Reactive Epithelial Hyperplasia Research Articles

The value of Alcian blue periodic acid Schiff staining and Ki-67 expression in diagnosing gastric reactive epithelial hyperplasia and dysplasia

Objective: To investigate the clinicopathological characteristics of reactive epithelial hyperplasia and dysplasia in the stomach, as well as the clinical value of mucin special staining and proliferating cell nuclear antigen (Ki-67) in distinguishing the two gastric lesions. Methods: The clinical pathological data of 63 patients with gastric reactive epithelial hyperplasia, 54 patients with low-grade dysplasia, and 63 patients with high-grade dysplasia diagnosed from May 2018 to May 2021 in Beijing Chaoyang Hospital, Capital Medical University, Beijing, China were analyzed. Alcian blue periodic acid Schiff (AB-PAS) and Ki-67 staining were performed to examine the mucin staining pattern, number of Ki-67 positive cells, Ki-67 staining patterns in the three groups of lesions, and histopathologic characteristics. Results: The positive rates of AB-PAS in the reactive epithelial hyperplasia and gastric dysplasia groups were 87.3%(55/63) and 10.3%(12/117), respectively. The expression of AB-PAS in the reactive epithelial hyperplasia was gradually increased from the base to the surface of the epithelium. In low-grade dysplasia and high-grade dysplasia, there was no mucin present in the dysplasia epithelium. The difference between the two groups was statistically significant (P<0.01). The positive rate of Ki-67 in the epithelial reactive hyperplasia (>10%) was 81.0% (51/63), and the positive cells were mainly located in the neck and middle parts of the mucosal glands (58/63, 92.1%). In the low-grade dysplasia group, the positive rate of Ki-67 (>10%) was 90.7%(49/54); the positive cells were mainly located in the upper mucosa (33/54, 61.1%), showing a banded distribution pattern; in the high-grade dysplasia group, the positive rate (>10%) was 95.2%(60/63), and the positive cells were mainly located in the whole mucosa (49/63, 77.8%), showing a diffuse/diffuse scattered distribution pattern. The three groups had statistically different rates and distribution patterns of Ki-67 expression (P<0.01). Conclusion: The gastric epithelial reactive hyperplasia and dysplasia can be differentiated using clinicopathological features, AB-PAS staining and Ki-67 expression pattern.

An Analysis of the Clinical, Laboratory, and Histological Features of Striped, Punctate, and Nodular Gastric Antral Vascular Ectasia.

Gastric antral vascular ectasia (GAVE) commonly presents as linear striped ("watermelon stomach") or punctate phenotypes, to which a newly discovered nodular form was recently added. We performed a retrospective cohort study to detail and compare the clinical and histological characteristics of major GAVE phenotypes. In 136 GAVE patients (tertiary care ambulatory and inpatient, median age 61.3years, 73 men, and 63 women), clinical and laboratory results were recorded, with comorbidities, endoscopy indications, and complications of cirrhosis. In 74 patients, GAVE histopathology was cataloged by a pathologist masked to endoscopy results. Median age 61.3years, 73 men, and 63 women. GAVE phenotypes were: linear striped-62 (46%), punctate-32 (24%), and nodular-41 (30%). Endoscopy was commonly performed for variceal screening in linear striped (45%) and nodular (34%) GAVE and for gastrointestinal bleeding in punctate (41%) and nodular (29%) GAVE, respectively. Of 89 cirrhotic patients, 37.5% each had linear striped or nodular GAVE, 24.7% had punctate forms (p=0.03). Child-Turcotte-Pugh and Model for End-Stage Liver Disease scores were similar among phenotypes. Histologically, reactive epithelial hyperplasia and vascular ectasia were universal; smooth muscle proliferation was more common and consistent (78-86%) than microvascular thrombi (27-59%) and fibrohyalinosis (18-53%), which each varied with phenotype. Nodular GAVE is a gastric mucosal abnormality that is similar to the linear striped and punctate phenotypes, yet has distinct clinical and histological features. Increased awareness of nodular GAVE by endoscopists is needed to avoid its misdiagnosis as nonspecific antral nodules.

