Blue Rubber Bleb Nevus Syndrome

Back

Background

Blue rubber bleb nevus syndrome (BRBNS) is a rare condition that is characterized by numerous malformations of the venous system that significantly involve the skin and visceral organs.[1] This condition was initially discovered in 1860 by Gascoyen.[1] However, it was later made famous in 1958, by William Bennett Bean for which the disease has been termed "bean syndrome," later referenced as blue rubber bleb nevus syndrome.[1] BRBNS is an important condition due to the potential for significant bleeding which can be fatal.

Also see the article, Dermatologic Manifestations of Gastrointestinal Disease.

Note the images below.



View Image

Multiple scattered blue to black rubbery papules and nodules involving the mid-chest region.



View Image

Purple to blue/black papules involving the upper and lower lips.



View Image

Multiple blue to black pigmented, rubbery, blood-filled sacs, which are easily compressible involving the GI tract.

Pathophysiology

Skin manifestations can typically be found at birth, whereas, organ system involvement tends to appear later in life.[1] The internal organ system most frequently involved is the GI system, for which GI bleeding is a common symptom.[2] Therefore, GI bleeding can lead to anemia and severe cases of hemorrhage may require transfusion therapy.[2] Additional complications include telescoping of the intestines, volvulus, and necrosis of the intestinal mucosa.[3] In addition, multiple vascular blebs and nodules can be found throughout the body. Case reports have demonstrated involvement of the CNS, thyroid, parotid, eyes, oral cavity, musculoskeletal, oral cavity, lungs, liver, spleen, and bladder. Although, literature suggests the coexistence of CNS with GI symptoms, they are still rare.[3]

Histopathologic examination of the lesions will reveal ecstatic vascular dilated spaces filled with endothelial cells forming a single layer, surrounded by connective tissue.[4]

Etiology

The etiology of blue rubber bleb nevus syndrome (BRBNS) remains unknown.[5] The literature suggests that this condition occurs sporadically.[5, 6] A few reported cases have been associated with an autosomal dominant inheritance pattern, for which a locus was found on chromosome 9p.[5, 7]

Epidemiology

Frequency

Blue rubber bleb nevus syndrome (BRBNS) is a rare condition with about 200 cases reported in the literature.[6] The exact etiology of this disease remains unknown.[5] Most cases occur sporadically.[5, 6] A few reported cases have been associated with an autosomal dominant inheritance pattern with a locus found on chromosome 9p.[5, 7]

One case report of BRBNS was discovered to be associated with pancreatic lymphangiomas. The systemic vascular lesions found in that case were linked to a familial germ line functional mutation (Arg849Trp) in the TIE2 gene.[8]

Race

Blue rubber bleb nevus syndrome (BRBNS) has been reported to occur in people of all races;[9] however, whites appear to be most frequently affected.

Sex

Blue rubber bleb nevus syndrome (BRBNS) affects both males and females equally.[3, 6]

Age

Skin manifestations of blue rubber bleb nevus syndrome (BRBNS) typically can be present at birth or evident in early childhood.[1] Visceral organ involvement tends to appear later in life, traditionally around early adulthood.[1]

Prognosis

The morbidity related to this condition depends on the extent of GI involvement, ranging from minimal to invasive.[1, 10] To date the literature supports no evidence of a carcinogenetic or fatal conversion of this condition.[10] Therefore, the malignancy potential has not yet been determined.[10] A complication of this condition is profound GI hemorrhage, which can lead to death.[1, 10] Serial transfusions and periodic surveillance can modify the morbidity of the disease. Lesions involving bones and joints can cause profound discomfort and loss of function, requiring amputations in some cases. Rarely, CNS involvement can be fatal.[11]

The prognosis for blue rubber bleb nevus syndrome (BRBNS) depends on the extent of visceral organ involvement and complications related to the degree of symptoms. Most patients are expected have a normal life span.

History

The lesions of blue rubber bleb nevus syndrome (BRBNS) are asymptomatic; however, some may be spontaneously painful or tender to palpation. Patients with this condition may present for evaluation secondary to concerns related to its cosmetic appearance. BRBNS is characterized clinically by numerous violaceous to dark blue colored soft papules and nodules that are compressible in nature.[10] These lesions termed "blebs" contain a discriminate rubberlike consistency upon palpation.[10] Patients with BRBNS may note increased sweating on the skin overlying the lesion.

