- Email: [email protected]
Cervical Cystic Lymphangioma in a Patient With Blue Rubber Bleb Nevus Syndrome: Clinical Case Report and Review of the Literature
Cervical Cystic Lymphangioma in a Patient With Blue Rubber Bleb Nevus Syndrome: Clinical Case Report and Review of the Literature Elena Marı´n-Manzano,1 Agustin Utrilla Lo´pez,1 Enrique Puras Magallay,2 Carmen Cuesta Gimeno,1 and J.L. Marı´n-Aznar,3 Madrid and Granada, Spain
We present the case of a 9-year-old boy diagnosed with Blue Rubber Bleb Nevus Syndrome, who showed a very large left cervical cystic lymphangioma. He was previously subjected to various treatments for lesions in the intestinal tract including blood transfusions for anemia, sclerosis, enterotomies or resections. The tumor was resected without any complications and the anatomopathologic report confirmed this diagnosis. The blue cavernous hemangioma syndrome (or Blue Rubber Bleb Nevus Syndrome) is a rare disease characterized by cavernous angiomas involving the skin and gastrointestinal tract. Several cases of cystic lymphangiomas associated with this syndrome have been published recently and lymphomatous differentiation has been identified in the cells of cutaneous lesions. Given their common embryological origin, we underscore the importance of bearing in mind that it is possible for different types of vascular malformations to coexist in the same patient.
The blue cavernous hemangioma syndrome, or Blue Rubber Bleb Nevus Syndrome (BRBNS), is a rare disease associated with cavernous angiomas involving the skin and the gastrointestinal tract. It was described for the first time by Gascoyen1 in 1860; however, the term BRBNS was first coined by Bean2 in 1958.
CLINICAL CASE A boy was diagnosed with BRBNS at 4 years of age. He had a history of repeated episodes of anemia and No external funding has been received for this study. There are no conflict of interests with regard this paper. 1 Angiology and Vascular Surgery Service, Ramo´n y Cajal Hospital, Madrid, Spain. 2 Angiology and Vascular Surgery Service, Alcorco´n Foundation Hospital, Madrid, Spain. 3 Anatomical Pathology Service, Hospital Virgen de las Nieves, Granada, Spain.
Correspondence to: Elena Marı´n Manzano, MD, Servicio de Angiologı´a y Cirugı´a Vascular, Hospital Ramo´n y Cajal, Cta. Colmenar Viejo km 9,1, 28034 Madrid (Espan˜a), Spain, E-mail: [email protected] Ann Vasc Surg 2010; 24: 1136.e1-1136.e5 DOI: 10.1016/j.avsg.2010.02.052 Ó Annals of Vascular Surgery Inc.
was subjected to numerous blood transfusions and sclerotherapy in the stomach and colon. At the age of 6 years, 20 intestinal lesions were resected through enterotomies because of the presence of angiomatous lesions in the small intestine causing nonobstructive invaginations. In the immediate postoperative period, the patient suffered an episode of intestinal obstruction because of invagination and adherences and required intestinal resection. In 2006, the patient, at the age of 9, was presented for the first time in our center, with an early-stage soft, translucent, mobile tumor in the left supraclavicular region, which was not adhered to the surrounding structure (Fig. 1). Tumor growth was progressive, and although it was painless for the patient, it intensified and increased in size during bouts of coughing. During the patient’s physical examination, small lesions were observed, mainly distributed along the limbs. The lesions were of medium consistency and bluish in color, and were compatible with the small cutaneous cavernous angiomas. Echography and magnetic resonance were performed, confirming the presence of a 10 8 7 cm3 cervical cystic tumor in the retrojugular space, extending from the parathyroid region to the superior thoracic outlet, below the 1136.e1
1136.e2 Case reports
Fig. 1. Clinical image of left laterocervical cystic tumor.
