DIFFERENTIAL DIAGNOSIS OF ANTERIOR NECK SWELLING

1. DIFFERENTIAL DIAGNOSIS OF ANTERIOR NECK SWELLING DR. OLAYIWOLA ADEYEMI

2. DIFFERENTIALS • Goiter • Thyroglossal cyst • Branchial cyst • Lymphoma/ cold abscess • Pharyngeal pouch • Sebaceous cyst • Dermoid cyst • Lipoma

3. THYROID • ANATOMY • PHYSIOLOGY • PATHOLOGY • CLINICAL PRESENTATION • INVESTIGATION • MANAGEMENT

4. ANATOMY • An endocrine organ, consisting of 2 lateral lobes (which are pear shaped), joined by an isthmus over 2nd-4th tracheal rings. • A pyramidal lobe is sometimes present over the isthmus • Weighs 7-25g in Africans, and 15-25g in Caucasians • It is plastered to the trachea by the pre-tracheal fascia, thus causing the thyroid gland to move on swallowing • For goitre to be visible, the thyroid gland will be about 40-50g • Berry ligament: fusion of the pretracheal fascia with the thyroid capsule posteriorly

5. Arterial supply • Superior thyroid artery (from ext carotid artery) • Inferior thyroid artery (from thyrocervical trunk, the 1st branch of the subclavian artery) • Thyroidea ima artery: from the brachiocephalic artery • A diseased thyroid gland may acquire additional blood supply from neighbouring structures, especially the vessels • Venous drainage • Superior thyroid vein: drains into IJV or facial vein • Middle thyroid vein: drains into IJV • Inferior thyroid vein: drains into brachiocephalic (innominate) vein

6. ASSOCIATED NERVE • External laryngeal nerve: terminal branch of the superior laryngeal branch of the vagus: Supplies the cricothyroid muscle. It is in close proximity to the superior thyroid artery. • Recurrent laryngeal nerve: Supplies all the intrinsic muscles of the larynx except the cricothyroid. • It arises from the vagus. On the right side it crosses and hooks around the subclavian artery while on the left side it crosses and hooks around the aorta. It then ascends in the groove between the trachea and the oesophagus. It is closely related to the termination of the inferior thyroid artery. • The recurrent laryngeal nerve is usually found in Simon’s triangle, which is formed by the inferior thyroid artery superiorly, the common carotid artery laterally, and the oesophagus medially • Anatomical anomalies, more common on the right, include a nerve following a more lateral course which then runs obliquely, or even horizontal and is therefore more vulnerable to injury

8. PARATHYROID GLAND • Parathyroid gland: consists of bilateral superior and inferior glands which lie behind the thyroid. Each is ellipsoid, pea-sized, and of a reddish-brown colour. • The glands lie within 1–2 cm of the intersection of the recurrent laryngeal nerve and the inferior thyroid artery. • The superior glands lie above and behind the nerve. The inferior glands lie below and ventral to the nerve.

9. PHYSIOLOGY • Thyroid Hormones are amine hormones and so their synthesis is based on the amino acid tyrosine. The primary synthetic organ of Thyroid Hormones is the thyroid gland which produces about twenty times more T4 compared to T3. T4 is then converted to either T3 or rT3 by the enzyme 'Iodinase' which is present throughout the body's tissue • thyroid follicles which are the basic units of thyroid hormone synthesis. • The thyroid follicles are surrounded by a lining of follicular epithelial cells and contain an acellular lumen full of proteinacious material termed the Thyroid Colloid

10. Iodine absorption and transport: thyroid gland stores 90% of iodide at any given time • Transport to thyroid gland is regulated by TSH and follicular content of iodide • Iodide oxidation to iodine and organification: both process are catalyzed by thyroid peroxidase • Coupling: MIT and DIT to form T3 and T4 • Storage and release: T3 and T4 all attaches to thyroblobulin and stored in the colloid thyroglobulin molecule • Peripheral conversion: liver, kidney and other tissue. Drugs such as PTU, propanolol and corticosteroid prevent peripheral conversion

11. T3 is 5times more potent than T4 • Half life of T4 is 6-7days and T3 1-2days • T4 is the major circulating hormone and bound more to plasma protein • TSH has 2 subunit alpha and beta • Physiologic function of thyroid hormone • Normal human growth & development esp CNS • Maintain metabolic homeostasis affecting all organ system

13. GOITRE • A goitre refers to an enlarged thyroid gland from any cause • A thyroid gland is considered goitrous if the lateral lobes are larger than the terminal phalanx of the thumb of the person being examined. • For the goitre to be palpable, it’s weight must be at least 40g • Grading of Goitres (WHO-1960) • Grade 0: the goitre is not palpable nor visible, even with the neck extended • Grade 1: The goitre is palpable. • Ia: Goitre is palpable with neck extended but is not visible even with the neck extended. • Ib: Goitre is palpable in neck extension and normal position, but visible only with the neck extended • Grade 2: Goitre is visible with neck in normal position • Grade 3: Large goitre, visible from a distance • Grade 4: Moinstrous goitre

