Degree Of Epithelial Atypia Research Articles

Incidence and Diagnosis of Ampullary Carcinoma in Dhulikhel Hospital, Kathmandu University Hospital

Background Endoscopy from a suspected ampulla of vator may establish an early preoperative diagnosis of ampullary carcinoma. However, information regarding the diagnostic accuracy of this procedure is limited and variable.
 Objective To study the preoperative diagnostic accuracy of Endoscopic/ERCP appearance of ampullary tumors with that of endoscopic biopsy.
 Method Among patients who were performed endoscopy during a one year period; a suspicious ampulla of vator was seen in 44 cases. Endoscopic biopsy specimens were classified into four groups based on the degree of epithelial atypia: group 1 (no evidence of malignancy), group 2 (presence of dysplasia), group 3 (suspicious of malignancy) and group 4 (positive for malignancy). In each case comparison was made between the pre-endoscopic biopsy clinical diagnosis and endoscopic appearance.
 Result Endoscopic biopsy diagnosis of malignancy (group 4) were seen in 22 cases, Suspicious of malignancy (group 3) in 3 cases, dysplasia (group 2) in 9 cases and no evidence of malignancy (group 1) in 10 cases. Pre-endoscopic diagnostic accuracy of endoscopy/ ERCP was 50% compared to the diagnosis by biopsy.
 Conclusion Diagnostic accuracy of endoscopy/ERCP was 50% compared to the diagnosis by biopsy. A diagnosis of non malignancy in the forceps biopsy material does not rule out the presence of cancerous foci in ampullary neoplasms.

Appendiceal mucocele: A rare presentation

Mucocele of the appendix is a descriptive term that implies a dilated appendiceal lumen caused by abnormal accumulation of mucus. Mucocele is found in 0.2-0.3% of all appendectomy specimens. The male to female ratio is 1:4 and the average age at the time of diagnosis is over 50 years.Appendiceal mucocele can be histologically divided into three groups, focal or diffuse, mucosal hyperplasia without epithelial atypia, mucinous cystadenoma with some degree of epithelial atypia and mucinous cystadenocarcinoma.We report a case of benign mucocele of the appendix, which presented as persistent vomiting and lower abdominal pain.

Indoleamine 2,3‐dioxygenase expression in early keratocyte neoplasia of the lower lip correlates to the degree of cell atypia

Actinic cheilitis (AC) is an early keratocyte neoplasia with inflammation that occurs in the lip vermillion with the potential to develop into invasive squamous cell carcinoma (SCC). The expression of the intracellular enzyme indoleamine 2,3-dioxygenase (IDO) by antigen-presenting cells and/or tumor cells has been described to arrest T cell proliferation by degrading the essential amino acid tryptophan from the environment. The expression of IDO in AC may support cancer progression by inhibiting T cell-mediated rejection responses. The aim of this study was to identify the cellular nature and extent of IDO expression in early keratocye neoplasia of the lower lip (n=25), and to correlate IDO expression to the severity of epithelial atypia (KIN I°- KIN III°) and to the extent of actinic inflammation. The expression of IDO was analyzed together with expression markers for T-cells (CD3), myeloid DCs (S100, CD11c), macrophages (CD68, CD11c), and Langerhans cells (CD1a) by immunohistochemistry and immunofluorescence analysis. Analyses showed that IDO was expressed in myeloid S100(+) CD11c(+) DCs. The expression of IDO correlated significantly with the degree of epithelial atypia (P=0.0005) but not to the extent of inflammation (P=0.4283). Expression of IDO in early atypic skin epithelial conditions might be a predictor to promote carcinogenesis.

