Paraneoplastic cerebellar degeneration with anti-Yo antibodies and an associated submandibular gland tumor: a case report.

BACKGROUND: As a debilitating syndrome, paraneoplastic cerebellar degeneration (PCD) remains challenging to treat. Further, anti-Yo antibody (directed against human cerebellar degeneration-related protein 2) detection in patients with PCD is associated with unsatisfactory responses to existing therapies. Here, we present the case of a 60-year-old woman who developed PCD with anti-Yo antibodies and a submandibular gland tumor. CASE PRESENTATION: A 60-year-old woman presented with a 5-day history of unsteadiness of gait and inadequate coordination of her extremities, along with truncal instability. Although walking without aid was possible, dysmetria of all four limbs, trunk, and gait ataxia was observed. While routine biochemical and hematological examinations were normal, the patient's blood was positive for anti-Yo antibodies. When the neurological symptoms deteriorated despite administration of intravenous methylprednisolone, fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) images with contrast enhancement were performed, which showed a tumor in the left submaxillary gland. She underwent total left submandibular gland resection, including the tumor; histological and immunohistochemical results revealed a salivary duct carcinoma. She was administered intravenous methylprednisolone, followed by 10 plasma exchange sessions, intravenous immunoglobulins, and cyclophosphamide therapy. Following treatment, her symptoms were not alleviated, even after the reduction of anti-Yo titers. CONCLUSIONS: Although tumor detection was delayed, early tumor detection, diagnosis, and PCD treatment are essential because any delay can result in the progression of the disorder and irreversible neurological damage. Therefore, we recommend that the possibility of a salivary gland tumor should be considered, and whole-body dual-modality CT, including the head and neck, and FDG-PET should be performed at the earliest for patients with well-characterized paraneoplastic antibodies when conventional imaging fails to identify a tumor.

[A Case of Transverse Colon Cancer Complicated by Eosinophilic Granulomatosis with Polyangiitis].

A man in his 50s had undergone steroid therapy for eosinophilic granulomatosis with polyangiitis(EGPA). Since an examination for malignant tumors revealed type 0-Ⅰsp(cT1aN0M0)and type 2(cT2N0M0)lesions in the proximal and mid- transverse colon, respectively, he was referred to our department. Endoscopic resection was performed on the proximal lesion. After the confirmation of curative resection, laparoscopic partial colectomy(transverse colon)and D3 lymph node dissection were performed on the mid-transverse lesion. Because of the patient's favorable postoperative course, he was discharged from the hospital on POD17. Since steroids and immunosuppressants may cause immunological abnormalities and malignant tumors, such patients should be strictly followed up.

[A Case of Unresectable Gastric Cancer Who Underwent Conversion Surgery after SP Therapy and Achieved Long-Term Survival].

The case was a man in his 60s. With a complaint of loss of appetite, a peripheral type 3 lesion was found from the lower body of the stomach to the vestibule, and a biopsy revealed poorly differentiated adenocarcinoma. CT examination revealed that the tumor had invaded the left lobe of the liver and the transverse colon, and that the para-aortic lymph nodes were swollen and multiple nodules of the gastrocolonic mesentery were found. After 6 courses of S-1 plus cisplatin(SP)therapy were performed, the tumor shrank and lymph node swelling and nodule disappearance were observed. Laparotomy and pyloric gastrectomy, partial liver resection, D2 dissection, and Roux-en-Y reconstruction were performed. As a result of histopathological examination, R0 was resected. After the operation, S-1 was taken orally for 1 year, and no recurrence or metastasis has been observed 6 and a half years after the operation. This time, we report a valuable case in which SP therapy was successful for unresectable gastric cancer and long-term survival was obtained by conversion surgery.

[A Case in Which S-1 plus CDDP and S-1 Therapy Responded to Liver Metastasis Recurrence after Gastric Cancer Operation].

