論文 - 加勢田　馨

Determination of poor prognostic immune features of tumour microenvironment in non-smoking patients with lung adenocarcinoma

Kinoshita, T., Kudo-Saito, C., Muramatsu, R., Fujita, T., Saito, M., Nagumo, H., Sakurai, T., Noji, S., Takahata, E., Yaguchi, T., Tsukamoto, N., Hayashi, Y., Kaseda, K., Kamiyama, I., Ohtsuka, T., Tomizawa, K., Shimoji, M., Mitsudomi, T., Asamura, H. and Kawakami, Y.

Eur J Cancer 86   15 - 27 2017年11月

ISSN  1879-0852

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We have previously demonstrated that the prognostic significance of tumour-infiltrating CD8(+) T cells significantly differs according to histological type and patient smoking habits in non-small cell lung cancer (NSCLC). This work suggested that infiltrating CD8(+) T cells may not be activated sufficiently in the immunosuppressive microenvironment in non-smokers with adenocarcinoma. To understand the immunogenic microenvironment in NSCLC, we characterised immune cells comprehensively by performing an immunohistochemical evaluation using an alternative counting method and multicolour staining method (n = 234), and assessed immune-related gene expression by using genetic analytical approaches (n = 58). We found that high infiltration of activated CD8(+) T cells expressing interferon gamma (IFN-gamma) and granzyme was correlated with postoperative survival in patients with non-adenocarcinoma. On the contrary, CD8(+) T-cell accumulation was identified as a worse prognostic factor in patients with adenocarcinoma, particularly in non-smokers. Infiltrating CD8(+) T cells were significantly less activated in this microenvironment with high expression of various immunoregulation genes. Potentially immunoregulatory CD8(+) FOXP3(+) T cells and immunodysfunctional CD8(+) GATA3(+) T cells were increased in adenocarcinoma of non-smokers. CD4(+) FOXP3(+) regulatory T cells expressing chemokine receptor-4 (CCR4)- and chemokine ligand (CCL17)-expressing CD163(+) M2-like macrophages also accumulated correlatively and significantly in adenocarcinoma of non-smokers. These characteristic immune cells may promote tumour progression possibly by creating an immunosuppressive microenvironment in non-smoking patients with lung adenocarcinoma. Our findings may be helpful for refining the current strategy of personalised immunotherapy including immune-checkpoint blockade therapy for NSCLC.

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Clinical and pathological characteristics of EGFR mutation in operable early-stage lung adenocarcinoma

Yotsukura, M., Yasuda, H., Shigenobu, T., Kaseda, K., Masai, K., Hayashi, Y., Hishida, T., Ohtsuka, T., Naoki, K., Soejima, K., Betsuyaku, T. and Asamura, H.

Lung Cancer 109   45 - 51 2017年07月

ISSN  1872-8332

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OBJECTIVES: Over the past decade, the biological and clinical characteristics of lung cancer with epidermal growth factor receptor (EGFR) mutation have been well studied. However, most studies have focused on advanced inoperable cancer, and not on resected early-stage lung adenocarcinoma. We aimed to elucidate the differences in the clinicopathological characteristics and postoperative prognosis according to the EGFR mutation status in early-stage lung adenocarcinoma. MATERIALS AND METHODS: We retrospectively collected clinical and pathological data from 369 patients with pathological stage I or II lung adenocarcinoma who underwent complete resection. Clinicopathological characteristics and postoperative prognosis were compared depending on the EGFR mutation status, using the Chi-squared test and the log-rank test, respectively. RESULTS AND CONCLUSION: Of the 369 patients, 160 (43.3%) had EGFR mutation, of which 64 (40.0%) were exon 19 deletion (Del-19) and 90 (56.3%) were exon 21 point mutation L858R. Although there was no difference in overall survival (OS) between patients with and without EGFR mutation (p=0.086), tumors with EGFR mutation were associated with a lower consolidation to tumor ratio (CTR) (p <0.001) and a higher incidence of a lepidic growth pattern by pathological evaluation (p <0.001) compared to those without EGFR mutation. Among tumors with EGFR mutation, there was no difference in OS (p=0.140) between Del-19 and L858R. Tumors with L858R were associated with a lower CTR (p=0.046), and tended to have a higher incidence of a lepidic growth pattern by pathological evaluation (p=0.073) compared to those with Del-19. In conclusion, although EGFR mutation status was not a prognostic indicator after surgery in early-stage lung adenocarcinoma, L858R and Del-19 had different radiological and pathological features.

