小儿卡波西型血管内皮瘤19例临床分析

doi:10.3969/j.issn.1674-8115.2021.04.016

摘要/Abstract

摘要：

目的·探讨小儿卡波西型血管内皮瘤（Kaposi form hemangioendothelioma，KHE）的临床特点及治疗策略。方法·回顾2009年1月—2017年12月上海交通大学医学院附属新华医院收治的19例KHE患儿的临床资料，统计分析病例的一般特点、肿瘤性状、是否合并卡萨巴赫-梅里特（卡梅）现象（Kasabach-Merritt phenomenon，KMP）、治疗方法和转归等。比较出现KMP的患儿和未出现KMP的患儿在肿瘤是否累及表皮以及深部肌肉上的差异。结果·19例KHE患儿中男性13例（68.4%），女性6例（31.6%）。发病于1岁以内17例（89.5%），其中12例（63.2%）为出生时即发现。发生部位为头颈部6例，躯干4例，四肢9例；未见多部位发病者。累及表皮者13例（68.4%），表现为皮肤大面积不规则紫红色、质硬、皮温增高的包块；未累及表皮者6例（31.6%），表现为皮下质硬、活动度差的包块。7例（36.8%）患儿发病后伴有KMP。出现KMP患儿与未出现KMP患儿在肿瘤是否累及表皮上的差异无统计学意义（P=0.617），而在肿瘤是否累及深部肌肉上的差异存在统计学意义（P=0.017）。所有病例最终均经手术病理确诊（肿瘤完全切除8例、部分切除5例、活检6例），术中发现肿瘤均呈实质性，并呈侵袭性生长。术前使用普萘洛尔治疗者7例，均无明显效果；口服糖皮质激素治疗者10例，其中5例肿瘤缩小后手术切除；且单用糖皮质激素治疗的有效率优于单用普萘洛尔（P=0.044）。糖皮质激素治疗效果不佳者中有2例联合长春新碱治疗后肿瘤最终缩小。术后随访2~5年，肿瘤完全切除者未见复发，未完全切除者术后予口服激素治疗也可实现带瘤生存。结论·KHE多婴儿期起病，肿瘤累及深部肌肉时更易出现KMP。临床表现典型者应尽早手术切除，不典型者可活检明确诊断。合并KMP或无手术条件者可尝试采用糖皮质激素治疗或联合长春新碱治疗。普萘洛尔治疗效果不佳，但可作为一种诊断性治疗的手段。

关键词: 卡波西型血管内皮瘤, 卡萨巴赫-梅里特（卡梅）现象, 糖皮质激素, 治疗

Abstract:

Objective· To assess the clinical characteristics and treatment strategies of Kaposi form hemangioendothelioma (KHE) in children.

Methods· The retrospective study was carried out on 19 cases of children diagnosed with KHE from January 2009 to December 2017 in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine.The general demographics, tumor characteristics, presence or absence of Kasabach-Merritt phenomenon (KMP), treatment and outcome were statistically analyzed. The difference between the children with KMP and without KMP were compared in whether the tumor involved the skin and the deep muscles.

Results· Of the 19 children with KHE, 13 (68.4%) were male and 6 (31.6%) were female; 17 children (89.5%) presented within the first year of life and 12 children (63.2%) were detected at birth; 6 cases occurred on head and neck, 4 cases in the trunk, 9 cases in the extremities, and none was multifocal.Seven cases (36.8%) were complicated with KMP after onset. There was no significant difference in cutaneous lesions (P=0.617), while there was a significant difference in deep muscles involvement (P=0.017) between the cases complicated with KMP and without KMP. All cases were diagnosed on the basis of histopathology and immunohistochemistry after operation, in which 8 were completely removed, 5 were partially excised, and 6 were performed biopsy. All the tumors were substantial and aggressive growth. Seven children were treated by propranolol before operation but no obvious effect was found. Ten children were given oral corticosteroids, and five of them were found tumor shrinking and underwent operation. The treatment of corticosteroids resulted in higher effect than that of propranolol (P=0.044). Two children who showed resistance to corticosteroids accepted a combination therapy of corticosteroids and vincristine, and the tumor shrank at last. During the follow-up of 2 to 5 years, the cases which performed complete resection were without recurrence, and those who accepted partial excision also survived with postoperative corticosteroids treatment.

Conclusion· Most KHE cases occur in infancy. The cases might be predisposed with KPM when the tumors involve the deep muscles. The children with typical clinical features should undergo operation as soon as possible. Besides, those with atypical characters should take biopsy to achieve definite diagnosis. The cases with KMP or with giant tumors that are impossible to be removed could be given corticosteroids treatment with or without vincristine. Although propranolol showed a poor curative effect, it could be used for a diagnostic treatment.

