*Article* **The Prevalence and Treatment Costs of Non-Melanoma Skin Cancer in Cluj-Napoca Maxillofacial Center**

**Cosmin Ioan Faur 1, Mădălina Anca Moldovan 1,\*, Mădălina Văleanu 2, Horat,iu Rotar 1, Laura Filip <sup>1</sup> and Rares, Călin Roman <sup>1</sup>**


**Abstract:** *Background and Objectives:* An increasing incidence of non-melanoma skin cancer (NMSC) is noted, as well as an increasing cost of the treatment, with NMSC becoming a public health problem. We aimed to investigate the prevalence and treatment costs of surgically treated NMSC from the Oral and Maxillofacial Surgery Department of Cluj-Napoca County Hospital. *Materials and Methods:* We retrospectively analyzed the clinical data and the charge data of hospitalization from the informatic system of Cluj-Napoca County Hospital. All patients benefited from standard surgical excision with the reconstruction of the post-excisional defect. A statistical analysis of the costs related to the patients' features, period and conditions of hospitalization, materials, medication, and paraclinical investigations was performed. *Results:* Between 2015 and 2019, 133 patients with NMSC were addressed to our department, with basal cell carcinoma (BCC) being four-fold higher than squamous cell carcinoma (SCC). Most NMSC cases were diagnosed in stage I or II, and they benefited from local reconstruction. The treatment costs progressively increased in the last five years, reaching a total cost of EUR ~13.000 in 2019. The treatment cost per episode was higher for SCC compared to BCC, while the total cost of treatment in 5 years was higher for BCC. Low income, immunosuppression, comorbidities, flap reconstruction option, long-lasting surgery, and prolonged hospitalization were associated with an increased cost of the treatment. *Conclusion:* The prevalence and treatment cost of surgically treated NMSC of the head and neck region increased in the last five years, with high-cost drivers being related to patients and treatment options.

**Keywords:** non-melanoma skin cancer; head and neck cancer; hospitalization costs

#### **1. Introduction**

Non-melanoma skin cancer (NMSC) is an important health problem due to increased incidence in the last years and the increased morbidity and costs of the treatment [1,2]. However, the real incidence of NMSC is unknown. The World Health Organization (WHO) estimates 2–3 million malignant skin tumors per year which are most likely under-reported, especially in light of a recent study that estimated 3.3 million people who suffered from 5.4 million NMSC cases, part of them presenting more than one skin tumor [3]. In addition, the GLOBOCAN project of the International Agency for Research on Cancer reported an incidence of 1,198,000 new cases of NMSC (excluding basal cell carcinoma) in all sites worldwide in 2020, which was four-fold higher than malignant melanoma (324.000 new cases) [1]. The incidence of NMSC in the European population varies depending on geographical area, histopathological type, and age [4]. The prevalence of head and neck NMSC reported in Northeastern Romania was 72.5% and in Poland was 90% [5,6].

Most histopathological variants of the NMSC are basal cell carcinoma (BCC) (75–80%) and squamous cell carcinoma (SCC) (20–25%), the remnant variants (1%) being Merkel cell

**Citation:** Faur, C.I.; Moldovan, M.A.; V ˘aleanu, M.; Rotar, H.; Filip, L.; Roman, R.C. The Prevalence and Treatment Costs of Non-Melanoma Skin Cancer in Cluj-Napoca Maxillofacial Center. *Medicina* **2023**, *59*, 220. https://doi.org/10.3390/ medicina59020220

Academic Editors: Adriana Neagos, Daniela Vrinceanu, Codrut Sarafoleanu and Mahmut Tayyar Kalciogu

Received: 28 November 2022 Revised: 3 January 2023 Accepted: 19 January 2023 Published: 23 January 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

carcinoma, sebaceous carcinoma, apocrine adenocarcinoma, and other rare tumors [7]. In Europe, BCC presents a high incidence in Western Europe, especially in the Netherlands (87.5/100,000 person-years), Switzerland, and Italy (70/100,000 person-years), and a low incidence in Central and Eastern Europe, with Croatia presenting the lowest incidence (33.6/100.000 person-years). In addition to BCC, SCC has a high incidence in Western Europe (Switzerland 28.9/100.000 person-years), followed by Northern Europe, and a low incidence in Central and Eastern Europe (Croatia 8.9/100,000 person-years) [1–4].

The risk factors for developing NMSC are fair skin, increased number of freckles, sunburns, sun exposure, radiation, and immunosuppression [4–8]. Owing to the UVassociated risk, Australia and New Zealand are the countries with the highest risk of developing NMSC [1]. In addition, aging is an independent risk factor for the occurrence of head and neck NMSC. The head and neck region is prone to developing NMSC, being a highly sun-exposed area [5,6].

