10.14639/0392-100X-suppl.1-41-2021-15
Non-melanoma Skin cancer, including cutaneous squamous cell carcinoma and basal cell carcinoma, is the most common form of malignancy in the Caucasian population, and the skin of the head and neck is the site most involved. They should not be underestimated; in particular, high-risk lesions and advanced skin cancers require accurate diagnostic work up, aggressive surgical treatment and should be managed by the head and neck surgeon, the dermatologist and the plastic surgeon. Cutaneous head-neck malignancies are often overlooked or not routinely treated with a multidisciplinary surgical approach. Similarly, for primary head and neck cancers with involvement of surrounding skin, the involvement of the dermatologist and the plastic surgeon could better define an adequate diagnosis and treatment planning. The management of these patients presents both therapeutic and ethical problems, because the poor prognosis is burdened by facial disfigurement, open malodorous wounds and intractable pain. Therefore, in patients with advanced disease that is not candidate to radical surgery, palliative surgery with flap reconstruction could take place and could be proposed to improve quality of life.
application/xml
1827-675X
1696
en
Marzia Salgarello
https://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
palliative surgery
When is a surgical multidisciplinary approach required in the management of head and neck non-melanoma skin cancer and in advanced head and neck pathologies involving skin?
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https://www.actaitalica.it/
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Annual congress report
2021-05-14
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2021-05-14
2021-05-14
145-157
1
Marzia Salgarello
2021/05/14
10.14639/0392-100X-suppl.1-41-2021-15
145
Otorhinolaryngology and Head-Neck Surgery Unit, “A. Gemelli” Hospital Foundation IRCCS, Catholic University of the Sacred Heart, Rome, Italy
1827-675X
palliative surgery
157
When is a surgical multidisciplinary approach required in the management of head and neck non-melanoma skin cancer and in advanced head and neck pathologies involving skin?
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ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41(SUPPL.1):S145-S157; doi: 10.14639/0392-100X-suppl.1-41-2021-15




When is a surgical multidisciplinary approach required
in the management of head and neck non-melanoma
skin cancer and in advanced head and neck
pathologies involving skin?
Quando è indicato un approccio chirurgico multidisciplinare nel management
dei tumori primitivi cutanei non melanocitari della testa e del collo e dei tumori
localmente avanzati del distretto testa-collo con interessamento della cute?
Giovanni Almadori1, Eugenio De Corso2, Stefano Settimi2, Giovanni Di Cintio2, Dario Antonio Mele2, Francesca Brigato2,
Gaetano Paludetti2, Marzia Salgarello3
1
  Cervico-Facial Oncological Surgery Unit, “A. Gemelli” Hospital Foundation IRCCS, Catholic University of the Sacred Heart, Rome, Italy;
2
  Otorhinolaryngology and Head-Neck Surgery Unit, “A. Gemelli” Hospital Foundation IRCCS, Catholic University of the Sacred Heart, Rome,
Italy; 3 Plastic and Reconstructive Surgery Unit, “A. Gemelli” Hospital Foundation IRCCS, Catholic University of the Sacred Heart, Rome, Italy


SUMMARY
Non-melanoma Skin cancer, including cutaneous squamous cell carcinoma and basal cell car-
                                                                                                      Received: September 29, 2020
cinoma, is the most common form of malignancy in the Caucasian population, and the skin of
                                                                                                      Accepted: January 14, 2021
the head and neck is the site most involved. They should not be underestimated; in particular,
high-risk lesions and advanced skin cancers require accurate diagnostic work up, aggressive sur-
                                                                                                      Correspondence
gical treatment and should be managed by the head and neck surgeon, the dermatologist and the         Eugenio De Corso
plastic surgeon. Cutaneous head-neck malignancies are often overlooked or not routinely treated       Otorhinolaryngology, Head and Neck Surgery,
with a multidisciplinary surgical approach. Similarly, for primary head and neck cancers with         “A. Gemelli” Hospital Foundation IRCCS, Catholic
involvement of surrounding skin, the involvement of the dermatologist and the plastic surgeon         University of the Sacred Heart
could better define an adequate diagnosis and treatment planning. The management of these pa-         largo A. Gemelli 8, 00168 Rome, Italy
tients presents both therapeutic and ethical problems, because the poor prognosis is burdened by      E-mail: eugenio.decorso@policlinicogemelli.it
facial disfigurement, open malodorous wounds and intractable pain. Therefore, in patients with
advanced disease that is not candidate to radical surgery, palliative surgery with flap reconstruc-   Funding
tion could take place and could be proposed to improve quality of life.                               None.

KEY WORDS: non-melanoma skin cancer, head and neck cancer, multidisciplinary team,                    Conflict of interest
head and neck reconstruction, palliative surgery                                                      The Authors declare no conflict of interest.

