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Abstract Introduction A choriocarcinoma is a malignant neoplasm normally arising in the gestational trophoblast, gonads and, less frequently, the retroperitoneum, mediastinum and pineal gland. Primary choriocarcinomas of the renal pelvis are extremely rare. Case presentation We report a case of primary choriocarcinoma of the renal pelvis in a 38-year-old Greek woman of reproductive age, presenting with a sudden development of intracerebral hemorrhage due to metastatic lesions. The diagnosis was established with a renal biopsy, along with an elevated serum level of beta-human chorionic gonadotropin. An extensive diagnostic work up confirmed the origin of the choriocarcinoma to be the renal pelvis. Conclusion Extragonadal choriocarcinomas are rare neoplasms that require extensive laboratory and imaging studies to exclude a gonadal origin. Moreover, this is the first case of severe intracerebral hemorrhage as the initial presentation of primary choriocarcinoma of the renal pelvis. Nonetheless, choriocarcinomas should be considered in the differential diagnosis of women of reproductive age.

Background: Hepatocellular carcinoma is one of the most common cancers in the world due to its association with chronic hepatitis infections. Amongst the most usual metastasis of hepatocellular carcinoma are the lymph nodes, the lungs and the bones. Soft tissue metastases are extremely rare. Case presentation: Herein, we report the case of a 73-years-old male patient who presented with cervical and upper extremities muscle pain along with paresthesias and a palpable mass on the cervical region. Conclusion: This unusual clinical manifestation along with the above-described rare presentations of hepatocellular carcinoma must be taken into account, especially among patients with chronic hepatitis infections. [ABSTRACT FROM AUTHOR]

Granular cell tumor, which is thought to recapitulate a Schwann cell phenotype, is a very rare neoplasm that belongs to soft tissue tumors. It can be classified as benign, atypical or malignant, based on specific histological criteria, with the majority of cases exhibiting an indolent behavior. Its biology and clinical course are poorly understood and its optimal management is yet to be defined, given the rarity of cases. Here we describe an atypical granular cell tumor in the upper middle back skin that evolved after a thirty-year indolent period. Despite complete surgical removal, the patient experienced a recurrence, both local and in the lungs, following an aggressive clinical course. Data on management of metastatic disease are extremely scarce, comprised exclusively of case reports. Therefore, we administered to the patient systemic therapy according to soft tissue sarcoma guidelines, which led to disease progression, with fatal outcome. In conclusion, recurrent and/or metastatic granular cell tumor is a rare disease that can be life-threatening, for which response to different therapies is unknown. The biologic behavior of atypical and malignant granular cell tumor is quite different from its benign counterpart, evoking soft tissue sarcomas, and its diagnosis should alert clinicians. The role of adjuvant chemotherapy and radiation therapy in this setting should be explored, to limit disease recurrence., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Diabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic renal disease (non-DRD) among patients with DM. The 'Gold standard' for the differential diagnosis between DKD and non-DRD is kidney biopsy, although no real consensus exists. Thus, this study intends to associate the clinical and biochemical profile of patients with DM and renal disease with the histopathological data of kidney biopsy.In addition, we aimed to evaluate the role of kidney biopsy, especially when other causes, other than DM, are highly suspected among patients with DM and kidney disease., Methods: Thirty two patients with T2DM and nephrotic range levels of proteinuria or with co-existing factors pointing towards a non-diabetic origin of kidney disease were studied, retrospectively. All 32 patients underwent kidney biopsy and were classified according to histopathological findings into 3 groups: a) isolated diabetic kidney disease (DKD), b) non-diabetic kidney disease (NDKD) and c) mixed kidney disease (MKD)., Results: Fifteen out of the 32 patients had findings of an isolated DKD, while 17 out of 32 patients suffered from NDKD (13 patients) or MKD (4 patients). DKD patients were younger (p = 0.016) and had a higher HbA1c value (p = 0.069, borderline statistical significance), while the NDKD patients had significantly shorter disease duration (p = 0.04). Furthermore, the incidence of diabetic retinopathy (DR) was lower among the NDKD patients (p < 0.001), who had also significantly less interstitial fibrosis (p = 0.02). Finally, the presence of DR, higher levels of interstitial fibrosis and longer T2DM duration were recognized as factors, which were positively associated with DKD., Conclusion: This study advocates the usefulness of kidney biopsy in patients with T2DM and nephrotic range levels of proteinuria, especially when DR is absent and shorter disease duration is observed., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 The Authors. Published by Elsevier Inc.)