Presenting complaints and symptoms are directly related to the degree and extent of organ system involvement. Fatigue and weakness may be due to underlying occult blood loss. Other symptoms that could prompt emergent evaluation include hematemesis, melena or frank rectal bleeding. When bone is involved, symptoms may include joint pain or impaired ambulation. Extracutaneous lesions may also result in epistaxis, hemoptysis, hematuria, or menorrhagia. Other rare complications include dementia, ataxia and coagulopathy.[12] Patients may present with blindness due to cerebral or cerebellar cavernomas that may hemorrhage into the occipital lobes.[3]

Physical Examination

Physical findings in blue rubber bleb nevus syndrome (BRBNS) are divided into cutaneous and extracutaneous manifestations.

Cutaneous manifestations of BRBNS

Skin lesions are usually multiple, protuberant, dark blue, compressible blebs, a few millimeters to several centimeters in diameter and can vary in morphological shape. The lesions have a characteristic rubbery consistency upon palpation. They may range from few in number to hundreds of skin lesions. See the image below:



View Image

Lower extremity cutaneous lesions described in blue rubber bleb nevus syndrome, consisting of blue rubbery papules and nodules with an easily compress....

Three types of cutaneous lesions have been described in BRBNS: (1) blue, rubbery, blood-filled sacs with a smooth or wrinkled surface that are easily compressible and promptly refill when pressure is removed; (2) large, disfiguring, cavernous lesions that may compress vital structures; and (3) blue, irregular macules.

The color of cavernous lesions may appear red, purple-red, blue, or black, and morphology varies from flat to elevated, occasionally pedunculated, nodules.

Lesions may exhibit tenderness to palpation or underlying hyperhidrosis.

BRBNS skin lesions rarely bleed unless traumatized.

The progression in size and number of blebs may occur with advancing age.

The lesions are principally located on the upper limbs, trunk, and perineum, but they may occur anywhere.[13]

One case report has even described a unilateral configuration of linear lesions following the lines of Blaschko.[14]

Using polarized light, the dermatoscopic features reveal homogeneous macular blue to red-purple lesions that are separated by linear white bands.[4, 15]

Extracutaneous manifestations of BRBNS

The GI tract is the most common visceral organ affected. The small bowel is the most predominant region involved; however, vascular malformations can occur in any site in the body from the oral cavity to the anal mucosa. In contrast to the skin lesions, the GI lesions often have a tendency to bleed. They may spontaneously rupture, causing acute hemorrhage and death. However, most bleeding from the GI tract tends to progress relatively slowly, resulting in minor, chronic, and occult blood loss. This can eventually lead to an iron deficiency anemia from the ongoing bleeding. A case of thrombocytopenia and disseminated intravascular coagulation has been reported in association with BRBNS. Other complications include intussusception, volvulus, and bowel infarction. These diagnoses should be considered in patients with BRBNS and abdominal pain.

Orthopedic manifestations[16, 17] include skeletal bowing, pathologic fractures, bony overgrowth, and articular derangement. Bone deformities may arise as a result of pressure effects from adjacent vascular lesions. Vertebral lesions have caused spinal cord compression and vertebral collapse, and the lesions may extend into joint spaces affecting range of motion.[18] Extensive lesions also have been reported on the feet, impairing ambulation. Debilitating enlargement occasionally requires amputation of the affected limb.

Blue rubber bleb nevi have been reported in the skull, CNS, thyroid, parotid, eyes, oral cavity, lungs, pleura, pericardium, musculoskeletal system, peritoneal cavity, mesentery, kidney, liver, spleen, penis, vulva, and bladder.

Recurrent thromboembolic events from shunts in visceral lesions led to the development of pulmonary hypertension in one case,[19]  and another reported pulmonary stenosis.[20]

Complications

The rare complications of blue rubber bleb nevus syndrome (BRBNS), include, acute GI hemorrhage and central nervous system involvement, which result in death.

