Chinese Journal of Cancer Case Research Yue鄄M in Li1 ,2 , Peng鄄H ui Liu1 , Yu鄄H ai Zhang 1, Huo鄄S heng Xia 1, Liang鄄Li ang Li 1, Yi鄄M ei Qu 1, Yong Wu 1, Shou鄄Y un Han1 , Guo鄄Q ing Liao 1 and Yong鄄D ong Pu 1 Abstract Castleman s disease is a slowly progressive and rare lymphoproliferative disorder. Here, we report a 爷 55鄄ye ar鄄ol d woman with superior mediastinal Castleman s disease being misdiagnosed for a long term. 爷 We found a 4.3 cm mass localized in the superior mediastinum accompanied with severe clinical symptoms. The patient underwent an exploratory laparotomy, but the mass failed to be totally excised. Pathologic examination revealed a mediastinal mass of Castleman s disease. After radiotherapy of 30 Gy 爷 by 15 fractions, the patient no longer presented previous symptoms. At 3 months after radiotherapy of 60 Gy by 30 fractions, Computed tomography of the chest showed significantly smaller mass, indicating partial remission. Upon a 10鄄m onth follow鄄up , the patient was alive and free of symptoms. Key words Castleman s disease, radiotherapy, case report 爷 Castleman s disease is a rare lymphoproliferative  Previously, she had paroxysmal dull pain in the chest for  爷 disorder witha low incidence and very slowly progressive  4 years without obvious incentives; unfortunately, no  behavior. It is difficult to be diagnosed and patients are  attention was paid to it. The chest pain aggravated since  usually misdiagnosed. We analyzed the clinical data of a  April, 2009, accompanied by cough, white phlegm,  patient with superior mediastinal Castleman s disease  hoarse voice, and cough after drinking water. No fever,  爷 hospitalized in the 309 Hospital of the Chinese PLA. It  night sweats, or weight loss was observed. Chest  has been 4 years since the onset to the appearance of  computed tomography (CT) done in another hospital in  obvious symptoms and another half a year to definite  April, 2009 showed a mass localized in the superior  diagnosis. The patient underwentcombinatorial antibiotic  mediastinum with a maximum diameter of 4.3 cm.  therapy, anti­tuberculosis treatment for 6 months, and  Routine blood test, erythrocyte sedimentation rate,  hormone therapy for 2 months, suffering from long­term  biochemical test, and tumor marker test were normal, as  physical pain and financial burden. This indicates a lack  was abdominal ultrasonography. Thoracic operation was  of clinical knowledge on this disease. Thus, we reviewed  conducted, during which no clear boundary between the  the literatureof Castleman s disease. mass and surrounding blood vessels was found. As a  爷 result, the mass could not be excised and only an  incisional biopsy was performed. Postoperative  Case Report  pathologic examination showed reactive hyperplasia of  lymph nodes accompanied by charcoal particle deposit.  Thepatient was a 55­year­old woman hospitalized in  The patient was clinically suspected to have mediastinal  the Department of Oncology, the 309 Hospital of the  tuberculosis lymphadenitis and was given an  anti­tuberculosis treatment for almost half a year. No  Chinese PLA on December23, 2009 for 4 years of chest  pain which was further aggravated for 8 months.  obvious relief occurred and the patient suffered from  somasthenia with a weight loss of about 10 kg in 6  months. A chest CT performed in November, 2009 found  no obvious change in the superior mediastinal mass  (Figure 1).  1C ancer Center, PLA 309 Hospital, Beijing 100091, P. The patient came to the 309 Hospital of the Chinese  R. China 2C ancer Center, The General Hospital of PLA, Beijing 100853, 曰 PLA for further treatment. Results of the tuberculin  P. R. China (PPD) test and MycoDot TM test were both negative.  Yong鄄do ng Pu, Cancer Center, PLA 309 As a result, the Department of Tuberculosis excluded  Hospital, Beijing 100091, P. R. China. Tel +86鄄10 鄄66 775074; Email: [email protected]. 