Cutaneous malignancy is a common disease in

Transcription

1 ORIGINAL ARTICLE PATTERNS OF LYMPH NODE SPREAD OF CUTANEOUS SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK Tom J. Vauterin, MD, 1 Michael J. Veness, MMed (Clin Epi), FRANZCR, 2 Garry J. Morgan, FRACDS, FRACS, 2 Michael G. Poulsen, FRANZCR, 3 Christopher J. O Brien, AM, MS, MD, FRACS 1 1 Sydney Head and Neck Cancer Institute and Sydney Cancer Centre, Royal Prince Alfred Medical Centre and University of Sydney, Sydney, Australia. chris.obrien@cs.nsw.gov.au 2 Head and Neck Cancer Service, Westmead Hospital and University of Sydney, Sydney, Australia 3 Southern Zone Radiation Oncology (SZRO) Service, South Brisbane, Australia Accepted 23 December 2005 Published online 16 June 2006 in Wiley InterScience ( DOI: /hed Correspondence to: C. J. O Brien Presented by T. V. at the Sixth Annual Meeting of the Australian and New Zealand Head and Neck Society, Adelaide, November VC 2006 Wiley Periodicals, Inc. Abstract: Background. Among patients with cutaneous squamous cell carcinoma (SCC) of the head and neck, recent studies have shown that those with involvement of the parotid gland also have a high incidence of neck node involvement. Treatment of the neck by either surgery or radiotherapy is therefore recommended among patients with parotid SCC, even if clinical examination is negative. The aim of this study was first to analyze patterns of metastatic spread in the parotid and cervical lymph nodes and then to correlate the pattern of involved nodes with the primary cutaneous site in order to guide the appropriate extent of surgery, should neck dissection be used to treat the neck in patients with parotid SCC. Methods. A cohort of 209 patients with cutaneous SCC of the head and neck and clinically evident regional metastatic disease was reviewed retrospectively from 3 Australian institutions. The distribution of involved nodes was obtained from pathology reports; the anatomic sites of primary cutaneous cancers were then correlated with these findings. Results. Among 209 patients, 171 (82%) had clinical parotid involvement. Of these, 28 had clinical neck disease, whereas 143 had parotid disease alone. Thirty-eight (18%) patients had neck disease only. A total of 199 patients were treated surgically, whereas 10 received radiotherapy alone. Surgery included 172 parotidectomies and 151 neck dissections (93 of which were elective). Primary sites were cheek (21.7%), pinna (20.4%), temple (15.8%), forehead (15.8%), postauricular region (5.9%), neck (5.3%), anterior scalp (5.3%), posterior scalp (3.3%), periorbital (3.3%), nose (2.6%), and chin (0.6%). Among pathologically positive necks, level II was most frequently involved (79%). Level IV (13%) and level V (17%) were only involved in extensive lymph node disease, the exception being for isolated level V metastases from the posterior scalp. Conclusions. Primary sites were mainly localized to the lateral aspect of the head. Among patients with cutaneous SCC involving the parotid and neck, level II was the most commonly involved neck level. The distribution of involved nodes suggests that in a patient with parotid involvement and a clinically negative neck with an anterolateral primary, a supraomohyoid neck dissection, always including the external jugular lymph node(s) would be appropriate. In the case of a posterior primary, level V should be dissected as well. In patients with parotid SCC and a clinically positive neck, a comprehensive neck dissection is recommended. VC 2006 Wiley Periodicals, Inc. Head Neck 28: , 2006 Keywords: metastatic skin cancer; neck dissection; cutaneous SCC; lymph nodes; parotid Cutaneous malignancy is a common disease in Australia, with most skin cancers arising in the head and neck region. Although the incidence of Lymph Node Spread in Cutaneous HNSCC HEAD & NECK DOI /hed September

2 squamous cell carcinoma (SCC) is lower than basal cell carcinoma (BCC), SCC still accounts for approximately 20% of cutaneous cancers, occurring in approximately 250 to 300/100,000 Australians yearly. 1 Cutaneous SCC has definite metastatic potential, with studies suggesting an overall regional metastatic rate of approximately 5% for non head and neck sites. 2 The exact rate of lymph node metastases from cutaneous SCC of the head and neck remains uncertain; however, it is known that the parotid gland is a common site for metastatic spread. In a previous study from our institution, it was reported that patients with a metastatic cutaneous SCC involving the parotid also had a high incidence of clinical (26%) as well as occult neck disease (35%). 3 The appropriate treatment for the clinically negative neck among patients with parotid SCC remains unclear, with elective radiotherapy and elective neck dissection being reasonable and effective options. 