Pregnancy and BRBNS

Pregnancy has been shown to increase the size of vascular lesions due to the changes in the circulating hormones most evident by the third trimester.[21] Therefore, vascular malformations may manifest sporadically or increasing in size during pregnancy.[21]

In a study by Suksamanapun et al, they suggest that pregnant women, who may have the option to deliver vaginally with BRBNS, must consider the potential for underlying complications.[22] Pregnant women with BRBNS should undergo routine obstetrical care as well as obtain baseline laboratory evaluation and then monthly monitoring due to increased risk for hematological complications.[22] The studies suggest fibrinogen and D-dimers are to be monitored monthly to evaluate for associated clotting dysfunction. A thorough genital examination should also be performed in the antenatal period evaluating for genital hemangiomas or vascular malformations which may complicate the delivery process.[22]

Laboratory Studies

The following laboratory studies might be warranted:

Imaging Studies

Radiographic imaging of suspected bone and joint involvement can be useful in identifying fractures, bony overgrowth, and articular abnormalities. Radiographic images in blue rubber bleb nevus syndrome (BRBNS) may be useful in suspected bone or joint involvement to detect fractures, bony overgrowth, and articular derangement. Radiographic contrast techniques may detect GI lesions, but endoscopy is considered to be superior.

MRI has been described as a useful tool for detecting extracutaneous lesions and for screening asymptomatic family members.[23]

Technetium Tc-99m–labeled red blood cell imaging may be helpful to localize or delineate the extent of bleeding in patients with blue rubber bleb nevus syndrome.[24]

CT scans can be useful to assess for underlying complications such as volvulus, intussusception, infarction, and GI bleeding.[2]

Procedures

Endoscopy may be warranted in blue rubber bleb nevus syndrome (BRBNS). GI lesions may be demonstrated by endoscopic examination or by radiographic contrast techniques. Upper GI endoscopy is more sensitive than an upper GI series and colonoscopy more useful than a barium enema. Endoscopy also provides the opportunity to treat and diagnose the lesions.[25, 26]

Histologic Findings

Histopathologic examination of skin blue rubber bleb nevus syndrome (BRBNS) lesions reveals vascular tissue with tortuous, blood-filled ectatic vessels, lined by a single layer of endothelium, with surrounding thin connective tissue. Dystrophic calcification may be present. See the image below.



View Image

Histopathology reveals blood-filled vessels, composed of single layers of endothelium, surrounded by connective tissue.

Medical Care

The literature suggests no standard of care or systemic treatment regimen is available for blue rubber bleb nevus syndrome (BRBNS). One report of BRBNS indicated the successful use of interferon-beta to treat the manifestations of disseminated intravascular coagulation in one patient with disseminated skin and GI venous malformations.[27] Another report describes long-term subcutaneous octreotide therapy as successful as decreasing GI bleeding in BRBNS.[28]  One report describes successful treatment with oral sirolimus.[29]

Surgical Care

Surgical treatment of cutaneous lesions in blue rubber bleb nevus syndrome (BRBNS)

The treatment of cutaneous lesions is not usually required. Treatment is rendered for cosmetic purposes or for the management of symptomatic lesions. Malignant transformation of BRBNS lesions has not been reported.

Methods to remove lesions include electrodesiccation and curettage, liquid nitrogen, and excision. These treatment options can lead to recurrent skin lesions and abnormal healing, such as hypertrophic scars. Successful treatment without scarring has been reported with the use of the carbon dioxide laser. Treatment of 225 lesions without recurrence was reported with the use of the carbon dioxide laser.[30]

Surgical treatment of extracutaneous lesions in BRBNS

Bleeding from GI lesions is usually managed conservatively with iron supplementation and blood transfusions when necessary. Endoscopic coagulation or removal is an effective modality for repeated bleeding. Experience with endoscopic sclerotherapy suggests that it is ineffective and complicated by the development of ulcerations and strictures. Other therapeutic management modalities for BRBNS include Nd:YAG laser, bipolar or argon plasma coagulation, band ligation, sclerotherapy and snare resection.[31, 32]

One study even reported the successful treatment of mucocutaneous lesions of BRBNS with NdYag.[33]

The literature suggests treatment options include glubran 2 injections, which have been successfully used in the management of gastric varices.

Other treatments described include endoscopic obliteration of cavernous hemangiomas with n-butyl-2-cyanoacrylate (Histoacryl).[31]

When traditional methods fail and the vascular lesions are confined to a segment of the GI tract, resection of the involved segment of gut may be indicated. This approach should be used with caution because recurrences may occur after excision.[34] Diffuse and scattered lesions or those where operation is not feasible should be treated conservatively.