BCC causes significant morbidity due to local destructive spread and high local recurrence risk but has low metastatic potential [9]. On the contrary, SCC has a high propensity for metastatic spread, and hence a poor prognosis. SCC mortality is usually associated with locoregional and distant metastases [10]. The 5-year survival rates of NMS depend on age, immunosuppression status, surgical margins, and tumor features being higher for BCC compared to SCC [11]. Overall, NMSC has a better prognostic than other skin cancers, such as malignant melanoma or Merkel carcinoma [12,13].

NMSC treatment can be conducted by standard surgical excision, Mohs micrographic surgery, or destructive methods, such as curettage, cautery, cryosurgery, photodynamic therapy, and the application of local drugs [14]. Surgical excision, which encompasses 85% of cases, reports a five-year cure rate of 99% for BCC and 97% for SCC [15]. The cost of cancer treatment is high, being an economic and clinical burden to the National Healthcare system, as well as an economic burden to individuals [13]. The NMSC diagnosis and treatment costs are more expensive than those of malignant melanoma, due to higher incidence, even though the cost of malignant melanoma is higher per person-year [16,17]. Moreover, the NMSC treatment costs increased in the last years more than other skin cancers, being four-fold more expensive than malignant melanoma treatment [15–18]. BCC has a higher total cost of treatment compared with SCC [19]. Generally, the costs of head and neck cancers are higher compared with other locations, and the patients tend to be poorer and to have accrued lower levels of education than patients with other cancers [13,15,20]. Moreover, head and neck NMSC treatment has a higher cost than other anatomical regions, with the highest cost in nose BCC and auricle SCC tumors [5,16,19]. The costs also vary in different geographical areas due to different incidence and treatment protocols [21].

NMSC is not usually reported to a cancer database, hence the incidence and cost of the treatment are difficult to assess. Moreover, there are a few studies that discuss the head and neck NMSC treatment costs, and from our knowledge, none are reported in Romania. We aim to evaluate the prevalence and the direct costs of surgical treatment of head and neck NMSC from the Maxillofacial Surgery Department of Cluj-Napoca County Hospital.

#### **2. Materials and Methods**

We conducted a retrospective study on patients who were addressed to the Oral and Maxillofacial Surgery Department of Cluj-Napoca County Hospital between the first of January 2015 to the 31st of December 2019. We enrolled the patients who were hospitalized for at least 24 h in our department and had a histopathological result of head and neck BCC or SCC and primary or recurrent tumors. All the patients were treated by surgical excision and reconstruction of the defect. We excluded the patients who had an inconclusive histopathologic result, melanoma, Merkel cell skin cancer, or other rare malignant skin tumors, as well as benign skin lesions and the patients that underwent oncological treatment. All the included patients were staged according to American Joint Committee on Cancer (eighth edition) [22,23]. The patients' comorbidities were classified based on the American Society of Anesthesiologists (ASA) risk stratification to have an objective assessment of

the general health status [24]. Not all the patients responded to education formation and economical status at hospital admission. This study was approved by the Ethics Committee of "Iuliu Hatieganu" University of Medicine and Pharmacy (AVZ 20/03.02.2022), and it is in accordance with the updated Declaration of Helsinki.

#### *2.1. Data Collection and Cost Analysis*

We reviewed the clinical data and the charge data of hospitalization from the informatic system of Cluj-Napoca County Hospital. The data extracted from the electronic medical records included the following: patients' demographics and associated medical diagnoses; the results of histopathological examinations; tumor characteristics, such as site; clinical and pathologic stage; treatment modality; and the discharge bill. The histopathological subtypes were classified according to the major pattern present in the specimen, many of them (89%) having 2 or more histopathological variants in the same specimen. We categorized the treatment after standard surgical excision as per primam closure, skin graft, and local flap reconstruction.

We analyzed only the direct costs of care related to the hospitalization for NMSC surgical treatment (hospitalization accommodation costs, material costs, medication costs, and paraclinical examinations costs), without assessment of the direct costs of follow-up or the indirect (e.g., productivity costs) or intangible costs (e.g., monetary value of health loss and reduces the quality of life) [21,25]. The costs were presented as total treatment costs for NMSC, BCC, and SCC tumors and as individual mean costs of the tumors' treatment related to the number of patients or episodes of cancer. A patient is defined as a person that suffered from at least one malignant skin tumor in the time interval. An episode (of cancer) is defined as a malignant skin tumor of a patient treated in one setting appointment (hospitalization). Hence, the means of cost per episode and per patient were constructed.

The costs are reported in Euros, with an exchange medium rate calculated after the Romanian National Bank rank (e.g., 5-year medium exchange rate Euro-RON). In addition, the costs are adjusted to the inflation rate up to 2022, according to the Romanian National Bank.

#### *2.2. Statistical Analysis*

The SPSS 25.0 software (SPSS Inc, Chicago, IL, USA) was used for statistical analysis and data description. The level of statistical significance was set at α =0.05. Mean ± standard deviation was used to describe normally distributed continuous quantitative data and absolute and relative frequencies (%) were used for qualitative data.

