PDGFRB and NOTCH3 Mutations are Detectable in a Wider Range of Pericytic Tumors, Including Myopericytomas, Angioleiomyomas, Glomus Tumors, and Their Combined Tumors.

Pericytic tumors are subclassified as myopericytomas, myofibromas, angioleiomyomas, and glomus tumors according to the current World Health Organization classification. These pericytic tumors form a continuous morphologic spectrum, including those with combined morphology. However, to our knowledge, no widely accepted criteria for classifying tumors with combined morphology are available. Recent studies have identified platelet-derived growth factor receptor-beta (PDGFRB) gene mutations in a subset of myofibromas, myopericytomas, and myopericytomatoses but not in angioleiomyomas. NOTCH receptor 3 (NOTCH3) mutations have been reported in a subset of infantile myofibromatosis. To assess their potential role in classifying pericytic tumors, we investigated PDGFRB and NOTCH3 mutations in 41 pericytic tumors of variable morphology, including some combined forms. Our results show these mutations to be present in a variety of pericytic tumors, such as myopericytomas (PDGFRB, 3/11; NOTCH3, 4/11), myopericytomatoses (1/2; 1/2), myofibromas (3/6; 0/6), angioleiomyomas (2/13; 3/13), and glomus tumors (5/9; 1/9). Point mutations were identified in 3 tumors in PDGFRB exon 12 (Y562C, S574F, and G576S), 12 tumors in PDGFRB exon 14 (M655I, H657L, and N666K), and 9 tumors in NOTCH3 exon 25 (A1480S/T, D1481N, G1482S, T1490A, E1491K, G1494S, and V1512A). All PDGFRB mutations and NOTCH3 G1482S, T1490A, and G1494S mutations were classified as "deleterious/damaging" by ≥4 of 6 pathogenicity prediction tools in silico. Five-mutation-positive tumors, including 1 myopericytoma-angioleiomyoma, 2 myopericytomatoses-myofibroma, 1 myofibroma-myopericytoma and 1 angioleiomyoma-myopericytoma, were of combined morphology. Therefore, we found PDGFRB and NOTCH3 mutations to be detectable in a much wider variety of pericytic tumors than previously reported and confirmed myopericytomas, myofibromas, angioleiomyomas, and glomus tumors as members harboring PDGFRB or NOTCH3 mutations. Our results thus suggest that PDGFRB or NOTCH3 mutations are not useful for subclassifying members of the pericytic tumor family.

MALAT1 functions as a transcriptional promoter of MALAT1::GLI1 fusion for truncated GLI1 protein expression in cancer.

BACKGROUND: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a cancer biomarker. Furthermore, fusion of the MALAT1 gene with glioma-associated oncogene 1 (GLI1) is a diagnostic marker of plexiform fibromyxoma and gastroblastoma; however, the function of this fusion gene remains unexplored. METHOD: In this study, we elucidate the structure and function of the MALAT1::GLI1 fusion gene. To this end, we determined a transcriptional start site (TSS) and promoter region for truncated GLI1 expression using rapid amplification of the 5' cDNA end and a luciferase reporter assay in cultured cells transfected with a plasmid harboring the MALAT1::GLI1 fusion gene. RESULTS: We found that the TATA box, ETS1 motif, and TSS were located in MALAT1 and that MALAT1 exhibited transcriptional activity and induced expression of GLI1 from the MALAT1::GLI1 fusion gene. Truncated GLI1, lacking SUMOylation and SUFU binding sites and located in the nucleus, upregulated mRNA expression of GLI1 target genes in the hedgehog signaling pathway. CONCLUSIONS: We demonstrate a distinct and alternative function of MALAT1 as a transcriptional promoter for expression of the MALAT1::GLI1 fusion gene. Our findings will aid future research on MALAT1 and its fusion gene partners.

Immunoglobulin G deposition on proximal tubules and the tubular basement membrane in acute tubular injury complicated with focal segmental glomerulosclerosis (FSGS): A possible prediction tool for subclinical FSGS.

