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Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii
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Review paper

High-frequency ultrasound in the diagnosis and treatment of skin neoplasms

Maria Płocka
1
,
Rafał Czajkowski
1

  1. Department of Dermatology and Venereology, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
Adv Dermatol Allergol 2023; XL (2): 204-207
Online publish date: 2023/05/31
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Introduction

Cutaneous malignancies are the most common cancers worldwide [1], therefore their early detection determines increase of morbidity and survival. Since the introduction of ultrasound in 1979 to measure cutaneous thickness [2], skin imaging has kept progressing, resulting in the invention of high-frequency ultrasonography (HFUS). This non-invasive method precisely depicts lesion characteristics, therefore increases diagnostic accuracy [3], reduces the need for biopsy [4] or supports excision planning.

Although the conventional ultrasound scanner may assist dermatological diagnosis, HFUS assessment is more accurate as wave resolution and penetration are frequency-dependent – with higher frequency wavelength diminishes, which results in lower ultrasound penetration and better resolution imaging of the skin and subcutaneous tissues [5].

According to the DERMUS Group guidelines [6], HFUS needs minimum 15 MHz frequency to differentiate between skin layers [7] (preferably 15–22 MHz [8], the lowest frequencies designated for deeper lesions). HFUS accompanied by colour Doppler imaging and spectral curve analysis evaluates tumour vascularities [6]. Colour Doppler ultrasound differentiates benign from malignant lesions by depicting vessel size, intra- and peritumoral circulation [9]. It also evaluates inflammation – high disease activity areas [10] show increased blood flow. Three-dimensional reconstruction based on large-scale serial tissue sections [11] may be performed.

Digital HFUS images should be stored for long-term follow-up combined with clinical observations and prospective histological outcomes [12].

Melanoma

Melanoma is a skin cancer with the lowest survival [12] and a rapidly rising incidence rate [13]. HFUS depicts melanoma as hypoechoic, inhomogeneous [14], oblong or oval, well-bordered by hyperechoic epidermis. In ulcerated malignancies the epidermis may be non-continuous or irregular [15].

In colour Doppler examination melanoma – as an angiogenic tumour – is hypervascular. The flow signal is easier to detect in lesions thicker than 2 mm. Vascularization corresponds with lymph node involvement and survival rate.

Preoperative HFUS may determine excision margin as HFUS-measured cancer’s thickness resembles histopathologic results [1622] especially in superficial melanomas, while evaluation of nodular and vertically spreading tumours is less reliable [23]. The correlation is adequate in neoplasms thicker than 2 mm, often enabling one-time excision without widening resections. Thinner lesions should be excised or reassessed with a 100 MHz probe [15, 21]. HFUS-measured cancer thickness might be slightly overestimated due to peritumoral inflammation [24] and post-excision tissue dehydration [15, 25, 26].

Hinz et al. indicated that 1325-nm optical coherence tomography (OCT) is more precise than 20 MHz HFUS in melanomas thinner than 1 mm [27]. However, Meyer et al. compared 25 MHz HFUS with 930 nm OCT, concluding that OCT is less accurate than HFUS in evaluating tumour thickness, especially when the cancer’s depth exceeds 0.5 mm [21].

Postoperatively, HFUS surveils regional lymph node basins [28], detects satellite and in-transit melanoma metastases [29] as well-defined, hypoechogenic, rather homogenous, dermal or hypodermal structures [30, 31].

Basal cell carcinoma (BCC)

BCC constitutes the vast majority of non-melanoma skin cancers (NMSCs) and is the most common human malignancy [32].

HFUS presents BCC as an oval or subtly irregular well-bordered hypoechoic lesion with hyperechoic areas representing microcalcifications, corneous cysts or nests of apoptotic cells – “flower cotton” [33]. The presence of minimum seven hyperechoic spots (characteristic for morpheaform or micronodular BCC) indicates a high risk of recurrence [34]. BCC may be accompanied by low-flow vessels inside or at the bottom of the tumour [35]. The characteristics are isoechogenic sebaceous glands (“blurry tumour”) [36] and peritumoral inflammation (“angles at the bottom”), which enlarges HFUS-measured tumour thickness [25].

