The Journal of Laryngology & Otology (2014), 128, 552–554. © JLO (1984) Limited, 2014 doi:10.1017/S0022215114000905

Triple primary cancers of the head and neck: case report and literature review M ADAMS, R CAFFREY Department of Otolaryngology/Head and Neck Surgery, Altnagelvin Area Hospital, Derry, Northern Ireland, UK

Abstract Background: Coincident thyroid and head and neck squamous cell carcinomas are rare. This paper presents a case of synchronous laryngeal squamous cell carcinoma, follicular thyroid carcinoma and micropapillary thyroid carcinoma. Methods: A PubMed search was performed for articles describing synchronous thyroid and head and neck squamous cell carcinomas, using the search terms ‘thyroid cancer’, ‘cancer of the head and neck’, ‘synchronous’ and ‘synchronous neoplasm’. Results: The literature suggests that the head and neck squamous cell carcinoma stage is a better predictor of outcome than the extent of surgical treatment of the thyroid gland in synchronous malignancies. Conclusion: The decision regarding surgical treatment of the thyroid in synchronous thyroid and head and neck squamous cell carcinomas should take several factors into account. The head and neck squamous cell carcinoma stage is the strongest predictor of outcome, although patient-related factors and the location of malignant thyroid tissue may also affect management. Key words: Thyroid Cancer; Head And Neck Neoplasms; Synchronous Neoplasms

Introduction Squamous cell carcinoma (SCC) of the head and neck often requires radical surgery, and the prognosis for more advanced disease is guarded. However, well-differentiated thyroid carcinoma can often be successfully treated with surgery and adjuvant therapies. Overall patient survival can be as high as 80 per cent at 20 years. Synchronous head and neck SCC and thyroid cancer is extremely rare and can present a treatment dilemma.

Case report We report the case of a 69-year-old man with a long history of laryngeal dysplasia. The patient first presented to an otolaryngologist in November 1995 (aged 53 years) with painless dysphonia. He had been a pipe smoker for around 25 years and consumed 24 units of alcohol per week. Flexible laryngoscopy showed thickened mucosa on the left vocal fold. Microlaryngoscopy and biopsy revealed carcinoma in situ of the left vocal fold. He underwent endolaryngeal cold-steel resection until negative histology findings were obtained. The patient stopped smoking and was kept under close review. Approximately seven years later, an area of leukoplakia was seen on the left vocal fold. Biopsy again revealed severe dysplasia. At this stage, the decision was made to proceed with endolaryngeal laser resection. After a further three years, a suspicious lesion was seen on the right vocal fold. Biopsy showed carcinoma in situ and further laser resection was undertaken. The patient was kept under close follow up but two years later his voice quality deteriorated. Accepted for publication 14 January 2014

Microlaryngoscopy and biopsy at this stage showed grade 2 tumour (T2) SCC involving the left side of the epiglottis and the aryepiglottic fold. The tumour–node–metastasis (TNM) staging was T2N0M0. After a multidisciplinary team (MDT) review, the patient underwent external beam radiotherapy. The patient suffered a recurrence after three years. Biopsy revealed a T2 SCC of the left vocal fold with no palpable cervical lymphadenopathy. Contrast-enhanced computed tomography of the neck and chest showed glottic thickening and a small pleural-based nodule in the right lower lobe. No cervical lymphadenopathy or thyroid nodule was seen. After a MDT discussion, he proceeded to total laryngectomy. Left hemi-thyroidectomy was performed along with the laryngeal resection because there was a clinical suspicion of extra-laryngeal spread. The immediate peri-operative period was uneventful. A final histopathological specimen was classified as T2N0MX, indicating a moderately differentiated SCC of the epiglottis and left vocal fold. However, a specimen containing the left thyroid lobe showed a highly invasive T3 follicular thyroid carcinoma (Figure 1). The patient therefore underwent a completion right hemithyroidectomy during the same admission. Histopathological examination of the right thyroid lobe revealed a papillary microcarcinoma (Figure 2). The patient was referred to a medical oncologist for consideration of radioiodine (I-113) ablation therapy. However, he was deemed too unfit for this and the decision was made to treat with thyroxine hormones for thyroidstimulating hormone suppression.