Immunofluorescent deposition of immunoglobulin G (IgG) in the tubular basement membrane (TBM) has been evaluated in the diagnosis of various diseases; however, few studies have investigated the immunofluorescence of acute tubular injury (ATI). Herein, we attempted to clarify IgG expression in the proximal tubular epithelium and TBM in ATI due to various causes. Patients with ATI with nephrotic-range proteinuria, including focal segmental glomerulosclerosis (FSGS, n = 18) and minimal change nephrotic syndrome (MCNS, n = 8), ATI with ischemia (n = 6), and drug-induced ATI (n = 7), were enrolled. ATI was evaluated by light microscopy. CD15 and IgG double staining and IgG subclass staining were performed to evaluate immunoglobulin deposition in the proximal tubular epithelium and TBM. IgG deposition was identified in the proximal tubules only in the FSGS group. Furthermore, IgG deposition in the TBM was observed in the FSGS group showing severe ATI. IgG3 was predominantly deposited by the IgG subclass study. Our results indicate that IgG deposition in the proximal tubular epithelium and TBM suggests the leaking of IgG from the glomerular filtration barrier and its reabsorption by proximal tubules, which may predict disruption of the glomerular size barrier, including subclinical FSGS. FSGS with ATI should be included as a differential diagnosis when IgG deposition in TBM is observed.

Vulvar angiomyofibroblastoma is molecularly defined by recurrent MTG1-CYP2E1 fusions.

Angiomyofibroblastoma (AMF), a rare benign vulvovaginal mesenchymal tumour, poses a diagnostic challenge due to histologic and immunohistochemical overlap with other vulvar mesenchymal tumours. Recently, MTG1-CYP2E1 fusion transcripts were reported in 5/5 AMFs; no other genetic alterations have been described to date. Herein, we sought to investigate the frequency of the MTG1-CYP2E1 fusion and the presence of other potential genetic alterations in a cohort of AMFs (n = 7, patient age range: 28-49 years). Tumours demonstrated classic morphologic features including alternating hypo/hypercellular areas, capillary channels surrounded by epithelioid/spindled tumour cells, and variable amounts of mature adipose tissue. reverse transcription-polymerase chain reaction (RT-PCR) for MTG1-CYP2E1 fusion, performed in all seven cases, showed the fusion transcript in five of six cases (one case with technical failure). Two tumours, including the one lacking the fusion, were subjected to targeted next-generation sequencing (104 genes) and a sarcoma fusion assay (28 genes); the fusion negative AMF also underwent RNA sequencing. No additional mutations, copy number alterations, or fusion genes were identified with the assays employed. We conclude that the majority of AMFs harbour recurrent MTG1-CYP2E1 fusion transcripts and identification of this fusion may aid in the diagnosis.

Standardization of evaluation method and prognostic significance of histological response to preoperative chemotherapy in high-grade non-round cell soft tissue sarcomas.

BACKGROUND: Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); however, the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis. METHODS: Using data and specimens from the patients who had registered in the Japan Clinical Oncology Group study, JCOG0304, a phase II trial evaluating the efficacy of perioperative chemotherapy with doxorubicin (DOX) and ifosfamide (IFO), we evaluated histological response to preoperative chemotherapy at the central review board. RESULTS: A total of 64 patients were eligible for this study. The percentage of viable tumor area ranged from 0.1% to 97.0%, with median value of 35.7%. Regarding concordance proportion between pathologists, the weighted kappa coefficient (κ) score in all patients was 0.71, indicating that the established evaluation method achieved substantial agreement score. When the cut-off value of the percentage of the residual tumor area was set as 25%, the p-value for the difference in overall survival showed the minimum value. Hazard ratio of the non-responder with percentage of the residual tumor < 25%, to the responder was 4.029 (95% confidence interval 0.893-18.188, p = 0.070). CONCLUSION: The standardized evaluation method of pathological response to preoperative chemotherapy showed a substantial agreement in the weighted κ score. The evaluation method established here was useful for estimating of the prognosis in STS patients who were administered perioperative chemotherapy with DOX and IFO. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

Primary Site Identification of Soft-Tissue Mass: Things to Know in MRI Assessment.

