10. Other tumor entities – Thyroid Cancer
10.1 Lymphomas
Primary thyroid lymphomas are rare and account for about 2-5% of all thyroid malignancies and about 2% of all extranodal lymphomas [1277], [1278]. According to data from a Southern Danish tumor registry, the incidence in the 1980/90s was 2 per 1 million inhabitants [1279].
The vast majority (70 %) are high-grade B-cell lymphomas (DLBCL dominates), followed by MALT lymphomas and much rarer follicular lymphomas [1277]. The majority of patients have a localized tumor stage 1-2 [1277], [1280]. Women are overrepresented (3:1) [1277], [1279]. Hashimoto's thyroiditis represents a predisposition in that 2/3 of the patients had pre-existing Hashimoto's thyroiditis and in half of the cases the transformation from Hashimoto's thyroiditis via a low grade lymphoma to a high grade lymphoma could be traced [1279].
Clinically, intrathyroid lymphoma presents as a rapidly growing neck tumor often with tracheal or laryngeal compression [1281], [1282]. Cervical lymph nodes are common, B-symptoms rare [1283]. The sonographic image usually shows a homogeneous, markedly hypoechoic lesion with dorsal sound enhancement, but without calcification or necrosis [1282], [1284], [1285]. A thyroid scintigraphy is unnecessary in most cases [1286]. The diagnosis can be confirmed in around three quarters of patients by fine needle aspiration [1282]. In the case of unclear findings, sonographically assisted punch biopsy has further reduced the role of open surgical tissue removal. However, this may be necessary to determine the lymphoma subtype [1283]
Recommendations for diagnostics, particularly for punch biopsy, can be found under [4.11].
The treatment of intrathyroid lymphoma shall be determined in the interdisciplinary tumor board and is usually multimodal.
- Consensus
- Strong consensus (100%)
A multimodal approach consisting of antibody therapy, chemotherapy and radiotherapy is used therapeutically, particularly for high-grade lymphomas [1283]. In mixed patient collectives, 5-year survival after radiochemotherapy was 74% [1287] and 85% [1288].
Surgical treatment of primary thyroid lymphoma alone is controversial, but in selected cases with stage IE disease it can bring the disease under local control (295). Surgical treatment may be indicated on an emergency basis in the event of airway obstruction [1283].
10.2 Thyroid metastases of extrathyroidal primary tumors
In patients with a history of tumor disease, suspicious nodules in the thyroid gland should also be investigated with regard to intrathyroid metastasis.
- Consensus
- Strong consensus (100%)
Metastases of extrathyroidal primary tumors in the thyroid gland are very rare and often only occur in patients with advanced tumor disease. For this reason, management and prognosis are not well established [1289]
In routine clinical practice, metastases account for only 0.2 % of all thyroid malignancies [1290] and are a rarity in view of the fact that thyroid malignancies are rare per se. In a review by Chung et al., metastases of an extrathyroidal tumor were found in 1.4-3% of cases in patients who underwent surgery for thyroid malignancy [1291]. In a retrospective analysis by Wang et al., 21/1,754 patients who underwent FNAC of a thyroid nodule were diagnosed with metastasis of an extrathyroidal tumor. This corresponds to a rate of 1.2 % [1289].
In autopsies, however, metastases are somewhat more common. In a study over a 16-year period, the rate was 0.9% of all autopsies and 13% of patients with known tumor disease. Lung metastases were the most common (33%), followed by breast carcinoma (8%) and renal cell carcinoma (8%) [1292].
In contrast to the autopsy studies, renal cell carcinoma is the leading tumor type in the clinical series [1291], [1293], [1294], [1295]. In the meta-analysis by Chung et al. it was the most common primary tumor at 48%, followed by colorectal, lung and breast carcinomas [1291]. The reason for the observation that renal cell carcinoma leads in clinical diagnosis is primarily its slow progression. The time interval between initial diagnosis and the appearance of thyroid metastases has a long latency. In a small study, it was 84 months [1296] and is given as 68 months by Chung et al. Patients with thyroid metastases from other tumor entities (lung, colorectum, etc.) are usually diagnosed at an advanced tumor stage, and the primary tumor type rather than the thyroid metastasis is then significant for survival [1295], [1297].
In the majority of cases, the clinical symptoms (appearance of cervical swelling, visible and palpable thyroid nodules, hoarseness, difficulty swallowing, shortness of breath, etc.) are indicative and suggest metastasis to the thyroid gland.
The smaller part is discovered by chance during staging examinations such as PET, CT or sonography of the soft tissues of the neck [1291].
In this situation, FNAC (see Chapter Fine needle aspiration cytology of the thyroid gland) also provides the correct diagnosis for the majority of patients [1297], [1298].