RIASSUNTO                                                                                               How to cite this article: Almadori G, De Corso
I tumori della pelle non melanocitari, che comprendono soprattutto il carcinoma squamo-                 E, Settimi S, et al. When is a surgical multi-
cellulare e il carcinoma basocellulare, sono i tumori maligni più frequenti nella popolazio-            disciplinary approach required in the manage-
ne caucasica, e la cute della testa e del collo rappresenta la sede più coinvolta. Tali tumori          ment of head and neck non-melanoma skin
non dovrebbero essere sottovalutati, in particolare le cosiddette lesioni ad alto rischio e i           cancer and in advanced head and neck patholo-
tumori cutanei avanzati richiedono un iter diagnostico più accurato e un trattamento chi-               gies involving skin? Acta Otorhinolaryngol
rurgico più aggressivo, che dovrebbe essere gestito coinvolgendo il chirurgo testa-collo, il            Ital 2021;41(SUPPL.1):S145-S157. https://doi.
                                                                                                        org/10.14639/0392-100X-suppl.1-41-2021-15
dermatologo e il chirurgo plastico. Le neoplasie primitive cutanee del distretto testa-collo
sono spesso trascurate e non sono routinariamente discusse in seno a teams chirurgici mul-
                                                                                                      © Società Italiana di Otorinolaringoiatria
tidisciplinari. Allo stesso modo, per i tumori primari della testa e del collo con infiltrazione      e Chirurgia Cervico-Facciale
cutanea, il coinvolgimento del dermatologo e del chirurgo plastico può più efficacemente
definire la diagnosi e pianificare il trattamento. La gestione di questi pazienti pone proble-                       OPEN ACCESS
mi sia terapeutici che etici, perché la prognosi infausta è gravata da importanti inestetismi
facciali, ferite aperte maleodoranti e dolore intrattabile. Pertanto, anche nei pazienti con          This is an open access article distributed in accordance with
                                                                                                      the CC-BY-NC-ND (Creative Commons Attribution-Non-
malattia avanzata non suscettibile di chirurgia radicale, la chirurgia potrebbe ugualmente            Commercial-NoDerivatives 4.0 International) license. The
trovare spazio, ma con finalità palliativa, al fine di migliorare la qualità di vita.                 article can be used by giving appropriate credit and mentio-
                                                                                                      ning the license, but only for non-commercial purposes and
PAROLE CHIAVE: tumori della cute non melanocitari, tumori testa-collo, trattamento                    only in the original version. For further information: https://
multidisciplinare, ricostruzione del distretto testa-collo, chirurgia palliativa                      creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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Introduction                                                      with very advanced head and neck tumours, originating or
                                                                  extending to the skin, may be considered not eligible for a
Non-melanoma Skin Cancer (NMSC) is the most common                radical surgery (due to vascular infiltration, distant metas-
form of malignancy in the Caucasian population, and the           tasis or extension to the skull base), but they may benefit
skin of the head and neck is the site most involved. Basal        from a “palliative surgery”, a concept introduced about fifty
cell carcinoma (BCC) and cutaneous squamous cell car-             years ago 4. Thanks to advances in reconstructive surgery,
cinoma (CSCC) make up the majority of these tumours 1,            in particular the use of regional and free flaps, palliative
while a less frequent histotype is the neuroendocrine tu-         resection and reconstruction is now a reasonable treatment
mor that arise from Merkel cells, an insidious carcinoma          option 5.
originating in most of cases on the facial skin. Early stages     A narrative review of the literature was performed to thor-
should not be undervalued because of their propensity to          oughly investigate on both primary head and neck skin
local invasion and heterogeneity; therefore, inadequate           cancer and involvement of facial skin by head and neck
treatment can lead local recurrences and uncontrolled skin        tumours, in particular to highlight when surgical multidis-
cancer requiring complex surgery, high patient morbidity          ciplinary approach is recommended.
and even death 2. Finally, personalized treatment should be
tailored taking into account the best oncological outcome
and the best aesthetic and functional results.                    Primary skin cancers
The anatomic complexity of the head and neck district and         Non-melanoma skin cancers
the overlap between the operating fields of the ENT sur-          Every year about 3.5 million of NMSC are treated all over
geon, the plastic surgeon and the dermatologist, lead to an       the world and almost 75,000 new cases are diagnosed annu-
even more complex surgical approach to NMSC; neverthe-            ally 6. Skin cancer rates have been increasing since the ’70s,
less, the histological heterogeneity of tumors involving the      passing from an incidence rate of 8 per 100,000 to 31 per
skin of the scalp, the face and the neck, often requires a        100,000 nowadays, with an increase of about 290% 7. Risk
surgical multidisciplinary approach to these lesions, with        factors for skin malignancy include cumulative sun expo-
the aim of a balanced outcome in terms of oncological radi-       sure and/or sunburns, Fitzpatrick skin types I and II, ion-
cality and aesthetical result. Usually, the dermatologist is      izing radiation, acquired or inherited immunosuppression,
involved in the management of small primary skin tumors,          genetic factors, presence of areas of chronic inflammation
due to his predominant role in the diagnosis of these le-         after burn or trauma. UVB radiations (290 to 320 nm) may
sions; however, a complete dermatologic evaluation of the         cause direct DNA damage and are involved in aetiology of
skin in all districts is often required by other specialists in   NMSC. In particular, intense and intermittent sun exposure
case of systemic and diffuse tumors, such as Merkel cell          during first years of life represent a risk factor for BCC and
carcinoma. On the other hand, advanced primary NMSCs              cumulative UV radiation dose seems to be associated with
of the head and neck, with their infiltrative growth pattern,     CSCC 8.
may involve subcutaneous tissue, muscle, bones, peripheral        The Basal Cell Carcinoma (BCC) is an epithelial malig-
nerves, and lymph nodes, thus requiring an ENT surgical           nancy characterized by slow growth, that develops from
approach. Finally, primary head and neck cancers origi-           epidermis basal layer. It has an age-adjusted incidence and
nating from the epithelial surface of the upper aerodiges-        prevalence of 226 and 343 per 100,000 persons per year,
tive tract (UADT) and from other structures of the head           respectively; it presents locally destructive behaviour, but
and neck district, such as salivary glands and bone, may          it rarely gives metastasis, occurring in approximately 0.003
extend to surrounding structures and involve the skin of          percent to 0.1 percent of cases 9. BCC is the most common
the face and the neck; in these advanced cases, the coop-         skin malignancy all over the world, occurring in almost 80%
eration between the ENT surgeon and the plastic surgeon           of cases in head and neck region, with high prevalence on
often represents the most convenient approach in order to         nose skin 10. BCC is associated with intermittent recreation-
perform a radical and functional resection of the tumours         al sun exposure, and genetic factors such as mutations in
and a concurrent reconstruction with favorable aesthetic re-      cell-cycle control genes (i.e. TP53, PTCH1, Sonic Hedge-
sults 3. The management of these patients is complex and          hog pathway) are common. Genetic syndromes like Gorlin
challenging for all the specialists involved and it poses both    syndrome and xeroderma pigmentosum also play a role in
therapeutic and ethical problems, due to the extended re-         some BCCs 11. Types of BCC are nodular (most common
section and the reduction in terms of quality of life after       variant), superficial multifocal, sclerosing, infiltrative and
such a surgery. However, although the oncologic radicality        morpheaform. About 20% of BCC show infiltrative growth
should always be the primary aim of the surgeon, patients         pattern with high recurrence rate. Morpheaform BCC pre-



