Review
Unusual variants of non-Langerhans cell histiocytoses

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Histiocytic syndromes represent a large, heterogeneous group of diseases resulting from proliferation of histiocytes. In addition to the classic variants, the subset of non-Langerhans cell histiocytoses comprises rare entities that have more recently been described. These last include both forms that affect only the skin or the skin and mucous membranes, and usually show a benign clinical behavior, and forms involving also internal organs, which may follow an aggressive course. The goal of this review is to outline the clinical, histologic, and ultrastructural features and the course, prognosis, and management of these unusual histiocytic syndromes.

Section snippets

Definition

In 1985, Wood et al5 first described as ICH an unusual, distinctive variant of cutaneous histiocytosis whose cardinal features, distinguishing it from LCH, were: (1) lack, on ultrastructural study, of Birbeck granules; (2) absence, on histology, of epidermotropism; and (3) lack of extracutaneous involvement.

Furthermore, advances in the immunophenotypic characterization of histiocytic dendritic cells and macrophages subsequently led to the demonstration that the IC expressed both LC and

Definition

PNH is a normolipemic non-LCH affecting the skin and mucous membranes with no signs of spontaneous regression of the lesions. “Progressive nodular histiocytosis” is the name suggested in 1985 by one of us30 to encompass several cases reported in the literature with similar clinical and histopathologic features,31, 32, 33, 34 including the first one described as “progressive nodular histiocytoma” by Taunton et al35 in 1978. Up until now, very few universally accepted reports of PNH existed, and

Definition

HPMH was first described in 1988 by Bork and Hoede46 as a new non-LCH resembling PNH in its clinical course, but differing from it by several clinical and histopathologic characteristics, notably an autosomal-dominant inheritance and mucinous degeneration.

Age of onset and incidence

The disease is very rare and affects almost exclusively women; only 11 patients from 6 different families,46, 47, 48, 49, 50, 51 in addition to two sporadic cases,52, 53 have been reported. Indeed, we observed a male patient and his daughter

Definition

ECD is a rare, multisystem non-LC histiocytoxanthomatosis first described by William Chester55 and Jakob Erdheim in 1930.

Age of onset and incidence

ECD primarily affects middle-aged and older adults.55 The term “Erdheim-Chester disease” was first coined by Jaffe56 in 1972 and, since reporting began in the literature, there have been approximately 180 cases recorded.

Clinical findings

The disease can involve almost any organ system; thus, the clinical presentation of patients with ECD differs on a case-to-case basis, mostly because of the

Definition

In 1970, Silverstein et al71 coined the term “sea-blue histiocyte syndrome” to describe a primitive idiopathic storage disease in which many organs were infiltrated by the so-called SBH. SBH are large macrophages whose cytoplasm is filled with granules staining blue or blue–green with Giemsa. Up until now, approximately 60 cases of SBHS have been published. In addition to the primary form of SBHS, it is now clear that there are secondary forms related to a wide variety of conditions, including

Conclusions

The clinical, histologic, and ultrastructural findings and the course, prognosis, and management of 5 unusual histiocytic disorders have been reviewed. Although their classification still remains controversial, we suggest lumping all these entities into the wide group of non-LCH. In ICH, the proliferating cells express both macrophage markers, such as KP1 (CD68), and LC markers, such as S-100 and CD1a. Thus, ICH was proposed to be a separate entity showing an overlap between LCH and non–LCH. We

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      Citation Excerpt :

      Delayed or erroneous diagnosis is common, and from symptom-onset to diagnosis can span from months to decades. As mentioned, ECD shares clinical features with LCH (Table 2) but bears little clinical similarity to other non-LCH histiocytoses, with the exception of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease).24,25 Although infiltration of nearly every organ system has been reported in ECD,26-31 the tissues most commonly affected include the skeleton, retroperitoneum, and orbit in addition to the cardiovascular, pulmonary, neurologic, and endocrine systems (Figure 3).

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    Funding sources: None.

    Conflicts of interest: None declared.

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