Unusual multifocal intraosseous papillary intralymphatic angioendothelioma (Dabska tumor) of facial bones: a case report and review of literature
© LI et al.; licensee BioMed Central Ltd. 2013
Received: 1 June 2013
Accepted: 17 September 2013
Published: 24 September 2013
Papillary intralymphatic angioendothelioma (PILA) or Dabska tumor is extremely rare, and often affects the skin and subcutaneous tissues of children. Since its first description by Dabska, only a few intraosseous cases have been described in the literature and none of them presents with multifocal osteolytic lesion of bones. We present a case of unusual multifocal intraosseous PILA in facial bones occurring in a 1 year 3 month old male child. Computed tomography (CT) scan revealed multifocal osteolytic lesions were located at the left zygoma, left orbital bone and right maxillary. Histologically, the lesions were ill-defined and composed of multiple delicate interconnecting vascular channels with papillae formation which projected into the lumen lined by atypical plumped endothelial cells. The vascular channels were also lined by plump cuboidal endothelial cells with focal hobnailed or “match-head” appearance. In some areas, endothelial cells formed solid-appearing aggregates with vessel lumens. By immunohistochemistry, the tumor cells were positive for CD31, CD34 and D2-40 at varying intensity. A final diagnosis of intraosseous PILA was made. To the best of our knowledge, this case is the first case of primary multifocal osseous PILA.
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KeywordsPapillary intralymphatic angioendothelioma Dabska tumor Osteolytic lesion Differential diagnosis
Papillary intralymphatic angioendothelioma (PILA) or Dabska tumor is a locally aggressive, rarely metastasizing vascular lesion characterized by lymphatic- or vascular-like channels and papillary endothelial proliferation. The tumor is extremely rare, and often affects the skin and subcutaneous tissues of children . Since its first description in 1969 by Dabska et al. only 33 cases have been described in the literature [2–13]. PILA does not appear to have any particular predilection site, but many of the reports were in dermis and subcutaneous tissues of head, neck, and extremities. Only a few cases of this tumor have also been described in deeper locations, including spleen, tongue, testis, and bone [8, 10, 11, 13, 18]. So far, only two cases of intraosseous PILA have been described in the literature, with none of these cases originating from facial bone. Herein, we present first case of multifocal PILA arising in facial bones of a 1-year old boy. The clinical and histological features of this tumor, as well as differential diagnosis are discussed.
Clinical presentation and management
The surgical samples were routinely fixed in 10% neutral buffered formalin. The tissues were embedded in paraffin. Four micrometer-thick sections were stained with H&E. Immunohistochemical analyses were performed using the ChemMate Envision/HRP Kit (Dako, Glostrup, Denmark). The antibodies used in this study included a broad panel of antibodies against cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), vimentin, desmin, smooth muscle actin (SMA), CD31, CD34, D2-40, CD1a, CD68, S100 protein, Langerin, and Ki-67. The antibodies were obtained from Dako Cytomation (Glostrup, Denmark) and Santa Cruz Biotechnology (Santa Cruz, CA, USA).
Immunohistochemistry stains done on these lesions were positivity for CD34 and CD31. Staining for CD31 was stronger than that for CD34. Endothelial cells of lumens expressed CD31, CD34 and D2-40, but the intraluminal tumor cells were negative for D2-40 (F). These lesions did not express CD1a, S-100 protein, cytokeratin (AE1/AE3), EMA, langerin, CD68 and SMA. The Ki-67 labeling index of the lesions was low, accounting for 2% of the tumor (Figure 2D-F). Based on the pathological findings, the mutifocal intraosseous lesions of facial bones were diagnosed as papillary intralymphatic angioendothelioma (PILA) according to WHO diagnostic criteria .
Papillary intralymphatic angioendothelioma (PILA), originally termed as endovascular papillary angioendothelioma (EPA), or Dabska tumor, was first presented in 1969 by Maria Dabska where she presented cases occurring in 6 children. In her originally reported cases, EPA was regarded as malignant and termed “malignant endovascular papillary angioendothelioma” because two of six patients had lymph node metastases . Since then, a few reports of similar cases were published, often called “Dabska tumors.” In 1999, Fanburg-Smith JC and his colleagues described 12 similar cases and designated those tumors as “papillary intralymphatic angioendothelioma (PILA)” because of histologic and immunophenotypic evidence of lymphatic vessels . Moreover, a growing number of cases described in the literature and the accumulating knowledge reveal that presence of highly specific lymphatic endothelial marker D2-40 and tumor marker vascular endothelial cell growth factor receptor type 3 (VEGFR 3) suggest tumor’s lymphatic origin other than hemangioma [15, 16]. In 2002, World Health Organization (WHO) classification of tumors of soft tissue and bone accepted PILA as a rare entity, and identified it as a locally aggressive, rarely metastasizing “vascular lesion characterized by lymphatic-like channels and papillary endothelial proliferation” . In 2013, the latest edition of WHO tumor classification (4th edition) revised tumor description to “rarely metastasizing lymphatic vascular neoplasm”, which further supports lymphatic origin or differentiation of this tumor .
