Quantitative, microscopical, computer-aided diagnosis of endometrial hyperplasia or carcinoma in individual patients

There are many significant differences, but also considerable overlap between the quantitative histopathological features of mild and marked atypical endometrial hyperplasias and well and moderately differentiated carcinomas, thus preventing its application to individual patient care. To try to overcome this problem, a classification rule for the diagnosis in individual patients, using discriminant analysis has been developed. Utilizing nine quantitative features, all the above four groups can be adequately separated. None of the carcinomas was misclassified as hyperplasia, and only one case of marked atypical hyperplasia was erroneously classified as well differentiated carcinoma, but with a probability of carcinoma 0.75, hyperplasia 0.25. By contrast, the classification probabilities of all the confirmed carcinomas exceeded 0.90. Therefore, using 0.90 as a classification level ('threshold'), a reliable rule is obtained. A slightly more simple classification rule distinguishes between all the hyperplasias and all the carcinomas. In this way, all the cases of the test set were correctly classified. The classification rules can be used to select patients with benign disease for hormone therapy(Kistner 1973) as an alternative to hysterectomy, and can be programmed in an inexpensive microcomputer. The quantitative techniques are relatively easy, and are capable of being performed in most histopathological laboratories.     

Mucinous endometrial adenocarcinoma simulating microglandular hyperplasia of the cervix

A case of endometrial adenocarcinoma simulating microglandular hyperplasia (MGH) of the cervix is presented. A postmenopausal 53-year-old woman, with no previous history of taking exogenous hormones, presented with vaginal bleeding. An endometrial biopsy exhibited a tumor composed predominantly of a microglandular proliferation of tightly packed glands with mild to moderate atypia and mitotic figures. The majority of the tumor cells contained intracytoplasmic mucin. There were numerous neutrophils within the microglandular lumens and in the stroma. The tumor was focally positive for carcinoembryonic antigen and vimentin. The MGH-like proliferation, focally, had a transition to a conventional mucinous adenocarcinoma. Hysterectomy specimens showed a residual mucinous endometrial adenocarcinoma with no myometrial invasion, the uterine cervix was unremarkable. Four years following her hysterectomy the patient was well, with no evidence of disease. Pathologists need to be cautious about MGH-like changes in the endometrial biopsy of postmenopausal women and be aware of this type of endometrial cancer as it may be misdiagnosed.     

孕激素治疗增生子宫内膜和高分化子宫内膜样癌后的临床病理形态观察

目的：显微镜下观察孕激素治疗对不同增生子宫内膜和高分化子宫内膜样腺癌的组织病理学影响,为临床更好地管理孕激素治疗提供依据。方法：收集2010年至2014年86例增生不伴有非典型增生(包括简单型增生、复杂型增生)和非典型增生及高分化子宫内膜样癌患者在我院经孕激素正规治疗刮宫至少两次以上病例,其中刮宫次数最多者达11次,时间2个月到5年。两个高年资病理医师双盲法显微镜下观察激素治疗前后病理改变。结果：简单型增生50名,基本转归为正常子宫内膜;复杂型增生18名,治疗约半年后转为正常子宫内膜;但其中2例有复发或恶化。非典型增生不伴/伴癌变18例,孕激素治疗后刮宫,10例镜下显示好转或完全缓解。好转病例显示组织结构依然复杂,但腺体间质比例降低,间质蜕膜样变或者玻璃样变;高倍镜下腺上皮细胞核变温和,核膜光滑,核仁不明显,核浆比例降低,胞浆丰富,伴嗜酸性变、鳞状细胞化生或粘液化生。该类病例继续治疗后,转化为正常周期宫内膜。但有4例(22.2%)在1~2年后复查,又出现非典型增生,甚至癌变。另有2个病例,治疗3个月后刮宫,镜下依然为非典型增生改变,证明孕激素治疗无效。结论：1)简单型增生过孕激素治疗效果好,3~6个月后刮宫,基本恢复正常周期。2)对非典型增生及癌变患者,因容易复发和恶化,按2014NCCN诊疗规范治疗坚持用药并定期复查非常有必要。3)非典型增生伴/不伴癌变病例,细胞学好转先于组织学。4)对治疗无效者,需要根据患者生育要求及时手术治疗。5)根据孕激素治疗效果评价,增生不伴非典型增生患者,区分简单型和复杂型增生依然有必要性。     

Cutaneous lymphoid hyperplasia: a lymphoproliferative continuum with lymphomatous potential

