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A 74-year-old male was admitted to Departments of Surgery, Toyonaka Municipal Hospital (Osaka, Japan) for treatment of a pancreatic tumor. Contrast enhanced computed tomography (CT) revealed a mass with small cystic lesions in the pancreatic head and body. Fluorodeoxyglucose-positron emission tomography/CT revealed an abnormal uptake of fluorodeoxyglucose, corresponding to the mass lesions. Upper gastrointestinal endoscopy revealed rough mucosa near the opening of the accessory pancreatic duct, and the mucosa biopsy exhibited adenocarcinoma with no mucin observed. The preoperative diagnosis was pancreatic intraductal tubulopapillary neoplasm (ITPN) with cancerous lesions, and a total pancreatectomy with splenectomy was performed. The resected tissue specimen revealed a solid tumor occupying the entire pancreas with intraductal growth into the main pancreatic duct. Histological examination revealed high-grade dysplastic cells in a tubulopapillary growth pattern without overt mucin production beyond the pancreatic duct. Immunohistochemical staining analysis of the tumor was positive for cytokeratin (CK)7, CK19 and mucin (MUC)1, and negative for MUC2, MUC5AC, MUC6 and caudal type homeobox 2. The tumor was finally diagnosed as pancreatic ITPN with associated invasive cancer. The patient remains well without evident recurrence nine months post-surgery. ITPN is a rare type of epithelial neoplasm of the pancreas, and is characterized by intraductal tubulo-papillary growth, ductal differentiation, limited intracellular mucin production, and cellular dysplasia. The present case report may contribute to improved understanding of how to effectively treat patients with ITPN.

A 56-year-old woman was referred to our hospital because of epigastric discomfort and jaundice. Contrast-enhanced computed tomography and gastrointestinal endoscopy revealed an ampullary tumor. A biopsy specimen showed adenocarcinoma of the ampulla of Vater. The carbohydrate antigen (CA19-9) level was elevated, but insulin and glucagon levels were in the normal range. Based on a diagnosis of adenocarcinoma of the ampulla of Vater, we performed subtotal stomach-preserving pancreatoduodenectomy with regional lymph node dissection. Postoperative histopathological examinations indicated both neuroendocrine carcinoma (40%) and adenocarcinoma (60%) components in the ampulla of Vater and regional lymph node metastasis. According to the 2010 WHO Classification of Tumours of the Digestive System, the diagnosis of mixed adenoneuroendocrine carcinoma (MANEC) of the ampulla of Vater was confirmed. The patient was treated for 6 months with oral administration of TS-1 as adjuvant chemotherapy. Currently, the patient is alive without recurrence 8 months after surgery. MANEC of the ampulla of Vater is rare. It is a highly malignant tumor, and the standardization of its treatment, including surgery, chemotherapy, and radiotherapy requires further study.

Perineuriomas are uncommon benign peripheral nerve sheath tumors that include soft tissue, sclerosing, reticular, and intraneural variants. Soft tissue perineuriomas arise in a wide anatomic distribution and mostly in patients older than 20 years of age. We report an atypical perineurioma in a 7-year-old girl. The tumor, located in the tongue, was uniformly hypercellular. The tumor cells were spindle-shaped with a slender, elongated, bipolar, wavy cytoplasmic process formation and wavy elongated nuclei, and the architecture was composed of predominantly short fascicles with areas exhibiting a vague storiform pattern. Although the tumor cells generally appeared bland, the tumor showed worrisome features including an infiltrative pattern and occasional mitotic figures. Psammoma bodies were observed in the periphery of the tumor. Immunohistochemically, the cells were positive for epithelial membrane antigen, vimentin, claudin-1, and GLUT-1, but negative for S-100 protein, CD34, and type IV collagen. The authors document a case of soft tissue perineurioma with atypical histological features that occurred in the tongue of a child.

We present an experimental study of the light emission from dye-doped polymer random media dispersed with TiO2 particles of various sizes, shapes, and structures. Random lasing with nonresonant feedback, similar to that for spherically shaped particles that are used for conventional random lasers, is observed for almost all types of particles and aggregates. The efficiency of random lasing for each medium is analyzed using the relationship between the emission spectrum and the transport mean free path (TMFP), which is measured by enhanced backscattering experiments. Results show that the peak emission intensity depends strongly on the particle shape and structure, whereas the spectral linewidth is governed by the TMFP.

PURPOSE The objective of our study was to compare T2-weighted magnetic resonance imaging (T2WI), combined T2-weighted and dynamic imaging (Dynamic), and combined T2-weighted and diffusion-weighted imaging (DWI) in the identification of the site of prostate cancer. MATERIALS AND METHODS Before radical prostatectomy, 85 patients with prostate cancer underwent magnetic resonance imaging using a 1.5-T endorectal coil; we excluded 3 patients treated with neoadjuvant hormonal therapy. The sites of prostate cancer in 82 patients were predicted by T2WI alone, T2WI + Dynamic, and T2WI + DWI, and the results were compared with the step-section analysis of radical prostatectomy specimens. The peripheral zone (PZ) and the transition zone (TZ) of the prostate were divided into left and right halves. Only tumors with a diameter of more than 5 mm were considered significant. RESULTS The sensitivity, specificity, positive predictive value (PPV), and the area under the receiver operating characteristic (ROC) curve (Az) for the prediction of the site of prostate cancer in the PZ of the prostate were as follows: 42%, 94%, 93%, and 0.76 for T2WI alone; 48%, 96%, 96%, and 0.78 for T2WI + Dynamic; and 50%, 96%, 96%, and 0.81 for T2WI + DWI. The sensitivity, specificity, PPV, and Az for the prediction of the site of prostate cancer in the TZ of the prostate were as follows: 31%, 92%, 76%, and 0.66 for T2WI alone; 46%, 82%, 67%, and 0.65 for T2WI + Dynamic; and 48%, 94%, 85%, and 0.71 for T2WI + DWI. CONCLUSION The Az value for the prediction of prostate cancer in the PZ and those in the TZ of the prostate was the highest for the combined T2WI and DWI approach.

