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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 26  |  Issue : 2  |  Page : 188-192

Factors affecting lymph node involvement in non-melanoma skin cancers


Department of General Surgery, Government Medical College, Calicut, Kerala, India

Date of Submission31-Jul-2020
Date of Decision12-Aug-2020
Date of Acceptance17-Oct-2020
Date of Web Publication07-Nov-2020

Correspondence Address:
Dr. V Revathy
Department of General Surgery, Government Medical College, Calicut, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ksj.ksj_11_20

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  Abstract 


Introduction: Non-melanoma skin cancers (NMSCs) with lymph node involvement usually have aggressive clinical course with high rate of treatment failure and recurrence. Materials and Methods: The aim of the study was to find out the clinicopathological factors affecting lymph node involvement in NMSC. This study with 48 cases was conducted over a period of 1 year (May 2018–May 2019) in the histologically proven patients of NMSC of the general surgery department. Results: Lymph node-positive patients with and without prior lesions (chronic non-healing ulcers) were 12.5% and 10.4% of the total population, respectively. Conclusions: Of all factors affecting lymph node involvement assessed in this study, the presence of pre-existing lesions was the only one attaining statistical significance.

Keywords: Lymph node involvement, non-melanoma skin cancer, squamous cell carcinoma


How to cite this article:
Revathy V, Soman K C, Kumar SS. Factors affecting lymph node involvement in non-melanoma skin cancers. Kerala Surg J 2020;26:188-92

How to cite this URL:
Revathy V, Soman K C, Kumar SS. Factors affecting lymph node involvement in non-melanoma skin cancers. Kerala Surg J [serial online] 2020 [cited 2020 Dec 2];26:188-92. Available from: http://www.keralasurgj.com/text.asp?2020/26/2/188/300220




  Introduction Top


Skin cancer globally accounts for at least 40% of cases. The most common type is non-melanoma skin cancer (NMSC), with an incidence of at least 2–3 million people in a year.[1] Of NMSCs, about 80% are basal cell cancers and 20% of squamous cell cancers. These along with a number of less usual skin cancers (Merkel cell carcinoma, Kaposi's sarcoma, cutaneous T cell lymphoma, sarcomas like dermatofibrosarcoma) are known as NMSC.[1] NMSCs with lymph node involvement usually have aggressive clinical course with a high rate of treatment failure and poor survival. Local invasiveness is affected by the speed of growth, depth of dermal invasion, degree of differentiation of the tumour, anatomical site and presence of previous inflammation/trauma. The outlook for tumours arising in chronic scar and those which recur or persists after excision are worse.[2] Predictors of lymph node involvement in NMSC are a matter of interest in various studies as it can alter the management strategies. The aim of this study was to distinguish risk factors for lymph node metastasis.


  Materials and Methods Top


We studied the age, sex and site distribution of NMSC and the clinicopathological factors affecting lymph node involvement. It was a cross-sectional analytical study, conducted in the general surgery department in 2018–2019. We studied patients with clinically and histopathologically proven NMSC who underwent definite curative excision. Patients with a history of malignancy other than NMSC or a history of unrelated surgery to the affected region were excluded. Patients' details were collected from history, examination, imaging and histopathology report (HPR). The patients were grouped into two, those with lymph node involvement and those without. For those without lymph node involvement, ultrasonogram (USG) was done. Clinically or USG proven/suspicious cases were subjected to fine-needle aspiration cytology/biopsy. Finally, histopathologically proven cases were taken as lymph node positive and others as negative. Comparison was done between these two groups on the basis of the clinicopathological factors such as age, sex, occupation requiring sun exposure, immunosuppression, comorbidities, previous lesions, radiation, site of lesion, size, ulceration, fixity to deeper structures, features of systemic metastasis, lab values, imaging and HPR. The factors affecting lymph node involvement were thus analysed. Treatment given for both the groups was also studied. Statistical methods used were Student's t-test and Chi-square test using SPSS (Statistical Package for the Social Sciences) developed by Nie NH, Bent DH and Hull CH. Available in Windows.


