BACKGROUND & AIMS: BACKGROUND AND AIMS:Pancreatic cysts are increasingly diagnosed, mainly during abdominal imaging performed for other reasons. Between pancreatic cystic neoplasm, intraductal papillary mucinous neoplasms are the most common pre-malignant entities. Intraductal papillary mucinous neoplasms involving side branches overall harbor a low risk of malignancy, and in the recent past, a progressively more conservative approach has been consolidated. Purpose of this report is to summarize the evidence supporting the current practice for the management of branch duct intraductal papillary mucinous neoplasm and to offer a useful practical guide from first observation to post-operative follow-up. MATERIALS AND METHODS:Review of the most important scientific literature on intraductal papillary mucinous neoplasms was made. In this review article, we also report the experience of a high volume center in managing Pancreatic cystic neoplasms. RESULTS:The correct management during surveillance still is a matter of debate, since many guidelines have been published suggesting different clinical approaches. Recently, follow-up discontinuation has also been proposed in selected cases. CONCLUSION:Despite significant improvements made by the increase of evidence, selecting surgical candidates because of an increased risk of malignant progression remains an unsolved issue and a hot topic for pancreatologists.

背景与目标： 背景与目的：胰腺囊肿的诊断越来越多，主要是在出于其他原因进行的腹部成像过程中。在胰腺囊性肿瘤之间，导管内乳头状粘液性肿瘤是最常见的恶性前实体。涉及侧支的导管内乳头状粘液性肿瘤总体上具有较低的恶性风险，并且在最近的过去，已逐渐加强了一种保守的方法。本报告的目的是总结支持分支导管导管内乳头状粘液性肿瘤治疗的现有证据，并为从首次观察到术后随访提供有用的实用指南。
材料与方法：对导管内乳头状黏液性肿瘤的最重要的科学文献进行了综述。在这篇评论文章中，我们还报告了处理胰腺囊性肿瘤的高容量中心的经验。
结果：监测期间的正确管理仍是一个有争议的问题，因为已经发布了许多指南，建议采用不同的临床方法。最近，在某些情况下也提出了随访中止的建议。
结论：尽管证据增加取得了显着改善，但由于恶性进展风险增加而选择手术候选者仍是一个尚未解决的问题，并且是胰腺科医生的热门话题。

BACKGROUND & AIMS: BACKGROUND:Obstructive sleep apnoea (OSA) can be caused by neoplasms involving the upper aerodigestive tract. Currently, many of these patients have this diagnosis missed, as most adults diagnosed with OSA do not undergo adequate head and neck examination including flexible nasendoscopy. We performed a review of the literature to shed light on this phenomenon and outline the pathologies and issues surrounding this sub-population of patients diagnosed with OSA. METHODS:A scoping review of the literature was conducted on head and neck neoplasms presenting with OSA. Data were extracted on demographics, clinical presentation, histopathology, treatment and patient outcomes. RESULTS:Sixty-seven articles were included, describing 79 patients. Mean age was 45.8 years, and 77.2% were male. Symptoms of OSA were present for an average of 29.2 months before a diagnosis of causative neoplasm was made. Forty-two different benign and malignant histopathological entities were reported. At diagnosis, the causative pathology of 100% of patients was visible on head and neck examination including flexible nasendoscopy, while only 53.2% were visible on trans-oral examination. One-third of patients had commenced inappropriate treatment for OSA, including three who had undergone sleep surgical procedures. The majority of patients were treated with surgery alone (72.2%). CONCLUSION:Although rare, neoplasms of the upper aerodigestive tract should be considered as a cause of OSA, especially in patients experiencing other symptoms in addition to the typical symptoms of OSA. They should particularly be considered in patients with comparatively lower body mass index or those with worsening OSA without an apparent cause identified.