Cutaneous lymphoid hyperplasia (CLH) has been proposed to be the benign end of a continuum of lymphoproliferative disorders with cutaneous lymphoma at its malignant extreme. An intermediate condition, known as "clonal CLH," was first recognized by us and shown to be a transitional state capable of eventuating in overt lymphoma. To better determine the prevalence of dominant clonality and risk of lymphoma among CLH cases, we studied the immunohistology and clonality of fresh-frozen samples from 44 CLH patients referred to a multidisciplinary cutaneous lymphoproliferative disorders program. Using a large panel of lymphoid markers, the cases were divided into 38 typical mixed B-cell/T-cell type CLH and 6 T-cell-rich type (T-CLH), the latter containing > 90% T cells. Of the 44 patients, 38 had solitary or localized lesions (4 cases of T-CLH), and 6 had regional/generalized lesions (2 cases of T-CLH). Forty cases were of idiopathic etiology. Suspected etiologies among 4 other cases included mercuric tattoo pigment, doxepin, clozapine, and bacterial infection. Immunoglobulin heavy chain (IgH) and T-cell receptor (TCR)-gamma gene rearrangements (GR) were studied using polymerase chain reaction assays, which are approximately 80% sensitive. Overall, 27 cases (61%) showed clonal CLH: 12 IgH+ (27%; 3 cases of T-CLH); 13 TCR+ (30%; 1 case of T-CLH); and 2 IgH+/TCR+ (4%; neither case was T-CLH). Two cases (4%; 1 case of T-CLH) progressed to cutaneous B-cell lymphoma. Both of these patients presented with regional lesions. Our findings indicate that clonal overgrowth is common in CLH, links CLH to lymphoma, and probably involves both B- and T-cell lineages (although TCR GR by B cells and vice versa could not be ruled out). The high prevalence of dominant clonality in our series may have resulted from the sensitivity of our PCR assays as well as patient selection.     

Patterns of reactivity with the monoclonal antibodies HMFG1 and HMFG2 in normal endometrium, endometrial hyperplasia and adenocarcinoma

Using an indirect immunoperoxidase technique the expression of the epitopes in human milk fat globule (HMFG) membranes detected by the monoclonal antibodies HMFG1 and HMFG2 was studied in the normal endometrium and in cases of cystic glandular hyperplasia, glandular hyperplasia with architectural atypia (complex hyperplasia), glandular hyperplasia with cytological atypia (atypical hyperplasia) and invasive adenocarcinoma. Luminal reactivity with HMFG1 was seen in cases of normal endometrium, cystic glandular hyperplasia and glandular hyperplasia with architectural atypia. In contrast most cases of glandular hyperplasia with cytological atypia and invasive adenocarcinoma also showed areas of cytoplasmic reactivity. Reactivity with HMFG2 was scanty.     

Complexity of glandular architecture should be reconsidered in the classification and management of endometrial hyperplasia

The 2014 World Health Organization (WHO) classification of endometrial hyperplasia (EH) defines premalignant EH based on only cytologic atypia, disregarding architecture complexity. We aimed to assess the impact of architecture complexity on the risk of cancer in non‐atypical EH. A systematic review and meta‐analysis was performed by searching electronic databases form their inception to October 2018. All studies assessing the rates of progression to cancer in non‐atypical EH (simple vs complex) were included. Pooled relative risk (RR) for cancer progression was calculated; a p‐value < 0.05 was considered significant. Eight studies with 1066 women were included. The risk for progression of non‐atypical EH to cancer was significantly higher in complex EH than in simple EH (p < 0.0001), with an RR of 4.90. In conclusion, the complexity of glandular architecture significantly increases the risk of cancer in non‐atypical EH. Complex non‐atypical EH may be regarded as a low‐risk premalignant lesion rather than a benign condition.     

Cellular immunity and T-lymphocyte subsets in young children with acute measles

The changes occurring in the T-cell subsets during acute symptomatic measles were examined in ten malnourished and 18 well nourished hospitalized children younger than 5 years of age (median age 14 months). A significant decrease in total lymphocyte count was observed, which was due mainly to a decrease in helper/inducer T lymphocytes, whereas the suppressor/cytotoxic T-lymphocyte subset remained unchanged. Consequently, helper/suppressor ratio decreased significantly during the acute phase of the disease. A reduced response to mitogens (PHA, Con A, PWM) was also observed. Malnourished infants showed a trend toward a deeper depression in both helper and suppressor T cells during the acute phase than well nourished children, whereas the helper/suppressor ratio remained similar in the two groups.     

