Eur Arch Otorhinolaryngol DOI 10.1007/s00405-014-3297-7
RHINOLOGY
Extranodal sinonasal Rosai-Dorfman disease: a clinical study of 10 cases Hong-Gang Duan • Chun-Quan Zheng • De-Hui Wang • Guo-Qiang Ding • Ji-Qin Luo Chao-Ping Zang • Chang Yu
•
Received: 30 July 2014 / Accepted: 17 September 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Sinonasal Rosai-Dorfman disease (S-RDD) is a rare form of RDD limited to the sinonasal cavity. Multipatient studies of Chinese S-RDD and documentation of its clinical spectrum are rare. This study aimed to identify the clinical profiles of Chinese S-RDD. Medical records of and tissue sections from 10 patients diagnosed with S-RDD between 2007 and 2014 were reviewed. Data on clinical presentations, endoscopy signs, imageological change, treatment and outcome were analyzed. The mean age of five male and five female patients at the first visit was 40.3 years and the mean follow-up period was 58.6 months. Based on the lesion sites, five cases were divided into an anterior sinonasal group, accompanied by symptoms of epistaxis, nasal obstruction and nasal dorsal deformity. Five other cases were divided into a posterior sinonasal group, accompanied by symptoms of hyposmia, epistaxis and nasal obstruction. Endoscopy signs and imageological changes in the anterior group showed diffuse infiltration of the RDD lesion under the septum mucosa, but in the posterior group the RDD lesions often showed as formations on polyps. At the end of follow-up, only one case spontaneously resolved without surgery; two H.-G. Duan Department of Otolaryngology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China C.-Q. Zheng (&) D.-H. Wang G.-Q. Ding J.-Q. Luo C.-P. Zang Department of Otolaryngology, Affiliated Eye and Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Fen-yang Road 83, Shanghai 200031, China e-mail: [email protected] C. Yu Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China
cases in the anterior sinonasal group and three cases in the posterior sinonasal group recurred after endoscopic surgery, but surgery can result in short-term symptomatic control and restoration of function in all cases. S-RDD of the anterior and posterior sinonasal cavity may have different clinical characteristics; endoscopic surgery is effective for short-term symptomatic control and restoration of function for S-RDD. Keywords Rosai-Dorfman disease Sinonasal disease Endoscopic surgery
Introduction Rosai-Dorfman disease (RDD) is a rare histolytic proliferative disorder that was first recognized as a unique entity by Rosai and Dorfman in 1969 under the term sinus histiocytosis with massive lymphadenopathy [1]. Massive painless cervical lymphadenopathy in children or young adults is the most typical form of RDD. Extranodal involvement has been reported in 43 % of cases, and nasal cavity and paranasal sinuses involvement has been reported in 11 % of cases [2]. Therefore, extranodal sinonasal Rosai-Dorfman disease (S-RDD) is an important type of RDD. It has been reported that the incidence of RDD differs according to region, and it is more common in individuals of African descent [3]. Wang et al. [4] also confirmed that cutaneous RDD in China is a distinct form of the disease with age and possibly race distributions that are different from RDD that is found in Western countries. Therefore, S-RDD in China may also have different clinical characteristics.
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Chen et al. [5] reviewed the English-language literature published between 1969 and 2010 and found that 126 cases of S-RDD were reported. However, there were few multipatient studies of Chinese S-RDD; most of the studies reported on single cases, and studies that focused on the pathology and documentation of its clinical spectrum were rare [6]. In order to improve the diagnosis and therapy level, its clinical characteristics may need to be summarized. Our study on the clinical profiles and disease spectrum reports on ten cases of Chinese patients with S-RDD. In terms of mean age, we found that the patients in this series were older than the patients in the series of studies of Western countries, and patients with S-RDD can be divided into two groups depending upon the lesions site, the symptoms and the characteristics of the endoscopic and image studies; this approach can improve the diagnosis efficiency of S-RDD. As far as we know, our study is the first report with the most cases of Chinese S-RDD.