4 8 If elective neck dissection is combined with therapeutic parotidectomy, it is important that the appropriate lymph node levels be dissected. It is our hypothesis that this may vary with the anatomic site of the primary cancer, if that site can be identified. The aim of this study was not to recommend surgery over radiotherapy, but rather to improve our overall knowledge about the patterns of metastatic spread of cutaneous SCC and, where possible, to correlate this to the primary site to use this information to guide the extent of surgery if an elective neck dissection is used to treat patients with metastatic SCC of the parotid gland. FIGURE 1. Anatomic zones of the head and neck used in the present study. MATERIALS AND METHODS This retrospective study included patients from 3 Australian tertiary centers: Royal Prince Alfred Hospital (n ¼ 98), Westmead Hospital (n ¼ 97), and the Southern Zone Radiation Oncology Service (n ¼ 14). All patients had clinically evident and pathologically proven metastatic SCC involving the parotid gland and/or the neck and a minimum of 2 years follow-up. Some of these patients were also part of a separate study on the prognosis of cutaneous SCC with metastasis to the parotid and/or neck. 9 Patterns of metastatic involvement of cervical nodes were analyzed and, by carefully reviewing the history of excised skin lesions, an attempt was made to identify a primary index lesion. Where a primary index cancer could be identified, its anatomic site was correlated with the position of the pathologically involved nodes. These primary skin lesions were divided into 11 different anatomic areas: anterior scalp, posterior scalp, forehead, temple, periorbital, pinna, postauricular, nose, cheek, chin, and neck (Figure 1). Primary SCC arising from the lips was excluded because the lips are anatomically included with the oral cavity, despite the fact that cancer of the lip is mainly caused by sun exposure. The forehead and temple proved to be 2 regions where delineation was most variable between different observers. For this study, the margins of the forehead region were defined as follows: (1) medially, the midline; (2) superiorly, the hairline in young adulthood; (3) inferiorly, the eyebrow; and (4) laterally, the surface landmark corresponding to the temporal line. The 2 remaining margins of the temple were then defined as follows: (1) inferiorly, the zygomatic arch; and (2) posteriorly, the connecting line between the right and left pinna. Although much effort was used to 786 Lymph Node Spread in Cutaneous HNSCC HEAD & NECK DOI /hed September 2006

3 assign the primaries to these anatomic regions, it is recognized that an overlap between adjacent sites could occur. Parotid lymph node metastases were surgically excised by means of a superficial, near-total, or total parotidectomy. Types of neck dissection ranged from radical and modified radical to selective dissections. Pathology reports were carefully examined for involvement of the parotid gland and the neck, with emphasis on levels containing positive nodes. The importance of the external jugular node(s), lying adjacent to the external jugular vein at the anterior of the sternomastoid muscle, is well recognized; however, it was not always possible to differentiate involvement of this nodal site reliably from level II nodes, lying deep to the sternomastoid muscle in the upper neck. Table 1. Types of neck dissection. Therapeutic Elective Total Comprehensive RND MRND Selective I III I IV Other Total Abbreviations: RND, radical neck dissection; MRND, modified radical neck dissection. Table 2. Incidence and distribution of involved neck levels in pathologically positive neck dissections. Neck Levels involved, % n positive I II III IV V Elective N0* Therapeutic N0y cpþ cp Total Abbreviation: ND, neck dissections. *All patients having elective ND had clinical parotid disease and parotidectomy. In the therapeutic groups, some patients had clinical positive parotid (cpþ) and some did not (cp ). RESULTS Among 209 patients treated between July 1980 and December 2001, 169 were men and 40 were women. Ages ranged from 34 to 104 years, with a median of 71 years. All patients had a minimum of 2 years follow-up. All had clinical metastatic SCC in either the parotid gland or neck, or both. The median time interval between the treatment of the primary lesion and treatment of the regional metastasis was 13 months (range, 0 to 109 months). Among 209 patients, 171 had clinical parotid disease, and 28 of these also had clinical neck disease. Therefore, 143 had SCC in the parotid only. A total of 66 patients had clinical neck disease, including the 28 with parotid disease and 38 who had neck involvement alone. Only 14%, therefore, had disease in both the parotid and neck clinically. Ten patients were treated with radiotherapy alone, whereas pathologic information was available from 199 surgically treated patients. Surgical treatment