背景与目标： 背景：阻塞性睡眠呼吸暂停（OSA）可由累及上消化道的肿瘤引起。当前，由于大多数被诊断患有OSA的成年人没有接受包括软性鼻内窥镜检查在内的充分的头颈部检查，因此许多此类患者的诊断均未通过。我们对文献进行了回顾，以阐明这种现象，并概述围绕诊断为OSA的患者这一亚群的病理学和问题。
方法：对出现OSA的头颈部肿瘤进行文献范围的回顾。提取了有关人口统计学，临床表现，组织病理学，治疗和患者预后的数据。
结果：共纳入67篇文章，描述了79例患者。平均年龄为45.8岁，男性为77.2％。诊断为致病性肿瘤之前，平均出现OSA症状29.2个月。报告了42种不同的良性和恶性组织病理学实体。在诊断时，包括软性鼻内窥镜检查在内的头颈检查可见100％患者的病因病理，而经口检查仅可见53.2％的病因。三分之一的患者开始对OSA进行不适当的治疗，包括三名接受了睡眠外科手术的患者。大多数患者仅接受手术治疗（72.2％）。
结论：尽管罕见，上消化道肿瘤应被认为是OSA的病因，尤其是在除了OSA的典型症状之外还出现其他症状的患者中。对于体重指数相对较低的患者或OSA恶化且未发现明显原因的患者，应特别考虑使用它们。

BACKGROUND & AIMS: :Fli-1 protein, a member of the ETS family of DNAbinding transcription factors, is involved in cellular proliferation and tumorigenesis. Approximately 90% of Ewing's sarcoma/primitive neuroectodermal tumors (ES/PNET) have a specific translocation, t(11;22)(q24;q12), which results in fusion of EWS to Fli-1, and production of an EWS-Fli-1 fusion protein. We have recently shown that immunohistochemistry for the carboxy terminal of Fli-1 protein is sensitive and highly specific for the diagnosis of ES/PNET. In our earlier study we noted that among normal tissues only endothelial cells and small lymphocytes expressed Fli-1. Fli-1 expression in vascular neoplasms has not been previously studied. Formalin-fixed paraffin-embedded tissue from 54 vascular tumors and 75 nonvascular tumors were immunostained for Fli-1 (1:120, Sc 356, Santa Cruz Biotechnology, Santa Cruz, CA), after steam heat-induced epitope retrieval. Only cases with >10% of cells showing nuclear staining were accepted as positive. Cases without positive internal controls (endothelium and small lymphocytes) were not scored. Positive internal controls were present in 122 of 129 cases (95%). One vascular tumor (Kaposi's sarcoma) and 7 nonvascular tumors (2 epithelioid sarcomas and 5 carcinomas) without internal controls were not scored. Fli-1 was expressed by 50 of 53 vascular tumors scored (94%), including 20 of 22 angiosarcomas, 11 of 12 hemangioendotheliomas, 7 of 7 hemangiomas, and 12 of 12 Kaposi's sarcomas. In contrast, Fli-1 expression was absent in the 68 nonvascular tumors scored (0 of 68), including 16 sarcomas, 7 melanomas, and 45 carcinomas. The results of this study strongly suggest a role for Fli-1 as a novel marker of both benign and malignant vascular tumors. The sensitivity (94%) and specificity (100%) of Fli-1 with regards to the cases evaluated in this study equal or exceed those of the established vascular markers, CD31, CD34, and von Willebrand factor. As the first nuclear, rather than cytoplasmic or membranous marker of endothelium, Fli-1 immunostaining also generally lacks cytoplasmic staining artifacts that are the result of endogenous peroxidases or biotin.

