. Summary and Conclusion Proteus syndrome is a complex disorder of unknown etiology. The name of the condition comes from the Greek god Proteus, ‘the polymorphous,’ who could change his shape at will to avoid capture.3 It is hypothesized that an unknown sporadic postzygotic gene mutation gives rise to chimeric tissues.11 The clinical features of Proteus syndrome are highly variable and include disproportionate tissue overgrowth, vascular malformations, lipomatosis, and epidermal nevi. People with Proteus syndrome may exhibit one or many characteristics of the syndrome. Currently, there is no specific molecular marker or diagnostic test
e109
to aid in diagnosis. To further complicate the clinical picture, a patient’s clinical manifestations may overlap with other overgrowth or hamartomatous disorders. In describing certain features of Proteus syndrome, the term ‘hamartomatous’ refers to a non-neoplastic overgrowth of tissue growing in its native site but in a disorganized manner.10 The differential diagnosis includes several other syndromes such as Klipper-Trenaunay, Parkes Weber, epidermal nevus, Maffucci, neurofibromatosis, Bannayan-Riley-Ruvalcaba and lipomatosis. The diagnostic criteria for Proteus syndrome have recently been revised.8,9,12 Various neoplasms may complicate Proteus syndrome, which several reports have divided into common (subcutaneous hemangiomas, lymphangiomas and lipomas) and uncommon neoplasms.11 Approximately 30 uncommon neoplasms have been reported, most often in the genital tract, parotid gland and central nervous system.11 Reported neoplasms of the genital tract include serous cystadenoma with nuclear atypia,11 papillary adenocarcinoma of the testes,13 and mesothelioma of the testicular tunica vaginalis.14 A total of 3 female patients with Proteus syndrome have been reported to have ovarian cysts.4e6 Kousseff reported a patient with a 5.3 4.2-cm cyst that was not accompanied by sexual precocity.4 A second case occurred in a 30-year-old woman who underwent a hysterectomy for uterine leiomyoma with ovarian cysts of unknown size.5 The third case of bilateral ovarian cysts of unknown size occurred in a girl with multiple meningiomas.6 The authors of these reports did not specify the specific histologic types of the cysts. In this report, we presented a case of a unilateral ovarian dermoid cyst accompanied by an ipsilateral paratubal cyst in a 5-year-old girl. This is most likely the first case of simultaneous ovarian and paratubal cysts in a patient with Proteus syndrome. In the revised diagnostic criteria for Proteus syndrome, ‘‘bilateral
Fig. 3. A. Ovarian mature cystic teratoma (H&E 40); B. Paratubal cyst (H&E 40).
e110
Hong et al: Cysts in Proteus Syndrome
ovarian cystadenomas’’ is currently included as part of category B. Although our case does not meet this criterion, the patient possessed other characteristic morphologic features that led to a firm diagnosis of Proteus syndrome. In this case, the presence of ipsilateral ovarian and paratubal cysts deserves special mention. These manifestations may prove to be more common components of the wide variety of manifestations in Proteus syndrome. In addition, the possibilities of underlying ovarian cyst required for surgical treatment should be considered in Proteus syndrome.
References 1. Cohen MM Jr, Hayden PW: A newly recognized hamartomatous syndrome. Birth Defects Orig Artic Ser 1979; 15:291 2. Wiedemann HR, Burgio GR, Aldenhoff P, et al: The proteus syndrome. Partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections. Eur J Pediatr 1983; 140:5 3. Happle R: Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J Am Acad Dermatol 1987; 16:899
4. Kousseff BG: Pleiotropy versus heterogeneity in Proteus syndrome. Pediatrics 1986; 78:544 5. Maassen D, Voigtla¨nder V: Proteus syndrome. Hautarzt 1991; 42:186 6. Bouzas EA, Krasnewich D, Koutroumanidis M, et al: Ophthalmologic examination in the diagnosis of proteus syndrome. Ophthalmology 1993; 100:334 7. Cohen MM Jr: Overgrowth syndromes: an update. Adv Pediatr 1999; 46:441 8. Biesecker LG, Happle R, Mulliken JB, et al: Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet 1999; 84:389 9. Turner JT, Cohen MM Jr, Biesecker LG: Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases. Am J Med Genet A 2004; 130:111 10. Hoey SE, Eastwood D, Monsell F, et al: Histopathological features of Proteus syndrome. Clin Exp Dermatol 2008; 33:234 11. Gordon PL, Wilroy RS, Lasater OE, et al: Neoplasms in proteus syndrome. Am J Med Genet 1995; 57:74 12. Cohen MM Jr: Proteus syndrome: an update. Am J Med Genet C Semin Med Genet 2005; 137:38 13. Hornstein L, Bove KE, Towbin RB: Linear nevi, hemihypertrophy, connective tissue hamartomas, and unusual neoplasms in children. J Pediatr 1987; 110:404 14. Malamitsi-Puchner A, Dimitriadis D, Bartsocas C, et al: Proteus syndrome: course of a severe case. Am J Med Genet 1990; 35:283