The diagnostic reliability of cytologic typing in primary lung cancer with a review of the literature

To evaluate the growing tendency in recent years to attribute more diagnostic reliability to cytologic methods, we investigated the accuracy of cytologic typing in specimens obtained from bronchopulmonary material by five different clinical sampling methods, comparing the cytologic diagnoses with the known histologic diagnoses. The study consisted of 232 cytologic specimens from 157 cases of primary lung cancer. Of the 232 specimens, 173 (75%) were correctly typed and 59 (25%) incorrectly typed with respect to the appropriate histologic diagnoses. When all sampling methods were considered together, the study demonstrated that well-differentiated epidermoid carcinoma and "oat cell" and spindle-polygonal anaplastic carcinomas yielded high cytologic typing accuracies. In poorly differentiated tumors, bronchioloalveolar cell carcinoma and bronchogenic adenocarcinoma, the correct cytologic typing was much lower. The different tumor types and their degrees of differentiation seem to be the decisive factors in cytologic typing accuracy. The findings of this study were compared with those of others and were found to be consistent with the results of even larger series of cases. For some types the typing accuracy was higher than that reported in other series, whereas for other types, e.g., adenocarcinomas, it was lower.     

Establishment and characterization of a human colonic cancer cell line expressing carbohydrate antigen 19-9 and carcinoembryonic antigen]

Colonic cancer cell strain KE43 was established from a human colonic cancer diagnosed histologically as a predominantly well differentiated adenocarcinoma with minute foci of poorly differentiated adenocarcinoma. The well differentiated adenocarcinoma cell line was identified as the major morphological picture in xenografts of KE43 and 58 in nude mice, but this changed to poorly differentiated adenocarcinoma in passage 105. Doubling time of this cancer cell line was 22.5 hours in passage 105. The modal numbers of chromosomes were 41 and 76. Cancer cells could be heterotransplanted in 100% of the nude mice. The tumor cells produced and secreted CA19-9, CEA and Laminin into the spent medium. This cell line appears to provide a useful system for studying colonic cancer in vivo and in vitro.     

Histologic and cytologic patterns of lung cancer in 2,580 men and women over a 15-year period

This paper describes the relative frequencies and changes in the morphologic patterns of lung cancer, as documented in the histologic and cytologic specimens from 2,580 patients diagnosed and treated at Duke University Medical Center over a period of 15 consecutive years. During the first five years, the relative frequencies of the various types of lung cancers were, in descending order, squamous cell carcinoma (43.1%), large cell undifferentiated carcinoma (22.5%), adenocarcinoma of the acinar type (18.6%), small cell undifferentiated carcinoma (11.6%), bronchioloalveolar carcinoma (3.5%) and adenosquamous carcinoma (0.7%). During the second and third five-year periods, squamous cell carcinoma remained the most common neoplasm, but declined to 35.7%, while adenocarcinoma of the acinar type became the second most common lung cancer at 22.0%. The absolute and relative incidences of lung cancer in women showed a striking increase from 21.8% to 29.9%. During this same period, adenocarcinoma of the acinar type replaced squamous cell carcinoma as the most common primary lung cancer in women.     

Endometrial and endocervical secretion: the search for histochemical differentiation