Morphology of collagen fibers and elastic system fibers in actinic cheilitis

Actinic cheilitis (AC) is a premalignant condition intimately related to exposure of the lips to sun rays. The objective of this study was to evaluate the elastic and collagen fibers in the lamina propria of AC. The degree of epithelial atypia was correlated with the quantity of elastic and collagen fibers. Fifty-one cases were investigated. One slide was stained with hematoxylin-eosin for the evaluation of atypia, the second was stained with Weigert's resorcin-fuchsin for the assessment of elastic fibers, and the third slide was stained with Mallory's trichrome for the analysis of collagen fibers. Ordinal logistic regression analysis revealed a significant correlation between the presence of atypia and collagen fibers (P<0.05). It was concluded that there seems to be a reduction in the quantity of collagen fibers in cases of moderate and severe atypia. No correlation was observed between the degradation of elastic system fibers and the grade of dysplasia.

A study of actinic cheilitis treatment by two low-morbidity CO2 laser vaporization one-pass protocols

Therapeutic approaches to chronic actinic cheilitis focus on the removal or destruction of diseased epithelium. The CO(2) laser has become an important therapeutic alternative, achieving clinical resolution in around 90% of patients. Although many laser physical parameters have been reported, some are known for their low potential for scar induction without compromising the success of the results. The aim of this clinicohistological study was to compare the therapeutic responses to two low-morbidity protocols involving a single laser pass. A total of 40 patients with chronic multicentric and microscopically proven disease were randomly submitted to two conservative CO(2) laser protocols using a bilateral comparative model. The degree of histological atypia of the epithelium was determined in 26 patients both pre- and postoperatively for both protocols. Other histological phenomena were assessed in addition to this central analysis parameter. Clinical recurrence occurred in 12.5% of patients for each protocol, together with a significant reduction in the degree of epithelial atypia (p < 0.001), which was occasionally complete. However, no difference was found between the protocols (p > 0.05). Using these morphological parameters it was not possible to determine whether postoperative epithelial atypias in part of the sample were reactive or residual in nature. A few patients may show minor postoperative lesions. Due to their potential to achieve clinical and importantly microscopic resolution, the studied protocols may be used for mild through moderate dysplastic epithelium and clinically diffuse disease.

Actinic cheilitis: histopathology and p53

Chronic actinic cheilitis (AC) is a precursor of squamous cell carcinoma (SCC) of the lip. To evaluate the histopathological characteristics that may help to identify AC more susceptible to carcinomatous transformation, to assess the p53 protein expression in AC, and to determine the value of the p53 expression as a marker of transformation into SCC of the lip. Seventy cases of chronic AC were reviewed, 31 of which were associated with SCCs. The samples were obtained from pathology reports of AC and SCC of the lip. Histopathology and immunohistochemical expression of the p53 protein were evaluated in isolated AC and in AC adjacent to SCC. The intensity of the inflammatory infiltrate in the corium was the only histopathological finding significantly associated both with the presence of an invasive tumor and with the degree of epithelial atypia. Most AC (85%) were immunoreactive to the p53 protein. The p53 protein expression in cheilitis was not statistically associated with any other histopathological criteria. An intense inflammatory infiltrate in AC was predictive of an adjacent invasive SCC. In this study, the p53 protein immunoreactivity was not a marker of malignant transformation.

Intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized cystic neoplasm of the pancreas, histologically classified by the degree of epithelial atypia and by the presence or absence of invasion of the cyst wall. To the authors' knowledge, the cytologic features of this neoplasm are poorly characterized, especially with respect to tumor grade. Thirty-three endoscopic ultrasound (EUS)-guided pancreatic fine-needle aspiration biopsy (FNAB) samples and 1 pancreatic duct brush specimen from 25 patients with a histologically confirmed IPMN were retrospectively reviewed. Blinded to tumor grade, background mucin, inflammation, necrosis, overall cellularity, the presence of gastrointestinal-contaminating epithelium, architecture of cell clusters, and nuclear and cellular morphology were evaluated. In cases in which special stains for mucin were performed, the diagnostic utility of these stains was assessed. These cytologic features were subsequently correlated with the histologic diagnosis. The 34 cytology samples represented 4 adenomas, 15 IPMN-moderate dysplasias, 7 intraductal carcinomas, and 8 IPMNs with invasive carcinoma. Extracellular mucin was present in 97% of all cases; 53% had thick, viscous, "colloid-like" mucin. Special stains for mucin were positive in 6 of 11 cases (54%), helping to identify thin mucin in only 2 cases. Gastrointestinal contamination did not appear to create diagnostic difficulty due to an apparent dual (dysplastic-nondysplastic) epithelial population, but only 4 adenomas were evaluated in this study. Necrosis distinguished IPMN with carcinoma from IPMN-adenomas and IPMN with moderate dysplasia (P < .00001), and was more often observed with invasion than IPMN-carcinoma in situ (P < .05). Tight epithelial cell clusters with hyperchromatic nuclei and a high nuclear to cytoplasmic ratio was more significant in IPMN of at least moderate dysplasia (P = .03). Pale nuclei with parachromatin clearing was found to be a nuclear feature that was suspicious for at least carcinoma in situ (P < .001). In addition, significant background inflammation (neutrophils and histiocytes) was found to be more characteristic of IPMN with at least carcinoma in situ (P = .002). The presence of thick, "colloid-like" mucin is noted in half of the IPMN cases, but was not found to be specific to grade. The absence of such mucin does not exclude an IPMN. The presence of tight epithelial cell clusters is consistent with a neoplasm of at least moderate dysplasia, and abundant background inflammation and parachromatin clearing correlated with the presence of at least carcinoma in situ. Necrosis was the only feature found to be strongly suggestive of invasion.

Salivary Gland Tumors with a Prominent Oncocytic Component

To review aspirates from histologically documented oncocytomas and Warthin's tumor (WT) to highlight the cytomorphologic findings and determine the difficulties encountered in typing oncocytepredominant aspirates. Over a 19-year period (1982-2000) we reviewed aspirates from 45 cases with an oncocyte preponderance. In 24 of them tissue for histologic examination was available (5 oncocytomas and 19 WT). In 4 of the 5 histologically documented oncocytomas the aspirates were cellular, with oncocytic epithelial cells in sheets, papillary fragments and singly. Epithelial atypia was minimal and lymphoid component absent, though scant proteinaceous material with a sprinkling of lymphocytes was seen. In WT moderate (35%) to abundant (28%) oncocytic epithelial cells were seen predominantly in a sheetlike arrangement with occasional papillary fragments and single cells. A variable quantity of lymphoid component was seen in 90% of the aspirates, with 88% of them showing a proteinaceous background accompanied by necrotic debris in 43% of cases. Squamous metaplasia was identified in 30% of cases, with 3 showing atypical squamous cells. In four cases the lymphoid component was scant and oncocytes abundant, and both possibilities were entertained. Fine needle aspiration cytology is fairly accurate in the preoperative diagnosis of WT. When the lymphoid component, mucus and necrotic background are minimal or absent, the tumors can be confused with oncocytoma. In oncocytoma, the oncocytic epithelial cells are more often seen in papillary fragments, acini and singly in comparison to WT, where sheets of oncocytic cells are observed. Some degree of epithelial atypia can be seen in oncocyte-predominant benign lesions. Squamous metaplasia, especially if accompanied by atypia and necrosis, can prove challenging.

Endometrial brush cytology of advanced postmenopausal endometrium: does endometrial intraepithelial neoplasia exist in the absence of hyperplasia?

