Endoscopic radiofrequency ablation may improve overall survival in patients with inoperable ampullary carcinoma.

OBJECTIVES: Patients with advanced ampullary carcinoma (AC) who are unsuitable for surgery are most likely to have poor outcomes. The role of endoscopic radiofrequency ablation (RFA) in this population has not been fully defined. We aimed to assess the short- and long-term outcomes of RFA in a large cohort of AC patients. METHODS: In this retrospective study, data of consecutive patients with pathologically proven AC who underwent successful endobiliary RFA and/or stent placement were collected. All patients did not undergo surgical resection. The primary outcome was overall survival (OS). The secondary outcomes included clinical success and adverse events. RESULTS: A total of 85 patients, 50 in the RFA plus stenting group and 35 in the stenting alone group, were identified. The median OS was significantly longer in the RFA group than in the stenting alone group (16.9 vs. 9.8 months, P < 0.001). In multivariable Cox analysis, RFA (hazards ratio 0.408; 95% confidence interval 0.235-0.706; P = 0.001) was the only independent OS predictor. Eight patients with stage II tumors, exclusively from the RFA group, survived for more than 3 years. Clinical success was comparable between the two groups (96% vs. 100%, P = 0.231). Early adverse events between the two groups were similar (10% vs. 2.9%, P = 0.206); however, late biliary/pancreatic stenoses occurred in three RFA patients who were successfully managed with endoscopic interventions. CONCLUSIONS: Endoscopic RFA appears to prolong patients' survival with acceptable safety; it may therefore be a feasible treatment option for patients with inoperable ampullary cancers.

Identification of important genes and drug repurposing based on clinical-centered analysis across human cancers.

Identification of the functional impact of mutated and altered genes in cancer is critical for implementing precision oncology and drug repurposing. In recent years, the emergence of multiomics data from large, well-characterized patient cohorts has provided us with an unprecedented opportunity to address this problem. In this study, we investigated survival-associated genes across 26 cancer types and found that these genes tended to be hub genes and had higher K-core values in biological networks. Moreover, the genes associated with adverse outcomes were mainly enriched in pathways related to genetic information processing and cellular processes, while the genes with favorable outcomes were enriched in metabolism and immune regulation pathways. We proposed using the number of survival-related neighbors to assess the impact of mutations. In addition, by integrating other databases including the Human Protein Atlas and the DrugBank database, we predicted novel targets and anticancer drugs using the drug repurposing strategy. Our results illustrated the significance of multidimensional analysis of clinical data in important gene identification and drug development.

Postoperative adjuvant transcatheter arterial chemoembolization improves the prognosis of patients with huge hepatocellular carcinoma.

BACKGROUND: Surgical resection of huge hepatocellular carcinoma (HCC, ≥ 10 cm) is potentially curative. More adjuvant treatments are needed to reduce relapses in these patients. We evaluated the influence of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) on the prognosis of huge HCC. METHODS: Data from consecutive patients who underwent curative resection for huge HCC in our center were retrospectively collected. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients who did and did not undergo PA-TACE. Propensity score matching (PSM) was used. RESULTS: Among the 255 enrolled patients, 93 underwent PA-TACE. The clinical outcomes were significantly better in the PA-TACE group than those in the non PA-TACE group (5-year RFS rate: 33.5% vs. 18.0%; 5-year OS rate: 47.0% vs. 28.0%, all P < 0.001). After PSM, similar results were obtained (5-year RFS rate: 28.8% vs. 17.6%, P < 0.001; 5-year OS rate: 42.5% vs. 25.0%, P = 0.004). PA-TACE decreased the possibility of early recurrence (< 2 years, crude cohort: P < 0.001, PSM cohort: P < 0.001) but not late recurrence (≥ 2 years, crude cohort: P = 0.692, PSM cohort: P = 0.325). Multivariable Cox regression analysis suggested that PA-TACE was an independent protective factor prolonging early RFS, RFS and OS. CONCLUSIONS: PA-TACE is a safe intervention for huge HCC patients after liver resection and improves outcomes.