OBJECTIVE: To determine the ideal histochemical stain to differentiate between non-neoplastic and neoplastic endocervix and endometrium. STUDY DESIGN: A total of 90 cases representing nonneoplastic cervix, non-neoplastic endometrium, endocervical adenocarcinoma and endometrial adenocarcinoma were stained with toluidine blue (TB); methylene blue (MB); mucicarmine (MUC); periodic acid-Schiff before and after diastase digestion (PAS, PAS-D); Alcian blue, pH 2.5 (AB); and periodic acid-Schiff after Alcian blue, pH 2.5 (PAB). Cases were blinded and randomly divided between two pathologists for evaluation of the staining and the staining distribution of the glandular epithelium by means of a 36-color scheme. RESULTS: The majority of non-neoplastic endocervix samples stained blue with MB (57%), fuchsia with MUC (70%), magenta with PAS (77%) and PAS-D (73%) and dark turquoise with AB (70%). The majority of non-neoplastic endometrium samples stained slate blue with TB (60%) and pink with PAS-D (53.3%). There is statistical difference (p < 0.05) in the color of the epithelium and secretions between the non-neoplastic cervix and endometrium. The malignant glands of endocervical origin could be differentiated significantly (p = 0.043) from non-neoplastic endocervical epithelium by MUC. The epithelium of the non-neoplastic endometrium is significantly differentiated from malignant endometrium using TB (p = 0.015) and MB (p = 0.038). Endocervical carcinoma could be significantly differentiated from endometrial carcinoma by MB. The staining in endocervical adenocarcinoma and endometrial carcinoma was predominantly present in both apical and cytoplasmic locations compared to their non-neoplastic counterparts (endocervix, p = 0.003; endometrium, p = 0.049). CONCLUSION: This study showed that a panel of histochemical stains could differentiate glandular cells of endocervical epithelium from endometrium.     

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions
This paper reports the cytological findings based on air-dried smears in a retrospective series of 143 cases of endocervical adenocarcinoma, combined adenocarcinoma-squamous carcinoma and adenosquamous carcinoma drawn from the files of the BC Cancer Registry. Cervical cytology smears were available before biopsy in 131 patients, but in 18 cases the cytology showed no abnormality. Malignant changes or high-grade atypia of glandular and/or squamous cells (defined as moderate or severe dyskaryosis) were detected in 103 cases. In 46 cases, only a high-grade squamous abnormality was detected. Low-grade glandular and/or squamous lesions were detected in nine cases and one showed atypical endometrial-type glands. The cervical smears of 64 cases were reviewed in detail to determine the important cytomorphological criteria of in situ and invasive adenocarcinoma in air-dried smears, the technique used for preparing PAP smears in British Columbia. Endocervical cells were absent in four cases. Numerous (>10) groups of glandular cells were present in 51 cases. Important clues to the diagnosis of adenocarcinoma included crowding of nuclei, stratification of nuclei, loss of polarity, syncytial balls and papillary groups of glandular cells, nuclear enlargement, nuclear pleomorphism, and the presence of free-lying atypical glandular cells. Nuclear hyperchromatism, chromatin pattern, nuclear borders, nuclear membranes, and numbers and morphology of nucleoli were not helpful criteria in our material. Criteria enabling reliable distinction between in situ and invasive adenocarcinoma and/or mixed adenocarcinoma-squamous carcinoma could not be established.     

Glandular lesions of the cervix on thin-layer Pap tests. Validity of cytologic criteria used in identifying significant lesions

OBJECTIVE: To determine the cytologic features that are most helpful in characterizing significant glandular lesions of the cervix observed on the ThinPrep (TP) Pap test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) and to compare these features with those published for conventional smears. STUDY DESIGN: Thirty-nine TP preparations with cytologic evidence of glandular lesions of the cervix and histologic and/or clinical correlation were studied. These lesions included (1) 11 cases of benign/reactive conditions; (2) 10 cases of adenocarcinoma in situ (AIS), of which 1 had both AIS and carcinoma in situ; (3) 1 case of invasive adenocarcinoma; (4) 15 cases of squamous intraepithelial lesions and squamous cell carcinoma, including 4 with glandular involvement, and (5) 2 cases of adenosquamous cell carcinoma. These cases were reviewed by the first author without knowledge of the histologic diagnosis. Twenty-five previously published cytologic criteria were used to evaluate glandular cells on TP slides. Statistical analysis was performed using Fisher's exact test to determine the significance of the features studied. RESULTS: All glandular lesions had cytologic features on TP similar to those previously described on conventional smears. However, TP slides demonstrated enhanced nuclear features but less-preserved architectural patterns. Reactive lesions showed minimal overlapping without hyperchromasia or mitotic figures and with normal nuclear/cytoplasmic ratios. AIS and invasive adenocarcinoma cases had similar features. Increased cellularity and overcrowding were prominent, whereas feathering, rosettes and cell strips were present but subtle. CONCLUSION: Glandular lesions of the cervix on TP slides shared many of the characteristic features reported for conventional smears. However, nuclear details were more pronounced in TP slides, while architectural patterns, although present, were relatively subtle.     

