Relation Between Immunohistochemical Expression of Hippo Pathway Effectors and Chronic Hepatitis Induced Fibrosis in Egyptian Patients.

OBJECTIVE: Chronic hepatitis is a global health problem especially in Egypt. Hepatic fibrosis is a common end clinical manifestation of many chronic liver diseases. Although it is a wound-healing process, excessive accumulation of fibrillary collagen leads to architectural damage, cirrhosis and liver failure. Recently, a few studies have linked Hippo pathway effectors of yes-associated protein (YAP) and its paralog transcriptional coactivator with PDZ-binding motif (TAZ) to extracellular matrix deposition and ongoing fibrosis. MATERIAL AND METHOD: Immunohistochemical expression of YAP and TAZ were analyzed in 121 liver needle core biopsies (91 core biopsies of chronic viral hepatitis, 20 biopsies of autoimmune hepatitis and 10 normal liver cores). RESULTS: YAP and TAZ nuclear localization was absent in all normal liver cores. Autoimmune hepatitis cases showed higher nuclear expression of both YAP and TAZ in comparison to chronic viral cases. YAP and TAZ expression were correlated with severity of hepatocyte injury together with fibrosis in chronic viral cases but these correlations were absent in AIH cases despite the pronounced increase of YAP and TAZ nuclear localization. CONCLUSION: The correlation between Hippo effectors activation and fibrosis in chronic viral hepatitis patients emphasize their role in the development and advancement of hepatic scarring and highlight the use of both YAP and TAZ as novel targets to ameliorate liver fibrosis.

Signet Ring Dermatofibroma, a Rare and Confusing Variant.

Dermatofibroma is a common cutaneous benign fibrohistiocytic tumour, which is usually diagnosed without difficulty. In this report we demonstrated a signet ring variant of dermatofibroma as a rare variant of this common neoplasm together with the possible differential diagnosis.The presence of signet cells in cutaneous neoplasm does not necessarily means malignancy. Signet ring dermatofibroma is a rare variant eliciting differential diagnostic problems which can be solved by careful histopathological examination, searching for the classic areas and the help of immunohistochemistry.

The role of IL-28, IFN-γ, and TNF-α in predicting response to pegylated interferon/ribavirin in chronic HCV patients.

The primary goal of HCV therapy is to achieve a sustained virological response (SVR). Many host and viral factors influence the treatment response. Cytokines play an important role in the defense against viral infections, where successful treatment of hepatitis C depends on a complex balance between pro- and anti-inflammatory responses. In the present study, we investigated the relationship between the presence and percentage of some cytokines (IL-28, IFN-γ, and TNF-α) regarding different clinicopathological parameters including response to therapy in chronic HCV patients using immunohistochemical technique. This study was carried out on 64 chronic HCV patients (34 responders and 30 non-responders). Of cases, 54% showed IL-28 expression, which was associated with low AST (p = 0.002) and low HAI score (p = 0.006). Of cases, 67 and 45% showed IFN-γ and TNF-α expression, respectively, where the median percentage of TNF-α expression was higher in grade II spotty necrosis compared to grade I. Some inflammatory cytokines expressed by intrahepatic inflammatory cells in chronic HCV patients promote inflammation and injury (pro-inflammatory) such as TNF-α. Other cytokines aid in resolving inflammation and injury (anti-inflammatory) such as IL-28. The balance between these cytokines will determine the degree of inflammatory state. None of the investigated cytokines proved its clear cut role in affecting response to therapy, however, their levels varied between responders and non-responders for further investigations to clarify.

Sebaceous trichofolliculoma of the cheek in a 65-year-old man.

Sebaceous trichofolliculoma is considered as hamartomatous lesion with follicular differentiation. In this study, we demonstrated a classic histopathologic picture of sebaceous trichofolliculoma in a 65-year-old male presented with large sized right cheek swelling.

The prognostic role of tumor-associated macrophages and dendritic cells in classic Hodgkin's lymphoma.

Tumor-associated macrophages (TAMs) and dendritic cells (DCs) may play a role in tumor progression as a part of the tumor microenvironment in many neoplasms, including those in Hodgkin's lymphoma. The current study investigated the relationship between the presence and density of macrophages and dendritic cells in the background of classic Hodgkin's lymphoma (CHL) and different clinicopathological parameters, including survival and response to therapy. CD68 and CD1a immunohistochemical staining were used to detect and highlight macrophages and dendritic cells, respectively, in 61 cases of CHL. CD68 was expressed in all studied cases, with no significant association with the studied parameters. In total, 54.1% (33/61) of cases showed CD1a expression. High CD1a expression (>7%) was associated with localized lymphadenopathy (p=0.01), early stage (p=0.005), and good revised international prognostic index (R-IPI) (p=0.07). Hodgkin's lymphoma cases that showed high CD68 and low CD1a were associated with adverse prognostic parameters such as advanced stage (p=0.03) and generalized lymphadenopathy (p=0.05). Old age (>60 years) (P=0.005), poor R-IPI (P=0.010), and negative CD1a expression (P=0.045) were significantly associated with poor outcome. Finally, our study demonstrated the importance of the presence and density of DCs in determining progression and prognosis in CHL. A certain interaction between TAMs and DCs may affect the progression of CHL. Further investigation is required to clarify whether TAMs release certain factors that decrease the number or function of DCs.

