Dermatology: Practical and Conceptual Observation | Dermatol Pract Concept 2017;7(3):10 47 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Introduction Merkel cell carcinoma (MCC) is a highly malignant and uncom- mon neuroendocrine tumor of the skin. Polyomavirus infection and ultra-violet light exposure are known etiological factors in this cutaneous malignancy [1]. MCC has an aggressive behav- ior with early metastases and frequent recurrences [2]. It often develops on chronically sun-damaged skin, particularly on the head and neck of elderly patients [3]. MCC commonly presents clinically as a rapidly growing shiny erythematous or violaceous papule, plaque or nodule. Due to its non-specific clinical appear- ance, MCC is frequently overlooked or misdiagnosed and it is not uncommon that the histopathologic diagnosis of MCC takes the dermatologist by surprise [3]. Dermoscopic assessment of vascular structures in solitary small pink lesions—differentiating between good and evil Shamir Geller1, Melissa Pulitzer2, Mary Sue Brady3, Patricia L. Myskowski1 1 Dermatology Service, Department of Medicine Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA 2 Department of Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA 3 Department of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA Key words: dermoscopy, Merkel cell carcinoma Citation: Geller S, Pulitzer M, Brady MS, Myskowski PL. Dermoscopic assessment of vascular structures in solitary small pink lesions— differentiating between good and evil. Dermatol Pract Concept 2017;7(3):10. DOI: https://doi.org/10.5826/dpc.0703a10 Received: February 27, 2017; Accepted: April 11, 2017; Published: July 31, 2017 Copyright: ©2017 Geller et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Shamir Geller, MD, Dermatology Service, Memorial Sloan Kettering Cancer Center, 16 East 60th Street, New York, NY 10022, USA. Tel. 646 888 6032. Email: shamirgeller@gmail.com The diagnosis of a single small pink papule poses a real challenge to the clinician, as the differential diagnosis of such lesions includes benign entities such as a neurofibroma or hemangioma, as well as aggressive and potentially fatal skin malignancies such as amelanotic melanoma or Merkel cell carcinoma (MCC). The absence of a benign vascular pattern and the presence of atypical vascular features under dermoscopy direct the clinician to proceed to histologic evaluation in order to rule out a malignant process in such lesions. The diagnosis of MCC is particularly problematic, given that this tumor usually lacks specific clinical diagnostic features. Low clinical suspicion for MCC may result in delayed diagnosis and poor outcomes. The dermoscopic features of MCC are also non-specific, most commonly including milky-red areas and linear irregular vessels. We report a patient who presented with two discrete pink papules on different digits that appeared three years apart. Dermoscopy helped to diagnose a harmless hemangioma in the first lesion, and a MCC in the latter. The malignant tumor was diagnosed and excised expeditiously, with no evidence of metastatic spread. ABSTRACT https://doi.org/10.5826/dpc.0703a10 mailto:shamirgeller@gmail.com 48 Observation | Dermatol Pract Concept 2017;7(3):10 Three years later, the patient returned for another follow- up visit at which time she pointed out a new red papule on the dorsal middle digit of her left hand. Three months earlier she had noticed a small red “dot” on her finger that gradu- ally grew in size to a 3 mm papule. On physical exam, an erythematous shiny red papule was identified. Dermoscopic examination of the papule showed linear irregular blood ves- sels (Figure 1b). The rest of the patient’s skin was of normal appearance, and no lymphadenopathy was present. A biopsy of the lesion demonstrated a cutaneous neuroendocrine (Merkel cell) carcinoma (Figure 2). Immunohistochemical stains were positive for CK20 and Merkel cell polyomavi- rus, supporting the diagnosis. The patient was referred for a complete excision of the digital tumor and a sentinel lymph node biopsy. At resection there was no evidence of residual or metastatic disease, demonstrating early (stage Ia) disease [13]. Discussion The diagnosis of a single pink papule can be extremely challenging for the clinician. Most pink papules are banal benign skin lesions. Rapid growth, ulceration, or pain are Several studies have aimed to characterize the dermoscopic appearance of MCC, however no specific pattern has been identified [4-8]. Atypical