A unique case of ganglioneuroma mimicking a lipomatous tumor in a 73-year-old man is reported. The tumor was incidentally found on radiography performed for unrelated reasons. Because of the fat element, CT and magnetic resonance imaging suggested myelolipoma inside or outside the right adrenal gland. The laparotomy indicated that the tumor was located on the right adrenal gland. It was well circumscribed but not encapsulated, and was approximately 2 cm in diameter. Microscopically, ganglioneuromatous component was scattered in the background of a large amount of adipose tissue. Because the presence of such a large amount of adipose tissue seems to be rare in ganglioneuromas, its histogenesis is discussed.

Reported herein is an unusual case of intrahepatic cholangiocarcinoma with lymphoepithelioma-like appearance in a 64-year-old man who was found to have an intrahepatic mass without cirrhosis. The tumor had two distinct histological patterns with dense lymphoplasmacytic infiltrate. The first was similar to nasopharyngeal undifferentiated carcinoma; the second pattern was a well-differentiated adenocarcinoma. Transition between the two components was observed in the same duct. Immunohistochemistry indicated that the tumor was immunoreactive with AE1/AE3 and cytokeratin (CK) 7, but negative for CEA and CK20. Stromal inflammatory infiltrate primarily consisted of plasma cells and lymphocytes. Immunohistochemical examination and in situ hybridization for EBV showed no integration of the virus in the tumor cells. Intrahepatic lymphoepithelioma-like carcinoma is rare, and most are associated with EBV. Only three cases were not associated with EBV. The authors would like to add one more example of the tumors not associated with EBV.

A 64-year-old man presented with epigastric discomfort and nausea. Laboratory analyses revealed increased levels of total and direct bilirubin, and increased levels of aminotransferases. Computed tomography revealed the presence of a mass in the distal common bile duct. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography revealed a 25 mm filling defect in the distal common bile duct, and biopsy of the lesion disclosed the presence of tubular adenoma. Using fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) revealed an increased accumulation of the tracer in the lesion, with a maximum standard uptake value (SUVmax) of 3.3. The patient received a pylorus-preserving pancreatoduodenectomy. The histopathological examination revealed a tubular adenoma with low-grade atypia. The patient remains alive 15 months following the surgery, with no evidence of recurrence of the adenoma. 18F-FDG PET has been successfully applied in clinical practice to detect a wide variety of tumor types, including lymphoma, lung, colon and bile duct cancer. In the present study, a case of bile duct adenoma with low-grade atypia was reported, revealing the uptake of 18F-FDG. 18F-FDG PET may be able to detect premalignant tumors of the bile duct, although whether 18F-FDG PET is able to differentially discriminate between diagnoses of adenoma and carcinoma of the bile duct remains to be fully elucidated, and the assessment of further case studies is required.

An 80-year-old man underwent colonoscopy for proctorrhagia. Conventional white-light imaging showed a superficially flat and elevated lesion that appeared to be a submucosal tumor of the sigmoid colon. Chromoendoscopy with Indigo Carmine showed that the margin of the tumor was covered with normal epithelium but that there was a slight depression on its surface. Magnification endoscopy with Crystal Violet staining revealed the amorphous surface structure of the depressed lesion, but the surrounding mucosa showed a normal pit pattern. Endoscopic ultrasonography demonstrated that a hypoechoic mass was located in the submucosal layer, and a biopsy specimen obtained from the surface of the lesion showed evidence of adenocarcinoma. We then performed sigmoidectomy on the patient. Immunohistochemically, the tumor cells were positive for two mismatch repair proteins (MLH1 and MSH2), but in situ hybridization revealed that the specimen was negative for the Epstein – Barr virus. We finally diagnosed the lesion as adenocarcinoma with a dome-like phenotype of the sigmoid colon.

Background Recently, it has become increasingly recognized that pulmonary hypertension (PH) is a particularly threatening result of left-sided heart disease. However, there have been few investigations of the impact of cardiopulmonary exercise testing (CPX) variables on PH in dilated cardiomyopathy (DCM). We evaluated the usefulness of crucial CPX variables for detecting elevated pulmonary arterial pressure (PAP) in patients with DCM. Methods Ninety subjects with DCM underwent cardiac catheterization and CPX at our hospital. Receiver operator characteristic (ROC) analysis was performed to assess the ability of CPX variables to distinguish between the presence and absence of PH. Results Overall mean values were: mean PAP (mPAP), 18.0 ± 9.6 mmHg; plasma brain natriuretic peptide, 233 ± 295 pg/mL; and left ventricular ejection fraction, 30.2 ± 11.0%. Patients were allocated to one of two groups on the basis of mean PAP, namely DCM without PH [mean PAP (mPAP)

A 74-year-old man with chronic hepatitis C was diagnosed with liver tumors. Contrast-enhanced computed tomography (CT) and ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) revealed hepatocellular carcinomas(HCC) in segments 8 (S8)and 5/8 (S5/8), and detected a lymph node (LN) swelling of 75 mm diameter in the posterior aspect of the pancreatic head. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) was positive for the swollen LN (SUVmax 12.3), but negative for the intrahepatic HCCs. The alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) values were elevated, and soluble interleukin- 2 receptor levels were also increased (1,440 U/mL). Based on a diagnosis of HCCs with either LN metastasis, or with malignant lymphoma, partial hepatectomy (S8 and S5/8), lymphadenectomy (#13LN), and cholecystectomy were performed. Histopathological examination indicated well differentiated HCC in S5/8, and moderately to poorly differentiated HCC in S8, while poorly differentiated HCC was detected in the LN. Therefore, the final diagnosis was HCCs with metastasis to #13LN originating from the HCC in S8. At present, the patient is alive without further extrahepatic recurrence. The extent of FDG accumulation is related to the degree of differentiation of the HCC; furthermore, there are discrepancies between the FDG uptake in intrahepatic and extrahepatic lesions.

