Foteini Karasavvidou

A case of membranous nephropathy associated with Sjögren syndrome, polymyositis and autoimmune hepatitis.

Sjögren syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, especially lacrimal and salivary. The immunologic process which occurs in this syndrome is B cell hyperactivity, which results in production of autoantibodies and immune complexes. SS can exist as a primary disorder or in association with other autoimmune processes. A usually mild, proximal and insidious inflammatory myopathy can occur in patients with SS with a broad clinical and pathological spectrum. Interstitial nephritis with mild proteinuria and tubular dysfunction is the most common renal manifestation of SS, but glomerular involvement due to immune complex deposition may also rarely occur [Goules et al. 2000]. There is an association of SS with hepatic abnormalities, as evidenced by abnormal liver biochemical tests or histological characteristics of primary biliary cirrhosis (PBC), portal tract fibrosis, or autoimmune hepatitis [Abraham et al. 2004]. The pathogenetic mechanism of liver involvement in SS is not clear, but it is possible that hepatic and salivary gland damage share a similar pathology. The combination of Sjögren syndrome with kidney, liver and muscle involvement in one entity is extremely rare and data in the literature are remarkably sparse. We present a case of a 43-year-old female patient suffering from SS accompanied by polymyositis, membranous nephropathy and autoimmune hepatitis.

Fascin Determination in Urothelial Carcinomas of the Urinary Bladder : A Marker of Invasiveness

CONTEXT Invasion and the depth of invasion affect significantly the prognosis in urothelial carcinomas. The histopathologic evaluation of invasion may be problematic in some cases. Application of new immunohistochemical markers may facilitate the assessment of invasion. Fascin, one of these markers, is an actin-bundling protein involved in tumor cell migration. Fascin expression is increased in various carcinomas. Prior to this research, to our knowledge, only one study exists regarding fascin expression in urothelial carcinomas. OBJECTIVE To characterize the expression of fascin in additional cases of urothelial carcinoma and to verify statistically a relationship between fascin overexpression and invasiveness in these tumors. DESIGN We examined fascin immunoreactivity in 116 specimens of urothelial carcinomas obtained from 116 patients including 96 men and 20 women. Fifty-eight cases were ranked as low-grade carcinomas, pTa stage, and 58 cases were ranked as high-grade carcinomas--11 were ranked as stage pTa, 21 were ranked as pT1, and 26 were ranked as pT2 carcinomas. Fascin immunoreactivity was assessed semiquantitatively in tumor cells. In each case, we ascribed 3 immunoreactivity scores, one for extent, one for intensity, and a combined immunoreactivity score. RESULTS The combined immunoreactivity score was significantly higher in invasive carcinomas. In addition, strong staining was observed exclusively in invasive carcinomas. None of the pTa tumors demonstrated intense staining, including those ranked at the higher grade. CONCLUSIONS Our results point to an association between fascin immunostaining and urothelial carcinoma invasiveness and suggest that fascin overexpression may be a marker of aggressive urothelial carcinomas.

Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome in a 52-Year-Old Female: A Case Report and Review of the Literature

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare entity first described in 1975, affecting mainly young women and adolescents. We present a case of a 52-year-old female patient (one of the oldest in the literature) who complained of fever, anorexia, nausea, and vomiting. After she was admitted to our hospital, laboratory tests revealed tubular proteinuria, elevated erythrocyte sedimentation rate (ESR), anemia, and renal insufficiency (serum creatinine 4.2 mg/dL) with metabolic acidosis. Ophthalmologic examination revealed anterior uveitis (iritis) and renal biopsy showed acute tubulointerstitial nephritis. The diagnosis of TINU syndrome was established and the patient was treated with oral corticosteroids. All symptoms and ophthalmologic abnormalities disappeared after 6 weeks of treatment. Renal function also recovered completely and remained stable at follow-up. TINU syndrome should be considered in the differential diagnosis of unexplained tubulointerstitial nephritis, especially in the presence of ocular findings. Corticosteroid therapy is still controversial, but it helps in the quick resolution of renal and mainly eye abnormalities.

p53 and Cyclooxygenase-2 Expression are Directly Associated with Cyclin D1 Expression in Radical Prostatectomy Specimens of Patients with Hormone-Naïve Prostate Cancer