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Clinicopathological and prognostic features of surgically resected pathological stage I lung adenocarcinoma harboring epidermal growth factor receptor and K-ras mutation.

Kaseda K, Asakura K, Kazama A, Ozawa Y

Thoracic Cancer 8 （ 3 ） 229 - 237 2017年05月

査読有り,  ISSN  1759-7714

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BACKGROUND: This study aimed to evaluate mutations of the epidermal growth factor receptor (EGFR) and K-ras genes and their clinicopathological and prognostic features in patients with resected pathological stage I adenocarcinoma. METHODS: We examined 224 patients with surgically resected lung adenocarcinoma and analyzed the prognostic and predictive value of these mutations in 162 patients with pathological stage I adenocarcinoma. RESULTS: Mutations of the EGFR and K-ras genes were detected in 100 (44.6%) and 19 (8.5%) of all tumors, and in 81 (50.0%) and 17 (10.5%) of the pathological stage I tumors, respectively. EGFR mutations were significantly associated with female gender, smoking habit (never smoker), and low grade. By contrast, K-ras mutations were significantly associated with male gender, smoking habit (ever smoker), and the presence of mucinous components. No significant differences were observed in recurrence-free or overall survival between the EGFR-mutant, K-ras-mutant, and wild-type groups (five-year recurrence-free survival 77.8% vs. 87.8% vs. 79.5%; five-year overall survival 82.8% vs. 82.4% vs. 79.2%, respectively). Multivariate analysis showed that neither EGFR nor K-ras mutation was an independent prognostic factor. CONCLUSIONS: The present study demonstrated that pathological stage I adenocarcinoma harboring EGFR and K-ras gene mutations have distinct clinicopathological features. The presence of these mutations alone were not prognostic factors in patients with resected pathological stage I adenocarcinoma.

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Risk Factors for Predicting Occult Lymph Node Metastasis in Patients with Clinical Stage I Non-small Cell Lung Cancer Staged by Integrated Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Kaseda K, Asakura K, Kazama A, Ozawa Y.

World Journal of Surgery 40 （ 12 ） 2976 - 2983 2016年12月

研究論文（学術雑誌）, 査読有り,  ISSN  1432-2323

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BACKGROUND: Lymph nodes in patients with non-small cell lung cancer (NSCLC) are often staged using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). However, this modality has limited ability to detect micrometastases. We aimed to define risk factors for occult lymph node metastasis in patients with clinical stage I NSCLC diagnosed by preoperative integrated FDG-PET/CT. METHODS: We retrospectively reviewed the records of 246 patients diagnosed with clinical stage I NSCLC based on integrated FDG-PET/CT between April 2007 and May 2015. All patients were treated by complete surgical resection. The prevalence of occult lymph node metastasis in patients with clinical stage I NSCLC was analysed according to clinicopathological factors. Risk factors for occult lymph node metastasis were defined using univariate and multivariate analyses. RESULTS: Occult lymph node metastasis was detected in 31 patients (12.6 %). Univariate analysis revealed CEA (P = 0.04), SUV(max) of the primary tumour (P = 0.031), adenocarcinoma (P = 0.023), tumour size (P = 0.002) and pleural invasion (P = 0.046) as significant predictors of occult lymph node metastasis. Multivariate analysis selected SUV(max) of the primary tumour (P = 0.049), adenocarcinoma (P = 0.003) and tumour size (P = 0.019) as independent predictors of occult lymph node metastasis. CONCLUSIONS: The SUV(max) of the primary tumour, adenocarcinoma and tumour size were risk factors for occult lymph node metastasis in patients with NSCLC diagnosed as clinical stage I by preoperative integrated FDG-PET/CT. These findings would be helpful in selecting candidates for mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration.

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Value of the Glasgow Prognostic Score as a Prognostic Factor in Resectable Non-Small Cell Lung Cancer

Yotsukura, M., Ohtsuka, T., Kaseda, K., Kamiyama, I., Hayashi, Y. and Asamura, H.

