假肌源性血管内皮瘤(pseudomyogenic hemangioendothelioma,PHE)是一种罕见的中间性血管源性肿瘤,形态上与多种软组织肿瘤有相似性,容易误诊.现报道1例假肌源性血管内皮瘤,结合文献复习对本病的病理形态特征、鉴别诊断、免疫组化及分子遗传学等进行探讨.

目的 探讨痔疮被覆鳞状上皮黏膜中人乳头瘤病毒(HPV)感染情况及其致瘤性.方法 选取中日友好医院痔疮标本6208例,筛选鳞状上皮黏膜中含有典型及不典型挖空细胞的痔疮样本135例,同期30例未见挖空样细胞的痔疮样本作为对照组.免疫组化检测标本中P16的表达,PCR杂交法检测HPV病毒并分型.结果 含挖空细胞病例占总送检痔疮病例的2.17％(135/6208).实验组病例被覆上皮轻度不典型增生(80例)、中度不典型增生(21例)、重度不典型增生/原位癌(19例)、肛周鳞状细胞癌(15例),四组HPV感染阳性率分别为77.50％(62/80)、71.43％(15/21)、42.11％(8/19)、73.33％(11/15),其中高危型 HPV 的感染率分别为 11.29％(7/62),33.33％(5/15),100％(8/8),90.91％(10/11).检测出 P16 阳性率为 51.85％(70/135),HPV 分子亚型中 56 例单一低危型感染,23例单一高危型感染及17例混合亚型感染.结论 痔疮被覆鳞状上皮中HPV感染较低,组织学中的挖空细胞是重要提示,对于伴有挖空细胞的痔疮应进行HPV分子亚型与免疫组化P16的联合检测.

涎腺分泌性癌(secretory carcinoma of salivary gland,SCSG),是一种少见的低度恶性肿瘤,因其类似乳腺分泌性癌而得名.Skalova等[1]于2010年首次报道.WHO(2017)第4版涎腺肿瘤分类中正式提出并独立命名为分泌性癌[2].组织学上该肿瘤排列方式多样,可呈实性巢状、微囊状、小管样、乳头囊或滤泡状,但大囊性单房或多房生长模式罕见[3],国内报道极少.本文报道1例单房囊性生长的涎腺分泌性癌,并回顾了相关文献以提高对该病的认识.

患者,女性,22岁,无明显诱因出现反复剑突下疼痛4年余,每次持续10 min左右,可自行缓解.就诊于外院,门诊查"胃镜"提示"胃底黏膜隆起,慢性非萎缩性胃炎","超声胃镜"提示胃底黏膜下隆起(NET?或其他?).2019-09于外院行"内镜下胃黏膜隆起切除术",2019-12来我院进行病理会诊.镜检:病变较小,主要位于黏膜下层,肿瘤细胞呈梭形,核质比高,边缘可见淋巴细胞聚集,局灶累及肌层,肿瘤间可见大量胶原,散在肥大细胞浸润,核分裂少见.

目的 探讨类似卵巢性索肿瘤的子宫肿瘤(UTROSCT)的临床病理特点.方法 回顾性分析5例UTROSCT的临床特征,总结其组织学形态及免疫组化表达特点,并进行随访.结果 患者年龄40～60岁(平均49.2岁,中位52岁).3例以阴道出血就诊,1例因子宫肌瘤切除发现,1例因体检发现黏膜下肌瘤就诊.3例肿瘤组织位于内膜部位,1例位于肌壁间,1例位于内膜及肌层.4例患者随访18～ 147个月不等(平均95.5个月),无一例复发或转移.组织学上可见巢状、小梁状、条索样、片状或Sertorli管样结构;肿瘤细胞可呈上皮样,具有丰富的、泡沫状或透明的胞质,也可呈短梭形或卵圆形,胞质稀少;细胞异型性小,核分裂象少见.免疫组化显示肿瘤细胞表达AE1/AE3 (4/4)及vimentin(3/3),不同程度地表达性索标志物α-inhibin (5/5)、calretinin(5/5)、CD99 (5/5)、MelanA (2/3),激素受体ER (3/4)、PR(4/4),及CD10(4/5),不表达平滑肌标志物SMA(0/2).Ki-67增殖指数2％～10％.结论 UTROSCT是一类特殊的子宫肿瘤,绝大部分呈良性经过,病理形态具有性索样的分化特点,组织结构多样,可表达多种性索及上皮标记物,分子改变与卵巢性索肿瘤及子宫内膜间质肿瘤不同,可资鉴别.