The spectrum of soft-tissue mass is varied, including neoplastic and nonneoplastic/inflammatory lesions. However, soft-tissue tumors have similar imaging findings and, therefore, the diagnosis of soft-tissue mass is challenging. Although careful assessment of the internal characteristics on imaging can often narrow the differential diagnoses, the differential diagnosis may be out of the question if identification of the soft-tissue mass origin is missed. The purpose of this article is to review the imaging findings and the essential anatomy to identify the primary site of the soft-tissue mass, and discuss the associated potential pitfalls. In order not to fall into a pitfall, recognition of characteristic imaging findings indicating the origin of the soft-tissue mass and anatomical knowledge of the normal tissue distribution are necessary. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

Catastrophic antiphospholipid syndrome with Epstein-Barr virus-associated hemophagocytosis: A clinicopathological conference.

Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of antiphospholipid syndrome associated with multiorgan thrombosis in a short term. We present the case of a 14-year-old immunocompetent girl who developed renal, intestinal, and pulmonary infarction; thrombocytopenia; and hemolytic anemia within 1 week. She was diagnosed with thrombotic microangiopathy. Hence, plasma exchange and corticosteroid therapy were initiated, which improved thrombocytopenia. However, the patient's platelet count decreased. Her general condition gradually worsened with eventual death. An autopsy revealed multiple infarctions in the kidneys bilaterally, jejunum, ileum, and pulmonary parenchyma. Microthrombi were not detected. Massive hemophagocytosis was observed in the splenic pulp, lymph nodes, and bone marrow. Several Epstein-Barr viruses (EBVs)-encoded small ribonucleic acid (RNA)-positive lymphocytes were also found in the bone marrow. The presence of antibodies to both viral capsid antigen-immunoglobulin G and EBV nuclear antigen indicated past infection. Antiphospholipid antibody was positive after her death. The patient was finally diagnosed with CAPS and EBV-associated hemophagocytosis, possibly due to EBV reactivation. Establishing a clinical diagnosis of CAPS was relatively difficult because two different causes of thrombocytopenia, CAPS and hemophagocytosis, led to a difficulty in understanding this case's pathogenesis.

Poorly Differentiated Cervical Squamous Cell Carcinoma Resembling Giant Cell Carcinoma of the Lung: Extreme Morphology of This Tumor and Its Clinical Course.

Giant cell tumor is a highly aggressive tumor characterized by a marked proliferation of pleomorphic, bizarre giant cells usually observed in the lungs. The importance of histopathological imaging and the clinical course of this tumor are unknown. The objective of our report was to investigate whether these components affect treatment outcomes and prognosis compared to conventional cancers. A 40-year-old woman with cervical cancer showed leukocytosis and elevated granulocyte colony simulating factor (G-CSF). The patient underwent a radical abdominal hysterectomy. Pathology revealed a poorly differentiated squamous cell carcinoma of the cervix, similar to giant cell carcinoma. The patient recovered from the disease and is alive 37 months after concurrent chemoradiotherapy (CCRT). Leukocytosis and G-CSF were normalized after treatment. This was our second case of giant cell carcinoma of the cervix. Cumulative data on giant cell carcinoma are limited, thus we considered the prognostic significance of the presence of giant cell carcinoma in uterine carcinoma.

Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Case Report.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are extremely rare, occurring in less than 1% of uterine stromal tumors, and they are considered to have a low malignant potential. Due to the small number of cases, no standard treatment has been defined. A 77-year-old woman with postmenopausal bleeding was admitted to our department. Imaging studies revealed a substantial mass around 30 mm in size on the anterior uterine wall. A total hysterectomy and bilateral salpingo-oophorectomy were performed for further diagnosis and treatment. The tumor revealed histopathological findings of a sex cord-like growth pattern in the form of fascicles, cords, or small nests. Immunohistochemical findings revealed that the tumor cells were positively reactive to alpha-SMA, calretinin, CD99, estrogen receptor, and progesterone receptor, collectively diagnosed as UTROSCT. No recurrence was observed over 12 months after treatment. We experienced the treatment of UTROSCT, an extremely rare tumor that occurs in elderly women. Although most cases of UTROSCT have a benign clinical course, several cases of recurrence and metastasis have been reported. It should be followed up for a long term after treatment.