14. Retrosternal goitre • Substernal • Intrathoraxic • plunging

15. Simple (non-toxic) Goitre: refers to a goitre with normal thyroid hormone production (not increased nor decreased) which is not neoplastic • Endemic or Sporadic • Endemic: > 10% of the community has goitre. • Diffuse (colloid or hyperplastic) or Nodular • Diffuse hyperplastic is found in increased physiologic demand eg puberty, pregnancy, lactation etc • Toxic Goitre • Toxic diffuse goitre (Grave’s disease): • A form of primary thyrotoxicosis. Has more eye signs • Toxic multinodular goitre- plummer’s disease • A form of secondary thyrotoxicosis. Tends to have more cardiac signs • Toxic solitary nodule (toxic adenoma) • Toxic malignant goitre: rare

16. Inflammatory Goitre • Auto-immune thyroiditis: • Hashimoto's thyroiditis • Chronic lymphocytic thyroiditis • Infective: • Acute thyroiditis • Suppurative: thyroid abscess • Non-suppurative: bacterial, viral • Subacutethyroiditis • Chronic thyroiditis e.g. tuberculosis, syphilitic thyroiditis. • Granulomatous: De-quervain’sthyroiditis • Fibrosing: Riedel's thyroiditis • Others: Amyloid thyroid disease • Neoplastic goitre • Benign • Malignant: primary or secondary

17. PATHOLOGY • Simple goitre • Caused by increased TSH stimulation of the gland due to physiologic or pathologic deficiency of thyroid hormones • Physiologic states: Puberty, Menstruation, Pregnancy, Lactation. There is increased need for thyroid hormones at these times due to increased metabolic rates. In order to meet the increased needs, TSH stimulates the gland • Pathologic states: • inadequate intake (I2 deficiency in soil of endemic areas, non-iodized salt), • inadequate I2 absorption, • goitrogens which cause inadequate I2 uptake into the thyroid gland (Ca2+ in limestone areas, drugs, cassava fumes), • deficient trapping & concentration of I2 by the gland (from drugs like perchlorate, thiocyanate, nitrate), • Genetic factors

18. Endemic goitre is caused by • deficient dietary I2intake • Goitrogens in food (eg cassava fumes contain cyanogenicglucosides which yield thiocyanate as a metabolic by-product. The thiocyanate inhibits iodine uptake by the thyroid gland) • excessive calcium salts in water supply. • Toxic goitre • Hyperthyroidism: excess thyroid hormone secretion from the thyroid gland • Thyrotoxicosis: excess thyroid hormones in the circulation, the excess being from excess release of thyroid hormones from the thyroid gland or from other sources (such as exogenous T3 & T4, ectopic thyroid tissue, diet, etc)

19. GRAVES DISEASE • Auto-immune diffuse, toxic goitre • Epid • M:F = 1: 5-10 • Affects 2% of the female population • Age: commoner in 3rd-5th decades of life • Risk factors • Has a strong family ppreponderance/hereditary component. When an identical twin has it, the 2nd twin also develops graves’ disease in 25% of cases. However, no clear genetic defect has been identified • Smoking & 2nd hand smoke exposure associated with the eye manifestations but not the thyroid manifestations • Eye-signs: due to retro-bulbar collagen deposition • Symptoms: due to excess thyroid hormone in circulation

20. Pathology • Auto-immune disease • Ab: TSH-receptor activating Ab • TSI: IgG that acts as LATS, activating the thyroid follicle in a longer and slower way than TSH • TGI (thyroid growth immunoglobulins): bind directly to TSH receptor • TBII (Thyrotrophin binding-inhibiting immunoglobulins): inhibit the normal union of TSH with its receptor • Trigger for auto-Ab production not known • Genetic basis: HLA-DR3 plays a role • Viral or bacterial infection (eg Yersiniaenterocolitica): they may trigger Ab which cross-react with the TSH receptor via antigenic mimicry

21. Toxic multinodular goitre • Excessive thyroid hormone formation from functionally autonomous thyroid nodules, which do not require stimulation by TSH • Pathology • Iodine deficiency leads to deficient T3/T4 formation • Compensatory thyroid cell hyperplasia, leading to the multinodular goitre appearance • Increased replication leads to risk of mutation of the TSH receptor • The mutated TSH receptor can become active, leading to excess T3/T4 production- hyperthyroidism

