Malignant meningioma with adenocarcinoma-like metaplasia: demonstration of intestinal phenotype.

Meningiomas show a diverse histopathologic appearance, often referred to as metaplastic changes; however, adenocarcinoma-like metaplasia is an extremely rare condition. Here, we present a novel case. A dura-based bulky mass located in the right frontotemporal region was identified radiologically in an 83-year-old woman. The tumor, yellow to ash-gray in color, was subtotally removed. Histopathological examination revealed robust adenocarcinoma-like structures within a conventional meningothelial neoplasm. Meningioma elements showed a WHO grade I to III histology. Morphological and immunophenotypic transition between meningothelial and columnar epithelial cells was confirmed on detailed observation. It was of note that the adenocarcinomatous components shared an immunophenotype with intestinal epithelium, expressing CDX2, MUC2 and cytokeratin 20. The present case could be differentiated from secretory meningioma based on distinct cellular atypia, lack of intracytoplasmic lumina and pseudosammoma bodies, and the intact status of the KLF4 gene. In addition, the morphological and immunophenotypic transition excluded the possibility of metastatic carcinoma within meningioma. This is the first reported case of meningioma with adenocarcinoma-like metaplasia harboring an intestinal immunophenotype.

Distinct Clinicopathologic Features and Possible Pathogenesis of Localized ALK-positive Histiocytosis of the Breast.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare emerging entity characterized by systemic or localized proliferation of histiocytes harboring ALK rearrangements. Breasts are reportedly affected by ALK-positive histiocytosis. Here, we evaluated 2 localized cases of breast ALK-positive histiocytosis through a comprehensive clinicopathologic, molecular, and genomic analysis to further delineate this entity and better understand its pathogenesis. The cases involved 2 undiagnosed ALK-positive spindle-cell breast lesions. Both cases were Asian women aged 30s to 40s who underwent excisions for asymptomatic breast masses. Macroscopically, both lesions were well-circumscribed, solid masses. Microscopically, both lesions were predominantly composed of fascicles with uniform, bland spindle cells, admixed with epithelioid histiocyte-like cells and lymphoid aggregates. Immunohistochemically, the spindle and epithelioid cells coexpressed ALK and histiocytic markers (eg, CD68, CD163). Genetically, both lesions harbored KIF5B-ALK, confirmed by fluorescence in situ hybridization and polymerase chain reaction-direct sequencing analyses. Combining these results, both cases were successfully diagnosed as ALK-positive histiocytosis. Furthermore, no common or previously annotated somatic alterations were identified by whole-exome sequencing. One case harbored clonal immunoglobulin gene rearrangements according to the polymerase chain reaction-based BIOMED-2 protocol. Therefore, ALK-positive histiocytosis can be accurately diagnosed through a combination of morphologic, immunohistochemical, and molecular analyses. In this entity, breast cases may have distinct clinicopathologic features: Asian women aged 30s to 40s, asymptomatic masses, and predominant spindled morphology. For pathogenesis, ALK rearrangements could be the driver alteration, and a subset of ALK-positive histiocytosis may harbor a lymphoid lineage. These findings can be utilized to improve the diagnosis of ALK-positive histiocytosis and better understand its pathogenesis.

Mucinous cystadenoma of the pancreas with huge mural hematoma.

A 60-year-old woman was referred for evaluation of a cystic mass in the pancreatic body that extended to the tail. Transabdominal ultrasonography demonstrated an oval cystic mass 24 cm in diameter, filled with debris. On the cyst wall there was a wide-based, smooth-surfaced, heterogeneous high-echoic protrusion that was 5 cm in diameter. On CT the protrusion showed internal enhancement. Endoscopic pancreatography showed no intraductal mucin or communication with the cyst. A distal pancreatectomy was performed under the diagnosis of mucinous cystadenocarcinoma. Grossly there was a brownish, hemispherical protrusion into the thin monolocular cyst. The cut surface of the protrusion showed a peripheral yellow-brownish area and an internal wine-colored area. Histopathologically the cyst wall consisted of tall columnar cells without atypical nuclei, ovarian-type stroma beneath the epithelium, and fibrotic tissue with abundant capillary vessels, suggestive of a mucinous cystadenoma. The protrusion was composed of peripheral organized hematoma without a covering epithelium, and internal hemorrhage and many capillary vessels, with no evidence of tumor cell necrosis. These histopathological findings appear to be similar to those of chronic expanding hematoma. The formation of a huge mural hematoma in a mucinous cystic neoplasm can occur as a repair process after the breaking of intrawall vessels.