The comparison of the means was performed by the Student t-test for normally distributed data of two independent groups. The non-parametric Mann–Whitney and Kruskal–Wallis tests were used to compare the means of two independent groups with nonnormal distribution. The Kruskal–Wallis test was also used for the comparison between more than two groups with non-normal distribution, and then the Tukey HSD test was used for post hoc analysis. Chi-Square or Fisher Exact tests were used to compare qualitative variables. Univariate regression analysis was used to estimate costs.

#### **3. Results**

#### *3.1. Demographical and Epidemiological Consideration of the Population*

From a total of 195 patients who were addressed for skin tumors to our service between 2015 and 2019, 144 patients presented malignant tumors, including 133 (92%) BCC and SCC patients (Figure 1). This study enrolled 102 (76%) BCC patients, 27 (20%) SCC patients, and 4 (4%) patients with both skin cancers, which presented 152 episodes of cancer. Most of the BCC tumors were nodular (66 tumors), infiltrative (33 tumors), or basosquamous (13 tumors) differentiated, the rest (8 tumors) being less frequent histopathological BCC variants. SCC grading revealed 11 well-differentiated, 18 intermediate-differentiated, and 3 poorly differentiated tumors, with only 5 of the SCC tumors (15%) being non-keratinizing lesions. Sixteen patients had two NMSCs with different localizations, excised during the 5-year period (eleven BCC patients, one SCC, and four patients had one BCC and one SCC).

One 74-year-old female patient presented four hospitalizations between 2018 and 2019 for BCC tumors located in different head and neck regions.

**Figure 1.** Year distribution of the skin cancer patients.

The mean ± standard deviation age of the NMSC patients was 67 ± 13 years, being slightly increased for SCC subpopulations (69 ± 15 years) compared to SCC ones (67 ± 13 years). The maximum prevalence of NMSC episodes was in the seventh decade of life, as can be seen in Table 1. The male-to-female ratio was 1.3:1 and most of the patients (60.53%) had an urban place of residence. In addition, most of the patients (61 subjects) that responded to the admission questionnaire did have any education following high school, and only 32 patients had university studies. In addition, many of these patients had low-income economic status.

**Table 1.** Non-melanoma skin cancer epidemiology and treatment costs.



#### **Table 1.** *Cont.*

\* Statistical analysis of episode comparison between BCC and SCC subsets; \*\* average treatment costs of NMSC related to the cancer episodes; \*\*\* statistical analysis of NMSC cost between different subsets.

We found 148 primary tumor excisions of NMSC (117 BCC and 31 SCC) and 4 recurrence tumor excisions (3 BCC and 1 SCC). The tumor distribution in the head and neck regions is seen in Table 1. The nasal and cheek regions were highly involved by NMSC tumors. The skin malignant tumors were diagnosed frequently in stage I (97 tumors) or II (31 tumors) and were frequently managed by radical excision (146 tumors) with flap reconstruction (84 cases) or primary closure (50 cases) (Table 1). The surgical defects located in nasal, cheek, and orbital regions often required flap reconstructions, and the ones located in frontal and temporal areas had more primary closures than flap reconstructions (*p* < 0.05) (Figure 2).

The surgical excisions and reconstructions last less than 1 h or between 1 and 2 h for most of the tumors (Table 1). The patients were hospitalized between 1 (61 patients) and 10 days (1 stage IV patient), with a median (Q1, Q3) of 2 (1;3) days of hospital staying. A total of 342 days (264 BCC and 78 SCC) were needed for the head and neck skin cancer treatment in the 5 years.

Even if the first stage of NMSC cases were frequently surgically treated in less than one hour, there was no statistical significance regarding the correlation between the tumor stage and the time required by surgery to be performed (Figure 3). However, there was a statistically significant correlation between the tumor stage and the hospitalization days. Stages I and II were mostly treated within one to three days of hospitalization (Figure 4). In addition, the days of hospitalization were statistically correlated with the type of reconstruction, with primary closure and skin grafts requiring fewer hospitalization days than local flap reconstruction (Figure 5). On the contrary, the hospitalization days were not statistically correlated with ASA risk, even though most ASA risk I patients required one to three days of hospitalization (Figure 6).

**Figure 3.** Correlation between tumor stage and time required to perform surgery.

**Figure 4.** Correlation between tumor stage and days of hospitalization.

**Figure 5.** Correlation between days of hospitalization and type of reconstruction.

**Figure 6.** Correlation between days of hospitalization and ASA risk.

#### *3.2. The Cost of NMSC Treatment*

The direct costs of NMSC in 5 years of treatment were approximately EUR 45.000, with an average cost/patient and cost/episode of EUR 336 and EUR 294, respectively. The costs of treatment/episode had a statistically significant increase (*p* = 0.03) from EUR 228 in 2015 to EUR 352 in 2019, with a mean increase of approximately 28 EUR/year (Figure 7). The total treatment cost/5 years was more expensive (approximately EUR 34.000) for BCC than SCC (approximately EUR 11.300). However, the average treatment cost/patient was higher for SCC (EUR 352) than for BCC (EUR 316). The most expensive treatment (EUR 2064) was applied to a temporal BCC patient that was hospitalized for 10 days in 2017.