vascular structures were found to be of the most diagnostic significance in MCC, most commonly linear irregular vessels and milky-red areas [6]. These dermo- scopic findings are not specific and can be found in other types of cutaneous malignancies such as hypomelanotic / amelanotic melanoma [9] and melanoma metastasis [10], skin metastases from solid tumor [11], and other skin tumors [7]. Case Report A 74-year-old Caucasian female has been followed by our clinic for more than ten years after a diagnosis in 2005 of a CD4+ small/medium pleomorphic T-cell lymphoma. In 2013 the patient presented with an erythematous papule on the sec- ond finger of her right hand. Dermoscopic examination of the lesion revealed red-purple lacuna suggestive of a hemangioma [12] (Figure 1a). Because of the patient’s history of cutane- ous T-cell lymphoma, a skin biopsy was performed, and the diagnosis of hemangioma was confirmed histologically. The lesion completely regressed after the biopsy was taken. Figure 1. Clinical presentation (upper pictures) and dermoscopic appearance (lower pictures) of two digital pink papules appearing three years apart. (a) A solitary pink papule on the lateral aspect of the second digit on the right hand with red-purple lacunes under dermoscopic examination, compatible with a hemangioma. (b) A pink solitary papule on the dorsal aspect of the third finger on the left. Dermoscopy shows linear irregular blood vessels with a diffuse milky-white background. [Copyright: ©2017 Geller et al.] Observation | Dermatol Pract Concept 2017;7(3):10 49 structures on dermoscopy as the only clue of the alarming diagnosis [9]. A linear irregular vascular pattern consists of straight vessels of irregular shape, size, and distribution. It is a well- known dermoscopic feature in skin tumors and has been described in multiple cutaneous malignancies that appear as pink or skin-colored lesions [7,9,11]. Linear irregular vessels correlate with small diameter, abnormally structured and het- erogeneously dense blood vessels that are seen in the context of tumor angiogenesis [15]. In amelanotic and hypomelanotic melanoma, a predominance of linear irregular vessels on der- moscopy has been reported to have a sensitivity of 34% and a specificity of 80% for melanoma [9]. Vascular structures also predominate the appearance of amelanotic cutaneous melanoma metastases under dermoscopy, in which irregular linear vessels are identified in 45% of lesions [10]. Similarly, cutaneous metastases of solid tumors often present with a vascular dermoscopic pattern, with linear irregular vessels seen in 77% [11]. Linear irregular vessels can also be identi- fied in other uncommon skin tumors such as adnexal tumors as well as in MCC [7,8]. clinical features that suggest a malignant process, though such clues are not always present. Dermoscopy is a useful diagnostic aid in approaching such lesions, as it elucidates the morphology and distribution of blood vessels and other features such as white shiny structures that may focus the differential diagnosis [14]. In small pink lesions such as a hemangioma, the diagnosis can be made by identifying the dominant vascular components of red lacunae, pale septae and milky-red areas that form a specific and diagnostic dermoscopic pattern. In other pink lesions, the presence of non-dominant, even subtle vascular structures seen on dermoscopy, when integrated with the overall morphologic appearance, may suggest a possible diagnosis. For example, the presence of glomerular vessels in an erythematous scaly lesion is suggestive of Bowen’s disease [12]. In some cases, neither the gross morphology nor the dermoscopic features are diagnostically specific. In these cases, the presence of atypical blood vessels may prompt the clinician to perform a biopsy in order to rule out malignancy. Amelanotic mela- noma may present as an unremarkable pink papule that may show predominantly linear irregular and dotted vascular Figure 2. Histopathology of the two lesions on the fingers: (a) Pink papule on the right hand (see Figure 1a) shows large numbers of dilated vessels within the dermis compatible with capillary hemangioma. (b) Pink papule on the 3rd finger left hand (see Figure 1b) reveals dermal nodular infiltrate of small blue round-oval cells. A cluster of dilated blood vessels were noted on the upper periphery of the dermal tumor correlating with the focal linear irregular vessels seen under dermoscopy (hematoxylin and eosin stain). [Copyright: ©2017 Geller et al.] 50 Observation | Dermatol Pract Concept 2017;7(3):10 with guidelines for multidisciplinary management. Cancer. 