Materials and methods Patients and clinical analysis The medical records of inpatients diagnosed with S-RDD were reviewed in the Affiliated Eye and Ear, Nose and Throat Hospital of Fudan University between 2007 and 2014. The diagnoses were based on either initial or subsequent biopsies, and all of the histologic specimens were confirmed by pathologists. Of the ten patients, seven underwent multiple biopsies from different sites or at different time points. Biopsies were performed on two of those seven patients because the first diagnosis was not clear; five patients underwent biopsies for the purpose of chronological follow-up and/or staged surgical removal of the lesions. Follow-up evaluations included an endoscopy every month for the first three months and an endoscopy once every three to six months thereafter until full recovery. Clinical history, photography, lesion site, number of biopsies, laboratory and image studies and the follow-up course were reviewed. Histopathological and immunohistochemical analysis The biopsy specimens were fixed in formaldehyde solution, embedded in paraffin and stained with hematoxylin and eosin. Immunohistochemical studies included soluble protein-100 protein (S-100), CD68, vimentin, alpha1-antichymotrypsin (AACT), lysozyme and white cell common antigen (LCA) stains in each lesion (all from DakoCytomation, Glostrup, Denmark). The 3,30 -diaminobenzidine (DAB) straining method was used. Each biopsy specimen
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was reviewed by two pathologists using light microscopy. A result was judged as being positive depending upon the number of positive cells in the specimen and the intensity of the stain. The diagnostic criteria for RDD were (1) the presence of large, pale-stained histiocytes with evidence of emperipolesis and (2) S-100 positivity of these histiocytes [4].
Results Clinical profiles and lesion types Eleven cases were identified with a diagnosis of S-RDD between 2007 and 2014. After excluding one case in which the patient did not complete his follow-up, ten cases (five males and five females, ratio 1:1) were included in the study. The mean age at the first visit was 40.3 years (range: 16–62 years) and the average course with S-RDD was 4.4 years (range: 0.5–10 years).The average number of times a biopsy was taken was 2.2 (range: 1–8 times). The symptoms are presented in Table 1 and the clinical data are presented in Table 2. Of the 10 cases in our sample, seven cases (70 %) were purely extranodal lesions and three cases (30 %) were both nodal and extranodal lesions. Meanwhile, based on the physical examination, endoscopic examination and image studies, five cases (50 %) were divided into an anterior sinonasal group, in which the lesions were located mainly in the cartilaginous nasal septum, and two cases (20 %) in which the lesions was out the range of nasal septum and had spread to the nasal dorsum. Another five cases (50 %) were divided into a posterior sinonasal group, in which the lesions were located mainly in the nasal cavity and paranasal sinuses, and one case (10 %) was out the range of nasal cavity and paranasal sinuses and had intracranial and orbital involvement. The endoscopy signs of S-RDD are
Table 1 Symptoms of sinonasal Rosai–Dorfman disease
Symptom
Patients (10) No
%
Nasal obstruction
7
70
Epistaxis
6
60
Hyposmia
6
60
Nasal dorsum deformity
2
20
Dyspnea
2
20
Facial asymmetry
1
10
Diminution of vision
1
10
Aural fullness
1
10
Eur Arch Otorhinolaryngol Table 2 Clinical findings, lesion sites, number of biopsies and outcomes for ten patients with sinonasal Rosai-Dorfman disease in China No
Age/ sex
Symptom
Site of nose involvement
Other extra-nodal involvement
Site of lymph involvement
Number of biopsies
Follow-up
1
53/F
Epistaxis
Nasal septum
No
No
1
78 months, excision without recurrence
2
62/M
Epistaxis, nasal obstruction
Nasal septum
No
Cervical lymph node
1
72 months, spontaneously resolved
3
44/F
Lesion of nasal dorsum, epistaxis
Nasal septum
No
No
1
39 months, excision with recurrence
4
53/F
Lesion of nasal dorsum
Nasal septum
No
No
2
6 months, excision without recurrence
5
32/F
Nasal septum
Trachea
No
2
6
33/F
Nasal obstruction, dyspnea, epistaxis, hyposmia Nasal obstruction, dyspnea, epistaxis, hyposmia
Nasal cavity, nasal sinuses
Trachea, hard palate
Cervical lymph node
8
64 months, excision with repeated recurrence 84 months, excision with repeated recurrence
7
21/M
No
1
31/M
Nasal cavity, nasal sinuses Nasal cavity, nasal sinuses, nasopharynx
Facial, orbital
8
Nasal obstruction, facial asymmetry, hyposmia Nasal obstruction, aural fullness, hyposmia
No
No
2
9
58/M
Nasal obstruction, hyposmia, diminution of vision
Nasal cavity, nasal sinuses
Anterior skull base, intracranial involvement
No
2
120 months, excision with recurrence
10
16/M
Nasal obstruction, hyposmia, epistaxis
Nasal cavity, nasal sinuses
No
Cervical lymph node
2
6 months, excision without recurrence
