Biomedical subjects
Publications and source records attributed to N J Carr.
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We reviewed 84 cases coded as mesenteric lipodystrophy (ML), mesenteric panniculitis (MP), or retractile mesenteritis and sclerosing mesenteritis (SM), grading fibrosis, inflammation, and fat necrosis, and evaluating clinical subgroups. There was no gender or racial predominance. Patient age range was 23-87 years (average 60). Patients most often presented with abdominal pain or a palpable mass. A history of trauma or surgery was present in four of 84 patients. The most common site of involvement was the small bowel mesentery as a single mass (58 of 84) with an average size of 10 cm, multiple masses (15 of 84), or diffuse mesenteric thickening (11 of 84). All patients had some degree of fibrosis, chronic inflammation, and fat necrosis. Although a few patients showed a sufficient prominence of fibrosis, inflammation, or fat necrosis to permit a separation into SM, MP, or ML, respectively, in most patients these three components were too mixed for a clear separation. The clinical, demographic, and gross features did not help in defining these three entities. Contributors diagnosed 12 as sarcoma. Of 39 patients followed beyond the postoperative period, none died of these lesions. We conclude that SM, MP, and ML appear to represent histologic variants of one clinical entity, and in most cases "sclerosing mesenteritis" is the most appropriate diagnostic term.
AIM: To determine the effect of dilute hydrochloric acid on the in situ end labelling (ISEL) reaction, with and without a variety of different proteolytic enzymes. METHODS: Sections of tissue fixed in buffered formalin were pretreated with trypsin, protease XIV (at two different concentrations), or protease XXIV (for two different incubation times), with and without subsequent 1 M hydrochloric acid treatment. The results were compared with those obtained using hydrochloric acid alone, with proteinase K, and pepsin pretreatment, and with no pretreatment. RESULTS: When hydrochloric acid was added to the sections in addition to trypsin, protease XIV, and protease XXIV, there was a significant increase in ISEL reactivity in both apoptotic nuclei and morphologically normal nuclei. Hydrochloric acid alone had no significant effect. CONCLUSIONS: Hydrochloric acid has a distinctive effect on the ISEL reaction that is dependent on prior proteolytic digestion.
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Flow cytometric DNA ploidy analysis has been reported to be more objective and sensitive than morphologic evaluation as a surveillance method in patients with Barrett esophagus (BE) for the development and progression of precancerous lesions. Such analyses are typically performed using fresh samples that require a separate or "jumbo" biopsy, are prone to false DNA aneuploidy if not promptly processed, and do not allow for retrospective studies. The feasibility of performing flow cytometric DNA analysis on paraffin-embedded biopsies was studied to circumvent some of these problems using 12 squamous esophageal mucosa with inflammation and 58 BE cases showing varying degrees of dysplasia. Among the BE cases, 12 had no dysplasia, 20 were indefinite for dysplasia, 14 had low grade dysplasia, and 12 had high grade dysplasia. Satisfactory histograms were obtained in 86% of the analyzed samples. Among cases with adequate histograms, DNA aneuploidy was identified in 77% with high grade dysplasia, 16% with low grade dysplasia, 23% of indefinite for dysplasia, and 0% without dysplasia. One of the esophagitis samples was also DNA aneuploid. Correlation of DNA aneuploidy and degree of dysplasia is highly significant (P = .001). The authors have demonstrated that routinely processed paraffin-embedded biopsies can be used for flow cytometric ploidy analysis. DNA aneuploidy was highly correlated with degree of dysplasia and serves as a quantitative prognostic indicator for prospective as well as retrospective studies of the evolution of BE to carcinoma.
This report covers hyperplastic and neoplastic lesions of the human vermiform appendix that, although unusual, are likely to be encountered by general surgical pathologists. Topics include epithelial neoplasms, hyperplastic polyps, diffuse epithelial hyperplasia, pseudomyxoma peritonei, goblet cell and tubular carcinoid tumors, neuroma, and neurogenous hyperplasia. We discuss recent advances in the prognosis and management of appendiceal carcinoma, current controversies regarding the relationship between ovarian and appendiceal epithelial neoplasms, the concept of the mucinous tumor of uncertain malignant potential (UMP), and practical aspects of reporting pseudomyxoma peritonei. Classical carcinoid tumors are beyond the scope of this article, and primary neoplasms that are so rare they occur in the literature only as isolated case reports are not covered.
