Postradiation Cutaneous Angiosarcoma After Treatment of Breast Carcinoma is Characterized by MYC Amplification in Contrast to Atypical Vascular Lesions After Radiotherapy and Control Cases

Clinicopathological, Immunohistochemical and Molecular Analysis of 66 Cases

T Mentzel; H U Schildhaus; G Palmedo; R Büttner; H Kutzner

Mod Pathol. 2012;25(1):75-85.

Abstract and Introduction

Abstract

Postradiation cutaneous vascular lesions after treatment of breast carcinoma comprise a heterogeneous group of benign, atypical, and malignant lesions and are best regarded as points along a morphological spectrum. We analyzed a series of cutaneous angiosarcomas after treatment of breast cancer in comparison with control cases and cases of atypical vascular lesions with special emphasis on the expression and amplification of MYC. The 66 cases were divided into control cases (5), cases in which a slight vascular proliferation was seen after radiotherapy of breast cancer (12), cases of atypical vascular lesions after radiotherapy (16), cases of postradiation cutaneous angiosarcomas (25), and cases of angiosarcomas of skin and soft tissues unrelated to radiotherapy (8). None of the control cases (2 M, 3 F, 20–76 years), of cases showing slight vascular proliferation, dermal fibrosis and inflammation after radiotherapy of breast cancer (12 F, 48–79 years), of cases of atypical vascular lesions after radiotherapy (16 F, 29–81 years), and of cases of angiosarcomas of skin and soft tissues unrelated to radiotherapy (3 M, 5 F, 25–92 years) showed an amplification of MYC by FISH analysis. In striking contrast, in all cases of postradiation cutaneous angiosarcomas (25 F, 46-95 years), MYC amplification was found by FISH analysis in a variable number of counted nuclei. Immunohistochemically, strong positive nuclear staining for MYC and prox-1 was seen in cases of postradiation cutaneous angiosarcoma, whereas control cases and cases of atypical vascular proliferation after radiotherapy were negative for MYC, and stained only focally positive for prox-1 in a number of cases. In conclusion, the presence of MYC amplification represents an important additional diagnostic tool in the distinction of postradiation cutaneous angiosarcomas from atypical vascular lesions after radiotherapy. Immunohistochemical stainings for MYC are useful for mapping of these lesions and for careful tumor margin control.

Introduction

Cutaneous angiosarcomas occur in three main clinical settings: so-called idiopathic angiosarcoma arising most frequently in sun-damaged skin of the face in elderly patients, rare lymphedematous angiosarcoma arising in patients with chronic lymphedema, and postradiation cutaneous angiosarcoma, usually occurring in patients with a history of radiation therapy for breast cancer. In addition to postradiation angiosarcoma, benign and atypical vascular proliferations after radiotherapy have been described. Benign lymphangiomatous papule usually presents as a solitary, well-circumscribed, and superficially located dermal neoplasm that is composed of dilated, lymphangioma-like vascular spaces lined by slightly enlarged but uniform endothelial cells without increased atypia and proliferative activity, and endothelial multilayering is usually not present.^[1,2] Atypical vascular lesions following radiotherapy for breast cancer are solitary or multicentric vascular lesions composed of either superfially located, lymphangioma-like vascular lesions or of narrow and dissecting vascular proliferations that may show focally anastomosing spaces. The lining endothelial tumor cells may contain hyperchromatic nuclei, but significant cytologic atypia, an increased mitotic rate and infiltration of subcutaneous tissue are not seen.^[3] During the last 15 years it has been shown that there is significant clinical and morphological overlap between benign, atypical, and malignant vascular proliferations after radiotherapy, neoplasms that are best regarded as points along a morphological spectrum, and that exact classification especially on a small biopsy may cause significant diagnostic problems.^[4] In addition, shared mutations of the p53 tumor suppressor gene emphasize that atypical and malignant radiation-induced vascular changes are closely related.^[5] Most recently it has been reported, that so-called secondary cutaneous angiosarcomas (postradiation angiosarcomas and lymphedema-associated angiosarcomas) show high-level amplifications of MYC at locus 8q24.21 in contrast to primary cutaneous angiosarcomas.^[6] We decided to study benign, atypical, and malignant vascular proliferations after radiotherapy in order to compare immunohistochemical expression of MYC and the presence or absence of MYC amplifications in these lesions.

