HEIDI C. WERNER
HISTORY OF PRESENT ILLNESS
A 2-year-old American-African male was brought to the emergency department by his mother for evaluation of swelling under his chin. His mother had noted the swelling 2 days prior and he complained of difficulty swallowing prior to coming to the emergency department. He had no history of fever, difficulty breathing, increased snoring, rash, night-sweats, or weight loss.
The patient was born at 32 weeks gestation with a birth weight of 1300 g and was hospitalized for 2-3 months. His perinatal course was complicated by episodes of central apnea which warranted a home apnea monitor until the age of 4 months. He had an inguinal hernia repaired prior to discharge from the hospital. The mother had been treated with rifampin due to a positive tuberculin skin test. Her chest radiograph was reportedly normal. The child had never received a tuberculin skin test.
T 38.1°C; HR 113 bpm; RR 24/min; BP 103/73 mmHg; Weight 12.9 kg
In general, the child was alert and watchful in no acute distress. The tympanic membranes were normal in appearance and mobility. There was no nasal discharge. The neck was supple with a full range of motion. There was a 2 × 2 cm mobile lymph node in the right submandibular area. It was not erythematous or tender. There were also 2 × 4 cm mobile, nontender postcervical, and postauricular nodes. There was shotty axillary, anterior cervical and inguinal adenopathy. The chest was clear to ausculation. There were two small subcentimeter hyperpigmented macules on the upper back. There were no other skin lesions.
The WBC count was 7600/mm3 with 22% segmented neutrophils, 2% eosinophils, 66% lymphocytes, and 10% monocytes. The hemoglobin and platelet counts were normal. The total bilirubin was 0.4 mg/dL. AST and ALT were 40 U/L and 21 U/L, respectively. Erythrocyte sedimentation rate was 1 mm/h. Epstein-Barr virus titers revealed undetectable levels of viral capsid antigen (VCA) IgM, VCA IgG, and Epstein-Barr nuclear antigen antibody, consistent with no previous or current evidence of Epstein-Barr virus infection. A tuberculin skin test using purified protein derivative (PPD) and anergy panel were placed.
COURSE OF ILLNESS
The patient was discharged to home with a presumptive diagnosis of lymphadenitis caused by nontuberculous mycobacteria. He saw his pediatrician because of progressive cervical lymphadenopathy, which was now bilateral. His erythrocyte sedimentation rate increased to 67 mm/h. During the course of his evaluation, the patient had negative titers for toxoplasmosis, cat-scratch disease, and cytomegalovirus. A neck CT (Figure 13-8) prompted consideration of a diagnosis that was confirmed by lymph node biopsy.
FIGURE 13-8. Neck CT reveals multiple markedly enlarged lymph nodes along the internal jugular chains bilaterally, most prominent at the bilateral jugulodigastric regions. The largest lymph node measures 3.1 cm by 2.6 cm on the right, 2.6 cm by 2.7 cm on the left. There are also prominent lymph nodes along the spinal accessory chains, supraclavicular regions, and superior mediastinum.
DISCUSSION CASE 13-4
Lymph node enlargement, in the acute setting, has a broad differential diagnosis (Table 13-5) with infectious etiologies being the most common. With progressive and massive lymph node enlargement (Figure 13-8), lack of fever and negative infectious testing, oncologic diagnoses become more likely and biopsy is indicated. Rosai-Dorfman disease is a unique entity that is characterized by self-limited proliferation of the histiocytes.
TABLE 13-5. Causes of peripheral lymphadenopathy in children.
The progression of this child’s neck mass and the elimination of the other causes of massive neck swelling prompted the biopsy of the lymph nodes. The lymph node biopsy revealed an infiltration of histiocytes filling the sinus of the lymph nodes as well as positive staining for S-100. This finding in the context of the clinical presentation confirmed the diagnosis of sinus histiocytosis with massive lymph adenopathy (SHML) or Rosai-Dorfman disease.This disease, first described in 1969, is thought to be caused by a massive over response of the immune system with production of histocytes in response to a viral trigger. The lymph nodes become greatly enlarged and then regresses spontaneously.
INCIDENCE AND EPIDEMIOLOGY OF ROSAI-DORFMAN DISEASE
The incidence of this condition is unknown and presumed to be rare. No single etiologic agent has been determined. There is a male predominance in both Caucasian and African American children. Most cases have been described in children although there are reports across the age spectrum.
Clinical presentation is usually that of painless bilateral cervical adenopathy that continues to increase in size despite attempted therapies (87% of cases). Other nodal sites include the mediastinum, retroperitoneal, axillary, and inguinal areas. There are also reports of extra-nodal involvement in nasal cavity, salivary glands, sinuses, tonsils, trachea, eyes, and orbit. Leukocytosis, hypochromic, normocytic anemia, and elevated ESR are common laboratory findings.
Lymph node histology. The diagnosis is based on histologic findings on biopsy. Histiocytes with benign cytologic characteristics fill the sinus of the affected lymph nodes. The histiocytes contain normal appearing lymphocytes within their cytoplasm. This finding is termed lymphophagocytosis or emperipolesis. In contrast to typical histiocytes, the histiocytes in Rosai-Dorfman also strongly express S-100 protein, a family of proteins that regulate intracellular processes such as cell growth and motility, cell cycle regulation, transcription, and differentiation.
Radiologic studies. Lymphadenopathy in children with Rosai-Dorfman disease typically involves the cervical nodes. Lymph node enlargement is massive and bilateral; the enlarged lymph nodes are not tender. These enlarged lymph nodes can be easily visualized on CT, ultrasound, and MRI, though no specific imaging characteristics allow differentiation of lymphadenopathy in Rosai-Dorfman disease from other disease processes causing lymph adenopathy.
Treatment is primarily supportive and spontaneous resolute is frequently observed. Yet, lymph-adenopathy may increase and lead to airway compromise necessitating artificial airway support. Surgery may be required for lymph node debulking when they compress the airway or vital organs. There are anecdotal reports of varying degrees of improvement with corticosteroids, methotrexate, or mercaptopurine.
1. Rosai J, Dorfman FR. Sinus histiocytosis with massive lymphadenopathy: a pseudolymphomatous benign disorder. Cancer. 1972;30:1174-1188.
2. Faucar E, Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): review of the entity. Semin Diagn Pathol. 1990;7:19-73.
3. Ünal ÖF, Köyba S, Kaya S. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Internat J Pediatr Otorhinolaryn. 1998;44:173-176.
4. Ahsan SF, Madgy DN, Poulik J. Otolaryngologic manifestations of Rosai-Dorfman disease. Internat J Pediatr Otorhinolaryn. 2001;59:221-227.
5. McGill TJI, Wu CL. Weekly clinicopathological exercises: case 19-2002: a 13-year-old girl with a mass in the left parotid gland and regional lymph nodes. N Engl J Med. 2002;346:1989-1996.