Intestinal spirochetosis: clinicopathological features with review of the literature.

OBJECTIVE: The purpose of this study is to evaluate the clinical presentation of patients with intestinal spirochetosis, as it is has not been well described in the literature. METHODS: We studied 15 patients with colonic biopsies that showed spirochetosis. The study group consisted of 11 males and 4 females, 10 of the males were heterosexual and one was homosexual. None of these patients were clinically immunocompromized. A colonoscopy was performed for evaluation of different symptoms. The histological diagnosis of spirochetosis was made on H&E examination and confirmed by Giemsa and/or Steiner stain. There was no evidence of associated active or any specific colitis in any of the cases. The control group consisted of 30 patients, 16 males and 14 females that were matched for age and clinical indications for obtaining a colonic biopsy. RESULTS: Colonic mucosa with prominent brush border-like surface colonized with large amounts of spirochetes was noted in all 15 cases in the study group and in none of 30 cases in the control group. The clinical presentation in patients with spirochetosis was compared to the control group. Of the spirochetosis patients 86% presented with some form of clinical symptoms compared with 13% of controls. These symptoms included chronic watery diarrhoea in 40% spirochetosis patients vs 5% in controls; a change in bowel habit was present in 33% of spirochetosis patients vs 3.3% in controls. The endoscopic appearance in spirochetosis patients was reported as normal in six patients, 'polyoid' in seven patients, erythematous in one patient and 'lesion' in one patient. CONCLUSION: These findings suggest that colonic spirochetosis affects a heterogenous group of patients, the majority of whom presented with gastrointestinal symptoms. The variable clinical findings may be related to the infecting organism and the condition may not be harmless in all patients.

Expression of survivin, YB-1, and KI-67 in sporadic adenomas and dysplasia-associated lesions or masses in ulcerative colitis.

Sporadic adenomas are said to exhibit an orderly growth pattern with a reversal of proliferative and apoptotic cell distribution as compared with normal colonic crypts. Dysplastic polyps of patients with ulcerative colitis (UC) may represent dysplasia-associated lesions or masses (DALM) with a high associated cancer risk, or, alternatively, may represent sporadic adenomas. Histologic criteria to differentiate between sporadic adenomas and DALM have not focused on the balance between cell renewal and cell loss. The expression of the novel anti-apoptosis gene product, survivin, and the proliferation markers, Ki-67 and Y-box binding protein (YB-1), were investigated by immunohistochemical localization in sporadic adenomas and DALM lesions of patients with UC. In adenomas, KI-67 was expressed preponderantly at the luminal aspect of the polyp, whereas its expression was diffuse in DALM. Survivin was detected diffusely in both adenomas and DALM. YB-1 showed positive staining in the deep aspect of adenomatous glands but only to a minor degree at the surface, whereas both deep and diffuse expression patterns of YB-1 were seen in DALM. The authors conclude that DALM and sporadic adenomas exhibit different patterns of cellular proliferation and that molecular markers of cell proliferation, Ki-67 and YB-1, may be useful to distinguish sporadic adenomas from DALM. However, the similar expression of survivin suggests that the underlying mechanisms that regulate apoptotic cell death are uniform in these lesions.

Glut-1 expression in dysplastic and regenerative lesions of the colon.

Monosaccaride transporter proteins are responsible for transmembrane transport of monosaccarides into cells. Glucose transporter protein 1 (Glut-1) is most prevalent in the cell membranes of erythrocytes and facilitates transport of glucose in tissues with barrier functions, i.e. blood brain barrier. Expression of Glut-1 in malignant tumors is increased due to increased metabolic need of the proliferating cell populations. In colorectal adenomas and carcinomas, membranous expression of Glut-1 has been associated with higher grade of tumors and decreased survival time. We studied the expression of Glut-1 in dysplastic proliferations of the colon which included sporadic adenomas and dysplasia associated lesions (DALM) in patients with ulcerative colitis and reactive/regenerative proliferations of the colon, including non-dysplastic chronic colitis, acute colitis and ischemia. Two patterns of Glut-1 expression were detected. Most adenomas and DALMs showed at least focal membranous expression of Glut-1. In addition a second staining pattern was recognized which consisted of prominent supranuclear dots. This pattern of staining was not only seen in adenomas and DALM but also in non-dysplastic areas immediately surrounding sporadic adenomas, in regenerative chronic colitis and in areas surrounding acute inflammation. Areas away from dysplasia did not show any positive staining for Glut-1. We conclude that two distinct patterns of Glut-1 expression may be found in colonic epithelial proliferation: membranous staining, associated with dysplasia, and, heretofore not described, supranuclear staining which may be related to Glut-1 expression secondary to expression of specific growth factors and not necessarily related to dysplasia.

Polypoid dysplasias in ulcerative colitis and sporadic adenomas: genetic approach to the differential diagnosis (review).

