廣島 健三

Common variable immunodeficiency (CVID) is a heterogeneous subset of immunodeficiency disorders. Recurrent bacterial infection is the main feature of CVID, but various non-infectious complications can occur. A 42-year-old woman presented with cough and abnormal chest X-ray shadows. Laboratory tests showed remarkable hypogammaglobulinemia. Computed tomography revealed multiple consolidation and nodules on the bilateral lung fields, systemic lymphadenopathy, and splenomegaly. A surgical lung biopsy specimen provided the final diagnosis of lymphoproliferative disease in CVID, which was grouped under the term granulomatous lymphocytic interstitial lung disease. Interestingly, the lung lesions of this case resolved immediately after the initiation of intravenous immunoglobulin monotherapy.

We herein report a case of Rosai-Dorfman disease (RDD) overlapping with IgG4-related disease (IgG4-RD), which presented as diffuse interstitial lung disease with a perilymphatic pattern, followed by submandibular gland and eyelid swelling. The pathological findings of the submandibular gland biopsy specimen were indicative of IgG4-RD alone. We diagnosed the patient with RDD with overlapping IgG4-RD. However, the optimal method for differentiating between these two entities is still controversial. It is important that clinicians are aware that RDD should be included in the differential diagnoses of diffuse interstitial lung disease with a perilymphatic pattern and that RDD can overlap with IgG4-RD.

Objectives: Homozygous deletion (homo-d) of the p16 (CDKN2A) gene, as determined by fluorescence in situ hybridization (FISH), helps differentiate malignant pleural mesothelioma (MPM) from reactive mesothelial hyperplasia (RMH). Heterozygous deletion (hetero-d) has also been identified variably in p16 FISH. This study aimed to investigate the significance of homo-d and hetero-d of p16 in the diagnosis and prognosis of MPM. Materials and methods: p16 FISH was performed in 93 MPMs and 47 RMHs. Real-time polymerase chain reaction (PCR) and methylation specific PCR (MSP) were also performed for cases in which DNA was available. Overall survival (OS) was assessed via the Kaplan-Meier method and logranlc test. Results: Cutoff values for homo-d and hetero-d were set at 10% and 47%, respectively, based on p16 FISH results in RMH. In MPM, 80/93 (86.0%) were homo-d positive, and 15/93 (16.1%) were hetero-d positive. No RMH was homo/hetero-d positive. In nine cases of MPM with the low homo-d (<30%)/high hetero-d (>47%) pattern, FISH with a shorter probe caused a slight increase (from 20.1% to 26.5%) in the mean percentage of homo-d and a decrease in that of hetero-d (from 59.6% to 55.6%). Four cases in which the low homo-d/high hetero-d pattern was maintained with the shorter probe were further analyzed by real-time PCR, which separated them into a two (n = 2) or one allele deletion group (n = 2). MSP revealed no promoter methylation in the two cases with one allele deletion. The OS was significantly shorter in homo-d positive cases (n = 24) than homo-d negative cases (n = 5, p = 0.0002) in the 29 MPM cases with follow-up data. Also, low homo-d/high hetero-d cases (n = 5) had a significantly better prognosis than high homo-d (>30%) cases (n = 17, p = 0.011). Conclusions: Within p16 homo-d positive MPMs with poorer prognosis, the low homo-d/high hetero-d pattern may belong to a better prognostic subgroup in homo-d positive MPMs. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Aims Peritoneal malignant mesothelioma (PMM) is an uncommon tumour, accounting for only 7-9% of all mesotheliomas in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging. Methods To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine mesothelial-associated markers (calretinin, AE1/AE3, CK5/6, CAM5.2, D2-40, WT-1, HBME1, thrombomodulin), adenocarcinoma-associated markers (CEA, BerEP4, MOC31, ER (estrogen receptor), PgR, TTF-1, Claudin-4, Pax8), and malignant-related and benignrelated markers (epithelial membrane antigen (EMA), desmin, GLUT-1, CD146 and IMP3), and FISH to examine for homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 22 PMMs (M:F= 18:4; subtypes: 16 epithelioid, 6 biphasic), 11 PPSCs and 23 RMHs. Results Seventeen of the mesotheliomas (four PMM from women) were classified as diffuse, while five were localised. Calretinin was 91% positive in PMM, but negative in PPSC (specificity, 100%). BerEP4, Claudin-4 and PAX8 were all 100% positive in PPSC (specificities, 100%, 95% and 95%, respectively, for excluding PMM). For distinguishing PMM and RMH, sensitivity for EMA in mesothelioma was 68%, while for IMP3 and GLUT-1 it was 64% and 50%, respectively, all with high specificities. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/13 PMMs, but in 0/11 RMHs. Conclusions Calretinin and BerEP4 may be the best positive markers for differentiating PMM from PPSC. EMA, in combination with IMP3 and desmin, is useful, and homozygous deletion of 9p21 may be helpful, for differentiating PMM from RMH.

