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Woods et al. J Cancer Metastasis Treat 2022;8:22 https://dx.doi.org/10.20517/2394-4722.2022.28 Page 5 of 14

the number of nodal metastases [44,49] . It has been suggested that an increasing number of metastatic lymph
nodes, separately from the presence of extranodal extension, is an independent predictor of disease-specific
survival in cutaneous SCC of the head and neck and could be incorporated into AJCC staging [50-52] .
However, alternative staging systems for regional spread of cutaneous SCC have been proposed, which may
give better stratification . These staging systems are often used for research purposes leading to
[53]
inconsistency in the significance of parotid involvement in staging. Examples of commonly used staging
systems include the Brigham and Women’s system , Clark’s N1S3 system , O’Brien’s parotid and neck
[54]
[55]
node system , and the Immunosuppression, Treatment, Extranodal spread, and Margin status prognostic
[56]
score .
[57]
[58]
For MCC, multiple staging systems have been described ; however, a distinct AJCC TNM staging system,
separate from other NMSC, is now most commonly used. Any regional nodal involvement is classified as
stage N1, while regional nodal involvement with in-transit metastasis is classified as stage N3. Stage N2
disease is classified by the presence of in-transit metastasis without nodal disease present. Overall, stage III
disease is denoted by any primary tumor size or unknown primary, with regional lymph node involvement.

For cutaneous adnexal tumors of the head and neck, regional lymph node staging is important due to its
impact on prognosis . Staging, along with other NMSC, is according to the 8th edition AJCC system.
[37]

SURGICAL MANAGEMENT
Multiple guidelines exist to assist decision making in the management of NMSC. However, this can be a
challenge as evidence from high-quality clinical trials is rare . When possible, surgery remains the
[59]
mainstay of management of this disease, including in cases of regional spread.

Squamous cell carcinoma
Reported rates of metastatic spread from the superficial parotid nodes to the cervical lymph nodes in SCC
range from 13%-35% [56,60-62] . Moreover, since metachronous metastasis is common, some research has
suggested elective treatment of the neck and parotid in advanced stage or high-risk cutaneous SCC [21,63-68] .
However, no prospective study has demonstrated a clinically substantial survival benefit to elective neck
dissection compared to therapeutic neck dissection after nodal metastasis has developed, and recent data
reports worse overall survival in those undergoing elective neck dissection [69,70] . Elective treatment of the
neck in regionally metastatic head and neck NMSC remains controversial and prospective trials are needed
to clarify optimal management.

For clinically node-negative high-risk SCC, depending on their age, co-morbidities, and risk factors,
sentinel lymph node biopsy or observation with or without imaging may be considered alternatives to
elective neck dissection and parotidectomy [21,70,71] . Although sentinel lymph node biopsy is a viable tool in
head and neck melanoma and is also used in MCC, it is rarely used in other head and neck cutaneous
malignancies outside of clinical trials [72-74] . Issues with sentinel lymph node mapping in the head and neck
include proximity of the injection site to the draining basins, unpredictable lymphatic drainage, multiple
sentinel nodes per patient, higher risk of false-negative results, and mapping to the parotid gland in
19%-44% of cases with a small chance of risk to the facial nerve in dissection .
[75]
Up to 75% of nodal metastases from cutaneous SCC of the head and neck are present in the parotid
[76]
gland . Typical management of this presentation, when resectable, is surgery followed by adjuvant
radiation , because radiation alone for clinically positive disease is associated with worse survival
[77]
[78]
outcomes . For cases with involved cervical nodes, in which parotid nodes are not clinically present but