Predictors of Nodal Metastasis in Cutaneous Head and Neck Cancers

Current Oncology Reports https://doi.org/10.1007/s11912-022-01249-5 HEAD AND NECK CANCERS (EY HANNA, SECTION EDITOR) Predictors of Nodal Metastasis in Cutaneous Head and Neck Cancers Albert Y. Han1,2,3 · Maie A. St. John1,2,3 Accepted: 15 May 2021 © The Author(s) 2022 Abstract Purpose of Review The complex and varied drainage patterns in the head and neck present a challenge in the regional control of cutaneous neoplasms. Lymph node involvement significantly diminishes survival, often warranting more aggressive treatment. Here, we review the risk factors associated with lymphatic metastasis, in the context of the evolving role of sentinel lymph node biopsy. Recent Findings In cutaneous head and neck melanomas, tumor thickness, age, size, mitosis, ulceration, and specific histology have been associated with lymph node metastasis (LNM). In head and neck cutaneous squamous cell carcinomas, tumor thickness, size, perineural invasion, and immunosuppression are all risk factors for nodal metastasis. The risk factors for lymph node involvement in Merkel cell carcinoma are not yet fully defined, but emerging evidence indicates that tumor thickness and size may be associated with regional metastasis. Summary The specific factors that predict a greater risk of LNM for cutaneous head and neck cancers generally include depth of invasion, tumor size, mitotic rate, ulceration, immunosuppression, and other histopathological factors. Keywords Cutaneous cancer · Squamous cell carcinoma · Melanoma · Regional metastasis · Parotid metastasis Introduction Cutaneous neoplasms are clinically categorized into melanoma and non-melanoma skin cancers. Non-melanoma skin cancers include cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), and other less common tumors including sarcomas and adnexal tumors. BCC typically undergoes localized slow growth and rarely metastasizes, but cSCC, melanoma, and other malignancies often spread to regional and distant sites, which can significantly impact the clinical course of the disease and patient outcomes. The exact incidence of This article is part of the Topical collection on Head and Neck Cancers. * Maie A. St. John 1 Department of Head and Neck Surgery, University of California Los Angeles (UCLA), Los Angeles, CA, USA 2 UCLA Head and Neck Cancer Program, UCLA Medical Center, 10833 Le Conte Ave, 62‑132 CHS, Los Angeles, CA 90095, USA 3 Jonsson Comprehensive Cancer Center, UCLA Medical Center, Los Angeles, CA, USA cSCC is unknown as cSCCs are often excluded in national tumor registries. However, a recent estimate indicated a global prevalence of 3.1 million cases of malignant melanoma and 2.2 million cases of cSCC in 2015 [1]. Despite the relatively small surface area of the head and neck region, approximately 60-70% of cSCCs [2] and 20% of cutaneous melanomas [3] arise in the head and neck. Cutaneous cancers of the head and neck often spread via the lymphatic system toward the neck, frequently involving the intraparotid lymph nodes depending on the location of the primary tumor. The drainage pattern in the head and neck assumes a general division between the anterior and posterior skin zones with a proposed watershed zone in between (Fig. 1) [4]. The posterior head and neck regions drain to the occipital, postauricular, cervical level V, and supraclavicular fossa. In contrast, the anterior head and neck regions drain to the anterior cervical chains, as well as the parotid and preauricular nodes [5]. Approximately 20–40% of head and neck neoplasms spread to lymph nodes outside of clinically predicted levels [6, 7]. When using a sentinel lymph node biopsy (SLNB) in the head and neck or trunk regions, preoperative lymphoscintigraphy or SPECT/CT is recommended to guide the location of interval (in-transit) nodes that might harbor disease [8]. Although not yet the 13 Vol.:(0123456789) Current Oncology Reports indicators, along with recurrence number and grade, that accurately identified patients with cSCC of the ear who might benefit from neck dissection. Tumor Size Fig. 1  Predicted pattern of metastasis of head and neck cutaneous melanoma proposed by O’Brien et al. The orange area represents the “watershed area” from which unpredictable drainage can occur ( Adapted from O’Brien et al. American Journal of Surgery) [4] standard of care, the literature supports the use of SPECT/ CT as it has been found to increase the SLN yield, resulting in a greater ability to detect metastatic involvement [9]. Cutaneous Squamous Cell Carcinoma of the Head and Neck The prognosis for patients with cSCC of the head and neck (cSCCHN) is excellent when diagnosed early. However, a subset of these patients develops lymph node metastasis (LNM) and ultimately experiences poorer outcomes. LNM develops in 5% of patients after resection of the primary lesion [10]. If found at presentation or after treatment, LNM is associated with a higher 5-year mortality [11]. Involvement of the lymph nodes also increases the likelihood of recurrence to approximately 51% and decreases the 3-year disease-specific survival to 52%, even with adjuvant treatment [12]. Therefore, understanding the risk factors for metastasis in cSCCHN is critical for early identification of patients who need more aggressive, often multimodal, management. Depth of Invasion Tumor depth of invasion (DOI) has been consistently reported as a risk factor for metastasis whether measured in Breslow thickness or histological depth [13]. The relative risk is higher for patients with tumors with a DOI cutoff of > 2 mm [14]. In one recent study, no metastasis was observed for superficial lesions with DOIs of less than 2 mm [10]. Tumor invasion beyond subcutaneous fat was associated with nodal metastasis (subhazard ratio 7.2) [15]. In a prediction model proposed by Wermker et al. [16], tumor depth and invasion of cartilage were two of the four 13 A tumor size greater than 20 mm was associated with disease progression, including regional metastasis [13]. For the current eighth edition staging system developed by the American Joint Committee on Cancer (AJCC), the primary tumor staging is determined by the dimensions of the tumor: T1 (2 cm or less in diameter) and T2 (greater than 2 cm but less than or equal to 4 cm). Tumor size is often associated with LNMs and worse survival with discrete cutoffs (e.g. greater than 20 mm in the greatest dimension) or as a continuous variable [17, 18, 19, 20]. Tumor size was also an independent predictor of nodal metastasis (> 20 mm) with a HR of 2.22 [10]. In a large study of 6,000 patients in New Zealand, tumor size as a continuous was a prognosticator of LNM with HR 1.41 (p < 0.0001) [21]. Alternative measurements of the tumor size, such as tumor volume greater than 2,500 mm, were significantly associated with LNMs as well [22]. Subsite Certain sites of the head and neck appear to be associated more with LNMs. During development, t (...truncated)