Appendiceal Orifice Inflammation in Severe Ulcerative Colitis and Its Resolution With Infliximab and Plant-based Diet as First-line Therapy.

Appendiceal orifice inflammation, which is often observed in mild or moderate distal ulcerative colitis, was observed in a case of severe UC. Appendiceal orifice inflammation resolved after new induction therapy for severe UC: infliximab and a plant-based diet as first-line therapy.

Detection of MED12 mutations in mesenchymal components of uterine adenomyomas.

Adenomyoma of the uterus is a biphasic nodular lesion composed of a mesenchymal component with smooth muscle differentiation and a glandular epithelium. The neoplastic nature of uterine adenomyomas has been controversial because some are considered to be nodular adenomyosis. MED12 mutations are involved in the pathogenesis of uterine smooth muscle tumors (leiomyomas and leiomyosarcomas) and biphasic tumors of the breast (fibroadenomas and phyllodes tumor). To investigate the histogenesis of uterine adenomyomas, we performed pathological and genetic analyses, including Sanger sequencing of MED12. In total, 15 cases of uterine adenomyomas were retrieved and assessed for clinicopathological factors. Immunohistochemistry for smooth muscle actin, desmin, and CD10 was performed. Exon 2 of MED12 was Sanger sequenced using DNA obtained by macrodissection of the adenomyomas. For cases that were positive for somatic MED12 mutations, we next performed microdissection of the mesenchymal and epithelial components. The DNA extracted from each component was further analyzed for MED12 mutations. MED12 mutations were detected in two adenomyomas (2/15, 13%), all in a known hot spot (codon 44). In both lesions, MED12 mutations were detected in multiple spots of the mesenchymal component. The epithelial component did not harbor MED12 mutations. The relatively low frequency of MED12 mutations suggests that not all adenomyomas are leiomyomas with entrapped glands. However, the results of our study suggest that a subset of uterine adenomyomas are true mesenchymal neoplasms.

A case of Russell body gastritis with multifocal lesions.

Russell body gastritis is an extremely rare gastritis characterized by abundant infiltration of plasma cells with Russell body and eccentric nuclei, known as Mott cells. An 81-year-old Japanese woman with Helicobacter pylori and hepatitis C virus infection complaining of abdominal discomfort underwent upper gastrointestinal endoscopy, which detected an elevated lesion 2 cm in diameter at the anterior wall of the gastric body. A histological examination of the lesion revealed the infiltration of numerous Mott cells with an abundant eosinophilic crystal structure and eccentric nuclei in the lamina propria, resulting in a pathological diagnosis of Russell body gastritis. Endoscopic submucosal dissection (ESD) was performed subsequently. The histological findings of the resected specimen were compatible with those of Russell body gastritis. Upper gastrointestinal endoscopy performed 2 months after endoscopic submucosal dissection revealed the presence of new multiple flat elevated lesions in the antrum up to 1 cm in diameter, distant from the site of endoscopic submucosal dissection. A histological examination revealed a few Mott cells in the biopsy specimens taken from the new lesions. In turn, H. pylori eradication therapy was performed 1 month after the detection of the new lesions. One year after the eradication therapy, follow-up upper gastrointestinal endoscopy revealed that multiple lesions had almost disappeared, and the histological examination of the gastric biopsy specimens confirmed the disappearance of Mott cells. We herein report a case of Russell body gastritis in which multifocal lesions were observed after endoscopic submucosal dissection, and which was subsequently treated by H. pylori eradication therapy.

Hepatocellular carcinoma in otherwise sonographically normal liver.

PURPOSE: Hepatocellular carcinoma (HCC) on normal liver is very rare. The goal of this study was to determine the clinical manifestations and the role of ultrasonography (US) in the diagnosis of HCC arising in normal liver. METHODS: The clinical data and US findings in 12 cases of surgically resected HCC in normal liver were retrospectively analyzed. RESULTS: The patients were asymptomatic, had no hepatocarcinogenic factor, and hepatic function tests were almost normal in most cases. HCCs were large, encapsulated, and solitary, and there were predominantly well-differentiated or moderately differentiated in most cases. US showed a hypoechoic rim and lateral shadowing, suggestive of peritumoral capsule formation, and on contrast-enhanced US (CEUS), the tumor was hyperenhanced in arterial phase and washed out in postvascular phase, revealing typical HCC findings. CONCLUSIONS: US raises suspicion of HCC by showing lateral shadowing on grayscale ultrasound and hypervascularity on CEUS of the lesion.