Conjunctival reactive epithelial hyperplasia in a black African patient- a case report

Background: Reactive hyperplasia can occur in any part of the body but of concern is occurrence adjacent to certain neoplasm such as cutaneous fibrous histiocytoma, granular cell tumor, spitz nevus and melanoma. Ocular reactive epithelial hyperplasia is not as common as ocular reactive lymphoid hyperplasia. This is the first reported case in our environment. The patient was concerned about his cosmetic appearance, comments of friends and fear of eye problem in future. We report the case of a 32 year old patient with painless, progressive swelling of the conjunctiva following stone injury to the eye while on a bike 5 years earlier. A traumatic conjunctival cyst to rule out melanoma was the initial diagnosis. We therefore, managed the case by excision biopsy and histology report was in keeping with conjunctival reactive epithelial hyperplasia. One year after removal, he was free of any swelling and had no complaints. Conclusion: Excision biopsy is effective and it will assist in ruling out neoplasm and taking care of the patient’s cosmetic problem.

Basal Cell Carcinoma-Associated Paratumoral Follicular and Epidermal Hyperplasia

Reactive epithelial hyperplasia is a well-known phenomenon which occurs adjacent to certain neoplasms such as cutaneous fibrous histiocytoma, granular cell tumor, Spitz nevus, and melanoma. We report 46 cases of paratumoral follicular and epidermal hyperplasia associated with basal cell carcinoma (BCC). This reactive process associated with BCC has certain characteristic features. It is focal, superficial, and predominantly folliculocentric. It may resemble other tumors such as squamous cell carcinoma and may appear in sections where BCC is absent. The recognition of this entity may help dermatopathologists avoid misdiagnosing this process as a tumor and can suggest further search (section through the block or rebiopsy) when this reactive phenomenon is seen in sections without the associated BCC.

Evaluating colonic biopsy specimens to distinguish acute self-limited colitis from inflammatory bowel disease: No final answer yet

The authors’ objective in this study was to evaluate whether examination of histologic features in rectal mucosal biopsy specimens could reliably distinguish acute self-limited colitis (ASLC, defined as a single episode of diarrheal disease with no recurrence for a minimum of 2 years’ follow-up) from acute onset inflammatory bowel disease (AOIBD) of <3 months’ duration. The study design was a retrospective blinded review of coded rectal mucosal specimens by two independent observers (C.S., R.H.) using a standardized checklist of histologic features. The results of this review were then correlated with clinical outcome based on a minimum of 2 years’ follow-up (mean follow-up, -5 years). The study population included 52 patients ultimately shown to have ASLC, 51 with AOIBD, and 30 with chronic inflammatory bowel disease of >4 months’ duration. When the data were analyzed, the most characteristic histologic features of ASLC were normal crypt architecture and acute inflammation in the lamina propria, whereas AOIBD featured (singly or in combination) diffusely abnormal crypt architecture (including crypt branching, distortion, and atrophy); mixed acute and chronic inflammation in the lamina propria, numerous plasma cells, lymphoid aggregates, or increased lymphocytes at the base of the lamina propria just above the muscularis mucosae (or a combination of these); isolated giant cells; epithelioid granulomas; goblet cell mucin depletion; and reactive epithelial hyperplasia. Findings in the AOIBD group were identical to those in the patients with chronic IBD. In a multivariate analysis, normal architecture and acute inflammation were independent indicators of ASLC, whereas branched crypts, mixed acute and chronic inflammation in the lamina propria, basal plasmacytosis, and isolated giant cells were independent markers of AOIBD. Overall, the histologic features had a >90% predictive value in distinguishing ASLC from AOIBD, even if the biopsies were obtained a week or more after the onset of symptoms. The authors conclude that evaluation of rectal mucosal specimens is a useful adjunct in evaluating patients with acute onset diarrheal diseases.

Diagnostic Utility of Cell Cycle and Apoptosis Regulatory Proteins in Verrucous Squamous Carcinoma