HFUS may designate small, non-infiltrative BCCs for conservative treatment like photodynamic therapy or laser ablation [37]. Being crucial in follow-up, HFUS supports or re-evaluates the decision either of non-invasive or surgical management as it indicates cancer recurrence [19]. If surgery is necessary, HFUS helps to reduce excision margins or – contrarily – avoid an incomplete procedure [38]. This asset results from high HFUS accuracy in measuring tumour thickness, comparable with histopathology, which enhances radical treatment [16] and positive prognosis.

Cutaneous squamous cell carcinoma (cSCC)

Squamous cell carcinoma derives from squamous cells of epidermis and mucous membranes [39], in 80% of cases [40] presenting as a cutaneous form, more invasive than BCC [41].

HFUS-assisted lesion evaluation or follow-up of postoperative basin and surrounding lymphatic structures is advised in: recurrent cSCCs, poorly differentiated tumours, bigger than 2 cm in diameter or thicker than 2 mm, invading nerves, vessels, lymph routes and high-risk anatomical sites (lips, ears and perineum) [42, 43]. HFUS depicts cSCC as an irregular heterogeneous tumour, fully hypoechoic, tending to invade deeper tissues [44]. Discrete tumour vascularization can be found, with vessels amplified peripherally [35].

Merkel cell carcinoma (MCC)

MCC is a rare but boosting in morbidity highly aggressive neuroendocrine malignancy [45]. HFUS depicts MCC as a poorly-defined (except for well-bordered satellitosis), non-calcified dermal lesion tending to invade subcutaneous tissues [46]. The mainly hypoechoic MCC mass shows hyperechoic zones, mostly with posterior acoustic enhancement and thickening of epidermis [47]. Colour Doppler ultrasonography pictures the tumour interior as richly vascularized, the flow being less intense in recurrent lesions and more vivid in cutaneous satellitosis.

HFUS differentiates hypoechoic skin malignancies [48], precisely preoperatively marks tumour margins to avoid local recurrence [49] and detects MCC metastases – subcutaneous, in-transit or affecting lymph nodes – thus enabling to assess tumour staging that determines treatment methods and prognosis.

HFUS: role and limitations in dermatology

Ultrasonography in dermatology is increasingly more widespread as a highly retriable, non-invasive method. Especially valuable are high-frequency probes, which support locoregional staging and follow-up, detecting early local or nodal recurrences. HFUS also indicates prognostic factors implicating advised management, based on the estimated recurrence risk, metastases and survival rate.

HFUS may reduce excision biopsies in benign-looking cases – diminishing patient’s stress, functional impairment, costs of materials and specialists’ work. In lesions of greater oncological alert HFUS helps to select excision margins, enabling faster diagnosis, effective treatment [50] and potentially preventing premature death.

A crucial HFUS application is to detect skin malignancies infiltrating relevant anatomical structures, especially head tumours. Ultrasound is faster available than computed tomography or magnetic resonance imaging but equally accurate in descrying calvarium invasion [51]. Preoperative HFUS maps neurovascular peritumoral structures to lower the operation’s risk and lift its aesthetic effect [52]. It can also support an aggressive management, reducing metastases and recurrence rate.

Despite diagnostic advancements, some skin cancers still present high morbidity and mortality. While the emphasis on discovering groundbreaking therapies for critically ill patients is fully appropriate, we should primarily struggle for the earliest possible neoplasm diagnosis. To achieve that we need to raise patients’ awareness of cancer prevention and alarming symptoms, as well as clinicians’ competencies and utmost oncological caution.

