Histiocyotses Flashcards
What do all histocytes come from?
A common CD34+ progenitor in the bone marrow
What are the different histocytes?
Langerhans cell, mononuclear cell/macrophage, derma dendrocyte/dendritic cells [two types: 1. Type 1 derma dendrocyte and type 2 dermal dendrocyte]
What distinguished a Langerhans cell?
Potent APC that migrates to and from the epidermis
Stains + for CD1a, S100, and Langerin (CD207, most specific because it stains Birbeck granules
Birbeck granules are pathognomonic on electron microscopy
What distinguishes a mononuclear cell/macrophage?
MIgrates to and from the dermis and has phagocytic and APC abilities
Stains + for: CD68 and HAM56
What distinguishes the dermal dendrocytes/dendritic cells?
Type I: dermal dendrocyte, versatile factor XIIIa+ cell. Resides in the papillary dermis, involved in antigen presentation, phagocytosis, collagen production and wound healing
Type II derma dendrocyte: Less known, CD34+, lives in the reticular dermis
What is the major morphological difference between the histiocytic proliferations?
There is a high degree of overlap within the specific entities but a significant difference between the larger groups (non-langerhans vs langerhans histocytoses)
What is the primary determinant of prognosis in Langerhans cell histiocytosis?
Degree of systemic involvement (which is why the new classification system classifies these based on systemic involvement)
Is progression from skin-only Langerhan’s cell histiocytosis to systemic common?
No
What are good prognositc indicators for systemic Langerhan’s cell histiocytosis?
>2 years old and no involvement of the liver, lung, spleen, or hematopoietic system (100% survival)
What are features of bag prognosis in Langerhans cell histiocytosis?
BRAF V600E mutation and failure to reponsd to tx by 6 weeks
What types of malignancy are most common with Langerhans cell histiocytosis?
AML, ALL, other hemotologic malignancies
What genetic mutations are seen in Langerhans cell histiocytosis?
BRAF V600E [60% of pts] (also melanoma and papillary throid cancer) and MAP2K1 mutations which lead to ERK activation
What stains are + in Langerhans cell histiocytosis?
S100+, CD1a+, Langerin+
What notable stains are negative in Langerhans cell histiocytosis?
Factor XIIIa, CD68, and HAM56
What is the histology of Langerhans cell histiocytosis?
Dense proliferation of Langerhans cells with reniform nuclei and eosinophils in papillary dermis, with single and nested Langerhans cells in the epidermis
What forms of Langerhans cell histiocytosis start before the age of 2?
Letterer-Siwe and Congenital self-healing reticulohistiocytosis
What is the clinical presentation of Letterer-Siwe Langerhans cell histiocytosis?
Acute, disseminated visceral, and cutaneous lesions
- These are 1-2 mm pink seborrheic papules/pustules/vesicles on the scalp, flexural neck/axilla, perineum trunk
- Petechiae, purpura, scale, crust, erosion, impetiginization and tinder fissures common
What is the prognosis of Letterer-Siwe Langerhans cell histiocytosis?
Poor
Extensive visceral and painful osteolytic bone lesions; thrombocytopenia and anemia all suggest poor prognosis
What is a clue to the diagnosis of Letterer-Siwe Langerhans cell histiocytosis as compared to sebborrheic dermatitis?
The papules in this are more descrete than in seb derm, also can see petechiae, and purpura which should not be seen commonly in seb derm
What is the typical age of onset for Letterer-Siwe Langerhans cell histiocytosis?
Always less than 2 y/o
What is the most common age for Hand-Schüller-Christian Langerhans cell histiocytosis?
2-6 y/o
What is the clinical presentation of Hand-Schüller-Christian Langerhans cell histiocytosis?
Mostly radiographic
There is a triad: diabetes insipidus, osteolytic bone lesions (cranium), exophthalmos (least common)
-Skin lesions happen in 30% and look similar to Letterer-Siwe
What is the management of Hand-Schüller-Christian Langerhans cell histiocytosis?
The DI can be treated with vasopressin; bone lesions cured with curettage
What is diabetes insipidous seen in Hand-Schüller-Christian Langerhans cell histiocytosis?
Invasion into the posterior pituitary by histocytes