Postmenopausal uterine bleeding is an indication to sample the endometrium for diagnostic purposes. The endometrial brush cytologies of 20 advanced postmenopausal women collected at the time of hysterectomy in order to benchmark the expected morphology of postmenopausal endometrial brushings were reviewed. No women had symptoms or gross findings of primary endomyometrial disease. Endometrium was collected at the surgical pathology laboratory using the Tao Brush and CytoRich Fixative System. After formalin fixation of the uterus, the entire endometrium was embedded for routine histology. Sixteen endometrial brushings and matched endometrial sections showed endometrial atrophy, one brushing showed many ciliated epithelial cells, and three brushings showed focal (less than 10%) epithelial-cell atypia. In two atypias, abnormal endometrial epithelial-cell sheets contained enlarged, clear nuclei with nuclear notches and grooves resembling papillary thyroid cancer. One case showed no histological counterpart to this finding. The other case showed thickening of the pericornual fundic endometrium with cystic glands. The third case with epithelial atypia showed abnormal endometrial-cell sheets with nuclei resembling atypical hyperplasia or type I endometrial adenocarcinoma; corresponding endometrial tissue sections showed rare, irregular glands and back-to-back gland clusters with equivalent nuclear features. Atypical epithelium may be found in atrophic uteri in the absence of gross endometrial thickening. This may be a common event related either to de novo intraepithelial dysplasia in a noncycling endometrium or to hyperplasia that has partly regressed with estradiol withdrawal. This study shows that, in addition to endometrial intraepithelial carcinoma (EIC), isolated atypical glands with morphological and immunohistochemical features of atypical hyperplasia or type I endometrial adenocarcinoma may be found in grossly normal advanced postmenopausal endometrium of asymptomatic patients. This atypical epithelium is readily apparent in endometrial brush preparations, but requires serial sectioning of the endometrium to be demonstrated histologically. We have not established the natural history of this lesion, and in the absence of EIC or gross endometrial thickening indicative of atypical hyperplasia, we do not know whether this degree of epithelial atypia should be an indication for hysterectomy.

Multiple colorectal neoplasms in a young adult with hypogammaglobulinemia

We report on a 22-year-old man with congenital hypogammaglobulinemia who developed multiple colorectal neoplasms. An immunodeficiency had been diagnosed in the patient since two years of age, and this time many tumors of the sigmoid colon and rectum were detected by barium enema and fiberscopy. Abdominoperineal resection was performed, and the resected specimen revealed 29 polyps, including 9 adenocarcinomas and 20 adenomas. The carcinomas, measuring 0.8 to 11.0 cm in size, showed various depths of invasion, and the adenomas, measuring 0.2 to 1.5 cm in size, showed various degrees of epithelial atypia. DNA analysis demonstrated that the tumors were heterogeneous, showing different DNA index and ploidy patterns. The pathogenetic relation between malignancy and immunodeficiency is also reviewed.

Endoscopic biopsy has limited accuracy in diagnosis of ampullary tumors

Endoscopic biopsy specimens and surgically resected specimens in a collective series of 78 Japanese patients with ampullary tumor were retrospectively reviewed to investigate the clinical implications of endoscopic biopsy. Endoscopic biopsy specimens were classified into five groups based on the degree of epithelial atypia: group 1 (no atypia), group 2 (mild atypia), group 3 (moderate atypia or adenoma), group 4 (severe atypia or carcinoma in situ), and group 5 (invasive carcinoma). Final diagnosis of the 78 resected ampullary tumors was adenoma in five cases, carcinoma in 27 cases, and both adenoma and carcinoma in 46 cases. Biopsy accuracy of carcinoma (group 4 or 5) was 70% (51 of 73) overall in 73 carcinoma cases. Biopsy accuracy was 50% (7 of 14) in the intramural protruding type, 64% (21 of 33) in the exposed protruding type, and 88% (23 of 26) in the ulcerating type. The diagnostic accuracy of adenoma (group 3) was 80% (4 of 5) in five cases of ampullary adenoma. In 18 (25%) of the 73 carcinoma cases, biopsy diagnosis was adenoma (group 3), whereas carcinoma was found in the deeper layers of surgically resected specimens. Biopsy diagnosis of adenoma does not rule out the possibility of deeper carcinoma in ampullary tumors.