shown in Fig. 1a–c, and the imageological change of S-RDD is shown in Fig. 2. The patients were monitored clinically with a mean follow-up period of 58.6 months (range 6–120 months). At the end of follow-up, only one case spontaneously resolved without surgery, and two cases in the anterior sinonasal group and three cases in the posterior sinonasal group recurred after endoscopic surgery; two cases in the anterior sinonasal group and two cases in the posterior sinonasal group did not experience recurrence. Although five cases experienced recurrence, surgery can result in short-term (mean 2.3 years, range 1–7 years) symptomatic control and restoration of function in those cases. Histopathological studies Grossly, excisional biopsy tissue was received in multiple pieces, with the largest fragment measuring 2.5 cm at its greatest dimension, and it appeared yellowish tan and slightly lobulated (Fig. 1d). Microscopic examination revealed obvious light-staining bands alternating with dark-staining bands at low magnification in eight cases (Fig. 1e, f); light-staining and darkstaining bands are not obvious in two of the cases. The
66 months, excision with recurrence 51 months, Second excision without recurrence
visible light-staining bands were full of large histiocytic cells, which contained vesicular nuclei with distinct nucleoli, delicate nuclear membranes and abundant pale-toeosinophilic cytoplasm. Some of the histiocytic cells contained intact erythrocytes, lymphocytes and plasma cells, a process known as emperipolesis (Fig. 1g). Dark-staining bands are rich in chronic inflammatory cells, mainly small lymphocytes and plasma cells, and neutrophils were found to be infiltrating in two cases. Fibrosis appeared in six lesions and typical fibrous nodules formed in one case. Immunohistochemical studies showed that the histiocytic cells were strongly reactive with antibodies against S-100 protein in all ten cases (Fig. 1g) and with CD68 in six cases (Fig. 1h). However, the same cells were nonreactive with antibodies directed against CD1a, leukocyte common antigen and desmin. All of the immunohistochemical studies had satisfactory positive and negative controls.
Discussion In our study, the patients’ mean age (40.3 years) and the male/female ratio (1:1) are basically in keeping with the
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Fig. 1 The endoscopic signs and histopathological studies of sinonasal Rosai- Dorfman disease. a The S-RDD of the anterior sinonasal cavity showed as septum mucosa thickening; b the S-RDD of the posterior sinonasal cavity showed as a polypoid lesion in the middle meatus; c the S-RDD lesion at the subglottic airway; d the biopsy sample from the nasal cavity showed as a yellow nodule; e, f histologically, S-RDD shows a characteristic pattern of alternating
light and dark areas on low-power magnification (H and E, E 950; F 9100); g the clear area is comprised of histiocytes with polygonal shapes and abundant clear cytoplasm containing some lymphocytes (emperipolesis) (H and E, 9400); (h, i) the infiltrating histiocytes in S-RDD are characterized by a strong reaction to S-100 protein and CD68 (SAB immunohistochemical stain, 9200, H S100; I CD68)
previous series of S-RDD in Taiwan (44.0 years; male/ female ratio: 1:1), but in our study the patients were older than the patients in the series that examined S-RDD in Western counties (20.0 years; male/female ratio: 1:1) [2, 7]. This is probably because patients in Taiwan and Mainland China share the same culture and race, which is different from Western countries. In addition, systemic symptoms (fever, malaise) and hematological and immunological abnormalities were commonly seen in systemic RDD but they were not found in this present series. In this present series, three cases (30 %) had cervical lymphadenopathy involvement and four cases (40 %) had another extranodal involvement, which is different from Hsiao et al. [7] study, which reported that 50 % of the cases had lymph node involvement and 66.7 % had RDD in another
extranodal site. This may be due to the statistical differences caused by the small sample size of our study. Unlike other research studies, this study paid particular attention to the sites of the lesions. Based on the physical, endoscopic and image examinations, we were able to accurately locate the lesion sites. In five cases, the lesion site was located mainly in the anterior sinonasal cavity, varying from being limited to just the cartilaginous nasal septum to encroaching upon the nasal bone and nasal dorsal subcutaneous tissue. In five other cases, the lesions were located in the posterior sinonasal cavity, varying from being limited to the bilateral nasal cavity to the sinuses, and even encroaching upon the nasopharynx, orbital and intracranial tissue. We then divided the ten cases into two groups and discussed the characteristics of each group.
