8例儿童卵巢颗粒细胞瘤临床病理特征及预后分析

doi:10.3969/j.issn.1674-8115.2022.02.009

摘要/Abstract

摘要：

目的·探讨儿童卵巢颗粒细胞瘤（granulosa cell tumor，GCT）的临床病理特征和预后。方法·收集上海市儿童医院2008年6月至2018年6月共8例卵巢GCT患儿的临床病理资料和随访资料，总结其临床病理学特征并分析预后情况。结果·患儿发病年龄为2~12岁（中位年龄6.5岁）。2例为成人型颗粒细胞瘤（adult granulosa cell tumor，AGCT），6例为幼年型颗粒细胞瘤（juvenile granulosa cell tumor，JGCT）。首发症状均表现为腹痛或腹部包块。6例患儿并发性早熟症状；其中5例为真性性早熟，1例为假性性早熟。外周血性激素水平均有不同程度的改变。肿瘤最大径4~22 cm（平均12.8 cm），大体形态呈囊实性。AGCT在光学显微镜下可见明显核沟，并有微滤泡结构，内含嗜酸性物质，即特征性的Call-Exner小体；JGCT具有大小不等的滤泡结构，内含嗜碱性分泌物，滤泡壁内层由粒层细胞构成，周围可被卵泡膜细胞环绕，未见Call-Exner小体，核沟少见。免疫组织化学检测结果显示：所有患儿α抑制素（α-inhibin）和CD99均为阳性，上皮细胞膜抗原（epithelial membrane antigen，EMA）均为阴性，5例钙网膜蛋白阳性，5例广谱细胞角蛋白（cytokeratin，CK）阳性，Ki-67增殖指数为5%~50%，3例雌激素受体（estrogen receptor，ER）阳性，6例孕激素受体（progesterone receptor，PR）阳性，翼状螺旋/叉头转录因子2（forkhead transcription factor 2，FOXL2）在2例AGCT和6例JGCT中均高表达，2例AGCT和3例JGCT中见散在SOX9（SRY-box transcription factor 9）阳性细胞。所有病例接受手术治疗，其中5例术中发现肿瘤破裂或转移，1例腹水病理检测结果为可疑阳性。8例GCT患儿术后随访19~155个月，均健康存活。结论·儿童卵巢AGCT与JGCT临床特征相似且各自具有典型的组织病理学特征。选择合适的免疫组织化学检测方法，有助于同其他儿童卵巢肿瘤进行鉴别诊断。即使发生肿瘤破裂，儿童卵巢GCT经彻底手术等治疗，预后仍良好。

关键词: 儿童, 颗粒细胞瘤, 卵巢肿瘤, 临床病理特征, 预后

Abstract:

Objective·To investigate the clinicopathological features and prognosis of ovarian granulosa cell tumor (GCT) in children.

Methods·The clinicopathologic and follow-up data of 8 patients with ovarian GCT in Shanghai Children's Hospital from June 2008 to June 2018 were collected and retrospectively studied to summarize the clinicopathological features and analyze the prognosis.

Results·The age of onset in this group ranged from 2 to 12 years with median age of 6.5 years. Two cases were adult granulosa cell tumor (AGCT) and six cases were juvenile granulosa cell tumor (JGCT). The first symptoms were abdominal pain or abdominal mass. Six patients were complicated with symptoms of precocious puberty, including 5 cases of true precocious puberty and 1 case of pseudo precocious puberty. The levels of peripheral blood sex hormones changed to varying degrees. Gross examination showed that the tumor masses ranged from 4 to 22 cm in the greatest dimension (average 12.8 cm). All of the 8 tumors were mixed solid-cystic in appearance. Under light microscope, AGCT showed obvious nuclear sulcus and microfollicular structure, containing eosinophilic substances, namely characteristic Call-Exner bodies. JGCT had follicular structures of different sizes, containing basophilic secretions. The inner layer of the follicular wall was composed of granular cells, which could be surrounded by follicular membrane cells. No Call-Exner bodies were found, and nuclear sulcus were rare. The results of immunohistochemistry showed that α-inhibin and CD99 were positive, and epithelial membrane antigen (EMA) were negative in all the cases. In 5 cases calretinin were positive, and in 5 cases cytokeratin (CK) were positive. Ki-67 proliferation index was 5%?50%. There were 3 estrogen receptor (ER) positive cases and 6 progesterone receptor (PR) positive cases. Forkhead transcription factor 2 (FOXL2) was highly expressed in 2 cases of AGCT and 6 cases of JGCT. SRY-box transcription factor 9 (SOX9) positive cells were scattered in 2 cases of AGCT and 3 cases of JGCT. All the cases were treated with standard surgery. Tumor rupture or metastasis was found in 5 cases, and ascites was suspiciously positive in 1 case. Eight children with ovarian GCT were followed up for 19?155 months, and all of them survived in good health.

Conclusion·The clinical features of AGCT and JGCT in children's ovaries are similar and have typical histopathological features respectively. The selection of suitable immunohistochemical detection method is helpful for differential diagnosis of ovarian tumors in children. The prognosis of ovarian GCT in children is good even with tumor rupture after radical surgery.

Key words: children, granulosa cell tumor (GCT), ovarian neoplasm, clinicopathological feature, prognosis

中图分类号:

R725.8

邢正文, 吴滢, 王雪莉, 王庆煜, 王文婷, 李治, 张彬, 金晶. 8例儿童卵巢颗粒细胞瘤临床病理特征及预后分析[J]. 上海交通大学学报(医学版), 2022, 42(2): 192-196.