A 55-year-old man underwent distal gastrectomy and D2 lymph node dissection for type 2 gastric cancer of the antrum. One year later, CEA elevation was discovered, and contrast-enhanced abdominal computed tomography(CT)revealed a 40 mm mass in the liver(S8), which was judged to be a metastatic recurrence of the gastric cancer.S -1 plus CDDP was administered in 5 courses, followed by regular treatment with S-1 alone.Two years after the recurrence was diagnosed, the patient's CEA level was found to be normal, and CT revealed almost total scarring.After 2 more years, there was still no sign of recurrence, so, with the patient's consent, we discontinued the chemotherapy.Eight years after the gastrectomy, a 10mm nodular shadow was observed in the left lower lung lobe, and resection was performed.Despite the earlier diagnosis of gastric adenocarcinoma, this mass was considered a primary lung adenocarcinoma, and the patient died of small-cell lung cancer 11 years and 8 months after the gastrectomy.It is notable that the liver metastasis in this case responded to the S-1 plus CDDP and S-1 therapies, and this response is considered in light of the literature.

Can synaptophysin be used as a marker of breast cancer diagnosed by core-needle biopsy in epithelial proliferative diseases of the breast?

The differential diagnosis of epithelial proliferative disease using core needle biopsy (CNB) is problematic because it is difficult to differentiate between intraductal papilloma, ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Many studies have reported that breast cancer lesions are positive for neuroendocrine (NE) markers, whereas only a small number of studies have reported immunopositivity for NE markers in normal mammary tissues or benign lesions. We asked whether NE factors could be used as markers of breast cancer. We determined the immunopositivity rate of synaptophysin, an NE marker, in 204 lesions excised from the breast using CNB in patients who visited a university-affiliated comprehensive medical facility and examined whether synaptophysin is a marker of breast cancer. The specimens were classified as synaptophysin-negative cases (56 benign, 99 malignant); equivocal cases (<1 %: 2 benign, 15 malignant); and synaptophysin-positive cases (1 benign, 31 malignant). The sensitivity, specificity, positive predictive value, and negative predictive value for malignancy of the lesions classified as synaptophysin positive were 23.3 %, 98.2 %, 96.9 %, and 36.1 %, respectively. The respective values for lesions classified as equivocal were 11.6 %, 96.6 %, 88.2 %, and 36.1 %. Synaptophysin may provide a marker of breast cancer diagnosed by CNB.

Use of washing cytology from removed self-expandable metal stents for biliary strictures: a novel cytology method.

Removability is one of the important features of biliary covered self-expandable metal stents (CSEMS). In this study, we evaluated the diagnostic ability of washing cytology of removed CSEMS. For 14 removed CSEMS that had been placed for the biliary strictures (12 malignant, 2 benign), the surface of CSEMS was washed with saline, and pathological examination of the washing liquid as cytology (CSEMS washing cytology) was performed. The specimen sampling rates and sensitivity for malignancy of CSEMS washing cytology were 92.9 % and 41.7 %, respectively. Sensitivity according to the primary disease was 60.0 % for bile duct cancer and 20 % for pancreatic cancer. Sensitivities based on the methods of stent removal were 16.7 % and 66.7 % for removal through the channel of the scope and with the scope, respectively. Therefore, it is possible that sensitivity of CSEMS washing cytology is higher in bile duct cancer and for removal with the scope. In conclusion, CSEMS washing cytology may have potential as a pathological diagnostic method.

Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment.

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Nucleos(t)ide analogue (NA) therapy effectively reduces the incidence of HCC, but it does not completely prevent the disease. Here, we show that dysregulation of microRNAs (miRNAs) is involved in post-NA HCC development. We divided chronic hepatitis B (CHB) patients who received NA therapy into two groups: 1) those who did not develop HCC during the follow-up period after NA therapy (no-HCC group) and 2) those who did (HCC group). miRNA expression profiles were significantly altered in CHB tissues as compared to normal liver, and the HCC group showed greater alteration than the no-HCC group. NA treatment restored the miRNA expression profiles to near-normal in the no-HCC group, but it was less effective in the HCC group. A number of miRNAs implicated in HCC, including miR-101, miR-140, miR-152, miR-199a-3p, and let-7g, were downregulated in CHB. Moreover, we identified CDK7 and TACC2 as novel target genes of miR-199a-3p. Our results suggest that altered miRNA expression in CHB contributes to HCC development, and that improvement of miRNA expression after NA treatment is associated with reduced HCC risk.

Effectiveness of computer-aided diagnosis (CADx) of breast pathology using immunohistochemistry results of core needle biopsy samples for synaptophysin, oestrogen receptor and CK14/p63 for classification of epithelial proliferative lesions of the breast.

