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Purpose: Recent literature data indicate a key role of apoptosis in the pathogenesis of inflammatory bowel disease. The aim of the study was to evaluate the expression of Bax, Bid, Bcl-2 and Bcl-xl in non-dysplastic and dysplastic epithelium in inflamated mucosa of patients with ulcerative colitis. Methods: The study consists of 18 patients with diagnosed ulcerative colitis. The expression of proteins was determined immunohistochemically. Results: Lack of Bax expression in normal epithelium of the inflamed intestinal mucosa (94.4%) and a weak expression of this protein were found in dysplastic glandular cells (67%). The Bax expression of dysplastic epithelium correlates with reduced severity of chronic inflammation (p<0.005). Bid expression in non-dysplastic glands was found in 67% of cases vs. 16% in dysplastic epithelium that was associated with the occurrence of epithelial erosions or ulcers (p<0.05). Moderate cytoplasmic expression of Bcl-xl was noted in 27.7% of patients in normal epithelium and in 66.1% within dysplastic lesions. Bcl-xl expression in dysplastic glandular cells correlated with the presence of neutrophils in the lamina propria (p <0.05). Conclusions: The immunohistochemical expressions of Bax, Bcl-2 and Bcl-xl increase and Bid protein expression decreases in dysplastic glandular tubes as compared to non-dysplastic intestinal epithelium in inflamed mucosa, which may suggest an imbalance of controlled cell death in ulcerative colitis. [ABSTRACT FROM AUTHOR]

Introduction: Sjögren's syndrome is an autoimmune disease belonging to the group of collagenases. It is characterized by lymphocytic infiltration of the exocrine glands, leading to their impairment or complete dysfunction. The inflammatory process usually involves cells of the salivary or lacrimal glands. However, also other organs and systems can be affected. Purpose: The presentation of a Sjögren's syndrome case. The pathologist's role in the disease diagnosis. Case presentation: A 63-year-old female patient with the enlarged left parotid salivary gland and symptoms of xerostomia and xerophtalmia was referred for ultrasound imaging and fine-needle aspiration biopsy (FNAB). Ultrasonography revealed inhomogeneous echostructure of the salivary gland with multiple tiny, oval, hypoechoic areas, hyperechoic zones of fibrosis and enhanced vascularization of the gland. The pathological analysis of FNA showed a benign lymphoepithelial lesion, and Sjögren's syndrome was suggested. Blood serum analysis found anti Ro-52 (SS-A), anti-La (SS-B) and anti-ANA antibodies at 1:1,000 titer. Sjögren's syndrome was diagnosed based on accessory investigations and the clinical condition of the patient. Conclusions: The pathomorphological analysis of fine-needle aspiration biopsy of the salivary gland contributed to the diagnosis of Sjőgren's syndrome in the patient. [ABSTRACT FROM AUTHOR]

Introduction: Malignant mixed tumor (MMT) is an exceedingly rare cutaneous adnexal carcinoma with a significant risk for aggressive behavior and a propensity for metastasis. This tumor occurs in a wide age range and is twice as common in woman than in men. MMT shows a predilection for the trunk and the extremist's foremost hands and feet. MMT may be confused clinically with many benign and malignant lesions. Therefore the histopathological and immunohistochemical examination is required for the correct diagnosis and treatment. Purpose: To present a case of MMT localized in the left toe with a special attention focused on its histopathology and differential diagnosis. Case presentation: A 56-year-old female was admitted with a nodular lesion on the left toe. A painless mass had been presented for one year with a significant increase in size within the past three month. The patient underwent wide surgical excision. Histopathologically for the lesion was diagnosed it as a malignant mixed tumor. Immunohistochemical examination revealed positive reaction for cytokeratin AE1/AE3/PCK26, vimentin and S-100. Histochemical reaction for PAS in the chondromyxoid tumor stroma was negative. Conclusion: Correct histopathological diagnosis and complete excision with wide disease-free margins before metastasis result in MMT free survival. [ABSTRACT FROM AUTHOR]