子宫内膜非典型增生过长24例临床病理分析

目的：分析子宫内膜复杂性增生过长伴非典型性临床病理特点，方法；对２４例子宫内膜复杂性增生过长伴非典型性子宫内膜进行光镜观察及免疫组化染色。结果２４例中，４例发展为子宫内膜腺癌，７例痊愈，１０例好转，３例在随访中，内膜癌患者地ＰＣＮＡ检测均为阳性高表达，结论：子宫内膜复杂性增生过长伴非典型性，其病变的发展是双向的，即可癌变，也可逆转，预后评估取决于患者的年龄及免疫组化检测的结果。     

慢性乙型肝炎抗病毒治疗后病毒学应答与特异性细胞免疫的关系

目的探讨阿德福韦酯治疗慢性乙型肝炎（CHB）患者病毒学应答与HBV特异性细胞毒性T淋巴细胞（CTL）的关系。方法51例CHB患者,HBVDNA阳性（HBVDNA≥I×10^4拷贝／ml,HBeAg阳性32例（62．75％）、丙氨酸转氨酶（ALT）〉2×正常值上限（ULN）、人白细胞抗原（HLA）-A2阳性,用阿德福韦酯10mg,口服,每日1次。观察治疗72周后HBVDNA转阴和HBeAg血清学转换与HBV特异性CTL的关系。结果阿德福韦酯治疗72周后,HBVDNA转阴（〈500拷贝／m1）39例（76．47％）,其HBV特异性CTL（0．81％±0．06％）,高于12例（23．53％）的HBVDNA未转阴者（0．66％±0．06％）,t=7．93,P〈0．01,IqBeAg血清学转换8例（25％）,其HBV特异性CTL（0．97％±0．07％）,高于24例（75％）的无HBeAg血清学转换者（0．67％±0．07％）,t=7．61,P〈0．01。结论阿德福韦酯治疗CHB患者病毒学应答和血清学应答与HBV特异性CTL水平升高有关。     

Phyllodes tumor of the prostate with exuberant glandular hyperplasia

Reported herein is an unusual case of prostatic phyllodes tumor with exuberant glandular hyperplasia that led to misdiagnosis of adenocarcinoma. The tumor was detected in a 52-year-old man who had a 1 year history of dysuria. Adenocarcinoma of the prostate was diagnosed from a needle biopsy specimen. The patient received hormonal therapy for 6 months and underwent radical prostatectomy. Histologically, the tumor had an atypical stromal cell proliferation and elongated slit-like glands characteristic of a phyllodes tumor. The tumor was also accompanied by a florid proliferation of small acini, most of which lacked basal cells, a common manifestation of adenocarcinoma in the overall tumor area. The following features of the resected tumor were helpful for concluding that these acini were benign: lack of cytological anaplasia in spite of structural atypia, presence of scattered basal cells confirmed by immunohistochemistry (high-molecular-weight cytokeratin), and histological transition from these acini to apparently benign slit-like glands. The final diagnosis was then made as 'phyllodes tumor of the prostate with exuberant glandular hyperplasia'. Atypical stromal cells might provide a clue for the recognition of this rare tumor at initial diagnosis by needle biopsy.     

术前诊断为子宫内膜不典型增生的子宫内膜癌患者的处理

目的分析和总结术前诊断为子宫内膜不典型增生的子宫内膜癌患者的临床特点及治疗方法。方法 2005年1月至2010年12月北京协和医院妇产科行全子宫切除术后病理诊断为子宫内膜样癌的患者共计404例,其中44例术前子宫内膜活检病理提示子宫内膜不典型增生(AEH),回顾性分析这些患者的临床特点,采用SPSS 13.0统计学软件进行分析。结果 44例术前诊断为AEH的患者中,39例(89%)患者未行子宫内膜癌分期术,子宫切除术后病理均为高分化子宫内膜样癌(100%),14例(32%)年轻患者保留了双侧卵巢,9例(20%)患者给予辅助放疗。中位随诊时间52个月,无复发病例。和绝经后患者相比,绝经前患者术后深肌层浸润(1/22及4/22)及淋巴血管间隙浸润(0/22及3/22)更少,但无统计学差异。比较AEH组和术前诊断为子宫内膜样癌的患者(EC组),AEH组高分化子宫内膜样癌的比例明显高于EC组(P=0.000);辅助化疗率和复发率明显低于EC组(P=0.003和0.019)。结论术前诊刮为AEH的子宫内膜癌患者预后好,年轻患者充分评估后可以考虑保留卵巢,绝经后患者AEH伴发子宫内膜样癌的风险增高,且更容易合并深肌层浸润、淋巴血管间隙受累等高危因素。     

