boards’ fodder

Histiocytosis
Amy Reinstadler, MD (Updated July 2015*)

Most common
Histiocytosis Age group Other findings Histology
mucocutaneous sites
Langerhans cell histiocytoses (previously Histiocytosis X)
Letterer–Siwe Young infants Scalp, face trunk, but- • Visceral and bone More epidermotropism,
(<2 years) tocks (resembles seb- lesions fewer foamy cells
orrheic dermatitis) • More fulminant course
• Fever, anemia,
lymphadenopathy
• Hemorrhagic Langerhans
component may cells (reniform
resemble blueberry nuclei; may be
muffin baby foamy or resem-
ble Touton
histiocytes)
Hand– Children May resemble • Diabetes insipidus with epidermo- Less epidermotropism,
Schüller–Christian beyond Letterer-Siwe or may • Bone lesions (skull) tropism; mixed more foamy cells, more
infancy be papulonodular or • Exophthalmos infiltrate (+mast giant cells
granulomatous ulcer- cells)
ation in intertriginous
areas Birbeck gran-
ules on electron
Eosinophilic Older children Skin lesions rare. Bone lesions primarily; microscopy Less epidermotropism,
granuloma and young Nodulo-ulcerative more benign course fewer foamy cells, more
adults lesions in mouth, S100+ diffuse infiltrate with
perineal, perivulval, or CD1a+ eosinophils, histiocytes,
retroauricular CD68- and giant cells

Congenital self-heal- Congenital Widespread, local- Spontaneous resolution +/- Birbeck granules on
ing reticulohistiocy- ized, or single lesion in several months; usu- electron microscopy
tosis (Hashimoto– ally no systemic disease
Pritzker disease)
Non-Langerhans cell histiocytoses
Cutaneous, self-resolving
Juvenile Young infants - Head and neck • Rare eye and visceral • Nodular or diffuse
xanthogranuloma (~75% occur > upper trunk > lesions; can lead to infiltrate of histiocytes,
in 1st year of extremities blindness lymphocytes, and
life) - Small nodular form: • Oral JXG is rare; eosinophils (early)
multiple 2–5 mm usually on lateral • Foamy histiocytes
papules tongue or midline of and Touton giant
- Large nodular form: the hard palate cells (late)
one or few 1-2 cm • When associated Dendritic cell • Dermoscopy: orange-
nodules with NF1, 20x marker: yellow background
increased risk of Factor XIIIa+ with a subtle peripheral
developing juvenile erythematous border
myelomonocytic Macrophage with linear branched
leukemia1 markers: vessels (“setting
CD68+ sun”)2
Benign cephalic Young infants Face and neck Usually none, spontane- HAM56+/- Diffuse dermal non-
histiocytosis ous resolution Mac387 +/- foamy histiocytes with
sparse lymphocytes
Langerhans cell and eosinophils
markers:
Reticulohistiocytoma Adults Head (solitary lesion) None CD1a- Circumscribed dermal
S100- nodule with oncocytic
CD34- mononuclear histio-
cytes, multinucleate
giant cells with ground
glass cytoplasm
Generalized eruptive <4 and Widespread (axial); Spontaneous resolution Superficial and mid der-
Amy Reinstadler, histiocytosis adults occasional mucosal mis with a uniform infil-
MD, is a dermatology involvement in adults trate of histiocytes and
resident at University a few lymphocytes
of California, Irvine. Indeterminate cell Adults and Widespread > face • Uncommon visceral Immunophenotypic profile–antigenic
histiocytosis children and neck and bone lesions markers of both LCH (S100+, CD1a+)
• Ocular involvement and non-LCH (CD68+, Factor XIIIa+,
has been described HAM56+)
• Usually self limited
No Birbeck granules

D­R irections
in
esidency p. 1 • Winter 2011
 boards’ fodder
Histiocytosis
Amy Reinstadler, MD (Updated July 2015*)