was as follows. There were 172 parotidectomies, and 165 of these were therapeutic, whereas 7 were elective procedures, in cases in which a therapeutic neck dissection was done and the parotid was thought to be at risk of harboring subclinical disease. Among the 172 parotidectomies, 125 were combined with a neck dissection and 47 were not. Of the 151 neck dissections performed, 58 were for clinically evident neck disease, whereas 93 were elective dissections carried out in patients having parotidectomies for clinical parotid disease. The types of neck dissection performed in the therapeutic and elective setting are shown in Table 1. A total of 125 neck dissections were combined with a parotidectomy, and 26 patients had neck dissection alone. The incidence and distribution of involved neck nodes and levels are shown in Table 2 and Figure 2. A total of 71 patients had pathologically proven metastatic disease in the neck, from elective neck dissections, therapeutic dissections with clinically positive parotid, and therapeutic dissections for clinical neck disease only. Among the 93 elective neck dissections, 19 (20%) were pathology positive and, among these, 11% were positive in level I, 89% in level II, and 32% in level III. Levels IVand V were almost never involved. Among the 25 therapeutic dissections with a clinically positive parotid, 20 (80%) were pathology positive, 25% involved level I, 80% involved level II, and 55% involved level III. In contrast with elective neck dissection, level IV and level V involvement occurred in 40% and 35% of these therapeutic dissections, respectively. Among the 33 clinically positive necks with clinically negative parotid, there was a high rate of involvement of level II, followed by levels I and V. Overall, level II nodes were involved in 79% of the 71 positive neck dissections. Lymph Node Spread in Cutaneous HNSCC HEAD & NECK DOI /hed September

4 FIGURE 2. Distribution of involved neck levels in pathologically positive neck dissections, divided into elective neck dissection (nþ19 positive dissections), therapeutic neck dissection with clinically positive parotid (thera cpþ) 20 positive dissections, and therapeutic neck dissection for clinical neck disease only (thera cp ), 32 positive dissections. A primary skin lesion was identified in 73% of 208 patients. In the remaining patients, an index lesion could not be identified because multiple skin lesions had been previously treated, and so these patients were not included in the correlation with nodal distribution. The most prevalent primary sites of cutaneous SCC in the head and neck region were the cheek and pinna, followed by the temple and forehead. Table 3 shows the anatomic distribution of primary sites in decreasing order of incidence. The areas on the lateral aspect of the head made up most of the primary lesions. In our study, lesions of the neck and posterior aspect of the head were more frequent than those of the anteroinferior part of the face. In Table 4, parotid and neck level involvement are correlated with the anatomic distribution of the different skin lesions. The primary sites on the lateral aspect of the head (cheek, pinna, temple) mainly metastasized to the parotid and level II. The forehead, postauricular, anterior scalp, and neck regions also followed that pattern. The posterior scalp had a relatively high incidence of level V involvement. The anterior part of the face (although there were limited numbers) frequently metastasized to level I and III and escaped the parotid. The higher rate of involvement of levels I, III, IV, and V with cancers of the pinna and the cheek appeared to be attributable to the involvement of multiple nodes in those cases. No isolated nodal metastases in level IV or V were seen with pinna and cheek primary SCC. Moreover, no isolated level IV node metastasis was recorded with any lesion. There were only 3 isolated level V node metastases: 2 cases with the primary lesion on the posterior scalp, and 1 case in which no primary lesion could be found. Forty-eight percent of the 71 pathologically positive necks consisted of single nodal metastases in level II. The involvement of more than 2 levels accounted for 11%, and this was, as previously mentioned, mostly in pinna and cheek primaries. DISCUSSION Cutaneous SCC is common in Australia and frequently involves the skin of the head and neck. These cancers can metastasize to both the intraglandular lymph nodes of the parotid and the lymph nodes in the neck. The aim of this study was to document patterns of metastatic spread of head and neck skin cancer according to the pri- Table 3. Anatomic distribution of the primary sites. n % Cheek Pinna Temple Forehead Postauricular Neck Anterior scalp Posterior scalp Periorbital Nose Chin Total Lymph Node Spread in Cutaneous HNSCC HEAD & NECK DOI /hed September 2006

