子宫颈浸润性复层产黏液性癌1例并文献复习

目的探讨子宫颈浸润性复层产黏液性癌(invasive stratified mucin-producing carcinoma, ISMC)的临床病理学特征、诊断及鉴别诊断。方法观察1例ISMC的临床病理特征及免疫表型,并复习文献。结果患者女性,45岁,体检发现HPV16型阳性。大体上,于子宫颈处见一暗褐色菜花样新生物,大小2.0 cm×2.0 cm,似侵犯肌层。镜下肿瘤细胞类似于复层产黏液性上皮内病变(stratified mucin-producing intraepithelial lesion, SMILE),肿瘤排列呈巢团状,在间质内浸润性生长,可见促纤维增生性反应及炎细胞浸润。肿瘤周边可见原位腺癌(adenocarcinoma in situ, AIS)成分。肿瘤表面可见SMILE成分,局部可见SMILE累及腺体成分。PAS及AB染色阳性。免疫表型:肿瘤细胞CK7、p16及CEA弥漫强阳性,CK5/6及p63灶阳性,Ki-67增殖指数约80%。结论 ISMC是近年来提出的组织学形态类似于SMILE的浸润性肿瘤,尚未收入WHO(2014)女性生殖系统肿瘤的一种新的病理学实体肿瘤,易误诊为其他类型的癌,确诊需要结合组织病理学、免疫组化及特殊染色等综合分析。     

粗针活检诊断子宫颈微偏腺癌4例及临床病理分析

目的 总结B超引导下子宫颈微偏腺癌(minimal deviation adenocarcinoma,MDA)的粗针穿刺活检组织病理学形态、免疫组化及组织化学染色、病理诊断和鉴别诊断等要点,结合文献分析粗针穿刺活检方法用于临床早期诊断子宫颈MDA的优势及可行性.方法 对4例临床疑为MDA的患者,在B超引导下进行深部粗针穿刺活检,经常规HE染色、免疫组化及特殊染色后,镜下观察做出病理诊断,与该患者根治切除标本进行对比分析.结果 镜下见子宫颈深部穿刺标本的纤维和平滑肌组织中,散在分化较好的子宫颈型黏液性腺体,但腺体形态不规则,细胞轻至中度异型以及周围纤维组织增生性的间质反应,并且可见腺体邻近大血管;免疫组化染色腺上皮CEA阳性,AB/PAS特殊染色阳性.根治切除标本进一步明确了MDA的诊断,证实术前的子宫颈深部组织粗针穿刺活检获得的组织学证据,足以支持MDA的病理诊断.结论 MDA病变位置较深,间质浸润是明确诊断的最主要依据,粗针穿刺可做到子宫颈深部(深度>5 mm)活检,作为MDA早期诊断的一种方法具有一定的优势和可行性.     

子宫颈微偏腺癌4例临床病理分析

目的探讨子宫颈微偏腺癌(minimal deviation adenocarcinoma, MDA)的临床病理学特征、免疫表型、诊断及鉴别诊断。方法回顾性分析4例子宫颈MDA的临床病理资料,行HE及免疫组化EnVision法染色,并复习相关文献。结果 4例患者平均年龄42岁,临床均出现子宫颈肥大;3例行根治性手术+放疗,1例行活检+放疗+化疗;镜下肿瘤由黏液性腺体构成,腺体和细胞分化良好,呈浸润性生长,超出正常子宫颈腺体分布范围,间质反应明显;免疫表型:MUC6、CK7、CEA、p53均阳性,Ki-67增殖指数10%～30%,p16、ER、PR均阴性。术后随访12～40个月,2例出现转移,其余2例未见复发和转移。结论子宫颈MDA临床罕见,属于分化极好的胃型黏液腺癌。因缺乏特异性的临床症状、体征及辅助检查,常导致误、漏诊。结合组织学形态和免疫组化可明确诊断。     

子宫颈微偏腺癌临床病理分析

子宫颈微偏腺癌（minimal deviation adenocarcinoma,MDAC）是女性生殖系统极少见的肿瘤,由于其分化程度很高。细胞形态常与子宫颈黏液腺上皮细胞相似,往往造成活检时的漏诊。现报道4例子宫颈MDAC,对其临床病理形态学、组织化学和免疫表型特征进行观察分析,并探讨其诊断和鉴别诊断。     