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BACKGROUND: The current understanding of appendiceal epithelial tumors is based on series composed of relatively small numbers of patients and on case reports. The aim of this study was to perform clinicopathologic correlation, particularly concerning prognosis, on a relatively large series of patients with epithelial tumors and tumor-like lesions of the human vermiform appendix. METHODS: One hundred eighty-four cases of simple mucoceles, hyperplastic polyps, adenomas, carcinomas, and mucinous tumors of uncertain malignant potential (UMP) were reviewed. Retrospective follow-up data were obtained in carcinoma and UMP tumor cases. RESULTS: Most neoplasms were of the mucinous type characteristic of the appendix, but a small fraction were nonmucinous and resembled neoplasms typical of the spectrum encountered in the colorectum. Both benign and malignant conditions in some cases showed acellular mucin dissecting the appendiceal wall and mucin outside the appendix. Immunostains were sometimes helpful in identifying epithelial cells within mucus, but hematoxylin and eosin and mucin stains were adequate in most cases. Two factors were significantly associated with survival by multivariate analysis: the presence of mucin outside the right lower quadrant of the abdomen and the presence of epithelial cells in the peritoneal cavity outside the appendix. CONCLUSIONS: The distribution of mucin within the abdomen and the presence of cells outside the visceral peritoneum of the appendix are important prognostic factors that should be recorded in these neoplasms. Tumors designated as UMP lesions behave in a benign or low grade fashion.
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We report a series of 13 lesions of the human vermiform appendix in which a carcinoid component was associated with a separate non-carcinoid epithelial component that included an adenoma-like lesion of the mucosal epithelium. We use the term dual carcinoid/epithelial neoplasia to describe this phenomenon. The carcinoid component was insular/trabecular in nine cases, tubular in one case and of goblet cell type in three. The epithelial component was a mucinous cystadenoma in four, a mucinous tumour of uncertain malignant potential in three, and a mucinous cystadenocarcinoma in six. No intermediate cell population was seen and in three cases the carcinoid and epithelial components were in different parts of the appendix, leading us to suggest that these lesions may be true 'collision' tumours in which two neoplasms have arisen in the same organ. The prognosis appears to be no worse than for either of the components alone, but conclusions regarding these lesions must be guarded on account of their rarity and the small numbers available for study.
AIMS: To compare proliferating cell nuclear antigen (PCNA) immunoexpression in hyperplastic polyps, adenomas, and inflammatory cloacogenic polyps of the human colon and rectum using paraffin wax embedded tissue. METHODS: The monoclonal antibody PC10 was used to demonstrate PCNA immunoreactivity in 88 polypoid lesions from 68 patients. Cases in which immunoexpression was completely absent were excluded, leaving 32 hyperplastic polyps, 31 adenomas, and seven inflammatory cloacogenic polyps for analysis. Labelling indices for the upper and lower third of each lesion and for adjacent normal mucosa were calculated. RESULTS: The upper third labelling indices for adenomas were substantially higher than those for hyperplastic polyps or normal mucosa, whereas those for the upper thirds of hyperplastic polyps and normal mucosa did not differ greatly. The differences between the lower third samples were not significant. In 16 (50%) hyperplastic polyps positive cells persisted onto the luminal surface. Some adenomas showed the most intense staining and the highest labelling indices in the upper third, with strong staining of surface cells; this pattern was not seen in the other lesions. The inflammatory cloacogenic polyps did not show a consistent pattern of immunoexpression. CONCLUSIONS: Differences in cell kinetics between adenomas, hyperplastic polyps, and normal mucosa may be shown in formalin fixed, paraffin wax embedded tissue using PC10 as a marker of proliferative activity. PCNA expression also persists into the upper portions of hyperplastic polyps. Assuming that hyperplastic polyps are hypermature lesions with a slower rate of cell migration, this finding suggests that there may be an alteration in PCNA protein metabolism.