Risk Factors for Fibrocystic Breast Disease and Its Histopathologic Components&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

The relationship between various sociodemographic, reproductive, and other factors to the occurrence of fibrocystic breast disease was evaluated in a case-control study undertaken at five Connecticut hospitals from 1979 to 1981. The study groups comprised 590 women with biopsy-proven fibrocystic breast disease and 1,018 women with other surgical conditions. Among the premenopausal women, multivariate analysis suggested that high socioeconomic status, Jewish religion, low parity, a history of benign breast disease, a history of breast cancer in the mother or a sister, and low Quetelet index were associated with increased odds ratios (OR) for fibrocystic breast disease. Similar analysis for the postmenopausal women revealed increased OR for women with high socioeconomic status, a late age at menopause, and a history of benign breast disease. Current smokers as well as those who had had a tubal sterilization had significantly reduced odds of fibrocystic disease. There was no convincing evidence of linear trends according to degree of epithelial atypia for any of the variables considered. Although some variation in the OR emerged in the analysis according to selected histologic components, the results provided little evidence that women with biopsy specimens exhibiting gross cysts, sclerosing adenosis, papillary hyperplasia, or papillomatosis showed epidemiologic similarities with breast cancer patients.

Immunocompetent cells in uterine cervical lesions of human papillomavirus origin.

To elucidate the local immunological reactions operative in the human papillomavirus (HPV)-induced lesions of the uterine cervix, a total of 150 cervical biopsies containing a dysplastic or a neoplastic change with (CO, 97 cases) or without (NCO, 53 cases) a coexistent HPV lesion (a flat, an inverted or a papillomatous condyloma) were subjected to ANAE (acid alpha-naphthyl acetate esterase) staining of the immunocompetent cells; B and T lymphocytes, mononuclear phagocytes (MPS cells). In addition, HPV antigens were demonstrated by an indirect immunoperoxidase-PAP method. Age of the patients did not influence the proportions of B, T and MPS cells. Degree of epithelial atypia was inversely related to proportion of B cells in NCO but not in CO series, and directly related to proportions of T cells in CO series, the latter T cell increase being most probably ascribable to the appearance of suppressor T cells. Unlike in the different types of skin warts (caused by divergent HPV types), the type of the cervical condyloma did not affect the proportions of B, T and MPS cells, suggesting a common HPV type as a causative agent of the latter. MPS and T cells were more numerous in HPV-positive condylomas than in HPV-negative ones, supporting the concept that cell-mediated immune mechanisms recognize the surface antigens of the virus-transformed cells coded by the viral genome in the host cell nuclei (HPV+). The findings are discussed in terms of the immune mechanisms involved in rejection of HPV lesions in general, and those of the uterine cervix especially. The full significance of these mechanisms can only be understood when adequate follow-up data of the lesions are at hand.

Condylomatous epithelial changes in the uterine cervix and their relationship to cervical carcinogenesis.

Two hundred twenty-six (226) women with histologically verified dysplastic or neoplastic epithelial lesions in the uterine cervix were assessed for the presence (CO-series) or absence (N-CO-series) of the three newly established types of condylomatous lesions. Both the CO-series and the N-CO-series comprised 113 patients. Histologic changes fulfilling the previously outlined criteria of the (a) flat, (b) inverted and (c) papillomatous condylomas were found in association with all degrees of epithelial atypia, from mild dysplasia to frankly invasive carcinoma. The flat type was most common, comprising 69% of all condylomas. The inverted and papillomatous types were relatively rare, with frequencies of 18.6% and 12.4%, respectively. The mean age of the patients in the CO-series was 30.9 years, that of the N-CO-series patients was 39.3 years (p less than 0.0001). The causal relationship between the cervical condylomas and cervical carcinoma is discussed. The conclusion is drawn that this possibility needs to be seriously considered when searching for a venereally transmitted agent as an etiologic factor of cervical carcinoma.