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sents as a yellow plaque, similar to a scar, with indistinct      expression profiling and molecular analyses, has been hy-
margins, that extends widely intradermally. Ulcus terebrans       pothesized to originate from Merkel cell precursors (po-
is another aggressive type of BCC that invades underlying         tentially derived from epidermal stem cells or hair follicle
structures such as large vessels, bones and meninges; it          stem cells), pre-B cells, pro-B cells or dermal fibroblasts.
could be fatal due to haemorrhage or infection 12.                Because normal Merkel cells are terminally differentiated
Cutaneous Squamous Cell Carcinoma (CSCC) arises from              and do not undergo cell division, they are unlikely to be the
keratinocytes with a locally destructive and metastatic po-       cell of origin for MCC. Merkel cells derives embryologi-
tential. It affects 100/100,000 men and 50/100,000 women          cally from neural crest cells and are receptor cells to soma-
per year, representing the second most common skin can-           tosensory afferents for touch discrimination. MCC has an
cer. Risk factors are similar to BCC, but specific factors are    occurrence rate of 0.6/100,000 people per year. The skin
HPV infections, most commonly correlated to HPV 16 and            face is the most common location at about 25%. The risk
18, but also types 31, 33, and 38 have been implicated 13.        factors are sun exposure, immunosuppression and poly-
The most common gene mutations are TP53, mutations in             omavirus (MCPyV) infection; this virus can be found inte-
the RAS family of human oncogenes (HRAS, KRAS) and                grated in the genome of more than 80% of tumours 19. MCC
PTCH1. Deletions in CSCC involve several chromosomes,             carcinogenesis can be initiated by the clonal integration of
including 3p, 9p, 9q, 13q, 17p and 17q, with a higher de-         the MCPyV genome or UV-mediated DNA damage caused
gree of genomic instability compared with BCC and more            by chronic exposure to sunlight, since UV exposure could
frequent presence of aneuploid cells 14. The develop of SCC       also play a part in viral carcinogenesis by causing local im-
follows the classic pattern of cancers from precursor le-         munosuppression. UV radiation induces the expression of
sions (mild, moderate, severe dysplasia) to tumour progres-       inflammatory mediators and functional alterations in the
sion, and subsequent metastasis. Histologic grades range          antigen-presenting dendritic cells, which result in a cascade
from well differentiated, that show keratinization and der-       of events that modulate immune sensitivity. MCC clinical-
mal invasion of round tumour margin, to poorly differenti-        ly presents as a nodular lesion with rapid growth pattern,
ated without keratinization and cellular organization, with       nontender, fleshcolored or blue-red colored and, due to the
blurred borders and projections into surrounding tissues 15.      nonspecific presentation, clinical diagnosis of MCC is often
The risk of developing lymph node metastasis in patients          delayed. Treatment consists of surgical excision with wide
with CSCC is 3 to 5%, but increases in high-risk patients         margins and particular attention to deep margin. Postopera-
with high rates (> 10 to 20%) 16. Regional nodes can be           tive radiation is becoming accepted as the standard treat-
divided into two groups: parotid (preauricular and parotid        ment. Before the advent of immunotherapy, no evidence
tail) and cervical nodes (levels I to V). The site of a CSCC      supported adjuvant chemotherapy benefit 20. However, over
is a determinant of the potential lymph node metastasis.          the last few years, the presence of PD-1 and PD-L1 has
For lesions in the lateral aspect of the head, metastases are     been demonstrated within tumour and immune cells. For
commonly identified in parotid, level II and external jugu-       the checkpoint inhibitors pembrolizumab and avelumab,
lar nodes. Parotid nodes represent the first echelon of lym-      responses of about 50% have been shown 21.
phatic from the forehead, anterior scalp, temple, face and        Dermatofibrosarcoma Protuberans (DFSP) is a rare low-
ear. Facial lesions tend to metastasize also to level I and II;   grade soft tissue sarcoma; it is locally aggressive, with high
while anterior lesions of the scalp, ear, temple, and fore-       rates of local recurrence but less than 5% tend to metasta-
head usually metastasize also to level II. Lesions posterior      size. DFSP affects 0.8 to 4 cases per million annually and
to the tragus usually metastasize to level V or to occipital      most commonly arises in the 3rd decade of life, but also
nodes. Drainage to contralateral nodes occurs in 10% of           pediatric cases occur. Only 14% of DFSP involve head and
patients, in particular in midline cancers 17.                    neck. Patients with unresectable positive margins or meta-
Bowen disease, also referred as squamous cell carcinoma           static disease may gain benefit from radiation or the tyros-
in situ, appears as a well demarcated, erythematous plaque        ine kinase inhibitors 22.
that slowly enlarges. Ulceration and induration are hall-         Malignant tumors of the adnexa (Fig. 2) derive from the
marks of the transformation to SCC. Progression to inva-          pilosebaceous unit and sweat glands, eccrine and apocrine.
sive SCC occurs at 5% per lesion per year. Treatment op-          Among them, tumours that show a predilection toward
tions include excision, electrodessication, and curettage 18.     head and neck district are sebaceous carcinoma, primary
                                                                  cutaneous mucinous carcinoma, microcystic adnexal car-
Non-epithelial skin cancers                                       cinoma and malignant cylindroma. Risk factors include
Merkel cell carcinoma (MCC) (Fig. 1) is a neuroendo-              previous irradiation and immunosuppression. Neck nodal
crine tumour that, on the basis of histomorphology, gene          metastasis are reported in 8% of cases but are often under-