First published online 22 May 2014


FIG. 1 Photomicrograph of follicular thyroid carcinoma extending beyond the capsule and invading a vein. (H&E; ×40)


We searched the PubMed database using the terms ‘thyroid cancer’, ‘cancer of the head and neck’, ‘synchronous’ and ‘synchronous neoplasm’. Non-English language articles were excluded. The occurrence of simultaneous primary cancers of the head and neck is not uncommon, as seen for other sites in the body. The concept of ‘field carcinogenesis’ has been discussed in this context.1 The most common synchronous malignancies found in head and neck SCC are those of the lung, oesophagus and stomach, reflecting the commonality of risk factors for these diseases.2 The synchronous occurrence of head and neck SCC and thyroid carcinoma is, on the other hand, much rarer. In reported series to date, the incidence varies between 0.003 and 1 per cent.3 Cases of simultaneous occurrence of different types of thyroid cancer in the same gland have been reported.4 However, ours is the only known case of multiple thyroid carcinomas arising synchronously with head and neck SCC. Synchronous thyroid cancer may be detected in head and neck SCC patients in one of three ways: (1) a palpable

FIG. 2 Photomicrograph of microinvasive papillary thyroid carcinoma, showing papillary nuclear features of nuclear crowding, chromatin clearing, micronucleoli and longitudinal grooves. (H&E; ×400)

553 thyroid nodule may be found at the time of index surgery for head and neck SCC (with or without confirmation by intra-operative frozen section analysis); (2) a metastatic thyroid cancer may be unexpectedly found in lymph nodes following neck dissection for head and neck SCC; or (3) an occult thyroid cancer may be incidentally found in a thyroid lobe resected as part of the planned surgery for head and neck SCC. In the first instance, a suspicious thyroid lesion palpated at the time of head and neck SCC resection can be confirmed by intra-operative frozen section analysis. A total thyroidectomy may be subsequently performed as part of the index procedure. In the second and third instances, more complicated therapeutic dilemmas arise. The significance of incidentally discovered thyroid tissue in cervical lymph nodes has been debated recently. In some cases, no clinical or radiological abnormality could be demonstrated within the thyroid gland itself. One school of thought has therefore viewed these as benign inclusions or ‘lateral aberrant thyroid tissue’.5 Clinically occult thyroid cancer has also been postulated to be distinct from clinically overt disease in terms of its cancer-related biology.6 Gilbert et al. reported 29 cases of incidental thyroid cancer and head and neck SCC in a series of 2538 neck dissections carried out in Pennsylvania, USA.7 Seven of these patients underwent total thyroidectomy at the time of surgery for palpable thyroid nodule confirmed by frozen section analysis. The remainder underwent hemithyroidectomy for suspected SCC invasion of the thyroid gland. Fourteen patients died during a 52-month follow up, all as a result of their SCC. Of the remaining 15 patients alive at follow up, only 7 had undergone completion thyroidectomy with or without radioiodine ablation. It was therefore suggested that the likely prognosis of the head and neck SCC should determine the extent of treatment required for incidentally discovered thyroid cancer. Similarly, some authors have suggested that no further treatment is required in patients in whom incidental thyroid cancer is found in lymph nodes resected for head and neck SCC and in whom no clinically significant abnormality can be demonstrated in the thyroid gland itself. For instance, Goepfet and Callender hypothesise that patients undergoing neck dissection are a self-selecting population at a high risk of head and neck SCC recurrence and mortality.8 Guzzo et al. reported a series of 33 cases of associated head and neck SCC and thyroid carcinoma. In 2 patients, a palpable node was identified at surgery and confirmed by frozen section analysis, 13 patients had a planned hemithyroidectomy as part of the treatment for head and neck SCC, and in 18 patients with no thyroid resection incidental thyroid cancer was found in cervical lymph nodes. Twenty-three patients underwent adjuvant radiotherapy as part of their head and neck SCC treatment. After a mean of 45 months (range, 21–151 months) follow up, the thyroid cancer did not recur in any of these patients, regardless of the extent of surgical resection of the thyroid gland. Notably, five-year disease-free survival for head and neck SCC was only 5.6 per cent.9 The use of adjuvant radiotherapy as part of head and neck SCC treatment may be an important factor. A fairly recent large series examining the use of radiotherapy for residual thyroid cancer showed disease-free survival of 86 per cent.10 Indeed, other authors have reported a 10-year recurrence rate of only 1 per cent following hemithyroidectomy for early papillary carcinomas.11

554 Another series of eight patients with synchronous SCC of the tongue and thyroid carcinoma was reported in 1992.12 During a mean follow up of 6 years (range 7 months to 18 years), 3 patients died as a result of SCC progression and 1 died from respiratory disease. Recurrence of thyroid cancer was not seen in any of the patients, including those who had no surgical treatment of the thyroid gland itself.