Zhengwen XING, Ying WU, Xueli WANG, Qingyu WANG, Wenting WANG, Zhi LI, Bin ZHANG, Jing JIN. Analysis of clinicopathologic features and prognosis of eight children with granulosa cell tumor of ovary[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2022, 42(2): 192-196.

图/表 4

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Number	Age/year	First symptom	Clinical development	Type of precocious puberty	FIGO stage	Lesion	Follow-up/month	Relapse
1	7	Abdominal pain	No	No	ⅡA	Left ovary	32	No
2	4	Abdominal pain	Breast development with tenderness	Falsehood	ⅠA	Left ovary	115	No
3	2	Abdominal block	Breast development， enlarged uterus	Authenticity	ⅠA	Left ovary	60	No
4	6	Abdominal block	Breast development	Authenticity	ⅠC	Right ovary	155	No
5	4	Abdominal block	Breast development， precocious uterus	Authenticity	ⅠC	Right ovary	112	No
6	7	Abdominal block， abdominal pain	Enlarged uterus	Authenticity	ⅢC	Left ovary	83	No
7	8	Abdominal block， abdominal pain	Enlarged uterus	Authenticity	ⅢB	Left ovary	34	No
8	12	Abdominal pain	Slightly enlarged uterus	No	ⅠB	Bilateral ovaries	19	No

Number	Age/year	First symptom	Clinical development	Type of precocious puberty	FIGO stage	Lesion	Follow-up/month	Relapse
1	7	Abdominal pain	No	No	ⅡA	Left ovary	32	No
2	4	Abdominal pain	Breast development with tenderness	Falsehood	ⅠA	Left ovary	115	No
3	2	Abdominal block	Breast development， enlarged uterus	Authenticity	ⅠA	Left ovary	60	No
4	6	Abdominal block	Breast development	Authenticity	ⅠC	Right ovary	155	No
5	4	Abdominal block	Breast development， precocious uterus	Authenticity	ⅠC	Right ovary	112	No
6	7	Abdominal block， abdominal pain	Enlarged uterus	Authenticity	ⅢC	Left ovary	83	No
7	8	Abdominal block， abdominal pain	Enlarged uterus	Authenticity	ⅢB	Left ovary	34	No
8	12	Abdominal pain	Slightly enlarged uterus	No	ⅠB	Bilateral ovaries	19	No

Number	E₂/ （pmol·L^-1）	P/ （nmol·L^-1）	TES /（nmol·L^-1）	PRL/ （mIU·L^-1）	SHBG/ （nmol·L^-1）	LH/ （IU·L^-1）	FSH/ （IU·L^-1）	HCG/ （mU·mL^-1）
1	72.80	6.12	1.14	322.33	68.70	0.20	0.36	0.20
2	36.80	0.20	2.86	9.00	N/A	0.10	0.10	N/A
3	553.00	1.12	2.48	88.81	106.20	0.20	0.20	0.38
4	260.00	11.50	0.65	145.00	53.10	0.51	1.49	<<1.00
5	73.40	0.64	0.68	596.00	173.90	0.10	1.04	<<1.00
6	2 460.00	45.78	0.41	832.42	N/A	0.20	0.20	0.50
7	965.00	7.01	1.01	250.75	70.70	0.20	0.20	0.20
8	745.00	12.32	27.00	456.59	82.80	0.20	0.49	0.20

Number	E₂/ （pmol·L^-1）	P/ （nmol·L^-1）	TES /（nmol·L^-1）	PRL/ （mIU·L^-1）	SHBG/ （nmol·L^-1）	LH/ （IU·L^-1）	FSH/ （IU·L^-1）	HCG/ （mU·mL^-1）
1	72.80	6.12	1.14	322.33	68.70	0.20	0.36	0.20
2	36.80	0.20	2.86	9.00	N/A	0.10	0.10	N/A
3	553.00	1.12	2.48	88.81	106.20	0.20	0.20	0.38
4	260.00	11.50	0.65	145.00	53.10	0.51	1.49	<<1.00
5	73.40	0.64	0.68	596.00	173.90	0.10	1.04	<<1.00
6	2 460.00	45.78	0.41	832.42	N/A	0.20	0.20	0.50
7	965.00	7.01	1.01	250.75	70.70	0.20	0.20	0.20
8	745.00	12.32	27.00	456.59	82.80	0.20	0.49	0.20

Number	Histological type	Maximum diameter/cm	Nuclear splits/10HPF	Calretinin	α-inhibin	CD99	FOXL2	SOX9	EMA	CK	ER	PR	Ki-67
1	AGCT	5	3	40%+	50%+	+	85%+	10%+	-	+	-	100%+	5%+
2	AGCT	6	7	+	+	+	90%+	5%+	-	+	90%+	95%+	15%+
3	JGCT	10	7	-	+	+	90%+	10%+	-	+	-	100%+	20%+
4	JGCT	13	4	+	+	+	100%+	-	-	+	95%+	85%+	10%+
5	JGCT	4	26	-	+	+	95%+	5%+	-	-	95%+	90%+	10%+
6	JGCT	22	62	-	+	+	100%+	-	-	-	-	-	50%+
7	JGCT	19	25	20%+	+	50%+	95%+	5%+	-	-	-	-	30%+
8	JGCT	12， 15	67	+	+	+	95%+	-	-	+	-	95%+	35%+