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Figure 1. Eighty-three years old woman with parotid gland metastases of a cutaneous Merkel-cell carcinoma of the upper eyelid (treated 1 year before); the
patient presented a clinical palsy of the inferior branches of facial nerve. (A) external appearance of the tumour; (B) harvesting of the ALT flap with preservation
of the vascularized femoral-cutaneous sensory nerve for facial nerve reconstruction; dimensions: 9 x 8 cm; (C) insetting of the flap and distal anastomosis of the
vascularized femoral-cutaneous nerve to the marginalis mandibulae nerve; the proximal anastomosis was performed on the inferior branch of facial nerve; (D) final
result after vascular anastomosis; (E) functional result with smile after 6 months.



evaluated; distant metastasis incidence is quite rare. Local                        history and physical examination with palpation of draining
recurrence rate is about 6% after surgical excision. Surgery                        lymph node basins, tissue biopsy (i.e., shave, punch, or ex-
is the gold-standard, RT can be useful as adjuvant treatment                        cisional) remains the standard of care for diagnosing non-
for positive margins or presence of perineural invasion 23.                         melanoma skin cancers 24. However, in case of the sampling
                                                                                    error with punch and shave biopsies, in 11 to 19% of cases
Diagnosis of primary skin cancers                                                   a more aggressive histologic subtype may be missed 25,26.
Diagnosis of primary skin cancers is usually clinical, with                         Patients commonly report a remote history of a previously
subsequent histological confirmation. Following a thorough                          resected cutaneous malignancy, which may explain new-on-



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Figure 2. Seventy-nine years old woman with sebaceous carcinoma of the skin, extended to the external ear and parotid gland. (A) external appearance of the
large tumour;(B) surgical resection of the tumour and total parotidectomy (with facial nerve preservation) extended to the lobule and the concha of the external ear;
(C) ALT flap harvesting; dimensions: 13 × 10 cm; (D) insetting of the flap and anastomosis on the external carotid artery and internal jugular vein (double venous
anastomosis); (E) Final result after 1 month.



set neck adenopathy, facial paresthesia, or a facial nerve pa-                       ferential diagnosis 27. MCC usually spreads to the regional
ralysis. Complaints that suggest perineural invasion include                         lymph nodes; thus, sentinel lymph node biopsy (SLNB; that
facial weakness, hypesthesia, dysesthesia, and paresthesia.                          is removal and examination of the sentinel node) represents
A recurrent lesion may present as a slow growing subcuta-                            an important staging procedure and if the lymph nodes of the
neous mass that invades the deep facial or neck muscula-                             draining basin are clinically negative, it should be considered
ture. A complete dermatologic examination is necessary for                           and planned at the same time as the wide local excision. The
the patient with NMSC in order to find out eventual second                           presence of occult nodal metastasis, in fact, is a strong prog-
primary tumours, especially in the suspect of a MCC, and                             nostic factor and clinically occult nodal micrometastases are
dermoscopic examination of the lesions can be helpful in dif-                        present in about 30% of patients 21.



