Complex glandular pattern is an aggressive morphology that predicts poor prognosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant neoplasm with various morphologies. Recognition of histological patterns that can predict prognosis is important in pathological examination. Recently, the complex glandular pattern was defined as a morphology associating the poor prognosis in lung adenocarcinoma. We investigated the significance of the complex glandular pattern in PDAC by performing a retrospective analysis. Among 240 consecutive cases of conventional PDACs, 21 cases in which complex glandular pattern constituted >50 % of the total tumor volume (CG-PDACs) were identified. The prevalence of CG-PDAC was 8.8 % among all preoperative therapy-naïve and surgically resected conventional PDACs. Compared to the control PDACs (n = 95), the CG-PDACs were characterized by significantly higher prevalence of small- to medium-sized artery invasion (71.4 % vs. 14.7 %, p < 0.0001), intratumoral necrosis (59.1 % vs. 16.8 %, p < 0.0001), tumor budding (mean: 15.5 vs. 12.5 per 0.785 mm2, p = 0.04), significantly higher Ki67 proliferative index (mean: 75.0 % vs. 54.7 %, p < 0.0001), and the HNF1α-/KRT81+ (quasi-mesenchymal) immunophenotype (42.9 % vs. 19.0 %, p = 0.004). In Kaplan-Meier analyses, the CG-PDAC patients achieved significantly worse disease-free survival (DFS) and overall survival (OS) compared to the control PDAC patients; the respective median DFS and OS were 6.3 and 17.7 months for CG-PDACs, and 22.6 and 52.8 months for control PDACs. A multivariate Cox regression analysis showed that predominance of complex glandular pattern was an independent prognostic factor (hazard ratio: 2.95; 95 % confidence interval: 1.46-5.98; p = 0.003). Our results provide new insights into the complex glandular pattern in conventional PDACs as a novel and potentially useful prognostic factor.

Capillary hemangioma involved in filar lipoma: A case report.

Filar lipomas are a subtype of spinal lipomas wherein adipose tissue accumulation is restricted to the filum terminale. Embryologically, filar lipomas are considered to occur because of the failure of secondary neurulation, although the precise mechanism is not yet completely understood. Involvement of ectopic mesodermal, ectodermal, and endodermal tissues in spinal lipomas has been occasionally reported, and the origin of these ectopic tissues has been supposed to be migration of pluripotent tissues, which exist during secondary neurulation. We report an infantile case of capillary hemangioma involved in filar lipoma. To our knowledge, this is the first report of a case of intradural extramedullary capillary hemangioma at the filum terminale. We suspected that the filar lesion arose during the late phase of secondary neurulation based on the clinical, anatomical, and histological characteristics.
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Chemical separation of Mo and W from terrestrial and extraterrestrial samples via anion exchange chromatography.

A new two-stage chemical separation method was established using an anion exchange resin, Eichrom 1 × 8, to separate Mo and W from four natural rock samples. First, the distribution coefficients of nine elements (Ti, Fe, Zn, Zr, Nb, Mo, Hf, Ta, and W) under various chemical conditions were determined using HCl, HNO3, and HF. On the basis of the obtained distribution coefficients, a new technique for the two-stage chemical separation of Mo and W, along with the group separation of Ti-Zr-Hf, was developed as follows: 0.4 M HCl-0.5 M HF (major elements), 9 M HCl-0.05 M HF (Ti-Zr-Hf), 9 M HCl-1 M HF (W), and 6 M HNO3-3 M HF (Mo). After the chemical procedure, Nb remaining in the W fraction was separated using 9 M HCl-3 M HF. On the other hand, Nb and Zn remaining in the Mo fraction were removed using 2 M HF and 6 M HCl-0.1 M HF. The performance of this technique was evaluated by separating these elements from two terrestrial and two extraterrestrial samples. The recovery yields for Mo, W, Zr, and Hf were nearly 100% for all of the examined samples. The total contents of the Zr, Hf, W, and Mo in the blanks used for the chemical separation procedure were 582, 9, 29, and 396 pg, respectively. Therefore, our new separation technique can be widely used in various fields of geochemistry, cosmochemistry, and environmental sciences and particularly for multi-isotope analysis of these elements from a single sample with significant internal isotope heterogeneities.