sternocleidomastoid muscle which displaced the carotid artery medially. Additionally, a 5-cm wide cystic lobulation in the pretracheal space was also seen(Fig. 2). The gammagraphy that was performed with technetium 99 ruled out the presence of ectopic thyroid tissue. Given the clinical suspicion of cystic lymphangioma, a surgical treatment was indicated. Complete tumor resection was performed through a transverse cervicotomy by penetrating below the internal jugular vein up to the superior mediastinum (Figs. 3, 4), after controlling the cervical vascular bundle. There were no postoperative complications and the patient showed good wound healing. Hence, he was discharged after 48 hours. The anatomopathologic study of the surgical piece confirmed the diagnosis of cystic lymphangioma. The patient had no history of first- or seconddegree vascular malformation, thus, the diagnosis of cystic lymphangioma was associated with a sporadic case of BRBNS. Hence, no genetic screening study was conducted. At the 6-month follow-up, the patient remained asymptomatic, without showing evidence of cervical relapse. He was subjected to periodic clinical and endoscopic controls performed by the gastroenterologist to rule out relapses.
Annals of Vascular Surgery
Fig. 2. Axial slice of an nuclear magnetic resonance (NMR) image showing a left cervical cystic collection, extending to the superior thoracic outlet, below the sternocleidomastoid muscle.
DISCUSSION Vascular malformations occur as a result of disorders in vascular morphogenesis. Depending on the affected vessel, these alterations may be capillarial, venous, arterial, or lymphatic. The embryology of the vascular system is closely linked to the morphogenesis of other mesenchymal tissues. This explains the reason for more than one component (capillarial, arterial, lymphatic, or venous) being observed in vascular malformations and the presence of associated soft-tissue and skeletal overgrowth.3 By definition, all vascular malformations are congenital, although they may not become clinically evident until adolescence or adulthood. These malformations grow because the vessels progressively dilate, in response to traumatisms, or because of hormonal changes during puberty or pregnancy. Vascular malformations are never known to regress spontaneously. The blue cavernous hemangioma syndrome is a vascular malformation characterized by cavernous angiomas involving the skin and the gastrointestinal tract. The cutaneous lesions are multiple, protuberant, bluish, compressible, hyperhidrotic, and although typically asymptomatic, they may be
Vol. 24, No. 8, November 2010
Case reports 1136.e3
Fig. 3. Surgical resection of cervical cystic lymphangioma through a transverse supraclavicular approach.
Fig. 4. Surgical piece showing surgical site with exposition of left carotid artery and left jugular vein.
painful in some cases. They usually do not bleed spontaneously. They are either present at birth or develop during the first years of life, although they may only become clinically evident on reaching adolescence, and with age, they increase in number and size. The management of vascular malformations is limited to excision or laser ablation. Gastrointestinal lesions usually affect the small intestine and frequently bleed spontaneously, causing chronic anemia owing to iron deficit, and occasionally massive hemorrhages. They may also cause volvulations and intestinal infarction. Endoscopy is the ideal diagnostic method for intestinal lesions, although gammagraphic studies with marked red blood cells and capsule endoscopy studies play an important role in the study of occult hemorrhages.4 The treatment is based on iron supplementation and elective blood transfusions. To treat massive hemorrhages, the options are surgical resection, sclerosis or endoscopic band ligations, laser photocoagulation, or interferon therapy.5 Other treatments include corticosteroids, interferon-a, vincristine, and somatostatin analogues, such as octreotide (because it reduces blood flow to the gastrointestinal tract).5,6 Other affected regions that have been studied are the nasopharyngeal, ocular, thyroid, musculoskeletal, retroperitoneal, pleuro-pericardial, and
