Resident Program - Case of the Month

Discussion

Gorham-Stout Syndrome (Vanishing bone disease)
Gorham-Stout syndrome is an aggressive form of skeletal angiomatoses; Drs. Gorham and Stout first described this disease. It usually affects children or young adults, characterizes by progressive destruction/absorption of osseous matrix, and overgrowth of vascular structures. It involves multiple bones including the skull, the maxillofacial region, the spine and pelvis, the proximal parts of the appendicular skeleton, like this case, the proximal femur. The dilated cystic lesions can be noted grossly. The alkaline phosphatase may be slightly elevated. It is sporadic, and there is no evidence of hereditary transmission, and no gender predilection.

Radiograph features: The distinctive appearance on radiographs is: the involved bones demonstrate regions of complete lytic lesions, the residual ends tapered to show a characteristic feature of “licked candy stick”.

Microscopic features: The viable bones with remodeling changes (minimal osteoclastic activities at leading edge), multiple vascular spaces lined by attenuated endothelium, the vascular lesions are usually not numerous enough to produce mass-like lesion. However, evidence of local bone progressive resorption is usually present. Correlation with imaging studies is recommended.

Immunohistochemistry: Benign lymphovascular proliferation with network of thin-walled vessels highlighted by CD31, CD34, and D2-40. Due to the variable and unpredictable clinical course of massive osteolysis, and the reported serious complications in some cases, the treatment of choice is still evolving: surgical resection, radiation therapy, embolization, and systemic therapies i.e., bisphosphonates, sirolimus, steroids, and interferon-α have all been tried with various progressions.

Differential Diagnosis

1. Epithelioid Hemangioendothelioma: A male predominant disease (male-to-female ratio is 3.5:1) with variable age range. Synchronous lesion in paired bones (tibia and fibula) is common. Grossly, the tumor shows well-demarcated mass with irregular, peripheral margins. Histologically, the lesion reveals cords or clusters of round to polygonal epithelioid endothelial cells with/without narrow anastomosing vascular channels, large vascular lumens are usually not present. Some tumor cells show prominent intracytoplasmic vacuoles indicative of primitive vascular lumina; erythrocytes may be present in these vacuoles. The intracytoplasmic vacuoles may mimic signet ring cells. Mixed inflammatory cells are frequently noted. The lesion may also have focal focal myxoid/chondroid stroma. Tumor cells show variable expression of CD31, CD34, and ERG. Some tumors express epithelial membrane antigen (EMA) and cytokeratin (low molecular weight).
   
   
2. Angiosarcoma: Contrary to Gorham-Stout syndrome, Angiosarcoma rarely occurs in patients younger than 30 years old, with a male-to-female ratio about 1.5:1.  Grossly, the lesion usually has spongy, bloody red tissue with foci of trabecular bone; solid areas with necrosis are also frequently noted. Histologically, the lesion demonstrates blood vessels with irregular configuration; malignant endothelial cells often grow in solid stratified clusters and create intraluminal tufts or papillae. In poorly differentiated patterns, the vascular pattern may not be well appreciated. Neoplastic cells have higher degree of cytologic atypia and frequent mitotic figures. Necrosis and hemorrhage are also present. Tumor cells express CD31, CD34, and ERG. Cytokeratin is typically negative in angiosarcoma, except for the epithelioid pattern.
   
   
3. Lymphangioma/Lymphangiomatosis: There is no sex pre¬dilection. The disease affects all age groups, but most cases present in young individuals. The disease is a benign bone/soft tissue tumor composed of lymphatic vessels, which rarely involves spine. If involves multiple discrete bone with/without soft tissue involvement, it is named as lymphangiomatosis. Clinical symptoms depend on extent of disease. Grossly, the lesion shows sponge-like cavities, which is filled with clear or straw-colored fluid. Histologically, the lesion shows thin-walled vascular spaces lined with flat endothelial cells. The vascular spaces may have irregular configuration, and are filled with proteinaceous fluid, erythrocytes are frequently noted in vascular spaces. The endothelial cells express D2-40, CD31, and CD34.
   
   
4. Aneurysmal Bone Cyst: Most of the cases (~75%) presents in the first two decades of life. Male-to-female ratio is about 1.3:1. Grossly, the lesion shows expanded destructive change with blood/ serosanguineous fluid filled cavities, which is separated by thin, tan white fibrous septa. Radiograph shows characteristic lytic lesion with "blow out" or marked expansion of bone.  The fluid-fluid levels present in the cystic spaces. Histologically, the wall of blood-filled cystic spaces is composed of spindle cells without an endothelial lining. Scattered osteoclast-like giant cells, fibroblasts, inflammatory cells, and reactive woven bone are present in the fibrous septa, which is lacking smooth muscle.  Foci of chondroid area are also characteristic of aneurysmal bone cysts. There is no atypical mitosis or stromal cell nuclear anaplasia. Immunohistochemistry is noncontributory, however, cytogenetic and molecular studies identified presence of t(16;17).

References

1. Leong S et al: The radiologic diagnosis and treatment of typical and atypical bone hemangiomas: Current Status. Can Assoc Radiol J. 67(1):2-11, 2016
2. Arbajian E et al: A benign vascular tumor with a new fusion gene: EWSR1-NFATC1 in hemangioma of the bone. Am J Surg Pathol. 37(4):613-6, 2013
3. Wenger DE et al: Benign vascular lesions of bone: radiologic and pathologic features. Skeletal Radiol. 29(2):63-74, 2000
4. Cannon SR: Massive osteolysis. a review of seven cases. J Bone Joint Surg Br. 68(1):24-8, 1986
5. Wold LE et al: Vascular lesions of bone. Pathol Annu. 20 Pt 2:101-37, 1985
6. Bogdan Czerniak et al: Dorfman and Czerniaks Bone Tumors. Chapter 13: 903-931, 2016
7. Vasileios S Nikolaou et al: Vanishing bone disease (Gorham-Stout syndrome): A review of a rare entity. World J Orthop. 18; 5(5): 694-698, 2014