Introduction: Malignant melanoma is a neoplasm arising from the melanocyte cells of the skin. Of all cancers diagnosed in Poland in 2009, it was the twelfth most-common cancer in men and the fourteenth in women. However, this type of cancer is characterized by a quick development of metastases and a high mortality rate. Melanoma usually metastasizes to the lymph nodes, then infiltrates the lungs, brain, liver, bones, and gastrointestinal tract, for example, the small intestine. Purpose: To present two cases of metastatic melanoma with a poor prognosis involving the small intestine. Case presentation: In the first case, a 50-year-old male patient with abdominal pain and distension was admitted to hospital and qualified for surgical treatment. The second case, a 45-year-old male patient, presented with severe abdominal pain and sudden obstruction of the gastrointestinal tract. Both patients had previous medical histories of malignant melanoma found on the skin of the subscapular area. The pathomorphological reports confirmed metastatic melanoma of the small bowel. The patients underwent partial resection of the small bowel with end-to-end anastomosis. Conclusion: Patients with metastatic melanoma originating from the small intestine had a poor prognosis. Due to the difficult diagnostic control of melanoma that develops on the skin and insufficient therapy for advanced stage cancer, we should develop early diagnostics for cutaneous melanoma through cancer prevention education in the population. [ABSTRACT FROM AUTHOR]

Purpose: The aim of study was to detect PRL-3 protein in sera of patients with colorectal cancer. Methods: The study group consisted of 22 patients with colorectal carcinoma and 10 healthy controls. The serum concentration of PRL-3 protein was evaluated by the ELISA method. Results: In the study group with colorectal cancer, the level of PRL-3 protein in preoperative sera was negative (<0.115ng/ml) in 7 cases while the mean value of PRL-3 concentration was 0.616ng/ml (range 0.206-2.072ng/ml) in 15 patients. No statistically significant differences between the study group and healthy controls were observed. Our data showed that increase in level of PRL-3 protein in sera of patients with colorectal cancer is associated with greater tumor size (p<0.05). Conclusions: PRL-3 protein was found to be present in sera of patients with colorectal cancer. However, our study indicates lack of clinical usefulness of determining the levels of PRL-3 in the sera of patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: In Poland, cervical screening tests are performed in the group of women aged 25 to 59 years. The aim of the study was to evaluate the usefulness of the Bethesda System in assessing cervical smears. Methods: Results of gynecological cytologies performed in the UPDC in the period of 01 August 2011 - 31 July 2012 were analyzed. Of the material, cases subjected to histopathological analysis in correlation with cytological outcome were chosen. Results: Of 19,887 patients who underwent cytology, 603 had atypical epithelial cells. In 83/603 cases, histopathological specimens were available for analysis. The level of cytological and histopathological compatibility was the highest in the HSIL group (75%), being the lowest in patients with LSIL (40%). It should be emphasized that in HSIL cases, histological specimens showed no evidence of normality. Conclusions: The level of cytological and histopathological compatibility was the highest in the HSIL group (75%). The compatibility was the lowest in the LSIL group (40%). It should be emphasized that in HSIL cases, histological specimens showed no evidence of normality. [ABSTRACT FROM AUTHOR]

