Dermatology MCQ - Infiltrative and Neoplastic Disorders - Langerhans cell histiocytosis

A 2-year-old child presents with a widespread, seborrhea-like eruption involving the scalp, retroauricular folds, and intertriginous areas. The rash is erythematous, scaly, and has a purpuric quality. The child is also noted to have chronic otitis media and failure to thrive. A skin biopsy of one of the lesions is most likely to reveal which of the following histopathological findings?

A. Non-caseating granulomas composed of epithelioid histiocytes and multinucleated giant cells.
B. A diffuse dermal infiltrate of foamy histiocytes with Touton giant cells.
C. A dense dermal infiltrate of histiocytes with "coffee-bean" shaped nuclei, positive for CD1a and S-100 on immunohistochemistry, accompanied by eosinophils.
D. A lichenoid infiltrate of atypical lymphocytes with epidermotropism and Pautrier microabscesses.
E. Subcorneal pustules filled with neutrophils.

Correct Answer: C. A dense dermal infiltrate of histiocytes with "coffee-bean" shaped nuclei, positive for CD1a and S-100 on immunohistochemistry, accompanied by eosinophils.

Answer and Explanation

The correct answer is C. This question describes a classic presentation of multisystem Langerhans cell histiocytosis (LCH) in an infant, historically known as Letterer-Siwe disease. The key clinical clues are the seborrhea-like but purpuric rash in an intertrigous distribution, combined with systemic signs (otitis media, failure to thrive). The pathognomonic histopathological feature of LCH is an infiltrate of Langerhans cells, which have characteristic grooved or "coffee-bean" shaped nuclei. These cells are identified by their immunophenotype: they are CD1a and S-100 positive. The presence of eosinophils is a common accompanying feature.

Why the Other Options are Incorrect:

• A. Non-caseating granulomas...: This describes the histology of sarcoidosis or a foreign body reaction, not LCH.

• B. A diffuse dermal infiltrate of foamy histiocytes...: This describes xanthogranulomas or other non-Langerhans cell histiocytoses (e.g., juvenile xanthogranuloma). Touton giant cells are a hallmark of these disorders.

• D. A lichenoid infiltrate of atypical lymphocytes...: This describes mycosis fungoides (cutaneous T-cell lymphoma). The malignant cells in this condition are T-cells, not histiocytes.

• E. Subcorneal pustules filled with neutrophils: This is the hallmark of Sneddon-Wilkinson disease (subcorneal pustular dermatosis) or impetigo, not LCH.

Additional High-Yield Information for Exams:

• Histopathology & Immunohistochemistry: The diagnosis is confirmed by biopsy.

  • Light Microscopy: Infiltrate of histiocytes with abundant, pale cytoplasm and characteristically indented, grooved, or kidney-shaped nuclei.

  • Immunohistochemistry: The cells are CD1a+ and S-100+. The demonstration of CD1a positivity is diagnostic. Langerin (CD207) is another highly specific marker.

  • Electron Microscopy: Would show Birbeck granules (tennis-racket shaped cytoplasmic organelles), but this is rarely needed for diagnosis today.

• Clinical Spectrum: LCH has a wide spectrum of disease:

  • Single-System Disease: E.g., a solitary lytic bone lesion (eosinophilic granuloma) or isolated skin disease. This has an excellent prognosis.

  • Multisystem Disease: Involves two or more organ systems. This is the severe form, as described in the question. High-risk organs include the liver, spleen, and bone marrow.

• Differential Diagnosis: The cutaneous eruption can be mistaken for:

  • Seborrheic Dermatitis: But this is not purpuric and the child is otherwise well.

  • Candidal Intertrigo: Would show yeast and pseudohyphae on KOH preparation.

  • Langerhans Cell Histiocytosis: The purpuric nature of the lesions is a critical red flag that distinguishes it from benign mimics.

• Prognosis: Prognosis depends on the extent of disease. Single-system disease has a >95% survival rate. Multisystem disease, especially in infants and with involvement of "risk organs" (liver, spleen, bone marrow), has a poorer prognosis.

• Management & Rationale:

  • Rationale: The goal is to treat the disease to prevent organ dysfunction and long-term sequelae (e.g., diabetes insipidus from pituitary involvement, sclerosing cholangitis from liver involvement).

  • Staging: A full workup is mandatory for any child with proven LCH to determine the extent of disease. This includes skeletal survey, CBC, LFTs, and imaging of the pituitary.

  • First-line Treatment: For multisystem disease, the standard is systemic chemotherapy. Vinblastine and prednisone are commonly used. For refractory cases, cladribine is highly effective.

  • Targeted Therapy: A majority of LCH cases have mutations in the BRAF V600E gene, and BRAF inhibitors (e.g., vemurafenib) are now used for refractory or high-risk disease.