Comparison of glycopeptide in lung cancer tissues of different histological types

The glycopeptide was studied in the pulmonary cancer tissues of three different histological types including squamous cell carcinoma, undifferentiated cell carcinoma, and adenocarcinoma. The glycopeptide preparation was made by digesting the lung cancer tissues with proteolytic enzymes followed by removal of enzymes and undigested protein. The comparison of the relative proportion of the glycopeptide, which migrated toward the anode slower than hyaluronic acid, and was stained with both alcian blue and PAS, and contained higher sialic acid, was carried out among three different histologic types of lung cancer. This glycopeptide was highest in adenocarcinoma, followed by undifferentiated cell carcinoma, and was lowest in squamous cell carcinoma.     

Extrauterine malignancies. Role of Pap smears in diagnosis and management.

OBJECTIVE: To further elucidate the cytologic manifestations of extrauterine malignancies, to evaluate their possible distinction from primary cervical malignancies and to analyze their clinical significance and role in staging. STUDY DESIGN: Papanicolaou (Pap) smears in 33 cases with abnormal cells originating in histologically proven extrauterine carcinomas were evaluated. These cases came from the files of the Medical College of Pennsylvania and Lankenau Hospitals. RESULTS: Ovary, gastrointestinal tract and breast were the three most frequent primary sites, accounting for 28 of the 33 cases (85%). The histologic types encountered were adenocarcinoma, 29 cases (88%); mucoepidermoid carcinoma, 1 (3%); small cell carcinoma, 1 (3%); cloacogenic carcinoma and large cell lymphoma, 1 (3%). The following diagnoses were rendered at the time of initial evaluation: adenocarcinoma consistent with metastasis, 21 cases; carcinoma, primary versus metastatic, 2; adenocarcinoma, suspicious for endometrial primary, 2; suspicious for carcinoma, 1; and atypical glandular cells, 7. CONCLUSION: The yield for positive Pap smear diagnoses in extrauterine malignancies is best in patients with an established diagnosis of a primary neoplasm. The degree of tumor differentiation and extent of tumor involvement did not appear to correlate with diagnostic yield. There appeared to be no statistically significant association of tumor diathesis with primary versus metastatic carcinoma and presence or absence of documented local involvement of the endometrium, cervix or vagina. Therefore, while Pap smears can serve as a diagnostic tool in the evaluation of extrauterine malignancies, they are best utilized as an adjunct to tumor staging and patient management.     

Spontaneous differentiation of cultured human pulmonary adenocarcinoma cells

During cultivation of the cells of dimorphous poorly differentiated glandular and squamous cell pulmonary carcinoma, one can see the predominance of the cells of poorly differentiated pulmonary adenocarcinoma with a gradual transition to a high-differentiated pulmonary adenocarcinoma. The cells of high-differentiated pulmonary adenocarcinoma exhibited marked capacity for agglutination induced by PHA and Con A, as well as high levels of dehydrogenase and hydrolase activity.     

Psammoma bodies in fine needle aspirates from thyroids containing nontoxic hyperplastic nodular goiters

Psammoma bodies present in fine needle aspiration (FNA) smears with typical cytologic features of colloid goiter from five patients raised the possibility of coexistent papillary carcinoma. However, subsequent careful histologic examination of the entire thyroidectomy specimens did not show occult carcinoma in any of the cases. The psammoma bodies were identified in the stroma next to the foci of papillary hyperplasia in each case. They were small, often equal in size to or slightly larger than the follicular epithelial cell nuclei, and could be misinterpreted as epithelial cell nuclei. These findings suggest that the presence of psammoma bodies in an FNA smear cytologically consistent with a colloid goiter should raise the possibility of coexistent papillary hyperplasia or neoplasia. However, because of the strong statistical association of psammoma bodies with malignant thyroid neoplasms, histologic confirmation is mandatory in such cases.     

