Clinicopathological Study of Resected and Recurrent Cases of Intrahepatic Intraductal Papillary Neoplasm of the Bile Duct.

BACKGROUND/AIM: This study aimed to characterize intraductal papillary neoplasm of the bile duct (IPNB) in patients undergoing initial and recurrent surgical resection and to evaluate the appropriateness of surgical treatment strategies. PATIENTS AND METHODS: This study included 14 patients who underwent liver resection for intrahepatic IPNB. We assessed intraoperative and postoperative clinicopathological factors in patients undergoing both initial and recurrent surgeries. RESULTS: Four patients experienced recurrence after initial surgery; all underwent pancreaticoduodenectomy. Postoperative complications were classified as Clavien-Dindo Grade 1-2 in three patients and Grade IIIb in one patient. There were no in-hospital deaths. CONCLUSION: Pancreaticoduodenectomy for recurrent cases following hepatectomy for IPNB is considered safe within an acceptable range and contributes to a favorable long-term prognosis.

Squamous cell carcinoma of ear and temporal bone: A retrospective study on clinicopathological predictors.

BACKGROUND: Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to retrospectively evaluate the predictive effect of clinicopathological variables on the 5-year overall survival (OS) rate of ETBSCC patients in a single tertiary medical center in Tianjin, China. METHODS: A cohort of 44 patients with diagnosed ETBSCC from December 2012 to August 2022 were retrospectively studied. Univariate and multivariate analysis were, respectively, performed for the assessment of clinicopathological predictors, including sex, age, history of chronic suppurative otitis media (CSOM), lesion side, diameter, the choice of surgical approach, parotidectomy, neck dissection, adjuvant therapies, T stage, lymph node metastasis, tumor grade, margin, perineural invasion (PNI), and Ki-67 index. RESULTS: Seventeen females and 27 males were included, with the mean age of 65 years old, ranging from 36 to 89 years. The 5-year OS rate was 43% (mean 51 months, 95% confidence interval [CI] = 39-64). Significant prediction of a worse prognosis for 5-year OS rate was observed under univariate analysis for advanced T stage, positive margin, identified PNI, and higher Ki-67 index, respectively. Advanced T stage was confirmed to be an independent prognostic factor strongly affecting 5-year OS rate among this cohort of patients using a multivariate cox proportional hazard model. CONCLUSION: We found that clinicopathological parameters, especially postoperative pathological parameters, play a critical role in predicting the prognosis of ETBSCC patients.

Clinical, microbiological, immunological and hormonal profiles of patients with granulomatous mastitis.

Various studies on the etiology and other aspects of granulomatous mastitis (GM) have been performed; however, a lot of controversies have arisen. The present study aimed to present the clinicopathological findings and identify the sensitivity and resistance of isolated bacteria in patients with GM. In this cross-sectional study 63 female patients with a confirmed histopathological diagnosis of GM were included. A core needle biopsy was conducted for the patients to obtain a sample for histopathological examination and bacterial culture. In total, 46 types of antibiotics were used to determine the sensitivity and resistance of each isolated bacterial species. All the medical and clinical records of the patients were acquired through the completion of a questionnaire form in person or, if necessary, through the evaluation of their medical records in the database of the relevant center. The majority of the patients were in the premenopausal or perimenopausal period. GM was unilateral in 58.7% of the patients. The most common symptom was pain, followed by fever and chills. The mean ranges of the erythrocyte sedimentation rate, C-reactive protein, IL-6, IL-17, C5a, white blood count, neutrophil-to-lymphocyte ratio, and prolactin tests were significantly elevated in comparison to the normal ranges. In total, nine different bacterial species were isolated from the bacterial culture of the core biopsy samples, and 50% of the isolated bacterial species were sensitive to trimethoprim-sulfamethoxazole. Since there is no consensus on the etiology of GM, any additional studies related to this aspect expand the current understanding of this puzzling condition.