Background: Loss of BAP1 by immunohistochemistry (IHC) and CDKN2A(p16) deletion by fluorescence in situ hybridization (FISH) have been proposed to distinguish malignant mesothelioma (MM) from atypical reactive mesothelial proliferations (ARMP) in effusions but it is uncertain whether both tests are needed routinely. Methods: Paraffin embedded blocks from 67 effusions (32 MM, 35 ARMP) were evaluated with BAP1 IHC. 38 of them (17 MM, 21 ARMP) were also analyzed with CDKN2A (p16) FISH. Criteria for MM were absence of BAP1 nuclear staining in >50% of atypical mesothelial cells in the presence of a positive internal control, and/or CDKN2A(p16) homozygous or hemizygous deletion pattern in >15% or >41.5% of atypical mesothelial cells, respectively. Sensitivity (SS), specificity (SP), positive, and negative predictive values (PPV, NPV) for MM were calculated. Results: 17 of 32 MM were correctly diagnosed by IHC (SS 53.1%, SP 85.7%, PPV 77.3%, NPV 64.3% for MM). In the subset of 38 cases studied by IHC and FISH, the SS, SP, PPV, and NPV of IHC for MM were 41.2, 81.0, 63.6, and 63.0%, respectively. 7 of 17 MM were diagnosed by FISH (SS 41.2%, SP 100%, PPV 100%, NPV 67.7% for MM). Conclusion: BAP1 IHC and CDKN2A(p16) FISH yield similar sensitivities for MM in paired samples but FISH has a higher specificity. To diagnose effusions with atypical mesothelial cells, use of both tests is optimal. However, BAP1 IHC alone may be sufficient to diagnose MM when clinical, imaging, and cytologi-cal findings strongly suggest MM. (C) 2016 Wiley Periodicals, Inc.

Background. It has been reported that the coexistence of lung cancer and pulmonary tuberculosis is occasionally noted. Clinicians should always be cautious of the possibility of such a coexistence. Case. A 75-yearold male with lung cancer and mediastinal lymph node metastasis (adenocarcinoma, cT2aN3M0, IIIB) was treated by induction chemotherapy followed by left upper lobectomy. Because a palpable new lesion in the lower lobe was identified, partial resection was also performed. In addition to carcinoma (pT2aN1M0 IIA) of the upper lobe, the lower lobe mass was diagnosed as tuberculoma. A postoperative sputum examination revealed pulmonary tuberculosis and antituberculous medications were administered. Because a small mass shadow adjacent to bullae of the lower lobe was not recognized before chemotherapy, tuberculoma might appear after chemotherapy. Conclusion. We should be aware of the possibility of concomitant lung cancer and tuberculosis during cancer treatment because an immediate diagnosis and treatment are necessary