J Thorac Oncol 11 （ 8 ） 1311 - 1318 2016年08月

ISSN  1556-1380

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BACKGROUND: Over the past decade, the Glasgow prognostic score (GPS), which is based on serum C-reactive protein and albumin levels, has been reported to be associated with the prognosis of patients with several types of inoperable and operable cancers. However, its applicability to operable non-small cell lung cancer (NSCLC) has not yet been established. METHODS: We retrospectively collected data from patients with pathological stage I or II NSCLC who underwent complete resection. A total of 1048 patients were categorized as either GPS-0 (n = 817 [78.0%]), GPS-1 (184 [17.6%]), or GPS-2 (47 [4.5%]). Survival curves were estimated using the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the relationship between prognosis and GPS status. RESULTS: The 5-year overall survival (OS) rates were 91.2%, 78.3%, and 75.8% for GPS-0, GPS-1, and GPS-2, respectively. There were significant differences in OS between GPS-0 and GPS-1 (p < 0.001) and between GPS-0 and GPS-2 (p < 0.001). Ten variables demonstrated to be associated with OS in a univariate analysis were subjected to a multivariate analysis. The results showed that male sex (p = 0.031), vascular invasion (p < 0.001), lymph node metastasis (p < 0.001), and GPS (p = 0.025) were significantly associated with OS. CONCLUSIONS: A high GPS is significantly associated with poor OS. Although the biological mechanism that underlies this association is not clear, this inflammation-based score may be a useful indicator of the prognosis in patients with resectable NSCLC.

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Identification of false-negative and false-positive diagnoses of lymph node metastases in non-small cell lung cancer patients staged by integrated (18F-)fluorodeoxyglucose-positron emission tomography/computed tomography: A retrospective cohort study

Kaseda, K., Watanabe, K., Asakura, K., Kazama, A. and Ozawa, Y.

Thorac Cancer 7 （ 4 ） 473 - 80 2016年07月

ISSN  1759-7706

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BACKGROUND: The aim of this study was to evaluate the diagnostic accuracy of integrated (18) F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in hilar and mediastinal lymph node (HMLN) staging of non-small cell lung cancer (NSCLC), and to investigate potential risk factors for false-negative and false-positive HMLN metastases. METHODS: We examined the data of 388 surgically resected NSCLC patients preoperatively staged by integrated FDG-PET/CT. Risk factors for false-negative and false-positive HMLN metastases were analyzed using univariate and multivariate analyses of clinicopathological factors. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of integrated FDG-PET/CT in detecting HMLN metastases were 47.4%, 91.0%, 56.3%, 87.7%, and 82.5%, respectively. On multivariate analysis, the maximum standardized uptake value (SUVmax) of the tumor (P = 0.042), adenocarcinoma (P = 0.003), and tumor size (P = 0.017) were risk factors for false-negative HMLN metastases, and history of lung disease (P = 0.006) and tumor location (central; P = 0.025) were risk factors for false-positive HMLN metastases. CONCLUSIONS: The present study identified risk factors for false-negative and false-positive HMLN metastases in NSCLC patients staged by preoperative integrated FDG-PET/CT. These findings would be helpful in selecting appropriate candidates for mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration.

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Solitary pulmonary metastasis from occult papillary thyroid carcinoma

Kaseda K, Watanabe K, Sakamaki H, Kazama A.

Thoracic Cancer 7 （ 2 ） 261 - 3 2016年03月

ISSN  1759-7706

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Pulmonary metastases from thyroid carcinoma typically cause a micronodular or miliary pattern throughout both lungs. Metastasis consisting of a solitary pulmonary nodule measuring 20 mm in diameter is rare. Here we report a case of a 66-year-old woman without a history of papillary thyroid carcinoma who presented with a pulmonary nodule measuring 20 mm in diameter, found on chest computed tomography during a health checkup. The patient underwent a right lobectomy. Microscopic examination showed well-differentiated papillary adenocarcinoma. Immunohistochemical findings were consistent with a diagnosis of pulmonary metastasis from papillary thyroid carcinoma. Solitary metastasis to the lung from occult thyroid carcinoma is quite rare, but if a pulmonary nodule is encountered in a patient without a history of thyroid carcinoma, the possibility must be considered.