Clinical Diagnostic Accuracy of Parkinson's Disease: Where Do We Stand?

BACKGROUND: Clinical diagnostic accuracy of Parkinson's disease (PD) remains suboptimal. Changes in disease concept may have improved clinical diagnostic accuracy in the past decade. However, current clinical diagnostic criteria have not been validated against neuropathological confirmation. OBJECTIVES: This study aims to provide up-to-date clinical diagnostic accuracy data and validate current clinical diagnostic criteria for PD against neuropathology. METHODS: A retrospective review of medical records of consecutive patients with parkinsonism from the Queen Square Brain Bank was performed between 2009 and 2019. Clinical diagnosis was documented at early (within 5 years of motor symptom onset) and final stages and categorized by movement disorder experts or regular clinicians. Movement Disorder Society Parkinson's disease (MDS-PD) diagnostic criteria were retrospectively applied. Diagnostic accuracy parameters (sensitivity, specificity, positive/negative predictive value, and accuracy) were calculated using neuropathological diagnosis as the gold standard. RESULTS: A total of 267 patients (141 PD and 126 non-PD parkinsonism) were included. Clinical diagnostic accuracy was 97.2% for experts, 92.5% for the MDS clinically probable PD criteria, and 90.3% for clinicians. Similar figures were obtained when applied at an early stage (91.5%, 89.5%, and 84.2% diagnostic accuracy, respectively). MDS clinically established early PD criteria demonstrated very high specificity (98.4%) at early stages. CONCLUSIONS: Our results showed an important improvement in PD clinical diagnostic accuracy in clinical practice over the past decade, more marked at early stages of the disease. MDS-PD diagnostic criteria is a valid tool in clinical practice and research for the identification of PD patients showing excellent sensitivity and specificity, although movement disorder experts' diagnosis remains the gold standard PD diagnosis during life. © 2023 International Parkinson and Movement Disorder Society.

H3K27M Mutation Doesn't Mean Worse Prognosis in Old Patients.

Objective: Diffuse midline glioma (DMG), H3K27 altered is a new entity that has become widely recognized. However, studies concerning DMG in adult patients remain rare. We did a retrospective study covering the largest amount of patients to date to analyze the clinicopathological characteristics of diffuse glioma in midline structures of the adult. Methods: We reviewed 108 cases of adult DMG, collected their clinical data, and pathological results including H3K27 mutation. Summarized their features and the connection with overall survival in different age groups. Results: Among 108 cases, 79 tumors were located at the thalamus. 38 patients had H3K27M mutation, whose average age was 35.7 years. The median overall survival of H3K27M-mutant gliomas and the 80 H3K27M wild-type gliomas were both 12 months. For young patients (age ≤ 35), The median survival time of the H3K27M-mutant was 18 months, while that of the H3K27M wild-type was 37 months. For older patients (age>35), the median survival time of the H3K27M-mutant was 16 months, while that of the H3K27M wild-type was 13 months. Other clinicopathological factors including sex, tumor location, the approach of surgery, histological grade, ATRX, and P53 were statistically irrelevant to prognosis. Conclusion: The DMG in adults mainly occurred in the thalamus. H3K27M mutations tend to happen more frequently in young adults, and this genetic alteration results in a worse outcome only in young patients (≤35). For old patients, age is the only independent prognostic factor. Patients who underwent different surgical operations including biopsy, subtotal resection, and total resection had similar prognoses.

Corrigendum: H3K27M mutation doesn't mean worse prognosis in old patients.

[This corrects the article DOI: 10.3389/fonc.2022.912166.].

Epithelioid sarcoma: A clinicopathological study of 12 head and neck cases.

