Endocervical-like mucinous borderline tumors of the ovary: clinicopathological features and electron microscopic findings

Endocervical-like mucinous borderline tumor (EMBT) is a distinct entity of the ovary that seems to be underrecognized. It occurs with relatively high frequency in Japanese women. Compared with intestinal-type mucinous borderline tumor (IMBT), more frequent bilateral occurrence, paucilocular cysts, association with endometriosis, absence of pseudomyxoma but possible association of peritoneal implants and lymph node metastases, and lower mortality rate are the characteristic features. Histologically, it consists of a mixture of two types of epithelium, tall columnar mucinous cells and stratified eosinophilic cells. Electron microscopy revealed that they were endocervical glandlike mucinous cells and ciliated columnar epithelium reminiscent of the fallopian tube. As the mixture of EMBT and serous borderline tumor (seromucinous borderline tumor) occurs, these findings may show that the tumor shows MÜllerian origin with two-way differentiation, or differentiation toward endocervical glands with metaplastic features as seen in reactive endocervical lesions.     

Macroscopic and microscopic characteristics of low grade appendiceal mucinous neoplasms (LAMN) on appendectomy specimens and correlations with pseudomyxoma peritonei development risk

Low grade appendiceal mucinous neoplasm (LAMN) is the primary source of pseudomyxoma peritonei (PMP). PMP may develop after seemingly complete resection of primary tumor by appendectomy, which is unpredictable due to lack of reliable prognostic indicators. We retrospectively reviewed 154 surgically resected LAMNs to explore if any of the macroscopic and microscopic characteristics may be associated with increasing risk of PMP development. Our major findings include: (1) As compared to those without PMP, the cases that developed PMP were more frequent to have (a) smaller luminal diameter (<1 cm) and thicker wall, separate mucin aggregations, and microscopic perforation/rupture, all suggestive of luminal mucin leakage; (b) microscopic acellular mucin presenting on serosal surface and not being confined to mucosa; and (c) neoplastic epithelium dissecting outward beyond mucosa, however, with similar frequency of neoplastic cells being present in muscularis propria. (2) Involvement of neoplastic cells or/and acellular mucin at surgical margin did not necessarily lead to tumor recurrence or subsequent PMP, and clear margin did not absolutely prevent PMP development. (3) Coexisting diverticulum, resulted from neoplastic or non-neoplastic mucosa being herniated through muscle-lacking vascular hiatus of appendiceal wall, was seen in a quarter of LAMN cases, regardless of PMP. The diverticular portion of tumor involvement was often the weakest point where rupture occurred. In conclusion, proper evaluation of surgical specimens with search for mucin and neoplastic cells on serosa and for microscopic perforation, which are of prognostic significance, should be emphasized.     

Duct-Acinar-Islet Cell Tumor of the Pancreas

Two cases of pancreatic tumor consisting of duct, acinar, and islet components are reported. Both tumors measured about 1.0 cm in diameter and were without definite fibrous encapsulation. Histo-logic, immunocytochemical, and electron microscopic studies revealed three distinct cell populations: duct, acinar, and islet cells. Both endocrine and exocrine components were seen within the same cell nest. Islet components predominated in both cases. Nearly all the cells in the islet component were positive for insulin. Few cells positive for glucagon, somatostatin, or pancreatic polypeptide were present within the tumor cell nests. Duct cells were the least conspicuous cellular element of the tumor; they were positive for mucin and immuno-reactive for cytokeratin and carcinoembryonic antigens (CEA). The acinar component was the minor element of the tumor in both cases. Electron micro-scopic study also confirmed three different cell populations in the tumor: duct cells arranged in a ductal structure with intercellular attachments and microvilli, islet cells containing beta granules, and acinar cells with zymogen granules. The tumors presented herein indicate that both their endocrine and exocrine components might have been derived from a common precursor. The implication and significance of the differentiation of different cells within the same tumor is discussed in relation to the concept of an amine precursor uptake and de-carboxylation (APUD) system.     

