RESULTS
Demographic characteristics of the study group according to primary site, age, and side
Patients were mainly males (n=94, 59.87 %) as compared to females (n= 63, 40.13 %). The age of the study group ranged from 1 to 79 years, with a mean age of 28.50±20.3 years. Submandibular and upper neck sharing the same percentage as most frequent primary location of presentation, while lower lateral neck was the lowest with 29.4% and 4.2% respectively. Some of the neck masses were found in the left side (n = 32, 25.4 %), but the majority were found in the midline (n = 48, 38.8 %), followed by the right side of the neck (n = 44, 35.6 %). Furthermore, the side of neck mass differed significantly among age groups. Most of the masses presented in the midline area (submental and infrahyoid) in age groups < 34 years old and right side in age groups >35 years as shown in Table 1.
Characteristics of the study group according to primary location and diagnoses
The primary location was divided into submental area (Ia; n=23, 19.33%), submandibular area (Ib; n=35, 29.41%), infrahyoid area (VI; n=21, 18%), upper lateral neck (II, III; n=35, 29.41%), and lower lateral neck (IV, V; n=5, 4.2%).
Moreover, the neck masses were classified into 6 groups according to histopathological diagnosis: reactive (n = 22, 14.01 %), congenital masses (n = 57, 36.31%), benign tumors (n = 20, 12.74 %), infectious lesions (n = 17, 10.83 %), malignant tumors (n = 21, 13.38 %), and other neck masses (n = 20, 12.74 %).
The neck masses that resulted from the non-specific inflammatory process were classified as reactive (n = 22). They divided into reactive lymphadenopathy (n=15), florid reactive follicular hyperplasia (n=3), Kikuchi Fujimoto disease (n=1), acute necrotizing lymphadenitis (n=1), traumatic neuroma (n=1), or Castleman disease (n=1). All benign congenital masses were cystic (n = 57). Thyroglossal duct cysts (n = 24) and branchial cleft cysts (n = 25) were the most diagnosed congenital neck masses. Other reported congenital cysts included dermoid cysts (n = 8).
Infectious lesions of the neck were found in 17 cases. The most common neck masses of this origin were reported as: tuberculosis (n=5), abscesses (n = 4), and non-specific granulomatous lymphadenitis (n = 3). There were also 4 reported cases of toxoplasmosis and single cases of acute panniculitis. Benign neoplastic masses amounted to 12.74 % of cases (n = 20). Most of these cases were lipoma (n = 11), followed by pleomorphic adenoma (n = 3). Moreover, four cases of vascular lesions were reported. One was a Masson’s hemangioma, and two were cavernous hemangiomas, while the last case was a non-specific vascular lesion. Other observations included a single case report of eccrine poroma and ancient schwannoma.
Malignant neoplastic masses represented 13.38 % (n = 21) of all cases. Most cases were lymphoma (n=12), divided into Hodgkin’s (n=7) and non-Hodgkin’s (n=5). The metastatic squamous cell carcinoma was presented in 4 cases, while other carcinomas were 3 cases of metastatic papillary thyroid carcinoma and a single case of adenoid cystic carcinoma. Single cases of chronic lymphocytic leukemia and non-specific malignant neoplastic process were reported (Table 2).
Neck masses not fitting in the previously mentioned categories were classified as others (n = 20). These included 19 cases epidermoid cysts and a single case of atypical lymphoid hyperplasia. None of these cases occurred in patients older than 55 years.
Relationship of gender according to primary location, side, and diagnosis
The correlation of the age/gender with other categories (primary location, side, and diagnosis) was examined. No significant association was found between gender category and side, although male patients were presented mainly with left or midline rather than the right side. Moreover, males presented with a higher percentage (not significant) of masses in the submandibular, lower lateral neck and infrahyoid but lower percentage in the upper lateral neck and submental area. On the other hand, no significant association found between diagnosis and gender. However, females showed a higher percentage of infectious, benign, and malignant tumors compared to males (Table 3).