背景与目标： ：Fli-1蛋白是ETS DNA结合转录因子家族的成员，参与细胞增殖和肿瘤发生。约90％的尤因肉瘤/原始神经外胚层肿瘤（ES / PNET）具有特定的易位t（11; 22）（q24; q12），这导致EWS与Fli-1融合并产生EWS-Fli -1融合蛋白。我们最近显示，Fli-1蛋白羧基末端的免疫组织化学对ES / PNET的诊断是敏感和高度特异性的。在我们的早期研究中，我们注意到在正常组织中只有内皮细胞和小淋巴细胞表达Fli-1。 Fli-1在血管肿瘤中的表达以前尚未进行过研究。在蒸汽热诱导的抗原决定簇回收后，对来自54个血管肿瘤和75个非血管肿瘤的福尔马林固定石蜡包埋的组织进行Fli-1（1：120，Sc 356，Santa Cruz Biotechnology，Santa Cruz，CA）的免疫染色。只有细胞> 10％表现出核染色的病例才被视为阳性。没有阳性内部对照（内皮和小淋巴细胞）的病例没有评分。 129例病例中有122例（95％）存在阳性内部对照。没有内部对照的1个血管肿瘤（卡波西肉瘤）和7个非血管肿瘤（2个上皮样肉瘤和5个癌）均未评分。 Fli-1在53个评分为血管的肿瘤中表达50个（94％），包括22个血管肉瘤中的20个，12个血管内皮瘤中的11个，7个血管瘤中的7个和12个卡波济肉瘤中的12个。相比之下，评分的68例非血管肿瘤（68例中的0例）不存在Fli-1表达，包括16例肉瘤，7例黑素瘤和45例癌。这项研究的结果强烈暗示Fli-1作为良性和恶性血管肿瘤的新标志物的作用。对于本研究中评估的病例，Fli-1的敏感性（94％）和特异性（100％）等于或超过已建立的血管标志物CD31，CD34和von Willebrand因子。作为内皮的第一个核标记而不是细胞质或膜质标记，Fli-1免疫染色通常还缺少由于内源性过氧化物酶或生物素导致的细胞质染色伪影。

BACKGROUND & AIMS: :In this study serum cholesterol was measured in different types of human hematologic malignancies characterized by a wide range of cell proliferation. In all tumoral types a significant decrease of HDL cholesterol was observed, whereas total serum cholesterol generally remained unchanged. Another interesting observation of our study was the apparent inverse correlation between the extent of cell proliferation in these neoplastic disorders and the level of HDL cholesterol. Since a decrease of HDL cholesterol was previously observed, in our laboratory, in different experimental models of normal and neoplastic cell proliferation, we suggest that the decrease of HDL cholesterol may be a generalized phenomenon related to massive cellular growth in normal and malignant processes.

背景与目标： ：在这项研究中，以各种细胞增殖为特征的不同类型的人类血液系统恶性肿瘤中的血清胆固醇水平得到了测定。在所有肿瘤类型中，均观察到HDL胆固醇显着降低，而总血清胆固醇通常保持不变。我们研究的另一个有趣观察结果是这些肿瘤性疾病中细胞增殖程度与HDL胆固醇水平之间呈明显负相关。由于以前曾观察到HDL胆固醇降低，因此在我们的实验室中，正常和肿瘤细胞增殖的不同实验模型中，我们建议HDL胆固醇降低可能是与正常和恶性过程中大量细胞生长有关的普遍现象。

BACKGROUND & AIMS: :The value of intraoperative echo-contrast ultrasound (US) as compared with plain US was studied in 19 patients presenting with malignant liver tumors. The contrast medium SHU 454 was intraoperatively injected via the portal venous system or the biliary tract. Using intraoperative echo-contrast US, extremely small liver tumors could be sought in a limited area of the liver. In comparison with plain US, the former technique resulted in better demarcation of especially small tumors, which were seen as echo-poor areas in relation to the surrounding liver tissue.

背景与目标： ：在19例恶性肝肿瘤患者中研究了术中超声造影（US）与普通超声相比的价值。术中通过门静脉系统或胆道注射造影剂SHU 454。使用术中回声对比US，可以在肝脏的有限区域中寻找极小的肝肿瘤。与普通美国相比，前一种技术可以更好地划分特别小的肿瘤，这些肿瘤相对于周围的肝组织而言被认为是回声较差的区域。

BACKGROUND & AIMS: :Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can exhibit a wide spectrum of macroscopic and microscopic appearances. This not only causes occasional difficulties for the reporting pathologist in distinguishing these tumours from other lesions, but is also relevant clinically. As evidence accumulates, it becomes clear that multiple macroscopic and histological features of these neoplasms are relevant to the risk for malignant transformation and, consequently, of prime importance for clinical patient management. The need for detailed reporting is therefore increasing. This review discusses the panoply of gross and microscopic features of IPMN as well as the recommendations from recent consensus meetings regarding the pathology reporting on this tumour entity.

