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
At what age does congenital self-healing reticulohistiocytosis occur?
Starts at birth or shortly therafter
What is the clinical presentation of congenital self-healing reticulohistiocytosis?
Skin-limited form
Rapidly self-healing; shows widespread (more than solitary) red or purple-brown papulonodules that can have erosion
What age does eosinophilic granuloma occur in?
Older children, 7-12 y/o
What is the clinical presentation of eosinophilic granuloma?
Localized from of langerhans cell histiocytosis. Usually solitary and asymptomatic bone lesions (cranium>ribs, spine, long bones)
-Very rare to involve the skin or mucosa
What is a common presenting symptom of eosinophilic granuloma?
Spontaneous fracture often the presenting sign
Treatment for eosinophilic granuloma?
Bone lesions can be treated with currette
What stains help distinguish non-Langerhans cell histiocytoses?
All are CD68+, +/- Factor XIIIa
All are negative for Langerin
S100 is negative in all except indeterminate cell histiocytoses and Rosai-Dorman
CD1a is negative in all except indeterminate cell histocytosis
What is the most common presenting ages for juvenile xanthogranuloma?
0-2 (15% at birth and 75% by first year)
What is the prognosis of juvenile xanthogranuloma?
Spontaneous resolution in 3-6 years
What are the most common locations for juvenile xanthogranuloma?
Head/neck>upper trunk
What is the clinical apperence of juvenile xanthogranuloma?
One to few lesions>> numerous/widespread
- Lesions are pink to red/yellow papules
Mucosal involvement in juvenile xanthogranuloma?
Can occur rarely
Ocular involvement in juvenile xanthogranuloma?
0.5% have involvement of unilateral eye (Iris most common) leading to hyphema, glaucoma and can lead to blindness
What specialty should be consulted for new dx of juvenile xanthogranuloma?
Ophthalmology
What are risk factors for ocular involement in juvenile xanthogranuloma?
Multiple lesions and children <2yrs
What should be watched for if a pt has JXG and NF-1?
20x increased risk of JMML
What is the histology of juvenile xanthogranuloma?
Well-circumscribed, dense dermal infiltrate of foamy lipidized histiocytes. Touton giant cells and eosionphils are seen; loss of rete ridges and can see ulceration
*CD68 +
What is the age of onset of benign cephalic histiocytosis?
Infants < 1y/o usually
What is the presentation of benign cephalic histiocytosis?
Numerous (more lesion than typical JXG) red-brown macules and papules of face/neck that may progress of upper torso
Probably a JXG variant
What is the course of benign cephalic histiocytosis?
Self-limited, no internal or mucosal involvement
What is the histology of benign cephalic histiocytosis?
Known for intracytoplasmic “comma-shaped/worm-like” bodies on electron microscopy, otherwise very similar to JXG but no Touton giant cells, minimal to no lipidized histiocytosis
What is the age of onset for generalized eruptive histiocytosis?
Adults
20-50 y/o more than kids
What is the clinical presentation of generalized eruptive histiocytosis?
Recurrent eruption of hundreds of small (<1cm) red-brown papules in axial distribution (trunk, proximal extremities> face)
Heal with hyperpigmentation
What is the prognosis of generalized eruptive histiocytosis?
Self limited; no internal or mucosal involement
What is the presentation of indeterminate cell histiocytosis?
Solitary and generalized variants exist
Eruption clinically and histologically indistiginguishable from benign cephalic histiocytosis and generalized eruptive histiocytosis (requires immunostains to distinguish)
Prognosis of indeterminate cell histiocytosis?
Rare visceral and bone lesions with occasional fatal cases
What stains help distinguish indeterminate cell histiocytosis?
S100+, CD1a+, Langerin negative (this is what distinguishes it from LCH)
What is the age of presentation most commonly for necrotizing xanthogranuloma?
50’s
Clinical presentation of necrotizing xanthogranuloma?