Primary breast carcinomas with neuroendocrine features: Clinicopathological features and analysis of tumor growth patterns in 36 cases

Primary breast carcinoma with neuroendocrine features (NEBC) is an uncommon tumor. In the classification of WHO 2012, these tumors were categorized as: 1- neuroendocrine tumor, well-differentiated; 2- neuroendocrine carcinoma, poorly differentiated/small cell carcinoma; and 3- invasive breast carcinoma with neuroendocrine differentiation. In this study, we reviewed NEBC except poorly differentiated/small cell carcinoma variant in order to define the morphological growth patterns and cytonuclear details of these tumors. All breast surgical excision materials between 2007 and 2016 were re-evaluated in terms of neuroendocrine differentiation. Thirty-six cases showing positive staining for synaptophysin and/or chromogranin A in ≥50% of tumor cells were included in the study. All cases were female with a mean age of 67.4. Mean tumor diameter was 26 mm. Multifocality was noted in 5 cases. Grossly, they were mostly infiltrative mass lesions. T stages, identified in 34 cases, were as follows: 13 cases with pT1; 19 pT2 and 2 pT3. We described schematically 4 types of patterns depending on predominant growth pattern, except one case: 1) Large-sized solid cohesive groups (6 cases), 2) Small- to medium-sized solid cohesive groups with trabeculae/ribbons and glandular structures (6 cases), 3) Mixed growth patterns (20 cases), 4) Invasive tumor with prominent extracellular and/or intracellular mucin (3 cases). The tumor cells were mostly polygonal-oval with eosinophilic/eosinophilic-granular cytoplasm. The nuclei of tumor cells were mostly round to oval with evenly distributed chromatin. Only 5 cases showed high grade nuclear and histological features. Molecular subtypes of the cases were as follows: 33 luminal A, 2 luminal B, and 1 triple negative. NEBC should come to mind when a tumor display one of the morphological patterns described above, composed of monotonous cells with mild to moderate nuclear pleomorphism and abundant eosinophilic/eosinophilic granular or clear cytoplasm, especially in elderly patients.     

Pseudomyxoma peritonei and selected other aspects of the spread of appendiceal neoplasms

The varied aspects of spread of appendiceal neoplasms are reviewed with emphasis on the often clinically dramatic phenomenon known as pseudomyxoma peritonei, a term mostly used to describe grossly evident mucin within the peritoneal cavity. The majority of cases of pseudomyxoma peritonei result from tumors primary in the appendix, which are usually low-grade. On microscopic examination pseudomyxoma peritonei is typically characterized by large aggregates of mucin which may be relatively acellular or cellular containing strips of mucinous epithelium, mucinous epithelium encircling glands and cysts, or aggregates of mucinous epithelium lying within mucin pools. High-grade adenocarcinoma of the appendix may spread to the omentum and peritoneal surfaces without grossly striking mucin deposition and resemble spread of other high-grade gastrointestinal adenocarcinomas. In many cases of pseudomyxoma peritonei in females there is involvement of one, or more often, both ovaries. The size of the ovarian neoplasms characteristically dwarfs the often relatively unremarkable appearing appendix in these cases. The ovaries are typically multilocular, although one locule may dominate, and in cases in which the primary is a low-grade appendiceal mucinous neoplasm often have a "jelly-like" consistency. In cases of spread of frank adenocarcinomas the ovarian metastases typically have a more solid, albeit still somewhat gelatinous consistency. Microscopic examination of the ovaries typically shows surface involvement, a characteristic of spread to the ovaries in general, and the glands and cysts that replace most or all of the parenchyma are typically lined by tall mucin-rich cells with, in many cases, relatively bland microscopic features. In cases of frank adenocarcinoma, the tumors may mimic closely a primary mucinous adenocarcinoma of the ovary. Spread to the ovaries may also be seen in cases of frank intestinal-type adenocarcinoma primary in the appendix and the uncommon signet ring cell carcinoma of the appendix, the latter being one cause of the Krukenberg tumor. Occasional cases are reported in the literature of ovarian spread of goblet cell carcinoid tumor of the appendix, but in our opinion most of the primary tumors in those cases are better classified as adenocarcinomas, usually dominantly of signet-ring cell type, albeit sometimes with focal neuroendocrine differentiation. Other interesting aspects of spread of appendiceal neoplasms include to the lining of the uterus and the fallopian tube. In yet other cases the tumors may present clinically as incidentally discovered mucinous aggregates within hernia sac specimens or as a scrotal mass.     