pulmonary regions, and the central nervous system, among others.7-10 The differential diagnosis of this pathology must be performed by comparing it with other diseaseentities involving cutaneous and visceral vascular malformations, such as the RendueOsler disease (which also involves pulmonary lesions), the Maffucci syndrome (ossification disorder and achondroplasia), the KlippeleTrenaunayeWeber syndrome (asymmetric bone and soft tissue hypertrophy in one limb), and the Von HippeleLindau disease (cerebellar and retinal angiomatosis).4 Although there are some familial forms of BRBNS characterized by sex-linked inheritance or by autosomal dominant inheritance (locus in chromosome 9),7-9 most of the cases are sporadic. Most patients have a normal life expectancy. However, their prognosis depends on the extension of visceral involvement. Systemic complications may occur, including thrombocytopenia, chronic lymphatic leukemia, or consumption coagulopathy.5 No malignant transformation of lesions has been described. The cystic lymphangioma is a congenital hamartomatous malformation of the lymphatic system that typically presents during infancy, and has a tendency to grow unless it is completely
Gallego et al.4
Nobuhara et al.15
Patient Etiology
8-year-old female Sporadic
Clinical presentation
Ferropenic anemia
47-year-old female 25-year-old female Family history of hereditary Sporadic hemangiomatosis (dominant autosomal heredity) Pancreatic cyst Abdominal mass and digestive hemorrhage
Cutaneous lesions Trunk and right lower limb hemangiomas Costal mass
Cutaneous lesion treatment
Digestive lesions
Treatment of digestive lesions Other imaging tests
Costal mass extirpation Conservative (hemolymphangioma) Excision of cutaneous lesions (hemangiomas) Polyps (Endoscopy) Hemangiomas in the ascending colon and in the esophagus Electrocauterization
No
Abdominal echography Abdominal and cranial CAT scan (to rule out visceral lesions) Gammagraphy with Tc99 Endoscopic capsule Histologic (cutaneous lesions)
Abdominal CAT scan Abdominal echography Cholangiopancreatography Laparoscopic biopsy (pancreatic cystic lymphangioma) Genetic study of peripheral leukocytes (Arg849Trp mutation)
CAT, computerized axial tomography; NMR, nuclear magnetic resonance.
Trunk, lower limbs, tongue, and pharynx hemangiomas
Flu¨gge et al.17
Marı´n-Manzano et al. (present study)
Premature male neonate Sporadic
4-year-old male Sporadic
Giant hemorrhagic tumor on thigh and in the gluteal region Cavernous lymphangioma in genitalia and thigh Skin hemangiomas
Chronic anemia
Hemangiomas in limbs Cervical cystic lymphangioma (surgical extirpation) No.
Sclerosis and ethanolization
No
Retro- and intraperitoneal hemangiomas (uterus, vagina, and intestine) with right hydronephrosis Resection with right nephrectomy, hysterectomy, and right oophorectomy Abdominal echography Abdominal CAT scan Angio-NMR of the abdomen
Small intestine, pleural, and diaphragmatic hemangiomas
Small intestine hemangiomas
No
Endoscopic sclerosis Surgical enterotomies
No
Cervical NMR Cervical echography
Histologic (CD31, CD34, Factor Post-mortem histological Histologic VIII, D2-40, subendothelial diagnosis: Genital collagen type-IV deposits.) and thigh lymphangioma Lymphomatous differentiation
Annals of Vascular Surgery
Diagnosis
Trunk and lip hemangiomas
Patel et al.16
1136.e4 Case reports
Table I. The association’s caseload in BRBNS and lymphangioma
Vol. 24, No. 8, November 2010
extirpated. About 75% of all cases are localized in the neck area.10 The lesions are not potentially malignant, yet they continue to progress, relapse (because of incomplete surgical procedures), or become overinfected. The treatment of choice is considered to be complete surgical exeresis of the cyst, while preserving the adjacent structures, bearing in mind that partial resections entail a high relapse rate. Other valid therapeutic options are diathermy therapy, radiotherapy, percutaneous sclerotherapy,11,12 and the intralesional injection of OK-432 (Picibanil). The latter two options have shown greater promise.11-14 Since it was first described in 1860,1 about 200 cases of BRBNS have been currently published. This represents a low incidence rate, although the true incidence is hard to estimate because of its rareness. The cases of cystic lymphangiomas associated with BRBNS are very few4,15-17 (refer to the association’s disease caseload on Table I); however, this association has described other vascular malformations, such as the Von HippeleLindau disease. Lymphomatous differentiation has been identified in the cells of Blue Rubber Bleb Nevus cutaneous lesions (focal expression of D2-40 lymphatic endothelial marker and patch stage immunoexpression of type-IV collagen in the subendothelial basement membrane)16 and a potential expression of the TIE2 gene in the endothelial cells of the lymphangioma15 indicates that the vascular lesions in the BRBNS are not limited to venous malformations. In this article, we presented a case of cervical cystic lymphangioma in a patient with previous diagnosis of BRBNS. Because of their shared embryological origin, we underscored the importance of the possibility that different types of vascular malformations might coexist in the same patient. REFERENCES 1. Gascoyen GG. Case of nevus involving the parotid gland and causing death from suffocation: nevi of the viscera. Trans Pathol Soc Lond 1860;11:267.
