Mullerian adenosarcomas: an immunophenotypic analysis of 35 cases

Mullerian adenosarcomas (MAs) are rare mixed mesenchymal and epithelial neoplasms that occur most commonly in the uterus. Although the epithelial component is typically benign, the mesenchymal component of most adenosarcomas morphologically resembles that observed in endometrial stromal tumors and is responsible for their clinical behavior. Thus, the differential diagnosis usually includes not only low-grade endometrial stromal tumors, but also adenofibroma, carcinosarcoma, and embryonal rhabdomyosarcoma especially in small samples. The objective of this study was to ascertain the immunophenotypic profile of the epithelial and mesenchymal components of MAs and delineate possible differences between conventional mesenchymal areas and areas of sarcomatous overgrowth. Representative sections from 35 MAs, 28 of them without sarcomatous overgrowth (MA-NSO) and 7 with sarcomatous overgrowth (MA-SO), were included in the study. Thirty tumors arose in the uterus, 4 were pelvic, and 1 originated in the colon. Adequate blocks were selected and immunostained for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), CD10, WT1, smooth muscle actin, desmin, AE1/3 cytokeratin, CD34, calretinin, inhibin, c-kit, and Ki-67. The mesenchymal component expressed ER in 21/27 MA-NSOs but in only 1/7 MA-SOs (65% overall). PR was expressed in 21/26 MA-NSOs and 4/7 MA-SOs (76% overall), whereas AR was positive in 10/27 MA-NSOs and 5/7 MA-SOs (35% overall). CD10 was expressed in 23/28 MA-NSOs but in only 2/7 MA-SOs (71% overall), and WT1 positivity was seen in 22/27 MA-NSOs and 6/7 MA-SOs (79% overall). Sixty-seven percent of MAs expressed smooth muscle actin, 32% desmin, including both examples of MA-SOs with rhabdomyoblastic differentiation, and 25% expressed AE1/3 cytokeratin. CD34 expression was found in 35% of the tumors, but it was almost always patchy in distribution and weak in intensity, as was calretinin expression, seen only in 12% of the cases. Expression of c-kit and inhibin in greater than 5% of the tumor cells was not encountered. The median and mean Ki-67 labeling indices were 10% and 12%, respectively (range, <5% to 40%). The median and mean Ki-67 indices were both 5% in MA-NSOs compared with 30% and 28%, respectively, in MA-SOs. The epithelial compartment demonstrated expression for ER (24/32), PR (23/31), and AE1/3 cytokeratin (33/33); rare cases expressed CD10 (4 cases) and AR (1 case). In summary, the immunophenotype of most MAs resembled that of endometrial stromal tumors (positive for ER, PR, WT1, and CD10, with variable expression of muscle markers, AR and cytokeratin). The proliferative rate in the stromal component was strongly related to the presence of sarcomatous overgrowth. ER, PR, and CD10 expression was lost in MA-SOs relative to conventional low-grade stromal areas of mullerian/mesodermal adenosarcomas, reflecting the "dedifferentiation" of this component.     

Expression of CD56 and WT1 in ovarian stroma and ovarian stromal tumors

The immunophenotype of ovarian stroma and spindle cell tumors derived from ovarian stroma has not been well studied. We studied the expression of CD56, WT1, estrogen receptor-beta (ER-beta), progesterone receptor (PR), smooth muscle actin, S-100, CD34, and muscle specific actin in 16 normal ovaries, 17 ovarian fibromas, 11 ovarian cellular fibromas, 10 ovarian fibrothecomas, and 11 ovarian leiomyomas. In addition, we studied CD56 and WT1 expression in 7 cases of normal endometrium, 8 uterine smooth muscle tumors, 5 endometrial stromal tumors and 64 nongynecologic (GYN) spindle cell sarcomas. All normal ovaries, ovarian fibromas, fibrothecomas, and ovarian leiomyomas were positive for CD56 and WT1. Most of the normal ovaries, ovarian fibromas, ovarian fibrothecomas, and ovarian leiomyomata also expressed ER-beta and PR. Eight of 17 ovarian fibromas, 5 of 11 ovarian cellular fibromas, and 4 of 10 ovarian fibrothecoma with focal fibroblastic differentiation were positive for smooth muscle actin. A few cases of these tumors also expressed S-100 and CD34. Only rare cases of non-GYN spindle cell sarcomas expressed WT1. Our study results show that ovarian fibromas, fibrothecomas, and leiomyomas have a similar immunophenotype (positive for CD56, WT1, ER-beta, and PR) to that of ovarian stromal cells, supporting an ovarian stromal origin for these neoplasms. However, unlike normal ovarian stromal cells, ovarian fibromas, fibrothecomas, and leiomyomas can also show fibroblastic, smooth muscle, Schwannian, and solitary fibrous tumorlike differentiation. WT1 is a fairly specific marker for spindle cell tumors of gynecologic organs, including ovarian spindle cell tumors, endometrial stromal tumors, and uterine smooth muscle tumors. Non-GYN spindle cell sarcomas rarely express WT1. CD56 is strongly expressed in ovarian stromal cells but not in endometrial stromal cells. CD56 is often expressed by a wide variety of spindle cell sarcomas, thus, it has no value in differentiating GYN from non-GYN spindle cell tumors.     

