This study was performed to investigate the clinical manifestations, treatment methods, and prognosis of Rosai-Dorfman disease (RDD) with laryngeal involvement. Five clinical cases of RDD with laryngeal involvement diagnosed between 1986 and 2015 were retrospectively analyzed. The laryngeal lesions of these 5 patients mostly involved the glottis and subglottis, with the main symptoms being a hoarse voice and airway obstruction. In addition, the patients mostly exhibited a unilateral or asymmetric onset that was manifested by a laryngeal submucosal nodular mass. The patients were subjected to a regimen of hormone treatment combined with surgical resection. The median follow-up duration was 101 months (8–384 months). One case was lost, and the remaining 4 subjects are alive with disease. The follow-up examinations revealed that 4 subjects had stable laryngeal conditions, whereas one showed minor progression. RDD with laryngeal involvement is clinically rare and differs considerably from classical RDD in age of onset, gender composition, and extranodal involvement. The regimen of hormone treatment combined with surgical resection can stabilize the patient’s general condition and laryngeal lesion. Tracheotomies are recommended for patients with dyspnea. After their conditions stabilize, decannulation can be successfully performed in most cases. This therapeutic regimen generally delivers a good prognosis.
Rosai-Dorfman disease (RDD) was named after Rosai and Dorfman, who were the first to describe the illness in 1969 [
Between 1986 and 2015, there were 31 cases of RDD, and the diagnoses were confirmed pathologically in our hospital. Five cases of RDD with laryngeal involvement were retrospectively examined. General information such as gender, disease onset, clinical manifestations, laboratory tests, and pathological information were retrieved from the clinical records. Experienced senior pathologists were invited to further validate the laryngeal pathological sections of the 5 patients. During follow-up visits, the subjects were examined for their survival, previous treatment methods for the laryngeal lesions, and the corresponding efficacy. SPSS 17.0 was used for statistical analyses, and descriptive analysis was employed for general information. The study was approved by the Ethics Committee of Beijing Union Medical College Hospital.
The general information for all 5 patients is summarized in Table
The general information for the 5 RDD cases with laryngeal involvement.
Case number | Age upon RDD diagnosis (years) | Age upon laryngeal RDD diagnosis (years) | Gender | Onset of systemic symptoms | Sites of lymph node involvement |
---|---|---|---|---|---|
1 | 27 | 28 | M | Cervical lymphadenopathy | Neck, axilla |
2 | 34 | 36 | F | Cervical lymphadenopathy | Neck |
3 | 39 | 41 | M | Nasal obstruction and cervical lymphadenopathy | Neck, axilla, groin |
4 | 38 | 38 | M | Cervical lymphadenopathy | Neck, axilla |
5 | 45 | 45 | F | Hoarse voice, suffocation | NA |
The clinical features of larynges for the 5 RDD cases with laryngeal involvement.
Case number | Onset of laryngeal symptoms | Sites of laryngeal involvement | Events leading to discovery of laryngeal involvement | Sites of extranodal involvement |
---|---|---|---|---|
1 | Hoarse voice | Glottis and subglottic region | Laryngoscopy due to hoarse voice | Skin |
2 | NA | Subglottic region | Laryngoscopy due to nasal obstruction | Nasal cavity |
3 | Hoarse voice | Glottis and subglottic region | Laryngoscopy due to hoarse voice | Nasal cavity, pharynx, submandibular gland |
4 | NA | Glottis and subglottic region | Routine laryngoscopy | Nasal cavity, pharynx |
5 | Hoarse voice and suffocation | Glottis and subglottic region | Routine laryngoscopy | NA |
All 5 patients were found to have laryngeal lesions via laryngoscopy, which mostly involved the glottis and subglottis. In particular, the subglottic lesions were more pronounced than the glottic lesions, which often presented as unilateral or asymmetric lesions with the onset of disease and manifested a laryngeal submucosal nodular mass, a tough texture, and resistance to bleeding. In addition, some of the laryngeal tumors were solid and cystic in nature and contained mucus in the lumen (Figure
A laryngoscopic view of a classical case of RDD with laryngeal involvement. (a) This picture shows that the nodular lesions with smooth surfaces were mainly present in the right vocal cord and the posterior region of the subglottic area. (b) This picture shows that the nodular lesions with smooth surfaces were mainly present in the right vocal cord and the anterior region of the subglottic area. (c) This picture shows that the nodular, ulcer-free lesions with smooth surfaces were mainly present in the right vocal cord and entire subglottic area. (d) This picture shows the nasopharyngeal manifestation of the same patient in panel (c). The white arrowhead points to nasopharyngeal nodular lesions with smooth mucous membranes; the black star indicates the nasal septum.