The patient was a 73-year-old male with advanced gastric cancer in the lesser curvature of the antrum.Abdominal computed tomography revealed multiple liver metastases(S5, S8).He was diagnosed with clinical Stage IV gastric cancer (cT3N0M1H1).He received 3 courses of combined neoadjuvant chemotherapy with capecitabine, cisplatin, and trastuzumab because immunostaining indicated the tumor was human epidermal growth factor receptor 2(HER2)-positive.The therapeutic response, as assessed by imaging studies, was partial for the primary lesions and stable for liver metastases.Distal gastrectomy, D2 lymph node dissection, and S5 extended subsegmentectomy of the liver were performed.Histopathological findings indicated that both the primary tumor and liver metastases were neuroendocrine carcinoma.The patient declined post-operative adjuvant chemotherapy and he is alive 6 months after the surgery with no evidence of recurrence.Surgery with neoadjuvant chemotherapy appears to be a promising option for advanced gastric cancer with liver metastases.

A black-colored and well-circumscribed renal tumor in a 71-year-old woman is reported. The tumor was unique in that it was rich in vasculature and exclusively composed of perivascular epithelioid clear cells. Morphological features were reminiscent of conventional renal cell carcinoma (RCC). However, immunohistochemical examinations showed that the tumor cells did not express any epithelial markers, but diffusely and intensely expressed a melanocytic marker, gp-100/HMB-45. Another striking feature of the tumor was a large amount of cytoplasmic pigment that made the tumor wholly black. The pigment was not stained with Berlin-blue, completely bleached with potassium permanganate, and stained with Fontana-Masson staining, which suggests that the pigment was melanin. Morphological features and immunohistochemical findings indicated that the present tumor was an extreme example of a perivascular epithelioid clear cell tumor with a large amount of melanin, which has not been previously reported. One should be aware of the pure form of perivascular epithelioid clear cell tumor of the kidney because it is sometimes very difficult to differentiate this tumor from conventional RCC. Immunohistochemical examinations and the presence of cytoplasmic melanin can help the differentiation.

背景:glomus腫瘍は毛細血管の先端にある神経筋性装置に由来する良性腫瘍で, そのほとんどは四肢末端や爪床に発生する. 胃粘膜下腫瘍として発生し, 術中迅速細胞診にて推定し得たglomus腫瘍を経験したので報告する.症例:32歳, 女性. 高度貧血の原因精査の過程で, 出血を伴う胃粘膜下腫瘍が認められた. 術中の捺印細胞診では, 単一で異型度の低い腫瘍細胞が結合性の強い小集塊を形成しているのが認められた. クロマチンパターンが均上一で結合性の強い像からglomus腫瘍が疑われた. 組織診断において細胞像を反映する典型的なglomus腫瘍の像が確認され, 免疫組織染色の結果も併せて診断が確定した.結論:小型類円形の均一な腫瘍細胞からなる胃粘膜下腫瘍としてはcarcinoid腫瘍が鑑別にあげられるが, 腫瘍細胞の結合性の強さやクロマチンの性状から, その鑑別は比較的容易と考えられた.

背景:尿路腫瘍や尿路結核に対して腸管による代用膀胱・尿管の形成や, 腸管による膀胱拡大術が行われる. そのような治療を受けた患者の代用膀胱や腸管・膀胱吻合部に腫瘍が発生することが知られている. 尿管狭窄により回腸・膀胱吻合術を受けた女性の膀胱に巨大な絨毛腫瘍 (villoustumor) を経験したので, その細胞像を文献的考察も含めて報告する.症例:61歳, 女性. 6年前に腎結核のため右腎摘出. 26年前に尿管狭窄のため左腎盂尿管部回腸膀胱吻合術を受けた. 血尿と膣前庭に腫瘤を自覚して受診した. 尿道から粘液産生性の巨大な腫瘤が露出しており, 膀胱内は粘液と腫瘤で充満していた. 尿細胞診で軽度の異型を示す高円柱上皮からなる細胞集塊が認められた. 摘出膀胱には非浸潤性の巨大な腸型絨毛腫瘍 (villous tumor) が認められた.結論:尿路・腸管吻合術を受けた患者での特異な腫瘍発生を認識しておく必要があ

A case of esophageal carcinoma exclusively composed of adenocarcinoma simulating an esophageal gland duct in a 61-year-old man is presented. The tumor arose as a slightly elevated lesion in the middle intrathoracic esophagus. It was almost completely overlaid with non-neoplastic stratified squamous epithelial cells. Beneath the overlying surface epithelium, an adenocarcinoma that was bilayered in structure diffusely invaded both the mucosal and submucosal layers. Although the tumor consisted exclusively of adenocarcinomatous cells, a keratinizing squamous cell carcinoma component was focally observed. The invasive carcinoma was focally continuous with the small area of the surface squamous epithelial layer, which was confirmed to be neoplastic by immunohistochemistry. Morphological and immunohistochemical examinations suggested that the adenocarcinomatous component arose from the esophageal surface epithelium and clearly differentiated into an esophageal gland duct. It is important to consider the possibility of this type of adenocarcinoma when diagnosing a ductal or glandular lesion of the esophagus in small biopsy specimens.

A 43-year-old man presented with dyspnea on exertion. Right heart catheterization demonstrated pulmonary arterial hypertension (PAH). He was treated with bosentan, sildenafil and intravenous epoprostenol. Despite the administration of such intensive therapy, the patient's condition deteriorated to a World Health Organization functional class (WHO-FC) of IV. He participated in a clinical trial of imatinib for PAH. After three months of treatment with imatinib, the chest X-ray and echocardiography findings improved, and the WHO-FC class was III. One year after, however, the PAH worsened again, and the patient died 2.6 years after the first diagnosis. At autopsy, patchy capillary proliferation was observed in the lungs. The definitive diagnosis was pulmonary capillary hemangiomatosis.