Orthopedic lesions are managed with orthotics and supportive measures, unless impaired function necessitates surgery.

An 8-month old infant with bleeding hemangiomas of the rectum and colon was successfully treated with argon plasma coagulation. This treatment resulted in long-term success.[35]

In one report, an aggressive surgical approach to the treatment of blue rubber bleb nevus syndrome was attempted in 10 patients. GI venous malformations were identified endoscopically and then treated by wedge resection, polypectomy, suture ligation, segmental bowel resection, or band ligation. Only one patient developed recurrent GI bleeding.[36]

Multiple hemangiomas of the terminal ileum and colon were treated endoscopically in an adult female with the argon plasma coagulator.[37]

Consultations

Patients with blue rubber bleb nevus syndrome (BRBNS) should be referred to a gastroenterologist for management of GI manifestations.

Orthopedics should be consulted to assist in the care management of bone or joint related complications.

Additional referrals should be made to the appropriate specialists and treatment teams depending on the extent and nature of organ system involvement.

Genetic testing and counseling should be considered in cases with familial occurrence.

Long-Term Monitoring

The formation of new GI lesions in blue rubber bleb nevus syndrome (BRBNS) may continue to occur; therefore, periodic GI and hematologic surveillance studies should be instituted.

Author

Basil S Cherpelis, MD, Associate Professor, Chief of Dermatologic Surgery, Department of Dermatology and Cutaneous Surgery, Associate Professor, Department of Oncologic Sciences, University of South Florida College of Medicine; Consulting Staff, Moffitt Cancer Center, Tampa General Hospital, and James A Haley Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Neil Alan Fenske, MD, Chairman, Department of Dermatology and Cutaneous Surgery, Professor, Department of Dermatology and Cutaneous Surgery, Department of Pathology and Cell Biology, Department of Oncologic Sciences, Medical Director, Health Cosmetic and Laser Center, University of South Florida College of Medicine

Disclosure: Received none from Abbvie for speaking and teaching; Received none from Valeant for speaking and teaching.

Specialty Editors

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Disclosure: Nothing to disclose.

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Hoka Lisa Nyanda, MD, Academic Chief Resident, Department of Dermatology and Cutaneous Surgery, University of South Florida College of Medicine

Disclosure: Nothing to disclose.

