Recognition and pathological features of periampullary region adenocarcinoma with an indeterminable origin.

Determination of the primary tumor in periampullary region carcinomas can be difficult, and the pathological assessment and clinicopathological characteristics remain elusive. In this study, we investigated the current recognition and practices for periampullary region adenocarcinoma with an indeterminable origin among expert pathologists through a cognitive survey. Simultaneously, we analyzed a prospective collection of cases with an indeterminable primary tumor diagnosed from 2008 to 2018 to elucidate their clinicopathological features. All cases with pathological indeterminable primary tumors were reported and discussed in a clinicopathological conference to elucidate if it was possible to distinguish the primary tumor clinically and pathologically. From the cognitive survey, over 85% of the pathologists had experienced cases with indeterminable primary tumors; however, 70% of the cases was reported as pancreatic cancer without definitive grounds. Interpretation of the main tumor mass varied, and no standardized method was developed to determine the primary tumor. During a prospective study, 42 of the 392 periampullary carcinoma cases (10.7%) were considered as tumors with a pathological indeterminable origin. After the clinicopathological conferences, 21 (5.4%) remained indeterminable and were considered final indeterminable cases. Histological studies showed that the tumors spread along both the bile duct and main pancreatic duct; this was the most representative finding of the final indeterminable cases. This study is the first to elucidate and recognize the current clinicopathological features of periampullary region adenocarcinomas with an indeterminable origin. Adequate assessment of primary tumors in periampullary region carcinomas will help to optimize epidemiological data of pancreatic and bile duct cancer.

A case of recurrent constrictive pericarditis induced by pericardial substitution with an expanded polytetrafluoroethylene membrane.

A 72-year-old man presented with recurrent constrictive pericarditis, which developed 6 months after pericardiectomy, and pericardial substitution with an expanded polytetrafluoroethylene membrane. Re-pericardiectomy was performed. A new thick membranous structure had grown under the expanded polytetrafluoroethylene membrane anterior to the right ventricle, and was firmly adhered to the epicardium. This new structure exhibited collagenous fiber-based fibrotic thickening, and resembled a foreign body reaction. It was surmised that recurrence of constrictive pericarditis may have been induced by the expanded polytetrafluoroethylene membrane. Heart failure resolved after the operation; however, the patient died of respiratory failure on postoperative day 6.

Protein induced by vitamin K absence or antagonist II (PIVKA-II) producing large cell neuroendocrine carcinoma (LCNEC) of lung with multiple liver metastases: A case report.

A 78-year-old man was admitted to our hospital for multiple lung and liver tumors. Initial clinical diagnosis was hepatocellular carcinoma (HCC) with lung metastases because of a high value of serum protein induced by vitamin K absence or antagonist II (PIVKA-II) (6,705 mAU/mL). However, a review of a prior CT showed the lung tumor had existed 6 months before liver tumors were detected. The tumors progressed rapidly and the patient died 37 days after admission. Autopsy revealed that both lung and liver tumors exhibited the histology of large cell neuroendocrine carcinoma (LCNEC). Immunohistochemistry revealed that the tumor cells expressed not only neuroendocrine markers but also PIVKA-II diffusely. Hepatoid differentiation was not detected. Background liver did not show any chronic liver disease. The final diagnosis was PIVKA-II producing LCNEC of the lung with multiple liver metastases. PIVKA-II producing tumors other than HCC are extremely rare. To our best knowledge, this is the first case report of PIVKA-II producing neuroendocrine tumors of the lung.

Low Expression of S100P Is Associated With Poor Prognosis in Patients With Clear Cell Adenocarcinoma of the Ovary.

OBJECTIVE: The S100P protein stimulates cell proliferation and survival, thereby contributing to cancer progression. The purposes of this study were to evaluate S100P expression in ovarian clear cell adenocarcinoma and to determine whether S100P expression was correlated with the clinicopathological features or prognoses of patients with clear cell adenocarcinoma. METHODS: We examined S100P expression in 30 ovarian clear cell adenocarcinoma specimens using immunohistochemistry analysis. The Kaplan-Meier method was used for analysis of overall survival, and comparisons were made based on the log-rank test. RESULTS: Negative staining for nuclear S100P was associated with a poor prognosis as compared with that of positive staining for nuclear S100P in specimens from patients with clear cell adenocarcinoma. CONCLUSIONS: These data suggested that S100P may serve as an independent prognostic factor and marker for acquired resistance to chemotherapeutic drugs in clear cell adenocarcinoma.

