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07 October 2023: Articles  USA

Locally Invasive Papillary Intralymphatic Angioendothelioma Arising Within a Lymphatic/Venous Malformation

Challenging differential diagnosis, Rare disease

Reham Al-Refai1ABDEF*, Doaa Morrar1AEF, Ahmed Bendari1AEF, Sunder Sham1AEF, Pamela Unger1AEF, Morris Edelman2AEF

DOI: 10.12659/AJCR.940602

Am J Case Rep 2023; 24:e940602




BACKGROUND: Papillary intralymphatic angioendothelioma (PILA) is a rare vascular tumor affecting children and young adults, with less than 50 cases reported in the literature. This tumor typically presents in the extremities, exhibits borderline behavior, and has a prominent lymphatic phenotype. Originally thought to be malignant, PILA was later recognized for its borderline behavior and lymphatic features, leading to its current classification as a “rarely metastasizing lymphatic vascular neoplasm”.

CASE REPORT: We present the case of a 10-year-old girl with a 6-year history of a right facial venous malformation, which was ultimately diagnosed as PILA in the background of lymphatic/venous malformation (LVM). After undergoing surgical excision of a right facial soft-tissue tumor, histopathological examination revealed scattered lymphatics and thin-walled vascular channels with blood in skeletal muscle and fibroadipose tissue. Intraluminal papillary proliferation of vascular spaces lined by cytologically bland spindle cells was observed, along with Kaposiform morphology and small-vessel proliferation. Immunohistochemical staining confirmed endothelial cell markers (D2-40, ERG, CD34, and CD31) and numerous CD3(+) lymphocytes in the lumen, surrounded by CD3(+) T lymphocytes and CD20(+) B lymphocytes in the surrounding stroma. The tumor lacked pleomorphism, significant mitotic activity, and necrosis.

CONCLUSIONS: PILA presents a diagnostic challenge and should be considered in the differential diagnosis of cutaneous vascular neoplasms. Long-term follow-up is crucial due to its borderline behavior and potential for local invasiveness and metastasis. Accurate diagnosis, aided by characteristic histological and immunohistochemical features, is essential for appropriate management of this rare vascular tumor.

Keywords: Hemangioendothelioma, Neoplasms, vascular malformations, Child, Female, young adult, Humans, Vascular Neoplasms, Vascular Diseases, Soft Tissue Neoplasms, Skin Neoplasms


Papillary intralymphatic angioendothelioma (PILA) is a rare vascular tumor defined in the latest edition of the WHO tumor classification as a “rarely metastasizing lymphatic vascular neoplasm” [1]. The lesion, first reported by Dabska in 1969, was believed to be malignant because 2 of the 6 cases had lymph node metastasis [2]. In 1998, a study conducted by Fanburg-Smith et al renamed the tumor PILA, considering its borderline behavior and prominent lymphatic phenotype [1]. Less than 50 cases of PILA have been described in the literature [3]. Most cases occur in the soft tissue; however, other sites have been reported in the literature [3].

Case Report

A 10-year-old girl presented with a history of a right facial venous malformation. Six years ago, she had undergone multiple embolizations. At our institution, she underwent surgical excision of a right facial soft-tissue tumor. Gross examination revealed it was 4.5 cm in the greatest dimension and showed aggregates of tan-yellow to tan-brown, irregular soft-tissue fragments. No previously submitted material was available for review.