BACKGROUND Pulmonary hypertension (PH) because of left-sided heart disease carries a poor prognosis. We investigated whether non-ischemic dilated cardiomyopathy (DCM) with PH is associated with poor prognosis. METHODS AND RESULTS A total of 256 consecutive DCM patients were enrolled. We measured the ratio of the maximum first derivative of left ventricular pressure (LVdP/dtmax)/systolic blood pressure and pressure half-time (T1/2) as cardiac function. Patients were allocated to 2 groups on the basis of mean pulmonary arterial pressure (mPAP), namely DCM without PH group (mPAP

Background Peak oxygen consumption (peak VO 2 ) and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) are prognostic in heart failure. We investigated whether LGE-CMR and peak VO 2 combined had additive value in risk stratifying patients with nonischemic dilated cardiomyopathy (DCM). Methods and Results Fifty-seven DCM patients underwent CMR and cardiopulmonary exercise testing. Cardiac events were cardiac death, hospitalization for decompensated heart failure, or lethal arrhythmia. Twenty-five (44%) were LGE-positive. The median peak VO 2 was 18.5 mL·kg -1 ·min -1 . On multivariate analysis, positive LGE ( P = .048) and peak VO 2 ( P = .003) were independent cardiac event predictors. Cardiac event risk was significantly higher with positive LGE and peak VO 2 -1 ·min -1 than with negative LGE and peak VO 2 ≥ 18.5 mL·kg -1 ·min -1 (hazard ratio 12.5; 95% CI 1.57–100; P = .017). In 3 patient groups (group A: no LGE, peak VO 2 ≥ 18.5 mL·kg -1 ·min -1 , n = 18; group B: positive LGE or peak VO 2 -1 ·min -1 , n = 24; group C: positive LGE and peak VO 2 -1 ·min -1 , n = 15) during follow-up (71 ± 32 months), group C had higher cardiac event rates than the others. Conclusions Combined assessment of LGE-CMR and peak VO 2 provides additive prognostic information in ambulatory DCM.

We evaluated the clonality of seborrheic keratoses using a polymorphism due to the random inactivation of one of two X chromosomes in females. Thirty-eight seborrheic keratoses obtained from the skin of females with polymorphism of the human androgen receptor (HUMARA) locus were examined by a fluorescent polymerase chain reaction procedure, which allowed accurate measurement of the peak intensities of each HUMARA allele. The epithelial portion of seborrheic keratosis and normal control epidermis adjacent to the seborrheic keratosis were removed by laser capture microdissection. As biopsied specimens of seborrheic keratoses contained small amounts of normal epidermis, the effect of digestion by a restriction enzyme (HhaI) recognizing the nonmethylated active sites was compared between seborrheic keratoses and normal control epidermis in only five seborrheic keratosis cases. Disappearance or significant reduction in intensity of one of two HUMARA alleles was observed after HhaI digestion in seborrheic keratoses, but not in the normal control epidermis. Although the skewing of the polymorphism was not corrected by the normal control epidermis in the remaining 33 seborrheic keratosis cases, one of two HUMARA peaks practically disappeared after HhaI digestion in 20 of 33 seborrheic keratosis cases. In total, 25 of 38 seborrheic keratoses were considered to be monoclonal. The histologic type of seborrheic keratoses did not affect clonality.

The microphthalmia (mi) locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (MITF). We have reported that expression of several genes was impaired in cultured mast cells (CMCs) of mi/mi mice due to a defective transactivation ability of mutant MITF (mi-MITF). We also found that mi/mi CMCs did not express a receptor (MC1R) for α-melanocyte-stimulating hormone. The overexpression of the wild-type (+/+) MITF but not mi-MITF normalized the expression of the MC1R in mi/mi CMCs, indicating the involvement of +-MITF in the MC1R gene expression. Next, we analyzed the promoter region of the MC1R gene by the transient cotransfection assay. The luciferase construct under the control of the MC1R promoter and the cDNA-encoding +-MITF or mi-MITF were cotransfected into NIH/3T3 fibroblasts. The cotransfection of +-MITF but not mi-MITF increased the luciferase activity. There were five CANNTG motifs recognized by bHLH-Zip-type transcription factors in the cloned promoter region. We found +-MITF bound two of five CANNTG motifs, and both motifs were essential for the transactivation of the MC1R gene by +-MITF. These results indicated that +-MITF directly transactivated the MC1R gene through these two motifs.

The proopiomelanocortin (POMC)-derived neuropeptide α-melanocyte stimulating hormone (α-MSH) is known to modulate some aspects of inflammation through direct effects on T cells, B cells, and monocytes. To determine whether α-MSH might similarly influence mast cell responsiveness, mast cells were examined to see if they expressed the receptor for α-MSH, melanocortin-1 (MC-1), and whether α-MSH altered mast cell function. We thus first identified MC-1 on bone marrow cultured murine mast cells (BMCMC) and a murine mast cell line (MCP-5) employing flow cytometry and through detection of specific binding. Subsequent treatment of mast cells with α-MSH increased the cAMP concentration in a characteristic biphasic pattern, demonstrating that α-MSH could affect intracellular processes. We next examined the effect of α-MSH on mediator release and cytokine expression. IgE/DNP-human serum albumin-stimulated histamine release from mast cells was inhibited by ∼60% in the presence of α-MSH. Although activation of BMCMC induced the expression of mRNAs for the inflammatory cytokines IL-1β, IL-4, IL-6, TNF-α, and the chemokine lymphotactin, mRNAs for IL-1β, TNF-α, and lymphotactin were down-modulated in the presence of α-MSH. Finally, IL-3-dependent proliferative activity of BMCMC was slightly but significantly augmented by α-MSH. Taken together, these observations suggest that α-MSH may exert an inhibitory effect on the mast cell-dependent component of a specific inflammatory response.

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). Mutant alleles of mi,Mior, and Miwh are deletion or point mutation of the basic domain by which MITF binds DNA. The basic domain also has nuclear localization potential. In the present study, we compared the mast cell abnormalities ofMior/Mior andMiwh/Miwh mice with those ofmi/mi mice, of which many have been described by us. The number of mast cells in the skin of Mior/Miorsuckling mice was remarkably decreased from that observed inmi/mi suckling mice, but the number was normal in the skin ofMiwh/Miwh suckling mice. The decrease in skin mast cells was more severe in the mi/mi embryos than inmi/mi suckling mice, but the magnitude of the decrease was comparable between Mior/Mior embryos and Mior/Mior suckling mice. The poor mRNA expression of granzyme B and tryptophan hydroxylase genes was observed in all cultured mast cells (CMCs) derived from the spleens ofMiwh/Miwh,Mior/Mior, and mi/mi mice. However, the poor expression of mouse mast cell protease-4 (MMCP-4), MMCP-5, and MMCP-6 was observed only inMior/Mior and mi/mi CMCs. MITF encoded by Miwh mutant allele (Miwh-MITF) showed deficient but demonstratable DNA binding, but mi-MITF and Mior-MITF did not show any DNA binding ability. Although Miwh-MITF and Mior-MITF showed normal nuclear localization potential, the potential was significantly impaired in mi-MITF. The rank order of mast cell abnormality (mi/mi >Mior/Mior >Miwh/Miwh) appears to be related to the functional abnormality of MITF encoded by each mutant gene.