For worldwide HFUS application, training of medical doctors is necessary. Clinicians should attend practical courses and conduct HFUS regularly, preferably minimum 300 evaluations yearly [6]. Ultrasonographers should be trained in skin pathology to correlate HFUS images and physical examination with histopathology. Apart from education costs, HFUS machine may be a substantial expense.

HFUS should be evaluated in comparison to other advanced real-time three-dimensional (and high-priced) imaging methods, like line-field confocal OCT (LC-OCT), which combines standard OCT with reflectance confocal microscopy, thus achieving optimum penetration and excellent resolution for assessing cutaneous malignancies, especially NMSCs [53, 54]. LC-OCT shows a higher resolution than HFUS [55], unfortunately being significantly more time-intensive, which limits its broad-based clinical use.

Conflict of interest

The authors declare no conflict of interest.

References

1 

Linares MA, Zakaria A, Nizran P. Skin cancer. Prim Care 2015; 42: 645-59.

2 

Alexander H, Miller DL. Determining skin thickness with pulsed ultra sound. J Invest Dermatol 1979; 72: 17-9.

3 

Dorrell DN, Strowd LC. Skin cancer detection technology. Dermatol Clin 2019; 37: 527-36.

4 

Schneider SL, Kohli I, Hamzavi IH, et al. Emerging imaging technologies in dermatology: Part I: Basic principles. J Am Acad Dermatol 2019; 80: 1114-20.

5 

Bagatin E, Caetano LVN, Soares JLM. Ultrasound and dermatology: basis principles and main applications in dermatologic research. Expert Rev of Dermatol 2013; 8: 463-77.

6 

Wortsman X, Alfageme F, Roustan G, et al. Guidelines for performing dermatologic ultrasound examinations by the DERMUS group. J Ultrasound Med 2016; 35: 577-80.

7 

Lucas VS, Burk RS, Creehan S, et al. Utility of high-frequency ultrasound: moving beyond the surface to detect changes in skin integrity. Plast Surg Nurs 2014; 34: 34-8.

8 

Bard RL. High-frequency ultrasound examination in the diagnosis of skin cancer. Dermatol Clin 2017; 35: 505-11.

9 

Wortsman X. Sonography of facial cutaneous basal cell carcinoma. A first-line imaging technique. J Ultrasound Med 2013; 32: 567-72.

10 

Wortsman X, Wortsman J, Sazunic I, et al. Activity assessment in morphea using color Doppler ultrasound. J Am Acad Dermatol 2011; 65: 942-8.

11 

Liu P, Zhu JY, Tang B, et al. Three-dimensional digital reconstruction of skin epidermis and dermis. J Microsc 2018; 270: 170-5.

12 

Guy GP Jr, Thomas CC, Thompson T, et al.; Centers for Disease Control and Prevention (CDC). Vital signs: melanoma incidence and mortality trends and projections - United States, 1982-2030. MMWR Morb Mortal Wkly Rep 2015; 64: 591-6.

13 

Rastrelli M, Tropea S, Rossi CR, et al. Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. In Vivo 2014; 28: 1005-11.

14 

Reginelli A, Belfiore MP, Russo A, et al. A preliminary study for quantitative assessment with HFUS (high-frequency ultrasound) of nodular skin melanoma breslow thickness in adults before surgery: interdisciplinary team experience. Curr Radiopharm 2020; 13: 48-55.

15 

Lassau N, Lamuraglia M, Koscielny S, et al. Prognostic value of angiogenesis evaluated with highfrequency and colour Doppler sonography for preoperative assessment of primary cutaneous melanomas: correlation with recurrence after a 5 year follow-up period. Cancer Imaging 2006; 6: 24-9.

16 

Pellacani G, Seidenari S. Preoperative melanoma thickness determination by 20-MHZ sonography and digital videomicroscopy in combination. Arch Dermatol 2003; 139: 293-8.

