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Case Report/Case Series |

Dermoscopy and Confocal Microscopy of Nested Melanoma of the Elderly Recognizing a Newly Defined Entity FREE

Caterina Longo, MD1; Iris Zalaudek, MD1,2; Simonetta Piana, MD3; Giovanni Pellacani, MD4; Aimilios Lallas, MD1; Camilla Reggiani, MD4; Giuseppe Argenziano, MD1
[+] Author Affiliations
1Units of Dermatology and Skin Cancer, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy
2Department of Dermatology, Medical University of Graz, Graz, Austria
3Pathology, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy
4Department of Dermatology, University of Modena and Reggio Emilia, Italy
JAMA Dermatol. 2013;149(8):941-945. doi:10.1001/jamadermatol.2013.321.
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Published online

ABSTRACT

Importance  Nested melanoma of the elderly is a newly identified histopathologic variant of superficial spreading melanoma, characterized by intraepidermal large nests. However, the clinical, dermoscopic, and confocal aspects have been depicted only partially.

Observations  In our cases series, nested melanoma was a flat, irregularly shaped lesion with variably pigmented and irregularly distributed globules on dermoscopic examination. Confocal microscopy revealed the presence of a “clod” pattern made of large compact nests with variable atypia. These findings correlated well with histopathologic features.

Conclusions and Relevance  Nested melanoma of the elderly should be included in the differential diagnosis when a flat pigmented lesion, showing dermoscopically an irregular globular pattern, is seen in a patient older than 60 years.

Figures in this Article

Nested melanoma of the elderly represents a distinct morphologic variant of superficial spreading melanoma, typified by the presence of large intraepidermal nests. Recently, specific histopathologic criteria of this melanoma subtype have been identified, allowing its differentiation from conventional superficial spreading melanoma.1,2 However, the clinical, dermoscopic, and confocal features of this newly identified histopathologic entity have been depicted only partially. In this case series, we aimed to describe the distinctive dermoscopic and confocal features of nested melanoma of the elderly to guide clinicians in recognizing this melanoma subtype.

REPORT OF CASES

Case 1

A 65-year-old woman with a history of melanoma was referred for her periodic skin examination. A suspicious pigmented lesion was noticed on her back. Clinically, the lesion differed from the neighboring nevi because of the large size (1.4 cm) and irregular shape and color. Dermoscopically, the lesion was asymmetric and characterized by a prevalent globular pattern with pigmented globules varying in size and color (Figure 1).

Place holder to copy figure label and caption
Figure 1.
Pigmented Lesion

Case 1. A, Clinically suspicious pigmented lesion (rectangle) on the back of a 65-year-old woman. B, The lesion differs from the neighboring nevi by being larger (1.4 cm) and darker. C, Dermoscopically (original magnification ×10), the lesion is asymmetric and characterized by a prevalent globular pattern with pigmented globules varying in size and color.

Graphic Jump Location

Confocal microscopy revealed the presence of a predominant “clod” pattern at the dermoepidermal junction. The clod pattern was made by large and compact dense nests that filled the interpapillary space while distorting and enlarging it (Figure 2). On close examination, cytologic atypia was found within the nests (Figure 3).

Place holder to copy figure label and caption
Figure 2.
“Clod” Pattern

Case 1. A, Confocal mosaic showing a “clod” pattern at the dermoepidermal junction (scale bar = 500 µm) composed of regularly spaced large compact nests. B, Histopathologic features show a predominantly nested pattern of large intraepidermal and junctional nests (hematoxylin-eosin, original magnification ×40).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Cytologic Atypia

Case 1. A, Confocal image showing detail of the nests, which were characterized by cytologic atypia (arrows) (scale bar = 50 µm). B, Histopathologic features show the presence of large intraepidermal nests. The melanocytes within the nests show mild to moderate cytologic atypia and prominent nucleoli (hematoxylin-eosin, original magnification ×400).

Graphic Jump Location

The lesion was excised and subsequent histopathologic examination revealed a junctional melanocytic proliferation with a predominant nested pattern. This was typified by striking, mostly roundish nests of regular size and shape along the dermoepidermal junction. Cytologic atypia within the nests also was evident, together with a minor single cell growth pattern and focal epidermotropism. With the combined clinical, dermoscopic, confocal, and histopathologic features, a final diagnosis of melanoma in situ was made.