22. THYROID MALIGNANCY • Pathologic types: • Primary (95%) • Follicular cells: • Differentiated (90%): Follicular, Papillary • Undifferentiated: Anaplastic • Para-follicular cells: Medullary • Lymphoid cells: Lymphoma • Others: Fibrosarcoma, Squamous cell CA, Mucoepidermoid CA • Secondary (5%): • Metastatic (esp from kidney, breast, GIT) • Local infiltration (from upper aerodigestivesquamous cell CA)

23. PAPILLARY THROID CA • Commonest in Europe & America (60-70%). Less common in Nigeria (20-35%) and Asia/India (40%). • Commoner in areas with non-endemic goitre • Affects younger age-group. Highest incidence 3rd-4thdecade • Sex: Female: Male = 3:1 • Slow growth, seldom encapsulated • Low-grade malignancy • Multiple foci common. Microscopic intraglandular spread to the contralateral lobe occurs in 90% of cases • Histologically, the tumour shows papillary projections with psammoma bodies and characteristic pale empty nuclei (Orphan Annie-eyed nuclei)

24. Metastasis is mainly by lymphatic spread. Haematogenous spread is rare • Thus, presents more with loco-regional disease. Cervical lymph node enlargement may be the 1st presentation (the thyroid may be impalpable in presence of cervical lymph enlargement) • Late distant metastasis (to cervical and upper mediastinalnodes • Prognosis good, compared to follicular CA

25. FOLLICULAR THYROID CA • Commonest type seen in Africa/Nigeria (50-60%). Less common in Europe/America (20-40%); India (30%) • Commoner in areas with endemic goitre, due to low I2 in these areas • Age: affects older age group. Highest incidence: 5th decade • Sex: Female: Male = 3:1 • Prognosis: Poor. Mortality rate is twice that of papillary cancer

26. Arise de-novo or from pre-existing multinodular goitre • Slow-growing, highly vascular, macroscopically encapsulated but microscopically, there is invasion of the vascular spaces in the capsular region. • Multiple foci seldom seen • Low grade or high grade (Hurthle cell) subtype. • Hurthle cell tumours: a variant of follicular neoplasmwhich contains abundant oxyphil cells (Hurthle or Askanazy cells) histologically. Associated with a poorer prognosis. All Hurthle cell neoplasms are malignant

27. Metastasis: Mainly haematogenousto distant sites such as bone, lungs, liver, brain. Bone metastasis is usually osteolytic, warm, highly vascular, pulsatile, localised and common in flat bones such as skull (frontoparietal aspect), ribs, scapula,sternum. • Lymph node involvement much less common than in papillary carcinoma. Metastasis can concentrate radio-iodine (hot spots)

28. Hurthle cell CA • They are a variant of follicular neoplasm • Contain abundant oxyphil cells (Hurthle or Askanazy cells) histologically. • Does not take up 131I, unlike other follicular tumors. • Secretes thyroglobulin • 99Tc-sestamibi scan is used for localisation • Affects regional lymph nodes more than follicular CA • All Hurthle cell neoplasms are malignant, so associated with a poorer prognosis.

29. Medullary CA • An APUDoma, of neural crest origin. 5% of thyroid malignancies • Arises from the parafollicular cells (C-cells) of the thyroid gland, derived from the ultimobranchial body. (C-cells are more abundant in the upper pole of the thyroid gland) • Secretes calcitonin and CEA; thus both are used as tumour markers • Sporadic (75%), Familial (25%) • Sporadic: confined to one lobe. Occurs at any age (though commonly 50-70yrs of age) with no sex preponderance • Familial: multicentric. Both lobes are affected. Occurs before 30yrs • Familial syndromic: associated with MEN IIa & IIb (Sipple’s disease) • Familial non-syndromic: not associated with MEN • The ones associated with MEN are associated with secretion of serotonin & prostaglandin (watery diarrhoea, flushing), histamine, calcitonin • It is not TSH dependent; and does not take up radioactive iodine. • Spread mainly to lymph nodes

30. Anaplastic • 5-10% of thyroid tumors. Commoner late in life • Rapid growth, hard consistency, small cell and giant cell subtypes. • Poor prognosis • De-novo or associated with a concurrent well-differentiated thyroid CA • Spreads locally (leading to obstruction of thetrachea and oesophagus) or via lymph nodes • It is radio-sensitive • Lymphoma: 5% of thyroid malignancy. 70-fold risk in Hashimoto's thyroiditis (which causes hypothyroidism, with consequent increased TSH production). May be the diffuse histiocytic type or the low grade B-cell lymphoma (Maltoma) type. Has good response to radiation therapy.

