Dermatology MCQ - Infiltrative and Neoplastic Disorders - Juvenile xanthogranuloma

An 18-month-old infant is brought to the clinic for a rapidly growing, dome-shaped, rubbery, reddish-yellow nodule on the scalp that appeared 2 months ago. The lesion is 1.5 cm in diameter and is asymptomatic. The child is otherwise healthy. A biopsy is performed and reveals a dense dermal infiltrate of foamy histiocytes and numerous Touton giant cells. Which of the following is the most accurate statement regarding the diagnosis and associated risk?

A. This is a juvenile xanthogranuloma, a benign self-resolving lesion that can rarely be associated with neurofibromatosis type 1 and an increased risk of juvenile myelomonocytic leukemia.
B. This is a Langerhans cell histiocytosis, which requires systemic workup for potentially life-threatening visceral involvement.
C. This is a Spitz nevus, a benign melanocytic lesion that should be excised to rule out spitzoid melanoma.
D. This is a mastocytoma, which may blister and cause flushing due to mast cell degranulation.
E. This is a pilomatricoma, a benign tumor of hair matrix origin that is often hard and rock-like on palpation.

Correct Answer: A. This is a juvenile xanthogranuloma, a benign self-resolving lesion that can rarely be associated with neurofibromatosis type 1 and an increased risk of juvenile myelomonocytic leukemia.

Answer and Explanation

The correct answer is A. This question describes the classic presentation of a juvenile xanthogranuloma (JXG). The key clues are the age of the patient (infant/toddler), the rapid growth of a rubbery, reddish-yellow nodule, and the pathognomonic histology showing foamy histiocytes and Touton giant cells (characterized by a ring of nuclei surrounded by a foamy cytoplasm). JXG is a benign, self-resolving condition. However, a critical high-yield fact is its well-documented association with neurofibromatosis type 1 (NF1). Children with both NF1 and JXG have a significantly increased risk of developing juvenile myelomonocytic leukemia (JMML).

Why the Other Options are Incorrect:

• B. Langerhans cell histiocytosis: LCH cells have grooved "coffee-bean" nuclei and are CD1a+/Langerin+, not foamy histiocytes. LCH can be severe and requires systemic workup, whereas solitary JXG does not.

• C. Spitz nevus: This is a melanocytic lesion, often pink or tan, composed of epithelioid or spindled melanocytes. It does not contain foamy histiocytes or Touton giant cells.

• D. Mastocytoma: This lesion is composed of mast cells, not histiocytes. It has a characteristic Darier's sign (urtication upon rubbing) and does not contain Touton giant cells.

• E. Pilomatricoma: This is a tumor of the hair matrix that feels very firm or "rock-hard" due to calcification. Histology shows basaloid cells and "shadow" or "ghost" cells, not a granulomatous infiltrate.

Additional High-Yield Information for Exams:

• Histopathology: The hallmark is a dense, non-encapsulated dermal infiltrate of:

  • Histiocytes with abundant, vacuolated (foamy) cytoplasm.

  • Touton Giant Cells: A specific type of multinucleated giant cell with a central ring of nuclei and a peripheral rim of foamy cytoplasm.

  • Other inflammatory cells like eosinophils and lymphocytes may be present.

  • Immunophenotype: The cells are Factor XIIIa+, CD68+, and are negative for CD1a and S-100, which distinguishes them from Langerhans cells.

• Clinical Presentation:

  • Solitary JXG: Most common presentation. Typically appears in the first year of life and undergoes spontaneous involution over months to years.

  • Multiple JXG: Less common. Can be associated with systemic involvement (eyes, lungs, liver, etc.), though this is rare.

• Differential Diagnosis: The main differential for a yellow-red nodule in a child includes JXG, Spitz nevus, mastocytoma, and pilomatricoma, as listed above.

• Associated Conditions & Prognosis:

  • NF1 and JMML: This is the most critical association. The triad of café-au-lait macules, JXG, and JMML is a recognized syndrome. Any child with JXG should be examined for signs of NF1.

  • Ocular JXG: JXG in the eye (iris, ciliary body) can cause hyphema (blood in the anterior chamber) and glaucoma, potentially leading to blindness. An ophthalmologic exam is recommended for infants with multiple JXG or a solitary JXG on the head/neck.

  • Prognosis: For the vast majority of patients with solitary cutaneous JXG, the prognosis is excellent, with spontaneous resolution.

• Management & Rationale:

  • Rationale: The primary goal is accurate diagnosis to provide reassurance and to screen for the rare but serious systemic associations.

  • First-line for a classic solitary lesion: Clinical diagnosis, reassurance, and observation. A biopsy is often performed to confirm the diagnosis.

  • Screening:

    • A thorough physical examination for signs of NF1 (axillary freckling, other café-au-lait spots, neurofibromas).

    • Consider an ophthalmologic examination in high-risk infants.

  • Treatment: Treatment is rarely needed. Indications include functional impairment, persistent bleeding, or cosmetic concern. Options include surgical excision or intralesional corticosteroid injection.