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Research Letter |

Transillumination as a Means to Differentiate Melanocytic Lesions Based on Their Vascularity FREE

Vitaly Terushkin, BS; Stephen W. Dusza, DrPH; Nizar A. Mullani, BS; Madeleine Duvic, MD; George Zouridakis, PhD; Martin Weinstock, MD, PhD; Rhett Drugge, MD; Victor G. Prieto, MD, PhD; Atam Dhawan, PhD; Claire Terry, RTT; Rakhshandra Talpur, MD; Ashfaq A. Marghoob, MD
Arch Dermatol. 2009;145(9):1060-1062. doi:10.1001/archdermatol.2009.191.
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Published online

Angiogenesis is an important facet of tumorigenesis. One method to characterize this process in pigmented lesions is to assess architectural patterns of vascular structures with tools such as dermoscopy1 and reflectance confocal microscopy.2 Dermoscopic studies have shown distinct vascular patterns in melanoma vs benign pigmented lesions.1 In addition, investigators have measured the number of blood vessels using lectin agglutinin I to label microvessels in excised lesions and have shown that melanomas contain more blood vessels than dysplastic nevi (DN), and DN have more blood vessels than other benign nevi.3 These data suggest that characterizing angiogenesis within a lesion may potentially help distinguish between different melanocytic lesions. Studies using laser Doppler perfusion imaging have already shown that it is possible to noninvasively categorize lesions by measuring velocity of blood flow.4,5

In this pilot study, we investigated the use of a novel instrument, the Nevoscope (TransLite, Sugar Land, Texas), which combines side-transillumination (TL) to measure blood volume with cross-polarization (XP) for superficial imaging, to differentiate melanocytic lesions based on vascularity. The patented TL method6 makes the skin translucent and allows examination of lesion vascularity and pigmentation.

The study data were collected at the MD Anderson Cancer Center, Houston, Texas, where 80 patients with suspect pigmented lesions smaller than 1 cm in diameter were prospectively recruited during routine skin examinations to undergo biopsy. After a clinical diagnosis by an expert dermatologist was recorded, the Nevoscope was used to image the lesions. Punch biopsy specimens of suspect lesions were obtained, and the biopsy specimens were submitted for histopathologic diagnosis.

Nevoscope Imaging. This device uses XP and TL to create dermoscopic and blood-volume images, respectively. Side-transillumination directs light into the skin at a 45° angle from the periphery of the lesion. This light, focused under the skin, behaves as a virtual light source and uniformly transilluminates a small area of the skin within the circular area defined by the fiberoptic ring light. All chromophores, including melanin, oxyhemoglobin, and deoxyhemoglobin, are involved. Thus, TL imaging provides information on blood volume and melanin content. Deoxygenated blood, specifically, absorbs light wavelengths between 580 nm and 650 nm and appears dark red on transillumination. On the other hand, XP images are formed via surface reflection and provide information on melanin content.

Image Acquisition and Lesion Classification. Side-transillumination and XP images were obtained prior to biopsy. An automated procedure for accurate boundary detection was used.7 Next, the area within the boundary was quantified from the TL and XP images. Fifty melanocytic lesions were used in the analysis; they included 6 congenital nevi (CN), 5 intradermal nevi, 18 DN with mild atypia, 15 DN with moderate atypia, 2 DN with severe atypia, and 4 malignant melanomas (MMs). Junctional melanocytic nevi with atypia and DN with congenital features were grouped into the DN category. Criteria for characterizing DN based on cytologic atypia are discussed elsewhere.8

Statistical Analysis. Descriptive statistics were used to describe the study lesions. A ratio (TL/XP = [melanin area + blood volume area]/melanin area) of the XP and TL areas was computed for each lesion; this value was taken as an indirect measure of the lesion's vascularity and was used as the outcome measurement. It was hypothesized that this ratio would equal 1 for benign lesions and exceed 1 for more vascular lesions such as MMs and DN.

Mean TL/XP ratios were calculated for each lesion category and compared between categories using the t test. Linear regression was used to assess trends in TL/XP ratios across lesion categories; this analysis was performed with and without CN. The reason for excluding CN is that they are inherently more vascular than other melanocytic lesions.1,9

Figure 1 shows Nevoscope images of a moderately dysplastic nevus. The TL image demonstrates less pigmentation and less contrast than the XP image. However, the TL image appears larger owing to the vascular component at the periphery.