Pseudomyxoma peritonei is a disease of MUC2-expressing goblet cells

Pseudomyxoma peritonei, a syndrome first described by Karl F. Rokitansky in 1842, is an enigmatic, often fatal intra-abdominal disease characterized by dissecting gelatinous ascites and multifocal peritoneal epithelial implants secreting copious globules of extracellular mucin. Although past interest in the syndrome has focused on the questions of the site of origin (appendix versus ovary), mechanisms of peritoneal spread (multicentricity, redistribution phenomenon, or metastasis), and the degree of malignant transformation present (adenoma, borderline tumor, or carcinoma), another important question is the mechanism behind the accumulation of extracellular mucin, the real cause of the disease's morbidity and mortality irrespective of the site of origin, mechanism of peritoneal spread, or transformed status of its epithelium. Taking advantage of the recently cloned human mucin genes, we decided to investigate this question. Our studies revealed that pseudomyxoma peritonei is a disease of MUC2-expressing goblet cells. These cells also express MUC5AC but the latter mucin is not specific for pseudomyxoma peritonei. MUC2 expression accounts for the voluminous deposits of extracellular mucin (mucin:cell ratios exceeding 10:1) and distinguishes pseudomyxoma peritonei secondarily involving the ovary from primary ovarian mucinous tumors with peritoneal implants. Because mucinous tumors of the appendix similarly express MUC2, the MUC2 expression profile also supports an appendiceal rather than ovarian origin for pseudomyxoma peritonei. Increased steady-state mRNA is observed in pooled cases of pseudomyxoma peritonei but does not occur on the basis of gene rearrangement or gene amplification. Primary epithelial cell cultures obtained from pseudomyxoma peritonei express MUC2 whose levels can be epigenetically regulated. These lines up-regulate MUC2 expression in response to both methylation inhibition by 5-azacytidine and exposure to Pseudomonas aeruginosa lipopolysaccharide, both of whose effects can be suppressed by genistein pretreatment. Both immunocytochemical as well as in situ hybridization studies with ancillary digital image analysis reveal that MUC2 expression in cases of pseudomyxoma peritonei is independent of the degrees of malignant transformation that are present and, in fact, reflects the constitutive levels of expression observed in normal goblet cells of the appendix. Extracellular mucin accumulates dramatically in pseudomyxoma peritonei because the number of MUC2-secreting cells dramatically increase and because this MUC2 has no place to drain. These studies suggest that pseudomyxoma peritonei should be regarded as a disease of MUC2-expressing goblet cells whose MUC2 expression might be susceptible to pharmacological targeting.     

Mucin production in medullary carcinoma of the thyroid

Mucin production in medullary carcinoma of the thyroid is rarely mentioned in the literature. We studied 36 cases of medullary carcinoma; 32 lesions were sporadic and four were genetic variants. In 15 cases (42%), mucin production was demonstrated by histochemical means. In six cases (17%), the mucin was only extracellular; in three (8%), it was mostly extracellular, but with foci of intracellular deposits; and in six cases (17%), it was equally extracellular and intracellular. Mucin secretion could be demonstrated in both the primary thyroid tumor and the nodal metastases. No consistent correlation could be demonstrated between the histologic pattern, the staining properties of the tumor cells, and the sporadic or genetic occurrence of the tumor. Mucin was more frequently identified in medullary carcinomas (42%) than in other carcinomas (9.1%) of the thyroid gland. As mucin can be identified in approximately half of the medullary carcinomas, this primary thyroid lesion should be considered a possible source for a cervical node containing mucin positive carcinoma cells.     