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OBJECTIVE: The purposes of this study were to determine the frequency and characteristics of calcification and fibrosis in mesenteric carcinoid tumor as seen on CT scans and to evaluate their possible role in diagnosis. MATERIALS AND METHODS: The CT findings in 29 cases of proved mesenteric carcinoid tumor were analyzed retrospectively. Tumors were assessed for size, margin, density, radiating strands, calcification, and associated thickening of the small-bowel wall. Matching histologic sections were available for 21 of the cases. They were reviewed independently for histologic pattern, degree of fibrosis, degree of infiltration along neurovascular bundles, necrosis, lymph node architecture, and calcification or ossification within the mass. CT and pathologic findings were then assessed for possible relationships. RESULTS: Calcification was detected by CT in 70% (21 of 30) of mesenteric masses. Three patterns of calcification were noted: small, stippled calcification (n = 11); coarse, dense calcification (n = 7); and diffuse calcification (n = 3). All calcification was localized within areas of poorly cellular mature fibrous tissue. The degree of radiating strands detected by CT tended to increase with the degree of fibrosis seen histopathologically (p = .06). CONCLUSION: Calcification in mesenteric carcinoid tumors was observed by CT in most cases of this series. The triad of a calcified mesenteric mass, radiating strands, and adjacent bowel-wall thickening should be considered highly suggestive of carcinoid tumor.
OBJECTIVE: To compare an alternative treatment for lower extremity burns with the standard in-hospital treatment, in an attempt to shorten hospital stay. DESIGN: A case-control series. SETTING: A university-affiliated hospital. PATIENTS: All patients with a burn isolated to a lower extremity were treated over an 8-month period with split-thickness skin grafting (STSG), Unna paste dressing, immediate mobilization and early discharge. This group was compared with matched controls from the preceding 8 years treated with STSG, occlusive burn gauze dressing, bed rest and hospitalization. MAIN OUTCOME MEASURES: Duration of hospital stay and graft viability. RESULTS: Thirteen patients with an average wound size of 131 cm2 were treated with Unna paste and had a graft viability of greater than 95% and a burn-scar rating equivalent to that of patients treated with the earlier regimen. The duration of hospital stay decreased from a mean of 12.9 days to 1.4 days, with no complications. This translated into a saving of $10,350 per patient. CONCLUSIONS: This alternative treatment is safe, inexpensive and effective and is recommended as the treatment of choice for uncomplicated, noncircumferential lower extremity burns.
OBJECTIVES: The detection of aneuploidy in colonic mucosa by flow cytometric DNA analysis has been advocated as an indicator of high risk for ulcerative colitis (UC) patients developing colon carcinoma. To date, studies have primarily utilized fresh tissue and have had two limitations: a significant number of possible false-positive findings (aneuploidy in the absence of detectable dysplasia) that may be due to DNA degradation, and the inherent inability to perform retrospective studies. The latter has compromised the adequate assessment of flow cytometric DNA analysis for its clinical utility in UC patients. Our objective was to attempt to overcome the limitations that have been present in DNA analysis by flow cytometry. METHODS: After having established, in our laboratory, an optimal method that allowed reliable DNA analysis on paraffin-embedded mucosal biopsy specimens, we conducted three separate studies to address the above problems associated with DNA analysis with fresh colonic samples: 1) comparison of DNA analysis between fresh and paraffin-embedded colonic mucosal samples from UC patients without dysplasia, 2) correlation between morphology and DNA ploidy on paraffin-embedded tissues showing no dysplasia and various degrees of dysplasia, and 3) sequential analysis of fresh, normal colonic mucosal samples to further evaluate possible causes of false aneuploidy. RESULTS: We observed 1) that there is discordance in DNA ploidy between paraffin-embedded and fresh samples showing no dysplasia in that aneuploidy was found in 33/46 (72%) of fresh samples, whereas 3/40 (7.5%) were aneuploid by biopsies from the corresponding anatomic sites. 2) There is excellent correlation between dysplasia and DNA ploidy results with paraffin-embedded tissue, i.e., none of 16 samples negative for dysplasia, none of seven samples indefinite for dysplasia, and seven of eight samples positive for dysplasia were aneuploid. 3) DNA degradation produced a spurious, near-diploid aneuploid peak in a normal colonic mucosal sample when it was left in saline more than 1 hr before analysis. CONCLUSIONS: The above-described results demonstrate that performing flow cytometric DNA analysis with formalin-fixed paraffin-embedded biopsy samples is feasible and that this technique may provide more reliable ploidy results than does the use of fresh samples, when rapid refrigeration and/or freezing of the fresh samples cannot be accomplished consistently, and will permit retrospective DNA ploidy studies assessing risk of cancer in UC patients.
