Granulomatosis with Polyangiitis Presenting with Thrombovasculitic and Necrotizing Pachy- and Leptomeningitis Accompanied by a Brain Tumor-like Lesion.

We report a case of granulomatosis with polyangiitis (GPA) presenting with hypertrophic pachymeningitis with a huge brain tumor-like lesion. A 57-year-old man acutely developed consciousness disturbance. Magnetic resonance imaging revealed a right frontal lobe mass with thickened, contrast-enhanced dura. Computed tomography revealed sinusitis and multiple lung nodules. The presence of proteinase 3-anti-neutrophil cytoplasmic antibody indicated GPA. Histopathology of the excised brain tissues revealed thrombovasculitis with heavy neutrophilic infiltration in the pachy- and leptomeninges covering an ischemic cerebral cortex. The patient improved with corticosteroids and rituximab. Our case warrants considering GPA as a cause of hypertrophic pachymeningitis with brain-tumor like lesions.

Myasthenic crisis appearing after resection of intracardiac ectopic thymoma with superior vena cava syndrome.

BACKGROUND: We describe herein an extremely rare case of intracardiac ectopic thymoma-only two pure cases have been reported to date-associated with myasthenia gravis, an infrequent complication of ectopic thymoma. CASE PRESENTATION: A 71-year-old woman with superior vena cava syndrome was found to have a large mass mainly located in the right atrium. Tumor resection under cardiopulmonary bypass was performed. The pathological diagnosis was type AB ectopic thymoma. The postoperative course was complicated by progressive respiratory failure, and she was diagnosed with myasthenic crisis based on clinical signs and the edrophonium test. The patient recovered and was weaned from prolonged mechanical ventilation after receiving intravenous immunoglobulin, and was subsequently discharged uneventfully. CONCLUSIONS: This is the first report of myasthenic crisis due to intracardiac ectopic thymoma. Residual thymoma is a risk factor for the development of post-thymectomy myasthenia gravis, and long-term follow-up is required.

Pediatric plexiform fibromyxoma: A PRISMA-compliant systematic literature review.

BACKGROUND: Plexiform fibromyxoma (PF) is a rare gastric mesenchymal tumor, with approximately 80 cases reported to date. Gastrointestinal stromal tumor, the most common primary mesenchymal tumor of the stomach, shows different biological and clinical characteristics between adult and pediatric patients. OBJECTIVES: This systematic literature review was conducted to elucidate the pathological and clinical features of pediatric PF compared to adult PF. METHODS: MEDLINE (1948 to March 2018) and EMBASE (1947 to March 2018) were searched, and all English articles that reported clinical data on PF patients were identified. Two authors independently reviewed the articles and extracted data to assess immunohistochemistry, sex, chief complaint, tumor size, tumor-related mortality, and tumor recurrence and metastasis. RESULTS: A total of 41 reports with 80 PF patients (of whom 70 were adult PF and 10 were pediatric PF patients) confirmed by histological and immunohistochemical findings were included. Of a total of 80 tumors, 62 (78%) were located in the gastric antrum, 42 (65%) presented with ulceration, and 48 (74%) were resected by partial gastrectomy. Median tumor size of the resected specimen was larger in pediatric PF than in adult PF cases (5.3 cm vs 4.0 cm, P = .036). However, there was no difference between pediatric and adult PFs in immunohistochemical expression, sex predominance, chief complaint, tumor-related mortality, and tumor recurrence and metastasis during the follow-up periods. CONCLUSION: Other than increased tumor growth in pediatric PFs, PF is a single disease entity with similar pathological features and benign clinical behavior regardless of onset age.

A new case of zoonotic onchocercosis in northern Kyushu, Japan.

A case of zoonotic onchocercosis has been found in a resident who lived in Iizuka City, Fukuoka Prefecture, Japan for some time. A 24-year-old male developed a painful nodule on the middle finger of his right hand. The nodule was surgically removed from the vagina fibrosa tendinis of the finger at Beppu Medical Center, Beppu City, Oita Prefecture in 2012. The causative agent was identified as a female Onchocerca dewittei japonica based on its histopathological characteristics. The identity of the filarioid has been confirmed by sequencing the cox1 gene. The present study indicates that the zoonotic onchocercosis caused by O. dewittei japonica has been concentrated in northeast Kyushu.

KIT (CD117) Expression in Benign and Malignant Sweat Gland Tumors.