Histopathological evaluation plays a key role in the diagnosis of colorectal cancer (CRC). Tumor-related local inflammation is regarded as a novel prognostic parameter. Neutrophils constitute one of the main types of inflammatory cells. The aim of the present study was to evaluate the prognostic value of intratumoral tumor-associated neutrophils (intraTANs), stromal TANs (stromaTANs) and necrosis, as well as their combined parametric value in formalin-fixed paraffin-embedded tissue sections from patients with CRC. For this purpose, a retrospective study of 160 patients with CRC who underwent surgery was conducted. The association of intraTANs, stromaTANs, necrosis and their combined parametric value with the clinicopathological features of patients with CRC was examined. The Kaplan-Meier method and the log-rank test were used to compare survival curves. To identify independent prognostic factors, uni- and multivariate Cox proportional hazards regression models were used. StromaTANs were associated with lymph node metastasis (P=0.049) and tumor deposits (P=0.041). In addition, necrosis was found to be associated with venous (P=0.003), lymphatic (P=0.007) and perineural (P=0.015) invasion, as well as with lymph node metastasis (P=0.033), the number of invaded lymph nodes (P=0.012), and lymph node pouch invasion (P=0.043). Furthermore, necrosis was found to be associated with the white blood cell count (P=0.030), neutrophil count (P=0.011), the combined neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (NLR-PLR) (P=0.038), and the combined platelet and NLR (PLT-NLR status) (P=0.030), as well as with the serum carcinoembryonic antigen (CEA) levels following surgery (P=0.011) and the monocyte-to-lymphocyte ratio (P=0.023). The combined parametric value was found to be associated with pT stage (P=0.049), venous (P=0.034) and lymphatic (P=0.026) invasion, and with serum CEA levels prior to surgery (P=0.029). The analysis of the 3-year disease-free survival (DFS) time revealed that tumor growth [hazard ratio (HR), 2.070; 95% CI, 1.837-3.808; P=0.003] and the combined parametric value (intraTANs, stromaTANs and necrosis, HR, 1.577; 95% CI, 1.372-3.032; P=0.028) were independent factors for patients with CRC. Taken together, the findings of the present study demonstrated that the combined value of neutrophils and necrosis examined in the cancerous tissue may be used as a prognostic factor for the 3-year DFS time in patients with CRC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Jakubowska et al.)

The efficacy of cancer immunotherapy has been actively explored in the treatment of various malignant neoplasms of the gastrointestinal tract. In light of recent reports, the present study aimed to investigate the combination of the absolute lymphocyte count (ALC), percentage of tumor-infiltrating lymphocyte (TILs) and tumor progression status in patients with colorectal cancer (CRC) who underwent surgery. The medical records of 160 patients diagnosed with CRC were retrospectively reviewed. TILs were determined as a percentage of mononuclear inflammatory cells in the total intratumoral or stromal area as determined in five high power fields (magnification, x200-400), at the invasive front and in the centre of the tumour. Blood samples were obtained within 3 days prior to and 7 days following the surgical treatment. The assessment of the TIL percentage was performed in the tissue at the invasive front and in the centre of the primary tumour mass in combination with the determination of ALC in whole blood samples. The samples were obtained prior to and after surgery from patients with CRC, and the tumour progression status was also assessed (TILs/ALC/tumour progression status). A significant association was observed between the percentage of TILs in the main mass of tumour and the tumour size (P=0.031), the pT stage (P=0.049) and the incidence of necrosis (P=0.037) following surgery. The histological type was associated with the evaluated combined parameters prior to surgery (P=0.046). Lymph node pouch invasion was associated with TILs at the invasive front of tumour and with ALC prior to and after surgery (P=0.006 and P=0.037). Furthermore, the data indicated that the percentage of TILs located on the invasive front and centre of the tumour, and the ALC prior to and following surgery correlated with the treatment status (P=0.032, P=0.018, P≤0.001 and P≤0.001). A significant association was noted between eight features and evaluated combined parameters following surgery. These included the tumour size (P=0.021), TNM stage (P<0.001), tumour deposits (P=0.001), incidence of necrosis (P=0.042) and lymph node metastasis (P<0.001). Furthermore, the degree of invasion of venous (P<0.001), lymphatic (P<0.001) and perineural (P<0.001) sites was also significantly associated with TILs, ALC obtained after surgical treatment and tumor progression status. The data demonstrated that local and systemic chronic inflammation was associated with tumour progression in patients with CRC., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021, Spandidos Publications.)

