趙小曉 石玉香 倪海春 謝永輝 章宏峰
【摘要】 胎盤部位滋養(yǎng)細胞腫瘤(PSTT)是一種罕見的妊娠滋養(yǎng)細胞疾病。該文報道了1例罕見的PSTT,該例為29歲女性患者,因停經(jīng)52 d、異常陰道出血2 d前來就診,予清宮術(shù),宮腔刮出物送病理檢查,其鏡下瘤細胞為大、多角,胞質(zhì)嗜酸,形態(tài)似中間滋養(yǎng)細胞,局部查見小片游離腫瘤細胞往肌組織之間穿插,可見腫瘤細胞從血管外向血管腔內(nèi)浸潤,并取代血管壁。免疫組織化學染色示廣譜細胞角蛋白、細胞角蛋白8/18、GATA-3、CyclinE陽性,CD10、胎盤催乳素部分陽性,人絨毛膜促性腺激素主要表達于多核中間滋養(yǎng)細胞,余指標均陰性,Ki-67標記指數(shù)20%。患者術(shù)后恢復良好。該例診治提示,育齡期女性停經(jīng)或異常陰道出血要高度警惕PSTT,結(jié)合組織學形態(tài)及免疫組織化學檢測,可以對PSTT做出正確診斷,PSTT的鑒別診斷需排除胎盤部位過度反應等滋養(yǎng)細胞疾病。
【關(guān)鍵詞】 胎盤部位滋養(yǎng)細胞腫瘤;病理診斷;鑒別診斷;治療;預后
【Abstract】 Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease (GTD). In this article, we reported one rare case of PSTT. The female patient, aged 29-year old, was admitted to our hospital due to menopause for 52 d and abnormal vaginal bleeding for 2 d. She received curettage and the uterine specimen was collected for pathological examination. Microscopically, the tumor was composed of a relatively monotonous population of polygonal cells with moderately abundant cytoplasm consistent with the appearance of extravillous (intermediate) trophoblast. A small mass of free tumor cells were observed to penetrate into muscular tissues in partial areas. The tumors cells were infiltrated from the outside into the vascular lumen and replaced the vascular wall. Immunohistochemical staining revealed that the tumor cells were positive for PCK, CK8/18, GATA-3 and CyclinE, and partially positive for CD10 and HPL. HCG was mainly expressed in multicore intermediate trophoblast. And the other parameters were negative. Ki-67 Li was 20% positive. The patient was recovered well after surgery. The diagnosis and treatment of this case prompt that the possibility of PSTT should be considered for young women presenting with menopause or abnormal vaginal bleeding. Histological morphology combined with immunohistochemical detection can make an accurate diagnosis of PSTT. PSTT should be distinguished from other GTDs, such as exaggerated placental site (EPS).