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The most widely adopted staging system for staging CSCC                             extending beyond subcutaneous fat (into deeper layers, such
and BCC is the TNM Classification of Malignant Tumours,                             as the fascia, muscle, perichondrium, and periosteum) have
8th Edition (Tab. I). Moreover, basing on clinical and path-                        an 11-fold higher risk of metastasis compared with more
ological features, both CSCC and BCC are classified in                              superficial tumours 29; the presence of poor differentiation
Low-Risk Lesions and High-Risk Lesions, according to the                            is associated with worse prognosis than well-differentiated
risk of local relapse and locoregional diffusion. High-Risk                         CSCC, in particular local recurrence risk (7 vs 2%) and
BCC and CSCC require more accurate diagnostic work up                               metastatic risk (7 vs 3%) 30. Primary skin cancers involv-
and more aggressive surgical treatment 28. As showed in                             ing sun-exposed areas of the head and neck do not usually
Table II and Table III, BCC and CSCC share most of the                              require imaging for size assessment. In particular, low-risk
prognostic factors, such as: location, poorly defined bor-                          T1 and T2 tumours rarely exhibit nodal metastasis and are
ders, recurrent lesion, immunosuppressed patient, site of                           staged primarily by clinical examination without additional
prior radiotherapy, perineural involvement, and aggressive                          imaging. However, the presence of adverse prognostic fac-
histologic subtype. Squamous cell carcinomas have a few                             tors resulting from pathological examination, including
unique high-risk features, including chronic inflammatory                           those that increase T stage or those that increase risk clas-
process (e.g., Marjolin ulcer), rapidly growing tumours,                            sification, is often an indicator of aggressive behavior and
neurologic symptoms, poor differentiation, depth greater                            may indicate additional imaging to assess occult nodal me-
than 6 mm, lymphovascular invasion. For example, CSCC                               tastasis. These imaging modalities may include computed



Table I. TNM Staging of BCC and CSCC, AJCC 8th Edition.
                                                                            T-staging
 Tx      Primary tumor cannot be assessed
 T0      No evidence of primary tumor
 Tis     Carcinoma in situ
 T1      Tumor smaller than or equal to 2 cm in greatest dimension
 T2      Tumor larger than 2 cm, but smaller than or equal to 4 cm in greatest dimension
 T3      Tumor larger than 4 cm in maximum dimension or minor bone erosion or perineural invasion or deep invasion
 T4a     Tumor with gross cortical bone/marrow invasion
 T4b     Tumor with skull base invasion and/or skull base foramen involvement
                                 N-staging BCC                                                                N-staging CSCC
 NX      Regional lymph nodes cannot be assessed                                   NX    Regional lymph nodes cannot be assessed
 N0      No regional lymph node metastasis                                         N0    No regional lymph node metastasis
 N1      Metastasis in a single ipsilateral lymph node, 3 cm or smaller in         N1    Metastasis in a single ipsilateral lymph node, 3 cm or smaller in
         greatest dimension and ENE (-)                                                  greatest dimension and ENE (-)
 N2a     Metastasis in a single ipsilateral node larger than 3 cm but not larger   N2a   Metastasis in a single ipsilateral node 3cm or smaller in greatest
         than 6 cm in greatest dimension and ENE (-)                                     dimension and ENE (+) or Metastasis in a single ipsilateral node
                                                                                         larger than 3 cm but not larger than 6 cm in greatest dimension and
                                                                                         ENE (-)
 N2b     Metastasis in multiple ipsilateral nodes, none larger than 6 cm in        N2b   Metastasis in multiple ipsilateral nodes, none larger than 6 cm in
         greatest dimension and ENE (-)                                                  greatest dimension and ENE (-)
 N2c     Metastasis in bilateral or contralateral nodes, none larger than 6 cm     N2c   Metastasis in bilateral or contralateral nodes, none larger than 6 cm
         in greatest dimension and ENE (-)                                               in greatest dimension and ENE (-)
 N3a     Metastasis in a lymph node larger 6 cm in greatest dimension and          N3a   Metastasis in a lymph node larger 6 cm in greatest dimension and
         ENE (-)                                                                         ENE (-)
 N3b     Metastasis in any node(s) and ENE (+)                                     N3b   Metastasis in a single ipsilateral node larger than 3 cm in greatest
                                                                                         dimension and ENE (+); or multiple ipsilateral, contralateral, or
                                                                                         bilateral nodes any with ENE (+); or a single contralateral node of any
                                                                                         size and ENE (+)
                                                                           M-staging
 M0      No distant metastasis
 M1      Distant metastasis




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Table II. BCC: prognostic factors for local recurrence or metastases.
                                                                                       Low-risk                                                     High-risk
 Clinical features
    Location/size                                                                 Area L < 20 mm                                                Area L > 20mm
                                                                                  Area M < 10 mm                                                Area M > 10mm
                                                                                                                                                     Area H
   Borders                                                                           Well defined                                                Poorly defined
   Primary vs recurrent                                                               Primary                                                      Recurrent
   Immunosuppression                                                                  Negative                                                      Positive
   Site of Prior RT                                                                   Negative                                                      Positive
 Pathological features
   Subtype                                                                       Nodular, superficial                                     Aggressive growth patterns
   Perineural involvement                                                            Negative                                                      Positive
Area H: “mask areas” of face (central face, eyelids, eyebrows, periorbital, nose, lips [cutaneous and vermilion], chin, mandible, preauricular and postauricular skin/sulci, temple, and
ear), genitalia, hands, and feet
Area M: cheeks, forehead, scalp, neck, and pretibia
Area L: trunk and extremities (excluding hands, nail units, pretibia, ankles, and feet)