Neuroendocrine and mucinous differentiation in signet ring cell carcinoma of the stomach: evidence for a common cell of origin in composite tumors

Composite tumors are rare neoplasms containing a mixture of 2 different cellular components present in roughly equal proportions. It is hypothesized that composite tumors arise from a multipotential stem cell with subsequent bidirectional differentiation. We present an unusual composite tumor of the stomach composed equally of signet ring cell carcinoma and low-grade neuroendocrine carcinoma. Twenty-one additional patients with signet ring cell carcinomas of the stomach were studied to determine the prevalence of neuroendocrine differentiation by morphology and immunohistochemistry for synaptophysin and chromogranin A. Immunohistochemistry for mucins 5AC and 2 was performed to assess for divergent differentiation toward foveolar and intestinal mucin phenotypes, respectively, and to evaluate for any potential relationship with neuroendocrine differentiation. We found morphologic evidence of neuroendocrine carcinoma in 4 (19%) of 21 consecutive signet ring carcinomas. E-cadherin immunostaining was subsequently performed on these 4 tumors plus the index case. All 5 tumors demonstrated concordance between the signet ring and neuroendocrine components. There was no distinct relationship to mucin 5AC/mucin 2 profiles, with the exception that all 11 intramucosal signet ring cell carcinomas from 4 patients with germ line cadherin 1 gene mutations were composed exclusively of mucin 5AC+ signet ring cells that lacked intestinal mucin and neuroendocrine differentiation. The concordant E-cadherin status in the neuroendocrine and signet ring cell tumor components and the frequent admixture of mucin 5AC+ cells with foveolar differentiation and mucin 2+ cells with intestinal differentiation may support the hypothesis that composite tumors arise from a common stem cell with bilineage or multilineage differentiation.     

Duct-islet cell tumor of the pancreas. A case report with immunohistochemical and electron microscopic findings

A case of pancreatic tumor with features of both duct and islet cell components was found incidentally at autopsy in a 76-year-old male who had died of intrahepatic cholangiocarcinoma. The tumor, measuring about 1.0 cm in diameter, was located in the pancreatic tail. The tumor was composed of two distinct cell populations, islet cells and duct cells. Immunocytochemically, nearly all of the former cells were positive for insulin but negative for cytokeratin, carcinoembryonic antigen (CEA) and mucin, while the latter were positive for cytokeratin, CEA and mucin but negative for insulin. Additionally, a majority of the tumor cells that had formed islet-like structures were positive for neuron-specific enolase (NSE), whereas NSE-positive cells were found only rarely in duct components. Electron microscopy confirmed the presence of two cell populations. Simultaneous occurrence of duct and islet cell components in a single pancreatic tumor indicates an intimate histogenetic relationship between pancreatic endocrine and duct cells.     

Histochemistry and electron microscopy in the diagnosis of small mucous cells in carcinoma of the stomach

One hundred and two cases of poorly differentiated adenocarcinoma were obtained from 71 surgical and 31 biopsy specimens of the stomach. These tumours produced both intracellular and extracellular mucins, which were demonstrated to be neutral mucins, N-acetyl sialomucins, sulphomucins and O-acetyl sialomucins. The majority of tumours (85.3%) secreted two or more kinds of mucins simultaneously, but only a small proportion (14.7%) produced a single kind of mucin. Ultrastructurally, three types of mucin granules were identified; these differed in shape and density. Tumour cells containing intracellular mucins or mucin granules were designated as mucous cancer cells and further subdivided into small, large and goblet mucous cells; tumour cells having neither mucins nor glandular differentiation were designated as undifferentiated cancer cells. These histochemical distinctions, supported by the electron microscopical observations, may be useful to demonstrate early malignant foci in gastric biopsies.     

