Cytologic diagnosis of vaginal papillary squamotransitional cell carcinoma. A case report

BACKGROUND: Papillary squamous and squamotransitional cell carcinomas of the cervix and vagina are infrequent morphologic variants of squamous cell carcinoma that may be underdiagnosed due to a bland histologic appearance. To our knowledge, this entity has not been previously detected by Pap smear evaluation. CASE: Vaginal wall pap smears were collected from a patient with a previous hysterectomy for microinvasive cervicovaginal squamous cell carcinoma and extensive carcinoma in situ. The smears were characterized by: (1) large, darkly staining, three-dimensional, branching, papillary epithelial fragments with prominent fibrovascular cores and lined with loosely cohesive epithelial cells; (2) a highly cellular background population of dissociated single epithelial cells with features of severe dysplasia, including hyperchromatic, coarse chromatin; scant, delicate, frayed cytoplasm and karyorrhectic debris; (3) syncytial aggregates of severely dysplastic epithelial cells morphologically similar to the single cells; and (4) lack of a recognizable, morphologically distinct "transitional cell" population. CONCLUSION: Papillary squamotransitional cell carcinoma of the vagina is a rare morphologic variant of squamous cell carcinoma that should be distinguished from benign vaginal squamous papillomas, condylomatous lesions and verrucous carcinoma. However, this lesion is also related to human papillomavirus infection, particularly the high-risk types. Papillary squamotransitional cell carcinoma can be suspected on Pap smear when high grade squamous intraepithelial lesion features are found in combination with three-dimensional papillary tissue fragments with prominent fibrovascular cores.     

Scanning electronic microscopy study of nasopharyngeal carcinoma

The nasopharyngeal carcinoma is a greatly interesting model of study. Its morphology has been studied in 8 patients affected by squamous cells carcinoma (4 cases) and by undifferentiated carcinoma (4 cases). By means of a fibre-optic pharyngoscope equipped with mechanical biopsy forceps, biopsies have been taken and subsequently studied by scanning electron microscopy (SEM). Squamous cells carcinoma is characterized by large, flattened elements, generally equipped with a network of microridges. Irregular microvilli or smooth apices have been observed too. Desquamating elements often accumulated in waves or vortices, as far as little cornified structures have been described. Undifferentiated carcinoma shows a great morpho-structural disorder. In a rugged surface, it is possible to observe element highly varying for size and shape. The apical plasmalemma is characterized by pleomorphic microvilli, while it must be emphasized the presence of little pseudopod-like extrusions of some cellular apices. Ciliated elements have been observed too, whose apical specializations are distorted or irregularly disposed. Necrotic zones are particularly frequent, in which bacteria or mycetes proliferate. The role of SEM in the study of this tumour is emphasized, because of the close relation between epithelial patterns and natural history of nasopharyngeal carcinoma.     

The cervical epithelial surface. III. Scanning electron microscopic study in atypias and invasive carcinoma in mice.

The anatomy of the epithelial surface of the uterine cervix was investigated in 31 mice with scanning electron microscope (SEM). The cervox of 20 mice was painted twice a week during five months with 3,4-benzpyrene (BP) in acetone and in 11 mice with acetone alone. Only two of the 15 acetone or BP treated animals with histologic normal epithelium showed similar structures as those described earlier for the normal cervical epithelium of untreated mice. The remaining 13 animals had regular mosaics, intermediate or cobblestone structures covered with irregular microvilli with or without long, finger-like protrusions. Irregular mosaics, intermediate or cobblestone structures were seen in atypical epithelium. In atypias Grade III and in invasive carcinoma irregular cobblestone structures with cellular overlapping were present. Atypical and invasive carcinoma were usually furnished with irregular microvilli, irregular fragmented microrugae and finger-like protrusions. The proportion of mice having anisovillosis with finger-like protrusions increased with increasing degree of epithelial severity. Since pathologic SEM changes were observed in some treated mice having normal histology the possibility was entertained that alterations at the cellular membrane level may preceed the nucleocytoplasmic changes required for the recognition of atypical epithelium in conventional histologic preparations.     

Snail-dependent and -independent epithelial-mesenchymal transition in oral squamous carcinoma cells.

