Multiple angiosarcomas of both breasts: a case report.

BACKGROUND: Primary angiosarcomas of the breast are rare and highly aggressive. We herein report a rare case of multiple angiosarcomas detected concurrently in both breasts. CASE PRESENTATION: A 49-year-old woman visited a doctor after noticing a lump in her right breast. At that time, mammography and ultrasonography revealed no abnormal findings in either breast. She was referred to our hospital 5 months later, because screening mammography had revealed a focal asymmetric density in her right breast. Ultrasonography showed ill-defined hyper- and hypo-echoic lesions in both breasts. Magnetic resonance imaging disclosed five heterogeneously enhanced masses (5.8 cm in maximum diameter) in the right breast and six enhanced masses (approximately 1-3 cm in diameter) in the left breast. Histological examination of core needle biopsies revealed proliferation of irregularly shaped vascular channels lined by atypical endothelial cells throughout the adipose tissue and lobules of the breasts, leading to a diagnosis of well-differentiated angiosarcoma. The lesions were assumed to be primary angiosarcomas, because she had neither a history of breast surgery nor of radiation therapy. She underwent bilateral mastectomies and postoperative chest wall irradiation. Computed tomography 11 weeks after the surgery revealed multiple, small, subcutaneous nodules in the chest wall that were suspected of being angiosarcoma metastases. We started chemotherapy (weekly paclitaxel 80 mg/m2), which achieved shrinkage of these nodules within 2 months. CONCLUSIONS: Early diagnosis, immediate initiation of local and systemic therapies, and intensive follow-up are important in improving the prognosis of angiosarcomas.

Immunohistochemical and molecular detection of the expression of FGF23 in phosphaturic mesenchymal tumors including the non-phosphaturic variant.

BACKGROUND: Phosphaturic mesenchymal tumors (PMTs) are rare neoplasms that are often associated with tumor-induced osteomalacia (TIO) due to excessive serum levels of fibroblast growth factor 23 (FGF23). PMTs share overlapping histologic features with other types of tumors; thus, accurate pathological diagnosis may be challenging. We performed an immunohistochemical examination of FGF23 expression in PMTs and other types of tumors, together with pertinent molecular analyses. METHODS: Seven PMTs (5 with TIO and 2 without TIO) and 46 other types of bone and soft tissue tumors were retrieved, and immunohistochemistry was performed using a commercially available anti-FGF23 antibody. In addition, FGF23 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR), using RNA extracted from formalin-fixed, paraffin-embedded tissues. RESULTS: Immunohistochemical analysis of FGF23 expression showed distinct, punctate staining in the cytoplasm in 5 PMTs with TIO, whereas FGF23 expression was negative in the 2 PMTs without TIO and the other 46 tumors. FGF23 mRNA expression was detected in all 4 PMTs examined, as well as in 1 chondromyxoid fibroma and 1 myxoid liposarcoma. The real-time RT-PCR data showed that the relative expression levels of the FGF23 mRNA tended to be higher in PMTs with TIO than in PMTs without TIO, or in the chondromyxoid fibroma specimen. CONCLUSIONS: Our data suggested that the feasibility of immunohistochemical detection of FGF23 may depend on the level of secreted FGF23 from tumor cells. Thus, immunohistochemistry for FGF23 is an useful diagnostic adjunct for PMT, although its utility appears to be limited in cases without TIO.

Clinicopathological Implications of Wingless/int1 (WNT) Signaling Pathway in Pancreatic Ductal Adenocarcinoma.

Pancreatic cancer is still one of the most lethal malignancies in the world, and a more thorough understanding of its detailed pathogenetic mechanisms and the development of more effective therapeutic strategies are urgently required. Pancreatic ductal adenocarcinoma (PDA), the most common type of pancreatic cancer, is characterized by consistent genetic abnormalities such as point mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) and in the tumor suppressor protein p53 (TP53) genes. Alterations in intracellular core signal pathways have also been shown to induce the development or progression of PDA. The Wingless/int1 (WNT) signal pathway plays a pivotal role in embryonic development, cellular proliferation and differentiation, and dysregulation of WNT signaling can lead to neoplastic transformation in a variety of organ systems, including the pancreas. Recent studies have shown that altered WNT signaling is associated with a poor prognosis in patients with PDA, suggesting that the pathway is a predictor of patients' survival and a potential therapeutic target of PDA. In this review, the clinicopathological implications of WNT signaling in PDA are highlighted.