Case reports 1136.e5
2. Bean WB. Blue rubber bleb nevi of the skin and gastrointestinal tract. In: Bean WB ed. Vascular Spiders and Related Lesions of the Skin. Springfield, MA: Charles Thomas Publishers; 1958. pp 178-185. 3. Fishman SJ, Muliken JB. Vascular anomalies. A primer for pediatricians. Pediatr Clin North Am 1998;45:1455-1477. 4. Gallego PM, Arcocha TM, Lo´pez Casado MA, et al. Usefulness of labelled red cell scintigraphy in Blue Rubber Bleb Nevus syndrome. Rev Esp Med Nucl 2009;28:18-21. 5. Fishman SJ, Smithers J, Folkman J, et al. Blue rubber bleb nevus syndrome: surgical eradication of gastrointestinal bleeding. Ann Surg 2005;241:523-528. 6. Liu Q, Chen YP, Li YM. Blue rubber bleb nevus syndrome: a report of one case associated with recurrent epistaxis. Chin Med J 2007;120:731-733. 7. Domini M, Aquino A, Fakhro A, et al. Blue rubber bleb nevus syndrome and gastrointestinal haemorrhage: which treatment? Eur J Pediatr Surg 2002;12:129-133. 8. Carvalho S, Barbosa V, Santos N. Blue rubber-bleb nevus syndrome: report of a 151 familial case with a dural arteriovenous fistula. Am J Neuroradiol 2003;24:1916-1918. 9. Arguedas M, Shorf G, Wilcox M. Congenital vascular lesions of the gastrointestinal tract: blue rubber bleb nevus and klippeltrenaunay syndromes. South Med J 2001;94:405-410. 10. Gilbey LK, Girod CE. Blue rubber bleb nevus syndrome: endobronquial involvement presenting as chronic cough. Chest 2003;124:760-763. 11. Arzoz Fa`bregas M, IbarzServio Ll, Areal Calama J, et al. Linfangioma quı´stico. Nuestra experiencia. Actas Urol Esp 2006;30:723-727. 12. Won JH, Kim BM, Kim C, et al. Cystic lymphangioma. Our experience. Percutaneous sclerotherapy of lymphangiomas with acetic acid. J Vasc Interv Radiol 2004;15:595-600. 13. Alonso J, Barbier L, Alvarez J, et al. OK432 (picibanil) efficacy in an adult with cystic cervical lymphangioma. A case report. Med Oral Patol Oral Cir Bucal 2005;10:362-366. 14. Claesson G, Kuylenstierna R. OK-432 therapy for lymphatic malformation in 32 patients (28 children). Int J Pediatr Otolaryngol 2002;65:1-6. 15. Nobuhara Y, Onoda N, Fukai K, et al. TIE2 gain-of-function mutation in a patient with pancreatic lymphangioma associated with blue rubber-bleb nevus syndrome: report of a case. Surg Today 2006;36:283-286. 16. Patel RC, Zynger DL, Laskin WB. Blue rubber bleb nevus syndrome: novel lymphangiomatosis-like growth pattern within the uterus and immunohistochemical analysis. Hum Pathol 2009;40:413-417. 17. Flu¨gge R, Mu¨ller KM. Multilocular hemangiomatosis in combination with a lymphangioma in a premature infant. Relationship to "blue rubber bleb nevus.". Zentralbl Allg Pathol 1967;110:481-489.