Case 2

A 70-year-old woman sought consultation for the presence of a solitary growing lesion on her right calf. Clinically, the variegated lesion was 2.5 × 2 cm (Figure 4).

Place holder to copy figure label and caption
Figure 4.
Predominant Globular Pattern With Pigmented Globules

Case 2. A, Solitary growing lesion on the right calf of a 70-year-old woman. B, Clinically, the variegated lesion is 2.5 × 2 cm. C, Dermoscopy (original magnification ×10) reveals a predominant globular pattern with pigmented globules showing striking variation for color and distribution within the lesion.

Graphic Jump Location

Dermoscopically, the pattern was predominantly globular, with pigmented globules showing striking variation for color and distribution within the lesion. On confocal microscopy, the lesion exhibited a prevalent clod pattern with large nests. Pagetoid spread was focally present along with cytologic atypia at the dermoepidermal junction (Figure 5). Histopathologic examination revealed an early invasive melanoma (Breslow thickness of 0.4 mm) with a striking nested pattern of growth. The nests were composed of monomorphous, small, pigmented cells alternating with occasional single atypical, larger melanocytes.

Place holder to copy figure label and caption
Figure 5.
Melanocytes

Case 2. A, Confocal image at the epidermal level (scale bar = 50 µm) allows the observation of the pagetoid spread of melanocytes (arrows). B, At the dermoepidermal junction level (scale bar = 50 µm), confocal examination reveals the presence of pleomorphic melanocytes corresponding to cytologic atypia (circle).

Graphic Jump Location
Case 3

A 56-year-old man was referred for the presence of a growing lesion on his calf. Clinically, the lesion was an irregularly pigmented, flat 0.6-mm lesion on its major axis (Figure 6). Dermoscopically, there was asymmetry in color and structure, with irregularly distributed dots and globules over a light to dark brown structureless background. Histopathologic examination revealed an in situ melanoma composed of large intraepidermal nests of atypical melanocytes.

Place holder to copy figure label and caption
Figure 6.
Nested Melanoma In Situ

Case 3. A, Clinical view of a nested melanoma in situ. B, Dermoscopy (original magnification ×10) reveals an asymmetric lesion with a structureless pattern and irregularly distributed brown to black dots and globules.

Graphic Jump Location

DISCUSSION

Nested melanoma of the elderly is a newly described histopathologic variant of superficial spreading melanoma.1,2 Histopathologic criteria include the presence of a nested pattern, with striking large cut nests, regularly shaped and sized, and evenly scattered along the dermoepidermal junction. Sharp lateral circumscription, focal areas of lentiginous proliferation of melanocytes at the dermoepidermal junction, and occasional pagetoid scattering of melanocytes are also described. This melanoma usually occurs in adults older than 60 years and presents as a thin melanoma with a mean Breslow thickness of less than 1 mm. Using array comparative genomic hybridization, multiple genomic aberrations have been found in this melanoma type.1 A similar pattern also has been found in a control group of superficial spreading melanomas, outlining that nested melanoma can be considered a special variant of superficial spreading melanoma.

Kutzner et al1 reported the dermoscopic features of these melanomas, including asymmetry, multicomponent overall structure, irregular blotches, atypical pigment network, and large, irregular dots and globules. In our study, we observed the same repetitive and quite monotonous dermoscopic pattern, typified by a prevalent globular pattern with globules varying in shape, color, and distribution. Remarkably, all melanomas arose in the elderly and were large in size.

Recent data support the evidence that a globular pattern is commonly found in growing melanocytic nevi, correlating with the physiologic growth of nevi in young adults.37 Conversely, the presence of globules is unlikely in the elderly, whose nevi are usually fewer than those in young adults and mostly represented by intradermal nevi with a homogeneous pattern. Thus, the presence of a large pigmented lesion with an irregular globular pattern in the elderly should raise suspicion of melanoma.