Clinicopathological features of intraosseous PILAs described in present and previous reports
Age (year) /
Left medial knee
NED at 12
EF (1999) 
pain for a year and
tenderness over the
medial distal femur
NED at 50
pain for a year
with a wider
The present case
NED at 24
left side of face
Since cases of intraosseous PILA are so rare, the diagnosis should be only made by strict histological and clinical manifestation. According to the WHO criteria, PILA appears similar to cavernous lymphangiomas. The cuboidal or hobnail endothelial cells lining the vascular structures are characterized by a high nuclear cytoplasmic ratio and an apically placed nucleus that produces a surface bulge, accounting for the term "hobnail" or "matchstick". Immunohistochemically, vascular endothelial markers such as Von-Willebrand factor, CD34, CD31 and Fli-1 are commonly positive in most of tumors at varying intensities in each case, which help identify and diagnose the tumor as a type of vascular neoplasms. Of these markers, CD31 has been the best marker for this tumor because of its high sensitivity and specificity for vascular endothelial cells. CD31 usually has more immunohistochemical intensity than CD34 . Moreover, the presence of podoplanin (D2-40) and vascular endothelial growth factor receptor-3 (VEGFR3) have been also confirmed by immunohis-tochemical staining, which are highly specific lymphatic endothelial markers and suggest that the tumor is more similar to a tumor of lymphatic origin [12, 15]. However, the absence of D2-40 and CD34 in tumor cells could also be found in several previously reported cases . In the present case, irregular vascular channels lined by endothelial cells with a “hobnail” appearance, papillary projections with a central hyaline core and scarce mitotic figures help identify the tumor as a “hobnail” hemangioendothelioma. The immuno-positivity of D2-40 points to a lymphatic origin of this tumor.
Intraosseous PILA usually show osteolysis in radiological examination (especially multifocal osteolytic lesions of bones in our current case), it is often misdiagnosed as eosinophilic granuloma of bone preoperatively. However, eosinophilic granuloma of bone shows clonal neoplastic proliferation of Langerhans cells that express CD1a, S-100 and Langerin. The absence of those specific Langerhans cell markers will rule out the diagnosis of eosinophilic granuloma. Importantly, two particular types of vascular lesions, retiform hemangioendothelioma and papillary endothelial hyperplasia (Masson's lesion), may also be confused with the PILA, because of presence of “hobnail” cells or irregular papillary projections in vascular channels. Retiform hemangioendothelioma is a locally aggressive vascular tumor and characterized by distinctive arborizing blood vessels lined by endothelial cell with “hobnail” morphology. The elongated, branched vessels impart a pattern reminiscent of rete testis. That histological appearance is not consistent to the PILA. Papillary endothelial hyperplasia, also known as Masson's lesion, is a reactive endothelial proliferation secondary to vascular thrombosis. The lesion shows branching papillary projections, many of which are free-floating in the vascular lumens. Thrombotic material is usually present in the vascular lumens. Moreover, these histologically similar vascular lesions do not express D2-40 and VEGFR3, which are specific markers for PILA. In addition, epithelioid hemangioendothelioma of bone has recently been reported in literature , and lymphangioma-like Kaposi sarcoma may infrequently be encountered in clinical practice . These tumors might be confused with PILA because of endothelial cells proliferation and vascular structure with immunopositivity of vascular markers. However, presences of “hobnail” cells and papillary projections in vascular channels support the diagnosis of PILA.
Although PILA was identified initially as a “low-grade angiosarcoma”, following-up in more recent series demonstrated no local recurrence or metastasis . Most of cases have excellent prognosis with complete, wide excision . But high-grade angiosarcoma arising within a Dabska tumor suggests the tumor’s malignant potential in individual case . Dabska performed a 30-year review of this tumor and the outcomes of the 6 patients she presented in 1969. Three of the original 6 cases were locally aggressive, with tumor invasion into deeper structures. Only one patient ultimately died of widespread pulmonary metastases . However, Up to now, no other articles have been written describing the malignant metastatic potential of the tumor, although the tumor has been described to occur in lymph node . In the present case there was no evidence of any nodal involvement or distant metastasis and the child was doing well on last follow up after 24 months of surgery. However, PILA can be locally invasive with a potential to metastasize, a long-term follow-up should be performed to supervise the locoregional recurrence.
Because of its rarity and histological complexity, there exist diagnostic challenges for pathologists to differentiate PILA from other benign, intermediate or malignant vascular lesions. It is important to be able recognize this tumor in order to avoid potential misdiagnosis and improper management of afflicted patients. Our additive case is also presented for its rarity of site. It is the first case of intraosseous PILA with multiple lesions of facial bones. The diagnosis of intraosseous PILA is difficult and should be made cautiously. Besides confirmation by strict morphological criteria, immunohistochemical analysis is helpful for demonstrating the lymphatic phenotype of tumor.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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