目的:探讨胃黏膜活检标本中淋巴细胞、中性粒细胞与幽门螺旋杆菌(HP)感染情况、分子分型及感染强度的相关性.方法:回顾性收集中日友好医院2018年1月～2020年12月期间送检的胃镜活检标本共56648例,采用实时荧光定量PCR方法检测HP的感染情况、分子分型及感染强度.结果:HP阳性患者中淋巴滤泡(LF)和中性粒细胞的检出率均明显高于HP阴性组(均P＜0.01).HP Ⅰ型与Ⅱ型的胃炎患者中,LF检出率差异无统计学意义(P＞0.05),而不同分级活动性胃炎的检出率差异有统计学意义(P＜0.01).不同HP感染强度的胃炎患者中LF形成、胃炎活动性差异均有统计学意义(均P＜0.01).胃炎活动度Ⅲ级伴LF患者中HP的阳性率高达95.6％.结论:胃黏膜活检患者中,淋巴滤泡形成、中性粒细胞均与HP相关.淋巴滤泡形成伴中性粒细胞浸润对推断HP感染有辅助作用.

Objective:To analyze the value of folate receptor-positive circulating tumor cells (FR +-CTC) in the diagnosis and efficacy evaluation of patients with small cell lung cancer (SCLC). Methods:The data of 59 patients with SCLC and 14 patients with benign pulmonary diseases treated in China-Japan Friendship Hospital from May 2017 to October 2019 were retrospectively analyzed. Folate receptor targeted detection was used to detect the level of FR +-CTC in the blood of SCLC patients. The levels of serum progastrin-releasing peptide (Pro-GRP), neuron-specific enolase (NSE), cytokeratin 19 fragment 21-1 (Cyfra21-1) , and carcinoembryonic antigen (CEA) were detected by using chemiluminescence. The median ( P25, P75) was used as all the detection indexes. Mann-Whitney U test was used for pairwise comparison, Spearman correlation test was used to analyze the correlation between two variables, and receiver operator characteristic (ROC) curve was used to evaluate the diagnostic efficacy. Results:The level of FR +-CTC in 59 patients with SCLC was 11.00 FU/3 ml (7.10 FU/3 ml, 14.50 FU/3 ml), and the positive rate of FR +-CTC in patients with SCLC was 66.10% (30/59); the level of FR +-CTC in 14 patients with benign pulmonary diseases was 6.75 FU/3 ml (5.03 FU/3 ml, 7.85 FU/3 ml), and the positive rate of FR +-CTC in 14 patients with benign pulmonary diseases was 14.29% (2/14). The level of FR +-CTC in patients with SCLC was higher than that in patients with benign pulmonary diseases, and the difference was statistically different ( U = 33.50, P < 0.01). The expression level of FR +-CTC was not related to age, gender and smoking history in SCLC patients (all P>0.05). The expression level of FR +-CTC in patients with extensive-stage was higher than that in patients with limited-stage, and the difference was statistically significant ( P < 0.05). Tumor markers Pro-GRP, NSE, Cyfra21-1 and CEA were compared with FR +-CTC, and the ROC curve was drawn; the results showed that FR +-CTC had better sensitivity (71.2%) and specificity (92.90%) in the diagnosis of SCLC. For SCLC patients who received chemotherapy, the decrease range of FR +-CTC in patients with partial remission and stable disease was greater than that in patients with the progression of disease, and the differences were statistically significant (all P < 0.05). Conclusion:FR +-CTC can assist the diagnosis and disease staging of SCLC. For patients receiving chemotherapy, continuous detection of circulating tumor cells can help to evaluate the efficacy of chemotherapy and provide a reference for the choice of clinical treatment.

髓样/淋巴或混合谱系白血病蛋白3(myeloid/lymphoid or mixed lineage leukemia3,MLL3),又名赖氨酸甲基转移酶2C(lysine methyltransferase 2C,KMT2C),为 KMT2家族的成员之一,位于7q36.1,具有65个外显子,编码一种核蛋白,是对组蛋白3赖氨酸4(histone 3 lysine 4,H3K4)进行甲基化修饰的酶,H3K4甲基化通常与转录活性相关,二甲基和三甲基化的H3K4与基因启动子的激活有关,而单甲基化则与基因增强子[1,2]有关.MLL家族基因被认为与组织的生长调控、肿瘤发生有关.MLL3被发现镶嵌于一种与SET1相关的蛋白复合物中,.该复合物在人类中有6种亚型.MLL3/4蛋白复合物是调节基因增强子区H3K4单甲基化的重要的复合物,MLL3蛋白复合物是包含9个亚基的巨大复合物[3].

