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11 Tumors ofthePharynx
277
Most cases are, however, are advanced at the time of presentation, and the overall survival rate rarely exceeds 25% in any series. General local control rates have been reported to be around 80% [48]. Distant metastatses occur in approxi­mately 25% of patients. The lungs, liver, and bones are the main organs affected. The principle cause of death is local tumor recurrence. Distant metastases, second primary cancers, and co­morbid diseases are secondary causes.
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12. Chua DTT, Sham JST, Choy D, et al. Preliminary report of the Asian-Oceanian clinical oncology asso­ciation randomized trial comparing cisplatin and epi­rubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregion­ally advanced nasopharyngeal carcinoma. Cancer. 1998;83:2270–83.
13. King WWK, Ku PKM, Mok CO, Teo PML.Nasopharyngectomy in the treatment of recur­rent nasopharyngeal carcinoma: a twelve-year experi­ence. Head Neck. 2000;22:215–22.
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15. To EWH, Teo PML, Ku PKM, Pang PCW.Nasopharyngectomy for recurrent nasopharyn­geal carcinoma: an innovative transnasal approach through a mid-face deglove incision with stereotactic navigation guidance. Br J Oral Maxillofacial Surg. 2001;39:55–62.
16. Chan ATC, Teo PML, Leung WT, Johnson PJ.Role of chemotherapy in the management of nasopharyngeal carcinoma. Cancer. 1998;82:1003–12.
17. Gillison ML, Koch WM, Capone RB, etal. Evidence for a causal association between human papilloma­virus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709–20.
18. Mork J, Lie AK, Glattre E, et al. Human papillo­mavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 2001;344:1125–31.
19. D’Souza G, Kreimer AR, Viscidi R, et al. Case­control study of human papillomavirus and oropha­ryngeal cancer. N Engl J Med. 2007;356:1944–56.
20. Isayeva T, Li Y, Maswahu D, Brandwein-Gensler M.Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review. Head Neck Pathol. 2012;6(Suppl 1):S104–20. https://doi.
org/10.1007/s12105- 012- 0368- 1. Epub 2012 Jul 3.6.
21. Le QT, Giaccia AJ. Therapeutic exploitation of the physiological and molecular genetic altera­tions in head and neck cancer. Clin Cancer Res. 2003;9:4287–95.
22. Fakhry C, Gillison ML. Clinical implications of human papillomavirus in head and neck cancers. J Clin Oncol. 2006;24:2606–11.
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16. Head and neck cancer. In: Kantarjian HM, Wolff RA, Koller CA, editors. The MD Anderson manual of medical oncology. 2nd ed. New York: McGraw-Hill;
2011.
24. Feng FY, Kim HM, Lyden TH, Haxer HJ, Worden FP, Feng M, et al. Intensity-modulated chemoradio-
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therapy aiming to reduce dysphagia in patients with oropharyngeal cancer: clinical and functional results. J Clin Oncol. 2010;28(16):2732–8.
25. Shiley SG, Hargunani CA, Skoner JM, Holland JM, Wax MK.Swallowing function after Chemoradiation for advanced stage oropharyngeal cancer. Otolaryngol Head Neck Surg. March 2006;134(3):455–9.
26. Kies MS, Holsinger FC, Lee JJ, William WN Jr, Glisson BS, Lin HY, et al. Induction chemotherapy and cetuximab for locally advanced squamous cell carcinoma of the head and neck: results from a phase II prospective trial. J Clin Oncol. 2010;28(1):8–14.
27. Licitra L, Perrone F, Bossi P, etal. High-risk human papillomavirus affects prognosis in patients with sur­gically treated oropharyngeal squamous cell carci­noma. J Clin Oncol. 2006;24:5630–6.
28. Weinberger PM, Yu Z, Haffty BG, etal. Molecular classication identies a subset of human papilloma­virus—associated oropharyngeal cancers with favor­able prognosis. J Clin Oncol. 2006;24:736–47.
29. Mellin H, Friesland S, Lewensohn R, etal. Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int J Cancer. 2000;89:300–4.
