Cutaneous Radiation-Associated Angiosarcoma After Cervical Cancer Treatment: A Case Report

Cong-Cong Xu, Wei Zhang, Hao Chen

Department of Pathology, Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu 210042, China.

Abstract Introduction: Cutaneous radiation-associated (cRAA) angiosarcoma is a rare malignant neoplasm derived from vascular endothelial cells, but a relatively commonly recognized complication of radiation therapy.Here, we present a patient with cRAA, who undergone radiochemotherapy for cervical cancer 11 years ago.Case presentation:A 48-year-old woman presented with a 6-month history of painless purple skin plaques and nodules on her lower abdomen and right thigh.The patient had undergone radiochemotherapy for cervical cancer 11 years ago.A skin biopsy showed a diffuse proliferation of irregular anastomosing dilated vascular structures with atypical endothelial cells.She was diagnosed as cRAA according to clinical and histological manifestations.Discussion:cRAA is a rare malignant neoplasm but it is a complication of radiation therapy.The incidence of cRAA has increased in recent years.Clinical and pathological manifestations are highly varied.Radical resection is the preferred treatment.Conclusion: Patients with suspicious violaceous lesions should undergo biopsy.Clinical suspicion and pathological examination are of the utmost importance for cRAA.

Keywords: cutaneous angiosarcoma, radiation therapy

Introduction

Cutaneous angiosarcoma (cAS) is a rare aggressive malignant neoplasm derived from vascular endothelial cells that carries a poor prognosis and has a high rate of recurrence.1cAS is typically divided into three distinct groups: primary sporadic angiosarcoma, chronic lymphedema-associated angiosarcoma,and cutaneous radiationassociated angiosarcoma (cRAA).2cRAA is a rare complication of radiation therapy used to treat breast cancer or other kinds of cancer.Early diagnosis is important to achieve the best possible outcomes, but the diagnosis is often delayed because of variable clinical and pathological features.Treatment options for all three subtypes of cAS are still limited.

Herein, we report a case of cRAA after cervical cancer treatment.This case highlights the need for clinicians to consider a diagnosis of cRAA in similar cases.

Case report

A 48-year-old woman presented with painless purple skin plaques and nodules on her lower abdomen and right thigh for 6months, with no systemic symptoms.Six months ago, she developed several hematoma-like lesions on her lower abdomen without any obvious cause.The lesions increased in number over time and subsequently spread to the right lower limb.Some papules and nodules developed gradually.The patient had undergone surgery and radiochemotherapy for cervical cancer 11years ago.Regular follow-up had shown no evidence of cervical cancer recurrence.She had no history of trauma or family history of cutaneous diseases.

Physical examination revealed indurated purple plaques and nodules on her lower abdomen (Fig.1A) and right thigh(Fig.1B).The lesions were firm with a hard texture.A skin biopsy showed a diffuse proliferation of irregular anastomosing dilated vascular structures dissecting through collagen bundles, and atypical endothelial cells with hyperchromatic nuclei lining the vascular spaces(Fig.1C).Hemorrhage was seen in the dermis and subcutaneous adipose tissue.Immunohistochemical examination showed atypical endothelial cells that were positive for CD31, CD34, VIII factor, and c-MYC(Fig.1D),and negative for cell keratin,carcinoembryonic antigen,S100,leukocyte common antigen.On the basis of the clinical and histopathological results, a diagnosis of cRAA was made.

Figure 1. Clinical and pathological manifestations of cutaneous radiation-associated angiosarcoma in a 48-year-old woman.Photographs shows indurated purple plaques and nodules on her lower abdomen (A) and right thigh (B).(C) Hematoxylin-eosin staining of a biopsy specimen shows a widely infiltrating tumor composed of irregular vascular structures dissecting through collagen bundles (×200), (D)Immunohistochemical staining shows c-MYC positivity (×200).

The patient refused surgery and underwent interventional treatment in another hospital.There was no evidence of recurrence during 8months of follow-up,and the patient gave her informed consent for case report.

Discussion

cRAA,also called cutaneous postradiation angiosarcoma,is a rare malignant neoplasm but a relatively commonly recognized complication of radiation therapy.The latency period between radiation and cRAA is 2 to 30years(median 6years).3Breast cancer is the most common antecedent disease of cRAA.However, cRAA also occurs in patients with gynecologic malignancies, hematolymphoid malignancies, head and neck squamous cell carcinomas, and rectal carcinomas.

cRAA typically occurs as a violaceous plaque in the field of prior irradiation, but the initial appearance may be asymptomatic.The appearance of papules, nodules,plaques, and ulcerations indicates disease progression.Pathological manifestations are highly varied, ranging from dilated vascular structures with largely inconspicuous endothelial cells to active pleomorphic cells with poorly defined vascular structures.CD31 and CD34 are commonly used as immunohistochemical markers for the diagnosis of cAS.Other markers include ETS-related gene,Claudin-5, von Willebrand factor, BNH9, VIII factor,and c-MYC.4

The differential diagnoses of cRAA include primary angiosarcoma,Kaposi sarcoma(KS),and atypical vascular lesion (AVL).Primary angiosarcoma presents as a mass,while cRAA presents as a flatter rash.cRAA should be considered in patients with radiation exposure, especially those who present with purplish-pink plaques.Both KS and cRAA have similar manifestations such as slit-like vascular structures and spindle cell morphology.5However, nuclear atypia is less prominent in KS than in cRAA.Furthermore, nuclear expression of human herpesvirus-8 is seen in KS.AVL appears as a skin-colored vesicle or papule and develops within 3years after radiation or surgery.cRAA may show focal overlapping features of AVL in small or superficial biopsies.However, cRAA expresses the anti-c-MYC antibody, which may help distinguish cRAA from AVL.

Radical resection is the preferred treatment for cRAA and is associated with reduced recurrence rates.6Solid evidence supports paclitaxel as first-line therapy for advanced cAS.Microtubule-targeting agent, histone deacetylase inhibitor, and vascular endothelial growth factor receptor inhibitor have been studied in different phase trials.7However, the role of these new therapies remains uncertain.

cRAA carries a poor prognosis.The determinants of survival may include tumor sizes larger than 5cm, age older than 50years, margin positivity, and high-grade histology.8Patients with suspicious violaceous lesions should undergo biopsy and evaluation by an experienced multidisciplinary sarcoma team.

Source of funding

This work was supported by the CAMS Innovation Fund for Medical Sciences (No.CIFMS-2017-I2M-1-017) and the PUMC Youth Fund (No.3332017168).