Cytological diagnostic clues in poorly differentiated squamous cell carcinomas of the breast: Streaming arrangement,necrotic background,nucleolar enlargement and cannibalism of cancer cells

Objective

Squamous cell carcinoma (SCC) is a rare histological type of breast cancer. The cytological diagnosis of non‐keratinising, poorly differentiated SCC is often difficult, and distinguishing it from invasive ductal carcinoma or apocrine carcinoma (AC) is especially challenging. We aimed to define the diagnostic cytological features of poorly differentiated SCC of the breast.

Methods

We studied the cytological findings of poorly differentiated SCC (n=10) and compared them to those of IDC (n=15) and AC (n=14). The following six cytological features were evaluated: streaming arrangement, nucleolar enlargement, dense nuclei, cannibalism, atypical keratinocytes and necrotic background.

Results

SCC exhibited significantly higher frequencies of streaming arrangement (70% vs 6.7%, P=.002), nucleolar enlargement (80% vs 27%, P=.02), and necrotic background (80% vs 36%, P=.002) than invasive ductal carcinoma. The detection of two or three of these features yielded a higher sensitivity (80%) and specificity (93%) for the diagnosis of SCC. Streaming arrangement (70% vs 0%, P<.001), cannibalism (60% vs 0%, P=.002), and a necrotic background (80% vs 36%, P=.047) were all significantly more frequent in SCC than in AC. When distinguishing SCC from AC, the presence of two or three of these features yielded a high sensitivity (80%) and specificity (100%).

Conclusions

Cytological features such as a streaming arrangement, a necrotic background, nucleolar enlargement and cannibalism are useful indicators for the diagnosis of SCC of the breast. As such, greater attention should be paid to these morphological features in daily clinical practice.     

The disturbances of the zinc concentration in the blood in selected neoplasms

A study was carried out on 92 patients (58 males and 34 females) aged 42–76 treated for malignant neoplasm of the gastrointestinal tract (54 patients with colorectal carcinoma, 38 with gastric carcinoma). In all patients, the zinc serum concentration was measured and the results obtained were referred to some epidemiological-clinical factors (sex, age, primary cause of cancer, the stage of clinical progression, and histological type). The results showed that the most pronounced hypozincemia occurred in male patients with mucous membrane carcinoma of the stomach.     

KLN205—A murine lung carcinoma cell line

Summary KLN205 cells, a cloned cell line established from the Nettesheim lung carcinoma, grow in various synthetic media such as MEM, Fisher's or Roswell Park Memorial Institute Medium (RPMI) with the addition of 5 to 20% fetal bovine serum (FBS), calf serum (CS) or horse serum (HS). They grow optimally in minimum Eagle's medium plus nonessential amino acids (NEAA) plus 5 to 10% FBS or HS. The cells are transplantable to DBA/2, BDF₁, AKD₂F₁, and BALB/c, but not to C3H/He or ICR mice. The growth curves, plating efficiency, ultrastructural characteristics, modal number of chromosomes and transplantability to mice of various strains are almost the same for early and late passages of cells passaged in vitro. These parameters for 16th and 36th passages were: doubling time, 31 and 33 hr; plating efficiency, 12.4±1.2 and 14.6±2.6%; modal number of chromosomes, 73 and 76; lung colony formation in DBA/2, 50 and 45.9/mouse; and subcutaneous tumor diameter 24.5 and 27.4 mm, respectively. Only the numbers of lung colonies formed in BDF₁ mice were different: 24.4/mouse with 16th passage cells, and 10.2/mouse with 36th passage cells. The results suggest that KLN205 is a relatively stable cultured cell line through 36 passages. As was expected, immunosuppression by higher concentrations of triaminolone acetonide (TA) enhanced lung colony formation in BDF₁ mice. On the other hand, a low concentration of TA inhibited lung colony formation in DBA/2 mice, which was unexpected. These results suggest that KLN205 offers a model for investigations on metastases to lungs as well as chemotherapy for lung carcinoma. This work was supported by the National Cancer Institute of Canada.     