30. Li W, Thompson CH, O’Brien CJ, etal. Human pap­illomavirus positivity predicts favourable outcome for squamous carcinoma of the tonsil. Int J Cancer. 2003;106:553–8.
31. Ragin CC, Taioli E.Survival of squamous cell carci­noma of the head and neck in relation to human papil­lomavirus infection: review and meta-analysis. Int J Cancer. 2007;121:1813–20.
32. Worden FP, Kumar B, Lee JS, etal. Chemoselection as a strategy for organ preservation in advanced oro­pharynx cancer: response and survival positively associated with HPV16 copy number. J Clin Oncol. 2008;26:3138–46.
33. Fakhry C, Westra WH, Li S, etal. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100:261–9.
34. Pignon JP, Bourhis J, Domenge C, etal. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC collaborative group. Meta-analysis of chemotherapy on head and neck cancer. Lancet. 2000;355(9208):949–55.
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38. Haddad R, Colevas AD, Tishler R, etal. Docetaxel, cisplatin, and 5-uorouracil-based induction che­motherapy in patients with locally advanced squa­mous cell carcinoma of the head and neck: the Dana Farber cancer institute experience. Cancer. 2003;97(2):412–8.
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https://doi.org/10.3109/00016489.2013.785018.
Epub 2013 May 6.
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41. Holsinger FC, Motamed M, Garcia D, etal. Resection of selected invasive squamous cell carcinoma of the pyriform sinus by means of the lateral pharyngotomy approach: the partial lateral pharyngectomy. Head Neck. 2006;28(8):705–11.
42. Ogura JH. “How I do it”—head and neck. A tar­geted problem and its solution. Hyoid muscle ap reconstruction in subtotal supraglottic laryngec­tomy: a more rapid rehabilitation of deglutition. Laryngoscope. 1979;89(9 Pt 1):1522–4.
43. Chevalier D, Watelet JB, Darras JA, etal. Supraglottic hemilaryngopharyngectomy plus radiation for the treatment of early lateral margin and pyriform sinus carcinoma. Head Neck. 1997;19(1):1–5.
44. Kania R, Hans S, Garcia D, etal. Supracricoid hemi­laryngopharyngectomy in patients with invasive squa­mous cell carcinoma of the pyriform sinus. Part II: incidence and consequences of local recurrence. Ann Otol Rhinol Laryngol. 2005;114(2):95–104.
45. Laccourreye O, Ishoo E, de Mones E, et al. Supracricoid hemilaryngopharyngectomy in patients with invasive squamous cell carcinoma of the pyri­form sinus. Part I: technique, complications, and long­term functional outcome. Ann Otol Rhinol Laryngol. 2005;114(1 Pt 1):25–34.
46. Steiner W, Ambrosch P, Hess CF, etal. Organ pres­ervation by transoral laser microsurgery in piriform sinus carcinoma. Otolaryngol Head Neck Surg. 2001;124(1):58–67.
47. Martin SA, Marks JE, Lee JY, etal. Carcinoma of the pyriform sinus: predictors of TNM relapse and sur­vival. Cancer. 1980;46(9):1974–81.
48. Hoffman HT, Karnell LH, Shah JP, et al. Hypopharyngeal cancer patient care evaluation. Laryngoscope. 1997;107(8):1005–17.
t.me/Dr_Mouayyad_AlbtousH
Benign Thyroid Disease
MahmoudSakr
12
12.1 Introduction
12.1.1 Surgical Anatomy
The thyroid gland is a brownish-red and highly vascular endocrine gland located anteriorly in the lower neck, extending from the level of the fth cervical vertebra (C5) down to the rst tho­racic (T1). The normal gland weighs between 20 and 35g in adults and consists of two elongated lateral lobes with superior and inferior poles connected by a median isthmus overlying the second to fourth tracheal rings. The superior poles extend toward the oblique line of the thy­roid cartilage, lying deep to the sternothyroid muscle, and supercial to the cricothyroid mus­cle [1]. A conical pyramidal lobe often ascends from the isthmus or the adjacent part of either lobe (more often the left) toward the thyroid car­tilage to which it may be attached by a brous or bromuscular band, the levator of the thyroid gland. Remnants of the thyroglossal duct may persist as accessory nodules or cysts of thyroid tissue between the isthmus and the foramen cecum of the tongue base. Usually, two pairs of parathyroid glands (PTGs) lie in proximity to the thyroid gland.
