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Fibrous dysplasia (FD) is a monostotic or polyostotic benign bone lesion with spindle-cell proliferation in woven bone and stroma. Rarely, cartilaginous differentiation can be seen in the lesions of FD. FD with massive cartilaginous differentiation is called fibrocartilaginous dysplasia (FCD) and is considered a rare variant of FD. Although pathological findings of FD show irregular immature bone formation without osteoblastic rimming in fibrous tissue, and rarely show very small amounts of cartilage, histological images of FCD are said to show that cartilage with a relatively high cell density is present in the majority and that FD-like findings are seen in parts of it. The most characteristic feature of FCD on images is calcification in the lesions reflecting cartilaginous tissue. On the other hand, typical radiographic findings of FD include shadows with a ground-glass appearance and thinning and bulging of the cortical bone, the observation if calcification is not usual. Therefore, in the diagnosis of FCD, differentiation from multiple enchondromatosis, Ollier disease, chondrosarcoma, and chondrosarcoma secondary to FD is necessary, and it seems important to make a careful diagnosis based not only on the pathological findings but also on imaging and clinical findings. Herein, we report on a case of FD of the proximal femur associated with intralesional extensive cartilaginous differentiation in which a pathological fracture occurred during follow-up, with a review of the literature.

Xanthogranulomas are known to develop in the gallbladder and kidney. Xanthogranuloma of the stomach is a rare disease, and to the best of our knowledge, only a few cases have been reported to date. The present patient was a 64-year-old man who underwent a wide resection of the stomach following a Billroth-I reconstruction for a gastric ulcer ~40 years prior to the current presentation. Due to tarry stools, a gastrointestinal endoscopy was performed, leading to identification of an ulcerated gastric lesion located at the previous suture line at the lesser curvature of the remnant stomach. This lesion was elevated, appearing to indicate a submucosal tumor. Positron emission tomography revealed uptake of fluorodeoxyglucose radiotracer by the tumor. Although not indicated by the biopsy specimens, a malignant tumor of the remnant stomach was suspected, in the form of a malignant gastrointestinal tumor or remnant gastric cancer. Curative resection of the tumor was successfully performed. Histological examination of the resected specimens revealed xanthogranulomatous inflammation consisting of foamy histiocytes and plasma cells, however, no cancer cells were observed. The tumor was diagnosed as xanthogranulomatous gastritis that mimicked a malignant tumor of the remnant stomach. The present study therefore indicates that inflammatory tumors should be considered in the differential diagnosis of malignant tumors.

Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with both inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7 defines an extremely aggressive myeloid cancer whose molecular pathogenesis and optimal therapeutic strategy still remain unclear. We established a new MDS/AML cell line, YCU-AML1, and its patient-derived xenograft (PDX) model from a high-risk MDS patient who later transformed into AML harboring both t(3;3)(q21;q26.2) and monosomy 7. YCU-AML1 cells propagated in co-culture system with stromal cells in granulocyte macrophage colony-stimulating factor (GM-CSF)-dependent manner. CD34+ bone marrow cells derived from our PDX model showed high EVI1 and low GATA2 expression. Moreover, mutational profile of our MDS/AML model was consistent with recently published mutational spectrum of myeloid malignancies with inv(3)/t(3;3). These data suggest that YCU-AML1 cells and its MDS/AML model strongly mimics a high-risk human myeloid cancer with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7 in terms of both clinical phenotype and molecular basis. We believe our model can be used as a feasible tool to further explore molecular pathogenesis and novel treatment strategy of high-risk MDS/AML with t(3;3)(q21;q26.2) and monosomy 7.

Background: Ossifying fibroma arising in the sinonasal tract is rare. Its treatment includes complete resection; however, this can be challenging to perform due to the well-vascularized nature of the fibroma. Some surgical techniques can control intraoperative hemorrhage; however, to date, no reports have assessed the use of preoperative embolization. Methods: We report a case of a child with ossifying fibroma arising from the ethmoid sinus, which was resected by endoscopic surgery using preoperative transarterial embolization. Conclusions: Embolization was effective in decreasing intraoperative hemorrhage. No complications related to the procedure or operation were encountered. Preoperative embolization should be considered for better control of the bleeding that occurs in ossifying fibromas, similar to that in other well-vascularized tumors. Keywords: Preoperative embolization, Pediatric ossifying fibroma, Paranasal ossifying fibroma, Endoscopic skull base surgery

Objective The vertical margin of neuroendocrine tumors (NETs) removed by endoscopic mucosal resection (EMR) is often tumor-positive. We examine the treatment results of endoscopic mucosal resection with a ligation device (EMR-L) for the removal of duodenal NETs located in the submucosal layer without metastasis. EMR-L can be performed with less technical skill, and the ligation device reduces the rate of positive vertical margin. Methods Ten consecutive patients with 10 duodenal NETs resected by EMR-L were enrolled. All of the lesions were located in the submucosal layer, were assessed to be free of metastasis, and were confirmed to be NETs pathologically by an endoscopic biopsy. The endoscopic results, pathological results, and prognosis were all examined. Results The en bloc resection rate and endoscopic complete resection rate were both 100%. Complete resection was achieved pathologically in 7 lesions (70.0%). The vertical margins were negative in all cases. Lymphatic vessel invasion was observed in three patients, all of whom underwent additional surgery with lymph node dissection (one of them also exhibited blood vessel invasion and a positive horizontal margin). No evidence of residual tumors or lymph node metastasis was observed in any of the patients. No recurrence was observed in any of the 10 patients (mean follow-up period: 18.6 months). One patient (10.0%) experienced intraoperative bleeding. Perforation occurred in 1 patient (10.0%), but the condition was managed well by conservative therapy. Conclusion EMR-L was an acceptable method for endoscopically resecting submucosal duodenal NETs, and the NETs resected by EMR-L were tumor-negative in the vertical margins.

Objectives: The aim of this study was to assess a three-dimensional (3D) correlation between preoperative 3D bone single photon emission CT (SPECT)/CT, which allows the visualization of radiotracer uptake on 3D volume-rendered CT images, and histopathological characteristics in the medication-related osteonecrosis of the jaw (MRONJ). Methods: We conducted a full histopathological assessment of the resected jaws in four patients with Stage 2 or 3 MRONJ. The pathologic results were classified as follows: necrosis without any tissue vascularity (N + V-), necrosis with both vascularity and acute inflammatory cell infiltration due to bacterial infection (N + V+I+), necrosis with regenerative vasculature but no inflammatory cell infiltration (N + V+I-), and chronic inflammation without massive necrosis (N-V +I+). These classifications were correlated with imaging results. Results: The N + V- areas visually represented the area of necrotic bone exposed to the oral cavity and were consistent with defect area of radioisotope uptake in SPECT/CT. The N + V- areas were surrounded by the N + V+I + areas where increased radiotracer uptake was clearly seen. Also, abnormal uptake was found in both of the N + V+I- and N-V +I+ areas. The extensive surgical resections from necrotic core to bloody viable margins were performed in all cases, although one had the recurrence of MRONJ at the margin showing abnormal uptake that histologically represented the N + V+I- area. Conclusions: Radiologic–pathologic correlation of MRONJ could be achieved using 3D SPECT/CT. The presence of regenerative vascularity with necrosis or inflammation seemed to determine bone metabolism in MRONJ. The recurrence of MRONJ was observed in one case, and 3D SPECT/CT had preoperatively depicted the recurrence site.

