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The case of a 76-year-old man with multiple primary cancers that were treated with nivolumab is presented. Six years earlier, he was diagnosed with multiple myeloma (MM) and was treated with several chemotherapies. He was also diagnosed with gastric cancer with liver metastasis and primary lung cancer by upper gastrointestinal endoscopy and computed tomography (CT). Nivolumab treatment was given as third-line therapy, and it was effective for gastric and lung cancers. But MM worsened, and the patient died. There is no standard treatment for multiple primary cancers, and the development of effective treatments for multiple primary cancers is important.

We report a case of secondary diffuse large B-cell lymphoma (DLBCL) after azacitidine (AZA) treatment in a 63-years-old man with myelodysplastic syndrome. The patient suffered from febrile neutropenia after 10 cycles of AZA treatment. Despite the performance of a whole-body CT scan, which showed a multifocal low-density area in the liver and a multifocal nodular shadow in the lung, no malignant neoplasms could be detected. An autopsy was performed 6 months later, and a histopathological examination of the lesions of the liver and lung revealed the infiltration of large round-shaped tumor cells with necrotizing lesions. Immunohistochemically, the tumor cells were positive for CD20 and EBER, indicating EBV-positive DLBCL as a secondary malignancy.

We report a rare case of composite lymphoma comprising extranodal NK/T-cell lymphoma, nasal type, (ENKL) and diffuse large B-cell lymphoma (DLBCL) in a 70-year-old man complaining of fatigue. Computed tomography showed multiple consolidations in both lungs, and ENKL was diagnosed from transbronchial lung biopsy. Positron emission tomography also detected abnormal uptake in the stomach, and DLBCL was diagnosed from subsequent gastroscopy. Two courses of chemotherapy including rituximab achieved reduction in DLBCL, but ENKL proved resistant to this treatment and progressed. Concomitant ENKL and DLBCL have not been previously described among reports of composite lymphomas.

The Working Group of the Japanese Society of Clinical Cytology was assembled to assess the current status of breast cytology in Japan by conducting a large-scale survey regarding the accuracy of fine-needle aspiration biopsy (FNAB) in Japan. We collected data and investigated the status of breast cytological diagnosis at 12 different cooperating facilities in Japan, and re-evaluated their false-negative and false-positive cases. Among 30,535 individuals who underwent a breast cytological examination, analyses were conducted on 10,890 individuals (35.7%) in whom cytological diagnoses were confirmed by histology. Among these patients, the cytological diagnosis had an inadequate rate of 17.7%, an indeterminate rate of 7.8%, a positive predictive value of 'malignancy suspected' cells of 92.4%, an absolute sensitivity of 76.7%, a complete sensitivity of 96.7%, a specificity of 84.3%, a positive predictive value of 'malignant' cells of 99.5%, a false-negative value of 3.31%, a false-positive value of 0.25% and an accuracy rate of 88.0%. Subsequently, 297 false-negative and 23 false-positive cases were re-evaluated and several factors were characterized (i.e. histological type, tumor size and misread points). This survey collected data from a large number of cases for breast FNAB. Based on our survey, the accuracy of FNAB in Japan was relatively high compared with the goal of assessment of diagnostic accuracy. However, there were some false-negative and false-positive cases. Improvements in accuracy resulting from the learning points in the present study will lead to more useful and reliable diagnostic tools in clinical practice.

虫垂原発の癌はまれで, 特に虫垂原発低分化型癌の報告例は少ない. 今回我々は虫垂腫瘍を疑い手術を施行し, 術後病理所見から低分化腺癌と診断した1症例を経験したので報告する. 症例は63歳の女性. 右下腹部に限局した疼痛を訴え当院を受診した. 腹部超音波検査で右側腹部に52×32mm大のhypoechoic massを認めた. 腹部造影CT検査では, 上行結腸外側に接する50×30×50mmの辺縁に造影効果を認める内部は不均一な低吸収域のcystic massがあり虫垂腫瘍の診断で, 結腸右半切除術 (D3) を施行した. 病理組織所見から虫垂原発低分化腺癌と診断した. 術後1年6か月でCA19-9が185U/mlと上昇したため精査したところ, 右卵巣転移を認め, 切除した. 初回手術後2年9か月経過した現在, 再発の徴候なく生存中である. 原発性虫垂癌は比較的まれな疾患であり, なかでも低分化腺癌は自験例を含め4例が報告されているのみであり, 極めてまれである.