Diagnosis relationship according to age group
Although no significant association was found between the age on one hand and primary location on the other hand (Tables 4), there was a significant association between age category and diagnosis as shown in Table 5. Malignant tumors were seen in the elderly group, with 42.2% of malignant results occurring in the age category of 55 years and more, followed by 20.6% in the category 35 to 55 years. On the other hand, benign lesions were mainly in the younger population; around 71% occurred in ages 34 and younger, with almost half of them congenital in nature. In addition, Malignant lesions had a significantly higher mean age by 20 and 24 years than benign and other lesions respectively (Table 6). Moreover, the mean age was significantly higher on the right side than the midline by 12 years difference. The mean age was also significantly higher in submandibular than the submental location by a mean difference of around 18 years as shown in Tables 7-8.
TableI: Age Category distribution according to side
|
Side
|
Less than 20
|
20 to 34
|
35 to 54
|
55 and more
|
P value
|
Chi square
|
|
Left
|
6 (14.3)
|
14 (35)
|
9 (36)
|
3 (18.8)
|
0.027
|
14.180
|
|
Midline
|
23 (54.7)
|
15 (37.5)
|
4 (16)
|
5 (31.2)
|
|
Right
|
13 (31.0)
|
11 (27.5)
|
12 (48)
|
8 (50)
|
Table II: Type of malignancy and number of Cases
|
Type of Malignancy
|
Number of Cases
|
|
Hodgkin’s Lymphoma
|
7
|
|
Metastatic Papillary Thyroid Carcinoma
|
2
|
|
Chronic Lymphocytic Leukemia
|
1
|
|
Metastatic Squamous Cell Carcinoma
|
4
|
|
Non-Hodgkin’s Lymphoma
|
4
|
|
Marginal B-Cell Lymphoma
|
1
|
|
Adenoid cystic carcinoma
|
1
|
|
Non-specific malignant neoplastic process
|
1
|
Table III: Gender and clinical data
|
Clinical Characters
|
Female N (%)
|
Male N (%)
|
p-value
|
Chi-Square
|
|
Side
|
|
|
|
|
|
Left
|
11 (21.6)
|
21 (28.8)
|
0.173
|
3.506
|
|
Midline
|
17 (33.3)
|
31 (42.4)
|
|
Right
|
23 (45.1)
|
21 (28.8)
|
|
Primary Location
|
|
|
|
|
|
Lower Lateral Neck
|
0 (0)
|
5 (6.8)
|
0.192
|
6.094
|
|
Infrahyoid
|
7 (15.2)
|
14 (19.2)
|
|
Submandibular
|
12 (26.1)
|
23 (31.5)
|
|
Submental
|
9 (19.6)
|
14 (19.2)
|
|
Upper Lateral Neck
|
18 (39.1)
|
17 (23.3)
|
|
Diagnosis
|
|
|
|
|
|
Benign congenital
|
22 (34.9)
|
35 (37.2)
|
0.404
|
5.0944
|
|
Benign tumor
|
9 (14.3)
|
11 (11.7)
|
|
Infectious
|
9 (14.3)
|
8 (8.5)
|
|
Malignant
|
11 (17.5)
|
10 (10.6)
|
|
Other
|
6 (9.5)
|
14 (14.9)
|
|
Reactive
|
6 (9.5)
|
16 (17.1)
|
Table IV: Age Category distribution according to primary location
|
Primary Location
|
Less than 20
|