Solitary metastasis of a clear cell ovarian adenocarcinoma to the small bowel mucosa.

Metastasis of ovarian carcinoma to the small bowel parenchyma without peritoneal dissemination is uncommon. A 63-year-old woman underwent surgery for a clear cell adenocarcinoma of the ovary and received adjuvant chemotherapy. Eighteen months after the operation, she presented with recurrent occult bowel hemorrhage without evidence of an abdominal mass. Nine months later, a rapidly growing abdominal mass was detected. Laparoscopy revealed a solitary tumor of the ileum covered with an intact serosal layer. Partial ileectomy was performed for tumor resection. Histological examination revealed cells resembling the primary ovarian tumor in the mucosal surface of the small bowel along with an intact serosa. The tumor cells were positive for cytokeratin 7 and negative for cytokeratin 20, suggesting an ovarian origin. This is the first report of solitary metastasis of an ovarian carcinoma to the small bowel parenchyma without peritoneal dissemination. Metastasis to the small bowel should be considered in ovarian carcinoma patients with occult gastrointestinal hemorrhage.

Cytologic findings of low grade endometrial stromal sarcoma with sex cord-like differentiation: a case report.

BACKGROUND: To report the cytologic characteristics of low grade endometrial stromal sarcoma with sex cord-like differentiation. CASE: A 49-year-old woman presented with hypermenorrhea, menorrhalgia and anemia. With a diagnosis of degenerated leiomyoma of the uterus, simple total hysterectomy was conducted. Histologic examination revealed cells with ovoid to short, spindle-shaped nuclei resembling endometrial stromal cells proliferating in a space-occupying manner and compressing and partially infiltrating the myometrium. Some tumor cells were arranged in sex cord-like form, and hyalinization was observed in the center of the cord. Low grade endometrial stromal sarcoma with sex cord-like differentiation was diagnosed. Touch imprint cytologic examination of the tumor showed cells containing scanty cytoplasm and ovoid to spindle-shaped nuclei with little atypia; they were scattered individually, aggregated in clusters, or arranged in cord or glandular form. Hyaline-like substance was present in abundance. The histologic characteristics of the endometrial stromal sarcoma with sex cord-like differentiation were confirmed by touch imprint cytology of the tumor. CONCLUSION: In this case of low grade endometrial stromal sarcoma with sex cord-like differentiation, cytologic examination revealed hyaline substance and tumor cells aligned in cord or glandular form.

Malignant peritoneal mesothelioma: quantitative analysis of asbestos burden.

Malignant mesotheliomas develop commonly in the pleural cavity and rarely arise in the peritoneal cavity. It is well established that asbestos exposure is related to malignant pleural mesothelioma, but the asbestos burden in the abdominal cavity in patients with malignant peritoneal mesothelioma has not been well studied. The purpose of the present study was therefore to report on an autopsy case of malignant peritoneal mesothelioma with quantitative analysis of the asbestos burden in tissues from the pleura and organs in the abdominal cavity. The patient was a 67-year-old man with a history of asbestos exposure. The peritoneum was thickened with diffuse tumor proliferation. This patient was diagnosed as having malignant peritoneal epithelioid mesothelioma. The number of asbestos fibers was >10,000/g dry tissue in all samples examined except in the small intestine. The number of asbestos fibers in the stomach was 53,000/g, which was higher than that in a control asbestosis subject. The existence of numerous asbestos fibers found in the abdominal cavity suggests that asbestos stimuli are related to the tumorigenesis of malignant peritoneal mesothelioma.

Akt/protein kinase B overexpression as an accurate prognostic marker in adult diffuse astrocytoma.

