Epithelial Pseudostratification Research Articles

PATHOLOGICAL STUDY ON LARYNGOTRACHEITIS IN LAYERS

A clinical conditions resembling infectious laryngotracheitis were diagnosed amongst 20,000 , 18,000 , 16,000 and 17,500 respectively, 28-30 weeks old, ISA brown layers.
 The hens had nasal discharges, moist rales, coughing and gasping. Hemorrhagic mucous was ejected during sneezing, lacrirnation, conjunctivitis with facial swelling with eyes partially or completely" closed.
 Postmortum examination of dead and affected hens revealed hemorrhagic tracheitis with thin pseudomembrane formation. The larynx, congested with petechia on mucous membrane, Infraorbital sinus contained clear thick fluid.
 Histopathological examination of trachea showed hypertrophy, of epithelial pseudostratification of the mucosal cell surface, extensive hemorrhages and desquamative necrotizing tracheitis with
 mononuclear cells infiltration. Multinucleated gaint cells in theciliated epithelium containing round, oval shaped intranuclear A
 inclusion bodies. The lamina propiia shows edema, marked‘ congestion with lymphocytic infiltration.A presumptive diagnosis of laryngotracheitis was made.

1788 Colchicine Toxicity Presenting as Esophagitis

INTRODUCTION: Colchicine, a commonly prescribed medication for numerous medical conditions, is notorious for causing harm in the stomach and small intestine. Less commonly, damage can occur in other organs, such as the esophagus. CASE DESCRIPTION/METHODS: A 72-year-old male with a history of gout presented to the gastroenterology clinic with a several month progression of pyrosis and dysphagia. Upper endoscopy was performed which revealed erosive esophagitis. Biopsies were obtained which revealed mitotic arrest of the cells in metaphase. On review of his medications, he had been on long-term colchicine therapy for management of his gout. DISCUSSION: Colchicine, an anti-inflammatory medication, acts at the cellular level by interrupting mitosis. This is achieved through disrupting neutrophil microtubules and ultimately preventing neutrophil migration and adhesion, thus, decreasing the inflammation associated with diseases, such as gout. Microscopically, mitotic arrest is commonly seen in metaphase with evidence of ringed mitoses, glandular cell apoptosis, and epithelial pseudostratification. Within the gastrointestinal tract, colchicine is most notable for causing side effects such as diarrhea and nausea. However, due to its prevention of cellular division, it can cause injury to rapidly proliferating cells within the gastrointestinal tract. Most commonly, this occurs in the small bowel and gastric antrum. We present a rare case in which evidence of colchicine toxicity is identified within the esophagus. In our patient, colchicine was discontinued and he was treated with proton pump inhibitor therapy with improvement of his symptoms.