Heparanase expression and localization in different types of human lung cancer

Background

Heparanase is the only known mammalian glycosidase capable of cleaving heparan sulfate chains. The expression of this enzyme has been associated with tumor development because of its ability to degrade extracellular matrix and promote cell invasion.

Methods

We analyzed heparanase expression in lung cancer samples to understand lung tumor progression and malignancy. Of the samples from 37 patients, there were 14 adenocarcinomas, 13 squamous cell carcinomas, 5 large cell carcinomas, and 5 small cell carcinomas. Immunohistochemistry was performed to ascertain the expression and localization of heparanase.

Results

All of the tumor types expressed heparanase, which was predominantly localized within the cytoplasm and nucleus. Significant enzyme expression was also observed in cells within the tumor microenvironment, such as fibroblasts, epithelial cells, and inflammatory cells. Adenocarcinomas exhibited the strongest heparanase staining intensity and the most widespread heparanase distribution. Squamous cell carcinomas, large cell carcinomas, and small cell carcinomas had a similar subcellular distribution of heparanase to adenocarcinomas but the distribution was less widespread. Heparanase expression tended to correlate with tumor node metastasis (TNM) staging in non-small cell lung carcinoma.

Conclusion

In this study, we showed that heparanase was localized to the cytoplasm and nucleus of tumor cells and to cells within the microenvironment in different types of lung cancer. This enzyme exhibited a differential distribution based on the type of lung tumor.General significanceElucidating the heparanase expression patterns in different types of lung cancer increased our understanding of the crucial role of heparanase in lung cancer biology. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.     

LIPOSOMAL DAUNORUBICIN OVERCOMES DRUG RESISTANCE IN HUMAN BREAST,OVARIAN AND LUNG CARCINOMA CELLS

ABSTRACT

Multi-drug resistance due in part to membrane pumps such as P-glycoprotein (Pgp) is a major clinical problem in human cancers. We tested the ability of liposomally-encapsulated daunorubicin (DR) to overcome resistance to this drug. A widely used breast carcinoma cell line originally selected for resistance in doxorubicin (MCF7ADR) was 4-fold resistant to DR compared to the parent MCF7 cells (IC₅₀ 79 nM vs. 20 nM). Ovarian carcinoma cells (SKOV3) were made resistant by retroviral transduction of MDR1 cDNA and selection in vinblastine. The resulting SKOV3MGP1 cells were 130-fold resistant to DR compared to parent cells (IC₅₀ 5700 nM vs. 44 nM). Small-cell lung carcinoma cells (H69VP) originally selected for resistance to etoposide were 6-fold resistant to DR compared to H69 parent cells (IC₅₀ 180 nM vs. 30 nM). In all three cases, encapsulation of DR in liposomes as Daunoxome (Gilead) did not change the IC₅₀ of parent cells relative to free DR. However, liposomal DR overcame resistance in MCF7ADR breast carcinoma cells (IC₅₀ 20 nM), SKOV3MGP1 ovarian carcinoma cells (IC₅₀ 237 nM) and H69VP small-cell lung carcinoma cells (IC₅₀ 27 nM). Empty liposomes did not affect the IC₅₀ for free DR in the three resistant cell lines, nor did empty liposomes affect the IC₅₀ for other drugs that are part of the multi-drug resistance phenotype (etoposide, vincristine) in lung carcinoma cells. These data indicate the possible value of liposomal DR in overcoming Pgp-mediated drug resistance in human cancer.     

Oral squamous cell carcinoma in capuchin monkeys (Cebus apella). Report of two cases.

Two neoplasms were observed in two feral male Cebus apella monkeys of approximately 12 and 14 years of age. Histologically, the tumors were well-differentiated squamous cell carcinomas, one affecting the soft and hard palates reaching the nasal cavity and the other involving the oral cavity floor and the inferior maxillar.     