References

  1. Suksamanapun N, Trakarnsanga A, Akaraviputh T. Blue rubber bleb nevus syndrome. Endoscopy. 2011 Dec. 43 Suppl 2 UCTN:E411-2. [View Abstract]
  2. Senturk S, Bilici A, Miroglu TC, Bilek SU. Blue rubber bleb nevus syndrome: imaging of small bowel lesions with peroral CT enterography. Abdom Imaging. 2011 Oct. 36(5):520-3. [View Abstract]
  3. Huang W, Rhodes A. A Case of Blue Rubber Bleb Nevus Syndrome with Gastrointestinal and Central Nervous System Involvement. Pediatr Dermatol. 2011 Oct 20. [View Abstract]
  4. Turk BG, Turkmen M, Karaarslan IK, et al. Blue rubber bleb nevus syndrome: a case report with dermatoscopic features. Clin Exp Dermatol. 2011 Mar. 36(2):211-3. [View Abstract]
  5. Krishnappa A, Padmini J. Blue rubber bleb nevus syndrome. Indian J Pathol Microbiol. 2010 Jan-Mar. 53(1):168-70. [View Abstract]
  6. Agnese M, Cipolletta L, Bianco MA, Quitadamo P, Miele E, Staiano A. Blue rubber bleb nevus syndrome. Acta Paediatr. 2010 Apr. 99(4):632-5. [View Abstract]
  7. Hasosah MY, Abdul-Wahab AA, Bin-Yahab SA, Al-Rabeaah AA, Rimawi MM, Eyoni YA. Blue rubber bleb nevus syndrome: extensive small bowel vascular lesions responsible for gastrointestinal bleeding. J Paediatr Child Health. 2010 Jan. 46(1-2):63-5. [View Abstract]
  8. Nobuhara Y, Onoda N, Fukai K, Hosomi N, Ishii M, Wakasa K. 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(3):283-6. [View Abstract]
  9. Fleischer AB Jr, Panzer SM, Wheeler CE. Blue rubber bleb nevus syndrome in a black patient: a case report. Cutis. 1990 Feb. 45(2):103-5. [View Abstract]
  10. Yuksekkaya H, Ozbek O, Keser M, Toy H. Blue rubber bleb nevus syndrome: successful treatment with sirolimus. Pediatrics. 2012 Apr. 129(4):e1080-4. [View Abstract]
  11. Park CO, Park J, Chung KY. Blue rubber bleb nevus syndrome with central nervous system involvement. J Dermatol. 2006 Sep. 33(9):649-51. [View Abstract]
  12. Esposito C, Giurin I, Farina A, Ascione G, Miele E, Staiano A. Blue rubber bleb nevus: an uncommon cause of intestinal intussusception. Eur J Pediatr. 2012 Jul. 171(7):1139-40. [View Abstract]
  13. Starr BM, Katzenmeyer WK, Guinto F, Pou AM. The blue rubber bleb nevus syndrome: a case with prominent head and neck findings. Am J Otolaryngol. 2005 Jul-Aug. 26(4):282-4. [View Abstract]
  14. Xu Y, Zhou B, Zhang M, Luo D. An unusual case of blue rubber bleb nevus syndrome with unilateral linear distribution. Indian J Dermatol Venereol Leprol. 2013 Mar-Apr. 79(2):269-70. [View Abstract]
  15. Mejia-Rodriguez S, Valencia-Herrera A, Escobar-Sanchez A, Mena-Cedillos C. Dermoscopic features in Bean (blue rubber bleb nevus) syndrome. Pediatr Dermatol. 2008 Mar-Apr. 25(2):270-2. [View Abstract]
  16. McCarthy JC, Goldberg MJ, Zimbler S. Orthopaedic dysfunction in the blue rubber-bleb nevus syndrome. J Bone Joint Surg Am. 1982 Feb. 64(2):280-3. [View Abstract]
  17. Doi T, Masumoto N, Sonoda M, Nakayama H, Mizuno Y. Blue rubber bleb nevus syndrome with knee joint disorder. Pediatr Int. 2016 Apr 26. [View Abstract]
  18. Garen PD, Sahn EE. Spinal cord compression in blue rubber bleb nevus syndrome. Arch Dermatol. 1994 Jul. 130(7):934-5. [View Abstract]
  19. Giordano C, Battagliese A, di Gioia CR, et al. Blue rubber bleb nevus syndrome and pulmonary hypertension: an unusual association. Cardiovasc Pathol. 2004 Nov-Dec. 13(6):317-22. [View Abstract]
  20. Singal A, Vohra S, Sharma R, Bhatt S. Blue Rubber Bleb Nevus Syndrome with Musculo-skeletal Involvement and Pulmonary Stenosis. Indian Pediatr. 2016 Jun 8. 53 (6):525-7. [View Abstract]
  21. Ochiai D, Miyakoshi K, Yakubo K, Fukuiya T, Yoshimura Y. Familial blue rubber bleb nevus syndrome in pregnancy with spinal epidural involvement. Case Rep Obstet Gynecol. 2013. 2013:141506. [View Abstract]
  22. Bouchghoul H, Nizard J. Pregnancy and blue rubber bleb nevus syndrome. Eur J Obstet Gynecol Reprod Biol. 2013 Jul. 169(2):415-6. [View Abstract]
  23. Shannon J, Auld J. Blue rubber bleb naevus syndrome associated with cortical blindness. Australas J Dermatol. 2005 Aug. 46 (3):192-5. [View Abstract]