BACKGROUND: Akt/Protein kinase B (PKB) is a common downstream molecule of Ras signaling essential for cell survival. In an attempt to find a novel prognostic marker of diffuse astrocytoma, we performed an immunohistochemical analysis of Akt/PKB with regard to patient survival and regrowth patterns. METHODS: Twenty-four adult patients with diffuse astrocytoma were similarly managed without early post-operative radiotherapy and followed up for a median period of 7.5 years. They were analysed by immunohistochemistry for Akt/PKB expression as well as p53 protein accumulation, epidermal growth factor receptor (EGFR) expression, and MIB-1 labeling index. The prognostic significance of each molecular covariate was tested by multivariate analysis using Cox's proportional hazard model including age, performance status, and extent of surgical resection. FINDINGS: Akt/PKB overexpression significantly correlated with both shorter overall survival (OS) and progression-free survival (PFS) (p = 0.0110). All the Akt/PKB-positive patients with post-operative residual tumours experienced tumour recurrences, whereas only a small fraction of the Akt/PKB-negative individuals had recurrences (p = 0.0070). Invasive recurrence into surrounding brain occurred only in the Akt/PKB-overexpressed tumours. In contrast, MIB-1 labeling index correlated only with OS, while p53 protein accumulation correlated only with PFS. The Cox's proportional hazard model identified Akt/PKB overexpression as a significant prognostic factor for shorter PFS (p = 0.0117). CONCLUSION: These results show that Akt/PKB overexpression would be suggestive of malignant progression and invasive regrowth of diffuse astrocytoma, and it can serve as a novel prognostic marker for this tumour.

High serum level of plasminogen activator inhibitor-1 predicts histological grade of intracerebral gliomas.

BACKGROUND: No serum marker is currently available for the diagnosis and treatment of gliomas. Plasminogen activator inhibitor-1 (PAI-1) controls the proteolytic activity in cancer cells and cellular migration during angiogenesis. PATIENTS AND METHODS: To verify the potential of PAI-1 as a serum marker for gliomas, the serum PAI-1 concentrations were measured by ELISA in 57 glioma patients and 34 healthy volunteers. RESULTS: We found significantly higher serum levels in the patients with high-grade gliomas than in the healthy volunteers (p = 0.0009, unpaired t-test) and those with low-grade tumors (p = 0.0074). Furthermore, high-grade glioma patients with a low serum level of PAI-1 survived significantly longer than those with high levels (p = 0.0082). Immunohistochemical analysis using anti-PAI-1 antibody revealed dense and spotty staining in the high-grade tumor tissues from the patients with high serum PAI-1 levels. CONCLUSION: These results suggest that the serum PAI-1 level can be a marker for the prediction of histological grade in intracerebral glioma.

Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block bad-mediated apoptosis in human pancreatic cancer cell lines.

Pancreatic cancer still remains a serious health problem with <5% 5-year survival rate for all stages. To develop an effective treatment, it is necessary to identify a target molecule that is crucially involved in pancreatic tumor growth. We previously observed that Pim-3, a member of the proto-oncogene Pim family that expresses serine/threonine kinase activity, was aberrantly expressed in human and mouse hepatomas but not in normal liver. Here, we show that Pim-3 is also expressed in malignant lesions of the pancreas but not in normal pancreatic tissue. Moreover, Pim-3 mRNA and protein were constitutively expressed in all human pancreatic cancer cell lines that we examined and colocalized with the proapoptotic protein Bad. The ablation of endogenous Pim-3 by small hairpin RNA transfection promoted apoptosis, as evidenced by increases in a proportion of cells in the sub-G(1) fraction of the cell cycle and in phosphatidyl serine externalization. A proapoptotic molecule, Bad, was phosphorylated constitutively at Ser(112) but not Ser(136) in human pancreatic cancer cell lines and this phosphorylation is presumed to represent its inactive form. Phosphorylation of Bad and the expression of an antiapoptotic molecule, Bcl-X(L), were reduced by the ablation of endogenous Pim-3. Thus, we provide the first evidence that Pim-3 can inactivate Bad and maintain the expression of Bcl-X(L) and thus prevent apoptosis of human pancreatic cancer cells. This may contribute to the net increase in tumor volume or tumor growth in pancreatic cancer.

Up-regulation of CXC chemokines and their receptors: implications for proinflammatory microenvironments of ovarian carcinomas and endometriosis.