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Pulmonary arterial enlargement predicts cardiopulmonary complications after pulmonary resection for lung cancer: a retrospective cohort study

Asakura, K., Mitsuboshi, S., Tsuji, M., Sakamaki, H., Otake, S., Matsuda, S., Kaseda, K. and Watanabe, K.

J Cardiothorac Surg 10   113 2015年09月

ISSN  1749-8090

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BACKGROUND: The finding of pulmonary arterial enlargement on computed tomography has been reported to be associated with pulmonary hypertension. On the other hand, pulmonary hypertension is a known risk factor for thoracic surgery. We investigated whether pulmonary arterial enlargement predicts cardiopulmonary complications following pulmonary resection for lung cancer. METHODS: We reviewed 237 consecutive patients who underwent pulmonary resection for lung cancer. Preoperative patient characteristics (sex, age, Brinkman index, cardiopulmonary comorbidities, cardiothoracic ratio, pulmonary function, and pulmonary arterial enlargement) and surgical data (surgical procedure, pathological stage, postoperative complications, mortality, and length of postoperative hospital stay) were analyzed. In order to evaluate preoperative pulmonary arterial enlargement, we measured the diameter of the main pulmonary artery at its bifurcation and that of the ascending aorta at its widest point using chest computed tomography and calculated the ratio of the former diameter to the latter. RESULTS: In all, 16 patients developed postoperative cardiopulmonary complications and 221 did not. One patient died from postoperative pneumonia. The mean age of patients who developed postoperative cardiopulmonary complications was significantly higher than that of those who did not (78 +/- 5 years vs 69 +/- 9 years, P=0.0001). The pulmonary artery-to-ascending-aorta ratio was significantly higher in patients who developed postoperative complications than in those who did not (0.94 +/- 0.15 vs. 0.81 +/- 0.11, P=0.03). Other preoperative patient characteristics and surgical data did not differ significantly between the groups. On multivariate analysis, pulmonary artery-to-ascending-aorta ratio (0.1-point increase; odds ratio 2.3, 95 % confidence interval 1.5-3.5; P=0.0002) and age (1-year increase; odds ratio 1.2, 95 % confidence interval 1.1-1.3; P=0.03) were found to be independent predictors of postoperative cardiopulmonary complications. CONCLUSIONS: A finding of pulmonary arterial enlargement on computed tomography is a potential predictor of postoperative cardiopulmonary complications after lung cancer surgery.

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Surgical resection of lung adenocarcinoma after crizotinib treatment: report of a case

Kaseda K, Watanabe K, Asakura K, Kazama A.

World Journal of Surgical Oncology 13   74 2015年02月

ISSN  1477-7819

　概要を見る

A 45-year-old female was diagnosed as having lung adenocarcinoma harboring an anaplastic lymphoma kinase (ALK) rearrangement, stage IV (T2bN3M1b). She was treated with crizotinib as second-line chemotherapy. The clinical stage after crizotinib treatment was ycT2aN0M0, stage IB. We performed a left lower lobectomy and lymph node dissection aimed at local control and pathological confirmation of the remaining tumor. The final pathological stage was ypT2aN2M0, stage IIIA with Ef 1b. To the best of our knowledge, this is the first case report of surgical resection in ALK rearrangement-positive lung adenocarcinoma after crizotinib treatment.

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胸腺原発MALTリンパ腫の1切除例

加勢田 馨

日本呼吸器外科学会雑誌 2014年12月

Surgery for secondary pneumothorax caused by Hermansky-Pudlak syndrome

Kaseda K, Goto T, Emoto K, Hayashi Y.

Eur Respir J 44 （ 6 ） 1714 - 5 2014年12月

ISSN  1399-3003

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Carbon monoxide-releasing molecule attenuates allograft airway rejection

Ohtsuka, T., Kaseda, K., Shigenobu, T., Hato, T., Kamiyama, I., Goto, T., Kohno, M. and Shimoda, M.