Clinicopathological features of primary leiomyosarcoma of the gastrointestinal tract following recognition of gastrointestinal stromal tumours.

AIMS: We aimed to elucidate the clinicopathological and immunohistochemical features of leiomyosarcoma (LMS) of the gastrointestinal (GI) tract. METHODS AND RESULTS: We encountered seven cases of GI-LMS in the colon (n = 4), rectum (n = 1), jejunum (n = 1) and stomach (n = 1). They ranged from 1 to 25 cm (median, 8.5 cm) in size and had high mitotic counts (median 38 per 50 high-power fields). Morphologically, the tumours were composed mainly of spindle cells with eosinophilic cytoplasm and various degrees of nuclear atypia and pleomorphism. Immunohistochemically, the tumours were positive for α-smooth muscle actin (86%), muscle-specific actin (71%), desmin (86%), calponin (71%), h-caldesmon (57%) and smoothelin (71%). All were negative for KIT, CD34, protein kinase C theta and DOG1. Local recurrence and distant metastasis occurred in one and three patients, respectively. We then reviewed 55 cases of GI-LMS from the era following the recognition of gastrointestinal stromal tumours. Among 29 of 55 cases for whom follow-up information was available, the estimated 5-year overall survival rate was 51.6%; tumour size ≥5 cm was correlated significantly with shorter overall survival time (P = 0.0016), while mitotic count (≥50 or ≥100 per 50 high-power fields) proved to be no prognostic factor. CONCLUSIONS: GI-LMSs have distinctive clinicopathological and immunohistochemical features and exhibit aggressive biological behaviour.

A case of apoplectic lymphocytic hypophysitis complicated by polymyalgia rheumatica.

A case of apoplectic lymphocytic hypophysitis complicated by polymyalgia rheumatica (PMA) is described. A 72-year-old man was admitted to our hospital due to severe headache. Two months prior to admission, the patients had exhibited recent-onset stiffness and myalgia of shoulder and pelvic girdle that was compatible with PMR. Magnetic resonance imaging revealed a mass lesion in the pituitary fossa with focal hemorrhage. Endocrinologic studies demonstrated hypopituitarism. The headache and myalgia were improving with corticosteroid treatment; however, a trans-sphenoidal surgery was performed due to visual field loss. A white-colored mass was resected, and histologic examination showed diffuse infiltration of lymphocytes and plasma cells consistent with lymphocytic hypophysitis. Post-operatively, the headache and visual field loss resolved completely. This is the first documented case of apoplectic lymphocytic hypophysitis complicating PMR, and a possible mechanism for this rare association was discussed.

Histological Remission during Corticosteroid Therapy of Overlapping Nonalcoholic Steatohepatitis and Autoimmune Hepatitis: Case Report and Literature Review.

Concurrence of nonalcoholic steatohepatitis (NASH) with autoimmune hepatitis (AIH) is a rare condition that is challenging to diagnosis, due to the relatively high prevalence of autoantibodies in NASH. It is also difficult to determine the most effective treatment as corticosteroids are likely to worsen NASH despite being effective in the treatment of AIH. In this case report, we present a female diagnosed with NASH-AIH overlap with accompanying diabetes mellitus, who successfully achieved normalization of serum alanine aminotransferase levels following prednisolone therapy and weight loss. A follow-up liver biopsy performed 40 months after the initial diagnosis showed only minimal inflammatory infiltrates in the portal area without any NASH histology. Resolution of NASH, in conjunction with a reduction in hepatic fibrosis, might suggest that prednisolone itself does not aggravate steatohepatitis, but rather prevents disease progression. Appropriate immunosuppressive treatment may therefore be an important component of the optimum therapy for NASH-AIH overlap.

Thyroid papillary carcinoma with solid sclerosing change in IgG4-related sclerosing disease.

