The term angiosarcoma actually includes several neoplasms, which is a soft tissue cancer. In ths page however, we report on a particular and rare form of lymphangiosarcoma called Papillary intralymphatic angioendothelioma.
Related Terms: Dabska tumor, lymphedema, Angiosarcoma, Malignant endovascular papillary angioendothelioma, Soft tissue, Histology, Papillary intralymphatic angioendothelioma, Retiform hemangioendothelioma.
Papillary intralymphatic angioendothelioma. Also known as Dabska tumor was described in 1995, by Drs, Enzinger and Weiss. It has a distinctive histologic architecture of anastomosing vascular channels with intravascular papillary outpouchings projecting, sometimes in a glomeruluslike pattern, into a lumen lined by atypical columnar endothelial cells. Only approximately 30 patients have been described. (1)
This is a rare low-grade angiosarcoma. It most commonly affects the skin of children, although it has been and is found also in chronic lymphedema. As a low grade malignancy, it is slow growing as compared to other forms of angiosarcoma. This malignancy accounts for aproximately 1.6% of all soft tissue sarcomas.
Predisposing factors include chronic lymphedema of the extremities, preexisting vascular lesions, and prior radiation, often as therapy for other malignancies. (2)
Symptoms include a slow-growing painless intradermal nodule usually in the skin. There has been one case however in the tongue of a 67 year old man. ir also may occur with a large congenital lymphangioma circumscriptum.
Differental diagnosis includes: Acquired Digital Fibrokeratoma, Acute Hemorrhagic Edema of Infancy, Angiolymphoid Hyperplasia with Eosinophilia, Infantile Hemangioma, Kaposi Sarcoma
Treatment is generally a wide local excision. Additional treatment may depend on the extent of
Katherine A Ward BA, Phillip M Ecker MD, Rebekah R White CNP, Tanya E Melnik MD, Evin H Gulbahce MD, Mark S Wilke MD, Omar P Sangueza MD Dermatology Online Journal 16 (4): 4 University of Minnesota
The term angiosarcoma, encompasses several neoplasms, all of which exhibit a malignant process derived from endothelial cells of the vessels. The most common form of angiosarcoma is highly aggressive, often fatal, and usually affects the head and neck region of elderly white men. Other low-grade forms of angiosarcoma, including papillary intralymphatic angioendothelioma, also known as Dabska tumor, are less invasive, affect a wider age range, and offer a better prognosis. There are several predisposing factors that increase the risk of angiosarcoma and include chronic lymphedema of the extremities, preexisting vascular lesions, and prior radiation, often as therapy for other malignancies. We report an unusual case of a very small, low-grade angiosarcoma on the thigh of an adult female with no known predisposing risk factors.
Angiosarcoma is a rare vascular-derived malignancy that accounts for approximately 1.6 percent of soft tissue sarcomas . The classical presentation of angiosarcoma is an erythematous or bruise-like lesion of the skin [2, 3, 4]. The majority of angiosarcoma cases occurs in the elderly, with a median age of 75 years . Men are 2 to 3 times more likely than women to present with angiosarcoma [3, 6, 7]. There are several predisposing factors that increase the risk of angiosarcoma and include chronic lymphedema of the extremities, preexisting vascular lesions, and prior radiation, often as therapy for other malignancies [6,7, 8]. The vast majority of cutaneous angiosarcomas involve the head or neck [5, 6]. Fewer than 10 reported cases of angiosarcoma have arisen in the lower extremities in the absence of predisposing factors . We report an unusual case of a very small, low-grade angiosarcoma, also known as papillary intralymphatic angioendothelioma, on the thigh of an adult female with no known predisposing risk factors.
In May 2009, a 58-year-old female presented with a 3-month history of a dark pink, papule on the left thigh. She had no history of skin cancer but past medical history revealed eczema. The remainder of her medical history was unremarkable.
Physical examination revealed a 5 x 8 mm erythematous papule on the left anterior lateral thigh (Figure 1). The differential diagnosis for the lesion on the thigh at the time of visit included dermatofibroma, basal cell carcinoma, and inflamed nevus. The lesion was biopsied to confirm the diagnosis.