The human epidermal growth factor receptor 2 (HER2) is recognized as an oncogene as well as a therapeutic target in various cancers. Certain patients with advanced extramammary Paget's disease (EMPD) have also been reported to express HER2, which is therefore considered a therapeutic target for EMPD. However, an accurate methodology to determine HER2-positive EMPD has not been established. To assess the optimal methods for detection of HER2-positive EMPD, 73 EMPD samples were analyzed by immunohistochemical (IHC) staining, fluorescence in situ hybridization (FISH), and the HER2 testing algorithm for breast cancer of the American Society of Clinical Oncology/College of American Pathologists, which combined the results of IHC staining and FISH. The results showed discordance in the rate of positive IHC staining and FISH results. While 68.6% (24/35) of the metastatic samples showed equivocal or positive IHC staining, only 37.1% (13/35) were positive by FISH. To assess the accuracy of these methods, the degree of HER2 expression detected by each method was correlated with the staining profiles of activated downstream signaling pathways involving phosphorylated p44/42 MAPK (Thr202/Tyr204) (p-ERK1/2) and phosphorylated AKT (Ser473) (p-AKT). Among 16 lymph node metastasis samples, all HER2-positive samples as determined by the testing algorithm stained positively for both p-ERK1/2 and p-AKT. On the other hand, 10-14.3% of the samples determined by FISH or IHC showed negative staining for p-ERK1/2 and p-AKT. The results showed that combining the results of IHC and FISH according to the HER2 testing algorithm is a useful method for accurately evaluating HER2-positive EMPD.

The patient was a 54-year-old female who presented with the chief complaint of melena. Lower gastrointestinal endoscopy detected a type 1 tumor extending from the anal canal to the rectum. CT did not detect any distant metastasis. Proximal D3 lymphadenectomy with laparoscopic abdominoperineal resection was performed for stage IA rectal cancer. In the histopathological examination, the tumor was identified as stage IIIa adenosquamous carcinoma. Although the patient underwent postoperative adjuvant chemotherapy with S-1, a recurrent left lateral lymph node tumor was detected on CT and PET 12 months later. The patient underwent the treatment with mFOLFOX + bevacizumab for 6 months. However, the tumor continued to progress, and therefore, extended lateral lymphadenectomy was performed 21 months after the first surgery. The patient did not undergo postoperative adjuvant therapy and is alive without recurrence 90 months after the first surgery and 70 months after the reoperation. Adenosquamous carcinoma of the rectum is a rare histological type of colorectal cancer for which there is no effective treatment besides surgical resection, and its prognosis is known to be worse than that of adenocarcinoma. Since there has been no report of long-term survival after extended lateral lymphadenectomy for recurrent lateral lymph node tumors following surgery for adenosquamous carcinoma of the rectum, herein, we report the case with a review of the literature.

Background Lipoblastomas are rare benign tumors that arise from embryonic white fat and almost always occur in babies and children. Here, we report a case of a giant popliteal lipoblastoma in a 23-month-old Japanese girl that was successfully treated via complete resection. Case presentation Our patient was a 23-month-old Japanese girl. At 6 months of age, she presented at a nearby hospital with a mass on the popliteal side of her lower right leg. She had no symptoms and was diagnosed as having a benign adipose tumor via magnetic resonance imaging. The mass gradually increased in size, and she was referred to our hospital at 1 year and 11 months of age. A physical examination and radiology revealed a localized mass 13 × 10 × 7 cm in size in the aforementioned area that restricted knee movement and caused proximal tibia deformity. Magnetic resonance imaging showed a giant circumscribed subcutaneous mass with multiple partitions that was hyperintense on T1-weighted and T2-weighted images but not fat-saturated on T2-weighted images. Based on these findings, she was diagnosed as having a lipoblastoma. Because the mass surrounded her popliteal artery and vein and part of the popliteal nerve, surgical resection was considered risky, and we opted to simply observe her. However, owing to rapid growth of the mass and the worsening of symptoms, she underwent complete resection at 2 years and 6 months of age. A histological examination confirmed the diagnosis of a lipoblastoma. She was discharged from our hospital 3 days after surgery with no symptoms. She could walk without pain at the 6-month follow-up, and no local recurrence was observed. Conclusions We successfully treated a giant popliteal lipoblastoma without complications by performing a total resection. Our report provides evidence that lipoblastomas should be considered for surgical resection when they progress or symptoms appear.

Post-transplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), and it is associated almost exclusively with Epstein-Barr virus (EBV). We herein report 2 cases of EBV-associated PTLD after allogeneic HSCT localized in the adrenal gland. Both patients developed adrenal tumor within 3 months after HSCT and were successfully treated with rituximab or tapering immunosuppressive agents. Both remained alive without recurrence. A literature review revealed 12 reported cases of PTLD involving the adrenal gland, but the adrenal gland was involved as one of the lesions of advanced-stage PTLD after SOT. To the best of our knowledge, this is the first report to show cases of isolated EBV-associated adrenal PTLD after HSCT. PTLD should be recognized as one of the causes of isolated adrenal tumor after HSCT.

Introduction The role of sentinel lymph node biopsy (SLNB) in patients with ipsilateral breast tumor recurrence (IBTR) remains to be elucidated. The aim of this study was to evaluate feasibility and validity of SLNB in patients with IBTR. Methods A prospective database of 1172 patients with clinically node-negative breast cancer who underwent SLNB from January 2005 to December 2013 at Keio University Hospital was analyzed and 35 patients with IBTR underwent SLNB. Sentinel lymph nodes (SLNs) were detected using a combined method of blue dye and radioisotope or indocyanine green fluorescence in cases with failure of identification by blue dye and radioisotope. Results Twenty-two patients had previous SLNB, eight had previous axillary lymph node dissection (ALND), and five had no previous axillary surgery. Overall, SLNs were successfully identified in 28 (80.0%) of 35 patients. The identification rate in patients with previous SLNB, ALND and no axillary surgery was 81.8% (18/22), 75% (6/8) and 80% (4/5), respectively ( P = 0.52). Aberrant drainage outside the ipsilateral axilla was found more frequently in patients with previous ALND compared with SLNB and no axillary treatment (37.5% vs. 4.5% vs. 0%, P = 0.048). No axillary recurrence was observed after median follow-up of 40.3 months from the second surgery for IBTR. Conclusions SLNB is a technically feasible and valid procedure for staging and treatment of regional lymph nodes in patients with IBTR.