Rare combination of familial adenomatous polyposis and gallbladder polyps.

Familial adenomatous polyposis is associated with a high incidence of malignancies in the upper gastrointestinal tract (particularly ampullary adenocarcinomas). However, few reports have described a correlation between familial adenomatous polyposis and gallbladder neoplasms. We present a case of a 60-year-old woman with familial adenomatous polyposis who presented with an elevated mass in the neck of the gallbladder (measuring 16 mm × 8 mm in diameter) and multiple small cholecystic polyps. She had undergone a total colectomy for ascending colon cancer associated with familial adenomatous polyposis 22 years previously. The patient underwent laparoscopic cholecystectomy under a preoperative diagnosis of multifocal gallbladder polyps. Pathologic examination of the resected gallbladder revealed more than 70 adenomatous lesions, a feature consistent with adenoma of the gallbladder. This case suggests a requirement for long-term surveillance of the biliary system in addition to the gastrointestinal tract in patients with familial adenomatous polyposis.

Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P = 0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P = 0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P = 0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P = 0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.

The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma.

Ewing sarcoma (ES) is a high-grade malignant neoplasm primarily affecting children and young adults. The diagnosis of ES is often difficult because of its broad differential diagnosis comprising a diverse group of small round cell tumors (SRCTs). Although the identification of tumor type-specific fusion genes by molecular testing is the gold standard for the diagnosis of ES, such approaches are not always available in a routine pathology practice. Thus, a reliable immunohistochemical marker is required. A recent study using a limited number of tumor samples has shown that NKX2.2, a putative transcriptional target of EWSR1-FLI1, is a useful marker for the diagnosis of ES. In the present study, the immunohistochemical expression of NKX2.2 was evaluated on 46 genetically confirmed ES and 85 non-ES SRCTs, together with comparative assessment of CD99 and other molecular targets of EWSR1-FLI1, including NR0B1, E2F3, and EZH2. NKX2.2 was expressed in 37 (80 %) of the ES samples with a mostly diffuse and strong staining pattern, and 14 (16 %) of the non-ES SRCTs, including olfactory neuroblastomas, extraskeletal myxoid chondrosarcoma, mesenchymal chondrosarcoma, small cell carcinomas, and Merkel cell carcinoma, also expressed this marker. The sensitivity and specificity of the NKX2.2 expression in this cohort were 80 and 84 %, respectively. The specificity when combined with CD99 was 98 %, with exceptional expression of both markers in only two non-ES SRCTs, including one case each of mesenchymal chondrosarcoma and small cell carcinoma. NR0B1, E2F3, and EZH2 were less sensitive for specific markers for ES when applied singly or in any combination. In conclusion, the study reinforces that NKX2.2 is a useful immunohistochemical marker for ES, and that the combination of CD99 and NKX2.2 is a powerful diagnostic tool that can differentiate ES from other SRCTs.

Pancreatic somatostatinoma diagnosed preoperatively: report of a case.

CONTEXT: Somatostatinoma is a rare neoplasm of the pancreas. Preoperative diagnosis is often difficult. CASE REPORT: We report a 72-year-old woman with a pancreatic head tumor measuring 37 mm in diameter, and enlargement of the lymph nodes on the anterior surface of the pancreatic head and the posterior surface of the horizontal part of the duodenum. Laboratory data showed an elevated plasma somatostatin concentration. Examination of a biopsy specimen of the pancreatic head mass obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) showed histopathological features of a neuroendocrine tumor. Immunohistochemical staining showed that the tumor cells were positive for somatostatin, leading to a preoperative diagnosis of pancreatic somatostatinoma. The patient underwent pylorus-preserving pancreaticoduodenectomy. The plasma somatostatin concentration decreased progressively after surgery. CONCLUSIONS: A rare case of pancreatic somatostatinoma with lymph node metastases was presented. Immunohistochemical analysis of a biopsy specimen obtained by EUS-FNA was useful for preoperative diagnosis.

Desmin-positivity in spindle cells: under-recognized immunophenotype of lipoblastoma.

