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.
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.
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.
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; Dmax, 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.
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 |
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.
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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.
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Details
1 Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China
2 Molecular Oncology Laboratory of Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
3 Department of Toxicological Pathology, Safety Evaluation Center, Shenyang Research Institute of Chemical Industry, Shenyang, Liaoning, China
4 Department of Colorectal Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
5 Department of Pathology, Shenyang Red Cross Hospital, Shenyang, Liaoning, China