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Fig. 2 Imageological change of sinonasal Rosai- Dorfman disease. a Lateral X-ray view of the soft tissues of the neck. There is an RDD lesion at the back wall of the trachea with narrowing of the airway; b, c CT showed that the RDD lesion was limited to the cartilaginous nasal septum (case 2); d, e) CT showed that the RDD lesion exceeded the cartilaginous nasal septum and spread to the nasal dorsal (case 2),
and the enhanced—scanning CT showed that the lesion was significantly strengthened; f, g CT showed that the RDD lesion was limited to the nasal cavity and paranasal sinuses (case 8); (h, i) MRI showed that the RDD lesion exceeded the nasal cavity and paranasal sinuses, with intracranial involvement, and the enhanced-scanning MRI showed that the lesion was significantly strengthened (case 4)
We found that the symptoms, endoscopy signs and images of S-RDD were different in the two groups. The common symptoms of the anterior sinonasal group were epistaxis, nasal obstruction and nasal dorsal deformity when the lesion encroached upon the nasal dorsa subcutaneous tissue. The common symptoms of the posterior sinonasal group were hyposmia, epistaxis, nasal obstruction and epistaxis. If the RDD lesion encroached upon the orbital and intracranial tissue, the patient complained of headache and diminished vision. In the anterior sinonasal group, endoscopy showed signs of RDD diffuse lesion infiltration under the mucosa; however, in the posterior sinonasal group, the RDD lesions often showed as formations on polyps. This trend was very obvious in the CT and
MRI images. This could lead to endoscopic biopsy in outpatients, which was difficult for patients in the anterior sinonasal group but relatively easy for patients in the posterior sinonasal group. The focus on the differential diagnoses of the two groups was different. Diffuse lesion infiltration under the septum mucosa and encroachment of the lesion into the nasal dorsa subcutaneous tissue were similar to the nasal type of NK/T lymphoma, which is often accompanied by nasal septum mucosal thickening and surrounding facial tissue swelling [8]. Polypoid lesions are similar to nasal carcinomas or nasal polyps, but nasal carcinomas are often located in the lateral cavity and the polyps are often located in the middle nasal meatus or olfactory cleft, which is
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different from S-RDD in which the lesion is located in the bilateral sinonasal and not in the middle nasal meatus or olfactory cleft. Although the final diagnosis is based on histopathological examination, these clinical features can help pathologists improve their diagnostic efficiency. It is generally accepted that the majority of RDD cases have a benign course and treatment is not necessary. Therapy is only needed by patients with extranodal RDD that has vital organ involvement or those with nodal disease that cause life-threatening complications [9]. However, in those series, only one case in the anterior sinonasal group spontaneously resolved, which is consistent with Chen et al.’s report in which only one of 126 cases of sinonasal RDD spontaneously resolved. There is no ideal treatment for sinonasal RDD or general RDD; however, in general, surgery, steroids, chemotherapy and radiology, used alone or in combination, have been reported with variable responses [10–13]. Most of our patients underwent endoscopic surgery and, at the end of follow-up, two cases of lesions in the anterior sinonasal group and three cases of lesions in the posterior sinonasal group recurred after endoscopic surgery. However, treatment can result in short-term symptomatic control and restoration of function. Therefore, we agree with the opinion of Ku et al. [14] that although no specific treatment can guarantee a sustained remission of this disease, surgery for loco-regional lesions can result in symptomatic control and restoration of function. The advantages of this study include its emphasis on the symptoms and different diagnoses correlated to lesion sites, which is rarely mentioned in other studies. Although this is the report that investigated the greatest number of Chinese sinonasal RDD cases, the total number of cases (10) still limits the ability to compare the treatment outcome of this study to the results of studies investigating different therapy methods. We believe that subsequent studies with larger sample sizes are necessary to explore the nature of this rare disease.
Conclusion Sinonasal RDD is a rare disease in China. Depending upon the lesion sites, it can be divided into either anterior sinonasal RDD or posterior sinonasal RDD, both of which have different clinical characteristics. Although endoscopic
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surgery often leads to recurrence, it can result in short-term symptomatic control and restoration of function.