Growth process of small pancreatic carcinoma: a case report with imaging observation for 22 months.

This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the low-echoic mass as a benign intraductal mucinous-papillary neoplasm (IPMN) based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.

Promoter hypomethylation of SKI in autoimmune pancreatitis.

The relationship between methylation abnormality and autoimmune pancreatitis (AIP)-a representative IgG4-related disease-has not yet been elucidated. We identified SKI might have a significant methylation abnormality in AIP through methylation array analysis using the Illumina Infinium Human Methylation 450K BeadChip array, and investigated the relationship of SKI with AIP clinicopathological features. The methylation rate of SKI was assessed by quantitative SYBR green methylation-specific PCR, and the degree of SKI expression in tissue specimens was assessed by immunohistochemistry in 10 AIP cases, 14 cases of obstructive pancreatitis area in pancreatic ductal adenocarcinoma (PDA) without a history of AIP, and 9 normal pancreas (NP) cases. The SKI methylation ratio was significantly lower in AIP than in PDA and NP. Additionally, the immunohistochemical staining-index (SI) score for SKI was significantly higher in AIP than NP, although there was no significant difference between AIP and PDA. There was a strong negative correlation between SI score and SKI methylation ratio, and between the serum concentrations of IgG4 and the SKI methylation ratio. There was a moderate positive correlation between the serum concentrations of IgG4 and SI. SKI is thought to be an oncogene indicating that SKI hypomethylation and carcinogenesis might be linked to AIP. Furthermore, the correlation between serum concentrations of IgG4 and SKI methylation levels suggest SKI might be involved in the pathogenesis of AIP. However, the role of SKI has not been clearly elucidated. Further studies are needed to understand further the function of SKI.

Distribution of intraductal lesions in small invasive ductal carcinoma of the pancreas.

AIMS: To investigate the distribution of intraductal lesions in small invasive ductal carcinoma (IDC) of the pancreas. METHODS: In 21 cases with IDCs microscopically < or = 20 mm in diameter, the intraductal lesions around a mass were studied histologically and mapped according to the pancreatic intraepithelial neoplasia (PanIN) classification. RESULTS: PanIN-3, PanIN-2, PanIN-1B and PanIN-1A were found in 17, 10, 20 and 21 of 21 cases, respectively, and were divided into lesions in adjacent and distal areas, respectively defined as within and beyond 10 mm from the mass as follows: 100% (17/17), 100% (10/10), 95.0% (19/20) and 90.5% (19/21) in the former, while 23.5% (4/17), 50.0% (5/10), 90.0% (18/20) and 95.2% (20/21) in the latter. PanIN-3 lesions were predominantly found in the area adjacent to the mass. In some cases, significant PanIN-3 appeared to show a consecutive geographic extension around the mass via the main pancreatic duct (MPD). The distance of PanIN-3 spread was within 25 (mean 10.5) mm from the mass edge. PanIN-2 lesions were found in the area adjacent to the mass and discontinuous with the mass or PanIN-3 lesions. PanIN-1B and PanIN-1A tended mainly to exist sporadically throughout the entire pancreas. In the MPD, PanIN-3 was found in 14 (82.4%) of 17 cases and in 36 (32.1%) of 112 lesions, which was most frequent in intraductal lesions. CONCLUSIONS: PanIN-3 lesions might be an intraductal extension of the main tumor. The resection margin of 25 mm, at least longer than 11 mm, from the mass edge will be necessary.

Methylation of Tumor Suppressor Genes in Autoimmune Pancreatitis.

OBJECTIVES: Autoimmune pancreatitis (AIP) is a representative IgG4-related and inflammatory disease of unknown etiology. To clarify mechanisms of carcinogenesis resulting from AIP, we focused on methylation abnormalities and KRAS mutations in AIP. METHODS: Six tumor suppressor genes (NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK, and p16) that exhibited hypermethylation in pancreatic carcinoma were selected for quantitative SYBR green methylation-specific polymerase chain reaction in 10 AIP specimens, 10 pancreatic adenocarcinoma cases without history of AIP containing carcinoma areas (CAs) and noncarcinoma areas (NCAs), and 11 normal pancreas (NP) samples. KRAS mutation in codons 12, 13, and 61 were also investigated using direct sequencing. RESULTS: Hypermethylation events (≥10%) were identified in NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK, and p16 in 1, 2, 2, 0, 2, and 0 CA cases, respectively, but not in these 6 candidate genes in AIP, NCA, and NP. However, the TFPI2 methylation ratio was significantly higher in AIP than NCA and NP. Direct sequencing results for KRAS showed no single-point mutations in AIP. CONCLUSIONS: These are the first studies characterizing methylation abnormalities in AIP. AIP's inflammatory condition may be related to carcinogenesis. Further study will elucidate methylation abnormalities associated with carcinogenesis in AIP.