5 Table 4. Parotid and neck level involvement according to primary site. Cheek Pinna Temple Forehead Postauricular Anterior scalp Neck Posterior scalp Periorbital Nose Chin n ppþ I II III IV V Abbreviation: ppþ, pathologically positive parotid. mary site. This information has potential implications when surgery is contemplated to treat the clinically negative neck in patients with SCC involving the parotid gland. In our study, the lateral aspect of the head (cheek, pinna, and temple) was the most common site of origin, followed by lesions of the forehead and postauricular region. Comparison of our data with the literature is difficult because of different anatomic subdivisions and limited numbers of patients in other studies. In Table 5, we compared our data with the data of investigators reporting on the incidence of primary lesions, which have metastasized. 4,6 8,10 Although most were localized to the cheek, ear, temple, and forehead region, we noted that in some studies the nose was more frequent a site. In view of this diversity of subdivision, an international standardization of the anatomic breakup of the head and face (with clear definition of the borders) would seem beneficial. The issue of lymphatic drainage patterns of the skin of the head and neck has been addressed in previous studies from 1 of the institutions participating in the present study, Royal Prince Alfred Hospital. 11,12 That research focused on cutaneous melanoma and compared clinical pathologic and lymphoscintographic findings. Sentinel node biopsy has become the standard investigation to evaluate clinically negative lymph nodes in patients with malignant melanoma. However, sentinel node biopsy technique may not be as applicable to patients with cutaneous SCC because of the lower metastatic rate to regional lymph nodes (5%), compared with melanoma, which ranges from 15% to 20%. 13 Despite this, researchers have investigated the use of sentinel node biopsy in patients with high-risk cutaneous SCC. Its current role remains investigational, although patients with unfavorable SCC (recurrence, thickness > 4 mm, size > 2 cm) may have an incidence of meta- Table 5. Comparison with literature of anatomic sites of metastatic cutaneous SCCs of the head and neck. This study, P&N (n ¼ 152) Dinehart and Pollack 7, RDE (n ¼ 27) % by study and site of locoregional Mþ del Charco et al 4, P only (n ¼ 71) Kraus et al 10, P&N (n ¼ 45) Jol et al 6, P&N (n ¼ 41) Jackson and Ballantyne 8, P&N&EP (n ¼ 125) Cheek Preauricular Ear Temple Forehead Anterior scalp Posterior scalp Postauricular Neck Periorbital Nose Chin Lips Dorsum of hand Abbreviations: P, parotid lymph nodes; N, neck lymph nodes; RDE, regional distal lymph nodes and extranodal sites; EP, extension into parotid. Lymph Node Spread in Cutaneous HNSCC HEAD & NECK DOI /hed September

6 Table 6. Comparison with literature of neck levels involved among patients with metastatic cutaneous SCC of the head and neck region (excluding lip and oral cavity primaries). n Primary pnþ I (%) II (%) ext jug (%) III (%) IV (%) V (%) occ (%) This study % nose % Kraus et al % nose? % Netterville et al % nose % Chu and Osguthorpe % nose static spread to regional nodes of the head and neck, which warrants sentinel node sampling. 14 Overall, the present authors do not favor routine elective lymphadectomy for cutaneous SCC, by means of either formal regional node dissection or sentinel node biopsy, because the disease is very common and nodal involvement is relatively uncommon. A limited number of studies 10,15,16 have described levels of neck involvement (Table 6). Our findings confirm the generally high incidence of level II metastases. Studies with a higher incidence of level I involvement than our study have a high incidence of primary skin cancers involving the nose. There are 2 clear limitations to this study. First, not all neck dissections were comprehensive, with 20% of the therapeutic and more than 65% of the elective dissections being selective dissections. Therefore, we do not have information about the pathologic node status of every level in every neck. Second, there is a lack of information on involved superficial lymph nodes, particularly the external jugular lymph node(s). This node (usually only 1) lies superficial to the anterior border of the sternomastoid muscle and is not part of a specific level, but it is a common site for metastatic spread. We have previously drawn attention to this node and recommended that it be removed in any lymphadenectomy for cutaneous cancer, including SCC and melanoma. 