Nobuyuki Tanida

Difference in cytokine production in acute and chronic rejection of rat lung allografts

Abstract  In Brown Norway to Lewis rat lung transplantation, short‐term administration of cyclosporine produces permanent adoption of allografts; however, the adopted grafts show symptoms of chronic rejection. To clarify the difference in cytokine production in acute an chronic rejection of the allografts, an immu‐nohistochemical study was performed. In acute rejection, positive cells for respective cytokines were observed in infiltrating cells, increasing in number as the days after transplantation passed, and reaching a maximum on the fifth day. The strongest reactivity was observed perivenously. In chronic rejection, TNF‐α positive cells were observed in the perivascular and peribron‐chial regions, especially around class II positive epithelia. The number of positive cells was, however, less than that in the vascular phase of acute rejection. Few cells were positive for IL‐lβ, IFN‐γ and, unexpectedly, for IL‐4. These facts indicate the functional difference of infiltrating cells between acute and chronic rejection.

Pleural‐changes in the lung allograft during acute rejection

Abstract To ascertain the cause of pleural fibrosis in lung allografts, pleural changes were investigated in rat syngeneic and allogeneic lung grafts. The pleura of lung syngeneic grafts showed no pathological changes except for mild edema on the first day after transplantation. In lung allografts, recipient cells migrated into the subpleural tissue early after transplantation (latent phase). In the vascuar phase, recipient lymphocytes in the subpleural tissue increased in number, while almost all alveolar structures were free from infiltration. Both CD4‐positive and CD8‐positive cells infiltrated in almost equal numbers with macrophages. The subsets of infiltrating cells were similar to those of the perivascular and peribronchial areas. In the late vascular or alveolar phase, fibro‐blasts were observed among the infiltrating cells, and fibrotic changes started. In the destructive phase, collagen formation with marked pleural thickening was dominant. Pulmonary acute rejection should be treated at least up to the late vascular phase to prevent pleural fibrosis.

Intractable chest pain in a patient whose postpneumonectomy space was managed with sulfur hexafluoride.

A 50-year-old man who had undergone right pneumonectomy 1 year previously was referred to our department following the sudden onset of severe chest pain. Since the operation, his postpneumonectomy space had been managed with sulfur hexafluoride. On admission, the pressure in the postpneumonectomy space was found to be more than +60 cmH2O. The chest pain was relieved after the sulfur hexafluoride had been drained and the pressure released. Thus, it is advisable to inject sulfur hexafluoride stepwise into the postpneumonectomy space of patients with long-standing fluid accumulation.

Acantholytic squamous cell carcinoma of the gallbladder mimicking adenocarcinoma: Letter to the Editor