12.1.1.1 Fascia andLigaments
The thyroid gland is enveloped by a brous cap­sule condensed from the pretracheal fascia. The anterior suspensory ligament extends from the
superior-medial aspect of each thyroid lobe to the cricoid and thyroid cartilages. The postero- medial aspect of the gland is attached to the side of the cricoid cartilage, rst and second tracheal rings, by the posterior suspensory ligament (Berry’s ligament), which is responsible for the movement of the thyroid gland and related structures during swallowing. On its way to the larynx, the recur­rent laryngeal nerve (RLN) usually passes deep to Berry’s ligament or between the main ligament and its lateral leaf [2]. Modern surgical resection of the thyroid gland involves a “capsular dissec­tion.” The maintenance of the capsule helps reduce damage to the plexus of veins that lie on its surface and its highly vascular parenchyma. Additionally, it reduces the chance of injury to the adjacent neurovascular structures.
12.1.1.2 Arterial Supply
The arterial supply to the thyroid gland comes from the superior and inferior thyroid arteries and, occasionally, the thyroidea ima. These arter­ies have abundant collateral anastomoses with each other, both ipsilaterally and contralaterally.
M. Sakr (*) Department of Surgery, Faculty of Medicine, Alexandria University, Alexandria, Egypt
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024 M. Sakr (ed.), Head and Neck and Endocrine Surgery,
https://doi.org/10.1007/978-3-031-64102-2_12
t.me/Dr_Mouayyad_AlbtousH
Superior Thyroid Artery (STA)
The superior thyroid artery (STA) arises as the rst branch of the external carotid artery (ECA)
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M. Sakr
and passes in a caudal direction to join the supe­rior pole of the thyroid. It has close relations to the external branch of the superior laryngeal nerve (SLN), which lies deep into the artery before turning medially to supply the cricothy­roid muscle. High ligation of the STA during thy­roidectomy places this nerve at risk of inadvertent injury that alters pitch regulation. The STA divides into anterior and posterior branches. From the posterior branch, a small parathyroid artery passes to the superior PTG [3].
Inferior Thyroid Artery (ITA)
The inferior thyroid artery (ITA) arises from thyrocervical trunk, a branch of the subclavian artery, and passes in the tracheaesophageal groove into the postero-lateral aspect of the each lobe. It has a variable branching pattern and a variable relationship with the RLN, most commonly passing in front of the nerve. The RLN can be found after it emerges from the superior thoracic outlet, in a triangle bounded laterally by the common carotid artery (CCA), medially by the trachea, and superiorly by the thyroid gland [4]. Another hint to the location of the RLN is the “Zuckerkandl tubercle,” an extension of the thyroid, close to Berry’s liga­ment. On rare occasions, the nerve may pass directly from the vagus to the larynx, close to the superior thyroid vessels [5].
Thyroidea Ima Artery
The “thyroidea ima” is a single artery that arises from the brachiocephalic artery or the arch of the aorta. It enters the thyroid gland at the inferior border of the isthmus and is present in <10% of patients.
12.1.1.3 Venous Drainage
Veins of the thyroid gland form a plexus of ves­sels lying in the substance and on the surface of the gland. This plexus is drained by three pairs of veins. The superior and middle thyroid veins drain into the internal jugular vein (IJV), while the inferior thyroid veins follow different paths on each side. The right passes anterior to the innominate artery to the right brachiocephalic vein or anterior to trachea to the left brachioce-
phalic vein. On the left side, drainage is to the left brachiocephalic vein. Occasionally, both inferior veins form a common trunk called the “thyroid ima vein,” which empties into the left brachioce­phalic vein.