Table III. CSCC: prognostic factors for local recurrence or metastases.
                                                                                       Low-risk                                                     High-risk
 Clinical features
    Location/size                                                                 Area L < 20 mm                                                Area L > 20 mm
                                                                                  Area M < 10 mm                                                Area M > 10 mm
                                                                                                                                                     Area H
   Borders                                                                           Well defined                                                 Poorly defined
   Primary vs recurrent                                                               Primary                                                       Recurrent
   Immunosuppression                                                                  Negative                                                       Positive
   Site of Prior RT or chronic inflammatory process                                   Negative                                                       Positive
   Rapidly growing tumours                                                            Negative                                                       Positive
   Neurologic symptoms                                                                Negative                                                       Positive
 Pathological features
   Degree of differentiation                                             Well or moderately differentiated                                    Poorly differentiated
   Acantholytic, adenosquamous, desmoplastic or                                     Negative                                                        Positive
   metaplastic (carcinosarcomatous) subtypes
   Depth: thickness or level of invasion                       < 6 mm and no invasion beyond subcutaneous fat                  > 6 mm or invasion beyond subcutaneous fat
    Perineural, lymphatic, or vascular involvement                               Negative                                                       Positive
Area H: “mask areas” of face (central face, eyelids, eyebrows, periorbital, nose, lips [cutaneous and vermilion], chin, mandible, preauricular and postauricular skin/sulci, temple, and
ear), genitalia, hands, and feet
Area M: cheeks, forehead, scalp, neck, and pretibia
Area L: trunk and extremities (excluding hands, nail units, pretibia, ankles, and feet)



tomography (CT) of the neck and/or magnetic resonance                                          sion, and orbital disease. Patients with bulky lymph node
(MR) imaging with contrast enhancement. Stage III-IV                                           metastasis should also be evaluated for distant metastasis
cancers routinely undergo imaging prior to therapy, includ-                                    with a CT scan of the chest 31,32.
ing a neck CT and/or MR imaging with contrast enhance-
ment, as well as other modalities, such as a positron emis-                                    Management of primary skin cancers
sion tomography (PET)-CT scan. CT is generally preferred                                       Low-risk NMSC and small MCC could be managed by a
over MRI for evaluating the primary tumour, the status of                                      single specialist (usually plastic surgeon or dermatologist),
the lymph nodes, and the presence of bony invasion. MRI                                        without multidiciplinary surgical approach. Surgical exci-
is better for the detection of perineural spread, dural inva-                                  sion is the gold standard and margin assessment is manda-



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tory. In this way, 5-years disease-free survival is 95-98%                         skin lesions, including certain highly aggressive tumours,
for BCC and 92% for CSCC 33,34. Management of high-risk                            such as those invading bone, major nerve branches, or with
NMSC and larger MCC is more complex. Surely, the treat-                            involvement of the parotid gland, are typically best ap-
ment of choice is surgical removal, whether by convention-                         proached with a multidisciplinary surgical team, involving
al surgery or Mohs micrographic surgery. Recommended                               the head and neck surgeon 36,37. Lesions with nodal spread
margins range from 4 to 6 mm for low-risk BCC and CSCC                             at diagnosis should be multidisciplinary treated as well.
to 10 to 15 mm for high-risk lesions 35. These wider mar-                          Nevertheless, cutaneous head-neck malignancies are often
gins are impractical for all regions of the head and neck, but                     overlooked or not routinely discussed in a multidisciplinary
only for those with such substantial tissue laxity as to allow                     surgical approach involving both the head and neck sur-
closure of resultant large defects. Therefore, very extensive                      geon and the dermatologist and the plastic surgeon 38.




Figure 3. Fifty-four years old man with adenocarcinoma of the parotid gland extended to the skin of the parotid region. (A) external appearance of the tumour;
(B) harvesting of the double pedicled chimeric ALT flap with a skin paddle and vastus lateralis paddle; dimensions: 12 x 12 cm; (C) insetting of the chimeric flap
and vascular anastomosis; (D) final result after 1 month.