Determination of microsatellite instability (MSI)/mismatch repair (MMR) status in cancer has several clinical implications. Our aim was to integrate MSI/MMR status from patients tested in Greece to assess the prevalence of MSI-high (MSI-H)/deficient MMR (dMMR) per tumor type, testing patterns over time and concordance between MSI and MMR status. We retrospectively recorded MSI/MMR testing data of patients with diverse tumor types performed in pathology and molecular diagnostics laboratories across Greece. Overall, 18 of 22 pathology and/or molecular diagnostics laboratories accepted our invitation to participate. In the 18 laboratories located across the country, 7916 tumor samples were evaluated for MSI/MMR status. MSI/MMR testing significantly increased in patients with colorectal cancer (CRC) and other tumor types overtime ( p < 0.05). The highest prevalence was reported in endometrial cancer (47 of 225 patients, 20.9%). MSI-H/dMMR was observed in most tumor types, even in low proportions. Among 904 tumors assessed both for MSI and MMR status, 21 had discordant results (overall discordance rate, 2.3%). We reported MSI-H/dMMR prevalence rates in patients with diverse cancers, while demonstrating increasing referral patterns from medical oncologists in the country overtime. The anticipated high rate of concordance between MSI and MMR status in paired analysis was confirmed.

Background: Limited information exists on epidermal growth factor receptor (EGFR) molecular epidemiology in Greece. Next-generation sequencing (NGS) is the recommended method for EGFR genotyping in NSCLC. The Idylla Biocartis platform is a fully automated system for actionable EGFR mutation detection., Research Design and Methods: We describe the prevalence of EGFR mutations in NSCLC patients in two high-volume clinical centers in Greece and compare key methods used for their determination. Eight hundred and fifty-seven FFPE samples from NSCLC patients were tested for EGFR mutations at University of Crete (UoC; n  = 324) and at Evangelismos Hospital, Athens (Evangelismos; n  = 503)., Results: The prevalence of EGFR mutations was 11.1% in the whole cohort (11.5% in non-squamous). The detection rate was 11.0% by NGS, 9.8% by Sanger and 11.3% by Idylla for the whole cohort (12.0% in non-squamous). The agreement between Idylla and Sanger was 93.2%. A targetable EGFR mutation was detected in 10.0% using tissue NGS alone, and in 16.0% using concurrent Idylla ct EGFR testing., Conclusion: The frequency of EGFR mutations was as expected for a Caucasian population. The Idylla EGFR test performance is comparable to reference methods and with a shorter TAT. Adding a concurrent plasma Idylla test to tissue NGS testing increases the detection rate of EGFR mutations in NSCLC.

Cytomegalovirus (CMV) infection/disease has been repeatedly reported in patients treated with immune-checkpoint inhibitors (ICIs) and most commonly involves patients with relapsed/refractory (R/R) immune-related adverse events (irAEs). In the current study, we present a patient with melanoma who developed CMV gastritis during treatment with pembrolizumab in the absence of irAEs and without previous or current immunosuppression. Moreover, we review the literature regarding CMV infection/disease in patients treated with ICIs for solid malignancies. We present the currently available data on the pathogenesis, clinical characteristics, endoscopic findings, and histologic features and highlight the potential differences among cases complicating R/R irAEs versus those occurring in patients who are immunosuppression naive. Finally, we discuss the currently available data regarding potential useful diagnostic tools as well as the management of these patients., Competing Interests: Potential conflicts of interest. PD reports personal fees from Novartis, Amgen, Janssen, and Roche. JH reports the following: financial compensation (to the institute) for advisory roles by Achilles Therapeutics, BioNTech, BMS, GSK, Immunocore, Iovance Bio, Instill Bio, Ipsen, MSD, Molecular Partners, Novartis, Pfizer, PokeAcel, Roche, Sanofi, and T-Knife; personal fees for advisory roles in Neogene Therapeutics, Scenic, grant support (all paid to the institute) by Amgen, Asher Bio, BioNTech, BMS, MSD, Novartis; and owner of stock options in Neogene Therapeutics. HG reports grants and personal fees from BMS and MSD and personal fees from Novartis, Pierre Fabre, Amgen, Sanofi/Regeneron, and Pfizer. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Cutaneous angiosarcoma (CAS) is an aggressive tumour of vascular or lymphatic origin. Although relatively rare, it needs to be recognized and treated early. CAS typically arises on the head or neck as a bruise or raised purplish-red papule or plaque. However, it can sometimes resemble a benign skin lesion, leading to delay in diagnosis and consequent poor patient outcome. CAS may be mistaken for inflammatory, autoimmune or infectious disease, or for a benign skin tumour or post-traumatic lesion. We analyse the atypical clinical forms of this aggressive tumour and review the literature., (© 2022 British Association of Dermatologists.)