A Case of Severe Esophagitis in a Patient with Gout

Colchicine is a frequently used medication, most commonly for gout. We present a case of severe esophagitis with histopathologic finds consistent with colchicine toxicity. There are few reported cases of this adverse effect, and histopathology has only recently been documented. We hope to shed light on this significant and potentially under recognized complication of a commonly used medication. A 36-year-old male with alcoholism and gout presented with a week of central chest pain, profound odynophagia, and inability to tolerate solids or liquids. He reported minimal NSAID use. Exam was unremarkable. Elevated creatinine, transaminases and lipase were noted. Esophagogastroduodenoscopy revealed 16cm of LA grade D esophagitis with no bleeding, duodenal bulb erythema and diffuse atrophic mucosa in the second portion of the duodenum. Pathology demonstrated esophageal inflammation extending into the muscular layer with ulcerated mucosa and numerous arrested mitoses consistent with colchicine toxicity. Chronic peptic duodenitis without dysplasia was also noted. Further history revealed patient had been taking very large amounts of colchicine three months prior with doses of more than 20 tablets at a time. Colchicine was discontinued. He was diagnosed with LA grade D esophagitis with evidence of colchicine toxicity, duodenitis, alcoholic hepatitis and pancreatitis, and gout flare. Steroid taper, proton pump inhibitor, sucralfate, and vitamins were prescribed with symptomatic improvement. Alcohol and NSAID cessation were advised. Frequently prescribed for gout and pericarditis, colchicine has a long history of use. Colchicine prohibits polymerization of microtubules which is fundamental to chemotaxis, degranulation, and mitosis. Toxicity, in acute overdose or long-term use, can lead to significant morbidity and mortality such as multi-organ failure and death. Impaired hepatic and renal function decrease clearance of colchicine by ten and three-fold respectively. The most commonly involved areas are those with rapid proliferation, including the duodenum and gastric antrum. Pathologic findings are arrested mitoses, epithelial pseudostratification and loss of polarity. The typical site of gastrointestinal tract injury by colchicine is the small bowel. Our case highlights that there is more widespread involvement of the GI tract in colchicine toxicity than previously reported. Furthermore, colchicine can induce severe esophagitis and significant patient symptomatology.1717_A Figure 1. Esophagogastroduodenoscopy with LA Grade D esophagitis in the middle third of the esophagus.1717_B Figure 2. 400x magnification of H&E stain with arrested mitoses in the esophageal epithelium. Scattered characteristic ring mitoses due to colchicine.1717_C Figure 3. 200x magnification of phosphohistone H3 (PHH3) stain of esophageal epithelium highlighting numerous characteristic ring mitoses (brown) in the setting of colchicine toxicity.

Case Report of Pathognomonic Findings of Severe Colchicine Effect in the Esophagus, a Rarely Reported Site of Colchicine Effect

Colchicine, a medication commonly used to treat gout, interferes with the cell cycle and can injure rapidly reproducing cells, including proliferative cells in gastrointestinal mucosa, primarily in the small bowl. Esophageal injury is rarely reported, and when reported is typically mild. A case is reported of severe injury to esophageal mucosa secondary to colchicine. A 47-year-old male with a medical history of systemic lupus erythematosus, intermittently treated with corticosteroids for 2 years, recently treated with azithromycin therapy for upper respiratory infection and hydroxychloroquine for polyarthritis, presented with dyspnea and severe substernal chest pain, exacerbated by deep inspiration, and ameliorated by leaning forward. Physical examination revealed an afebrile man with stable vital signs and no friction rub. Laboratory tests revealed Hb=12.6 g/dl, creatinine=1.33 mg/dl, CRP=3.4 mg/dl, ESR=51 mm/hr, D-Dimer=1140 ng/ml, and troponin level was within normal limits. EKG revealed PR segment depression and upwardly concave ST elevation, findings suggestive of pericarditis. Echocardiogram revealed no pericardial effusion. CT angiogram of chest was negative for pulmonary embolus, but showed prominent distal esophagus wall. Patient was admitted for acute pericarditis, likely viral versus lupus pericarditis. Patient treated with prednisone 50 mg/ day and colchicine 0.6 mg twice daily with significant symptomatic improvement. Esophagogastroduodenoscopy revealed LA grade C reflux esophagitis and nonbleeding small gastric ulcers. He was treated with an oral proton pump inhibitor and discharged home. Pathological examination of esophageal biopsies revealed mild chronic gastritis at the gastroesophageal junction, with cytotoxic colchicine effect, but no intestinal metaplasia, dysplasia, or H. pylori infection. Colchicine prevents tubulin protein polymerization, prevents mitotic spindle formation and causes mitotic arrest during metaphase. The pathognomonic histopathologic finding is ring mitoses accompanied by increased glandular cell apoptosis and epithelial pseudostratification. Small bowel is the most severely affected site in the GI tract by colchicine, but in the present case the esophagus was significantly affected, a highly uncommon finding. Colchicine toxicity typically manifests soon after therapy initiation; in the current case endoscopic biopsies were performed one day after receiving 3 doses of colchicine therapy. The irregular arrangement of nuclei, increase in mitotic figures, and hyperchromatism of nuclei are pathognomonic of colchicine, but this finding can occasionally mimic dysplasia. Nontoxic doses of colchicine do not cause mucosal changes, except in areas with increased cell proliferation, such as a hyperplastic polyp, where nontoxic levels of colchicine can cause mitotic arrest and ring figures, and mimic a sessile serrated adenoma. These pathologic findings should be assessed in conjunction with clinical presentation to avoid missing the diagnosis of colchicine toxicity.Figure: Esophagogastroduodenoscopy showing deep linear erosions in distal esophagus. The lesions are unlikely from Mallory-Wiess tear in the absence of antecedent vomiting.Figure: Medium power photomicrograph of esophageal squamous mucosa showing brisk mitotic activity involving almost the entire thickness of the epithelium. Right inset shows high power view of characteristic ring mitosis associated with colchicine effect.Figure: Medium power photomicrograph of gastric cardial epithelium at gastroesophageal junction showing brisk mitotic activity in columnar epithelial cells. Right inset shows a high power view of numerous mitotic figures.