We report a 38-year-old woman with a left lung tumor presenting as obstructive pneumonia. Bronchoscopic examination revealed a polypoid tumor filling the left main bronchus. The tumor was partially resected by a snaring procedure for diagnostic purposes. Microscopic examination revealed a submucosal tumor located underneath normal bronchial epithelium. The tumor was composed of sheets of uniform oval to cuboidal cells encompassing numerous blood vessels. Immunohistochemically, the tumor cells exhibited smooth muscle markers, but were negative for neuroendocrine markers. The diagnosis of primary pulmonary glomus tumor was therefore made. Subsequent bronchoscopic intervention allowed us to pin-point the origin of the tumor: superior segmental B6a/b. She underwent a left lower lobe superior segmental resection successfully. Glomus tumors are relatively rare soft tissue tumors, and those of bronchopulmonary origin are exceedingly rare clinical condition. Among primary lung tumors, the carcinoid tumor is a mimic of the glomus tumor, and differentiating these tumors is known to be difficult, especially using small biopsy samples. In the present case, a large tissue sample obtained by bronchoscopic snaring was quite useful for the correct preoperative diagnosis. Because of the disease rarity, malignancy grade estimation of visceral glomus tumors has not been clearly addressed. Recently, the histopathological diagnostic criteria for malignant glomus tumors was defined in the WHO classification of soft tissue and bone tumors 4th edition. Here we also reviewed the literature on primary bronchopulmonary glomus tumors with special attention to the current concept of malignancy grade estimation.

Background: Idiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute exacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery. Pirfenidone is an anti-fibrotic agent known to reduce disease progression in IPF patients. A phase II study was conducted to evaluate whether perioperative pirfenidone treatment could reduce the incidence of postoperative AE-IPF patients with lung cancer. Methods: Pirfenidone was orally administered to IPF patients who were candidates for lung cancer surgery; pirfenidone was dosed at 600 mg/day for the first 2 weeks, followed by 1200 mg/day. Surgery was performed after at least 2 weeks of 1200-mg/day administration. The primary endpoint was non-AE-IPF rate during postoperative days 0-30, compared to the null value of 80 %, and the secondary endpoint was safety. Radiologic and pathologic diagnoses of IPF and AE-IPF were confirmed by an independent review committee. Results: From June 2012 to January 2014, 43 cases were enrolled, and 39 were eligible (full analysis set [FAS]). Both pirfenidone treatment and surgery were performed in 36 patients (per protocol set [PPS]). AE-IPF did not occur in 37/39 patients (94.9 % [95 % confidential interval: 82.7-99.4 %, p = 0.01]) in the FAS, and in 38/39 patients (97.2 % [95 % confidential interval: 85.5-99.9 %, p = 0.004] in the PPS. A grade 5 adverse event (death) occurred in 1 patient, after AE-IPF; no other grade 3-5 adverse events were observed. Conclusions: Perioperative pirfenidone treatment is safe, and is promising for reducing AE-IPF after lung cancer surgery in IPF patients.

背景. 中縦隔に発生する神経内分泌癌は極めて稀である。症例. 51歳女性。主訴は四肢感覚異常、前医で施行した胸部X線で胸部異常陰影を認め、当科紹介となった。胸部CTでは上〜中縦隔にかけて、上大静脈を圧排する72×52mmの腫瘤を認めた。超音波気管支鏡下針生検(EBUS-TBNA)を施行し、未分化癌の診断となった。全身検索で原発巣を疑う所見を認めず、縦隔悪性腫瘍または原発不明癌縦隔リンパ節転移が疑われた。術前化学放射線治療後に、縦隔腫瘍摘出術を施行した。免疫染色では、synaptophysin、CAM5.2、EMAは陽性、TTF-1は陰性であったが、腫瘍周囲に胸腺組織を認めず、large cell neuroendocrine carcinoma(pTxN2M0)と診断した。術後放射線照射を追加し、術後15ヵ月現在無再発生存中である。結論. 胸腺神経内分泌腫瘍との鑑別が困難であった中縦隔神経内分泌癌の1例を経験した。術前に良悪性ばかりではなく組織型を診断することは困難ではあるが、EBUS-TBNAは中縦隔腫瘍の診断に有用であった。(著者抄録)