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Surgical management of all skin malignancies is dictated         reported incidence of 9-11% 44. It is usually associated with
by the location and extent of the tumour. Small lesions of       locally advanced diseases, either primary head and neck tu-
the face and neck can be excised elliptically in the plane       mours and recurrent ones. Therefore, skin invasion always
of skin tension with excellent aesthetic results and surgical    indicates a T4 tumour, regardless of tumour site (major sal-
defects resulting from resection can be closed primarily af-     ivary glands, oral cavity, paranasal sinuses) and it is a sign
ter wide undermining. However, skin grafts are best suited       of poor outcome. In fact, patients with direct skin invasion
to the part of the face with minimal facial motion, such as      have a 7-months median survival. According to the same
the tip or lateral aspect of the bridge of the nose, the tem-    authors, involvement of facial skin is prognostically better
ple or the parotid region where facial movement is minimal       for duration of survival than involvement of neck skin 45.
with excellent cosmetic results (Fig. 3). Local flaps are pre-
ferred to repair larger surgical defects or those requiring      Diagnosis, staging and prognostic factors
full-thickness reconstruction, because they provide the best     Diagnosis of head and neck tumours involving the skin,
functional and aesthetic outcome. Primary closure of the         is initially clinical based on detailed history and accurate
donor site defect usually can be accomplished with ease          physical examination. If a primary tumour is identiﬁed,
with proper planning of local skin flaps. The blood supply       its site of origin, visual characteristics, palpatory ﬁndings,
of facial skin and soft tissues is extremely rich because the    and physical signs of local extension and invasion of adja-
terminal branches of the external carotid artery provide a       cent structures should be noted, and biopsy should be per-
major source of blood to the facial skin, which allows use of    formed. Imaging plays an integral role in the evaluation of
axial flaps. In addition, an extensive subdermal anastomot-      head and neck tumours. Imaging can help deﬁne the extent
ic network facilitates the use of random flaps. Examples of      of the primary tumour as well as the presence, volume, and
axial skin flaps are nasolabial, glabellar, Mustardé cheek,     location of regional and distant metastases. In addition, im-
and temporal forehead. Examples of random flaps are cer-         aging is helpful in detecting synchronous or metachronous
vical, rhomboid, and bilobed. If local flaps are not suita-      primary tumours that may not be evident clinically. CT and
ble, consideration should be given to regional or free flaps     MRI can complement each other to enhance the anatomic
for appropriate repair of large surgical defects (Figs. 4,5).    deﬁnition of selected tumours. PET/TC is particularly help-
Moreover, we have to highlight the role of neck dissection       ful in evaluating patients with advanced head and neck can-
in the management of skin cancer. In case of cN+, neck dis-      cers for distant metastases and post-therapy recurrence 46.
section is mandatory; in case of cN0, a recent manuscript        When a surgical reconstruction with locoregional or micro-
stated that elective neck dissection should be performed in      vascular free flap is required, in case of large resection, an
case of T3-T4 disease, regardless of other risk factors 39.      ultrasound perforator assessment is needed by a radiolo-
                                                                 gist experienced in the evaluation and study of perforator
Head and neck cancers with skin                                  vessels. Radiologist using Doppler technique performs an
                                                                 analysis of best perforator, selecting the vessel with the
involvement                                                      largest caliber, and marking on the skin its fascial emer-
Head and neck squamous cell carcinomas (HNSCC) repre-            gency site and subcutaneous direction, in order to evalu-
sent a group of aggressive tumors, genetically complexed         ate the orientation of cutaneous island flap, creating a pre-
and difficult to treat. Males are affected significantly more    operative mapping in order to optimize the reconstructive
than females, with a ratio ranging from 2:1 to 4:1, between      procedure 47-49.
50 and 70 years old 40. Exposition to carcinogens, e.g. to-
bacco smoke and alcohol abuse, and human papilloma               Management of head and neck cancer with skin involvement
virus (HPV) infection are considered the most important          Surgical management of head and neck malignancies
etiological factors 41. Approximately 30 to 40% of patients      with skin involvement poses several problems about the
with HNSCC present with stage I or II (early stage disease).     management of these patients because the poor progno-
Five-year overall survival in patients with stage I or II dis-   sis is burdened by facial disfigurement, open malodorous
ease is typically from 70 to 90 percent. Loco-regionally ad-     wounds, and intractable pain. Chemoradiation is often con-
vanced (stage III-IV) HNSCC is associated with a high risk       sidered the standard of care for patients with inoperable
of both local recurrences and distant metastases. Combined       disease. However, it does not adequately address the above-
modality approaches (surgery, RT, and/or chemotherapy)           mentioned problems related to skin involvement, whereas
are generally required to optimize the chances for long-         extensive skin involvement is often amenable to surgery.
term disease control 42,43. Skin involvement by non-cutane-      Moreover, open wounds treated with chemoradiation will
ous head and neck cancer is an infrequent finding, with a        often enlarge and become more problematic. Yamazaki et



                                                                                                                                 S153
G. Almadori et al.




Figure 4. Young thirty-five years old woman with squamous cancer of the upper lip and buccal mucosa extended to the mandible and the skin of cheek. (A) ex-
ternal appearance of the large tumour; (B) harvesting of the osteocutaneous fibula flap; dimensions: 20 x 8 cm; (C) result after the tumour resection; the mandible
titanium plate was applied before the resection in order to guide the osteotomies; (D) mandible reconstruction with the fibula flap and face resurfacing with a large
DIEP flap; dimensions: 28 x 10 cm; (E) immediate final result.



al. aimed to elucidate the influence of skin invasion in pa-                         option offering good oncological outcomes (in terms of
tients with recurrent head and neck cancer treated with re-                          overall survival, relapse and metastasis free survival and
irradiation using stereotactic radiotherapy. They described                          salvageability) and functional results. At this purpose, a
that the skin invasion positive group showed a lower re-                             close cooperation between otolaryngologist and plastic
sponse rate, a lower local control and a lower progression                           surgeon should be encouraged. In patients with persistent
free survival than the skin invasion negative group 50. In                           or recurrent disease that is not amenable to radical surgery,
this scenario, thanks to reconstructive advances by use of                           palliative surgery with reconstruction with regional or free
microvascular free flaps, perforator or not, single or mul-                          flaps could take place and could be proposed to improve
tiple, salvage surgery with curative intent is an effective                          quality of life and quality of death. In a pioneering case