Fetal gut-like differentiation in gallbladder cancer.

Adenocarcinomas showing fetal gut-like (enteroblastic) differentiation can arise in a variety of organs and are frequently accompanied by an elevated serum α-fetoprotein (AFP) level. However, no study has investigated fetal gut-like differentiation in gallbladder cancer in detail. Herein, we performed morphological and immunohistochemical analyses of fetal gut-like differentiation in 49 consecutive gallbladder cancer cases. The expression of Sal-like protein 4 (SALL4), an embryonic stem cell marker reported to represent fetal gut-like differentiation, as well as other oncofetal proteins, including glypican-3 (GPC3) and AFP, was assessed. We found 1 case of fetal gut-like adenocarcinoma that coexisted with conventional-type adenocarcinoma. The fetal gut-like adenocarcinoma component revealed diffuse immunoreactivity for SALL4 and partial positivity for AFP, whereas the conventional-type adenocarcinoma component was negative. We also found 2 poorly differentiated adenocarcinomas with hepatoid morphology and 1 clear cell carcinoma, none of which showed SALL4 positivity. In other conventional-type adenocarcinomas, focal immunoreactivity for SALL4 and GPC3 was occasionally observed. The overall positivity rates for SALL4 and GPC3 were 12.2% (6/49) and 16.3% (8/49), respectively. SALL4 and GPC3 expression was not associated with clinicopathological factors, including T category, lymphovascular invasion, and lymph node metastases. In conclusion, fetal gut-like adenocarcinoma was found in 2% of our gallbladder cancer series. We conclude that fetal gut-like adenocarcinoma is a distinct histological subtype of gallbladder cancer, characterized by SALL4 expression.

[A Case of Transverse Colon Cancer Metastasized to the Spermatic Cord after Resection of Peritoneal Dissemination].

We report a rare case of spermatic cord metastasis from colon cancer. A man in his 50s underwent extended right hemicolectomy for transverse colon cancer followed by resection of a peritoneal recurrence. After receiving adjuvant chemotherapy for 6 months, he became aware of a right inguinal mass. A spermatic cord tumor was noted on computed tomography(CT) and FDG/PET-CT. He underwent radical orchiectomy. The resected tumor was histologically compatible with the colon cancer. Although he received additional chemotherapy, right inguinal recurrence was resected 6 months after orchiectomy. Colon cancer is the second most common origin, after gastric cancer, of metastatic spermatic tumor. As several metastatic routes have been reported, peritoneal seeding is mostly suspected in this case.

Cutaneous polyarteritis nodosa in a patient with Crohn's disease.

A 19-year-old Japanese woman with a 4-year history of Crohn's disease (CD) developed high fever, polyarthralgia, and painful subcutaneous nodules of the legs. A skin biopsy showed panarteritis with fibrinoid necrosis in the deep dermis. Endoscopic examination showed aphthous lesions in the entire colon. She was diagnosed with cutaneous polyarteritis nodosa (PAN) associated with CD. Steroid therapy improved her symptoms. To our knowledge, this is the first Japanese case of cutaneous PAN associated with CD.

Purkinje cell loss in the cerebellar flocculus in patients with ataxia with ocular motor apraxia type 1/early-onset ataxia with ocular motor apraxia and hypoalbuminemia.

We genetically screened patients with ataxia with ocular motor apraxia type 1 (AOA1)/early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), with a Japanese variant form of Friedreich's ataxia. Three patients were found to have a homozygous insertion mutation of the aprataxin gene (689insT). An elder sister of a patient in this series died of cerebral hemorrhage at the age of 45, and underwent autopsy. In her cerebellar cortex, the mean density of Purkinje cells in the flocculus had predominantly decreased to 6.7% of normal controls, whereas the Purkinje cells in the other areas of the cerebellar hemisphere had decreased to 78.2%. This suggests that the cerebellar flocculus is the primary affected lesion in AOA1/EAOH, which should be associated with ocular motor apraxia.

Dynamic contrast-enhanced magnetic resonance imaging in radiotherapeutic efficacy in the head and neck tumors.