Potential pathogenetic link between angiomyofibroblastoma and superficial myofibroblastoma in the female lower genital tract based on a novel MTG1-CYP2E1 fusion.

Angiomyofibroblastoma and superficial myofibroblastoma are distinctive benign mesenchymal tumors occurring in the female lower genital tract. Despite their significant overlapping clinicopathologic features, including the presence of bland-looking spindle or oval cells with myofibroblastic or myoid differentiation, the tumors have been regarded as separate entities. Although subepithelial, hormone-sensitive mesenchymal cells of the female lower genital tract are considered as their potential common progenitor cells, their potential kinship or pathogenetic similarities remain elusive. Based on the identification of a novel RNA sequencing-based MTG1-CYP2E1 fusion transcript in an angiomyofibroblastoma index case, we investigated an additional ten samples of the tumor and its site-specific histological mimics, including eight superficial myofibroblastomas, four deep angiomyxomas, four cellular angiofibromas, three fibroepithelial stromal polyps, and eight non-site-specific mesenchymal tumors occurring in the female lower genital tract. Using reverse transcription-polymerase chain reaction, we showed that the MTG1-CYP2E1 fusion transcripts were consistently detectable in angiomyofibroblastomas (5/5, 100%) and often in superficial myofibroblastomas (3/5, 60%) but were not detected in the other examined site-specific or non-site-specific mesenchymal tumors. Our immunohistochemical experiments showed that CYP2E1, an isoenzyme belonging to the cytochrome P450 superfamily, exhibited increased positivity in tumors with MTG1-CYP2E1 than was observed in fusion-negative tumors (RR = 6.56, p = 0.001). The results of our study provide further evidence supporting the assertion that angiomyofibroblastoma and superficial myofibroblastoma represent phenotypic variants of site-specific mesenchymal tumors and share a common oncogenic mechanism.

Primary clear cell sarcoma of the femur: a unique case with RT-PCR and direct sequencing confirmation of EWSR1/ATF1 fusion gene.

BACKGROUND: It is very rare for clear cell sarcomas (CCS) to arise in the bone. During diagnosis, it is important to distinguish primary CCS of bone from bone metastasis of melanoma because this difference fundamentally changes the therapeutic options. Recently, characteristic fusion genes of CCS have been detected using reverse transcription polymerase chain reaction (RT-PCR) or direct sequencing which allowed to distinguish CCS from melanoma. However, there was no study applying these analyses with positive results. In this case, we describe the use of fusion gene analysis to diagnose a primary CCS of the bone. CASE PRESENTATION: A 36-year-old male presented with a four-months history of left knee pain. Magnetic resonance imaging showed a lesion in the left femoral medial epicondyle. Histological examination of the biopsy specimen revealed proliferating oval or rounded cells. These cells had clear cytoplasm arranged in fascicles or compact nests with frequent deposits of brown pigment. Furthermore, immunohistochemistry analysis revealed that tumor cells were positive for S-100 protein, HMB-45, Melan-A, and SOX10. It stained negative for CD34 and BRAF v600e. Conclusively, detection of the EWSR1/ATF1 fusion gene using RT-PCR and direct sequencing confirmed that the lesion was a primary CCS of the bone. Wide-margin resection and reconstruction with a tumor endoprosthesis were performed. CONCLUSIONS: Herein, we diagnosed a rare case of primary CCS of the bone by detecting EWSR1/ATF1 fusion gene using RT-PCR and direct sequencing. Since fluorescence-in situ hybridization (FISH) and RT-PCR could show false positive by mainly due to technical problems, it is better to perform direct sequencing to confidently diagnose the tumor as a primary CCS especially at very rare site such as bone.

Synchronous Occurrence of Ovarian Seromucinous Carcinoma and Endometrial Mucinous Carcinoma: A Case Report.