Diagnostic accuracy of hysteroscopy in endometrial hyperplasia

Objectives: To determine the diagnostic accuracy of hysteroscopy in the diagnosis of endometrial hyperplasia in women with abnormal uterine bleeding. Methods: From 1993 through 1995, 980 women referred to our institution for abnormal uterine bleeding underwent diagnostic hysteroscopy with eye direct biopsy of the endometrium in case of macroscopic abnormalities. Hysteroscopic features were compared with pathologic findings in order to detect the reliability of the endoscopic procedure. Statistical analysis was performed with the McNemar test. Results: Positive predictive value of hysteroscopy in the diagnosis of endometrial hyperplasia accounted for 63%. In fact hysteroscopic diagnosis of endometrial hyperplasia was confirmed at pathologic examination in 81 out of 128 patients. Sensitivity and specificity of the endoscopic procedure accounted for 98% and 95%, respectively. Negative predictive value accounted for 99%, as only two cases of atypical hyperplasia were missed at hysteroscopy. Positive predictive value was higher in postmenopausal patients compared to women in the fertile age (72 vs. 58%). Conclusions: Overall, results appear encouraging, since no case of endometrial hyperplasia was missed by hysteroscopy. The high diagnostic accuracy, associated with a minimal trauma, renders hysteroscopy the ideal procedure for both diagnosis and follow-up of conservative management of endometrial hyperplasia.     

苦参素联合甘草酸二铵对慢性乙型肝炎患者细胞免疫影响的研究

目的探讨苦参素联合甘草酸二铵对慢性乙型肝炎（CHB）患者特异性细胞免疫的影响。方法63例CHB患者随机分为2组,苦参素联合甘草酸二铵组（联合组）32例,用苦参素葡萄糖注射液600mg,静脉滴注,每日1次,1个月后改为苦参素胶囊200mg口服,每日3次,2个月。甘草酸二铵注射液150mg加入10％葡萄糖注射液250ml中静脉滴注,每日1次,1个月后改为甘草酸二铵胶囊150mg口服,每日3次,2个月;苦参素组（单用组）31例,只用苦参素,用法用量同治疗组。比较两组患者的HBV特异性细胞毒T细胞（CTL）、T细胞亚群、Th1、Th2水平的变化和HBV-DNA、HBeAg阴转率。结果联合组治疗3个月后,HBV特异性CTL、CD4＋、Th1高于治疗前,也高于单用组治疗后（P〈0．01）。HBV-DNA和HBeAg阴转率两组比较差异无统计学意义（P〉0．05）。结论苦参素联合甘草酸二铵能进一步提高CHB患者的HBV特异性CTL、CD4＋和Th1水平。     

The peripheral blood compartment in patients with Graves' disease: activated T lymphocytes and increased transitional and pre‐naive mature B lymphocytes

Graves'' disease (GD) is an autoimmune disease that involves aberrant B and T lymphocyte responses. Detailed knowledge about lymphocyte subpopulation composition will therefore enhance our understanding of the pathogenesis of GD and might support the development of new immunomodulatory treatment approaches. The aim of this study was to gain detailed insight into the composition of the peripheral blood lymphocyte compartment in GD before and during anti-thyroid drug therapy. Major B and T lymphocyte subpopulations were investigated by flow cytometry in peripheral blood from newly diagnosed GD patients (n = 5), GD patients treated with anti-thyroid drugs (n = 4), patients with recurrent GD (n = 7) and healthy controls (HC; n = 10). In GD patients, numbers of activated T lymphocytes [human leucocyte antigen D-related (HLA-DR)⁺ and CD25⁺] were increased. The B lymphocyte compartment in GD was characterized by significantly higher numbers of transitional (CD38^highCD27⁻, P < 0·03) and pre-naive mature (CD38^lowCD27⁻IgD⁺CD5⁺, P < 0·04) B lymphocytes, while memory populations were slightly decreased. The increased numbers of CD5⁺, transitional and pre-naive mature B lymphocytes correlated positively with fT4 plasma levels. GD is associated with increased numbers of activated T lymphocytes and transitional and pre-naive mature CD5⁺ B lymphocytes within the peripheral blood. The increase in CD5⁺ B lymphocytes was due mainly to an increase in transitional and pre-naive mature B lymphocytes. Increased fT4 plasma levels might be associated with this increase in transitional and pre-naive mature CD5⁺ B lymphocytes.     

HOXA11在子宫内膜单纯性增生和内膜癌中表达增加

目的探讨HOXA11基因在子宫内膜单纯性增生和子宫内膜癌中表达的意义,以及与雌激素受体(estrogen receptor,ER)、孕激素受体(progestogene receptor,PR)表达的关系。方法用免疫组化法检测增生期子宫内膜、子宫内膜单纯性增生及子宫内膜癌组织中HOXA11、ER及PR蛋白的表达。结果在子宫内膜单纯性增生和内膜样腺癌中,HOXA11的表达明显高于增生期子宫内膜(P<0.05),而ER、PR的表达明显低于增生期内膜(P<0.05)。结论HOXA11的过度表达可能参与了子宫内膜异常增生或癌变的过程;这种效应可能与ER、PR表达下降相关。