References 1. Rosai J, Dorfman RF (1969) Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Arch Pathol 87:63–70 2. Foucar E, Rosai J, Dorfman R (1990) Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): review of the entity. Semin Diagn Pathol 7:19–73 3. Lauwers GY, Perez-Atayde A, Dorfman RF, Rosai J (2000) The digestive system manifestations of Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy): review of 11 cases. Hum Pathol 31:380–385 4. Wang KH, Chen WY, Liu HN, Huang CC, Lee WR, Hu CH (2006) Cutaneous Rosai-Dorfman disease: clinicopathological profiles, spectrum and evolution of 21 lesions in six patients. Br J Dermatol 154:277–286 5. Chen HH, Zhou SH, Wang SQ, Teng XD, Fan J (2012) Factors associated with recurrence and therapeutic strategies for sinonasal Rosai-Dorfman disease. Head Neck 34:1504–1513 6. Chang YC, Tsai MH, Chen CL, Tsai CH, Lee AY (2003) Nasal Rosai-Dorfman disease with intracranial involvement: a case report. Am J Otolaryngol 24:183–186 7. Hsiao CH, Tsai TF, Yang TH, Liu CM (2006) Clinicopathologic characteristics of Rosai-Dorfman disease in a medical center in northern Taiwan. J Formos Med Assoc 105:701–707 8. Aozasa K, Zaki MA (2011) Epidemiology and pathogenesis of nasal NK/T-cell lymphoma: a mini-review. Sci World J 11:422–428 9. Pulsoni A, Anghel G, Falcucci P, Matera R, Pescarmona E, Ribersani M (2002) Treatment of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): report of a case and literature review. Am J Hematol 69:67–71 10. Hadjipanayis CG, Bejjani G, Wiley C, Hasegawa T, Maddock M, Kondziolka D (2003) Intracranial Rosai-Dorfman disease treated with microsurgical resection and stereotactic radiosurgery Case report. J Neurosurg 98:165–168 11. Oka M, Kamo T, Goto N, Nagano T, Hirayama Y, Nibu K (2009) Successful treatment of Rosai-Dorfman disease with low-dose oral corticosteroid. J Dermatol 36:237–240 12. Horneff G, Jurgens H, Hort W, Karitzky D, Gobel U (1996) Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): response to methotrexate and mercaptopurine. Med Pediatr Oncol 27:187–192 13. Cooper SL, Chavis PS, Fortney JA, Watkins JM, Caplan MJ, Jenrette JR (2008) A case of orbital Rosai-Dorfman disease responding to radiotherapy. J Pediatr Hematol Oncol 30:744–748 14. Ku PK, Tong MC, Leung CY, Pak MW, van Hasselt CA (1999) Nasal manifestation of extranodal Rosai-Dorfman disease— diagnosis and management. J Laryngol Otol 113:275–280
RHINOLOGY
Extranodal sinonasal Rosai-Dorfman disease: a clinical study of 10 cases Hong-Gang Duan • Chun-Quan Zheng • De-Hui Wang • Guo-Qiang Ding • Ji-Qin Luo Chao-Ping Zang • Chang Yu
•
Received: 30 July 2014 / Accepted: 17 September 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Sinonasal Rosai-Dorfman disease (S-RDD) is a rare form of RDD limited to the sinonasal cavity. Multipatient studies of Chinese S-RDD and documentation of its clinical spectrum are rare. This study aimed to identify the clinical profiles of Chinese S-RDD. Medical records of and tissue sections from 10 patients diagnosed with S-RDD between 2007 and 2014 were reviewed. Data on clinical presentations, endoscopy signs, imageological change, treatment and outcome were analyzed. The mean age of five male and five female patients at the first visit was 40.3 years and the mean follow-up period was 58.6 months. Based on the lesion sites, five cases were divided into an anterior sinonasal group, accompanied by symptoms of epistaxis, nasal obstruction and nasal dorsal deformity. Five other cases were divided into a posterior sinonasal group, accompanied by symptoms of hyposmia, epistaxis and nasal obstruction. Endoscopy signs and imageological changes in the anterior group showed diffuse infiltration of the RDD lesion under the septum mucosa, but in the posterior group the RDD lesions often showed as formations on polyps. At the end of follow-up, only one case spontaneously resolved without surgery; two H.-G. Duan Department of Otolaryngology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China C.-Q. Zheng (&) D.-H. Wang G.-Q. Ding J.-Q. Luo C.-P. Zang Department of Otolaryngology, Affiliated Eye and Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Fen-yang Road 83, Shanghai 200031, China e-mail: [email protected] C. Yu Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China
cases in the anterior sinonasal group and three cases in the posterior sinonasal group recurred after endoscopic surgery, but surgery can result in short-term symptomatic control and restoration of function in all cases. S-RDD of the anterior and posterior sinonasal cavity may have different clinical characteristics; endoscopic surgery is effective for short-term symptomatic control and restoration of function for S-RDD. Keywords Rosai-Dorfman disease Sinonasal disease Endoscopic surgery
Introduction Rosai-Dorfman disease (RDD) is a rare histolytic proliferative disorder that was first recognized as a unique entity by Rosai and Dorfman in 1969 under the term sinus histiocytosis with massive lymphadenopathy [1]. Massive painless cervical lymphadenopathy in children or young adults is the most typical form of RDD. Extranodal involvement has been reported in 43 % of cases, and nasal cavity and paranasal sinuses involvement has been reported in 11 % of cases [2]. Therefore, extranodal sinonasal Rosai-Dorfman disease (S-RDD) is an important type of RDD. It has been reported that the incidence of RDD differs according to region, and it is more common in individuals of African descent [3]. Wang et al. [4] also confirmed that cutaneous RDD in China is a distinct form of the disease with age and possibly race distributions that are different from RDD that is found in Western countries. Therefore, S-RDD in China may also have different clinical characteristics.