12.1.1.4 Lymphatics
Lymphatic drainage of the thyroid gland is exten­sive with intra-glandular and sub-capsular lym­phatic drainage into the IJV.Immediate lymphatic drainage ows to the peri-glandular lymph nodes (LNs), to the pre-laryngeal (Delphian), pretra­cheal, and para-tracheal nodes along the RLN and then to mediastinal LNs. Regional metasta­ses of thyroid carcinoma can also be found later­ally, higher in the neck along the IJV.This can be explained by tumor invasion of the pretracheal and para-tracheal nodes causing an obstruction of normal lymph ow.
12.1.1.5 Innervation andRelated
Nerves
Principal innervation of the thyroid gland derives from the autonomic nervous system. Parasympathetic bers come from the vagus nerves, and sympathetic bers are distributed from the superior, middle, and inferior ganglia of the sympathetic trunk [6]. The relationship of the thyroid gland to the RLN and the external branch of the SLN is of major surgical signicance because damage to these nerves leads to disabil­ity in phonation or difculty in breathing. Both nerves are branches of the vagus nerve.
Recurrent Laryngeal Nerve (RLN)
The right RLN arises from the vagus nerve, loops posteriorly around the subclavian artery, and ascends behind the right lobe of the thyroid. It enters the larynx behind the cricothyroid muscle and the inferior cornu of the thyroid cartilage and innervates all the intrinsic laryngeal muscles except the cricothyroid. The left RLN comes from the left vagus, loops posteriorly around the arch of the aorta, and ascends in the tracheae­sophageal groove (TEG) posterior to the left lobe of the thyroid, where it enters the larynx and innervates the musculature in a similar fashion as the right nerve. The RLN may not lie in the TEG
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12 Benign Thyroid Disease
281
and thus it is vulnerable to injury if not visualized and traced up to the larynx during thyroidectomy. In addition, it has a variable relationship to the ITA as it often passes anterior, posterior, or through the branches of the ITA.Ligation of this artery may be dangerous if the nerve is not identi­ed rst. Moreover, in the presence of large nod­ules, the RLNs may not be in their “regular” anatomical location but may be found even ante­rior to the thyroid gland. Finally, there may be a “non-RLN,” which occurs more on the right side (0.6%) than on the left side (0.04%) and is asso­ciated with vascular anomalies.
External Branch oftheSuperior Laryngeal Nerve (SLN)
The external branch of SLN innervates the crico­thyroid muscle. It is important to the pitch of voice as the cricothyroid muscle is the tensor of the vocal cords. In most cases, this nerve lies close to the vascular pedicle of the superior pole of the thyroid lobes descending on the fascia of the inferior pharyngeal constrictor. In some patients, it lies on the anterior surface of the thy­roid lobe, making the possibility of damage dur­ing thyroidectomy even greater [7].
12.1.1.6 Parathyroid Glands (PTGs)
The PTGs are small glands that secrete parathy­roid hormone (PTH) that controls serum calcium (Ca) homeostasis. In about 80% of cases, four glands are present; two on each side, but three to six glands have been reported. Because of their small size, their delicate blood supply, and their usual anatomical position adjacent to the thyroid gland, these glands are at risk of being accidently removed, traumatized, or devascularized during thyroidectomy.
The superior PTGs arise embryologically from the fourth pharyngeal pouch. They descend only slightly during embryologic development, and their position remains quite constant, being adjacent to the posterior surface of the middle part of the thyroid lobe, often just anterior to the RLN as it enters the larynx. The inferior PTGs arise from the third pouch, along with the thy­mus; hence, they often descend with the thymus and have a wide range of distribution in adults,
from just beneath the mandible to the anterior mediastinum [8]. With experience, one becomes much more capable of recognizing the PTGs by their tan appearance and small vascular pedicle and of differentiating them from either LNs or adipose tissue [9].
