子宫颈浸润性复层产黏液的癌6例临床病理分析

目的 探讨子宫颈浸润性复层产黏液的癌(invasive stratified mucin-producing carcinoma, ISMC)的临床病理学特征及预后。方法 回顾性分析2019～2021年褔建省肿瘤医院诊治的6例子宫颈ISMC的临床病理学及免疫表型特征，并复习相关文献。结果 6例均可见经典的ISMC形态，实性癌巢由胞质内黏液多少不等的复层上皮细胞组成，边界较圆钝，巢周细胞呈栅栏状排列，类似子宫颈产黏液的复层上皮内病变。转移灶与原发灶形态一致或癌巢较不规则。免疫表型：肿瘤细胞p16、CEA、CK7、CK8/18均阳性，ER、PR、PAX8和Syn均阴性，CK5/6、p40阴性或灶性阳性，Ki-67增殖指数为70%～80%。结论 子宫颈ISMC是新近命名的HPV相关的腺癌亚型，具有独特的形态学及免疫表型特征，预后较其它HPV相关腺癌差，识别子宫颈癌中ISMC成分具有临床意义。     

子宫颈腺癌中HPV16/18感染对p16Ink4a、Rb蛋白表达的影响

目的研究16、18型人乳头瘤病毒(HPV16/18)DNA与细胞周期相关蛋白p16Ink4a、Rb在子宫颈腺癌中的表达情况及HPV16/18感染对p16Ink4a、Rb蛋白表达的影响。方法采用组织微阵列技术结合原位杂交和免疫组化EliVision二步法标记检测HPV16/18DNA和p16Ink4a、Rb蛋白在86例子宫颈腺癌、15例子宫颈腺上皮异型增生及24例慢性子宫颈炎组织中的表达。结果子宫颈腺癌组和子宫颈腺上皮异型增生组HPV16/18DNA阳性表达率分别为65·1%和46·7%,均明显高于慢性子宫颈炎组8·3%(P<0·01);p16Ink4a蛋白在子宫颈腺癌组的阳性表达率为74·4%,显著高于慢性子宫颈炎组33·4%(P<0·01)。Rb蛋白在子宫颈腺癌组的阳性表达率为33·7%,低于慢性子宫颈炎组45·8%,但差异无显著性(P>0·05)。HPV16/18感染与子宫颈腺癌的病理分级和组织学类型无关,但与p16Ink4a蛋白表达呈正相关(P<0·05)。p16Ink4a与Rb蛋白表达与子宫颈腺癌的病理分级有关,G2、G3组p16Ink4a阳性表达率明显高于G1组(P<0·05),G3组Rb阳性表达率明显低于G1组(P<0·05)。p16Ink4a表达与子宫颈腺癌组织学类型有明显相关性,子宫内膜样腺癌p16Ink4a阳性表达率明显高于透明细胞腺癌(P<0·05)。结论子宫颈腺癌的发生与HPV16/18感染有关,HPV16/18感染可能影响p16Ink4a、Rb蛋白表达,使子宫颈腺上皮发生癌变并促进恶性发展。     

子宫颈鳞状细胞癌伴子宫内膜及双侧输卵管扩散1例并文献复习

目的探讨子宫颈鳞状细胞癌伴子宫内膜及输卵管黏膜扩散的临床病理学特征。方法回顾性分析1例子宫颈鳞状细胞癌伴子宫内膜及双侧输卵管扩散的临床病理学及免疫表型特征、HPV检测结果,并复习相关文献。结果眼观:子宫颈外口见一隆起型肿块,肿块大小3.0 cm×2.5 cm×1.7 cm,向上累及宫颈管内口;子宫宫腔内未见明显肿块,子宫内膜菲薄且较光滑;双侧输卵管及卵巢未见明显肿块。镜检:子宫颈中分化浸润性鳞状细胞癌,浸润性病灶周围可见原位癌区域,癌组织浸润至子宫颈管壁周围纤维脂肪组织,并见脉管内癌栓形成及神经侵犯现象,肿瘤向下侵犯阴道壁上1/3;子宫内膜经全部取材制片,镜下见宫角处局灶子宫内膜表面黏膜上皮呈原位鳞状细胞癌改变,周围子宫内膜呈萎缩性改变,且与子宫颈鳞状细胞癌不相连续;双侧输卵管伞部黏膜上皮均见局灶原位鳞状细胞癌成分,周围输卵管黏膜上皮及间质均未见癌组织,未见脉管内癌栓。双侧卵巢未见明显异常。免疫表型:子宫颈、子宫内膜、输卵管肿瘤p16均阳性,输卵管肿瘤WT-1阴性,肿瘤CK5/6阳性,Ki-67增殖指数为60%;HPV-DNA检测子宫颈、子宫内膜及输卵管均显示HPV16型感染阳性。结论子宫颈鳞状细胞癌伴子宫内膜及双侧输卵管扩散的相关病例较为罕见,其发生机制可能与HPV感染有关。     