Steroid-responsive atypical marginal zone hyperplasia of the lip in a child.

Atypical marginal zone hyperplasia (AMZH) is a recently described disease entity seen mainly in children. AMZH most commonly affects tonsils and appendices. Cutaneous AMZH is rare. The authors report here a recurrent AMZH in the lip of a 9-year-old child who presented originally with a lip swelling for approximately 3 months. The lip lesion recurred after each incomplete excision for 4 times. Pathologically, the lesion demonstrated marginal zone B-cell hyperplasia with kappa monoclonality by flow cytometry and immunohistochemistry studies. Lymphoepithelial lesions were noted with involvement of minor salivary glands. Polymerase chain reaction for immunoglobulin heavy-chain gene rearrangement has been repeatedly negative. Polymerase chain reaction for Borrelia species DNA was negative on both paraffin-embedded tissue and plasma. Serum antibodies IgG and IgM for Helicobacter Pylori were positive. A diagnosis of AMZH was made. Two courses of anti H. Pylori therapy did not improve the lip lesion, which completely regressed after a course of prednisone therapy. With differential diagnosis of cutaneous marginal zone lymphoma, the case illustrated diagnostic challenges, especially with recurrent lesions. This is the first case of recurrent cutaneous AMZH that has uncharacteristic kappa light-chain restriction. AMZH should be considered in children with mucocutaneous lesions with features of marginal zone lymphoma.

Dyserythropoiesis in a child with pyruvate kinase deficiency and coexistent unilateral multicystic dysplastic kidney.

Pyruvate kinase (PK) deficiency is the commonest enzyme deficiency in the glycolytic pathway leading to hemolytic anemia secondary to decreased Adenosine Triphosphate (ATP) synthesis in the red cells. synthesis. PK deficiency due to mutations in the PKLR (1q21) gene leads to highly variable clinical presentation ranging from severe fetal anemia to well compensated anemia in adults. We describe dyserythropoiesis in the bone marrow of a child with transfusion dependent anemia and unilateral multicystic dysplastic kidney (MCDK) mimicking Congenital Dyserythropoietic Anemia type I (CDA type I). Persistently low erythrocyte PK levels and double heterozygous mutations present in the PKLR gene confirmed the diagnosis of PK deficiency.

Pathologic assessment of hepatocellular carcinoma in the era of immunotherapy: a narrative review.

Background and Objective: Immune checkpoint inhibitor (ICI)-based therapy has achieved impressive success in various cancer types. Several ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma (HCC) in recent decade. Meanwhile, numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival, respectively. In this review, we aim to summarize some pragmatic histomorphologic, immunohistochemical, and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for HCC. Methods: We searched PubMed using the terms hepatocellular carcinoma, immunotherapy, immune checkpoint inhibitor, immune checkpoint blockade, conversion therapy, neoadjuvant therapy, adjuvant therapy, biomarker, pathologic evaluation, pathologic assessment till February 2023. Key Content and Findings: Although there is no consensus regarding the pathologic evaluation of relevant HCC specimens, it is encouraging that a few of studies have concentrated on this field, and moreover, the methods and parameters noted on other cancer types are also worthy of reference. For the pathologic assessment of HCC specimens underwent immunotherapy, a suitable sampling scheme, identifying immunotherapy-related pathologic response, and quantification of pathologic response rate should be emphasized. For the patients of HCC who are scheduled to receive immunotherapy, tumor-infiltrating lymphocyte, intratumoral tertiary lymphoid structure, programmed cell death ligand 1, Wnt/ß-catenin, microsatellite instability and mismatch repair, tumor mutational burden and tumor neoantigen, as well as some other signaling pathways are the potential predictive biomarkers of treatment response of ICI. Conclusions: The management of HCC in the era of immunotherapy arises a brand-new pathological challenge that is to provide an immunotherapy-related diagnostic report. Albeit many related researches are preclinical or insufficient, they may tremendously alter the immunotherapy strategy of HCC in future.

