UPMC Dermatopathology "Case of the Month" Presentations
UPP - Department of Dermatology, Dermatopathology Unit
Case Authors: Robin P. Gehris, MD, Douglas S. Kress, MD, Suzan Obagi, MD, Drazen Jukic, MD, PhD
OCTOBER 2004 CASE OF THE MONTH
DISCUSSION & DIAGNOSIS
DIAGNOSIS
Final Diagnosis: These pathologic findings are consistent with a diagnosis of cavernous hemangioma (also known as cavernous malformation or venous malformation).
DISCUSSION
Histopathology:
Hematoxylin and eosin staining of a four-millimeter punch biopsy performed on a lesion from the father's back revealed a network of dilated vascular channels in the deep dermis. The vessel walls were composed of a single, thin endothelial layer surrounded by fibrous tissue. This venous malformation was noted to dissect between both eccrine glands and erector pili muscles. No lymphatic or arterial components were visualized, and no glomus cells were seen in the walls of the dilated vessels. [see: FIGURE 5, FIGURE 6, FIGURE 7 ].
Cavernous hemangiomas can occur in isolation or as multiple lesions, in which case one should suspect an underlying syndrome. The two predominant syndromes characterized by the appearance of multiple cavernous hemangiomas are Bean syndrome (also known as blue rubber bleb nevus syndrome) and Mafucci's syndrome.
Bean syndrome is most commonly distributed sporadically but can also be transmitted in an autosomal dominant fashion. It is characterized by the appearance either at birth or in early childhood of multiple soft, easily-compressible red-blue macules or papules located on the trunk, face and upper arms; however, new lesions may occur later in life and in any location. Nahm et al. report a series of three cases, one of which was detected first on prenatal ultrasound and the others of which had no evident cutaneous lesions at birth. Three subtypes of Bean syndrome have been described: Type I presents with a large venous malformation which can be disfiguring and obstruct other tissues; Type II, the most common subtype, presents with multiple "nipple-like" rubbery blue nodules that are easily compressible but can be associated with pain; Type III presents with less dramatic blue-black macules or papules that may even merge with nearby pigmented lesions and may blanch with pressure. Importantly, patients with any of these subtypes can also develop similar lesions in extracutaneous sites, notably the gastrointestinal tract, lung, kidney, oral mucosa and central nervous system, leading to
complications in these areas. By far the most common of the above extracutaneous sites of involvement is the gastrointestinal tract, specifically the small intestine. Patients should therefore be screened for occult or overt gastrointestinal blood loss, since the lesions in this location are prone to frequent bleeding and can lead to a chronic low-grade anemia if left untreated. Cases of thrombocytopenia and low-grade but chronic consumptive coagulopathy have been described secondary to numerous vascular malformations. Cavernous hemangiomas in the GI tract can also serve as lead-points for an intussusception or volvulus, leading to acute ischemia. The clinical differential diagnosis of the blue rubber bleb nevus syndrome is a familial syndrome with multiple glomangiomas. While this has also been described to be transmitted as an autosomal dominant trait, it can occur sporadically. In contrast to a single glomangioma, which is often painful, multiple glomangiomas are not characteristically symptomatic. They can clinically appear similar to the cavernous hemangiomas in blue rubber bleb nevus syndrome; however on histopathology they are distinguished by the presence of several layers of glomus cells lining the cavernous vascular channels.
Mafucci's syndrome, on the other hand, is characterized by cavernous hemangiomas, lymphatic malformations and phlebectasias in combination with multiple endochondromas, which can result in bony deformities and fractures. An important implication of Mafucci's syndrome is the future risk for development of chondrosarcomas and angiosarcomas in up to 50% of patients, a risk that does not accompany Bean syndrome.
Finally, a cavernous hemangioma may be seen alone or as part of any other other combined vascular malformation, such as arteriovenous or lymphaticovenous malformations, in which case they are not usually associated with a specific heritable syndrome.
Based on the combination of the clinical findings illustrated above and the histopathologic confirmation of cavernous hemangiomas, a diagnosis of Bean syndrome, likely of the subtype III, was made. Both our patient and her father were hence screened with routine blood and platelet counts as well as a mean corpuscular volume and reticulocyte count, all of which were well within normal limits. They also obtained stool heme occult testing, which was positive for blood in the father. He has since been referred to gastroenterology for a colonoscopy to rule out cavernous hemangiomas in the bowel; he has also been referred to nephrology to investigate the cause of the renal lesion that was detected on CT scan, secondary to the concern that this lesion could represent a cavernous hemangioma that could be intermittently bleeding or causing a temporary obstruction coincident with his intermittent boughts of acute flank and abdominal pain.
Treatment options for the cavernous hemangiomas in Bean syndrome include surgical resection, electrodessication, selective sclerotherapy and laser. Of those listed, the pulsed dye laser has been reported as the most effective way to treat multiple lesions with the lowest risk for recurrence. However, in the absence of morbidity or patient concern, expectant management is also a reasonable option. It is recommended that periodic heme occult testing be performed to rule out GI involvement. If suspected, an appropriate thorough workup should follow, including abdominal x-ray to look for phleboliths in intestinal lesions that may have thrombosed, barium studies to rule out filling defects (although this study has low sensitivity, as smaller lesions may easily be missed), angiography to visualize actively bleeding lesions, endoscopy or CT/ MRI. The family discussed in this report will be closely followed on a biannual basis to monitor for any associated extracutaneous involvement of Bean syndrome.
REFERENCES
1. Barnhill RL, Busam KJ, Crowson AN, et al. Textbook of Dermatolpathology. 1998.
2. Boon LM, Mulliken JB, Enjolras O, Vikkula M. Glomoveous Malformations (Glomangioma) and Venous Malformation: Distinct Clinicopathological and Genetic Entities. Arch Dermatol 2004; 140(8): 971-976.
3. Jackson JF, Przlepa KA. Blue Rubber Bleb Nevus. Online Mendelian Inheritance in Man.
4. Nahm WK, Moise S, Eichenfield LF, Paller AS, Nathanson L, Malicki DM et al. Venous lamformations in blue rubber bleb nevus syndrome: Variable onset of presentation. J Am Acad Derm 2004; 50(5): S101-106.