OBJECTIVES: To determine the clinicopathological features of epithelioid sarcoma presenting in head and neck region (HNES) and elucidate diagnostic key points and treatment options for HNES. MATERIALS AND METHODS: A total of 12 HNES cases were collected in our department from 2010 to 2020. Their clinical information and pathological features were documented, and relevant follow-up was performed. Immunohistochemistry was carried to analyze the protein markers of HNES. RESULTS: Of the 12 HNES cases, 10 were primary tumors and 2 were metastasized from foot and shoulder, respectively. The patients with primary tumors were significantly younger than those with metastasized ones (22.7 vs 41.5, p = .0157), and male patients outnumbered female patients (3:1). Of all HNES cases, 9 were classic subtype, and 3 were proximal subtype. HNES patients had a poor prognosis, with 5-year overall survival of 41.5% and 5-year relapse-free survival of 22.5%. A loss of INI1 was identified as the hallmark of HNES with 83.3% (10/12) of HNES cases presenting as EZH2 positive. CONCLUSIONS: HNES is more prevalent at younger ages and in males, has a poor prognosis, and exhibits a greater proportion of classic subtype than proximal subtype. EZH2 inhibitor has therapeutic potential in HNES.

Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia.

INTRODUCTION: The aged brain frequently exhibits multiple pathologies, rather than a single hallmark pathology (pure pathology [PurP]), ranging from low/intermediate levels of additional pathology (LowP) to mixed severe pathology (mixed SevP). We investigated the frequency of PurP, LowP, and mixed SevP, and the impact of additional LowP on cognition. METHODS: Data came from 670 cases from the Brains for Dementia research program. Cases were categorized into PurP, mixed SevP, or a main disease with additional LowP; 508 cases had a clinical dementia rating. RESULTS: 69.9% of cases had LowP, 22.7% had PurP, and 7.5% had mixed SevP. Additional LowP increased the likelihood of having mild dementia versus mild cognitive impairment (MCI) by almost 20-fold (odds ratio = 19.5). DISCUSSION: Most aged individuals have multiple brain pathologies. The presence of one additional LowP can significantly worsen cognitive decline, increasing the risk of transitioning from MCI to dementia 20-fold. Multimorbidity should be considered in dementia research and clinical studies.

Contribution of Alzheimer's disease neuropathologic change to the cognitive dysfunction in human brains with Lewy body-related pathology.

This study investigated the clinicopathological relationship between cognitive dysfunction and Lewy body-related pathology (LRP), and the role of Alzheimer's disease neuropathologic change (ADNC) in affecting this relationship in the Chinese population. A total of 127 brains with antemortem cognition assessment were collected. The postmortem neuropathological classification of LRP and staging of ADNC were evaluated. Pairwise correlation and ordered logistic regression analysis showed that LRP had a moderate correlation with Global Everyday Cognition scores. The proportion of the people with intermediate and high levels of comorbid ADNC increased with the deterioration of LRP. The fit of the cognition prediction model improved when we incorporated both LRP and ADNC into the model compared with LRP alone. Our study indicated that comorbid ADNC can variably present in patients with Lewy body disease. A combination of LRP and concurrent ADNC improves the prediction of cognitive dysfunction compared with LRP alone. These findings may suggest the potential benefit of combined therapeutic approaches targeting concurrent pathological pathways for the Lewy body diseases in the Chinese population.

[Generalized granuloma annulare: A clinicopathological study]. / Granulome annulaire généralisé : étude anatomoclinique.