目的:分析非小细胞肺癌罕见驱动基因突变特点及其与临床病理特征的相关性.方法:收集中日友好医院病理科2018年11月～2019年12月间送检的630例非小细胞肺癌患者手术切除标本.使用荧光定量PCR法对标本的驱动基因进行联合检测,包括EGFR、KRAS、NRAS、BRAF、PIK3CA、HER2基因突变,以及ALK、ROS1、RET基因融合.结果:标本整体基因突变阳性率为63.49％,融合阳性率为6.35％,全部野生型的病例占30.16％.罕见驱动基因改变占全部驱动基因改变的27.27％ (120/440).EGFR突变病例中,罕见突变位点占9.63％ (31/322).EGFR20外显子插入突变及HER2突变均与患者年龄负相关(r=-0.108、r=-0.191,P＜0.05).RAS突变与肿瘤大小正相关(r=0.159,P＜0.05),并与性别及组织学分型具有相关性(P＜0.05).ALK、ROS1、RET融合均与组织学包含微乳头成分正相关(r=0.097、r=0.105、r=0.136,P＜0.05).ALK融合与组织学分型以及淋巴结转移的相关性具有统计学意义(P＜0.05).结论:非小细胞肺癌罕见驱动基因突变虽然发生率较低,但包含一种以上罕见突变的患者比例较高.这些驱动基因突变与临床病理特征的关系多种多样,大多与组织学分型相关.

目的 采用叶酸受体靶向PCR技术(LT-PCR)定量检测小细胞肺癌(SCLC)患者血液标本中循环肿瘤细胞(CTC)含量,分析CTC对SCLC患者化疗效果的预测价值.方法 收集42例SCLC患者的血液标本,采用LT-PCR定量检测CTC含量.化学发光法检测血清肿瘤标志物胃泌素释放肽前体(pro-GRP)、神经元特异性烯醇化酶(NSE)及癌胚抗原(CEA)含量.SCLC患者化疗后根据实体瘤RECIST评级分为完全缓解(CR)、部分缓解(PR)、病情稳定(SD)、疾病进展(PD)及死亡组,采用Kruskal-Wallis H检验比较各组间总体差异,Mann-Whitney U检验进行组间两两比较,双变量相关分析用Spearman相关检验.结果 LT-PCR检测结果表明,CTC在SCLC患者中的表达水平为12.05(7.55,15.81)FU/mL,其阳性率为71.43％(30/42),CTC的表达水平与SCLC患者年龄、性别、吸烟史无关(P均>0.05),而与临床分期有关(P<0.05);CTC的表达水平与pro-GRP、NSE及CEA均无关(P均>0.05);化疗获益组(PR组、SD组)与PD组患者CTC的表达水平差异有统计学意义(P均<0.05);CR患者中1例CTC表达阴性,死亡患者中1例CTC表达阳性;pro-GRP、NSE及CEA在不同化疗评级SCLC患者中的表达水平差异均无统计学意义(P均>0.05).结论 CTC可用于辅助诊断SCLC分期,对SCLC患者的化疗效果具有预测能力,CTC水平越高患者的化疗疗效评级越差.其预测效能优于pro-GRP、NSE及CEA.

目的 明确KRAS、NRAS、HRAS、BRAF、TERT基因在甲状腺细针穿刺标本中的表达特点,并评价这些基因对细胞学辅助诊断方面的应用价值.方法 回顾性研究中日友好医院病理科2019年3月至8月期间送检的甲状腺细针穿刺标本360例,每例标本均包含细胞涂片以及穿刺组织1管.涂片经95％乙醇固定后,行巴氏染色,细胞学结果依据Bethesda分级系统读片.另一瓶穿刺组织保存在生理盐水中,经核酸提取,并用实时定量PCR法进行基因检测.结果 标本无法诊断或不满意43例(11.94％),良性病变67例(18. 61％),意义不明确的细胞非典型病变或意义不明确的滤泡性病变37例(10. 28％),滤泡性肿瘤或可疑滤泡性肿瘤17例(4.72％),可疑乳头状癌34例(9.44％),乳头状癌162例(45.00％).BRAF V600E突变166例(46.11％),KRAS 2号外显子突变1例(0.28％),NRAS3号外显子突变12例( 3. 33％), HRAS 3号外显子突变2例(0. 56％) ,TERT启动子突变3例(0.83％).其中NRAS突变伴有BRAF突变1例,TERT启动子突变3例均伴有BRAF突变.BRAF基因突变与患者细胞学诊断结果的相关性具有统计学意义(P＜0.05);TERT基因与性别及淋巴结转移与否的相关性具有统计学意义(P＜0.05);NRAS突变与细胞学诊断结果的相关性具有统计学意义(P＜0.05).结论 几种基因突变中,以BRAF基因突变最为常见,且对于辅助诊断的应用价值较高;在RAS基因中又以NRAS突变居多;而TERT启动子突变一般与BRAF基因突变伴随.

