Dysplastic Cases Research Articles

Conventional Pap smear and liquid based cytology for cervical cancer screening - a comparative study

The study was undertaken to evaluate liquid based cytology (Pap spin) and to compare the sensitivity of Pap spin with conventional Pap smear. Pap smears were taken from 160 patients with gynaecologic complaints with Ayre's spatula and endocervical cytobrush and slides prepared. The residual material on both the spatula and cytobrush were rinsed in Pap spin collection fluid and centrifuged. Direct smears were prepared from the cell button, fixed and stained by Papanicolaou stain. Colposcopy was performed in patients with abnormal smears and biopsy was performed in suspected malignant or dysplastic cases. LSIL and HSIL was diagnosed in 27 (64.4%) cases, mostly between 21-40 years, Commonest presenting complaint was discharge per vaginum seen in 68 (42.5%) cases. Cytological abnormality was found in 42 cases (26.2%) by Pap spin method, whereas conventional Pap smear detected abnormality in only 24 cases (15%). 133 cases (83.1%) were satisfactory for evaluation on Pap spin and 51 cases (31.9%) on conventional Pap smear. The commonest atypical finding on colposcopy was acetowhite area in 14 cases (31.1%). Sensitivity of Pap spin and conventional Pap smear was 97.6% and 53.7% respectively and specificity was 50% in each. Pap spin is strongly advocated in the best interest of public health as it improves the sample quality and reduces the likelihood of false negative results.

Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions.

The matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes, which are responsible for the breakdown of the extracellular matrix components in pathological and physiological conditions. They are involved in basement membrane disruption, stroma and blood vessel penetration, metastasis and more recently there is evidence that they participate in tumor growth and angiogenic events. Matrix metalloproteinase 2 and 9 (MMP 2 and 9) belong to the gelatinases, a subgroup of MMPs, and have the capacity to degrade the triple helix type IV collagen of basal lamina of the basement membrane. With the present study, we tried to demonstrate the expression of MMP-9 immunohistochemically, comparatively in benign, premalignant and malignant lesions of the larynx. We studied 154 laryngeal lesions including 55 squamous cell carcinomas, 8 in situ carcinomas, 54 cases of dysplasia (of low and intermediate grade), 13 papillomas and 24 cases of keratosis. Overexpression of MMP 9 was observed in 74.4% and 50% in invasive and in situ squamous cell carcinomas respectively. In dysplastic cases, in papillomas and in keratoses the percentage of overexpression was 62.9%, 61.53% and 54.16% respectively and the expression of MMP-9 was significantly higher in invasive squamous cell carcinomas compared to dysplasias (p=0.000004). Also significantly higher was the expression of MMP-9 in dysplastic cases compared to papillomas (p=0.023). The MMP-9 expression was related neither to survival nor to the other available clinicopathological parameters (tumor size, grade, clinical stage, lymph node status and patient age). In conclusion, our study indicates that the expression of MMP-9 is up-regulated in a stepwise fashion, with two main steps, the first one, when a dysplastic lesion evolves and the next one, when the dysplasia progresses to invasive carcinoma.

Spontaneously Stabilized Severe Dysplastic Spondylolisthesis without Operation

Surgical management is the accepted treatment choice for grade III or IV spondylolisthesis, and many satisfactory clinical and radiologic follow-up results have been reported. Very little, however, has been written about long-term results in preteenage patients in whom dysplastic spondylolisthesis has been treated nonoperatively, especially in those who have > or =50% displacement of the fifth lumbar vertebra on the sacrum. We report an unusual case of spontaneous stabilization of severe dysplastic spondylolisthesis in an 8-year-old girl who presented with grade III spondylolisthesis of L5-S1 and was followed up for >14 years in the absence of surgical intervention. On presentation, she complained of a restriction in forward bending and tightness of hamstrings, but she was undisturbed in her daily activities. Initial radiographs showed severe dysplastic spondylolisthesis; however, magnetic resonance imaging (MRI) performed at age 9 years showed that the amount of listhesis was much less than that seen in the initial radiograph. Routine radiographic follow-ups were chosen over early operative measures until she became a teenager. There was no change in the slip, and unusually a gradual ossification of the cartilaginous promontory of the S1 and the posterior lip of the L5 was observed. At 22 years old, the patient is asymptomatic and not conscious of her cosmetic appearance. Surgical treatment has generally been indicated for patients with grade III or IV spondylolisthesis, because slippage progression has been noted in most reported cases. However, MRI may be a tool for predicting which dysplastic spondylolisthesis cases are more likely to progress and therefore circumvent surgical intervention, while maintaining an excellent outcome.