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Chen et al. [5] reviewed the English-language literature published between 1969 and 2010 and found that 126 cases of S-RDD were reported. However, there were few multipatient studies of Chinese S-RDD; most of the studies reported on single cases, and studies that focused on the pathology and documentation of its clinical spectrum were rare [6]. In order to improve the diagnosis and therapy level, its clinical characteristics may need to be summarized. Our study on the clinical profiles and disease spectrum reports on ten cases of Chinese patients with S-RDD. In terms of mean age, we found that the patients in this series were older than the patients in the series of studies of Western countries, and patients with S-RDD can be divided into two groups depending upon the lesions site, the symptoms and the characteristics of the endoscopic and image studies; this approach can improve the diagnosis efficiency of S-RDD. As far as we know, our study is the first report with the most cases of Chinese S-RDD.
Materials and methods Patients and clinical analysis The medical records of inpatients diagnosed with S-RDD were reviewed in the Affiliated Eye and Ear, Nose and Throat Hospital of Fudan University between 2007 and 2014. The diagnoses were based on either initial or subsequent biopsies, and all of the histologic specimens were confirmed by pathologists. Of the ten patients, seven underwent multiple biopsies from different sites or at different time points. Biopsies were performed on two of those seven patients because the first diagnosis was not clear; five patients underwent biopsies for the purpose of chronological follow-up and/or staged surgical removal of the lesions. Follow-up evaluations included an endoscopy every month for the first three months and an endoscopy once every three to six months thereafter until full recovery. Clinical history, photography, lesion site, number of biopsies, laboratory and image studies and the follow-up course were reviewed. Histopathological and immunohistochemical analysis The biopsy specimens were fixed in formaldehyde solution, embedded in paraffin and stained with hematoxylin and eosin. Immunohistochemical studies included soluble protein-100 protein (S-100), CD68, vimentin, alpha1-antichymotrypsin (AACT), lysozyme and white cell common antigen (LCA) stains in each lesion (all from DakoCytomation, Glostrup, Denmark). The 3,30 -diaminobenzidine (DAB) straining method was used. Each biopsy specimen
123
was reviewed by two pathologists using light microscopy. A result was judged as being positive depending upon the number of positive cells in the specimen and the intensity of the stain. The diagnostic criteria for RDD were (1) the presence of large, pale-stained histiocytes with evidence of emperipolesis and (2) S-100 positivity of these histiocytes [4].
Results Clinical profiles and lesion types Eleven cases were identified with a diagnosis of S-RDD between 2007 and 2014. After excluding one case in which the patient did not complete his follow-up, ten cases (five males and five females, ratio 1:1) were included in the study. The mean age at the first visit was 40.3 years (range: 16–62 years) and the average course with S-RDD was 4.4 years (range: 0.5–10 years).The average number of times a biopsy was taken was 2.2 (range: 1–8 times). The symptoms are presented in Table 1 and the clinical data are presented in Table 2. Of the 10 cases in our sample, seven cases (70 %) were purely extranodal lesions and three cases (30 %) were both nodal and extranodal lesions. Meanwhile, based on the physical examination, endoscopic examination and image studies, five cases (50 %) were divided into an anterior sinonasal group, in which the lesions were located mainly in the cartilaginous nasal septum, and two cases (20 %) in which the lesions was out the range of nasal septum and had spread to the nasal dorsum. Another five cases (50 %) were divided into a posterior sinonasal group, in which the lesions were located mainly in the nasal cavity and paranasal sinuses, and one case (10 %) was out the range of nasal cavity and paranasal sinuses and had intracranial and orbital involvement. The endoscopy signs of S-RDD are
Table 1 Symptoms of sinonasal Rosai–Dorfman disease
Symptom
Patients (10) No
%
Nasal obstruction
7
70
Epistaxis
6
60
Hyposmia
6
60
Nasal dorsum deformity
2
20
Dyspnea
2
20
Facial asymmetry
1
10
Diminution of vision
1
10
Aural fullness
1
10
Eur Arch Otorhinolaryngol Table 2 Clinical findings, lesion sites, number of biopsies and outcomes for ten patients with sinonasal Rosai-Dorfman disease in China No
Age/ sex
Symptom
Site of nose involvement
Other extra-nodal involvement
Site of lymph involvement
Number of biopsies
Follow-up
1
53/F
Epistaxis
Nasal septum
No
No
1
78 months, excision without recurrence
2
62/M
Epistaxis, nasal obstruction
Nasal septum
No
Cervical lymph node
1
72 months, spontaneously resolved
3
44/F
Lesion of nasal dorsum, epistaxis
Nasal septum
No
No
1
39 months, excision with recurrence
4
53/F
Lesion of nasal dorsum
Nasal septum
No
No
2
6 months, excision without recurrence
5
32/F
Nasal septum
Trachea
No
2
6
33/F
Nasal obstruction, dyspnea, epistaxis, hyposmia Nasal obstruction, dyspnea, epistaxis, hyposmia
Nasal cavity, nasal sinuses
Trachea, hard palate
Cervical lymph node
8
64 months, excision with repeated recurrence 84 months, excision with repeated recurrence