Histologically, the tissue showed scattered lymphatics and thin-walled vascular channels with blood in skeletal muscle and fibroadipose tissue. The vascular channels had attenuated flattened endothelial lining with intervening fibrosis. Small scattered groups of dilated vascular spaces were dis-tended with small lymphocytes and showed papillary endoluminal proliferation. These vascular spaces were lined by larger cells with oval nuclei and inconspicuous nucleoli. They are surrounded by cytologically bland spindle cell proliferation with “Kaposiform” morphology, lymphoid aggregates, and small-vessel proliferation. Hemosiderin deposits were present. There was no pleomorphism, minimal or absent mitotic activity, or necrosis (Figure 1). Immunohistochemical staining revealed thin-walled vessels lined by D2-40 (+, variable), ERG (+), CD34(+), and CD31(+) endothelial cells. The lining of the intraluminal papillary proliferations was D2-40(+, strong), ERG (+), CD34(+), and the lumen was filled with numerous CD3(+) lymphocytes (Figure 2). The surrounding stroma showed an admixture of CD3(+) T lymphocytes and CD20(+) B lymphocytes (Figure 3). The lesion was negative for cytokeratin AE1/AE3 expression.


In 1969, Maria Dabska described 6 cases of a unique vascular tumor in the skin and subcutaneous tissue, which she diagnosed as malignant endovascular papillary angioendothelioma, which was referred to as a Dabska tumor [2]. Fewer than 50 cases have been described in the literature [3]. This rare tumor occurs predominantly in infants, children, and young adults, but it can also occur in the elderly. There is a slight female predilection (M: F ratio: ~0.7: 1) [4]. The disease typically affects the dermis and subcutaneous tissues of the extremities and, to a lesser extent, the trunk, head, and neck. A few cases have been reported in deeper locations, including the spleen [5], tongue [6], and testis [7], and 4 cases have been reported in bones [4]. Several congenital cases have been reported, as many of these tumors develop from previously benign vascular tumors such as cavernous hemangiomas and lymphangiomas [8–11]. Hemangiomas, commonly known as infantile hemangiomas (IH), are common benign tumors characterized by endothelial cell proliferation [12]. The histopathological examination reveals a multinodular pattern fed by a single arteriole, consisting of hyperplastic endothelial cells and pericytes [12,13]. While most hemangiomas resolve without treatment, complicated cases can be managed with oral propranolol or oral prednisone, and surgical excision may be considered for improved treatment outcomes [13]. To the best of our knowledge, this is the first report of PILA development in the context of a lymphatic/venous malformation.

Histologically, PILA is composed of a proliferation of spindle- to polygonal-shaped, slightly atypical cells that form interconnecting capillaries and cavernous vascular cavities, forming intraluminal papillary projections. The papillae have hyaline cores and are covered with slightly atypical cuboidal endothelial cells that have a hobnail or “match-head” appearance. Patients may exhibit solid areas and glomeruli-like structures. Mitosis and necrosis are usually absent [10]. Immunohistochemically, tumor cells express pan-endothelial markers, such as CD31 and ERG, and less often CD34, as well as lymphatic endothelial markers such as podoplanin (D2-40), VEGFR3, and PROX1[14].

The differential diagnosis of PILA is limited because it has distinct histological features. Those include retiform hemangioendothelioma, papillary endothelial hyperplasia (Masson’s hemangioma), epithelioid hemangioma, and lymphangioma-like Kaposi sarcoma. The first 2 differentials may be confused with PILA because of the presence of “hobnail” cells and papillary projections. Retiform hemangioendothelioma is a low-grade, locally aggressive, and rarely metastasizing malignant vascular tumor with elongated vessels that resemble the rete testis. Papillary endothelial hyperplasia (Masson’s hemangioma) is a benign, reactive, intravascular papillary endothelial proliferation characterized by vascular thrombosis and papillary projections. Papillae have hyaline or fibrin cores associated with thrombotic material and are often free-floating in the vascular lumen. To help distinguish PILA from epithelioid hemangioma and lymphangioma-like Kaposi sarcoma, immunohistochemistry, such as D2-40, will highlight the lymphatic origin of hobnail cells in PILA. In Kaposi sarcoma, nuclear HHV8 (LANA1) staining is a diagnostic tool used for this entity [7,14].

PILA have a high rate of local recurrence and rarely metasta-size. Six patients reported in 1969 were reviewed by Dabska 30 years later; 3 of the original 6 cases were locally aggressive, with tumor invasion into deeper structures, including bone, musculature, fascia, and/or tendons, and 1 patient died as a result of pulmonary metastases [15]. A case of angiosarcoma arising within a PILA has been previously described [16].

