Solitary extranodal Rosai-Dorfman disease of the mandible: an exceedingly rare presentation.

Sinus histiocytosis with massive lymphadenopathy, generally known by the name of Rosai-Dorfman disease is a rare benign condition principally affecting cervical lymph nodes. Concurrent extra-nodal disease frequently occurs, however, solitary extra-nodal disease involving the mandible is exceedingly rare with less than five reported cases in the English literature. We describe a case of primary involvement of the mandible in a 27-year-old female, and discuss the differential diagnosis of this disease with other histiocytic lesions.

INTRODUCTION

Sinus histiocytosis with massive lymphadenopathy is a rare benign disease, primarily affecting cervical lymph nodes. It is commonly known as Rosai-Dorfman disease after the physicians who first described it in 1969.1 The disease is exceedingly rare with an estimated prevalence of 1 in 200,000.2 Sole extranodal disease is present in about 20 to 25 percent cases3-5, while simultaneous nodal and extranodal disease is present in 40 to 50 percent of the patients at the time of presentation.3,6-8 Even after five decades, the exact etiology is still unknown. The disease mainly affects adolescents and young adults and has a slight predilection for males and Africans Americans.6 It is a benign, self-limiting disease; however, it can be locally destructive and fatal in rare instances.1,6,7 The head and neck region is the most commonly involved area by nodal as well as extra-nodal disease.1,6-9 The sinonasal tract is the most common extranodal site within the head and neck region; however, the involvement of skin, soft tissues, orbit, salivary glands, larynx, tonsils, thyroid, ear, and facial bones have all been noted.6,8-11 Meanwhile, the mandible can also be involved; however, the solitary primary involvement of mandible is extremely rare with only a handful of cases identified in the literature.10,12,13 Herein we describe a case of solitary primary involvement of the mandible in a 27-year-old female.

CASE PRESENTATION

A 27-year-old morbidly obese African American, gravida 1, para 0 female presented during the first trimester of her pregnancy with swelling in the right jaw and loosening of teeth. The patient also complained of localized pain but denied fever, weight loss, and other constitutional symptoms. On examination, there was a tender swelling of the right mandible. A biopsy was performed that showed mixed inflammation with numerous foamy histiocytes suggestive of Rosai-Dorfman disease. A CT scan was subsequently performed to delineate the extent of the disease to rule out nodal disease and other possible areas of involvement. The CT scan demonstrated a lytic lesion involving much of the body of the right side of the mandible, extending into the mentum of the mandible and crossing the midline into the anterior aspect of the left body of the mandible (Figure 1 A-C). The lesion showed avid radiotracer uptake on scintigraphy (Figure 1D). Needle core biopsies were performed of the suspicious lymph nodes, which on histopathologic evaluation showed reactive hyperplasia. The patient subsequently underwent a segmental mandibulectomy.

Figure 1

CT scan demonstrating lytic lesion involving bilateral mandible (A – Coronal; B – Sagittal and C – Axial plane). Avid radio tracer uptake on scintigraphy (D).

The gross specimen received in pathology consisted of a 14.0 cm segment of the mandible with teeth number 19-27 and 31-32 (Figure 2 A-D). Teeth 17-18 and 28-30 had been removed previously. The mandible was markedly asymmetric with an enlarged and bulging right lateral portion. Sectioning revealed a gray, soft, focally cystic mass involving two-thirds of the resected segment of the bone. Histologic evaluation showed a locally destructive lesion composed of numerous foamy histiocytes, admixed with lymphocytes, neutrophils, and scattered eosinophils and plasma cells infiltrating into the peri-mandibular soft tissue (Figure 3 A-B).

Figure 2

Gross images of the specimen demonstrating entire specimen – A; anterolateral aspect – B; inner aspect – C and cystic portion – D.

Figure 3

Photomicrograph demonstrating diffuse proliferation of histiocytes (A – H&E, 100X) causing local bone destruction (B – H&E, 100X). Histiocytes exhibiting emperipolesis. (C – H&E, 200X, D – H&E, 400X).

Some of the histiocytes also demonstrated emperipolesis (Figure 3 C-D). Immunohistochemical stains showed the histiocytes to be positive for CD68 and S100 while negative for CD1a (Figure 4). The morphology and immunohistochemical profile were consistent with Rosai-Dorfman disease. The concomitantly removed submandibular gland and suspicious lymph nodes showed no evidence of involvement by the disease. The patient underwent reconstruction with osteomycocutaneous fibular flap.

Figure 4

Histiocytes exhibiting diffuse immunoreactivity in with CD68 (A – 200X) and S100 (B – 200X).

DISCUSSION

Rosai-Dorfman disease is a benign proliferation of histiocytes that usually presents as massive but painless lymphadenopathy.1 Adolescents and young adults are the most commonly affected age groups. Nodal disease most commonly manifests in the cervical lymph nodes, and extranodal disease also occurs most commonly in the head and neck region.1,6-9 Primary extra-nodal disease is well documented and mainly affects the sinonasal tract.6,8 Multiple organ systems can be involved in up to 40% of patients.8 Bone involvement is also known, however, primary, solitary, disease of the facial bones is extremely rare.6,10-16 Our patient presented with a solitary lesion of the mandible.