子宫颈病变中HPV L1蛋白和p16的表达

目的 研究HPV L1蛋白和p16在子宫颈各种病变中的表达情况,探讨它们在子宫颈病变进展中的预测价值.方法 应用免疫组化方法检测41例各种子宫颈病变(CIN1级18例、CIN2级9例、CIN3级8例和浸润性鳞状细胞癌6例)中HPV L1蛋白和p16的表达.结果 HPV L1蛋白在各种子宫颈病变中的阳性率为26.8%.其中HPV L1在CIN1中的阳性表达率为38.9%,CIN2为44.4%,CIN3和浸润性鳞状细胞癌均无表达.p16在各种子宫颈病变中的阳性率为68.3%,其在CIN1中的阳性表达率为38.9%,CIN2为77.8%,CIN3和浸润性鳞状细胞癌均表达阳性.100%CIN3和浸润性鳞状细胞癌为p16+/HPV L1-,而61.1% CIN1中为p16-/HPV L1+或p16-/HPV L1-.结论 随着子宫颈病变的进展,HPV L1阳性表达率降低而p16阳性表达率增高.p16+/HPV L1-提示子宫颈鳞状上皮内瘤变有进展的可能,而p16-/HPV L1+和p16-/HPV L1-可能为无进展的或潜在消退的子宫颈病变.     

子宫颈混合性腺神经内分泌癌1例并文献复习

目的探讨子宫颈混合性腺神经内分泌癌(mixed adenoneuroendocrine carcinoma,MANEC)的临床病理学特征。方法对1例子宫颈MANEC进行免疫组化和HPV分子分型检测,并复习相关文献。结果患者52岁,因阴道异常出血、流液数天入院。MRI提示子宫颈占位,行残余子宫颈、双侧附件切除及盆腔淋巴结清扫术。镜检:瘤组织由神经内分泌癌及原位腺癌两种成分构成,两种成分位于同一病变的不同区域,且均 30%。免疫表型:神经内分泌癌区域Syn、Cg A、CD56和p16均阳性;原位腺癌区域p16、CK7、CK20和CDX-2均阳性,Ki-67增殖指数为60%。两种组织均呈HPV18型阳性。结论子宫颈MANEC较为罕见,病理诊断主要依靠病理检查及免疫表型,预后较差。     

子宫颈病变中p16INK4A 蛋白表达及其与HPV16/18感染的关系

目的 探讨p16INK4A 蛋白在子宫颈鳞癌(SCC)和子宫颈上皮内肿瘤(CIN)中的表达及其与HPV16/18感染的关系.方法 用原位杂交法检测HPV16/18在25例子宫颈癌、45例CIN及10例慢性子宫颈炎中的表达,同时用免疫组化EliVision法检测p16INK4A 蛋白的表达.结果 (1)与慢性子宫颈炎相比,CIN Ⅱ级、CIN Ⅲ级、浸润癌HPV16/18杂交信号阳性率显著增高(P<0.01);(2)子宫颈鳞癌组织、CIN Ⅰ级、CIN Ⅱ级、Ⅲ级及慢性子官颈炎标本中p16INK4A 蛋白阳性率分别为100.0%、20.0%、46.7%、100.0%和10.0%;(3)在子宫颈鳞癌及CIN HPV16/18感染的标本中p16INK4A 蛋白表达均是阳性.结论 子宫颈鳞癌的形成与HPV感染、p16INK4A 蛋白过表达是呈正相关关系,p16INK4A蛋白可能作为子宫颈鳞癌及CIN的标志物,对子宫颈癌筛查和预防有重要意义.     