背景与目标： 胰腺的导管内乳头状黏液性肿瘤（IPMN）可以表现出广泛的宏观和微观外观。这不仅给报告病理学家带来了偶尔的困难，难以将这些肿瘤与其他病变区分开来，而且在临床上也很重要。随着证据的积累，很明显，这些肿瘤的多种宏观和组织学特征与恶性转化的风险有关，因此，对临床患者管理至关重要。因此，越来越需要详细的报告。这篇综述讨论了IPMN的总体和微观特征，以及最近关于该肿瘤实体病理报告的共识会议的建议。

BACKGROUND & AIMS: OBJECTIVES:Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas encompasses a spectrum of neoplasms with both morphological and immunohistochemical variations of mucin glycoproteins. Recently, a consensus nomenclature and criteria were histologically defined for classifying these variants of IPMNs into gastric, intestinal, pancreatobiliary, and oncocytic types. The purpose of this study was to determine associations between the histological types and clinicopathological features in patients with IPMN. METHODS:Sixty-one patients with IPMN operated upon at Tohoku University Hospital between 1988 and 2006 were retrospectively analyzed. RESULTS:Our series included 27 gastric-, 29 intestinal-, 4 pancreatobiliary-, and 1 oncocytic-type IPMNs. Statistically, the types of IPMN were significantly associated with the histological diagnoses, macroscopic types, and survival of the patients. Characteristically, the gastric-type IPMNs were likely to be diagnosed as benign, to be confined to branch ducts, and to have fair prognoses. On the other hand, the intestinal-type IPMNs were likely to be diagnosed as malignant, occupy the main duct, and have poor prognoses. Because of the small number of pancreatobiliary-type IPMNs and only 1 case of oncocytic-type IPMN, we were unable to determine any of their clinicopathological characteristics in our series. CONCLUSIONS:Evaluation of the histological types of IPMN may help to predict the clinical course of patients with IPMN and to design improved clinical management for these patients.

背景与目标： 目的：胰腺导管内乳头状粘液性肿瘤（IPMN）涵盖了一系列黏蛋白糖蛋白的形态学和免疫组化变异的肿瘤。最近，在组织学上定义了共识命名法和标准，以将IPMN的这些变体分类为胃，肠，胰胆管和溶细胞型。这项研究的目的是确定IPMN患者的组织学类型与临床病理特征之间的关联。
方法：回顾性分析1988年至2006年在东北大学医院手术的61例IPMN患者。
结果：我们的系列包括27胃，29肠，4胰胆管和1吞噬型IPMNs。从统计学上讲，IPMN的类型与患者的组织学诊断，宏观类型和生存率显着相关。特征性地，胃型IPMNs可能被诊断为良性，局限于分支导管，并且预后良好。另一方面，肠型IPMN可能被诊断为恶性，占据主导管且预后较差。由于胰胆管型IPMN的数量很少，而仅1例胞浆型IPMN，我们无法确定其在本系列中的任何临床病理特征。
结论：对IPMN的组织学类型进行评估可能有助于预测IPMN患者的临床病程，并为这些患者设计更好的临床治疗方法。

BACKGROUND & AIMS: :Few patients with cancer, including those with acute myeloid leukemia and high-grade myeloid neoplasms, participate in clinical trials. Broadening standard eligibility criteria may increase clinical trial participation. In this retrospective single-center analysis, we identified 442 consecutive newly diagnosed patients from 2014 to 2016. Patients were considered eligible if they had performance status 0-2, normal renal and hepatic function, no recent solid tumor, left ventricular ejection fraction (EF) ≥ 50%, and no history of congestive heart failure (CHF) or myocardial infarction (MI); ineligible patients failed to meet one or more of these criteria. We included 372 patients who received chemotherapy. Ineligible patients represented 40% of the population and had a 1-79-fold greater risk of death (95% CI 1.37, 2.33) than eligible patients. Very few patients had cardiac co-morbidities, including 2% with low EF, 4% with prior CHF, and 5% with prior MI. In multivariable analysis, ineligibility was associated with decreased survival [HR 1-44 (95% CI 1-07, 1-93)]. Allogeneic transplantation, performed in 150 patients (40%), was associated with improved survival [HR 0-66, 95% CI (0-48, 0-91)]. Therefore, standard eligibility characteristics identify a patient population with improved survival. Further treatment options are needed for patients considered ineligible for clinical trials.