The Classic: Revision of Aseptic Loose Total Hip Arthroplasties

The Classic: Revision of Aseptic Loose Total Hip Arthroplasties

A FAMILY STUDY AND THE NATURAL HISTORY OF PRENATALLY DETECTED UNILATERAL MULTICYSTIC DYSPLASTIC KIDNEY

We document the inheritance pattern of multicystic dysplastic kidney in 3 affected families and screen first-degree relatives of a cohort of children with prenatally detected multicystic dysplastic kidney for renal anomalies. The study also afforded an opportunity to document the natural history of prenatally detected multicystic dysplastic kidney. We identified 3 families during clinical treatment of children with prenatally detected multicystic dysplastic kidneys. Other members of these families were evaluated with renal ultrasonography. For the family screening study index cases were identified from a fetal uropathy database. A total of 94 first-degree relatives (52 parents, 35 full siblings and 7 half siblings) of 29 children with prenatally detected multicystic dysplastic kidneys were studied with urinary tract ultrasonography, blood pressure measurement, urinalysis and plasma biochemistry. Two families had affected sibling pairs, 1 of which also had a half sibling with vesicoureteral reflux. The third family included 3 individuals with multicystic dysplastic kidney and 1 with renal agenesis thought to have resulted from involution of multicystic dysplastic kidney. This family is consistent with autosomal dominant inheritance with variable expressivity and reduced penetrance. In the screening study ultrasonography did not demonstrate significant renal anomalies in any of the 94 first-degree relatives of the multicystic dysplastic kidney index cases. Followup assessment of prenatally detected multicystic dysplastic kidneys in index cases demonstrated total involution in 52% at a median age of 6.5 years with no multicystic dysplastic kidney related morbidity. Multicystic dysplastic kidney can be familial but is most commonly a sporadic anomaly. Formal screening of relatives is not recommended. Followup data on a cohort of children with prenatally detected multicystic dysplastic kidney add further support to conservative management.

Comparison of BrdU and cyclin A as markers of the S-phase in oral precancerous lesions.

A study comparing bromodeoxyuridine (BrdU) and cyclin A as markers of cells in the S-phase in oral precancerous lesions was performed. These were also compared with the growth fraction (GF) as assessed by Ki-67. Biopsies of 15 lesions were obtained, presenting clinically as leukoplakia or erythroplakia of the lateral tongue or floor of mouth. Half of each biopsy was incubated in BrdU and routinely fixed and processed. Sequential sections from each block were cut and stained immunohistochemically with antibodies against the following proteins: BrdU, Ki-67 and cyclin A. Stained sections were quantified and the labelling indices (LI) expressed per 100 of the total nucleated cell population (%) and per millimetre basement length (/mm). The mean LI% for BrdU was 11.24% (SD 2.83), for cyclin A it was 12.76% (SD 3.88) and the GF% was 29.25% (SD 11.88). The mean LI/mm for BrdU was 40.93/mm (SD 11.88), for cyclin A it was 47.59/mm (SD 18.28) and the GF/mm was 110.72/mm (SD 49.30). The BrdU and cyclin A indices were significantly correlated with each other. In the more dysplastic cases, the cyclin A LI was quantitatively much larger than that for BrdU, suggesting that the protein was being overexpressed. It was concluded that as a tool to study the kinetic aspects of the cell cycle in dysplastic lesions cyclin A was limited by the fact that it is overexpressed. In minimally dysplastic lesions and normal epithelia, however, cyclin A may be a viable alternative to BrdU for the study of the S-phase.

The differentiation of true adenomas from colitis-associated dysplasia in ulcerative colitis: A comparative immunohistochemical study

Adenomas in areas involved by ulcerative colitis (UCA) are difficult to identify because of their morphological similarity to ulcerative colitis-associated dysplasia (UCD) and have an uncertain biology. Recently, a set of morphopathologic criteria were published for the diagnosis of UCA versus UCD. As a first step to analyze these criteria, we studied p53 and bcl-2 expression in groups of UCA and UCD along with a sporadic adenoma control group. Ninety lesions from UC areas (62 patients) were examined, including 24 UCA without high-grade dysplasia (HGD) and 66 UCD consisting of 43 polypoid and 23 flat dysplastic lesions (29 with HGD). Immunohistochemical p53 and bcl-2 expression were evaluated semiquantitatively, P53-positive cases were significantly less frequent in the UCA (4%) versus the UCD group (30%, P = .01) and the polypoid UCD subgroup (35%, P = .005). Moderate or strong bcl-2 expression was significantly more frequent in the UCA than in the UCD group (96% v 70%, P = .01) and in the UCA versus both polypoid and flat UCD subgroups. Comparison of UCA with low-grade dysplastic polypoid UCD cases alone showed a difference just below significance for p53 ( P = .07). p53 and bcl-2 expression rates were very similar in the UCA group and the sporadic adenoma ( n = 25) control group. These results show that UCA has phenotypic features more similar to sporadic adenomas than UCD and supports the concept that adenomas in UC have a biology different from UC-associated dysplasia.

Overexpression of human telomerase RNA is an early event in oesophageal carcinogenesis.