Differentiating malignant pleural mesothelioma (MPM) cells morphologically from reactive mesothelial hyperplasia cells is problematic. Homozygous deletion (HD) of p16 (CDKN2A), detected by FISH, is a good marker of malignancy and is useful to differentiate between these cells. However, the correlation between the p16 status of effusion smears and that of the underlying MPM tissues has not been investigated. We used p16-specific FISH to investigate 20 cases of MPM from which both effusion cytologic smears and histologic specimens were available. In five cases, histologic specimens included both an invasive component and surface mesothelial proliferation. In 14 cases (70%), MPM cells in both tissue sections and effusion smears were p16 HD-positive. Conversely, MPM cells in the remaining six tumors (30%) were p16 HD-negative in both tissue sections and effusion smears. For all five MPM cases with surface mesothelial proliferations and invasive components, the effusion smears, surface mesothelial proliferations, and invasive MPM components all displayed p16 deletion. Moreover, the extent to which p16 was deleted in smears highly correlated with the extent of p16 deletion in tissues. The p16 deletion percentages were also similar among smears, tissue surface proliferations, and invasive components. In cases with clinical and radiologic evidence of a diffuse pleural tumor, detection of p16 deletion in cytologic smear samples may permit MPM diagnosis without additional tissue examination. However, the absence of p16 deletion in cytologic smear samples does not preclude MPM. This study demonstrated the correlation between the p16 deletion status of effusion cytology and that of underlying malignant pleural mesothelioma (MPM) tissues by fluorescence in situ hybridization (FISH) analysis for MPM cases in which both materials were available. To the best of our knowledge, this is the first study to evaluate the correlation of p16 FISH status in MPM between cytologic and histologic specimens. If p16 FISH status of cytologic preparations can predict that of the underlying MPM, it may be possible to diagnose MPM in cytologic preparations in cases with clinical and radiological evidence of a diffuse pleural tumor.

Background Chrysotile had been used in asbestos textile workshops in Southeast China but a clear relation to mesothelioma is lacking. Methods All patients diagnosed with mesothelioma from 2003 to 2010 at Yuyao People's Hospital were re-evaluated by multiple expert pathologists with immunohistochemistry and asbestos exposure data were collected. Results Of 43 patients with a mesothelioma diagnosis, 19 peritoneal and nine pleural cases were finally diagnosed as mesothelioma. All were females, and the mean age of the patients with peritoneal or pleural mesothelioma was 52.4 and 58.2 years, respectively. All these cases had a history of domestic or occupational exposure to chrysotile. Two-thirds of the patients were from two adjoining towns with multiple small asbestos textile workshops. Contamination of tremolite was estimated to be less than 0.3%. Conclusions This is a report of mesothelioma in women exposed to chrysotile asbestos at home and at work, with an over-representation of peritoneal mesothelioma. (C) 2015 Wiley Periodicals, Inc.

A 67-year-old male with a history of asbestos exposure presented with fever, cough, and dyspnea and was found to have diffuse granular shadowing in both lungs, right pleural effusion, and hilar and mediastinal lymphadenopathy upon chest computed tomography. For definitive diagnosis, a thoracoscopic lung biopsy was performed. Intraoperative findings showed no remarkable macroscopic changes in the visceral and parietal pleura, although a high level of hyaluronic acid in the pleural effusion was noted. Histological findings showed proliferation of atypical cells with round-to-oval nuclei, prominent nucleoli, and eosinophilic cytoplasms. These cells were arranged into sheets or tubules and were located predominantly in the lung parenchyma. Lymphovascular invasion was conspicuous. Immunohistochemically, tumor cells were positive for calretinin, D2-40, and CK5/6, focally positive for Ber-EP4, but negative for WT-1, TTF-1, CEA, and MOC31. Fluorescence in situ hybridization for the tumor suppressor p16 revealed homozygous deletion in the tumor cells. Therefore, we diagnosed the tumor as diffuse intrapulmonary malignant mesothelioma (DIMM). The patient had a poor response to chemotherapy and died 1 year after diagnosis. Although rare, DIMM should be considered when patients present with multiple, tiny intrapulmonary nodules, regardless of macroscopic pleural changes. Furthermore, this is the first report on p16 status in DIMM.