Endometrioid carcinoma is the most common histological type of concurrent synchronous cancers of the uterus and ovary. Here we report a case of synchronous seromucinous carcinoma of the ovary and mucinous carcinoma of the endometrium with a literature review. A 51-year-old multiparous female complained of irregular bleeding and shortness of breath. Computed tomography revealed a large pelvic mass that consisted of cystic and solid components, a tumor of the endometrium, and a large amount of pleural effusion. An endometrial biopsy indicated adenocarcinoma, and adenocarcinoma cells were found in the pleural fluid. The patient with advanced ovarian cancer or endometrial cancer with massive pleural effusion received three courses of neoadjuvant chemotherapy (NAC) with paclitaxel and carboplatin followed by interval debulking surgery (IDS). The NAC was effective, and IDS was performed with no gross residual lesions. The post-operative diagnosis was seromucinous carcinoma of the ovary in FIGO (2014) stage IVA (ypT3cNxM1a) and mucinous carcinoma of the endometrium in FIGO (2008) stage IA (ypT1aNXM0). Three courses of postoperative TC therapy were performed, and maintenance therapy with Bevacizumab is ongoing. The patient is well without evidence of recurrence, sixteen months after surgery.

Alteration in tumoural PD-L1 expression and stromal CD8-positive tumour-infiltrating lymphocytes after concurrent chemo-radiotherapy for non-small cell lung cancer.

BACKGROUND: Consolidation treatment with an anti-PD-L1 antibody, durvalumab, following concurrent chemo-radiotherapy (cCRT) has become a new standard of care for locally advanced non-small cell lung cancer (NSCLC). The rationale of PD-L1 blockade after cCRT is based on preclinical evidence suggesting that chemotherapy and radiotherapy up-regulate tumoural PD-L1 expression, which has not been shown in clinical studies. METHODS: To examine alteration in tumoural PD-L1 expression (tumour proportion score, TPS) and density of stromal CD8-positive tumour-infiltrating lymphocytes (CD8 + TILs) after cCRT, paired NSCLC samples obtained before and after cCRT were reviewed in comparison with those obtained before and after drug therapy. RESULTS: PD-L1 expression was significantly up-regulated after cCRT (median TPS, 1.0 at baseline versus 48.0 after cCRT; P < 0.001), but not after drug therapy. There was no significant correlation between baseline TPS and post-cCRT TPS. CD8 + TIL density was significantly increased after cCRT (median, 10.6 versus 39.1; P < 0.001), and higher post-cCRT CD8 + TIL density was associated with a higher pathologic response and with a favourable survival (P = 0.019). CONCLUSION: Tumoural PD-L1 expression was up-regulated after cCRT, which provides pathologic rationale for PD-L1 blockade following cCRT to improve prognosis. Stromal CD8 + TIL density was also increased after cCRT, and higher post-cCRT CD8 + TIL density was a favourable prognostic indicator.

MUC4 expression in meningiomas: under-recognized immunophenotype particularly in meningothelial and angiomatous subtypes.

AIMS: MUC4 is a transmembrane glycoprotein that plays a role in cell growth signalling and is expressed in various epithelial tissues. Gene expression profiling and immunohistochemical analyses revealed that MUC4 is also constantly and specifically expressed in low-grade fibromyxoid sarcomas and sclerosing epithelioid fibrosarcomas among the mesenchymal tumours, and immunohistochemical detection of MUC4 is extremely useful for their diagnoses. In our routine pathological practice, we noticed that meningiomas are also often positive for MUC4, which has not yet been reported previously, despite the extensive scrutiny of its expression in soft tissue tumours. METHODS AND RESULTS: We examined immunohistochemically the expression of MUC4, progesterone receptor (PgR) and somatostatin receptor 2A (SSTR2A) in 140 meningiomas of various histological subtypes and 123 other mesenchymal tumours, including intracranial or sinonasal tumours and peripheral nerve sheath tumours. MUC4 was expressed in 130 meningiomas (92.9%). MUC4 expression was constant and almost diffuse in meningothelial and angiomatous subtypes, whereas it was limited in 5% or fewer tumour cells or absent in 26 of 28 fibrous meningiomas. All other mesenchymal tumours examined were negative for MUC4. PgR and SSTR2A were expressed in 94 (67.1%) and 134 (95.7%) meningiomas, respectively. Five of six SSTR2A-negative meningiomas focally expressed MUC4. CONCLUSIONS: MUC4 is expressed variably but almost consistently in meningiomas, particularly in meningothelial or angiomatous subtypes. Its immunohistochemical detection is useful to distinguish meningiomas from other intracranial or head and neck mesenchymal tumours, particularly those with epithelioid features. Our study could expand a variety of MUC4-positive mesenchymal tumours.

