Medial lingual lymph node metastasis in carcinoma of the tongue

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Case Report

Medial lingual lymph node metastasis in carcinoma of the tongue$ Kohtaro Eguchi a,b,*, Shigeo Kawai c, Masayoshi Mukai a, Hiroaki Nagashima a, Satoshi Shirakura a, Taro Sugimoto a, Takahiro Asakage d a

Division of Otolaryngology - Head and Neck Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan b Department of Clinical Anatomy, Tokyo Medical and Dental University Graduate School, Tokyo, Japan c Division of Pathology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan d Department of Head and Neck Surgery, Tokyo Medical and Dental University Graduate School, Tokyo, Japan

A R T I C L E I N F O

A B S T R A C T

Article history: Received 2 January 2019 Accepted 8 March 2019 Available online xxx

Lingual lymph node metastases are rarely seen in carcinoma of the tongue, and these nodes are not removed during neck dissection. Lingual lymph nodes are classified into medial and lateral groups, and metastasis to the former is extremely rare. A 55-year-old male with squamous cell carcinoma of the tongue, (stage T4aN0M0), underwent hemiglossectomy with neck dissection and free flap reconstruction. The lingual septum had a mass, 8 mm in size, which was diagnosed as medial lingual lymph node metastasis on histopathology. The patient developed multiple distant metastases and died of disease 18 months after the initial surgery. The presence of medial lymph node metastasis could result in contralateral neck metastases and worsen prognosis. Such cases may warrant more intensive therapy than recommended by current guidelines. © 2019 Elsevier B.V. All rights reserved.

Keywords: Lingual lymph nodes Lingual carcinoma Cancer Medial lingual nodes Lymph node metastasis

1. Introduction Lingual lymph node (LLN) metastases are rarely seen in carcinoma of the tongue, and these metastatic nodes are not usually resected during neck dissection [1]. LLNs are classified into medial (MLLN) and lateral (LLLN) groups [2]. Evidence on metastasis to this anatomical site is scarce, and its impact on clinical practice, is poorly understood. Here we report a case, in which a metastatic lymph node was detected in the lingual septum. MLLN metastases are extremely rare and are, therefore, not well recognized by head and neck

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This paper was presented at the 28th annual meeting of the Japan Society for Head and Neck Surgery. * Corresponding author at: Division of Otolaryngology - Head and Neck Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, Japan. E-mail address: [email protected] (K. Eguchi).

surgeons. In the following report, we share the lessons learned from our experience with this case. 2. Case report A 55-year-old male presented at our department with a history of swelling of the tongue, for 2 months. On examination, he had a protruding, 40 mm  20 mm lesion, with a thickness of approximately 10 mm, on the right border of the tongue. The biopsy revealed squamous cell carcinoma (SCC). Enhanced computed tomography (CT) revealed a lesion invading the genioglossus muscle, but revealed no lymph node, or distant metastases. Ultrasound examination revealed no lymph node metastases (Fig. 1). The patient refused magnetic resonance imaging (MRI), owing to severe claustrophobia. He was diagnosed with SCC of the tongue, stage T4aN0M0 (UICC 7th edition) and underwent right hemiglossectomy with right extended supraomohyoid neck dissection (levels 1–4), and a free radial forearm flap reconstruction. An 8 mm, elastic, firm,

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Please cite this article in press as: Eguchi K, et al. Medial lingual lymph node metastasis in carcinoma of the tongue. Auris Nasus Larynx (2019), https://doi.org/10.1016/j.anl.2019.03.003

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Fig. 1. Initial findings. (a) Macroscopic findings: lesion on the right border of tongue, measuring 40  20  10 mm. (b) Ultrasound examination shows no lymph node metastases. (c) Enhanced computed tomography showing a lesion invading the genioglossus muscle. No lymph node or distant metastases are seen.

round mass was identified intraoperatively, while incising the lingual septum. Since the mass resembled a metastatic lymph node, additional partial resection of the left genioglossus and geniohyoid was performed, with the intent of achieving clear resection margins (Fig. 2). Histopathological examination revealed that the mass involved a lymph node with SCC metastasis. Therefore, a diagnosis of metastasis to the MLLN was made (Fig. 3). The pathological diagnosis was that of SCC of the tongue; stage pT4a N2b, with no extranodal extension (ENE), or positive margins. The tumor thickness was 15.9 mm, with minor vascular invasion. A total of 3 nodes showed metastases. The patient was followed up without adjuvant therapy as both, ENE and margins were negative. A lymph node, 9 mm in size, was detected in the left side of the neck on routine follow-up CT scan and on ultrasonography 6 months after the initial surgery. Nodal cytology confirmed SCC, and a modified radical neck dissection was performed. Total 6 metastatic nodes were detected on pathology, which were positive for ENE. After 8 months of the initial surgery, the patient underwent adjuvant concomitant chemo-radiation with tri-weekly cisplatin at a dose of 100 mg/m2 and local radiation therapy to a dose of 66 Gy, at 2 Gy per fraction, per day. Multiple distant metastases were detected in the lung, spine, thyroid, and liver on CT scan, 14 months after the initial surgery. Palliative radiation therapy was administered to the lung and spine to a dose of 8 Gy, in a single fraction. Since the disease had relapsed within 6 months of receiving cisplatin, the

