Takayuki Murase

Thymic neuroendocrine tumor (thymic carcinoid): a clinicopathologic study in 15 patients

BACKGROUND Thymic neuroendocrine tumor (carcinoid tumor) is rare, and prognosis for patients with this tumor has been difficult to predict. METHODS The medical records of 15 patients were reviewed, and the patients were classified according to tentative TNM classification and histologic grade. RESULTS Ten (66.7%) of 15 patients were male. Lymph node metastases were identified in 9 (60%) of 15 patients at the time of resection. There were one grade 1, nine grade 2, and five grade 3 tumors. Total resection was possible in 13 patients. Distant metastases developed in 10 (76.9%) of these 13 patients, although no local recurrence developed. Of these 10 patients, 6 died of distant metastases 5 to 25 months after the recurrence. Three patients are still alive, with metastases to the bone, spleen, and pleura 1 to 24 months after the diagnosis of recurrence. Two patients are presently tumor free (T1N0, grade 3 and T3N2, grade 2), but only 1 has survived beyond 5 years. CONCLUSIONS Thymic neuroendocrine tumor must be regarded as a malignant neoplasm that is prone to metastasize to mediastinal lymph nodes and to distant sites, even after total excision. Neither T and N classification nor histologic grade has been successful in predicting the outcome of a patient with this tumor. More aggressive management, including adjuvant therapies and reexcision of subsequent tumors, may result in increased survival.

Immunohistochemical study of autoimmune pancreatitis using anti-IgG4 antibody and patients' sera

Aims : Autoimmune pancreatitis (AIP), characterized by raised serum IgG4 levels, is frequently complicated by disorders of extrapancreatic organs. The aim of the present study was to examine immunohistochemically which extrapancreatic organs are affected, and whether an autoantibody to such organs is present in the serum of AIP patients.

Influence of histochemical and immunohistochemical stains on polymerase chain reaction.

The polymerase chain reaction (PCR) analysis of DNA extracted from tissue sections can be applied to a variety of research and diagnostic protocols. To analyze selectively the specific areas of tissue, a direct microdissection of histochemically or immunohistochemically stained sections, if satisfactory for PCR, is helpful. However, the influence of various staining methods on PCR has been poorly investigated. In this study, paraffin sections of formalin-fixed lymph node samples were histochemically stained with Mayer’s hematoxylin, eosin Y, methyl green, or May-Grunwald solution and immunostained for CD45 using 3,3′-diaminobenzidine (DAB), DAB with cobalt ion (DAB-Co), or new fuchsin as the chromogen. In addition, unstained sections were treated with trypsin, microwave, or pressure cooker, the techniques frequently used in immunostains for antigen unmasking. DNA was extracted from each section, and the PCR efficiency in amplifying a 110 bp portion of the beta-globin gene was evaluated by two parameters: the cycle count in which the first visible band was obtained (CYCLEmin) and the maximum amount of PCR products (CONCmax). The hematoxylin stain showed a significantly prolonged CYCLEmin (P <.01) and lower CONCmax (P <.05) in comparison with unstained and untreated control sections. The May-Grunwald stain showed a prolonged CYCLEmin (P <.01), although the CONCmax was not significantly different from that of the control (P =.051). The eosin and methyl green stains showed no effects against PCR. In immunostains, the DAB-Co method showed a lower CONCmax (P <.05), whereas the CYCLEmin was not prolonged. The DAB and new fuchsin methods had no untoward effects. Antigen-unmasking treatments showed deteriorating effects on PCR. The trypsin treatment significantly prolonged the CYCLEmin (P <.01), and the PCR amplification did not reach the “plateau” level with a maximum of 60 cycles. The PCR efficiency was worse in microwave or pressure cooker treatment, with neither CYCLEmin nor CONCmax being obtained. When target areas from sections for subsequent PCR amplification are microdissected, methyl green is most suitable as a dye for nuclear staining. The immunohistochemical visualization with DAB or new fuchsin yields no unfavorable effects. A successful PCR amplification may not be expected in sections that are pretreated in a microwave oven or pressure cooker.

Prognostic Significance of p27 and Ki-67 Expression in Mucoepidermoid Carcinoma of the Intraoral Minor Salivary Gland

p27 and Ki-67, a universal cyclin-dependent kinase inhibitor and a proliferative cell marker, respectively, have been useful in predicting clinical aggressiveness in various human tumors. We studied clinicopathologic significance of these molecules in mucoepidermoid carcinoma of the intraoral minor salivary gland. Expression of p27 and Ki-67 was assessed immunohistochemically in primary mucoepidermoid carcinomas from 31 patients without distant metastasis at surgery. Correlation each of p27 and Ki-67 expression was analyzed with various clinicopathologic parameters including age, sex, primary tumor site, tumor size, nodal metastasis, clinical stage, and histologic grade. The latter was evaluated using a point-scoring scheme of Auclair et al. that consists of five histologic factors (intracystic component, neural invasion, necrosis, mitosis, and anaplasia). p27 expression was correlated inversely with histologic grade (P = .007), but with none of other factors. When the correlation of p27 expression was further examined with each of the histologic factors, it was correlated significantly with intracystic component, but not with neural invasion, necrosis, mitosis, or anaplasia. Ki-67 expression was correlated significantly with histologic grade only in the clinicopathologic factors (P < .0001), and in the histologic factors, with necrosis, mitosis, and anaplasia. Multivariate prognostic analyses were performed to identify independent risk factors for both disease-free and overall survivals. Large tumor size (P = .031, relative risk = 5.5) and low p27 expression (P = .012, relative risk = 5.2) were risk factors for worse disease-free survival. Low p27 expression (P = .015, relative risk = 15.2) was selected as a risk factor for worse overall survival. Other factors including age, sex, tumor site, nodal status, clinical stage, histologic grade, and Ki-67 did not emerge as independent risk factors in either prognostic analysis. These data suggest that p27 may be useful in estimating prognosis of the patients who have mucoepidermoid carcinoma of the intraoral minor salivary gland.

