Blue color is found in a wide range of malignant and benign melanocytic and nonmelanocytic lesions and in lesions that result from penetration of exogenous materials, such as radiation or amalgam tattoo or traumatic penetration of particles. Discriminating between different diagnostic entities that display blue color relies on careful patient examination and lesion assessment. Dermoscopically, the extent, distribution, and patterns created by blue color can help diagnose lesions with specificity and differentiate between benign and malignant entities. This article provides an overview of the main diagnoses whereby blue color can be found, providing simple management rules for these lesions.
Key points
- •
Blue color can be found in a wide range of malignant and benign melanocytic and nonmelanocytic lesions as well as in lesions that result from penetration of exogenous materials.
- •
Careful patient examination and lesion assessment by integrating dermoscopy in clinical practice is useful to discriminate between different diagnostic entities that display blue color.
- •
As a fundamental rule, all blue nodular lesions that do not fulfill clear-cut clinical and dermoscopic criteria for a specific benign lesion with high confidence should be excised to avoid the risk of delaying or missing the diagnosis of a nodular melanoma.
Introduction
Colors that are seen under dermoscopic examination of skin lesions emanate from the presence of different chromophores in the epidermis and dermis, including melanin, hemoglobin, and collagen. The colors depend on the anatomic level of skin at which these chromophores are located. Blue color in lesions that are not vascular in origin is mostly related to a dermal localization of melanin, arranged as either extracellular melanin granules or located within cells arranged as solitary units (eg, melanophages) or as clusters of cells (eg, melanocytic nests in a nevus or aggregates of basaloid neoplastic cells in basal cell carcinoma). Thus, blue color can be found under dermoscopy in a wide range of melanocytic and nonmelanocytic lesions. Of these, lesions that show diffuse bluish pigmentation on dermoscopy can be particularly challenging to diagnose with specificity. The assessment of colors under dermoscopy is influenced by the type of dermatoscope that is being used for the analysis: polarized light dermoscopy (PD) versus nonpolarized light dermoscopy (NPD). More specifically, under PD, blue colors appear darker and different shades of brown and blue seem to be highlighted compared with NPD. In particular, peppering and blue-white structures (BWSs) are seen better with NPD. The reason for these differences, simplistically stated, is that PD allows for better visualization of light coming from deeper layers of the dermis than NPD, because the polarized filters of PD block light that is back-scattered from more superficial layers (eg, epidermis and dermal-epidermal junction). This difference, however, between PD and NPD does not seem to affect the overall lesion pattern and the diagnostic accuracy.
This article reviews the diagnoses that appear predominantly blue in color under dermoscopy and the management rules for the various blue lesions in clinical practice.
Introduction
Colors that are seen under dermoscopic examination of skin lesions emanate from the presence of different chromophores in the epidermis and dermis, including melanin, hemoglobin, and collagen. The colors depend on the anatomic level of skin at which these chromophores are located. Blue color in lesions that are not vascular in origin is mostly related to a dermal localization of melanin, arranged as either extracellular melanin granules or located within cells arranged as solitary units (eg, melanophages) or as clusters of cells (eg, melanocytic nests in a nevus or aggregates of basaloid neoplastic cells in basal cell carcinoma). Thus, blue color can be found under dermoscopy in a wide range of melanocytic and nonmelanocytic lesions. Of these, lesions that show diffuse bluish pigmentation on dermoscopy can be particularly challenging to diagnose with specificity. The assessment of colors under dermoscopy is influenced by the type of dermatoscope that is being used for the analysis: polarized light dermoscopy (PD) versus nonpolarized light dermoscopy (NPD). More specifically, under PD, blue colors appear darker and different shades of brown and blue seem to be highlighted compared with NPD. In particular, peppering and blue-white structures (BWSs) are seen better with NPD. The reason for these differences, simplistically stated, is that PD allows for better visualization of light coming from deeper layers of the dermis than NPD, because the polarized filters of PD block light that is back-scattered from more superficial layers (eg, epidermis and dermal-epidermal junction). This difference, however, between PD and NPD does not seem to affect the overall lesion pattern and the diagnostic accuracy.
