Hematopathology Fellowship

血液病理学奖学金在吸引杰出的 申请人，并为他们提供血液病理学培训，强调优秀的 临床诊断和专业诊断工具，包括分子诊断和流动 细胞仪该奖学金自2000年以来一直得到ACGME的认可， 在美国病理学委员会颁发的认证考试中通过率为100%。 毕业研究员继续在学术医学领域建立独立的职业生涯，包括 近年来在贝勒大学医学院、马约诊所、 斯隆凯特琳纪念癌症中心和克利夫兰诊所。鼓励研究员 参与临床研究，并成功完成了各种 主题，下面简单介绍一下。我们已进行研究，探讨 滤泡性淋巴瘤（FL）的细胞因子微环境。FL的特征是组成性的 Bcl-2的表达作为t的结果（14;18）。有证据表明淋巴结中的因素 与肿瘤内T细胞、巨噬细胞和树突状细胞相关的微环境在肿瘤的发生发展中起着重要作用。 在疾病过程中的作用。我们生成了FL（N = 50）的蛋白质组细胞因子谱， 滤泡增生（FH; N = 23）。共检测10种细胞因子 多重酶联免疫吸附测定：IL-1 β、IL-2、IL-4、IL-5、IL-8、IL-10、IL-13， IL-12 p70、肿瘤坏死因子-α和干扰素-γ。每种细胞因子总体上显示 FL中的蛋白质浓度较低，但IL-4除外，其接近5倍 FL组高于FH组（P = .005）。使用反相蛋白质微阵列（RPMAs），我们评估了 细胞因子下游几种细胞内信号蛋白的激活状态 受体。FL的基础Erk磷酸化水平比FH高约4倍（P <.001），与Mek相似; Stat-6显示弱的基础磷酸化 FL组的这一比例大约是FH组的两倍（P = 0.012）。最后，FL 微环境中含有增加的IL-4水平，具有显著的肿瘤基础磷酸化 的Erk。这些发现表明IL-4、Erk和可能的Stat-6可能在生物学中起作用。 FL，并可能作为未来治疗的目标。在另一项研究中，我们评估了 FL甲基化组的重塑。新兴技术允许对癌症进行广泛的分析 基因组相对于良性细胞的差异DNA甲基化。亚硫酸氢盐修饰的DNA 使用免疫组织化学方法分析反应性增生或滤泡性淋巴瘤（FL）的淋巴结。 商业C/UpG基因分型测定。259个差异甲基化靶点 (DMT)分布在FL中的183个独特基因中。 福尔马林固定、石蜡包埋和冷冻的手术病理学复制显示， 在不同存档的组织标本中保存癌症甲基化组。分析 DMT谱与FL中普遍表观基因组重塑过程一致， 主要影响非淋巴基因。在咨询中看到的一个新案例的例子导致 一位实习生同事发表了一份病例报告移植后淋巴增生 免疫抑制性疾病（PTLD）可能作为免疫抑制的并发症发生在具有以下特征的患者中： 接受了实体器官或骨髓移植大多数PTLD是B细胞谱系，而 T细胞增殖是罕见的。大多数B细胞病变与 EB病毒感染。B细胞和T细胞PTLD在同一组织中的发生率 这是一个非常罕见的病例，以前只发表过6例。我们报告了一个 一名63岁的男性，从2011年开始发生2例异时性EB病毒相关PTLD， 心脏移植后10年首先开发了多态性B细胞PTLD， 免疫抑制治疗部分停止后完全消退。然后 31个月后出现单形性T细胞PTLD。患者于17个月后死亡， 疾病进展。我们强调这种情况下，需要大量的诊断挑战 谱系评估和分类的辅助研究。这些研究往往需要在 有免疫抑制史的患者。

The Hematopathology Fellowship has been highly successful in attracting outstanding applicants and in providing them with training in hematopathology, emphasizing outstanding clinical diagnosis, and specialized diagnostic tools including molecular diagnostics and flow cytometry. The fellowship has been ACGME accredited since 2000, and graduating fellows have had a 100% pass rate on the accrediting examination given by the American Board of Pathology. Graduating fellows gone on to establish independent careers in academic medicine, including appointments in recent years at Baylor University School of Medicine, The Mayo Clinic, Memorial Sloan Kettering Cancer Center, and the Cleveland Clinic. Fellows are encouraged to participate in clinical research, and have successfully completed studies on a variety of topics, as briefly mentioned below. We have undertaken studies to examine the influence of the cytokine microenvironment in Follicular lymphoma (FL). FL is characterized by constitutive expression of Bcl-2 as a consequence of t(14;18). Evidence suggests factors in the lymph node microenvironment, related to intratumoral T cells, macrophages, and dendritic cells, play a role in the disease process. We generated proteomic cytokine profiles of FL (N = 50) and follicular hyperplasia (FH; N = 23). A total of 10 cytokines were assayed using ultrasensitive multiplex enzyme-linked immunosorbent assays: IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-13, IL-12p70, tumor necrosis factor-alpha, and interferon-gamma. Each cytokine showed overall lower protein concentrations in FL, with the exception of IL-4, which was nearly 5 times higher in FL than FH (P = .005). Using reverse-phase protein microarrays (RPMAs), we evaluated the activation state of several intracellular signaling proteins downstream of cytokine receptors. Basal Erk phosphorylation was approximately 4 times greater in FL than FH (P < .001), with similar findings for Mek; Stat-6 showed weak basal phosphorylation that was approximately twice as high in FL than in FH (P = .012). In conclusion, the FL microenvironment contains increased levels of IL-4, with prominent tumor basal phosphorylation of Erk. These findings suggest IL-4, Erk, and possibly Stat-6 may play a role in the biology of FL and may serve as targets for future therapies. In another study we evaluated the remodeling of the FL methylome. Emerging technologies allow broad profiling of the cancer genome for differential DNA methylation relative to benign cells. Bisulfite-modified DNA from lymph nodes with either reactive hyperplasia or follicular lymphoma (FL) were analyzed using a commercial C/UpG genotyping assay. Two hundred fifty-nine differentially methylated targets (DMT) distributed among 183 unique genes were identified in FL. Comparison of matched formalin-fixed, paraffin-embedded and frozen surgical pathology replicates showed the complete preservation of the cancer methylome among differently archived tissue specimens. Analysis of the DMT profile is consistent with a pervasive epigenomic remodeling process in FL that affects predominantly nonlymphoid genes. An example of a novel case seen in consultation led to the publication of a case report by a fellow trainee. Posttransplant lymphoproliferative disorders (PTLDs) may occur as a complication of immunosuppression in patients who have received solid organ or bone marrow allografts. Most PTLDs are of B-cell lineage, whereas T-cell proliferations are rare. The majority of B-cell lesions are associated with Epstein-Barr virus infection. The occurrence of both B-cell and T-cell PTLDs in the same patient is extremely rare and only 6 cases have been previously published. We reported a case of a 63-year-old man who developed 2 metachronous Epstein-Barr virus-related PTLDs beginning 10 years after heart transplantation. A polymorphic B-cell PTLD developed first that completely regressed after immunosuppressive therapy was partially withdrawn. Then, a monomorphic T-cell PTLD developed 31 months later. The patient died 17 months later owing to disease progression. We highlight the diagnostic challenge of this case that required numerous ancillary studies for lineage assessment and classification. Such studies are often needed in patients with a history of immunosuppression.