We report herein improved methods for the safe and successful completion of endoscopic papillectomy (EP). Between January 2008 and November 2011, 12 patients underwent double-snare retracting papillectomy for the treatment of lesions of the major duodenal papilla. The main outcomes were en bloc resection rates, pathological findings, and adverse events. All of the patients (mean age, 60.1 years; range, 38 to 80 years) were diagnosed with ampullary adenoma by endoscopic forceps biopsies prior to endoscopic snare papillectomy. En bloc resection by double-snare retracting papillectomy was successfully performed for all lesions (median size, 12.3 mm), comprising six tubular adenomas, one tubulovillous adenoma, three cases of epithelial atypia, one hamartomatous polyp, and one case of duodenitis with regenerative change. Significant hemorrhage and pancreatitis were observed in one case after EP. Adenoma recurrence occurred in three patients during follow-up (median, 28.5 months) at a mean interval of 2 months postoperatively (range, 1 to 3 months). No serious adverse events were observed. Double-snare retracting papillectomy is effective and feasible for treating lesions of the major duodenal papilla. Further treatment experience, including a single-arm phase II study, needs to be accumulated before conducting a randomized controlled study.

// Saeko Hayashi 1 , Hikaru Sasaki 1 , Tokuhiro Kimura 2,7 , Takayuki Abe 3 , Takumi Nakamura 1 , Yohei Kitamura 4 , Tomoru Miwa 1 , Kaori Kameyama 5 , Yuichi Hirose 6 and Kazunari Yoshida 1 1 Department of Neurosurgery, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan 2 Department of Pathology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan 3 Center for Clinical Research, Department of Preventive Medicine and Public Health, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan 4 Department of Neurosurgery, Saiseikai Utsunomiya Hospital, Takebayashi, Utsunomiya, Tochigi, Japan 5 Division of Diagnostic Pathology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan 6 Department of Neurosurgery, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Aichi, Japan 7 Present address: Department of Pathology, Yamaguchi University Graduate, School of Medicine, Minami-kogushi, Ube, Yamaguchi, Japan Correspondence to: Hikaru Sasaki, email: // Keywords : total 1p19q loss; 1p19q codeletion; astrocytic; ATRX; p53 Received : March 08, 2015 Accepted : April 02, 2015 Published : May 11, 2015 Abstract The prognostic significance of 1p19q loss in astrocytic gliomas has been inconclusive. We collected 57 gliomas with total 1p19q loss from among 218 cases of WHO grade-II/III gliomas operated at Keio University Hospital between 1990 and 2010. These tumors were classified as oligodendroglial or “astrocytic” by a WHO-criteria-based institutional diagnosis. Chromosomal copy number aberrations (CNAs), IDH 1/2 mutations, MGMT promoter methylation, and expression of p53 and ATRX were assessed. Survival outcome was compared between the two histological groups. Of the 57 codeleted gliomas, 37, 16, and four were classified as oligodendroglial, “astrocytic”, and unclassified, respectively. Comparative genomic hybridization revealed that although chromosome 7q/7 gain was more frequent in “astrocytic” gliomas, other CNAs occurred at a similar frequency in both groups. None of the “astrocytic” gliomas showed p53 accumulation, and ATRX loss was found in three of the 15 “astrocytic” gliomas. The estimated overall survival (OS) curves in the patients with codeleted oligodendroglial and “astrocytic” gliomas overlapped, and the median OS was 187 and 184 months, respectively. Histopathological re-assessment by a single pathologist showed consistent results. Gliomas with total 1p19q loss with “astrocytic” features have molecular and biological characteristics comparable to those of oligodendroglial tumors.

Basaloid squamous cell carcinoma (BSCC) is a relatively rare, malignant disease of the esophagus. The prognosis of patients with BSCC is thought to be poorer than that of typical squamous cell carcinoma (SCC), but the treatment strategy for BSCC is generally the same as that for typical SCC. This study examined the diagnosis, the clinical and pathological characteristics, and the results of therapy in patients with BSCC. The medical records for 13 patients with pathologically confirmed esophageal BSCC were extracted. The pretreatment endoscopic diagnosis and the pathological diagnosis after resection were reviewed for each patient, and the histological features and patient outcome were examined. We especially focus on histological difference and endoscopic findings of the 13 patients with BSCC. Macroscopically, BSCC was mainly visualized as an elevated lesion with normal epithelium on the surface layer which indicated the tumor growth into submucosa. Further pathological examination allowed the 13 BSCC patients to be grouped into 2 groups according to differences in the microscopic appearances of the BSCC cancer cells: a typical BSCC pattern and a pattern similar to that of poorly differentiated SCC. Six of the patients who received an esophagectomy as the primary treatment died, and only 1 patient survived. Two patients who received chemoradiotherapy before an esophagectomy did not develop recurrences. Almost all the patients who died as a result of the recurrence of esophageal cancer had a lymph node recurrence. Prognoses of BSCCs with a pattern similar to that of poorly differentiated SCC without preoperative chemotherapy were poorer than BSCCs with a typical BSCC pattern, while BSCC with a pattern similar to poorly differentiated SCC with preoperative chemotherapy showed good prognoses than BSCC without preoperative chemotherapy. BSCC esophageal cancer mainly appears as an elevated lesion with submucosal growth, which can be diagnosed preoperatively by understanding of macroscopic characteristics of esophageal BSCC. The outcome of the BSCC patients in the present study was relatively poor, while pretreatment diagnosis of BSCC influences the strategy of treatment and pathological diagnosis including histological difference of BSCC may lead to appropriate treatment and better prognosis of esophageal BSCC.

The number of long-term breast cancer survivors with a risk of late recurrence is increasing. Hormone-receptor-positive patients have greater risks of late recurrence. Although several studies demonstrated that extended adjuvant endocrine therapy reduces the incidence of late recurrence, it remains unclear which hormone-receptor-positive patients have greater risks of late recurrence. Hormone-receptor-positive breast cancer patients were retrospectively selected from the prospective database of primary breast cancer patients treated at Keio University Hospital from January 1989 to December 2003. Late recurrence was defined as initial recurrence after 5 years from the initial surgery. We evaluated the clinicopathologic features of breast cancer patients with late recurrence. At a median follow-up of 10.9 years (range, 5.1-23.8), 371 patients had no recurrence, 90 had early recurrence (within 5 years), and 83 had late recurrence. Multivariate analysis revealed that >4 involved lymph nodes were significant risk factors for late recurrence (P < .001), whereas 1-3 positive nodes were not. Endocrine therapy significantly reduced the incidence of late recurrence (P < .001). After menopause, adjuvant therapy with aromatase inhibitors resulted in longer disease-free survival than tamoxifen (10-year disease-free survival: 97.6% vs 89.7%, P = .0955). High nodal involvement was significantly correlated with late recurrence in hormone-receptor-positive breast cancer patients. Hormone-receptor-positive breast cancer patients who receive adjuvant endocrine therapy with tamoxifen alone might be candidates for extended endocrine therapy.

Shprintzen-Goldberg syndrome is a rare systemic connective tissue disorder characterized by craniosynostosis, skeletal abnormalities, infantile hypotonia, mild-to-moderate intellectual disability and cardiovascular anomalies. To our knowledge, this is the first report of a Shprintzen-Goldberg syndrome patient who developed a thoraco-abdominal aortic aneurysm. The aneurysm grew rapidly necessitating emergent thoraco-abdominal aortic replacement. The postoperative course was uneventful, and a careful lifetime follow-up was planned.

Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a 3-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity against human leukocyte antigen (HLA)-DR15, which was possessed by both the first and the second donor, peaked at 12 945 on the day before the second LTx. Antithymocyte globulin, plasma exchange along with i.v. immunoglobulin, rituximab, and the local infusion of prostaglandin E1, steroids, and Mesilate gabexate through a portal catheter were provided to save the second graft. To our knowledge, this is the first report to show a clear association between de novo DSA and acute AMR within 7 days of a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted HLA. The rapid decision to carry out retransplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.

We herein report a child case of autoimmune hepatitis (AIH) accompanied with Graves' disease. Elevated aminotransferase levels were found in a 12-year-old Japanese girl with Graves' disease. In her first liver biopsy, necrosis and inflammation was limited to the centrilobular area, while the second biopsy showed different findings. Namely, portal injury newly appeared, including interface hepatitis, which represents the histological characteristics of AIH. As the histological findings at the onset of AIH do not always show typical findings, a re-biopsy is considered to be important in individuals suspected to have AIH. AIH should be included in the differential diagnosis of liver dysfunction in Graves' disease, even in children.

Angiosarcoma is a rare malignant tumor with an aggressive clinical course and a poor prognosis. Intraperitoneal angiosarcoma, especially originating from the omentum, is extremely rare. We report a case of radiation-induced angiosarcoma of the omentum that arose in a 38-year-old female seven years after concurrent chemoradiotherapy for cervical cancer. The primary tumor was unknown until diagnostic laparoscopy revealed an unresectable omental mass. Pathological examination revealed high-grade malignant cells positive for endothelial markers. Although the small number of cases limits the consensus on optimal therapy for advanced angiosarcoma, the patient was managed successfully by taxane-based chemotherapy, leading to complete response and consequent complete cytoreductive surgery. Our report is the fifth case of radiation-induced angiosarcoma of the omentum, and all have developed after treatment for gynecologic cancer. Although very rare, this complication should be considered after radiation therapy in cancer treatment, particularly given the increasing importance of this therapy.

Context Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal lymphoma with a favorable prognosis. Objective To provide information on long-term outcomes that would facilitate establishment of the optimal management strategy for thyroid lymphoma. Design, Setting, and Participants Medical records of 107 patients (median age 67 years, 20 males, 87 females) who were diagnosed with localized thyroid MALT lymphoma stage IE or IIE at Ito Hospital were retrospectively reviewed. Main Outcome Measure Overall and event-free survival (EFS). Results Initial treatments included radiation therapy (RT) alone (n = 58), combined modality therapy (CMT) (n = 48), or chemotherapy alone (n = 1). All 107 patients responded to the treatment, six of whom experienced relapse. Only one patient died of lymphoma. The 5-year overall survival (OS) and EFS rates were 94% [95% confidence interval (CI), 87% to 97%] and 92% (95% CI, 85% to 95%), respectively, and the 10-year OS and EFS rates were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Of the 106 patients with information available on adverse events, 71 patients (67%) developed hypothyroidism after primary thyroid lymphoma treatment. The CMT group showed additional chemotherapy-induced adverse reactions in the form of neutropenia, neuropathy, constipation, and pneumonia. The 5-year OS rates of patients treated with CMT and RT were 93% (95% CI, 81% to 98%) and 94% (95% CI, 84% to 98%), respectively. Conclusions Long-term outcomes of localized thyroid MALT lymphoma are favorable with all initial treatment modalities.

Endoscopic full-thickness resection (EFTR) is expected to make possible minimally invasive local resection of early gastric cancer (EGC). However, no consensus exists regarding how far an optimal safety margin should be set in determining the resection area by endoscopy. We aimed to investigate the optimal lateral margin of EGC which could be a candidate for EFTR by measuring the subepithelial extent (SE) of tumors.In 60 surgically resected submucosal EGCs 4 cm or smaller, 595 prepared slides which showed lateral tumor borders both on the epithelial surface and on the subepithelial layer were assessed. The distance between the epithelial and the subepithelial tumor edge was measured under microscopic observation, followed by analyses of the relationship between the measured SE and the histological characteristics.The average and the median SE were 1.1 mm (standard deviation 1.8 mm) and 0.3 mm (range 0-12.3 mm), respectively. The 99th percentile was 8.8 mm. With regard to the histological type, the median SE was significantly greater in diffuse-type tumor than in intestinal-type tumor (0.9 mm vs 0 mm, p0.0001). With regard to the location of the subepithelilal tumor edge, the median SE was significantly greater in the submucosal layer than in the mucosal layer (2.6 mm vs 0.3 mm, p0.0001).In most lesions, the SE was less than 1 cm. A safety margin may be set at 1 cm in EFTR of submucosal EGC.

Primary thyroid lymphoma (PTL) develops mostly in middle-aged and older females. However, the optimal treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL), which accounts for most PTL cases, is unclear. Rituximab is a promising drug that, in combination with traditional combination therapy, has demonstrated an increased antitumor effect without a substantial increase in toxicity. In this study, treatment outcomes of elderly patients with thyroid DLBCL who underwent rituximab-including combination therapy were analyzed.Between January 2005 and December 2011, 43 patients 60 years of age or older (median 71 years, range 60-80 years) were diagnosed as having stage IE (n=12) or stage IIE (n=31) DLBCL, and three courses of R-CHOP therapy (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, adriamycin 40 mg/m2, vincristine 1.4 mg/m2, and prednisolone 100 mg/body) and involved field irradiation were planned. Treatment outcomes of these patients were retrospectively reviewed.Two patients terminated the treatment because of interstitial pneumonia during R-CHOP therapy. Only one patient showed treatment resistance and the regimen was changed; 42 patients (98%) responded to the treatment. Five-year overall survival and event-free survival were 87% (95% confidence interval [95% CI], 64-96%) and 74% (95% CI, 50-89%), respectively.The results of the present study indicate that rituximab-including combination therapy was effective for elderly patients with thyroid DLBCL. A multicenter, long-term observational study is needed to confirm this, and additional refinement of the treatment protocol is required to optimize the antitumor effect.

Tumor size and lymphovascular invasion are known high-risk factors for lymph node and distant metastasis in patients with rectal carcinoid tumors. However, the optimal treatment for these tumors remains controversial.The aim of this paper is to compare the outcome of local or radical resection between patients with high-risk (tumor size10 mm or lymphovascular invasion) disease and those with low-risk (tumor size ≤10 mm, no lymphovascular invasion) disease.Patients with rectal carcinoid tumors treated between January 1990 and March 2010 were identified retrospectively and classified into low- and high-risk groups.In total, 83 patients with rectal carcinoid tumors were included, 53 (64%) of whom were identified as low-risk and 30 (36%) as high-risk. Local resection was performed in 50 (60%) low-risk and 24 (29%) high-risk patients, and postoperative recurrence was observed in one (1%) of the high-risk patients who underwent local resection and one (11%) who underwent radical resection. No recurrence was observed in the low-risk group. Kaplan-Meier analysis of the patients who underwent local resection revealed that the 10-year disease-free survival rate was 100% in the low-risk group and 83.3% in the high-risk group.There was no significant difference in outcome between local and radical resection.