BACKGROUND: Granuloma annulare (GA) is a benign granulomatous skin disorder that is generalized (GGA) in 15 % of cases. Although many case reports describe a relationship between GGA and systemic diseases, few large series have been published, and their association is debated. We present herein a series of GGA in order to describe their clinical and histological features. PATIENTS AND METHODS: We included all biopsy-proven cases of GA presenting at the dermatopathology laboratory of Strasbourg where generalized (i.e. over 10 lesions). Clinical features were obtained from patients' medical files. RESULTS: We included 35 GGA, with a sex ratio of 0.5. The mean age was 54 years. Lesions were annular or non-annular in equal measure and were symptomatic in 25 % of cases. Most patients (77 %) had an associated disease, already known in 60 % of cases, including dyslipidemia (27 %), diabetes mellitus (20 %), immunosuppressive drugs (17 %), atopy (17 %), auto-immune disease (17 %), hematological disease (14 %), and cancer (9 %). Histological analysis revealed the predominant pattern to be interstitial (54 %) rather than palisading (20 %), having no correlation with clinical type. Eosinophils were frequent (46 %) in GA but were not correlated with systemic disease or drug taking. Among the 40 % of patients treated, 50 % had a successful outcome on topical corticosteroids, doxycycline, antimalarial drugs or phototherapy. DISCUSSION: GGA differs from localized GA, which is mostly associated with an already known systemic disease, whether metabolic, infectious or neoplastic, uncorrelated with clinical or histological features, and screening is necessary.

Clinicopathological features and outcomes of diabetic kidney disease with extracapillary hypercellularity: a Japanese single-center experience.

BACKGROUND: The prognostic significance of glomerular extracapillary hypercellularity (EXHC) in diabetic kidney disease (DKD) is unclear. The aim of this study was to investigate the clinicopathological features and outcomes of DKD patients with EXHC. METHODS: We studied 70 cases of renal biopsy-confirmed type 2 DKD that were diagnosed between 2004 and 2014 and compared the clinicopathological features and outcomes of 22 patients with EXHC (EXHC group) with those of 48 patients without EXHC (control group). All of the patients were Japanese. We assessed the renal biopsy specimens based on the Renal Pathology Society classification system. Clinical and laboratory data were collected at the time of the renal biopsy, and renal outcomes were assessed based on progression to end-stage renal disease (ESRD) requiring renal replacement therapy. The median duration of the observation period was 3 years. RESULTS: In pathological features, nodular sclerosis (Kimmelstiel-Wilson lesions) was observed more frequently in the EXHC group than in the control group (63.6% vs. 35.4%, P = 0.027). There were no significant intergroup differences in clinical features or renal outcomes. Univariate and multivariate Cox regression analyses of all patients showed that a high level of proteinuria, a low initial eGFR, and severe interstitial inflammation were poor prognostic factors. CONCLUSIONS: EXHC is related to nodular sclerosis, which is a known risk factor for ESRD. Careful observation is needed during the follow-up of DKD patients with EXHC, although there were no significant differences in renal outcomes between the EXHC and control groups.

Beta1- and Beta2-Adrenoceptors Expression Patterns in Human Non-small Cell Lung Cancer: Relationship with Cancer Histology.

Assessment of Beta-AR protein expression on tumour tissues might be a plausible strategy to select cancer patients who can benefit from Beta-blockers therapy. The aim of this study is to evaluate the differences between resected tissue specimens from primary lung cancer (adenocarcinoma (ADC) and squamous cell carcinoma (SCC)) in terms of expression pattern of Beta1- and Beta2-AR in both tumour and adjacent surrounding non-tumour tissue. This retrospective study was based on the analysis of 80 patients with histologically confirmed diagnosis of primary Non-Small Cell Lung Cancer (NSCLC) who received surgical treatment. The cases were carefully selected in order to obtain the most homogeneous sample in terms of histologic subtype (40 ADCs and 40 SCCs) and clinical stage (10 each). Beta1- and Beta2-AR expression was determined by immunohistochemistry and the staining evaluated by semi-quantitative scoring using the H-score method. In our NSCLC series, Beta1- and Beta2-AR are differentially expressed. Beta1-AR expression is present at low levels in both SCC and ADC. Likewise, when compared with the matched surrounding non-tumour tissues, Beta1-AR expression level was significantly lower in both histologic subtypes. Conversely, Beta2-AR is highly expressed in both histologic subtypes, but clearly highly expressed in ADC when compared with SCC and with their matched surrounding non-tumour tissue. Overall, this clinicopathological study highlights the differential expression of Beta1- and Beta2-AR in ADC and SCC. Repurposing non-selective Beta-blockers in oncologic setting might be a suitable therapeutic strategy for lung ADC. Graphical abstract.