Most common
Histiocytosis Age group Other findings Histology
mucocutaneous sites
Cutaneous, persistent/progressive
Papular xanthoma Any Generalized; None. Affected Foamy macrophages
occasionally on individuals are usually and Touton giant cells.
mucous membranes normolipidemic Factor XIIIa+ No chronic inflamma-
CD68+ tory cells
Progressive nodular Any Nodules on trunk and Normolipidemic HAM56+
Histiocytes, foam cells,
histiocytoma papules widespread
spindled cells
(including genitals)
Cutaneous with frequent systemic involvement
Necrobiotic Teens to Periorbital > trunk, Paraproteinemia (IgG • Broad zones of hyaline necrobiosis
xanthogranuloma adults exremities kappa), hepa- tospleno- and granulomatous foci composed of
megaly, lympho-prolifer- histiocytes, foam cells, and multinucleate
ative disease giant cells (Touton and foreign body
type)
• Cholesterol clefts may be present
Multicentric Adults Head, hands, fingers • Arthritis (often • Nodular infiltrate of histiocytes with
reticulohistiocytosis (usually >30) (‘coral bead’ appear- destructive) ground glass cytoplasm
ance periungually), • Up to 30% with internal • Bizarre multinucleated giant cells
ears, and articular malignancy • Mixed infiltrate
regions of the limbs; • Assoc with • CD68+, S100-
mucosa (oral, naso- hyperlipidemia,
pharyngeal) + PPD, systemic
vasculitis, and
autoimmune disease
Rosai–Dorfman Kids and Eyelids and malar Massive • Affected lymph nodes with dilated
Disease (Sinus young adults area Lymphadenopathy (most sinuses containing neutrophils,
Histiocytosis often cervical) lymphocytes, plasma cells, and
with Massive in a subset of patients, histiocytes with large vesicular nuclei
Lymphadenopathy fever, hyper-gamma- and abundant cytoplasm
(SHML) globulinemia • Cutaneous lesions with dense dermal
infiltrate of histiocytes with scattered
lymphocytes, plasma cells and
H Syndrome3 Mean age Hyperpigmentation LAD, HSM, hearing loss,
neutrophils
~20 and hypertrichosis heart anomalies, hypo-
• Emperipolesis
(inner thighs and gonadism, low height,
• S100+, CD68+, CD1a-
shins) hyperglycemia, hallux
valgus
Xanthoma Young adults, Flexural areas to Diabetes insipidus, • Histiocytes, foam cells, spindle cells,
disseminatum children widespread > osteolytic bone lesions; Touton cells, and a moderate number of
mucosa (oral, normolipemic chronic inflammatory cells
nasopharyngeal) • CD68+, factor XIIIa +, S100-, CD1a-
Systemic, with rare cutaneous involvement
Erdheim–Chester Usually adults Dermal and subQ • Primarily a disease of • Lipidized histiocytes involve the dermis,
disease but can be nodules, xanthelas- long bones of lower often with extension into the subcutis
any age mas/ xanthomas, limbs producing • CD68+, factor XIIIa+, CD1a−, and
intertrigo-like lesions, patchy medullary S100−
pretibial dermopathy, sclerosis with sparing +/- Touton giant cells
pigmented patches on of epiphyses
the lips and mucosa • BRAF V600E mutation
in 54%
Hemophagocytic Usually in Jaundice and non- Fever, splenomegaly, • Non-specific spongiosis and a mild
lymphohistiocytosis infancy/ early specific morbilliform liver dysfunction, cytope- perivascular infiltrate of lymphocytes and
childhood but rash nia, hypofibrinogenemia, histiocytes
can be any and tissue hemophago- • S100-, CD68+
age cytosis
References:
1. Mallory M, Bryer BM, Wilson BB. JAAD Grand Rounds quiz. Café-au-lait macules and enlarging papules on the face. J Am Acad Dermatol. 2013
Feb;68(2):348-50.
2. Pretel M, Irarrazaval I, Lera M, Aguado L, Idoate MA. Dermoscopic “setting sun” pattern of juvenile xanthogranuloma. J Am Acad Dermatol. 2015 Jan;72(1
Suppl):S73-5.
3. Molho-Pessach V, et al. H syndrome: The first 79 patients. J Am Acad Dermatol 2014;70(1):80-87.
4. Kornik RI, Naik HB, Lee CC, Estrada-Veras J, Gahl WA, Cowen EW. Diabetes insipidus, bone lesions, and new-onset red-brown papules in a 42-year-old man.
J Am Acad Dermatol. 2013 Jun;68(6):1034-8.

D­Rirections
*Reviewed and updated July 2015 by: Alina Goldenberg, MD, Elise Herro, MD, and Sharon Jacob, MD.
in
Winter 2011 • p. 2 esidency