A major problem in the diagnosis of verrucous squamous cell carcinoma is the lack of readily reproducible objective criteria for distinguishing this malignant lesion from reactive epithelial hyperplasia. Both lesions are characterized by thickened (well-differentiated) squamous epithelium without cellular atypia and subjacent stroma densely infiltrated by lymphocytes and plasma cells. This study was carried out to evaluate the use of cell cycle and apoptosis-related regulatory proteins in the diagnosis of verrucous carcinoma. The study materials consisted of representative formalin-fixed and paraffin-embedded tissue blocks from 19 cases of verrucous carcinoma, 18 classic squamous cell carcinoma, and 14 squamous epithelial hyperplasia (acanthosis). The immunohistochemical expression of the following of cell cycle and apoptosis-related regulatory proteins was evaluated using avidin-biotin complex detection technique: p16, p21, p53, Ki67, and retinoblastoma gene product (RBGP) (also known as retinoblastoma protein [pRb]). Expression of Ki67 was detected only in the single basal layer of the epithelium in all 14 cases of acanthosis. In verrucous carcinoma, Ki67 was detected in basal and suprabasal cells in the lower third of the neoplastic epithelium in 19 of 19 cases (100%). In neoplastic squamous epithelium with frankly invasive squamous cell carcinoma, Ki67 was diffusely expressed throughout the entire thickness of the epithelium as well as in the underlying invasive tumor nests. The pattern of p53 expression was similar to that of Ki67 in all the experimental groups, with a Pearson correlation coefficient of 0.98. In addition, immunohistochemical expression of p53 in the hyperplastic squamous epithelium was very weak, in contrast to the more intense immunoreactivity observed in verrucous carcinoma and classic squamous cell carcinoma. There was an overlapping in the expression of p16, p21, and RGBP in all the experimental groups, being present in more than half the thickness of the epithelium in 50% to 100% cases in each study group. We therefore conclude that the pattern of Ki67 and p53 expression in verrucous carcinoma is readily reproducible and distinctly different from that observed in epithelial hyperplasia and that seen in invasive squamous cell carcinoma. Thus Ki67, and p53 immunostains are reliable adjuncts that may be helpful in resolving diagnostic problems associated with verrucous carcinoma.

Expression of p63 protein and mRNA in oral epithelial dysplasia

Abnormalities in the TP53 are regarded as the most consistent findings in oral squamous cell carcinoma. Two related members of the TP53 family, p73 and p63, have shown remarkable structural similarity to TP53, indicating possible functional and biological interactions. The aim of the present study was to investigate the expression of p63 protein and mRNA in oral epithelial dysplasia. Immunohistochemical p63 staining was compared for samples from 90 male patients with buccal epithelial dysplasias and 15 healthy individuals with normal buccal mucosa and 15 subjects with reactive epithelial hyperplasia of the oral mucosa secondary to traumatic insult. The buccal lesions consisted of mild, moderate and severe epithelial dysplasias (30 samples in each category). The mRNA expression using reverse transcription polymerase chain reaction (RT-PCR) was also included for a subset of available fresh tissue specimens (four samples in each category of mild and moderate epithelial dysplasia; five samples in severe epithelial dysplasia; five samples in each of normal and reactive epithelial hyperplasia). Nuclear p63 staining was demonstrated predominantly in the basal layers of the epithelium of the normal buccal mucosa and reactive epithelial hyperplasia specimens. For epithelial dysplasia lesions, however, staining was not restricted to the basal layers, extending to the middle spinous layer for samples in the mild category, with p63 immunoexpression observed across almost the full thickness of the dysplastic epithelium for analogous moderate and severe specimens. Compared with normal/reactive hyperplastic mucosa, p63 staining in the dysplastic mucosa was significantly increased. The severity of dysplasia was increased with the increase of p63 staining. Furthermore, Delta Np63mRNA was identified in all of the fresh tissue samples whereas expression of transactivation (TA) isotype was not detected. A subset of moderate epithelial dysplasia and severe variant showing p63-positive staining has undergone malignant transformation to squamous cell carcinomas in about 5 years follow-up. Our results indicate that impaired p63 immunoexpression (predominantly Delta N isoform) is associated with the severity of oral epithelial dysplasias and up-regulation of p63 may play a role in the early stage of human oral tumorigenesis.

Mucosal biopsy diagnosis of colitis: Acute self-limited colitis and idiopathic inflammatory bowel disease

Background/Aims : Rectal biopsy specimen changes distinguish acute self-limited colitis (ASLC) from idiopathic inflammatory bowel disease (IBD). This study aimed to determine whether these histological criteria are also valid for acute-onset IBD. Methods : Blind analysis of colorectal biopsy specimens from 52 patients with ASLC, 51 patients with acute-onset (< 3 months) IBD, and 30 patients with chronic IBD was performed. Results : Histological features of ASLC are normal crypt architecture and acute lamina propria inflammation, but mixed acute and chronic inflammation can be found. Histological features of IBD are diffusely abnormal crypt architecture, crypt atrophy, mixed lamina propria inflammation, basal plasmacytosis, basal lymphoid aggregates, basal lymphoid hyperplasia, isolated giant cells, epithelioid granulomas, goblet cell mucus depletion, and reactive epithelial hyperplasia. Changes of chronic IBD were present in biopsy specimens as early as 7 days after the onset of symptoms. Conclusions : Rectal biopsy specimens are useful in distinguishing ASLC from acute-onset IBD even if the biopsy specimens are not obtained during the first 4 days of the illness. There were no significant differences in histology between acute-onset and chronic IBD.