12.1.1.7 Micro-anatomy (Histology)
The thyroid gland is formed of connective tissue stroma and parenchyma of endocrine cells. The connective tissue (true) capsule of the thyroid gives off multiple brous septa (trabeculae) passing into the gland, carrying blood vessels, nerves, and lymphatics to form lobules. The gland is further divided into 20–40 much smaller functional subunits called follicles that store a colloid substance that functions as a hormone store. The colloid is maintained by a single layer of follicular epithelial cells sitting on a basal lam­ina. These follicles are surrounded by fenestrated capillaries, lymphatics, and so-called para­follicular or C-cells.
Microscopically, each lobe or lobule is made of two types of secretory cells; follicular cells that secrete thyroxin (T4) and tri-iodothyronine (T3), and in smaller number, the para-follicular or clear cell (C-cells), which secrete thyrocalci­tonin. The follicles are separated from each other by a highly vascular connective tissue, and each follicle is lined with a single layer of attened to low columnar epithelium depending on their degree of activity.
Oncocytes (Hürthle cells, oxyphilic cells, and Ashkenazy cells) are large follicular cells with abundant deeply eosinophilic granular cytoplasm and numerous mitochondria. They are commonly seen in long-standing Graves’ disease, autoim­mune thyroiditis, radiation-induced thyroiditis, follicular-derived neoplasms, and some adeno­matoid goiters [1012].
12.1.2 Physiology
The function of the thyroid gland is to synthesize, store, and secrete T4 and T3. Mono-iodotyrosin (MIT) and di-iodotyrosine (DIT) are also found in thyroid venous blood.
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Inorganic iodide (I−) is absorbed from gastro­intestinal tract and actively trapped by the acinar cells of the thyroid gland via a transport mecha­nism that is frequently called the “I-trapping mechanism” or “I-pump.” A transporter named “pendrin” is located on the luminal surface of the follicular cell and is responsible for allowing pas­sage of I− into the follicle. In the acinar cells, I− is oxidized to iodine (I2) and bound to the third posi- tion of tyrosin molecules with the aid of the enzyme thyroid peroxidase (TPO) to form MIT, and then to the fth position to form DIT.Two DIT molecules then undergo an oxidative con- densation with the release of an alanine residue and the formation of T4. Condensation of MIT with DIT results in T3 formation. These reactions occur while the tyrosin molecules are attached to thyroglobulin (Tg). The peptide bonds between the iodinated residues and Tg are broken by pro­teases in lysosomes, and so T4, T3, DIT, and MIT are liberated into the cytoplasm. The iodinated tyrosins are de-iodinated by a microsomal iodo­tyrosin dehalogenase. Then, T3 and T4 are released into the circulation [13].
Most circulating T3 derives from peripheral conversion of T4, which is really a pro-hormone and is signicantly less potent than the more met­abolically active hormone T3. In the blood, the majority of circulating T3 and T4 is bound to the plasma proteins, mainly thyroxin-binding globu­lin (TBG) and pre-albumin. It is only the ‘free’ unbound forms of hormones that are metaboli­cally active, and T3 is quick acting within few hours while T4 acts more slowly from 4 to 14days.
Production of T3 and T4 is regulated by the hypothalamic-pituitary-thyroid axis, which is a multi-loop feedback circuit. The production of T3 and T4 from the thyroid is stimulated directly by the thyroid-stimulating hormone (TSH), pro­duced by the anterior pituitary. Levels of T3 and T4 are also increased indirectly by thyrotrophin­releasing hormone (TRH), which is produced by the hypothalamus in response to low levels of T3/ T4 and acts on the pituitary to increase TSH pro­duction. Conversely, TRH and TSH production
are suppressed by high levels of T3 and T4. Additionally, TRH production is also suppressed by high levels of TSH.Thus, the circulating lev­els of active thyroid hormones are normally self­regulating [14].
The thyroid also contains “para-follicular C-cells,” which produce “calcitonin” that reduces serum Ca levels, counteracting the actions of PTH, by inhibiting osteoclast activity in bone, renal resorption of Ca, and absorption of Ca in the intestines. Blood levels of PTH are far more clinically relevant to Ca homeostasis than calci­tonin, and no exogenous replacement for calcito­nin is required following thyroidectomy.