整合分析基因表达与拷贝数变异识别癌症的驱动基因及调控子miRNAs

目的:通过整合分析基因的表达与拷贝数变异(CNV)识别癌症的驱动基因及调控子mi RNAs。方法:通过整合基因表达与CNV数据,分别计算了乳腺癌、结肠癌、肺癌、肾癌、膀胱癌、头颈癌六种癌症中mi RNAs的调控得分,提出了一个识别驱动基因和显著调控子mi RNAs的方法。结果:本文研究发现,CNV区域上编码的基因相比于非CNV区域上编码的基因更倾向于受mi RNAs调控。但是,癌相关CNV区域上的基因相比正常CNV区域上的基因更少受mi RNAs调控。本研究识别出了EXOSC4、ZNF7、BOP1等原癌基因,以及mi R-488、mi R-27a、mi R-454等在多种癌症中都起调控作用的调控子mi RNAs。结论:本文的方法为癌症研究带来了新的启发,这些具有调控扩增基因过表达作用的mi RNAs的发现,有助于我们更进一步了解癌基因表达的复杂调控机制,进而推动癌症的诊断、治疗和预后。     

The potential usefulness of monoclonal antibodies in the determination of histologic types of lung cancer in cytologic preparations

Two monoclonal antibodies (MAbs) were tested for their reactivity with antigens of exfoliated malignant cells in respiratory secretions of lung cancer patients. MAb CE 407 was developed from tissue culture cell line SW 756, derived from human uterine cervical squamous cell carcinoma; MAb BL 99-57 was developed from cell line T-24, derived from human transitional cell bladder cancer. MAb CE 407 reacted preferentially with squamous cell carcinomas (80%) and with some (44%) of the adenocarcinomas of the lung; BL 99-57 reacted with 76% of the adenocarcinomas, but only with 27% of the squamous cell carcinomas of the lung. The reactivity of BL 99-57 was more apparent in well-differentiated adenocarcinomas (89% positive), but less in poorly differentiated adenocarcinomas (65% positive). Neither of these antibodies reacted with antigens of small cell anaplastic carcinoma. These two MAbs may be useful in differentiating histologic types of lung cancer in cases that are difficult to diagnose morphologically and/or in which tissue is not available for study.     

The localization of thrombospondin-1 (TSP-1), cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG) TSP receptor, and matrix metalloproteinase-9 (MMP-9) in colorectal cancer

Thrombospondin-1 (TSP-1) is a 450 kDa matrix bound glycoprotein involved in tumor invasion, metastasis, and angiogenesis. One of the receptors involved in TSP-1 mediated tumor cell adhesion and metastasis is the cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG) receptor. One mechanism of TSP-1 in promoting tumor cell metastasis involves the up-regulation of matrix metalloproteinase-9 (MMP-9) expression, specifically through the CSVTCG TSP-1 receptor. TSP-1 and its CSVTCG receptor has been implicated in tumor progression in a variety of cancers including breast adenocarcinomas, head and neck squamous cell carcinomas, and pancreatic carcinomas. In this study, we examined 99 cases of colorectal cancer by immunohistochemical analysis to investigate 1) the localization of TSP-1 and CSVTCG TSP-1 receptor, 2) the relationship with MMP-9, and 3) the correlation of expression with clinical staging. Strong expression of TSP-1 was observed in the submucosa or the serosa adjacent to the tumor. Positive staining for CSVTCG TSP-1 receptor was observed in tumor cells and microvessels. MMP-9 was also expressed in tumor cells. In addition, staining intensity of CSVTCG TSP-1 receptor was higher in poorly differentiated adenocarcinoma than well or moderately differentiated adenocarcinoma. Tumors in which inflammatory cells stained strongly for CSVTCG TSP-1 receptor correlated with decreased incidence of distant metastasis and angiogenesis. These data were consistent with our previous studies for breast, pancreatic, and head and neck carcinoma. They suggest an important role for TSP-1 and CSVTCG TSP-1 receptor in tumor progression in colorectal cancer.     