Lanthanum Deposition in the Gastroduodenal Mucosa of Dialysis Patients.

Lanthanum (La) carbonate (LC) is one of the most popular phosphate binders used in dialysis patients with end-stage renal disease. Only a small amount of LC is believed to be absorbed from the gastrointestinal (GI) tract because LC strongly binds to dietary phosphate and forms insoluble complexes. La deposition in the gastroduodenal mucosa has been recently identified. Endoscopically, La deposition is demonstrated as whitish lesions of varying sizes and shapes in the gastroduodenal mucosa. Microscopically, La deposition is characterized by histiocytic reaction or small foreign body granulomas containing gray or brown materials mainly in the lamina propria of the GI mucosa. Some histiocytes containing La can migrate into regional lymph nodes via the lymphatic flow. The amount of La deposition in the gastroduodenal mucosa is correlated with the total dose of LC administration, and La deposition is almost consistently observed in LC-treated dialysis patients. Although the detailed mechanism of La deposition in the GI tract is still unclear, several factors, such as gastric pH and metaplastic change of the mucosal epithelium, may be involved in the La deposition in the gastroduodenal mucosa. Here we present an overview of the feature of La deposition in the GI tract.

Inhibition of WNT/ß-catenin signaling under serum starvation and hypoxia induces adipocytic transdifferentiation in human leiomyoma cells.

Fatty metamorphosis is an uncommon alteration in uterine leiomyoma (i.e., lipoleiomyoma), and the pathogenetic mechanisms underlying this phenomenon remain poorly understood. Because a conditional deletion of ß-catenin, a major transducer of the canonical Wingless/integrated (WNT) pathway, in the developing mouse uterus can induce adipogenesis in the myometrium, it is hypothesized that inhibition of the WNT/ß-catenin signaling may be also involved in the development of fat cells within uterine leiomyoma. In the current study, which was performed to address this point, intracytoplasmic lipid droplets were detectable in cultured human leiomyoma cells by treatment with a potent tankyrase inhibitor, XAV939, which antagonizes ß-catenin, in a serum-starved culture medium without additional adipogenesis-inducing agents or supplements, and showed increasing accumulation in a time-dependent manner. In addition, the induction of fat cells was greatly enhanced under hypoxic conditions (i.e., 2.5% O2)-recapitulating the local in vivo situation of uterine leiomyoma-in comparison to that under normoxic conditions (i.e., 21% O2). The marker genes of differentiated fat cells such as ADIPOQ and PLIN were highly expressed in leiomyoma cells that were treated with XAV939 under hypoxia and serum starvation, whereas the immunohistochemical expression of desmin-a cytoskeletal protein representing smooth muscle differentiation-was downregulated, which appears in line with the switch in differentiation. The results of our study suggest that the inhibition of canonical WNT/ß-catenin signaling under the stress due to hypoxia and serum starvation can initiate adipocytic transdifferentiation or metaplasia in human uterine leiomyoma cells, which is potentially related to the development of lipoleiomyoma.

Demographics, management and treatment outcomes of benign and malignant retroperitoneal tumors in Japan.

OBJECTIVES: To show the demographics, type of treatment and clinical outcomes of patients with retroperitoneal tumors in Japan. METHODS: We carried out a retrospective analysis of patients with retroperitoneal tumors treated between 2000 and 2012 at 12 university hospitals in Japan. Histology was re-evaluated using the 2013 World Health Organization classification. RESULTS: A total of 167 patients were included in the analysis. The number of diagnosed patients increased over the 12-year study period. Liposarcoma and schwannoma were the most common histological types among intermediate/malignant and benign tumors, respectively. The intermediate/malignant tumors were larger and were more frequently found in older people. Surgical resection was the primary treatment for 151 patients. The median survival duration for patients with malignant tumors was 91 months, and was significantly shorter than that for patients with benign and intermediate tumors (P < 0.01). R2 resection was associated with significantly shorter survival than R0/R1 resection for malignant tumors (P < 0.01), but not for intermediate. Grossly complete resection of the recurrent tumors improved survival. CONCLUSION: The number of patients diagnosed with retroperitoneal tumors increased over time. R2 resection of primary tumors was found to be associated with poor prognosis in malignant tumors, but not in intermediate tumors. Complete surgical resection of recurrent tumors was associated with a better oncological outcome.