17,18 In past pathology reports in our centers, this node has probably been included as a level II node, contributing to a high level II involvement. In the study by Chu and Osguthorpe, 16 involvement of the external jugular node and occipital nodes was also highlighted. In the present study, other superficial lymph nodes, such as facial, occipital, and retroauricular nodes were so infrequently involved that no significant conclusions could be drawn. We do recommend a thorough clinical examination preoperatively and, when there is suspicion of involvement, these nodes should be excised. Our data have clearly shown that the metastatic pattern of cutaneous SCC is largely predictable on anatomic grounds in many cases (Figure 3). The lateral aspect of the head and forehead mainly metastasized to the parotid and level II. Cancers from the neck skin drained to level II, including external jugular nodes. Primary sites in the posterior aspect of the head occasionally spread to the parotid but level V was especially at risk. A dissection in that setting should also incorporate the occipital nodes. The anteroinferior aspect of the face drained mainly to the lymph nodes in levels I, II, and III. FIGURE 3. Patterns of lymph node spread of cutaneous squamous cell carcinoma of the head and neck. This illustration is original and based on the findings of the current study, but we acknowledge similarities to the style used by Jackson and Ballantyne Lymph Node Spread in Cutaneous HNSCC HEAD & NECK DOI /hed September 2006

7 This study provides further understanding of patterns of lymphatic spread of skin cancers of the head and neck. Patients with metastatic SCC involving the parotid gland have a high incidence of neck involvement, and we have previously recommended that the clinically negative neck be treated in this patient group. Neck treatment may involve surgery or radiotherapy, depending on the clinical setting and clinician and patient preferences. If a neck dissection is undertaken in a patient with metastatic cutaneous SCC in the parotid gland, information about the primary site is important to consider. In a clinically negative neck with an anterolateral primary, a supraomohyoid neck dissection would be appropriate; however, in the case of a posterior primary, level V should be dissected as well. In a clinically positive neck, a comprehensive neck dissection is recommended. REFERENCES 1. Zablow AI, Eanelli TR, Sanfilippo LJ. Electron beam therapy for skin cancer of the head and neck. Head Neck 1992;14: Joseph MG, Zulueta WP, Kennedy PJ. Squamous cell carcinoma of the skin. The incidence of metastases and their outcome. Aust NZ J Surg 1991;62: O Brien CJ, McNeil EB, McMahon JD, et al. Incidence of cervical node involvement in metastatic cutaneous malignancy involving the parotid gland. Head Neck 2001;23: del Charco JO, Mendenhall WM, Parsons JT, Stringer SP, Cassisi NJ, Mendenhall NP. Carcinoma of the skin metastatic to the parotid area lymph nodes. Head Neck 1998;20: Dona E, Veness MJ, Cakir B, et al. Metastatic cutaneous squamous cell carcinoma to the parotid: the role of surgery and adjuvant radiotherapy to achieve best outcome. Aust NZ J Surg 2003;73: Jol JA, van Velthuysen ML, Hilgers FJ, et al. Treatment results of regional metastasis from cutaneous head and neck squamous cell carcinoma. Eur J Surg Oncol 2003; 29: Dinehart SM, Pollack SV. Metastasis from squamous cell carcinoma of the skin and the lip. J Am Acad Dermatol 1989;21: Jackson GL, Ballantyne AJ. Role of parotidectomy for skin cancer of the head and neck. Am J Surg 1981;142: Andruchow JL, Veness MJ, Morgan GJ, et al. Implications for clinical staging of metastatic cutaneous SCC of the head and neck based on a multicentre study of treatment outcomes. Cancer 2006;106: Kraus DH, Carew JF, Harrison LB. Regional lymph node metastasis from cutaneous squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 1998;124: O Brien CJ, Uren RF, Thompson JF, et al. Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy. Am J Surg 1995; 170: Pathak I, O Brien CJ, Petersen-Schaeffer K, et al. Do nodal metastases from cutaneous melanoma of the head and neck follow a clinically predictable pattern? Head Neck 2001;29: de Wilt JH, Thompson JF, Uren RF, et al. Correlation between preoperative lymphoscintigraphy and metastatic nodal disease sites in 362 patients with cutaneous melanomas of the head and neck. Ann Surg 2004;239: Wagner JD, Evdokimow DZ, Weisberger E, et al. Sentinel node biopsy for high-risk nonmelanoma cutaneous malignancy. Arch Dermatol 2004;140: Netterville JL, Sinard RJ, Bryant GL, et al. Delayed regional metastasis from midfacial squamous carcinomas. Head Neck 1998;20: Chu A, Osguthorpe JD. Nonmelanoma cutaneous malignancy with regional metastasis. Otolaryngol Head Neck Surg 2003;128: O Brien CJ, Shah JP, Balm AJ. Neck Dissection and parotidectomy for melanoma. In: Thompson JF, Morton DL, Kroon BB, editors. Textbook of melanoma. London: Martin Dunitz, p O Brien CJ, Fisher SR, Pathak I. Neck dissection and parotidectomy. In: Balch CM, Houghton AN, Sober AJ, Soong S-J, editors. Cutaneous melanoma. St. Louis, MO: Quality Medical Publishing, p Lymph Node Spread in Cutaneous HNSCC HEAD & NECK DOI /hed September