12.1.3 Investigating theThyroid
Gland
12.1.3.1 Serological Investigations/
Thyroid Function Tests
The serum level of TSH should be routinely mea­sured, while T3 and T4 levels are required if TSH level is abnormal (Table 12.1). When hypothy­roidism is conrmed, thyroid peroxidase (TPO) antibodies should be requested to check for auto­immune thyroid disease such as Hashimoto’s thyroiditis. Serum Thyroglobulin (Tg) level does not help in the initial management of thyroid nodule and is not recommended. Serum Tg levels may be elevated in patients with cancer, but are not diagnostic, since similar increases are seen in benign thyroid disorders. However, serum Tg is
Table 12.1 Serological tests in thyroid disease
TSH Normal Not needed Euthyroid Decreased
Increased
Additional testing Diagnosis
– Free T4 – Free T4
normal
– Free T4 – Free T4
– Free T4
normal
– Free T4
– Hyperthyroid – T3 thyrotoxicosis – Non-thyroid disease
or drugs
– Thyroid resistance or
pituitary tumor
– Subclinical
hypothyroid
– Hypothyroid
t.me/Dr_Mouayyad_AlbtousH
12 Benign Thyroid Disease
useful in the follow-up of patients after total thy­roidectomy (TT) for well-differentiated thyroid cancer (WDTC). A level >10ng/mL is a reliable indicator of locally recurrent or metastatic dis­ease and predicts the need for ablative dose of
131
[15, 16].
Basal plasma calcitonin levels may be useful if medullary thyroid carcinoma (MTC) is sus­pected. In addition, pheochromocytoma is asso­ciated with MTC in multiple endocrine neoplasia (MEN) Type II, presenting with sympathetic ner­vous system hyperactivity [17].
12.1.3.2 Imaging Studies
283
I
Ultrasonography (US)
Ultrasonography (US) is the imaging study of choice for thyroid nodules. It can identify nod­ules too small to be palpated, the presence of multiple nodules, central or lateral neck lymph­adenopathy, and provide accurate measurements of nodule diameter, allowing serial scans and bet­ter assessment of growth. Additionally, it allows the characterization of nodules by sonographic features that suggest malignancy. Comet tail sign and coarse calcication suggest very low risk of malignancy. Hypo-echoicity and absent halo with indistinct margin are associated with moderate risk of malignancy. The presence of micro­calcication is highly suggestive of malignancy, especially papillary thyroid carcinoma (PTC) (Fig.12.1) [18].
Color ow patterns are categorized as (a) Type 1: no blood ow, (b) Type 2: peri-nodular ow, and (c) Type 3: intra-nodular blood ow (peri­nodular vessels may or may not be present). Although nonspecic, thyroid cancers may have internal hypervascularity, whereas benign nod­ules may have peripheral vascularization. However, type 3 vascularization can be found in both benign and malignant nodules [19]. Completel avascular nodules are more likely to be benign.
There is certainly some subjectivity to sono­graphic features, which cannot, alone, reliably distinguish malignant from benign lesions but are very useful in selecting the site within a nodule for ne needle aspirate biopsy (FNAB) in order
Fig. 12.1 Ultrasonography showing hypoechoic, ill­dened margin, and micro-calcications. Biopsy proved to be a papillary thyroid carcinoma (PTC)
to improve diagnostic yield or select appropriate nodules to aspirate within a multinodular goiter (MNG) [20, 21].
Magnetic Resonance Imaging (MRI) andComputed Tomography (CT)
Magnetic resonance imaging (MRI) is superior to scintigraphy in evaluating retrosternal goiters (RSGs). It is noninvasive, easily tolerated, and unlike contrast media used with CT; contrast media used in MRI does not inuence thyroid function. CT scan gives structural information about the gland and its relationship to adjacent structures. Both CT and MRI are relatively expensive and have a limited ability in distin­guishing between benign and malignant lesions. However, they are necessary in some cases for staging and planning surgery. Indications of CT and/or MRI include the presence of a xed thy­roid mass, hemoptysis indicating pulmonary metastasis, cervical LNs, and RSGs. They can also show involvement of the larynx, pharynx, trachea, esophagus, or major blood vessels [22].