p28(GANK) prevents degradation of Oct4 and promotes expansion of tumor-initiating cells in hepatocarcinogenesis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is believed to arise from tumor-initiating cells (T-ICs), although little is known about their stem cell-like properties. METHODS: We quantified levels of p28(GANK) (Gankyrin), OV6, and Oct4 in 130 human HCC samples using immunohistochemistry. Magnetic-activated cell sorting was used to isolate OV6+ HCC cells. T-IC properties were evaluated by quantitative reverse-transcription polymerase chain reaction, flow cytometry, and spheroid formation. We used a coimmunoprecipitation assay to study interactions among p28(GANK), Oct4, and WWP2. Tumorigenicity and pulmonary metastasis were examined in nonobese diabetic and severe combined immunodeficient mice. RESULTS: In HCC samples, high levels of p28(GANK) correlated with expansion of OV6+ tumor cells; the combination of high levels of p28(GANK) and OV6 was associated with progression of HCC. p28(GANK) was predominantly expressed in liver T-ICs, isolated by magnetic sorting, and undifferentiated primary HCC spheroids. Increased levels of p28(GANK) in T-ICs increased their percentages in HCC samples, expression of stem cell genes, self-renewal potential, chemoresistance in vitro, and tumorigenicity and ability to develop into pulmonary metastases in mice. Conversely, knockdown of p28(GANK) reduced their T-IC properties. p28(GANK) likely activates liver T-ICs by impeding ubiquitination and degradation of the transcription factor Oct4 by WWP2. In support of this concept, levels of p28(GANK) correlated with those of Oct4 in HCC samples. CONCLUSIONS: p28(GANK) activates and maintains liver T-ICs in HCCs by preventing degradation of Oct4. Inhibitors of p28(GANK) might therefore be developed to inactivate T-ICs and slow tumor progression.

High expression of proline-rich tyrosine kinase 2 is associated with poor survival of hepatocellular carcinoma via regulating phosphatidylinositol 3-kinase/AKT pathway.

BACKGROUND: The peritumoral environment has been implicated to be important in the process of metastasis and recurrence in hepatocellular carcinoma (HCC). Our aims were to assess the prognostic value of proline-rich tyrosine kinase 2 (Pyk2) in HCC and investigate related molecular mechanism. METHODS: Expression of Pyk2 was tested by immunohistochemistry in tissue microarrays containing 141 paired HCC samples. Correlation between Pyk2 and vascular endothelial growth factor (VEGF) expression in clinical samples was analyzed by Spearman rank correlation. Matrigel invasion, anchorage-independent growth assay and immunoblotting were performed to study the effect of Pyk2 on the invasion and progression of HCC cells and phosphoinositide 3-kinase (PI3K)/AKT pathway activation. RESULTS: Higher Pyk2 density in both tumor and peritumor was associated with lower overall survival (P = 0.044; P = 0.041, respectively), serum AFP levels > 1,000 ng/ml (P = 0.013; P = 0.032, respectively) and postoperative distant metastasis (both P < 0.001). However, only higher peritumoral Pyk2 density was related to lower disease-free survival (P = 0.014) and vascular invasion (P = 0.035). A significant correlation between Pyk2 and VEGF density in tumor or peritumoral liver tissue was observed (r = 0. 3133, P = 0.0002; r = 0.5176, P < 0.0001, respectively). Immunoblotting showed that Pyk2 activated PI3K-AKT pathway to upregulate VEGF expression in HL-7702, SMMC-7721 and HepG2 cells. CONCLUSIONS: High Pyk2, especially peritumoral Pyk2 was associated with poor survival, disease recurrence, and metastasis in HCC. PI3K-AKT pathway was involved in Pyk2-mediated VEGF expression during HCC progression and invasion.

