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Complex karyotype in a case of cutaneous lymphangiosarcoma associated with chronic lymphedema of the lower limb

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Abstract

Lymphangiosarcoma is a rare malignant neoplasm of endothelial cells. The term is used to describe an angiosarcoma associated with chronic lymphedema. The skin of the head and neck region is the most common site of origin. Rather few cytogenetic studies on lymphangiosarcoma are reported in the literature. We here describe a case of an 87-year-old woman, with a history of recurring lymphangitis and with an ulcerated nodular lesion of the leg. The histological diagnosis was a malignant neoplasm of vascular origin, with the morphological and immunohistochemical features of a lymphangiosarcoma. A series of antibodies (CD31, CD34, vimentin, podoplanin and HHV-8), conventional and molecular cytogenetic and Spectral Karyotyping (SKY-FISH) analyses were used to study this case.

The immunohistochemical evaluation revealed that the neoplasm was positive for vimentin, CD31, CD34 and podoplanin and negative for HHV-8. The proliferation rate (Ki-67) was about 70%. Karyotype was defined using conventional cytogenetic and SKY-FISH. In addition, high-level of amplification was observed with MYC split signal probe.

The morphological and immunohistochemical evaluations supported the diagnosis of lymphangiosarcoma. Moreover, the cytogenetic and molecular findings contributed towards accurately defining the karyotypic aberrations of this rare sarcoma.

Introduction

Cutaneous lymphangiosarcoma is a rare malignant neoplasm of endothelial cells that accounts for less than 1% of all sarcomas [4]. A reliable distinction between lymphangiosarcoma and sarcoma with blood vascular differentiation is currently not feasible, however, lymphangiosarcoma is the term applied to an angiosarcoma associated with chronic lymphedema [4], [19]. This latter entity has been more frequently described in association with chronic lymphedema of the upper limb after mastectomy and radiotherapy for breast carcinoma [8], [23], [24]. In addition, it can arise in chronic, congenital or acquired, lymphedema of the lower limb [1]. These forms are considered as secondary angiosarcomas in contrast with de novo or primary forms.

Lymphangiosarcoma usually arises in elderly individuals and the prognosis is generally poor, with only 15% of patients being alive five years after diagnosis and treatment [19].

In order to differentiate lymphangiosarcoma from hemangiosarcoma, a number of lymphatic markers for immunohistochemistry have been recently proposed [13]. These include antibodies directed against Prox-1, vascular endothelial growth factor-3 (VEGFR-3), lymphatic vessel hyaluronan receptor-1 (LYVE-1) and podoplanin (recognized by the D2-40 clone). In particular, in the distinction between lymphatic and hematic endothelia podoplanin showed high specificity [2], [11], [13]. Furthermore, Mankey et al. [13] observed an association between D2-40 immunoreactivity and a hobnail pattern of malignant cells, suggesting that the concept of lymphangiosarcoma, originally based upon clinical findings, may evolve into a pathological definition based on morphological ground.

Here we report the morphological and immunohistochemical features of a rare case of cutaneous angiosarcoma of the leg. In addition, we performed on this case both a conventional and a molecular cytogenetic analysis and compared our results with a review of the previously reported data.

Section snippets

Histopathology and immunohistochemistry

We fixed tumor samples in buffered formalin (formaldehyde 4% w/v and acetate buffer 0.05 M) and routinely processed them to paraffin wax. Serial sections were stained with hematoxylin and eosin (H&E) for the histopathological evaluation.

For immunohistochemistry, 3 μm-thick sections were mounted on poly-L-lysine coated slides, deparaffinized, followed by the avidin–biotin complex (ABC) procedure according to Hsu et al. [9]. Immunoreactions were counterstained with Harris’ hematoxylin. The

Clinical case report

An 87-year-old woman, with a history of hypertension, phlebitis of the lower limbs, recurring lymphangitis and a pelvic fracture, presented with an ulcerated nodular lesion of the right leg, with a greatest diameter equal to 1.3 cm, which was biopsied and diagnosed as angiosarcoma. After a few days, a secondary lesion appeared on the skin of the right thigh, associated with a septic state, so the patient was treated with amputation of the lower limb; she did not receive chemotherapy or

Discussion

We reported a rare case of cutaneous lymphangiosarcoma of the leg, including morphological and cytogenetic features. The tumor arose in a patient with a long dated history of chronic lymphedema, confirming that this condition is a risk factor for the development of lymphangiosarcoma [1], [22], [23], [29]. The histopathological and immunohistochemical profile of the neoplastic cells were fully consistent with those of an angiosarcoma. The lack of HHV-8 ruled out a Kaposi's sarcoma. The strongly

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