Under confocal microscopy, a grossly regular clod pattern (patient 1) was observed at low magnification, with atypical cells within the nests visible only at higher magnification. In the case of thicker melanomas (patient 2), the stereotypical confocal characteristics of melanoma,8,9 such as pagetoid spread and cytologic atypia, were also visible at low magnification.

Remarkably, the correct diagnosis of nested melanoma of the elderly should always rely on a good clinicopathologic correlation. In case 1, the lesion was difficult to interpret for the pathologist, and only a careful evaluation of combined clinical, dermoscopic, confocal, and histopathologic features led to the correct diagnosis of melanoma in situ.

In conclusion, nested melanoma of the elderly should be included in the differential diagnosis when a flat, large pigmented lesion, showing dermoscopically an irregular globular pattern, is seen in a patient older than 60 years.

ARTICLE INFORMATION

Accepted for Publication: January 30, 2013.

Corresponding Author: Iris Zalaudek, MD, Dermatology and Skin Cancer Unit, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Viale Risorgimento 80, 42100 Reggio Emilia, Italy (iris.zalaudek@gmail.com).

Published Online: June 5, 2013. doi:10.1001/jamadermatol.2013.321.

Author Contributions: Drs Longo, Zalaudek, Piana, Pellacani, Reggiani, and Argenziano had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Longo.

Acquisition of data: Longo, Zalaudek, Piana, Lallas, and Reggiani.

Analysis and interpretation of data: Longo, Pellacani, and Argenziano.

Drafting of the manuscript: Longo.

Critical revision of the manuscript for important intellectual content: Longo, Zalaudek, Piana, Pellacani, Lallas, and Argenziano.

Administrative, technical, or material support: Lallas and Argenziano.

Study supervision: Longo, Zalaudek, Piana, Reggiani, and Argenziano.

Conflict of Interest Disclosures: None reported.

REFERENCES

Kutzner  H, Metzler  G, Argenyi  Z,  et al.  Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests. Mod Pathol. 2012;25(6):838-845.
PubMed   |  Link to Article
Pennacchia  I, Garcovich  S, Gasbarra  R, Leone  A, Arena  V, Massi  G.  Morphological and molecular characteristics of nested melanoma of the elderly (evolved lentiginous melanoma). Virchows Arch. 2012;461(4):433-439.
PubMed   |  Link to Article
Zalaudek  I, Grinschgl  S, Argenziano  G,  et al.  Age-related prevalence of dermoscopy patterns in acquired melanocytic naevi. Br J Dermatol. 2006;154(2):299-304.
PubMed   |  Link to Article
Pellacani  G, Scope  A, Ferrari  B,  et al.  New insights into nevogenesis: in vivo characterization and follow-up of melanocytic nevi by reflectance confocal microscopy. J Am Acad Dermatol. 2009;61(6):1001-1013.
PubMed   |  Link to Article
Zalaudek  I, Docimo  G, Argenziano  G.  Using dermoscopic criteria and patient-related factors for the management of pigmented melanocytic nevi. Arch Dermatol. 2009;145(7):816-826.
PubMed   |  Link to Article
Piliouras  P, Gilmore  S, Wurm  EM, Soyer  HP, Zalaudek  I.  New insights in naevogenesis: number, distribution and dermoscopic patterns of naevi in the elderly. Australas J Dermatol. 2011;52(4):254-258.
PubMed   |  Link to Article
Zalaudek  I, Schmid  K, Marghoob  AA,  et al.  Frequency of dermoscopic nevus subtypes by age and body site: a cross-sectional study. Arch Dermatol. 2011;147(6):663-670.
PubMed   |  Link to Article
Pellacani  G, Guitera  P, Longo  C, Avramidis  M, Seidenari  S, Menzies  S.  The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions. J Invest Dermatol. 2007;127(12):2759-2765.
PubMed
Longo  C, Zalaudek  I, Argenziano  G, Pellacani  G.  New directions in dermatopathology: in vivo confocal microscopy in clinical practice. Dermatol Clin. 2012;30(4):799-814, viii.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.
Pigmented Lesion