Molecular abnormalities in the epithelial cells of endometriosis and their relevance to carcinogenesis of the ovary have been well studied. On the other hand, the differences of proinflammatory microenvironments between endometriosis and ovarian carcinomas have not been well documented yet. In this study, the expression patterns of CXC chemokines (IL-8, ENA-78, GRO-alpha, I-TAC, Mig, and SDF-1) and their receptors (CXCR2, CXCR3, and CXCR4) were compared among 12 ovarian carcinomas, 8 endometriosis, and 6 normal ovaries using quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. The CXCR3-mediated signaling in ovarian carcinoma cells in vitro was also investigated. In quantitative reverse transcriptase polymerase chain reaction, ENA-78 was up-regulated both in endometriosis and carcinomas, whereas I-TAC was detected exclusively in carcinomas. CXCR3 was up-regulated both in carcinomas and endometriosis. However, immunohistochemical studies revealed that the localization of CXCR3 in carcinomas was distinctively different from that in endometriosis. In carcinoma-endometriosis coexisting cases, CXCR3-positive lymphocytes in benign lesions decreased in proportion as CXCR3-positive tumor cells replaced the tissues. CXCR3 was also detected in ovarian carcinoma cell lines in vitro. Administration of interferon gamma (IFN-gamma)-inducible chemokines induced extracellular signal-regulated kinase phosphorylation in these carcinoma cells. The results indicated that CXC chemokines might contribute to the progression of ovarian carcinomas and endometriosis in different manners. Aberrant expression of IFN-gamma-inducible chemokines and CXCR3 in carcinoma cells in association with reduced CXCR3-positive immune cells raised the possibility that IFN-gamma-inducible chemokines might not exert effective antitumor immune responses but that they might work in favor of tumor progression.

Neurofibromatosis type 2 in an infant with multiple plexiform schwannomas as first symptom.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder that is caused by inactivating mutations or a loss of both alleles in the NF2 tumor-suppressor gene. Bilateral vestibular schwannomas are considered to be the hallmark of this disease, with hearing loss and tinnitus which are caused by these tumors, usually presenting as the initial symptoms. In addition to other tumors and ocular findings, skin abnormalities also occur in NF2, however, they are not so characteristic as neurofibromatosis type 1 (NF1). We herein report a case of NF2 which occurred in a 5-year-old boy. He had multiple cutaneous tumors but did not have any symptoms related to vestibular schwannomas. He also had multiple depigmented spots. A histopathological examination revealed these tumors to be plexiform schwannomas; we therefore suspected NF2. As a result of magnetic resonance imaging with gadolinium enhancement, bilateral vestibular schwannomas were detected and a final diagnosis of NF2 was thus made. The association between NF2 and multiple depigmented spots is unknown, we therefore consider that multiple cutaneous plexiform schwannomas may strongly suggest an association with NF2.

Cathepsin D is a potential serum marker for poor prognosis in glioma patients.

Cathepsin D is an aspartyl protease involved in protein catabolism and tissue remodeling which can be secreted from cancer cells. To identify a potential serum marker for gliomas, we investigated the gene expression levels of cathepsin D in 87 tissue samples and measured the protein concentrations in sera of glioma patients. The tissue samples consisted of 43 glioblastomas, 13 anaplastic astrocytomas, 22 astrocytomas, and 9 normal brain tissues. The results of real-time quantitative reverse transcription-PCR analysis showed that cathepsin D transcript levels became significantly higher as the glioma grade advanced (P = 0.0466, glioblastoma and anaplastic astrocytoma; P = 0.0008, glioblastoma and astrocytoma; P = 0.0271, glioblastoma and normal brain tissue; unpaired t test). Immunohistochemical analysis with anti-cathepsin D antibody revealed dense and spotty staining in the tumor cells with high transcript levels. The low expression of cathepsin D significantly correlated with long survival of the glioma patients. Furthermore, the glioblastoma patients with high gene expression of cathepsin D lived significantly shorter than those with low expression (P = 0.0104, Cox-Mantel log-rank test) and frequently had leptomeningeal dissemination (P = 0.0016, chi2 test). The multivariate analysis confirmed that the cathepsin D expression level was an independent predictor for short survival (P = 0.0102, Cox proportional hazard regression model). Measurement of the serum cathepsin D concentrations by ELISA showed a significant increase in the patients with high-grade gliomas as compared with the low-grade tumors (P = 0.0081, chi2 test). These results collectively suggest that cathepsin D could be a potential serum marker for the prediction of aggressive nature of human gliomas.