Prostate cancer (PCa) is a potentially curable disease when diagnosed in early stages and subsequently treated with radical prostatectomy (RP). However, a significant proportion of patients tend to relapse early, with the emergence of biochemical failure (BF) as an established precursor of progression to metastatic disease. Several candidate molecular markers have been studied in an effort to enhance the accuracy of existing predictive tools regarding the risk of BF after RP. We studied the immunohistochemical expression of p53, cyclooxygenase-2 (COX-2) and cyclin D1 in a cohort of 70 patients that underwent RP for early stage, hormone naïve PCa, with the aim of prospectively identifying any possible interrelations as well as correlations with known prognostic parameters such as Gleason score, pathological stage and time to prostate-specific antigen (PSA) relapse. We observed a significant (p = 0.003) prognostic role of p53, with high protein expression correlating with shorter time to BF (TTBF) in univariate analysis. Both p53 and COX-2 expression were directly associated with cyclin D1 expression (p = 0.055 and p = 0.050 respectively). High p53 expression was also found to be an independent prognostic factor (p = 0.023). Based on previous data and results provided by this study, p53 expression exerts an independent negative prognostic role in localized prostate cancer and could therefore be evaluated as a useful new molecular marker to be added in the set of known prognostic indicators of the disease. With respect to COX-2 and cyclin D1, further studies are required to elucidate their role in early prediction of PCa relapse after RP.

Lack of prognostic significance of p16 and p27 after radical prostatectomy in hormone-naïve prostate cancer

BackgroundLoss of normal cell cycle control is an early event in the evolution of cancer. The expression of cyclin-dependent kinase (CDK) inhibitors p16 and p27 has been previously associated with progression of prostate cancer (PC). 70 patients diagnosed with early stage PCwere treated with radical prostatectomy (RP) at our institution and their tumor specimens were immunohistochemically evaluated for expression of p16 and p27. Available clinical data of time to PSA recurrence were correlated with the examined parameters and combined with pre-operative PSA level, Gleason score and pathological TNM (pT) stage assessment.ResultsNuclear overexpression of p16 was not associated with time to biochemical failure (BF) (p = 0.572). Same was the case for nuclear p27 overexpression (p = 1.000). Also, no significant correlations were found between either p16 or p27, and pre-operative PSA level, pT stage and Gleason grade. pT stage emerged as the only independent prognostic factor for biochemical recurrence (p = 0.01).ConclusionsThese data question previously reported data supporting the prognostic relevance of both p16 and p27 proteins in early PC.

Primary Renal Epithelioid Hemangioendothelioma

Background: Epithelioid hemangioendothelioma (EH) is a rare vascular neoplasm with an unpredictable malignant potential that has been described mainly in soft tissue, liver, and lung. Case Report: We report a case of a primary renal EH in a 54-year-old woman who presented with a 3-month history of abdominal pain. Abdominal ultrasound and computed tomography scan revealed a solitary mass of 4.0 ×3.2 cm in the outer surface of the right kidney. Nephron-sparing surgery was performed. On the basis of the histological and immunohistochemical findings, the diagnosis of EH was made. The patient was free of disease 6 months after surgery. Conclusions: Although EH may have a histologically benign appearance and can be treated using a nephron-sparing approach, this neoplasm is potentially malignant urging the need for a long-term follow-up in these patients.

AFP-producing hepatoid adenocarcinoma of the stomach: a case report

Hepatoid gastric adenocarcinoma is a distinct variant of gastric carcinoma which represents a comparatively small percentage of the disease and in many cases is producing high serum alpha-fetoprotein (AFP). We report a case of an 85 year old woman who presented with epigastric and right upper quadrant pain and was found in a CT scan to have multiple liver nodules and a gastric antrum mass as well as an elevated AFP level of 155000 IU/ml. An endoscopic biopsy of the antral mass showed hepatoid variant of gastric adenocarcinoma. The patient refused any further treatment and died 4 months after diagnosis. Hepatoid gastric adenocarcinoma is considered to have a poor prognosis, although cases with survival of several years have been reported. Poor outcome in most of the cases is due to the fact that, as in our patient, metastatic disease is already present at diagnosis.