KIT (CD117, c-kit) is a receptor tyrosine kinase involved in the tumorigenesis of several neoplasms. KIT is expressed by the secretory cells of normal sweat glands. We studied the KIT expression and KIT mutational status in various benign and malignant tumors of eccrine and apocrine glands. We included a total of 108 cases comprising 10 benign and 6 malignant sweat gland tumors, and KIT expression was immunohistochemically detected (positive rate): 10 syringomas (0%), 8 poromas (25%), 20 mixed tumors (40%), 21 spiradenomas (43%), 1 cylindroma (0%), 5 hidradenomas (40%), 7 syringocystadenoma papilliferum cases (0%), 1 papillary hidradenoma (100%), 2 tubulopapillary hidradenomas (50%), 8 hidrocystomas (29%), 2 adenoid cystic carcinomas (100%), 5 porocarcinomas (20%), 6 apocrine carcinomas (33%), 10 extramammary Paget diseases (30%), 1 spiradenocarcinoma (100%), and 1 syringocystadenocarcinoma papilliferum (0%). Most KIT-positive cells were luminal cells, arising from glandular structures. We performed polymerase chain reaction-single-strand conformation polymorphism for detecting KIT mutational status. All cases showed no mutations at hot spots for KIT (exons 9, 11, 13, and 17). KIT mutation does not seem to be mechanism for KIT expression, but the expression may be from native sweat glands.

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

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

Sarcomatoid carcinoma of the remnant stomach: report of a case.

We herein report a case of sarcomatoid carcinoma that developed in a remnant stomach. A 76-year-old male with a history of distal gastrectomy for a duodenal ulcer 28 years earlier underwent investigation for a tumor in the remnant stomach. An endoscopic survey showed a round elevated tumor measuring 6 cm in diameter, and a biopsy specimen suggested carcinosarcoma. A total gastrectomy of the remnant stomach was performed, and the excised tumor was identified to be a malignant neoplasm consisting of both carcinomatous and sarcomatous components. A diagnosis of sarcomatoid carcinoma was made since the epithelial markers were positive even in the mesenchymal elements of the tumor. To our knowledge, only 4 cases of sarcomatoid carcinoma of the stomach have been reported in the English literature so far.

A case of synchronous metastasis of breast cancer to stomach and colon.

A case of synchronous metastasis of breast cancer to the stomach and colon is reported. A 38-year-old woman with a history of bilateral breast cancer was admitted for endoscopic examination because of occult blood. Endoscopic examination showed elevated lesions on the mucosal surface of the stomach and cecum. Histopathological examination of the biopsy specimens obtained from both sites showed adenocarcinoma, comprised of tumor cells with structural and nuclear atypia, which were similar to those of the primary breast cancer cells. In immunohistochemical analysis, these tumor cells stained positive for ER. Therefore, we diagnosed a synchronous metastasis of breast cancer to the stomach and colon. Synchronous metastasis of breast cancer to the stomach and colon without liver metastasis or peritoneal dissemination is extremely rare, with only 4 reported cases existing in literature.

Synchronous double tumor of breast cancer and gastrointestinal stromal tumor in a patient with neurofibromatosis type 1: report of a case.

We report a rare case of synchronous double tumor formation of breast cancer and gastrointestinal stromal tumor (GIST) in a patient with neurofibromatosis type 1(NF-1). A 76-year-old woman with a history of NF-1 who had undergone left modified mastectomy for breast cancer seven years previously was admitted to our hospital because of a right breast tumor and abdominal discomfort. Computed tomography revealed an enhanced irregular tumor in the right breast and peripheral enhanced tumors in the abdomen. The patient underwent right modified mastectomy and laparoscopic tumor resection combined with small intestine surgery. Histopathological examination revealed the presence of invasive lobular carcinoma in the right breast and GIST in the abdomen. The synchronous development of breast cancer and GIST in a patient with NF-1 is extremely rare, with this being the second case ever reported.

[Recurrent advanced gastric cancer diagnosed 20 years after partial gastrectomy].

A 67-year-old woman underwent partial gastrectomy (por2+sig, stage IIIA) for gastric cancer. She was admitted to our hospital because of swelling of her left neck lymph nodes 20 years after surgery. A biopsy specimen revealed poorly differentiated adenocarcinoma with signet-ring cell carcinoma. We diagnosed recurrence of gastric cancer and gave chemotherapy, but she died of myelosuppression and disseminated intravascular coagulation 2 years later. On autopsy, we examined all organs except the brain, but the primary lesion was not recognized. We concluded that this case was late recurrence after partial gastrectomy for advanced gastric cancer.