Thyroid Scintigraphy
The use of radionuclide agents is helpful in delin­eating the presence, size, and function of thyroid nodules. Scanning with
123
I has the advantages of
low-dose radiation (30 mrad) and a short half-life
t.me/Dr_Mouayyad_AlbtousH
284
M. Sakr
(12–14h). This compares favorably with the use
131
of
I with a higher dose (500 mrad) and a longer
half-life (8–10days).
123
I scanning is usually used for patients with a suspected lingual thyroid or RSG, whereas
131
I is used in patients with WDTC to screen for distant metastasis. Malignancy occurs in 15–20% of “cold” nodules and, addi­tionally, in 5–9% of nodules with uptake that is “warm” or “hot,” mandating continued aggres­sive approach to clinically suspicious nodules even if they are not “cold” [23].
Technetium-pertechnetate-99m (
99m
Tc) is also used for evaluation of thyroid nodules. It is trapped by the thyroid, but not organied, and has a short half-life and a low radiation dose. Screening with
99m
Tc also shows uptake in sali­vary glands and major vascular structures, and therefore, requires a higher sophistication of interpretation [16].
12.1.3.3 Biopsy
Fine Needle Aspiration Cytology (FNAC): Free-Hand or US-Guided
The most important step (cornerstone) in the management of thyroid nodules is FNAC. Free­hand or palpation-guided FNAC has a sensitivity of 65–98% and a specicity of 72–100% [24]. The US-guided FNAC improves the accuracy of FNAC. The acellular or nondiagnostic (Thy 1) aspirate is reduced from 14% to 8% with US-guidance [25], sensitivity increases from 92 to 98%, and specicity from 69 to 71% [26]. It can also be used to help localize impalpable nod­ules, lesions <1cm, or when initial FNAC was nondiagnostic.
The indications for FNA are all thyroid nod­ules with a maximal diameter >1cm and smaller nodules with suspicious features on US.A lower limit for the maximal diameter does not exist; however, there are technical difculties in the sampling procedure in tiny lesions (<0.5 cm), even under US-guidance [27]. The aims of the FNAB include the following [27]:
– To conrm the benign diagnosis of a nodule
justifying the clinicians for a conservative
approach avoiding an unnecessary surgery.
– To conrm the clinical diagnosis of a diffuse
goiter like Hashimoto’s thyroiditis or subacute de Quervain thyroiditis.
– To recognize an aggressive thyroid tumor and
to recognize or at least to suspect a clinically relevant low-grade tumor among all nodular enlargements of thyroid.
– To classify or to suspect some tumor types
demanding a special therapeutic approach such as MTC, lymphoma, anaplastic carci­noma, or metastatic carcinoma.
– To clarify eventual postoperative enlarge-
ments in the thyroid region, differentiating mainly between residual or recurrent disease versus granulomas or LN enlargements.
– To explore various neck enlargements outside
the thyroid gland, mainly cystic lesions of the neck, and differentiating between ectopic thy­roid cysts, thyroglossal cysts, branchial cysts, and cystic degenerated LN metastases of PTC.
– To conrm the presence of LN metastases.
Fine-needle aspiration cytology is not suc­cessful in (1) detection of a microscopic focus of PTC, (2) differentiation of follicular adenoma from follicular carcinoma, (3) determination of the extent of a thyroid tumor, (4) exclusion of LN metastases, and (5) the safe recognition of a para­thyroidal lesion [28].
Cytology results can be placed in ve diag­nostic categories (Thy 1–Thy 5) as indicated by the British Thyroid Association (BTA) Guidelines [24] (Table 12.2). The probability of a benign thyroid nodule being accurately diagnosed as benign from a single FNAC is 90%. However, the accuracy of diagnosis increases signicantly to 98% if two separate aspirates were performed on separate occasions [29].