背景与目标： ：很少有癌症患者，包括患有急性髓性白血病和高级别髓样肿瘤的患者参加临床试验。扩大标准资格标准可能会增加临床试验的参与度。在这项回顾性单中心分析中，我们确定了2014年至2016年连续442例新诊断的患者。如果患者的表现状态为0-2，肾和肝功能正常，没有新的实体瘤，左心室射血分数（EF），则认为该患者合格）≥50％，无充血性心力衰竭（CHF）或心肌梗塞（MI）的病史；不符合条件的患者未达到这些标准中的一项或多项。我们纳入了372例接受化疗的患者。不合格的患者占总人口的40％，死亡风险比合格的患者高1-79倍（95％CI 1.37，2.33）。极少数患者有心脏合并症，包括2％的低EF，4％的先前CHF和5％的先前MI。在多变量分析中，不合格与生存率降低相关[HR 1-44（95％CI 1-07，1-93）]。在150例患者中进行了同种异体移植（40％），与存活率提高相关[HR 0-66，95％CI（0-48，0-91）]。因此，标准的资格特征确定了具有改善生存率的患者人群。对于认为不适合进行临床试验的患者，需要进一步的治疗选择。

BACKGROUND & AIMS: :Nearly 20 years ago, the first description of a translocation involving chromosome 17 on which USP6 resides was described. Since then, not only the culprit gene but also many fusion partners, leading to transcriptional activation of USP6, have been detected. The first neoplasm known to harbor USP6 rearrangements was aneurysmal bone cyst. Since then, other entities like nodular fasciitis, myositis ossificans, fibro-osseous pseudotumor of digits, and a subgroup of fibromas of tendon sheath, probably representing tenosynovial nodular fasciitis, have been added to the list of USP6-rearranged lesions. Remarkably, all of them share clinical as well as morphological characteristics, and authors have suggested that these entities actually belong to the same spectrum. This review summarizes the current knowledge regarding USP6-rearranged lesions and further elaborates on how these neoplasms relate to one another. We propose to call these lesions UAN (Usp6-associated neoplasm).

背景与目标： ：近20年前，首次描述了涉及USP6所在的17号染色​​体的易位。从那时起，不仅发现了罪魁祸首基因，而且还发现了许多融合伴侣，导致USP6的转录激活。已知具有USP6重排的第一个肿瘤是动脉瘤性骨囊肿。从那时起，其他实体，如结节性筋膜炎，骨化性肌炎，指骨纤维性假瘤以及可能代表腱鞘结节性筋膜炎的肌腱鞘纤维瘤亚组，已被添加到USP6重排病变中。值得注意的是，它们都具有临床和形态特征，并且作者建议这些实体实际上属于同一光谱。这篇综述总结了有关USP6重排病变的当前知识，并进一步阐述了这些肿瘤之间的相互关系。我们建议将这些病变称为UAN（与Usp6相关的肿瘤）。