Pseudomyxoma peritonei: A cytohistopathologic study of nine cases

Cytologic examination of seven peritoneal fluids from nine patients with pseudomyxoma peritonei revealed papillary clusters and isolated neoplastic cells. In all patients, one or both ovaries were replaced by proliferating (borderline) mucinous epithelial tumors of grade I–II intestinal type while three patients had synchronous appendiceal tumors of similar morphologic appearance. Four of the nine patients demonstrated positive correlation between the presence of neoplastic cells in the ovarian interstitial mucin (pseudomyxoma ovarii), the extraovarian peritoneum, and the free peritoneal fluid. Two patients demonstrated a negative correlation. The submission of an inadequate amount of ovarian or appendiceal tissue for histologic examination may account for the discordance in three patients. It is concluded that pseudomyxoma peritonei is a distinct clinicopathologic entity which can be subdivided into two types, acellular and cellular. This distinction, unlike the specific cytomorphologic features, may have prognostic significance. Diagn Cytopathol 1996;15:144–150. © 1996 Wiley-Liss, Inc.     

胰腺囊实性肿瘤八例临床病理学观察

目的 观察胰腺囊实性肿瘤的临床病理特点,分析其分化表型,探讨其组织发生。方法 组织学、免疫组化和电镜技术。结果 ８例患者均为女性,年龄１４￣３３岁,平均２５．３岁,手术后均无复发。肿瘤较大,有包膜,由实性肿瘤与囊性坏死区混合组成。组织学上,肿瘤细胞较一致,均由实性片块、假乳头样及两者的过渡型生长方式组成。瘤细胞退变、出血、泡沫细胞和胆固醇裂隙常见。免疫组化：８例均表达α－１－抗胰蛋白酶和溶菌酶,６     

Cytodiagnosis of pseudomyxoma peritonei in cases suspected of ovarian tumours

The cytologic features in four cases of pseudomyxoma peritonei are described in ascitic fluid specimens which were received from female patients suspected of ovarian masses. The findings in the fluid included cells of mesothelial origin and spindle-shaped fibroblasts with a significant amount of background mucin. This was confirmed by mucicarmine and Alcian blue stains. A cytologic diagnosis of pseudomyxoma peritonei was possible in all four cases. The above findings were further substantiated since mucinous ovarian neoplasms were found in all the cases.     

Duct-Islet Cell Tumor of the Pancreas. A Case Report with Immunohistochemical and Electron Microscopic Findings

A case of pancreatic tumor with features of both duct and islet cell components was found incidentally at autopsy in a 76 year old male who had died of intrahepatic cholan-giocarcinoma. The tumor, measuring about l.0cm in diameter, was located in the pancreatic tail. The tumor was composed of two distinct cell populations, islet cells and duct cells. Immunocytochemically, nearly all of the former cells were positive for insulin but negative for cytokeratin, carcinoembryonic antigen (CEA) and mucin, while the latter were positive for cytokeratin, CEA and mucin but negative for insulin. Additionally, a majority of the tumor cells that had formed islet-like structures were positive for neuron specific enolase (NSE), whereas NSE-positive cells were found only rarely in duct components. Electron microscopy confirmed the presence of two cell populations. Simultaneous occurrence of duct and islet cell components in a single pancreatic tumor indicates an intimate histogenetic relationship between pancreatic endocrine and duct cells. Acta Pathol Jpn 39: 328 335, 1989.     

Bim与BCSG1蛋白在乳腺癌中的表达及临床意义研究

目的 探究Bcl-2相互作用细胞凋亡调节因子(Bim)与乳腺癌特异性基因1(BCSG1)蛋白在乳腺癌中的表达及临床意义.方法 选取我院2015年1月至2017年2月期间收治的60例乳腺癌患者,通过外科手术收集60例患者乳腺癌组织以及癌旁组织,通过免疫组织化学染色检测两种组织中Bim与BCSG1蛋白表达情况,分析不同分期、不同分化程度、不同病理、不同直径和是否转移情况下Bim与BCSG1蛋白表达差异.结果 免疫组织化学染色结果显示:Bim与BCSG1在乳腺癌组织中高表达,而在癌旁组织中低表达,比较差异有统计学意义(P＜0.05);肿瘤直径≥4cm、低分化程度、浸润性乳腺癌、Ⅲ-Ⅳ期和远处转移的乳腺癌患者,Bim与BCSG1阳性率明显高于肿瘤直径＜4cm、高度分化、中度分化、非浸润性乳腺癌、Ⅰ-Ⅱ期和非转移的乳腺癌患者(P＜0.05).结论 Bim和BCSG1蛋白在乳腺癌组织中高表达,且表达水平与肿瘤大小、分期、浸润、分化程度和转移性密切相关.     

