Tertiary Lymphoid Structures in Colorectal Cancers and Their Prognostic Value.

BACKGROUND: Tumor-infiltrating lymphocytes (TIL) in tumour stroma are considered to be involved in the elimination of malignant cells and prevention of metastasis formation. TIL consist of T lymphocytes including cytotoxic lymphocytes that are a constituent part of the effector mechanism of anti-tumour immunity and B lymphocytes that can form tertiary lymphoid structures (TLS). TLS has been described in several solid tumours and colorectal carcinoma (CRC), and the influence on the local and systemic anti-cancer response. AIM: This study aimed to quantify the presence of TLS in CRC patients and to determine their role in tumour progression. PATIENTS AND METHODS: The study included 103 patients with CRC who underwent surgery at the University Clinic of Digestive Surgery in Skopje, whose operative material was analysed at the Institute of Pathology, Medical Faculty in Skopje. The density of TLS was determined and correlated with the neoplasm status of local growth (T), positive lymph nodes, lymphatic invasion, and stage of the disease and tumour grade. RESULTS: The density of TLS was significantly higher in patients with higher stage, lower T status, and negative lymph nodes, in patients with no lymphatic invasion and with better-differentiated tumours. CONCLUSION: The density of TLS plays an important role in controlling the tumour growth, and it can be a parameter for neoplasm progression in CRC patients. The density of TLS influences the control of tumour progression.

EBV Positive Gastric Carcinomas and Their Clinicopathological Characteristics.

BACKGROUND: The understanding of the etiopathogenesis of gastric carcinoma (GC) can be a base for development of new therapeutic methods to reduce mortality and to increase survival in patients with GC. The percentage of Epstein - Barr virus (EBV) positive gastric carcinomas is uncertain, and the etiologic importance of EBV in the pathogenesis of GC has still not been elucidated. AIM: This study aimed to determine the percentage of EBV associated GC as well as to determine their clinicopathological characteristics. MATERIAL AND METHODS: The study included 80 patients with GC who were analysed for ethnicity, local growth of a tumour (T status), the presence of nodal metastases (N), the presence of distant metastases (M), stage of the disease and degree of carcinoma differentiation. For detection of EBV, immunostainings were performed on tumour tissue and the peripheral non-tumour gastric mucosa. RESULTS: Positive immunostaining with an antibody against EBV was found in 19 (23.75%) of the 80 patients with gastric carcinomas. EBV immunostainings were significantly different in patients with or without metastasis and between patients of Macedonian and Albanian ethnicity (p < 0.0001, p < 0.009, respectively). EBV immunoexpression was significantly associated with the presence of distant metastases and with patients of Albanian ethnicity. CONCLUSION: Association of EBV immunostainings with distant metastasis in patients with GC suggests the influence of EBV infection on the progression of gastric carcinoma. Due to scarce and doubtful literature data on EBV associated GC, further studies are necessary to determine the role of EBV regarding aetiology, treatment and prognosis in patients with EBV associated gastric carcinoma.

HER2 Positive Gastric Carcinomas and Their Clinico-Pathological Characteristics.

BACKGROUND: HER2 protein expression in gastric carcinoma, in correlation with existing, acknowledged prognostic factors which include the parameters that determine the TNM stage of the disease, could become the basis for ongoing research in the field of molecular targeted and personalised therapy. AIM: To determine the expression of the HER2 protein in gastric carcinoma and to correlate the expression of a HER2 protein with clinicopathological characteristics of the disease. MATERIAL AND METHODS: The data of HER2 protein expression and the parameters of the TNM classification were obtained from the histopathological reports of the Institute of Pathology in Skopje, and for the clinical stage we used patient's files from the University Clinic for Abdominal Surgery in Skopje. RESULTS: The analysis of the correlation of HER2 protein expression and TNM classification parameters pointed out a significant correlation between HER2 protein expression and intragastric localisation of gastric carcinoma (P = 0.005), and the tumour grade of differentiation (P = 0.034). There was also a positive correlation between HER2 protein expression pattern and positive lymph nodes in patients with gastric carcinoma (P = 0.03). The expression pattern of HER2 +++ was significantly more common registered in patients with positive lymph nodes (P = 0.03). CONCLUSION: The expression of HER2 protein could represent a biological marker with prognostic and predictive value in patients with gastric carcinoma. Considering the high mortality rate in patients with gastric carcinoma and lack of international standardised therapeutic approach, research of the role and significance of HER2 overexpression and Trastuzumab therapy may prove useful in the development of new therapeutic strategies.

Tumour Lymphocytic Infiltration, Its Structure and Influence in Colorectal Cancer Progression.