Transpl Int 27 （ 7 ） 741 - 7 2014年07月

ISSN  1432-2277

　概要を見る

Acute rejection after lung transplantation is the main risk factor for the development of bronchiolitis obliterans (BO). Carbon monoxide (CO) can provide anti-inflammatory effects and may serve to limit tissue injury in airway transplant. Here, we tested the ability of carbon monoxide releasing molecule-2 (CORM-2) to prevent airway rejection. Tracheal grafts from BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Experimental groups were treated with multiple doses of CORM-2. Histopathological evaluation of luminal obliteration was blindly reviewed. Immunohistochemistry and real-time RT-PCR analyses were performed. Allografts treated with CORM-2 revealed a striking reduction of thickening in epithelial and subepithelial airway layers (P < 0.01) at day 7 in orthotopic trachea transplantation model compared with allografts treated with vehicle. In heterotopic trachea transplantation model, CORM-2 treated allografts showed a reduction of luminal obliteration (P < 0.01) at days 14 and 21. There was also a concordant decrease in CD3(+) lymphocytes and macrophages in CORM-2 treated allografts. IFN-gamma, IL-2 and IL17A mRNA expressions were reduced dramatically by systemic administration of CORM-2. These data implicate CORM-2-derived CO has an important protective function in experimental BO, and may represent a target for the therapeutic intervention of chronic lung allograft rejection.

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Solitary glandular papilloma of the peripheral lung: a report of two cases

Kaseda K, Horio H, Harada M, Hishima T.

World Journal of Surgical Oncology 19 2014年05月

Surgical treatment of a solitary pulmonary metastasis from eyelid sebaceous carcinoma: report of a case

Kaseda K, Ohtsuka T, Hayashi Y, Emoto K, Asakura K, Kamiyama I, Goto T, Kohno M.

World Journal of Surgical Oncology 23 2014年04月

Carcinoids among multiple lung tumorlets: carcinoids or aggregates of tumorlets?

Kaseda K, Izumi Y, Hayashi Y, Goto T, Ohtsuka T, Kohno M.

Pathology International 64 （ 2 ） 91 - 3 2014年02月

ISSN  1440-1827

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Aldehyde dehydrogenase 1 expression in cancer cells could have prognostic value for patients with non-small cell lung cancer who are treated with neoadjuvant therapy: identification of prognostic microenvironmental factors after chemoradiation

Zenke, Y., Ishii, G., Ohe, Y., Kaseda, K., Yoshida, T., Matsumoto, S., Umemura, S., Yoh, K., Niho, S., Goto, K., Ohmatsu, H., Kuwata, T., Nagai, K. and Ochiai, A.

Pathol Int 63 （ 12 ） 599 - 606 2013年12月

ISSN  1440-1827

　概要を見る

Prognostic factors for patients with non-small cell lung cancer (NSCLC) who have been treated with neoadjuvant therapy have not been fully assessed. The purpose of this study was to analyze prognostic biomarkers in NSCLC after treatment with neoadjuvant therapy, with special reference to the immunophenotypes of both the cancer cells and stromal cells. A total of 52 patients with NSCLC who were treated with neoadjuvant therapy followed by complete resection were included. We examined the expressions of nine markers in the cancer cells and stromal cells. The 5-year disease-free survival rate of patients with high aldehyde dehydrogenase 1 (ALDH1) expression levels in their cancer cells was significantly lower than those with a low ALDH1 level (47.3% vs. 21.5%, respectively; P = 0.023). The other molecules expressed in cancer cells did not exhibit any prognostic value. In NSCLC without neoadjuvant therapy (case control, n = 104), expression of ALDH1 in cancer cells was not correlated with prognosis (P = 0.507). A multivariate analysis identified ALDH1 expression in cancer cells as significantly independent prognostic factors for disease-free survival (P = 0.045). The current study indicated that the immunophenotypes of ALDH1 in cancer cells could have prognostic value for patients with NSCLC who are treated with neoadjuvant therapy.

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Identification of intravascular tumor microenvironment features predicting the recurrence of pathological stage I lung adenocarcinoma

Kaseda, K., Ishii, G., Aokage, K., Takahashi, A., Kuwata, T., Hishida, T., Yoshida, J., Kohno, M., Nagai, K. and Ochiai, A.