We present the case of a 9-year-old boy diagnosed with Blue Rubber Bleb Nevus Syndrome, who showed a very large left cervical cystic lymphangioma. He was previously subjected to various treatments for lesions in the intestinal tract including blood transfusions for anemia, sclerosis, enterotomies or resections. The tumor was resected without any complications and the anatomopathologic report confirmed this diagnosis. The blue cavernous hemangioma syndrome (or Blue Rubber Bleb Nevus Syndrome) is a rare disease characterized by cavernous angiomas involving the skin and gastrointestinal tract. Several cases of cystic lymphangiomas associated with this syndrome have been published recently and lymphomatous differentiation has been identified in the cells of cutaneous lesions. Given their common embryological origin, we underscore the importance of bearing in mind that it is possible for different types of vascular malformations to coexist in the same patient.
The blue cavernous hemangioma syndrome, or Blue Rubber Bleb Nevus Syndrome (BRBNS), is a rare disease associated with cavernous angiomas involving the skin and the gastrointestinal tract. It was described for the first time by Gascoyen1 in 1860; however, the term BRBNS was first coined by Bean2 in 1958.
CLINICAL CASE A boy was diagnosed with BRBNS at 4 years of age. He had a history of repeated episodes of anemia and No external funding has been received for this study. There are no conflict of interests with regard this paper. 1 Angiology and Vascular Surgery Service, Ramo´n y Cajal Hospital, Madrid, Spain. 2 Angiology and Vascular Surgery Service, Alcorco´n Foundation Hospital, Madrid, Spain. 3 Anatomical Pathology Service, Hospital Virgen de las Nieves, Granada, Spain.
Correspondence to: Elena Marı´n Manzano, MD, Servicio de Angiologı´a y Cirugı´a Vascular, Hospital Ramo´n y Cajal, Cta. Colmenar Viejo km 9,1, 28034 Madrid (Espan˜a), Spain, E-mail: [email protected] Ann Vasc Surg 2010; 24: 1136.e1-1136.e5 DOI: 10.1016/j.avsg.2010.02.052 Ó Annals of Vascular Surgery Inc.
was subjected to numerous blood transfusions and sclerotherapy in the stomach and colon. At the age of 6 years, 20 intestinal lesions were resected through enterotomies because of the presence of angiomatous lesions in the small intestine causing nonobstructive invaginations. In the immediate postoperative period, the patient suffered an episode of intestinal obstruction because of invagination and adherences and required intestinal resection. In 2006, the patient, at the age of 9, was presented for the first time in our center, with an early-stage soft, translucent, mobile tumor in the left supraclavicular region, which was not adhered to the surrounding structure (Fig. 1). Tumor growth was progressive, and although it was painless for the patient, it intensified and increased in size during bouts of coughing. During the patient’s physical examination, small lesions were observed, mainly distributed along the limbs. The lesions were of medium consistency and bluish in color, and were compatible with the small cutaneous cavernous angiomas. Echography and magnetic resonance were performed, confirming the presence of a 10 8 7 cm3 cervical cystic tumor in the retrojugular space, extending from the parathyroid region to the superior thoracic outlet, below the 1136.e1
1136.e2 Case reports
Fig. 1. Clinical image of left laterocervical cystic tumor.