BACKGROUND & AIMS: BACKGROUND AND PURPOSE:Radiotherapy is used to reverse or prevent local tumour growth but is also a carcinogen in its own right. A recent audit of post-radiotherapy second malignancies in this institution revealed a striking preponderance of tumours originating near the outside edge of the treatment field. Since this finding suggests the existence of a critical subtherapeutic dose range predisposing to tumourigenesis, we attempted to define and reduce this radiation scatter dose. MATERIALS AND METHODS:We undertook a dosimetric review of 6 MV scatter from a linear accelerator in sites matching the putative tumourigenic region, and then extended this analysis to patients and tissue phantoms. RESULTS:A wide range of radiation scatter doses was confirmed-for example, doses 3 cm from the field edge varied from 1.7 to 22% of the therapeutic dose depending upon the field parameters. Scatter doses were then assessed in a sample of eight patients undergoing standard breast radiotherapy. Contralateral breast sites 4-12 cm from the midline received 4-10% of the therapeutic dose, or 200-500 cGy for a 50 Gy treatment, approximating historical estimates of the tumourigenic range. The deep component of this scatter dose from medial field breast irradiation was reduced 19% simply by replacing the 15 degrees medial tangential field wedge with a 30 degrees lateral wedge. Other manoeuvres which reduced contralateral breast dose by up to 46% included making the posterior field edges co-planar and shielding the breast during medial field irradiation. CONCLUSIONS:These results suggest that the risk of radiogenic second malignancies could be significantly decreased by careful attention to the treatment details. Greater awareness of these measures may prove particularly relevant to the conservative management of young patients with good-prognosis breast neoplasms such as ductal carcinoma in situ.

背景与目标： 背景与目的：放射疗法用于逆转或预防局部肿瘤的生长，但它本身也是一种致癌物。该机构最近对放疗后第二次恶性肿瘤的审核显示，在治疗区域外缘附近出现的肿瘤占优势。由于这一发现表明存在着导致肿瘤发生的关键亚治疗剂量范围，因此我们试图确定并减少这种辐射散射剂量。
材料与方法：我们对与假定的致瘤性区域相匹配的部位中的线性加速器对6 MV散射进行了剂量学评估，然后将该分析扩展至患者和组织体模。
结果：证实了广泛的辐射散射剂量，例如，距离野外边缘3 cm的剂量取决于野外参数，从治疗剂量的1.7％到22％不等。然后在接受标准乳房放射治疗的八名患者的样本中评估了散射剂量。距中线4-12厘米的对侧乳房部位接受了4-10％的治疗剂量，对于50 Gy的治疗，则为200-500 cGy，近似于致瘤性范围的历史估计值。只需通过用30度的外侧楔形物代替15度的内侧切向场楔形物，就可将来自内侧视场乳房照射的散射剂量的深层成分减少19％。将对侧乳房剂量减少多达46％的其他方法包括使后场边缘共面并在内侧场辐射期间屏蔽乳房。
结论：这些结果表明，通过密切注意治疗细节可以显着降低放射源性第二恶性肿瘤的风险。对这些措施的更多认识可能与保守治疗乳腺肿瘤预后良好的年轻患者（例如导管原位癌）特别相关。

BACKGROUND & AIMS: PURPOSE:Transanal endoscopic microsurgery (TEM) is a technique that has found its place in routine practice due to its minimal invasive character and associated low morbidity. The purpose of this study was to assess the influence of anatomical variables of rectal neoplasms as well as surgeon experience on postoperative complications in patients undergoing TEM at a tertiary care center. METHODS:Data from 288 patients undergoing TEM over a 16 year period were entered in a prospective data base. Anatomical data of rectal neoplasms, operative data, and early postoperative outcome were analyzed retrospectively. RESULTS:Overall surgical complications [OR 7.0 (1.5-45,5); p < 0.01] and bleeding [OR 222 (82 - 14316); p < 0.01] correlated with the localization of the neoplasm on the lateral wall of the rectum. Furthermore there was a trend for more surgical overall complications as well as bleeding in neoplasms with a diameter of >2 cm and neoplasms located >8 cm from the anal verge. Complications did not correlate with the number of TEM procedures performed. CONCLUSION:TEM resection of neoplasms located on the lateral rectal wall have a higher risk of bleeding. The learning curve for transanal endoscopic microsurgery appears to be negligible in surgeons with experience in minimal invasive surgery.