20 to 34
|
35 to 54
|
55 and more
|
P value
|
Chi square
|
|
Lower Lateral Neck
|
1 (2.4)
|
2 (5.3)
|
1 (4.2)
|
1 (7.2)
|
0.104
|
18.392
|
|
Infrahyoid
|
11 (26.8)
|
4 (10.5)
|
3 (12.5)
|
3 (21.4)
|
|
Submandibular
|
9 (22)
|
9 (23.7)
|
9 (37.5)
|
7 (50)
|
|
Submental
|
11 (26.8)
|
10 (26.3)
|
1 (4.2)
|
0 (0)
|
|
Upper Lateral Neck
|
9 (22)
|
13 (34.2)
|
10 (41.6)
|
3 (21.4)
|
Table V: Age Category distribution according to diagnosis category
|
Diagnosis
|
Less than 20
|
20 to 34
|
35 to 54
|
55 and more
|
P value
|
Chi square
|
|
Congenital
|
25 (51)
|
19 (35.8)
|
11 (32.4)
|
2 (10.5)
|
<0.0001
|
45.555
|
|
Benign tumors
|
0 (0)
|
9 (17)
|
7 (20.6)
|
4 (21)
|
|
Infectious
|
8 (16.3)
|
4 (7.6)
|
3 (8.8)
|
2 (10.5)
|
|
Malignant tumors
|
0 (0)
|
5 (9.4)
|
7 (20.6)
|
8 (42.2)
|
|
Other
|
7 (14.3)
|
8 (15.1)
|
5 (14.7)
|
0 (0)
|
|
Reactive
|
9 (18.4)
|
8 (15.1)
|
1 (2.9)
|
3 (15.8)
|
Table 6: The diagnosis relationship with age as continuous scale
|
Diagnosis Comparison
|
M±SE
|
n (Group 1)
|
n (Group 2)
|
P-value
|
F-value
|
|
Malignant
|
Benign
|
20.2±3.01
|
20
|
115
|
< 0.05
|
12.49
|
|
Benign
|
Other
|
3.7±3.01
|
115
|
20
|
Not Significant
|
|
Other
|
Malignant
|
23.9±3.93
|
20
|
20
|
< 0.05
|
|
* M, Mean Difference; n, sample size; SE, standard error.
|
| |
|
|
|
|
|
|
|
|
Location Comparison
|
M±SE
|
n (Group 1)
|
n (Group 2)
|
P-value
|
F-value
|
|
Submenal
|
Midline
|
6.57±3.9
|
22
|
21
|
Not Significant
|
4.17
|
|
Midline
|
Submandibular
|
11.77±3.55
|
21
|
34
|
Not Significant
|
|
Submandibular
|
Upper Lateral
|
5.99±3.08
|
34
|
35
|
Not Significant
|
|
Upper Lateral
|
Lowr Lateral
|
8.60±6.11
|
35
|
5
|
Not Significant
|
|
Lowr Lateral
|
Submenal
|
20.95±6.34
|
5
|
22
|
Not Significant
|
|
Submenal
|
Submandibular
|
18.34±3.5
|
22
|
34
|
< 0.05
|
|
Submandibular
|
Lowr Lateral
|
2.61±6.13
|
34
|
5
|
Not Significant
|
|
Lowr Lateral
|
Midline
|
14.38±6.36
|
5
|
21
|
Not Significant
|
|
Midline
|
Upper Lateral
|
5.78±5.53
|
21
|
35
|
Not Significant
|
|
Upper Lateral
|
Submenal
|
12.35±3.48
|
35
|
22
|
Not Significant
|
|
* M, Mean Difference; n, sample size; SE, standard error.
|
| |
|
|
|
|
|
|
|
|
able 7: The side relationship with age as continuous scale
Table 8: The primary location relationship with age as continuous scale
|
Side Comparison
|
M±SE
|
n (Group 1)
|
n (Group 2)
|
P-value
|
F-value
|
|
Right
|
Midline
|
11.97±2.79
|
44
|
47
|
< 0.05
|
4.99
|
|
Midline
|
Left
|
9.19±3.05
|
47
|
32
|
Not Significant
|
|
Left
|
Right
|
2.78±3.09
|
32
|
44
|
Not Significant
|
|
* M, Mean Difference; n, sample size; SE, standard error.