**Figure 7.** Direct treatment costs of NMSC: (**a**) total costs/5 years for SCC and BCC; (**b**) the increasing NMSC treatment costs/episode during 5 years of analysis; (**c**) the increasing BCC and SCC treatment costs/episode during 5 years of analysis.

Additional to the costs of the surgery and the accommodation, the total direct costs of treatment included EUR 2774 for the drugs administrated during the hospitalization, EUR 2384 for the supplies, and EUR 5670 for the paraclinical examinations for the 5 years of analysis. However, the costs of the surgery and the accommodation cannot be differentiated and individually assessed due to the lack of data illustrated in the informatic system of the hospital. The details of the treatment costs are seen in Table 2. Except for the medication, the medium cost of the supplies and paraclinical examination was higher for SCC in comparison with BCC.

**Table 2.** Averages of direct cost details of head and neck skin cancers for five years of treatment related to patient and episode of cancer.


The average cost per day of treatment for NMSC was EUR 131, with SCC being more expensive to treat (EUR 138) in comparison with BCC (EUR 127). However, the cost increased with the days of hospitalization, being 9-fold higher for more than 7 days of hospital staying than for 1 day of hospitalization.

#### *3.3. Cost of NMSC Treatment Related to the Demographical and Clinical Features*

Starting from the third decade of life, the treatment cost of NMSC statistically significantly increased (*p* = 0.04) by approximately 10% to 25% per decade (Table 1). The male patients and the subjects that had a rural place of living presented higher costs of treatment, however, without any statistical significance. Moreover, the patients that underwent technical schools and subjects with lower income presented higher costs of treatment, with the economic status classification being the only statistically significant result (*p* = 0.004).

Immunosuppression was a general status-related factor that influenced the treatment costs, with immunosuppressed patients presenting a statistically significant higher cost of treatment compared with the non-immunosuppressed subjects (Table 1). ASA risk classification also statistically increased the cost of NMSC, with the third class presenting a 39% higher cost compared to the first class.

The orbital region presented the highest cost of NMSC treatment. In addition to tumor location, the tumor stage did not present statistical significance, even if stage IV had approximately 4-fold increased treatment costs compared to stage I.

Re-excision costs were 1.57-fold higher than radical treatment of a primary tumor, without any statistical significance. In addition, standard excision surgery associated with flap reconstruction or surgery that lasts more than two hours presented the highest treatment cost (*p* < 0.001).

#### **4. Discussion**

The prevalence of NMSC tumors of the head and neck region in our study (approximately 90% of the malignant skin tumors) was higher than that reported in northeastern

Romania, however, the BCC to SCC ratio (4:1) was in accordance with the literature [1,5,6]. In addition, we had similar results regarding the age-related risk for NMSC development, with approximately 80% of the episodes of cancer in our research occurring in subjects older than 60 years, with a slightly increased age of SCC subjects [21,26]. We found that the nose was the most frequent tumor site for NMSC lesion development.

We identified increasing costs of NMSC treatment per year in the last 5 years, which could be attributed to the increasing number of patients and to the treatment costs of cancer episodes, expected to be much higher in the next years as the costs were constantly raising by 28 EUR/year. The increasing costs of the treatment rely on the new technologies and better quality of life offered by the new therapies [27]. However, our findings underestimate the real total costs of NMSC treatment, which has a complex calculation [20,26]. The direct cost of treatment represents approximately 72% of the total cost related to NMSC treatment, without including the oncological treatment, follow-up, patients' loss of income, quality-oflife changes, and economic reintegration [21,25]

We included only patients that were addressed to a Maxillofacial hospital, without subjects that were treated by other specialists, such as Plastic Surgery or Dermatology physicians, where the treatment options and the associated costs may be different from our standard surgical excision [15,21,26]. In addition, this research was limited to the hospitalized patients and charge data, aiming to identify the economic burden of the healthcare system and to observe the cost distribution patterns and high-cost drivers. However, the costs of hospitalized patients are higher than ambulatory-treated patients [15]. Still, the cost of NMSC treatment in Romania is cheaper than in other countries, such as Australia or other Northern or Western European countries [21,26].