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                                                                                             Management of advanced head and neck cancer involving facial skin




Figure 5. Sixty-four years old man with relapse of oral cavity cancer extended to the left maxillary sinus and the zygomatic skin. (A) external appearance of the
tumour; (B) surgical result after extended total left maxillectomy; (C) insetting of the osteocutaneous fibula flap; dimensions: 17 x 7 cm; cutaneous paddle was
used for the reconstruction of the oral cavity; (D) a second ALT flap was used to resurface the zygomatic region; (E) detail on the anastomosis of both the pedicles
on the external carotid artery and jugular vein, with fat as stabilization; (F) final result after 1 month.



series, reported in 1993, in which 13 patients underwent                            common being the radial forearm (78%). With this form
palliative resection, there was an increased survival of 20                         of management, the authors reached a mean survival of 23
months beyond the median survival of the other patients.                            months, and six patients were still alive at follow up of 4.5
Thanks to the common use of microvascular free flaps in                             years 52. Furthermore, this approach does not obviate the
head and neck surgery, the prognosis of these patients has                          opportunity to undergo further chemoradiation.
improved, as well. Jang et al. reported a median survival
of 9.5 months (range: 1-30 months) 51. Stravianos et al. re-
viewed a case series of 31 patients: all patients underwent
                                                                                    Conclusions
surgical resection with free flap reconstruction, the most                          Multidisciplinary surgical approach in the management of



                                                                                                                                                            S155
G. Almadori et al.




Table IV. Recommendations.                                                        10
                                                                                       Lee KJ, Soyer HP. Cutaneous keratinocyte cancers of the head and
                                                                                       neck: epidemiology, risk factors and clinical, dermoscopic and reflec-
 Indication                                   Surgical multidisciplinary
                                                                                       tance confocal microscopic features. Oral Oncol 2019;98:109-117.
                                                      approach
                                                                                       https://10.1016/j.oraloncology.2019.09.019
    Low-risk NMSC                                      Optional                   11
                                                                                       Ouyang YH. Skin cancer of the head and neck. Semin Plast Surg
    Recurrent NMSC                                  Recommended                        2010;24:117-126. https://doi.org/10.1055/s-0030-1255329
    Very extensive NMSC (T3, T4a, T4b)          Strongly recommended              12
                                                                                       Karagas MR, Stukel TA, Greenberg ER, et al. Risk of subsequent ba-
                                                                                       sal cell carcinoma and squamous cell carcinoma of the skin among
    Nodal metastasis at diagnosis               Strongly recommended
                                                                                       patients with prior skin cancer. Skin Cancer Prevention Study Group.
    Head and neck cancer with skin              Strongly recommended                   JAMA 1992;267:3305-3310.
    involvement                                                                   13
                                                                                       Jemal A, Simard EP, Dorell C, et al. Annual Report to the Nation on
                                                                                       the Status of Cancer, 1975-2009, featuring the burden and trends in
                                                                                       human papillomavirus(HPV)-associated cancers and HPV vaccina-
                                                                                       tion coverage levels. J Natl Cancer Inst 2013;105:175-201. https://
head and neck carcinomas involving the skin and high-risk                              doi.org/10.1093/jnci/djs491
primary skin cancer of head and neck district, is strongly                        14
                                                                                       Ashton KJ, Weinstein SR, Maguire DJ. Chromosomal aberrations in
recommended. Low-risk NMSCs and small MCC are rou-                                     squamous cell carcinoma and solar keratoses revealed by comparative
                                                                                       genomic hybridization. Arch Dermatol 2003;139:876-882. https://
tinely treated in some regions by community practitioners                              doi.org/10.1001/archdem.139.7.876
and dermatologists; however, national cancer networks                             15
                                                                                       McGuire JF, Ge NN, Dyson S. Nonmelanoma skin cancer of the head
should establish an integrated approach involving both the                             and neck I: histopathology and clinical behavior. Am J Otolaryngol
head and neck surgeon and the plastic surgeon to care for                              2009;30:121-133. https://doi.org/10.1016/j.amjoto.2008.03.002
patients with certain high-risk CSCC and BCC and large
                                                                                  16
                                                                                       Veness MJ, Palme CE, Morgan GJ. High-risk cutaneous squamous
                                                                                       cell carcinoma of the head and neck: results from 266 treated patients
MCC (Tab. IV). Cooperation between otolaryngologist and                                with metastatic lymph node disease. Cancer 2006;106:2389-2396.
plastic surgeon is extremely helpful in order to better plan                           https://doi.org/10.1002/cncr.21898
surgical treatment, including safe oncological excision and                       17
                                                                                       Ebrahimi A, Moncrieff MD, Clark JR, et al. Predicting the pattern
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                                                                                       of the head and neck based on location of the primary. Head Neck
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                                                                                       Kao GF. Carcinoma arising in Bowen’s disease. Arch Dermatol
                                                                                       1986;122:1124-1126.
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