Key words: Kaposi form hemangioendothelioma (KHE), Kasabach-Merritt phenomenon (KMP), corticosteroid, treatment

中图分类号:

R726

曹金俊, 谢伟, 朱晓东, 夏昊. 小儿卡波西型血管内皮瘤19例临床分析[J]. 上海交通大学学报(医学版), 2021, 41(4): 514-518.

Jin-jun CAO, Wei XIE, Xiao-dong ZHU, Hao XIA. Clinical analysis of Kaposi form hemangioendothelioma in 19 children[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(4): 514-518.

图/表 6

表1 KHE患儿临床资料

Tab 1 Clinical data of children with KHE

Characteristic	Without KMP (n=12)	With KMP (n=7)	P value
Gender/n (%)			0.617
Male	9 (75.0)	4 (57.1)
Female	3 (25.0)	3 (42.9)
Onset age/n (%)			0.547
Antenatal	1 (8.3)	0 (0)
At birth	6 (50.0)	5 (71.4)
<1 year	3 (25.0)	2 (28.6)
≥1 year	2 (16.4)	0 (0)
Location/n(%)			0.165
Head and face	5 (41.7)	1 (14.3)
Trunk	1 (8.3)	3 (42.8)
Extremity	6 (50.0)	3 (42.8)
Operation/n(%)			0.435
Completely removed	6 (50.0)	2 (28.6)
Partially excised	2 (16.7)	3 (42.8)
Biopsy	4 (33.3)	2 (28.6)
Prognosis/n(%)			0.350
Cured	7 (58.3)	2 (28.6)
Survival with tumor	5 (41.7)	5 (71.4)

图1 KHE的CT影像Note:A. Normalscan. B. Contrast-enhanced CT.

Fig 1 CT image of one case of KHE

图2 KHE的MRI影像Note:A. T1-weighted imaging. B. T2-weighted imaging.

Fig 2 MRI image of one case of KHE

图3 KHE的病理检查结果Note:A. H-E staining shows spindle cells and vascular lumen (×400). B. Immunohistochemistry staining suggests CD34 expression（×100).

Fig 3 Pathological examination results of KHE

表2 KMP与肿瘤累及部位的关系

Tab 2 Relationship between KMP and tumor involvement sites

Lesion involvement	Without KMP (n=12)	With KMP (n=7)	P value
Skin/n (%)			0.617
Yes	9 （69.2）	4 （30.8）
No	3 （50.0）	3 （50.0）
Deep muscle/n (%)			0.017
Yes	5 （41.7）	7 （58.3）
No	7 （100.0）	0 （0）

图4 患儿糖皮质激素治疗前后对比Note:A. The child accompanied by KMP had a large area of purplish red mass with high skin temperature in the left shoulder dorsum atbirth, which could not be surgically removed. B. The child was diagnosed as KHE by biopsy, who had accepted treatment of glucocorticoid for two weeks before the biopsy without obvious tumor regression，but with KMP improved and platelets returned to normal level. And three months treatment of glucocorticoid after biopsy, the tumor progressively reduced during follow-up.