乳腺黏液囊肿样病变临床病理特征分析

目的探讨乳腺黏液囊肿样病变的临床病理特征及其诊断和鉴别诊断。方法对9例乳腺黏液囊肿样病变进行临床病理分析。以SP法对细胞角蛋白AE1／AE3、平滑肌肌动蛋白（SMA）、p63、c-erbB-2和053进行免疫组织化学染色,组织化学为AB和PAS法染色。结果患者均为女性,年龄23-43岁（平均34岁）,乳腺均可触及肿物。肿物切面呈多囊性胶冻样。镜下可见多发性、充满黏液的囊肿,囊腔衬覆扁平-立方-柱状上皮,其中3例上皮有乳头状增生,1例有不典型增生。间质内可见黏液湖,其内无漂浮细胞。囊内及间质黏液呈AB及PAS染色阳性。囊肿衬覆上皮细胞及2例黏液湖内漂浮的上皮细胞团AE1／AE3阳性。囊肿上皮细胞外侧扁平肌上皮呈SMA、p63阳性。c-erbB-2和p53染色均阴性。结论乳腺黏液囊肿样病变是一种独立的良性病变,容易误诊,需与黏液癌等肿瘤进行鉴别。     

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。     

宫颈微偏腺癌的临床病理分析

目的探讨宫颈微偏腺癌的临床及病理形态特征、诊断要点及有辅助诊断意义的免疫组织化学指标,以提高及时诊断的准确性.方法收集13例诊断为宫颈微偏腺癌的临床病理资料,分析其特征,5例作免疫组织化学(LDP法)和组织化学(Foot)染色(以正常宫颈腺体为对照);随访其疗效.结果临床主要表现为水样白带,宫颈肥大,增粗变硬和糜烂,宫旁韧带增厚或硬.病理特征为腺体增生,有轻度异型性,有向间质浸润的反应,或浸至宫颈间质层.癌胚抗原3+,Ki-67+～3+,p53蛋白+～3+,AB/PAS+或2+,Foot染色腺体基底膜部分缺失.结论诊断宫颈微偏腺癌应结合临床表现,指出宫颈腺体有无不典型增生,并深取组织(>5 mm)或高频电力锥切宫颈活检,可及时诊断,防止漏诊.     

子宫颈黏液腺癌21例病理诊断分析

目的 对子宫颈黏液腺癌病理诊断过程的分析旨在为早期诊断、减少漏诊总结经验.方法 回顾性分析21例子宫颈黏液腺癌的病理诊断过程;采用LABC法免疫组化检测CEA及Ki-67的表达.结果 21例子宫颈黏液腺癌诊断中,漏诊3例(14.3%),其中1例为TCT漏诊,2例为子宫颈活检漏诊;4例(19.0%)子宫颈活检诊断为子宫颈原位腺癌、浸润不能除外,后经LEEP术确诊为子宫颈浸润性黏液腺癌;1例(4.8%)子宫颈活检诊断为慢性子宫颈炎,经LEEP术确诊为子宫颈浸润性黏液腺癌;12例(57.1%)直接由子宫颈活检确诊为子宫颈黏液腺癌;1例(4.8%)经诊刮诊断为腺癌,无法确定组织学类型,术后确诊为子宫颈黏液腺癌.免疫组化染色显示,其中10例CEA表达阳性(47.6%),Ki-67表达均升高(>20%).结论 从细胞学及组织形态学上,掌握子宫颈黏液腺癌的诊断要点,可以减少漏诊,及早做出正确的诊断,为患者赢得宝贵的手术时间.     

严重急性呼吸综合征患者尸解肺标本的病理改变和致病机制研究

目的研究严重急性呼吸综合征（SARS）患者尸解肺标本的病理改变和致病机制。方法观察了2003年4-7月期间死于SARS的6例患者的肺标本,并采用光镜、电镜、Masson三色染色和免疫组织化学染色方法（EnVision法）进行研究。结果肺标本的病理形态改变：（1）6例的双肺均可见到弥漫性实变病灶,肺重量明显增加;（2）6例均可见到弥漫性肺泡损伤,包括透明膜形成、肺泡腔内水肿／出血、纤维素沉积和肺泡上皮细胞脱屑,AE1／AE3免疫组织化学染色显示肺泡上皮细胞的完整性明显破坏;（3）Ⅱ型肺泡上皮细胞轻度增生,有一定异型性,细胞体积增大,胞质呈双染性和颗粒状,胞质内可见小脂肪空泡聚集（5／6）;（4）6例中有5例可见巨细胞在肺泡内浸润,巨细胞大多AEl／AE3阳性（5／6）,少数CD68阳性（2／6）;（5）组织学形态和免疫组织化学染色证实肺泡腔内和肺泡间隔内有多量巨噬细胞浸润（6／6）;（6）6例中有5例可见巨噬细胞噬红细胞象;（7）6例中有5例可见肺纤维化,包括肺泡间隔和肺间质增宽（5／6）、肺泡腔内渗出物机化（6／6）和胸膜增厚（4／6）。Masson三色染色证实胶原纤维明显增生,免疫组织化学染色显示大多数为Ⅲ型胶原。光镜和免疫组织化学染色显示5例有明显的成纤维细胞／肌纤维母细胞增生灶;（8）5例可见支气管黏膜鳞状上皮化生;（9）6例患者均可见血栓;（10）2例同时合并其他感染,1例合并细菌感染,另1例合并真菌感染。此外,电镜发现在肺泡上皮细胞和肺血管内皮细胞的胞质内有冠状病毒样颗粒。结论SARS冠状病毒直接损伤肺泡上皮细胞、巨噬细胞明显浸润和成纤维细胞／肌纤维母细胞显著增生在SARS的致病机制中起重要作用。     