AIMS: The aim of this study was to develop a computer-aided diagnosis (CADx) system for identifying breast pathology. METHODS: Two sets of 100 consecutive core needle biopsy (CNB) specimens were collected for test and validation studies. All 200 CNB specimens were stained with antibodies targeting oestrogen receptor (ER), synaptophysin and CK14/p63. All stained slides were scanned in a whole-slide imaging system and photographed. The photographs were analysed using software to identify the proportions of tumour cells that were positive and negative for each marker. In the test study, the cut-off values for synaptophysin (negative and positive) and CK14/p63 (negative and positive) were decided using receiver operating characteristic (ROC) analysis. For ER analysis, samples were divided into groups with <10% positive or >10% positive cells and decided using receiver operating characteristic (ROC) analysis. Finally, these two groups categorised as ER-low, ER-intermediate (non-low and non-high) and ER-high groups. In the validation study, the second set of immunohistochemical slides were analysed using these cut-off values. RESULTS: The cut-off values for synaptophysin, <10% ER positive, >10% ER positive and CK14/p63 were 0.14%, 2.17%, 77.93% and 18.66%, respectively. The positive predictive value for malignancy (PPV) was 100% for synaptophysin-positive/ER-high/(CK14/p63)-any or synaptophysin-positive/ER-low/(CK14/p63)-any. The PPV was 25% for synaptophysin-positive/ER-intermediate/(CK14/p63)-positive. For synaptophysin-negative/(CK14/p63)-negative, the PPVs for ER-low, ER-intermediate and ER-high were 100%, 80.0% and 95.8%, respectively. The PPV was 4.5% for synaptophysin-negative/ER-intermediate/(CK14/p63)-positive. CONCLUSION: The CADx system was able to analyse sufficient data for all types of epithelial proliferative lesions of the breast including invasive breast cancer. This system may be useful for pathological diagnosis of breast CNB in routine investigations.

Immunohistochemical analysis of insulin-like growth factor 1 and its receptor in sporadic schwannoma/peripheral nerve sheath tumour.

OBJECTIVE: To investigate the immunohistochemical localization of insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) in archival specimens of sporadic schwannoma. METHOD: This study retrospectively analysed the immunolocalization of IGF-1 and IGF-1R in schwannoma specimens collected from all patients with sporadic schwannoma that were treated by two institutions in Japan. The study also evaluated the association between the extent of the IGF-1 and IGF-1R immunoreactivity and several clinicopathological characteristics (age, sex and maximum tumour dimension). RESULTS: The study examined a total of 29 sporadic schwannoma specimens. IGF-1 and IGF-1R immunoreactivity was detected in the majority of the specimens regardless of their anatomical location. IGF-1 and IGF-1R were not co-localized. There was no association between the extent of the IGF-1 and IGF-1R immunoreactivity and the clinicopathological characteristics of the patients. CONCLUSIONS: As IGF-1 and IGF-1R immunoreactivity was detected in the majority of sporadic schwannoma specimens regardless of their anatomical location, these findings suggest that an IGF-1/IGF-1R loop could play a role in the tumorigenesis and progression of schwannomas via an autocrine-paracrine mechanism.

A primary pulmonary glomus tumor: a case report and review of the literature.

A case of a glomus tumor originating from the lung is reported. A 43-year-old female had undergone resection of a right lung tumor following a clinical diagnosis of carcinoid, sclerosing hemangioma, or other sarcoma. Histologically, the tumor comprised uniform small round to oval cells with centrally located nucleus, a clear cytoplasm, and apparent cell borders. The tumor also showed a focally hemangiopericytomatous pattern with irregularly branching or dilated vessels. Electron microscopy revealed smooth muscle differentiation of the tumor cells. Immunostaining further revealed that the tumor cells expressed smooth muscle actin, h-caldesmon, muscle specific actin (HHF-35), but not cytokeratin, epithelial membrane antigen, synaptophysin, or chromogranin A. Based on these findings, a diagnosis of primary pulmonary glomus tumor was established. Glomus tumors of the lung are very rare and only 21 cases have been reported to date. The histological features of the present tumor and the relevant literature are discussed.