1 2 3 4

Next Section

Abstract and Introduction
Materials and Methods
Results
Discussion
References

Table 1. Clinical findings of 66 patients with radiation-induced vascular lesions
Case	Gd	Age (ys.)	Location	Diagnosis	Treatment/follow-up
1	F	36	Buttock	HE	Excision
2	M	20	Leg	Hobnail HE	Excision
3	F	76	Rectum	Proctitis	Biopsy
4	M	71	Rectum	Proctitis	Biopsy
5	F	70	Breast	BCC	Excision
6	F	54	Breast	Increase of vessels	Biopsy
7	F	49	Breast	Increase of vessels	Biopsy
8	F	67	Breast	Ulceration, radiodermatitis	Excision
9	F	49	Breast	Radiodermatitis, erosion	Excision
10	F	74	Breast	Radiodermatitis	Biopsy
11	F	71	Breast	Radiodermatitis	Biopsy
12	F	65	Breast	Radiodermatitis	Biopsy
13	F	76	Breast	Ulceration, radiodermatitis	Excision
14	F	74	Breast	Radiodermatitis	Biopsy
15	F	48	Breast	Radiodermatitis	Biopsy
16	F	51	Breast	Radiodermatitis	Biopsy
17	F	79	Breast	Fibrosis, few vessels	Biopsy
18	F	44	Breast	AVL	CE, NSR at 15/12
19	F	63	Axilla	BLAP	CE, NSR at 12/12
20	F	55	Breast	AVL	CE, no follow-up
21	F	55	Breast	AVL (2 lesions)	CE, no follow-up
22	F	65	Breast	AVL	CE, NSR at 84/12
23	F	60	Breast	AVL	CE, NSR at 32/12
24	F	81	Breast	AVL	Biopsy, no follow-up
25	F	65	Breast	AVL	CE, R at 12 months, CE
					NSR 60 months later
26	F	64	Breast	BLAP	CE, no follow-up
27	F	58	Breast	AVL	Biopsy, multiple lesions, appear and disappear, no progression at 36/12
28	F	57	Breast	AVL	CE, NSR at 144/12
29	F	29	Breast	AVL	CE, NSR at 27/12
30	F	65	Breast	AVL	CE, NSR at 24/12
31	F	46	Breast	AVL (multiple lesions)	Multiple biopsies, no progression at 12/12
32	F	40	Breast	AVL	CE, no follow-up
33	F	51	Breast	AVL (two lesions)	CE, NSR at 18/12
34	F	72	Upper arm	Angiosarcoma of ST	CE, no follow-up
35	M	92	Lower leg	Cutaneous angiosarcoma	CE, no follow-up
36	M	25	NA	Angiosarcoma of ST	CE, no follow-up
37	M	61	Neck	Angiosarcoma of ST	Marginal excision, no follow-up
38	F	51	Chest wall	Angiosarcoma of ST	R at 18/12
39	F	46	Breast	Angiosarcoma of ST	CE, MTS at 110/12
40	F	43	Breast	Angiosarcoma of ST	CE, no follow-up
41	F	50	NA	Angiosarcoma of ST	CE, no follow-up
42	F	65	Breast	Cutaneous angiosarcoma	CE, R at 7/12, CT
43	F	67	Breast	Cutaneous angiosarcoma	CE, NSR at 10/12
44	F	73	Breast	Cutaneous angiosarcoma	CE, R at 30/12, DOD at 34/12
45	F	84	Breast	Cutaneous angiosarcoma	CE, NSR at 31/12
46	F	95	Breast	Cutaneous angiosarcoma	Biopsy, lost to follow-up
47	F	75	Breast	Cutaneous angiosarcoma	CE, NSR at 12/12
48	F	64	Breast	Cutaneous angiosarcoma	CE, no follow-up
49	F	63	Breast	Cutaneous angiosarcoma	CE, R at 36/12, NSR at 12/12
50	F	75	Breast	Cutaneous angiosarcoma	CE, R at 18/12, NSR at 5/12
51	F	56	Breast	Cutaneous angiosarcoma	CE, R, MTS, DOD at 60/12
52	F	83	Breast	Cutaneous angiosarcoma	DOD at 5/12
53	F	63	Breast	Cutaneous angiosarcoma	CE, MTS, DOD at 8/12
54	F	70	Breast	Cutaneous angiosarcoma	CE, CT, DOD at 24/12
55	F	62	Breast	Cutaneous angiosarcoma	CE, no follow-up
56	F	46	Breast	Cutaneous angiosarcoma	Biopsy, no follow-up
57	F	68	Breast	Cutaneous angiosarcoma	CE, R and lymph node MTS, DOD at 24/12
58	F	70	Breast	Cutaneous angiosarcoma	CE, NSR at 30/12
59	F	74	Breast	Cutaneous angiosarcoma	CE, NSR at 7/12
60	F	68	Breast	Cutaneous angiosarcoma	CE, NSR at 8/12
61	F	78	Breast	Cutaneous angiosarcoma	CE, R at 9/12
62	F	66	Breast	Cutaneous angiosarcoma	CE, no follow-up
63	F	57	Breast	Cutaneous angiosarcoma	CE, NSR at 28/12
64	F	69	Breast	Cutaneous angiosarcoma	CE, NSR at 5/12
65	F	71	Breast	Cutaneous angiosarcoma	CE, recent case
66	F	54	Breast	Cutaneous angiosarcoma	CE, recent case