Pin1和Cyclin D1在人类5种常见肿瘤中的表达及其意义

目的研究人类的肽基脯氨酰异构酶(Pin1)在人类几种重要的肿瘤(肺癌、前列腺癌、乳腺癌、宫颈癌和胃癌)中的表达及与细胞周期蛋白CyclinD1的关系,并探讨它们在肿瘤的发病机制、诊断和治疗中的意义。方法随机收集33例正常组织和171例癌组织(包括37例肺癌、35例前列腺癌、31例乳腺癌、36例宫颈癌和32例胃癌)。采取免疫组织化学Envision法显示Pin1和CyclinD1的表达。结果Pin1和CyclinD1在正常组织中不表达或者低表达,而在各种癌组织中有普遍性的高表达,在肺癌组织、前列腺癌组织、乳腺癌组织、胃癌组织和宫颈癌组织中,Pin1的表达率分别为48·7%、65·7%、48·4%、15·6%和69·4%,CyclinD1的表达率分别为56·8%、60·0%、54·8%、40·6%和58·3%。Pin1和CyclinD1在癌组织中的表达明显高于正常组织中的表达(P<0·05)。Pin1和CyclinD1蛋白在肺癌、前列腺癌、乳腺癌和宫颈癌中表达呈显著正相关(P<0·05)。而Pin1和CyclinD1蛋白在胃癌中的表达相关性不显著(P>0·05)。结论Pin1和CyclinD1在多种肿瘤的发生、发展过程中具有重要作用,如肺癌、前列腺癌、乳腺癌、宫颈癌和胃癌,Pin1与细胞周期代谢或调控有关。Pin1在某些肿瘤(如肺癌、前列腺癌等)中可作为肿瘤标记的参考指标。     

Un adénocarcinome mucineux non kystique (carcinome colloïde) du pancréas de découverte fortuite à la TEP-TDM au 18F-FDG : à propos d’un cas

Colloid carcinoma (CC) of the pancreas, also known as mucinous noncystic carcinoma, is a rare histological variant of pancreatic cancer which had been included in the past under the category of ordinary ductal carcinoma, a tumor with a dismal prognosis, or was frequently misdiagnosed as mucinous cystadenocarcinoma. As CC has a better prognosis than pancreatic ductal carcinoma, early detection of CC by 18 FDG PET SCAN is of great value for the therapeutic management of patients. We report the case of a 66-year-old patient who underwent 18 FDG PET SCAN as part of a post-therapy evaluation of a moderately differentiated carcinoma of the stomach treated with surgery and chemotherapy, in whom a hypermetabolic focus of the body of the pancreas was discovered incidentally. The anathomopathological diagnosis was in favor of a low-grade mucinous noncystic carcinoma of the pancreas. Thus, 18 FDG PET SCAN allowed the discovery of an infraradiological CC synchronous with a gastric adenocarcinoma and provided information on its metabolic activity as well as locoregional and distant staging, which are important prognostic markers and which could improve the therapeutic management of the patient.     

HER2 testing in gastric and esophageal adenocarcinoma: new diagnostic challenges arising from new therapeutic options

Abstract

Adenocarcinomas of the esophagus and stomach constitute a substantial number of cancer cases worldwide. Most patients in the United States are diagnosed at an advanced or metastatic stage and, therefore, the prognoses have been poor. New treatments are needed to augment standard surgical and medical management. Recent studies have shown that a subset of esophageal and gastric adenocarcinomas overexpress the HER2 protein, similar to the overexpression seen in breast cancer. Because trastuzumab, a monoclonal antibody to the HER2 receptor, has been used with success in primary and HER2 positive metastatic breast cancers, the phase III ToGA trial was designed to assess the impact of trastuzumab in patients with HER2 positive gastric cancers. They have reported an increase in overall survival time for patients treated with chemotherapy and trastuzumab compared to those treated with chemotherapy alone. They have reported an increase in overall survival time for patients treated with chemotherapy and trastuzumab compared to those treated with chemotherapy alone. This means that accurate HER2 testing in gastric and esophageal carcinomas is necessary. While the breast cancer scoring system can be used to determine HER2 status in most cases, modifications are necessary to accommodate the heterogeneity and incomplete membrane staining that are observed more frequently in gastric cancers. An understanding of the scoring modifications is required for proper stratification of gastric cancer patients for treatment.     