patient was treated with nivolumab at a dose of 3 mg/m2, twice a week. The disease progressed despite continued treatment, and the patient died of disease, 18 months after the initial surgery. 3. Discussion This case demonstrates that MLLN metastases have significant implications. MLLN metastases have been reported to have a negative impact on prognosis [3,4], which was reflected in this case. LLNs were first recognized in 1898, when Kuttner identified lymph nodes adjacent to the sublingual gland, and Rouvier classified them into MLLNs and LLLNs in 1938. Katayama et al., reported from their anatomical study, that the prevalence of MLLNs and LLLNs were 15.1% and 30.2%, respectively. However, later studies suggested that the prevalence was between 8.6% and 9.5%, with no consensus established to this day [5] (Table 1). LLNs were first recognized clinically when Ozeki et al. reported MLLN metastasis in 1985 [3]. Subsequent reports of LLN metastases are increasing. The incidence of LLN metastases is reported to be about 8%, and it is therefore believed that LLNs do not usually behave as sentinel nodes [6]. Metastases to the LLNs are usually to the lateral group, and this case is only the 7th MLLN metastasis reported, in English and Japanese literature [3,4,7,8]. The evidence for MLLN metastases, including its incidence, pathological features, and anatomical relationships, is therefore scarce. Histopathology in

Please cite this article in press as: Eguchi K, et al. Medial lingual lymph node metastasis in carcinoma of the tongue. Auris Nasus Larynx (2019), https://doi.org/10.1016/j.anl.2019.03.003

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Fig. 2. Surgical findings. (a) An 8-mm large, elastic, firm, round mass in the lingual septum. (b) Asterisk showing the medial lingual lymph node; the dotted line shows the resection line of the contralateral deep lingual muscles. (c,d) Star showing the right deep lingual muscles; the triangle shows the left deep lingual muscles.

Fig. 3. Pathological findings of medial lingual lymph node. (a) Gross findings of the surgical specimen (right tongue, coronal section): a 7-mm large lymph node (arrow) was located in the lingual septum between the genioglossus and the geniohyoid. The lymph node was discontinuous with the primary lesion (asterisk). (b) Medial lingual lymph node. Extra nodal extension was negative (Hematoxylin and eosin staining). (c) Metastatic squamous cell carcinoma in the medial lingual lymph node (Hematoxylin and eosin staining).

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Table 1 Anatomical studies of lingual lymph nodes (LLNs) [5]. Year

Author

Anatomic data

1898

Kuttner

1938

Rouviere

1943

Katayama

1967

Mashkov

1972

Feind

2015

Ananiana

Depicted two-three nodules at the lower mandibular margin situated posterior and anterior to the sublingual salivary gland. First grouped the LLNs into rare median and more prominent lateral. Stated the incidence of medial and lateral LLNs as 15.1 and 30.2%, respectively. Found LLNs within tongue musculature in 8.6% of 104 cadavers investigated. Grouped LLNs as regional draining lymph nodes of the oral tongue. Described LLNs as a group of interrupting nodules located along the collecting trunks of the tongue and the sublingual salivary gland. Identified 7 lateral LLNs in 5 of 21 cadavers dissected (23.8%).

a

The work of Ananian et al. is added from their original table.

reflected the outcome of the cases reported previously. There is a complex lymphatic network in the musculature of the tongue [9,10], which may lead to contralateral neck node metastasis in cancers of the tongue. Although metastases to the MLLN are rare, they are a matter of concern if detected, as there is a high risk of contralateral nodal metastasis, and death. MLLN metastases may be considered as an independent factor for poor prognosis, and such cases deserve more intensive treatment, such as additional contralateral neck dissection, or wider radiation fields. Unfortunately, MRI could not be performed in this case owing to the patient’s claustrophobia. The metastasis to the MLLN was not detected on the CT scan and the ultrasound examination, but an MRI would have provided more accurate radiological information regarding the nodal architecture. In this case, an MRI could have detected this unfavorable metastasis, and influenced the treatment plan and prognosis. 4. Conclusion