子宫颈产生黏液的复层上皮内病变6例临床病理分析

目的探讨子宫颈产生黏液的复层上皮内病变的临床病理学特征、诊断、鉴别诊断及预后特点。方法收集6例子宫颈产生黏液的复层上皮内病变的临床病理资料,分析其临床病理特征及免疫表型。结果 6例子宫颈产生黏液的复层上皮内病变患者年龄28～33岁,平均29. 5岁。患者3例因体检发现,3例以不规则出血就诊。5例行细胞学检查阳性,6例行HPV检测均提示高危型感染。显微镜下病变与周围间质边界清晰,腺腔内由复层未成熟圆形、卵圆形细胞核与含黏蛋白的空泡大小不等的上皮细胞混合构成。5例伴子宫颈高度鳞状上皮内病变,1例伴子宫颈原位腺癌。6例子宫颈产生黏液的复层上皮内病变均表达p16和CEA,不表达ER和vimentin,其中5例p63散在表达,Ki-67增殖指数高,特殊染色PAS、AB-PAS均阳性。2例行全子宫切除,4例行子宫颈锥切。随访6～40个月,未见复发。结论子宫颈产生黏液的复层上皮内病变是一种少见的、发生于年轻女性的特殊类型子宫颈原位腺癌,与高危型HPV密切相关,常伴其他病变。典型的组织病理学表现结合免疫表型可明确诊断,治疗可酌情采用宫颈锥切,需密切随访。     

高危型人乳头状瘤病毒DNA检测及p16INK4A蛋白表达在子宫颈腺癌诊断中的意义

目的观察p16^INK4A（简称p16）蛋白在子宫颈腺癌和子宫内膜腺癌中的表达及其和高危型人乳头状瘤病毒DNA（HPVDNA）在这两种腺癌中的鉴别诊断价值。方法用免疫组织化学EliVision法检测30例子宫颈腺癌和10例子宫内膜腺癌中p16蛋白的表达情况;并用原位杂交法检测20例子宫颈腺癌和10例子宫内膜腺癌中HPVDNA。结果在30例子宫颈腺癌中21例p16蛋白阳性（70％）,而10例子宫内膜腺癌中3例为阳性。在子宫颈腺癌中p16蛋白呈弥漫性细胞核和细胞质阳性,在子宫内膜腺癌中呈不规则斑点状阳性表达,而且总体强度较弱。HPv16和18在20例子宫颈腺癌中9例（45％）阳性,即细胞核内观察到点状棕黄色颗粒。10例子宫内膜腺癌均为阴性。结论鉴于p16蛋白的表达模式比HPV DNA的检测敏感性高,且易于操作,故建议将其作为区分宫颈癌和子宫内膜腺癌的辅助指标,特别是在活检或诊刮时应增加p16蛋白和HPV DNA的检测。     

子宫颈腺样基底细胞癌4例临床病理观察

目的探讨子宫颈腺样基底细胞癌的临床病理特征、诊断、鉴别诊断及预后特点,以提高对该病的认识及避免过度治疗。方法对4例子宫颈腺样基底细胞癌的临床及病理资料进行回顾性分析,运用常规HE、免疫组化EnVision法染色及原位杂交技术进行检测,并复习相关文献。结果 4例子宫颈腺样基底细胞癌患者年龄53~67岁,平均61.5岁,4例患者均行全子宫+双侧附件切除术。镜下见癌组织由形态单一、分化良好的基底样小细胞组成,排列成小巢状或条索状。癌巢周边见栅栏状排列的细胞核,部分癌巢中央形成囊性腔隙,也可见腺样或鳞状分化。4例患者均伴子宫颈上皮内病变(cervical intraepithelial neoplasia,CIN)。免疫表型:肿瘤细胞CK5/6、CK8/18、CK19、p16、p40、p53、BCL-2和p63均阳性,ER、CK7、CEA、CD117和S-100均阴性。原位杂交检测:HPV16/18阳性。4例患者随访19~62个月,均未见复发及转移。结论子宫颈腺样基底细胞癌属于罕见但预后较好的肿瘤,因预后不同,需与腺样囊性癌、基底样鳞状细胞癌、神经内分泌癌及腺鳞癌鉴别。治疗可选择全子宫切除术或宫颈锥切术,不推荐放、化疗。     

