Review
The utility of GLUT1 as a diagnostic marker in cutaneous vascular anomalies: A review of literature and recommendations for daily practice

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Abstract

Objective

To assess the utility of GLUT1 as an immunohistochemical marker in the diagnostics of cutaneous vascular anomalies.

Methods

A systematic literature search was conducted for studies on GLUT1 staining patterns in cutaneous vascular lesions. Data was grouped according to the latest ISSVA classification for vascular anomalies.

Results

Vascular tumors: GLUT1 staining was positive in 368/386 (95%) of infantile hemangiomas. Congenital hemangiomas (16 cases) and kaposiform hemangioendotheliomas (62 cases) were all negative for GLUT1. Angiosarcomas were GLUT1 positive in 12/39 (31%) and epithelioid hemangioendotheliomas in 2/27 (7%) of cases. Vascular malformations: All vascular malformations (33 arteriovenous malformations, 16 capillary malformations, 64 lymphatic malformations, 54 venous malformations, 3 venous-lymphatic malformations and 3 capillary venous-lymphatic malformations) were negative for GLUT1 staining. Unclassified vascular anomalies: Angiokeratomas were GLUT1 positive in 1/15 (7%) and verrucous hemangiomas in 71/100 (71%) of cases. Microvenular hemangiomas were negative for GLUT1 in all 9 cases.

Conclusions

GLUT1 can be used as an additional diagnostic tool in cutaneous vascular lesions. A negative GLUT1 stain renders a diagnosis of infantile hemangioma unlikely. A positive GLUT1 stain excludes vascular malformations and is suggestive of infantile hemangioma. One must be cautious, however, that the final diagnosis is made through interpretation of all clinical and diagnostic features, and not based on GLUT1 staining alone.

Introduction

‘Vascular anomalies’ is an umbrella term used for lesions that stem from abnormalities in either blood vessels, lymphatic vessels, or both. Historically, the nomenclature for these vascular lesions has been vague and contradicting [1]. The first organized classification was published by Mulliken and Glowacki in 1982, distinguishing vascular tumors (lesions growing by endothelial hyperplasia, likehemangiomas) from vascular malformations (lesions with quiescent endothelium, considered localized defects of vascular morphogenesis) [2]. This basic classification system was adopted by the International Society for the Study of Vascular Anomalies (ISSVA) in 1993 [3]. Over the years, imaging techniques, immunohistochemistry and genetic studies have allowed for new diagnostic and classification opportunities in vascular anomalies, leading to various ISSVA classification updates [4], [5], [6]. Nonetheless, unambiguous classification of vascular anomalies remains a challenge. Wassef et al. published an introduction into the latest ISSVA classification update in 2015, striving for uniform classification of vascular anomalies by pathologists, clinicians, and researchers [6].

In 2000, North et al. found that the endothelial cells of infantile hemangiomas (IH) are immunoreactive for the Glucose Transporter Type 1 (GLUT1), contrary to the vascular endothelium in normal skin. They did not find comparable immunostaining in vascular malformations, rendering GLUT1 a potential marker for IH [7]. This led to new hypotheses regarding the origin of infantile hemangiomas, translating into the placental embolization theory of IH that still has supporters this day [8]. Although of undisputed scientific value, the clinical applicability of GLUT1 staining in infantile hemangiomas has not been addressed. Therefore, we aimed to define the utility of GLUT1 in the diagnostics of cutaneous vascular anomalies.

Section snippets

Materials and methods

The objective of this study was to assess the utility of GLUT1 staining in the diagnostics of cutaneous vascular anomalies. We searched PubMed for studies reporting on GLUT1 immunostaining patterns for different types of vascular anomalies (primary outcome). The search strategy was designed to entail all entities recognized by the latest ISSVA classification [Table 1] in combination with “GLUT1”. Exclusion criteria were: studies of non-cutaneous vascular anomalies; studies where GLUT1 was not

Results

Our search rendered 197 results. Title and abstract screening led to the exclusion 156 citations. Out of the 41 remaining citations, 21 relevant papers were included [Table 2]. The results of data extraction are discussed below. Findings are summarized in Table 3.

Discussion

In order to clarify the role of GLUT1 as a diagnostic tool in cutaneous vascular lesions, we reviewed published cases reporting on GLUT1 staining in vascular anomalies. Infantile hemangiomas were investigated most frequently, and nearly all tumors (95%) were positive for GLUT1. With this near ubiquitous GLUT1 immunoreactivity, it can be suspected that IH endothelium might inherently possess the Glucose Transporter Type 1. Similarly, North et al. argue that at least two out of four lesions that

Funding

None.

Conflicts of interest

None to declare.

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