背景与目标： 目的：经肛门内镜显微外科手术（TEM）由于其微创特征和较低的发病率而在常规实践中占有一席之地。这项研究的目的是评估在三级护理中心进行TEM的患者中直肠肿瘤的解剖变量以及外科医生经验对术后并发症的影响。
方法：将前瞻性数据库中输入来自288名在16年内接受TEM的患者的数据。回顾性分析直肠肿瘤的解剖学数据，手术数据和术后早期结局。
结果：总体手术并发症[OR 7.0（1.5-45,5）; p <0.01]和出血[OR 222（82-14316）； p <0.01]与肿瘤在直肠侧壁上的定位有关。此外，直径> 2 cm的肿瘤和距肛门边缘> 8 cm的肿瘤有更多的外科手术总体并发症以及出血的趋势。并发症与所执行的TEM手术数量无关。
结论：直肠外侧壁肿瘤的TEM切除有较高的出血风险。经肛门内镜显微外科手术的学习曲线在具有微创手术经验的外科医生看来可以忽略不计。

BACKGROUND & AIMS: :Many case reports have indicated the occurrence of monoclonal gammopathy of uncertain significance (MGUS) or multiple myeloma (MM) in patients with Ph-negative myeloproliferative neoplasms (MPN), but few cohorts of patients have been published. This study concerns 667 patients newly diagnosed with polycythemia vera (PV) or essential thrombocythemia (ET) who were tested for monoclonal (M) protein at diagnosis (13.9% of patients). The overall survival of patients with M protein was dramatically lower than that of patients without M protein (12.7 versus 22.4 years; p = .0132). Univariate analysis identified the presence of M protein as a potential risk factor for the secondary occurrence of myelofibrosis (p = .02), myelodysplastic syndrome (p = .043), and MM/Waldenstrom macroglobulinemia (p < .0001). Our cohort shows that the presence of M proteins in patients with PV or ET leads to a poor prognosis. We believe that testing for M protein could help practicians to identify such patients.

背景与目标： ：许多病例报告表明，在Ph阴性骨髓增生性肿瘤（MPN）患者中发生了意义不明的单克隆丙种球蛋白病（MGUS）或多发性骨髓瘤（MM），但很少有患者队列发表。这项研究涉及667名新诊断为真性红细胞增多症（PV）或原发性血小板增多症（ET）的患者，他们在诊断时接受了单克隆（M）蛋白测试（占患者的13.9％）。有M蛋白的患者的总生存率显着低于无M蛋白的患者（分别为12.7年和22.4年； p = 0.132）。单因素分析确定M蛋白的存在是继发性骨髓纤维化（p = .02），骨髓增生异常综合症（p = .043）和MM / Waldenstrom巨球蛋白血症（p <.0001）的潜在危险因素。我们的队列研究表明，PV或ET患者中M蛋白的存在会导致预后不良。我们认为对M蛋白的检测可以帮助从业人员识别此类患者。

BACKGROUND & AIMS: :HACE1 is an E3 ubiquitin ligase located in 6q21, the genomic region frequently deleted in natural killer (NK) cell malignancies. Here, we report HACE1 as a candidate tumor suppressor gene silenced through a combination of deletion and cytosine phosphate guanine island hypermethylation. We detected deletion of HACE1 in malignant NK cell lines (6 of 9, 67%) and primary biopsies (5 of 15, 33%) by quantitative PCR, with most of the specimen showing cytosine phosphate guanine island hypermethylation in the remaining allele, leading to low mRNA transcription. The ectopic expression of HACE1 in an HACE1-null NK cell line led to apoptosis and G2/M cell cycle arrest. Moreover, HACE1 expression was up-regulated in IL-2-activated normal NK cells and NK cells cocultured with an engineered NK cell target, K562 Clone 9.mbIL21, suggesting its role in the regulation of NK cell homeostasis. In conclusion, HACE1 is another potent tumor suppressor gene located within the 6q21 region, and loss of function of multiple tumor suppressor genes within 6q21 may be a critical determinant of NK cell lymphomagenesis.