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that expression of several genes was impaired in cultured mast cells (CMCs) ofmi/mi mice due to a defective transactivation ability of mutant MITF (mi-MITF). Because attachment of mi/mi CMCs to fibroblasts is impaired, we examined the expression of integrin genes in mi/mi CMCs in the present study. Among the integrin genes examined, the expression of integrin 4 subunit was barely detectable in mi/mi CMCs, and the 4 protein was not detected by flow cytometry either. The specific adhesion to vascular cell adhesion molecule-1 (VCAM-1), the ligand for 4 subunit, was observed in +/+ CMCs but not in mi/mi CMCs, indicating that the expression of integrin 4 subunit at a functional level did not occur in mi/mi CMCs. In the promoter region of the 4 subunit gene, there was a CACTTG motif to which normal MITF (+- MITF) bound. The coexpression of +-MITF but not of mi-MITF transactivated the promoter of the 4 subunit gene. The deletion or mutation of the CACTTG motif abolished the transactivation by +-MITF, suggesting that +-MITF directly transactivated the gene encoding 4 subunit of integrin.© 1998 by The American Society of Hematology.

Mouse mast cell protease (MMCP) mRNA expression was examined by in situ hybridization histochemistry. Peritoneal mast cells (PMCs) of WBB6F 1 -+/+ mice expressed MMCP-2, MMCP-4, MMCP-5, and MMCP-6 mRNAs, but did not express MMCP-1 mRNA. When proliferation of PMCs was induced by culturing them in methylcellulose with T cell-derived cytokines, cells in mast cell colonies expressed MMCP-1 mRNA. These mast cells were transferred to a suspension culture to induce further proliferation. The phenotype of the resulting PMC-derived cultured mast cells was similar to that of bone marrow-derived cultured mast cells. When 10 5 PMC-derived cultured mast cells or 10 5 bone marrow-derived cultured mast cells were injected into the stomach wall of mast cell-deficient WBB6F 1 - W/W v mice, mast cells that appeared in the mucosa and muscularis propria were similar to mast cells in the stomach of intact WBB6F 1 -+/+ mice, indicating the injected cells adapted to a new tissue environment. In contrast, when 10 5 PMCs were injected into the stomach wall of WBB6F 1 - W/W v mice, the injected PMCs did not adapt to the mucosa. When 20 PMCs were injected, they proliferated and adapted to the mucosal environment. The present results suggest that PMCs adapt to new environments when proliferation occurs before redifferentiation.

A 73-year-old woman who had underwent right lower lobectomy for adenocarcinoma of the lung( S10,pT1aN0M0, stage I A) 5 years before, visited our hospital with back pain. Whole body computed tomography (CT) revealed the enlargement of the abodominal lymph nodes surrounding the celiac artery,which was positive for fluorodeoxyglucose-positron emission tomography( FDG-PET). Open biopsy of the lymph node was performed and histopathological diagnosis was metastases of adenocarcinoma.Additional immunohistological examination showed positive findings for cytokeratin( CK) 7 and thyroid transcription factor( TTF)-1, but negative for CK20, suggesting the lesion to be metastases of lung cancer. Abdominal lymph node should be kept in mind in patients with lower lobe lung cancer.

The Ws mutant allele of rats represents a 12-base deletion at the tyrosine kinase domain of the c-kit gene. Although homozygous Ws/Ws rats were deficient in both connective tissue-type mast cells (CTMC) and mucosal-type mast cells (MMC), mast cells did develop when bone marrow cells of Ws/Ws rats were cultured in the presence of concanavalin A-stimulated spleen cell conditioned medium (ConA-SCM). Although the proliferative response of rat cultured mast cells (RCMC) derived from Ws/Ws rats to ConA-SCM was comparable to that of RCMC derived from control normal (+/+) rats, the proliferative response of Ws/Ws RCMC to rat recombinant stem cell factor (rrSCF; a ligand for the c-kit receptor tyrosine kinase) was much lower than that of +/+ RCMC. However, a slight c-kit kinase activity was detectable in Ws/Ws RCMC, and the proliferation of Ws/Ws RCMC was accelerated when rrSCF was added to ConA-SCM. Because CTMC contain rat mast cell protease-I (RMCP- I) and MMC contain RMCP-II, the phenotype of +/+ and Ws/Ws RCMC in various culture conditions was evaluated by immunohistochemistry of RMCPs. Both +/+ and Ws/Ws RCMC showed the MMC-like phenotype (RMCP-I- /II+) when they were cultured with ConA-SCM alone. Most +/+ RCMC and about half of Ws/Ws RCMC acquired a novel protease (RMCP-I+/II+) phenotype when they were cultured with rrSCF alone. However, because the number of Ws/Ws RCMC dropped to one-tenth in the medium containing rrSCF alone, the absolute number of Ws/Ws RCMC with the RMCP-I+/II+ phenotype did not increase significantly. The effect of rrSCF in inducing the novel phenotype was suppressed when ConA-SCM was added to rrSCF. In contrast, +/+ and Ws/Ws RCMC cocultured with +/+ fibroblasts showed the RMCP-I+/II+ phenotype even in the presence of ConA-SCM. Moreover, a fibroblast cell line derived from SI/SI mouse embryos that did not produce SCF did not support the survival of both +/+ and Ws/Ws RCMC but did induce the RMCP-I+/II+ phenotype in about half of +/+ and Ws/Ws RCMC when their survival was supported by the addition of ConA- SCM. The normal signal transduction through the c-kit receptor did not appear to be prerequisite for the acquisition of the RMCP-I+/II+ phenotype.