Clinicopathologic study of the putative precursor lesions of epithelial ovarian cancer in low-risk women

Possible precursor lesions for epithelial ovarian cancer (EOC) have been defined in the ovaries of women with contralateral EOC, with breast cancer susceptibility gene (BRCA)-1 mutations, or with positive family history. We aimed to investigate the prevalence of these lesions in women without any recognizable risk and to correlate these lesions with clinical ovulatory markers. The study group consisted of 184 women who were operated for benign gynecological conditions. Patients were requested to fill a questionnaire about anthropometric characteristics and medical and reproductive history. Oophorectomy specimens were examined for presence of epithelial inclusion cysts (EIC), cortical invaginations (CI), stromal hyperplasia (SHPP), epithelial pseudostratification (EPS), and surface papillomatosis (SP). Women with EIC were older, had lower age at menarche, and had higher menarche-to-pregnancy and menarche-to-operation time. SHPP was found to be related with age, menarche-to-operation time, history, and the duration of oral contraceptive use. Women with SP had lower age at menarche, lower menopausal age, and longer duration of hormone replacement therapy. No significant correlations were established between CI and any clinical parameters. Only one patient had EPS. Our findings suggest that these lesions correlate closely with reproductive features. Exact mechanisms that lead to development of these lesions should be clarified before implying them as precursor lesions of EOC.

Differential expression of matrix metalloproteinases and interleukin‐8 during regeneration of human airway epithelium in vivo

In many airway diseases, the airway epithelium is severely damaged and has to regenerate rapidly to restore its function. The regeneration process involves chronological steps of epithelial cell migration, proliferation, stratification, and differentiation. The present study has used an in vivo humanized airway xenograft model in nude mice that mimics the regeneration dynamics of human airway epithelium after severe injury, and human-specific molecular tools, to study the expression profiles of epithelial matrix metalloproteinases (MMPs)-7 and -9, of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and of the pro-inflammatory cytokine interleukin-8 (IL-8) during the different steps of human airway epithelium regeneration. It was found that during the cell migration and proliferation steps, airway epithelial cells expressed IL-8 at a high level, whereas airway epithelial pseudo-stratification and surface airway epithelial differentiation were associated with increased expression of MMPs and a progressive decrease in IL-8. Interestingly, immunohistochemical analysis revealed exclusive expression of MMPs at the apical part of the well-differentiated regenerated airway epithelium, and incubation of the regenerating epithelial cells with MMP inhibitors led to abnormal epithelial differentiation. These data provide new insight into the temporal expression of MMPs and IL-8 during the regeneration of airway epithelium and demonstrate the involvement of these factors during the different steps that lead to restoration of a well-differentiated and functional airway epithelium.

Pure primary squamous cell carcinoma of the ovary: a case report and review of the literature

Pure primary squamous cell carcinoma of the ovary: a case report and review of the literature

Colchicine toxicity: distinct morphologic findings in gastrointestinal biopsies.