|
| |
|
|
|
|
|
|
|
|
DISCUSSION
Solitary neck masses represent a wide array of pathologies. From benign process such as inflammatory, benign tumors, reactive and congenital neck masses, which are the most common neck masses in pediatric and young adult age groups, to malignant neoplastic masses which related to older age group. Timely assessment of the mass location [i], and survival of head and neck malignancy is proved to be inversely associated with stage of disease at the diagnosis time.[ii] , [iii]
A study by Khader et al. [iv] had investigated the cancer incidence in Jordan. They found a 60.5% increase in the number of cancer cases in Jordan over 14 years between 2000-2013. They emphasize on detect cancer at early stages to reduce associated morbidity and mortality. In this study, we investigated a clinical scenario in which, a patient will present to clinic with a complain of solitary neck mass. The first approach of investigation was toward basic major classification of benign versus malignant process. However, in our analysis, we generated other group due to the fact that we included superficial masses, mostly skin masses, which are part of presentation at clinic. The second approach of diagnosis analysis was based on causative mechanism, which might influence the treatment method. E.g., the infectious cause differs from congenital or vascular benign tumors or reactive mass. The malignant neoplastic mechanism was kept as one category since it is shares importance of early diagnosis even sometimes differ in treatment strategy. E.g., lymphoma treatment is mainly chemotherapy, which is different from metastatic carcinoma that mainly treated with surgery. However, both share the importance of early diagnosis which influence survival, treatment option and treatment outcome.
The anatomical location of neck masses did not differ significantly between the age groups or gender (p-value 0.104 and 0.192, respectively). However, upper neck and submandibular location were the most frequent since these are the first echelon lymph nodes for reactive, infectious and malignant metastasis , also salivary glands are within upper neck location.
The results showed that the midline of the neck was the most frequent side for the occurrence of masses. This result can be explained since thyroglossal and dermoid cysts occur most frequently in midline location. Also, congenital masses were the most common finding among all age groups under 55 years old.[v] This result is consistent with previous results of Al-chateau et al., in which they found that the highest prevalence of congenital masses occurred in the first and second decades of life with 38% and 32%, respectively.[vi]
Like other studies, among the congenital masses, thyroglossal duct cysts and branchial cysts represent 86% of cases, while dermoid cysts represent the remnant 14%. This finding could also be explained by the fact that the benign congenital masses are embryologically distinct, and malformations stem from anomalies resulting from defective closure or persistent remnants following thyroid migration, which form dermoid cysts thyroglossal duct cysts, respectively. [vii] [viii] [ix] [x]
According to the results obtained in the current investigations, about (13.4%) were malignant neck masses and the age group most involved was >55 years (p-value <0.0001). Among the malignant neck masses, lymphoma was the leading variant (57.1%), followed by metastatic squamous cell carcinoma and papillary thyroid carcinoma (28.5%). Although the exclusion criteria included patient of known case of carcinoma, these results are regional metastasis or unknown primary carcinoma process or occult primary carcinoma . Although Thyroid masses were excluded since these cases has specific location and presentation, papillary thyroid carcinoma could present in the neck. Gleeson et al. reported that metastatic squamous cell carcinoma or lymphoma should be considered in the absence of infectious signs in patients over 40 years. [xi]
Patients with a mean age above 55 were more likely to have neoplastic masses. Our findings suggest that age can be a risk factor for a worse outcome when diagnosing neck masses. Other studies have also reported increasing patient age as a predictive factor for neoplastic masses in the neck. [xii] [xiii] [xiv]. Rowicki et al. reported that adults older than 40 have the highest incidence of malignancy.[xv]
Reactive masses may be non-specific lymphadenopathy presenting as neck masses. In a study by Al Kadah et al., a non-specific reactive hyperplasia occurred in 35.5 % of cases.[xvi] In this study, localized non-specific reactive lymphadenopathy occurred in 68% of cases, while florid reactive follicular hyperplasia happened in 13.6%. Moreover, a single case of Kikuchi Fujimoto disease, acute necrotizing lymphadenitis, and Castleman disease. Another cause of non –lymphatic reactive neck masses was traumatic neuroma presented in a single case.