Fine Needle Aspiration Cytology of a Primary Malignant Peripheral Nerve Sheath Tumor Arising in the Parotid Gland A Case Report

BACKGROUND Malignant peripheral nerve sheath tumor (MPNST) is an uncommon mesenchymal neoplasm showing nerve sheath differentiation, usually arising in large nerves of the trunk and extremities. Primary location in the parotid gland is rare. We describe fine needle aspiration (FNA) findings in a case of MPNST in the parotid gland. Differential diagnostic problems encountered in interpretation are discussed. CASE A 39-year-old man underwent FNA of a well-circumscribed, painless, mobile mass of the parotid gland. Smears were cellular, with clusters of tightly packed spindle or oval cells arranged in a storiform or whorled pattern, showing clearly malignant features. Elongated nuclei with tapered ends and many angulated nuclei were encountered. The background contained abundant necrotic material with dispersed malignant nuclei. Neoplastic cells were positive for vimentin and weakly positive for S-100 and negative for cytokeratins 8 and 18 and HMB-45. Cytologic diagnosis was positive for malignant cells consistent with a spindle cell sarcoma, with morphologic features compatible to neural differentiation, confirmed by histologic examination. CONCLUSION This case illustrates that attention to moiphologic criteria suggestive of nerve sheath phenotype supported by immunocytochemical data is extremely helpful and reliable in the diagnostic approach to MPNSTs, even in rare locations.

Simultaneous clinical resolution of focal segmental glomerulosclerosis associated with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab

BackgroundAlthough renal involvement in advanced haematological malignancies is common, glomerulonephritis associated with lymphoproliferative disorders is rare, and the related pathogenetic mechanisms are still poorly understood. We present a rare case of chronic lymphocytic leukaemia(CLL)-associated focal segmental glomerulosclerosis with nephrotic-range proteinuria.Case presentationA 53-year-old Caucasian man, previously healthy, with no history of hypertension, alcohol use or smoking presented with rapid weight gain, massive peripheral oedema, and hypertension. Laboratory findings included a white blood cell count of 49,800 cells/mm3 with an absolute lymphocyte count of 47,000 cells/mm3, serum albumin of 2.3 g/dL, urea 65 mg/dL, and creatinine 1.5 mg/dL. A 24-hour urine collection contained 7.1 g protein and significant haematuria. A peripheral blood smear showed mature lymphocytosis and smudge cells. Diagnostic imaging showed mild paraaortic lymphadenopathy with no renal abnormalities. Bone marrow aspiration and trephine biopsy showed diffuse and focal infiltration with B-CLL lymphocytes. Percutaneous renal biopsy revealed total sclerosis in 3/21(14%) of the glomeruli and focal and segmental solidification and sclerosis in 4/21 (19%) glomeruli. A regimen of fludarabine, cyclophosphamide and rituximab was successful in inducing remission of the CLL and clinical resolution of the nephritic-range proteinuria.ConclusionsA multidisciplinary approach to monitor both the malignancy and the glomerular lesions is crucial for the optimal management of paraneoplastic glomerulonephritis. Although chemotherapy with fludarabine, cyclophosphamide and rituximab successfully treated CLL-associated nephrotic syndrome in our patient, further studies are required to confirm efficacy in this setting.

INCENP (inner centromere protein) is overexpressed in high grade non-Hodgkin B-cell lymphomas.

Inner centromere protein (INCENP) is a member of the Chromosomal Passenger Complex (CPC), which is a four member protein complex essential for proper completion of mitosis and cell division (cytokinesis). Inappropriate chromosomal segregation and cytokinesis due to deregulated expression of chromosome passenger proteins may lead to aneuploidy and cancer including lymphomas. According to our knowledge this is the first study investigating immunohistochemical expression of INCENP in lymphoma cases and cancer tissues in general. Our purpose was to characterize the expression of INCENP in cases of non-Hodgkin B-cell lymphomas, to compare the immunoreactivity between low and high grades and to evaluate the correlation between INCENP and MIB-1 labeling indices. We examined INCENP and MIB-1 immunoreactivity in paraffin sections of 55 samples of non-Hodgkin B-cell lymphomas, obtained from 55 patients, 31 men and 24 women. Thirty were of high grade and 25 were of low grade. Our results showed significantly higher nuclear immunohistochemical expression of INCENP in high grade B-cell lymphomas versus low grade ones. Also INCENP expression was significantly correlated with MIB-1 labeling index. Taken together our results point to a possible association between increased INCENP immunostaining and B-cell lymphoma aggressiveness and also stress the need for further investigating the expression of INCENP and other mitotic regulatory proteins in lymphomas and other malignant neoplasms.