Background Osteoid osteoma accounts for approximately 10% of all benign bone tumors. The most common sites of osteoid osteoma are the subcortical shaft and metaphyses of long bones, but any other skeletal bone site can be involved. The acetabulum is a rare site according to past reports. This site presents challenges to optimal management because it is anatomically difficult to approach, and because its rarity leads to limited experience with therapeutic procedures. Here, we report for the first time a rare case of osteoid osteoma in the acetabulum that was successfully treated via resection of the nidus and ablation using a standard electrosurgical generator under computed tomographic guidance. Case presentation A 9-year-old Japanese girl presented at a clinic with left hip pain without apparent cause for 1 month. She was diagnosed as having coxitis simplex. However, her pain did not change for 1 year and she was admitted to another hospital where osteoid osteoma in her left acetabulum was suspected. She was then referred to our hospital approximately 1 year after first symptom presentation, where she presented with severe left hip pain and was completely unable to walk. Computed tomography examinations revealed a well-demarcated 5 mm mass with bone sclerosis in her left acetabulum. The mass was characterized by low intensity on T1 and high intensity on T2 magnetic resonance images. These findings were consistent with osteoid osteoma of left acetabulum. She underwent computed tomography-guided resection of nidus and ablation using a standard electrosurgical generator. A histological examination confirmed acetabular osteoid osteoma. Complete pain relief was achieved after the procedure and she experienced no complications. She could walk without any pain at the final follow-up 1 year post-treatment and no local recurrence was observed. Conclusions We successfully treated acetabulum osteoid osteoma without any symptom recurrence by computed tomography-guided resection and ablation using a standard electrosurgical generator. In addition, we preserved our patient’s sciatic nerve and triradiate cartilage. Our report provides evidence that a computed tomography-guided procedure should be considered the treatment of choice for osteoid osteoma of the acetabulum because it is a less invasive alternative to en bloc resection.

The curability of chemotherapy-resistant hepatoblastoma (HB) largely depends on the achievement of radical surgical resection. Navigation techniques utilizing indocyanine green (ICG) are a powerful tool for detecting small metastatic lesions. We herein report a patient who underwent a second living donor liver transplantation (LDLTx) for multiple recurrent HBs in the liver graft following metastasectomy for peritoneal dissemination with ICG navigation. The patient initially presented with ruptured HB at 6 years of age and underwent 3 liver resections followed by the first LDLTx with multiple sessions of chemotherapy at 11 years of age. His alpha-fetoprotein (AFP) level increased above the normal limit, and metastases were noted in the transplanted liver and peritoneum four years after the first LDLTx. The patient underwent metastasectomy of the peritoneally disseminated HBs with ICG navigation followed by the second LDLTx for multiple metastases in the transplanted liver. The patient has been recurrence-free with a normal AFP for 30 months since the second LDLTx. To our knowledge, this report is the first successful case of re-LDLTx for recurrent HBs. Re-LDLTx for recurrent HB can be performed in highly select patients, and ICG navigation is a powerful surgical tool for achieving tumor clearance.

Background: This study aimed to examine family history among Japanese ovarian cancer patients and to investigate the TP53 status of fallopian tube epithelial and ovarian cancer cells in a Japanese BRCA1 mutant case that may be associated with the transformed state in hereditary ovarian cancer. Methods: One hundred and two primary ovarian cancer patients were retrospectively evaluated in this cross-sectional study. The family history of cancer was determined in probands. In a BRCA1 mutant case, p53 immunostaining and direct sequencing, followed by laser-capture microdissection, were performed for the fallopian tube, considered the origin of ovarian cancer. Results: Nine of 102 (8.8%) families were regarded as having hereditary breast–ovarian cancer syndrome, two families (2.0%) were diagnosed with Lynch syndrome and six patients harbored BRCA1 or BRCA2 mutations. One case underwent risk-reductive salpingooophorectomy as a BRCA1 mutant carrier was retrospectively diagnosed as occult cancer. Common TP53 mutations were detected in cancer and fallopian tube epithelial cells in the case. Conclusions: Here, we integrate family cancer history and histology in ovarian cancer cases as well as TP53 status in a BRCA1 mutant case into a discussion regarding carcinogenesis in a Japanese population. The TP53 status for the BRCA1 mutant case examined here supports the recently proposed theory that ovarian cancer develops because of BRCA1 or BRCA2 inactivation and/or TP53 mutations.

Hurthle cell carcinoma (HCC) is a rare form of thyroid carcinoma and is considered an oxyphilic variant of follicular thyroid carcinoma. However, little is known about its biological characteristics or clinical behavior. We conducted a retrospective study to determine whether the prognosis of HCC differs from that of ordinary follicular thyroid carcinoma (OFC). The subjects were the 558 patients with follicular thyroid carcinoma who underwent initial surgery at our institution between 1989 and 2010 and consisted of 73 patients with HCC and 485 patients with OFC. There were 410 females and 148 males, and their median age was 51 years. A univariate analysis was conducted in relation to cumulative cause-specific survival (CSS) according to the Kaplan–Meier method for the following variables: age at the time of initial surgery, gender, tumor size, invasiveness, distant metastasis at presentation, and histological type (HCC vs OFC). Differences between groups were analyzed for significance by the log-rank test. Multivariate analysis was performed by using the Cox proportional hazard model. A total of 4 patients (5.5 %) in the HCC group had distant metastasis compared with 106 patients (21.9 %) in the OFC group. Significant factors in relation to CSS in the univariate analyses were age, tumor size, and invasiveness, but there were no significant differences between the HCC group and the OFC group. Multivariate analysis showed that age, tumor size, and distant metastasis at presentation were significant factors. HCC does not have a poorer prognosis than OFC.

Because of its low incidence, the clinical characteristics of the salivary duct carcinoma (SDC) based on a statistical analysis with a large number of patients remain to be elucidated, and thus it has been impossible to standardize the optimal treatments of SDC including adjuvant systemic therapy.The present study aimed to determine the prognostic factors along with the clinical outcomes of patients with SDC and to evaluate the expression of several receptor molecules as treatment targets.We performed a statistical analysis and immunohistochemical examination of 16 patients with SDC who had undergone initial treatment in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine from 1996 to 2010.The 3-year disease-free survival (DFS) and cause-specific survival (CSS) rates were 29.2% and 72.7%, respectively. At the time of the analysis, 6 patients are alive without the disease, 2 patients are alive with distant metastasis, whereas 7 patients had died of distant metastasis, and 1 patient had died of another cause (pulmonary embolism). We examined the prognostic value of the clinico-pathological factors such as age, sex, T classification, N classification, clinical stage, primary site, histological pre-existence of pleomorphic adenoma. A univariate analysis revealed that DFS was significantly correlated with age (p = 0.049), T classification (p = 0.018), and clinical stage (p = 0.029), whereas no factor was found to be correlated with CSS. A multivariate analysis demonstrated that age (or = 61 vs.or = 60, risk ratio (RR) = 5.423, p = 0.042) and T classification (3, 4 vs. 1, 2, RR = 1.087, p = 0.020) were the independent prognostic factors for DFS. Positive expressions of HER2, ER (estrogen receptor), PR (progesterone receptor), AR (androgen receptor), and MIB-1 (index20%) were found in 50%, 6%, 13%, 100%, and 69%, respectively. However, none of them showed significant correlation with survival.Frequent expressions of HER-2 and AR in SDC suggest that these receptors can be suitable molecular targets of systemic therapy for patients with SDC in which distant metastasis seems to be the largest obstacle to improving survival. In order to assess the efficacy of anti-HER-2 therapy and anti-androgen therapy for each receptor-positive SDC, a multi-institutional joint research system should be organized.