To the Editor: Acantholysis, the loosening of cell–cell contact, is an uncommon characteristic of squamous cell carcinoma (SCC). Histologically, an acantholytic SCC (ASCC) is composed of pseudoglandular or pseudoacinar nests with central acantholysis and cohesive peripheral tumor cells. The most frequent site of ASCCs is the skin. Except in the oral cavity, only three cases of ASCC in the digestive tract (the esophagus, cecum, and pancreas, respectively) have been described. The aim of this study was to present the clinicopathological features of a patient with gallbladder ASCC; to the best of our knowledge, this is the first reported case. An 86-year-old Japanese man with no medical history of malignancy was admitted to our hospital for treatment of an incidentally detected gallbladder tumor. Gallstones were absent. Although, serum levels of carcinoembryonic antigen (CEA) and carbonic anhydrase 19-9 (CA19-9) were normal, computed tomography confirmed that the mass was enhanced after administration of a contrast agent (Fig. S1a,b). Extended cholecystectomy and lymphadenectomy were performed. Grossly, the mass was 26mm, dome-shaped, and solid and was located in the fundus (Fig. 1a). A whole-mount preparation of the gallbladder mass was performed, and 10 hematoxylin and eosin (HE)-stained sections of the mass were prepared. Histologically, it contained distinctive polygonal carcinoma cells, as well as nests and cords, which were findings associated with desmoplasia. The tumor nests and cords were frequently discohesive, resulting in pseudoglandular and pseudoacinar features (Fig. 1b–e). Keratin was absent, and dyskeratotic cells were not apparent; however, intercellular bridges were identified in cohesive nests (Fig. S1c) and pseudoglandular/pseudoacinar nests (Fig. 1c). A very small amount of spindle tumor cells was included, but sarcomatous growth was not seen. The superficial portion of the tumor consisted of necrotic and fibrinous areas. Focal biliary intraepithelial neoplasia 3 (BilIN-3) was observed in the mucosa near the periphery of the tumor. BilIN-3 was detected in only one of the 10 HEstained sections and was not connected to the invasive cancer with serial sections. There was no squamous metaplasia in the background mucosa. The tumor cells were negative for periodic acid-Schiff, Alcian blue, and mucicarmine. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin 5 (CK5, clone XM26, Fig. 1d), p40 (clone BC28, Fig. 1e), and E-cadherin (clone NCH-38), focally positive for MUC1 (clone DF3) and negative for CEA (clone II-7), CA19-9 (clone 1116-NS-19-9), MUC2 (clone M53), MUC5AC (clone 45M1), MUC6 (clone CLH5), smooth muscle markers, and CD34 (clone My10, Fig. S1d). Some acantholytic polygonal tumor cells expressed less CK5 (Fig. 1d), p40 (Fig. 1e), and E-cadherin than others, and these polygonal tumor cells also expressed vimentin (clone V9). Poorly differentiated adenocarcinoma was suspected on low-power magnification; however, SCC was diagnosed, mainly because of intercellular bridges in the tumor nests, negative mucin staining, and diffuse CK5 and p40 immunoreactivity. A diagnosis of ASCC was applicable because of the dominant acantholytic pattern (approximately 60%). The tumor was at a pathologic stage of pT2b, pN1, M0 (American Joint Committee on Cancer prognostic stage group IIIB), and the patient is currently disease-free 5 months after surgery. Pure SCCs, such as the present tumor, are rare, accounting for only 1.3% (8/606) of primary gallbladder carcinomas. Unlike most pure SCCs of the gallbladder (88%, 7/8 cases), the tumor described herein was not substantially keratinized and had few dyskeratotic cells, further highlighting its rarity. The tumor cells showed focal positivity for MUC1, which is consistent with a previous report. Pathologically, our case might be misdiagnosed as an adenocarcinoma because of the many pseudoglandular and pseudoacinar structures. Careful evaluation was essential for reaching a correct diagnosis, requiring detection of intercellular bridges, centrally located nuclei, and the lack of a true glandular structure. Specific staining for mucin and immunostaining for CK5 and p40 were useful for distinguishing from SCC from adenocarcinoma. In our case, a diagnosis of adenosquamous carcinoma might be applicable because BilIN-3 (carcinoma in situ) was found around the periphery of the tumor; however, no continuity between the BilIN-3 and invasive cancer was identified. Other differential diagnoses in our case include carcinosarcoma: focal sarcomatoid growth can accompany gallbladder SCC development. In our case, carcinosarcoma was not diagnosed because the spindle cell component and vimentin-positive tumor cells showed no sarcomatous growth. Skin ASCCs can exhibit pseudoangiosarcomatous growth, but this growth pattern was absent in our case.

Application of Sulfur Hexafluoride into Pleural Space Reduced Pulmonary Shunt in Chronically Atelectatic Lobe After Sleeve Resection—A Case Report

A seventy-three-year-old man had undergone right sleeve upper lobectomy. The bronchial anastomotic site occluded because of granulation that had been treated with yttrium aluminum garnet (YAG) laser initially. He refused reopera tion or YAG laser surgery at the time of reocclusion of the anastomotic site. He complained of exertional dyspnea, and his blood gas analysis showed hypoxe mia. The authors injected sulfur hexafluoride into pleural space of the patient to reduce pulmonary shunt in chronically atelectatic lobes. Blood gas analysis just after injection of sulfur hexafluoride gas into pleural space showed increase of oxygen tension, suggesting decrease in shunting. With the management of pleu ral space through use of sulfur hexafluoride, he leads a normal daily life without exertional dyspnea.