Infection-related and congenital masses had a lower age distribution. Granulomatous lymphadenitis and tuberculosis represent 47% of infectious masses. In recent study, the majority of mycobacterial lymphadenitis cases occurs in submandibular and cervical lymph nodes in children under the age of five.[xvii] In our study, mycobacterial lymphadenitis cases mainly occurred in patients younger than 20 years. Another study conducted in Turkey also found that tuberculous lymphadenitis represents 40% of inflammatory masses. There was a significant higher occurrence of inflammatory masses in patients aged 0 - 20 years than those with ages equal to or higher than 41. [xviii]
All of the other types of neck masses occurred in patients younger than 55 years old and included cutaneous cysts.[xix] In which epidermoid cysts presented in 95% while atypical lymphoid hyperplasia presented in a single case. In a study by Al-Khateeb et al., epidermal inclusion cysts were found in 49% of patients with cutaneous cysts, with 68% in the neck.[xx] Similar findings were shown in a study by Golden et al., where epidermal inclusion cysts were found in 79% of the study patients with cutaneous head and neck cysts.[xxi] Although this study has investigated 16 years retrospectively and shown significant results that can influence the differential diagnosis of clinically solitary neck mass, there is a need for future multicenter studies with larger number of patients to diagnose and investigate these cases.
In conclusion, northern Jordanian patients >55 years of age are more susceptible to have malignant neck masses and therefore they should be cautiously evaluated and diagnosed. The diagnostic accuracy of this approach needs to be confirmed in a large multicenter study with a larger number of patients.
Acknowledgements
We thank Dr. Nour Abdo, an associate professor at the Faculty of Public Health and Community Medicine, Jordan University of Science and Technology, for assistance with biostatistical methods and her comments that significantly improved the manuscript.
REFERENCES
[1]- Pynnonen MA, Gillespie MB, Roman B, Rosenfeld, RM, Tunkel DE, Bontempo L, et al. Clinical Practice Guideline: Evaluation of the Neck Mass in Adults. Otolaryngology-Head and Neck Surgery 2017; 157(2S), S1–S30. doi:10.1177/0194599817722550
2 - Alvi A, Johnson, JT. The neck mass. Postgraduate Medicine 1995; 97(5), 87-97. doi:10.1080/00325481.1995.11945993
3- Schwetschenau E, Kelley DJ. The adult neck mass. Am Fam Physician. 2002 Sep 1;66(5):831-8. PMID: 12322776.
4- Jackson DL. Evaluation and Management of Pediatric Neck Masses: An Otolaryngology Perspective. Physician Assist Clin. 2018;3(2):245-269. doi:10.1016/j.cpha.2017.12.003
5- Yehuda M, Schechter ME, Abu-Ghanem N, et al. The incidence of malignancy in clinically benign cystic lesions of the lateral neck: our experience and proposed diagnostic algorithm. Eur Arch Otorhinolaryngol. 2018;275(3):767-773. doi:10.1007/s00405-017-4855-6
6- Robbins KT, Clayman G, Levine PA, et al. Neck Dissection Classification Update: Revisions Proposed by the American Head and Neck Society and the American Academy of Otolaryngology–Head and Neck Surgery. Arch Otolaryngol Head Neck Surg. 2002;128(7):751–758. doi:10.1001/archotol.128.7.751
7- Seoane, J., Alvarez–Novoa, P., Gomez, I., Takkouche, B., Diz, P., Warnakulasiruya, S., Seoane–Romero, J.M. and Varela–Centelles, P. Early oral cancer diagnosis: The Aarhus statement perspective. A systematic review and meta-analysis. Head Neck, 38: E2182-E2189. (2016), doi.org/10.1002/hed.24050.
8- Coca-Pelaz, A., Takes, R.P., Hutcheson, K. et al. Head and Neck Cancer: A Review of the Impact of Treatment Delay on Outcome. Adv Ther 35, 153–160 (2018). https://doi.org/10.1007/s12325-018-0663-7
9- Gatta, GemmaHackl, M. et al. Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 population-based study, European Journal of Cancer, Volume 51, Issue 15, 2130 – 2143, doi.org/10.1016/j.ejca.2015.07.043
10- Khader YS, Sharkas GF, Arkoub KH, Alfaqih MA, Nimri OF, Khader AM. The Epidemiology and Trend of Cancer in Jordan, 2000-2013. J Cancer Epidemiol. 2018;2018:2937067. Published 2018 Oct 17. doi:10.1155/2018/2937067
11- Shuaibu IY, Sholadoye TT, Ajiya A, Usman MA, Aliyu HO. Paediatric neck masses in Zaria: A review of clinical profile and treatment outcome. Afr J Paediatr Surg. 2021;18(4):205-209. doi:10.4103/ajps.AJPS_134_20
12- Al-Khateeb TH, Al Zoubi F. Congenital neck masses: a descriptive retrospective study of 252 cases. J Oral Maxillofac Surg. 2007 Nov;65(11):2242-7. doi: 10.1016/j.joms.2006.11.039. PMID: 17954320.
