Primary renal angiosarcoma: A case report and literature review

Abstract

Kidney angiosarcomas usually metastasize from the skin, soft tissue, or visceral primary lesions, whereas primary renal angiosarcomas are rare. We report a case of primary renal angiosarcoma with morphological features similar to those of anastomosis hemangioma. Microscopically, there were multiple irregular anastomosing vascular spaces or channel‐like labyrinthine structures, and the tumor cells were positive for CD31, CD34, FLI‐1, PAX8, and vimentin; focally positive for factor VIII, CD10, and Ki‐67 (approximately 5%); and uniformly‐negative for CK, S‐100, and Melan‐A. The diagnosis of angiosarcoma depends on morphological and immunohistochemical examinations.

1

INTRODUCTION

Angiosarcoma is a rare malignant tumor that accounts for approximately 1– 2% of soft tissue sarcomas, shows no characteristic signs, and its imaging is non‐specific. At one extreme, an angiosarcoma might resemble a benign hemangioma, and at the other extreme, an undifferentiated carcinoma, malignant melanoma, or other soft tissue sarcoma. A variable combination of surgery is considered the best treatment, and the application of chemotherapy as a palliative treatment is used for patients who are considered terminal and inoperable, with local recurrence or distant metastasis. Angiosarcomas are associated with a high degree of malignancy, aggressive progression, and poor prognoses.

2

CASE REPORT

A 43‐year‐old woman was admitted for a medical examination owing to a right kidney mass without any symptomatology. An ultrasound showed a right renal poorly‐defined lesion without a blood flow signal. Computed tomography showed the upper pole of the right kidney, which presented a round‐like mass that measured 5 cm in diameter, with heterogeneous density, and multiple areas of hypodense necrosis (Figure a). The perfusion test showed that the blood flow of the upper renal perfusion was sparse (Figure b). Grossly, the tumor was dark red with a vague outline in the superior pole of the right kidney. Microscopically, the tumor showed the blurring of borders (Figure a) and an infiltrating type of growth (Figure B). Multiple irregular anastomosing vascular spaces or channels (Figure c) were lined by heterotypic endothelial cells that formed intraluminal buds, projections, or papillae, with variable degrees of cytological pleomorphism, large hyperchromatic nuclei, prominent nucleoli, and clear cytoplasm. Some areas of increased minor neutrophils were also observed (Figure d). Immunohistochemistry showed that the tumor cells were strongly and diffusely positive for CD31 (Figure e), CD34, FLI‐1 (Figure f), PAX8, and vimentin; focally positive for factor VIII, CD10, and Ki‐67(approximately 5%); and uniformly negative for CK, S‐100, and Melan‐A. These findings indicated that the tumor was a well‐differentiated angiosarcoma. The repeated computed tomography examination showed no local recurrence or distant metastasis at 12 months after surgery.

3

DISCUSSION

Primary renal angiosarcoma is rare and was first reported by Prince, with 67 cases documented in the literature. Including the present case, a total of 68 cases are described in Table . This type of cancer has a male predominance and a mean patient age of 61 years (range 24–95 years). Symptoms only include flank discomfort or microscopic hematuria, without specific presentation, in the early stages, whereas the advanced cases often present flank pain, gross hematuria, or abdominal mass. Radiological imaging usually appears as a renal mass that is virtually indistinguishable from renal cell carcinoma.

