An autopsy case of corticobasal syndrome with pure diffuse Lewy Body Disease.

Corticobasal syndrome (CBS) is associated with diverse pathological substrates such as tau, prion protein, transactive response and, rarely, alpha synuclein. We report the case of a54-year-old man, who presented with asymmetric levodopa-poor-responsive parkinsonism, frontal lobe signs and behavioral changes. He was diagnosed with CBS, and postmortem analyses revealed Lewy body disease Braak stage VI without comorbid pathologies. Retrospectively, the clinical course of our patient and previous reports indicate that CBS plus mood changes and autonomic dysfunction, including reduced uptake of metaiodobenzylguanidine, are predictive factors of Lewy body pathology, even if the clinical picture is atypical.

Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma.

OBJECTIVES: The diagnostic utility of En1 in the histopathologic differentiation of eccrine porocarcinoma (EPC) from invasive squamous cell carcinoma (SCC) was investigated. METHODS: Expression of En1 and CK19 in 16 cases of EPC was immunohistochemically examined and compared with that in 32 cases of SCC. RESULTS: In all 16 EPCs, En1 was expressed in 3% to 100% of tumor cells. In 20 of the 32 SCCs, En1 was expressed in 3% to 90% of tumor cells. A total of 13 of the 16 EPCs and five of the 32 SCCs were judged as En1 positive, with a cutoff value of 25%. In addition, 11 of the 16 EPCs and four of the 32 SCCs were CK19 positive. The frequencies of En1- and CK19-positive cases were significantly higher in EPCs than in SCCs. In a logistic regression analysis for predicting EPC, En1 and CK19 were independent markers. When expression patterns of En1 and CK19 were combined, none of the 32 SCCs was both positive. In contrast, 15 of the 16 EPCs were positive for either En1 or CK19. CONCLUSIONS: A combination of En1 and CK19 expression can improve the accuracy of histologic diagnosis of EPC.

A controlled inflammation and a regulatory immune system are associated with more favorable prognosis of progressive multifocal leukoencephalopathy.

OBJECTIVE: In the present study, we analyzed the inflammatory profiles of brain tissues obtained from patients with progressive multifocal leukoencephalopathy (PML) due to John Cunningham (JC) virus infection to identify potential prognostic factors. METHODS: The study included seven patients (two men, five women) who had been pathologically diagnosed with PML, and all of whom were HIV negative. Fixed brain samples were analyzed via hematoxylin and eosin (HE) staining and Klüver-Barrera (KB) staining. We then performed immunohistochemistry (IHC) specific to JC virus capsid proteins (VP1 and VP2/3) and lymphocyte surface markers (CD4, CD8, CD138, and PD-1). RESULTS: The mean age at onset was 53.4, while the mean duration until biopsy/autopsy was 4.7 months. Four patients were included in the good prognosis (GP) group, while three were included in the poor prognosis (PP) group. Pathological analysis revealed a significantly larger number of CD4-positive T-cell infiltrations (P = .029) in the GP group, along with a preserved CD4:CD8 ratio. Larger numbers of CD138-positive plasma cells were also observed in the GP group (P = .029) than in the PP group. Linear regression analyses revealed a significant association between the numbers of CD138-positive plasma cells and PD-1-positive cells (R2 = 0.80). CONCLUSIONS: Viral loads in the cerebrospinal fluid, a controlled inflammatory response mediated by CD4- and CD8-positive T cells, and plasma cells are associated with PML prognosis. Our findings further indicate that regulatory plasma cells may regulate inflammatory T-cell activity via a PD-1/PD-L1 immuno-checkpoint pathway, thereby protecting the uninfected brain from excessive immune-mediated damage during an active JC virus infection.

[A Case of Double Cancer of Intrahepatic Cholangiocarcinoma and Gastric Carcinoma with Difficult Diagnosis of the Primary Tumor with Peritoneal Metastasis].

Double cancer of intrahepatic cholangiocarcinoma and gastric cancer is rare. A 62-year-old man underwent gastrectomy for gastric cancer. The pathological findings were tub1>tub2, m, ly0, v0, n0, Stage I A. Two years and a month later, a liver tumor(diameter of 3 cm)and a pelvic mass(diameter of 2.5 cm)were observed. Metastasis from gastric cancer was suspected and chemotherapy(SOX)was administered. However, after 5 courses, CT revealed worseningof the liver tumor (diameter of 12 cm)and pelvic mass(diameter of 3 cm). Intrahepatic cholangiocarcinoma and its peritoneal metastasis were also suspected. There was a limit to treatment with chemotherapy, and it was difficult to judge whether to target gastric cancer or intrahepatic cholangiocarcinoma for chemotherapy. In addition, the lesions were localized in the right lobe of the liver and the pelvis. Therefore, we decided to perform resection. As a second-stage operation, pelvic mass extraction and portal vein embolization were performed first. The pathological result of the pelvic mass assessment was mucinous carcinoma. Subsequently, expansive right hepatectomy was performed. The pathological findings were also suggestive of mucinous carcinoma, which was finally diagnosed as intrahepatic cholangiocarcinoma and peritoneal dissemination. Six months after the surgery, several recurrent nodules were observed in the pelvis and GEM plus CDDP was initiated. Currently, 1 year after surgery, there are no restrictions in the activities of daily life of the patient and he is treated on an outpatient basis.