Sinusoidal Obstruction Syndrome and Postoperative Complications Resulting from Preoperative Chemotherapy for Colorectal Cancer Liver Metastasis.

BACKGROUND/AIM: The aim of this study was to investigate the effects of preoperative chemotherapy on the healthy, metastasis-free part of the liver in colorectal cancer patients with liver metastasis, and the relationship between chemotherapy and postoperative complications. PATIENTS AND METHODS: Our study included 90 cases of colorectal cancer liver metastasis resected after preoperative chemotherapy. The patients were divided into three groups according to the received chemotherapy regimen: 20 cases received mFOLFOX6, 54 cases a combination of mFOLFOX6 with bevacizumab, and 16 cases a combination of mFOLFOX6 and cetuximab or panitumumab. RESULTS: The mean numbers of sinusoidal injuries for each chemotherapy type were compared. The group treated with the combination of mFOLFOX6 and bevacizumab showed a lower extent of sinusoidal injury relative to other groups; this intergroup difference became increasingly remarkable as the number of chemotherapy cycles increased. Complications of various extents were found in all three groups, but no significant differences were observed between the three groups. CONCLUSION: In cases where preoperative chemotherapy was extended over a long period, combined use of bevacizumab was thought to be effective because of stabilization of disturbed liver hemodynamics resulting from sinusoidal injury suppression effects, allowing effective distribution of anti-cancer agents to tumors.

Sarcomatous Component in Pancreatic Adenosquamous Carcinoma: A Clinicopathological Series of 7 Cases.

BACKGROUND/AIM: The aim of this study was to examine the clinicopathological features of pancreatic adenosquamous carcinoma (PASC). PATIENTS AND METHODS: Our study included seven patients who underwent resection of PASC. RESULTS: PASC is characterized by large tumors and strong infiltration into the major blood vessels and other organs, forcing many patients to undergo extended resections. In addition, all patients experienced liver metastasis recurrence following surgery, with a very poor prognosis. Histopathologically, a poorly differentiated sarcomatous component existed in all patients in addition to an adenocarcinoma component and squamous carcinoma component. Although P40 staining for the sarcomatous component was positive along with squamous carcinoma, E-cadherin expression disappeared while vimentin was expressed. It has been suggested that it is highly likely that these sarcomatous components are derived from squamous carcinoma and have an impact on prognosis. CONCLUSION: The sarcomatous component may be related to the biological malignancy of PASC.

Clinicopathological Study of Resections of Intraductal Papillary Neoplasm of the Bile Duct.

BACKGROUND/AIM: The aim of this study was to examine the clinicopathological features of intraductal papillary neoplasm of the bile duct (IPNB) and investigate their relationships with intraductal papillary mucinous neoplasm (IPMN). PATIENTS AND METHODS: Our study included 104 patients who underwent resection of tumors that showed papillary growth within the bile duct and pancreas. RESULTS: Comparisons were performed based on subtypes and histological grades. The presence of various histological grades was confirmed in both the IPNB group and the IPMN group, and statistical significance was found in the between-group comparisons of subtypes and histological grades. It was shown that while all patients who underwent IPNB resection did not match the classifications proposed by Nakanuma et al., they did reflect classification characteristics. CONCLUSION: IPNB and IPMN have common clinical histological features. Common features between IPNB subtype classifications were also identified, which may provide novel diagnostics.

Clinicopathologic study of 10 cases of gastric adenocarcinoma with hepatoid or enteroblastic differentiation.