31. CLINICAL EVALUATION • Presenting complaint usually anterior neck swelling • Onset • How it was noticed • Progression • Ulceration • Discharge • Constiturional symptoms • Compressive symptoms • Dyspnea • Dysphagia • Dysphonia • snorring

32. Toxic status • Common symptoms of hypo/ hyperthroidism • HPERTHYROIDISM HYPOTHYROIDISM • Nervousness memory loss • Anxiety lethargy • Insomnia somnolence • Heat intolerance cold intolerance • Hyperactivity sluggishness • Palpitations • Weight loss weight gain • Diarrhea constipation • Amenorrhea menstral irregularity

33. EYE SYMPTOMS • Grittiness of the eyes: earliest symptom • Pain, excessive tears, red eye, photophobia, blurred vision • Prominence of the eyes. • Diplopia, reduced visual acuity

34. History of aetiology • Where patient has lived • Presence of goitre within the community or family • Source of water • Use of iodized salt • Childhood exposure to radiation • Consumption of goitrogenic food ( cassava, garbage etc) • Cough syrup abuse • Usage of antithyroid drugs • Use of amilodipine or lithium • Trauma • History of TB

35. History of complication • History of care • comorbidity

36. Detailed examination • General physical examination • Examination of the goiter • Eye signs • Exompthalmus • Lig lag (Von graefe’s sign) • Lid retraction (Dalrymple’ssign) • Staring gaze (stellwag sign): • Joffroy’s sign: absent fore-head creases on superior gaze • Mobius sign: Inability to maintain convergence of the eyes • Naffziger sign • Ophthalmoplegia (myopathy)

37. INVESTIGATION • To confirm diagnosis • Neck ultrasound: shows if the mass is solid, cystic or a complex mass (combination of solid and cystic). Also shows cervical lymph nodes. On doppler interrogation, shows involvement of carotid artery/IJV. Can also guide FNAC/trucut biopsy • Fine needle aspiration cytology (FNAC): • Useful in diagnosing papillary, medullary, anaplastic carcinoma and lymphoma.(and colloid goitre) • Not so useful in follicular CA because it does not show capsular/vascular invasion which differentiate between benign follicular adenoma and malignant follicular CA. • Has a high false-negative rate(thus lobectomy is superior to it if there is a strong clinical suspicion

38. FNAC result • Thy1: Non-diagnostic • Thy2: Non-neoplastic • Thy3: Follicular • Thy4: Suspicious for malignancy • Thy5: Malignant • Thyroid function test: TSH is the most important • Neck X-ray: AP and Lat • Thoraxic inlet X-ray • Indirect laryngoscopy/ fibre optic laryngoscopy: : to rule out abductor cord paralysis from recurrent laryngeal nerve involvement, Laryngeal infiltration by the tumor and other Laryngeal pathology (eg hoarseness in a goitrous patient may be due to papilloma of the vocal cord)

39. LAT AP

40. Radio-iodine uptake test (Scintigraphy scan): 123I is used. The swelling may be 'cold' or ‘hot’. • Most thyroid malignancies are cold; they do not take up radio-iodine • However, degenerated nodules of simple multi-nodular goitre & all forms of thyroiditis also do not take up radio-iodine • The liver, bones and lungs are also scanned for metastases. • CT Scan and MRI • To prepare for Rx • FBC • Urinalysis; RBS • E/U/Cr/Ca/PO4 • IDL • ECG • Group & Xmatch

41. INDICATIONS FOR MEDICAL TREATMENT • Thyrotoxicosis in pregnancy: medical treatment is used to make the pt euthyroid during pregnancy, the pt then has surgery after delivery (once the pregnant patient on anti-thyroid drugs is euthyroid, place her on once daily thyroid replacement to prevent development of goitre in the fetus) • Children • Poor risk patient • Recurrence of toxic symptoms after previous thyroidectomy

42. INDICATIONS FOR SURGERY • Cosmesis • Failure of medical therapy: : if anti-thyroid drugs are poorly tolerated, required in large prolonged doses or recurrence after successful medical treatment • Pressure symptoms • Suspicion or malignancy: solitary nodule that doesn’t take up radio-iodide • Toxic goitres • Inflammatory conditions: Riedel’s struma and Hashimoto’s disease. • Emergency thyroidectomy: it’s only indication is rapid development of life-threatening pressure symptoms, due to intra-thyroid haemorrhage

43. THYROID SURGERY • LOBECTOMY • SUBTOTAL THROIDECTOMY • NEAR TOTAL THROIDECTOMY • TOTAL THYROIDECTOMY

44. COMPLICATION • IMMEDIATE • Injuries to contiguous structures • Recurrent laryngeal nerve • Tracheal • Parathyroid gland • Hemorrhage • EARLY • Laryngeal edema • Laryngeal spasm • Tracheomalacia • Tension hematoma • hypocalcaemia

45. LATE • Hypothyroidism • Hypoparathyroidism • recurrence

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