A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary

The distinction of ovarian clear cell carcinomas (CCCs) from high-grade serous carcinomas (HG-SCs) is sometimes a diagnostic challenge. With the recognition that CCCs respond poorly to conventional chemotherapy there are efforts to initiate clinical trials for CCC, making accurate diagnosis critical. The purpose of this study was to test and validate a set of antibodies that could aid in the diagnosis of CCC, using a series of cases from different centers in North America. Using a test set of 133 CCCs, we identified the following markers: Cyclin E, estrogen receptor, hepatocyte nuclear factor (HNF)-1beta, Ki-67, p21, p53, and Wilms tumor (WT)1 that show significant discrimination from 200 HG-SCs. For validation, these markers were characterized on an independent set of 104 CCCs from 3 other centers. There were no significant differences in expression of these 7 markers between the independent test and validation sets of CCC. Combining all CCC cases (N=237), HNF-1beta showed the highest sensitivity (82.5%) and specificity (95.2%) for CCC, and WT1 for HG-SC (sensitivity: 79.9%, specificity: 97.4%). A diagnostic panel consisting of WT1, ER, and HNF-1beta demonstrated nearly identical performance as a panel using all 7 markers in distinguishing CCCs from HG-SCs, correctly classifying 84% of cases. Three percent of cases were misclassified and 13% carried an uninformative triple negative immunophenotype. CCCs show a distinct, reproducible immunophenotype, compared with HG-SCs, and a panel of 3 immunomarkers can serve as a diagnostic aid in problematic cases.     

Ependymomas of the central nervous system and adult extra-axial ependymomas are morphologically and immunohistochemically distinct--a comparative study with assessment of ovarian carcinomas for expression of glial fibrillary acidic protein

Extra-axial ependymomas are very rare but have been reported in the ovary, broad ligament, sacrococcygeal region, lung, and mediastinum. The histogenesis is obscure, and a thorough immunohistochemical analysis is lacking. We reviewed the morphologic and immunohistochemical features of 5 extra-axial ependymomas occurring in adults, 1 arising in an infantile sacrococcygeal teratoma, and a control group of 10 central nervous system (CNS) ependymomas in adults. All cases were evaluated for expression of epithelial membrane antigen, estrogen receptor (ER), progesterone receptor (PR), WT1, CD99, CK18, AE1:3, CAM 5.2, 34betaE12, CK7, CK20, synaptophysin, chromogranin, and glial fibrillary acidic protein (GFAP) using formalin-fixed, paraffin-embedded tissue. One hundred twelve ovarian carcinomas in 3 tissue microarrays were also studied with GFAP. The adult extra-axial cases demonstrated more architectural variability than the CNS cases. We observed that both the CNS and adult extra-axial ependymomas expressed GFAP diffusely, whereas only 9 stage III, high-grade ovarian serous papillary carcinomas stained with GFAP (2 strongly and diffusely and 7 exhibiting focally weak expression). There were significant immunophenotypic differences between adult extra-axial and CNS ependymomas, with extra-axial cases preferentially expressing 34betaE12 (60% vs. 0%), CK18 (100% vs. 20%), CAM 5.2 (60% vs. 10%), CK7 (80% vs. 10%), ER (100% vs. 10%), and PR (80% vs. 20%). Two spinal cord ependymomas expressed CK18, 1 expressed CK7, and 1 expressed CAM 5.2. CNS ependymomas more frequently expressed CD99 (100% vs. 20%). The following stains were not differentially expressed: epithelial membrane antigen (expressed in 2 of 15 cases, including both extra-axial and CNS ependymomas), synaptophysin (1/15), chromogranin (0/15), WT1 (8/15), AE1:3 (10/15), and CK20 (0/15). The ependymal elements of the sacrococcygeal tumor failed to express 34betaE12, CK18, CAM 5.2, and CK7, like most CNS ependymomas. The morphologic and immunophenotypic differences between extra-axial and CNS ependymomas suggest that they derive from distinct precursors and/or differentiate along distinct pathways. The differential diagnosis of extra-axial ependymomas is extensive, and GFAP expression in primary ovarian serous carcinomas, although rare, could theoretically contribute to diagnostic difficulties. ER and PR expression in extra-axial ependymomas may provide targets for hormonal therapy.     