[Neoadjuvant chemotherapy with intraperitoneal paclitaxel for advanced gynecologic cancer].

OBJECTIVES: We evaluated safety and activity of intraperitoneal paclitaxel [=PTX (ip)] for neoadjuvant chemotherapy (NAC) of patients with advanced gynecologic cancer. METHODS: 13 patients with gynecologic cancer who had diffuse peritoneal dissemination received PTX (ip) with systemic chemotherapy (TC regimen) for NAC. After 3-6 courses of NAC, interval debulking surgery (IDS) was done. At IDS, we explored intraperitoneal cavity and debulked as much as possible, and examined pathological effects of NAC. RESULTS: PTX (ip) was well tolerated with apparent anti-cancer activity. Eleven patients were done with IDS after 3-6 NAC courses. Ten of 11 patients were completed an optimal surgery without extended resections. Eight of 11 patients with IDS had grade 2 (5 cases) or grade 3 (3 cases) effects of pathological examination. CONCLUSION: According to this exploratory research, we considered PTX (ip)=80 mg/m2 with PTX (iv)=115 mg/m2 and CBDCA (iv) AUC=4 as an optimum drug dose. Although evaluated in a small number of patients, PTX (ip) appeared to have safety and anti-cancer activity, and should be evaluated further.

Duodenal Gastrointestinal Stromal Tumor Treated by Wedge Resection in a Patient with Neurofibromatosis Type 1: Report of a Case and Review of the Japanese Literature.

A case of duodenal gastrointestinal stromal tumor (GIST) treated by wedge resection in a patient with neurofibromatosis type 1 (NF-1) is reported. A 55-year-old man with a history of NF-1 was admitted for surgery for a duodenal tumor. Upper gastrointestinal endoscopy revealed a 2.5 cm duodenal submucosal tumor. Abdominal computed tomography showed a homogenously enhanced mass in the third portion of the duodenum. The patient successfully underwent wedge resection of the duodenal tumor. Histological examination revealed proliferation of spindle tumor cells arranged in a bundle pattern. This tumor was immunohistochemically positive for c-Kit and CD34, and negative for S-100 and α-SMA. A mitotic count showed 3 mitoses per 50 high-power fields. The tumor was diagnosed as a low-risk GIST. The patient's postoperative course was uneventful. GIST in a patient with NF-1 is rare, only 27 cases being reported in the Japanese literature.

PDGF-BB is a novel prognostic factor in colorectal cancer.

PURPOSE: Human platelet-derived growth factor BB (PDGF-BB) is thought to be involved in human malignancies. Its overexpression has been reported in some human tumors. However, its expression in colorectal cancer has not been studied. We thus investigated the clinicopathological and biological significance of PDGF-BB gene expression in human colorectal cancer. EXPERIMENTAL DESIGN: Using real-time reverse transcription-PCR, we evaluated PDGF-BB expression status and correlated data with clinicopathological parameters in 60 patients with colorectal cancer. Additionally, we established a colorectal cancer cell line expressing PDGF-BB and investigated its effects on cell invasion and proliferation. RESULTS: The incidence of vascular invasion was significantly greater in patients expressing PDGF-BB at a high level than in those at a low level (P < .05). Patients with high PDGF-BB expression had a significantly poorer survival rate than those with low PDGF-BB expression (P < .05). A multivariate analysis demonstrated that PDGF-BB expression was an independent prognostic factor. We demonstrated in vitro that cells transduced with PDGF-BB showed greater invasiveness (P < .05) and migration (P < .001) than did mock transduced cells. In a xenograft study, cells transduced with PDGF-BB had higher proliferation rates than mock transfected cells. CONCLUSION: PDGF-BB expression may be a new prognostic indicator for patients with colorectal cancer.

A case of an alpha-fetoprotein-producing intrahepatic cholangiocarcinoma suggests probable cancer stem cell origin.