The coexistence of low-grade mucinous neoplasms of the appendix and appendiceal diverticula: a possible role in the pathogenesis of pseudomyxoma peritonei.

We examined 38 appendectomies with diagnoses of mucocele, diverticulum, or adenoma to study the coincidence of appendiceal diverticula and appendiceal low-grade mucinous neoplasms and to examine the possible role of diverticula in the pathogenesis of pseudomyxoma peritonei. Invasive adenocarcinomas and retention cysts were excluded (six cases). Cases were classified as adenomas or mucinous tumors of unknown malignant potential, with or without diverticula. Medical records were reviewed for multiple parameters, including presenting symptoms, presence of pseudomyxoma peritonei, and presence of associated malignancies. Binomial statistics were used to calculate the probability that the observed prevalence of low-grade mucinous neoplasms and diverticula together was significantly different from the expected prevalence of diverticula or low-grade mucinous neoplasms alone, using historical controls from the literature. Twenty-five percent of the total cases (8 of 32) contained both a low-grade mucinous neoplasm (7 cystadenomas and 1 mucinous tumor of unknown malignant potential) and a diverticulum. Thus, 8 of 19 low-grade mucinous neoplasms (42%) were associated with diverticula. Of the appendices with both low-grade mucinous neoplasms and diverticula, three contained dissecting acellular mucin within the appendiceal wall, four showed diverticular perforation, and one had pseudomyxoma peritonei associated with the ruptured diverticulum. A significant percentage (P < .001) of cases contained low-grade mucinous neoplasms and diverticula together. The case of coexistent low-grade mucinous neoplasm, diverticulum, and pseudomyxoma peritonei suggests that diverticula could play a role in the pathogenesis of pseudomyxoma peritonei. This could occur either by involvement of preexisting diverticula by the neoplasm or by distention of the appendiceal lumen by mucin, leading to increased intraluminal pressure and subsequent diverticulum formation at a weak area in the wall. Either mechanism might allow low-grade mucinous neoplasms to penetrate the appendiceal wall more easily.     

Morphology of borderline mucinous ovarian tumors

The examination of structures of the tumor tissues taken from 47 patients with borderline mucinous tumours of the ovary showed that the tumors belonging to this group, like their serous analogues, were an indistinctly limited nosological entity that characterizes a particular stage in the malignant transformation of the epithelium as evidenced by a wide range of structures that are interchangable from mucinous adenofibroma to mucinous carcinoma. Death may result from pseudomyxoma or dissemination that follows the pattern seen in cancer. The latter generally stems from small-sized areas of occult cancer which are detectable from a retrospective analysis of the material available. Intraoperative laceration of the tumor makes no contribution to the occurrence of peritoneal pseudomyxoma. The results of the histochemical study into the mucosa indicated that the tumor cells were heterogeneous in mucosaccharides. The cells which were completely free from acid fractions in the presence of neutral mucins were identified. Disregarding the features indicated, one can reasonably reject the fact that the neoplasm is of mucinous character as judged from alcian blue-stained specimens.     

