Concordance of the histological diagnosis of type 1 autoimmune pancreatitis and its distinction from pancreatic ductal adenocarcinoma with endoscopic ultrasound-guided fine needle biopsy specimens: an interobserver agreement study.

The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss' к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.

Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder.

Aberrant activation of the Ras/Raf/ERK (extracellular-signal-regulated kinase)-MAPK (mitogen-activated protein kinase) pathway is involved in the progression of cancer, including urothelial carcinoma; but the negative regulation remains unclear. In the present study, we investigated pathological expression of Spred2 (Sprouty-related EVH1 domain-containing protein 2), a negative regulator of the Ras/Raf/ERK-MAPK pathway, and the relation to ERK activation and Ki67 index in various categories of 275 urothelial tumors obtained from clinical patients. In situ hybridization demonstrated that Spred2 mRNA was highly expressed in high-grade non-invasive papillary urothelial carcinoma (HGPUC), and the expression was decreased in carcinoma in situ (CIS) and infiltrating urothelial carcinoma (IUC). Immunohistochemically, membranous Spred2 expression, important to interact with Ras/Raf, was preferentially found in HGPUC. Interestingly, membranous Spred2 expression was decreased in CIS and IUC relative to HGPUC, while ERK activation and the expression of the cell proliferation marker Ki67 index were increased. HGPUC with membranous Spred2 expression correlated significantly with lower levels of ERK activation and Ki67 index as compared to those with negative Spred2 expression. Thus, our pathological findings suggest that Spred2 counters cancer progression in non-invasive papillary carcinoma possibly through inhibiting the Ras/Raf/ERK-MAPK pathway, but this regulatory mechanism is lost in cancers with high malignancy. Spred2 appears to be a key regulator in the progression of non-invasive bladder carcinoma.

Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis.

In patients presenting with synchronous or metachronous multiple lung cancer (MLC), it is important to distinguish between multiple primary lung cancer (MP) and intrapulmonary metastasis (IM). The present study was aimed at investigating the mutational profiles of synchronous/metachronous MLC and to compare the classification of paired tumors by multiplex gene mutation analysis with the histopathological evaluation. We carried out targeted sequencing of 20 lung cancer-related oncogenes using next-generation sequencing (NGS) in 82 tumors from 37 MLC patients who underwent surgical resection at our department. The patients were diagnosed as MP or IM cases based on the Martini and Melamed criteria, histopathological and gene mutational evaluations. Matching mutations between paired tumors was observed in 20 (54%) patients, who were diagnosed as IM cases by mutational evaluation. Patients who could not be clearly diagnosed by histopathological evaluation were classified as equivocal cases. Among the histopathological IM cases (n = 7), six (86%) were confirmed as IM cases also by mutational evaluation, and most of the paired tumors of these cases (n = 5) harbored multiple matching mutations. Among the histopathological MP cases (n = 17), mutational evaluation yielded a discordant diagnosis in eight (47%) cases. Of these, the paired tumors of four cases harbored multiple matching mutations, suggesting that the mutational diagnosis might be more suitable in these patients. Our findings suggest that multiplex mutational analysis could be a useful complementary tool for distinguishing between MP and IM in addition to histopathological evaluation.

Molecular Subtypes of Breast Cancers from Myanmar Women: A Study of 91 Cases at Two Pathology Centers