  Results Top


Forty-eight adult patients more than 18 years with clinically and histologically proven NMSC (by excision/wedge/incision biopsy), who subsequently underwent definitive curative excision of primary carcinoma, were selected. 67% of the patients were male. The mean age of presentation was 62.6 years (27–87). Maximum patients were seen in the age group of 61–80 years, 28 (58.33), followed by 41–60 years, 15 (31.25), followed by 61–80 and least on 21–40 [Figure 1].
Figure 1: Distribution of non-melanoma malignancy of skin by age range

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83% of the patients were having squamous cell carcinoma (SCC). 23% of the patients had lymph nodes involved. 38% of the patients presented with head-and-neck NMSC. 45.5% of lymph node-positive patients had lesions in the extremities. 27% of the people had prior lesions. 83% of the patients had lesions of size >2 cm and 81% had depth >4 mm. 68.75% of the patients presented with well differentiated, 10.4% with moderately differentiated and 4.2% with poorly differentiated SCC. 4.16% of the patients had tumours with lymphovascular invasion and 15% with positive margins. 42% of the patients had T3, 41% had T2 and 17% had T1 lesions. The only statistically significant factor affecting lymph node involvement was the presence of prior lesions. Lymph node positivity as well as negativity was found to be distributed predominantly between 60 and 80 years. There was no statistical relation between age and lymph node involvement [Figure 2].
Figure 2: Age and lymph node positivity

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Thirty-two (66.7%) patients were male and 16 (33.3%) were female. Among the lymph node-positive cases, majority were male and they make 16.67% of total population. Only 6.25% of total patients were lymph node-positive females [Figure 3]. Twenty-five (52.08%) patients had no comorbidities, whereas 23 (47.91%) had comorbidities. Of the 25 patients with no comorbidities, 5 (10.4%) were lymph node positive, whereas of the 23 patients with comorbidities, 6 (12.5%) were lymph node positive.
Figure 3: Sex and lymph node positivity

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73% of the patients did not have any previous lesions, whereas 27% had previous lesions in the form of non-healing ulcers, scars, sinuses and burns. Of the patients who had prior lesions, 6 (12.5%) had positive lymph nodes and 7 (14.6%) did not have lymph nodes. Lymph node-positive patients with and without prior lesions were 12.5% and 10.4% of the total population, respectively. The presence of such lesions had a statistically significant relation with lymph node involvement. Lesions of the head and neck 18 (37.5%) had maximum percentage of lymph node positivity which was about 45.5% of the lymph node positive patients. This was followed by extremities (16 [33.3%]) and trunk (4 [8.33%]). These are detailed in [Figure 4]. There was no statically significant relation between site of lesion and lymph node involvement.
Figure 4: Site distribution of primaries in lymph node-positive cases

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The lymph node positivity of lymph nodes in different regions is depicted in [Figure 5]. This was maximum in the extremities (5 out of 16).
Figure 5: Lymph node positivity in different regions

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22.91% of the total patients were having lesion size more than 2 cm with lymph node involvement and 60.41% had the same range of size without lymph node involvement. As the size increased, percentage of lymph node positivity also increased, but was not statistically significant. 20.83% of the total patients had depth more than 4 mm with lymph node involvement, whereas only 2.08% had depth ≤4 mm with lymph node involvement. As depth increases, lymph node positivity increases, but not statistically significant. Lymph node positivity was noted in 11 (23%) patients and the rest 37 (77%) were negative. 20.83% of the total patients had depth more than 4 mm with lymph node involvement, whereas only 2.08% had depth ≤4 mm with lymph node involvement. As depth increases, lymph node positivity increased, but this was not statistically significant. Among the study population, 60.41% of the patients were SCC without lymph node involvement and 22.91% with lymph node involvement. 14.58% of the patients were having basal cell carcinoma (BCC) without lymph node. 2.08% of the patients had other lesions with no lymph node involvement [Figure 6] and [Figure 7].
Figure 6: Type of lesions involved

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Figure 7: Lymph node secondaries in different malignancies