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。     

Advanced gastric carcinoma with a complete intestinal metaplasia phenotype associated with early intestinal-type carcinoma

An unusual case of synchronous gastric carcinomas occurred in a 28-year-old man with a family history of gastric disease. Two tumor foci were identified: a well-differentiated advanced carcinoma with the phenotypic properties of complete intestinal metaplasia and an early intestinal-type carcinoma. Histochemical and immunohistochemical stains to demonstrate complete intestinal metaplasia, ie, Alcian blue pH 2.5/periodic acid-Schiff, high iron diamine/Alcian blue pH 2.5, CD10, and MUC2, were all positive in the advanced adenocarcinoma. Of all markers used, only high iron diamine/Alcian blue pH 2.5 and Alcian blue pH 0.5 were positive in the early carcinoma. In these cases, mistakes frequently are made during examination of endoscopic biopsies. Fortunately, the advanced adenocarcinoma was low grade (the patient has shown no signs of disease at 6 years postsurgery). Histopathologic, histochemical, and immunohistochemical findings suggest that an extensive substrate of complete intestinal metaplasia (corpus) and of complete and incomplete intestinal metaplasia (antrum) can be associated with two independent tumors with different phenotypes.     

Identification of mucin-secretion characteristics in cells from serous effusions: consideration of histochemical and immunohistochemical aspects

Fourty-two cell-blocks of serous effusions (thirty malignant and twelve reactive) were tested by anti Secretory Component Ab (policlonal) using the s.-Ab method, and by histochemical tests: PAS, PAS Diastase and Alcian blue pH 2.5. Immunohistochemical and histochemical features were compared to identify their meaning and correlation in epithelial mucin detection. This study suggests the evident correlation between SC and PAS diastase (better than between SC and Alcian blue) and possibility to replace the old traditional test of PAS diastase with anti SC antibody (much more sensible than PAS diastase) in routine mucin detection histochemical tests.     

ARGYROPHIL REACTIVE CELLS IN THE NORMAL UTERUS AND DIFFERENTIATED ENDOMETRIAL ADENOCARCINOMA

Argyrophil cells were seen in 2 of 134 cervical tissue blocks obtained from 18 uteri, but none in the endometrium. In 10 of 30 cases of differentiated endometrial adenocarcinoma cells contained argyrophil granules stained with Grimelius method. These argyrophil reactive glandular cells gave positive d-PAS and Alcian blue (pH 2.5, PH 1.0) reactions, but gave no argyrophil reaction with PAS-Grimelius double staining method. It was also demonstrated that these glandular cells contained sulphomucins, because High iron diamine (HID) method gave positive reaction with HID-Alcian blue pH 2.5 double staining. Dense granules, which were submicroscopically seen in cells of well differentiated endometrial adenocarcinomas, were diagnosed as exocrine secretory granules, because of their localization in the cytoplasm and distinct morphological transformation from condensed vacuoles into mature secretory granules. From these findings, argyrophil granules which were seen in cells of the differentiated endometrial adenocarcinomas were thought not to correspond to endocrine granules but mucosubstances.     

