Table 3:
Group C histiocytoses with predominantly cutaneous or mucosal involvement
| Age, sex | Typical locations | Appearance | Clinical differential diagnosis | Evolution and associated conditions | Immunophenotype | |
|---|---|---|---|---|---|---|
| Papular xanthoma* | Adolescents and adults younger than 40 years; male more often than female | Trunk, limbs, head and neck | Solitary yellowish papule or nodule | .. | .. | CD68+, CD163+, FXIIIa−, CD1a− |
| Solitary reticulohistiocytoma | Median age 35 years; male and female equally often | Trunk, limbs, head | Solitary, small (5 mm in diameter) papulonodular lesion | Juvenile xanthogranuloma; dermatofibroma; cyst | Usually no regression | CD68+, CD163+, FXIIIa+/−, CD1a− |
| Juvenile xanthogranuloma | Children more commonly than young adults; male more often than female | Head, neck, upper trunk; buccal possible; any site possible | Single nodule bigger than 2cm in diameter, or multiple papules that are reddish progressing to yellow-brown | Mastocytoma; Spitz naevus; other histiocytoses; dermatofibroma | Gradual involution | CD68+, CD163+, FXIIIa+, CD1a− |
| Benign cephalic histiocytosis | Infants (<1 year); male and female equally often | Head and neck, mostly face; spares mucosae | Multiple papules that are red-brown or sometimes yellowish | Flat warts; juvenile xanthogranuloma; generalised eruptive histiocytosis; mastocytosis | Regression over months or years (median 4 years) | CD68+, CD163+, FXIIIa+, CD1a− |
| Generalised eruptive histiocytosis | Young adults more commonly than children; male more often than female | Trunk and proximal limbs; spares skin folds and mucosae | Innumerable macules and papules that are flesh-coloured to red | Multiple juvenile xanthogranulomas; benign cephalic histiocytosis; xanthoma disseminatum; sarcoidosis; mastocytosis | Involution most often, or progression to xanthogranuloma, xanthoma disseminatum, or nodular progressive histiocytosis in several months or years | CD68+, CD163+, FXIIIa+, CD1a− |
| Nodular progressive histiocytosis | Median age 50 years; male and female equally often | Frequent: buccal, laryngeal, ocular, and genital involvement Possible: face (with leonine appearance), trunk | Multiple or disseminated pink, yellow-orange, or red-brownish lesions up to 5 cm in diameter; two distinct types: deep nodules to tumours, or superficial xanthomatous papules | Generalised eruptive histiocytosis; multiple juvenile xanthogranulomas; xanthoma disseminatum; progressive hereditary mucinous histiocytosis; sarcoidosis; leprosy | Progression | CD68+, CD163+, FXIIIa+, CD1a− |
| Xanthoma disseminatum | Young adults; male more often than female | Any skin, eyelid, skin folds; mucosae involved in 50% of patients, sometimes life-threatening | Hundreds of lesions: symmetrical, coalescing, round to oval, orange to yellow-brown papules and nodules | Multiple juvenile xanthogranuloma; generalised eruptive histiocytosis; eruptive xanthomas | Slow involution over years, or progression; sometimes associated with MGUS, multiple myeloma, or Waldenström’s disease | CD68+, CD163+, FXIIIa+, CD1a− |
| Multicentric reticulohistiocytosis | Median age 40 years; male more often than female | Face, head; periungual (coral bead); mucosae (oral, pharyngeal, nasal) involved in 50% of patients | Flesh-coloured or pink-reddish-brown papules and nodules; pruritus | RDD; leprosy; sarcoidosis; fibroblastic rheumatism | Possible regression but frequent recurrence; symmetrical destructive polyarthritis; rarely lung, heart, or nodal involvement; 25% of patients have an associated cancer, autoimmune disease, or dyslipidaemia | CD68+, CD163+, FXIIIa−, CD1a− |
| Necrobiotic xanthogranuloma | Median age 55 years; male and female equally often | Face, mostly periocular; frequent eye involvement; trunk | Xanthelasmas on upper eyelids, confluent nodules forming firm yellowish plaques; telangiectasias; ulceration; atrophy | Xanthelasma; normolipaemic xanthomas; ECD; lipoidic necrobiosis | In almost all cases: monoclonal gammopathy Possibly: multiple myeloma, CLL, lymphomas | CD68+, CD163+, FXIIIa−, CD1a− |
| Hereditary† progressive mucinous histiocytosis | Younger than 18 years; female more often than male | Face; hands; forearm; legs | Flesh-coloured or red-brown symmetrical papules | Nodular progressive histiocytosis; generalised eruptive histiocytosis; lichen planus; multiple dermatofibromas | No regression | CD68+, CD163+/−, XIIIa+/−, CD1a− |
MGUS=monoclonal gammopathy of undetermined significance. RDD=Rosai-Dorfman-Destombes disease. ECD=Erdheim-Chester disease. CLL=chronic lymphocytic leukaemia.
*
A normolipaemic xanthoma.
†
Most cases are hereditary but there are rare sporadic cases.