The recommendation for lobectomy or thyroidectomy for local control and to avoid complications should be made in the interdisciplinary tumor board, taking into account the overall clinical situation.
- Consensus
- Consent (92%)
In the case of indifferent FNAC or isolated metastasis to the thyroid gland, thyroidectomy can be considered in terms of local control and avoidance of complications (tracheotomy, recurrent nerve palsy, e.g.) [1299], [1300], [1301]. In terms of overall survival, however, surgery is controversially discussed. While Papi et al. found that surgery had no effect on overall survival, Hegerova et al. reported improved (albeit not statistically significant) overall survival after thyroidectomy [1294], [1302].
References
[1277] Graff-Baker, A, Roman, SA, Thomas, DC, Udelsman, R, Sosa, JA, Prognosis of primary thyroid lymphoma: demographic, clinical, and pathologic predictors of survival in 1,408 cases., Surgery, 2009. 146 (6)(6): p. 1105-15., https://pubmed.ncbi.nlm.nih.gov/19958938/
[1278] Ohye, H, Fukata, S, Hirokawa, M, [Malignant lymphoma of the thyroid]., Nihon Rinsho, 2007. 65 (11)(11): p. 2092-8., https://pubmed.ncbi.nlm.nih.gov/18018576/
[1279] Pedersen, RK, Pedersen, NT, Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study., Histopathology, 1996. 28 (1)(1): p. 25-32., https://pubmed.ncbi.nlm.nih.gov/8838117/
[1280] Skacel, M, Ross, CW, Hsi, ED, A reassessment of primary thyroid lymphoma: high-grade MALT-type lymphoma as a distinct subtype of diffuse large B-cell lymphoma., Histopathology, 2000. 37 (1)(1): p. 10-8., https://pubmed.ncbi.nlm.nih.gov/10931213/
[1281] Compagno, J, Oertel, JE, Malignant lymphoma and other lymphoproliferative disorders of the thyroid gland. A clinicopathologic study of 245 cases., Am J Clin Pathol, 1980. 74 (1)(1): p. 1-11., https://pubmed.ncbi.nlm.nih.gov/7395811/
[1282] Matsuzuka, F, Miyauchi, A, Katayama, S, Narabayashi, I, Ikeda, H, Kuma, K, et.al. Clinical aspects of primary thyroid lymphoma: diagnosis and treatment based on our experience of 119 cases., Thyroid, 1993. 3 (2)(2): p. 93-9., https://pubmed.ncbi.nlm.nih.gov/8369658/
[1283] Walsh, S, Lowery, AJ, Evoy, D, McDermott, EW, Prichard, RS, Thyroid lymphoma: recent advances in diagnosis and optimal management strategies., Oncologist, 2013. 18 (9)(9): p. 994-1003., https://pubmed.ncbi.nlm.nih.gov/23881987/
[1284] Luo, J, Huang, F, Zhou, P, Chen, J, Sun, Y, Xu, F, et.al. Is ultrasound combined with computed tomography useful for distinguishing between primary thyroid lymphoma and Hashimoto's thyroiditis?, Endokrynol Pol, 2019. 70 (6)(6): p. 463-468., https://pubmed.ncbi.nlm.nih.gov/31529457/
[1285] Aiken, AH, Imaging of thyroid cancer., Semin Ultrasound CT MR, 2012. 33 (2)(2): p. 138-49., https://pubmed.ncbi.nlm.nih.gov/22410362/
[1286] Sakorafas, GH, Kokkoris, P, Farley, DR, Primary thyroid lymphoma (correction of lympoma): diagnostic and therapeutic dilemmas., Surg Oncol, 2010. 19 (4)(4): p. e124-9., https://pubmed.ncbi.nlm.nih.gov/20620043/
[1287] Onal, C, Li, YX, Miller, RC, Poortmans, P, Constantinou, N, Weber, DC, et.al. Treatment results and prognostic factors in primary thyroid lymphoma patients: a rare cancer network study., Ann Oncol, 2011. 22 (1)(1): p. 156-164., https://pubmed.ncbi.nlm.nih.gov/20587509/
[1288] Watanabe, N, Noh, JY, Narimatsu, H, Takeuchi, K, Yamaguchi, T, Kameyama, K, et.al. Clinicopathological features of 171 cases of primary thyroid lymphoma: a long-term study involving 24553 patients with Hashimoto's disease., Br J Haematol, 2011. 153 (2)(2): p. 236-43., https://pubmed.ncbi.nlm.nih.gov/21371004/