Sclerosing hemangioma with metastases to multiple nodal stations.

We present a case of a large pulmonary sclerosing hemangioma with metastases to multiple lymph nodal stations and suspected contralateral pulmonary metastasis. Four cases (including the present) have been reported to have lymph node metastasis, and all had large tumors exceeding 3.5 cm in diameter. Accordingly, resection of sclerosing hemangioma is advisable while the tumor is small. Even in cases with a large sclerosing hemangioma, lymph node metastasis may be uncommon. However lymph node dissection may be necessary to detect lymph node metastasis in selected cases.

False-positive and true-negative hilar and mediastinal lymph nodes on FDG-PET : Radiological-pathological correlation

ObjectiveTo compare histological findings of FDG-PET false-positive and true-negative hilar and mediastinal lymph nodes.MethodsSixty-seven lymphnode areas in 11 patients who were diagnosed to have N3 lymph nodes by FDG-PET and underwent surgery were histologically examined, and the histopathological findings in false-positive and true-negative lymph nodes were compared. Lymph nodes with higher accumulation of FDG than the surrounding mediastinum level were judged as positive. On histological sections, proportions of macrophages and lymphocytes, amount of coal dust deposit, presence of silicotic nodules, long- and short-axes of the largest node, and volume of macrophages and lymphocytes were evaluated. Correlations between the above-mentioned factors and FDG accumulation were evaluated.ResultsFDG uptake was not correlated with the proportion of macrophages and lymphocytes, coal dust amounts, or the presence of silicotic nodules. The long- and short-axes of the largest node in the false-positive areas were significantly longer than those in the true-negative areas (p = 0.01, and 0.001, respectively). Volumes of lymph nodes (mean ± SD: 150 ± 190 mm3) and macrophages (78 ± 71 mm3) in false-positive areas were markedly larger than those in true-negative areas (68 ± 87 mm3, p = 0.0009 and 34 ± 54 mm3, p = 0.0001, respectively). The volume of lymphocytes was also larger in false-positive areas but less markedly.ConclusionOur study suggested that false-positive results of FDG-PET in hilar and mediastinal lymph nodes were closely related to the size of lymph node and the volume of macrophages.

Mott cell tumor of the stomach with Helicobacter pylori infection

A plasma cell tumor of the stomach with unusual histology is reported. Macroscopically, the tumor formed two ulcers in the gastric body, and microscopic examination revealed proliferation of plasma cells producing immunoglobulin G kappa monotypic immunoglobulin, with metastatic infiltration in some perigastric lymph nodes. Most of these plasma cells had various‐sized Russell bodies in the cytoplasm; hence the tumor may be called Mott cell tumor. The Russell bodies showed a strong affinity to concanavalin A by lectin immunohistochemistry, compared with those in reactive Mott cells. In addition, Helicobacter pylori (H. pylori) infection was proved by Gimenez stain and immunohistochemistry. The mixture of some centrocyte‐like cells and presence of reactive lymph follicles with follicular colonization by tumor cells suggest that this lesion may be a variant of mucosa‐associated lymphoid tissue lymphoma in association with H. pylori infection. The patient has shown no evidence of recurrence of the tumor after 11 years of follow up.

Thymic sarcomatoid carcinoma with skeletal muscle differentiation: report of two cases, one with cytogenetic analysis.

Thymic sarcomatoid carcinoma with skeletal muscle differentiation: report of two cases, one with cytogenetic analysis

MYB, MYBL1, MYBL2 and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma

Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and the long‐term prognosis is poor. In this study, we examined alterations of AdCC‐associated genes, MYB, MYBL1, MYBL2 and NFIB, and their target molecules, including MYC. The results were correlated to clinicopathological profile of the patients.

Nasal NK-cell Lymphoma Followed by Relapse in the Uterine Cervix

We report a case of nasal natural killer (NK)-cell lymphoma in a 51-year-old Japanese woman who showed a later relapse in the uterine cervix. The nasal NK-cell lymphoma regressed after local radiation therapy. Six months after the diagnosis while the patient was being treated with chemotherapy for a subclinical tumor, a mass lesion of the uterine cervix was noticed by follow-up computed tomography. Giemsa-stained vaginal smear showed lymphoid tumor cells with large azurophilic granules, leading to a rapid diagnosis of cervical involvement by NK-cell lymphoma. The chemotherapy regimens were immediately changed, but the patient died 2 months after the relapse with an overall survival of 8 months. This case may be of value in elucidating the biological behavior and natural history of NK-cell lymphoma.