Mucin histochemical analysis of minute gastric differentiated adenocarcinoma

Fifty-six surgically resected intramucosal differentiated adenocarcinomas (DA) of the stomach with a maximum diameter of less than 5 mm were analyzed by mucin histochemistry. Gastric type phenotypic expression was observed in 41.1% of cases, intestinal type in 28.6% and gastric-intestinal type in 28.6% of all cancers. Gastric type phenotypic expression was the most frequent. As the tumor diameter increased, the incidence of DA with gastric phenotype tended to decrease. Intestinal metaplasia of the cancer's surrounding mucosa was absent or slight in DA with gastric phenotype, but moderate to severe in DA with gastric-intestinal phenotype and intestinal phenotype. Morphologically and mucin histochemically, intestinal metaplasia surrounding DA with gastric phenotype was immature and incomplete compared with DA with gastric-intestinal phenotype or intestinal phenotype. It is suggested that a large amount of DA with gastric phenotype is histogenetically derived from the gastric gland proper without intestinal metaplasia. However, as the tumor grows and intestinal metaplasia progresses, intestinal type phenotypic expression appears and then DA with gastric phenotype changes into DA with gastric-intestinal phenotype or intestinal phenotype.     

Intestinal phenotypes in pediatric gallbladder epithelium

The aim of this study was to characterize the physiologic expression of “intestinal” features in gallbladders of infants and children. The study group consisted of 56 pediatric (age, 2 weeks to 7 years) and 15 adult (15-25 years) patients who underwent incidental cholecystectomy during surgery for other lesions. All gallbladders examined were histologically unremarkable without inflammation, gallstones, or neoplasia. The presence of goblet cells and the expression of cytokeratin 7, cytokeratin 20, mucin core protein 2, and caudal-related homeobox protein 2 were examined. Intestinal features were frequently detected in the pediatric gallbladders: goblet cells in 34 cases (61%), cytokeratin 20 expression in 25 (45%), mucin core protein 2 expression in 32 (57%), and caudal-related homeobox protein 2 expression in 16 (29%). In contrast, none of these features was identified in adult gallbladders. The expression of mucin core protein 2 was mostly restricted to goblet cells in pediatric gallbladders, whereas cytokeratin 20 and caudal-related homeobox protein 2 were expressed in both goblet and nongoblet cells. Cytokeratin 7 was diffusely and consistently expressed in both pediatric and adult gallbladder epithelium including goblet cells. Intestinal features became less frequent with age and were scarce in children aged 6 to 7 years. Thus, goblet cells were identified in 14 (93%) of 15 children aged <1 year, together with the common expression of cytokeratin 20 (73%), mucin core protein 2 (93%), and caudal-related homeobox protein 2 (53%). In conclusion, intestinal features are physiologically present in gallbladder epithelium of children, particularly those aged <6 years. Intestinal metaplasia, as associated with cholangiopathy or carcinogenesis in adult patients, may represent an immature phenotype of biliary epithelium.     

乳腺神经内分泌型导管内癌

目的对乳腺神经内分泌型导管内癌（E-DCIS）的临床病理特点、预后和鉴别诊断进行探讨。方法用光镜、免疫组织化学EnVision法行嗜铬素A、突触素和神经元特异性烯醇化酶（NSE）染色和消化PAS、消化阿辛蓝和嗜银染色,对18例具有E-DCIS特征的乳腺癌进行观察。结果具有E-DCIS特征的乳腺癌具有以下特点：（1）好发于老年女性,平均年龄71岁。最常见的临床症状为乳腺肿块或乳头溢液。（2）E-DCIS呈导管内肿瘤细胞的膨胀性生长,在肿瘤周边常可见导管内乳头状瘤。（3）肿瘤细胞呈多边形,卵圆形或梭形,胞质丰富,嗜酸性或细颗粒状。细胞核往往只有轻一中度异型,消化PAS或AB染色显示细胞内或细胞外存在黏液,有些肿瘤细胞呈印戒细胞样。（4）〉50％的肿瘤细胞表达嗜铬素A、突触素和NSE中的至少两种,部分病例CD56和CD57染色阳性。（5）E-DCIS中常可见到肿瘤细胞向邻近导管的派杰样扩散,且在膨胀性生长的导管内不存在肌上皮成分。这两点有助于E-DCIS与导管上皮增生的鉴别。结论E-DCIS是一种低度恶性的乳腺导管内癌,有其独特的组织形态、免疫组织化学特征,应作为一种独立的导管内癌类型加以认识。