The expression of hepatocyte nuclear factor-4alpha, a developmental regulator of visceral endoderm, correlates with the intestinal phenotype of gastric adenocarcinomas.

AIMS: Hepatocyte nuclear factor (HNF)-4alpha is a developmental regulator of the visceral endoderm, which is expressed in the embryonic gut and later in the adult intestine and colon. However, adult gastric mucosa does not express HNF-4alpha. We investigated the possible involvement of HNF-4alpha in intestinal metaplasia and the intestinalisation of gastric adenocarcinomas. METHODS: Thirty-five cases of adenocarcinomas and 46 cases of adjacent non-neoplastic mucosa with (22 lesions) or without (24 lesions) intestinal metaplasia were immunostained for HNF-4alpha. The gastric or the intestinal phenotype was also examined using immunohistochemistry for MUC5AC, MUC2, CD10, and gastric-type mucin (GTM). Adenocarcinomas were classified into the gastric type (G-type, 42.9%), the mixed gastric and intestinal type (GI-type, 31.4%), and the intestinal type (I-type, 25.7%). RESULTS: The HNF-4alpha expression was exclusively seen in glandular cells with intestinal metaplasia, which was correlated with MUC2 expression (p<0.05) and inversely correlated with MUC5AC expression (p<0.05). All adenocarcinomas more or less expressed HNF-4alpha, with an intense expression being seen in the I-type (p<0.01) and in well-differentiated adenocarcinomas (p<0.03). CONCLUSIONS: HNF-4alpha expression is associated with the intestinal phenotype of non-neoplastic and neoplastic gastric glandular cells, suggesting a possible involvement in the establishment and/or maintenance of the intestinal phenotype of the gastric mucosa and adenocarcinomas.

Sentinel node micrometastasis and distant failure in breast cancer patients.

BACKGROUND: Lymphatic mapping and sentinel lymph node (SN) biopsy has rapidly replaced axillary lymph node dissection for clinically node-negative breast cancers. Because of a short follow-up period when the procedure was new, there were few reports of the clinical recurrence rate in breast cancer patients treated with SN biopsy. The present study attempts to clarify the occurrence of distant failure after SN biopsy, especially in breast cancer patients with SN micrometastasis. METHODS: The subjects consisted of 375 cases with clinically node-negative breast cancer, who had undergone SN biopsies. Chemotherapy and/or hormonal therapy was recommended based on the pathological primary tumor characteristics. The patients with SN micrometastasis also received adjuvant therapy equal to node-positive patients. RESULTS: Examinations of lymph nodes indicated metastases in 73 cases. Among the invasive cancers, 54 cases had macrometastasis, 19 cases had micrometastasis and 241 cases had a tumor free SN. The median follow-up period ws 30 months (range 6 to 66 months). Distant relapse rates per person-years were 0.3% in the cases with tumor free SN and 3.3% among the macrometastatic cases. However, systemic disease was not observed in the cases with SN micrometastasis. CONCLUSIONS: These results may show that upstaging due to SN investigation increases the number of cases who should receive anti-cancer drugs, and consequently reduces the distant relapse rate. Further studies in a large number of cases as well as longer follow-up are needed to determine the prognostic significance of SN micrometastasis.

Molecular classification and survival prediction in human gliomas based on proteome analysis.

The biological features of gliomas, which are characterized by highly heterogeneous biological aggressiveness even in the same histological category, would be precisely described by global gene expression data at the protein level. We investigated whether proteome analysis based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry can identify differences in protein expression between high- and low-grade glioma tissues. Proteome profiling patterns were compared in 85 tissue samples: 52 glioblastoma multiforme, 13 anaplastic astrocytomas, 10 atrocytomas, and 10 normal brain tissues. We could completely distinguish the normal brain tissues from glioma tissues by cluster analysis based on the proteome profiling patterns. Proteome-based clustering significantly correlated with the patient survival, and we could identify a biologically distinct subset of astrocytomas with aggressive nature. Discriminant analysis extracted a set of 37 proteins differentially expressed based on histological grading. Among them, many of the proteins that were increased in high-grade gliomas were categorized as signal transduction proteins, including small G-proteins. Immunohistochemical analysis confirmed the expression of identified proteins in glioma tissues. The present study shows that proteome analysis is useful to develop a novel system for the prediction of biological aggressiveness of gliomas. The proteins identified here could be novel biomarkers for survival prediction and rational targets for antiglioma therapy.