背景与目标： ：HACE1是一种E3泛素连接酶，位于6q21，这是自然杀伤（NK）细胞恶性肿瘤中经常缺失的基因组区域。在这里，我们报告HACE1作为通过删除和胞嘧啶磷酸鸟嘌呤岛高甲基化的组合而沉默的候选肿瘤抑制基因。我们通过定量PCR检测到恶性NK细胞系（占9个，占67％）中HACE1的缺失（占15％，占活检中的5个，占33％），大多数标本显示其余等位基因中的胞嘧啶磷酸鸟嘌呤岛甲基化过度，降低mRNA转录。 HACE1无效的NK细胞系中HACE1的异位表达导致细胞凋亡和G2 / M细胞周期停滞。此外，HACE1表达在被IL-2激活的正常NK细胞和与工程NK细胞靶标K562 Clone 9.mbIL21共培养的NK细胞中被上调，表明其在调节NK细胞稳态中的作用。总之，HACE1是另一个位于6q21区域内的有效抑癌基因，而6q21内多个抑癌基因的功能丧失可能是NK细胞淋巴瘤发生的关键决定因素。

BACKGROUND & AIMS: :Immunohistochemistry has come to occupy a key position among the armamentarium of tools pathologists apply to the evaluation of lung and pleural neoplasms. This technique uses antibodies that bind to specific antigens, usually proteins, enabling microscopic detection of the antigens. Over the last several decades, an impressive array of antibodies has become commercially available, and many of these antibodies have become integrated into the routine practice of pathology. Evaluation of tissue or cytology samples with these antibodies can facilitate determination of tumor type and site of origin. Comments citing results of immunohistochemical staining with these antibodies frequently appear in pathology reports and may be difficult to translate for those less familiar with the technique. This review presents, in two parts, common diagnostic applications of immunohistochemistry with information about strategies taken for frequently encountered differential diagnostic scenarios. This article is the second of the two parts and focuses on immunohistochemical approaches to differentiating primary pulmonary from metastatic adenocarcinomas, mesotheliomas from carcinomas, and various types of spindle cell neoplasms. Potential future directions involving therapeutic and prognostic biomarkers are also discussed.

背景与目标： ：免疫组织化学已在病理学家用于评估肺和胸膜肿瘤的工具的武器库中占据重要位置。该技术使用与特定抗原（通常是蛋白质）结合的抗体，从而可以对抗原进行微观检测。在过去的几十年中，令人印象深刻的抗体阵列已经可以商业获得，并且这些抗体中的许多已经整合到病理学的常规操作中。用这些抗体评估组织或细胞学样本可有助于确定肿瘤类型和起源部位。引用这些抗体的免疫组化染色结果的评论经常出现在病理报告中，对于不太熟悉该技术的人可能很难翻译。这篇综述分两部分介绍了免疫组织化学的常见诊断应用，以及有关针对经常遇到的差异诊断方案采取的策略的信息。本文是这两个部分的第二部分，重点介绍了免疫组织化学方法，以区分原发性肺与转移性腺癌，间皮瘤与癌以及各种类型的梭形细胞瘤。还讨论了涉及治疗和预后生物标志物的潜在未来方向。

BACKGROUND & AIMS: :The distribution of antigenic determinants on a cellular level in serous ovarian neoplasms was evaluated using polyclonal and two monoclonal antibodies (OC 125 and 10B). The expression of antigens was estimated by an immunofluorescence test on each cell fraction isolated by density centrifugation from cystic fluids of individual malignant and benign ovarian tumors, taking into account the density and cytomorphologic features of cell subpopulations. It was found that the studied antibodies recognized different antigenic determinants. Significant immunologic heterogeneity of cells among and within individual tumors was shown. Our studies show the value of isolated cell subpopulations for comparing the reactivity of different antibodies and estimating their immunodiagnostic potency.

背景与目标： ：使用多克隆抗体和两种单克隆抗体（OC 125和10B）评估了浆液性卵巢肿瘤中抗原决定簇在细胞水平上的分布。考虑到细胞亚群的密度和细胞形态特征，通过免疫荧光试验对通过密度离心从单个恶性和良性卵巢肿瘤的囊性液体中分离出的每个细胞级分评估抗原的表达。发现所研究的抗体识别不同的抗原决定簇。显示了单个肿瘤之间和之内的细胞的显着免疫异质性。我们的研究表明，分离的细胞亚群可用于比较不同抗体的反应性并评估其免疫诊断能力。