Background Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma that has unusual ultrastructural and molecular features. However, unlike other soft tissue sarcomas, it does not have specific clinical symptoms or radiological features, which can make its diagnosis difficult. Nevertheless, extraskeletal myxoid chondrosarcoma has a rare gene fusion (EWSR1-NR4A3) that is useful for making a differential diagnosis. Case presentation A 43-year-old Japanese man presented with a soft tissue mass in his right thigh. A physical examination and radiography revealed a large soft tissue mass. During magnetic resonance imaging, the mass exhibited isointensity on T1-weighted images and high intensity on T2-weighted images, as well as gadolinium enhancement at the side edge of the partition structure. Thus, we considered a possible diagnosis of a malignant myxoid soft tissue tumor, such as myxoid liposarcoma, myxofibrosarcoma, or metastatic carcinomas, including myoepithelial tumor and neuroendocrine tumor, and performed an incisional biopsy to make a definitive diagnosis. The pathological findings revealed a lobulated tumor with a myxoid structure and atypical spindle-shaped cells that created eosinophilic cord-like forms. Immunohistochemistry revealed that the tumor was positive for S-100 and negative for synaptophysin, chromogranin A, and pan keratin (AE1/AE3). The percentage of Ki-67 was 10 % in the hot spot area. Based on these clinicopathological findings, we initially considered the possibility of a myxoid liposarcoma, although we did not observe any lipoblasts. Therefore, we considered the possibility of an extraskeletal myxoid chondrosarcoma. As this tumor is very rare, we searched for the EWSR1-NR4A3 gene fusion using fluorescence in situ hybridization, which confirmed the diagnosis of extraskeletal myxoid chondrosarcoma. Positron emission tomography-computed tomography did not identify any obvious metastases, and we performed radical resection of our patient’s vastus medialis and femur with a 3 cm margin. After the resection, we treated his resected femur using liquid nitrogen, and reconstructed his femur using autogenous fibula and plate fixation. No local recurrence or metastasis was observed at the 1-year follow-up. Conclusion Genetic testing is useful for diagnosing extraskeletal myxoid chondrosarcoma based on the presence of the EWSR1-NR4A3 gene fusion.

Immunoassays (IAs) are widely used to measure concentration of serum estradiol (E2) despite some limitations including cross-reactivity. Liquid chromatography-tandem mass spectrometory (LC-MS/MS) for E2 measurement has a theoretically greater specificity and sensitivity than IAs. We report a case with unexpected discrepancy in E2 values measured by IA and LC-MS/MS.A 7-year-old girl was referred because of an ovarian tumor. Physical examinations revealed prepubertal statuses. Serum E2 with ECLIA was 69 pg/mL. GnRH stimulation test revealed a prepubertal response. On imaging studies, the diagnosis was mature teratoma of the right ovary. After tumor enucleation, the diagnosis was pathologically confirmed. E2 with ECLIA decreased to 11 pg/mL. Preoperative E2 with LC-MS/MS was 1.15 pg/mL.We conclude the preoperative E2 with ECLIA was falsely high. We speculate the antibody used in ECLIA had cross-reactivity to endogenous compounds. LC-MS/MS should be considered when high serum E2 measured with IA is inconsistent with physical and/or endocrinological data.

Radioiodine ablation after total thyroidectomy is the generally accepted treatment for patients with widely invasive follicular thyroid carcinoma (FTC). The therapeutic strategy for minimally invasive FTC, on the other hand, is still a matter of controversy. The histological diagnosis of minimally invasive FTC is often made after lobectomy. The aim of this study was to determine the factors associated with the development of distant metastases in patients with minimally invasive FTC.Between 1989 and 2006, 251 patients with minimally invasive FTC underwent initial surgery at our hospital. Their median follow-up period was 7.2 years. There were 194 women and 57 men. Their mean age at the time of surgery was 46 years. Distant metastases were diagnosed in 54 patients (21.5%). In 22 of them distant metastases were diagnosed at the time of the initial surgery (M1), and in the other 32 they were diagnosed during the follow-up period. Age at initial surgery, sex, primary tumor size, histological findings (differentiation, and extent of vascular and capsular invasion), completion total thyroidectomy, and distant metastases at initial surgery were assessed as prognostic factors for distant-metastases-free survival (DMFS) and cause-specific survival (CSS). The Kaplan-Meier method and log-rank test were used to analyze time-dependent variables. The Cox proportional hazard model was used to perform the multivariate analysis.Univariate analysis showed that age (45 years or older) and primary tumor size (4 cm or more) were significant prognostic factors related to postoperative distant metastases in the group of 229 patients without distant metastases at time of the initial surgery. The cumulative survival rate was significantly poorer in M1 patients, patients aged 45 years or older, and patients whose primary tumor size was 4 cm or more. Multivariate analysis showed that age was a significant prognostic factor both for DMFS and CSS.Age was the most powerful prognostic factor for patients with minimally invasive follicular thyroid cancer. The prognoses of patients younger than 45 years old were excellent and distant metastases rarely occurred. Routine completion total thyroidectomy and radioiodine ablation is thought unnecessary for these patients.

Anaplastic transformation of differentiated thyroid carcinoma (DTC) is a rare event with a poor clinical outcome. It usually occurs in the primary site or in regional lymph nodes, but rarely in distant metastatic lesions.A 55-year-old woman with persistent pain in the left hip joint visited our hospital. She had a history of DTC that had been surgically removed 12 years earlier. Clinical images showed a tumorous mass in the left pelvis, indicative of bone metastasis. The patient underwent surgery to remove the tumor and remained stable until local recurrence was found 5 weeks after the surgery. The patient subsequently underwent radiation therapy; however, she died of respiratory failure due to lung metastases 2 months after the surgery for the recurrent lesion. The surgical specimens were diagnosed as anaplastic thyroid carcinoma, indicating that anaplastic transformation of thyroid follicular carcinoma occurred in the metastatic skeletal lesion. In addition, the patient had an unusually high white blood cell count throughout the course. Based on elevated serum granulocyte colony-stimulating factor (G-CSF) levels and positive immunostaining for G-CSF in the surgical specimens, the patient was diagnosed with paraneoplastic leukocytosis.To our knowledge, this is the first case of anaplastic transformation of DTC arising in a metastatic bone lesion described in the literature. In addition, the present case also exhibited severe leukocytosis accompanied by elevated serum G-CSF levels. Clinicians should be aware of the possibility of this occurring in their patients with DTC, as this development calls for a rapid change from observational follow-up to aggressive treatment.