Heterogeneity of Breast Cancer Clinical Characteristics and Outcome in US Black Women—Effect of Place of Birth

Breast cancer mortality in black women is disproportionately high; reasons for this phenomenon are still unclear. In addition to socioeconomic factors, the biology of the tumor may play a role. We analyzed 1,097 incident invasive breast cancer cases diagnosed between 2000 and 2010 in black US women from Long Island and Brooklyn. Thirty‐five percent of women had an estrogen receptor (ER) negative tumor, 46% a progesterone receptor (PR) negative tumor. ER, PR negative tumors were diagnosed at an earlier age (55.8 versus 55.3 years), at a later stage (p = 0.06), were larger in size (p = 0.04), and more frequently treated with neo‐adjuvant chemotherapy (p = 0.06) than ER, PR positive tumors. Determinants of shorter survival were: ER, PR negativity (HR: 2.2, 95% CI: 1.4–3.4), age, and stage at diagnosis (HR: 2.0; 95% CI: 1.5–2.7). ER, PR negative breast cancer born outside of the US experienced a significantly worse survival than ER, PR negative women who were born in the US. ER, PR negative tumors in black women born outside the US, mainly in the Caribbean, are biologically more aggressive than the same size and age‐matched tumors in black women born in the US. Our study suggests that environmental exposures in the country of origin may impact on host cancer interactions and cancer outcome.     

Inguinal smooth muscle tumors in women-a dichotomous group consisting of Müllerian-type leiomyomas and soft tissue leiomyosarcomas: an analysis of 55 cases

Assessment of the biological potential of smooth muscle tumors can be difficult and depends primarily on tumor site, stage, and histologic parameters. In this study, we examined the clinicopathologic and immunohistochemical features of 55 noncutaneous inguinal smooth muscle tumors of women (age range, 20 to 82 y; median, 57 y). Histologically, 23 tumors were considered as leiomyomas. They showed low mitotic activity (range, 0 to 6 mitoses/10 high-power fields, without atypical mitotic figures), minimal cytologic atypia, and absence of coagulative necrosis. Fifteen of these tumors histologically resembled conventional uterine leiomyomas and 8 resembled their variants: lipoleiomyomas (n = 2) and epithelioid variants (n = 6). The mean size was 7.8 cm, and half of the tumors with specified location arose in association with the round ligament. Immunohistochemical expression of estrogen receptor (ER) and/or Wilms tumor protein (WT1) was detected in most cases (83%), supporting Müllerian derivation. Follow-up data (range, 10 to 29 y; median, 13 y) on 11 patients showed that all were alive without disease or death from unrelated causes. The second group, classified as leiomyosarcomas, consisted of 32 mitotically active smooth muscle tumors, almost invariably with atypical mitotic figures, and exhibiting significant cytologic atypia. These patients were older than those with leiomyomas, and their tumors were mostly subcutaneous with a mean tumor size of 5.4 cm. Two leiomyosarcomas showed a femoral vein origin, but none were associated with the round ligament. All but 3 leiomyosarcomas were negative for ER. Follow-up data on 13 patients (range, 2 mo to 30 y; median, 4.5 y) showed that 5 died of metastatic sarcoma. Six individuals were alive without disease (median, 16 y), and 2 died of unrelated causes. In conclusion, inguinal smooth muscle tumors in women are a dichotomous group. They consist of ER/WT1-positive Müllerian-type leiomyomas resembling uterine leiomyomas with an excellent prognosis and conventional LMSs that are usually ER/WT1-negative and show a variable malignant course. Separation of these 2 categories is important for prognostication and optimal patient management, and is aided by immunohistochemical studies for ER and WT1.     

Computer-assisted immunocytochemical determination of breast cancer steroid receptors. Frozen sections vs paraffin sections

Previously we have demonstrated that determination of oestrogen (ER) and progesterone (PR) receptors by immunocytochemical assay (ICA) on frozen sections (FS) and cytological smears with image analysis is effective for evaluating steroid receptors. The aim of this study was to determine concordance between ER and PR assessed by ICA on FS and paraffin sections (PS) both evaluated by image analysis. There were 115 breast carcinomas selected. For all cases, ER and PR determination was performed on FS and PS. Computer-assisted image analysis was performed using CAS 200. Results were expressed as percent positive area of neoplastic nuclei compared with total nuclear area of the examined neoplastic cells. Good correlation was demonstrated for both ER (r=0.759; concordance=83.4%) and PR (r=0.800; concordance=87.8%). The unexpected relatively low concordance for ER led to further investigations. We divided the 115 cases in two groups. The first group included specimens from our hospital; the second group specimens from suburban hospitals. In the first group there was better correlation for both ER (r=0.897) and PR (r=0.915) with a concordance of 91.5% and 93.6%, respectively. In the second group, correlation was worse for both ER (r=0.724) and PR (r=0.708), with a concordance of 77.9% and 83.9% respectively. From analysis of discordant cases we conclude that reduction in correlation and concordance with increased false negative cases in group 2 are probably due to delayed fixation. Our data suggest that ICA with automated image analysis is efficient in evaluating ER and PR on paraffin section only when the tumour samples are correctly fixed.     