MR imaging of normal perivascular space expansion at midbrain.

BACKGROUND AND PURPOSE: A previous investigation of the MR imaging findings in the midbrain reported expanded perivascular (PV) spaces in only the ponto-mesencepalic junction (PMJ) in 20% of healthy subjects, whereas pathologically expanding PV spaces have been reported at the mesencephalo-diencephalic junction (MDJ) as multi-lobulated, cystic lesions with signal intensity compatible with that of CSF that cause aqueductal stenosis. To clarify the anatomical distinctions between normally expanded and pathologically expanding PV spaces, we defined their distribution in the normal midbrain by using high-spatial-resolution MR imaging. METHODS: Heavily T2-weighted MR imaging was performed in 115 adult subjects with neurologic complaints without cerebral disease. Histologic studies were performed from two normal midbrain blocks. RESULTS: Expanded PV spaces were visible at the PMJ in 87% of subjects and at the MDJ in 63% of subjects. On axial images, ovoid or linear lesions with signal intensity compatible to CSF were present behind the cerebral peduncle at both the PMJ and MDJ. These areas varied from less than 1 mm to 5 mm (maximum diameter on coronal sections). Histologic studies confirmed the distribution of expanded PV spaces, as noted on MR images. CONCLUSION: This study, by using high-spatial-resolution MR imaging, revealed that expanded PV spaces were visible at the PMJ and MDJ. Our finding of expanded PV spaces normally present at the MDJ may be related to pathologically expanding PV spaces, which should be kept in mind as a differential diagnosis for intraparenchymal cystic lesions in the midbrain with signal intensity compatible to CSF.

Evidence for hepatocellular differentiation in alpha-fetoprotein-negative gastric adenocarcinoma with hepatoid morphology: a study with in situ hybridisation for albumin mRNA.

AIM: Hepatoid adenocarcinoma, a putative chemosensitive tumour, is defined as a tumour with aberrant hepatocellular differentiation occurring in extrahepatic organs such as the stomach, usually in the gastrointestinal tract. Differentiation in the hepatocellular direction is usually supported by the production of alpha-fetoprotein (AFP) and, more recently, albumin (ALB) mRNA. We investigated ALB mRNA to address whether adenocarcinoma with hepatoid morphology, regardless of AFP production, can be diagnosed solely by morphological criteria as a hepatoid adenocarcinoma. METHODS: We performed in situ hybridisation (ISH) and immunohistochemistry (IH) for ALB mRNA on AFP-negative gastric adenocarcinomas with hepatoid morphology. AFP-positive hepatoid adenocarcinomas and AFP-negative conventional gastric adenocarcinomas were also investigated as positive and negative controls, respectively. RESULTS: All three gastric adenocarcinomas with hepatoid morphology with no evidence of AFP production stained positive for ALB mRNA, thus providing evidence of differentiation in the hepatocellular direction. Three of five cases of AFP-positive hepatoid adenocarcinoma of the stomach were positive for ALB mRNA, while 11 cases of AFP-negative conventional gastric adenocarcinoma were negative. CONCLUSION: The present study demonstrates that, irrespective of AFP production, gastric adenocarcinoma with morphological patterns suggestive of hepatoid differentiation should be diagnosed as hepatoid adenocarcinoma with important prognostic implications.

Genetic origin and imprinting in hydatidiform moles. Comparison between DNA polymorphism analysis and immunoreactivity of p57KIP2.