Place holder to copy figure label and caption
Figure 1.

A moderately dysplastic nevus. A, Side-transillumination. B, Cross-polarization. An automated boundary detection method was used to create the outline shown surrounding both images (black outlines).

Graphic Jump Location

The mean TL/XP ratios and SDs for the 50 analyzed images are as follows: 1.24 (0.26) for CN; 0.98 (0.22) for intradermal nevi; 1.13 (0.21) for DN with mild atypia; 1.21 (0.14) for DN with moderate atypia; 1.24 (0.07) for DN with severe atypia; and 1.25 (0.21) for MMs. Figure 2 demonstrates an increase in lesion vascularity from benign intradermal nevi to MMs. This trend is significant when CN are excluded (P = .02).

Place holder to copy figure label and caption
Figure 2.

Lesion scatterplot. Scatterplot of side-transillumination (TL)–cross-polarization (XP) ratios by lesion category. CN indicates congenital nevi; DN, dysplastic nevi; IDN, intradermal nevi; and MM, malignant melanoma.

Graphic Jump Location

In this pilot study we present a novel device, the Nevoscope, that combines 2 imaging techniques, XP and TL, to assess vascularity of pigmented lesions. We have demonstrated a trend in increasing blood volume from mild DN to moderate DN to severe DN to MM. As expected, the highest TL/XP ratio was seen in melanoma, supporting previous studies that have shown the impact of neoangiogenesis in cutaneous neoplastic processes.10 In addition, these data support laser Doppler perfusion imaging studies4,5 as well as pathologic reports3 describing increased blood velocity and blood microvessel count, respectively, in the different types of melanocytic tumors.

Interestingly, the TL/XP ratio increased as a function of atypia in DN. This finding raises a question of the significance of neoangiogenesis in the evolution of DN. Additional studies are warranted to investigate the feasibility of using this instrument as an aid to diagnose melanocytic neoplasms and to further characterize neoangiogenesis in DN.

ARTICLE INFORMATION

Correspondence: Dr Marghoob, Memorial Sloan-Kettering Cancer Center, 160 E 53rd St, New York, NY 10022 (marghooa@mskcc.org).

Author Contributions: Mr Mullani and Dr Duvic had full access to all 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: Mullani, Prieto, and Dhawan. Acquisition of data: Mullani, Duvic, Weinstock, Drugge, Terry, and Talpur. Analysis and interpretation of data: Terushkin, Dusza, Mullani, Zouridakis, Weinstock, Drugge, Prieto, Dhawan, and Marghoob. Drafting of the manuscript: Terushkin, Dusza, Mullani, Drugge, Prieto, and Talpur. Critical revision of the manuscript for important intellectual content: Terushkin, Dusza, Mullani, Duvic, Zouridakis, Weinstock, Drugge, Prieto, Dhawan, Terry, and Marghoob. Statistical analysis: Dusza and Mullani. Obtained funding: Mullani and Duvic. Administrative, technical, and material support: Mullani, Duvic, Weinstock, Dhawan, and Terry. Study supervision: Dusza, Mullani, Duvic, and Marghoob.

Financial Disclosure: Mr Mullani is the owner of TransLite. The company was created after the data collection portion of the study was completed.

Funding/Support: This research was supported in part by National Cancer Institute grant 1 R41 CA76759-01A1 (Mr Mullani and Dr Duvic).

Role of the Sponsors: The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript.

Additional Contributions: Josep Malvehy, MD, helped in the data analysis portion of this study; Narin Apisarnthanarax, MD, helped to recruit and obtain informed consent from patients.

