Are You Confident of the Diagnosis?
Characteristic findings on physical examination
Spindle cell hemangiomas (SCH) present as slowly growing, vascular-appearing, solitary or multiple, dermal or subcutaneous nodules with a preference for the distal extremities. Deeper lesions may appear skin-colored, but superficial SCH are frequently blue. Both may contain phleboliths, which are palpated as hard palpable nodules within the lesion.
SCH are often found within or associated with other vascular malformations such as in the setting of Klippel-Trenaunay syndrome. Many patients give a history of SCH appearing at sites of prior trauma, injection, or excision.
Multifocal lesions can be a manifestation of Mafucci syndrome.
SCH seem to occur most commonly in middle-aged adults, but may appear at any age, and even have been reported to be present at birth. Occasionally, they may be described as painful, but more often they are asymptomatic. SCH are typically present for years before patients seek medical attention. Most patients present for evaluation because of aesthetic concerns.
The natural history of SCH includes a tendency to local expansion, recurrence after treatment, and, in those cases with Maffuci syndrome, multifocal disease.
Lesions tend to be confined to a specific region of the body. Despite locally aggressive behavior, however, metastasis virtually never occurs; long-term follow-up from multiple studies does not support the original concept that these lesions are a form of low-grade angiosarcoma. The one case of reported metastatic SCH likely represents a radiation-induced malignant transformation of SCH. The tendency towards recurrence likely is a result of occult contiguous intravascular growth.
Expected results of diagnostic studies
Magnetic resonance imaging (MRI) evaluation is well suited to determine the extent of the tumor; findings are similar to that of venous malformation, showing signal intensity greater than muscle on T1 and proton density spin echo images. There is also high signal intensity using T2-weighted spin echo magnetic resonance sequences. Phleboliths can often present as round low signal intensity flow voids, just as in venous malformations.
While the clinical appearance of these lesions should allow the experienced dermatologist to recognize that they are vascular tumors, specific diagnosis is most often made using tissue biopsy with punch or shave biopsy. Histologic evaluation of the tissue will often reveal a proliferation of well-circumscribed nodules that are “biphasic” in nature and consist of spindle cells containing a stromal component which separates cavernous endothelial lined spaces.
The spindle cells making up this stromal component do not manifest atypia, and mitoses are few. The cells are organized into fascicles and slit-like spaces. The dilated vascular channels often contain thrombi and are lined by plump endothelial cells, which may have foci of cytoplasmic vacuoles. Many SCH seem to arise within malformed venous channels or near large veins or arteries.
The thrombi and plump endothelial cells are features that differentiate SCH histologically from Kaposi’s sarcoma and intravascular papillary endothelial hyperplasia—two diagnoses often entertained when examining SCH under the microscope. Also, the slit-spaces do not show a prominent presence of erythrocytes in SCH, but they do in Kaposi’s sarcoma and intravascular papillary endothelial hyperplasia.
There are also differences in the immunohistochemical staining patterns, including human herpesvirus 8 (HHV-8) positivity in Kaposi’s sarcoma, which is not present in SCH. SCH does not exhibit the infiltrative growth pattern, significant nuclear atypia, high mitotic rate, and atypical mitotic figures that characterize angiosarcoma.
Who is at Risk for Developing this Disease?
Spindle cell hemangioma is a rare tumor that most often is sporadic in nature, and often associated with pre-existing vascular anomalies such as varicosities, lymphedema, and the venous malformations of Klippel-Trenaunay syndrome. Less commonly, multifocal SCH lesions are found in association with Maffuci syndrome.
Spindle cell hemangiomas occur almost equally in males and females. The age distribution is wide, but most reported cases seem to occur in the second to fourth decades.
What is the Cause of the Disease?
The etiology of spindle cell hemangioma is not clearly known at this time. The literature contains a great deal of discussion regarding the fundamental nature of these lesions. On one side are those that argue for a reactive origin (much like a pyogenic granuloma), with evolution of the architecture through cyclical processes of thrombosis and organization. Others feel that these are vascular hamartomas, secondarily modified by reactive changes.
On the other side of the spectrum are those who feel SCH is a benign vascular neoplasm, with growth and development that is unrelated to trauma or any reactive process.
This entity was originally described in 1986 by Weiss and Enzinger as a low-grade form of angiosarcoma. It seems that this classification was errant. They suggested that this was a malignant tumor based on its tendency to recur and because one case in their series showed regional lymph node metastasis after radiation therapy.
