Clinical Investigations Received: October 25, 2016 Accepted: November 18, 2016 Published online: January 19, 2017
Dermatology 2017;233:74–79 DOI: 10.1159/000454857
Dermoscopy of Granuloma Annulare: A Clinical and Histological Correlation Study Enzo Errichetti a Aimilios Lallas c Zoe Apalla c Alessandro Di Stefani b Giuseppe Stinco a
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Department of Experimental and Clinical Medicine, Institute of Dermatology, University of Udine, Udine, and Division of Dermatology, Catholic University of the Sacred Heart, Rome, Italy; c First Department of Dermatology, Aristotle University, Thessaloniki, Greece
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Keywords Dermoscopy · Granuloma annulare · Granulomatous skin diseases · Histology · Inflammoscopy
Abstract Background: Dermoscopy of granuloma annulare has been investigated by several studies, but none of them took into account the variability of dermoscopic findings according to clinical characteristics and/or histological subtype. Objective: To describe the dermoscopic features of classic granuloma annulare and seek possible dermoscopic clues related to specific clinical findings/histological subpatterns. Methods: A representative dermoscopic image of a target lesion (the most active lesion underwent histological examination) was retrospectively assessed for the presence of specific morphological findings, correlating them with clinical variables, i.e. disease duration and extension (localized or generalized) and clinical aspect (annular or non-annular) and localization (trunk or extremities) of the biopsied lesion, and with histological subtype. Results: A total of 25 lesions from 25 subjects were analysed; an “interstitial” histological variant was detected in 11 cases, while a “palisading granuloma” histological pattern was found in 14 instances. The
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most common dermoscopic findings included blurry vessels having variable appearance (dotted, linear-irregular, and branching) over a more or less evident pinkish-reddish background, followed by whitish and/or yellowish-orange areas. Additional findings were rosettes, crystalline structures, and whitish scaling. No difference (p > 0.05) in the frequency of dermoscopic features according to clinical findings was found, while we observed a strict association (p < 0.001) between the presence of yellowish-orange structureless areas on dermoscopy and “palisading granuloma” histology. Conclusion: The dermoscopic aspect of granuloma annulare is independent from clinical features but varies according to histological subtype, with the detection of yellowish-orange colour being indicative of the “palisading granuloma” variant. © 2017 S. Karger AG, Basel
Introduction
Granuloma annulare (GA) is a relatively common, benign, inflammatory dermatosis of uncertain aetiology, classically presenting with localized or generalized, skincoloured to violaceous, non-scaly, dermal papules/nodEnzo Errichetti Institute of Dermatology Santa Maria della Misericordia University Hospital Piazzale Santa Maria della Misericordia 15, IT–33100 Udine (Italy) E-Mail enzoerri @ yahoo.it
Study design Patients with biopsy-confirmed GA (n = 25)
For each patient, a significant dermoscopic picture of the target lesion was selected from databases (total lesions = 25)
All the retrieved pictures were retrospectively evaluated for the presence of specific morphological findings
moscopic analyses carried out on GA so far has taken into account the variability of dermoscopic findings according to clinical features or histological subtype. The lack of the latter correlation is a relevant limitation as it is well known that cutaneous disorders presenting histological heterogeneity may display different dermoscopic findings depending on specific pathological subpatterns [13]. The aim of our study was to describe the dermoscopic features of classic GA and correlate them with pathological findings in order to find dermoscopic clues related to specific histological subpatterns, thus better characterizing dermoscopy of this dermatosis. Additionally, we also investigated possible links between dermoscopic and clinical features. Materials and Methods
Evaluation of possible correlations between each dermoscopic finding and specific histological subtypes/clinical features
Fig. 1. Flow chart of study design.
Figure 1 displays the study design in a flow chart. For further details, see the supplementary materials (for all online suppl. material, see www.karger.com/doi/10.1159/000454857) [7, 25].