Recent evidence suggests that some cancers may originate from cancer stem cells, which may derive from carcinogenesis of normal stem cells. A hepatic progenitor cell population, which gives rise to hepatocytes and cholangiocytes, has been suggested in humans, though whether these cells can give rise to malignant tumors has not been confirmed. We report here a case of an alpha-fetoprotein (AFP)-producing intrahepatic cholangiocarcinoma (ICC) in an 81-year-old woman with chronic hepatitis C viral infection, suggesting malignant transformation of hepatic stem cells as a mechanism for hepatic neoplasia. Abdominal computed tomography revealed a low-density mass with surrounding enhancement measuring 5 cm x 5 cm in segments IV and VIII of the liver. The preoperative serum levels of tumor markers were 1.7 ng/ml of carcinoembryonic antigen, 22 mAU/ml of protein induced by vitamin K absence or antagonist II, 43.4 U/ml of carbohydrate antigen 19-9, and 1,560 ng/ml of AFP. Following central bisegmentectomy of the liver, serum AFP levels decreased dramatically. Histologically, the tumor cells showed indistinct glandular structures with abundant fibrous stroma. Immunohistochemical analysis demonstrated that the neoplastic cells reacted strongly to antibodies against AFP and cytokeratin (CK) 7. In addition, cancer cells showed partially positive reaction to anti-CK14, a liver stem cell marker, and to anticluster designation (CD) 133, a hematopoietic stem cell marker, and negative reaction to antihepatocyte paraffin (HepPar) 1. These data may indicate that the tumor was derived from a normal liver stem cell that underwent oncogenic transformation.

Cronkhite-Canada syndrome associated with schizophrenia.

Here, we report a case of Cronkhite-Canada syndrome in a patient with schizophrenia. A 64-year-old man, who had been diagnosed as having a schizophrenic disorder at the age of 30, presented with alopecia, atrophic nail changes, hyperpigmentation of the skin, and inflammatory polyposis of the stomach and colon. Endoscopic ultrasonography of the stomach and colon revealed diffuse mucosal thickening with small hypoechoic areas, corresponding to edema of the lamina propria. After treatment with parenteral hyperalimentation and tranexamic acid, his physical findings and polyposis gradually improved. This is the first report of Cronkhite-Canada syndrome in a patient with schizophrenia.

A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease.

AIM: To study a more accurate quantification of hepatic fibrosis which would provide clinically useful information for monitoring the progression of chronic liver disease. METHODS: Using a cDNA microarray containing over 22000 clones, we analyzed the gene-expression profiles of non-cancerous liver in 74 patients who underwent hepatic resection. We calculated the ratio of azan-stained: total area, and determined the morphologic fibrosis index (MFI), as a mean of 9 section-images. We used the MFI as a reference standard to evaluate our method for assessing liver fibrosis. RESULTS: We identified 39 genes that collectively showed a good correlation (r > 0.50) between gene-expression and the severity of liver fibrosis. Many of the identified genes were involved in immune responses and cell signaling. To quantify the extent of liver fibrosis, we developed a new genetic fibrosis index (GFI) based on gene-expression profiling of 4 clones using a linear support vector regression analysis. This technique, based on a supervised learning analysis, correctly quantified the various degrees of fibrosis in both 74 training samples (r = 0.76, 2.2% vs 2.8%, P < 0.0001) and 12 independent additional test samples (r = 0.75, 9.8% vs 8.6%, P < 0.005). It was far better in assessing liver fibrosis than blood markers such as prothrombin time (r = -0.53), type IV collagen 7s (r = 0.48), hyaluronic acid (r = 0.41), and aspartate aminotransferase to platelets ratio index (APRI) (r = 0.38). CONCLUSION: Our cDNA microarray-based strategy may help clinicians to precisely and objectively monitor the severity of liver fibrosis.

Loss of MAL expression in precancerous lesions of the esophagus.

BACKGROUND: We have identified a novel function of MAL (T-cell differentiation-related gene) as a candidate suppressor gene in esophageal cancer. As the role of MAL expression in esophageal carcinogenesis is as yet undetermined, MAL expression in a rat multi-step carcinogenic model and in precancerous lesions of the human esophagus was investigated. Microarray analysis between MAL-transfectant and control cells was also carried out to clarify how MAL confers its anti-tumor effects. MATERIALS AND METHODS: (1) In the rat model, MAL expression levels in laser microdissected normal esophageal epithelium, dysplastic tissues and carcinoma tissues were examined by reverse transcription (RT)-PCR. (2) Immunostaining with MAL antibody was performed in 10 dysplastic lesions adjacent to cancer in six cases of esophageal cancer. (3) We established a MAL transfectant using a Tet-off vector in esophageal cancer cells and performed microarray analysis under MAL-positive and MAL-negative conditions. RESULTS: (1) In the rat model, MAL mRNA expression was observed only in the normal samples. (2) MAL expression was observed distinctively in differentiated or keratinized normal tissues and was not observed in either dysplastic lesions or carcinoma tissue. (3) Up-regulated genes in MAL-positive cells included keratin 18 (transfectant/control = 2.94) and keratin 10 (t/c = 2.82). CONCLUSION: MAL expression was lost in dysplastic lesions of the rat carcinoma model as well as the human esophagus. The up-regulated keratins revealed by microarray analysis and the strong staining of the differentiated normal tissues in immunohistochemical study support the role of MAL as a regulator of differentiation in esophageal epithelium.