This article reviews the diagnoses that appear predominantly blue in color under dermoscopy and the management rules for the various blue lesions in clinical practice.
Melanocytic lesions
Blue Nevi
Blue melanocytic nevi represent the prototypical melanocytic neoplasm that is typified by a predominantly blue color under dermoscopy. The authors acknowledge that what is referred to clinically and dermoscopically as blue nevus actually represents various subtypes of melanocytic nevi that have in common a predominantly dermal proliferation of pigmented melanocytes on histopathology. Dermoscopically, blue nevi show a structureless, uniform steel-blue coloration ( Fig. 1 ) that corresponds on histopathology to the presence of heavily pigmented melanocytes in the reticular dermis. Blue nevi are typically devoid of other dermoscopic criteria, such as pigment network, although multiple colors (blue, black, and brown) can be observed in a small percentage of lesions. Recently, Di Cesare and colleagues confirmed that the prototypical dermoscopic feature of blue nevi is homogeneous bluish to steel-blue pigmentation. This feature was significantly more frequent in blue nevi compared with melanomas and pigmented basal cell carcinomas, with a specificity of 99% and 96.8%, respectively, and a sensitivity of 48.4%.
The clinical and dermoscopic diagnosis of blue nevus is usually straightforward and relies on the dermoscopic observation of diffuse, homogeneous bluish to steel-blue pigmentation in absence of specific melanoma criteria, and, importantly, on the clinical history of a long-standing, stable lesion. When lesion history is not available and, particularly in adult patients, when the lesion at hand is new or changing, a biopsy should be strongly considered to rule out the diagnosis of melanoma or melanoma metastasis.
Spitz/Reed Nevi
Dermoscopically, pigmented Spitz/Reed nevi (PSRN) often display a starburst pattern typified by multiple peripheral streaks or peripherally located pigmented globules, whereas the center of the lesion usually shows a homogeneous pattern ranging in color from blue-gray to brown-black.
Clinically, PSRN presents as a flat or papular lesion that often arises on the face, limbs, and buttocks of children or young adults. Patient age is an important factor in determining whether a lesion with bluish color clinically and a starburst pattern dermoscopically is managed as a PSRN or melanoma; at times, melanoma can be completely indistinguishable from PSRN, clinically and dermoscopically. Furthermore, under confocal microscopy, PSRN often shows the presence of cytologic atypia, pagetoid spread, and architectural disorder, confocal features that overlap with those seen in melanoma; thus, confocal microscopy cannot always reliably differentiate between PSRN and melanoma.
The difficulty clinicians may face in discriminating PSRN from melanoma is also encountered in the histopathologic analysis of so-called spitzoid lesions, and discordant diagnoses (of melanoma vs PSRN) are not infrequent when multiple pathologists review the slides of a given spitzoid neoplasm. Thus, prompt excision of any pigmented lesion that shows spitzoid features on clinical and dermoscopic examination should be performed in adults, including young adults after puberty, to avoid missing melanoma. Finally, new molecular analysis techniques may potentially enhance the diagnostic discrimination between PSRN and melanoma in the future.
Melanoma
The presence of blue color is a common dermoscopic finding in melanoma. In melanoma, blue color is often admixed with white; thus, these dermoscopic structures have been named BWSs. BWSs are often classified according to the clinical palpability of the area showing the blue color (eg, flat, palpable, and purely nodular melanoma). Foci of BWSs that are clinically flat often signify the presence of regression on histopathology, whereas palpable or nodular BWSs often signify melanomas in which the proliferation of neoplastic cells is present in the dermis (ie, invasive melanoma). A blue color that is associated with black color (BB rule; discussed later) typically occurs in nodular melanomas that lack, or have a limited, junctional component.
Regression (Flat Blue-white Structures)
Dermoscopically observed regression (flat BWSs) mostly appears as white scarlike depigmentation that is usually whiter in color than the surrounding skin, admixed with granularity or peppering (speckled multiple blue-gray granules within the hypopigmented areas). On histopathology, regression shows fibrosis and a bandlike infiltrate of melanophages in the superficial dermis as well as a thin epidermis with effacement of the rete ridges.