新疆地区贲门腺癌HPV、HP感染和p53异常改变的病理生物学意义

目的了解人乳头瘤病毒（HPV）、幽门螺杆菌（HP）感染及p53突变在新疆不同民族贲门癌发生、发展中的作用。方法应用PCR技术对90例贲门腺癌（包括哈族29例,维族30例,汉族31例;癌组织高、中、低不同分化程度分别有17、55、18例）及21例切缘正常组织进行HPV16／18和HP的检测,并用免疫组化LSAB法检测以上病例的p53异常表达;同时应用上述不同方法分别检测20例胃窦部腺癌HPV16／18、HP感染和p53的表达。结果HPV16／18和HP感染及t）53在新疆贲门腺癌患者中的阳性检出率分别为34．4％（31／90）,14．4％（13／90）和73．33％（66／90）,在切缘正常组织中的检出率分别为0、0、4．76％（1／21）;它们的阳性检出率在癌和非癌组织间差异均存在显著性（P〈0．05）;哈、维、汉各民族之间HPV16／18、HP及p53的阳性率的差异均无统计学意义（P〉0．05）;HPV16／18和HP感染阳性率与贲门腺癌病理分级及淋巴结转移无明显相关（P〉0．05）;p53的阳性表达与组织分级无关（P〉0．05）,而与淋巴结转移相关（P〈0．05）;贲门腺癌患者中p53与HPV16／18和HP的感染之间未发现相关关系（P〉0．05）。胃窦部腺癌患者中HPV16／18及HP阳性检出率分别为10％（2／20）、55％（11／20）与其在贲门腺癌的阳性检出率差异有显著性（P〈0．05）,胃窦部腺癌组织中p53的阳性检出率为80％（16／20）,与其在贲门腺癌的阳性检出率差异无显著性（P〉0．05）。结论（1）HPV16／18感染和p53的异常表达在贲门癌变过程中可能具有重要的作用,而HP感染与贲门癌的发生关系不大;胃窦部HPV16／18感染率较低,而HP感染检出率较高;（2）贲门癌组织中HPV16／18、HP感染和p53的异常表达与肿瘤病理分级和民族之间均无明显相关;p53的阳性表达与淋巴结转移相关;（3）p53的异常表达与HPV16／18或HP感染在胃贲门、幽门区腺癌的发生可能均有重要作用。     

Bloom''s syndrome with porokeratosis of Mibeili and multiple cancers of the skin, lung and colon

A 38-year-old Japanese male with Bloom's syndrome (BS) and porokeratosis of Mibelli (PM) developed multiple carcinomas of the skin and lung. There were multiple, spontaneous chromosomal aberrations and frequent sister chromatid exchanges (SCE). Cutaneous delayed-type hypersensitivity reactions were defective and serum IgM was decreased. The lung cancer was treated with radiation, which was effective but caused a severe pulmonary atelectasis and esophageal stricture. The patient expired one-and-a-half years later because of pneumonia. Autopsy disclosed an adenocarcinoma of the colon. The concurrent PM was considered responsible for the occurrence of multiple skin cancers.     