乳腺浸润性微乳头状癌的研究现状

乳腺浸润性微乳头状癌(IMPC)是乳腺浸润性癌的一种特殊类型,其发生率低,临床表现及影像学特征与普通的乳腺浸润性导管癌没有显著区别。这种病理类型可与普通浸润性导管癌混合出现,也可表现为单纯的浸润性微乳头状癌。但浸润性微乳头状癌具有独特的组织学形态及分子结构,决定了其病理学分级较高、易于发生淋巴结转移的侵袭性生物学行为特点。多数浸润性微乳头状癌在影像学上表现为边缘不清的不规则肿块影,常伴有微小钙化。其特征性病理形态为细胞膜上皮抗原(EMA)在肿瘤细胞簇外周的细胞和基质中腔隙边缘特异性染色,同时显微镜下瘤细胞表面发现微绒毛结构,说明了瘤细胞簇周围的空隙样结构实际上是管状腔隙,瘤细胞呈"极向倒转"方式排列。IMPC具有高度淋巴血管浸润倾向,局部复发率高,是一种预后较差的类型。本文对近年来关于乳腺浸润性微乳头状癌的研究进展进行了综述。     

腹腔镜手术意外发现胆囊癌的诊治体会

目的:探讨腹腔镜胆囊切除术中(laparoscopic cholecystectomy,LC)遇到意外胆囊癌(unexpected gallbladder carcinoma,UGC)的诊断和治疗。方法:回顾性分析我院1998年6月-2010年12月LC术中遇到的11例意外胆囊癌的临床资料。结果:术中探查结合快速病理明确诊断8例,3例术后石蜡病理证实为胆囊癌。开腹手术6例,单纯腹腔镜胆囊切除2例,3例腹腔内广泛转移,行腹腔镜胆囊姑息性切除术;结论:行LC前应加强对胆囊癌的警惕与认识。术中应常规检查胆囊标本,有怀疑者及时行冰冻切片检查。UGC确诊后应尽早开腹行根治性和扩大根治性切除术,并采取必要措施防止肿瘤种植转移。     

Design,synthesis and biological evaluation of 4-aniline-thieno[2,3-d]pyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma

MAP Kinase Interacting Serine/Threonine Kinase 1 (MNK1) play important roles in the signaling transduction of MAPK pathways. It is significantly overexpressed in renal clear cell carcinoma and head-neck squamous cell carcinoma tissues in both mRNA and protein levels. Based on the crystallographic structure of MNK1 protein and binding modes analysis of known MNK inhibitors, we have designed and synthesized a series of 4-aniline-thieno[2,3-d]pyrimidine derivatives as potential MNK1 inhibitors. These synthetic compounds are tested in biochemical and cell proliferation assays, and six of them display potent inhibitory capacity against MNK1 kinase and cancer cell lines. Compound 12dj with strongest inhibitory capacity is transferred to molecular mechanism studies, and the results indicated that 12dj remarkably suppresses the phosphorylation of EIF4E, a substrate of MNK1. And the expression levels of MNK1, ERK1/2 and pERK1/2 are not affected by compound 12dj incubation in SUNE-1 and 786-O cells. In summary, our works suggested that these novel 4-aniline-thieno[2,3-d]pyrimidine based MNK1 inhibitors might be attractive lead compounds for targeted therapy of renal cell carcinoma and nasopharyngeal carcinoma.     