IgG4-related sclerosing disease (IgG4-RSD) is an inflammatory and fibrosing disorder characterized by lymphoplasmacytic inflammation with infiltration of various organs, including the pancreas, bile ducts, lung, kidney, and retroperitoneum. As for malignancy in IgG4-RSD, only limited literature is available. We report here a case of thyroid papillary carcinoma showing unique morphology in IgG4-RSD. Solid tumor nests were surrounded by dense IgG4-positive plasma cells and fibrosis at both the primary site and metastatic lymph nodes. In contrast the background thyroid showed focal lymphocytic thyroiditis. IgG4-related sclerosing sialadenitis and autoimmune pancreatitis were also diagnosed, and prednisolone treatment improved symptoms and serum IgG4 abnormality. To the best of our knowledge, this is the first documentation of a malignancy of the thyroid gland occurring in a background of IgG4-RSD. A brief review of the literature on the relationship between IgG4 and malignancy is included.

First Japanese patient treated with parathyroid hormone peptide immunization for refractory hypercalcemia caused by metastatic parathyroid carcinoma.

Patients with unresectable parathyroid carcinoma develop severe hypercalcemia, bone fractures and renal failure, and become unresponsive to conventional treatments. It has been shown that successful induction of anti-parathyroid hormone (PTH) antibodies, using PTH peptide fragments for immunisation, normalized serum levels of calcium as well as improved clinical symptoms. Here, we report our experience of PTH immunization in a Japanese female suffering from refractory hypercalcemia and renal failure caused by unresectable metastatic parathyroid carcinoma. Upon immunization, there were apparent clinical responses including reduction of serum levels of Ca along with anti-PTH antibodies induction. Therefore, we concluded that PTH immunization was an effective treatment against hypercalcemia caused by metastatic parathyroid carcinomas that are unresponsive to conventional treatments.

Apical membrane localization of glycogen synthase kinase 3beta protein in normal colon epithelium and aberrant distribution in colorectal cancer.

Glycogen synthase kinase 3beta (GSK-3beta) was subsequently shown to function in a wide range of cellular processes. GSK-3beta is a multifunctional serine/threonine kinase which performs a role in several signaling pathways including Wnt signal transduction. Recently, the activity of membrane-localized GSK-3beta has been shown to be crucial for initiation of Wnt cascade. In our study, the membrane localization of GSK-3beta was found on the apical membrane of normal epithelium, where co-localized and directly bound with MUC1. In colorectal cancer, depolarized cells showed the aberrant distribution of GSK-3beta on the cellular membrane with beta-catenin nuclear accumulation. The aberrant distribution of the membrane-localized GSK-3beta may contribute to the development of colorectal cancer.

Expression of angiopoietin-1, 2 and 4 and Tie-1 and 2 in gastrointestinal stromal tumor, leiomyoma and schwannoma.

AIM: To investigate the role of angiopoietin (Ang) -1, -2 and -4 and its receptors, Tie-1 and -2, in the growth and differentiation of gastrointestinal stromal tumors (GISTs). METHODS: Thirty GISTs, seventeen leiomyomas and six schwannomas were examined by immunohistochemistry in this study. RESULTS: Ang-1, -2 and -4 proteins were expressed in the cytoplasm of tumor cells, and Tie-1 and -2 were expressed both in the cytoplasm and on the membrane of all tumors. Immunohistochemical staining revealed that 66.7% of GISTs (20 of 30), 76.5% of leiomyomas (13 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-1. 83.3% of GISTs (25 of 30), 82.4% of leiomyomas (14 of 17) and 100% of schwannomas (6 of 6) were positive for Ang-2. 36.7% of GISTs (11 of 30), 58.8% of leiomyomas (10 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-4. 60.0% of GISTs (18 of 30), 82.4% of leiomyomas and 100% of schwannomas (6 of 6) were positive for Tie-1. 10.0% of GISTs (3 of 30), 94.1% of leiomyomas (16 of 17) and 33.3% of schwannomas (2 of 6) were positive for Tie-2. Tie-2 expression was statistically different between GISTs and leiomyomas (P < 0.001). However, there was no correlation between expression of angiopoietin pathway components and clinical risk categories. CONCLUSION: Our results suggest that the angiopoietin pathway plays an important role in the differentiation of GISTs, leiomyomas and schwannomas.