Psammocarcinoma is a serous peritoneal tumor arising from the ovary or the peritoneum and characterized by low-grade nuclear features, extensive psammoma bodies, and invasiveness. Only 62 cases have ever been documented, 30 primary peritoneal and 32 primary ovarian, most of which presented as small tumors. Adjuvant therapies, including chemotherapy and radiation, were performed in 12 of the primary peritoneal cases, without any clear evidence of benefit. We present a case of an unusually large primary peritoneal psammocarcinoma with unexpected outcome. The patient was a 38-year-old woman with a tumor of the peritoneum which adhered densely to the uterus and rectum and developed into the intra-abdominal cavity and retroperitoneal space. After adhesiolysis of the tumor and rectum, suboptimal surgical reduction left a 4 cm × 2 cm tumor segment. Postoperative chemotherapy, consisting of paclitaxel and carboplatin (TC) for 1 course, and cyclophosphamide and cisplatin (CP) for 5 courses, was conducted. The residual tumor responded completely to the chemotherapy and the patient is alive today, with no evidence of disease 15 months after the surgery. Our case implies that CP therapy is a potential regimen of postoperative remission-induction therapy for suboptimally resected primary peritoneal psammocarcinoma.

A 41-year-old man who had non-small cell lung cancer invading his right 3rd, 4th and 5th ribs with hilum lymph node swelling(cT3N1M0, cStage III A), received chemoradiation therapy, cisplatin(CDDP)/docetaxel, and 2 Gy/Fr of irradiation prior to surgery. But the therapy was discontinued due to interstitial pneumonitis on day 24, during 28 Gy of radiation. At that time, a PET-CT scan revealed the accumulation of FDG in the primary tumor, hilar lymph node, and one of the ipsilateral axillar lymph nodes, in which cancer cell presence was proven by aspiration needle cytology. We organized a radical operation even though the node status was classified to cStage IV, because ipsilateral axillary lymph nodes may be regarded as regional nodes for tumors invading the chest wall. Right upper lobectomy and chest wall resection were performed, and the ipsilateral hilar, mediastinal, and axillary lymphnode were dissected. Pathological findings showed no active cancer cell in the primary lesion and hilar lymph nodes(Ef. 3), but obvious metastasis in one of the axillary lymph nodes(pT0N0M1b, pStage IV). The patient received adjuvant chemotherapy(CDDP/vinorelbine), and is alive and tumor-free 10months after the resection.

Perineuriomas are uncommon benign peripheral nerve sheath tumors that include soft tissue, sclerosing, reticular, and intraneural variants. Soft tissue perineuriomas arise in a wide anatomic distribution and mostly in patients older than 20 years of age. We report an atypical perineurioma in a 7-year-old girl. The tumor, located in the tongue, was uniformly hypercellular. The tumor cells were spindle-shaped with a slender, elongated, bipolar, wavy cytoplasmic process formation and wavy elongated nuclei, and the architecture was composed of predominantly short fascicles with areas exhibiting a vague storiform pattern. Although the tumor cells generally appeared bland, the tumor showed worrisome features including an infiltrative pattern and occasional mitotic figures. Psammoma bodies were observed in the periphery of the tumor. Immunohistochemically, the cells were positive for epithelial membrane antigen, vimentin, claudin-1, and GLUT-1, but negative for S-100 protein, CD34, and type IV collagen. The authors document a case of soft tissue perineurioma with atypical histological features that occurred in the tongue of a child.

Proliferation of murine mast cells is induced by both T-cell-derived and fibroblast-derived growth factors. Because the most potent T-cell- derived mast cell growth factor, interleukin-3, promotes the migration of mast cells, we investigated whether fibroblast-derived growth factors had the chemoattractive activity as well. Conditioned medium (CM) of BALB/3T3 fibroblasts induced the migration of cultured mast cells (CMC) derived from normal (+/+) mice. BALB/3T3-CM contained the mast cell growth factor (MGF)/stem cell factor (SCF)/kit ligand (KL), which is the ligand for the receptor encoded by the W (c-kit) gene. CMC derived from the spleen of W/W mice lack the extracellular domain of the W (c-kit) receptor, and W/W CMC did not proliferate in response to BALB/3T3-CM. However, W/W CMC did migrate normally toward BALB/3T3-CM and, moreover, the antibody to the extracellular domain of the W (c- kit) receptor did not inhibit the chemoattractive activity of +/+ CMC toward BALB/3T3-CM. These results indicated that MGF/SCF/KL itself did not represent the major chemoattractive activity. On the other hand, BALB/3T3-CM induced neither proliferation nor migration of CMC derived from mi/mi mice. Both W/W and mi/mi mice are deficient in mast cells, but the present results suggest that the mechanism of the abnormality is different between W/W and mi/mi mice.

The Wsh is a mutant allele at the W (c-kit) locus of mice. Mice of Wsh/Wsh genotype have white hairs and black eyes. Although adult C57BL/6-Wsh/Wsh mice were not anemic, they showed a remarkable depletion of mast cells. Most homozygous or double heterozygous mutant mice at the W (c-kit) locus, of which mast-cell depletion was comparable to that of Wsh/Wsh mice, are deficient in germ cells. However, male and female Wsh/Wsh mice have an appreciable number of germ cells in their gonads. We investigated the mechanism of specific depletion of mast cells in Wsh/Wsh mice. Cultured mast cells (CMC) derived from the spleen of Wsh/Wsh mice neither attached to normal (+/+) fibroblasts nor survived in the coculture with +/+ fibroblasts. The c-kit messenger RNA (mRNA) was strongly expressed in +/+ CMC, but not detectable in Wsh/Wsh CMC. Despite the lack of c-kit mRNA in Wsh/Wsh CMC, the c-kit mRNA was normally detectable in the cerebellum and weakly detectable in the testis and spleen of Wsh/Wsh mice. No significant changes were found in the nucleotide sequence of the c-kit transcripts obtained from the cerebellum of Wsh/Wsh mice. Development of mast cells, erythrocytes, and germ cells in Wsh/Wsh mice appeared to be parallel with the magnitude of the c-kit gene expression in each cell type.