乳腺癌肉瘤的临床特点与病理生物学特性

目的探讨乳腺癌肉瘤的临床特点与病理生物学特性，为以手术为主的综合性治疗提供重要依据。方法回顾性分析经手术和病理学证实26例乳腺癌肉瘤的临床资料，并将30例乳腺癌作为免疫表型的对照组，研究该肿瘤的临床特点和病理生物学特性。结果乳腺癌肉瘤中癌成分〉50％者占61．54％，同侧腋淋巴结癌转移率达30．77％；肉瘤成分〉50％者占38．46％，同侧腋淋巴结内未见癌转移。免疫组化癌成分中EMA和CK阳性率均96．15％，P53、ER和PR阳性率分别为53．85％、61．54％和30．77％，Vimentin和S100阳性率分别为19．23％和15．38％。肉瘤成分中Vimentin和S100阳性率分别为96．15％和88．46％，EMA、CK、ER、PR和P53阳性率分别为19．23％、11．54％、7．69％、3．85％和3．85％。P53、ER、PR、Vimentin和S100与对照组差异有统计学意义（P〈0．05）；EMA和CK与对照组差异无统计学意义。结论乳腺癌肉瘤是由上皮和间叶成分混合而成的恶性肿瘤，因其成分不同，免疫表型差异较大。它具有双重侵袭性和极易复发的生物学特性，手术和放化疗是最佳的综合性治疗方法。     

食管癌组织雌、孕激素受体的测定及其临床意义

本研究采用免疫组化（ABC）法，对66例食管癌组织及21例正常人食管组织进行雌激素受体（ER）和孕激素受体（PR）的检测，结果发现，正常人食管组织不含ER，PR，食管癌组织ER阳性率为42．42％，（28／66），PR阳性率为43．94％（29／66），受体水平与食管癌患者性别，癌分化程度相关，而与年龄，TNM分期有无淋巴结转移无关，结果表明，采用ABC法检测石蜡包埋的食管癌组织ER和PR具有可靠性和敏感性，检测食管癌ER，PR，可为估价预后和指导临床进行内分泌治疗提供参考。     

Primary ovarian mucinous tumors with signet ring cells: report of 3 cases with discussion of so-called primary Krukenberg tumor

The distinction between a primary ovarian mucinous carcinoma or even a borderline mucinous tumor and a metastatic mucinous carcinoma may be difficult. A constellation of clinical, gross pathologic and morphologic features is used in this distinction. One of the most important morphologic features suggesting a metastatic mucinous carcinoma in the ovary is the presence of signet ring cells; these are considered rare in primary ovarian mucinous tumors. In this study, we report 3 primary ovarian mucinous tumors with a component of signet ring cells. The tumors arose in patients aged 27, 55, and 60, were unilateral, confined to the ovary and stage IA. They ranged from 9 to 27 cm; 1 was grossly a multiloculated cystic lesion and 2 were cystic and solid. In one case, the neoplasm had the architecture of a mucinous adenofibroma but had frankly malignant cells lining glands and forming solid aggregates of cells. A second tumor also had the background of an adenofibroma. The third was mostly a mucinous cystadenoma. In one case, endometriosis was present in the same ovary; teratomatous elements were not identified in any case. Immunohistochemistry, performed in 2 cases, showed both to be diffusely positive with CK7 and CA19.9, including the signet ring cells. CK20 was positive in both cases (1 focal; 1 diffuse). Estrogen receptor and CA125 were diffusely positive and carcinoembryonic antigen and CDX2 focally positive in 1 case. Chromogranin and synaptophysin were negative. Investigations to exclude a gastrointestinal neoplasm in 2 cases were negative. Features favoring a primary rather than a metastatic neoplasm are unilateral tumor, low stage, background of adenofibroma or cystadenoma, associated endometriosis in 1 case and an absence of features which are characteristic of secondary mucinous carcinomas in the ovary, such as surface tumor deposits, a nodular growth pattern, and lymphovascular permeation. Immunohistochemistry is of limited value because of overlapping immunophenotype between a primary ovarian mucinous tumor and a metastasis from the stomach, pancreas, biliary tree, appendix, or colorectum, the most likely primary sites for a secondary exhibiting similar features. Our study illustrates that signet ring cells occur rarely in a primary ovarian mucinous tumor; even when conspicuous the features differ from those of the usual Krukenberg tumor. At least some cases of so-called primary Krukenberg tumor may be similar to our cases. However, the designation primary Krukenberg tumor should not be used as, apart from the signet ring cells, a resemblance to a "true" Krukenberg tumor of the secondary type is limited. The tumors should be classified according to the underlying background neoplasm with a notation concerning the signet ring cell component.     