  24. Yarlagadda R, Menda Y, Graham MM. Tc-99m red blood cell imaging in a patient with blue rubber bleb nevus syndrome. Clin Nucl Med. 2008 May. 33(5):374-6. [View Abstract]
  25. Bak YT, Oh CH, Kim JH, Lee CH. Blue rubber bleb nevus syndrome: endoscopic removal of the gastrointestinal hemangiomas. Gastrointest Endosc. 1997 Jan. 45(1):90-2. [View Abstract]
  26. Gallo SH, McClave SA. Blue rubber bleb nevus syndrome: gastrointestinal involvement and its endoscopic presentation. Gastrointest Endosc. 1992 Jan-Feb. 38(1):72-6. [View Abstract]
  27. Apak H, Celkan T, Ozkan A, Yildiz I, Aydemir EH, Ozdil S, et al. Blue rubber bleb nevus syndrome associated with consumption coagulopathy: treatment with interferon. Dermatology. 2004. 208(4):345-8. [View Abstract]
  28. Gonzalez D, Elizondo BJ, Haslag S, Buchanan G, Burdick JS, Guzzetta PC, et al. Chronic subcutaneous octreotide decreases gastrointestinal blood loss in blue rubber-bleb nevus syndrome. J Pediatr Gastroenterol Nutr. 2001 Aug. 33(2):183-8. [View Abstract]
  29. Salloum R, Fox CE, Alvarez-Allende CR, Hammill AM, Dasgupta R, Dickie BH, et al. Response of Blue Rubber Bleb Nevus Syndrome to Sirolimus Treatment. Pediatr Blood Cancer. 2016 Jun 8. [View Abstract]
  30. Olsen TG, Milroy SK, Goldman L, Fidler JP. Laser surgery for blue rubber bleb nevus. Arch Dermatol. 1979 Jan. 115(1):81-2. [View Abstract]
  31. Mavrogenis G, Coumaros D, Tzilves D, Rapti E, Stefanidis G, Leroy J. Cyanoacrylate glue in the management of blue rubber bleb nevus syndrome. Endoscopy. 2011. 43 Suppl 2 UCTN:E291-2. [View Abstract]
  32. Morris L, Lynch PM, Gleason WA Jr, Schauder C, Pinkel D, Duvic M. Blue rubber bleb nevus syndrome: laser photocoagulation of colonic hemangiomas in a child with microcytic anemia. Pediatr Dermatol. 1992 Jun. 9(2):91-4. [View Abstract]
  33. Moser CM, Hamsch C. Successful treatment of cutaneous venous malformations in a patient with blue rubber bleb naevus syndrome by Nd:YAG laser. Br J Dermatol. 2012 May. 166(5):1143-5. [View Abstract]
  34. Nakajima H, Nouso H, Urushihara N, Fukumoto K, Yamoto M, Miyake H, et al. Blue Rubber Bleb Nevus Syndrome with Long-Term Follow-Up: A Case Report and Review of the Literature. Case Rep Gastrointest Med. 2018. 2018:8087659. [View Abstract]
  35. Ng WT, Kong CK. Argon plasma coagulation for blue rubber bleb nevus syndrome in a female infant. Eur J Pediatr Surg. 2003 Apr. 13(2):137-9. [View Abstract]
  36. Fishman SJ, Smithers CJ, Folkman J, Lund DP, Burrows PE, Mulliken JB, et al. Blue rubber bleb nevus syndrome: surgical eradication of gastrointestinal bleeding. Ann Surg. 2005 Mar. 241(3):523-8. [View Abstract]
  37. Ng EK, Cheung FK, Chiu PW. Blue rubber bleb nevus syndrome: treatment of multiple gastrointestinal hemangiomas with argon plasma coagulator. Dig Endosc. 2009 Jan. 21(1):40-2. [View Abstract]

Multiple scattered blue to black rubbery papules and nodules involving the mid-chest region.

Purple to blue/black papules involving the upper and lower lips.

Multiple blue to black pigmented, rubbery, blood-filled sacs, which are easily compressible involving the GI tract.

Lower extremity cutaneous lesions described in blue rubber bleb nevus syndrome, consisting of blue rubbery papules and nodules with an easily compressible smooth surface.

Histopathology reveals blood-filled vessels, composed of single layers of endothelium, surrounded by connective tissue.

Multiple scattered blue to black rubbery papules and nodules involving the mid-chest region.

Purple to blue/black papules involving the upper and lower lips.

Multiple blue to black pigmented, rubbery, blood-filled sacs, which are easily compressible involving the GI tract.

Lower extremity cutaneous lesions described in blue rubber bleb nevus syndrome, consisting of blue rubbery papules and nodules with an easily compressible smooth surface.

Histopathology reveals blood-filled vessels, composed of single layers of endothelium, surrounded by connective tissue.