Argyrophil reactive cells in the normal uterus and differentiated endometrial adenocarcinoma

Argyrophil cells were seen in 2 of 134 cervical tissue blocks obtained from 18 uteri, but none in the endometrium. In 10 of 30 cases of differentiated endometrial adenocarcinoma cells contained argyrophil granules stained with Grimelius method. These argyrophil reactive glandular cells gave positive d-PAS and Alcian blue (pH 2.5, PH 1.0) reactions, but gave no argyrophil reaction with PAS-Grimelius double staining method. It was also demonstrated that these glandular cells contained sulphomucins, because High iron diamine (HID) method gave positive reaction with HID-Alcian blue pH 2.5 double staining. Dense granules, which were submicroscopically seen in cells of well differentiated endometrial adenocarcinomas, were diagnosed as exocrine secretory granules, because of their localization in the cytoplasm and distinct morphological transformation from condensed vacuoles into mature secretory granules. From these findings, argyrophil granules which were seen in cells of the differentiated endometrial adenocarcinomas were thought not to correspond to endocrine granules but mucosubstances.     

Gall stones and carcinoma gall bladder

One hundred and fifty surgically resected gall bladder specimens were included in the study to evaluate the relationship between the prevalence of gall stones and histochemical alteration in sequential changes of metaplasia, dysplasia and neoplasia in gall bladder epithelium. Multiple sections were processed and stained with haematoxylin and eosin, Periodic acid Schiff's stain, Alcian blue (pH 2.5)/Periodic acid, Orcein/Alcian blue (pH 2.5) and Alcian Blue/Periodic acid/Potassium borohydride saponifications stains. Details of gall stones present were also noted. Prevalence of gall stones in gall bladders with metaplastic, dysplastic and neoplastic mucosal changes was significantly higher (P < 0.001) than those gall bladders which had no epithelial changes. Increase in sialomucin with a corresponding decrease in sulphomucin was observed from metaplasia to malignancy. Neutral mucin increased in metaplastic cells but was significantly reduced in neoplastic cells. Loss of O-acylation in sialmucin was also present in neoplastic cells. The histochemical changes suggest that chronic injury due to cholelithiasis induces appearance of neutral mucin positive metaplastic cells, which may further dedifferentiate to sialomucin containing dysplastic or neoplastic cells if the stimulation persists.     

Mucinous (colloid) adenocarcinomas secrete distinct O-acylated forms of sialomucins: a histochemical study of gastric, colorectal and breast adenocarcinomas

AIMS: Mucinous (colloid) adenocarcinomas represent a distinct group of tumours defined by the presence of large amounts of extracellular mucins. By using histochemical methods, we analysed mucins secreted by mucinous versus non-mucinous adenocarcinomas and looked for differential secretion profiles. METHODS AND RESULTS: Sixty-four adenocarcinomas were studied (23 colorectal, 17 gastric, and 24 breast tumours). Thirty-two tumours were of the colloid type. The following methods were applied to paraffin tissue sections: (i) Alcian blue (pH 2.5) and periodic acid-Schiff (PAS); (ii) high iron diamine and Alcian blue (pH 2.5); (iii) periodic acid borohydride, potassium hydroxide, and PAS; (iv) periodic acid-thionine Schiff, potassium hydroxide, and PAS; and (v) periodic acid-borohydride and PAS. Most adenocarcinomas secreted acidic mucins, with sialomucins predominating over sulfomucins, except for non-mucinous adenocarcinomas of the breast which showed predominant neutral mucins. All mucinous adenocarcinomas contained C9-O-acyl sialic acid as mono, di(C8,C9)-, or tri(C7,C8,C9)-O-acyl forms. Acidic mucins secreted by the majority of non-colloid adenocarcinomas consisted of non-O-acylated sialomucins. CONCLUSIONS: C9-O-acylation of sialic acid is a characteristic feature of mucinous adenocarcinomas and can be readily detected by histochemical methods.     

Do the cardiac glands exist? 7. The cow

The glands distributed in the narrow region of the abomasum contiguous to the omasum of the cow have been described as cardiac glands. We doubted this assertion and therefore performed histological and histochemical investigations of the glands to clarify their characteristics. 1. All glandular cells except the parietal cells in a few glands contiguous to the omasum react strongly to PAS, AB(pH 2.5), and PAS-AB(pH 2.5) staining, and moderately to AB(pH 0.5) staining. 2. Glandular cells at the base of these glands contain fine pepsinogen granules and a few parietal cells are distributed in these glands, indicating that they are undifferentiated gastric glands and that the so-called cardiac glands do not exist in the cow stomach. 3. Glandular cells in undifferentiated gastric glands are filled with PAS, AB(pH 2.5 and 0.5) and PAS-AB(pH 2.5) positive substances. Which gradually decrease and finally disappear with differentiation, remaining only in the neck (mucous neck cells) and the cells in the upper part of the glandular body (immature chief cells), in mature gastric glands. 4. Mature chief cells in differentiated gastric glands are distributed in the middle and lower bodies and base of the glands and contain a number of PAS and PAS-AB(pH 2.5) positive granules and a large number of coarse pepsinogen granules, while pepsinogen granules in the mucous neck cells and immature chief cells are finer. 5. In the cow the region in which undifferentiated gastric glands are located is very narrow. 6. Parietal cells in the cow stomach are numerous.(ABSTRACT TRUNCATED AT 250 WORDS)     