OBJECTIVE: To evaluate whether p57KIP2 expression is concordant with the result of DNA polymorphism analysis in molar pregnancy. STUDY DESIGN: Eleven molar pregnancies diagnosed by pathologic findings between October 2002 and April 2004 were studied. Histopathologic diagnosis, DNA polymorphism analysis and p57KIP2 immunohistochemistry were investigated. RESULTS: DNA polymorphism analysis identified 3 biparental conceptuses as well as 4 dispermic androgenetic complete moles (CMs) and 4 suggestive monospermic CMs. Distinctly positive nuclear immunoreactivity of p57KIP2 was observed in a significant proportion of the villous cytotrophoblast and mesenchyme (30-60% of cells positive) in 3 cases of biparental conceptuses proven by DNA polymorphism. In contrast, p57KIP2 expression was negative (< 5% positive cells) in either the villous cytotrophoblast or mesenchyme in 8 cases of androgenetic conceptuses proven by DNA polymorphism. In all 11, p57KIP2 immunostaining was observed in the nuclei of extravillous trophoblasts that served as internal positive controls. CONCLUSION: Negative p57KIP2 immunoreactivity (paternally imprinted, maternally expressed gene) was in perfect concordance with the androgenetic origin of molar pregnancies proven by DNA polymorphism. The results suggest that p57KIP2 immunoreactivity, which can be performed in routine pathologic examinations, is a promising ancillary diagnostic tool to differentiate androgenetic CM from biparental conceptuses.

Immunohistochemical expression of myoepithelial markers in adenomyoepithelioma of the breast: a unique paradoxical staining pattern of high-molecular weight cytokeratins.

To determine which immunohistochemical markers are useful for the identification of neoplastic myoepithelial cells in adenomyoepithelioma of the breast, the expression of seven myoepithelial markers (α-smooth muscle actin (α-SMA), calponin, p63, CD10, cytokeratin 5/6, cytokeratin 14, and S-100) was examined in 19 lesions from 16 patients. The lesion consisted of seven spindle and 12 clear cell lesions. For normal myoepithelial cells, α-SMA, calponin, and p63 were significantly more sensitive than cytokeratin 5/6, cytokeratin 14, and S-100. There was no significant difference in the expression of α-SMA, calponin, p63, and CD10 in neoplastic myoepithelial cells of adenomyoepithelioma regardless of spindle or clear cell types. In spindle cell lesions, high-molecular weight cytokeratins (HMWCK; cytokeratin 5/6 and cytokeratin 14) tended to show higher staining scores and S-100 showed lower staining scores than other markers. In clear cell lesions, HMWCK showed significantly lower staining scores than the other five markers. There was no significant difference in staining scores among the other five markers. HMWCK showed a unique paradoxical staining pattern in clear cell lesions, with diffusely positive inner epithelial cells and completely negative outer myoepithelial cells. Although the sensitivity of HMWCK in clear cell lesions is low, with this unique paradoxical staining pattern and relatively high sensitivity in spindle cell lesions, HMWCK could be useful in diagnosing adenomyoepithelioma. In choosing immunohistochemical markers, any of the seven markers are useful, but combining HMWCK and any one of α-SMA, calponin, and p63 would be a good panel for the diagnosis of adenomyoepithelioma.

Squamous predominance in mixed-epithelial papillary cystadenomas of borderline malignancy of mullerian type arising in endometriotic cysts: a study of four cases.

Mixed-epithelial papillary cystadenoma of borderline malignancy of mullerian type (MEBMM) is composed of a mixture of mullerian epithelial types, such as mucinous, serous, endometrioid, and squamous. Four cases of MEBMM with squamous overgrowth (MEBMMSO) were reviewed. The patients' median age was 56 years, and all cases were unilateral. The clinical stages were Ia (two cases), Ic (one case), and IV based on the presence of tumor cells in pleural fluid (one case). No recurrence was seen in three of the cases. In one of those three cases, there was no recurrence after undergoing surgery only; in the other two of those three cases, there was no recurrence after undergoing surgery and receiving postoperative chemotherapy. In the single case that was at stage IV at initial presentation, a recurrent MEBMMSO nodule was found at a second look 17 months after the initial surgery. In terms of gross findings, all of the tumors were cystic with intracystic papillary fronds. In addition, old endometriotic lesions lined the cysts. The tumors were mainly composed of a proliferation of squamous-type epithelium, with minor foci containing a mixture of other mullerian-type epithelia, especially mucinous. Intraepithelial infiltration by neutrophilic leukocytes was prominent. The differential diagnosis of MEBMMSO includes proliferating Brenner tumors.