The recently issued Bethesda System for Reporting Thyroid Cytopathology (BSRTC) [22], based on an NCI-sponsored conference (2007), is currently considered to be the most suitable for communicating ndings from thyroid smears (Table12.3).
A positive nding of a metastasis is princi­pally a safe diagnosis, whereas a negative smear does not exclude the presence of a metastasis since it might be missed by sampling. Cervical
t.me/Dr_Mouayyad_AlbtousH
12 Benign Thyroid Disease
285
Table 12.2 Diagnostic FNA categories and recom­mended actions (BTA guidelines) [24]
Category Description Thy 1
Thy 2
Thy 3 Follicular or Hurthle
Thy 4 Suspicious of
Thy 5 Diagnostic of
MDT multidisciplinary team
– Nondiagnostic,
insufcient sample
– Cyst containing
colloid or histiocytes only, in the absence of epithelial cells
– Benign,
nonneoplastic.
– Cyst containing
benign epithelial cells
cell lesion/suspected folic, or Hurthle tumor
malignancy
malignancy
Recommended action
– To repeat
FNAC (US guidance may help)
– If the cyst is
aspirated to dryness with no residual swelling, clinical/US follow-up alone may be sufcient
Repeat FNAC in 3–6months. Two nonneoplastic results 3–6months apart should exclude neoplasia
MDT discussion— diagnostic lobectomy
MDT discussion—Total thyroidectomy
MDT discussion—Total thyroidectomy
LN metastases frequently undergo extensive cys­tic degeneration, resulting in “acellular smears.” Cystic foci in LNs remain highly suspicious, even by negative FNA results. The measurement of thyroglobulin (Tg) in the cystic uid would be helpful option to conrm a suspicion if the amount of cancer cells is not sufcient for the diagnosis [27].
Core Biopsy (with or Without US-Guidance)
A core biopsy, preferably under US guidance, should be considered after two aspiration proce­dures showing nondiagnostic specimen (Thy 1) or when a thyroid lymphoma is suspected, typi­cally in an elderly woman or on a background of autoimmune thyroiditis.
12.1.3.4 Flexible Laryngoscopy
Indirect laryngoscopy is important to assess vocal cord movements. Patients with difculty breathing (increased respiratory rate or dimin­ished oxygen saturation) or stridor should be referred as an “emergency.”
12.2 Multinodular Goiter (MNG)
12.2.1 Introduction
Table 12.3
pathology recommended diagnostic categories [22]
Category Description I Nondiagnostic or unsatisfactory: Cyst uid
II Benign: Consistent with a benign follicular
III Atypia of undetermined signicance or
IV Follicular neoplasm or suspicious for a
V Suspicious for malignancy VI Malignant
Bethesda system for reporting thyroid cyto-
only—virtually acellular specimen, other (obscuring blood, clotting artifact, etc.)
nodule (adenomatoid nodule, colloid nodule, etc.), consistent with Hashimoto’s thyroiditis, consistent with granulomatous (subacute) thyroiditis
follicular lesion of undetermined signicance
follicular neoplasm
t.me/Dr_Mouayyad_AlbtousH
Goiter is derived from the Latin word ‘tumidum gutter,’ which means “swollen throat.” Thyroid Enlargement may be diffuse or nodular (multi­nodular or a solitary nodule), hormonal status may be euthyroid, hypothyroid, or hyperthyroid, and histologically, the enlarged thyroid may be benign or malignant.
Multinodular goiter (MNG), dened as an “enlarged thyroid gland with multiple nodules,” is a common condition with a marked female prepon­derance. It affects about 13% of the world’s popu­lation, ranging from 5% in the Americas to 32% in the Eastern Mediterranean area [30]. Iodine (I
2
deciency, naturally occurring goitrogens, thyroid growth factors (GFs), and heredity have been pos­tulated as possible causes of goiter [31]. Thyroid nodules may lead to a variety of clinical sequelae
)