Initial and follow-up evaluations on cerebrospinal fluid involvement by hematologic malignancy.

Central nervous system (CNS) involvement is a serious complication in hematologic malignancy, and early detection and management of CNS involvement in these cases significantly impact the prognosis. Currently, there is no consensus on the use of multiparametric flow cytometry (MFC) and conventional cytology (CC) testing for initial and follow-up cerebrospinal fluid (CSF) specimens to diagnose CNS involvement by hematologic malignancy. In our institution, after initial MFC and CC, two subsequent negative MFCs are required before discontinuing MFC. The aim of this study is to evaluate the outcome of this approach. CSF cytology and MFC reports were retrieved from Laboratory Information System, and data was reviewed. Between January 2020 and December 2021, 1789 CSF samples from 280 patients were submitted for CSF analysis. For those 517 CSF samples tested by both MFC and CC, 97 cases tested positive by both MFC and CC with 95% concordance. Eighteen cases were MFC + /CC - and 7 were MFC - /CC + . Thirty-six cases had initially positive MFCs followed by more than one MFC evaluation. Among those 36 cases, 22 cases (61.1%) converted to negative after the second follow-up sample, 9 cases (25%) were continuously positive for at least three samples, and 5 cases (13.9%) exhibited negative to positive conversion. Compared to negative CSF cases, positive CSFs had higher total nucleated cell count and higher total protein levels while red blood cells, glucose, and lactate dehydrogenase levels remained at comparable levels. The concordance between MFC and CC was excellent. The high incidence of positive MFCs on two or more follow-up samples and the high frequency of negative MFC to positive conversion indicate the necessity of repeated negative MFCs before discontinuing MFC. The fact that more than half of the positive cases converted to negative after the second CSF specimen and most follow-up positive cases can be detected by CC alone suggests it is adequate to use CC alone for follow-up CSF study after two consecutive negative MFCs.

Multiparameter flow cytometry and ClonoSEQ correlation to evaluate precursor B-lymphoblastic leukemia measurable residual disease.

Measurable residual disease (MRD) detection for precursor B-lymphoblastic leukemia (B-ALL) has become the standard of care. However, the testing methodology has not been standardized. We aim to correlate COG multiparameter flow cytometry (MFC) and ClonoSEQ techniques to assess the test characteristics, to study abnormal immunophenotype for B-ALL MRD, and to observe B-ALL clonal evolution and the impact of blinatumomab therapy on MFC testing. MFC and molecular reports were retrieved from electronic medical records and data was reviewed. Included in this study were 74 bone marrow samples collected from 31 B-ALL patients at our institution between January 2021 and March 2022. COG MFC and ClonoSEQ results were concordant in 59/74 samples (80%) with positive concordant results in 12 samples (16%) and negative concordant results in 47 samples (64%). Discordant results were seen in 15/74 samples (20%), with 14 samples (19%) showing ClonoSEQ + /MFC- results and only 1 sample (1%) showing MFC + /ClonoSEQ- result. ClonoSEQ + /MFC- cases had MRD values ranging from 1 to 1400 cells/million nucleated cells with 86% of cases showing MRD values of < 100 cells/million nucleated cells. Newly identified dominant sequences were detected using ClonoSEQ in 2/31 patients (6%) during follow-up. All 14 bone marrow samples from 8 patients, who had gone through blinatumomab immunotherapy, were MRD negative by MFC, but 3 cases were MRD positive by ClonoSEQ. Our results show strong correlation between COG MFC and ClonoSEQ (r = 0.96), and both methods are complementary. Clonal evolution may occur, and blinatumomab immunotherapy may impact MFC B-ALL MRD evaluation.

Camelid-derived CD38 antibody successfully circumvents epitope blockade by the therapeutic anti-CD38 antibody daratumumab.