Pulmonary changes following extracorporeal membrane oxygenation: Autopsy study of 23 cases

Extracorporeal membrane oxygenation (ECMO) has become an established mode of therapy in many centers for potentially fatal neonatal respiratory failure refractory to conventional therapy. We reviewed the findings of 23 autopsies of patients placed on ECMO therapy during the period from 1988 to 1992 at our institution in order to document the pulmonary histopathologic changes and to correlate such changes with the duration of treatment. Interstitial and intra-alveolar hemorrhages, as well as hyaline membrane formation, were the most common findings during the first few days of therapy. Reactive epithelial hyperplasia (bronchial and type II pneumocytes), squamous metaplasia, and smooth muscle hyperplasia were observed as early as 2 to 3 days after initiation of ECMO therapy. Interstitial fibrosis was noted only after 7 days of ECMO therapy. In three patients treated for 15, 19, and 21 days there was replacement of the terminal airways and alveoli by tall columnar and mucin-producing epithelium. Alveolar and bronchiolar calcifications were noted in seven of the 23 cases in this series. Pulmonary vascular changes were seen in association with persistent fetal circulation, meconium aspiration, and respiratory distress syndrome. These changes are most likely due to the compounded effect of ECMO and the underlying pulmonary insult.

Tobacco smoke enhances allergic bronchial sensitization in the guinea pig

Passive smoking has been shown to cause increased incidence of lower respiratory tract infection and wheezing in young children and an inceased risk of childhood asthma. To evaluate possible influence of tobacco smoke on allergic bronchial sensitization we exposed guinea pigs to tobacco smoke in 3 concentrations of clean air (control group) for 8 h on 5 consecutive days (median plasma cotinine 5. 0—25. 4—87, 2 ng/l). The animals were sensitized by repeated inhalation with ovalbumin. Histologic examination at the end of exposure revealed reactive epithelial hyperplasia and regenerative changes as well as inflammatory reaction mainly in the lung periphery, and histamine provocation showed increased bronchial reactivity at the end of tobacco smoke exposure. Sensitization was measured by specific bronchial provocation testing using body plethysmographic measurement of compressed air (CA) and specific anti‐ovalbumin‐antibodies of the IgG1‐subclass in the serum, measured by direct ELISA in ELISA units (EU). The group with the highest tobacco smoke exposure differed significantly in bronchial reactivity on specific bronchial provocation tests (p &lt; 0.005) compared with the control groups and showed elevated unspecific IgG1‐antibody levels indicating enhanced sensitization. We conclude that intensive exposure to tobacco smoke over a short period of 5 d can enhance inhalational allergic sensitization in the guinea pig and might explain the increased incidence of respiratory allergies in child passive smokers.

Involucrin as a diagnostic marker in oral lichenoid lesions

Thirty-eight biopsy specimens were examined for involucrin reactivity by an immunoperoxidase technique. The sampling consisted of specimens diagnosed as normal oral mucosa, reactive epithelial hyperplasia, lichen planus (LP), nonspecific lichenoid stomatitis (NLS), lichenoid dysplasia (LD), carcinoma in situ, and squamous cell carcinoma (SCCa) on routine hematoxylin and eosin examination. Findings were consistent with prior observations of involucrin reactivity in skin and cervical-vaginal mucosa. Specifically, conditions characterized by predominance of mature squamous epithelial cells (superficial layers of normal and hyperplastic oral epithelium, NLS, and LP) exhibited strong involucrin reactivity in such areas. In contrast, atypical or dysplastic lichenoid lesions (LD), as well as carcinoma in situ, despite squamoid differentiation, demonstrated irregular distribution of involucrin, suggesting disturbances in terminal differentiation. Invasive components of SCCa revealed markedly diminished involucrin expression. These findings support prior evidence that LP and LD are biologically distinct lesions. Clinically and microscopically, both may be morphologically similar. However, involucrin reactivity should be helpful in distinguishing difficult cases. Accordingly, we suggest that the use of involucrin immunoreactivity may prove to be a valuable adjunct in the separation of similar lichenoid oral conditions.