Race for the Case answers

Spring 2021 case by Angelia Stepien, DO, and Blake Robbins, DO

A 10-month-old male with no significant past medical or family history was referred to the clinic by his pediatrician for treatment of suspected molluscum contagiosum. On physical examination, numerous 2-3 mm yellow-brown dome-shaped papules were appreciated on the head, neck, upper trunk, and genitals. An initial biopsy revealed a histiocytic infiltrate with scattered lymphocytes confined to the papillary dermis. Subsequent specimens demonstrated foamy lipidized histiocytes and giant cells with a wreath-like arrangement of nuclei. Further analyses by hematology-oncology and ophthalmology were negative for leukemia and ocular abnormalities, respectively.

1. What is the primary diagnosis?
   Answer: Juvenile xanthogranuloma (JXG)

2. What is the most common extracutaneous site of involvement?
   Answer: The eye is the most common extracutaneous site for JXG. Ocular lesions develop in less than 0.5% of affected individuals and are more commonly seen in patients with multiple cutaneous JXGs. These usually occur before the age of 2 years old. Typically, ocular JXG will be unilateral and affect the iris. Serious complications including hyphema, uveitis, and glaucoma can result in blindness therefore, early referral to ophthalmology is critical.

3. What is the name given to the classic multinucleate histiocyte characteristic of this condition?
   Answer: JXG, neurofibromatosis 1 (NF-1), and juvenile myelomonocytic leukemia (JMML). JXG has been associated with NF-1, particularly when diagnosed before age 2. Case reports have observed a 20x increased risk of developing JMML in these patients.

4. What are the characteristic positive and negative immunohistochemistry markers for this entity?
   Answer: Touton giant cell. These are multinucleate giant cells that contain an eosinophilic core surrounded by nuclei in a ring-like fashion with a peripheral rim of foamy cytoplasm. Although seen in other entities, these are characteristic of JXG.

5. What are the characteristic positive and negative immunohistochemistry markers for this entity?
   Answer: JXG is a non-Langerhans cell histiocytosis and therefore will be CD68 and factor XIIIa positive. CD1a, S100, and CD207 (Langerin) will be negative.

List of abbreviations

JXG: juvenile xanthogranuloma
NF-1: neurofibromatosis 1
JMML: juvenile myelomonocytic leukemia
CD: cluster of differentiation

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