Patients with nodal disease usually present with painless lymphadenopathy with or without constitutional symptoms while signs and symptoms of extra-nodal disease depend on the site of involvement and invariably include localized swelling with or without pain. In the case of osseous lesions patients usually complain of swelling, which is sometimes accompanied by pain. Our patient presented in a similar fashion and since the involved bone was the mandible, the patient also reported loosening of her teeth. Alawi et al.12 reported a case with similar presentation to our case in a 32-year-old pregnant women. As mentioned in the case presentation our patient was also pregnant at the time of presentation. While it could be a mere coincidence, we suggest that extranodal Rosai-Dorfman disease with osseous involvement may have a predilection for pregnant females. This speculation is further strengthened by a case reported by Butler et al.17 Their patient had nodal disease that was exacerbated during two pregnancies and went into remission during the time in between the two pregnancies. Some authors have suggested autoimmunity as underlying basis for Rosai-Dorfman disease. This hypothesis is strengthened by presence of IgG4 positive plasma cells in the lesion.18-21 This suggests that the exacerbation during pregnancy may very well be associated with autoimmunity.

Radiologic appearance of Rosai-Dorfman disease can vary from a well-defined radiolucent lesion to a poorly defined mixed lesion with areas of sclerosis.14,15 The disease is locally destructive, and it is not uncommon to see the lesion extending into the surrounding soft tissue. In our patient, the CT scan demonstrated a lytic lesion involving much of the body of the mandible with no soft tissue extension, however, microscopically the lesion extended into the peri-mandibular soft tissue.

Other histiocytic diseases such as Langerhans cell histiocytosis and Erdheim-Chester disease can have a similar clinical and radiologic presentation.22-24 Additionally, even the morphology of these diseases can be quite similar.1,6,22-26 Subtle microscopic clues and immunohistochemistry aid in the differential diagnosis. The morphologic and immunohistochemical differences that may help in routine practice are summarized in Table 1. Recently Graces et al.27 demonstrated KRAS and MAP2K1 gene mutations in one-third Rosai-Dorfman disease cases of their study cohort. This mutation is in comparison to BRAF V600E mutation in Langerhans cell histiocytosis and Erdheim-Chester disease.28 In our patient, the lesion comprised of numerous foamy histiocytes, admixed with lymphocytes, neutrophils, and scattered eosinophils and plasma cells with some histiocytes exhibiting emperipolesis. The histiocytes were immunoreactive to CD68 and S100 while negative for CD1a confirming the diagnosis of Rosai-Dorfman disease. We did not perform a gene mutation analysis.

Table 1

Morphology and immunohistochemical profile of Rosai-Dorfman disease, Langerhans cell histiocytosis and Erdheim-Chester disease18-20

	Rosai-Dorfman disease	Langerhans cell histiocytosis	Erdheim-Chester disease
Morphology	Diffuse proliferation of large foamy histiocytes with vesicular nuclei and eosinophilic cytoplasm.Mixed inflammatory infiltrate composed of neutrophils, lymphocytes, plasma cells and rare eosinophils.Rare or no mitosis.Emperipolesis.	Diffuse proliferation of slightly smaller foamy histiocytes with grooved nuclei and eosinophilic cytoplasm.Mixed inflammatory infiltrate typically containing eosinophils.Rare mitosis.Rare or no emperipolesis.	Diffuse proliferation of small histiocytes with moderate amount of cytoplasm in a fibrotic background.Multinucleated giant cells.HemophagocytosisNo emperipolesis.
Immunohisto-chemical profile	CD68 and S100 positive.CD1a negative.	CD68, S100, CD1a and langerin (CD207) positive.	CD68 positive.S100 focally positive.CD1a negative.

Other disease processes that may mimic Rosai-Dorfman disease include xanthomatous lesions including soft tissue xanthoma and juvenile xanthogranuloma; infectious processes such as lepromatous leprosy; and lysosomal storage disorders such as Gaucher disease.29-34 Histiocytes in all these lesions except leprosy are usually S100 negative which can immensely aid the differential diagnosis. In lepromatous leprosy the macrophages loaded with mycobacteria are S100 positive, however, clinical presentation and fite staining for mycobacterial organism can aid the diagnosis.33,34

Treatment depends upon the extent of disease and varies with each individual patient. About 70% to 80% of patients have spontaneous improvement of symptoms without any treatment; however, there can be episodic exacerbations and remissions that may last for years.1,6,16,17,35-37 Severe, locally destructive and persistent disease may require treatment with surgery, and corticosteroids. Chemotherapy and rarely radiotherapy have also been tried with limited success.1,6,16,35-37 While there is no “ideal” treatment, the goal of treatment is to keep the disease under control and preserve the quality of life. In our patient, the disease presented as a solitary lesion which was locally destructive. Therefore, surgery was considered the treatment of choice.

Rosai-Dorfman disease has a protracted and indolent course. While the disease is usually self-limiting with an excellent prognosis, it can be persistent and even fatal in rare instances.3 More recent data shows that mortality rate can be up to 7%.21 Foucar et al’s.7 analysis of 14 fatal cases of the disease showed that the mean age the patients was 33 years. Autopsy was performed in eight of these patients which showed the Rosai-Dorfman disease to be culprit in only two cases while the cause of death in other cases was either some immunologic abnormality or unusual infections.7 The prognosis of solitary osseous lesions is generally excellent with rare recurrences.6,12,13,15 Thus far for our patient, her post-operative recovery has been without complications, and her prognosis appears to be excellent.