Victoria Alagiozian-Angelova

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients.

Patients with hepatocellular carcinoma who undergo orthotopic liver transplantation (OLT) are at risk for post-transplant tumor recurrence. The aim of this study was to evaluate whether expression of p53 and Ki-67 in hepatocellular carcinoma lesions present in explanted liver tissue was associated with time to tumor recurrence after OLT. Subjects consisted of 20 consecutive patients who underwent OLT and were found to have hepatocellular carcinoma in the liver explant. Immunostaining for p53 and Ki-67 was performed by standard methods. The presence of nuclear immunostaining in >10% of the tumor tissue was considered positive. Time to recurrence of hepatocellular carcinoma after OLT was compared between patients with positive and negative immunostaining by the log rank test. Multivariate analysis was performed using a Cox regression model to control for potentially confounding clinical factors. Time to post-transplant hepatocellular carcinoma recurrence was significantly more rapid in p53+ (P=0.0007) and Ki-67+ cases (P=0.001). These associations remained significant in multivariate analysis. Furthermore, time to recurrent hepatocellular carcinoma was significantly shorter in patients with a serum alpha feto-protein (AFP) level ≥100 ng/ml at time of diagnosis, compared to those with an AFP level <100 ng/ml (P=0.003). In conclusion, expression of p53 and Ki-67 in hepatocellular carcinoma lesions, and a serum AFP level ≥100 ng/ml were associated with more rapid recurrence of hepatocellular carcinoma after OLT. Identification of patients at risk for early post-transplant recurrence could be used to guide surveillance and adjuvant treatment strategies.

Effects of extensive splenomegaly in patients with myelofibrosis undergoing a reduced intensity allogeneic stem cell transplantation

Changes in spleen size postallogeneic haematopoietic stem cell transplantation (HSCT) in patients with primary myelofibrosis have been poorly characterized. We analysed 10 patients with myelofibrosis and splenomegaly following a reduced‐intensity allogeneic HSCT. All patients fully engrafted donor cells including five patients with extensive splenomegaly. Extensive splenomegaly was associated with a prolonged time to neutrophil and platelet recovery. In all 10 patients, a progressive reduction of splenomegaly was documented within 12 months post‐transplant and paralleled the reduction of marrow fibrosis. These findings suggest that myelofibrosis patients with extensive splenomegaly may proceed with allogeneic HSCT without prior splenectomy.

Excess of Proximal Microsatellite-Stable Colorectal Cancer in African Americans from a Multiethnic Study

Purpose: African Americans (AA) have the highest incidence of colorectal cancer compared with other U.S. populations and more proximal colorectal cancers. The objective is to elucidate the basis of these cancer disparities. Experimental design: Of note, 566 AA and 328 non-Hispanic White (NHW) colorectal cancers were ascertained in five Chicago hospitals. Clinical and exposure data were collected. Microsatellite instability (MSI) and BRAF (V600E) and KRAS mutations were tested. Statistical significance of categorical variables was tested by the Fisher exact test or logistic regression and age by the Mann–Whitney U test. Results: Over a 10-year period, the median age at diagnosis significantly decreased for both AAs (68–61; P < 0.01) and NHWs (64.5– 62; P = 0.04); more AA patients were diagnosed before age 50 than NHWs (22% vs. 15%; P = 0.01). AAs had more proximal colorectal cancer than NHWs (49.5% vs. 33.7%; P < 0.01), but overall frequencies of MSI, BRAF and KRAS mutations were not different nor were they different by location in the colon. Proximal colorectal cancers often presented with lymphocytic infiltrate (P < 0.01) and were diagnosed at older ages (P = 0.02). Smoking, drinking, and obesity were less common in this group, but results were not statistically significant. Conclusions: Patients with colorectal cancer have gotten progressively younger. The excess of colorectal cancer in AAs predominantly consists of more proximal, microsatellite stable tumors, commonly presenting lymphocytic infiltrate and less often associated with toxic exposures or a higher BMI. Younger AAs had more distal colorectal cancers than older ones. These data suggest two different mechanisms driving younger age and proximal location of colorectal cancers in AAs. Clin Cancer Res; 20(18); 4962–70. ©2014 AACR.

EBV positivity in primary cutaneous large B-cell lymphoma with immunophenotypic features of leg type: An isolated incidence or something more significant?

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Primary low grade follicular lymphoma of cranial vault mimicking lipoma at presentation.

the whole axilla field. In a recently published systematic review of radiation-induced bullous pemphigoid [4], 27 cases were found. The majority (89%) experienced blistering confined to the irradiated area, and there was no report of mucosal pemphigus. As in this case, most of the reported cases were breast carcinoma (78%). The use of hormonal therapy was reported in five cases. Although a possible correlation between PV and tamoxifen cannot be excluded, there is no reported case of tamoxifen-induced PV without radiotherapy. In the current case, the patient continued the tamoxifen treatment, which did not interfere with the PV recovery. It is unclear how radiation therapy acts as a triggering mechanism to induce PV. Several theories have been proposed. One is that radiotherapy itself changes antigenic properties and induces autoantibody formation through the alteration of the basal membrane with unmasking of the antigen [4,9]. Another possible explanation is that patients who developed PV after radiation may already have circulating low-titer anti-basement membrane antibodies, and the tissue damage through radiotherapy may enhance the deposition of antibodies [4,9]. This may explain the rarity of this radiation-induced side effect. The unusual development of mucosal ulcers after radiotherapy should raise a suspicion of this diagnosis.