Different from other studies, we could not find an association between the place of living or sex and NMSC increased cost. In the research of Tran et al. and Doran et al., urban place of residence or female patients presented higher costs of NMSC treatment compared with rural place of living and male patients [19,21]. Elderly patients presented a higher cost of treatment compared to young adults due to various arguments. Firstly, the prevalence of NMSC in senior people is higher compared to young adults [21,26]. Secondly, elderly people require special medical attention due to the increased prevalence of comorbidities, quantified in our study by the ASA risk. The patients classified as high ASA risk had a significantly higher cost compared to the low-risk subjects [20]. However, our results did not indicate a statistical correlation between the increased number of hospitalization and advanced ASA risk. In addition, immunosuppressed patients had a higher cost of treatment compared with non-immunosuppressed ones, with five out of the six immunosuppressed patients included in this study being aged more than 60 years old.

The increased costs of NMSC treatment for technical school and low-income patients were consistent with other research. The subjects that are exposed more to professional emissions and have low income are prone to developing NMSC cancers, and the treatment costs are higher compared with patients of other education and economic status [6,20]. However, we found a statistical significance of increasing costs related only to educational formation.

The head and neck NMSC treatment is more expensive than other anatomical regions, such as the thorax and limbs, but it is lower compared with head and neck mucosal malignancies (e.g., SCC of oral cavity or oropharynx) [19,20]. However, 19% of head and neck cancers are located on the skin [25]. Particularly, the orbital region had the highest cost of treatment per episode, which may be due to the difficulty of local reconstruction of this anatomical area [28,29]. These results are different from other research, where nasal and auricle NMSC had the highest treatment costs [5,16,19]. In our research, the nasal region presented an average cost of treatment per episode lower than the orbital region, but the total cost of treatment was the highest compared with other anatomical regions, due to the highest number of NMSC episodes.

Although the treatment cost of BCC per 5 years was higher compared to SCC, the BCC treatment cost per episode was cheaper than SCC, similar to other research [19,26]. These findings may be explained by the increased rates of BCC tumors and the more radical

treatment required by SCC tumors, as well as the more paraclinical examinations needed perioperatively by SCC tumors to evaluate the locoregional or distant metastasis [17,30,31].

Different from the study by Chen et al. that observed a significant increase in treatment costs in the advanced stages of the disease, we observed an approximately 4-fold increase in the treatment costs of stage IV compared with stage I, but our results had no statistical significance [15]. However, the costs may be related to the more complex surgical procedure and to the more careful postoperative medical attention in advanced stages compared to early stages [32].

The local flap was approximately 60% more expensive than the skin graft. The result of this type of reconstruction is more aesthetic compared to the skin graft due to its similar color and texture to the adjacent facial tissues [33]. Both variants of reconstruction are used for tumors of increased dimensions, where the primary closure is not possible. However, the local flaps require an increased procedure time compared to other types of reconstruction, with the time needed to perform the surgery also being a factor that increased the costs [25]. A procedure that lasts longer than 2 h has more than double the costs compared with surgeries that can be performed faster (1 h). In addition, the local flap required more days of hospitalization than the primary closure or skin graft.

In our study, the high length of hospitalization was associated with higher costs of treatment. This finding may rely on the general health status of the patient or on the complex surgical procedure that requires many days of medical attention [31]. However, we found a statistical correlation between the hospital stay and the reconstruction type and tumor stage, without ASA risk. The median length the hospitalization for NMSC patients was 2 days, indicating that the surgical treatment of NMSC can be performed as a fast-track surgery, especially for patients with low ASA risk and early stages of cancer.

We enrolled a limited number of patients, which may influence the statistical analysis. Due to COVID-19 lockdowns, the number of patients that were addressed to Oral and Maxillofacial Surgery for head and neck skin tumors was reduced, hence, we limited the inclusion criteria to the 31st of December 2019 [34]. However, the majority of included patients were clustered in stage I or II, similar to other research [35].

Another limitation of our study was the lack of capacity to particularly assess the cost of the surgical procedure due to the lack of specific data in our hospital's informatic system.

#### **5. Conclusions**

Non-melanoma skin cancers are an important health problem due to increasing prevalence and treatment costs in the last years. The factors that can increase the costs of the treatment are related to the patient, such as age, low income, immunosuppression, and comorbidities, and to the procedure, such as flap reconstruction option, long-lasting surgery, and prolonged hospitalization.

**Author Contributions:** C.I.F., M.A.M., H.R., L.F. and R.C.R. conceptualized the study design and wrote part of the manuscript; C.I.F., M.A.M. and R.C.R. collected the patients' medical history from the informatic system; M.V. performed the data analysis. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** This study was approved by the Ethics Committee of "Iuliu Hatieganu" University of Medicine and Pharmacy (AVZ 20/03.02.2022), and it is in accordance with the updated Declaration of Helsinki.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** All authors read and agreed on the submission form of the manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


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### *Case Report* **Tongue Base Ectopic Thyroid Tissue—Is It a Rare Encounter?**

**Balica Nicolae Constantin 1,2, Trandafir Cornelia Marina 1,2,\*, Stefanescu Horatiu Eugen 1,2, Enatescu Ileana <sup>3</sup> and Gluhovschi Adrian <sup>4</sup>**


**Abstract:** Failure in the embryological development of the thyroid in adults is rarely seen. We present the case of a 79-year-old female patient who complained of dysphagia and progressive upper respiratory obstruction, which started 12 months prior to her admission. An ENT clinical exam revealed a tongue base, spherical, well-defined tumour covered by normal mucosa. Further assessments established the diagnosis of the tongue base ectopic thyroid tissue. Due to the patient's symptoms, a transhyoid tongue base tumour removal was performed. The selected patient gave consent for participation and inclusion in this paper, in compliance with the 1964 Helsinki declaration.