Results
ules which may be discrete or coalesce to form annular or roundish plaques [1]. Such lesions may display variable histological patterns, i.e. “interstitial,” “palisading granuloma,” sarcoidosis-like, and mixed, with the first 2 being by far the most common [2]. Besides classic GA (localized and generalized), 3 other distinct clinicopathological variants have been described, including subcutaneous GA, perforating GA and patch-type GA [2]. Even though the clinical diagnosis of classic GA is usually straightforward when it presents with ring-like lesions localized on acral sites, the recognition of generalized or non-annular forms or cases affecting atypical areas may pose some difficulties, thus demanding histological examination to reach a definitive diagnosis [1, 2]. Over the last few years, several studies have shown that dermoscopy may be a useful tool to assist the non-invasive diagnosis of various inflammatory skin diseases [3– 19], including classic GA [20–24]. Indeed, albeit dermoscopic examination of this dermatosis has been reported to show heterogeneous findings, the use of such a technique may come in handy to support the distinction from its main differential diagnoses as they typically show a different appearance [20–24]. However, none of the der-
Twenty-five lesions from 25 subjects (7 men and 18 women; average age of 49.8 years, range: 20–69) were analysed. An annular morphology was observed in 16 (64%) patients, with the remaining 9 cases (36%) showing nonannular aspects. The trunk and extremities turned out to be the site of the target lesion in 7 (28.0%) and 18 (72.0%) instances, respectively. Seven (28.0%) patients presented a generalized involvement, while 18 (72.0%) subjects had a localized form; the average disease duration was 2.9 months (range of 1–7). Regarding the histology, the interstitial subtype was detected in 11 (44.0%) cases, while the palisading granuloma variant was found in 14 (66.0%) instances; no lesion displayed a sarcoidosis-like or mixed pattern. Dermoscopically, the most common non-vascular findings turned out to be whitish areas, observed in 16 (64.0%) lesions (including irregular, globular or irregular + globular areas in 11, 2 and 3 cases, respectively), and yellowish-orange structureless areas, detected in 15 (60.0%) instances (9 diffusely and 6 focally distributed) (Fig. 2, 3). Less frequent features included rosettes, crystalline structures and whitish scaling, being detected in 2 (8.0%), 4 (16.0%), and 2 (8.0%) cases, respectively. Regarding vascular structures, unfocused vessels were found in 22 (88.0%) lesions, with sparsely distributed dotted ones being the most common (13 cases; 52.0%), followed
Clinicopathological Correlations in Dermoscopy of GA
Dermatology 2017;233:74–79 DOI: 10.1159/000454857
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Color version available online
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whitish irregular areas. c The latter dermoscopic feature is likely to correspond to dermal areas of degenerated collagen bundles/mucin deposition on histology; histiocytes and lymphocytes among collagen bundles are also visible in the histological image. Haematoxylin and eosin stain. Original magnification ×40.
Color version available online
Fig. 2. GA with “interstitial” histology. a Clinical examination of a 54-year-old woman suffering from generalized GA shows several roundish reddish plaques on her back. b Polarized light dermoscopic examination of the target lesion (black arrow in a) displays unfocussed branching vessels over a faint pinkish background, along with “incidental” (sun-induced) brownish spots and several
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Fig. 3. GA with “palisading granuloma” histology. a Clinical examination of a 62-year-old woman shows an annular plaque on her right leg. b, c Polarized light dermoscopic examination of such a lesion displays several unfocussed branching vessels and sparse dotted vessels (arrowheads) over a faint pinkish background, “in-
cidental” (sun-induced) brownish spots, and a diffuse, annular, yellowish, structureless area (b), which histologically corresponds to the necrobiotic granulomatous inflammation in the dermis (c). Haematoxylin and eosin stain. Original magnification ×100.
by linear-irregular and branching vessels, seen in 11 (44.0%) and 7 (28.0%) lesions, respectively (Fig. 2, 3). A more or less evident pinkish-reddish background was observed in all lesions (25/25). From a statistical point of view, we found no difference (p > 0.05) in the frequency of dermoscopic features according to clinical morphology/localization of the target lesions and disease extension/duration. On the other hand, we observed a higher general prevalence (p < 0.001) of yellowish-orange structureless areas in lesions having a palisading granuloma histology (13 cases, 92.9%, com-
pared to those displaying an interstitial pattern in 2 cases, 18.2%), with both diffuse and focal distribution detected more commonly in the first histological subtype (9 vs. 0 and 4 vs. 2 cases, respectively), although only diffusely distributed areas reached statistical significance (p = 0.001). None of the other dermoscopic findings presented a significant difference in prevalence between the 2 histological subgroups (p > 0.01). Table 1 summarizes dermoscopic features observed in GA according to histological subtype, with relative p values.
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Dermatology 2017;233:74–79 DOI: 10.1159/000454857
Errichetti/Lallas/Apalla/Di Stefani/Stinco
Table 1. Dermoscopic features observed in 25 GA lesions according to the histological subtype (numbers with percentages in parentheses)
Dermoscopic finding
Lesions presenting an interstitial subtype (n = 11)
Lesions presenting a palisading granuloma subtype (n = 14)
p value
Yellowish-orange structureless areas Diffusely distributed Focally distributed Whitish areas Structureless irregular areas Globular areas Structureless irregular + globular areas Crystalline structures Rosettes Whitish scaling Unfocused vessels over a pinkish/ reddish background Sparse dotted vessels Linear-irregular vessels Branching vessels
2 (18.2) 0 (0.0) 2 (18.2) 6 (54.5) 4 (36.4) 1 (9.1) 1 (9.1) 3 (27.3) 1 (9.1) 1 (9.1)
13 (92.9) 9 (64.3) 4 (28.6) 10 (71.4) 7 (50.0) 1 (7.1) 2 (14.3) 1 (7.1) 1 (7.1) 1 (7.1)