The term hemangioendothelioma was applied to reflect what was thought to be the borderline nature of its biologic behavior. The World Health Organization originally created this term to denote lesions that have a biologic course somewhere between the hemangioma and a conventional angiosarcoma, meaning that these lesions had intermediate malignancy.
More recently, SCH has been considered as a reactive or benign vascular proliferation with very little, if any, malignant potential. This classification was based on the clinical behavior and immunohistochemical and flow cytometric characteristics of hundreds of lesions studied. Because the behavior of these lesions was benign in nature, they were relabeled as spindle cell hemangioma.
This terminology may be unfortunate as well, as these lesions are likely a reactive process, not a true neoplasm, and bear no relation to the more common “hemangioma of infancy.” Their tendency towards recurrence and growth of multiple lesions in the same area is likely related to the fact that approximately one-half of SCH have areas of intravascular growth.
Systemic Implications and Complications
Usually, spindle cell hemangiomas are a benign finding, with no systemic implications or associations. However, in rare cases, SCH can be found in association with Mafucci’s syndrome. This is discussed further below within unusual clinical scenarios to consider in patient management.
Treatment options are summarized in Table I.
|Local Excision||Interleukin-2 (intra-arterial and intralesional) —case report level|
|Wide Excision||Radiotherapy may have caused malignant change in one case|
Optimal Therapeutic Approach for this Disease
Treatment for spindle cell hemangiomas is often conservative, consisting of simple surgical excision. But more extensive lesions may require wide local excision.
Recurrence is not unusual (with some series showing up to a 60% recurrence rate) so wide local excision should be undertaken if feasible. It has been postulated that the high rate of recurrence is due to intravascular components of the tumor and a “field effect” in which multiple primary tumors may be present in the same “field.” Imaging the area to determine the extent of the tumor and to evaluate for clinically inapparent lesions may improve surgical outcomes.
In a case report from Japan wherein the authors used both intra-arterial and intralesional recombinant interleukin-2 (rIL-2) to treat a patient who had already undergone two surgeries with recurrence, the authors injected about 0.4 x 102 Japanese Reference Units (JRU) (one JRU is equivalent to 100 units of the NCI preparation) three times weekly for 2 weeks, and 0.4 x 106 JRU of rIL-2 was administered intra-arterially twice.
Angiography afterwards showed fibrosis and disappearance of vascular cavities. There was no recurrence after 2 years, and the authors postulated that the rIL-2 worked by inducing cytotoxic cells to come to the area, adhere to tumor cells, and destroy them.
Although there may be multiple agents that can be used in conjunction with surgery to prevent recurrence, it is not clear, based on the current evidence, which agents will be best and how they should be utilized.
Once the diagnosis has been made, MRI can be quite helpful in evaluating the extent and anatomic involvement of SCH. This should be undertaken before treatment, to guide intervention.
In the past, extensive and aggressive surgical procedures were undertaken to remove spindle cell hemangiomas; however, it is now clear that this is not a low-grade malignancy, as once thought. Rather, it is a benign (perhaps reactive) proliferation with a tendency to recur. This is crucial knowledge in guiding therapy.
Therapeutic approach should be guided by symptoms and location of a given lesion, along with patient preference and desire for aggressive intervention. Obviously, if tumors are encroaching on vital structures or causing functional issues, then this should push you towards more urgent intervention. Otherwise, the timeline for treatment should be guided by discussion with the patient.
Patients should be reassured that the overall prognosis for SCH is excellent. Even patients who experience multiple recurrences have little morbidity. Many times, the main consideration driving treatment is aesthetic in nature.
Large series have shown that there is virtually no chance of metastasis unless secondary environmental insults such as radiation occur. Patients should be warned of the high recurrence rates associated with this tumor. You can advise them that the lesions tend to recur or cluster in the same general area of the body. Close follow-up, with thorough skin examinations, should be sufficient to monitor for recurrence. Serial imaging is probably not necessary unless lesions are very extensive, deep within the subcutaneous tissues, or causing functional issues.
Unusual Clinical Scenarios to Consider in Patient Management
It is rare for patients with spindle cell hemangiomas to have Mafucci’s syndrome, but it is not rare for patients with Mafucci’s syndrome to have spindle cell hemangiomas. Mafucci’s is the association of enchondromas with superfical and deep venous malformations or, less commonly, mixed venous/lymphatic malformations.
In this clinical setting, the natural history and behavior of SCH may be different than “garden variety” SCH. Maffuci syndrome-associated SCH tends to present at a younger age, in the first or second decade. SCH in association with enchondromatosis also tends toward multifocality, and often involves unusual sites such as the abdomen, chest wall, or genitalia, rather than the more common acral presentation. SCH are often found in association with venous malformations.