患者男性,95岁,2015年8月行胸部CT检查发现右肺中叶混合密度磨玻璃结节(mGGN)(图1A,见封底),根据结节的直径和密度表现,临床考虑恶性病变可能性大.考虑到患者高龄,难以耐受有创性检查操作,与患者家属充分沟通病情及行进一步检查的相关风险,建议继续观察密切随访.2015年8月～2018年5月间,患者定期复查胸部CT显示右肺结节无明显变化(图1B,见封底),肿瘤标记物均阴性(表1).2018年8月患者无明显诱因出现咳嗽、咳少量白痰,胸片示右肺少量渗出性病变,予经验性抗感染治疗1周后咳嗽无明显减轻.

患者男性,71岁,吸烟史30年,因咳嗽、咳痰7d余,2016年11月29日就诊于我院.胸部CT示:右肺上叶尖段多毛刺结节.肿瘤标记物:CYFRA21-1测定4.09ng/ml,NSE、CEA、CA-153、CA-199、AFP、CA72-4Z正常范围.于2016年12月14日行肺部结节穿刺病理(图1,见插一)示:肺间质纤维化,局灶见少量异型增生的腺体,结合免疫组化考虑腺癌.免疫组化结果:CK7(+),Ki67(10％+),Napsina (+),TTF-1 (+),P40(-),CEA(+),P53(+),CK2(-).基因检测示:EGFR基因未检测到18、19、20、21外显子上的突变.

Objective: To study common problems in BRAF gene mutation detection, and conditions for repetition testing using thyroid fine needle aspiration specimens. Methods: A total of 8 644 cases of thyroid fine-needle aspiration specimens at China-Japan Friendship Hospital were collected between February, 2012 and July, 2018. BRAF gene mutation was detected by real-time PCR. Repeat testing was performed in 237 cases when the results were inconsistent with clinical or cytological diagnosis or when uncertain results were obtained. Results: The final positive rates of BRAF mutation was 22.0% (1 897/8 625). Nineteen cases were excluded due to inadequate DNA samples. The average Ct value of internal quality control was 16.061, and the average Ct value of the positive samples was 19.147. Among 237 repeat tests, 51.4% (19/37) continued to have poor DNA quality and 48.6% (18/37) had adequate DNA resulting in 1 positive case and 17 negative cases. In 40 repetition of initial negative cases, results were unchanged. In initial positive cases, 40.4% (40/99) with a difference of Ct value (between BRAF gene and internal quality control) between 8 to 12 turned negative after repetition, 69.8% (37/53) of these cases with a difference of more than 12 turned negative after repetition. The sensitivity and specificity of BRAF mutation were 83.97% and 96.94%, respectively. Conclusions: Difference between BRAF gene Ct value and internal quality control Ct value is recommended as a reliability index for the test result. Cases with a difference greater than 8 should be subjected to repeat testing.

Objective To analyze the clinicopathologic features of 6 cases of cervical lymphoma.Methods The HE and IHC slides were reviewed in 6 cases of cervical lymphoma.The patients' medical records were examined to obtain the information about the pertinent clinical findings,staging studies,and follow-up.Results The median age of the 6 cases was 48 years.5 cases were secondary involvement.4 cases presented abnormal vaginal bleeding or discharge.6 cases showed cervical masses.5 cases were diffuse large B-cell lymphoma,1 case was anaplastic large cell lymphoma.2 cases were died,3 cases were alive,and 1 case was unknown.Conclusion Cervical lymphomas are rare.Most of the cases are secondary involvement as part of a systemic disease.The most common presenting symptom is abnormal vaginal bleeding or discharge.The most frequent clinical finding is cervical mass.Majority of reported cases are diffuse large B-cell lymphoma.The most challengeable differential diagnosis is lymphoma-like lesion.Pathologic diagnosis should combine with clinical features.