**Keywords:** tongue base; ectopic thyroid tissue; dysphagia; upper airway obstruction

#### **1. Introduction**

Ectopic thyroid tissue is an embryologic defect. The disease involves the aberrant development of the thyroid gland from the foramen caecum to its inferior cervical position [1,2]. The causes and exact mechanism of this aberrant defect have not been clearly elucidated, even though some transcription factors seem to playa role in the migration of the thyroid [3]. Its prevalence is about 1 per 100,000–300,000 people, increasing to 1 per 4000–8000 in patients with thyroid disease [1,2]. It is mostly diagnosed in childhood, adolescence, and around menopause, with a slight prevalence in females [4].

Ectopic thyroid tissue can be found anywhere along the course of the thyroglossal duct [5]. The base of the tongue represents the most frequent location [6]. Other sites involved are the anterior tongue, the submandibular or sublingual region, the larynx, the trachea, the mediastinum, and the heart [7,8]. The differential diagnosis of ectopic thyroid tissue must include metastatic thyroid carcinoma [9].

Most ectopic thyroids are asymptomatic. The symptoms are related to the sites of the ectopic tissue and can cause dysphagia, dysphonia, bleeding, or even upper respiratory obstruction, and, therefore, patients are referred to an ENT specialist for their diagnosis and treatment.

The combination of diagnostic imaging techniques and hormonal biological examinations correlating with the clinical ENT examination plays a fundamental role in the diagnosis of an ectopic thyroid tissue.

There is no consensus for the optimal treatment of ectopic thyroid tissue due its rarity. Some authors recommend a "wait-and-see" policy to ascertain whether the patient is in a euthyroid status or if the asymptomatic ectopic tumour is small. If the tumour continues to enlarge, leading to the compression of surrounding structures with consecutive occurrences of algia, dysphagia, dysphonia, or upper respiratory obstruction, surgical treatment can be proposed. Conventionally, various external approaches have been described in the literature; recently, transoral surgery has gained increasing popularity as an alternative

**Citation:** Constantin, B.N.; Marina, T.C.; Eugen, S.H.; Ileana, E.; Adrian, G. Tongue Base Ectopic Thyroid Tissue—Is It a Rare Encounter?. *Medicina* **2023**, *59*, 313. https://doi.org/ 10.3390/medicina59020313

Academic Editors: Adriana Neagos, Daniela Vrinceanu, Codrut Sarafoleanu, Mahmut Tayyar Kalciogu and Silviu Albu

Received: 29 November 2022 Revised: 30 January 2023 Accepted: 6 February 2023 Published: 8 February 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

to external surgical treatment. Suppressive hormone therapy and ablative radioiodine therapy are described as alternative treatments for patients with lingual thyroid by some authors [3,4,10].

It is important to establish the periodic follow-up of patients with an endocrinologist specialist due to the post-operative hypothyroidism risk.

#### **2. Case Report**

A 79-year-old female patient with dysphagia and respiratory insufficiency was admitted to the ENT department. The symptomatology started twelve months prior to her admission to the hospital. She had no history of smoking and no alcohol intake. She was under medical treatment for hypercholesterolemia and high blood pressure.

The clinical ENT examination revealed no cervical adenopathy. The endoscopic examination (with a 70 degree rigid hypopharyngoscope) revealed a tongue base, spherical, solid, well-defined tumour covered by normal mucosa and obstructing the visualisation of the larynx (Figure 1).

**Figure 1.** 70 degrees rigid hypopharyngoscope shows the mass in the sublingual region.

By comparing the further assessments (neck ultrasonography, thyroid scintigraphy, and cervical region Magnetic Resonance Imaging MRI (Figure 2)), the diagnosis of a tongue base ectopic thyroid tissue was established.

**Figure 2.** Magnetic Resonance Imaging (MRI) imaging shows a mass in the sublingual region (arrow).

Due to the patient's symptomatology, the decision was made to perform surgical treatment with an external approach. Under general anaesthesia, we performed a tracheotomy

and a transversal superior incision at the level of the hyoid bone, externally excising the tongue base tumour (Figure 3).