Development of carcinoma in cases of ulcerative colitis is initiated out of regions of dysplasia. Dysplasia may present as single or multiple flat lesions, or as polypoid dysplasia (DALM-lesion). Dysplasia in DALM lesions may not be readily differentiated from that of sporadic adenomas by light microscopy. Such distinction, however, dictates therapeutic strategies. Since colectomy is treatment of choice in DALM lesions but removal of a sporadic adenoma is sufficient therapy, several attempts have been made to find markers to differentiate the two lesions. In recent years molecular genetic studies have demonstrated different genetic alterations in the dysplasia-carcinoma event in ulcerative colitis versus sporadic colorectal carcinoma, which may in fact help to differentiate the two entities. The diagnostic tools to differentiate DALM from sporadic adenomas are briefly described and a specific emphasis is given to the molecular genetic studies which may help in defining the specific entities.

BCL-2 expression and inhibin-A in adrenal neoplasms: a comparative study.

Differential diagnosis between adrenal cortical and adrenal medullary lesions may be difficult in many cases. Different immunohistochemical, histochemical tools as well as ultrastructural diagnostic techniques have been employed to aid in differentiating between these lesions. Recently, both inhibin-A and BCL-2 have been shown to stain selectively adrenal cortical tissue and its derived neoplasms but not adrenal medulla or pheochromocytomas. In this study we compared the staining reactions of inhibin-A and BCL-2 in cases of adrenal cortical adenomas and carcinomas as well as pheochromocytomas. We found that both inhibin-A and BCL-2 stained cortical derived tissues, but not medullary derived tissues. Staining intensity for inhibin-A was significantly weaker than for BCL-2. We found that fixation techniques may influence the staining reactivity, as some cases did not immunoreact with any of the antibodies. We conclude that both inhibin-A, and, preferentially, BCL-2 are useful additions to a staining protocol to help in the differential diagnosis of cortical and medullary neoplasms.

Gastric and esophageal intraepithelial lymphocytes in pediatric celiac disease.

Celiac disease (CD) is associated with marked mononuclear cell inflammation in the small intestinal mucosa. This study was performed to evaluate analogous changes in the gastric and esophageal mucosa of pediatric patients with CD, with emphasis on epithelial lymphocytosis. We evaluated intraepithelial lymphocytes (IELs) in 23 gastric (no.IELs/100 epithelial cells) and 14 esophageal mucosal biopsy specimens (IELs/hpf) from 23 pediatric cases of CD and 10 nonceliac matched controls. Four patients had postgluten withdrawal biopsy specimens reviewed, and one of these had further postgluten challenge biopsy specimens evaluated as well. Gastric specimens from the CD cases showed a significantly increased IEL count (20.5 +/- 14.4; range, 4-50) compared to controls (3.4 +/- 1.9; range, 1-8; p < 0.001), which also correlated directly with the histologic severity of the small intestinal disease as assessed by the degree of villous shortening. Sixteen (69.5%) of 23 gastric specimens showed > 8 IELs, which was the highest value obtained in control specimens. The four posttreatment specimens showed a significant reduction in the gastric IEL counts from a mean of 19.8 to 3.5 IELs/100 epithelial cells (p < 0.001). The single case that had a further postgluten challenge biopsy showed a return to the pregluten withdrawal IEL count. However, the degree of gastric intraepithelial lymphocytosis did not correlate with any of the clinical data, such as age, gender, presenting symptoms, or serum antibody levels (antigliadin, antireticulin, or antiendomysium). Furthermore, no differences were observed in the IEL count in CD esophageal specimens (5.3 +/- 2.6; range, 2-10) compared to controls (5.2 +/- 1.5; range, 3-8; p = 0.935). These findings suggest that an immune-mediated lymphocytic response linked to gluten occurs in the gastric epithelium, similar to that seen in the small intestine of pediatric patients with CD. Therefore, gastric intraepithelial lymphocytosis may represent a concurrent manifestation of CD rather than a separate entity in the pediatric population.

Androgen receptor immunohistochemistry on paraffin-embedded tissue.

Androgen deprivation remains the primary therapy for patients with metastatic prostate cancer. Response to hormonal manipulation, however, has been quite variable. Androgen receptor (AR) expression has been used to predict clinical response to antiandrogenic treatment. However, methods of detection of AR expression have been limited to receptor biochemical assays in cytosolic or nuclear fractions of frozen tissue homogenates with obvious contamination problems by nonmalignant epithelial and stromal cells. As a result, studies correlating AR expression with response to hormonal therapy have been limited and controversial. More recently, immunohistochemical methods of analysis have become available, but only on frozen tissue. We describe a simple method to evaluate ARs on formalin-fixed, paraffin-embedded tissue sections using antigen retrieval methods. Primary, as well as metastatic, prostate carcinomas showed nuclear staining for ARs. Secretory cells stained uniformly in hyperplastic and normal prostatic glands. The majority of stromal cells had strong nuclear positivity. All other cancers tested (colon, breast, lung, skin, kidney) were negative. This immunohistochemical technique allows evaluation of prostate cancer AR status in routinely processed tissues. Thus, application of this technology to archival material should permit assessment of whether AR expression is predictive of response to endocrine therapy in advanced prostate cancer.