Introduction: New Immuno- Checkpoint inhibitors (ICIs) functioning as PD-1- PDL-1 blockers are nowadays used in a majority of anticancer treatments. Many immune- related Adverse Events (irAEs) are published daily; severe skin toxicities, Stevens Johnson/ Toxic Epidermal Necrolysis (SJS/TEN) are seldom reported., Case Report: Herein, we present two interesting skin sever toxicity cases of lung cancer patients, undergoing PD-1- PDL-1 Immunotherapy. In both cases, a morbilliform rash with documented histological Toxic Epidermal Necrolysis Pattern /Stevens Johnson findings, was thoroughly studied., Management & Outcome: Both cases were therapeutically managed according to guidelines with different outcome., Discussion: Two focused cases of irAEs, is the rationale, to briefly review mechanisms of major toxicities caused by PD-1/PD-L1 blockade, and present all new data in their precise management. ICIs' association with SJS/ TEN still remains unclear; underlying urgent need for further studies. It is important to alert physicians to promptly identify life threatening irAEs. Being familiar, provides management efficacy, safe resolve and encourage beneficial balanced cost effective treatments.

During the current pandemic, we witnessed a rise of post-intubation tracheal stenosis (PITS) in patients intubated due to COVID-19. We prospectively analyzed data from patients referred to our institution during the last 18 months for severe symptomatic post-intubation upper airway complications. Interdisciplinary bronchoscopic and/or surgical management was offered. Twenty-three patients with PITS and/or tracheoesophageal fistulae were included. They had undergone 31.85 (±22.7) days of ICU hospitalization and 17.35 (±7.4) days of intubation. Tracheal stenoses were mostly complex, located in the subglottic or mid-tracheal area. A total of 83% of patients had fracture and distortion of the tracheal wall. Fifteen patients were initially treated with rigid bronchoscopic modalities and/or stent placement and eight patients with tracheal resection-anastomosis. Post-treatment relapse in two of the bronchoscopically treated patients required surgery, while two of the surgically treated patients required rigid bronchoscopy and stent placement. Transient, non-life-threatening post-treatment complications developed in 60% of patients and were all managed successfully. The histopathology of the resected tracheal specimens didn't reveal specific alterations in comparison to pre-COVID-era PITS cases. Prolonged intubation, pronation maneuvers, oversized tubes or cuffs, and patient- or disease-specific factors may be pathogenically implicated. An increase of post-COVID PITS is anticipated. Careful prevention, early detection and effective management of these iatrogenic complications are warranted.