[1289] Wang, X, Huang, Y, Zheng, Z, Cao, W, Chen, B, Wang, X, Metastases to the thyroid gland: A retrospective analysis of 21 patients., J Cancer Res Ther, 2018. 14 (7)(7): p. 1515-1518., https://pubmed.ncbi.nlm.nih.gov/30589032/
[1290] Straccia, P, Mosseri, C, Brunelli, C, Rossi, ED, Lombardi, CP, Pontecorvi, A, et.al. Diagnosis and Treatment of Metastases to the Thyroid Gland: a Meta-Analysis., Endocr Pathol, 2017. 28 (2)(2): p. 112-120., https://pubmed.ncbi.nlm.nih.gov/28332062/
[1291] Chung, AY, Tran, TB, Brumund, KT, Weisman, RA, Bouvet, M, Metastases to the thyroid: a review of the literature from the last decade., Thyroid, 2012. 22 (3)(3): p. 258-68., https://pubmed.ncbi.nlm.nih.gov/22313412/
[1292] Mistelou, A, Papadatos, SS, Kousi, C, Lampri, E, Mitsis, M, Vougiouklakis, T, et.al. Thyroid Gland as a Target of Secondary Malignancies - an Autopsy Study and Review Data., Folia Med (Plovdiv), 2019. 61 (2)(2): p. 277-288., https://pubmed.ncbi.nlm.nih.gov/31301659/
[1293] Heffess, CS, Wenig, BM, Thompson, LD, Metastatic renal cell carcinoma to the thyroid gland: a clinicopathologic study of 36 cases., Cancer, 2002. 95 (9)(9): p. 1869-78., https://pubmed.ncbi.nlm.nih.gov/12404280/
[1294] Hegerova, L, Griebeler, ML, Reynolds, JP, Henry, MR, Gharib, H, Metastasis to the thyroid gland: report of a large series from the Mayo Clinic., Am J Clin Oncol, 2015. 38 (4)(4): p. 338-42., https://pubmed.ncbi.nlm.nih.gov/23799287/
[1295] Cordes, M, Kuwert, T, Metastases of non-thyroidal tumors to the thyroid gland: a regional survey in middle franconia., Exp Clin Endocrinol Diabetes, 2014. 122 (5)(5): p. 273-6., https://pubmed.ncbi.nlm.nih.gov/24839221/
[1296] Queipo, FJ, Panizo, A, Yagüe, A, Ruiz-Azua, Y, Rodriguez, I, Gutiérrez-Pecharroman, A, et.al. Metastatic clear cell renal cell carcinoma to the thyroid gland: A clinico-pathological and immunohistochemical study of 8 cases and review of the literature., Rev Esp Patol, 2019. 52 (2)(2): p. 81-86., https://pubmed.ncbi.nlm.nih.gov/30902382/
[1297] Nixon, IJ, Coca-Pelaz, A, Kaleva, AI, Triantafyllou, A, Angelos, P, Owen, RP, et.al. Metastasis to the Thyroid Gland: A Critical Review., Ann Surg Oncol, 2017. 24 (6)(6): p. 1533-1539., https://pubmed.ncbi.nlm.nih.gov/27873099/
[1298] Surov, A, Machens, A, Holzhausen, HJ, Spielmann, RP, Dralle, H, Radiological features of metastases to the thyroid., Acta Radiol, 2016. 57 (4)(4): p. 444-50., https://pubmed.ncbi.nlm.nih.gov/25907117/
[1299] Ishikawa, M, Hirano, S, Tsuji, T, Ito, J, Management of metastasis to the thyroid gland., Auris Nasus Larynx, 2011. 38 (3)(3): p. 426-30., https://pubmed.ncbi.nlm.nih.gov/21239125/
[1300] Zhou, L, Chen, L, Xu, D, Shao, Q, Guo, Z, Ge, M, Breast cancer metastasis to thyroid: a retrospective analysis., Afr Health Sci, 2017. 17 (4)(4): p. 1035-1043., https://pubmed.ncbi.nlm.nih.gov/29937874/
[1301] Nixon, IJ, Whitcher, M, Glick, J, Palmer, FL, Shaha, AR, Shah, JP, et.al. Surgical management of metastases to the thyroid gland., Ann Surg Oncol, 2011. 18 (3)(3): p. 800-4., https://pubmed.ncbi.nlm.nih.gov/21046263/
[1302] Papi, G, Fadda, G, Corsello, SM, Corrado, S, Rossi, ED, Radighieri, E, et.al. Metastases to the thyroid gland: prevalence, clinicopathological aspects and prognosis: a 10-year experience., Clin Endocrinol (Oxf), 2007. 66 (4)(4): p. 565-71., https://pubmed.ncbi.nlm.nih.gov/17371476/