Disappearance of E-cadherin is a milestone for epithelial-mesenchymal transition (EMT), found both in carcinomas and in some fibrotic diseases. We have studied the mechanisms of EMT in oral squamous cell carcinoma (SCC) cells isolated from primary tumor (43A) and its recurrent tumor (43B). Whereas the cells from primary carcinoma displayed a typical phenotype of squamous epithelial cells including E-cadherin and laminin-332 (laminin-5), cells from recurrent tumor expressed characteristics of dedifferentiated, EMT-experienced tumors. 43B cells expressed E-cadherin repressors ZEB-1/deltaEF1 and especially ZEB-2/SIP1, which therefore appear as candidates for endogenous EMT in these cells. Differences between endogenous and exogenous EMT were assessed by transfecting 43A cells with SNAIL cDNA. SNAIL-transfected cells showed complete EMT phenotype with fibroblastoid appearance, vimentin filaments, E-cadherin/N-cadherin switch, lack of hemidesmosomes and, as a new feature of EMT, lack of laminin-332 synthesis. Upregulation of ZEB-1 and ZEB-2 was evident in these cells, suggesting that SNAIL can regulate these E-cadherin repressors. New monoclonal antibodies against SNAIL showed nuclear immunoreactivity not only in the SNAIL-transfected cells but also in carcinoma cells lacking production of Lm-332 and showing signs of EMT. These results suggest that changes in the epithelial cell differentiation program and EMT in SCC cells can result from the interplay among several E-cadherin repressors; however, SNAIL alone is able to accomplish a complete EMT.     

Case report: Metaplastic carcinoma presenting as a breast abscess

Metaplastic breast carcinoma (MBC) is a rare neoplasm containing a mixture of epithelial and mesenchymal elements. The epithelial component is usually ductal carcinoma but may include other variants of breast carcinomas including squamous carcinoma and osteogenic sarcoma. There is a relative paucity of data regarding such tumours. Metaplastic carcinoma carries a prognosis not dissimilar to that of comparable ductal carcinoma. This is the case of a 57 year old patient with MBC presenting with a breast abscess. A thorough literature search has not revealed any previous reports of MBC presenting as a breast abscess.     

Decreased plakophilin-1 expression promotes increased motility in head and neck squamous cell carcinoma cells

Desmosomes are prominent cell-cell adhesive junctions found in a variety of epithelial tissues, including the oral epithelium. The transmembrane core of the desmosome is composed of the desmosomal cadherins that interact extracellularly to mediate cell-cell adhesion. The cytoplasmic domain of desmosomal cadherins interact with plaque proteins that in turn interact with the keratin intermediate filament cytoskeleton. Plakophilin 1 is a major desmosomal plaque component that functions to recruit intermediate filaments to sites of cell-cell contact via interactions with desmoplakin. Decreased assembly of desmosomes has been reported in several epithelial cancers. We examined plakophilin-1 expression in an esophageal squamous cell carcinoma tissue microarray and found that plakophilin-1 expression inversely correlates with tumor grade. In addition, we sought to investigate the effect of plakophilin-1 expression on desmosome assembly and cell motility in oral squamous cell carcinoma cell lines. Cell lines expressing altered levels of plakophilin-1 were generated and the ability of these cells to recruit desmoplakin to sites of cell-cell contact was examined. Our results show that decreased expression of plakophilin-1 results in decreased desmosome assembly and increased cell motility and invasion. These data lead us to propose that loss of plakophilin-1 expression during head and neck squamous cell carcinoma (HNSCC) progression may contribute to an invasive phenotype.     

DNA profiles in dysplasia and carcinoma of the human esophagus

The nuclear DNA content was microspectrophotometrically measured in 16 resected esophagi having dysplasia, carcinoma in situ and/or early invasive squamous carcinoma. First, the epithelial thickness in (1) normal squamous esophageal epithelium and (2) dysplasia-carcinoma in situ areas was divided into three equal compartments (i.e., basal-parabasal, intermediate and superficial) in five cases. In the normal epithelium, while some of the nuclei in basal-parabasal normal squamous cells had elevated DNA values (corresponding to the natural DNA replication in these cells), intermediate and superficial (nonreplicating) normal squamous cells showed a more definite clustering about the 2c value. In the nonnormal epithelium, the percentage of cells with DNA levels exceeding the normal tetraploid value was highest for the intermediate zone. Therefore, in all 16 cases, normal intermediate cells were measured as internal controls, against which the DNA levels of cells in the intermediate compartment in the areas of dysplasia and/or carcinoma in situ were compared. In areas of dysplasia, two different DNA patterns were observed: one clustering around the normal diploid region and the other with aneuploid values. While the former corresponded to some of the lesions considered by conventional histologic examination to be slight and moderate dysplasias, the aneuploid pattern corresponded to the remaining slight and moderate dysplasias as well as to the severe dysplasias. The possibility that "diploid dysplasias" are reactive (i.e., nonneoplastic) lesions due to chronic inflammation or are "dormant" nonprogressive dysplasias, while aneuploid dysplasias are more aggressive lesions, seems to be substantiated by the fact that all areas with carcinoma in situ or with microinvasive squamous carcinoma had aneuploid nuclei.     