Since Dabska’s initial study, subsequent cases of PILA that have been completely excised have a low risk of local recurrence and metastasis. Our patient needs to be closely followed up because she is at a risk of local recurrence.


This case highlights the diagnostic challenge posed by PILA and emphasizes the importance of considering this rare tumor in the differential diagnosis of cutaneous vascular neoplasms. With its borderline behavior and potential for local invasiveness, as well as the possibility of metastasis, long-term follow-up is essential for all PILA cases. The identification of characteristic histological and immunohistochemical features aids in accurate diagnosis and appropriate management of this uncommon vascular tumor.


1.. Fanburg-Smith JC, Papillary intralymphatic angioendothelioma: World Health Organization classification of tumors of soft tissue and bone, 2013; 148-49, Lyon, IARC Press

2.. Dabska M, Malignant endovascular papillary angioendothelioma of the skin in childhood. Clinicopathologic study of 6 cases: Cancer, 1969; 24(3); 503-10

3.. Gambarotti M, Righi A, Sbaraglia M, Intraosseous papillary intralymphatic angioendothelioma (PILA): One new case and review of the literature: Clin Sarcoma Res, 2018; 8; 1

4.. Kaplan GO, Menku Özdemir FD, Orhan D, Papillary intralymphatic angioendothelioma: An extremely rare tumor: Jt Dis Relat Surg, 2021; 32(1); 245-48

5.. Katz JA, Mahoney DH, Shukla LW, Endovascular papillary angioendothelioma in the spleen: Pediatr Pathol, 1988; 8(2); 185-93

6.. Takaoka K, Sakurai K, Noguchi K, Endovascular papillary angioendothelioma (Dabska tumor) of the tongue: Report of a case: J Oral Pathol Med, 2003; 32(8); 492-95

7.. Bhatia A, Nada R, Kumar Y, Menon P, Dabska tumor (endovascular papillary angioendothelioma) of testis: A case report with brief review of literature: Diagn Pathol, 2006; 1; 12

8.. Cox JA, Bartlett E, Lee EI, Vascular malformations: A review: Semin Plast Surg, 2014; 28(2); 58-63

9.. Argani P, Athanasian E, Malignant endovascular papillary angioendothelioma (Dabska tumor) arising within a deep intramuscular hemangioma: Arch Pathol Lab Med, 1997; 121(9); 992-95

10.. Quecedo E, Martínez-Escribano JA, Febrer I, Dabska tumor developing within a preexisting vascular malformation: Am J Dermatopathol, 1996; 18(3); 302-7

11.. Emanuel PO, Lin R, Silver L, Dabska tumor arising in lymphangioma circumscriptum: J Cutan Pathol, 2008; 35(1); 65-69

12.. Hemangioma Investigator Group; Haggstrom AN, Drolet BA, Prospective study of infantile hemangiomas: Demographic, prenatal, and perinatal characteristics: J Pediatr, 2007; 150(3); 291-94

13.. Holland KE, Drolet BA, Infantile hemangioma: Pediatr Clin North Am, 2010; 57(5); 1069-83

14.. Castro EC, Galambos C, Prox-1 and VEGFR3 antibodies are superior to D2-40 in identifying endothelial cells of lymphatic malformations – a proposal of a new immunohistochemical panel to differentiate lymphatic from other vascular malformations: Pediatr Dev Pathol, 2009; 12(3); 187-94

15.. Schwartz RA, Dabski C, Dabska M, The Dabska tumor: A thirty-year retrospect: Dermatology, 2000; 201(1); 1-5

16.. Antosz Z, Zaniewski M, Kostecki J, Poreba R, Angiosarcoma arising within a malignant endovascular papillary angioendothelioma (Dabska tumor): Neuro Endocrinol Lett, 2010; 31(4); 454-56

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923