Activation of STAT3/5 signal pathways in complete mole and repression in choriocarcinoma cell lines.

OBJECTIVE: Because our previous study of microarray suggested that STAT5 and its downstream target, survivin, were up-regulated in complete mole (CM), we clarified the status of STAT-mediated signal transduction in CM and choriocarcinoma (CC). STUDY DESIGN: Proteins from 4 CM and normal villi and from 3 CC cell lines were subjected to Western blot (WB) analysis to evaluate STAT3 and 5 activation. After STAT and MEK inhibitor were added to these cells, the change in survivin expression was analyzed. Immunohistochemical staining was also done on CM and normal villi. RESULTS: WB showed that phosphorylated STAT3 and 5, which are active forms of STAT protein, as well as survivin, were significantly up-regulated in CM. Immunohistochemistry showed positive signals of pSTATs in the cytotrophoblast and syncytiotrophoblast layer in CM but not in normal villi. In contrast, the pSTAT signal was hardly detected by WB in CC cells. However, a high level of survivin expression was maintained in CC by activation of the MEK signal pathway. CONCLUSION: An activated STAT signal may contribute to hyperplastic cell growth of trophoblasts in CM. CC cells might be obtained independently of cytokine signals for tumor cell growth during the carcinogenic process.

Identification of molecular markers for metastasis-related genes in primary breast cancer cells.

Comparing differential gene expression profiles established by cDNA microarray between normal cells (N), primary carcinoma cells (T), and metastatic carcinoma cells (M) may determine those critical genes directly associated with progression and metastasis of breast cancer. Total RNA was extracted by laser microdissection (LMD) from 20 slices of T, N and M from 6 cases. After amplification by a T7-based system, differentially expressed genes between T, N and M were identified by cDNA microarray. In addition, to clarify the mechanism for altered gene expression, we determined the methylation status by sequencing after bisulfite treatment for intriguing genes. As a result, the expression of motility related protein-1 (MRP-1/CD9), peripheral myelin protein-22 (PMP-22), and caspase 3 (CASP-3) were down-regulated in M compared to T. We focused especially on MRP-1 and found that the expression status of MRP-1 was significantly inversely associated with stage of disease in 56 cases of breast cancer (P<0.05), and the relapse free survival in 5 years was significantly higher in MRP-1 positive cases than those negative cases (P<0.05). Conversely, overexpression, by 11-fold, of signal transduction and translation factors were observed in T compared to N. The cancer specific methylation was observed only in CASP-3 in a case. In conclusion, the establishment of the present assay allows us to detect genes directly associated with each cell population within tumor tissue and gives us clues to identify metastasis-related genes comprehensively in clinical breast cancer cases.

A novel mechanism in suppression of erythropoiesis during inflammation: a crucial role of RCAS1.

A novel human tumor-associated antigen, receptor-binding cancer antigen expressed on SiSo cells (RCAS1), induces apoptosis in normal human erythroid progenitor cells, which express putative RCAS1 receptors. In the present study, we investigated a possible role of RCAS1 produced by human peripheral blood monocytes (CD14-positive cells) and monocyte-derived macrophages. RCAS1 was immunohistochemically detected in monocytes as well as macrophages. When macrophages were stimulated with lipopolysaccharide (LPS), the expression of RCAS1 was remarkably enhanced. An increased production of RCAS1 mRNA was observed in LPS-stimulated macrophages by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Soluble RCAS1 molecules were only detected in the culture supernatants obtained from LPS-stimulated macrophages. Moreover, LPS-stimulated macrophages induced cell death of erythroid progenitor cells through RCAS1 production. These results suggest that macrophages may negatively regulate erythropoiesis at least in part through the production of RCAS1 molecules, and this may contribute to the pathogenesis of the anemia seen in patients with inflammatory disorders.