OBJECTIVES: To evaluate the efficacy of an anti-CD38 nanobody to detect plasma cells in a flow cytometry myeloma minimal residual disease (MRD) panel in patients treated with daratumumab and other immunotherapies. METHODS: Twenty-three bone marrow samples from as many patients were collected during or at the end of daratumumab treatment cycles. A 5-tube, 8-color flow cytometry MRD panel was performed. Dotplots were reviewed, and the median fluorescence intensity (MFI) was calculated. RESULTS: Patients' ages ranged from 45 to 77 years, and the cohort was made up of 13 men and 10 women who had undergone 2 to 24 cycles of daratumumab therapy at the time of myeloma MRD testing. In all 23 cases, therapeutic use of daratumumab impaired pathologists' ability to measure CD38 on plasma cells when using a conventional murine monoclonal antibody (anti-CD38 fluorescein isothiocyanate [FITC], clone T16; Beckman Coulter). In 21 of the 23 cases, the measurement of CD38 was restored when the anti-CD38 nanobody was employed. Compared with anti-CD38 FITC, the anti-CD38 Alexa Fluor 488 nanobody (Beckman Coulter) produced higher MFI and allowed measurement of a higher frequency of discernable plasma cells. CONCLUSIONS: The camelid-derived CD38 antibody successfully circumvents the steric inhibition of CD38 that the therapeutic use of daratumumab imparts and facilitates myeloma MRD plasma cell detection.

Acute myeloid leukemia with LRRFIP1::FGFR1 rearrangement and a complex karyotype.

We report a case of a 20-year-old man who presented with splenomegaly, hyperleukocytosis, anemia, and thrombocytopenia. A diagnosis of acute myeloid leukemia (AML) with LRRFIP1::FGFR1 rearrangement with complex karyotype was determined. Chromosome analysis showed a male karyotype: 46,XY,i(1)(q10),t(2;8)(q37;p11.2),der(5)t(1;5) (p22;q13)[17]46,XY[3]. Fluorescence in situ hybridization (FISH) analysis using the Cytocell FGFR1 break apart/amplification probe detected FGFR1 rearrangement with t(2:8) in 126/200 cells analyzed. Other FISH probes including 1p36/ 1q25 probes, del(5q) deletion probe, TLX3 break apart probe, and PDGFRB break apart probe were also utilized to confirm the other karyotypic abnormalities. Next-generation sequencing (NGS) SureSelectXT Custom DNA Target Somatic Detection detected RUNX1 gene mutation. NGS Archer FusionPlex (RNA) confirmed the LRRFIP1::FGFR1 rearrangement. This is the second reported case of AML with LRRFIP1::FGFR1 rearrangement and the first with a complex karyotype.

p28GANK overexpression accelerates hepatocellular carcinoma invasiveness and metastasis via phosphoinositol 3-kinase/AKT/hypoxia-inducible factor-1α pathways.

UNLABELLED: The overall survival of patients with hepatocellular carcinoma (HCC) remains poor, and the molecular mechanisms underlying HCC progression and aggressiveness are unclear. Here, we report that increased expression of p28(GANK) (Gankyrin, PSMD10, or p28) in human HCC predicts poor survival and disease recurrence after surgery. Patients with HCC who have large tumors, with vascular invasion and intrahepatic or distant metastasis, expressed high levels of p28(GANK) . Invasive tumors overexpressing p28(GANK) were featured by active epithelial-mesenchymal transition (EMT), and exhibited increased angiogenesis associated with vascular endothelial growth factor overexpression, whereas silencing p28(GANK) expression attenuated EMT and motility/invasion of tumor cells. The p28(GANK) activates phosphoinositide 3-kinase (PI3K)-V-akt Murine Thymoma Viral Oncogene Homolog (AKT)-hypoxia-inducible factor 1α (HIF-1α) signaling to promote TWIST1, vascular endothelial growth factor, and metalloproteinase 2 expression. Suppression of the PI3K-AKT-HIF-1α pathway interfered with p28(GANK) -mediated EMT and invasion. Consistently, we detected a significant correlation between p28(GANK) expression and p-AKT levels in a cohort of HCC biopsies, and the combination of these two parameters is a more powerful predictor of poor prognosis. CONCLUSION: These results present novel mechanistic insight into a critical role of p28(GANK) in HCC progression and metastasis.

