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Year : 2022  |  Volume : 67  |  Issue : 6  |  Page : 817-819
The tricky blue

1 From the Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Dermatology, IRCCS Policlinico di Sant'Orsola, Alma Mater Studiorum Università di Bologna, Italy
2 Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Pathology Unit, IRCCS Policlinico di Sant'Orsola, University of Bologna, Bologna, Italy
3 Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Pathology Unit, Ospedale Maggiore, Bologna, Italy, University of Bologna, Bologna, Italy
4 Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Ophthalmology, – IRCCS Policlinico di Sant'Orsola, – Alma Mater Studiorum University of Bologna, Italy

Date of Web Publication23-Feb-2023

Correspondence Address:
Francesca Pepe
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Dermatology, IRCCS Policlinico di Sant'Orsola, Alma Mater Studiorum Università di Bologna
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijd.ijd_769_22

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How to cite this article:
Pepe F, Corti B, Ricci C, Schiavi C, Roda M, Barisani A, Vaccari S. The tricky blue. Indian J Dermatol 2022;67:817-9

How to cite this URL:
Pepe F, Corti B, Ricci C, Schiavi C, Roda M, Barisani A, Vaccari S. The tricky blue. Indian J Dermatol [serial online] 2022 [cited 2023 Mar 23];67:817-9. Available from:


The eyelids, and in particular the eyelid margins, are special facial areas which are likely to present UV-damage and to be consequently subject to the development of non-melanoma skin cancer (NMSC), i.e., basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Precancerous lesions or malignant tumors of eyelid are often not adequately recognized, being consequently under-treated. We present a peculiar case of a 70-year-old Caucasian man with a blue lesion of the right lower eyelid margin. The lesion had occurred a few months before the visit and appeared as a millimetric blue macule [Figure 1]a. Based on these findings, the differential diagnosis included venous lake, BCC, blue nevus, apocrine hidrocystoma, and also malignant melanoma. Patient showed signs of photodamage on the face and arms due to its previous work in the farm. Dermoscopy showed a non-homogeneous bluish purple structureless area without eyelash disruption [Figure 1]b; there were scattered and perifollicular small white globules, signs of hyperkeratosis. An excisional biopsy was made, and histopathologic examination revealed focal parakeratosis of the epidermis, loss of polarity, disordered maturation of the keratinocytes, scattered mitosis, pleomorphic and hyperchromatic nuclei [Figure 2]a and [Figure 2]b. Immunohistochemistry was also performed on the BenchMark ULTRA automated immunostainer (Ventana Medical Systems-Roche Diagnostics, Switzerland), showing basal and para-basal hyper-expression of p53 (anti-p53, clone DO7, dilution ready to use/RTU) in atypical nuclei [Figure 2]c, together with lentiginous melanocytic hyperplasia; double staining for PRAME (negative) and MART-1 (positive)(anti-PRAME, clone EPR20330, dilution 1:5000; anti-Melan A/MART-1, clone A103, dilution/RTU) was performed, ruling out a malignant melanocytic lesion [Figure 2]d.
Figure 1: (a) Physical examination shows a blue macule of the right lower eyelid margin; (b) Dermoscopic examination: non-homogeneous bluish purple lesion and preservation of eyelashes [Fotofinder, 40x]

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Figure 2: (a and b) Epidermis of the eyelid shows focal parakeratosis, loss of polarity and disordered maturation, scattered mitotic activity (para-basal), keratinocytes with pleomorphic and hyperchromatic nuclei (a: H and E, original magnification 10x; b: H and E, original magnification 400x); (c and d) immunohistochemical analysis shows basal and para-basal hyper-expression of p53 in atypical nuclei (c: p53, original magnification 250x), with an accompanying lentiginous melanocytic hyperplasia [d: double staining for PRAME (brown) and MART1 (red), original magnification 250x]

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Based on the clinical and histological findings, a diagnosis of pigmented actinic keratosis (PAK) was made. There was no recurrence at clinic and dermoscopy after two years.

Actinic keratoses (AKs) are the clinical pictures of epidermal proliferation of dysplastic keratinocytes, caused by chronic sun exposure in fair-skinned individuals. AKs usually affect the sun-exposed body areas, head, neck, or arms and may sometimes progress to invasive SCC. In most cases, AKs appear as small, erythematous macules or plaques, often covered by yellow adherent scales, but could also present as pigmented macules or hypertrophic plaques.[1] The most common histopathological features of AK are focal parakeratosis with loss of the underlying granular layer, slightly thickened epidermis, atypia of the basal cell layer, scattered mitotic activity, hyperchromasia and pleomorphism. PAK is usually located on the face and has specific dermatoscopic clues, i.e., a rhomboidal pattern, an annular granular pattern, the “rosette sign,” white circles and the presence of grayish areas.[2]

In our case, the dermoscopic appearance did not reflect the classic dermoscopic criteria of PAK, and this could be explained by the peculiar histological features of mucocutaneous areas. Despite this, dermoscopy provided a good differential diagnosis among the possible above-mentioned lesions of the eyelid margin. Dermoscopy revealed the absence of purple-reddish structureless pattern typical of venous lake,[3] the lack of in-focus arborizing vessels suggestive of BCC,[4] or it did not identify the steel-blue homogeneous pigmentation of blue nevus.[5]

The pigmented presentation is usually due to an excessive amount of melanin in keratinocytes and in dermal melanophages. In our case, we hypothesize that the blue pigmentation may be linked to the increased number of dermal melanophages, as well as to the abnormal degranulation of melanosomes.

To our knowledge, only one previous case of PAK of the eyelid margin was reported in the literature: In this case described by Salama SD et al., the PAK clinically appeared as a brown macula without lashes. The first clinical hypothesis was lentigo maligna, but the histological examination revealed the correct diagnosis of PAK.[6] Our paper represents the first report of dermoscopic findings in a case of PAK of the eyelid margin.

The immunohistochemical findings, in particular the double staining for PRAME (negative) and MART1 (positive), allowed us to rule out a melanocytic proliferation and to diagnose a PAK. Further case reports are expected, in order to provide a better characterization of the clinical, dermoscopic, and histopathological features of these lesions.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Ertop Doğan P, Akay BN, Okçu Heper A, Rosendahl C, Erdem C. Dermatoscopic findings and dermatopathological correlates in clinical variants of actinic keratosis, Bowen's disease, keratoacanthoma, and squamous cell carcinoma. Dermatol Ther 2021:e14877.  Back to cited text no. 1
Kelati A, Baybay H, Moscarella E, Argenziano G, Gallouj S, Mernissi FZ. Dermoscopy of pigmented actinic keratosis of the face: A study of 232 cases. Actas Dermosifiliogr 2017;108:844-51.  Back to cited text no. 2
Lee JS, Mun JH. Dermoscopy of venous lake on the lips: A comparative study with labial melanotic macule. PLoS One 2018;13:e0206768.  Back to cited text no. 3
Williams NM, Navarrete-Dechent C, Marghoob AA, Abarzua-Araya Á, Salerni G, Jaimes N. Differentiating basal cell carcinoma from intradermal nevi along the eyelid margin with dermoscopy: A case series. J Am Acad Dermatol 2021;84:173-5.  Back to cited text no. 4
Longo C, Scope A, Lallas A, Zalaudek I, Moscarella E, Gardini S, et al. Blue lesions. Dermatol Clin 2013;31:637-47.  Back to cited text no. 5
Salama SD, Margo CE. Large pigmented actinic keratosis of the eyelid. Arch Ophthalmol 1995;113:977-8.  Back to cited text no. 6


  [Figure 1], [Figure 2]


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