Prognostic Evaluation of Nasopharyngeal Carcinoma with Bone-Only Metastasis after Therapy

PurposeTo evaluate the prognosis of nasopharyngeal carcinoma (NPC) patients who developed bone-only metastasis after primary treatment and the stratification of these patients into different risk groups based on independent prognostic factors.ResultsThe median follow-up time was 15.5 months (range, 2–67 months) for the whole cohort. The median overall metastatic survival (OMS) time and the 2-year estimate OMS rate were 26.5 months and 52%, respectively. Multivariate analysis indicated that patients with short metastases-free interval, multiple bone metastases sites, high serum lactic dehydrogenase levels, and treated with radiotherapy or chemotherapy alone had significantly worse outcomes. Patients were stratified into three different risk groups based on the number of adverse factors present. The OMS curves of the three groups were all significantly different (p<0.001).ConclusionSeverl prognostic factors were found to be associated with worse outcomes. According to the number of adverse factors present, bone-only metastasis patients can be stratified into three risk groups with significantly different prognoses. Such grouping may help in improving the design of clinical trials and in guiding individualized treatment for NPC patients with bone-only metastasis.     

Solid pseudopapillary tumor: an invasive case report of primary ovarian origin and review of the literature

Solid pseudopapillary neoplasm occurring as a primary tumor outside the pancreas is a rare event. We report a case of an ovarian primary occurring with an ill-defined cystic mass in a 39-year-old woman. The morphologic and immunohistochemical features of the ovarian neoplasm described in this report are compatible with those of solid pseudopapillary neoplasm of the pancreas. Histologically, the tumor cells of the case we report infiltrate into the ovarian parenchyma. Because of the diagnosis is not clear before surgery, the patient had a reoccurrence two months after the operation in which laparoscopic simple ovarian cystectomy and part ovarian tissue removal, followed by the right salpingo-oophorectomy. The case herein confirms that solid pseudopapillary neoplasm of the ovary belongs to the class of low-grade malignant tumor with certain invasiveness. The diagnosis should be taken into serious consideration in order to avoid missed diagnosis and delay treatment. Through this case we have a better understanding of the biological behavior of solid pseudopapillary neoplasm of the ovary.     

Cystic neoplasms of the exocrine pancreas

The increasing use of radiological imaging has led to greater detection of small and asymptomatic cystic lesions of the pancreas. Most are resectable, but not all are neoplastic. This review provides an update on the histopathology, immunohistochemistry, molecular biology, pathogenesis and management of cystic neoplasms of the exocrine pancreas. These include the serous, the mucinous cystic, the intraductal papillary mucinous and the solid pseudopapillary neoplasms. Recently reported variants are described and very rare cystic variants of other pancreatic epithelial and mesenchymal neoplasms are briefly mentioned.     

Fine-needle cytology of an eccrine spiradenoma of the breast: diagnosis made by a holistic approach.

Eccrine spiradenoma is a rather rare adnexal tumor of the skin. When the clinical presentation is that of a breast neoplasm, diagnosis can be difficult. As cytology was a new procedure for this tumor, the approach of choice appeared to be a holistic one. The cytologic picture showed bland groups of uniformly sized cuboid cells with scant cytoplasm, round to ovoid nuclei, and inconspicuous nucleoli, while in the groups rosettelike structures could be discerned. Only by integrating the data of clinical history, inspection, palpation, reaction on breast puncture, and immunologic findings could the diagnosis be made.     

Intraductal papillary mucinous neoplasm (IPMN) of the gastric-type with focal nodular growth of the arborizing papillae: a case of high-grade transformation of the gastric-type IPMN

We present a case of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, demonstrating a process of high-grade transformation of the gastric-type IPMN. An 83-year-old Japanese woman underwent pylorus-preserving pancreatoduodenectomy for removal of a multicystic mass of the pancreas head, which had been followed up for 7 years. The removed tumor was a low-grade gastric-type IPMN spreading in the branch ducts, focally forming an intraluminal nodular lesion. The nodular lesion was comprised of arborizing papillotubular proliferation of cuboidal to columnar epithelia with high-grade atypia, and was characterized by diffuse MUC1 expression and a gastric mucin phenotype (focal MUC5AC and MUC6 expressions). Therefore, the nodular lesion was consistent with the pancreatobiliary-type IPMN, and the present case suggests that the low-grade gastric-type IPMN may progress to a focal intraductal carcinoma over the years, and the pancreatobiliary-type IPMN may be one of the forms of such high-grade transformation of the gastric-type IPMN. One of the cystic lesions was an oligocystic-type serous cystic neoplasm (serous cystadenoma), which might be an incidental concomitance or have a common basis.     