sternocleidomastoid muscle which displaced the carotid artery medially. Additionally, a 5-cm wide cystic lobulation in the pretracheal space was also seen(Fig. 2). The gammagraphy that was performed with technetium 99 ruled out the presence of ectopic thyroid tissue. Given the clinical suspicion of cystic lymphangioma, a surgical treatment was indicated. Complete tumor resection was performed through a transverse cervicotomy by penetrating below the internal jugular vein up to the superior mediastinum (Figs. 3, 4), after controlling the cervical vascular bundle. There were no postoperative complications and the patient showed good wound healing. Hence, he was discharged after 48 hours. The anatomopathologic study of the surgical piece confirmed the diagnosis of cystic lymphangioma. The patient had no history of first- or seconddegree vascular malformation, thus, the diagnosis of cystic lymphangioma was associated with a sporadic case of BRBNS. Hence, no genetic screening study was conducted. At the 6-month follow-up, the patient remained asymptomatic, without showing evidence of cervical relapse. He was subjected to periodic clinical and endoscopic controls performed by the gastroenterologist to rule out relapses.
Annals of Vascular Surgery
Fig. 2. Axial slice of an nuclear magnetic resonance (NMR) image showing a left cervical cystic collection, extending to the superior thoracic outlet, below the sternocleidomastoid muscle.
DISCUSSION Vascular malformations occur as a result of disorders in vascular morphogenesis. Depending on the affected vessel, these alterations may be capillarial, venous, arterial, or lymphatic. The embryology of the vascular system is closely linked to the morphogenesis of other mesenchymal tissues. This explains the reason for more than one component (capillarial, arterial, lymphatic, or venous) being observed in vascular malformations and the presence of associated soft-tissue and skeletal overgrowth.3 By definition, all vascular malformations are congenital, although they may not become clinically evident until adolescence or adulthood. These malformations grow because the vessels progressively dilate, in response to traumatisms, or because of hormonal changes during puberty or pregnancy. Vascular malformations are never known to regress spontaneously. The blue cavernous hemangioma syndrome is a vascular malformation characterized by cavernous angiomas involving the skin and the gastrointestinal tract. The cutaneous lesions are multiple, protuberant, bluish, compressible, hyperhidrotic, and although typically asymptomatic, they may be
Vol. 24, No. 8, November 2010
Case reports 1136.e3
Fig. 3. Surgical resection of cervical cystic lymphangioma through a transverse supraclavicular approach.
Fig. 4. Surgical piece showing surgical site with exposition of left carotid artery and left jugular vein.
painful in some cases. They usually do not bleed spontaneously. They are either present at birth or develop during the first years of life, although they may only become clinically evident on reaching adolescence, and with age, they increase in number and size. The management of vascular malformations is limited to excision or laser ablation. Gastrointestinal lesions usually affect the small intestine and frequently bleed spontaneously, causing chronic anemia owing to iron deficit, and occasionally massive hemorrhages. They may also cause volvulations and intestinal infarction. Endoscopy is the ideal diagnostic method for intestinal lesions, although gammagraphic studies with marked red blood cells and capsule endoscopy studies play an important role in the study of occult hemorrhages.4 The treatment is based on iron supplementation and elective blood transfusions. To treat massive hemorrhages, the options are surgical resection, sclerosis or endoscopic band ligations, laser photocoagulation, or interferon therapy.5 Other treatments include corticosteroids, interferon-a, vincristine, and somatostatin analogues, such as octreotide (because it reduces blood flow to the gastrointestinal tract).5,6 Other affected regions that have been studied are the nasopharyngeal, ocular, thyroid, musculoskeletal, retroperitoneal, pleuro-pericardial, and