PURPOSE: The purpose to this study is to identify correlations between pathology and dynamic contrast-enhanced magnetic resonance imaging (MRI) and to assess the utility of this technique in the evaluation of radiation response for head and neck cancer. MATERIALS AND METHODS: MRI was prospectively performed after radiotherapy in 27 patients with various head and neck tumors. After bolus injection of contrast material, a dynamic study was performed using a spoiled gradient-recalled imaging sequence. The maximum slope of increase (MSI) on the time-intensity curve was displayed as a color-coded image. The ratio of MSI (MSIR) was obtained for tumor and normal muscles. Pathological specimens were obtained after MRI in all cases. Histological grading of irradiation changes was classified into 5 grades (0-4). Correlations between MSIR and histological grade were examined. RESULTS: Histologically, 18 tumors were classified as grade 2 (presence of viable tumor cells), 4 were grade 3 (nonviable tumor cells), and 5 were grade 4 (no tumor cells). Although the mean +/- SD of MSIR in patients with histological grade 2 or 3 was 7.4 +/- 7.9, MSIR in patients with grade 4 was 1.8 +/- 0.73, representing a significant difference ( P < .05). Every patient with grade 4 displayed an MSIR of 2.5 or less, although 5 of 22 patients with grade 2 or 3 had an MSIR of 2.5 or less. CONCLUSIONS: MSI quantitatively reflects response to radiotherapy for head and neck cancer. Color-coded MSI display is feasible for depicting permeability changes after radiotherapy.

Sarcomatoid variant of salivary duct carcinoma: clinicopathologic and immunohistochemical study of eight cases with review of the literature.

Salivary duct carcinoma (SDC) is an uncommon, high-grade tumor. We present 8 cases of sarcomatoid SDC, which has been defined recently as a rare variant of SDC. The 8 patients (5 men, 3 women) had a mean age of 63.6 years. Histologically, all tumors were characterized by a biphasic neoplasm composed of both SDC and sarcomatoid elements. In 3 cases, sarcomatoid components showed osteosarcomatous heterologous differentiation. A residual pleomorphic adenoma was detected in 5 tumors. The sarcomatoid component showed focal immunoreactivity for cytokeratin in 4 cases and epithelial membrane antigen in all 8 cases. Diffuse p53 immunostaining was detected in 3 cases, and it was coexpressed in both components. Our observations support the histogenetic theory of a common origin of the carcinomatous and sarcomatoid populations. Of the 13 patients, including our 8, reported to have sarcomatoid SDC arising in a major salivary gland and for whom long-term follow-up data were available, 7 have died of disease (mean survival, 15.6 months). These results indicate that sarcomatoid SDC is a highly aggressive tumor, similar to conventional SDC.

A resected case of a small hepatocellular carcinoma developing within the bile duct.

We experienced a resected case of a small hepatocellular carcinoma, which required differential diagnosis from intrahepatic cholangiocellular carcinoma. The patient was a 76-year-old man. While his course had been being observed because of hepatitis C antibody-positive liver cirrhosis, ultrasonographic examination of the abdomen revealed dilation of biliary branches in the anterior segment of the liver and a hyperechoic mass 10 mm in diameter at the origin of the branch. A dynamic computed tomography scan showed a high-density tumor in the early phase. After embolization of the right branch of the portal vein, resection of the right lobe of the liver and the extrahepatic bile duct was performed. A resected specimen showed a white-colored mass 8 mm in diameter at the origin of the anterior segmental biliary branch. In the pathological findings, the diagnosis was a poorly differentiated hepatocellular carcinoma with strong nuclear atypia; the tumor filled the bile duct, forming a trabecular structure. The immunohistological stains of the tumor were positive for cytokeratin (CK) 8, CK18, and HepParl and negative for alpha-fetoprotein, carcinoembryonic antigen, CA19-9, CK7, CK19, and CK20. There was atypia in the biliary lining epithelium adjacent to the tumor, and the hepatocellular carcinoma may have developed from the biliary epithelium.

Expression of tissue factor mRNA and invasion of blood vessels by tumor cells in non-small cell lung cancer.

PURPOSE: Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is also expressed in a wide range of cancer cells and plays an important role in cancer progression and metastasis, as well as in processes independent of the blood coagulation pathway. For example, by acting as an adhesion molecule enabling tissue invasion, TF may play a key role in the metastatic process and angiogenesis in non-small cell lung cancer (NSCLC). METHODS: To further investigate the role of TF on tumor cell invasion in NSCLC, we measured the TF mRNA expression in the tumors of 42 NSCLC patients using real-time quantitative reverse transcription - polymerase chain reaction carried out in a LightCycler. We then compared the TF mRNA expression with histological evidence of invasion of blood and lymphatic vessels by tumor cells. RESULTS: Although there was no significant relationship between the TF mRNA expression and the invasion of lymphatic vessels, the TF mRNA expression was significantly higher in tumors that invaded blood vessels (Log(10) TF mRNA/GAPDH mRNA = 2.16 +/- 0.18) than in those that did not (1.59 +/- 0.16; P = 0.03). CONCLUSION: These results suggest that TF plays a major role in blood vessel invasion by tumor cells in NSCLC.

