Indeterminate cell histiocytosis C96.0

The first case of histiocytosis of indeterminate (ICH) cells was published in 1985 (Fischer AS et al. 2021). ICH was originally thought to be a variant of Langerhans cell histiocytosis (LHC) because the lesional cells expressed both S100 and CD1a. However, they lacked Birbeck granules. It was then shown that the ICH cells expressed markers of the macrophage system KP1 (CD68), Ki-M1p, HAM56, and factor XIIIa (Fischer AS et al. 2021). This led to the proposal to list ICH as a distinct entity that has features of both LCH and non-Langerhans cell histiocytosis (NLCH). Some authors tend to consider ICH as a variant of non-Langerhans cell histiocytosis rather than an overlap of LCH and NLCH. This hypothesis is based on the observation that most reported cases of ICH have clinical features of NLCH (Fischer AS et al. 2021).

Indeterminate cell type (ICH) histiocytosis is a rare histiocytosis with less than 50 cases described in the literature.

In contrast to Langerhans cell histiocytosis, which occurs preferentially in children and adolescents, there is no clear predilection for sex or age in histiocytosis with indeterminate cell type. A congenital case has also been reported (Sidoroff A et al 1996; Levisohn D et al 1993).

In most cases, the disease occurs spontaneously. However, some cases appear to be an immune response to an inflammatory trigger such as scabies or pityriasis rosea . In these cases, the lesions of ICH were distributed according to the pattern of the previous disease, suggesting an isotopic response (Wolf R et al 1995).

The trunk and extremities are most commonly affected. However, involvement of the head and neck (with eyelids and ears) (Sidoroff A et al. 1996; Ratzinger G et al. 2005) and genitalia (Ratzinger G et al. 2005) has also been reported. Extracutaneous and mucosal involvement is rare, but bone, corneal, and conjunctival involvement have been reported (Fischer AS et al. 2021).

The clinical, dermatological picture is not clearly defined. Both solitary manifestations with single, uncharacteristic red-brown papules or plaques that may regress spontaneously have been described. Ulcerations are possible. Only in very isolated cases large-scale manifestations have been reported (see Fig.). Extracutaneous manifestations (bone, conjunctiva) are rare.

Results on different treatments with varying success are available: phototherapy, irradiation and chemotherapy.

Histiocytosis of indeterminate cells is described as benign with self-limited progression (Caputo R et al. 2005).

Disease progression with fatality has been reported (Sidoroff A et al 1996). Furthermore, ICH has been associated with malignancies: twice with low-grade B-cell lymphoma and once each with mast cell leukemia, myelomonocytic leukemia, and monocytic leukemia (Fischer AS et al. 2021).

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3. Fischer AS et al (2021) Indeterminate cell histiocytosis mimicking rosacea. Cureus 13:e12850.
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5. Ratzinger G et al (2005) Indeterminate cell histiocytosis: fact or fiction?. J Cutan Pathol 32:552-560.
6. Sidoroff A et al (1996) Indeterminate cell histiocytosis - ( Indeterminate cell histiocytosis - a clinicopathological entity with features of both X- and non-X histiocytosis. Br J Dermatol 134:525-532.
7. Tomaszewski MM et al.(1998) Unusual expression of S-100 protein in histiocytic neoplasms. J Cutan Pathol25:129-135.
8. Levisohn D et al (1993) Solitary congenital indeterminate cell histiocytoma. Arch Dermatol 129:81-85.
9. Wolf R et al (1995) Isotopic response. Int J Dermatol 34:341-348.