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Grading of the tumours included 33 (68.75%) well differentiated, 5 (10.41%) moderately differentiated, 2 (4.16%) poorly differentiated and 8 (16.67%) others. Among the well-differentiated cases, 7 out of 33 were lymph node positive, among the moderately differentiated, 2 out of 5 were positive and both poorly differentiated were node positive. Pearson's Chi-square showed P = 0.042 and hence not statistically significant [Figure 8]. As the extent of malignancy changed from well differentiated undifferentiated, the chance of lymph node negativity decreases from 54.16% to 0% of the total population which was statistically significant. The same pattern was observed in case of lymph node-positive lesions, i.e., the percentage of lymph node positivity decreased (from 14.58% to 4.16% of total cases) with change in differentiation from well differentiated to poorly differentiated. This may be because a vast majority of the patients, i.e., 82.5%, had well-differentiated lesions.
Figure 8: Lymph node positivity and grade of malignancy

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4.16% of the study population were having lymphovascular invasion. None of them had lymph node involvement. 16.67% of the total population had lymph node positivity and negative post-operative margin. Only 4.4% of the study population had positive margin. 14.8% of the total patients belonged to T3 stage with lymph node positivity, whereas maximum percentage of lymph node negativity (33.3% of the total population) was seen in T2 stage. As T stage increased, lymph node involvement also increased, but this was not statistically significant. Treatment of the lesions ranged from wide local excision (WLE) 23 (47.9%), WLE + graft/flap 3 (6.2%), WLE + node dissection 9 (18.7%), WLE + node dissection + graft/flap reconstruction 2 (4.2%), penectomy 5 (10.4%), penectomy + ilioinguinal block dissection 3 (6.3%), amputation 1 (2.1%), disarticulation 1 (2.1%) and amputation and nodal clearance 1 (2.1%). These are depicted in [Figure 9].
Figure 9: Treatment given for various lesions

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  Discussion Top


In our study, majority of the patients were male, which was similar to the study by de Lima Vazquez et al., who found 19% of the patients node positive at the time of presentation.[2] Other studies showed that with sentinel lymph node biopsy, subclinical nodal metastasis was identified in 12%–17%. Recent NCCN guidelines suggest strict follow-up for node-negative patients having high-risk clinicopathological features.[2] Age group of the patients varied between 38 and 87 years. The mean age of presentation was 62.6. Majority of the patients with lymph node positivity belonged to the age group of 61–80 years, accounting for about 10.41% of total patients. The mean age of presentation according to de Lima Vazquez et al. was 64.2.[3] About 38% of patients presented with head-and-neck malignancy, followed by extremities and genitalia. Lesions of the extremities had maximum percentage of lymph node positivity. 23% of the patients had lymph node involvement. However, according to various studies, lymph nodes involved occurred in 10.5% and 14% of the patients, respectively.[4]

Majority of the patients had SCC (83%). BCC accounted for about 15%. 2% of the patients had other than these two like.

Among the total cases, 60.41% were SCC without lymph node involvement and 22.91% were SCC with lymph node involvement. 14.58% of the patients were having BCC without lymph node. 2.08% of the patients had other than these lesions with no lymph node involvement. 73% of the patients did not have any previous lesions, whereas 27% had previous lesions in the form of non-healing ulcers, scars, sinuses and burns. Lymph node-positive patients with and without prior lesions were about 12.5% and 10.4% of the total population, respectively. The presence of such lesions has a statistically significant relation with lymph node involvement. This was also observed in the studies.[3],[5] 83% of the patients had lesions more than 2 cm. 22.91% of the total patients were having lesion size more than 2 cm with lymph node involvement. As the size increases, the percentage of lymph node positivity also increases, but this was not statistically significant. This may be due to inadequate lymph node clearance or biopsy in advanced cases. This was significant in the study by Kraus et al.[6] More than 5 cm lesions were associated with lymph node involvement, according to Haisma et al.[7] In their study, Moore et al.[1] observed that large sized lesions were having significant lymph node positivity.