**Figure 3.** Intraoperatory imaging (Arrow—Tumor).

The tracheotomy was performed for airway control following surgery. Nutrition was delivered via a naso-gastric feeding tube. The post-operative treatment included a large spectrum of antibiotics for prophylaxis, anti-reflux medical treatment, and non-opioid analgesics. The post-operative evolution was unremarkable. The tracheotomy cannula and the feeding tube were both maintained for seven days, and deglutition was normal after the removal of the feeding tube. The patient was free of symptoms two weeks after the surgical procedure. The patient was referred to an endocrinologist before and after the surgery for hormonal substitutive treatment. Circulating levels of thyroid hormones at baseline were thyroid stimulating hormone TSH 12.8 μU/mL, FT3 1.9 pg/mL, and FT4 8.9 pg/mL.

The patient started L-T4 replacement therapy 5–7 days after the surgery. The value of L-T4 was 100 μg per day. After two month under L-T4 replacement therapy, the TSH was3.0 μU/mL; FT 3 was 4.1 pg/mL;and FT4 was 11.5 pg/mL.

The anatomo-pathological exam revealed the ectopic thyroid tissue.

Six years after the surgery, there was no evidence of recurrence and no symptomatology.

#### **3. Discussion**

The first endocrine gland that occurs during foetal development is the thyroid gland [11]. The embryologic development implies an endodermal diverticulum (third or fourth week of gestation), which descends from the foramen caecum to the thyroid gland's final location (24th day) through the thyroglossal duct. The latter undergoes atrophy prior to the definitive formation of the thyroid [1,12,13]. Failure in thyroid migration along the path from the original region of the thyroid to its final cervical location causes ectopic thyroid tissue, which can be commonly found at any location from the tongue base to the mediastinum [14,15].

Many causes have been linked to the failure of thyroid migration, as well as to atypical morphological aspects of the thyroid, notably molecular, genetic, or epigenetic disorders [16,17].

In 70–90% of cases of ectopic foci of thyroid tissue, the ectopic tissue is the only thyroid tissue present, and the thyroid gland is absent [3,6,18]. It may occur at any age, from 5 months to 40 years, being more common at younger ages, with a high prevalence in females [1,2,19,20]. In the literature, only a few cases of a dual ectopic thyroid gland along with a cervical thyroid gland have been described [21]. In the literature, half of patients are euthyroid, and the rest are hypothyroid [3,6]. In our case the patient was referred to an endocrinologist for the supplementation hormonal treatment and follow-up.

The presence of an ectopic thyroid tissue can be asymptomatic, can cause local symptoms such as dysphagia, and can be the leading cause of death as described by Dr Hickman

in a case report of a new-born with a lingual thyroid who died from severe respiratory distress [7]. All diseases that can affect a normal thyroid can affect the ectopic thyroid tissue (adenoma, hyperplasia, inflammation, and rarely malignancy) [6,22]. The incidence of malignancy is estimated at 1% [19,23,24].

Massine et al. described a case of a 57-year-old patient with the diagnosis of a papillary carcinoma arising from a lingual thyroid and an invasive keratinising poorly differentiated squamous cell carcinoma from adjacent structures. The patient was treated by a total glossectomy, with a left elective neck dissection, supraglottic laryngectomy, and midline mandibulotomy with a rectus free flap [24].

The presence of an ectopic thyroid tissue is less frequently encountered in other anatomical spaces: the pancreas [25], porta hepatis [26], submucosa of the duodenum [27], and the iris [28]. In these cases, it is important for the clinician to rule out metastases from a thyroid carcinoma [29].

Sometimes the thyroid malignancy is excluded, but the ectopic tissue is confirmed at a distance from its normal path of embryological development. In those cases, the congenital defect is difficult to explain. Many theories are present in the literature. For example, the common origin of the intra-abdominal organs and the thyroid are from the endodermal germ layer. The presence of an ectopic thyroid tissue was found by Aiwen Ma et al. below the diaphragm, in a retroperitoneal mass between the superior border of the kidney, having a close interaction with the pancreatic hook [23,30].

However, the theory described previously does not explain the presence of the ectopic tissue in the adrenal gland because the adrenal cortex originates from the mesodermal layer while the medulla originates from the ectodermal layer. Many other explanations can be found in the literature: teratoma, metaplasia, and choristoma [23,31].

When a basilingual mass is found, a complete Ear, nose and throat examination (ENT) exam should be performed, and uncommon diseases should be kept in mind when examining any patient [32]. A cervical ultrasound is a valuable tool for identifying an ectopic thyroid tissue. Computed Tomography (CT) scans and MRI imaging are widely used to assess the exact location and extension of ectopic thyroid foci. Scintigraphy is highly sensitive in detecting thyroid tissue, which is used for the differentiation of the thyroid from other differential diagnoses. As has been previously described in the literature, a biochemical thyroid profile may be necessary in adult patients and in new-borns, as some studies suggest that hypothyroidism can be diagnosed in patients with ectopic thyroid tissue due to the absence of a functioning thyroid gland [11].