13- Nicollas R, Guelfucci B, Roman S, Triglia JM. Congenital cysts and fistulas of the neck. Int J Pediatr Otorhinolaryngol. 2000 Sep 29;55(2):117-24. doi: 10.1016/s0165-5876(00)00384-0. PMID: 11006451.
14- Jackson DL. Evaluation and Management of Pediatric Neck Masses: An Otolaryngology Perspective. Physician Assist Clin. 2018;3(2):245-269. doi:10.1016/j.cpha.2017.12.003
15- Tracy TF Jr, Muratore CS. Management of common head and neck masses. Semin Pediatr Surg. 2007 Feb;16(1):3-13. doi: 10.1053/j.sempedsurg.2006.10.002. PMID: 17210478
16- Quintanilla-Dieck L, Penn EB Jr. Congenital Neck Masses. Clin Perinatol. 2018;45(4):769-785. doi:10.1016/j.clp.2018.07.012
17- Gleeson M, Herbert A, Richards A. Management of lateral neck masses in adults. BMJ. 2000;320(7248):1521-1524. doi:10.1136/bmj.320.7248.1521
18- Bhattacharyya N. Predictive Factors for Neoplasia and Malignancy in a Neck Mass. Arch Otolaryngol Head Neck Surg. 1999;125(3):303–307. doi:10.1001/archotol.125.3.303
[1]9- Otto RA, Bowes AK. Neck masses: benign or malignant, Postgraduate Medicine, 1990; 88:1, 199-204, DOI: 10.1080/00325481.1990.11716372 .
20- Irani, Sousa & Zerehpoosh, Farahnaz & Sabeti, Shahram. Prevalence of Pathological Entities in Neck Masses: A Study of 1208 Consecutive Cases. Avicenna Journal of Dental Research. (2016). DOI:10.17795/ajdr-25614.
21- Rowicki T, Pietniczka-Załeska M, Dabrowska-Bień J. Diagnostyka róznicowa i leczenie guzów szyi w materiale oddziału Otolaryngologii Miedzyleskiego Szpitala Specjalistycznego w Warszawie [Differential diagnosis and treatment of neck masses. A study based on observation in Otolaryngology Department of Miedzyleski Specialistic Hospital in Warsaw]. Otolaryngol Pol. 2009 Sep-Oct;63(5):414-8. Polish. doi: 10.1016/S0030-6657(09)70153-2. PMID: 20169906.
22- Al Kadah B, Popov HH, Schick B, Knöbber D. Cervical lymphadenopathy: study of 251 patients. Eur Arch Otorhinolaryngol. 2015 Mar;272(3):745-52. doi: 10.1007/s00405-014-3315-9. Epub 2014 Oct 8. PMID: 25294051.
23- Winburn B, Sharman T. Atypical Mycobacterial Disease. [Updated 2022 Jan 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556117/
24- Balikci HH, Gurdal MM, Ozkul MH, Karakas M, Uvacin O, Kara N, et al. Neck masses: diagnostic analysis of 630 cases in Turkish population. European Archives of Oto-Rhino-Laryngology, 2013; 270(11), 2953–2958. doi:10.1007/s00405-013-2445-9.
25- Zito PM, Scharf R. Epidermoid Cyst. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499974/
26- Al-Khateeb TH, Al-Masri NM, Al-Zoubi F. Cutaneous cysts of the head and neck. J Oral Maxillofac Surg. 2009 Jan;67(1):52-7. doi: 10.1016/j.joms.2007.05.023. PMID: 19070748
27- Golden BA, Zide MF. Cutaneous cysts of the head and neck. J Oral Maxillofac Surg. 2005 Nov;63(11):1613-9. doi: 10.1016/j.joms.2005.08.002. PMID: 16243178.