Unusual B-Lymphoid Blastic Crisis as Initial Presentation of Chronic Myeloid Leukemia Imposes Diagnostic Challenges.

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder, characterized by reciprocal translocation t(9,22) (q34; q11), leading to increased myeloid proliferation. Most cases are diagnosed in the chronic phase (CP). However, a minority of cases can be present in the blastic phase (BP). In most patients with CML-BP, the blasts have a myeloid phenotype, however, in 20-30% of cases, the blasts have a lymphoid phenotype, mostly a B-cell phenotype. It is challenging to differentiate CML B-lymphoblastic phase (CML-BLP) from Ph + primary B-acute lymphoblastic leukemia (B-ALL) especially when the CML-BLP is the initial presentation of the disease, which is uncommon. We report here an unusual case of CML-BLP as an initial presentation of the disease without typical CML morphological findings. This case demonstrates diagnostic challenges and emphasizes the importance of an integrated approach using morphology, multiparametric flow cytometry, cytogenetic studies, and molecular studies to render an accurate diagnosis.

Molecular analysis of melanoma-induced sentinel lymph node immune dysfunction.

INTRODUCTION: Sentinel lymph nodes (SLNs) of melanoma patients show evidence of tumor-induced immune dysfunction. Our previous works have shown that IL-10 and IFNγ co-regulate indoleamine-2,3-dioxygenase (IDO)-expressing immunosuppressive dendritic cells (DCs) in melanoma SLNs. The goal of this study is to examine the relationship between melanoma SLN tumor burden and the degree of SLN immune dysfunction as a model to study tumor-induced immune dysfunction. We hypothesize that SLN tumor burden correlates with the degree of SLN immune dysfunction. METHODS: Patients undergoing SLN biopsy for clinical stages I and II melanomas were enrolled in the study under an IRB-approved protocol. During the SLN biopsy, non-hot and non-blue portion of the SLN was harvested, flash-frozen in liquid nitrogen, and mRNA was extracted. By using quantitative real-time PCR, gene expressions of cytokines (IL-4, IL-10, IFNγ, TGFß, GM-CSF) and the surrogates of immunosuppressive regulatory and effector cells (IDO-expressing DCs and Foxp3-expressing T-regs, respectively) were measured and correlated against the SLN tumor burden (MART1) and against each other. The data were log transformed for normalization. Statistical test used Student's t-test and stepwise multivariate regression analysis. Statistical significance was determined at P < 0.05. RESULTS: SLNs of 74 patients were analyzed in this analysis. Ten of seventy-four patients (13.5%) had tumor-positive SLNs. MART1 gene expression showed a significant difference between the SLN (+) and SLN (-) groups (P = 0.04). Among the various cytokines, multivariate analysis showed that only IFNγ gene expression correlated independently with MART1 gene expression (P < 0.0001, r = 0.91). Similar multivariate analyses show that IFNγ (P < 0.0001, r = 0.78), IL-10 (P = 0.0037, r = 0.60), and TGFß (P < 0.0001, r = 0.95) gene expressions correlated independently with IDO gene expression. IFNγ (P < 0.0001, r = 0.87) and GM-CSF (P = 0.042, r = 0.76) gene expressions correlated independently with Foxp3 gene expression. MART1 gene expression showed independent correlation with IDO (P = 0.0002, r = 0.75) and Foxp3 (P = 0.0002, r = 0.75) gene expressions. CONCLUSION: SLN tumor burden correlates with immunosuppressive IDO and Foxp3 expressions within the SLNs of melanoma patients. Our data are consistent with our theory that melanoma induces expressions of specific cytokines, which in turn, stimulate immune suppressors within the SLN. This study also supports our previous finding that IL-10 and IFNγ co-regulate IDO within the SLN. In our data, IFNγ is the sole cytokine that correlates with the SLN tumor burden and seems to play a central role in tumor-induced immunological changes in the SLN immune microenvironment.

