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Tirelli et al. J Cancer Metastasis Treat 2023;9:20 https://dx.doi.org/10.20517/2394-4722.2022.98 Page 7 of 11

[29]
facial artery and vein . Creighton et al. reported that PFN metastases were found in 10/145 (6.9%) of
cutaneous malignancies, especially when the primary tumor was located in the nose (3/7; 42.9%) and lip
[17]
(2/6; 33.3%), but also on the forehead, scalp and cheek . They suggested that the perifacial region should be
dissected in elective and completion lymphadenectomies for primary malignancies of the nose and lip [9,17] .
The fact that in skin cancers, the PMN are in fact more likely to be involved when the tumor is located close
to the course of the AFV could confirm the theory, already proposed for oral cavity cancer, that the PMN
collect metastatic cells that drain into the lymphatic system of the AFV [9,17,29] . [Table 1]

Perimarginal nodes in lip SCC
Although the involvement of level IB lymph nodes by lip cancer is well known, only one study specifically
analyzed the prevalence of PMN metastases from SCC in this area. Tirelli et al. demonstrated an incidence
of metastasis in 3/6 (50%) patients with primary lip cancer . Also in this case, it has to be noted that the lip
[9]
tumors drain through lymphatics close to the course of the labial arteries that drain directly into the AFV’s
lymphatic system.

RADIOLOGICAL ASPECTS
Radiological examination of the cervicolateral nodes has a fundamental role in head and neck cancer, and
ultrasound is a highly useful imaging modality in this setting. As reported by many authors, ultrasound has
high accuracy and sensitivity and is also inexpensive, especially when compared with other imaging
techniques such as MRI and CT [30-32] . Additionally, several studies have demonstrated that ultrasound and
CT have similar effectiveness [33-36] . The choice between CT and MRI for the study of the cervical lymph
nodes has been addressed by several investigations, at times with conflicting results [36-41] . Whenever possible,
these modalities should be used in combination to obtain the most effective and reliable results . In
[42]
DiNardo’s study, the role of imaging for the detection of submandibular metastases from oral cavity cancers
was still unclear. CT and MRI appear to be the most commonly used techniques for the detection of lymph
nodes and assessment of their size and features in metastatic disease [14,43,44] . However, some studies have
failed to demonstrate their effectiveness in providing an imaging assessment of level IB; in Carvalho et al.’s
study, for example, despite CT having high accuracy, sensitivity and specificity in the detection of
laterocervical metastases, its only false negative results were found in the submandibular region . A study
[45]
by Chaukar et al. analyzed 70 patients with oral SCC and N0, who subsequently underwent neck
dissection . The patients were studied with PET/CT, CT and ultrasound. The results show that for level IB
[46]
CT performed better in terms of specificity and accuracy compared with the other two modalities: CT
specificity was 86% compared with 72% for ultrasound and 71% for PET/CT, whereas its accuracy for level
[46]
IB was 81%, compared with 73% and 69% for ultrasound and PET/CT, respectively . These findings are
consistent with those of Jank et al., who compared the sensitivity and specificity of ultrasound and CT for
various laterocervical nodal levels in occult metastases from head and neck SCC . Here, the sensitivity of
[47]
ultrasound for level I was 80%, compared with 38% of CT, whereas specificity was 92% for CT and 80% for
ultrasound .
[47]
SURGICAL IMPLICATIONS
Over half of the patients with head and neck SCC experience locoregional recurrence, which is associated
[48]
with poor outcomes, and only about 10%-15% of patients who have locoregional relapses can be salvaged .
In the clinical experience of head and neck surgeons, the occurrence of relapses in the perimandibular area
is not infrequent, and distinguishing between nodal or local relapses is often not easy. These relapses are
challenging to treat and frequently require the sacrifice of a portion of the mandible. PMN metastasis is
often undetectable due to the fact that they tend to be micrometastases that go unnoticed in routine clinical
and radiological examination. The data therefore suggest that they should be removed in all cases