17 

Gambichler T, Moussa G, Bahrenberg K, et al. Preoperative ultrasonic assessment of thin melanocytic skin lesions using a 100-MHz ultrasound transducer: a comparative study. Dermatol Surg 2007; 33: 818-24.

18 

Bessoud B, Lassau N, Koscielny S, et al. High-frequency sonography and color Doppler in the management of pigmented skin lesions. Ultrasound Med Biol 2003; 29: 875-9.

19 

Lassau N, Spatz A, Avril MF, et al. Value of high-frequency US for preoperative assessment of skin tumors. Radiographics 1997; 17: 1559-65.

20 

Music MM, Hertl K, Kadivec M, et al. Pre-operative ultrasound with a 12-15 MHz linear probe reliably differentiates between melanoma thicker and thinner than 1 mm. J Eur Acad Dermatol Venereol 2010; 24: 1105-8.

21 

Meyer N, Lauwers-Cances V, Lourari S, et al. High-frequency ultrasonography but not 930-nm optical coherence tomography reliably evaluates melanoma thickness in vivo: a prospective validation study. Br J Dermatol 2014; 171: 799-805.

22 

Crisan M, Crisan D, Sannino G, et al. Ultrasonographic staging of cutaneous malignant tumours: an ultrasonographic depth index. Arch Dermatol Res 2013; 305: 305-13.

23 

Fernández Canedo I, de Troya Martín M, Fúnez Liébana R, et al. Preoperative 15-MHz ultrasound assessment of tumour thickness in malignant melanoma. Actas Dermosifiliogr 2013; 104: 227-3.

24 

Kaikaris V, Samsanavičius D, Maslauskas K, et al. Measurement of melanoma thickness: comparison of two methods: ultrasound versus morphology. J Plast Reconstr Aesthet Surg 2011; 64: 796-802.

25 

Seidenari S. High-frequency sonography combined with image analysis: a noninvasive objective method for skin evaluation and description. Clin Dermatol 1995; 13: 349-59.

26 

Blasco-Morente G, Garrido-Colmenero C, Pérez-López I, et al. Study of shrinkage of cutaneous surgical specimens. J Cutan Pathol 2015; 42: 253-7.

27 

Hinz T, Ehler L, Voth H, et al. Assessment of tumour thickness in melanocytic skin lesions: comparison of optical coherence tomography, 20-MHz ultrasound and histopathology. Dermatology 2011; 223: 161-8.

28 

Voit C, Mayer T, Kron M, et al. Efficacy of ultrasound b-scan compared with physical examination in follow-up of melanoma patients. Cancer 2001; 91: 2409-16.

29 

Solivetti FM, Desiderio F, Guerrisi A, et al. HF ultrasound vs PET-CT and telethermography in the diagnosis of in-transit metastases from melanoma:a prospective study and review of the literature. J Exp Clin Cancer Res 2014; 33: 96.

30 

Corvino A, Corvino F, Catalano O, et al. The tail and the string sign: new sonographic features of subcutaneous melanoma metastasis. Ultrasound Med Biol 2017; 43: 370-4.

31 

Catalano O, Caracò C, Mozzillo N, et al. Locoregional spread of cutaneous melanoma: sonography findings. Am J Roentgenol 2010; 194: 735-45.

32 

Work Group; Invited Reviewers; Kim JYS, Kozlow JH, Mittal B, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol 2018; 78: 540-59.

33 

Halip IA, Vâţă D, Statescu L, et al. Assessment of basal cell carcinoma using dermoscopy and high frequency ultrasound examination. Diagnostics 2022; 12: 735.

34 

Wortsman X, Vergara P, Castro A, et al. Ultrasound as predictor of histologic subtypes linked to recurrence in basal cell carcinoma of the skin. J Eur Acad Dermatol Venereol 2015; 29: 702-7.

35 

Wortsman X, Jemec GBE. Springer, New York 2013.

