Case 4 -

Papillary Intralymphatic Angioendothelioma (Dabska Tumor) Sharon W. Weiss Emory University School of Medicine Atlanta, GA

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Clinical History: An otherwise healthy 10 year old female was discovered to have an ill-defined mass of the thigh. At surgery an approximately 5 cm, partially cystic, white mass occupying the dermis and subcutis was removed. Case 4 - Figure 1 Low power view illustrating vascular malformation with intravascular endothelial papillations Case 4 - Figure 2 Vascular malformation showing clusters of tumor in/adjacent to wall. Case 4 - Figure 3 Clusters of tumor and lymphocytes adjacent to a lymphatic space Case 4 - Figure 4 Vascular malformation with intravascular endothelial papillations and nodules of tumor adjacent to lumen. Case 4 - Figure 5 Nodules of tumor adjacent to lymphocytes. Note vacuolization of some of the endothelial cells Case 4 - Figure 6 Intravascular endothelial papillations. Note hobnail endothelial cells covering surface of papillation and also lying free in the lumen Case 4 - Figure 7 Some of the hobnail cells show spindling and line attenuated vascular spaces reminiscent of a retiform hemangioendothelioma Case 4 - Figure 8 High power view illustrating cytologic features of hobnail endothelial cells: cuboidal shape, high nuclear cytoplasmic ratio, nuclear grooves, and cytoplasmic vacuolization. Case 4 - Figure 9 D240 immunostaining of hobnail endothelium. Introduction: This is an example of a "Dabska tumor" a low grade vascular tumor of childhood named for the Polish pathologist, Maria Dabska, who first described the lesion in 1969. [1] Based on the observation that the lesion is often associated with lymphatic vessels, Fanburg-Smith et al proposed a new name, "papillary intralymphatic angioendothelioma," (PILA) [2] which has since been adopted by the WHO. [3] Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: These lesions occur almost exclusively in children and young adults; most originate in the soft tissues of the extremity. Rarely, unusual sites such as bone [4] and spleen [5] are affected. Typically, Dabska tumors are ill- defined masses of the dermis and subcutaneous tissue that may impart a violaceous hue to the overlying skin. Some arise from a bone fide lymphangioma or vascular malformation, [6, 7, 8] as did your case. Those lesion may have grossly visible "cysts." There are four principal histologic features of this tumor, which are well displayed in your case: Vessels lined by hobnail endothelial cells (see below) Intravascular endothelial papillations Lymphocytes Lymphatic vessels At low power your lesion resembles a vascular malformation with large, irregular, thick- walled vessels surrounded by lymphoid aggregates. Smaller lymphatic channels can also be identified Vessels lined by the "hobnail" endothelial cells infiltrate the interstitium. Hobnail endothelial cells are a characteristic feature of this tumor, and the diagnosis should not be made in their absence. They are identified by their cuboidal shape, high nuclear-cytoplasmic ratio, finely stippled nuclear-chromatin pattern, nuclear clefts, and cytoplasmic vacuoles. Intravascular endothelial papillations lined by these hobnail cells and containing a central hyaline core of accumulated basement membrane material are seen within small and large vessels. Although there is a tendency to identify a vascular tumor with intravascular endothelial tufts as a Dabska tumor, keep in mind that endothelial tufting can be seen in other tumors, notably angiosarcoma. Thus the diagnosis of a Dabska tumor is made when the other criteria, particularly the presence of "hobnail" endothelium, are met as well. The endothelial cells within Dabska tumor have an immunophenotype that mirrors normal lymphatic endothelium. They usually express von Willebrand factor, CD31 and CD34 although staining of the first two is usually significantly less intense than the last. They also express the lymphatic markers VEGFR3 and podoplanin (D240) and lack an actin-positive cuff of pericytes as seen in vascular endothelium. [2, 3] Differential Diagnoses: The two principal lesions which enter the differential diagnosis are retiform hemangioendothelioma and angiosarcoma. The retiform hemangioendothelioma is a superficially located tumor that occurs in adults and is characterized by vessels having an elongated shape (resembling the rete testis). [9] Like the Dabska tumor these vessels are lined by hobnail endothelial cells and are associated with lymphocytes in a dense hyaline-like background. Intravascular papillations are either absent or few in number and lymphatic vessels are usually less prevalent. Having said all of this, retiform hemangioendotheliomas and Dabska tumors are closely related, and there are overlap cases. This has resulted in the suggestion to label both lesions as "hobnail hemangioendotheliomas" noting whether they are of the Dabska or retiform type. [10] The reason for making this distinction is that a small number of retiform hemangioendotheliomas do show more nuclear atypia and seem to have a greater propensity for regional node metastasis. Of the 14 cases reported by Rosai et al (median follow up of 7.25 years), one patient developed regional node metastases. We have also seen several cases in which greater nuclear atypia was associated with regional node metastasis. To the best of my knowledge, disseminated disease has not been documented. Angiosarcomas with prominent intravascular papillations occasionally lead to the mistaken diagnosis of a Dabska tumor. It is useful to recall that angiosarcomas rarely occur in children, and, when they do, they usually