A novel method for sentinel lymph node mapping using magnetite in patients with non-small cell lung cancer.

OBJECTIVE: The detection rate of sentinel lymph nodes in patients with non-small cell lung cancer using isosulfan blue dye is too low for clinical use. Although exposure to radioactivity is reportedly minimal, special procedures are nonetheless required when a radioactive isotope is used as a tracer. Therefore, to eliminate the need for a radioactive tracer and to obtain a better detection rate than is obtained with isosulfan blue dye, we have developed a novel method that employs magnetite as the tracer. The aim of the present study was to test the feasibility of this technique. METHODS: The tracer employed was ferumoxides, a colloidal superparamagnetic iron oxide of nonstoichiometric magnetite. Thirty-eight non-small cell lung cancer patients participated in the study; each received 5 mL of ferumoxides, injected around the tumor intraoperatively. Fifteen minutes after injection, lung resection and lymph node dissection were carried out. The magnetic force within the lymph nodes was measured using a highly sensitive handheld magnetometer ex vivo. All lymph nodes were also subjected to conventional histological analysis. RESULTS: The rate of detection of sentinel lymph nodes was 81.6% (31/38). The accuracy, sensitivity, and false-negative rates were 96.8% (30/31), 85.7% (6/7), and 14.3% (1/7), respectively. CONCLUSION: Intraoperative sentinel lymph node mapping using ferumoxides and a highly sensitive magnetometer is a safe, accurate, and sensitive way to detect sentinel lymph nodes in non-small cell lung cancer patients.

[Combination chemotherapy with nedaplatin and 5-fluorouracil for oral squamous cell carcinomas].

We used a new combination chemotherapy with nedaplatin (CDGP) and 5-fluorouracil (5-FU) in eleven fresh patients with oral squamous cell carcinomas. 5-FU was administered at a dose of 1,000 mg/body by continuous infusion for 24 hours on days 1 to 5. CDGP was administered at a dose of 80 or 100 mg/m2 by drip infusion for 120 minutes on day 5. The response rates of total (1- or 2-course) and 2-course group were 54. 5% and 83.3%, respectively. Adverse drug reactions were limited to two cases of grade 3 toxicity with anorexia. The combination chemotherapy with 5-FU and CDGP in place of cisplatin and 5-FU seemed to play an important role as neo-adjuvant chemotherapy for oral squamous cell carcinomas.

[Histopathological grading and clinical features of patients with mucoepidermoid carcinoma of the salivary glands].

In the 22 years between March 1979 and February 2001, we treated 16 patients--10 men and 6 women aged 10-80 years (mean: 44 years)--with mucoepidermoid carcinoma (MEC) of the salivary gland, evaluating them clinically and histopathologically. Tumor sites included 12 at the parotid gland, 3 at the submandibular gland, and 1 at the minor salivary gland. All tumors were graded histopathologically based on the criteria of Goode et al. as follows: low grade (n = 10), intermediate grade (n = 1), and high grade (n = 5). Female gender was associated with low grade MEC and male gender with high grade MEC (P < 0.05). The age at onset in high grade MEC was older than that in low grade MEC (P < 0.005). Lymph-node metastasis was detected in 7 out of the 16 patients (44%) associated significantly with high grade MEC (P < 0.05). Distant metastasis was detected in 4 of 16 patients (25%). Distant metastasis was significantly associated with high grade MEC (P < 0.05). Local recurrence was detected in 3 of 15 patients undergoing surgery (20%). No difference was seen in local recurrence frequency between low and high grade MEC. Survival was calculated with Kaplan-Meier's method. In all 16, 5-year survival was 86% and 10-year survival 75%. Five-year survival in low grade MEC was 100%, whereas that in high grade MEC was 67% (P < 0.05). In MEC of the salivary gland, it was suggested that the histopathological MEC grade evaluated by Goode's criteria significantly correlated with gender, age, lymph-node metastasis, distant metastasis, and 5-year survival.

A low-grade extraskeletal osteosarcoma.

The case of a 35-year-old woman with low-grade extraskeletal osteosarcoma of the left leg is presented. Radiographs showed peripheral ossification of the lesion, suggesting myositis ossificans. Most of the tumor was composed of cartilage, and the cellularity and cell atypia of the proliferating chondrocytes were mild to moderate. In the periphery, bone formation with a relatively clear margin and proliferation of spindle cells with minimal nuclear atypia were observed. The average percentage of cells positive for MIB-1 was 9.0%. A diagnosis of low-grade extraskeletal osteosarcoma was made on the basis of these histologic findings. The clinical course 47 months after a wide excision was uneventful.