BACKGROUND: The role of the immune system in the control of tumour progression has been stressed, recently. Many studies indicate the fact that the immune system can prevent tumour progression in several types of human malignant neoplasms including colorectal cancer. According to some authors, a higher density of "tumour-associated lymphocytes" (TAL), in malignant neoplasms, correlate with prolonged survival of patients. AIM: This study aims to determine the structure and the influence of the immune cells, TAL, in the progression of colorectal cancer (CRC). PATIENTS AND METHODS: The study included 103 patients with CRC operated at the University Clinic of Digestive Surgery in Skopje, whose operative material was analysed at the Institute of Pathology, Medical Faculty in Skopje. The structure of tumor-associated cells and their density were determined and were correlated with neoplasm's grade, local growth (T), positive lymph nodes, lymphatic invasion and stage of the disease. RESULTS: CD4+, CD8+ and CD20+ lymphocytes (Ly) were found in TAL. The density of TAL was significantly different in neoplasms with different T status, lymphatic invasion, patients with and without nodal metastasis and patients with a different stage of the disease. The density of CD4+, CD8+, and CD20+ cells were significantly different in neoplasms with different T. The density of CD8+ and CD20+ lymphocytes was lower in patients with nodal metastasis and higher stage. CONCLUSION: The density of tumor-associated lymphocytes can anticipate the disease progression in patients with colorectal cancer, and the density of TAL influences the control of tumour progression.

Solitary Fibrous Tumor of the Pancreas: A Case Report and Review of the Literature.

Pancreas is an extremely rare abdominal localization of the solitary fibrous tumor (SFT). It usually grows asymptomatically for a long time before a diagnosis can be made on the basis of symptoms and/or mechanical complications. Due to the rarity and nonspecific clinical presentation, this entity is diagnostically challenging. We present a 47-year-old man with a history of progressive epigastric pain for the last two weeks, and jaundice, who was admitted to hospital for further investigation. Cystadenocarcinoma was suspected based on the radiologic findings, and a pancreatoduodenectomy was performed. The removed portion of the pancreas contained a 3.5 × 2 × 1.8 cm well-circumscribed, but not encapsulated white tumor mass with smooth cut surface, cystic component and duct dilatation within the tumor and within the adjacent pancreatic tissue. Based on the histology and immunostaining profile, a diagnosis of the solitary fibrous tumor was made. One week post-operatively, the patient died due to surgical complications. Microscopic and immunohistochemical examinations are necessary for accurate diagnosis of cystic SFT of the pancreas. Because there is limited data regarding the biological behavior of SFT with extra-pleural localization the authors recommend clinical follow-up for SFT treatment if the criteria of malignancy are not met.

Hepatocellular Carcinoma: Risk Factors, Diagnosis and Treatment.

Hepatocellular carcinoma (HCC) is the most often primary cancer of the liver and is one if the leading cause of cancer-related death worldwide. The incidence of HCC has geographic distribution with the highest levels in countries with developing economies. Patients with hepatocellular carcinoma have poor prognosis despite the achievements in surgery techniques and other therapeutic procedures and it is a reason why continuous attention should be paid to this issue. This article provides an overview of this disease based on an extensive review of relevant literature. The article summarizes the current risk factors, diagnosis, staging and the management of HCC.

LEIOMYOSARCOMA OF THE COLON.

INTRODUCTION: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the digestive tract. Leiomyosarcomas of the gastrointestinal tract are rare mesenchymal neoplasms which grossly and histologically resemble gastrointestinal stromal tumors. They may be differentiated from gastrointestinal stromal tumors by using immunohistochemistry and they are typically positive for a smooth muscle actin and desmin and negative for c-kit, CD34 and DOG1.1. They often express calponin and h-caldesmon. CASE REPORT: We present a case of a 59-year-old male with anemia, weight loss, intermittent abdominal pain and right abdominal mass. Colonoscopy revealed an exophytic ulcerated neoplastic mass in the ascending colon and abdominal computed tomography scan showed an ill-defined heterogeneous tumor mass which surrounded almost the whole ascending colon. The patient underwent right hemicolectomy and partial resection of ileum. Histopathological examination revealed a leiomyosarcoma composed of atypical spindle cells positive for a smooth muscle actin, desmin and vimentin, and negative for c-kit, CD34, S100 and neuron specific enolase. The patient is alive 8 months after the operation, undergoing chemotherapy. CONCLUSION: We have concluded that the multimodal approach comprising chemotherapy and complete surgical resection controls the leiomyosarcomas.

Superficial leiomyomas of the gastrointestinal tract with interstitial cells of Cajal.

