Clinical Review & Education

Clinical Challenge | RADIOLOGY

A Young Patient With Painless Neck Swelling Keivan Shifteh, MD; Janet Mei, MD, MPH; Jacqueline A. Bello, MD

A Axial postcontrast T1-weighted MRI

B

Axial T2-weighted MRI

C

Positron emission tomography

Figure. A, Postcontrast T1-weighted fat-suppressed magnetic resonance imaging (MRI) of the brain demonstrated an approximately 2-cm destructive mass involving the left malar eminence of maxilla with homogeneous enhancement. B, Axial T2-weighted fat-suppressed MRI through the neck demonstrated unilateral right-sided neck adenopathy. C, Fluorodeoxyglucose F18-labeled positron emission tomography whole-body imaging demonstrated avid right cervical lymphadenopathy and innumerable avid foci involving the axial and appendicular skeleton.

A 7-year-old African American girl without significant medical history presented with progressive painless right-sided neck swelling for 2 months. Initially, she experienced fever and sorethroat.Physicalexaminationfindingsdemonstratedminimallytenderandnonmobile4-cm right submandibular space swelling. Laboratory examination findings were significant for leukocytosis with neutrophilia (white blood cell count, 19.8 K/μL; neutrophil count, 18.2 K/μL [to convert to ×109/L, multiply by 0.001]), anemia (hemoglobin level, 9.6 g/dL [to convert to g/L, multiply by 10.0]), elevated erythrocyte sedimentation rate (>130 mm/h), and elevated Creactive protein level (3.1 mg/dL [to convert to mg/L, multiply by 10]). Ultrasonography revealed multiple enlarged hyperemic lymph nodes within the right side of the neck, the largest measuring 3.4 × 2.4 × 2.1 cm in the submandibular space. She was treated with oral antibiotics without improvement. Ultrasonography at 1-month follow-up revealed interval enlargement of the lymph nodes, which appeared rounded in shape, without preservation of internal architecture. The mother reported that the patient lost 3.2 kg in 2 months, without any chills or night sweats, difficulty swallowing or breathing, change in voice, abdominal pain, recent travel, or exposure to animals or pets. Magnetic resonance imaging (MRI) demonstrated extensive unilateral right-sided neck adenopathy, the largest nodes measuring approximately 4 cm at level IB; an approximately 2-cm destructive mass involving the left maxillary malar eminence; and additional lesions involving the T4 vertebra and upper sternum (Figure, A and B). Fluorodeoxyglucose 18F-labeled positron emission tomography with computed tomography (FDG PET/ CT) demonstrated extensive FDG-avid right-sided cervical lymphadenopathy and innumerable FDG-avid lytic foci involving the axial and appendicular skeleton (Figure, C).

Diagnosis B. Rosai-Dorfman disease

Discussion With a tissue diagnosis of Rosai-Dorfman disease (RDD), the patient was started on high-dose steroid therapy (dexamethasone, 8 mg daily), with improvement of neck swelling. Clinical and imaging follow-up was scheduled. Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, is a rare idiopathic macrophage-related disorder initially described in 1969.1 The classic, or nodal, form most comjamaotolaryngology.com

WHAT IS YOUR DIAGNOSIS?

A. Langerhans cell histiocytosis B. Rosai-Dorfman disease C. Neuroblastoma D. Lymphoma

monly manifests as massive cervical lymphadenopathy predominantly affecting children and adolescents.2 Extranodal manifestations most commonly occur in the head, neck, skin, soft tissues, and bones. Fever, elevated erythrocyte sedimentation rate, weight loss, malaise, sweats, hypergammaglobulinemia, and anemia can be seen in RDD. In cases involving superficial lymph nodes, detection is typically achieved by ultrasonography. Once a tissue diagnosis is made, recommendation for whole-body CT or MRI is warranted to exclude other involved sites. On MRI, lesions are typically hypointense to isointense on T1-weighted images and isointense to hyperintense on T2-weighted images, demonstrating restricted diffusion,