36 

Wortsman X. Atlas of Dermatologic Ultrasound; Springer Science + Business Media: New York, NY, USA 2018; 23-5, 115-8, 311-3.

37 

Smucler R, Kriz M, Lippert J, et al. Ultrasound guided ablative-laser assisted photodynamic therapy of basal cell carcinoma (US-aL-PDT). Photomed Laser Surg 2012; 30: 200-5.

38 

Desai TD, Desai AD, Horowitz DC, et al. The use of high-frequency ultrasound in the evaluation of superficial and nodular basal cell carcinomas. Dermatol Surg 2007; 33: 1220-7.

39 

Dotto GP, Rustgi AK. Squamous cell cancers: a unified perspective on biology and genetics. Cancer Cell 2016; 29: 622-37.

40 

Moan J, Grigalavicius M, Baturaite Z, et al. The relationship between UV exposure and incidence of skin cancer. Photodermatol Photoimmunol Photomed 2015; 31: 26-35.

41 

Clayman GL, Lee JJ, Holsinger FC, et al. Mortality risk from squamous cell skin cancer. J Clin Oncol 2005; 23: 759-65.

42 

Humphreys TR, Shah K, Wysong A, et al. The role of imaging in the management of patients with nonmelanoma skin cancer: when is imaging necessary? J Am Acad Dermatol 2017; 76: 591-607.

43 

Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: management of advanced and high-stage tumors. J Am Acad Dermatol 2018; 78: 249-61.

44 

MacFarlane D, Shah K, Wysong A, et al. The role of imaging in the management of patients with nonmelanoma skin cancer: diagnostic modalities and applications. J Am Acad Dermatol 2017; 76: 579-88.

45 

Paulson KG, Park SY, Vandeven NA, et al. Merkel cell carcinoma: current US incidence and projected increases based on changing demographics. J Am Acad Dermatol 2018; 78: 457-63.e2.

46 

Eftekhari F, Wallace S, Silva EG, et al. Merkel cell carcinoma of the skin: imaging and clinical features in 93 cases. Br J Radiol 1996; 69: 226-33.

47 

Hernández-Aragüés I, Vázquez-Osorio I, Alfageme F, et al. Skin ultrasound features of Merkel cell carcinoma. J Eur Acad Dermatol Venereol 2017; 31: e315-8.

48 

Hernández Ibáñez C, Aguilar Bernier M, de Troya Martín M. Ultrasound in the management of non-melanoma skin cancer. Actas Dermosifiliogr 2015; 106 Suppl 1: 21-8.

49 

Reichgelt BA, Visser O. Epidemiology and survival of Merkel cell carcinoma in the Netherlands. A population-based study of 808 cases in 1993–2007. Eur J Cancer 2011; 47: 579-85.

50 

Jasaitiene D, Valiukeviciene S, Linkeviciute G. Principles of high-frequency ultrasonography for investigation of skin pathology. J Eur Acad Dermatol Venereol 2011; 25: 375-82.

51 

Elia F, Paolino G, Donati M, et al. Ultrasound pattern of a rare skin disease: multiple miliary osteoma cutis. J Ultrasound 2016; 19: 145.

52 

Hung EHY, Griffith JF, Ng AWH, et al. Ultrasound of musculoskeletal soft-tissue tumors superficial to the investing fascia. AJR 2014; 202: W532-40.

53 

Ruini C, Schuh S, Sattler E, Welzel J. Line-field confocal optical coherence tomography – practical applications in dermatology and comparison with established imaging methods. Skin Res Technol 2021; 27: 340-52.

54 

Suppa M, Fontaine M, Dejonckheere G, et al. Line-field confocal optical coherence tomography of basal cell carcinoma: a descriptive study. J Eur Acad Dermatol Venereol 2021; 35: 1099-110.

55 

Wan B, Ganier C, Du-Harpur X, et al. Applications and future directions for optical coherence tomography in dermatology. Br J Dermatol 2021; 184: 1014-22.

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