Thyroid nodule differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]

Overview

Neck masses can be mistaken with thyroid nodules. The most important neck masses that can be mistaken with thyroid nodules include: Thyroglossal duct cyst, Parathyroid cancer, parathyroid cyst, Branchial cleft cyst. While the diagnosis of a thyroid nodule is established, thyroid nodule should be differentiated based on benign or malignant features and the type of nodule.

Thyroid nodule differential diagnosis

Neck masses can be mistaken with thyroid nodules. While the diagnosis of a thyroid nodule is established, thyroid nodule should be differentiated based on benign or malignant features and the type of nodule:

Disease Nodule property Spread Nodular growth Laboratory Imaging Pathology Associated mutation special consideration
LN Vessle Metastasis TSH FT4/T3
Benign Colloid adenoma
  • Noncancerous enlargement of thyroid tissue
  • May be painful
- - - Intermediate

Slow

NL NL
  • Iso- to hypoechoic
  • May have internal cystic or heterogeneous change
  • May have calcification
  • Multiple echogenic foci (of inspissated colloid) with comet tail artifac
--- May progress to carcinoma
Hashimoto's thyroiditis
  • Rarely painful
- - - Rapid

Intermediate

↓↓
  • Hypoechoic micronodules (1-6 mm) with surrounding echogenic septations
  • HLA-A
  • HLA-B
May be accompanied with fever

Autoimmune disease of thyroid gland

Cysts nodule
  • Most common cause of painful neck lesion
- - - Rapid

Intermediate

NL NL
  • Cystic non-calcified nodules
  • Follicular cells
  • Macrophages
  • RBC
  • Colloid
- Mostly due to degenerating thyroid adenomas
Follicular adenoma
  • Rarely painful
- - - Intermediate

Slow

↓↓
  • Thin peripheral halo
  • Predominantly cystic or mixed cystic and solid lesions
  • Isoechoic or predominantly anechoic
---
  • PAX8-PPAR gamma 1 
---
Hyperplastic nodule - - - Rapid

Intermediate

↓↓
Macrofollicular adenoma - - - Intermediate

Slow

↓↓
Microfollicular or cellular adenoma - - - Intermediate

Slow

↓↓
Hürthle cell adenoma - - - Intermediate

Slow

↑↓ ↑↓
Malignant Papillary carcinoma
  • Fixed
  • Painless
+ +
  • Pulmonary
  • Skeletal metastases
Intermediate

Slow

NL NL
  • Solitary mass usually with an irregular outline, located in the subcapsular region
  • Small punctate regions of echogenicity representing microcalcifications (psammoma bodies)
  • Unencapsulated and may be partially cystic
  • Papillae consisting of one or two layers of tumor cells surrounding a well-defined fibrovascular core
  • Large, oval, and appear crowded and overlapping nuclei
  • May contain hypodense powdery chromatin, cytoplasmic pseudoinclusions due to a redundant nuclear membrane, or nuclear grooves
  • RET/PTC
  • NTRK1
  • RAS
  • BRAF 
---
Follicular carcinoma
  • Fix
  • Painless
+ +
  • Bone
  • Lung
Intermediate

Slow

↑↓ ↑↓
  • Lesions are typically hypoechoic
  • Usually lacks cystic change
  • FLUS
  • Tumor capsule
  • Vascular invasion
  • RAS mutations
  • PAX8-PPAR gamma 1 
Most common thyroid cancer in iodine deficient areas
Medullary carcinoma Mainly manifest paraneoplastic symptoms: + -/+
  • Locally to neck
  • Can metastase to all body organ systems
Intermediate

Slow

NL NL
  • Unifocal
  • May present as multifocal
  • Hypoechoic
  • Microcalcifications
--- May be associated with other co-existing diseases

Associated with high levels of calcitonin

Anaplastic carcinoma + + Slow
  • Microcalcification
  • Infiltrative lesion
Cytologically malignant:
  • Huge nuclear-cytoplasmic ratio
  • Mitoses
  • P53
  • BRAF
Very malignant, always considered as stage IV
Primary thyroid lymphoma + -
  • MALT lymphoma less aggressive
  • Diffuse large cell lymphomas more aggressive
Intermediate

Slow

NL NL
  • Nodular (hypoechoic mass), diffuse (mixed echotexture) or mixed
  • Calcifications uncommon
  • BRAF
  • NRAS
  • MAPK 
May be associated with hashimoto thyroiditis
Metastatic carcinoma
  • Thyroid and extra thyroid manifestations
+ + + Intermediate

Slow

↑↓ ↑↓ - - - Malignant melanoma

Lung cancer

breast cancer

Renal cancer

Gastrointestinal cancer

Thyroglossal duct cyst
  • Mostly midline
  • Can be painful if get infected
- - --- --- NL NL
  • Cyst in subhyoid portion or lateral tip of the hyoid bone
--- --- ---
Branchial cleft cyst - +

May adhere to great vessels at the mandibular angle

--- --- NL NL --- --- ---
Neck abscess
  • Painful mass in the neck, may be accompanied with erythema
+ - --- Rapid NL NL
  • Cyst with hyperechoic debris containing pus
--- --- ---
Parathyroid cyst
  • Painless mass
- - --- Rapid

Intermediate

NL NL
  • Cystic lesion that is uniformly anechoic
--- --- ---
Parathyroid cancer + + +

Rarely distant metastases, mainly  thyroid gland, overlying strap muscles, recurrent laryngeal nerve, trachea, or esophagus

Slow

Intermediate

NL NL
  • Normal thyroid size with a complex echogenic structure
  • May contain hyperechoic solid part and several centrally located anechoic cavities
  • Tumor cells form branching cord surrounded by fat cells with areas of fibrosis and chronic inflammatory cells or abundant granular eosinophilic cytoplasm
  • FIHP
  • MEN1
---

References

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