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide. Patients with CRC are diagnosed based on various predictors, including performance status, clinicopathological factors and TNM classification. The aim of the present study was to analyze the neutrophil and lymphocyte counts, as well as the neutrophil-to-lymphocyte ratio (NLR) in pre- and postoperative blood samples of patients with CRC in correlation with specific anatomical variables and disease- free survival (DFS). The variables pre- and postoperative neutrophil count (preNEU and postNEU, respectively), lymphocyte count and NLR were significantly higher in cancer patients than those noted in healthy subjects (all P<0.001). PreNEU count correlated with tumor size, necrosis and tumor budding (R=0.204, P=0.014; R=0.189, P=0.023; R=-0.174, P=0.036, respectively). Moreover, postNEU was associated only with the histological type (R=0.174; P=0.047). The PreLYMPH count was correlated with distant metastasis (R=-0.153, P=0.046). PreNLR and postNLR were associated with the expression of various histological markers of disease progression. Analysis of DFS indicated that the postNEU count in the low group exhibited a tendency to lower DFS duration, although the results were not significant (P=0.055). In conclusion, the present study indicated a significant correlation between the factors analyzed in blood samples of CRC patients and the disease progression markers., (Copyright © 2020, Spandidos Publications.)

Background: Colorectal cancer is the third most common malignancy worldwide. Therefore, it is critically important to identify new useful markers that can be easily obtained in routine practice. Inflammation is a crucial issue in the pathogenesis and development of cancer., Aim: To evaluate the prognostic value of absolute monocyte count, monocyte to lymphocyte ratio (MLR), the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (NLR-PLR), and combined platelet and neutrophil-to-lymphocyte ratio (PLT-NLR) in peripheral blood samples of patients with colorectal cancer undergoing surgery., Methods: We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery, and 42 healthy controls. The status of absolute monocyte count, MLR, NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery. Haematologic factors were examined in correlation with the type of tumour growth, tumour size, histological type, percentage of mucinous component, grade of malignancy, Tumour-Node-Metastasis stage, venous, lymphatic and perineural invasion of cancer cells, status of lymph node invasion and the presence of cancer cell deposits. The Kaplan-Meier method and the long-rank test were used to compare survival curves. To determine independent prognostic factors, univariate and multivariate Cox proportional hazards regression models were applied., Results: The PLT-NLR status was correlated with tumour size and the presence of perineural invasion ( P = 0.015; P = -0.174, P = 0.037). Moreover, high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component (NLR-PLR: P = 0.002; P = 0.009; PLR-NLR status: P = 0.002; P = 0.007). The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery [HR = 2.903, 95%CI: (1.368-6.158), P = 0.005] and the status of lymph node metastasis [HR = 0.813, 95%CI: (0.653-1.013), P = 0.050] were independent prognostic factors in colorectal cancer patients., Conclusion: The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The presence of tumor cells in the large intestine stimulates hypoxia and local inflammatory mediators that activate numerous inflammatory cells, including a diverse lymphoid tumor cell population. The aim of the present study was to evaluate tumor-infiltrating lymphocytes (TILs) located in the invasive primary tumor, surrounding deposits of tumor cells and those present in distal metastatic cells in the liver of patients with colorectal cancer. Furthermore, the correlation of TILs with anatomical parameters was assessed. The study group included 123 patients with primary tumor colorectal cancer without distant metastasis, 25 cases with deposits of colorectal cancer cells and 15 cases of colorectal cancer liver metastasis. TILs were assessed in tissues stained with hematoxylin-eosin using light microscopy and evaluated by two independent pathologists blinded to the clinical information. Infiltration of TILs in the invasive front of primary tumor was stronger compared with those surrounding deposits of cancer cells and liver metastases (P<0.001). TILs in the invasive front of primary tumor masses were associated with various variables linked with tumor progression and inflammatory cell infiltrate. TILs distributed around the deposits of cancer cells were associated with postoperative treatment; however, those localized in the invasive front of liver metastases were correlated with preoperative therapy. In conclusion, TILs assessment in primary tumors of colorectal cancer, surrounding deposits of tumor cells and in the metastatic cells in the liver may be helpful in understanding the role of these cells in the organization of immune response., (Copyright: © Jakubowska et al.)