【Key words】 Placental site trophoblastic tumor;Pathological diagnosis;Differential diagnosis; Treatment;Prognosis
胎盤部位滋養(yǎng)細胞腫瘤(PSTT)指來源于胎盤種植部位的一種特殊類型的滋養(yǎng)細胞腫瘤,多見于育齡婦女,患者多表現(xiàn)為閉經(jīng)、流產(chǎn)、葡萄胎或足月妊娠后陰道不規(guī)則流血,容易被誤診或漏診。本文收集1例PSTT患者的診治資料,旨在提高臨床醫(yī)師對該病的認識水平,現(xiàn)報告如下。
病例資料
一、病史及??茩z查
患者女,29歲。因停經(jīng)52 d,異常陰道出血9 d,加重1 d于2019年2月8日收入院。患者已婚,孕3產(chǎn)2流產(chǎn)1。上次妊娠時間為2018年6月8日。末次月經(jīng)2018年12月18日。??茩z查:外陰發(fā)育正常,陰道暢,可見少許血液,宮頸輕度糜爛,舉痛疑似陽性,子宮前位,左側(cè)附件區(qū)稍增厚,右側(cè)附件區(qū)未見明顯異常。陰道后穹隆穿刺出4 ml不凝血。入院查血β-人絨毛膜促性腺激素(β-HCG)75.5 U/L。子宮附件超聲:子宮大小正常,內(nèi)膜厚約0.7 cm,宮腔內(nèi)未見明顯孕囊,左側(cè)卵巢旁混合回聲區(qū):考慮可疑異位妊娠包塊,右側(cè)附件區(qū)未見明顯異常,盆腔少量積液。
二、 診治過程
予清宮術(shù),宮腔刮出物送病理檢查。送檢標本常規(guī)用10%甲醛固定,石蠟包埋,3 ~ 4 μm厚切片,行HE染色、免疫組織化學SP法染色。肉眼觀察:均為暗紅血凝塊樣物一堆。顯微鏡檢:鏡下主要為增生期子宮內(nèi)膜,未見絨毛,局部查見小片游離腫瘤細胞往肌組織之間穿插(圖1A),瘤細胞大、多角,核不規(guī)則而深染,胞質(zhì)嗜酸,較濃厚;可見腫瘤細胞從血管外向血管腔內(nèi)浸潤,并取代血管壁(圖1B)。免疫表型:廣譜細胞角蛋白(PCK)、細胞角蛋白8/18(CK8/18)、GATA-3、CyclinE(+),CD10、胎盤催乳素(HPL,部分+,圖1C),HCG(少量+,主要在多核中間滋養(yǎng)細胞表達,圖1D);P63、4型黏蛋白(MUC4)、結(jié)蛋白Desmin、平滑肌肌動蛋白(SMA,-),Ki-67標記指數(shù)20%。診斷:PSTT。清宮術(shù)后患者回家休養(yǎng),定期復查血β-HCG及B超,至撰稿日未見明顯異常,恢復尚可。
討 論
PSTT是胎盤部位有惡性潛能的中間滋養(yǎng)細胞腫瘤,生物學行為編碼(ICDO)為1,較少見,發(fā)生率1/50 000 ~ 1/100 000,占妊娠滋養(yǎng)細胞疾病的1% ~ 2%,占妊娠滋養(yǎng)細胞腫瘤的比例小于0.25%[1-2]。PSTT多發(fā)生于育齡期女性,平均發(fā)病年齡33歲,常發(fā)生于子宮體或子宮底,但也有文獻報道個別發(fā)生于子宮頸[3]。主要癥狀為陰道出血、腹痛或者腹部包塊,也可以有子宮破裂或者腎病綜合征,可與葡萄胎、上皮樣滋養(yǎng)細胞腫瘤、絨毛膜癌同時發(fā)生[3]。腫瘤成分主要為中間滋養(yǎng)細胞,合體滋養(yǎng)細胞少或無,所以患者血清β-HCG一般比較低,本例患者β-HCG僅輕微升高。PSTT進展緩慢,大多數(shù)患者不發(fā)生轉(zhuǎn)移,預后良好,少數(shù)患者發(fā)生轉(zhuǎn)移,一旦轉(zhuǎn)移則往往廣泛播散,預后不良。不同的研究關(guān)于轉(zhuǎn)移的發(fā)生率各不相同,大致為10% ~ 35%[2]。隨著二孩政策的放開,PSTT發(fā)病呈現(xiàn)上升趨勢,PSTT的早期診斷顯得尤為重要,早期診斷可為患者提供最佳的治療方案和手術(shù)時機。