ER and PR Immunohistochemistry and HER2 FISH versus Oncotype DX: Implications for Breast Cancer Treatment

Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2) concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and Oncotype DX, a commercially available RT‐PCR‐based assay which recently began reporting biomarker results was assessed. ER concordance was 98.9% (262/265), Pearson correlation coefficient (r) = 0.42, and Spearman's rank correlation (ρ) = 0.25. Positive percent agreement for ER was 98.9% (262/265). One patient with discordant ER results was not offered hormone therapy based on the preferential use of Oncotype DX. PR was concordant in 91.3% (242/265), r = 0.80, ρ = 0.75, and Cohen's kappa (κ) = 0.63. Positive percent agreement for PR was 90.5% (218/241) and negative percent agreement was 100% (24/24). HER2 concordance was 99.2% (245/247), r = 0.35, ρ = 0.28, and κ = 0.12. Positive percent agreement for HER2 was 0% (0/2) and negative percent agreement was 100% (245/245). Of the three FISH HER2‐amplified cases, two were negative and one was equivocal, and all FISH HER2‐equivocal cases (n = 3) were negative by Oncotype DX. Patients that were FISH HER2‐amplified, Oncotype DX HER2‐negative did not receive trastuzumab. Although our results demonstrated high concordance between IHC and Oncotype DX for ER and PR, our data showed poor positive percent agreement for HER2. Compared to FISH, Oncotype DX does not identify HER2‐positive breast carcinomas. The preferential use of Oncotype DX biomarker results over IHC and FISH is discouraged.     

Correlation of her-2/neu gene amplification with other prognostic and predictive factors in female breast carcinoma

The purpose of this study was to determine if any relationship exists between Her-2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR), MIB-1, grade, size and age in female breast cancer. Five hundred and eighteen female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in which assessment of Her-2/neu amplification by fluorescence in-situ hybridization (FISH) has been performed, were reviewed retrospectively. Each patient was further assessed for ER, PR, MIB-1, grade, size and age at diagnosis. Chi-square analysis was then used to correlate the above observations. Overall gene amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%) were lobular. Her-2/neu gene was amplified in 37 (10%) out of 379 ER positive cases and in 39 (28%) out of 139 ER negative cases. Her-2/neu was amplified in 22 (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases. Amplification occurred in 18 (8%) out of 222 negative MIB-1 cases and amplified in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of 49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198 grade III tumors. Lobular carcinomas were not graded. Amplification was present in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%) out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her-2/neu was amplified in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women 40 years and younger. Comparison of these frequencies using chi-square test revealed statistically significant correlation between Her-2/neu amplification and ductal versus lobular carcinoma (p<0.0003), ER (p=0.0001) and PR (p<0.0001) negative tumors, over-expression of MIB-1 (p<0.0005) and high tumor grade (p=0.0009), while size of the tumor (p=0.08) and age of the patients (p=0.67) were not statistically significant. Correlation was found between Her-2/neu amplification and tumor type, high histological grade, ER and PR negative tumors, and high proliferative MIB-1 index. No correlation was found between size of the tumor and age of the patient with Her-2/neu amplification.     

Comparative analysis of alternative and traditional immunohistochemical markers for the distinction of ovarian sertoli cell tumor from endometrioid tumors and carcinoid tumor: A study of 160 cases