7
21/M
No
1
31/M
Nasal cavity, nasal sinuses Nasal cavity, nasal sinuses, nasopharynx
Facial, orbital
8
Nasal obstruction, facial asymmetry, hyposmia Nasal obstruction, aural fullness, hyposmia
No
No
2
9
58/M
Nasal obstruction, hyposmia, diminution of vision
Nasal cavity, nasal sinuses
Anterior skull base, intracranial involvement
No
2
120 months, excision with recurrence
10
16/M
Nasal obstruction, hyposmia, epistaxis
Nasal cavity, nasal sinuses
No
Cervical lymph node
2
6 months, excision without recurrence
shown in Fig. 1a–c, and the imageological change of S-RDD is shown in Fig. 2. The patients were monitored clinically with a mean follow-up period of 58.6 months (range 6–120 months). At the end of follow-up, only one case spontaneously resolved without surgery, and two cases in the anterior sinonasal group and three cases in the posterior sinonasal group recurred after endoscopic surgery; two cases in the anterior sinonasal group and two cases in the posterior sinonasal group did not experience recurrence. Although five cases experienced recurrence, surgery can result in short-term (mean 2.3 years, range 1–7 years) symptomatic control and restoration of function in those cases. Histopathological studies Grossly, excisional biopsy tissue was received in multiple pieces, with the largest fragment measuring 2.5 cm at its greatest dimension, and it appeared yellowish tan and slightly lobulated (Fig. 1d). Microscopic examination revealed obvious light-staining bands alternating with dark-staining bands at low magnification in eight cases (Fig. 1e, f); light-staining and darkstaining bands are not obvious in two of the cases. The
66 months, excision with recurrence 51 months, Second excision without recurrence
visible light-staining bands were full of large histiocytic cells, which contained vesicular nuclei with distinct nucleoli, delicate nuclear membranes and abundant pale-toeosinophilic cytoplasm. Some of the histiocytic cells contained intact erythrocytes, lymphocytes and plasma cells, a process known as emperipolesis (Fig. 1g). Dark-staining bands are rich in chronic inflammatory cells, mainly small lymphocytes and plasma cells, and neutrophils were found to be infiltrating in two cases. Fibrosis appeared in six lesions and typical fibrous nodules formed in one case. Immunohistochemical studies showed that the histiocytic cells were strongly reactive with antibodies against S-100 protein in all ten cases (Fig. 1g) and with CD68 in six cases (Fig. 1h). However, the same cells were nonreactive with antibodies directed against CD1a, leukocyte common antigen and desmin. All of the immunohistochemical studies had satisfactory positive and negative controls.
Discussion In our study, the patients’ mean age (40.3 years) and the male/female ratio (1:1) are basically in keeping with the
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Fig. 1 The endoscopic signs and histopathological studies of sinonasal Rosai- Dorfman disease. a The S-RDD of the anterior sinonasal cavity showed as septum mucosa thickening; b the S-RDD of the posterior sinonasal cavity showed as a polypoid lesion in the middle meatus; c the S-RDD lesion at the subglottic airway; d the biopsy sample from the nasal cavity showed as a yellow nodule; e, f histologically, S-RDD shows a characteristic pattern of alternating
light and dark areas on low-power magnification (H and E, E 950; F 9100); g the clear area is comprised of histiocytes with polygonal shapes and abundant clear cytoplasm containing some lymphocytes (emperipolesis) (H and E, 9400); (h, i) the infiltrating histiocytes in S-RDD are characterized by a strong reaction to S-100 protein and CD68 (SAB immunohistochemical stain, 9200, H S100; I CD68)
previous series of S-RDD in Taiwan (44.0 years; male/ female ratio: 1:1), but in our study the patients were older than the patients in the series that examined S-RDD in Western counties (20.0 years; male/female ratio: 1:1) [2, 7]. This is probably because patients in Taiwan and Mainland China share the same culture and race, which is different from Western countries. In addition, systemic symptoms (fever, malaise) and hematological and immunological abnormalities were commonly seen in systemic RDD but they were not found in this present series. In this present series, three cases (30 %) had cervical lymphadenopathy involvement and four cases (40 %) had another extranodal involvement, which is different from Hsiao et al. [7] study, which reported that 50 % of the cases had lymph node involvement and 66.7 % had RDD in another
extranodal site. This may be due to the statistical differences caused by the small sample size of our study. Unlike other research studies, this study paid particular attention to the sites of the lesions. Based on the physical, endoscopic and image examinations, we were able to accurately locate the lesion sites. In five cases, the lesion site was located mainly in the anterior sinonasal cavity, varying from being limited to just the cartilaginous nasal septum to encroaching upon the nasal bone and nasal dorsal subcutaneous tissue. In five other cases, the lesions were located in the posterior sinonasal cavity, varying from being limited to the bilateral nasal cavity to the sinuses, and even encroaching upon the nasopharynx, orbital and intracranial tissue. We then divided the ten cases into two groups and discussed the characteristics of each group.