Lipoblastoma is a distinct benign fatty tumor composed of adipocytes, lipoblasts, and primitive mesenchymal cells with a myxoid stroma. Lipoblastoma harbors characteristic fusion genes involving the PLAG1, resulting in aberrant expression of PLAG1. However, the nature of the primitive mesenchymal cells remains obscure. In our routine pathology practice, we noticed desmin-positive spindle mesenchymal cells in lipoblastomas, which is a hitherto poorly described phenomenon. Thus, we examined the expression of several myogenic markers including desmin in a variety of 95 mesenchymal tumors with fatty elements. Fourteen of the 15 lipoblastomas examined contained desmin-positive spindle cells, which also showed nuclear expression of PLAG1, whereas α-smooth muscle actin, muscle specific actin, h-caldesmon, and myogenin were negative. Some spindle cells in subsets of atypical lipomatous tumors/well differentiated liposarcomas (6/20), dedifferentiated liposarcomas (11/31) and pleomorphic liposarcomas (2/10) were positive for actins and/or desmin, supporting focal myofibroblastic or smooth muscle differentiation. The other tumors, including 11 myxoid/round cell liposarcomas, four spindle cell lipomas, and four lipofibromatoses, were negative for all of the myogenic markers assessed. The almost consistent desmin expression in spindle mesenchymal cells suggests a potential diagnostic utility of this marker and myofibroblastic phenotype of fractions in lipoblastoma cells.

[Serous cystadenoma of the pancreas showing enlargement on images: a case report].

Serious Cystadenoma (SCA) of the Pancreas is seldom malignant and is usually monitored over time. Here we report a case of SCA an enlarged cyst that had to be excised because it was difficult to diagnose by intraductal papillary-mucinous neoplasm (IPMN). The patient was a 58-year-old woman with thecoma of the right ovary accompanied by Meigs syndrome, who had undergone abdominal total hysterectomy and bilateral oophorectomy. Abdominal computed tomography scan (CT) showed a multilocular cyst 2.4 cm in diameter in the head of the pancreas. Fourteen months later, a periodic CT showed that the multilocular cyst had enlarged from 2.4 to 3.5 cm in diameter. Branch duct intraductal papillary-mucinous neoplasm (IPMN) with a tendency to enlargement and with mural nodule was suspected. Pylorus-preserving pancreatoduodenectomy (PPPD) was performed, and pathological findings revealed that the cyst was lined with a single layer of simple cuboidal epithelium. Periodic acid-Shiff staining, with and without diastase digestion, showed abundant glycogen within epithelial cells, yielding a definitive diagnosis of SCA. The ascites were probably due to the Meigs syndrome pressing the cyst, and the size of the cyst appeared smaller than the real size.

Aberrant calreticulin expression is involved in the dedifferentiation of dedifferentiated liposarcoma.

Liposarcomas are a representative group of soft tissue sarcomas with variably hampered adipogenesis, which is most exemplified by its dedifferentiated subtype. However, the factor(s) responsible for inhibiting adipocyte differentiation remains unknown. A recent gene expression profiling study identified several unique genes that were highly expressed in dedifferentiated liposarcoma, and the gene encoding calreticulin (CALR), a major Ca(2+)-buffering protein that can inhibit adipocyte differentiation, was found to be overexpressed. Thus, we investigated the expression of calreticulin in 45 cases of liposarcomas, including 15 dedifferentiated tumors, at both the protein and mRNA levels. Immunohistochemically, calreticulin was consistently expressed in the dedifferentiated areas of dedifferentiated liposarcomas and commonly observed in atypical stromal cells and/or lipoblasts in the well-differentiated areas (87%), whereas large vacuolated adipocytic cells in either the tumors or normal fat were essentially negative. These results were further supported by the findings of Western blot and quantitative RT-PCR analyses. Although abnormalities in 19p13.1-13.2 where CALR is localized were uncommon in the dedifferentiated liposarcomas examined by fluorescence in situ hybridization, expression of miR-1257, a putative microRNA that targets calreticulin, was suppressed in the dedifferentiated subtype. The down-regulation of calreticulin by small-interfering RNA could induce adipogenesis in dedifferentiated liposarcoma cells and reduce cell proliferation. Our results therefore suggest that aberrantly expressed calreticulin in dedifferentiated liposarcoma is involved in its dedifferenitation and/or tumor progression.