pulmonary regions, and the central nervous system, among others.7-10 The differential diagnosis of this pathology must be performed by comparing it with other diseaseentities involving cutaneous and visceral vascular malformations, such as the RendueOsler disease (which also involves pulmonary lesions), the Maffucci syndrome (ossification disorder and achondroplasia), the KlippeleTrenaunayeWeber syndrome (asymmetric bone and soft tissue hypertrophy in one limb), and the Von HippeleLindau disease (cerebellar and retinal angiomatosis).4 Although there are some familial forms of BRBNS characterized by sex-linked inheritance or by autosomal dominant inheritance (locus in chromosome 9),7-9 most of the cases are sporadic. Most patients have a normal life expectancy. However, their prognosis depends on the extension of visceral involvement. Systemic complications may occur, including thrombocytopenia, chronic lymphatic leukemia, or consumption coagulopathy.5 No malignant transformation of lesions has been described. The cystic lymphangioma is a congenital hamartomatous malformation of the lymphatic system that typically presents during infancy, and has a tendency to grow unless it is completely
Gallego et al.4
Nobuhara et al.15
Patient Etiology
8-year-old female Sporadic
Clinical presentation
Ferropenic anemia
47-year-old female 25-year-old female Family history of hereditary Sporadic hemangiomatosis (dominant autosomal heredity) Pancreatic cyst Abdominal mass and digestive hemorrhage
Cutaneous lesions Trunk and right lower limb hemangiomas Costal mass
Cutaneous lesion treatment
Digestive lesions
Treatment of digestive lesions Other imaging tests
Costal mass extirpation Conservative (hemolymphangioma) Excision of cutaneous lesions (hemangiomas) Polyps (Endoscopy) Hemangiomas in the ascending colon and in the esophagus Electrocauterization
No
Abdominal echography Abdominal and cranial CAT scan (to rule out visceral lesions) Gammagraphy with Tc99 Endoscopic capsule Histologic (cutaneous lesions)
Abdominal CAT scan Abdominal echography Cholangiopancreatography Laparoscopic biopsy (pancreatic cystic lymphangioma) Genetic study of peripheral leukocytes (Arg849Trp mutation)
CAT, computerized axial tomography; NMR, nuclear magnetic resonance.
Trunk, lower limbs, tongue, and pharynx hemangiomas
Flu¨gge et al.17
Marı´n-Manzano et al. (present study)
Premature male neonate Sporadic
4-year-old male Sporadic
Giant hemorrhagic tumor on thigh and in the gluteal region Cavernous lymphangioma in genitalia and thigh Skin hemangiomas
Chronic anemia
Hemangiomas in limbs Cervical cystic lymphangioma (surgical extirpation) No.
Sclerosis and ethanolization
No
Retro- and intraperitoneal hemangiomas (uterus, vagina, and intestine) with right hydronephrosis Resection with right nephrectomy, hysterectomy, and right oophorectomy Abdominal echography Abdominal CAT scan Angio-NMR of the abdomen
Small intestine, pleural, and diaphragmatic hemangiomas
Small intestine hemangiomas
No
Endoscopic sclerosis Surgical enterotomies
No
Cervical NMR Cervical echography
Histologic (CD31, CD34, Factor Post-mortem histological Histologic VIII, D2-40, subendothelial diagnosis: Genital collagen type-IV deposits.) and thigh lymphangioma Lymphomatous differentiation
Annals of Vascular Surgery
Diagnosis
Trunk and lip hemangiomas
Patel et al.16
1136.e4 Case reports
Table I. The association’s caseload in BRBNS and lymphangioma
Vol. 24, No. 8, November 2010
extirpated. About 75% of all cases are localized in the neck area.10 The lesions are not potentially malignant, yet they continue to progress, relapse (because of incomplete surgical procedures), or become overinfected. The treatment of choice is considered to be complete surgical exeresis of the cyst, while preserving the adjacent structures, bearing in mind that partial resections entail a high relapse rate. Other valid therapeutic options are diathermy therapy, radiotherapy, percutaneous sclerotherapy,11,12 and the intralesional injection of OK-432 (Picibanil). The latter two options have shown greater promise.11-14 Since it was first described in 1860,1 about 200 cases of BRBNS have been currently published. This represents a low incidence rate, although the true incidence is hard to estimate because of its rareness. The cases of cystic lymphangiomas associated with BRBNS are very few4,15-17 (refer to the association’s disease caseload on Table I); however, this association has described other vascular malformations, such as the Von HippeleLindau disease. Lymphomatous differentiation has been identified in the cells of Blue Rubber Bleb Nevus cutaneous lesions (focal expression of D2-40 lymphatic endothelial marker and patch stage immunoexpression of type-IV collagen in the subendothelial basement membrane)16 and a potential expression of the TIE2 gene in the endothelial cells of the lymphangioma15 indicates that the vascular lesions in the BRBNS are not limited to venous malformations. In this article, we presented a case of cervical cystic lymphangioma in a patient with previous diagnosis of BRBNS. Because of their shared embryological origin, we underscored the importance of the possibility that different types of vascular malformations might coexist in the same patient. REFERENCES 1. Gascoyen GG. Case of nevus involving the parotid gland and causing death from suffocation: nevi of the viscera. Trans Pathol Soc Lond 1860;11:267.