The prognostic value of Skp2 expression in Egyptian diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma worldwide. Both morphologically and prognostically, it represents a disease of a diverse spectrum. S-phase kinase-associated protein 2 (Skp2) is a member of mammalian F-box proteins, which displays S-phase-promoting function through ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor, p27. The aim of this study is to evaluate the prognostic value of Skp2 in DLBCL (70 cases) by immunohistochemical staining technique, and its correlation with the clinicopathological features and survival. Five (25%) control cases (reactive follicular hyperplasia) showed high Skp2 expression compared with 52.9% of DLBCL using 10% as a cutoff point with a significant difference (P=0.04). Skp2 was seen staining the large cells in proliferating germinal centers of the control group. High Skp2 expression in DLBCL was associated with several progressive parameters, such as advanced stage (P=0.036), involvement of more than one extranodal site (P=0.05), and high proliferation (P=0.0001). It was also significantly associated with the presence (P=0.007) and extent (P=0.002) of necrosis and inversely correlated with p27 expression (P=0.0001). From this study, Skp2 expression in DLBCL identified subset of cases characterized by aggressive features such as advanced stage, increased number of extranodal sites, high proliferation, and shorter survival time. The association of Skp2 with necrosis may be a reflection of its ability in promoting proliferative tumor capacity.

Adult pancreatic neuroblastoma, an unusual site and fatal outcome.

In this report, we describe a classic case of stroma rich neuroblastoma, nodular type in a 22 year old female presented with a pancreatic mass. This rare and unusual presentation elicits several differential diagnostic categories including solid pseudopapillary tumor, pancreatic endocrine tumor, pancreatoblastoma and PNET. In this report, we tried to differentiate between them depending on the histopathological features and using panel of epithelial and neuroendocrine markers. Although of the rarity of pancreatic neuroblastoma as a primary site of origin, however it should be considered in the differential diagnosis of pancreatic masses in children and young adult. Neuropil and ganglionic differentiation are helpful features to recognize neuroblastoma and differentiate them from other small blue cell tumors. The fatal outcome of adult neuroblastoma confirming the independence of age as a prognostic factor in this neoplasm regardless of stage and histology.

Intrarenal epidermoid cyst presented as an enlarged multicystic kidney.

This report describes a case of large multiple and multilocular epidermoid cysts affecting the left kidney of a 67 old male. The condition was accidentally discovered during the ultrasonography for left loin pain and revealed enlarged left kidney with picture suggestive of hydronephrosis. Grossly, the kidney was distorted cysts that were filled with a cheesy material. The histologic picture of an end stage kidney disease was apparent in the compressed renal parenchyma by these cysts that were identical to an epidermoid cyst elsewhere. In conclusion, although rare, epidermoid cyst of the kidney could cause serious kidney damage leading to an end stage kidney disease. Epidermoid cyst of the kidney could be multiple producing a picture similar to hydronephrosis and broadening the differential diagnosis of multicystic disease of the kidney.

Immunohistochemical profile of ephrin A4 expression in human osteosarcoma.

Ephrin receptors and ephrin ligands constitute one of the largest groups of tyrosine kinases. The division of ephrin receptors into type A or type B is determined by their ligand-binding specificities. Ephrin A4 as a ligand has a broad capacity to bind and stimulate different subtypes of ephrin A receptors. Little is known about the role of ephrins generally and ephrin A4 particularly in osteosarcoma. Ephrin A4 was immunohistochemically assessed on archival material from 46 primary osteosarcoma cases, 10 metastatic pulmonary lesions and 20 normal control bone specimens. Ephrin A4 was expressed in 100% of normal bone specimens, in 84.4% of primary osteosarcoma cases and in all metastatic pulmonary lesions. Cytoplasmic and nucleocytoplasmic patterns of ephrin A4 immunoreactivity were observed, with the predominance of the latter pattern in normal bone (100%), and in 43.5% of primary osteosarcoma cases, which showed a higher intensity of expression compared with normal bone (p<0.05). The cytoplasmic pattern is the only staining pattern seen in metastatic cases, which may suggest its role in enhancement of invasion and metastasis. The differences in the distribution of the two patterns of ephrin A4 may indicate a different biological activity of this molecule depending on its localization. The nuclear localization of ephrin A4 requires further investigation to clarify the mechanism and the significance of the nuclear trafficking of ephrin A4.