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Clinicopathologic analysis of choriocarcinoma as a pure or predominant component of germ cell tumor of the testis.

以绒毛膜癌为纯粹或主要成分的睾丸生殖细胞肿瘤临床病理分析

Alvarado-Cabrero I,Hernández-Toriz N,Paner GP

Abstract

Although well recognized in the literature, the contemporary clinicopathologic data regarding choriocarcinoma (CC) as a pure or the predominant component of a testicular germ cell tumor (GCT) are limited. Herein, we present a series of pure CC and predominant CC in mixed GCT of the testis obtained from a single oncology institution. A comprehensive histologic review of 1010 orchiectomies from 1999 to 2011 yielded 6 (0.6%) pure CC and 9 (0.9%) mixed GCT cases with a predominant CC component. Patients' ages ranged from 20 to 39 years (median 29 y). All patients had markedly elevated serum β-hCG levels (median 199,000 IU/mL) at presentation. All tumors were unilateral and involved the right (9/15) and left (6/15) testis. The mean tumor size was 6.5 cm (range, 1.5 to 8 cm). Histology was similar for pure CCs and the CC component of mixed GCTs. CC commonly showed expansile hemorrhagic nodular cysts surrounded by variable layers of neoplastic trophoblastic cells (mononucleated trophoblasts and syncytiotrophoblasts). The syncytiotrophoblasts usually covered columns of mononucleated trophoblasts and occasionally formed plexiform aggregates and pseudovillous protrusions. Immunohistochemical stains suggested a mixture of cytotrophoblasts (p63, HPL) and intermediate trophoblasts (p63, HPL weak +/-) in the columns of mononucleated cells. In the 9 mixed GCTs, CC comprised 50% to 95% (7/9 were ≥80% CC) of the tumor; 7 were combined with 1, and 2 were combined with 2 other GCT components. The non-CC components included teratoma (5/9), seminoma (2/9), yolk sac tumor (2/9), and embryonal carcinoma (2/9). Lymphovascular invasion, spermatic cord invasion, and tunica vaginalis invasion were present in 15/15, 5/15, and 1/12 cases, respectively. In mixed GCTs, these locally aggressive features were attributed to the CC component, except in 1 tumor in which it was also exhibited by the embryonal carcinoma component. Lymphovascular invasion was multifocal to widespread in 73% of tumors. The stages of the 15 tumors were: pT2 (10), pT3 (5); NX (1), N1 (4), N2 (5), N3 (5); and M1a (2) and M1b (13). Distant organ metastasis mostly involved the lungs (11) and liver (10). Follow-up information was available in 14 patients, all of whom received cisplatin-based chemotherapy. All 6 pure CC patients were dead of disease (range, 6 to 14 mo, median 9.5 mo). Follow-up of 8 patients with predominant CC (range, 10 to 72 mo, median 27 mo) showed that 5 died of the disease, and 1 was alive with disease and 2 were alive with no evidence of disease at 60 and 72 months of follow-up, respectively; these latter 2 patients were the only ones with M1a disease on presentation. This series confirms the proclivity for high-stage presentation including presence of distant metastasis, hematogenous spread, and poor outcome of testicular CC. Mixed GCT with a predominant CC component has similar tendency for high-stage presentation, marked elevation of serum β-hCG levels, and aggressive behavior compared with pure CC. This study also showed that distant metastasis by CC when only involving the lungs (M1a) may not be uniformly fatal with chemotherapy. The mononucleated trophoblastic columns in testicular CC appear to be a mixture of cytotrophoblasts and intermediate trophoblasts, similar to that described in gestational CC.

摘要

尽管目前文献中已认识到绒毛膜癌(CC)可作为睾丸生殖细胞肿瘤(GCT)的成分之一,但其作为单纯或主要成分的现代临床数据有限。在此,我们介绍一组在睾丸混合性GCT中以CC为单纯或主要成分的病例,这些病例来源于同一家肿瘤机构。对1999到2011年间的1010例睾丸切除术组织学切片进行了广泛的复习,从中找出了6例(0.6%)纯CC和9例(0.9%)以CC为主要成分的混合性GCT。患者年龄20~39岁(中位年龄29岁)。所有的患者血清β-hCG水平显著升高(中位数199,000 IU/mL)。所有的肿瘤都是单侧的,仅发生于右侧(9/15)或左侧(6/15)睾丸。肿瘤平均大小6.5cm(大小范围1.5到8cm)。单纯为CC的病变与混合性GCT中的CC病变组织学形态是相似的。CC通常表现为膨胀性出血性结节或囊肿,后者被层数不同的肿瘤性滋养叶细胞(单核样滋养叶细胞和合体滋养叶细胞)所包绕。合体滋养叶细胞通常覆盖于一群群的单核样滋养叶细胞表面,偶尔簇状聚集或形成假乳头样突起。免疫组化染色提示单核样滋养叶细胞群由细胞滋养叶细胞(p63,HPL)和中间型滋养叶细胞(p63,HPL弱+/-)混合而成。9例混合性GCT中,CC成分占整个肿瘤的50%到95%(7/9例含有≥80% CC成分);7例伴随有1种,2例伴随有2种其他的GCT成分。非CC成分包括畸胎瘤(5/9),精原细胞瘤(2/9),卵黄囊瘤(2/9),以及胚胎癌(2/9)。淋巴管浸润、精索浸润及鞘膜浸润的发生频率分别为15/15,5/15,1/12。在混合性GCT中,这些局部侵袭性的特点是CC成分的引起的,除了在1例肿瘤中胚胎性癌成分也表现出局部侵袭性。淋巴血管浸润在73%的病例中显示出多灶性到广泛性。15例肿瘤的分期分别是:pT2 (10), pT3 (5); NX (1), N1 (4), N2 (5), N3 (5); and M1a (2) and M1b (13)。远处器官转移大多累及肺(11例)和肝(10例)。14例患者获得随访信息,他们都接受了基于顺铂的化疗。所有6例单纯CC患者死于疾病本身(6到14个月,平均9.5个月)。以CC为主要成分的8例的随访结果显示5例死于疾病本身,1例带瘤生存,2例分别在随访时间60个月和72个月时无瘤生存。后2个病例是仅有的发病时分期为M1a的病例。这组病例证实了睾丸CC倾向于分期晚,表现为远处转移,血源性播散,预后差。与单纯的CC相比,以CC为主要成分的混合性GCT也显示出相似的分期晚趋势,血清β-hCG水平显著升高,具有侵袭性行为。本研究也显示CC发生仅仅累及肺的远处转移(M1a)时,进行化疗后可能并不都具有致命性。睾丸CC中的单核样滋养叶细胞群由细胞滋养叶细胞和中间型滋养叶细胞的混合而成,这与妊娠CC相似。

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