During influenza epidemics in Japan, the number of children with acute encephalopathies and encephalitis has recently increased. Although the pathophysiologies remain unclear, there is usually brain edema with evidence of damage to the blood-brain-barrier (BBB). We investigated the glial reaction and apoptosis in brains of eight such cases comprising two of acute necrotizing encephalopathy and six of influenza encephalopathy, and compared the results with those in five control brains. Apoptosis, evidenced by chromatin condensation and fragmentation in hematoxylin sections, in situ end labeling of fragmented DNA (TUNEL) and DNA laddering, was observed in neurons and glial cells in four brains with influenza encephalopathy. In the TUNEL-positive brains, the increase in microglia was greater than in the TUNEL-negative brains. Immunoreactivity for active-caspase 3, demonstrated by immunohistochemistry, and the overexpression of a caspase-cleaved fragment of poly(ADP-ribose) polymerase, demonstrated by Western blotting, indicated that activation of caspase 3 is involved in the apoptotic pathway in the brains of influenza encephalopathy cases. Apoptosis or specific pathological processes that cause apoptosis may give rise to aggravated encephalopathy.

Background Mucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma. Methods Expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma. Results The following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p = 0.036); MUC2 with histological type (mucinous carcinoma, p

Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p = 0.019), depth (p = 0.017) and curability (p = 0.007)], MUC5AC [tumor location (p = 0.063) and lymph node metastasis (p = 0.059)], and MUC16 [venous invasion (p = 0.016) and curability (p = 0.016)]. Analysis of 58 cases with survival data revealed five factors associated with a poor prognosis: poorly-differentiated or neuroendocrine histological type (p

Morphologic, lmmunohistochemical and lmmunogenetic studies were performed on 28 cases of primary gastric lymphoma from fresh frozen tissue. Eight cases were diagnosed as diffuse large B-cell lymphoma, four as follicular center lymphoma (follicular), five as mucosa-associated lymphoid tissue (MALT) lymphoma, three as plasmacytoma, and three as T-cell lymphoma, two as mantle cell lymphoma, one as follicular center lymphoma (diffuse, predominantly small cell), and one as lymphoplasmacytoid lymphoma, and one as Hodgkin's disease. From lmmunohistochemical studies, four types of morphologically similar low-grade lymphomas can be differentiated by a combination of various monoclonal antibodies. Cases of diffuse large B-cell lymphoma may have a germinal center origin. We observed lympho-epithelial lesions in cases of non-MALT lymphomas. We therefore consider that the current diagnostic criterion for MALT lymphoma may not always be valid. Except for cases of T-cell lymphoma and Hodgkin's disease, 17 out of 22 cases revealed clonal rearrangement bands of the JH gene. In situ hybridization (ISH) and polymerase chain reaction (PCR) studies revealed the presence of Epstein-Barr (EB) virus genomes in two and three cases, respectively. Epstein-Barr virus may play a role in lympho-magenesis, although on relatively rare occasions.

Carcinoid tumors located in the minor duodenal papilla are extremely rare, with only a few cases reported in the literature. Herein, we report the case of a 71-year-old man with a 12-mm carcinoid tumor at the minor duodenal papilla with lymph node metastases. Multidetector-row computed tomography with contrast enhancement revealed a 12-mm well-enhanced tumor in the duodenum. Upper gastrointestinal endoscopy showed a 12-mm submucosal tumor at the minor papilla of the duodenum. Biopsy specimens revealed a carcinoid tumor, and a subtotal stomach-preserving pancreatoduodenectomy was performed. Carcinoid tumors at the minor duodenal papilla have a high prevalence of nodal disease, even for tumors

Rheumatoid nodules in dermal or subcutaneous tissues, while indicative of rheumatoid arthritis, are very rare. It is even less common to identify these rheumatoid nodules by biopsy as well as in autopsy materials from lung tissue. These nodules may be single or multiple, which seldom cause respiratory symptoms. Here, a patient with diffuse pulmonary rheumatoid nodules and interstitial fibrosis throughout both lungs, is described. The patient, with articular symptoms and seropositivity, exhibited a rapid clinical course and died of respiratory failure 3 months after the appearance of dyspnea. Chest radiography indicated interstitial pneumonitis with bilateral diffuse peripheral shadows. At autopsy, numerous rheumatoid nodules and interstitial fibrosis had destroyed both lungs, such that no residual normal pulmonary tissue remained. It is believed that this was an extremely rare case exhibiting large numbers of rheumatoid nodules throughout the lungs. Findings with this patient indicate that, in patients with rheumatoid arthritis, clinical interstitial pneumonitis confirmed radiologically does not exclude the existence of rheumatoid lung nodules.