Cancer cells are characterized by a low antigenic immunogenicity, a rapid growth and an immunosuppressive effect on the extracellular matrix. These properties induce a weak immune response in colorectal cancer (CRC) carcinogenesis. It is therefore crucial to determine the composition of the inflammatory mass, including neutrophils, macrophages and eosinophils in the tumor tissue of patients with CRC, and to analyze other clinicopathological parameters. The present study included 144 patients diagnosed with CRC. Tissue samples obtained from routine histopathological diagnosis were stained with hematoxylin and eosin. Inflammatory cells were assessed in the invasive front and in the center of the tumor by light microscopy under a high-power magnification. The percentage of neutrophils in the invasive front was significantly higher compared with that in the center of the tumor mass (P<0.01). Macrophages and eosinophils were present in the invasive front and in the center of tumor mass in most cases. The presence of neutrophils, macrophages and eosinophils was correlated with various clinicopathological features. Patients with macrophages present in the center of tumor mass had longer disease-free survival time (P=0.041). In conclusion, the present study demonstrated that the inflammatory cell infiltrate served a significant role in the immune response of patients with CRC. It should be noted that the presence of macrophages localized in the stroma of the central part of the primary tumor mass was associated with the survival time of patients with CRC.

Squamous cell carcinoma (SqCC) of the breast should be differentiated between the primary skin keratinizing squamous carcinoma and squamous metaplastic cancer. In the current study, the cases of two patients who were diagnosed with SqCC originated from skin and the breast were discussed. A fine-needle aspiration biopsy confirmed the presence of atypical squamous cells. In both cases, the microscopic examination of the surgical specimen revealed a malignant neoplasm differentiated into SqCC characterized by keratinizing cancer cells with abundant eosiphilic cytoplasm with large, hyperchromatic vesicular nuclei. Immunohistochemical studies showed negative for progesterone and estrogen receptors and human epidermal growth factor receptor 2. Moreover, negative expression of cytokeratin 7 and 20 was confirmed. The diagnosis of the both tumors was established based on the detailed analysis of clinical, macroscopical and microscopical information. SqCC localized in the breast is a great diagnostic challenge in pathomorphology and more attention should be paid for analysis of such lesions in daily practice.

The local mechanisms of antitumor immune defense determine the development and organization of the tumor microenvironment, and the composition and relative proportions of the inflammatory cell population affect the quality and characteristics of the immune response. The aim of the present study was to conduct a quantitative morphological evaluation of two types of tumor-infiltrating lymphocyte (TILs) populations, including those located in the stroma and intraepithelial cancer structures, in the invasive front and the center of the tumor in patients with colorectal cancer (CRC). The study included 160 patients with CRC who had undergone surgery. The tissue material was stained with hematoxylin and eosin, as used in routine histopathological diagnosis, and the two TIL populations were observed and counted with light microscopy. The relative extent of infiltration of stromal and intraepithelial TILs into the front and center of the primary tumors was similar. The extent of infiltration by stromal TILs was negatively correlated with the morphological features of tumor progression including the cancer infiltration of blood vessels (P=0.016), the invasion of lymph vessels (P=0.007), perineural invasion (P=0.036), lymph node involvement (P=0.047) and distant metastases (P=0.032). The infiltration by intraepithelial TILs was positively correlated with a desmoplastic reaction (P=0.002). Disease-free survival time was statistically shorter in patients without intraepithelial TILs in the center of the primary tumor mass (P=0.049; hazard ratio = 1.45). These results confirm that the infiltration of TILs into the invasive front and center of the tumor in patients with CRC serves an important role in the invasion and progression of the disease, and should be considered in routine histopathological examinations.