Plasma cell leukemia producing monoclonal immunoglobulin E.

A 78-year-old male with lumbar pain and dim consciousness presented the clinical pictures of plasma cell leukemia (PCL) producing a large amount of monoclonal immunoglobulin E (IgE)/kappa protein. Laboratory investigation demonstrated an elevated serum calcium level and renal dysfunction. Systemic bone X-ray survey disclosed only a solitary osteolytic lesion. Circulating plasma cells demonstrated CD19(-)/CD56(-) and MPC-1(-)/CD49e(-)/CD45(+/-), the latter indicating the immature phenotype of the tumor cells. Bone marrow was occupied with immature, atypical plasma cells, of which cytoplasms were positive for IgE by direct immunofluorescence analysis. Chromosomes revealed a translocation of (11;14)(q13;q32), which is concordant with cyclinD1-protein overexpression by immunohistochemistry. He was treated with dexamethasone and vincristine, which somewhat improved the laboratory findings. He died of tumor progression after 4-month admission. The clinical and biological characteristics of IgE-producing PCL, a very rare type of plasma cell dyscrasia, are discussed, reviewing the past literature.

Intraductal carcinoma with complex fusion of tubular glands without macroscopic mucus in main pancreatic duct: dilemma in classification.

An 84-year-old man, who was being followed up after lobectomy for lung carcinoma, was referred for evaluation of a dilated main pancreatic duct (MPD) from the body to the tail. Endoscopic ultrasonography demonstrated a low-echo mass occupying the MPD from the body to the tail. Endoscopic retrograde pancreatography showed an occlusion of the MPD in the body, and brush cytology indicated malignant cells. Distal pancreatectomy was performed. Grossly, a white-yellow, irregular-shaped solid mass without macroscopic mucus filled the lumen of the MPD. Histologically, the mass consisted of a complex fusion of tubular glands with atypical nuclei, which did not have intracellular mucus and oncocytic cytoplasm. The tumor mass showed abrupt transition to the normal epithelium. Immunohistochemically the tumor cells were partially positive for mucin 1 (MUC1) and MUC6, and negative for MUC2, MUC5AC, and lipase. Unfortunately the patient died of brain metastasis from lung carcinoma 15 months later. A review of reported cases of intraductal tubular tumors of the pancreas showed that the present case involved characteristics and immunohistochemical staining pattern similar to those of intraductal tubular carcinoma, although it might not be described as a typical intraductal tubular carcinoma under the existing Japanese rules.

[Imaging of gastrointestinal stromal tumor (GIST): relation between CT findings and grade of malignancy].

PURPOSE: To report the relation between CT findings and the grade of malignancy in gastrointestinal stromal tumor (GIST), especially the uncommitted type of GIST. MATERIALS AND METHODS: A total of 14 patients with histologically proven GIST (uncommitted type) underwent CT. Tumors were divided into three grades. HISTOLOGICALLY: Benign (mitotic index [MI] < 2/10 high-power fields [HPF]), borderline (2/10 HPF < or = MI < or = 5/10 HPF), and malignant (5/10 HPF < MI). We evaluated tumor size, cystic component, margin, and early enhancement. RESULTS: All benign tumors were smaller than 5 cm, and most malignant tumors reached 5 cm. The size of borderline tumors was between the sizes of benign and malignant tumors. No benign tumors had cystic components, whereas all borderline and malignant tumors except for one case had cystic components. Only two huge malignant tumors had unclear margins. The relation between early enhancement and the grade of malignancy showed no tendency, but all duodenal tumors showed marked early enhancement irrespective of grade. CONCLUSION: The grade of malignancy of GIST (uncommitted type) and size, presence of cystic components, and margin were highly correlated. That is, 1) tumors smaller than 5 cm with no cystic components can be diagnosed as benign, whereas 2) tumors that have cystic components are borderline or malignant. 3) Tumors that have cystic components and unclear margin can be diagnosed as actively malignant.