Gd, gender; F, female; M, male; HE, hemangioma; BCC, basal cell carcinoma; AVL, atypical vascular lesion; BLAP, benign lymphangiomatous papule; CE, complete excision; R, local recurrence; MTS, metastases; DOD, died of disease; NSR, no sign of recurrence; ST, soft tissue; NA, not available; CT, polychemotherapy.

Table 2. Immunohistochemical findings and FISH analysis of 66 patients with radiation-induced vascular lesions
Case	IM MYC	IM prox-1	FISH MYC
1	−	−	NAMP
2	−	Focal +	NAMP
3	−	−	NAMP
4	−	−	NAMP
5	NA	NA	NAMP
6	−	−	NAMP
7	−	Focal +
8	−	−	NAMP
9	−	−	NAMP
10	−	−	NAMP
11	−	−	NAMP
12	−	−	NAMP
13	−	−	NAMP
14	−	−	NAMP
15	NA	NA	NAMP
16	−	−	NAMP
17	−	−	NAMP
18	−	+	NAMP
19	−	Focal +
20	−	Focal +
21	−	−	NAMP
22	−	Focal +
23	−	−	NAMP
24	−	Focal +	NAMP
25	−	Focal +	NAMP
26	−	Focal +	NAMP
27	−	Focal +	NAMP
28	Focal +		NAMP
29	−	−	NAMP
30	−	Focal +	NAMP
31	−	−	NAMP
32	−	Focal +	NAMP
33	−	Focal +	NAMP
34	−	−	NAMP
35	−	−	NAMP
36	−	−	NAMP
37	−	−	NAMP
38	−	−	NAMP
39	−	−	NAMP
40	−	−	NAMP
41	−	Focal +	NAMP
42	+	+	AMP in 46/52
43	+	Focal +	AMP in 12/54
44	+	−	AMP in 11/51
45	+	+	AMP in 48/54
46	+	−	AMP in 43/51
47	+	+	AMP in 39/50
48	+	+	AMP in 12/56
49	+	+	AMP in 43/55
50	+	+	AMP in 46/52
51	+	+	AMP in 18/50
52	+	+	AMP in 29/50
53	+	+	AMP in 48/55
54	+	+	AMP in 50/58
55	−	Focal +	AMP in 9/45
56	NA	NA	AMP in 7/50
57	+	+	AMP in 37/51
58	Focal +	−	AMP in 8/49
59	NA	NA	AMP in 15/49
60	+	+	AMP in 21/50
61	+	−	AMP in 79/100
62	+	−	AMP in 84/100
63	+	−	AMP in 85/100
64	+	NA	AMP in 24/49
65	+	NA	AMP in 48/50
66	NA	NA	AMP in 50/50

IM, immunohistochemistry; NA, data not available; NAMP, no amplification; AMP, MYC amplification in out of the nuclei counted.

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.