The main neoplasms in the differential diagnosis for primary ovarian tumors with a tubule-rich pattern are pure Sertoli cell tumor, endometrioid tumors (including borderline tumor, well-differentiated carcinoma, and the sertoliform variant of endometrioid carcinoma), and carcinoid tumor. Because traditional immunohistochemical markers [pan-cytokeratin (pan-CK), low molecular weight cytokeratin (CK8/18), epithelial membrane antigen (EMA), inhibin, calretinin, CD99, chromogranin, and synaptophysin] can occasionally have diagnostic limitations, the goal of this study was to determine whether or not any alternative markers [cytokeratin 7 (CK7), estrogen receptor (ER), progesterone receptor (PR), CD10, and CD56] have better diagnostic utility when compared with traditional markers for this differential diagnosis. Immunohistochemical stains for alternative, as well as traditional, markers were performed on the following primary ovarian tumors: pure Sertoli cell tumor (n = 40), endometrioid borderline tumor (n = 38), sertoliform endometrioid carcinoma (n = 13), well-differentiated endometrioid carcinoma (n = 27), and carcinoid tumor (n = 42). Extent and intensity of immunostaining were semiquantitatively scored. In addition, immunohistochemical composite scores (ICSs) in positive cases were calculated on the basis of the combination of extent and intensity scores. Cytokeratin 7 (CK7) was positive in 97% of endometrioid tumors, 13% of Sertoli cell tumors, and 24% of carcinoid tumors. The differences in the mean ICSs for endometrioid tumors versus Sertoli cell tumor or carcinoid tumor were statistically significant (P values ranging from <0.001 to 0.018). ER and PR were positive in 87% and 86% of endometrioid tumors, 8% and 13% of Sertoli cell tumors, and 2% each of carcinoid tumors, respectively. The differences in the mean ICSs for endometrioid tumors versus Sertoli cell tumor were statistically significant (P values ranging from <0.001 to 0.012). Among the epithelial markers, EMA seemed to be the most discriminatory but only slightly better than CK7, ER, or PR. Pan-CK and CK8/18 were not helpful. CD10 showed overlapping patterns of expression in all categories of tumors. Among the sex cord markers, CD10 was markedly less useful than inhibin or calretinin; CD99 was not discriminatory. CD56 showed overlapping patterns of expression in all categories of tumors. Among the neuroendocrine markers, CD56 was less useful than chromogranin or synaptophysin. When traditional immunohistochemical markers are problematic for the differential diagnosis of ovarian Sertoli cell tumor versus endometrioid tumors versus carcinoid tumor, adding CK7, ER, and/or PR to a panel of markers can be helpful. Endometrioid tumors more frequently express CK7, ER, and PR and show a greater extent of immunostaining in contrast to Sertoli cell tumor and carcinoid tumor. Compared with traditional epithelial markers, CK7, ER, and PR are nearly as advantageous as EMA. Inhibin is the most discriminatory sex cord marker, and CD10 is not helpful in the differential diagnosis. Chromogranin and synaptophysin are excellent discriminatory markers for carcinoid tumor, and CD56 is neither sufficiently sensitive nor specific enough for this differential diagnosis to warrant its use in routine practice.     

Clinical-pathological features and treatment modalities associated with recurrence in DCIS and micro-invasive carcinoma: Who to treat more and who to treat less

The primary aim in the management of DCIS is the prevention of recurrence and contralateral tumor. Risk factors for DCIS recurrence and appropriate treatments are still widely debated. Adjuvant therapies after surgical resection reduce recurrences and contralateral disease, but these treatments have significant financial costs, side effects and there is a group of low-risk patients who would not gain additional benefit. The aim of our analysis was to identify clinical-pathological features and treatment modalities associated with recurrence in DCIS and microinvasive carcinoma. In the Thomas Jefferson University Cancer Registry of Philadelphia, we identified 865 patients with DCIS or micro-invasive carcinoma treated between 2003 and 2013. Associations between recurrence and demographic factors (age at diagnosis, ethnicity), biological features (ER, PR and HER2) and treatment modalities (surgery, radiotherapy and endocrine treatment) were assessed. Our single institution register-based study showed that distribution of age at diagnosis and biological features did not significantly differ among ethnic groups. Younger women and micro-invasive carcinoma patients were more likely to undergo mastectomy, while African Americans were more likely to take endocrine therapy and undergo radiotherapy. In our sample only ER/PR negative DCIS were associated with significantly higher recurrence rate. Moreover, we reported a high rate of HER2 positive recurrences, suggesting that expression of this oncogene may represent a potential biomarker for DCIS at high risk of recurrence. To better define the molecular profile of the subgroup at worse prognosis might help to identify biomarkers predictive of recurrence or second tumors, identifying patients candidates for more appropriate treatments.     

MR Imaging Features of Triple‐Negative Breast Cancers

Triple‐negative (TN) breast cancers, which are associated with a more aggressive clinical course and poorer prognosis, often present with benign imaging features on mammography and ultrasound. The purpose of this study was to compare the magnetic resonance imaging features of TN breast cancers with estrogen (ER) and progesterone (PR) positive, human epidermal growth factor receptor (HER2) negative cancers. Retrospective review identified 140 patients with TN breast cancer who underwent a preoperative breast MRI between 2003 and 2008. Comparison was made to 181 patients with ER+/PR+/HER2? cancer. Breast MRIs were independently reviewed by two radiologists blinded to the pathology. Discrepancies were resolved by a third radiologist. TN cancers presented with a larger tumor size (p = 0.002), higher histologic grade (<0.001), and were more likely to be unifocal (p = 0.018) compared with ER+/PR+/HER2? tumors. MRI features associated with TN tumors included mass enhancement (p = 0.026), areas of intratumoral high T2 signal intensity (p < 0.001), lobulated shape (p < 0.001), rim enhancement (p < 0.001), and smooth margins (p = 0.005). Among the TN tumors with marked necrosis, 26% showed a large central acellular zone of necrosis.     