Destructive multisystem disease
Yellow xanthomatous plaques +/- ulceration
What is the most common locations for necrotizing xanthogranuloma?
Periorbital>>>other face, trunk, extremities
What are other manifestations of necrotizing xanthogranuloma?
50% have ophthalmic compliations, can also have hepatosplenomegaly, leukopenia and elevated ESR
What gammapathy is associated with necrotizing xanthogranuloma?
IgGkappa monoclonal gammopathy (>80%), a/w plasma cell dyscrasia or multiple myeloma
Histology of necrotizing xanthogranuloma?
Looks like palisading xanthogranuloma with cholesterol clefts
What is the age range for reticulohistiocytosis (multicentric reticulohistiocytosis and solitary reticulohistiocytoma)?
30-40’s very rare in children
What is the clinical presentation of multicentric reticulohistiocytosis?
F>M
Red-brown or yellow nodules
Acral sites are favored (head, dorsal hands > elbows)
50% have oral or nasopharyngeal lesions
What disease is often seen with multicentric reticulohistiocytosis?
Destructive arthritis –> arthritis mutilans in 45%
What is the presentation of the solitary form of solitary reticulohistiocytoma?
1 site is the head
Solitary, asymptomatic <1cm yellow-red nodule
What systemic sx’s are associated with multicentric reticulohistiocytosis?
Elevated ESR, fever, anemia
What important disease must be checked for in a pt with multicentric reticulohistiocytosis?
Solid organ maligancy, present in 30% of cases
What is the “coral bead” sign seen in multicentric reticulohistiocytosis?
Papules line up along the periungual region
What is the histology of multicentric reticulohistiocytosis?
Dermal infiltrate of mono- and multi-nucleated histiocytes with granular, pink-purple “ground glass” cytoplasm, often with a lacunae or empty white space
What are the 5 main cutaneous articular syndromes?
RA, SLE, Sarcoid, multicentric reticulohistiocytosis, EED
What is the most common age of onset for Rosai-Dorfman disease?
10-30 y/o
What is the clinical presentation of Rosai-Dorfman disease?
Multisystem dz of children or young audlts; massive but asymptomatic bilateral cervical LAD
Can also have fever/night sweats/wieght loss, elevated ESR, polyclonal hypergammaglobulinemia
What skin sites are most common in Rosai-Dorfman disease, and where do they occur?
1 sites are the eyelids and the malar cheek
Skin involvement happens in 10%
What is the morphology of the cutaneous lesions in Rosai-Dorfman disease?
Multiple red-brown or xanthomatous papules/plaques
Prognosis of Rosai-Dorfman disease?
Usually self-resolves
What is the histology of Rosai-Dorfman disease?
Pan-dermal infiltrate of very large, very foamy S100+/CD68+ histiocytes with emperipolesis, and abundant plasma cells
What is the most common age for xanthoma disseminatum?
<25 y/o
What is the clinical presentation of xanthoma disseminatum?
Triad: cutaneous xanthomas, mucosal xanthomas (oral and upper airway most commonly) and diabetes insipidus
Lesions are red-brown or yellow papules that coalesce into oddly-patterned xanthoma-like plaques (hashtag like patterns)
What anatomic areas are most affected by xanthoma disseminatum?
Symmetric flexural/intertriginous involvement
What things is xanthoma disseminatum associated with?
Normal lipid levels
A/w monoclonal gammopathy, plasma cell dyscrasia
What is the histology of xanthoma disseminatum?
Dense dermal infiltrates of many foam cells and occasional Touton giant cells
What is Erdheim-Chester?
Fever, bone lesions, diabetes insipidus, exophthalmos, CNS, Multiple internal organs involved. Skin can be involved in 25% of cases, usually eyelids and upper half of body and shows up with red-brown to yellow indurated nodules/plaques
What is the prognosis of Erdheim-Chester?
Bad, high mortality rate