Case reports 1136.e5
2. Bean WB. Blue rubber bleb nevi of the skin and gastrointestinal tract. In: Bean WB ed. Vascular Spiders and Related Lesions of the Skin. Springfield, MA: Charles Thomas Publishers; 1958. pp 178-185. 3. Fishman SJ, Muliken JB. Vascular anomalies. A primer for pediatricians. Pediatr Clin North Am 1998;45:1455-1477. 4. Gallego PM, Arcocha TM, Lo´pez Casado MA, et al. Usefulness of labelled red cell scintigraphy in Blue Rubber Bleb Nevus syndrome. Rev Esp Med Nucl 2009;28:18-21. 5. Fishman SJ, Smithers J, Folkman J, et al. Blue rubber bleb nevus syndrome: surgical eradication of gastrointestinal bleeding. Ann Surg 2005;241:523-528. 6. Liu Q, Chen YP, Li YM. Blue rubber bleb nevus syndrome: a report of one case associated with recurrent epistaxis. Chin Med J 2007;120:731-733. 7. Domini M, Aquino A, Fakhro A, et al. Blue rubber bleb nevus syndrome and gastrointestinal haemorrhage: which treatment? Eur J Pediatr Surg 2002;12:129-133. 8. Carvalho S, Barbosa V, Santos N. Blue rubber-bleb nevus syndrome: report of a 151 familial case with a dural arteriovenous fistula. Am J Neuroradiol 2003;24:1916-1918. 9. Arguedas M, Shorf G, Wilcox M. Congenital vascular lesions of the gastrointestinal tract: blue rubber bleb nevus and klippeltrenaunay syndromes. South Med J 2001;94:405-410. 10. Gilbey LK, Girod CE. Blue rubber bleb nevus syndrome: endobronquial involvement presenting as chronic cough. Chest 2003;124:760-763. 11. Arzoz Fa`bregas M, IbarzServio Ll, Areal Calama J, et al. Linfangioma quı´stico. Nuestra experiencia. Actas Urol Esp 2006;30:723-727. 12. Won JH, Kim BM, Kim C, et al. Cystic lymphangioma. Our experience. Percutaneous sclerotherapy of lymphangiomas with acetic acid. J Vasc Interv Radiol 2004;15:595-600. 13. Alonso J, Barbier L, Alvarez J, et al. OK432 (picibanil) efficacy in an adult with cystic cervical lymphangioma. A case report. Med Oral Patol Oral Cir Bucal 2005;10:362-366. 14. Claesson G, Kuylenstierna R. OK-432 therapy for lymphatic malformation in 32 patients (28 children). Int J Pediatr Otolaryngol 2002;65:1-6. 15. Nobuhara Y, Onoda N, Fukai K, et al. TIE2 gain-of-function mutation in a patient with pancreatic lymphangioma associated with blue rubber-bleb nevus syndrome: report of a case. Surg Today 2006;36:283-286. 16. Patel RC, Zynger DL, Laskin WB. Blue rubber bleb nevus syndrome: novel lymphangiomatosis-like growth pattern within the uterus and immunohistochemical analysis. Hum Pathol 2009;40:413-417. 17. Flu¨gge R, Mu¨ller KM. Multilocular hemangiomatosis in combination with a lymphangioma in a premature infant. Relationship to "blue rubber bleb nevus.". Zentralbl Allg Pathol 1967;110:481-489.