院 the possibility of tuberculosis and discontinued anti­  www.cjcsysu.com  CACA Chinese Anti鄄Ca ncer Association 351 Yue鄄M in Li et al. Radiotherapy of unicentric mediastinal Castleman s disease  爷 tuberculosis treatment. The pathologic specimen of the  capsule inside follicles (Figure 2). Lymph node  thoracic mass incised in April 2009 was consulted by  hyperplasia was then considered, supporting the  Departments of Pathology from several hospitals  diagnosis of Castleman s disease. A whole body  爷 including the Peking Union Medical College Hospital. In  positron emission tomography (PET)­CT scan was  the pathologic specimen, there was obvious diffuse  performed on October 30, 2009, showing a soft tissue  infiltration of lymphocytes with blood vessels proliferated  mass in the superior mediastinum with the maximal  and infiltrated into the follicles; immunohistochemical  diameter of 4.4 cm. The fluorodeoxyglucose (FDG)  assay for CD20 detected positive staining on the cell  uptake was slight and the maximum standardized uptake Figure 1. Computed tomography (CT) of the chest of the 55鄄ye ar鄄ol d woman before radiotherapy. The patient had chest pain for 4 years which was further aggravated for 8 months. A mediastinal tuberculosis lymphadenitis was suspected and the patient was given an anti鄄tu berculosis treatment for almost half a year. A 4 cm 伊 4 cm mass in the anterior superior mediastinum with remarkable intensity shows after contrast鄄en hanced scan. A B Figure 2. Histological examination of the thoracic tumor from the 55鄄ye ar鄄ol d woman. The patient underwent thoracic operation in April 2009 at another hospital, but the mass could not be completely resected. Therefore, a biopsy was performed for histological examination. A, lymphocytes diffuse in the mass and vessels penetrate into the follicles, indicating lymphoid hyperplasia (HE 伊20). B, positive staining for CD20 shows on the cell membrane (IHC 伊10). 352 Chin J Cancer; 2011; Vol. 30 Issue 5 Chinese Journal of Cancer Yue鄄M in Li et al. Radiotherapy of unicentric mediastinal Castleman s disease 爷 value (SUV) was 2.9. No other abnormality was found.  hoarse voice, and cough after drinking water were  In combination with the medical history, giant lymph  markedly relieved, but the chest CT scan showed no  node hyperplasia was considered (Figure 3).  obvious shrinkage of the mass. Radiotherapy was  The patient underwent hormone therapy for 2  continued, and the total dose was increased to 60 Gy by  months with no obvious response, then she was  30 fractions, until February 4, 2010. A chest enhanced  transferred to the Department of Radiotherapy in  CT scan performed on May, 2010 showed that the mass  December, 2009. Three­field intensity ­ modulated  was significantly smaller than before, indicating partial  radiotherapy (IMRT) was delivered to the mediastinal  remission (Figure 4). Upon follow­up until December  mass since December 23, 2009. After radiotherapy of 30  2010,the patient had no discomfort. Gy by 15 fractions, symptoms such as chest pain,  A B Figure 3. PET鄄CT scan of the chest of the 55鄄ye ar鄄ol d woman before radiotherapy. A, transverse scan of the chest; B, coronal scan of the chest. PET鄄CT before treatment shows a 4.4 cm mass in the anterior superior mediastinum with slightly elevated FDG uptake (SUV = 2.9). max Figure 4. Computed tomography of the chest 3 months after radiotherapy. The mediastinial tumor (2 cm 伊 3 cm) is obviously smaller than that before radiotherapy. The mass shows slight intensity after contrast鄄en hancement. www.cjcsysu.com  Chin J Cancer; 2011; Vol. 30 Issue 5 353 Yue鄄M in Li et al. Radiotherapy of unicentric mediastinal Castleman s disease 爷 Discussion  types, accounting for 89%; (3) it is mainly treated by  chemotherapy with adjuvant local radiotherapy. Most of  The pathogenesis of Castleman s disease is  this type is aggressive, accompanied with system  unclear. Recent researches found that t 爷his disease was  symptoms and a poor prognosis, especially the plasma  related to the infection of the human immunodeficiency  cell type. Median survival is about 27 months with a  virus (HIV) or the human herpes virus­8 (HHV­8).  5­year survival about 50%. Some cases could transfer to  HHV­8, a human lymphotropic virus, is associated with  lymphoma, Kaposi sarcoma, and dendritic reticulum cell  the onset and development of Kaposi sarcoma.  sarcoma [1,9] .  