This study assessed squamous cell papillomas of the human esophagus for the presence of human papillomavirus (HPV) and correlated the results with histological features. Twenty-three lesions obtained by endoscopic biopsy from 17 patients were studied, first by in situ hybridization (ISH) for HPV types 6-11, 16-18, 18, and 31-33-51, and second by the polymerase chain reaction (PCR) with amplification of multiple HPV types and demonstration of amplified product by ethidium bromide staining and Southern blot hybridization for HPV types 6-11, 16, and 18 in each case. Evidence of HPV DNA was found in only one lesion, which showed HPV type 6-11 by ISH and HPV positivity by Southern blotting of the amplified product after the PCR. This case exhibited histological features suggestive of HPV infection, although no morphological changes specific to the lesion were identified. The remaining 22 lesions, including those from cases in which multiple papillomas were present, were negative for HPV. The results show that HPV DNA is frequently not detectable in esophageal squamous cell papillomas, even when highly sensitive techniques are used. These findings are consistent with the hypothesis that other pathogenetic mechanisms, such as mucosal injury and repair, are important in the etiology of these lesions.
The aim of this study was to explore whether CD34 immunoreactivity can distinguish between different types of gastrointestinal stromal tumour, i.e. smooth muscle and neurogenic. We studied 87 stromal tumours from different sites in the gastrointestinal tract, as well as the omentum and mesentery, using a monoclonal antibody to CD34 (QBEND10). We also determined the immunoexpression of smooth muscle and muscle specific actins, S-100 protein, cytokeratin, desmin and vimentin. In addition, 15 cases of mesenteric fibromatosis were tested for CD34. Immunoexpression of CD34 was observed in 40 of the 87 stromal tumours and correlated with evidence of differentiation towards a smooth muscle phenotype. Large intestinal stromal tumours were less likely than gastric lesions to be CD34 positive. None of 15 cases of mesenteric fibromatosis was positive for CD34. We conclude that CD34 immunoexpression is seen in a proportion of stromal tumors of the gastrointestinal tract, mesentery and omentum, particularly those of smooth muscle type, and it may be useful as part of an immunohistochemical panel in the differential diagnosis of these neoplasms.
OBJECTIVES: The aim of this study was to correlate clinical and pathologic features of squamous cell papillomas of the human esophagus and investigate their pathogenesis and malignant potential. METHODS: Clinical and pathologic data on 25 patients were studied. RESULTS: All patients in whom the race was known were white, and the majority of lesions occurred in the distal esophagus. There were multiple lesions in five cases. Many cases showed endoscopic evidence of hiatus hernia, gastroesophageal reflux, or esophagitis. No examples of Barrett esophagus were found. No esophageal malignancies occurred, and no dysplasia was seen histologically. Evidence of recurrence was found in only two patients, but several synchronous or metachronous carcinomas of the oro-respiratory tract occurred. CONCLUSIONS: Although our findings do not exclude a viral etiology, they suggest a role for mucosal injury and regeneration in the pathogenesis of these lesions. The association with other malignancies may be significant.