Herpes simplex virus mucocutaneous tumoural lesions – Systematic review

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Highlights

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    Tumoral herpes "i.e. characteristic of a tumour" has a strong association with immunosuppression, mainly with HIV.

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    Occur mostly in the anogenital region and buttocks, associated with herpes type 2.

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    Lesions frequently measure more than 3 cm, and neoplasia is usually hypothesized.

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    Approximately half of the cases improved with acyclovir treatment.

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    Non-Standardised treatments include imiquimod, thalidomide and/or surgical excision.

Abstract

The goal was to characterize the clinical-epidemiological profile of patients with mucocutaneous tumoural herpes simplex virus (MCT HSV) lesions across the world. Two researchers extracted and independently reviewed data from the literature search engine PubMed/MEDLINE through October 2018. From 110 reported patients, the following data were available: the patients' ages ranged from 7 to 76 years; the majority was male (62.73 %–69/110) and immunosuppression was found in 97.25 % (106/109, missing 1) cases, of whom 88 were HIV- related. Lesions size varied from 0.2–13 cm, settling in the anogenital region in 76.36 % (84/110) patients; 84.13 % (53/63, missing 47) complained of pain and multiple recurrences were found in 44.94 % (40/89, missing 21) cases. On clinical basis, the initial hypothesis was neoplasia in 36/53 patients. Histopathological diagnosis was achieved in 90 % (90/100, missing 10) cases and was sample size-dependent. Type 2 HSV was detected in 86.07 % (68/79, missing 31) lesions. MCT HSV lesions recurrence after treatment was reported in 33.96 % (18/53, missing 57) patients. Pathophysiology is poorly understood. Physicians should be aware of MCT HSV lesions in immunosuppressed patients to avoid inappropriate therapeutic strategies.

Introduction

Mucocutaneous eruptions caused by herpes simplex virus (HSV) are common worldwide. The typical lesions are painful erythematous papules, vesicles and shallow ulcers [1,2]. Among the atypical forms, the tumoural (defined, in The Oxford English Dictionary, as "pertaining to, or characteristic of a tumour") has been reported in immune-compromised patients, mainly those infected by HIV [3]. Mucocutaneous tumoural herpes simplex virus (MCT HSV) form has also been described as nodular, hypertrophic, verrucous, vegetative or exophytic. These terms aim to reflect the voluminous aspect of the lesions, and are frequently used for other inflammatory skin conditions with clinical presentation of a tumour. Recognizing this entity is of paramount importance because it can be misinterpreted as neoplasms, leading to equivocal therapeutic strategy [[4], [5], [6], [7], [8], [9], [10], [11]].

To aid in their recognition and delineation, we systematically reviewed studies on MCT HSV lesions, focusing on 1) the clinical-epidemiological profile of patients; 2) major primary morphological features and topography; 3) primary causes of immunosuppression, and 4) potential occurrence in immunocompetent individuals. We investigated the pathogenetic mechanisms attributed to the development of this atypical form of HSV infection and postulate other hypotheses.

Section snippets

Materials and methods

A literature search was undertaken through the search engine PubMed/MEDLINE, through October 30, 2018, using the following uniterms: “herpes and hypertrophic”, “herpes and tumoural”, “herpes and vegetans”, “herpes and atypical” and “herpes and verrucous”. These uniterms are used in the literature to refer to a clinical presentation that resembles a tumour, in different diseases. Each article was fully and independently scrutinized by two researchers, with a view to tumoural HSV case reports. We

Results

The patients' age ranged from 7 to 76 years (mean: 43.39; median: 42.00; n: 89); 62.73 % (69/110) were male. The lesions developed in the anogenital region, intergluteal groove and on the buttocks in 76.36 % (84/110) cases. Also the face, including mouth and oral cavity, [[12], [13], [14], [15], [16], [17], [18]] nose [19,20], ear [7,19], conjunctiva [21] and periocular region [[21], [22], [23], [24], [25]] were affected. Less common sites were reported in 7.41 % (8/108, missing 2) patients,

Discussion

HSV is a common cause of mucocutaneous infection, and, genital herpes, the most common sexually transmitted disease in the world [1,2]. There are two major antigenic and biological types of herpes virus hominis: HSV-1 which primarily affects the mouth, lips, nostrils and adjacent skin, and HSV-2 which normally causes anogenital lesions [59]. Primary infection tends to be more painful and to last longer than recurrences [45]. Atypical forms appear as asymptomatic or painful localized

Pathogenesis

The pathogenesis of MCT HSV lesions has not been elucidated, but the results of clinical, histopathological and laboratory studies have provided some hypotheses.

Inflammatory process in cutaneous infections releases interleukins (ILs) and growth factors that act in keratinocytes. These produce cytokines that stimulate dermal dendritic cells to produce IL-1, IL-6 and TNF-α, which stimulate proliferation of keratinocytes and perpetuation of the process [38,64,73,74]. HIV infection of dermal

Conclusion

The tumoural variant of herpes is strongly associated with immunosuppression, mainly because of HIV. Occurrence is most common among males with an average age of 43 years, presenting in the anogenital region, intergluteal groove/and buttocks, and usually accompanied by pain. It may include plaque or mass, be ulcerated or not, single or multiple, and the diameter is greater than 3 cm, in most cases. Physicians must have a high level of suspicion in immunosuppressed patients, especially with

CRediT authorship contribution statement

Bruna Morassi Sasso: Data curation, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing - original draft. Michelle Etienne Baptistella Florence: Conceptualization, Investigation, Validation. Renata Ferreira Magalhaes: Validation, Visualization. Paulo Eduardo Neves Ferreira Velho: Validation, Visualization. Elemir Macedo de Souza: Validation, Visualization. Maria Leticia Cintra: Conceptualization, Resources, Validation, Visualization, Writing - review &

Declaration of Competing Interest

The authors have no conflict of interest and no source of funding.

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