PSTT鏡下無絨毛,腫瘤細胞以單核中間滋養(yǎng)細胞為主,雙核及多核滋養(yǎng)細胞少見,罕見合體滋養(yǎng)細胞成分,鏡下腫瘤細胞形態(tài)相對一致,比細胞滋養(yǎng)細胞大,圓形、卵圓形或多角形,少數(shù)可為梭形,胞質(zhì)豐富,淡染或嗜雙色性,有時可以見到胞質(zhì)透明的細胞。腫瘤細胞常呈片狀或條索樣排列,也可單個散在浸潤于肌壁間,將平滑肌纖維沖斷,但平滑肌無壞死改變,瘤細胞侵襲并取代血管壁,但是保留完整血管輪廓、血管內(nèi)皮細胞,所以鏡下出血不明顯,即使有也為局灶出血壞死,無絨癌般廣泛壞死,大多數(shù)病例中核分裂2 ~ 4個/10個高倍視野[1]。腫瘤細胞表達HPL、HCG、GATA-3、MUC4、CD10,其中HPL彌漫強陽性,HCG僅僅在分散的多核腫瘤細胞中陽性,腫瘤細胞上皮性標記PCK、AE1/AE3、CK18強陽性,Ki-67標記指數(shù)約10% ~ 30%。Kar等[4]研究指出PSTT中CyclinE彌漫強表達,CyclinE的積累可能參與滋養(yǎng)細胞的惡性轉(zhuǎn)化。Lu等[5]研究顯示PD-L1是滋養(yǎng)細胞腫瘤的敏感指標,可以用來區(qū)分滋養(yǎng)細胞來源。
PSTT的主要鑒別診斷有:①胎盤部位過度反應,無明確腫塊形成,有絨毛,單核滋養(yǎng)細胞和分散的多核滋養(yǎng)細胞混雜,核分裂少見或無,且Ki-67標記指數(shù)< 1%。②上皮樣滋養(yǎng)細胞腫瘤,廣泛壞死伴有營養(yǎng)不良性鈣化,且腫瘤周圍圍繞嗜酸性纖維樣物質(zhì),使腫瘤外觀呈“地圖樣”,血管浸潤不明顯。上皮樣滋養(yǎng)細胞腫瘤HPL局灶陽性或陰性、P63陽性,而PSTT HPL彌漫陽性、P63陰性。在滋養(yǎng)細胞疾病中,P63僅表達于絨毛膜型滋養(yǎng)細胞病變,而不表達于種植部位滋養(yǎng)細胞病變,是區(qū)分上皮樣滋養(yǎng)細胞腫瘤和PSTT比較好的標記[6]。③絨癌,其由細胞滋養(yǎng)細胞、中間滋養(yǎng)細胞和合體滋養(yǎng)細胞增生形成,偶爾腫瘤中細胞滋養(yǎng)細胞十分顯著,合體滋養(yǎng)細胞較少,此時與PSTT鑒別尤為重要。④胎盤部位結(jié)節(jié),病灶小而局限,無浸潤,表達P63,不表達或僅灶性表達HPL和CD146,且Ki-67標記指數(shù)通常< 5%。
PSTT與其他妊娠滋養(yǎng)細胞疾病不同,產(chǎn)生較少β-HCG,對化學治療不敏感,預后差別很大,目前沒有統(tǒng)一的預后影響因子[7]。手術(shù)是首選的治療方法,其原則是切除一切病灶,范圍包括全子宮切除及雙側(cè)附件切除[8]。高危PSTT患者(先前妊娠時間> 2 年、腫瘤細胞有絲分裂指數(shù)> 5 個/
10個高倍視野、有子宮外轉(zhuǎn)移)子宮切除后還應選擇聯(lián)合化學治療,化學治療方案為EMA-CO/EP-EMA[9-12]。最近Froeling等[13]研究顯示,F(xiàn)IGOⅢ期、Ⅳ期及先前妊娠時間≥48月的PSTT患者使用以鉑為基礎(chǔ)的高劑量化學治療方案能明顯改善預后。本文患者先前妊娠時間8個月、病灶局限,屬于低危年輕患者,該患者行清宮術(shù)后拒絕進一步治療,充分了解病情,自行要求出院。對于該類患者,出院時應告知其嚴密監(jiān)測月經(jīng)恢復情況、血清β-HCG水平,定期復查B超監(jiān)測子宮內(nèi)病灶情況,必要時行全子宮雙附件切除及化學治療。
參 考 文 獻
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(收稿日期:2019-08-13)
(本文編輯:林燕薇)