[Third ventricular chordoid glioma: report of a surgical case].

We reported a rare case of third ventricular chordoid glioma and reviewed the literature. A 25-year-old male presented with a two-year history of voracious appetite. Three months prior to admission, he developed progressive memory impairment. CT scan showed a well circumscribed, slightly hyperdense mass without calcification in the third ventricle. The 4.5-cm oval mass occupying the anterior part of the third ventricle was homogeniously enhanced on MR images after administration of contrast medium. Small cystic components were present in the periphery of the mass. CT-guided stereotactic biopsy was performed. Microscopically, epithelioid tumor cells were embedded in mucinous stroma containing a lympho-plasmacytic infiltration. The tumor cells were immunoreactive for GFAP and vimentin. The MIB-1-positive rate was 1.2%. The histological diagnosis was a chordoid glioma. One month after the biopsy, a right frontal craniotomy was performed to remove the tumor via the anterior transcallosal interfornitial approach. The tumor arising from the anterior part of the third ventricle wall was soft, mildly vascular and light-grayish. The tumor was completely resected. The histological findings were identical with those of the biopsy specimens. Postoperatively, the patient developed diabetes inspidus, hyperthermia, worsening memory impairment, and transient hyponatremia. The patient's symptoms gradually improved and follow-up MR images showed no evidence of recurrent tumor 17 months after the resection. Despite low-grade appearance, attachment of the tumor to the hypothalamus preclude complete resection, and this may result in tumor recurrence and less favorable prognosis in the current reports. Early detection and aggressive resection followed by stereotactic radiotherapy are important in the management of chordoid glioma.

Primary osteosarcoma of the uterine corpus: case report and review of the literature.

A rare case of rapidly growing osteosarcoma that developed in the uterine corpus of a 62-year-old woman is presented. The tumor occupied almost the entire pelvic cavity and extended into the abdominal cavity, with marked involvement of the intestines. Histopathologically, the tumor was composed of an osteoblastic component, accompanied by conspicuous bone formation, and a fibroblastic component. The tumor cells were positive for vimentin and osteocalcin, as well as desmin, alpha-smooth muscle actin and muscle-specific actin, but negative for h-caldesmon. The results indicated myofibroblastic differentiation in a part of the tumor. A review of 14 reported cases and our case of uterine osteosarcoma revealed that this tumor has a biologically aggressive nature, although its histopathological and immunohistochemical features are similar to those of osteosarcomas in soft tissue and bone. As the prognosis of patients with this tumor is poor, it is of importance to differentiate this tumor from other types of tumors arising from the uterine corpus.

Irradiated carcinoma of the tongue: correlation of MR imaging findings with pathology.

OBJECTIVE: MR imaging was prospectively correlated with pathologic findings to study whether MR imaging can differentiate viable from nonviable tumor tissue in the irradiated carcinoma of the tongue. SUBJECTS AND METHODS: MR examinations were performed after radiation therapy in 21 patients with carcinoma of the tongue. All patients underwent either a total glossectomy or hemiglossectomy after radiation therapy. Specimens were examined microscopically. Radiation changes were histologically graded into four groups (I, minimal cellular changes; II, presence of cellular changes and partial destruction of the tumor; III, only nonviable tumor cells; IV, no tumor cells). MR examinations included T2-weighted imaging, unenhanced T1-weighted imaging, dynamic contrast-enhanced imaging, and contrast-enhanced T1-weighted imaging. RESULTS: On unenhanced T1-weighted images, the lesion was hypointense, except for two patients with histologic grade III. On T2-weighted images, the lesion appeared hyperintense in 12 of 14 patients with viable tumor cells (grades I and II); however, the lesion was hypointense in four, and isointense in two of seven patients with nonviable tumor cells (grades III or IV). Contrast-enhanced T1-weighted images showed that the degree of contrast enhancement of the lesion was equal to or lower than that of a normal salivary gland in 18 of 21 patients. For the time of maximal enhancement of the lesion on dynamic imaging, there was no substantial difference between viable (grades I and II) and nonviable (grades III and IV) tumor tissue. CONCLUSION: The present study shows that T2-weighted imaging is feasible for differentiating viable from nonviable tumor tissue in irradiated carcinoma of the tongue.