OBJECTIVE: Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. MATERIALS AND METHODS: We analyzed 8 cases of superficial leiomyomas and one deep leiomyoma, received in our institutions as endoscopically or surgically obtained material. The tumor sections were immunohistochemicaly stained with CD117, CD34, NF, S100, αSMA, desmin, caldesmon and mast cell antigen. RESULTS: All leiomyomas showed diffuse positivity for αSMA, caldesmon and desmin. All of them had CD117 and CD34 positive cells morphologically identical to the interstitial cells of Cajal between smooth muscle fibers, 5 had S-100 and NF positive cells and 2 showed positivity for GFAP. The cells were found in different quantity; they were usually diffusely scattered through the tumors without predilection site, forming small groups in some areas. CONCLUSION: CD177, CD34, S-100 and NF positive cells are present in superficial leiomyomas and they may suggest common origin of GI stromal tumors.

Non-Tumor Cystic Lesions of the Adrenal Gland.

UNLABELLED: Adrenal cystic lesions are uncommon but due to the improved radiologic imaging techniques their appearance seems to increase. MATERIAL AND METHODS: We analyzed the clinical and radiological findings of 10 patients with adrenal cysts and the pathological features of the operative material. Standard dissection procedure and paraffin embedded tissue sections were made, stained by HE and immunohistochemically with CD34, CD 31, Factor 8, Podoplanin, CKWS and AE1/AE3 RESULTS: The mean age of the patients was 40.6 years; female to male ratio was 2.3:1. All the cysts were diagnosed as cystic lesions radiologically except one. The most present clinical symptom was abdominal pain. The diameter of the cysts measured from 2 to 7 cm. Four of the cysts were diagnosed as pseudocysts and six as endothelial. Six cysts were lined by CD34(+) and CD31(+) cells, four were lined by Factor 8(+) and podoplanin(+) cells and four had no lining. CONCLUSION: Endothelial cysts were more common cysts in our study and the immunohistochemical results suggested common vascular origin to all endothelial cysts and supported additional separation of angiomatous and lymphangiomathous adrenal vascular cysts.

Expression of matrix metalloproteinases 2, 7 and 9 in patients with colorectal cancer.

BACKGROUND/AIM: Matrix metalloproteinases (MMPs) are perceived to play a key role in tumor invasion and metastasis by their capacity to degrade basement membranes and extracellular matrix proteins. The aim of this study was to investigate the expressions of MMP-2, MMP-7 and MMP-9 in tumor tissue and their relation to clinicopathologic features in patients with colorectal cancer. METHODS: Specimens of resected colorectal cancer and surrounding normal tissue of 82 patients were immunohistochemically stained for MMP-2, MMP-7 and MMP-9. The results of immunohistochemical expression of MMPs were correlated with some clinical and pathologic parameters. RESULTS: Immunohistochemical expression of MMP-2 was more frequent in the patients with higher preoperative serum levels of carcinoembryonic antigen (CEA) (p = 0.047), MMP-2 (p = 0.018), MMP-9 (p = 0.036) and in those with lymph node metastasis (p = 0.018) and the advanced stage of the disease (p = 0.046). Expression of MMP-7 was more frequent in the patients with elevated preoperative serum levels of: CEA (p = 0.012), MMP-7 (p = 0.036), MMP-9 (p = 0.023) and with deeply invasive neoplasms (p = 0.027). MMP-9 cell expression was in a positive correlation with elevated preoperative serum levels of: CEA (p = 0.013), MMP-2 (p = 0.012), MMP-9 (p = 0.018) and depth of CRC invasion, ie T-parameter (p = 0.027). CONCLUSION: Immunohistochemical expression of MMPs is a useful indicator of the disease development and progression in patients with colorectal cancer.

Presenting colorectal carcinoma cases in our department.

BACKGROUND: Colorectal carcinoma is second commonest cancer causing death in Kosova. METHODOLOGY: In our study we present diagnostic methods, treatment, localization and laboratory findings in 155 patients, during 4 year period in patients with colorectal carcinomas treated in our clinic. RESULTS: Ninety four 94 (61.4%) of patients were male gender and 59 (38.6%) were female. Eritrosedimentation was elevated in 103 (67.3%) of patients, number of white blood cells was increased in 21 (7.2%) of patients and high level of glycemia is present in 11 (7.2%) of patients. The most involved age is from 41-50 years. The most common site of involvement was the rectum in 79 (51.6%), localization in sigma was in 37 (23.5%), the transverse colon in 21 (13.7%) of cases and the ascendant colon in 18 (11.1%) patients. Adenocarcinoma (98%) was the most common histiotype. CONCLUSION: We concluded, that all patients, especially with positive familial history must begin screening in age 40, during which colorectal carcinoma can be diagnosed in an early stage.