Gastric adenocarcinoma with hepatoid or enteroblastic differentiation (GAHED), known also as AFP-producing carcinoma, is a rare neoplasm. Ten cases with GAHED and 209 cases without GAHED were selected. Clinicopathological features of GAHED were investigated. The disease-free survival (DFS) of the GAHED group was compared with that of the non-GAHED group. Grossly, the tumours consisted of two early types and eight advanced types. Histologically, all tumours were composed of various proportions of tubular, cribriform, papillary, solid, and/or trabecular growth patterns of clear to slightly eosinophilic tumour cells. Hyaline globules were observed in all tumours. AFP and Hep-Par1 were immunoreactive in all tumours. In fluorescence in situ hybridisation of HER2 gene/chromosome 17, the amplification of HER2 gene was observed in two cases that showed positive reaction for HER2 protein. Clinical follow-up was available in nine cases. Regarding the clinical outcome, 3 and 6 patients were alive without disease and alive with disease, respectively. In a statistical analysis, the DFS of the GAHED group was significantly worse than that of the non-GAHED group. GAHED is morphologically characterised by various growth patterns of clear to slightly eosinophilic tumour cells and intracytoplasmic possession of hyaline globules. This tumour may have the potential to behave in an aggressive clinical fashion.

Clinicopathological and long-term prognostic features of membranous nephropathy with crescents: a Japanese single-center experience.

BACKGROUND: Three recent studies from the United States and China reported the clinicopathological features and short-term prognosis in patients with membranous nephropathy (MN) and crescents in the absence of secondary MN, anti-glomerular basement membrane (GBM) antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). METHODS: We compared clinicopathological and prognostic features in 16 MN patients with crescents (crescent group) and 38 MN patients without crescents (control group), in the absence of secondary MN, anti-GBM antibodies, and ANCA. Median follow-up periods in the crescent and control groups were 79 and 50 months, respectively. RESULTS: Decreased estimated glomerular filtration rates (<50 mL/min/1.73 m2), glomerulosclerosis, and moderate-to-severe interstitial fibrosis were more frequently observed in the crescent group than in the control group (P = 0.043, P = 0.004, and P = 0.035, respectively). Positive staining rates for glomerular IgG2 and IgG4 were significantly different between the 2 groups (P = 0.032, P = 0.006, respectively). Doubling of serum creatinine during follow-up was more frequently observed in the crescent group than in the control group (P = 0.002), although approximately two-thirds of patients in the crescent group were treated with immunosuppressive therapy. Crescent formation and interstitial fibrosis were risks for doubling of serum creatinine [hazard ratio (HR) = 10.506, P = 0.012; HR = 1.140, P = 0.009, respectively]. CONCLUSIONS: This is the first Japanese study demonstrating significant differences in clinicopathological and prognostic features between the 2 groups. Most patients in the crescent group may develop a long-term decline in renal function despite immunosuppressive therapy.

Vulvar cancer in Tunisia: Epidemiological and clinicopathological features multicentric study.

OBJECTIVE: To describe for the first time the epidemiologic and clinico-pathologic characteristics of vulvar cancer in Tunisia. DESIGN: Two parts are distinguished in this study: Part1: Multicentric retrospective study about the characteristics of all cancer cases diagnosed during a 17-years period (January 1998-December 2014) in three departments of Gynecology and Obstetrics: one in south Tunisia and two in the capital. Part 2: To determine the Incidence trend of invasive vulvar cancer in North Tunisia 1994-2009, on the basis of North Cancer Registry of Tunisia. RESULTS: A total of 76 cases of vulvar cancer were recorded. The median age at diagnosis was 65.4years and 86.9% of patients were more than 55years old. The symptomatology was dominated by vulvar pruritus in 48.7%. The average size of the tumor was 3.96cm. Stage III was the most frequent (53.7%) followed by stage II (28.3%). Only 10.4% of tumors were at stage I. The most common histologic type of vulvar malignancy was squamous cell carcinoma (SCC) (94.7%). Standardized incidence varied from 1.2/100 000 (1994) to 0.5/100 000 (2009). There was significant decrease of Standardized incidence (APC of -8.8% per year, 95% CI: -5.5%, -9.0%-p<0.001). CONCLUSION: Vulvar cancer in Tunisia is a rare disease, occurs mostly in elderly women, and is diagnosed at advanced stages. Our findings emphasize that a greater effort should be made to facilitate early diagnosis, as treatment in earlier stages is less extensive and potentially curative.