Background: Laparoscopic wedge resection is accepted as a curative treatment for small- and mediumsized gastroin-testinal stromal tumors (GISTs) of the stomach. Conventional methods involving surgical staplers require relatively large lateral margins, which may cause deformity and postoperative dysfunction of the gastric remnant. In this study, we introduce a novel technique called laparoscopic submucosal dissection (LSD) in which the defects of the stomach are minimized and a microscopic negative margin is secured. Methods: The normal seromuscular layer of the gastric wall was dissected with a 5 mm lateral margin. Then, the submucosal tissue was divided carefully using a monopolar electrosurgical device with a curved spatula tip. Results: The operation time was 170 min, and the amount of bleeding was very small. We confirmed an intact pseudo-capsule and marginal subserosal or submucosal tissue of the tumor by histological analysis. The postoperative course was uneventful with no complications. Endoscopy showed minimal deformity of the gastric remnant. Conclusions: We think that LSD is a curative and less invasive treatment for GIST of the stomach. Further investigations are necessary to evaluate the oncological and functional outcomes of this procedure.

Context:Heterozygous inactivating PAX8 mutations cause congenital hypothyroidism. Although more than 30 mutation carriers have been reported, no histological examination of the thyroid has been conducted.Objective:The objective of this study was to document the histological characteristics of the thyroid tissue harboring a PAX8 mutation.Subjects and Methods:The patient was a 40-yr-old female, whose two children had congenital hypothyroidism and an inactivating PAX8 mutation (p.K80_A84dup). She had normal thyroid function but had a thyroid nodule and received right hemithyroidectomy at age 28 yr. Mutation analyses using DNA derived from multiple sources, namely lymphocytes, nails, and laser capture microdissected thyroid samples, were performed.Results:The PAX8 mutation was detected in the lymphocytes; however, the level of the mutant allele was significantly lower than that of the wild-type allele. This finding was compatible with her somatic mosaic state. We reviewed the histology of her resected thyroid and found a characteristic lesion in the nonneoplastic tissue: dense aggregates of thyrocytes with absent or very small follicles, resembling a fetal thyroid in the late phase of development. Mutation analyses of laser capture microdissected thyroid samples revealed that the fetal-like tissue carried the PAX8 mutation, whereas surrounding morphologically normal tissue and adenoma tissue did not.Conclusions:In our case, the histology of PAX8 mutation-carrying thyroid tissue was characterized by the lack of follicular growth. Our observations provide the first evidence suggesting that the late phase of thyroid development is sensitive to the PAX8 gene dosage and can be disturbed by heterozygous inactivating PAX8 mutations.

Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. Here we report a retrospective study of the treatment and other factors associated with its outcomes.The medical records of 100 patients diagnosed with ATC at Ito Hospital between 1993 and 2009 were reviewed and pertinent information was extracted and analyzed.There were 80 women and 20 men, and their median age at diagnosis was 68 years (range, 41-90 years). Thirteen patients had a history of well-differentiated thyroid carcinoma. Six patients had a small ATC focus within a differentiated carcinoma. All cases were retrospectively staged according to the Union for International Cancer Control classification system, and the results were stage IVA in 11 cases, stage IVB in 31 cases, and stage IVC in 58 cases. Seventy patients underwent surgical treatment, and complete resection was performed in 24 of them. Seventy-eight patients received radiotherapy, and 58 of them received a total dose of ≥40 Gy. Twenty-seven patients received chemotherapy. Only 15 patients received multimodal therapy (surgery, radiotherapy, and chemotherapy). The 1-year survival rates according to stage were as follows: stage IVA, 72.7%; stage IVB, 24.8%; and stage IVC, 8.2%. Multivariate analysis identified age ≥70 years, white blood cell ≥10,000 mm(3), extrathyroidal invasion, and distant metastasis at the time of diagnosis as prognostic factors. Survival after complete resection was significantly better than after incomplete resection or no resection. The results also suggested that radiation doses of ≥40 Gy were associated with significantly longer survival.Although the prognosis of most patients with ATC continues to be poor, surgery, radiotherapy, and a combination of both improved the survival of patients with ATC.

Nephrogenic systemic fibrosis (NSF) is a fibrotic disease that presents with a history of renal dysfunction. The differential diagnosis generally includes scleromyxedema, systemic sclerosis, and morphea. Especially, scleromyxedema can be extremely difficult to distinguish microscopically. Although the fibrocytes in NSF are often positive for CD34 and procollagen-I, this is not specific for NSF. We identified positive iron staining in the skin of a patient with NSF and investigated whether this was a specific feature among 9 patients with NSF reported in Japan. We found that 6 of 9 patients showed positive iron staining in the dermal fibrocytes. The amount of iron deposition seemed to have no correlation with the degree of fibrosis or duration of the skin lesions but correlated with apparent history of the use of gadolinium-based contrast agents. As controls, skin biopsies from patients with scleromyxedema, morphea, and systemic sclerosis were evaluated by iron staining. None of these control patients showed iron deposition, indicating that positive iron staining may be specific to NSF and can be a useful tool for NSF diagnosis.

There are few large-scale reports of primary thyroid lymphoma (PTL). This study clinically and pathologically reviewed 171 patients with PTL and 24,553 patients with Hashimoto's disease at Ito Hospital between January 1990 and December 2004, to investigate the clinical features and the treatment outcomes of PTL. The median age of the patients with PTL was 67 years (range, 27-90 years). The pathological diagnosis of PTL patients included diffuse large B-cell lymphoma (DLBCL) (n=74), DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma (n=13), MALT lymphoma (n=80) and others (n=4). Of the 167 patients with B-cell lymphoma, treatment included combined modality therapy (CMT) (n=95), radiation therapy (RT) alone (n=60) and chemotherapy alone (n=6). Information on treatment was not available in six patients. Information on treatment response was available in 154 patients; 149 patients (97%) responded to treatment. According to the institutional treatment strategy of Ito Hospital, 45 of 54 patients with stage IE disease received RT alone, and 87 of 113 stage IIE patients received CMT. The 5-year overall survival rate was 85% (95% confidence interval, 79-91%). This study demonstrated that PTL showed good response to radiotherapy and chemotherapy and had a favourable prognosis.

A 46-year-old woman developed painful dysesthesia in her extremities and ataxic gait. She was diagnosed with Sjogren's syndrome, and her condition was diagnosed as sensory ataxic and painful neuropathy. Intravenous immunoglobulin therapy alleviated the ataxia and severe pain in her extremities. When she was 61-years-old, she developed dysphagia and dyspnea. Laryngoscopy showed tactile anesthesia on the epiglottis, indicating paresis of the superior laryngeal nerve. We considered that the primary cause of dysphagia was paresis of the internal branch of the superior laryngeal nerve, and carried out tracheostomy and high-dose intravenous methylprednisolone therapy (1 g/day × 3 days). Her dysphagia and aspiration gradually improved without following oral steroid therapy. Our case is the first report of the internal branch of superior laryngeal nerve paresis as a possible cause of dysphagia and aspiration in a patient with Sjogren's syndrome. Additional cases of Sjogren's syndrome with dysphagia should be investigated to confirm our findings.