Case 1. A, Clinically suspicious pigmented lesion (rectangle) on the back of a 65-year-old woman. B, The lesion differs from the neighboring nevi by being larger (1.4 cm) and darker. C, Dermoscopically (original magnification ×10), the lesion is asymmetric and characterized by a prevalent globular pattern with pigmented globules varying in size and color.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
“Clod” Pattern

Case 1. A, Confocal mosaic showing a “clod” pattern at the dermoepidermal junction (scale bar = 500 µm) composed of regularly spaced large compact nests. B, Histopathologic features show a predominantly nested pattern of large intraepidermal and junctional nests (hematoxylin-eosin, original magnification ×40).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Cytologic Atypia

Case 1. A, Confocal image showing detail of the nests, which were characterized by cytologic atypia (arrows) (scale bar = 50 µm). B, Histopathologic features show the presence of large intraepidermal nests. The melanocytes within the nests show mild to moderate cytologic atypia and prominent nucleoli (hematoxylin-eosin, original magnification ×400).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.
Predominant Globular Pattern With Pigmented Globules

Case 2. A, Solitary growing lesion on the right calf of a 70-year-old woman. B, Clinically, the variegated lesion is 2.5 × 2 cm. C, Dermoscopy (original magnification ×10) reveals a predominant globular pattern with pigmented globules showing striking variation for color and distribution within the lesion.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.
Melanocytes

Case 2. A, Confocal image at the epidermal level (scale bar = 50 µm) allows the observation of the pagetoid spread of melanocytes (arrows). B, At the dermoepidermal junction level (scale bar = 50 µm), confocal examination reveals the presence of pleomorphic melanocytes corresponding to cytologic atypia (circle).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 6.
Nested Melanoma In Situ

Case 3. A, Clinical view of a nested melanoma in situ. B, Dermoscopy (original magnification ×10) reveals an asymmetric lesion with a structureless pattern and irregularly distributed brown to black dots and globules.

Graphic Jump Location

Tables

References

Kutzner  H, Metzler  G, Argenyi  Z,  et al.  Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests. Mod Pathol. 2012;25(6):838-845.
PubMed   |  Link to Article
Pennacchia  I, Garcovich  S, Gasbarra  R, Leone  A, Arena  V, Massi  G.  Morphological and molecular characteristics of nested melanoma of the elderly (evolved lentiginous melanoma). Virchows Arch. 2012;461(4):433-439.
PubMed   |  Link to Article
Zalaudek  I, Grinschgl  S, Argenziano  G,  et al.  Age-related prevalence of dermoscopy patterns in acquired melanocytic naevi. Br J Dermatol. 2006;154(2):299-304.
PubMed   |  Link to Article
Pellacani  G, Scope  A, Ferrari  B,  et al.  New insights into nevogenesis: in vivo characterization and follow-up of melanocytic nevi by reflectance confocal microscopy. J Am Acad Dermatol. 2009;61(6):1001-1013.
PubMed   |  Link to Article
Zalaudek  I, Docimo  G, Argenziano  G.  Using dermoscopic criteria and patient-related factors for the management of pigmented melanocytic nevi. Arch Dermatol. 2009;145(7):816-826.
PubMed   |  Link to Article
Piliouras  P, Gilmore  S, Wurm  EM, Soyer  HP, Zalaudek  I.  New insights in naevogenesis: number, distribution and dermoscopic patterns of naevi in the elderly. Australas J Dermatol. 2011;52(4):254-258.
PubMed   |  Link to Article
Zalaudek  I, Schmid  K, Marghoob  AA,  et al.  Frequency of dermoscopic nevus subtypes by age and body site: a cross-sectional study. Arch Dermatol. 2011;147(6):663-670.
PubMed   |  Link to Article
Pellacani  G, Guitera  P, Longo  C, Avramidis  M, Seidenari  S, Menzies  S.  The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions. J Invest Dermatol. 2007;127(12):2759-2765.
PubMed
Longo  C, Zalaudek  I, Argenziano  G, Pellacani  G.  New directions in dermatopathology: in vivo confocal microscopy in clinical practice. Dermatol Clin. 2012;30(4):799-814, viii.
PubMed   |  Link to Article

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