Human esophageal carcinoma cells have fewer, but higher affinity epidermal growth factor receptors

Squamous cell carcinomas have recently been shown to contain increased numbers of epidermal growth factor (EGF) receptors. Since EGF has an important role in epithelial growth and differentiation, it is possible that modulation of its receptor may have an important role in neoplasia. In an attempt to further explore the relationship of EGF receptor expression to malignant transformation, we examined 14 squamous cell carcinoma cell lines of the esophagus for the number and affinity of EGF receptors. Seven cell lines were newly isolated by this laboratory and recently characterized. The seven additional cell lines were obtained from Japan (4 cell lines) and South Africa (3 cell lines). Surprisingly, we found that esophageal carcinomas contained lowered quantities of surface EGF receptors (2- to 100-fold) and that the affinity of the EGF receptor was increased (6- to 100-fold) when compared to normal esophageal epithelial cells. Moreover, the biologic response of esophageal carcinoma cells to EGF differed markedly from that of other squamous cell tumor cells exhibiting elevated numbers of receptors, such as A431 and SCC-15. Human esophageal carcinoma cells were maximally stimulated by the addition of 5 ng/ml of EGF, similar to normal esophageal keratinocytes, but in contrast to normal cells were not inhibited by the higher concentrations tested (up to 40 ng/ml). On the other hand, addition of any EGF to the medium (beyond that normally present in serum) was found to dramatically inhibit the growth of A431 and SCC-15 cells. Our findings indicate that squamous cell neoplasia is not dependent upon increased numbers of cell surface EGF receptors, that EGF receptor number may have a determinant role in EGF cell toxicity, and that the stimulatory response of cells to EGF may reflect a complex function of EGF receptor number, affinity, and occupancy.     

Fine needle aspiration cytology of high grade mucoepidermoid carcinoma of the breast: a case report

BACKGROUND: Primary mucoepidermoid carcinoma of the breast is a very unusual tumor. It is often misdiagnosed, masquerading under different diagnoses. The cytologic assessment is especially difficult when the lesion is high grade. One reported case was initially diagnosed by fine needle aspiration cytology. CASE: A 69-year-old woman presented with a 6 x 4-cm tumor located in the upper outer quadrant of the right breast. The first cytologic diagnosis suggested ductal carcinoma with atypical squamous metaplasia; further review disclosed that the clusters of epithelial ductal cells displayed a mixed pattern of glandular, squamous and intermediate cells. There also was a scant intracellular and extracellular mucous substance, confirming the diagnosis of mucoepidermoid carcinoma. Histochemistry and immunohistochemistry, performed on the tumor and lymph node metastases, showed cellular staining for periodic acid-Schiff, and keratin, epithelial membrane antigen and carcinoembryonic antigen demonstrated the epithelial origin. The high expression of Ki-67, as well as the finding of 24 metastasized nodes in the axilla, demonstrated the tumor's aggressiveness. CONCLUSION: Fine needle aspiration cytology is a very reliable tool in achieving a fast and accurate diagnosis of primary mucoepidermoid carcinoma of the breast.     

Comparative proteomics approach to screening of potential diagnostic and therapeutic targets for oral squamous cell carcinoma

This work demonstrates that a comprehensive strategy of proteomics identification combined with further validation and detailed functional analysis should be adopted in the field of cancer biomarker discovery. A comparative proteomics approach was utilized to identify differentially expressed proteins in 10 oral squamous carcinoma samples paired with their corresponding normal tissues. A total of 52 significantly and consistently altered proteins were identified with eight of these being reported for the first time in oral squamous carcinoma. Of the eight newly implicated proteins, RACK1 was chosen for detailed analysis. RACK1 was demonstrated to be up-regulated in cancer at both the mRNA and protein levels. Immunohistochemical examination showed that the enhanced expression of RACK1 was correlated with the severity of the epithelial dysplasia as well as clinical stage, lymph node involvement, and recurrence, which are known indicators of a relatively poor prognosis in oral squamous carcinoma patients. RNA interference specifically targeted to silence RACK1 could initiate apoptosis of oral squamous carcinoma cells. Taken together, the results indicate that RACK1 is up-regulated in oral squamous carcinoma, not only being closely related to cell proliferation and apoptosis but also linked to clinical invasiveness and metastasis in carcinogenesis. The observations suggest that RACK1 may be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of oral squamous carcinoma. Further this comprehensive strategy could be used for identifying other differentially expressed proteins that have potential to be candidate biomarkers of oral squamous carcinoma.     