Colchicine is an alkaloid with antimitotic ability used to treat a variety of medical conditions. Colchicine toxicity can result in multiorgan failure and death. The histopathologic features of colchicine toxicity in gastrointestinal biopsies have not been reported. Twenty-one gastrointestinal mucosal biopsies obtained from nine patients receiving oral colchicine therapy were studied. Immunohistochemical staining for Ki67 proliferation antigen was performed, and medical records of each patient were reviewed. All patients had a history of gout. Four patients with chronic renal failure also had clinical evidence of colchicine toxicity, and the other five patients did not. Distinct morphologic changes, seen as metaphase mitoses, epithelial pseudostratification, and loss of polarity, were seen in biopsy material from 4 of 4 (100%) patients with clinical colchicine toxicity. Three of these four cases (75%) also contained abundant crypt apoptotic bodies. These morphologic features were best seen in the biopsies from duodenum and gastric antrum, with relative sparing of the gastric body in the upper gastrointestinal tract. Ki67 staining demonstrated an expansion of the proliferating region in three available cases with clinical colchicine toxicity. These distinctive morphologic features were not seen in the five patients without clinical colchicine toxicity. These results indicate that colchicine toxicity can produce diagnostic morphologic features in gastrointestinal mucosal biopsies. Recognition of these features is important because colchicine toxicity can be fatal if undiagnosed clinically.

Absence of premalignant histologic, molecular, or cell biologic alterations in prophylactic oophorectomy specimens from BRCA1 heterozygotes.

The high mortality associated with ovarian carcinoma is largely a reflection of the inability to diagnose the disease at an early stage; the identification of a histologic lesion or molecular marker associated early stages of transformation would represent an important advance in understanding the natural history of this cancer. The existence of individuals with germline mutations in the ovarian and breast carcinoma susceptibility gene BRCA1 represents a unique opportunity to search for such premalignant alterations in ovarian tissues that are at unusually high risk for tumorigenesis. In this study, the authors addressed the hypothesis that pathologically normal ovaries removed from BRCA1 heterozygotes are likely to display premalignant histologic, molecular, and/or cell biologic alterations that may provide insight into early stages of ovarian tumorigenesis. Ovarian tissues from 18 BRCA1 heterozygotes and from 20 age-matched controls were examined in a blinded fashion for histologic evidence of surface epithelial pseudostratification, epithelial inclusion cysts, deep cortical invaginations of surface epithelium, increased stromal cell activity, and surface papillomatosis. Immunohistochemical analyses for expression of BRCA1, p53, and ERBB-2 and quantitation of cell proliferation (Ki-67 expression) and apoptosis (TUNEL assay), were also performed on all specimens. Although histologic alterations were observed, there was no difference in frequency between cases and controls. Analysis of BRCA1 expression revealed ubiquitous nuclear immunoreactivity in the surface epithelial cells of all ovaries. Similarly, no evidence was found of p53 overexpression in any ovarian tissue or of a difference in ERBB-2 expression between cases and controls. Finally, no differences were observed in epithelial cell proliferation or apoptosis. Clinically, normal ovaries from BRCA1 heterozygotes do not show evidence of premalignant alterations in histology, molecular markers, cell proliferation, or apoptosis, indicating that such changes are likely rare.

