Introduction

Rosai Dorfman disease, or Sinus histiocytosis with massive lymphadenopathy, is a rare idiopathic condition characterized by the proliferation of histiocytes. While lymph node involvement is the more common presentation (60%), extranodal manifestations (40%) (1,2) are also observed. This series outlines cases involving cervical nodes, perisplenic and aortocaval nodes, retroperitoneal nodes, breast, and nasopharynx.

Rosai Dorfman - Nodal Presentation:

Four cases (Table 1) demonstrated enlarged lymph nodes: a 4-year-old with cervical lymphadenopathy, a 31-year-old with autoimmune hemolytic anemia and abdominal lymphadenopathy, a 72-year-old male with painless lymphadenopathy, and a 71-year-old male with abdominal pain and retroperitoneal node enlargement. Neutrophilic leukocytosis, elevated ESR, and biopsy findings of sinus dilation, histiocytes with emperipolesis (Figure 1, Figure 2), and positive S100 (Figure 4) and CD68(Figure 5) staining were consistent.

Figure 1 : Lymph node - Sheets of histiocytes with emperipolesis (40 x)	Figure 2 : Lymph node - Sheets of histiocytes with emperipolesis (100 x)
	Figure 3: Breast - Sheets of histiocytes with emperipolesis (400x)
Figure 4: Lymph node - Immunohistochemistry for S100 - Positive in the histiocytes	Figure 5: Lymph node - Immunohistochemistry for CD68 - Positive in the histiocytes

Rosai Dorfman - Extranodal Presentation:

Two cases (Table 1) manifested extranodally: a 42-year-old with a breast lump and a 14-year-old with involvement of the nasopharynx and cervical nodes. Both cases exhibited histological features of Rosai Dorfman, including emperipolesis (Figure 3), positive S100 and CD68 staining. Imaging of extranodal presentations often mimicked malignancy.

Discussion:

Rosai-Dorfman disease, recognized as Sinus histiocytosis with massive lymphadenopathy, is an uncommon yet distinctive disorder characterized by the proliferation of histiocytes. While it most commonly presents with lymph node involvement (60%), approximately 40% of cases exhibit extranodal [1,2] manifestations. The extra nodal sites involved are nasal cavity, oral cavity, pharynx, paranasal sinuses, salivary glands, trachea, orbit, bone and skin[3]. Breast involvement is very rare - only 20 cases have been reported in literature.

In the nodal presentation subset, four distinct cases showcased enlarged lymph nodes, each presenting with unique clinical features. A 4-year-old male exhibited cervical lymphadenopathy, emphasizing the potential occurrence of Rosai-Dorfman in pediatric populations. The second case involved a 31-year-old female with a history of autoimmune hemolytic anemia and abdominal lymphadenopathy, presenting a diagnostic challenge due to its association with an underlying autoimmune condition. Additionally, two elderly males, ages 72 and 71, presented with painless lymphadenopathy and abdominal pain, respectively, further illustrating the diverse clinical scenarios associated with this disorder.

Histopathological examination of the nodal cases revealed sinus dilation and a distinctive feature known as emperipolesis, where histiocytes engulf intact lymphocytes. These findings, coupled with elevated levels of neutrophilic leukocytosis and raised ESR, align with established characteristics of Rosai-Dorfman disease. Importantly, positive immunohistochemical staining for S100 and CD68 provided conclusive evidence for the diagnosis, reinforcing the reliability of these markers in confirming the presence of histiocytic infiltration.

The extranodal presentation subset featured two cases, one involving the breast and another the nasopharynx. The breast case, a 42-year-old female with a lump, underscored the rarity of Rosai-Dorfman involvement in this organ, with only a limited number of cases reported in the literature. The nasopharyngeal case, a 14-year-old female, presented with breathing difficulties, highlighting the potential challenges in diagnosing extranodal manifestations that may mimic malignancies.

Comparisons with existing literature reveal that Rosai-Dorfman predominantly affects young and middle-aged individuals, with a median age around 36 years in the present study. Furthermore, nodal involvement was more prevalent than extranodal, aligning with broader trends observed in similar investigations. Cervical and submandibular(4) lymphadenopathy remained the common presentation in nodal cases, with bilateral, massive, and painless involvement noted in the majority.

Blood investigations consistently demonstrated neutrophilic leukocytosis and elevated ESR (3,5,6). across cases, further corroborating the systemic inflammatory nature of Rosai-Dorfman disease. However, challenges in diagnosis persisted, in nodal cases lymphoma(7) was the close differential diagnosis clinically; and in extranodal cases where clinical suspicion often leaned toward malignancy (8) due to FDG avid lesions observed in imaging studies.

Histological differential diagnoses, such as Langerhan cell histiocytosis and Erdheim Chester disease(9), were considered, emphasizing the importance of accurate diagnosis through a combination of clinical, histopathological, and immunohistochemical assessments. Though S100 and CD68 was positive, Langerhan cell histiocytosis was ruled out histologically by the absence of eosinophils and Langerhans cells with nuclear grooves. Erdheim Chester disease was ruled out due to presence of emperipolesis, absence of touton giant cells and positivity of S100.

Treatment modalities for Rosai-Dorfman encompass corticosteroids, immunosuppressive drugs, or surgical removal (1). Notably, the majority of cases display favorable responses to treatment, and the recurrence rate remains low. This underscores the potential for successful management and emphasizes the importance of early and accurate diagnosis to guide appropriate therapeutic interventions.

Conclusion:

In conclusion, this discussion highlights the diverse clinical presentations of Rosai-Dorfman disease, ranging from nodal to extranodal involvement. The diagnostic challenges, especially in extranodal cases, underscore the importance of a comprehensive approach involving clinical correlation, histopathological examination, and immunohistochemical analysis. The rarity of breast involvement and the successful management outcomes reinforce the need for increased awareness and understanding of this intriguing histiocytic disorder.

References

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