this case revealed that MLLNs have the normal structure of lymph nodes. It also found that the MLLNs are located in between the genioglossus and the geniohyoid, in the lingual septum, at a depth of three- quarters of the length from the mental spine. This case shows that MLLN metastases do occur, despite the low incidence, and it would be prudent to routinely evaluate the lingual septum in cases of carcinoma of the tongue, both, preoperatively, and during surgery. The present case indicates that MLLN metastases have a negative impact on prognosis. The past cases of MLLN metastases are listed in Table 2. The two patients, whose prognosis had been described, had both died of disease [3,4]. The prognosis of the other four cases was not presented, possibly because they were reports from pathologists, and radiologists, who were not aware of the subsequent clinical course. Bilateral lymph node metastases were found in all these four cases, and it may be reasonable to speculate that prognosis was poor. The case presented here had bilateral neck metastases, and the patient died of disease only 18 months after the initial surgery. This Table 2 Case reports of medial lingual lymph node (MLLN) metastases. YearAuthor

Findings

1985Ozeki et al. [3]

Cancer of the tongue (T3N3M0, SCC). MLLN found during resection. Patient exhibited local recurrence and died of disease 9 months after surgery. 1994Omura et al. [4] Cancer of the tongue (T3N2cM0, SCC). MLLN found in resected specimen. Patient exhibited local recurrence and died of disease 10 months after surgery. 1999Woolgar [7] Identified MLLN metastases in 3 of 118 oral and oropharyngeal cancer patients. Bilateral LN metastases were found in all 3 cases. No description of prognosis in the paper. 2017Tomblinson et al. [8]Identified MLLN metastasis (cancer of the tongue, T4aN2c) in 1 of 105 oral cancer cases. No description of prognosis in the paper. SCC, squamous cell carcinoma.

The nodal metastasis in this case was observed in an extremely rare anatomical group of lymph nodes, the MLLN. This experience demonstrates that MLLN metastasis may be an independent factor for poor prognosis, and head and surgeons should therefore be aware of this rare entity. Clinicians should also consider more intensive therapy than recommended, in case of MLLN metastases, to ensure better patient outcomes. Current evidence on lingual node metastases is poor; further accumulation of evidence is warranted. Conflicts of interest The authors have no conflict of interest to disclose. Funding None. References [1] Ando M, Asai M, Ono T, Nakanishi Y, Asakage T, Yamasoba T. Metastases to the lingual nodes in tongue cancer: a pitfall in conventional neck dissection. Auris Nasus Larynx 2010;37:386–9. [2] Rouvie`re H. Anatomy of the human lymphatic system. Ann Arbor, MI: Edwards Brother, Inc.; 1938. [3] Ozeki S, Tashiro H, Okamoto M, Matsushima T. Metastasis to the lingual lymph node in carcinoma of the tongue. J Maxillofac Surg 1985;13:277–81. [4] Omura K, Takemiya S, Shimada F, Makino S, Katahashi T, Honda T, et al. Lingual lymph node metastasis from tongue cancer. Jpn J Head Neck Cancer 1994;20:50–6 [in Japanese]. [5] Ananian SG, Gvetadze SR, Ilkaev KD, Mochalnikova VV, Zayratiants GO, Mkhitarov VA, et al. Anatomic-histologic study of the floor of the mouth: nthe lingual lymph nodes. Jpn J Clin Oncol 2015;45:547–54. [6] Suzuki M, Eguchi K, Shota I, Okada R, Kawada T, Kudo T. Lateral lingual lymph node metastasis in tongue cancer and the clinical classification of lingual lymph nodes. J Jpn Soc Head Neck Surg 2016;1:71–8 [in Japanese].

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ANL-2593; No. of Pages 5 K. Eguchi et al. / Auris Nasus Larynx xxx (2019) xxx–xxx [7] Woolgar JA. Histological distribution of cervical lymph node metastases from intraoral/oropharyngeal squamous cell carcinomas. Br J Oral Maxillofac Surg 1999;37:175–80. [8] Tomblinson CM, Nagel TH, Hu LS, Zarka MA, Hoxworth JM. Median lingual lymph nodes: prevalence on imaging and potential implications for oral cavity cancer staging. J Comput Assist Tomogr 2017;41:528–34.

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[9] Werner JA, Du¨nne AA, Myers JN. Functional anatomy of the lymphatic drainage system of the upper aerodigestive tract and its role in metastasis of squamous cell carcinoma. Head Neck 2003;25:322–32. [10] Fujimura A, Seki S, Liao MY, Hu X, Onodera M, Nozaka Y. Three dimensional architecture of lymphatic vessels in the tongue. Lymphology 2003;36:120–7.

Please cite this article in press as: Eguchi K, et al. Medial lingual lymph node metastasis in carcinoma of the tongue. Auris Nasus Larynx (2019), https://doi.org/10.1016/j.anl.2019.03.003