Telomerase, the ribonucleoprotein enzyme that elongates telomeres, is repressed in normal human somatic cells but is reactivated during tumour progression. The purpose of this study was to investigate the localization of human telomerase RNA (hTR) expression in human oesophageal dysplasia and cancer by using in situ mRNA hybridization (ISH) with avidin-biotin staining. Ki-67 immunoreactivity was also examined. We analysed 51 squamous cell carcinomas, 9 dysplasias and 60 normal mucosae. The integrity of the mRNA in each sample was verified by using a poly d(T)20 probe. Seventy-six samples (63%) showed no mRNA degradation; these included 30 carcinomas, 7 dysplasias and 39 normal mucosae. At the single-cell level, high levels of hTR expression were found in the cytoplasm and especially in the nucleus. Most (>90%) cancer cells demonstrated high levels of hTR expression in 29 (97%) of the 30 tumours. Most dysplastic cells also showed high levels of hTR in all 7 dysplastic cases. In all 39 normal mucosae, most basal cells indicated high levels of hTR expression, which were also seen in infiltrating lymphocytes. The distribution of hTR-expressing cells was similar to that of Ki-67-positive cells. These data suggest that overexpression of hTR may be correlated with the proliferative activity that defined by Ki-67 immunoreactivity and is an early event in carcinogenesis of the oesophagus.

Sucrase-Isomaltase Expression in Dysplasia Associated With Barrett's Esophagus and Chronic Gastritis

Aberrant cytoplasmic sucrase-isomaltase has been detected in colonic neoplasia, including dysplasia in ulcerative colitis. We investigated expression by immunostaining in 28 cases of Barrett's esophagus and 67 cases of chronic gastritis. Staining location (membrane or cytoplasmic) and percent positivity (< 1% = 0; 1-50% = 1+; > 50% = 2+) were record ed. Fifteen cases with Barrett's esophagus were negative for dysplasia, 1 was indefinite, and 12 were positive. All demonstrated surface membrane staining, while 2 of the 15 neg ative (1+) cases, 0 of the 1 indefinite case, and 11 of the 12 dysplastic (2+ in 7) cases revealed cytoplasmic positivity (P < .001). In chronic gastritis (23 were negative, 5 were indefinite, and 39 were positive) all revealed surface membrane staining, whereas cyto plasmic positivity was present in 1 of 23 negative (1+) cases, 1 of 5 indefinite cases, and 37 of 39 dysplastic (2+ in 18) cases (P < .001). In Barrett's esophagus and chronic gastri tis, cytoplasmic sucrase-isomaltase expression strongly correlates with the presence of dys plasia. Int J Surg Pathol 2(4).-281-286, 1995

Histological and immunochemical studies of oral leukoplakia: Phenotype and distribution of immunocompetent cells.

The phenotype and distribution of immunocompetent cells in oral leukoplakia with different levels of dysplasia were analyzed. Cells were identified in two compartments of the oral mucosa, the epithelium and subepithelial connective tissue. One hundred cases of neutral-buffered formalin-fixed paraffin embedded biopsy materials including 10 cases of acetone-fixed frozen tissue sections were studied immunohistochemically.In the main lymphoid population of each groups, the T lymphocytes predominated over the B lymphocytes. The lymphoid cells were present either as diffuse aggregates or organized in follicular patterns with or without germinal center-like structures. When present, B lymphocytes were seen to constitute the above mentioned structures. T lymphocytes made up the paracortical areas. A decrease in CD4/CD8 ratio was observed in cases with severe dysplasia. Specimens classified as mild to severe dysplasia presented a significant increase in the number of CD1a (+) dendritic Langerhans cells when compared with those of epithelial hyperplasia. A significant increase in macrophage count was also obtained in the subepithelial connective tissue of all dysplastic cases. A significant increase of CD57 (+) natural killer/killer cells in the subepithelial connective tissue and HLA-DR expression by the keratinocytes was observed in cases with severe dysplasia.Correlation and analysis of the results revealed an immunocellular reaction that varied according to the degree of dysplasia in oral leukoplakia. Immunologic events, i.e. decreased CD4/CD8 ratio, increased density of natural killer/killer cells and HLA-DR expression by keratinocytes, occurring simultaneously in severe dysplasia are speculated to be indicative of early malignant transformation.

Sunlight and dysplastic nevus risk. Results of a clinic-based case-control study

The dysplastic nevus (DN) is the most important risk factor and precursor for malignant melanoma. The authors compared the responses of 132 consecutive cases of DN, 186 consecutive cases of cutaneous melanoma, and 239 controls attending the same subspecialty clinic to questions regarding sun sensitivity, sun exposure, and other possible risk factors. Dysplastic nevus cases were younger than controls and were of a higher social class, as indicated by more years of formal education. Sun sensitivity (assessed by reported depth of tan after multiple exposures) was associated with both DN risk and melanoma risk after controlling for age and education in logistic regression analysis (P = 0.009 and 0.03, respectively), but for DN risk this association was nonlinear: the relative risks (versus deep tan) were 2.3 for average tanners, 2.8 for light tanners, and 1.6 for those who reported practically no tan. Sun exposure measures were not associated with DN risk after controlling for age and education, whether or not depth of tan was controlled in the analysis. These observations suggest a role for either sunlight or a trait linked with sun sensitivity in the development of dysplastic nevi.