[A Case of Solitary Metastasis to the Small Intestine from Sigmoid Colon Cancer after Treatment of Seven Multiple Cancers].

A 75-year-old woman who had undergone a Hartmann's operation for sigmoid colon cancer 2 years ago was hospitalized because she experienced small bowel obstruction several times. She had a treatment history of 6 other cancers, including 5 gastrointestinal tract cancers. However, the obstruction was relieved by conservative therapy each time. In September 2015, she was hospitalized for ileus. Abdominal computed tomography revealed that the lumen of intestine was partially dilated. Subsequently, a long tube was inserted, but the dilatation of the small intestine was not fully recovered. She was diagnosed with small intestinal obstruction due to adhesion, and she underwent an operation in October 2015. During the laparotomy, she was diagnosed with adhesion due to an intestinal tumor, and a partial intestinal resection, including the entire tumor, was performed. Because the tumor appearance and histological findings were very similar to those of sigmoid colon cancer, the tumor was diagnosed as a solitary metastasis of sigmoid colon cancer to the small intestine. Generally, peritoneal dissemination causes metastasis of colon cancer to the small intestine. However, this is a rare case because the lymphatic system or extra-wall invasion was the most likely cause of metastasis. Ileus repeating the improvement exacerbation, an examination must be performed while considering possible intestinal tumors, especially for a patient previously treated for multiple gastrointestinal cancers.

[Long Term Survival in a Case of Hilar Cholangiocarcinoma Treated with Chemotherapy and Surgery].

A 67-year-old man with elevated hepatobiliary enzymes was referred to our hospital for further examination. Computed tomography indicated hilar cholangiocarcinoma of Bismuth type Ⅳ and revealed invasion of the right hepatic artery and the left portal vein. We diagnosed locally advanced unresectable hilar cholangiocarcinoma, and performed 5 courses of chemotherapy with gemcitabine plus S-1. After chemotherapy, the tumor was significantly reduced in size and vascular invasions were alleviated, so we decided to perform surgical resection. An extended left hepatectomy with caudate lobe and extrahepatic bile duct resection was performed. Although the intraoperative pathological examination was positive for cancer at the hepatic margins, we did not perform further bile duct resection because of the difficulty. After the surgery, we administered adjuvant chemotherapy with gemcitabine for 5 courses. Another 8 courses of gemcitabine plus S-1 therapy were given because of elevation of CA19-9. The tumor marker levels normalized, and the patient is still alive without findings of recurrence 4 years after the first treatment. Multidisciplinary treatment with chemotherapy and surgery may suggest the possibility of increasing long term survival even for patients with locally advanced unresectable cholangiocarcinoma.

Lymphoepithelioma-like esophageal carcinoma with macroscopic reduction.

Esophageal lymphoepithelioma-like carcinoma (LELC) is extremely rare. We report the first case of esophageal LELC showing macroscopic reduction. A 67-year-old male presented with dysphagia and, by endoscopic examination, was found to have a significantly raised tumor of 10 mm in diameter in the thoracic esophagus. The biopsied material showed esophageal cancer. We performed endoscopic submucosal dissection. However, the tumor became flattened, similar to a scar, in only 2 mo. Histologically, the carcinoma cells had infiltrated the submucosal layer. Prominent infiltration of T lymphoid cells that stained positive for CD8 was observed around the carcinoma cells. Therefore, this lesion was considered to be an LELC with poorly differentiated squamous cells. Because the margin was positive, an esophagectomy was performed. Carcinoma cells were detected in the neck in one lymph node. The staging was T1N0M1b. However, the patient has been well, without adjuvant therapy or recurrence, for more than 5 years.

Anastomotic Recurrence of Sigmoid Colon Cancer over Five Years after Surgery.