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Fig. 2 Imageological change of sinonasal Rosai- Dorfman disease. a Lateral X-ray view of the soft tissues of the neck. There is an RDD lesion at the back wall of the trachea with narrowing of the airway; b, c CT showed that the RDD lesion was limited to the cartilaginous nasal septum (case 2); d, e) CT showed that the RDD lesion exceeded the cartilaginous nasal septum and spread to the nasal dorsal (case 2),
and the enhanced—scanning CT showed that the lesion was significantly strengthened; f, g CT showed that the RDD lesion was limited to the nasal cavity and paranasal sinuses (case 8); (h, i) MRI showed that the RDD lesion exceeded the nasal cavity and paranasal sinuses, with intracranial involvement, and the enhanced-scanning MRI showed that the lesion was significantly strengthened (case 4)
We found that the symptoms, endoscopy signs and images of S-RDD were different in the two groups. The common symptoms of the anterior sinonasal group were epistaxis, nasal obstruction and nasal dorsal deformity when the lesion encroached upon the nasal dorsa subcutaneous tissue. The common symptoms of the posterior sinonasal group were hyposmia, epistaxis, nasal obstruction and epistaxis. If the RDD lesion encroached upon the orbital and intracranial tissue, the patient complained of headache and diminished vision. In the anterior sinonasal group, endoscopy showed signs of RDD diffuse lesion infiltration under the mucosa; however, in the posterior sinonasal group, the RDD lesions often showed as formations on polyps. This trend was very obvious in the CT and
MRI images. This could lead to endoscopic biopsy in outpatients, which was difficult for patients in the anterior sinonasal group but relatively easy for patients in the posterior sinonasal group. The focus on the differential diagnoses of the two groups was different. Diffuse lesion infiltration under the septum mucosa and encroachment of the lesion into the nasal dorsa subcutaneous tissue were similar to the nasal type of NK/T lymphoma, which is often accompanied by nasal septum mucosal thickening and surrounding facial tissue swelling [8]. Polypoid lesions are similar to nasal carcinomas or nasal polyps, but nasal carcinomas are often located in the lateral cavity and the polyps are often located in the middle nasal meatus or olfactory cleft, which is
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different from S-RDD in which the lesion is located in the bilateral sinonasal and not in the middle nasal meatus or olfactory cleft. Although the final diagnosis is based on histopathological examination, these clinical features can help pathologists improve their diagnostic efficiency. It is generally accepted that the majority of RDD cases have a benign course and treatment is not necessary. Therapy is only needed by patients with extranodal RDD that has vital organ involvement or those with nodal disease that cause life-threatening complications [9]. However, in those series, only one case in the anterior sinonasal group spontaneously resolved, which is consistent with Chen et al.’s report in which only one of 126 cases of sinonasal RDD spontaneously resolved. There is no ideal treatment for sinonasal RDD or general RDD; however, in general, surgery, steroids, chemotherapy and radiology, used alone or in combination, have been reported with variable responses [10–13]. Most of our patients underwent endoscopic surgery and, at the end of follow-up, two cases of lesions in the anterior sinonasal group and three cases of lesions in the posterior sinonasal group recurred after endoscopic surgery. However, treatment can result in short-term symptomatic control and restoration of function. Therefore, we agree with the opinion of Ku et al. [14] that although no specific treatment can guarantee a sustained remission of this disease, surgery for loco-regional lesions can result in symptomatic control and restoration of function. The advantages of this study include its emphasis on the symptoms and different diagnoses correlated to lesion sites, which is rarely mentioned in other studies. Although this is the report that investigated the greatest number of Chinese sinonasal RDD cases, the total number of cases (10) still limits the ability to compare the treatment outcome of this study to the results of studies investigating different therapy methods. We believe that subsequent studies with larger sample sizes are necessary to explore the nature of this rare disease.
Conclusion Sinonasal RDD is a rare disease in China. Depending upon the lesion sites, it can be divided into either anterior sinonasal RDD or posterior sinonasal RDD, both of which have different clinical characteristics. Although endoscopic
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surgery often leads to recurrence, it can result in short-term symptomatic control and restoration of function.
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