Bi-allelic amplification of ATM gene in blastoid variant of mantle cell lymphoma: a novel mechanism of inactivation due to chromoanagenesis?

BACKGROUND: Mantle cell lymphoma (MCL) is derived from naïve CD5+ B-cells with the cytogenetic hallmark translocation 11;14. The presence of additional abnormalities is associated with blastoid variants in MCL (BMCL) and confers a poor prognosis. Many of these tumors also show deletion or loss of heterozygosity (LOH) of the ATM gene and biallelic ATM inactivation show significantly higher chromosomal imbalances. CASE PRESENTATION: Here we report a 52 year-old male who presented to the clinic with worsening dyspnea, fever, chills, diffuse lymphadenopathy, splenomegaly and leukocytosis with blastoid cells circulating in blood. The bone marrow aspirate showed about 40% abnormal blast-looking cells and biopsy revealed a remarkable lymphoid infiltrate. The patient was diagnosed with blastoid variant mantle cell lymphoma (BMCL). Chromosome analysis on bone marrow showed a complex karyotype. FISH analysis from B-cell lymphoma panel showed bi-allelic amplification of ATM gene. Other abnormalities were present including CCND1/IGH fusion, confirming the MCL diagnosis, in addition to RB1 and p53 deletion. High resolution SNP-microarray studies showed complex copy number changes, especially on chromosomes 7 and 11, consistent with chromoanagenesis. Microarray studies also showed LOH at the ATM locus indicating the amplification seen on FISH is not biallelic. CONCLUSION: To the best of our knowledge, ATM gene amplification is not previously reported in BMCL and our case suggests a novel mechanism of ATM inactivation caused by chromoanagenesis resulting in mutant allele specific imbalance with copy number gain.

Liver Resection Is Justified in Patients with BCLC Intermediate Stage Hepatocellular Carcinoma without Microvascular Invasion.

BACKGROUND: Large, multinodular (> 3 nodules and/or > 3 cm) hepatocellular carcinoma (HCC) is not an indication for liver resection based on the Barcelona Clinic Liver Cancer (BCLC) staging classification. We hypothesize that microvascular invasion (MVI) is a strong indication for surgery in these patients. METHODS: Between December 2009 and December 2010, a retrospective cohort of the patients with BCLC intermediate stage HCC undergoing surgical resection at Eastern Hepatobiliary Surgery Hospital was analyzed. Propensity score matching (PSM) was conducted to balance the patients with regard to their baseline characteristics. Survival analysis was performed according to the Kaplan-Meier method. Logistic regression was conducted to identify the predictors of MVI. Risk factors were evaluated using the Cox proportional hazards model. RESULTS: Among 323 patients, the MVI-negative group (26.0%) had a more favorable prognosis than did the MVI-positive group (5-year recurrence-free survival: 25.2% vs. 7.8%; 5-year overall survival: 49.5% vs. 24.0%). Similar results were identified after PSM. Compared with MVI-negative patients, MVI-positive patients experienced more early recurrence (< 2 years, P = 0.006), multinodular recurrence (P = 0.004), and extrahepatic recurrence (P = 0.026). Total bilirubin levels > 17.1 µmol/L, alpha fetal protein levels > 400 ng/mL, the presence of > 2 nodules, and the lack of a capsule were independent predictors of MVI. CONCLUSIONS: In BCLC intermediate stage HCC, MVI predicted an adverse recurrence pattern and poor prognosis and has the potential to be used as a reference index when deciding whether to operate. Factors predictive of MVI could assist in choosing preoperative treatment and postoperative surveillance.