2007;110(1):1-12. 3. Heath M, Jaimes N, Lemos B, et al. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol. 2008;58(3):375-381. 4. Dalle S, Parmentier L, Moscarella E, Phan A, Argenziano G, Thomas L. Dermoscopy of Merkel cell carcinoma. Dermatology. 2012;224(2):140-144. 5. Harting MS, Ludgate MW, Fullen DR, Johnson TM, Bichakjian CK. Dermatoscopic vascular patterns in cutaneous Merkel cell carcinoma. J Am Acad Dermatol. 2012;66(6):923-927. 6. Jalilian C, Chamberlain AJ, Haskett M, et al. Clinical and dermo- scopic characteristics of Merkel cell carcinoma. Br J Dermatol. 2013;169(2):294-297. 7. Lallas A, Moscarella E, Argenziano G, et al. Dermoscopy of un- common skin tumours. Australas J Dermatol. 2014;55(1):53-62. 8. Suárez AL, Louis P, Kitts J, et al. Clinical and dermoscopic features of combined cutaneous squamous cell carcinoma (SCC)/neuroen- docrine [Merkel cell] carcinoma (MCC). J Am Acad Dermatol. 2015;73(6):968-975. 9. Menzies SW, Kreusch J, Byth K, et al. Dermoscopic evaluation of amelanotic and hypomelanotic melanoma. Arch Dermatol. 2008;144(9):1120-1127. 10. Jaimes N, Halpern JA, Puig S, et al. Dermoscopy: an aid to the de- tection of amelanotic cutaneous melanoma metastases. Dermatol Surg. 2012;38(9):1437-1444. 11. Chernoff KA, Marghoob AA, Lacouture ME, Deng L, Busam KJ, Myskowski PL. Dermoscopic findings in cutaneous metastases. JAMA Dermatol. 2014;150(4):429-433. 12. Marghoob AA, Usatine RP, Jaimes N. Dermoscopy for the family physician. Am Fam Physician. 2013;88(7):441-450. 13. Edge SB. American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010. 14. Zalaudek I, Kreusch J, Giacomel J, Ferrara G, Catricala C, Argen- ziano G. How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part II. Nonmela- nocytic skin tumors. J Am Acad Dermatol. 2010;63(3):377-386. 15. Nishida N, Yano H, Nishida T, Kamura T, Kojiro M. Angiogenesis in cancer. Vasc Health Risk Manag. 2006;2(3):213-219. 16. Ng L, Beer TW, Murray K. Vascular density has prognostic value in Merkel cell carcinoma. Am J Dermatopathol. 2008;30(5):442- 445. 17. Stokes JB, Graw KS, Dengel LT, et al. Patients with Merkel cell carcinoma tumors < or = 1.0 cm in diameter are unlikely to harbor regional lymph node metastasis. J Clin Oncol. 2009;27(23):3772- 3777. The dermoscopic features of MCC have been assessed in several small case series, each involving ten to 12 MCC lesions [4-6]. The most consistent dermoscopic features in these studies were milky-red areas and linear irregular blood vessels [6]. These dermoscopic vascular features are not specific to MCC and they can be found in amelanotic mela- noma and other malignant skin tumors as described above. Increased vascular density has been shown to be significantly associated with a worse prognosis in MCC as in melanoma [16]. While the clinical and dermoscopic identification of scale over a pink lesion with milky-red areas and linear irreg- ular blood vessels could indicate a component of squamous differentiation in MCC [8], other attempts to correlate MCC dermoscopic features with other histopathologic components have failed [5]. However, in our case we show the correla- tion of linear irregular vessels noted on dermoscopy with the histopathological finding of clustered dilated vessels at the periphery of the tumor (Figure 2). Our case demonstrates that dermoscopic examination of MCC may provide subtle but crucial clinical clues enabling the early diagnosis of this aggressive tumor. In MCC, early detection enables expedi- tious treatment, and may prevent tumor progression and lead to improved survival [17]. In conclusion, dermoscopy is a helpful diagnostic tool that helps distinguish between benign and malignant tumors in patients with non-specific solitary pink lesions. The pres- ence of linear irregular vessels in a solitary pink lesion should prompt a biopsy in order to prevent delayed diagnosis in aggressive amelanotic skin malignancies. Acknowledgments: Dr. Shamir Geller is a recipient of a supplemental grant from the American Physicians and Friends For Medicine in Israel (APF). References 1. Rockville Merkel Cell Carcinoma Group. Merkel cell carcinoma: recent progress and current priorities on etiology, pathogenesis, and clinical management. J Clin Oncol. 2009;27(24):4021-4026. 2. Bichakjian CK, Lowe L, Lao CD, Sandler HM, Bradford CR, Johnson TM, Wong SL. Merkel cell carcinoma: critical review