Cancer Sci 104 （ 9 ） 1262 - 9 2013年09月

ISSN  1349-7006

　概要を見る

Histological vascular invasion (VI) by tumors is reportedly a risk factor influencing recurrence or survival after surgical treatment; however, few studies have evaluated which VI features affect recurrence or survival. The objective of this study was to evaluate how VI features affect recurrence in lung adenocarcinoma patients. We selected 106 patients with pathological stage I lung adenocarcinoma who showed VI and examined the properties of intravascular tumors associated with recurrence. First we investigated the relationship between the frequency of VI in a histological cross-section and the incidence of recurrence; however, a significant impact was not observed. Microscopic examination revealed the intravascular tumors were composed of not only cancer cells but also non-cancerous cells. To examine whether the characteristics of intravascular cancer cells and/or non-cancerous cells have prognostic value, we examined the expression levels of epithelial-mesenchymal transition-related markers in cancer cells and the numbers of infiltrating non-cancerous cells, including macrophages, endothelial cells, and fibroblasts. High levels of E-cadherin expression in the intravascular cancer cells were significant predictors of recurrence (P = 0.004), whereas the expressions of CD44, CD44 variant 6, and vimentin were not. Large numbers of intravascular CD204(+) macrophages (P = 0.016), CD34(+) microvessels (P = 0.007), and alpha-smooth muscle actin (+) fibroblasts (P = 0.033) were also significant predictors of recurrence. Our results indicated VI with abundant stromal cell infiltrates might be a predictor of recurrence and suggested the tumor microenvironment created by cancer cells and stromal cells within the blood vessel may play an important role during the metastatic process.

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Successful surgical resection of leiomyoma obstructing the trachea

Kaseda K, Anraku M, Goto T, Ohtsuka T, Kohno M, Izumi Y, Hayashi Y, Nomori H.

General Thoracic and Cardiovascular Surgery 61 （ 8 ） 476 - 8 2013年08月

ISSN  1863-6713

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We report a case of 51-year-old woman with a severely airway-obstructing leiomyoma who underwent successful tracheal resection. A preoperative tumor biopsy was avoided not to cause any risk of suffocation. At surgery, an endotracheal intubation distal to the tumor was achieved with a bronchoscopic guidance. A segmental resection of the trachea with a primary end-to-end anastomosis was performed via a half-splitting median sternotomy. Negative surgical margins for tumor were confirmed intraoperatively. Final pathological diagnosis was a primary tracheal leiomyoma. Definitive surgical resection is a treatment of choice for such airway-obstructing, wide-based leiomyoma. Although a bronchoscopic removal of the tumor is an alternative choice, the risks of suffocation, positive surgical margins, and perforation of the trachea need to be carefully discussed if it is considered.

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Aorticopulmonary paraganglioma

Hato, T., Kaseda, K., Harada, M. and Horio, H.

Gen Thorac Cardiovasc Surg 59 （ 12 ） 812 - 4 2011年12月

ISSN  1863-6713

　概要を見る

We describe a 61-year-old woman with an anterior mediastinal paraganglioma. The patient complained of a chronic cough that had lasted about 6 months. Her chest computed tomography (CT) showed a highly enhanced mediastinal tumor in the aorticopulmonary window. We surgically resected this tumor thorough a left anterior thoracotomy. Although numerous feeding vessels and firm adhesions with the pericardium hindered the procedure, macroscopically complete resection was achieved. Postoperatively, the tumor was diagnosed as an aorticopulmonary paraganglioma. As these highly enhanced tumors in the anterior mediastinum on CT images are unusual, a differential diagnosis including mediastinal hemangioma, epithelioid hemangioendothelioma, Castleman's disease, choriocarcinoma, metastatic tumor (especially from renal cell carcinoma), and paraganglioma should be considered.

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Rosai-Dorfman disease mimicking mediastinal lymphoma

Kaseda K, Horio H, Hishima T, Hato T, Harada M.

General Thoracic and Cardiovascular Surgery 59 （ 5 ） 385 - 7 2011年05月

ISSN  1863-6713

　概要を見る

Rosai-Dorfman disease is rare and typically presents with cervical lymphadenopathy. The disease is generally indolent and self-limited, but it carries a poor or fatal prognosis when it is advanced or when it involves and compresses vital structures. We herein report a rare case of Rosai-Dorfman disease affecting only the mediastinal-hilar region in a 66-year-old woman.

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