Cat Scratch Disease Is an Entity Often Diagnosed in Breast Imaging Department During Axillary Lymph Node Assessment.

Cat scratch disease (CSD) is an infectious disease process of generally immunocompetent children and young adults. This infection can be introduced through skin trauma by direct exposure to the saliva of an infected kitten or cat. CSD is typically associated with constitutional symptoms and self-limited regional lymphadenopathy. In the sole presence of swollen lymph nodes, however, the differential diagnosis for CSD is relatively broad, including an active infection, an ongoing inflammatory process, and a metastatic process. CSD can present as axillary lymphadenopathy without typical constitutional symptoms. With proper clinical and laboratory investigation, CSD can be accurately identified and correctly diagnosed, as demonstrated in this case series featuring five symptomatic young adults with axillary lymphadenopathy. Breast imaging clinic specializes in lymph node assessment because metastatic lymphadenopathy is one of the most common presenting signs of breast cancer. Most isolated axillary lymphadenopathy without breast mass is benign reactive lymphadenopathy, but biopsy is necessary to exclude malignancies, such as metastatic lymphadenopathy or lymphoma.

Impact of Surgical Margin on the Prognosis of Early Hepatocellular Carcinoma (≤5 cm): A Propensity Score Matching Analysis.

Aim: The influence of surgical margin on the prognosis of patients with early solitary hepatocellular carcinoma (HCC) (≤5 cm) is undetermined. Methods: The data of 904 patients with early solitary HCC who underwent liver resection were collected for recurrence-free survival (RFS) and overall survival (OS). Propensity score matching (PSM) was performed to balance the potential bias. Results: Log-rank tests showed that 2 mm was the best cutoff value to discriminate the prognosis of early HCC. Liver resection with a >2 mm surgical margin distance (wide-margin group) led to better 5-year RFS and OS rate compared with liver resection with a ≤2 mm surgical margin distance (narrow-margin group) among patients both before (RFS: 59.1% vs. 39.6%, P < 0.001; OS: 85.3% vs. 73.7%, P < 0.001) and after PSM (RFS: 56.3% vs. 41.0%, P < 0.001; OS: 83.0% vs. 75.0%, P = 0.010). Subgroup analysis showed that a wide-margin resection significantly improved the prognosis of patients with microvascular invasion (RFS: P < 0.001; OS: P = 0.001) and patients without liver cirrhosis (RFS: P < 0.001; OS: P = 0.001) after PSM. Multivariable Cox regression analysis revealed that narrow-margin resection is associated with poorer RFS [hazard ratio (HR) = 1.781, P < 0.001), OS (HR = 1.935, P < 0.001], and early recurrence (HR = 1.925, P < 0.001). Conclusions: A wide-margin resection resulted in better clinical outcomes than a narrow-margin resection among patients with early solitary HCC, especially for those with microvascular invasion and without cirrhosis. An individual strategy of surgical margin should be formulated preoperation according to both tumor factors and background liver factors.

Lymphoma-Associated Monoclonal Cryoglobulinemic Glomerulonephritis and Relationship with Hepatitis C Virus Infection: A Case Report.

We report a case of type I cryoglobulinemic glomerulonephritis in a patient with chronic hepatitis C who presented with acute renal failure. The renal biopsy revealed membranoproliferative GN (MPGN) due to cryoglobulinemia with unexpected monoclonal Kappa restriction on immunofluorescence microscopy, suggesting an underlying hematopoietic malignancy. The bone marrow biopsy revealed presence of marginal zone lymphoma. Our case raises awareness regarding possibility of monoclonality in the renal biopsy of HCV-infected patients and exemplifies the crucial role the renal biopsy plays in detecting lymphoid malignancies where clinical features are ambiguous.