[A Case of Carcinoma Showing Thymus-Like Differentiation (CASTLE) of the Thyroid].

The case presented herein was a 70-year-old woman who had no compliant, but had a mass in the lower part of the right lobe of the thyroid detected by ultrasound (US). The US image of the tumor, measuring 13 mm in diameter, showed a low and heterogeneous internal echo level with calcification and an irregular margin. The tumor appeared to extend to the adjacent sternothyroid muscle, and cervical lymph node swelling was detected in a computer tomography (CT) image, but no metastatic lesion was found by positron emission tomography (PET)-CT. In a fine needle aspiration cytology of the tumor, papillary thyroid carcinoma was suggested because of the atypical epithelial cells having some changes other than intranuclear inclusion bodies. A subtotal thyroidectomy and central neck lymph node dissection were performed. The excised tumor was histologically composed of irregular nests or sheets of atypical squamoid epithelial cells with some ductal structures that leached to the sternothyroid muscle and involved the right lower parathyroid gland. Carcinoma showing thymus-like differentiation (CASTLE) was diagnosed histopathologically and immunohistochemically with the following immunohistochemical results: Cluster of differentiation 5 (CD5) (+), tumor protein p63 (p63) (+), KIT proto-oncogene receptor tyrosine kinase (c-KIT(CD117)) (+), thyroglobulin (-), and thyroid transcription factor-1 (TTF-1) (-). CASTLE is a rare carcinoma of the thyroid that architecturally resembles thymic epithelial tumors. Many CASTLE patients have been misdiagnosed as other carcinomas, such as anaplastic carcinoma, poorly differentiated carcinoma or squamous cell carcinoma of the thyroid. Immunohistochemical examination, including CD5 played an important role in the final diagnosis of CASTLE, although the distinction from diagnosis as squamous cell carcinoma or mucoepidermoid carcinoma in Hematoxylin-Eosin staining was challenging in our case. Nodal metastasis and perithyroidal tumor extension of CASTLE can predict its worse prognosis. Thus, at least careful follow-up studies are mandatory in cases of CASTLE.

KIAA1199/CEMIP/HYBID overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND: KIAA1199 (also known as CEMIP or HYBID), a newly identified protein involved in hyaluronan degradation, has been suggested to play a critical role in cancer progression. The aim of this study was to investigate the expression and functional significance of KIAA1199 in pancreatic ductal adenocarcinoma (PDAC). METHODS: Using quantitative real-time RT-PCR, we analyzed KIAA1199 mRNA expression in 6 PDAC cell lines and frozen tissues from 14 patients with PDAC. We also used immunohistochemistry to analyze KIAA1199 protein expression in formalin-fixed, paraffin-embedded tissues from 98 patients with PDAC. The KIAA1199 expression pattern was then correlated with clinicopathological variables and patient outcome. The effect of KIAA1199 on migratory ability of PDAC cells was determined by KIAA1199 knockdown with small-interfering RNA (siRNA). RESULTS: The KIAA1199 mRNA expression was significantly higher in PDAC tissues than in the corresponding non-tumor tissues (P < 0.0001). Immunohistochemical analysis revealed high expression of KIAA1199 in 26 (26.5%) of 98 PDAC tissues. The overall survival was significantly shorter in patients with high KIAA1199 expression than in patients with low KIAA1199 expression (P = 0.0001). In multivariate analysis, high KIAA1199 expression (P = 0.003) and UICC stage (P = 0.003) were independent factors predicting poor prognosis. Furthermore, the KIAA1199 mRNA expression was higher in most PDAC cell lines and siRNA knockdown of KIAA1199 resulted in decreased migration. CONCLUSION: These findings suggest that overexpression of KIAA1199 may contribute to increased migration of PDAC cells and predict shorter survival after surgical resection.