occur in internal organs such as liver spleen. They typically grow in a more diffusely infiltrative pattern; their cells are of higher nuclear grade; and they essentially never contain the classic hobnail endothelial cells. Final Diagnosis: Papillary intralymphatic angioendothelioma (Dabska tumor) Case Discussion: Dabska tumors are considered within the group of vascular tumors known as "hemangioendotheliomas" to imply that they are borderline between benign hemangiomas and conventional angiosarcomas. [10] This term reflects their ability to recur but their limited capacity for metastasis compared to angiosarcoma. Hemangioendotheliomas can be further broken down into three subgroups: The first, to which the Dabska tumor belongs, consistently have a benign appearance, nearly always occur in children and young adults and display, in part, lymphatic vascular differentiation. Kaposiform hemangioendothelioma and retiform hemangioendothelioma are also members of this subgroup. The second more aggressive group display a wider range in histologic appearance, usually occur in adults, and display blood vascular differentiation. The epithelioid hemangioendothelioma is the principal member of this group, although the WHO considers it to be a variant of angiosarcoma. The last group is incompletely characterized and, hence, provisionally considered hemangioendotheliomas. Epithelioid-sarcoma-like hemangioendothelioma and composite hemangioendothelioma are good examples of this subgroup. Since Dabska tumors are so rare, it has been difficult to develop an understanding of their long term behavior and a rational approach to treatment. Another issue has been uncertainty as to whether all cases reported as Dabska tumors are examples of such. For example, cases reported as Dabska tumors in adults may represent angiosarcomas or other vascular tumors with prominent endothelial papillations. [11] If one restricts analysis of reported Dabska to those who meet the criteria described above, it appears that the tumor is very indolent. Of the 6 cases reported by Dabska, two developed regional lymph node metastases and one died of metastatic disease. [1, 12] On the other hand, none of the eight cases with follow up information reported by Fanburg-Smith developed either recurrence or metastasis. [2] Several other anecdotal cases in the literature also had a benign course. Usually an extended local or wide excision with clear margins is recommended coupled with follow up care with attention to regional lymph nodes. Conclusion(s): The Dabska is a rare, superficially located vascular tumor of childhood included under the rubric of hemangioendothelioma, tumors of borderline malignancy. This tumor features: hobnail endothelial cells, intravascular endothelial papillations, lymphocytes, and lymphatic vessels. Hobnail endothelium cells are identified by their cuboidal-columnar shape, high nuclear cytoplasmic ratio, finely stippled nuclear chromatin pattern, nuclear clefts, and cytoplasmic vacuoles. They also have an immunophenotype that mirrors normal lymphatic endothelium (D240 positive). Dabska tumors are closely related to retiform hemangioendothelioma, another borderline lesion characterized by hobnail endothelial cells. Since hobnail cells are a defining feature of both tumors, the diagnosis of either should not be made in their absence. Based on a small cadre of cases Dabska tumors metastasize to regional lymph nodes, but only an exceptional case has given rise to disseminated disease. In addition to retiform hemangioendothelioma, the differential diagnosis of the Dabska tumor includes angiosarcoma with intravascular papillations. But angiosarcomas rarely occur in children and feature more extensively infiltrating vessels lined by endothelium usually of high nuclear grade and without "hobnail" features. References: Dabska M: Malignant endovascular papillary angioendothelioma of the skin in childhood. Cancer 24:503, 1969. Fanburg-Smith, JC, Michal, M, Partanen et al: Papillary intralymphatic angioendothelioma (PILA): a report of twelve cases of a distinctive vascular tumor with phenotypic feature of lymphatic vessels. Am J Surg Pathol 23:1004, 1999. Fletcher, CDM, Unni, KK, Mertens, F: Tumors of Soft Tissue and Bone. World Health Organization Classification of Tumours, IARC Press, Lyon, France, 2002, pp. 163-177. McCarthy, EF, Lietman, Argani, P, Frassica, FJ: Endovascular papillary angioendothelioma (Dabska tumor) of bone. Skeletal Radiol 28:100, 1999. Rogers, B, Zeim, S, Crawford, B: Splenic papillary angioendothelioma in a 6 year old girl. Pediatr Hematol Oncol 29:808, 2007. Emanuel, PO, Lin, R, Silver, L et al: Dabska tumor arising in lymphangioma circumscriptum: J Cutan Pathol 35:65, 2008. Argani, P, Athanasian, E: Malignant endovascular papillary angioendothelioma (Dabska tumor) arising within a deep intramuscular hemangioma. Arch Pathol Lab Med 121:992, 1997. Quecedo, E, Martinez-Escribano, JA, Febrer, I et al: Dabska tumor developing within a pre-existing vascular malformation. Am J Dermatopathol 18:302, 1996. Calonje, E, Fletcher, CDM, Wilson-Jones, E, Rosai, J: Retiform hemangioendothelioma: a distinctive form of low- grade angiosarcoma delineated in a series of 15 cases. Am J Surg Pathol 18:115, 1994. Weiss, SW, Goldblum, JR: "Hemangioendothelioma: Vascular Tumors of Intermediate Malignancy" in Enzinger and Weiss's Soft Tissue Tumors, Mosby-Elsevier, pp. 693- 698, 2007. Yamada, A, Uematsu, K, Yasoshima, H et al: Endovascular papillary angioendothelioma (Dabska tumor) in an elderly woman. Pathology International 48:164, 1998. Schwartz, RA, Dabski, C, Dabska, M: The Dabska tumor: a thirty year retrospect. Dermatology: 201:1, 2000.