Primary pericardial synovial sarcoma is a rare disease. We herein report a case of synovial sarcoma that originated in the epicardium. A 13-year-old male visited our hospital with a fever and chest pain. Copious pericardial effusion and a large intrapericardial tumor were detected. An open-chest tumor resection was performed. A solid nodular tumor was observed in the pericardial cavity. The tumor was a polypoid mass that was pedunculated and grew from the inner surface of the pericardium near the origin of the SVC and ascending aorta. Histologically, the tumor cells were uniformly spindle shaped, with an ovoid or oval nucleus, and formed solid, compact sheets and fascicles. A storiform pattern was also observed. Based on the histopathological and immunohistochemical findings, and the fluorescence in situ hybridization detection of rearrangement of the SYT gene, a monophasic synovial sarcoma was diagnosed. We discuss the diagnosis and treatment of this case and review the pertinent literature.

Background: Transduction of human mesenchymal stem cells (MSCs) with type 5 adenoviruses (Ad5) is limited in the efficacy because of the poor expression level of the coxsackie adenovirus receptor (CAR) molecules. We examined a possible improvement of Ad-mediated gene transfer in MSCs by substituting the fiber region of type 5 Ad with that of type 35 Ad. Methods: Expression levels of CAR and CD46 molecules, which are the major receptors for type 5 and type 35 Ad, respectively, were assayed with flow cytometry. We constructed vectors expressing the green fluorescent protein gene with Ad5 or modified Ad5 bearing the type 35 fiber region (AdF35), and examined the infectivity to MSCs with flow cytometry. We investigated anti-tumor effects of MSCs transduced with interleukin (IL)-28A gene on human lung carcinoma cells with a colorimetric assay. Expression of IL-28A receptors was tested with the polymerase chain reaction. A promoter activity of transcriptional regulatory regions in MSCs was determined with a luciferase assay and a tumor growth-promoting ability of MSCs was tested with co-injection of human tumor cells in nude mice. Results: MSCs expressed CD46 but scarcely CAR molecules, and subsequently were transduced with AdF35 but not with Ad5. Growth of MSCs transduced with the IL-28A gene remained the same as that of untransduced cells since MSCs were negative for the IL-28A receptors. The IL-28A-transduced MSCs however suppressed growth of lung carcinoma cells co-cultured, whereas MSCs transduced with AdF35 expressing the beta-galactosidase gene did not. A regulatory region of the cyclooygenase-2 gene possessed transcriptional activities greater than other tumor promoters but less than the cytomegalovirus promoter, and MSCs themselves did not support tumor growth in vivo. Conclusions: AdF35 is a suitable vector to transduce MSCs that are resistant to Ad5-mediated gene transfer. MSCs infected with AdF35 that activate an exogenous gene by the cytomegalovirus promoter can be a vehicle to deliver the gene product to targeted cells.