Concerns over cancer development from exposure to environmental sources of densely ionizing, high linear energy transfer (LET) radiation, such as alpha-particles from radon, is a current public health issue. The study of tumors attributable to high LET irradiation would greatly augment our insights into the biological mechanisms of carcinogenesis. Chronic low-dose-rate internal exposure to alpha-radiation from thorium dioxide deposits following intravascular administration of the radiographic contrast agent Thorotrast is known to markedly increase the risk of cancer development, especially that of hepatic angiosarcomas and cholangiocarcinomas. Although the mechanism is hypothesized to be via cellular damage, DNA being a major target, wrought by the high LET alpha-particles, the specific genes and the actual sequence of events involved in the process of transforming a normal cell into a malignant one are largely unknown. To shed some light on the molecular mechanisms of cancer development during a lifetime exposure to alpha-radiation, we analyzed the most commonly affected tumor suppressor gene in humans, p53, in 20 Thorotrast recipients who developed cancer, mostly of hepatic bile duct and blood vessel origin. Of the 20 cases, 19 were found to harbor p53 point mutations. Moreover, the accompanying non-tumor tissues from these patients also had p53 mutations, albeit at lower frequency. The distribution pattern of the point mutations was significantly different between the non-tumor and tumor tissues, with most mutations in malignant tissues located in the highly conserved domains of the p53 gene. Our results support the idea that p53 mutations are important in the genesis of Thorotrast-induced tumors but that these point mutations are a secondary outcome of genomic instability induced by the irradiation. Additionally, non-tumor cells harboring p53 mutations may gain some survival advantage in situ but mutations in the domains responsible for the formation of structural elements critical in binding DNA may be necessary for a cell to reach full malignancy.

BACKGROUND. Previous studies have indicated that some patients with Hodgkin disease have an aggressive clinical course. However, their characteristics have not been elucidated. METHODS. Six patients initially diagnosed as having Hodgkin disease with subsequent transformation to CD30 positive non-Hodgkin lymphoma were clinically and immunohistochemically studied. Ten patients with classic anaplastic large cell lymphoma (ALCL) and 19 patients with classic Hodgkin disease were studied for comparison by immunohistochemistry. RESULTS. Five patients, excluding one whom the authors recently encountered, had an aggressive clinical course and died within approximately 1 year after diagnosis; four of them were autopsied. Common histologic findings in the six patients included sheets of atypical mononuclear cells and sinusoidal infiltration of small numbers of these cells, as well as Reed‐Sternberg cells or lacunar cells. Follow-up biopsies revealed histologic progression to ALCL in which sheets of atypical mononuclear or multinucleated cells spread throughout the lymph nodes. Immunohistochemically, epithelial membrane antigen, granzyme B, perforin, and pancadherin were expressed frequently in the six patients and in ALCL but were not expressed in Hodgkin disease. Latent membrane protein-1 (LMP-1) and Epstein‐Barr virus-encoded RNA (EBER-1) were totally negative in the six patients and in ALCL but were expressed frequently in Hodgkin disease. In contrast, LeuM1 (CD15) was expressed frequently in the six patients and in Hodgkin disease, whereas it was not expressed in ALCL. MT1 (CD43), UCHL-1 (CD45RO), and P80 were totally negative in the six patients and in Hodgkin disease, whereas they were expressed variably in ALCL. CONCLUSIONS. These results suggest that the six patients studied had intermediate phenotypes between ALCL and Hodgkin disease. The authors also suggest that patients with sheets of atypical mononuclear cells and sinusoidal infiltration of atypical mononuclear and multinucleated cells have an aggressive clinical course and should be treated with intensive chemotherapy. Cancer 1999;85:970 ‐9. © 1999 American Cancer Society.

An 81-year-old man with a 1 year history of Sjogren's syndrome and hypergammaglobulinemic purpura was admitted because of high fever and lymphadenopathy. Primary nodal plasmacytoma was suggested from the microscopic and immunohistochemical findings of an inguinal lymph node biopsy specimen. Although chemotherapy achieved a moderate response, the patient died 2 months later from respiratory and cardiac failure. We herein, is described a rare autopsy case of primary nodal plasmacytoma associated with Sjogren's syndrome, in which the clinical course was progressive and Epstein-Barr virus-encoded RNA 1 was positive in a small number of neoplastic plasma cells, showing some difference from previously reported cases.