Fine needle aspiration cytology of medullary carcinoma of the thyroid with a focus on rare variants: a review of 78 cases

S. Kaushal, V. K. Iyer, S. R. Mathur and R. Ray
Fine needle aspiration cytology of medullary carcinoma of the thyroid with a focus on rare variants: a review of 78 cases Background: The cytological features of variants of medullary carcinoma of the thyroid (MCT) are sparsely documented in the literature from case reports. Detailed cytomorphological analysis of MCT variants and features helping to distinguish them from usual MCT are presented here. Materials and methods: A total of 78 aspirates with a diagnosis of MCT over a period of 10 years were re‐evaluated. Cytomorphological details were reviewed and semiquantitatively analysed. Histology slides were reviewed in 36 cases. Results: Most aspirates showed classical features of dispersed polygonal or plasmacytoid cells with areas of spindling. In 54 aspirates, a definite cytological diagnosis of medullary carcinoma was made, which in 87.1% was based on cytomorphology alone and in 12.9% was based on immunocytochemistry for calcitonin. In 30.1% of aspirates from MCT, a guarded report of tumour was given in the absence of calcitonin immunocytochemistry. Of the 78 cases, nuclear grooves were seen in 5.1%, intranuclear cytoplasmic inclusions in 28.2%, cytoplasmic granularity in 23.1% and bizarre cells with abrupt anisocytosis in 85.9%. A follicular arrangement was seen in 14.1% and was more frequent in the follicular type (one case) and mixed follicular and medullary carcinoma (one case). Melanin production was seen in aspirates from two cases. One case of the giant cell type of MCT was seen, in which background cells showed large pleomorphic nuclei and numerous bizarre tumour giant cells, prompting a differential diagnosis with anaplastic carcinoma. One example each of the small cell type, paraganglioma‐like MCT and papillary MCT were seen. Conclusions: MCT has uniform cytological features in the majority of aspirates, including many of the histological variants. Searching for pigment in every aspirate of MCT may be rewarding. The giant cell type of MCT is rare and has to be differentiated from anaplastic carcinoma.     

Mucin-associated T antigens in benign and malignant epithelium of the gall bladder,extrahepatic bile ducts and ampulla of Vater

The mucin-associated antigens Tn, sialosyl-Tn (STn), T and sialosyl-T (STAg) antigens accumulate through aberrant and incomplete glycosylation in malignant epithelial cells. Their diagnostic and prognostic significance in tumours of the colon and cervix has been described, and a possible role for Tn antigen in cell-to-cell adhesion has been suggested. These antigens have been demonstrated through peanut agglutinin (PNA) lectin binding and more recently using specific monoclonal antisera. Differences between the two methods have been described, which may be due to fixation schedules and/or specificity. We have investigated the effect of fixation on the binding of biotinylated PNA lectin and compared its reactivity with the immunoreactivity of monoclonal antisera to Tn, STn, T and STAg antigens in benign and malignant epithelium of the gall bladder, extrahepatic bile ducts and ampulla of Vater. We found that short-term fixation in formol sublimate resulted in poor PNA binding. All other tested fixation schedules showed strong perinuclear binding, similar to that found on cryostat sections. When compared with monoclonal antisera, PNA binding demonstrated the lowest specificity in benign epithelium. In both benign and malignant epithelium, the two methods cannot substitute for each other. STn and STAg antigens were found to be oncodevelopmental throughout the extrahepatic biliary tract. When used in a panel, they are useful as diagnostic markers of malignancy in gall bladder epithelium.     

前列腺泡沫状腺癌1例报告并文献复习

目的探讨前列腺泡沫状腺癌(prostatic foamy gland carcinoma)的临床病理特点、鉴别诊断、治疗及预后。方法观察1例前列腺泡沫状腺癌的组织学、免疫组化,并复习前列腺泡沫状腺癌相关文献。结果前列腺泡沫状腺癌的临床表现与经典型前列腺癌相似。镜下瘤细胞以其具有黄色瘤样胞浆为特征。核的异型性不明显,也常缺乏明显增大的核仁,但有结构异常、浸润性生长方式和基底细胞层消失。其假良性细胞学表现使之易被误诊为良性病变,或者使肿瘤的Gleason分级被低估。结论前列腺泡沫状腺癌是一种有侵袭性生物学行为的特殊组织学类型前列腺癌。     