Mutant mice of mi/mi genotype are osteopetrotic and deficient in tissue mast cells due to a defect in osteoclasts and mast cells. In an effort to further understand the mechanisms behind why mi/mi mouse-derived cultured mast cells (mi/mi-CMC) responded to interleukin-3 (IL-3), but not to the proliferative stimuli presented by fibroblasts, mi/mi-CMC and congenic normal (+/+) mouse-derived CMC (+/+-CMC), both of which expressed the phenotypic characteristics of immature mast cells, were cocultured with Swiss albino/3T3 fibroblasts in a medium containing IL- 3. In the in vitro CMC/fibroblast coculture, mi/mi-CMC did not acquire the phenotypes of connective tissue-type mast cells (CTMC), while +/+- CMC did. In addition, attachment of mi/mi-CMC to the fibroblasts was found to be significantly lower than that of +/+-CMC. Because the interaction of c-kit product with its ligand (stem cell factor [SCF]) is known to play an important role not only in proliferation and differentiation of mast cells but also in attachment of CMC to fibroblasts, the expression and function of c-kit were investigated in mi/mi-CMC and +/+-CMC. Recombinant rat SCF (rrSCF164) induced a dose- dependent proliferation of +/+-CMC. Also, rrSCF164 induced +/+-CMC to acquire the phenotypes of CTMC in the medium containing IL-3. By contrast, rrSCF164 did not stimulate the proliferation of mi/mi-CMC nor induce a phenotypic change of the cells from immature mast cells to mature, CTMC-like mast cells. Immunoblotting with antiphosphotyrosine antibody showed that rrSCF164 induced considerable tyrosine phosphorylation of 145- to 165-Kd protein, the product of c-kit, in +/+- CMC, whereas tyrosine phosphorylation of the protein was barely detectable in mi/mi-CMC. Northern blot and flow cytometry analyses showed that mi/mi-CMC expressed much less c-kit at both protein and message levels than +/+-CMC. Further, mi/mi-CMC were found to differ from +/+-CMC in the expression of mouse mast cell protease-6 (MMCP-6) and MMCP-2 messenger RNA transcripts. These results suggest that the gene product of the mi locus may be important in regulating the expression of gene products such as c-kit, and that mast cell deficiency of mi/mi mice appears to be due, at least in part, to impaired signaling through the c-kit receptor because of the low c-kit expression.

The receptor encoded by the W (c-kit) locus (W receptor) is expressed on the surface of cultured mast cells (CMC) derived from normal (+/+) mice, whereas its ligand encoded by the Sl locus (Sl ligand) is expressed on the surface of fibroblast cell lines derived from murine embryos. Involvement of W receptors and Sl ligands in attachment of CMC to fibroblasts was investigated. CMC were cocultured with fibroblasts; nonattaching CMC were removed and the remaining CMC were counted. CMC derived from mice of the W/W genotype did not express the extracellular domain of W receptors, and attachment of W/W CMC to +/+ fibroblasts was significantly impaired. Fibroblasts derived from embryos of the Sl/Sl genotype did not express Sl ligands, and the attachment of +/+ CMC to Sl/Sl fibroblasts was also impaired. The Wv and W42 alleles are point mutations at the intracellular tyrosine kinase domain. Attachment of either Wv/Wv, W/Wv, or W/W42 CMC to +/+ fibroblasts was comparable with that of +/+ CMC. Moreover, the addition of monoclonal antibody against the extracellular domain of W receptors inhibited the attachment of +/+ CMC to +/+ fibroblasts. Thus, the extracellular domain of W receptors appeared to be necessary for attachment of CMC to fibroblasts.

Segmental infarction of the testis represents a rare entity in that there have been fewer than 40 cases documented in the literature. Like global infarction, segmental infarction of the testis can masquerade as a mass lesion or torsion of the testis. Reported herein is a very rare case of segmental testicular infarction due to atheroembolism in a 58-year-old man. The patient presented with severe left testicular pain and underwent left high orchiectomy on the clinical diagnosis of testicular torsion. The testis had a segmental hemorrhagic necrosis around which many cholesterol emboli were observed. This is the first report to describe cholesterol embolism-associated segmental testicular infarction.

We report a case of paratesticular rhabdomyosarcoma in a 16-year-old male. The patient with a mass in the right scrotum was at first diagnosed with testicular tumor. Right orchiectomy revealed paratesticular rhabdomyosarcoma. Para-aortic lymph node metastasis was pointed out by abdominal computed tomography. Although he received multidrug chemotherapy consisting of vincristine, adriamycin, cyclophosphamide, cisplatin, and actinomycin-D (IRS-III regimen 35 and IRS-IV regimen) without radiotherapy, he died twenty-one months after the operation.

Liposarcomas are most commonly found in the extremities, in the retroperitoneum and, less often, in the head and neck area. The spermatic cord is a rare site of origin, accounting for about 3-7% of all liposarcomas. We report two cases of liposarcoma of spermatic cord. Case 1. A 69-year-old male presented with complaints of a painless left inguinal mass. MRI showed a huge fatty mass in the left inguinal region. The mass was removed with left testis and spermatic cord. Histopathological examination revealed a well-differentiated and dedifferentiated liposarcoma. The surgical margin was positive, so re-resection was performed. Complete excision was achieved after re-resection. Case 2. A 63-year-old male with the difficulty urinating had a left scrotal mass. Left radical orchiectomy was performed. Histopathological examination revealed a well-differentiated liposarcoma. These are the 84th and 85th cases of liposarcoma of the spermatic cord reported in Japan.

We describe a case of cardiac myxoma in a 44-year-old Japanese man, who died after developing metastases in the skin, brain and muscle. A satellite tumor which was attached to the wall of the abdominal aorta induced marked hypertension due to obstruction of the renal arteries. Although the primary heart tumor had typical histological features of benign cardiac myxoma, the recurrent heart tumor, which was partly resected three months before the patient's death, showed apparently malignant characteristics resembling malignant fibrous histiocytoma (MFH). Since the histological features of the initial and recurrent tumors were different, the grade of malignancy was investigated using the cellularity of the tumor as an arbitrary criterion. A gradual but significant increase in the cellularity was observed over the course of five years. Immunohistochemically, tumor cells in the muscle metastasis contained vimentin and factor VIII-related antigen, and multinucleated giant cells in the recurrent heart tumor contained desmin, which is rarely detectable in MFH. Therefore, we considered that the present case represented malignant transformation of benign cardiac myxoma.