Recognition of Mafucci’s syndrome is important because approximately 15%-35% of these patients develop chondrosarcomas within their enchondromas. They can also develop angiosarcomas, fibrosarcomas, osteosarcomas, and lymphangiosarcomas.
These patients also develop a variety of other epithelial and mesenchymal neoplasms, including thyroid and pituitary adenomas; carcinomas of the ovary, liver, and pancreas; fibroadenomas of the breast; and central nervous system gliomas. In fact, some studies have estimated that the risk of Mafucci patients dying of some form of malignancy approaches 100%.
Rare locations for SCH have included pharyngeal, genital, and even (in one report) within the frontal bone. Intramuscular lesions have been reported as well. The MRI of the intramuscular lesions was quite similar to that of intramuscular venous malformations. En bloc excision was undertaken in most cases of intramuscular SCH, with good results.
What is the Evidence?
Ding, J, Hashimoto, H, Imayama, S, Tsuneyoshi, M, Enjoji, M. “Spindle cell haemangioendothelioma: probably a benign vascular lesion not a low-grade angiosarcoma. A clinicopathological, ultrastructural and immunohistochemical study”. Virchows Arch A Pathol Anat Histopathol. vol. 420. 1992. pp. 77-85. (One of the early articles to point out that spindle cell hemangioma is not a low-grade malignancy, but rather has a benign behavior with local spread and recurrence)
Perkins, P, Weiss, SW. “Spindle cell hemangioendothelioma. An analysis of 78 cases with reassessment of its pathogenesis and biologic behavior”. Am J Surg Pathol. vol. 20. 1996. pp. 1196-204. (A large case series that provides support for counseling patients that the overall prognosis for SCH is excellent, while reinforcing its high potential for recurrence)
Hisaoka, M, Kouho, H, Aoki, T, Hashimoto, H. “DNA flow cytometric and immunohistochemical analysis of proliferative activity in spindle cell haemangioendothelioma”. Histopathology. vol. 27. 1995. pp. 451-6. (Further evidence for the benign behavior of this tumor)
Hisaoka, M, Hashimoto, H, Iwamasa, T. “Diagnostic implication of Kaposi’s sarcoma-associated herpesvirus with special reference to the distinction between spindle cell hemangioendothelioma and Kaposi’s sarcoma”. Arch Pathol Lab Med.. vol. 122. 1998. pp. 72-6. (HHV-8 staining is positive in Kaposi’s and not SCH, allowing differentiation if there is diagnostic dilemma.)
Steinbach, LS, Ominsky, SH, Shpall, S, Perkocha, LA. “MR imaging of spindle cell hemangioendothelioma”. J Comput Assist Tomogr. vol. 15. 1991. pp. 155-7. (Describes the magnetic resonance findings of the entity)
Setoyama, M, Shimada, H, Miyazono, N, Baba, Y, Kanzaki, T. “Spindle cell hemangioendothelioma: successful treatment with recombinant interleukin-2”. Br J Dermatol. vol. 142. 2000. pp. 1238-9. (Case report of treatment of SCH with recombinant interleukin-2)
Garzon, MC, Enjolras, O, Frieden, IJ. “Vascular tumors and vascular malformations: evidence for an association”. J Am Acad Dermatol. vol. 42. 2000. pp. 275-9. (Interesting discussion of acquired vascular tumors, including SCH in the context of congenital vascular anomalies such as Klippel-Trenaunay syndrome)
Tronnier, M, Vogelbruch, M, Kutzner, H. “Spindle cell hemangioma and epithelioid hemangioendothelioma arising in an area of lymphedema”. Am J Dermatopathol. vol. 28. 2006. pp. 223-7. (Case of an SCH that presents in association with lymphedema)
Yáñez, S, Val-Bernal, JF, Mira, C, Echevarría, MA, González-Vela, MC, Arce, F. “Spindle cell hemangioendotheliomas associated with multiple skeletal enchondromas: a variant of Maffucci’s syndrome”. Gen Diagn Pathol. vol. 143. 1998. pp. 331-5. (A good discussion of the relationship between SCH and Maffucci’s syndrome)
Pellegrini, AE, Drake, RD, Qualman, SJ. “Spindle cell hemangioendothelioma: a neoplasm associated with Maffucci’s syndrome”. J Cutan Pathol. vol. 22. 1995. pp. 173-6. (Another good discussion of the relationship between SCH and Maffucci’s syndrome, again supporting the association)
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