A multifactorial analysis of steroid hormone receptors in stages I and II breast cancer.

It has been shown that the level of estrogen receptors (ER), and to some extent progesterone receptors (PR), correlate to a high degree to the response to endocrine therapy in advanced breast cancer patients. To evaluate the prognostic value of ER/PR in early breast cancer, 80 patients with stages I and II were studied. They all underwent modified radical mastectomy. Patients with stage I disease (negative LN) received no further treatment, while those with stage II received standard adjuvant chemotherapy. All the patients were followed for 4 years. The ER and PR were measured in each primary tumor by the glycerol density gradient method. Values of 10 fmole/mgm protein or greater were considered positive (+) and less than 10 fmole/mgm were considered negative (-). The results revealed: (1) Fifty-two patients (65%) had ER+, of which 44 (85%) were also PR+; 28 patients had ER-, of which 24 were also PR- (p less than 0.0001). (2) ER/PR correlated with age as 71% of the patients over age 50 had ER+/PR+, compared to 33% of those under age 50 (p less than 0.05). (3) Postmenopausal patients had a higher incidence of ER+/PR+. (4) Primary tumors less than 2 cm in size had higher ER+; 71% in those with stage I and 80% in stage II. (5) Fifty-eight per cent (38) of patients with ductal carcinoma had ER+/PR+, compared to 67% (4) with lobular carcinoma. (6) The disease-free survival of patients with ER+ tumors was significantly longer than those with ER- tumors (p less than 0.005) both in positive and negative LN patients. The same was true for PR+ compared to PR- (p less than 0.005), but only in those with stage II disease. The overall survival rates were similarly significant in favor of ER+ and PR+ patients (p less than 0.025), but only in stage II disease. It seems that the status of steroid hormone receptors has a major prognostic factor second only to the LN status.     

Retroperitoneal leiomyomas: a clinicopathologic and immunohistochemical study of 56 cases with a comparison to retroperitoneal leiomyosarcomas.

Most retroperitoneal smooth muscle tumors are believed to be malignant, and leiomyomas are considered very rare. This study was undertaken to determine the clinicopathologic features and long-term follow-up of 56 tumors diagnosed as retroperitoneal leiomyomas (LM) or smooth muscle tumors with an uncertain malignant potential (SMTUMP) in an effort to correlate their behavior and clinicopathologic features. These tumors were compared with a series of 11 cases of retroperitoneal leiomyosarcomas (excluding gastrointestinal stromal tumors). Histologic slides and immunohistochemistry for SMA, desmin, S-100 protein, HMB45, CD34, C-KIT, estrogen (ER) and progesterone (PR) receptor proteins, and MIB-1 were analyzed. All tumors diagnosed as LM and all but one SMTUMP were well-differentiated smooth muscle tumors that lacked atypia and coagulative necrosis. There was <1 mitosis per 50 high power field (HPF) in 38 tumors; no tumor had >3 mitoses/50 HPF. Most tumors had a striking resemblance to uterine smooth muscle tumors with common hyaline change and trabecular patterns. There were 51 females and 5 males ranging in age from 25 to 79 years (mean 45 years, median 43 years). These tumors were typically large, with a mean size of 16.2 cm and weight of 1600 g. Immunohistochemically, all 35 tumors studied were positive for alpha-SMA, 30 of 35 tumors were positive for desmin, and all were negative for CD117, S100 protein, and HMB45 and all but one for CD34. Steroid receptors were commonly present: ER in 20 of 29 cases and PR in 26 of 31 cases in the tumors of female patients. MIB-1 score was <2% in all of 28 cases. Long-term follow-up (mean 140 months) did not reveal metastases, but two patients had local recurrence; however, neither patient with recurrence demonstrated disease progression in follow-up. By contrast, all 11 leiomyosarcomas had at least mild atypia, and all were ER and PR negative. All cases had MIB-1-positive nuclei, but only four had >10% nuclei positive. Four patients died of disease, four were alive with recurrence, and three had no evidence of disease. A group of benign leiomyomas can be identified among retroperitoneal smooth muscle tumors. Most of these tumors resemble uterine leiomyomas by histology and positive hormone receptors, and they seem to have a good long-term prognosis with a small potential for local recurrence.     