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Clinical Review & Education Clinical Challenge

which improves with treatment. On FDG PET/CT, avid tracer uptake is seen, which decreases with treatment.3 Bone involvement, often multifocal, presents as sharply or poorly defined lytic intramedullary lesions within long bones, in metaphyseal more than epiphyseal locations. Neither periosteal reaction nor calcifications are typical; however, cortical destruction may occur.3 Prognosis varies from self-limiting to significant morbidity associated with specific forms (isolated nodal vs extranodal), symptoms, and involvement of vital organs. Depending on these factors, options for treatment include observation, steroid treatment, surgery, chemotherapy, and radiotherapy.4 Langerhans cell histiocytosis is the most common dendritic cell disorder. Bone lesions are the most common manifestation, predominantly in flat bones. Less common long bone involvement is easily confused with RDD-associated osseous lesions. Early lesions appear lytic, expansile, and aggressive; mature lesions have sharp, sclerotic margins. Magnetic resonance imaging depicts intramedullary lesions with extramedullary soft-tissue components that appear hypointense on T1-weighted images and hyperintense on T2weighted images. Lymph nodes are involved in approximately 20% of cases, mostly in the neck, manifesting as hard or soft matted nodes with lymphedema.5 Neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous system. Its natural history ranges from a benign course to terminal illness, with a median age at diagnosis of 19

benign clinicopathological entity. Arch Pathol. 1969; 87(1):63-70.

review of histiocytic disorders. Radiographics. 2014;34(7):2008-2024. doi:10.1148/rg.347130132

2. Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): review of the entity. Semin Diagn Pathol. 1990;7(1):19-73.

6. Swift CC, Eklund MJ, Kraveka JM, Alazraki AL. Updates in diagnosis, management, and treatment of neuroblastoma. Radiographics. 2018;38(2): 566-580. doi:10.1148/rg.2018170132

3. Mar WA, Yu JH, Knuttinen MG, et al. Rosai-Dorfman disease: manifestations outside of the head and neck. AJR Am J Roentgenol. 2017;208 (4):721-732. doi:10.2214/AJR.15.15504

7. Toma P, Granata C, Rossi A, Garaventa A. Multimodality imaging of Hodgkin disease and non-Hodgkin lymphomas in children. Radiographics. 2007;27(5):1335-1354. doi:10.1148/rg.275065157 8. Navarro SM, Matcuk GR, Patel DB, et al. Musculoskeletal imaging findings of hematologic malignancies. Radiographics. 2017;37(3):881-900. doi:10.1148/rg.2017160133

REFERENCES

4. Goyal G, Ravindran A, Young JR, et al; Mayo Clinic Histiocytosis Working Group. Clinicopathological features, treatment approaches, and outcomes in Rosai-Dorfman disease. Haematologica. 2020;105(2):348-357. doi:10.3324/haematol.2019.219626

1. Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy. a newly recognized

5. Zaveri J, La Q, Yarmish G, Neuman J. More than just Langerhans cell histiocytosis: a radiologic

ARTICLE INFORMATION Author Affiliations: Department of Radiology, Montefiore Medical Center, Bronx, New York. Corresponding Author: Keivan Shifteh, MD, Department of Radiology, Montefiore Medical Center, 111 E 210th St, Bronx, NY 10467 (kshifteh@ montefiore.org). Published Online: October 1, 2020. doi:10.1001/jamaoto.2020.1595 Conflict of Interest Disclosures: None reported. Additional Contributions: We thank the patient’s mother for granting permission to publish this information.

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months. Neuroblastoma arises anywhere throughout the sympathetic nervous system; a majority of tumors occur in the abdomen (65%) followed by the posterior mediastinum and thorax (14%).6 Although the tumor can metastasize to lymph nodes and potentially arise from the sympathetic ganglia in the neck, the absence of any thoracic and abdominal mass on CT in addition to this patient’s presenting age make neuroblastoma unlikely. Hodgkin lymphoma presents in children with painless cervical lymphadenopathy, similar to RDD. However, two-thirds of patients present with mediastinal involvement at diagnosis,7 which was not seen in this case. Lymphomas may involve bone marrow or cortical bone. Bone marrow involvement, best seen on MRI, appears hypointense on T1-weighted images and hyperintense on short T1 inversion recovery and T2-weighted images, with enhancement on postcontrast T1 images, and demonstrates focal or multifocal uptake on a background of diffuse uptake on FDG PET/CT. Cortical bone infiltration often has a permeative, osteolytic, or mixed lytic and sclerotic pattern.8 The imaging appearance of bone involvement in lymphoma differs from that in this case. Although rare, RDD should be considered in children or adolescents presenting with massive neck lymphadenopathy. Apart from classic nodal involvement, its extranodal manifestation is broad. Whole-body CT or MRI is recommended to detect other sites of involvement once nodal diagnosis is made. Imaging also helps in selecting appropriate biopsy sites to confirm the diagnosis of RDD.

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