Coxiella burnetii is a gram-negative bacterium that typically lives and multiplies within monocytes and macrophages of the host, being the etiologic agent of the zoonosis Q fever. Q fever is usually divided into acute and chronic forms, with a significant percentage of patients being asymptomatic. In the wide spectrum of the disease, neurological involvement seems to be extremely rare and peripheral neuropathy presenting with mononeuritis multiplex is one of the possible presentations with low rates of occurrence. Hereby, we present an unusual case of a 55-year-old male with fever and multiple mononeuritis attributed to Q fever and we summarize a short review of C. burnetii infection., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Dermato-neuro syndrome is a potentially fatal neurological complication of scleromyxedema consisting of fever, seizures, and coma. This is an overlooked scleromyxedema case of a 62-year-old female patient from 2-years ago. She was admitted to our ICU because of high fever, colloid speech, muscle ache, and nausea. Molecular methods in the cerebrospinal fluid for neurotropic viruses ruled out acute infectious encephalitis. Her thyroid hormones were within normal values while the serum protein electrophoresis confirmed the monoclonal gammopathy of immunoglobulin G lambda (IgG(λ)), known for the last 2 years. The subsequent bone-marrow biopsy excluded the development of multiple myeloma. The patient fulfilled fundamental diagnostic criteria of scleromyxedema (monoclonal gammopathy, normal thyroid function and the appearance of marked sclerosis and induration of the skin papules on the face, neck, extremities, and skin creases) presenting as dermato-neuro syndrome, which was histologically confirmed. She demonstrated a remarkable improvement after intravenous immunoglobulin treatment during the first 24 hours. Mimics of non-infectious acute encephalitis should include the clinical diagnosis of scleromyxedema, especially when patients present in the emergency department with acute fever, coma, and skin lesions of diffuse sclerodermoid and papular type., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite their suboptimal long-term patency, saphenous vein grafts are the most widely used conduits to achieve complete revascularization during coronary artery bypass grafting (CABG). Although vein storage critically impairs endothelial integrity, contradictory data concerning optimal storage solutions exist. The aim of this study is to explore any in vitro impact of cardioplegic solutions and temperature on vein grafts endothelial integrity during their storage., Materials and Methods: A single-center, prospective trial including 40 consecutive patients was conducted. Eligibility criteria included patients submitted to CABG receiving at least one vein graft. An excess segment of the graft was harvested and divided into four different parts. Each one of them was stored under different conditions; either in a conventional heparin-enriched blood solution or in a cardioplegic solution, at room temperature (20°C-22°C) and in the refrigerator (5°C). Endothelial integrity was evaluated via immunohistochemistry using an antibody against CD31., Results: Endothelial integrity (measured in a scale from 1-worst to 5-best) was significantly better after cardioplegic solution storage (2.83 ± 0.15 and 3.10 ± 0.13 in cold and room temperature, respectively) compared with storage in conventional solutions (2.23 ± 0.16 and 2.0 ± 0.15 in cold and room temperature, respectively). A significant effect of cardioplegic storage solution, as well as of cold temperature and cardioplegic solution interaction on endothelial preservation was reported, whereas storage temperature did not prove a significant factor by its own., Conclusions: Cardioplegic storage solutions result in significantly better endothelial preservation compared with conventional heparin-enriched blood solutions. The association with superior clinical outcomes remains to be proved., (© 2020 Wiley Periodicals, Inc.)

Aims: Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment., Methods and Results: Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re-evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15-85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow-up period was 122.3 (112-376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow-up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation., Conclusions: The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long-term follow-up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings., (© 2019 The Authors. Histopathology published by John Wiley & Sons Ltd.)

IgA nephropathy (IgAN) is one of the most common recurrent glomerulonephritis after renal transplantation. Rarely, it is accompanied with the presence of crescents that leads to rapid deterioration of renal function and graft loss. We present a 54-year-old patient with IgAN that received a cadaveric kidney allograft, but developed biopsy proven recurrent IgAN 7 months after renal transplantation. He was treated with intravenous steroids and angiotensin-converting enzyme inhibitor and remission was achieved. 4 years later, he presented again with heavy proteinuria, hematuria and deterioration of renal function. Allograft biopsy revealed recurrent IgAN with crescents, which was successfully treated with pulse intravenous steroids and six monthly doses of intravenous cyclophosphamide. This regime resulted in long-term sustained remission with a stable functioning graft 3 years later. Although it is not an established treatment as in native kidneys, intravenous cyclophosphamide should probably be considered in kidney transplants with potentially reversible recurrent crescentic IgAN.

Competing Interests: The authors declare no conflict of interest.