Pathology of a classical case of RDD with laryngeal involvement. (a) HE staining, 60x, the patches of histiocyte proliferation form nodular zones with light staining. (b) HE staining, 300x, classical histiocytes with large nuclei and low mitotic counts; engulfed lymphocytes are present in the cytoplasm. (c) Immunohistochemical analysis revealed that the histiocytes were S-100 positive.
The course of treatment and results of the follow-up visits are summarized in Table
The course of treatment and relevant efficacy for the 5 RDD cases with laryngeal involvement.
Case number | Follow-up |
Systemic regimen | Laryngeal treatment strategy | Condition of laryngeal lesions | Outcome |
---|---|---|---|---|---|
1 | 384 | Prednisone 20 mg × 4 W | Open surgery + tracheotomy | Stable | AWD |
2 | 165 | Prednisone 30 mg × 2 W | Open surgery + tracheotomy | Stable | AWD/LFU |
3 | 101 | Prednisone 30 mg × 2 W + cladribine 50 mg × 1 W | Endosurgery ×2 + tracheotomy | Slow progress | AWD |
4 | 98 | Prednisone 30 mg × 2 W | Endosurgery ×2 | Stable | AWD |
5 | 8 | Prednisone 30 mg × 2 W | Endosurgery + tracheotomy | Relieved | AWD |
Note: AWD, alive with disease; LFU, lost to follow-up.
The median follow-up duration of the cohort was 101 months (8–384 months). Among the patients, case #2 survived with the disease for the 165 months of follow-up but was later lost to follow-up. Case #3 underwent 2 operations and a treatment regimen with prednisone and cladribine, but the laryngeal lesions still exhibited slow progression. This subject is currently refusing another laryngeal operation and was therefore not decannulated. The remaining subjects all exhibited stable conditions, had no expiratory dyspnea, and were decannulated (Figure
The course of treatment and relevant efficacy for a classical case of RDD with laryngeal involvement. (a) The pretreatment laryngoscopy revealed a normal left vocal cord but involvement in the right vocal cord and subglottic area. The movement of the right vocal cord was restricted. (b) Review after 1 month of prednisone 30 mg × 2 W + cladribine 50 mg × 1 W showed no apparent changes in the laryngeal lesions. (c) A review of the laryngoscopy images generated 6 months after the endoscopic operation revealed that the subglottic tumors had almost disappeared and that the subglottic trachea displayed no apparent abnormalities. (d) A review 3 years after the first endoscopic surgery revealed progression of the lesions in the inferior and anterior regions of the glottis. (e) A review 3 years after the endoscopic surgery revealed that the subglottic lesions were partially obstructing the airway. Black stars indicate the lesions in the anterior region of the glottis, whereas white stars indicate the newly developed subglottic lesions.
RDD is a rare, nonmalignant type of histiocytosis that occurs mostly in the young and has the main clinical manifestations of giant and painless cervical lymphadenopathy, fever, and an elevated erythrocyte sedimentation rate [
Despite different clinical manifestations, the following pathological traits are still consistent between RDD with laryngeal involvement and classical RDD: the presence of dark and light colored patches that are visible under low magnification and are formed by nodular areas of distributed histiocytes and dense areas of inflammatory cell infiltration. Under high magnification, the lightly stained area comprises large histiocytes, which often contain engulfed lymphocytes. The extranodal lesions and the lymph node lesions were very similar, but the extranodal lesions showed more obvious fibrosis and fewer histiocytes, and emperipolesis was not common. The immunohistochemistry results suggested that these cells were S-100-positive, CD68-positive, and CD1a-negative; staining with GMS and PAS was negative, thereby excluding infectious diseases, which aids in differentiating RDD from other diseases [
Currently, there are no ideal treatments for RDD; however, it has been reported that 20% of patients exhibited spontaneous resolution [
RDD with laryngeal involvement is clinically rare and differs from classical RDD with regard to the age of onset and gender ratio. The patients who were treated with the regimen involving hormone administration and surgical resection exhibited stable laryngeal conditions. For individuals with dyspnea, tracheotomy should be considered, and once the condition stabilizes, decannulation can be performed. In general, the treatments resulted in good prognoses.
Yongjin Li is the co-first author.
The authors declare that there are no conflicts of interest regarding the publication of this article.