Background: Breast cancer is the most common cancer in Myanmar women. Revealing the hormonal receptor status, human epidermal growth factor receptor 2 (HER2) and Ki-67 expression is useful for estimating patient prognosis as well as determination of treatment strategy. However, immunohistochemical features and classification of molecular subtypes in breast cancers from Myanmar remain unknown. Methods: The clinicopathological features of 91 breast cancers from Myanmar women were examined. Immunohistochemistry was performed on tissue specimens with antibodies to estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki-67, cytokeratin (CK)5/6 and CK14. Immunohistochemistry-based molecular subtyping was conducted. Results: Breast cancers in Myanmar women were relatively large, high grade with frequent metastatic lymph nodes. Of the 91 patients, tumors with ER positive, PgR positive, and HER2 positive were 57.1%, 37.4%, and 28.6%, respectively. The most prevalent subtype was luminal B (HER2-) (39.6%), followed by HER2 (22.0%), triple negative (TN)-basal-like (12.1%), luminal A (11.0%), TN-null (8.8%) and luminal B (HER2+) (6.6%). The mean Ki-67 expression of 91 cases was 33.9% (33.9% ± 19.2%) and the median was 28% (range; 4%-90%). The mean Ki-67 expression of luminal A, luminal B, HER2 and TN-basal-like/ null was 7%, 30%, 40%, and 57%/43%, respectively. A higher Ki-67 expression significantly correlated with a higher grade, larger size and higher stage of malignancy. Conclusions: We, for the first time, investigated the histopathological features of breast cancers from Myanmar women. Myanmar breast cancers appeared to be aggressive in nature, as evidenced by high frequency of poor-prognosis subtypes with high level of Ki-67 expression.

Time-dependent image changes after ethanol injection into the pancreas: an experimental study using a porcine model.

BACKGROUND: Ethanol, a commonly available agent, has been used to successfully ablate cystic and solid lesions in the pancreas. The aim of this study is to investigate the effects of an ethanol injection into the porcine pancreas and observe the time-dependent image changes in the pancreatic parenchyma. METHODS: Pure ethanol was injected into the pancreatic tail using a 25-gauge EUS needle with direct ultrasound guidance under celiotomy: 1 mL and 2 mL were injected, respectively. The abdomen was closed after the injection. MRI was performed before the procedure, immediately after, and on postoperative day (POD) seven. Blood samples were taken before the procedure and on PODs one, three, five, and seven. The pigs were euthanised on POD seven. RESULTS: Immediately after the injection, linear high signal areas in the pancreatic tail on T2 and rounded speckled high signal areas on DWI images were detected in both animals, measuring 35 × 32 mm in the 1 mL injected pig and 42 × 38mm in the 2 mL injected pig. After POD seven, rounded high signal areas were noted on T2 images, measuring 22 × 18 mm and 36 × 28 mm respectively. On POD one, the 1 mL injected animal had a 53% elevation in serum amylase while the 2 mL injected animal had a 66% elevation. Histologically, cystic and necrotic changes in the parenchyma were observed, measuring 23 × 22 mm and 40 × 35 mm respectively. CONCLUSIONS: Our results, which are limited to normal pancreas, suggested that a 1 mL injection caused localised changes within the pancreas while a 2 mL injection induced more widespread changes beyond the pancreas. The effective area of ethanol was widespread immediately after injection, and then the area was reduced with cystic and necrosis changes.

Pancreatic Hepatoid Carcinoma Mimicking a Solid Pseudopapillary Neoplasm: A Challenging Case on Endoscopic Ultrasound-guided Fine-needle Aspiration.

A 59-year-old man was admitted to our hospital for treatment of a 45 mm pancreatic mass found during a medical examination. Endoscopic ultrasound-guided fine-needle aspiration cytology showed polygonal cells with pseudopapillary structures. The tumor cells were positive for nuclear/cytoplasmic ß-catenin and CD10, and negative for chromogranin A. After a tentative diagnosis of a solid pseudopapillary neoplasm, middle pancreatectomy was performed. Histologically, polygonal cells with abundant eosinophilic cytoplasm formed in the trabeculae and were immunohistochemically positive for HepPar1 and protein induced by vitamin K absence or antagonist-II. The tumor was finally diagnosed to be pancreatic hepatoid carcinoma. No recurrence occurred for 12 months, even without adjuvant chemotherapy.

Heart failure in which coronary spasms played an important role.

A 69-year-old woman was admitted for further examinations and treatment of chest pain. Emergency cardiac catheterization showed no significant stenosis on coronary angiograms; however, diffuse wall hypokinesis was observed on a left ventriculogram. After treating the patient's heart failure, cardiac catheterization was performed again. A spasm provocation test showed coronary spasms of the right and left coronary arteries. A right ventricular endomyocardial biopsy revealed denaturation and fibrosis of the myocardium under the endocardium, thus suggesting the presence of myocardial ischemia. This case highlights coronary spasms as a cause of heart failure.