Researches showed that HIV­positive Kaposi sarcoma  Surgical and radiotherapy are the principle  was usually accompanied by infection of HHV­8. In  treatments for unicenter type Castleman s disease  爷 addition, viral load was related to tumor activity and  (Table 1) [1,8­11] . Chronowski  . [1]  have reported 22  antiviral treatment was effective for tumor remission.  cases of Castleman s disease, admitting between 1988  爷 However, as Castleman s disease is rare, pathogenic  and 1999. Eight of the 12 patients with unicenter type  爷 mechanisms await further confirmation. Diagnosis of this  disease underwent surgical excision (including 2 cases  disease primarily depends on histological examination,  of partial excision) and the other 4 underwent radical  thus puncture or incisional biopsy should be carried out  radiotherapy. No disease progression­related death  forthwith. Pathologic types mostly consist of hyaline  occurred. Of the 2 patients who underwent a partial  vascular,plasma cell, and mixed variants.  excision, 1 had no systemic symptoms, and the other  The clinical manifestation of Castleman s disease  had mediastinal Castleman s disease accompanied with  爷 爷 includes unicenter and multicenter types, with unicenter  systemic symptoms such as fever, night sweats, and  type observed most frequently (81%). Characteristics of  weight loss. The symptoms were completely relieved  unicenter type Castleman s disease are as follows [1] : (1)  after partial excision, with no disease progression  爷 males and females have the same incidence, with a  observed after a 117­month follow­up. Radiotherapy for  median age of 37 years; (2) hyaline vascular type is  Castleman s disease mainly includes radical  爷 the major pathologic type,accountingfor 92%; (3) most  radiotherapy and preoperative neoadjuvant radiotherapy.  lesions are in the mediastinum, neck, axillary, and  Radical radiotherapy is suitable for patients with locally  retroperitoneal lymph nodes, and other rare locations  advanced and inoperable disease, patients unable to  include the intra­orbital region, hepatic portal,  endure operation due to medical disorders, or those who  subcutaneous region, parotid glands, kidney, and pelvic  refuse operation. Vries  . [12] summarized the data of  cavity [2­7] ; (4) the disease progresses very slowly, intact  32 patients who underwent radiotherapy or  surgical excision could cure the disease and partial  radiotherapy­based treatment, including 29 with unicenter  excision could significantly relieve symptoms. However,  type disease. The overall response rate of these 29  postoperativeadjuvant radiotherapy is recommended due  patients was 89.6%, with a complete remission rate of  to the possibility of relapse after partial excision [8,9] .  44.8%, a partial remission rate of 44.8%, and a stable  Characteristics of multicenter type Castleman s disease  disease rate of 10.4%. For most cases, radiotherapy of  爷 are as follows: (1) males and females have the same  40 to 50 Gy could achieve complete or partial remission.  incidence, with a median age of 53 years; (2) plasma  Preoperative neoadjuvant radiotherapy is suitable for  cell and mixed variant types are the major pathologic  patients with an obviously shrunk tumor after Reference No. of Patients Histology Treatment Response (follow鄄up ) Chronowski et al. [1] 6 5 HV, 1 M Complete resection CR (4-74 months) 2 HV Partial resection Symptom鄄fre e (31-117 months) 4 HV Radiotherapy Symptom鄄fre e* Neuhof et al. [8] 3 2 HV, 1 M Radiotherapy 1 CR, 2 NR Bowner et al. [9] 10 8 HV, 2 M Complete resection CR (9-37 months) 1 HV Partial resection Symptom鄄fre e (12 months) Bucher et al. [10] 2 HV Complete resection CR (5 years ) Veldhuis et al. [11] 1 PC Radiotherapy CR PC, plasma cell type; HV, hyaline vascular type; M, mixed type; CR, complete remission; PR, partial remission; NR, no response. *Two patients died of other diseases. 