Histiocytoses

Histiocytoses Introduction

Histiocytoses are proliferative disorders that share a common CD34 positive progenitor in the bone marrow, which differentiates into distinct histiocyte lineages. These include Langerhans cells, mononuclear macrophages, and dendritic cells, each with characteristic features and stains. Langerhans cells display kidney-shaped reniform nuclei, function as antigen-presenting cells migrating to and from the epidermis, and stain positive for langerin (CD207), CD1a, and S100. On electron microscopy, they demonstrate Birbeck granules, which have a classic tennis racquet appearance. Mononuclear macrophages migrate within the dermis and express CD68 and HAM56. Dermal dendritic cells exist as 2 types: type I cells that are factor XIIIa positive, and type II cells that express CD34. An abnormal proliferation of any of these histiocyte subtypes can result in histiocytoses, broadly categorized into Langerhans cell histiocytosis and non-Langerhans cell histiocytosis, with the latter demonstrating considerable clinical and histological overlap between its entities.

Langerhans Cells

• Kidney-shaped water bottle = Reniform (kidney-like) nuclei
• Kid holding a long-handle racket = Langerhans cell
• Standing on top = Antigen presenting cell migrating to and from the epidermis
• Long handle = Stains positive for langerin
• Maine 207 jersey = Langerin is aka CD207
• Bear = Presence of Birbeck granules (tennis racquet shaped on electron microscopy)
• #1 foam finger = Stains positive for CD1a
• Stack of $100 bills in front of the bear = Stains positive for S100

Mononuclear Cells/Macrophages

• Macrocage = Mononuclear cells/macrophages
• On the floor = Migrate to and from the dermis
• 68-plate = CD68 positive
• Ham on top of the plate = Stains positive for HAM56

Dendritic Cells

• Dendritic spiders = Dendritic cells (2 types)
• 1 spider forming a spiderweb on Friday the 13th = Type I dendritic cells are positive for factor XIIIa
• 2 spiders = Type II dermal dendritic cell
• On the calendar that says open 34 days a month = Type II dendritic cells are CD34 positive

Langerhans Cell Histiocytosis (LCH)

Langerhans’ cell histiocytosis is a malignancy of immature hematopoietic myeloid precursors rather than true Langerhans cells. It primarily affects young children between 1 and 3 years of age and occurs more commonly in white patients. Around 50 to 60% of cases harbor the BRAF V600E activating mutation, which predicts a poor prognosis and activates the MAP kinase pathway. Histologically, Langerhans’ cells with reniform nuclei are seen in the epidermis and stain positive for S100, CD1a, and langerin (CD207), with electron microscopy showing Birbeck granules. CD68 is also positive while HAM56 is negative. Prognosis is influenced by both the extent of systemic disease and involvement of critical risk organs including the liver, spleen, and bone marrow, necessitating a biopsy when multisystem disease is suspected. A skeletal survey is part of the initial evaluation, and bones are the most commonly affected sites, particularly the skull, followed by skin and liver. Clinically, infants may present with seborrheic dermatitis-like eruptions on the scalp and groin. Complications include diabetes insipidus, orthopedic deformities, hearing loss, and neurodegeneration. Survival is approximately 75% with risk organ involvement and 100% without. However, BRAF V600E mutations worsen prognosis by increasing risk of neurologic, pituitary, and multisystem disease. Treatment includes potent topical steroids for cutaneous disease, and systemic agents such as prednisone and vinblastine for diffuse disease.

Epidemiology and Pathogenesis

• Cancer crab = Langerhans’ cell histiocytosis is a malignancy of immature hematopoietic myeloid precursors, not true Langerhans’ cells
• Baby = Primarily affects young children, usually age 1 to 3 years old
• Baby is white = More common in white patients than black patients
• Raft with a V600 engine = BRAF V600E activating mutation in 50 to 60%
• Sad baby by the raft = BRAF V600E mutation predicts poor prognosis
• Holding a map = Activates the MAP kinase pathway

Histological Findings

• Kid holding long-handle tennis racket + bear = Langerhans’ cell histiocytes in the epidermis stain positive for S100, CD1a, and langerin/CD207
• 68 shaped plate = CD68 positive
• No ham on the plate = HAM56 negative

Clinical Features and Prognosis

• Baby covered in mud = Prognosis determined by the extent of systemic involvement
• Liver and spleen shaped couch = Risk organs include liver and spleen
• Bone on the couch = Bone marrow is also a risk organ (biopsy required in multisystem disease)
• Baby holding an X-ray radiograph = Skeletal survey required
• Baby sitting on couch holding skull = Most commonly affected organ is bone (80%), followed by skin and liver
• Skull = Skull is #1 bone involved
• Baby wearing red cap with snowflakes = Seborrheic dermatitis-like eruption with crusted papules on the scalp
• Red diaper = Accompanied groin involvement
• Water fountain = Diabetes insipidus
• Painting of asymmetric face = Orthopedic problems (facial asymmetry, vertebral collapse)
• Headphones = Hearing loss
• Unplugged headphone wire = Neurological issues (neurodegeneration)

Prognosis

• Baby with 3 quarters by risk organ couch = 75% 5-year survival with risk organ involvement
• Kid off the couch giving thumbs up = 100% survival with no risk organ involvement
• Sad baby by raft = BRAF V600E mutations predict poor prognosis, higher risk of neurologic and pituitary issues, multisystem disease with risk organ involvement

Treatment

• Hydrocooler with Clobetasol clovers = Potent topical steroids for mild cutaneous disease
• Moon = Prednisone for diffuse disease
• Vines being blasted = Vinblastine for diffuse disease