Oncocytic adrenocortical neoplasms--a clinicopathologic study of 13 new cases emphasizing the importance of their recognition

Oncocytic adrenocortical neoplasms (OANs) are a rare but important subtype of adrenal tumors with unique clinical and morphological features. We present 13 previously unpublished cases, of which 3 were classified as benign, 2 as having borderline malignant potential, and 8 as malignant according to the Lin-Weiss-Bisceglia criteria. Seven tumors (54%) showed evidence of endocrine activity. All were composed of more than 90% oncocytes confirmed immunohistochemically using the antimitochondrial antibody mES-13 and ultrastructurally in 4 cases. Small oncocytes were a frequent finding that challenges the conventional notion of oncocytes as necessarily having abundant cytoplasm. Most cases were immunoreactive for vimentin, synaptophysin, inhibin-α, melan A, and calretinin, the latter being a novel finding in this group of neoplasms. Cytokeratin positivity with AE1/AE3 and CAM5.2 was variable. The literature was comprehensively reviewed to identify all cases of OANs reported to date. Hormone production is not as uncommon as previously believed, occurring in 30%. The Lin-Weiss-Bisceglia criteria were retrospectively applied to all published cases with sufficient information and were shown to effectively separate tumors according to their future risk of recurrence and survival using Kaplan-Meier survival curves (log-rank test, P < .001 for both). The estimated overall median survival for malignant oncocytic neoplasms is 58 months (95% confidence interval = 27.5-88.5 months), providing the first preliminary evidence that the prognosis of malignant OANs is likely to be more favorable than conventional adrenocortical carcinomas, in which the reported median survival is between 14 and 32 months.     

A case of blastic plasmacytoid dendritic cell neoplasm with ecchymotic lesions on the whole body

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) derived from plasmacytoid dendritic cell precursors is a very rare, and characterized by cutaneous and bone marrow involvement and leukemic spread. The neoplasm presents with an aggressive behavior, and the clinical findings include cytopenia, particularly thrombocytopenia. The tumor cells are negative for antigens of T- and B- cell lines. However, these cells express CD4, CD56 and CD123, which are markers of plasmacytoid dendritic cells, and negative for Epstein-Barr virus (EBV). From this point of view, a 71-year-old man who was initially found to have a cutaneous mass on his face and thorax was reported here, and initially was diagnosed as “eczema”. The skin rashes then became aggravated on a trial of low dose topical corticosteroid for 2 months. According to skin biopsy, the tumor cells reveal an immature blastic appearance and positive for CD4 and CD56, negative for CD3, CD20, indicating a diagnosis of BPDCN. Here, we report the dismal course of a patient with BPDCN without accepting further therapy, and only survived 3 months.     

舌下腺皮脂腺腺癌一例

患者女,69岁,因发现左侧舌下肿物1月余于2018年8月20日入院。患者主诉1个月前无意中发现左侧舌下有一约大拇指大肿物,质软,无疼痛,无破溃,左侧颌下少许疼痛,无畏寒发热,无咽干咽痛。当时未予重视,现因肿物逐渐增大遂至东阳市人民医院就诊。专科查体:左舌下可见一约3.0 cm×3.0 cm大小肿物,质软,界欠清,活动度可,压痛阴性。口咽部MRI显示下颌骨内侧舌下腺走行区见斑片状、结节状异常信号影,边界尚清,较大者约2.3 cm×1.7 cm,T1WI呈低信号,T2WI呈稍高信号,增强后较明显强化,所见骨质未见明显破坏;诊断下颌骨内侧舌下腺走行区占位,考虑肿瘤,性质待定。患者于2018年8月26日在全身麻醉下行口底肿瘤局部扩大切除术+舌下腺摘除术+口腔颌面部软组织缺损局部黏膜瓣修复术:自左舌皱壁外侧做与牙龈缘平行的弧形切口,切开黏膜层,避开下颌下腺导管,顺舌下腺外侧潜行分离,远中钝分离舌神经及舌深动静脉,自后向前将舌下腺完整游离后摘除,舌下肉阜近导管开口处的溃疡瘢痕样组织予以切除。