原发性肝透明细胞癌影像学及临床分析

目的:探讨原发性肝细胞癌(PCCCL)的影像学及临床病理等特点,提高对肝透明细胞癌的认识,早期确诊、早期治疗、改善预后等,以避免临床误诊,并评价PCCCL的预后比例及疗效。方法:回顾性分析了2009年至2010年我院肿瘤科收治的3例肝透明细胞癌患者的临床资料、影像学质料,以及临床治疗和随访情况。结果:3例均为男性,2例行氩氦刀靶向消融治疗,1例行CT引导下射频消融治疗,术后随访半年2例过世,1例生存。结论:原发性肝细胞癌透明细胞型早期诊断尤为重要,及时手术切除及消融治疗是取得较好疗效的关键。     

Establishment of a new cell line of endometrioid carcinoma of the ovary and its chemosensitivity

A new cell line (NOE) of human ovarian endometrioid carcinoma was established and characterized. The cell line showed a short spindle-shaped morphology and continued to grow for more than 4 months without contact inhibition. The doubling time was approximately 15.5 h at the 10th passage. The chromosome number was aneuploid. The IC50 values of paclitaxel, cisplatin and carboplatin were 26.4 ng/mL, 2.4 microg/mL and 32.5 microg/mL, respectively. The NOE cells expressed estrogen receptor alpha. In nude mice, we confirmed tumor formation of NOE cells. These results indicated that NOE cells showed similar chemosensitivity and properties to those of the original tumor and might be useful in basic studies on the diagnosis, treatment and etiology of ovarian tumors.     

Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from breast carcinoma in effusions

Ovarian/primary peritoneal carcinoma and breast carcinoma are the gynaecological cancers that most frequently involve the serosal cavities. With the objective of improving on the limited diagnostic panel currently available for the differential diagnosis of these two malignancies, as well as to define tumour‐specific biological targets, we compared their global gene expression patterns. Gene expression profiles of 10 serous ovarian/peritoneal and eight ductal breast carcinoma effusions were analysed using the HumanRef‐8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real‐time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated ovarian from breast carcinoma samples. We identified 288 unique probes that were significantly differentially expressed in the two cancers by greater than 3.5‐fold, of which 81 and 207 were overexpressed in breast and ovarian/peritoneal carcinoma, respectively. SAM analysis identified 1078 differentially expressed probes with false discovery rate less than 0.05. Genes overexpressed in breast carcinoma included TFF1, TFF3, FOXA1, CA12, GATA3, SDC1, PITX1, TH, EHFD1, EFEMP1, TOB1 and KLF2. Genes overexpressed in ovarian/peritoneal carcinoma included SPON1, RBP1, MFGE8, TM4SF12, MMP7, KLK5/6/7, FOLR1/3, PAX8, APOL2 and NRCAM. The differential expression of 14 genes was validated by quantitative real‐time PCR, and differences in 5 gene products were confirmed by immunohistochemistry. Expression profiling distinguishes ovarian/peritoneal carcinoma from breast carcinoma and identifies genes that are differentially expressed in these two tumour types. The molecular signatures unique to these cancers may facilitate their differential diagnosis and may provide a molecular basis for therapeutic target discovery.     

鼻咽癌与miRNAs

鼻咽癌(nasopharyngeal carcinoma,NPC)是一种多基因遗传性疾病,好发生于我国华南、东南亚及部分非洲地区。近年来随着分子生物学及其技术的迅速发展,人们对鼻咽癌发生、发展及其生物学行为的研究已进入基因水平。microRNA(miRNA)是一类广泛存在于动植物体内的非编码小RNA,主要参与基因转录后水平调控。随着对miRNA研究的深入,发现肿瘤的细胞分化障碍、增殖失控、细胞永生化与miRNA密切相关。人类肿瘤组织与正常细胞组织间的miRNA表达水平和类型存在明显差异,提示miRNA可能是一类新的参与肿瘤发生的重要分子。本文就鼻咽癌与miRNA相关的研究进展作一综述。