Histogenesis of Epithelial Neoplasms of Human Gallbladder I: Dysplasia

In order to find a relationship between normal gallbladder epithelium and dysplastic epithelium, histological and histochemical examinations were made on gallbladder specimens obtained from cholecystetomies and special attention was paid to the relationship of the different metaplasias. Epithelial pseudostratification increases in mitotic figures and hyperchromatism accord well with the degrees of dysplasia of surface epithelium. The relationship of the ratio of cell and nuclear size and complexity of glandular branching is more meaningful in degrees of dysplasia of glandular epithelium. Epithelial dysplasia in the surface and glandular epithelium was divided into three types: mild, moderate and severe. This classification was made on the basis of specimens containing dysplasia selected from an extensive gallbladder material. The frequency of dysplasias of different degrees was clarified in 71 cholecystectomia gallbladders. No dysplastic changes were demonstrated in 47 gallbladders (66.2%), and in 10 of these metaplasia was present, 24 gallbladders (33.8%) exhibited dysplastic changes; metaplasia was present in 20 cases (83.3%) and in 14 (58.3%) in the dysplastic region. Severe dysplasia was present only in one case, moderate in 6 and mild dysplasia alone in 17 cases. Dysplasia was found in glands only in 3 cases. In dysplastic epithelium, the mucin reaction was similar to that in the metaplastic epithelium. It contained mainly nonsulphated acid mucin and neutral mucin. With gradually increasing degree of dysplasia the amount of mucin. With gradually increasing degree of dysplasia the amount of mucin clearly decreased. The present results indicate that dysplasia often develops in metaplastic epithelium.

Morphology and histochemistry of large intestinal polyps.

In order to assess the progress of the growth of large intestinal polyps into cancer, the epithelial height and the size of the epithelial nuclei were measured. Mucin histochemistry was also carried out. The increase of the histologic grade was based on the extent of epithelial pseudostratification; epithelial height became greater and epithelial nuclei increased in size. The histochemical mucin values were as follows: the total amount of murin in a given area increased in grade I epithelia in comparison with its behaviour in normal ones, and then decreased gradually with the increase in histologic grade. Neutral mucin became more conspicuous with the increase of epithelial pseudostratification. The amount of sulphated mucin decreased with the increase in histologic grade. In normal epithelia, sialomucin was rarely seen, but in grade I and II epithelia which did not show nuclear stratification the amount of sialomucin increased strikingly. It then decreased in amount with the increase in histologic grade. The noticeable increase of the amount of sialomucin in grade I and II epithelia can be thought of as a temporary pheomenon which appears in an early stage of carcinogenic process. The large intestinal polyps go through several stages before turning into cancer.

Development of the embryonic chick otic placode. I. Light microscopic analysis.

AbstractAt the 7–8 somite stage of embryonic chick development (29‐31 hours of incubation), a slightly elliptical island of thickened ectoderm appears laterally on either side of the most distal constricture of the rhombencephalon at the level of the anterior intestinal portal. The appearance and extent of this auditory placode is precisely correlated with the subjacent accumulation of neural crest cells. By 33 hours of incubation, there is a distinct depression in the developing otic placode, and by 40 to 45 hours, the placode is visibly invaginated, forming an epithelial vesicle or otocyst. Carefully staged embryos were serially sectioned, and the area underlying the developing otic placode was traced with a planimeter. It was found that placode size (area 60,000 μm2) is nearly unchanged from 30 to 42 hours of development. During this time interval, the placode cells first become columnar, show nuclear orientation, and then pseudostratify. The increase in placode cell number during this time interval is not likely to be the result of localized, accelerated cell division: the population doubling time of placode cells is eight and one‐half hours and the mitotic index of 2.5% is similar to that of cells in an equivalent area of adjacent, non‐placode forming head ectoderm. A model of otic placode formation is proposed which suggests that by 30 hours of development, a discrete population of placode forming cells is segregated from head ectoderm. Subsequent epithelial pseudostratification results from accumulation of this dividing population within the limits of the placode.

Well-differentiated adenoma at the anorectal junction.

Twenty-six cases of patients having adenomatous polyps at the anorectal junction are presented. Most polyps in this region were well-differentiated, and atypical polyps were infrequently seen. Well-differentiated adenomatous polyps in the anorectal junction were larger in average size than ordinary colorectal polyps having the same grade of epithelial pseudostratification. The reason adenomatous polyps at the anorectal junction grow to large sizes with only a relatively rare occurrence of malignant degeneration is discussed in relation to their specific location. Some well-differentiated adenomas were considered to develop secondarily in the bases of hemorrhoids or in pre-existing fibrous polyp that were the end result of hemorrhoids.