Dermatopathologic examination revealed an atypical vascular proliferation of the dermis composed of irregular vessels with slightly pleomorphic endothelial cells, prominent papillary projections into vascular spaces, and occasional mitotic figures (Figure 2). Immunohistochemical staining revealed positivity for CD-31 (Figure 3). The pathologic diagnosis was low-grade angiosarcoma, otherwise known as papillary intralymphatic angioendothelioma or Dabska tumor. The patient was scheduled for immediate wide local excision of the angiosarcoma. An elliptical excision to fascia measuring 70 x 23 mm achieved negative margins. No inguinal lymphadenopathy was appreciated. The patient returned after 14 days for suture removal and revealed a well-healing wound. The patient was referred to an oncologist who obtained a CT scan of the lungs, which revealed several pulmonary nodules that were felt to be most likely unrelated to the angiosarcoma. No additional treatments were undertaken given the patient’s otherwise excellent health. A follow-up CT scan in October 2009 revealed unchanged nodules since June 2009. On the patient’s last follow-up visit in December 2009, the patient was doing well, with no evidence of recurrence of the lesion or metastasis. The patient was instructed to return for routine skin exams every 3 months for the next 3 years.
The term angiosarcoma encompasses several neoplasms, all of which exhibit a malignant process derived from endothelial cells of the vessels [9, 10]. The spectrum of angiosarcoma is wide and has varying degrees of severity. The most common form of angiosarcoma is highly aggressive and occurs in the skin and superficial tissues of the elderly [5,11]. Approximately 60 percent of angiosarcomas are of this cutaneous form and roughly 50 percent occur in the head and neck [4, 5, 6, 12]. These high-grade angiosarcomas exhibit significant endothelial cell atypia and a tendency for extensive extravascular expansion . This invasive form of tumor is often fatal soon after diagnosis because of local recurrences and metastases, most often to the lung, followed by the lymph nodes . Meis-Kindblom et al. reported 53 percent mortality at a median interval of 11 months . The 5-year survival rate of cutaneous angiosarcoma is approximately 34 percent .
Other low-grade forms of angiosarcoma, such as Dabska tumor, more commonly known today as papillary intralymphatic angioendothelioma, present differently. Papillary intralymphatic angioendothelioma was first described in 1969 by Dabska et al. as malignant endovascular papillary angioendothelioma of the skin in childhood . Since then, approximately 30 cases of papillary intralymphatic angioendothelioma have been reported in the literature, 12 of which were in adults . It appears that papillary intralymphatic angioendothelioma may affect a wider age range than originally described. In a study of 12 cases, Fanburg-Smith et al. reported that the mean age of patients with papillary intralymphatic angioendothelioma was 30 years . The age range for all reported cases is from birth to 83 years . However, the finding of papillary intralymphatic angioendothelioma in an aged patient is still considered to be a rare event . Papillary intralymphatic angioendothelioma is deemed by most sources to be a low-grade angiosarcoma that most often occurs in the skin and subcutis . Unlike most high-grade angiosarcomas that typically occur in the head and neck regions, papillary intralymphatic angioendothelioma does not show a preference for a specific anatomic site. Reported cases of papillary intralymphatic angioendothelioma have arisen in the dermis or subcutis of the thigh, buttocks, abdomen, hand, heel, and tongue, as well as deeper locations including the testis, muscle, spleen, and bone [13, 18-23]. Cases of reported papillary intralymphatic angioendotheliomas have ranged in size from 1 to 40 cm . The prognosis for patients diagnosed with the tumor has been shown to be fairly good. At long-term follow-up, Dabska et al. reported only one case of metastatic disease to the axillary lymph nodes out of the original six cases described in 1969 . Fanburg-Smith et al. demonstrated no evidence of disease in the majority of the 12 cases in that study at follow-up . As a result of the low metastatic potential, papillary intralymphatic angioendothelioma has been classified as a low-grade malignancy .