Reported herein is an unusual case of intrahepatic cholangiocarcinoma with lymphoepithelioma-like appearance in a 64-year-old man who was found to have an intrahepatic mass without cirrhosis. The tumor had two distinct histological patterns with dense lymphoplasmacytic infiltrate. The first was similar to nasopharyngeal undifferentiated carcinoma; the second pattern was a well-differentiated adenocarcinoma. Transition between the two components was observed in the same duct. Immunohistochemistry indicated that the tumor was immunoreactive with AE1/AE3 and cytokeratin (CK) 7, but negative for CEA and CK20. Stromal inflammatory infiltrate primarily consisted of plasma cells and lymphocytes. Immunohistochemical examination and in situ hybridization for EBV showed no integration of the virus in the tumor cells. Intrahepatic lymphoepithelioma-like carcinoma is rare, and most are associated with EBV. Only three cases were not associated with EBV. The authors would like to add one more example of the tumors not associated with EBV.

Paragangliomas are rare neuroendocrine tumors that arise from hyperplastic paraganglionic cells and occur in or near the ganglia of the autonomic nervous system. Paragangliomas are classed as either functional or nonfunctional based on production of catecholamines. We report a case of retroperitoneal nonfunctional paraganglioma, which was successfully resected. A 26-year-old man presented with complaints of a mass palpable in his left lateral region. Blood and urine studies, including catecholamines, were within normal limits. Computed tomography and magnetic resonance imaging showed a solid cystic mass in the left retroperitoneal space without any distant metastasis. On exploration, there was an encapsulated, vascular mass 10 cm in diameter. There was no pedicle and no connection of the tumor to the abdominal or retroperitoneal organs. Complete excision of the tumor was performed smoothly. The postoperative period was uneventful. Histological findings were of paraganglioma, and there was no surgical margin. The patient did not receive any further treatment. Nine months after surgery, there were no signs of tumor recurrence.

A 77-year-old man was admitted to our hospital for a scheduled examination after transurethral resection of transitional cell carcinoma of urinary bladder. Tumor reccurence was found in the bladder by cystoscopic examination. Total cystectomy and unilateral cutaneous ureterostomy were performed. Histologically the tumor was composed of epithelial and sarcomatous elements. Therefore, we diagnosed this tumor as sarcomatoid carcinoma. The patient died of lung metastasis three months after operation. Autopsy findings showed lung metastasis and local reccurence which were composed of carcinomatous and sarcomatous elements. About 64 cases of sarcomatoid carcinoma of the urinary bladder have been reported in the Japanese literature and are reviewed briefly here.

We report a case of primary adenocarcinoma of the prostate producing carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). A 64-year-old man referred to our hospital with dysbasia. Two years ago, he was diagnosed with prostate cancer at another hospital and received radiotherapy and endocrine therapy. Serum CEA and CA 19-9 levels were increased to 3,990 ng/ml and 11,700 U/ml at the time of our hospitalization. However, his serum PSA level remained low. After hospitalization, the disease rapidly progressed and he died a month later. In the histology of autopsy specimen, the prostate showed no sign of malignancy, but bone showed metastasis of prostate cancer. Immunohistochemical staining for CEA and PSA demonstrated the existence of each protein in bone metastasis.

Lobular carcinoma of the breast is known to metastasize to unusual sites such as the gastrointestinal tract, peritoneum, and gynecologic organs. We report a patient with intraperitoneal metastases from lobular carcinoma who was originally treated for an unknown primary cancer. Ten years later, a tumor was found in her left breast and the diagnosis was changed to peritoneal metastases from invasive lobular carcinoma. Immunohistochemistry revealed that the metastases were high molecular weight cytokeratin (CK34betaE12) and estrogen receptor-positive, but were E-cadherin-negative. These results assisted in diagnosis. Surgeons should be aware of the characteristics of metastasis lobular carcinoma.

A total of 978 of transrectal prostate biopsies performed between January 1998 and December 2005 at Ikeda Municipal Hospital were reviewed to determine the usefulness of the systematic 12 core biopsy including the apex and transition zone (TZ). Prostate cancer was detected in 531 of the 978 cases (54.3%). The systematic 6 core biopsy was performed between 1998 and 2000. In this group the cancer detection rate was 40.8% (87 out of 213 cases). In the systematic 12 core biopsy group since 2001 the cancer detection rate was 58.0% (444 out of 765 cases). The cancer detection ratio in the systematic 12 core biopsy group was significantly higher than that in the 6 core group (p0.0001). In the subgroup whose prostate-specific antigen (PSA) value was in the gray zone (4. 1-10.0 ng/ml), the cancer detection rate was 22.9% (25 of 109 cases) in the systematic 6 core biopsy group and 45.7% (186 of 407 cases) in the systematic 12 core biopsy group. Of the 444 cases diagnosed as having prostate cancer by the systematic 12 core biopsy, 64 cases (14.4%) had positive cores only in additional cores from the apex and TZ. Our study revealed that the systematic 12 core prostate biopsy including the apex and TZ was useful for improving the cancer detection ratio of the prostate.

Among patients with negative initial biopsies of the prostate, 51 patients underwent total 59 repeat biopsies at the Department of Urology of Ikeda Municipal Hospital between January 1998 and April 2004. Overall 26 patients (44.1%) were confirmed to have cancer, 22 patients by second repeat biopsy (22/51), four patients by third biopsy (4/7) and none by fourth biopsy (0/1). Clinical parameters (age, PSA, PSA density, PSA velocity) were analyzed for the possibility to predict the pathological outcome. Significant differences between the positive biopsy group and the negative biopsy group were obtained in age, PSA level and prostatic volume. Of the diagnostic evaluations including palpation and imaging studies (DRE, TRUS, MRI), the most powerful predictor for prostate cancer seemed to be the MRI findings, especially in the cases of short-interval repeat biopsy. Biopsies directed at the positive lesion on MRI in addition to systematic prostate biopsies should be useful.