354 Chin J Cancer; 2011; Vol. 30 Issue 5 Chinese Journal of Cancer Yue鄄M in Li et al. Radiotherapy of unicentric mediastinal Castleman s disease 爷 radiotherapy which could be completely excised by  patients had fever, 4 had weight loss. Median follow­up  operation. Vries  . [12] reported a case of pelvic focal  was 65 months. All patients were treated by regimens  type Castleman s disease treated with neoadjuvant  mentioned above, and 4 (44%) achieved complete  爷 radiotherapy. Six weeks after a total radiation dose of 40  remission after chemotherapy. During follow­up, 5  Gy by 20 fractions, tumor diameter shrunk from 7.2 cm  patients lived with tumor, and 4 were disease­free.  to 4.7 cm. Complete surgical excision was performed  In recent years, along with the emergence of  and an intraoperative radiation boost of 10 Gy was  molecular targeted agents, rituximab was used to treat  delivered; no sign of recurrence was observed after 27  multicenter type Castleman s disease. Casquero  . [13]  爷 months. In our study, symptoms of the patient were  reported that among 12 patients who were given  nearly relieved after 30 Gy by 15 fractions, but CT scan  rituximab, 9 gained complete remission and 3 died of  showed no obvious change in the mass; thus, a boost to  primary disease. Another research showed that the  60 Gy by 30 fractions was delivered. At 3 months after  complete remission rate of HIV­positive Castleman s  爷 the completion of radiotherapy, chest enhanced CT  disease which relapsed after combined chemotherapy  showed partial remission of the tumor. During follow­up,  was up to 95.8% after treatment of rituximab and was  the patient had no discomfort, with general status and  72% at 1 year after treatment [14] . Researches also  body weight recovered to normal. The long­term survival  indicated that the effect of rituximab on CD20­positive  awaits further observation.  multicenter type Castleman s disease was exciting.  爷 Multicenter type Castleman s disease is mainly  Other drugs for this disease include thalidomide,  爷 treated with chemotherapy. Because this disease is  bortezomib, and the antiviral agent ganciclovir. Stary  lymphoproliferative, the most frequently used clinical  . [15]  reported a case of HIV­positive multicenter type  regimen is CHOP (cyclophosphamide, adrimycin,  Castleman s disease treated by thalidomide combined  爷 vincristine, and prednisolone). Other regimens include  with rituximab achieved complete remission. Complete  CAVD (cyclophosphamide, adrimycin, vincristine, and  remission of a case treated by bortezomib combined with  dexamethasone), MINE (mensa, ifosfamide,  rituximab was also reported [16] . Treating Castleman s  爷 mitoxantrone, and etoposide), and nitrogen mustard  disease with antiviral therapy is stillunder exploration.  combined with prednisone. Chronowski  . [1] reported 9  cases of multicenter type disease which was mainly of  Received: 2010­08­13; revised:2011­01­18;  mixed variant and plasma cell types. The median age  accepted: 2011­01­19 . was 53years, with 5 men and 4 women. Among them, 6  References 1 Chronowski GM, Ha CS, Wilder RB, et al. Treatment of 8 Neuhof D, Debus J. Outcome and late complications of 咱 暂 咱 暂 unicentric and multicentric Castleman disease and the role of radiotherapy in patients with unicentric Castleman disease [J]. radiotherapy [J]. Cancer, 2001,92(3):670-676. Acta Oncol, 2006,45(8):1126-1131. 2 Nistor C, Davidescu M, Ciuche A, et al. A rare case of 9 Bowne WB, Lewis JJ, Filippa DA, et al. The management of 咱 暂 咱 暂 unicentric plasma cell type Castleman s disease in the unicentric and multicentric Castleman s disease: a report of 16 爷 爷 mediastinum [J]. Pneumologia, 2010,59(1):32-35. cases and a review of the literature [J]. Cancer, 1999,85(3): 3 Karami H, Sahebpour AA, Ghasemi M, et al. Hyaline vascular- 706-717. 咱 暂 type Castleman s disease in the hilum of liver: a case report 10 Bucher P, Chassot G, Zufferey G, et al. Surgical management 爷 咱 暂 [J]. Cases J, 2010,3(3):74. of abdominal and retroperitoneal Castleman s disease [J]. 爷 4 Tang JQ, Yang YM, Xiong Y, et al. Surgical treatment and World J Surg Oncol, 2005, 3:33-41. 咱 暂 prognosis analysis of localized retroperitoneal Castleman 11 Veldhuis GJ, van der Leest AH, de Wolf JT, et al. A case of 咱 暂 disease: a study of 20 cases [J]. Zhonghua Wai Ke Za Zhi, localized Castleman s disease with systemic involvement: 爷 2009,47(22):1685-1688. 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