1

Clinical data of 68 patients

Case	Author	Age (years)	Sex	Site	Dmax (cm)	Mets at dx	Sites (subsequent and initial mets)
1	Qayyum et al.	86	M	R	12.3	Yes	Liver, lungs
2	Zhang et al.	52	M	L	8.0	Yes	Liver, bone
3	Liu et al.	75	M	R	4.0	No	No
4	Brown et al.	68	M	R	24.0	Yes	Liver
5	Brown et al.	64	M	L	30.0	No	No
6	Brown et al.	71	M	L	10.0	Yes	Peritoneal, periaortic LN
7	Brown et al.	72	M	L	NA	No	No
8	Brown et al.	29	F	L	3.7	NA	NA
9	Brown et al.	62	M	NA	NA	NA	NA
10	Brown et al.	67	M	R	NA	NA	NA
11	Brown et al.	95	M	R	15.5	NA	NA
12	Cason et al.	46	M	L	13.0	No	Bone, liver, soft tissue
13	Allred et al.	67	M	L	13.0	Yes	Lungs, liver
14	Peters et al.	74	M	L	19.0	Yes	Lungs, liver, wall, head
15	Prince et al.	51	M	L	10.0	No	No
16	Sabharwal et al.	67	M	L	13.0	Yes	Spleen
17	Chaabouni et al.	59	M	R	6.5	No	No
18	López Cubillana et al.	72	M	R	13.0	No	Bone and lung
19	Singh et al.	83	M	L	13.0	No	No
20	Askari et al.	24	M	R	9.0	No	No
21	Douard et al.	60	M	R	NA	Yes	Bone, lung
22	Terris et al.	47	M	L	19.0	Yes	Diaphragm, renal artery, liver, bone
23	Zenico et al.	56	M	L	20.0	No	No
24	Desai et al.	54	M	L	21.0	No	Bone
25	Johnson et al.	50	M	L	9.0	Yes	Liver, lung
26	Kern et al.	69	M	L	26.0	Yes	Lung
27	Kern et al.	52	M	L	8.0	Yes	Lung
28	Fukunaga et al.	61	M	L	8.0	No	Liver, bone, retroperitoneum
29	Adjiman et al.	36	M	R	10.5	Yes	Chest wall, skin
30	Papadimitriou et al.	68	M	L	10.0	No	No
31	Tsuda et al.	77	M	L	10.0	No	Retroperitoneum, liver
32	Leggio et al.	60	M	L	12.0	No	Spleen, peritoneum
33	Mordkin et al.	75	M	L	19.0	Yes	Spleen, bone, liver, soft tissue, oral cavity
34	Akkad et al.	58	M	R	4.5	No	No
35	Cerilli et al.	67	M	R	12.5	Yes	Renal vein
36	Aksoy et al.	55	M	L	13.0	No	No
37	Hiratsuka et al.	59	F	R	4.5	No	No
38	Aydogdu et al.	77	M	L	NA	NA	NA
39	Martínez‐Piñeiro et al.	66	M	L	11.5	No	Bone, liver, lungs
40	Lee et al.	63	M	NA	NA	NA	NA
41	Berretta et al.	67	M	NA	NA	NA	NA
42	Souza et al.	75	M	L	15.0	No	No
43	Costero‐Barrios et al.	71	M	L	18.0	No	Liver, retroperitoneum
44	Grapsa et al.	65	M	R	13.8	Yes	Liver, lung
45	Carnero López et al.	29	F	L	11.0	Yes	Lungs
46	Carnero López et al.	65	M	L	4.5	NA	NA
47	Pauli & Strutton	57	M	L	15.0	Yes	Lungs, bone
48	Yoshida et al.	78	M	L	18.0	Yes	Liver, bone
49	Juan et al.	81	F	NA	5.0	Yes	Liver, bone
50	Xuan	63	M	L	10.0	NA	NA
51	Yau et al.	38	F	R	13.0	Yes	Bone, LN
52	Garmendia et al.	51	M	NA	NA	NA	NA
53	Nguyen et al.	53	M	L	7.0	Yes	Lung
54	Limmer et al.	48	M	L	10.0	No	Lung, soft tissue, muscle
55	Matter et al.	62	M	L	18.0	No	Lung
56	Sanyal et al.	30	M	NA	NA	No	No
57	Testa et al.	NA	NA	NA	NA	NA	NA
58	Yamamoto et al.	68	M	R	7.0	No	No
59	Rüb et al.	59	M	L	18.0	No	Lungs, liver
60	Celebi et al.	57	M	R	14.0	No	Lungs, liver
61	Li et al.	69	F	L	NA	NA	NA
62	Witczak et al.	44	F	NA	NA	NA	NA
63	Lv et al.	56	M	L	10.4	No	Liver
64	Lan et al.	78	M	L	18.5	Yes	Lung, liver, mesenterium, peritoneum
65	Han et al.	51	M	L	8.0	Yes	Liver, bone
66	Han et al.	75	F	L	1.8	No	No
67	Han et al.	61	M	R	8.9	No	Lung
68	Our case	43	F	R	5.0	No	No
Case	Follow up (months)	Treatment	Outcome
1	NA	P	NA
2	NA	N	NA
3	6	N + Rad	NED
4	6	NA	DOD
5	11	NA	DOD
6	1	NA	DOD
7	NA	NA	NA
8	1	NA	DOD
9	NA	N	NA
10	NA	N	NA
11	2	N	DFUD
12	10	N + Rad + C	DOD
13	3	N + C	DOD
14	2	N	DOD
15	NA	N + Rad	AAW
16	1	N + C	NA
17	1	N	DOD
18	5	N + C	DOD
19	NA	NA	NA
20	4	N	DOD
21	3	N	DOD
22	10	N + Rad	DOD
23	4	N	DOD
24	4	N + C	DOD
25	NA	RD	DOD
26	1.5	N	DOD
27	3	N	DOD
28	13	N	DOD
29	NA	N	DOD
30	NA	N	AAW
31	21	N	DOD
32	8	N	DOD
33	NA	N + C + S	NA
34	30	N	NED
35	6	N + Rad	DOD
36	3	N + S	DOD
37	29	N	NED
38	NA	N	NA
39	5	N	DOD
40	NA	NA	NA
41	NA	N + C	NA
42	NA	N	DFUD
43	12	N + C + Rad	AWD
44	NA	NA	NA
45	5	N + C	DOD
46	NA	Nu	NA
47	2	N + Rad	DOD
48	13	N + I	DOD
49	9	N + C + Rad	DOD
50	NA	N	NA
51	3	N + C + Rad	DOD
52	NA	NA	NA
53	18	N + C	DOD
54	1	N	DOD
55	18	N + C + Rad	DOD
56	24	N + Rad	DOD
57	NA	NA	NA
58	19	N + Rad	NED
59	12	N + C	AWD
60	13	N + C	DOD
61	NA	NA	NA
62	NA	N	NA
63	3	N	AWD
64	2	N	AWD
65	NA	N	NA
66	24	N	AAW
67	3	N	AWD
68	12	N	AAW

The first 62 patients′ information comes from the summary of Omiyale.

