INTRODUCTION

Histiocytoses comprise a wide spectrum of diseases characterized by a build-up of cells believed to be macrophage progenitors. Their clinical manifestations might be minor, widespread, or even potentially fatal. Three categories made up the original categorization of histiocytosis, which was published in 1987 by the Working Group of the Histiocyte Society. These categories were malignant, non-LC-related, and Langerhans cell histiocytoses [1]. More recently, the rapid advances in understanding of pathogenesis processes have led to a new classification that incorporates tissue distribution and cellular origins in addition to histologic traits (Table 1) [2,3].

Table 1: Revised classification of histiocytocytic disorders.

The fact that histiocytoses with primarily cutaneous and mucocutaneous symptoms fall into a separate group is indicative of their significance to dermatology. Furthermore, cutaneous symptoms are a common feature of numerous systemic clinical forms, including malignant entities. The dominant significance of the skin has also been highlighted by several categorization systems for histiocytoses. As a result, the combined dermatologist’s and dermatopathologist’s skills are of paramount importance for a proper diagnosis [4].

Herein, we present a case series of forty patients diagnosed with histiocytosis in a relatively short period of time, indicating the immense need to identify and eliminate the possible factors contributing to this rise. We also divided the clinical presentations according to the age of patients at the time of presentation.

PATIENTS AND METHODS

This was a case series of a total of 40 patients presented between the years of 2014 and 2024. The study was conducted at the Center of Dermatology and Venereology, Medical City, Baghdad-Iraq. All patients included in the study were diagnosed with histiocytosis based on full history and clinical evaluation, with the aid of histopathological and immunohistochemical assessment. Full skin examination was performed, including checking against lymphadenopathy. Routine hematological and biochemical investigations, chest X-ray, abdominal ultrasonography, were conducted searching for evidence of internal organ involvement. Serological testing was performed for hepatitis C virus, and hepatitis B virus antigen (HbsAg), and human immunodeficiency virus (HIV).

RESULTS

A total of 40 patients with histiocytosis, 21 males and 19 females, were presented to the Dermatology Center, Baghdad Teaching Hospital, between the years 2014 and 2024.

All patients were evaluated and analyzed; their ages ranged from 2 months to 50 years. These cases were classified depending on age into the pediatric-childhood group and the adult group. The first group consisted of 27 (67.5%) patients, with 17 males and 10 females, their ages ranging from 2 to 60 months, with a mean of 31 months. The cutaneous manifestations of these patients were seborrheic dermatitis-like lesions in 13 (48.14.5%), xanthogranuloma in 8 (29.6%), and erythematous papular-papulonodular and noduloulcerative lesions in 6 (22.2 %) patients.

Individual lesions during early infancy were erythematous and/or purpuric papules, plaques, and patches, mainly involving the trunk and flexural areas (seborrheic dermatitis-like distribution) (Figs. 1a and 1b). However, older children had more ulcerative papulonodular lesions leaving an atrophic scar mainly on the extensor extremities in a distribution similar to that of atopic dermatitis in this age (Figs. 2a and 2b). Xanthogranulomatous lesions with yellow to orange lesions were either single mainly involving the head or multiple in the trunk. Histopathological features were mostly consistent with the clinical picture; for example, seborrheic dermatitis-like lesions showed a proliferative pattern of histiocytes with a band-like infiltrate invading the epidermis and causing ulcerations with wet crustations (Figs. 1c and 1d). Papular and nodular lesions, on the other hand, had a xanthomatous reaction with foamy histiocytes and few eosinophils throughout the dermis without an obvious granuloma. (Figs. 2c and 2d). However, xanthogranulomatous lesions had a granulomatous reaction with Touton giant cells in well-established lesions.