GRP78在食管鳞状细胞癌、不典型增生及正常食管鳞状上皮组织中的表达

目的：检测葡萄糖调节蛋白78（glucose—regulated proteins78,GRP78）在同一食管癌患者食管的鳞状细胞癌、不典型增生及正常鳞状上皮组织中的表达,研究GRP78与食管鳞状细胞癌发生发展的关系。方法：取90例食管鳞状细胞癌患者的病变组织,其病理切片中正常鳞状上皮组织、不典型增生组织和鳞状细胞癌组织均存在,用免疫组化的方法,检测GRP78在3种不同组织中表达的情况,分析G史P78与性别、年龄、浸润深度、分化程度、分期及淋巴结转移等参数之间的关系。结果：GRP78在食管正常鳞状上皮组织、不典型增生组织、鳞状细胞癌组织中的阳性表达率分别为7．8％、85．6％、47．8％,GRP78在正常食管组织、不典型增生组织、食管鳞癌组织3组中表达的差异有显著性意义（P〈0．01）。鳞状细胞癌组织中GRP78表达阴性者,年龄较阳性者大;GRP78表达与肿瘤分化程度、分期、淋巴结转移等有明显相关性。结论：GRP78在食管正常细胞向恶性细胞转化的过程中可能扮演了重要角色,检测GRP78的表达可能有助于对食管鳞状细胞癌的预防及早期诊断。     

Fine needle aspiration biopsy diagnosis of mucoepidermoid carcinoma. Statistical analysis

Fine needle aspiration (FNA) biopsy is an increasingly popular method for the evaluation of salivary gland tumors. Of the common salivary gland tumors, mucoepidermoid carcinoma is probably the most difficult to diagnose accurately by this means. A series of 96 FNA biopsy specimens of salivary gland masses, including 34 mucoepidermoid carcinomas, 51 other benign and malignant neoplasms, 7 nonneoplastic lesions and 4 normal salivary glands, were analyzed in order to identify the most useful criteria for diagnosing mucoepidermoid carcinoma. Thirteen cytologic criteria were evaluated in the FNA specimens, and a stepwise logistic regression analysis was performed. The three cytologic features selected as most predictive of mucoepidermoid carcinoma were intermediate cells, squamous cells and overlapping epithelial groups. Using these three features together, the sensitivity and specificity of accurately diagnosing mucoepidermoid carcinoma were 97% and 100%, respectively.     

Establishment and characterization of an osteopontin-null cutaneous squamous cell carcinoma cell line

Osteopontin (OPN) is a secreted glycoprotein implicated to function in cancer development and metastasis. Although elevated expression of OPN are observed in cancer cells of various types, in some cases, only the cells in the stromal region surrounding the tumor express OPN, suggesting distinct functional roles for this protein derived from host cells and from cancer cells. To provide a model for addressing the functions and mechanisms of host-derived OPN in cancer progression and metastasis, a cutaneous squamous cell carcinoma cell line (ONSC) that lacks the OPN gene, Spp1, was established. This line of cells was derived from a squamous cell carcinoma that developed in a female, OPN-null mouse subjected to two-stage skin carcinogenesis. Morphologically, ONSC cells resemble epithelial cells, and they express the epithelial markers, K1, K14, and p63, as confirmed by immunohistochemical analyses. Genomic analyses indicate the presence of mutated H-Ras and p53 genes. ONSC cells form colonies in soft agar and, subcutaneously injected into athymic nude mice, develop into squamous cell carcinomas that metastasize to the lungs. Lacking OPN expression, these squamous cell carcinoma cells provide a model to address the function of host OPN in the context of cancer progression and metastasis.     