81% of the patients had depth of invasion more than 4 mm. 20.83% of the total patients had depth more than 4 mm with lymph node involvement, whereas only 2.08% had depth ≤4 mm with lymph node involvement. As the depth increases, lymph node positivity increases, but was not statistically significant. This was significant as per the study by Kraus et al.[6] According to Brantsch et al.,[8] SCC greater than 2 mm had a higher risk of locoregional and distant spread. The degree of differentiation was not associated with lymph node involvement, but all the poorly differentiated and half of the moderately differentiated tumours had lymph node involvement. This was important predictor of nodal metastases.[1],[7],[9]

None of the patients had perineural invasion. 4.16% of the patients were having lymphovascular invasion and none of them had lymph node involvement. According to many authors,[1],[10] perineural and lymphovascular invasion had a significant association with lymph node involvement; 85% of patients had negative margin. Majority of the patients had T3 lesions with lymph node positivity. As T stage increases, lymph node involvement also increases, but is not statistically significant. This is not explainable.

The only statistically significant prognostic factor for lymph node metastasis in NMSC is the presence of previous lesions, which is included in the high-risk category as per the NCCN guidelines.[2],[10] The treatment of NMSC with lymph nodes is surgery. The treatment for node-negative NMSC is a controversy.

The limitations of this study are that the number is small and the period of follow-up is not long. Sentinel node biopsy was not regularly done.


  Conclusion Top


Two-third of the patients were male. Majority of the patients were between 60 and 80 years of age group. About four-fifth of the patients presented with SCC. Majority of the lesions were in head and neck. Two-third of the lesions were well differentiated. The only statistically significant factor associated with lymph node involvement was the presence of previous lesion. Size, depth or T stage increased lymph node involvement, but this was not statistically significant. Prior lesions were associated with lymph node involvement. If such patients present with clinically or radiologically node-negative disease, it would be better to consider sentinel lymph node biopsy or keep them under regular follow-up.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Moore BA, Weber RS, Prieto V, El-Naggar A, Holsinger FC, Zhou X, et al. Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck. Laryngoscope 2005;115:1561-7.  Back to cited text no. 1
    
2.
National Comprehensive Cancer Network. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCC Guidelines): Squamous Cell Skin Cancer. Vr. 2.2019.NCCN website. Published October 23, 2018. Available from: https://www.nccn.org. [Link accessed on 27 July, 2020].  Back to cited text no. 2
    
3.
de Lima Vazquez V, Sachetto T, Perpetuo NM, Carvalho AL. Prognostic factors for lymph node metastasis from advanced squamous cell carcinoma of the skin of the trunk and extremities. W Jour Surg Oncol. 2008;6:73.  Back to cited text no. 3
    
4.
Wermker K, Kluwig J, Schipmann S, Klein M, Schulze HJ, Hallermann C. Prediction score for lymph node metastasis from cutaneous squamous cell carcinoma of the external ear. Eur J Surg Oncol 2015;41:128-35.  Back to cited text no. 4
    
5.
Edwards MJ, Hirsch RM, Broadwater JR, Netscher DT, Ames FC. Squamous cell carcinoma arising in previously burned or irradiated skin. Arch Surg 1989;124:115-7.  Back to cited text no. 5
    
6.
Kraus DH, Carew JF, Harrison LB. Regional lymph node metasta-sis from cutaneous squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 1998;124:582-7.  Back to cited text no. 6
    
7.
Haisma MS, Plaat BEC, Bijl HP, Roodenburg JLN, Diercks GFH, Romeijn TR, et al. Multivariate analysis of potential risk factors for lymph node metastasis in patients with cutaneous squamous cell carcinoma of the head and neck. J Am Acad Dermatol 2016;75:722-30.  Back to cited text no. 7
    
8.
Brantsch KD, Meisner C, Schönfisch B, Trilling B, Wehner-Caroli J, Röcken M, Breuninger H. Evaluation for locoregional and distant metastases in cutaneous squamous cell and basal cell carcinoma. Lancet Oncol 2008;9:713.  Back to cited text no. 8
    
9.
Husseinzadeh N, Zaino R, Nahhas WA, Mortel R. The significance of histologic findings in predicting nodal metastases in invasive squamous cell carcinoma of the vulva. Gynecol Oncol 1983;16:105-11.  Back to cited text no. 9
    
10.
Gore SM, Shaw D, Martin RC, Kelder W, Roth K, Uren R, et al. Prospective study of sentinel node biopsy for high-risk cutaneous squamous cell carcinoma of the head and neck. Head Neck 2016;38 Suppl 1:E884-9.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]



 

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