Immunohistochemical analysis of the ubiquitin-conjugating enzyme UbcH10 in lung cancer: a useful tool for diagnosis and therapy

The ubiquitin-conjugating enzyme (UbcH10) plays important roles in the regulation of cell cycle progression. Recently, UbcH10 expression has been demonstrated in several human and experimental tumors, and proteasome inhibitors have been tested in trials for pulmonary neoplasms; however, the underlying mechanisms as well as the clinicopathological relevance of UbcH10 in the genesis and progression of lung cancer remain largely unknown. Therefore, the authors evaluated the expression of UbcH10 in human lung cancer and evaluated its possible diagnostic and prognostic use. They found that most cases of lung adenocarcinoma, squamous cell carcinoma, and large cell and small cell carcinoma were positive for UbcH10. The expression levels of UbcH10 progressively increased with decreasing degree of tumor differentiation. There was a statistically significant difference of UbcH10 positivity between grade I/III of lung adenocarcinoma (p=0.013) and squamous cell carcinoma (p=0.002). No significant differences were found between histological types (p=0.072). In the case of cell blocks prepared from pleural effusions, inflammatory and reactive mesothelial elements did not show appreciable UbcH10 expression, whereas neoplastic cells exhibited clear UbcH10 positivity. The results suggest that UbcH10 might represent a new and promising diagnostic and prognostic marker in both histologic and cytologic specimens of lung cancer.     

Membrane connectivity estimated by digital image analysis of HER2 immunohistochemistry is concordant with visual scoring and fluorescence in situ hybridization results: algorithm evaluation on breast cancer tissue microarrays

Because metaplastic carcinoma of the breast encompasses a great variety of histopathology, diagnostic challenges abound, especially within the realm of cytology. The authors compiled and studied an eight-case series comprised of metaplastic breast carcinomas and lesions initially suspicious cytologically for metaplastic carcinoma in order to assess the degree of cytologic-histologic correlation and to identify recurring problematic themes surrounding the cytology-based diagnosis of this neoplasm. The cytologic and histologic slides from eight cases suspicious for metaplastic breast carcinoma diagnosed by fine needle aspiration (FNA) were collected and analyzed through a seven-year retrospective search of case files at our institution. Based on cytologic characteristics, the cases were separated into three groups. Group 1 consisted of three cases presenting with poorly differentiated adenocarcinoma and squamoid components on FNA. Group 2 was composed of two cases that featured a monophasic, malignant ductal cell population on cytology, while the cytologic specimens for the third group of cases presented with a mesenchymal component with or without a malignant glandular constituent. Cytologic-histologic correlation was present in two of three cases demonstrating a mesenchymal component, and there was 100% sensitivity in the cytologic detection of those mesenchymal elements. However, in only one of three cases was there an accurate cytologic diagnosis of metaplastic carcinoma when squamoid changes were present on FNA. Both cases demonstrating only malignant glandular elements on cytologic specimens revealed an additional component of malignant squamous differentiation upon the examination of mastectomy-derived tissue. These results indicate that squamous-like changes identified on FNA should be interpreted with caution and that sampling error remains a problematic recurrence in cytology. Regardless, there appears to be promise concerning the accurate cytologic diagnosis of metaplastic carcinoma when the lesion is characterized by a mesenchymal component. A study implementing a larger case number is essential in determining the significance of these findings.     