The diagnosis of papillary intralymphatic angioendothelioma should be reserved for low-grade angiosarcomas with characteristic features, including irregular vascular channels lined by endothelial cells with a “hobnail” appearance, papillary projections with a central hyaline core, and scarce mitotic figures [16, 24]. Immunohistochemical staining has been used to aid in diagnosing papillary intralymphatic angioendotheliomas and includes positivity for D2-40, CD-31, and VEGFR3 [16, 25, 26]. These markers are strongly expressed in normal lymphatic endothelium and point to a lymphatic origin of papillary intralymphatic angioendotheliomas [16, 25, 26]. Diagnosing angiosarcoma is often difficult and delayed as a result of the rarity of this type of malignancy and confounding histologic assessment . The differential diagnosis for angiosarcoma often includes a wide spectrum of lesions depending on the degree of differentiation of the tumor. High-grade angiosarcomas must be differentiated from hemangiomas, Kaposi sarcomas, malignant melanomas, metastases, and vascular venous malformations . The differential diagnosis for low-grade angiosarcomas includes papillary intralymphatic angioendothelioma, spindle cell, epithelioid, or retiform hemangioendothelioma, and Masson’s papillary intravascular endothelial cell hyperplasia . There is no staging system for angiosarcoma .
Treatment of angiosarcoma differs greatly depending on the grade of the tumor. High-grade angiosarcomas present a systemic problem with high risk of metastases and are therefore often treated with wide local excision, followed by radiation or chemotherapy . Low-grade angiosarcomas, like papillary intralymphatic angioendothelioma, have little morbidity after surgical excision and thus no additional treatment may be necessary . However, the optimal treatment of angiosarcoma remains uncertain and further studies to investigate this are warranted.
Please refer to original article for references
Malignant endovascular papillary angioendothelioma, a rare but distinctive vascular tumour of childhood, was first described in 1969 by Maria Dabska.
Malignant endovascular papillary angioendothelioma of the skin in childhood. Clinicopathologic study of 6 cases. Cancer. 1969;24(3):503-10.
It was termed malignant because of its mitotic activity, areas of necrosis, and demonstrated ability to metastasize toregional lymph nodes.
Based on its good long-term prognosis and variable histologic features, this lesion is better classified as a borderline vascular tumour.
According to some authors Endovascular papillary angioendothelioma may not be a distinct entity and may well include a heterogeneous group of lesions.
Age: Mostly occurs in infants and children. Cases have also been reported in adults. Site: Slow growing pink or bluish-black nodule located in the skin or soft tissue . There is slight predominance in the head and neck region and extremities.
Presence of anastomosing vascular channels.
Prominent endothelial intraluminal papillary tufts with hyaline cores surrounded by lymphocytes.
The vascular spaces are lined ny monomorphic hobnail endothelial cells.
In some areas glomeruloid structures are identified.
The three cell types originally described are as follows: i) Lymphocyte-like cells Papillary endothelial proliferation with a central hyaline core is one of the most characteristic features ,however, this type of proliferation has been observed in other vascular tumours, such as angiosarcoma, retiform hemangioendothelioma and glomeruloid hemangioma.
Immunohistochemistry: Tumour cells are positive for vimentin, von Willebrand factor, CD31, and focally for CD34 and are negative for keratins, epithelial membrane antigen, S-100 protein, and desmin.
Differential diagnosis: Retiform hemangioendothelioma ; Hobnail hemangioma; Glomeruloid hemangioma; Intravascular papillary endothelial hyperplasia (Masson's tumour) ; Reactive angioendotheliomatosis; Angiosarcoma,
The term ' haemangioendotheliomata ' was introduced by Mallory FB. (J Exp Med 1908; 10 : 575-593) to include all 'tumours arising from blood vessel endothelium' and this term was not associated with the clinical behaviour of the tumours.
Stout AP (Ann Surg 1943; 118: 445-464) described the microscopic appearances of malignant tumours of blood vessels and linked the term hemangioendothelioma to malignant behaviour.
Later, Enzinger FM, Weiss SW (Soft tissue tumour, 2nd ed 1988: 533-544) described hemangioendotheliomas as vascular tumours of intermediate, borderline or low grade malignancy.
The term “hemangioendothelioma” has been used to designate various groups of vascular tumours. Some of these entities are benign non- neoplastic reactive lesions.
Fanburg-Smith JC, Michal M, Partanen TA, Alitalo K, Miettinen M.
Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Six childhood vascular tumors were designated as “malignant endovascular papillary angioendothelioma” by Dabska in 1969. Since then, a few reports of similar cases were published, often called “Dabska tumors.” Twelve similar cases were identified in review of vascular tumors from the authors' institutions. There were five men and seven women, including seven adults. Patient ages ranged from 8 to 59 years (mean, 30 years).
The tumors occurred in the dermis or subcutis of the buttocks or thigh (n = 6), thumb or hand (n = 3), abdomen (n = 2), and heel (n = 1). The tumor sizes ranged from 1 to more than 40 cm (mean, 7.0 cm). The unifying feature of all cases was distinctive intravascular growth of well-differentiated endothelial cells presenting as a matchstick columnar configuration, sometimes with a large production of matrix that was positive for collagen type IV. In half the cases, these intravascular proliferations had an associated actin-positive pericytic proliferation.
There was minimal cytologic atypia and rare to absent mitotic activity. Two cases had an adjacent lymphangioma, and two additional cases had clusters of lymphatic vessels adjacent to the tumor. All but two of the cases showed varying degrees of stromal or intraluminal lymphocytes. Occasional epithelioid endothelial cells were seen, but no cases had features typical of epithelioid, spindle cell, or retiform hemangioendothelioma. Tumor cells were positive for vimentin, von Willebrand factor, CD31, and focally for CD34 and were negative for keratins, epithelial membrane antigen, S-100 protein, and desmin. Vascular endothelial cell growth factor receptor type 3, a recently introduced marker for lymphatic endothelia, was positive in all eight cases that were studied, supporting a lymphatic phenotype. Follow-up in 8 of the 12 cases showed no evidence of recurrences, metastases, or residual disease during follow-ups ranging from 1 to 17 years (mean, 9 years).
Based on the proliferative borderline features and the lymphatic phenotype, we propose to designate these tumors as papillary intralymphatic angioendothelioma. Additional cases with extensive follow-up should be studied to rule out variants with malignant potential.
Benign infantile hemangioendothelioma (cellular hemangioma of infancy) Masson's vegetant intravascular hemangioendothelioma (intravascular endothelial hyperplasia) Spindle cell hemangioendothelioma/hemangioma Kaposiform hemangioendothelioma (locally aggressive)
Retiform hemangioendothelioma Polymorphous hemangioendothelioma Composite hemangioendothelioma : Dabska's malignant endovascular papillary - angioendothelioma
Studies and Abstracts
Retiform hemangioendothelioma developed on the site of an earlier cystic lymphangioma in a six-year-old girl.
Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours.Histopathology. 2005 Apr;46(4):396-402.
Endovascular papillary angioendothelioma (Dabska tumor) of the tongue: report of a case. J Oral Pathol Med.2003;32(8):492-5.
Vascular endothelial growth factor receptor-3 (VEGFR-3): a marker of vascular tumors with presumed lymphatic differentiation, including Kaposi's sarcoma, kaposiform and Dabska-type hemangioendotheliomas, and a subset of angiosarcomas.Mod Pathol. 2000 ;13(2):180-5.
The Dabska tumor: a thirty-year retrospect. Dermatology. 2000;201(1):1-5.
Papillary intralymphatic angioendothelioma (PILA): a report of twelve cases of a distinctive vascular tumor with phenotypic features of lymphatic vessels.
Endovascular papillary angioendothelioma (Dabska tumor) of bone. Skeletal Radiol. 1999 ;28(2):100-3.
Endovascular papillary angioendothelioma (Dabska tumor).Pathol Int. 1998;48(10):840-1.
Endovascular papillary angioendothelioma (Dabska tumor) in an elderly woman. Pathol Int. 1998;48(2):164-7.
Malignant endovascular papillary angioendothelioma (Dabska tumor) arising within a deep intramuscular hemangioma. Arch Pathol Lab Med. 1997;121(9):992-5.
Dabska tumor developing within a preexisting vascular malformation. Am J Dermatopathol. 1996;18(3):302-7
Malignant endovascular papillary angioendothelioma (Dabska tumor). A case report and review of the literature. Am J Dermatopathol. 1989;11(1):64-8.
Endovascular papillary angioendothelioma in children.Pediatr Dermatol. 1987;4(4):332-5.