Objectives: To report a case of intravascular lymphoma (IVL) in a Caucasian patient who presented with anasarca as his sole clinical sign., Material and Methods: A man presented with anasarca-type oedema and fatigue. After excluding heart failure, hepatic cirrhosis, nephrotic syndrome, hypothyroidism, AL-amyloidosis and adverse drug reaction which can all cause oedema, we turned our attention to capillary permeability disorders., Results: Closer review of the bone marrow aspirate demonstrated haemophagocytic histiocytosis, while core, renal and duodenal biopsies showed a B-cell IVL., Conclusion: The differential diagnosis of anasarca, a relatively common clinical sign, should include IVL although the diagnosis may still be challenging., Learning Points: Anasarca-type oedema is an unusual initial presentation of intravascular lymphoma (IVL) and is normally attributed to capillary permeability disorders.Two clinical forms of IVL have been recognized: a Western form and an Asian variant which is characterized by haemophagocytosis.Patients of Caucasian origin who have the clinical features of the Asian variant of IVL make the diagnosis of this condition even more challenging., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

We would like to present an interesting case operated on in our department and discuss the international bibliography about this issue. We also present some interesting images of this case. Our material is composed from a 68-year-old woman treated by the authors. She presented with a small murmur in the auscultation while she was asymptomatic and then she diagnosed with a tumor on of the left coronary cusp of the aortic valve with the characteristics of papillary fibroelastoma. On the basis of the potential embolic risk either of the mass itself or of associated thrombus and the possibility of further enlargement, the patient although asymptomatic at the time of diagnosis was referred for elective surgical excision of the mass. She underwent on median sternotomy and through extracorporeal circulation the mass has been excised with the preservation of the well-functioning valve. Through this case, we would like to discuss the bibliography for the decision making in these cases. Hence, the aim of our study is that we have to keep in mind that this kind of friable mass may be the cause of embolism, stroke or coronary artery occlusion and must be excided in a conservative setting, sparing the aortic valve.

Introduction: A choriocarcinoma is a malignant neoplasm normally arising in the gestational trophoblast, gonads and, less frequently, the retroperitoneum, mediastinum and pineal gland. Primary choriocarcinomas of the renal pelvis are extremely rare., Case Presentation: We report a case of primary choriocarcinoma of the renal pelvis in a 38-year-old Greek woman of reproductive age, presenting with a sudden development of intracerebral hemorrhage due to metastatic lesions. The diagnosis was established with a renal biopsy, along with an elevated serum level of beta-human chorionic gonadotropin. An extensive diagnostic work up confirmed the origin of the choriocarcinoma to be the renal pelvis., Conclusion: Extragonadal choriocarcinomas are rare neoplasms that require extensive laboratory and imaging studies to exclude a gonadal origin. Moreover, this is the first case of severe intracerebral hemorrhage as the initial presentation of primary choriocarcinoma of the renal pelvis. Nonetheless, choriocarcinomas should be considered in the differential diagnosis of women of reproductive age.

Isolated bilateral coronary artery ostial stenosis is a rare condition that has been associated with various diseases. We present the case of a 47-year-old male with bilateral coronary ostial stenosis. The patient's history was not significant for systemic diseases. The aorta had prominent signs of aortitis of unknown etiology, possibly due to a chronic mycotic process. The patient underwent emergency surgery and had an uneventful course. The two-year follow up is excellent.

Introduction: Sublingual salivary gland neoplasms are extremely rare, accounting for only 0.3-1% of all epithelial salivary gland tumors. Most of the sublingual tumors are malignant, adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC) being the most common histological types. The coexistence of two salivary gland tumors located in different major salivary glands is uncommon., Case Report: A rare case of two simultaneous tumors of the major salivary glands, one in the sublingual and the other in the contralateral parotid gland in a female patient is reported., Discussion: The diagnostic procedure followed, and the management of the patient, is outlined in the paper.

Introduction: Dermoid cysts of the floor of the mouth and submandibular space represent an unusual clinical entity., Case Report: A case of an enlarged median dermoid cyst in a young female adult causing obstruction of the airway is reported., Discussion: The need of an extraoral and intraoral incision for the removal of the cyst is discussed, along with a review of the literature.