Fig 4 Clinical progression of one case with glucocorticoid treatment

参考文献 27

1	Zukerberg LR, Nickoloff BJ, Weiss SW. Kaposiform hemangioendothelioma of infancy and childhood. An aggressive neoplasm associated with Kasabach-Merritt syndrome and lymphangiomatosis[J]. Am J Surg Pathol, 1993, 17(4): 321-328.
2	Croteau SE, Liang MG, Kozakewich HP, et al. Kaposiform hemangioendothelioma: atypical features and risks of Kasabach-Merritt phenomenon in 107 referrals[J]. J Pediatr, 2013, 162(1): 142-147.
3	Kelly M. Kasabach-Merritt phenomenon[J]. Pediatr Clin North Am, 2010, 57(5): 1085-1089.
4	李冰, 张茜, 赵志华, 等. 新生儿卡波西型血管内皮瘤伴K-M现象一例[J]. 中华儿科杂志, 2015, 53(2): 144-145.
5	高鹏飞, 舒曼, 谢钧韬, 等. 卡波西型血管内皮瘤13例临床分析[J]. 中华实用儿科临床杂志, 2017, 32(11): 841-844.
6	Drolet BA, Trenor CC, Brandão LR, et al. Consensus-derived practice standards plan for complicated Kaposiform hemangioendothelioma[J]. J Pediatr, 2013, 163(1): 285-291.
7	Ji Y, Yang K, Peng S, et al. Kaposiform haemangioendothelioma: clinical features, complications and risk factors for Kasabach-Merritt phenomenon[J]. Br J Dermatol, 2018, 179(2): 457-463.
8	Dasgupta R, Fishman SJ. ISSVA classification[J]. Semin Pediatr Surg, 2014, 23(4): 158-161.
9	Nakaya T, Morita K, Kurata A, et al. Multifocal Kaposiform hemangioendothelioma in multiple visceral organs: an autopsy of 9-day-old female baby[J]. Hum Pathol, 2014, 45(8): 1773-1777.
10	Ryu YJ, Choi YH, Cheon JE, et al. Imaging findings of Kaposiform hemangioendothelioma in children[J]. Eur J Radiol, 2017, 86: 198-205.
11	Fernández Y, Bernabeu-Wittel M, García-Morillo JS. Kaposiform hemangioendothelioma[J]. Eur J Intern Med, 2009, 20(2):106-113.
12	Gruman A, Liang MG, Mulliken JB, et al. Kaposiform hemangioendothelioma without Kasabach-Merritt phenomenon[J]. J Am Acad Dermatol, 2005, 52(4): 616-622.
13	Duan L, Renzi S, Weidman D, et al. Sirolimustreatment of an infant with intrathoracic Kaposiform hemangioendothelioma complicated by life-threatening pleural and pericardial effusions[J]. J Pediatr Hematol Oncol, 2020, 42(1): 74-78.
14	Tlougan BE, Lee MT, Drolet BA, et al. Medical management of tumors associated with Kasabach-Merritt phenomenon: an expert survey[J]. J Pediatr Hematol Oncol, 2013, 35(8): 618-622.
15	Chiu YE, Drolet BA, Blei F, et al. Variable response to propranolol treatment of Kaposiform hemangioendothelioma, tufted angioma, and Kasabach-Merritt phenomenon[J]. Pediatr Blood Cancer, 2012, 59(5): 934-938.
16	Filippi L, Tamburini A, Berti E, et al. Successful propranolol treatment of a Kaposiform hemangioendothelioma apparently resistant to propranolol[J]. Pediatr Blood Cancer, 2016, 63(7): 1290-1292.
17	Jiang RS, Hu R. Successful treatment of Kasabach-Merritt syndrome arising from Kaposiform hemangioendothelioma by systemic corticosteroid therapy and surgery[J]. Int J Clin Oncol, 2012, 17(5): 512-516.
18	Liu XH, Li JY, Qu XH, et al. Clinical outcomes for systemic corticosteroids versus vincristine in treating Kaposiform hemangioendothelioma and tufted angioma[J]. Medicine (Baltimore), 2016, 95(20): e3431.
19	Ji Y, Chen SY, Xiang B, et al. Sirolimus for the treatment of progressive Kaposiform hemangioendothelioma: a multicenter retrospective study[J]. Int J Cancer, 2017, 141(4): 848-855.
20	George ME, Sharma V, Jacobson J, et al. Adverse effects of systemic glucocorticosteroid therapy in infants with hemangiomas[J]. Arch Dermatol, 2004, 140(8): 963-969.
21	Fahrtash F, McCahon E, Arbuckle S. Successful treatment of Kaposiform hemangioendothelioma and tufted angioma with vincristine[J]. J Pediatr Hematol Oncol, 2010, 32(6): 506-510.
22	Peng SH, Yang KY, Xu ZC, et al. Vincristine and sirolimus in the treatment of Kaposiform haemangioendothelioma[J]. J Paediatr Child Health, 2019, 55(9): 1119-1124.
23	Hartman KR, Moncur JT, Minniti CP, et al. Mediastinal Kaposiform hemangioendothelioma and Kasabach-Merritt phenomenon in an infant: treatment with interferon [J]. J Pediatr Hematol, 2009, 31(9): 690-692.
24	Wang Z, Yao W, Sun H, et al. Sirolimus therapy for Kaposiform hemangioendothelioma with long-term follow-up[J]. J Dermatol, 2019, 46(11): 956-961.
25	Malhotra Y, Yang CS, McNamara J, et al. Congenital Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon successfully treated with low-dose radiation therapy[J]. Pediatr Dermatol, 2014, 31(5): 595-598.
26	Wang P, Zhou W, Tao L, et al. Clinical analysis of Kasabach-Merritt syndrome in 17 neonates[J]. BMC Pediatr, 2014, 14: 146.
27	Schaefer BA, Wang DH, Merrow AC, et al. Long-term outcome for Kaposiform hemangioendothelioma: a report of two cases[J]. Pediatr Blood Cancer, 2017, 64(2): 284-286.

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