Condylomatous Epithelial Changes in the Uterine Cervix and Their Relationship to Cervical Carcinogenesis

Two hundred twenty-six (226) women with histologically verified dysplastic or neoplastic epithelial lesions in the uterine cervix were assessed for the presence (CO-series) or absence (N-CO-series) of the three newly established types of condylomatous lesions. Both the CO-series and the N-CO-series comprised 113 patients. Histologic changes fulfilling the previously outlined criteria of the (a) flat, (b) inverted and (c) papillomatous condylomas were found in association with all degrees of epithelial atypia, from mild dysplasia to frankly invasive carcinoma. The flat type was most common, comprising 69% of all condylomas. The inverted and papillomatous types were relatively rare, with frequencies of 18.6% and 12.4%, respectively. The mean age of the patients in the CO-series was 30.9 years, that of the N-CO-series patients was 39.3 years (p less than 0.0001). The causal relationship between the cervical condylomas and cervical carcinoma is discussed. The conclusion is drawn that this possibility needs to be seriously considered when searching for a venereally transmitted agent as an etiologic factor of cervical carcinoma.

Morphologic survey of the condylomatous lesions in dysplastic and neoplastic epithelium of the uterine cervix.

One hundred eighty-four women with a histologically verified dysplastic or neoplastic lesion in the uterine cervical epithelium were histologically assessed with special reference to the presence of the various histological types of condyloma in these epithelial specimens. Histological changes fulfilling the previously outlined criteria of the flat, inverted, and papillomatous condylomas were encountered in 91 (49.4%) women. Condylomatous lesions were seen in association with all degrees of epithelial atypia from mild dysplasia to frankly invasive cervical carcinoma, which seemed to develop at significantly earlier age when concomitant condylomatous lesion was present than with its absence (p less than 0.001). The serious consideration of the relationship between the condylomatous lesions and the uterine cervical was emphasized.

A, B and H isoantigens in atypical oral epithelium

The red cell adherence (RCA) test was used for demonstration of blood group isoantigens A, B and H in epithelial lesions of the oral cavity. Study of normal squamous epithelium of the oral cavity with immunofluorescence showed the possible association of blood group isoantigens with the intercellular substance and their probable accumulation in spaces between desmosomes. In 31 cases of malignant tumors, a complete absence of isoantigens was found in 27 (87%), and partial loss in 2 (6.5%); in 2 cases of squamous cell carcinoma, the epithelial cells retained the isoantigen (6.5%). The second group of 34 cases included non-neoplastic changes such as leukoplakia, hyperkeratosis, dyskeratosis, pseudoepitheliomatous hyperplasia, or ballooning degeneration. A complete absence of isoantigens was found in 16 cases (47%), patchy distribution in 9 cases (26.5%); the remaining 9 cases (26.5%) retained the antigens. No correlation was found between the type and degree of epithelial atypia in non-neoplastic lesions and the absence of blood group substances. The loss of isoantigens A, B and H in neoplastic, pre-neoplastic, or even some regenerative or degenerative epithelial lesions suggests an aberration in their synthesis under abnormal conditions.

Experimental cervical dysplasia in the rhesus monkey: Estrogen as a cofactor with methylcholanthrene

A 1 per cent suspension of methylcholanthrene in mineral oil was applied topically to the uterine cervix of 16 mature rhesus monkeys. Eight of the 16 animals were allowed to menstruate physiologically and 8 received 20 mcg. of estradiol benzoate parenterally. Differences between the two groups involved both the thickness of the squamous epithelium and the degree of epithelial atypia. Among the estrogen-treated animals the squamous epithelium was hyperplastic and epithelial pegs were found deeper in the stroma by comparison with the non-estrogen-treated controls. The most striking difference between the two groups was in the degree of epithelial atypia. Among the 8 non-estrogen-treated animals there was only mild cellular atypia. Among the 8 estrogen-treated animals 4 exhibited advanced epithelial dysplasia.