Thin-layer cytology findings of papillary adenosquamous carcinoma of the cervix. Report of a case with histologic correlation and molecular analysis

BACKGROUND: Papillary squamotransitional cell carcinoma of the lower female genital tract is a rare form of malignancy with distinctive histologic features. To my knowledge, its adenosquamous counterpart has not been reported before. CASE: A 69-year-old woman presented with postmenopausal bleeding due to a bulky cervical tumor. The thin-layer cytology preparation (Autocyte, TriPath Imaging, Burlington, North Carolina, U.S.A.) was of high cellularity and contained multiple small, papillary clusters of basaloid to columnar cells. Discernible fibrovascular cores were noted. In the background were many loosely dispersed, bland-looking columnar cells as well as cells of high grade squamous intraepithelial lesion (CIN 3). On a diligent search, scattered adenocarcinoma cells containing distinct intracytoplasmic vacuoles were found. There were a small number of dyskaryotic squamous cells with bizarre shapes, assuming "tadpolelike" morphology. Histologic examination of the tumor biopsy showed a papillary tumor with central fibrovascular cores covered with mitotically active, poorly differentiated squamous cells that imperceptibly merged with abortive glandular structures. Molecular analysis using the polymerase chain reaction and restriction fragment length polymorphism revealed the presence of human papillomavirus type 16 DNA in the liquid-based cytology sample. CONCLUSION: Papillary adenosquamous carcinoma of the cervix shares some morphologic and even histogenetic overlaps with papillary squamotransitional cell carcinoma and, to a lesser extent, conventional endocervical adenocarcinoma. It may pose certain diagnostic dilemmas for the unwary. In view of its distinctive cytohistologic features, this tumor warrants greater recognition in gynecologic pathology.     

Chromatin texture in high grade prostatic intraepithelial neoplasia and early invasive carcinoma

OBJECTIVE: To evaluate individual nuclei from high grade prostatic intraepithelial neoplasia (PIN) lesions with early invasive carcinoma foci in the area of microinvasion and in the gland in which the microinvasion originated. STUDY DESIGN: High-resolution, digitized images of nuclei from defined locations were recorded and segmented, and karyometric variables were computed. These included a set of 93 features, which form a nuclear signature characterizing the spatial and statistical distribution of the nuclear chromatin. Nuclei in the glandular epithelium were recorded sequentially, along the basal cell layer, at increasing distances from the point of microinvasion and by random selection in the region of microinvasion. RESULTS: At a distance > 60 nuclear locations from the point of microinvasion, the nuclear signatures corresponded to those seen in high grade PIN. Between 40 and 20 nuclear locations removed from the microinvasion focus the signatures began to change gradually until at a distance of 15-5 locations they strongly resembled the signatures seen in adenocarcinoma. The total optical density decreased to values seen in adenocarcinoma, and the nuclear chromatin had finer granularity. While nuclei in high grade PIN followed a widely dispersed total optical density distribution suggestive of wide-ranging aneuploidy, the nuclei in the region of microinvasion exhibited a less dispersed and bimodal total optical density distribution. CONCLUSION: The chromatin texture signatures showed a clear trend: there was an obvious attenuation as the measured nuclei approached the microinvasion area. The decrease in total optical density at the microinvasion might suggest the emergence of one or two clones that can be responsible for the invasive phenotype.     

Nuclear volume estimates in prostatic atypical adenomatous hyperplasia

OBJECTIVE: To investigate nuclear volume estimates by the point-sampled intercepts method in atypical adenomatous hyperplasia (AAH) as compared with nodular hyperplasia and well-differentiated prostatic adenocarcinoma. STUDY DESIGN: The study group consisted of 27 formalin-fixed, paraffin-embedded, whole-mounted radical prostatectomy specimens that contained foci of nodular hyperplasia, atypical adenomatous hyperplasia and well-differentiated adenocarcinoma (Gleason pattern 1 and 2). Representative sections were selected for stereologic estimation of volume-weighted mean nuclear volume by the point-sampled intercepts method. On each focus, an average of five fields of vision were systematically chosen. RESULTS: The quantitative results indicate an increase in nuclear volume from nodular hyperplasia (209 +/- 65 micron 3) to AAH (237 +/- 85 micron 3) and prostate adenocarcinoma (436 +/- 106 micron 3). Significant differences were found (F = 39.0, P < .001) with two group comparisons (Scheffe's procedure) between prostate cancer and AAH (P < .001) or nodular hyperplasia (P < .001). The difference between AAH and benign hyperplasia was not signifcant. CONCLUSION: The results indicate that three-dimensional estimates of the nuclear size discriminate AAH and nodular hyperplasia from well-differentiated prostate adenocarcinoma. These findings suggest that AAH is probably a histologic variant of benign prostatic hyperplasia the exact relationship of which to prostatic adenocarcinoma remains to be determined.     