Paranuclear dot-like immunostaining for CD99: a unique staining pattern for diagnosing solid-pseudopapillary neoplasm of the pancreas

Solid-pseudopapillary neoplasm of the pancreas is a rare tumor of uncertain histogenesis that is characterized by a cystic and solid growth pattern with pseudopapillary structures. The differentiation of solid-pseudopapillary neoplasm from other pancreatic tumors is of great importance. However, it is sometimes difficult because of similarities in morphologic features and immunophenotype. CD99 is a diagnostically useful marker for Ewing sarcoma/primitive neuroectodermal tumor. The aim of this study was to investigate the diagnostic value of CD99 in solid-pseudopapillary neoplasm. We investigated immunohistochemical staining for CD99 in tissue microarray blocks from 55 cases of pancreatic solid-pseudopapillary neoplasm, 51 cases of pancreatic neuroendocrine tumor, and 54 cases of pancreatic adenocarcinoma. Biopsy specimens from 7 solid-pseudopapillary neoplasms, 6 acinar cell carcinomas, and 1 pancreatoblastoma were also investigated. All the solid-pseudopapillary neoplasm cells exhibited paranuclear dot-like immunoreactivity for CD99 regardless of the clinicopathologic or morphologic features. Forty of the 51 pancreatic neuroendocrine tumors were positive for CD99. Staining here was membranous, or membranous and cytoplasmic. Four of the 54 pancreatic adenocarcinomas and 1 pancreatoblastoma showed faint membranous staining. None of the acinar cell carcinomas was reactive for CD99. Our study has identified for the first time that pancreatic solid-pseudopapillary neoplasm exhibits a unique dot-like staining pattern for CD99. This could prove to be the most useful aspect of its immunoprofile for the definitive diagnosis of solid-pseudopapillary neoplasm and differentiation from other pancreatic tumors.     

复方米非司酮对早孕绒毛、蜕膜形态学及雌、孕激素受体的影响

目的　观察早孕绒毛、蜕膜形态学及雌孕激素受体的表达 ,对复方米非司酮及米非司酮进行比较性研究。　方法　 4 9例早孕者随机分为对照、米非司酮 (15 0mg/次 )及复方米非司酮 (含双炔失碳酯 5mg +米非司酮 30mg ,12h× 2 ) 3组。服药后 2 4h手术终止妊娠 ,取绒毛、蜕膜组织 ,应用链霉卵白素 过氧化物酶 (SP)免疫组织化学法观察绒毛、蜕膜雌激素受体(ER)、孕激素受体 (PR)的变化。　结果　米非司酮组少数绒毛间质水肿变性 ,蜕膜示小灶性变性、坏死 ,可见凋亡细胞 ;绒毛ER、PR着染强度及阳性细胞着染百分率较对照组明显增加 (P <0 .0 0 1,P <0 .0 5 ) ,蜕膜ER、PR染色强度与对照组比较无显著差异 ,但阳性细胞着染百分率显著下降 (P <0 .0 5 ) ;复方米非司酮组绒毛表面附多量纤维蛋白样物 ,部分间质水肿 ,蜕膜呈片状变性、坏死 ,凋亡细胞散在 ;绒毛ER、PR着染强度较对照组显著增加 (P <0 .0 5 ) ,阳性细胞着染百分率与对照组比较ER显著增加 (P <0 .0 5 ) ,PR略低但无显著差异 ;蜕膜ER、PR着染强度无显著差异 ,但阳性细胞着染百分率与对照组比较明显下降(P <0 .0 0 1)。　结论　复方米非司酮使蜕膜ER、PR阳性细胞着染百分率明显降低 ,蜕膜变性、坏死较甚 ,但对ER、PR着染强度的影响相对小 ,这可能有助于提     

Estrogen and Progesterone Receptor and p53 Gene Expression in Adenoid Cystic Cancer

Objectives The current study examined the role of estrogen receptors (ER), progesterone receptors (PR) and p53 expression in adenoid cystic carcinoma (ACC) to determine if simple expression or possible overexpression of these products might influence the development and natural course of this cancer. Study Design ER and PR status and p53 overexpression were retrospectively evaluated utilizing immunohistochemical evaluation of 47 ACC specimens. Methods Formalin-fixed paraffin-embedded tissues from 47 ACC specimens and 47 samples of normal salivary gland tissue were evaluated histochemically for the presence of ER, PR and p53. Immunoreactivity was scored using a 0 to +3 scale in which staining was either (0) negative, (+1) spotty, (+2) weakly positive, or (+3) strongly positive. Results ER was expressed in 8 of 47 tumors while PR was expressed in 4 of 47 tumors. p53 aberrations were demonstrated in 26 of 47 tumors. Tumors showed varying degrees of immunopositivity ranging from 0 to +3. Conclusions These studies suggest that p53 aberrations may be involved in ACC tumor progression and that ER and PR may play a role in ACC development.