High-grade pelvic osteosarcoma with intravascular extension to the right side of the heart: a case report and review of the literature.

We describe a rare case of high-grade osteosarcoma with intravascular extension to the right atrium and right ventricle in a 23-year-old woman. Osteosarcomas rarely metastasize to the heart, and only a few cases have been reported in the literature thus far. Diagnoses in some of these cases were made during investigation for severe cardiac failure and in most of these cases at autopsy. We describe a unique case of intravascular extension of the tumor embolus in a cordlike fashion from the left femoral vein to the right side of the heart that morphologically resembled a chondrosarcoma.

Aggressive primary splenic CD5 positive/Cyclin D1 negative B-cell lymphoma in a patient with chronic hepatitis B virus infection

tumours arise from diverse cellular lineages and have different management principles and prognosis. PANCH is a rare tumour in this region of uncertain cellular origin [2]. Histogenesis of glial and neuronal metaplasia in pituitary adenomas has been debated [3] suggesting that they arise from embryonal pituitary cell rests or have common hypothalamic origin. It is also hypothesized that sparsely granulated growth hormone (GH) producing adenoma cells can differentiate to the neuronal lineage [4]. Morphologically, the tumour is composed of chromophobe pituitary adenoma with varying ganglionic/ neuronal component with or without neuropil. PANCH has been described only as isolated reports or small case series (Table I), with vast majority being hormone secreting pituitary tumours with consequent increase in serum hormone levels [6,7,10]. GH and adrenocorticotropic hormone secreting tumours have a tendency towards glial differentiation [3,5,9]. They usually present with intracellular inclusion bodies like Crooke’s hyaline change. Only few non-secretory PANCH syndrome cases have been reported including this one. As in other pituitary tumours, surgery is the cornerstone of management of these tumours. Completely excised tumours, with no evidence of residual tumour on post-operative imaging, should be kept on close observation. In patients with gross residual disease, or progression on surveillance imaging, not amenable to further safe resection, definitive radiotherapy should be offered to improve outcome. In summary, non-secretory pituitary adenoma presenting with glioneuronal differentiation (PANCH) is an extremely rare entity with an unknown clinical course.

Lack of APC somatic mutation is associated with early-onset colorectal cancer in African Americans

African Americans (AAs) have higher incidence and mortality rates of colorectal cancer (CRC) compared with other US populations. They present with more right-sided, microsatellite stable disease and are diagnosed at earlier ages compared with non-Hispanic Whites (NHWs). To gain insight into these trends, we conducted exome sequencing (n = 45), copy number (n = 33) and methylation analysis (n = 11) of microsatellite stable AA CRCs. Results were compared with data from The Cancer Genome Atlas (TCGA). Two of the 45 tumors contained POLE mutations. In the remaining 43 tumors, only 27 (63%) contained loss-of-function mutations in APC compared with 80% of TCGA NHW CRCs. APC-mutation-negative CRCs were associated with an earlier onset of CRC (P = 0.01). They were also associated with lower overall mutation burden, fewer copy number variants and a DNA methylation signature that was distinct from the CpG island methylator phenotype characterized in microsatellite unstable disease. Three of the APC-mutation-negative CRCs had loss-of-function mutations in BCL9L. Mutations in driver genes identified by TCGA exome analysis were less frequent in AA CRC cases than TCGA NHWs. Genes that regulate the WNT signaling pathway, including SOX9, GATA6, TET1, GLIS1 and FAT1, were differentially hypermethylated in APC-mutation-negative CRCs, suggesting a novel mechanism for cancer development in these tumors. In summary, we have identified a subtype of CRC that is associated with younger age of diagnosis, lack of APC mutation, microsatellite and chromosome stability, lower mutation burden and distinctive methylation changes.

Su1993 Somatic Mutations in the Mismatch Repair System Are Responsible for a Majority of Unexplained Lynch Syndrome Cases: Time to Revise Lynch Syndrome Screening?

G A A b st ra ct s gastric tissue samples harvested from an independent population ofH. pylori-infected persons in New Orleans to assess expression and methylation status of HIF-1α in vivo. Gastric tissue specimens from African-American subjects harboring an increased risk for gastric cancer exhibited marked decreases in methylation of HIF-1α with increasing disease severity. The highest levels of HIF-1α methylation were found in patients with non-atrophic gastritis and this decreased as disease progressed to atrophic gastritis (0.5-fold) and intestinal metaplasia (0.2-fold), versus gastritis alone. Consistent with decreasing HIF-1α methylation status, gastric tissue from African-American patients harbored increased levels of HIF-1α expression with increasing disease progression and this was not observed in Caucasian patients. Collectively, these data indicate that H. pylori induces HIF-1α in gastric epithelial cells and this is augmented under conditions of iron deficiency. HIF-1α expression in vivo increases in conjunction with decreased HIF-1α methylation and the development of premalignant lesions, which may provide a mechanism underpinning the link between high altitude, iron depletion, and increased gastric cancer rates within the context of H. pylori infection.