Carcinoma of the Lower Uterine Segment (LUS): Clinicopathological Characteristics and Association with Lynch Syndrome

Endometrial cancer arises from the uterine body and fundus in many cases, but can also originate from the lower region of the uterine body through the upper region of the cervix. Such tumors are referred to as carcinoma of the lower uterine segment (LUS) or isthmus, and account for 3-6.3% of all cases of endometrial cancer. This relatively low incidence has permitted performance of only small-scale studies, but the clinical and pathological characteristics of carcinoma of the LUS in all these reports have differed from those of other endometrial cancers. Generally, endometrial cancer is classified into estrogen-dependent endometrioid adenocarcinoma (designated as type I), and non-endometrioid types that are less associated with estrogen and include poorly differentiated adenocarcinoma (type II). In some reports, carcinoma of the LUS has been found to have type II characteristics. Carcinoma of the LUS has also been associated with Lynch syndrome, a hereditary disease with frequent development of colorectal, endometrial, and ovarian cancers. Lynch syndrome is thought to be induced by mismatch repair gene mutation. The frequency of Lynch syndrome in cases of general endometrial cancer is 1-2%. In contrast, the frequency in patients with carcinoma of the LUS is much higher, with up to 29% of cases diagnosable with Lynch syndrome and a high frequency of hMSH2 mutation found in one study. This suggests that further investigation of the clinical and pathological characteristics of carcinoma of the LUS and the association with Lynch syndrome is required through performance of a large-scale survey.     

Age dependent association of endometrial polyps with increased risk of cancer involvement

Background

Most of gastric adenocarcinoma can be simply diagnosed by microscopic examination of biopsy specimen. Rarely the structural and cellular atypia of tumor cells is too insignificant to discriminate from benign foveolar epithelium.

Case presentation

A 67-year-old male presented with a gastric mass incidentally found on the abdominal computed tomography (CT) for routine medical examination. Gastric endoscopic examination revealed a huge fungating mass at the cardia and mucosal biopsy was performed. Microscopically the biopsy specimen showed proliferation of bland looking foveolar epithelia in the inflammatory background and diagnosed as foveolar epithelial hyperplasia. Because the clinical and endoscopic features of this patient were strongly suggestive of malignancy, the patient underwent radical total gastrectomy. The resected stomach revealed a huge fungating tumor at the cardia. The cut surface of the tumor was whitish gelatinous. Microscopically the tumor was sharply demarcated from surrounding mucosa and composed of very well formed glandular structures without significant cellular atypia, which invaded into the whole layer of the gastric wall. Tumor glands were occasionally complicated or dilated, and glandular lumina were filled with abundant mucin. Immunohistochemically the tumor cells revealed no overexpression of p53 protein but high Ki-67 labeling index. The tumor cells and intraluminal mucin were diffusely expressed MUC1 and MUC5AC and only focally expressed MUC2. On abdominal CT taken after 12 months demonstrated peritoneal carcinomatosis and multiple metastatic foci in the lung.

Conclusion

The clinicopathologic profiles of gastric extremely well differentiated adenocarcinoma of gastric phenotype include cardiac location, fungating gross type, very similar histology to foveolar epithelial hyperplasia, foveolar mucin phenotype, lack of p53 overexpressoin and high proliferative index.