NOB1在食管鳞状细胞癌中的表达及临床意义

目的研究NOB1基因在食管鳞状细胞癌（Esophageal squamous cell carcinoma,ESCC）中的表达及临床意义。方法利用免疫组织化学SP法检测59例ESCC及其相应（50例）的远端正常食管黏膜组织中NOB1的表达。结果 ESCC中NOB1的阳性率为71%,正常食管黏膜鳞状上皮中的阳性率为26%,两组比较,差异有统计学意义（P〈0.05）。NOB1的表达与ESCC的分化程度及淋巴结转移相关,与患者的性别,年龄以及肿瘤浸润深度无关。结论 NOB1在ESCC中表达升高,可能在ESCC发生发展过程中起重要作用。     

Atypical squamous cells as a diagnostic pitfall in pulmonary Wegener's granulomatosis. A case report

BACKGROUND: Wegener's granulomatosis (WG) is characterized by systemic, necrotizing, granulomatous inflammation accompanied by vasculitis. It classically involves the triad of the upper respiratory tract, lungs and kidneys. Isolated pulmonary lesions of WG may present in some patients as pulmonary masses, simulating neoplasms. The features of WG can be suggested by cytologic study. Atypical epithelial cells associated with WG have previously been reported as a cause of a false positive diagnosis of bronchoalveolar carcinoma. CASE: In this case the cytologic findings included atypical squamous cells in a background of acute, chronic and granulomatous inflammation. In several respiratory specimens the atypical squamous cells were incorrectly interpreted as diagnostic of squamous cell carcinoma. The correct diagnosis of WG was confirmed with open lung biopsy, which demonstrated necrotizing granulomatous inflammation with geographic necrosis and associated vasculitis. CONCLUSION: Markedly atypical squamous cells mimicking squamous cell carcinoma can be found accompanying the inflammatory process associated with WG and are a possible diagnostic pitfall. The possibility of WG as well as other inflammatory processes should always be considered in the differential diagnosis of squamous cell carcinoma of the lung. This case is the only reported case of WG in which atypical squamous cells were a diagnostic pitfall, initially suggesting a diagnosis of squamous cell carcinoma.     

GRP78 在食管鳞状细胞癌、不典型增生及正常食管鳞状上皮 组织中的表达

目的:检测葡萄糖调节蛋白78(glucose-regulated proteins 78,GRP78)在同一食管癌患者食管的鳞状细胞癌、不典型增生及正常鳞状上皮组织中的表达,研究GRP78与食管鳞状细胞癌发生发展的关系。方法:取90例食管鳞状细胞癌患者的病变组织,其病理切片中正常鳞状上皮组织、不典型增生组织和鳞状细胞癌组织均存在,用免疫组化的方法 ,检测GRP78在3种不同组织中表达的情况,分析GRP78与性别、年龄、浸润深度、分化程度、分期及淋巴结转移等参数之间的关系。结果:GRP78在食管正常鳞状上皮组织、不典型增生组织、鳞状细胞癌组织中的阳性表达率分别为7.8%、85.6%、47.8%,GRP78在正常食管组织、不典型增生组织、食管鳞癌组织3组中表达的差异有显著性意义(P<0.01)。鳞状细胞癌组织中GRP78表达阴性者,年龄较阳性者大;GRP78表达与肿瘤分化程度、分期、淋巴结转移等有明显相关性。结论:GRP78在食管正常细胞向恶性细胞转化的过程中可能扮演了重要角色,检测GRP78的表达可能有助于对食管鳞状细胞癌的预防及早期诊断。     

A spontaneous squamous cell carcinoma of the oral cavity in a squirrel monkey (Saimiri sciureus)

A spontaneous squamous cell carcinoma was diagnosed in the oral cavity of an adult female squirrel monkey (Saimiri sciureus). Immunohistochemical analysis of the neoplasm demonstrated cytokeratin and vimentin, but not S100 or desmin in the neoplastic epithelial cells.     

MACC1和C-Met在口腔白斑和口腔鳞状细胞癌中的表达及意义

目的:探讨分析MACC1和C-Met在正常口腔黏膜、口腔白斑及口腔鳞状细胞癌中的表达及其临床意义。方法:采用免疫组化SP法检测20例口腔黏膜、20例上皮异常增生白斑、50例口腔鳞癌组织中的MACC1、C-Met蛋白的表达情况,采用X2和spearman等级相关分析对结果进行判定。结果:MACC1、C-Met蛋白在异常增生型白斑和口腔鳞癌中的阳性表达率分别为50%、76%,35%、66%,均明显高于正常口腔黏膜(17.6%,5.0%),差异均有统计学意义(P0.05)。MACC1和C-Met蛋白表达与口腔鳞癌的分期、淋巴结转移及分化程度密切相关(P0.05)。Spearman等级相关分析显示口腔白斑及口腔鳞癌中MACC1和C-Met的表达呈现正相关(P0.05)。结论:MACC1和C-Met在上皮不典型增生性白斑和口腔鳞癌中高表达,二者在口腔黏膜白斑的癌变和口腔鳞癌的发生发展中可能起重要作用。