AAW, alive and well; abd, abdominal; AWD, alive with disease; C, chemotherapy; DFUD, died from unrelated disease; D_max, the maximum of diameter; DOD, died of disease; dx, diagnosis; F, female; I, immunotherapy; mets, metastasis; L, left; LN, lymph node; M, male; N, nephrectomy; NA, not available; NED, no evidence of disease; Nu, nephroureterectomy; P, palliative; R, right; Rad, radiotherapy; RD, rapid deterioration; S, splenectomy.

The lesions were mostly characterized by multinodular hemorrhagic masses with unclear boundaries that infiltrated into the surrounding tissue. The most distinguishing diagnostic morphological features were the vascular channels that were lined by neoplastic endothelial cells, which freely intercommunicated with one another in a sinusoidal fashion. Nevertheless, the histomorphology manifestations vary greatly due to the wide range of endothelial cell differentiation, from surprisingly well‐differentiated to completely undifferentiated phenotypes. Poorly differentiated angiosarcomas show tumor cells that become more atypical, close‐packed, and epithelioid or spindle‐shaped, which progressively associate with a loss of vascular channels. Furthermore, the tumor cells present with a tendency to form rudimentary vascular channels that look like a mesh, with red blood cells. Additionally, in some large and irregular spaces, a surfeit of neoplastic endothelial cells are arranged in sheets and present infiltrative behavior, forming small nests or cords. These structures look like intraluminal buds or papillae plexi. However, well‐differentiated angiosarcoma shows more obvious vasoformative growth, with complex anastomosing or labyrinthine channels that are lined by a single layer of neoplastic endothelial cells, which form intraluminal buds, projections, or papillae. The tumor cells are characterized by large hyperchromatic nuclei, prominent nucleoli, and clear cytoplasm. Most tumors are positive for endothelial markers, such as CD31, CD34, FLI‐1, and factor VIII, and negative for CD10, S100, Melan‐A, and HMB‐45. Although CD34 is a sensitive marker of vascular endothelial cells, CD31 is more sensitive and specific than CD34 and factor VIII in the diagnosis of angiosarcoma. Commonly, well‐differentiated angiosarcomas are positive for factor VIII; whereas poorly differentiated angiosarcomas are negative or weakly positive for factor VIII.

When tumor cells are poorly differentiated or undifferentiated, lack typical vascular structures, and are mainly composed of epithelioid or spindle cells, these tumors resemble undifferentiated sarcomas. Diversely, poorly differentiated sarcomas present with more or less areas that form obvious vascular channels and are positive for endothelial markers, such as CD31, FLI‐1, and factor VIII; whereas undifferentiated sarcomas show more heteromorphism and mitotic activity, with positivity for epithelial markers. Well‐differentiated angiosarcomas resemble benign hemangiomas, especially anastomosis hemangiomas, but the latter are characterized by large vascular channels that are lined by endothelial cells that are arranged in a monolayer without papillae and commonly present clear boundaries, without invasion into the surrounding tissues.

The management of angiosarcomas has no definite guidelines, and most cases are treated with radical nephrectomy. The subsequent use of chemotherapy and/or radiotherapy has been controversial. Recently, Azzarit showed that the application of vascular endothelial growth factor receptor 2 or vascular endothelial growth factor inhibitors might be a novel therapeutic option. Tumors <5 cm are associated with a significantly better prognosis than larger tumors. However, the prognostic indicator of tumor size, which was suggested by a recent study, should be 10 cm. According to our analysis (Figure  and Tables ), tumor size is only related to prognosis and not metastasis, and the cut‐off size value is 7.5 cm for accurately determining the prognosis. The survival of the metastasis group was significantly shorter than that of the non‐metastasis group. The liver, lung, and bone are the most frequent metastasis sites, which showed no differences between the initial and subsequent group.

2

Prognostic factors

	Death group	Survival group	t‐value	P‐value
Patient age (years)	58 ± 16.1	63 ± 10.3	1.093	0.280
Tumor size	13.6 ± 5.9	9.3 ± 5.7	2.264	0.028

3

Metastasis factors

	Metastasis	No metastasis	t‐value	P‐value
Patient age (years)	61 ± 12.8	60 ± 16.0	0.339	0.736
Tumor size	13.5 ± 4.9	10.2 ± 7.3	1.863	0.068

ACKNOWLEDGMENTS

This work was supported by grants from the Natural Science Foundation of Liaoning Province (No. 2014021018 to Shun‐Dong Dai) and the National Natural Science Foundation of China (No. 81401881 to Shun‐Dong Dai and No. 81573654 to Xin Tian).

CONFLICT OF INTEREST

The authors declare that they had read the article and there are no competing interests.