Objective: Mesothelial hyperplasia (MH) and fibrosing pleuritis (FP) can be difficult to distinguish from epithelioid (MM-E) and sarcomatoid (MM-S) malignant pleural mesotheliomas. GLUT-1 has shown variable results regarding its sensitivity and specificity when used to evaluate mesothelial proliferations. We evaluated the utility of GLUT-I immunostaining in differentiating MH and FP from MM-E and MM-S. Materials and methods: In this retrospective study, diagnostically well-characterized cases (MH = 31, FP = 29, MM-E = 41, MM-S = 29) were collected and manually stained for GLUT-1. All slides were visually scored by 2 pathologists; using the following system: 0%, 1+ 1-25%, 2+ 26-50% and 3+ >51% cells staining. Results: All benign cases (n= 60) were negative for GLUT-1 while 45 of 78 (58%) MM [21 of 41 (50%) MM-E, 21 of 29 (72%) MM-S and 3 of 3 biphasic mesothelioma (100%)] had 1+ to 3+ staining. Of the MM-E, 10 had 1+, and 11 had 2+ staining; of the MM-S 3 had 1+, 15 had 2+ and 3 had 3+ staining. Both sarcomatoid and epithelioid components of the 3 biphasic mesotheliomas revealed 1+ staining. All 5 desmoplastic MM were negative. Conclusions: Positive staining with GLUT-1 is helpful since it is present in half of MM-E and three-quarter of MM-S. Although all reactive mesothelial lesions were negative, the absence of immunoreactivity does not exclude the diagnosis of MM. As with all IHC stains used for diagnostic purposes, GLUT-1 has to be a part of a panel, and the results interpreted in the context of clinical, radiological and histological findings. (c) 2014 Elsevier Ireland Ltd. All rights reserved.

背景．大細胞肺癌は通常末梢肺に発生し，気道狭窄を来すことは稀である．症例．65歳男性．増悪する咳嗽，呼吸困難を主訴に近医を受診した．胸部CTにてリンパ節#4Rの位置に6.3×5.8 cm大の腫瘤を認め，気管への直接浸潤により気管分岐部直上は著明に狭窄していた．転院当日，窒息状態となり気管内挿管を行い人工呼吸器管理とした．翌日，全身麻酔下に硬性鏡にて腫瘍を部分切除後，Yステントを留置し，呼吸困難感は著明に改善した．病理診断は神経内分泌分化を示す大細胞癌で，遠隔臓器転移を認めず，cT4N2M0，stage IIIBと診断した．計60 Gyの放射線治療とシスプラチンとエトポシドによる化学療法を4コース施行して腫瘍は縮小を認め，治療終了1年半後にYステントは抜去した．結語．中枢気道狭窄を来し，Yステント留置後に化学放射線療法が奏功した神経内分泌分化を示す大細胞肺癌の1例を経験したので，報告した．<br>

背景．B3胸腺腫には稀に退形成（anaplasia）を認めることがあり，胸腺腫の特徴を保持しながら腫瘍の一部が異型性の強い上皮へ変化することが報告されている．症例．68歳男性．重症筋無力症合併胸腺腫に対し，ステロイド導入後に拡大胸腺摘除術を施行した．組織学的に腫瘍は大型の核を有する上皮細胞とリンパ球様細胞からなり，B3胸腺腫の所見であった．同時に胞巣の一部で，上皮細胞の核が大型になり扁平上皮への分化がみられた．免疫染色ではCD5とGlut-1が陰性で，Ki-67標識率は低値であり，胸腺腫の一部が異型性の強い扁平上皮に退形成したものと考えた．以上よりB3 thymoma with anaplasiaと診断した．結論．B3胸腺腫の一部に異型性の強い扁平上皮への分化を示す症例を報告した．World Health Organization分類2004年版ではこのような症例をB3 thymoma with anaplasiaと診断することを提起しており，本症例も同一のグループに属するものと考えられた．<br>