Differential diagnoses should include thyroglossal duct cysts without thyroid tissue, midline branchial cysts, lymphangioma, haemangioma, and minor salivary gland tumours [2,33].

If the diagnosis of an ectopic lingual thyroid is established and the patient presents obstructive symptomatology or a malignant disease is suspected, surgical treatment must be performed after a multidisciplinary examination of the patient.

The patients with an airway obstruction may include a tracheostomy as an emergency procedure or for airway control following surgery, as described in our report (severe postoperative oedema is frequent). Even though a tracheostomy is considered a routine surgical procedure, there area number of potential vessels that can be accidentally injured during the procedure. Injuries of the thyroidea-ima were described in some cases of percutaneous tracheostomy [34,35].A study by Laphatrada Yurasakpong et al. revealed the presence of the thyroidea-ima in approximately 3.8% population, with a decline in the prevalence of the thyroidea-ima over the generations. Awareness of this normal variant of neck anatomy is important when performing a tracheostomy [36]. In our report, this variant was not present.

The treatment of an ectopic lingual thyroid depends on several factors. In cases with no clinical symptoms, a substitutive therapy with thyroid hormones can be proposed. Ablative radioiodine therapy is reserved for cases when surgical therapy is contraindicated, and it is not usually used for young patients [13,24]. However, in our report, the size of the

lesion, the presence of local symptoms, and the presence of complications made us perform the surgical therapy.

The excision of q lingual ectopic thyroid tissue may be performed with a variety of approaches from intensive surgical procedures (Sistrunk technique, lateral pharyngotomy, and trahnsyoid incision) to simpler and more cost-effective procedures [24,37]. Extensive surgeries offer good results, but complications such as fistula formation, infection, and the presence of a cervical/facial scar may be unsatisfactory for patients with higher cosmetic requirements.

The intraoperatory risk of bleeding during a tongue base surgery is high. However, external surgeries offer better visualisation, especially for large masses, and the bleedings are easy to control during an open surgery. Some authors use midline mandibulotomy and tongue splitting techniques to achieve a good exposure and minimise the risk of injuries [38,39].

Initially used to excise all thyroglossal tract tissue involved in thyroglossal cyst, the Sistrunk technique can be used for the management of an ectopic lingual tissue. It can offer a satisfactory removal, and the majority of the post-operative course is surgically uneventful [40,41].

In our days there has been a progressive trend to approach thyroid ectopic tissue using transoral surgery/laser methods. A Korean team demonstrated the feasibility of a Sistrunk procedure by robot-assisted surgery via a retroarticular incision for a thyroglossal cyst [42].

Trans-oral robotic surgery (TORS) is known as a minimally invasive surgical technique, approved in 2009 by the Food and Drug Administration (FDA) for head and neck surgery [43]. It improves access and visualisation, avoiding the classical invasive open techniques (midline labiotomy, tongue splitting, and mandibulotomy) [44–46]. Compared to traditional surgeries techniques, it has a different anatomic perspective. It understands the muscular landmarks and vascular anatomy and it is important for minimising the surgical risks, notably the bleeding one. The development of TORS allows for less morbidity and offers better cosmesis post-operatively [47].

In order to avoid substitutive lifelong hormone therapy, in the literature a transplantation of the lingual thyroid tissue in the muscles of the neck has been described [48].

Clearly, there remain certain situations in which minimally invasive methods are not possible. Patient factors and the availability of surgical skills and technologies should be taken into account when managing a patient with a thyroid ectopic tissue.

In our ENT department, there are more than 2500 patients admitted annually. The incidence of an ectopic thyroid among the admitted patients is roughly one case every five years.

As with many previous case reports, we acknowledge that the present article has some limitations. The rarity of this entity in our centre is likely subject to variations in clinical practice outcomes, linked to the hospital turnover of patients and the resources available.

#### **4. Conclusions**

Ectopic thyroid tissue is a rare developmental anomaly. An accurate ENT evaluation and differential diagnoses should increase the suspicion of an ectopic thyroid tissue. In cases with mild symptoms, substitutive hormone treatment might be implied, while in cases with deglutition or respiratory impairment, surgical treatment seems to be the best option.

**Author Contributions:** Conceptualisation and methodology, B.N.C.; software, T.C.M.; validation, B.N.C. and S.H.E.; formal analysis, E.I.; investigation, T.C.M.; writing—original draft, B.N.C.; draft preparation, T.C.M.; writing—review and editing, G.A.; visualisation, S.H.E. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study was conducted in accordance with the Declaration of Helsinki and was approved by the ethical committee of the institution, CECS 55/25.11.2022 (2014 rev), and received Institutional SCMUT Approval: E-6701/24.11.2022.

**Informed Consent Statement:** Written informed consent was obtained from the patient to publish this paper.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


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