The incidence of anastomotic recurrence after curative resection of colorectal cancer is relatively low compared to that of other types of recurrence, such as hepatic, lung and local recurrence. However, almost all cases of anastomotic recurrence of colorectal cancer occur within 3 years after surgery. We experienced a rare case of anastomotic recurrence in whom colonoscopy revealed no signs of recurrence 3 years after surgery; however, anastomotic recurrence was detected over 5 years after surgery. A 60-year-old female with a history of surgery for cancer of the cecum in her forties underwent sigmoidectomy and right colectomy with D3 lymph node dissection for both stage IIA sigmoid colon cancer and stage IIA transverse colon cancer. Computed tomography and colonoscopy revealed no signs of recurrence 3 years after surgery; however, 5 years and 4 months after surgery, colonoscopy demonstrated surrounding flaring and swelling in the anastomotic area of the sigmoid colon, and a biopsy revealed an adenocarcinoma. Under the diagnosis of anastomotic recurrence over 5 years after surgery, lower anterior resection was performed. The patient has exhibited no other signs of recurrence in the 2 years since the last operation.

Selection of chemotherapy for glioblastoma expressing O(6)-methylguanine-DNA methyltransferase.

The therapeutic benefit of nitrosoureas or temozolomide for glioblastoma is limited mainly by O(6)-methylguanine-DNA methyltransferase (MGMT) expression. The aim of this study was to evaluate the effectiveness of various anticancer drugs for MGMT-positive glioblastoma. Seventy-four glioblastoma patients were administered various anticancer drugs according to drug sensitivity testing. For the individualization, drug-induced apoptosis was quantified by flow cytometry in the primary culture of surgically resected tumor cells. The MGMT protein expression was analyzed by immunohistochemistry. The median survival of the patients receiving the individualized chemotherapy was 19.4 months (95% CI, 15.9-22.1). The patients with negative MGMT immunostaining had significantly longer survival than those with positive MGMT immunostaining [median survival, 22.3 months (95% CI, 17.6-27.0) vs. 15.1 months (95% CI, 13.4-16.8); p=0.0188]. For MGMT-positive tumors, the platinum agents and the taxanes were more frequently selected for administration than the other categories of anticancer agents. The patient survival period of MGMT-positive glioblastomas treated with the platinum agents or the taxanes [median survival, 20.1 months (95% CI, 18.0-22.7)] was significantly longer than that of MGMT-positive tumors treated with nitrosoureas (p=0.0026), and was equivalent to that of MGMT-negative glioblastomas (p=0.3047). These results suggest that the platinum agents and the taxanes offer the best probability to be effective against immunohistochemically MGMT-positive glioblastomas.

Angiosarcoma arising in the breast following breast-conserving surgery with radiation for breast carcinoma.

We report a case of angiosarcoma arising in the breast following breast-conserving surgery with radiation therapy for breast carcinoma. The patient, a 49-year-old postmenopausal woman, had undergone breast-conserving surgery for invasive ductal carcinoma of the left breast (pT2 pN0 M0 Stage IIA). Adjuvant radiotherapy (50 Gy with a booster dose to the tumor bed of 10 Gy) was then performed for the residual breast tissue and the patient was treated with hormone therapy (tamoxifen, 20 mg daily) for 5 years. She presented with skin erosion with bleeding 10 years after the initial operation. Incisional biopsy revealed angiosarcoma of the breast, and total mastectomy was subsequently performed. The patient was the treated with chemotherapy (weekly paclitaxel, 80 mg/m2 x cycles) and has remained well without evidence of local or distant recurrence.

Endoscopic, histological and serologic findings of gastric hyperplastic polyps after eradication of Helicobacter pylori: comparison between responder and non-responder cases.

BACKGROUND: Evidence indicates that eradication of Helicobacter pylori leads to the disappearance of hyperplastic polyps in the stomach. However, there are some exceptions. We have compared endoscopic and serologic findings of responder and non-responder cases with hyperplastic polyps to try to identify the cause(s), other than H. pylori infection, of the formation or growth of gastric hyperplastic polyps. METHODS: We retrospectively studied 33 patients whose hyperplastic polyps disappeared after eradication of H. pylori and 10 patients whose hyperplastic polyps did not disappear after eradication. The patients were examined both endoscopically and serologically before, 1-3 months after and 12-15 months after the eradication. RESULTS: The responder and non-responder groups were similar with respect to age, sex, coexisting diseases, and histologic findings. The number and maximum size of polyps tended to be larger before treatment in the non-responder group than in the responder group. The serum gastrin level was higher in the non-responder group than in the responder group before, 1-3 months after and 12-15 months after the eradication (p=0.0096, p>0.2, p=0.0014). On histologic examination, similar reductions in the degree of inflammatory cell infiltration in the gastric mucosa of the antrum and body were seen in both the responder and non-responder groups. In the non-responders, the size and numbers of the polyps regressed in 5 of the 10 patients. The score of glandular atrophy in the antrum and the serum gastrin levels in the non-regressed cases was higher than those in the regressed cases at 1-3 and 12-15 months after eradication. CONCLUSION: Persistent high gastrin levels were found in the non-responder cases with gastric hyperplastic polyps.