Background. It is difficult to distinguish the development of granuloma along the staple line after segmentectomy from tumor recurrence. Case. A 70-year-old male underwent left S⁸ segmentectomy with lymph node dissection for early stage IA lung adenocarcinoma using video-assisted thoracic surgery. One year later, a routine chest CT scan disclosed a mass adjacent to the previous segmentectomy site. Although local recurrence of lung cancer was suspected, a bronchoscopic examination showed no recurrence, and the results of a bacteriological examination were nonspecific. Steroid therapy was therefore initiated based on our concern for the potential of organizing pneumonia. The mass lesion subsequently shrank in size, almost disappearing. Interval chest CT, however, demonstrated regrowth of the site of consolidation along the staple line. The steroid therapy was repeated; however, the area of consolidation continued to grow. Completion left lower lobectomy was thus performed, as the possibility of local cancer recurrence could not be excluded. At the time of thoracotomy, a hard white mass was palpated along the staple line in the left lower lobe. A pathological analysis revealed epithelioid granuloma with caseating necrosis, and Mycobacterium avium complex (MAC) grew from a culture of the specimen. Therefore, the lesion was thought to be a granuloma caused by MAC infection at the previous segmentectomy staple line. Conclusions. We herein report a rare case of pulmonary granuloma associated with non-tuberculous mycobacteriosis occurring at the staple line after segmentectomy for lung cancer. In addition to local recurrence or secondary primary lung cancer, the possibility of mycobacterial granuloma should be considered in cases in which pulmonary nodules are detected on the staple line after pulmonary resection.

背景．富細胞性神経鞘腫は，組織学的に細胞密度の高いAntoni Aの組織を主体とした腫瘍である．症例．65歳女性．主訴は腰痛．胸部CTで右肋骨横隔洞に局在する12 cm大の巨大腫瘤影を認めた．FDG-PETでFDG高度異常集積を認めたため悪性腫瘍を疑われ，腫瘍摘出術を施行された．腫瘍は表面平滑で被膜に包まれ，椎体と下行大動脈に強く固着していた．組織学的に，紡錐形細胞が密に増殖し，一部にfoamy macrophageの集簇を認めた．免疫染色はS-100蛋白陽性，Ki-67標識率は低値であり，富細胞性神経鞘腫と診断した．結論．肋骨横隔洞に発生した巨大富細胞性神経鞘腫の1例を報告した．細胞密度が高い本症例では，FDG-PETでの高度集積を認め，軟部腫瘍系の悪性腫瘍との鑑別を要した．

We examined the combinatory antitumor effects of adenoviruses expressing human mda-7/IL-24 gene (Ad-mda-7) and chemotherapeutic agents on nine kinds of human esophageal carcinoma cells. All the carcinoma cells expressed the melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24) receptor complexes, IL-20R2 and either IL-20R1 or IL-22R1, and were susceptible to Ad-mda-7, whereas fibroblasts were positive only for IL-20R2 gene and resistant to Ad-mda-7-mediated cytotoxicity. Sensitivity of these esophageal carcinoma cells to Ad-mda-7 was however lower than that to Ad expressing the wild-type p53 gene. We thereby investigated a possible combination of Ad-mda-7 and anticancer agents and found that Ad-mda-7 with 5-fluorouracil (5-FU), cisplatin, mitomycin C or etoposide produced greater cytotoxic effects than those by Ad-mda-7 or the agent alone. Halfmaximal inhibitory concentration values of the agents in respective cells were decreased by the combination with Ad-mda-7. Cell cycle analyses showed that Ad-mda-7 and 5-FU increased G2/M-phase and S-phase populations, respectively, and the combination augmented sub-G1 populations. Ad-mda-7-treated cells showed cleavages of caspase-8, -9 and -3 and poly (ADP-ribose) polymerase, but the cleavage levels were not different from those of the combination-treated cells. Ad-mda-7 treatments upregulated Akt phosphorylation but suppressed I kappa B-alpha levels, whereas 5-FU treatments induced phosphorylation of p53 and extracellular signal-regulated protein kinases 1 and 2. Molecular changes caused by the combination were similar to those by Admda-7 treatments, but the Ad-mda-7-mediated upregulation of Akt phosphorylation decreased with the combination. These data collectively suggest that Ad-mda-7 induced apoptosis despite Akt activation and that the combinatory antitumor effects with 5-FU were produced partly by downregulating the Ad-mda-7-induced Akt activation.

Ciliated muconodular papillary tumor(線毛性粘液結節性乳頭状腫瘍)は肺末梢部に発生し、線毛細胞と杯細胞が乳頭状増殖を示す稀な腫瘍である。今回我々は、本疾患の1切除例を経験したので報告する。(著者抄録)