Flat BWSs that show a combination of white scarlike areas and blue granularity are a dermoscopic finding that should raise suspicion for melanoma undergoing regression. Although the presence of flat BWSs can also be seen in nevi, the majority of these nevi usually reveal only blue color (ie, granularity) without white; moreover, the blue structure is most often centrally located in more than half of such nevi, whereas an irregular distribution (combination of a central and peripheral location) is most frequently found in melanomas. The extent of BWSs within the lesion is also important, in that the more widespread the BWS, the greater the suspicion for melanoma. Zalaudek and colleagues demonstrated that melanocytic lesions with BWSs covering more than 50% of the lesion area had a 44% probability of being histopathologically equivocal (ie, showing discordance between pathologists on the diagnosis of nevus vs melanoma), whereas lesions with BWSs covering less than 50% of the lesion area had a 91% probability of being diagnosed unequivocally as a nevus on histopathology. In summary, the presence of flat BWSs that includes both white and blue colors, that is, irregular in distribution or that involves more than 50% of the lesion, should prompt a clinician to excise the lesion to rule out melanoma.
The evaluation of lesions showing flat BWSs, however, also has to be considered in the context of a patient’s other nevi. Older patients with multiple nevi may have more than 1 lesion showing blue color as a result of an involution phenomenon. In contrast, a solitary lesion with blue color should always raise suspicion for melanoma.
When regression structures are extensive and advanced in the lesion, and other dermoscopic criteria are scant or absent, it could be difficult to determine whether the lesion at hand is melanocytic (ie, a fully regressed melanoma) or nonmelanocytic (ie, a seborrheic keratosis undergoing regression, termed, lichen planus–like keratosis ). In this scenario, confocal microscopy may support the clinical decision making process because it can enable the detection of subtle remnants of the melanocytic proliferation; for example, confocal observation of a proliferation of single atypical melanocytes or even aggregates of cells interspersed within a florid inflammatory infiltrate, is suggestive of the diagnosis of melanoma ( Fig. 2 ). Lichen planus, however, like keratosis typically shows on confocal imaging the presence of cordlike structures or bulbous projections admixed with a variable amount of melanophages. The detection of a remnant melanocytic proliferation on confocal examination, however, is not always reliable; thus, biopsy should be strongly considered in cases that lack additional clear-cut dermoscopic or confocal criteria for the diagnosis of seborrheic keratosis. This approach has led to better management of fully regressed melanomas; if left to their own devices, these melanomas can eventually disappear completely, potentially leading to the occurrence of melanoma metastases with an unknown primary tumor.
A peculiar morphology of dermoscopically observed regression, occurring preferentially in melanoma in situ, has been recently described. This early melanoma can display regression that appears reticula in distribution, seen as a coarse blue-gray net, with thick gray-blue lines (reticular blue areas) with large holes that correspond to pink-colored regression areas ( Fig. 3 ). The fading of the pigment network or of other dermoscopic structures results in areas of structureless light brown pigmentation. This reticular-type of regression can be found in so-called slow-growing melanomas that are characterized dermoscopically by the simultaneous presence of network and regression.
Blue-white Veil (Palpable Blue-white Structures)
Blue-white veil is a dermoscopic structure defined as an irregular, indistinct, confluent blue pigmentation with an overlying white, ground-glass haze ( Fig. 4 ). On histopathology, the blue-white veil seen on dermoscopy corresponds to an acanthotic epidermis with focal hypergranulosis and compact orthokeratosis overlying sheets of heavily pigmented neoplastic atypical melanocytes in the upper dermis. Among melanocytic neoplasms, blue-white veil is mostly seen in melanomas and PSRN. The presence of blue-white veil is associated with foci in the lesion that are clinically palpable, and thus, in the context of melanoma, blue-white veil signifies invasive melanomas. Additional dermoscopic criteria may be observed in the lesion, such as atypical network and vascular pattern, and taken together with the blue-white veil, these criteria usually point to the correct dermoscopic diagnosis of melanoma.