	Figure 1: a and b An infant with multiple erythematous papules and plaques over the head, trunk and flexural areas in a seborrheic –like dermatitis distribution. c and d; Microscopic view showing proliferative pattern of Langerhans histiocytosis; superficial dermal infiltrate of histiocytes with coffee bean nucleous and ample cytoplasm invading epidermis. H&E stain × 40 and ×100 respectively.
	Figure 2: a and b Multiple erythematous papules and plaques with ulcerated and crusted surface involving the extensor surfaces of extremities (c). Microscopic view showing patchy inflammatory infiltrate of foamy histiocyte in a xanthomatous reaction. H&E stain × 40 (d) H&E stain ×100

Almost all lesion diagnoses were established based on clinical and morphologic features of hematoxylin and eosin staining, whereas immunostaining results of S100 and CD1a were only helpful in some cases and, therefore, were unreliable.

The adult group consisted of 13 (32.5%) patients, 8 (61.53%) females and 5 (38.46%) males. Their ages ranged from 20 to 50 years. The clinical presentations were 5 (38.46%) patients with xanthogranuloma, noduloulcerative lesion in 4 (30.76%) cases, multiple papular-plaque lesions in 3 (23.07%) cases, and one (7.69%) patient presented with an ulcerative genital lesion (Fig. 3a –3c). The histopathological patterns in non-Langerhans histiocytosis were mainly a xanthogranulomatous reaction with Touton giant cells, whereas a xanthomatous reaction with foamy histiocytes was noted in a patient with papular, noduloulcerative lesions (Figs. 4a – 4c).

	Figure 3: a and b Multiple shiny erythematous papules and plaques over the extensor surfaces of extremities and back. c Large nodular lesions with some ulcerations in the periocular area.
	Figure 4: a, Symmetrical facial orange papules and plaques (b). Microscopic view showing xanthogranulomatous reaction with touton giant cells H&E stain × 100 (c). Positive CD68 immunostaining ×40.

DISCUSSION

Histiocytosis encompasses a group of disorders with proliferation of mononuclear phagocyte and dendritic cells in the skin and other organs. Histiocytosis is divided into Langerhans and non-Langerhans cell histiocytosis, which is further subdivided [5].

In many instances, it may be conceivable to determine which type of histiocytosis is present by the clinical appearance of the skin lesion. However, a skin biopsy is essential to confirm the diagnosis. Ideally, each of the different types has a different microscopic appearance and staining pattern. Nonetheless, that is not applicable in every case; in fact, many skin biopsies have misleading findings, and when it comes to immunostaining, results are disappointing more often than not.

In the present work, three histopathological patterns were noted in the pediatric group, and they we were in accordance with the clinical type of histiocytosis. These histological reactions included: proliferative, granulomatous, and xanthomatous. The proliferative pattern was noted to be associated with Langerhans histiocytosis, whereas granulomatous and xanthomatous patterns were associated with xanthogranulomatous and papular-plaque lesions, respectively. These findings were comparable to previous studies [6,7].

Histiocytosis in the adult group showed only two patterns: granulomatous and xanthomatous. The proliferative pattern was strikingly missing. This can be explained by the fact that most adult-type histiocytoses are of the non-Langerhans type. Thus, the patterns with which histiocytes form can greatly aid in the histopathological diagnosis of histiocytosis, especially if the immunostaining is unhelpful or even unavailable.

There has been an increasing number of histiocytosis cases over the last years, and these new cases have diverse cutaneous manifestations with two age peaks, infantile and childhood, presented mainly with seborrheic dermatitis-like pictures and xanthogranuloma. Meanwhile, the adult patients showed mainly xanthogranulomatous lesions. This uprising of cases could not well be explained, but we can speculate that environmental changes as a result of frequent wars with chemical exposures and subsequent epidemics of infections such as dermatophytosis and COVID-19 infection might explain this dramatic change in the incidence of histiocytosis, and this uprising goes parallel with an increase in other skin diseases such as lichen planus, mycosis fungoides, morphea, and Kaposi sarcoma [8–13].

CONCLUSION

With the increasing cases of histiocytosis in children and adult patients, a thorough clinical and histopathological study is mandatory. The diagnosis of Langerhans histiocytosis by histopathology is not always fruitful as could be negative or non-specific, hence repeated biopsies from different sites or at different times are required to reach a well-defined diagnosis. Accordingly, the clinical diagnosis remains the cornerstone in establishing the diagnosis, especially in countries where many of these tests are not available or where biopsies could even be refused.

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