Argenziano  GZalaudek  ICorona  R Vascular structures in skin tumors: a dermoscopy study. Arch Dermatol 2004;140 (12) 1485- 1489
PubMed
Scope  ABenvenuto-Andrade  CAgero  ALHalpern  ACGonzalez  SMarghoob  AA Correlation of dermoscopic structures of melanocytic lesions to reflectance confocal microscopy. Arch Dermatol 2007;143 (2) 176- 185
PubMed Link to Article
Barnhill  RLFandrey  KLevy  MAMihm  MC  JrHyman  B Angiogenesis and tumor progression of melanoma: quantification of vascularity in melanocytic nevi and cutaneous malignant melanoma. Lab Invest 1992;67 (3) 331- 337
PubMed
Ilias  MAWardell  KStucker  MAnderson  CSalerud  EG Assessment of pigmented skin lesions in terms of blood perfusion estimates. Skin Res Technol 2004;10 (1) 43- 49
PubMed Link to Article
Stücker  MHorstmann  INuchel  CRochling  AHoffmann  KAltmeyer  P Blood flow compared in benign melanocytic naevi, malignant melanomas and basal cell carcinomas. Clin Exp Dermatol 1999;24 (2) 107- 111
PubMed Link to Article
Dhawan  AP Apparatus and method for skin lesion examination.  US Patent5;146;923. 1992
Zouridakis  GDoshi  MMullani  N Early diagnosis of skin cancer based on segmentation and measurement of vascularization and pigmentation in Nevoscope images. Conf Proc IEEE Eng Med Biol Soc 2004;31593- 1596
PubMed
Shea  CRVollmer  RTPrieto  VG Correlating architectural disorder and cytologic atypia in Clark (dysplastic) melanocytic nevi. Hum Pathol 1999;30 (5) 500- 505
PubMed Link to Article
Tannous  ZSMihm  MC  JrSober  AJDuncan  LM Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management. J Am Acad Dermatol 2005;52 (2) 197- 203
PubMed Link to Article
Velasco  PLange-Asschenfeldt  B Dermatological aspects of angiogenesis. Br J Dermatol 2002;147 (5) 841- 852
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

A moderately dysplastic nevus. A, Side-transillumination. B, Cross-polarization. An automated boundary detection method was used to create the outline shown surrounding both images (black outlines).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Lesion scatterplot. Scatterplot of side-transillumination (TL)–cross-polarization (XP) ratios by lesion category. CN indicates congenital nevi; DN, dysplastic nevi; IDN, intradermal nevi; and MM, malignant melanoma.

Graphic Jump Location

Tables

References

Argenziano  GZalaudek  ICorona  R Vascular structures in skin tumors: a dermoscopy study. Arch Dermatol 2004;140 (12) 1485- 1489
PubMed
Scope  ABenvenuto-Andrade  CAgero  ALHalpern  ACGonzalez  SMarghoob  AA Correlation of dermoscopic structures of melanocytic lesions to reflectance confocal microscopy. Arch Dermatol 2007;143 (2) 176- 185
PubMed Link to Article
Barnhill  RLFandrey  KLevy  MAMihm  MC  JrHyman  B Angiogenesis and tumor progression of melanoma: quantification of vascularity in melanocytic nevi and cutaneous malignant melanoma. Lab Invest 1992;67 (3) 331- 337
PubMed
Ilias  MAWardell  KStucker  MAnderson  CSalerud  EG Assessment of pigmented skin lesions in terms of blood perfusion estimates. Skin Res Technol 2004;10 (1) 43- 49
PubMed Link to Article
Stücker  MHorstmann  INuchel  CRochling  AHoffmann  KAltmeyer  P Blood flow compared in benign melanocytic naevi, malignant melanomas and basal cell carcinomas. Clin Exp Dermatol 1999;24 (2) 107- 111
PubMed Link to Article
Dhawan  AP Apparatus and method for skin lesion examination.  US Patent5;146;923. 1992
Zouridakis  GDoshi  MMullani  N Early diagnosis of skin cancer based on segmentation and measurement of vascularization and pigmentation in Nevoscope images. Conf Proc IEEE Eng Med Biol Soc 2004;31593- 1596
PubMed
Shea  CRVollmer  RTPrieto  VG Correlating architectural disorder and cytologic atypia in Clark (dysplastic) melanocytic nevi. Hum Pathol 1999;30 (5) 500- 505
PubMed Link to Article
Tannous  ZSMihm  MC  JrSober  AJDuncan  LM Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management. J Am Acad Dermatol 2005;52 (2) 197- 203
PubMed Link to Article
Velasco  PLange-Asschenfeldt  B Dermatological aspects of angiogenesis. Br J Dermatol 2002;147 (5) 841- 852
PubMed Link to Article

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