Conclusion Synchronous thyroid carcinoma may be unexpectedly discovered during surgery for head and neck SCC, either in a thyroid lobe or in cervical lymph nodes resected as a planned part of the head and neck SCC resection. The decision about the extent of further synchronous thyroid carcinoma treatment is a difficult one and should be tailored to the individual patient. The prognosis of the head and neck SCC must be balanced against the risk of further morbidity or mortality from the thyroid cancer. Current evidence suggests that in patients at high risk of SCC recurrence and mortality, conservative management of the thyroid gland may be acceptable. The ability of the patient to withstand the potential complications of further thyroid surgery (e.g. laryngeal nerve palsy, hypocalcaemia, hypoparathyroidism), and the need for adjuvant radiotherapy, must also be considered. Such complications are likely to be more common if the thyroid bed is disturbed during the index head and neck SCC surgery (e.g. planned hemithyroidectomy) because of distorted anatomy and fibrosis. Given the potential complexities, the use of routine ultrasound evaluation of the thyroid gland prior to open surgery for head and neck SCC has recently been advocated.13 This would allow planned intraoperative frozen section analysis of any thyroid nodules, with subsequent total thyroidectomy if positive for malignancy.

Acknowledgements Thanks to Dr H Vasir and Dr C Flynn, Department of Pathology, Altnagelvin Area Hospital (Derry, Northern Ireland, UK), for preparing the photomicrographs. References 1 Yasuda M, Kuwano H, Watanabe M, Toh Y, Ohno S, Sugimachi K. P53 expression in squamous dysplasia associated with carcinoma of the oesophagus: evidence for field carcinogenesis. Br J Cancer 2000;83:1033–8 2 Chu PY, Chang SY, Huang JL, Tai SK. Different patterns of second primary malignancy in patients with squamous cell




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carcinoma of larynx and hypopharynx. Am J Otolaryngol 2010;31:168–74 Pacheco-Ojeda L, Michaeu C, Luboinski B, Richard J, Travagli JP, Schwaab G et al. Squamous cell carcinoma of the upper aerodigestive tract associated with well differentiated carcinoma of the thyroid gland. Laryngoscope 1991;101:421–4 Cupisti K, Raffel A, Ramp U, Wolf A, Donner A, Krausch M et al. Synchronous occurrence of a follicular, papillary and medullary thyroid carcinoma in a recurrent goitre. Endocr J 2005;52:281–5 Ansari-Lari M, Westra WH. The prevalence and significance of clinically unsuspected neoplasms in cervical lymph nodes. Head Neck 2003;25:841–7 Cheema Y, Olson S, Elson D, Chen H. What is the biology and optimal treatment for papillary microcarcinoma of the thyroid? J Surg Res 2006;134:160–2 Gilbert MR, Kim S. Incidental thyroid cancer found during surgery for head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 2012;147:647–53 Goepfet H, Callender DL. Differentiated thyroid cancer – papillary and follicular carcinomas. Am J Otolaryngol 1994;14: 167–79 Guzzo M, Quattrone P, Seregni E, Bianchi R, Mattavelli F. Thyroid carcinoma associated with squamous cell carcinoma of the head and neck: which policy? Head Neck 2007;29:33–7 Brierly J, Tsang R, Panzarella T, Bana N. Prognostic factors and the effect of treatment with radioactive iodine and external beam radiation on patients with differentiated thyroid cancer seen at a single institution over 40 years. Clin Endocrinol 2005;63: 418–27 Ito Y, Masuoka H, Fukushima M, Inoue H, Kihara M, Tomoda C et al. Excellent prognosis of patients with solitary T1N0M0 papillary thyroid carcinoma who underwent thyroidectomy and elective lymph node dissection without radioiodine therapy. World J Surg 2010;34:1285–90 Vassilopoulou-Sellin R, Weber RS. Metastatic thyroid cancer as an incidental finding during neck dissection: significance and management. Head Neck 1992;14:459–63 Farrag T, Lin F, Cummings C, Sciubba J, Koch W, Flint P et al. Importance of routine evaluation of the thyroid gland prior to open partial laryngectomy. Arch Otolaryngol Head Neck Surg 2006;132:1047–51

Address for correspondence: Mr Mark Adams, 29 Manse Park, Carryduff, Belfast BT8 8RX, Northern Ireland, UK Fax: 0044 2890 634091 E-mail: [email protected] Mr M Adams takes responsibility for the integrity of the content of the paper Competing interests: None declared

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Triple primary cancers of the head and neck: case report and literature review.

Coincident thyroid and head and neck squamous cell carcinomas are rare. This paper presents a case of synchronous laryngeal squamous cell carcinoma, f...
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