Aim: To investigate the incidence of KIT immunohistochemical staining in (GI) stromal tumors (GISTs), and to analyze the clinical manifestations of the tumors and prognostic indicators., Methods: We retrospectively analyzed 50 cases of previously diagnosed GISTs. Tissue samples were assessed with KIT (CD117 antigen), CD34, SMA, desmin, S-100, NSE, PCNA, Ki-67, and BCL-2 for immunohistochemical study and pathological characteristics were analyzed for prognostic factors., Results: Fifteen tumors (30%) were negative in KIT staining. A significant association was observed between gender (male patients: 14/15) and KIT-negative staining (P = 0.003).The patients's mean age was 56.6 years. Tumors developed in stomach (n = 8), small intestine (n = 5), large intestine (n = 1) and oesophagus (n = 1). The mean tumor size was 5.72 cm. The mitotic count ranged from 0-29/50 HPF (mean: 3.4) and 73% of tumors showed no necrosis. The majority of the tumors (67%) had dual or epithelioid differentiation. Tumors were classified as very low or low risk (n = 7), intermediate risk (n = 5), and high risk (n = 3) groups. Twelve (80%) patients were alive without evidence of residual tumor for an average period of 40.25 mo (12-82 mo); three patients developed metastatic disease to the liver and eventually died within 2-12 mo (median survival: 8.6 mo)., Conclusion: A small subgroup of GISTs fulfils the clinical and morphological criteria of these tumors, and lacks KIT expression. These tumors predominantly developed in the stomach, being dual or epithelioid in morphology, which are classified as low risk tumors and presented a better survival status than KIT-positive tumors. The ability to diagnose GISTs still depends on immunohistochemical staining but the research should extend in gene mutations.

Bcl-2 protein blocks apoptosis and is involved in human intrahepatic bile-duct development. Formalin-fixed, paraffin-embedded archival tissue from 42 HBV and HCV hepatitis [20 acute AH, 22 chronic hepatitis (CH)], 12 active cirrhosis (CR) and 20 hepatocellular carcinoma (HCC) was immunostained for bcl-2 protein. In all cases, bcl-2 protein was detected in portal and intralobular lymphocytes but not in hepatocytes or Kupffer cells. Bcl-2 was positive in the cytoplasm of small portal bile ducts of chronic hepatitis, while it was strongly expressed in newly formed bile-ductules of the limiting plate, mainly in CH with marked activity and CR. Bcl-2 was detected in small bile ducts in only one case of acute hepatitis and was not detected in any case of HCC. Bcl-2 seems to be involved in the regulation of growth and apoptosis of cholangiolar cells. Its expression in small bile ducts and in newly-formed ductules especially in CH with marked activity and CR, implies that the embryonic model of intrahepatic bile duct development may be recapitulated in chronic hepatic disease. Moreover, it supports evidence for the existence of the controversial long-lived stem population in the liver. Bcl-2 does not seem to be involved in hepatocarcinogenesis.

The aim of this study was to investigate the expression of bcl-2, p53 oncoproteins, and Ki-67 antigen in a series of transitional cell bladder carcinomas and its relation to the traditional prognostic indicators and patient's survival. One hundred six cases with transitional cell carcinoma (TCC) were examined for detection of bcl-2, p53 proteins, and Ki-67 antigen (MIB1 antibody). Bcl-2 immunohistochemical positivity was observed in 52% of TCCs and in 57% of low-grade and 44% of high-grade TCCs. Bcl-2 was also detected in normal urothelium and dysplastic lesions with basal cell expression, and negative staining was observed in carcinomas in situ. Tumor stage showed a significant inverse correlation with overall bcl-2 positivity. The loss of bcl-2 protein expression in higher-stage TCCs was statistically significant (Pt = .01). p53 protein was overexpressed in 50% of TCCs and more frequently in invasive and in carcinomas in situ than in superficial TCCs (Pt = .03). In contrast, detection of p53 was not observed in normal and dysplastic urothelium. p53 positivity was related to the degree of differentiation and to the stage of the disease (Pf = .01 and Pt = .03, respectively). Concerning Ki-67 antigen, its expression was found in 57.5% of TCCs. There was a strong overall correlation of Ki-67 with tumor stage (Pt = .002) and grade (Pf = .002). Univariate statistical analysis showed that the expression of p53 and Ki-67 was significantly correlated to poor prognosis (P = .02, P = .02, respectively). On multivariate analysis, none of these markers but only stage and grade were significantly correlated to prognosis (P = .02, P = .02, respectively). These findings suggest that overexpression of bcl-2 protein may be an early event in tumorigenesis. Tumors with loss of bcl-2 positivity and overexpression of p53 and Ki-67 had an unfavorable prognosis; however, in multivariate analysis, they had no independent prognostic value.