Diagnostic accuracy of parkinsonism syndromes by general neurologists.

INTRODUCTION: Movement disorder specialists can achieve a high level of accuracy when clinically diagnosing parkinsonism syndromes. However, data about the diagnostic accuracy among general neurologists is limited. OBJECTIVES: This study investigated the recent diagnostic accuracy of parkinsonism syndromes by general neurologists. METHODS: A retrospective examination of 1362 post-mortem cases diagnosed in the years 2000-2012 by neuropathologists was performed. Out of these cases, we identified 111 patients who received a clinical parkinsonism diagnosis during life and 122 patients who received a neuropathological diagnosis of a parkinsonism syndrome post-mortem including 11 incidental cases. RESULTS: Fifty-eight (75.3%) of the 77 patients who had received clinical Parkinson's disease (PD) diagnoses were confirmed after the neuropathological examination. The sensitivity of the clinical diagnosis for idiopathic Parkinson's disease (PD) was 89.2% and the specificity was 57.8%. The corresponding numbers for progressive supranuclear palsy (PSP) were 52.9% and 100%, and for multiple system atrophy (MSA) were 64.3% and 99.0%, respectively. CONCLUSIONS: Parkinson's disease is heavily overdiagnosed by general neurologists, whereas parkinsonism plus syndromes are underdiagnosed. Despite improvements in the diagnostic methods during recent decades and the development of diagnostic clinical criteria for parkinsonian syndromes, the diagnostic accuracy of Parkinson's disease remains relatively low, and 1/4 of diagnoses are incorrect.

Malignant transformation of hyperplastic gastric polyps: An immunohistochemical and pathological study of the changes of neoplastic phenotype.

In spite of the evidence that the malignant transformation of gastric hyperplastic polyps (HPs) is a rare event, it must always be taken into account during diagnosis. The aim of the current study was to clarify the mechanism of the malignant transformation of gastric hyperplasia polyps, with focus on phenotypic expression, cell proliferation and p53 overexpression. Immunohistochemistry for mucin phenotypic markers, including MUC1, MUC2, MUC5AC, MUC6, tight junction factors (claudin-3, -4 and -18), an intestinal phenotypic marker [caudal type homeobox 2 (Cdx2)], Ki-67 proliferative index and p53 overexpression, was performed on archival specimens of gastric polyps excised from six patients. Histologically, the intermingled components of several lesions were present in these polyps. Furthermore, the cancer components were predominantly differentiated adenocarcinoma. Immunohistochemically, all hyperplastic components expressed MUC5AC, but did not exhibit positivity for MUC2. Additionally, the majority of hyperplastic components were immunonegative for claudin-3, while claudin-3 positivity was observed in the majority of areas of dysplasia and carcinoma. Expression of claudin-4 was also observed in the majority of cases and claudin-18 was preserved in the hyperplastic, dysplastic and adenocarcinomatous lesions of all cases. Nuclear accumulation of Cdx2 was detected in almost all the samples with dysplasia and carcinoma, while nuclear p53 was detected in 24-80% of the dysplastic areas and >85% of the cancer components. The Ki-67 labeling index appeared to correlate with neoplastic progression. The observations provided evidence that the mechanism underlying malignant transformation of gastric HPs may occur by multistep carcinogenesis, such as the hyperplasia-adenoma (dysplasia)-adenocarcinoma sequence, and these neoplastic cells may acquire various phenotypes during this process.