Mochizuki K, Kondo T, Nakazawa T, Iwashina M, Kawasaki T, Nakamura N, Yamane T, Murata S-i, Ito K, Kameyama K, Kobayashi M & Katoh R (2010) Histopathology 57, 444–450 RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components Aims: To elucidate the genetic background of anaplastic transformation, RET rearrangements and BRAF mutation were studied in composite undifferentiated carcinomas (UCs) of the thyroid, which are UCs having papillary carcinoma (PC) components. Methods and results: Reverse transcription–polymerase chain reaction (RT–PCR) was performed for RET rearrangements and PCR for BRAF mutation in UC and PC components that were microdissected separately from seven composite UCs. Forty-two thyroid cancers with single component histology (14 UCs and 28 PCs) were also studied in the same manner. RET/PTC1 was undetectable in both components from all seven composite UCs, and RET/PTC3 was identified in both components of one composite UC. BRAF mutation was identified in both components from three composite UCs and only in the PC components from two composite UCs. In contrast, in thyroid carcinomas with single component histology, RET/PTC1 was detected in 11% of PCs and in none of the UCs, and RET/PTC3 was not found in any of the tumours studied. BRAF mutation was identified in 82% of PCs and in 21% of UCs. Conclusions: The high frequency of BRAF mutation and the absence of RET rearrangements in UC components from composite UCs supports the hypothesis that UCs may actually represent progressive malignant degeneration of a BRAF-mutated, well-differentiated thyroid carcinoma.

Introduction: COX-2 is one of the two isoforms of cyclooxygenase, an enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. COX-2 is considered to be associated with progression in various cancers, and its expression has been reported to have an impact on poor prognosis in head and neck squamous cell carcinomas (HNSCCs). Furthermore, COX-2 expression has been shown to be associated with resistance to anticancer drugs. However, the precise mechanism of COX-2 for chemoresistance in HNSCC is not fully elucidated. The aim of the present study was to investigate the impact of COX-2 on cancer stem cell property, and to reveal its effect on chemoresistance by in vitro and clinicopathological assays. Methods: We examined the chemoresistance to docetaxel with or without COX-2 inhibitor (celecoxib) in HNSCC cell lines (FaDu, Detroit512) by MTS assays. To evaluate the association of COX-2 expression with stemness property, we assessed alteration of expression levels of the genes related to cancer stem cell (CSC) property after exposure to celecoxib by quantitative real-time PCR. We also performed a sphere formation assay using ultra low attachment dishes and microscopic imaging. Moreover, we analyzed immunohistochemical expressions of COX-2 and clinicopathological factors by using matched samples of pre-treatment biopsy and surgical specimens from hypopharyngeal carcinoma patients who had undergone trans-oral tumor resection with preoperative induction chemotherapy including docetaxel. Results: Cell survival rate under exposure to docetaxel was decreased by addition of celecoxib. COX-2 inhibitor downregulated the expression of Oct3/4 and Nanog. Sphere formation was inhibited by co-culture with COX-2 inhibitor, especially in FaDu cells. Immunohistochemical study in biopsy specimens revealed a negative correlation between COX-2 expression in biopsy specimens and pathological effect of induction chemotherapy in surgical specimens. Conclusion: The present study suggests that COX-2 expression is associated with cancer stemness property, and inhibition of COX-2 has a possibility to enhance chemosensitivity in HNSCCs. Furthermore, initial COX-2 expression in biopsy specimens may predict the effect of chemotherapy in HNSCCs. These results indicate that COX-2 can be an attractive target for the treatment of HNSCC. Citation Format: Shin Saito, Hiroyuki Ozawa, Yorihisa Imanishi, Mariko Sekimizu, Yoshihiro Watanabe, Fumihiro Ito, Yuichi Ikari, Nana Nakahara, Kaori Kameyama, Kaoru Ogawa. COX-2 expression is associated with chemoresistance through cancer stemness property in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 914.

The relationship between the histological parameters of primary lesions and lymph node metastasis in supraglottic and hypopharyngeal cancers has not been elucidated. This analysis is important to evaluate the requirement for additional elective neck dissection when clinically node-negative cancers are treated by transoral surgery. This study included 40 previously untreated patients with supraglottic and hypopharyngeal cancers who underwent transoral en bloc tumor resection in two academic tertiary referral centers. Nodal status was confirmed by neck dissection for cases with findings or suspicion of lymph node metastases or by observation of clinically node-negative cases for more than 1 year. Patients’ medical records and pathological features were analyzed retrospectively. The correlation of histological parameters with lymph node metastases, including occult metastases, was evaluated by univariate and multiple logistic regression analyses. Univariate analysis showed that lymph node metastasis was correlated with tumor depth (P = 0.00087) and venous invasion (P = 0.027). Multiple logistic regression analysis showed that it was significantly correlated only with tumor depth (P = 0.007). Tumor depth is the most useful parameter for predicting lymph node metastases. In clinically node-negative cases, when tumor depth exceeds 1 mm, elective neck dissection must be considered and, when it is less than 0.5 mm, regular clinical follow-up is recommended. Patients with tumor depth between 0.5 and 1 mm should be carefully observed, since they also have a chance of developing nodal metastasis. Venous invasion also indicates high rates of nodal metastasis, therefore elective neck dissection must be considered for these cases.

A 74-year-old female was referred to our hospital for non-muscle invasive bladder tumors initially treated at another hospital. Preoperatively, computed tomography and magnetic resonance imaging demonstrated non-muscle invasive bladder tumors and a vaginal tumor. A second transurethral resection of the bladder tumors, transvaginal tumor resection, and systemic chemotherapy were performed. The histopathological appearances of both tumors were very similar and the diagnoses were urothelial carcinoma (UC). The pathogenesis of the vaginal UC was considered to be the primary UC or metastasis from the bladder UC. Vaginal UC is extremely rare and this is only the 15th report in the literature.

Rationale: Hypertrophic pachymeningitis (HP) is an uncommon, life-threatening disease that is seen in elderly patients with antineutrophil cytoplasmic antibody (ANCA) positivity. Proteinase-3 (PR3)-ANCA-positive HP has not been reported in adolescents. Here, we report the first case of adolescent PR3-ANCA-positive HP successfully treated with immunosuppressive therapy. Patient concerns: A 14-year-old female presented with fullness and pain in her right ear unresponsive to antibiotics. Laboratory tests showed an elevated C-reactive protein and PR3-ANCA positivity. Computed tomography and magnetic resonance imaging revealed mastoiditis in the right temporal bone. Surgical biopsy revealed severe fibrosis and prominent inflammatory-cell infiltration. She received prednisolone and methotrexate therapy, and then underwent a right mastoidectomy. Five months later, she developed headache, dysarthria, and multiple cranial nerve palsies. Further imaging revealed enhancement and thickening of the right hemispheric dura. Diagnosis: PR3-ANCA-positive HP. Interventions: She was successfully treated with steroid pulse therapy for 3 days, followed by high doses of prednisolone and intravenous cyclophosphamide. Outcome: The treatment resulted in significant improvement of her symptoms, laboratory data, and radiologic findings. Lessons: PR3-ANCA-positive HP can present not only in the elderly, but also in adolescence, and prompt diagnosis and treatment with immunosuppressive therapy is vital.