The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC). In addition, the correlation between cellular inflammatory infiltration, and anatomoclinical and histopathological features of patients was evaluated. The study involved 160 patients diagnosed with primary operable CRC. The local inflammatory infiltrate was assessed in the invasive front and center of the tumor using light microscopy with hematoxylin and eosin (H&E) staining, according to the Klintrup-Makinen criteria, tumor stroma percentage, and Glasgow microenvironment score. The inflammatory infiltrate in the invasive front of the tumor was correlated with gender (P=0.018), the invasion of blood vessels (P=0.020) and lymph vessels (P=0.038), the presence of tumor-infiltrating lymphocytes in the invasive front (P=0.033) and center (P<0.001) of the tumor, fibrosis (P<0.001), and the degree of desmoplasmic stroma (P=0.004). In contrast, inflammatory infiltration in the center of the tumor was associated with the tumor node metastasis stage (P=0.012), Dukes' stage (P=0.009), primary tumor stage (P=0.036), lymph node status (P=0.005), number of lymph nodes (P=0.006), invasion of lymph node pouches (P=0.021), size of lymph node metastasis (P=0.025) and the degree of desmoplasmic stroma (P=0.002). The low-group, who demonstrated an absent or weak inflammatory cell infiltrate in the invasive front of the tumor, had a statistically significant shorter disease-free survival (DFS) time (P=0.004). Inflammatory cell infiltrate in the invasive front was identified as an independent predictive factor in CRC (P=0.041). In conclusion, the degree of inflammatory cell infiltration in the invasive front of the primary tumor significantly affects various variables that determine disease progression and DFS rates of patients with CRC. Furthermore, the routine histopathological assessment of this parameter in tissue stained with H&E may have potential prognostic value.

Survivin is one of the apoptosis-related inhibitors that is associated with a more aggressive behavior and a poor prognosis in numerous types of malignancies, including colorectal cancer (CRC). The objective of the present study was to perform immunohistochemical tissue analysis of survivin expression and serum analysis of survivin levels in CRC patients. The study group consisted of 55 CRC patients. Survivin expression was assessed by immunohistochemistry in 38 patients using monoclonal antibodies. Color reactions were observed in the nucleus and cytoplasm of the cancer cells. The expression was defined based on the H-score method. The level of survivin was determined using the enzyme-linked immunosorbent assay method. A positive immunoreaction was observed in the tumor tissues of 84.2% (32/38) of patients with CRC, consisting of nuclear (63.2%; 24/38) and cytoplasmic (81.6%; 31/38) expression. The survivin nuclear expression was associated with tumor mass location and the presence of distant metastases (P=0.048 and P=0.026, respectively). Survivin was detected in the sera of 38.2% (21/55) of CRC patients and in 81.8% (18/22) of healthy individuals. Serum protein levels were found to correlate with hematocrit (P=0.035), hemoglobin (P=0.008) and albumin (P=0.045), but not with any of the investigated clinicopathological parameters. The immunohistochemical positive reaction of survivin in the nuclei of cancer cells may condition their proliferative capacity, which is associated with higher risk of developing metastatic foci. Thus, the present study suggests that the expression of survivin may have diagnostic implications in cancer of the colon and thus requires further research. By contrast, the survivin serum level in CRC patients appears to be diagnostically ineffectual for clinical use.

Pancreatic ductal adenocarcinoma (PDAC) is a rare neoplasm that affects the gastrointestinal system, and is characterized by a high mortality rate. It has been demonstrated that apoptosis has a significant role in the regulation of cancer cells. Therefore, the aim of the present study was to immunohistochemically assess the expression of proteins belonging to the caspase family, namely caspase-8, pro-caspase-3 and cleaved (active) caspase-3 in pancreatic cancer. The study group consisted of 29 patients exhibiting PDAC. Protein expression was evaluated by immunohistochemical methods. The expression of caspase-8 in normal cells was negative in 17.2% of cases and positive in 82.8% of cases. All cases demonstrated pro-caspase-3 expression in normal pancreatic cells, compared with 93.1% of cancer cells. Staining for activated caspase-3 was positive in 27 normal tissue cases, compared with positivity in only 10 cancer cases. Caspase-8 expression positively correlated with cleaved caspase-3 expression in the cytoplasm of cancer cells (P<0.002). Caspase-3 expression was identified to correlate with inflammatory peritumoral infiltration (P<0.015). No correlation was observed between caspase expression and any other clinicopathological parameters. The results of the present study demonstrated aberrant initiation of cancer cell apoptosis in PDAC via a decrease in caspase-8 expression, which may lead to disorders in the activation of effector caspase-3.