Light and electron microscopic study of the eyelids,conjunctiva-associated lymphoid tissue and lacrimal gland in Bilgorajska Goose (Anser <Emphasis Type="Italic">anser</Emphasis>)

Normal structure of the accessory organs of the eye is essential for normal eye physiology. Among the most important accessory organs of the eye are the eyelids, the conjunctiva-associated lymphoid tissue (CALT) and the lacrimal gland (LG). The aim of this study was to demonstrate the histological structure of the eyelids and LG by histochemical and ultrastructural analysis. The study was performed on 13 adult female Bilgorajska geese. Eyelid samples were stained with the Alcian blue (AB pH 2.5) and periodic acid-Schiff (PAS) methods. Staining methods used for LG were AB pH 2.5, aldehyde fuchsin (AF), PAS and Hale’s dialysed iron (HDI). Within the connective tissue of the eyelids, well-developed, diffuse, CALT follicles were observed, mostly under the conjunctival epithelium. Numerous lymphocytes were present within loose connective tissue. Staining of the eyelids with the PAS method demonstrated the presence of goblet cells of a mucous nature, and AB pH 2.5 staining indicated the presence of sulfated acid mucopolysaccharides. PAS staining of LG revealed the presence of secretory cells containing weakly PAS-positive granules. All epithelial cells of the corpus glandulae and the duct systems reacted positively to AB pH 2.5. HDI staining detected the presence of carboxylated acid mucopolysaccharides. Transmission electron microscopy investigations revealed two types of secretory epithelial cells in LG. Both types of LG cells contained drop-like secretory vesicles of different sizes with low or high electron density in cytoplasm, as well as small and large lipid vacuoles, and numerous small primary lysosomes.     

Expression of CDX2 and MUC2 in Barrett's mucosa

Barrett's mucosa is a risk factor for esophageal adenocarcinoma and should be detected at an early stage. It is defined by the presence of columnar epithelium with goblet cells in the lower esophagus, but histologic diagnosis can be uncertain in the absence of distinct goblet cells. We investigated 55 biopsies from 48 patients with endoscopically plain Barrett's esophagus and performed immunohistochemistry for CDX2 and MUC2. In addition, alcian blue (pH 2,5)/PAS staining was done. In histologically unequivocal Barrett's mucosa, nuclear expression of CDX2 in goblet cells and many columnar cells, as well as cytoplasmic positivity for MUC2 in goblet cells, could be observed. Alcian blue (pH 2,5)/PAS stained acidic mucins in goblet cells and in some non-goblet columnar cells. In six cases, no definite Barrett's mucosa was present, and no expression of MUC2 could be observed. In these biopsies, there was granular cytoplasmic and/or focal nuclear staining for CDX2 in non-goblet columnar epithelial cells, indicating their intestinal differentiation. We suggest that this peculiar mucosa is the precursor of unequivocal Barrett's mucosa and would designate it early Barrett's mucosa. Alcian blue for acidic mucins is inconsistent in this epithelium and does not reliably indicate early intestinal differentiation.     

Simple procedure for assessing relative quantities of neutral and acidic sugars in mucin glycoproteins: its use in assessing cyclical changes in cervical mucins.

A simple histochemical procedure for assessing relative amounts of neutral and acidic sugars in mucin glycoproteins, and its application in the study of cyclical changes of human cervical mucins, is described. This procedure, the saponification/selective periodate oxidation/borohydride reduction/alcian blue pH 2.5/periodic acid Schiff (KOH/PA*/Bh/Ab 2.5/PAS) method, uses a selective oxidation step to remove the PAS positivity of sialic acid; thus only neutral sugars stain positively with PAS, and acidic sugars (O-sulphate esters and carboxyl groups) stain with alcian blue. This differs from the KOH/Ab/PAS technique which stains sialic acid residues with both alcian blue and PAS. Applying the KOH/PA*/Bh/Ab 2.5/PAS technique to the study of cyclical changes of human cervical mucins, a decreased neutral:acidic sugar ratio in the secretory phase mucins compared with those of the proliferative phase was found. This difference was not seen with KOH/Ab/PAS staining in the same cases. The techniques and reagents used in this procedure can be easily applied in a clinical histopathology laboratory.