Summary of thyroid tumour:

Usually tumours seen are primary epithelial tumours. Adenomas are benign & carcinomas are malignant.

Classification

By it’s histogenic/differention properties:

  • Exhibiting follicular cell differentiation (95%)
  • Exhibiting C-cell differentition
  • Exhibiting follocular & C-cell differentiation

Types of thyroid tumours

Epithelial tumours

  • follicular adenoma (most common)
  • papillary adenoma
  • Hurthle cell (oncocytic) tumours
    • hyperfunctioning follicular cell
  • Undifferentiated carcinoma
    • Anaplastic
    • Sarcomatoid
  • Medullary carcinoma
  • Others:
    • Follicular carcinoma
    • Clear cell tumours
    • Squamous cell/mucinous
    • Poorly differentiated carcinoma (insular carcinoma)
    • C-cell hyperplasia
    • Other neuroendocrine lesions

Lymphoid tumours & tumour-like conditions

  • Malignant lymphoma
  • Plasmacytoma
  • Hodgkin’s disease
  • Langerhans’ cell granulomatosis
  • Rosai-Dorfman disease

Mesenchymal tumours

  • Benign
    • lipoma
    • hemangioma
    • lymphangioma
    • leiomyoma
    • neurilemoma
    • solitary fibrous tumour
  • Sarcoma
    • fibrosarcoma
    • liposarcoma
    • leipmyosarcoma
    • chondrosarcoma
    • osteosarcoma
    • malignant schwannoma
    • angiosarcoma

Other primary tumors & tumour-like conditions

  • Teratomas
    • Infants/Children: cystic/benign
    • Adults: Malignant
  • Parathyroid tumours
    • problems of diff diagnosis?
  • Amyloidosis
    • systemic disease/localised primary amyloid tumour
  • Malakoplakia
  • Extramedullary hematopoiesis
    • associated with myelofibrosis

Metastatic tumours

  • Direct extension
  • Blood-borne metastasis

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Follicular adenoma

Definition:

Benign encapsulated  tumour with follicular cell differentiation

  • solitary
  • surrounded completely by a thin capsul
  • compressed gland

image

*haemorrhagic, well-encapsulated

Microscopic patterns (not important)

  • normofollicular (simple)
  • macrofollicular (colloid)
  • microfollicular (fetal)
  • trabecular/solid (embryonal)
  • papillary

Secondary degenerations

  • Hemorrhage
  • Oedema
  • Fibrosis
  • Calcification
  • Bone formation (ossification)
  • Cystic degeneration

Differential diagnosis

  • Dominant nodule of nodular hyperplasia
    • clinical
  • Minimally invasive follicular carcinoma
    • gross
  • Follicular variant of papillary carcinoma
    • microscopic

image

Note the well defined capsule.

image

Hurthle cell adenoma: a variant of follicular adenoma.

Note the distinct nuclueses of the Hurthle cells.

Follicular carcinoma

  • Rare neoplasm
  • Woman, 30 years old, whites
  • Invasion of capsule, blood vessels / adjacent thyroid

image

Types

  • Minimally invasive
  • Widely invasive

Microscopy

  • Well-formed follicles
  • Poorly-formed follicles
  • Cribiform area
  • Trabecular formations
  • Predominantly solid growth pattern
  • Cytoplasmic clear changes
  • Mitotic activity & nuclear atypia

Diagnosis

  • Immunohistochemistry
    • **Epithelial membrane antigen (EMA)
    • thyroglobulin
    • low molecular weight keratin
    • basement menbrane components (laminin & type IV collagen)
  • ras point mutation (53%)

image

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Papillary carcinoma

image

Image: Gross papillary formation with central fibrosis

image

  • Follicular carcinoma: most common neoplasia
  • Papillary carcinoma: most common malignancy
  • Female, 40 years old
  • 90% thyroid malignancies in children

Gross feature:

  • Variable size
  • Solid, whitish, firm, clearly invasive
  • Less than 10% surrounded by a complete capsule
  • Marked cystic changes (10%)
  • Papillary formations evident to naked eye (finger-like projections)

Microscopy

1. Architectural features:

image

  • True papillae
    • Complex, branching & randomly oriented
    • Central fibrovascular core
    • Single/stratified lining of cuboidal cells

2. ***Nuclear features:

image

Image: Orphan Annie Eyes

  • Orphan Annie eyes
    • Ground glass nuclei (optically clear)
    • Nuclear pseudoinclusions
  • Nuclear grooves
  • Nuclear microfilaments

3. Psammoma bodies

image

Image: Laminated calcification, also seen in benign tumours & goiter

Diagnosis

  • Immunohistochemistry (not important, easily diagnose microscopically)
    • Keratin
    • Thyroglobulin
    • S-100 protein
    • EMA, CEA, Vimentin, Ceruloplastin
    • Estrogen receptor proteins
  • Oncogene alterations
    • RET & NTRK1 (tyrosine kinase ativity)
    • Activation of N-ras (point mutation)

Alot of morphologic variants, but nuclear features are seen in all.

Prognosis depends on

  • Females better prognosis
  • More than 40 yo
  • Extrathyroid extensions
  • History of previous irradiation
  • Tumour size
  • Capsule & Margins
  • Multicentricity**
  • Distant metastasis**
  • Poorly differentiated, squamous, or anaplastic foci
  • EMA & LeuMI positivity (good prognosis)
  • DNA ploidy

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Medullary carcinoma

Also known as

  • solid carcinoma
  • hyaline carcinoma
  • C-cell carcinoma

No capsule and composed of parafollicular C-cells

Gross:

  • solid, firm & non-encapsulated
    • but well circumscribed
  • Continuous fibrous capsule (rare)
  • Located in the midportion of upper half of the gland
  • Corresponding to a greater concentration of C-cells

Microscopy:

  • *Amyloid (stain +ve)
  • Solid proliferation
  • Round to polygonal cells
  • Granular amphophilic cytoplasm
  • Medium sized nucleus
  • Highly vascular stroma
  • Hyalinized collagen
  • Coarse calcification

image

Amyloid: stained with congo red birefringence

Diagnosis

  • Ultrastructurally
    • cytoplasmic dense-core variably sized secretory granules
  • Immunohistochemistry
    • *Calcitonin (+ve)
    • Keratin
    • NSE
    • Chromogranin A, B & C
    • Synaptophysin
    • Opioid peptides
    • CEA
  • **Negative for thyroglobulin
    • distinguishes from other thyroid cancer

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Anaplastic carcinoma

  • Elderly
  • Rapidly growing mass
  • **Hoarseness, dysphagia & dypsnea
  • Extrathyroid extentions (most)

Gross

  • highly necrotic
  • hemorrhagic
  • solid tumour mass

Microscopic (not important)

  • Cellular variants
    • Squamoid
    • Spindle clee
    • Giant cell
    • *Paucicellular
      • 1. Neutrophilic infiltration
      • 2. Prominent vascularization
      • 3. Cartilaginous/osseous metaplasia
  • Patterns of growth
    • Fascicular
    • Storiform
    • Palisading at the necrotic edges

Diagnosis

  • Ultrastructural
    • Epithelial differentiation
  • Immunohistochemistry
    • Keratin
    • Vimentin (Spindle cell)
    • Laminin
    • 390 & focal EMA & ECA (Basement membrane)

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Thyroid lymphoma

  • Primary malignant lymphoma
    • adult/elderly
    • females
  • Rapid enlargment
    • tracheal & laryngeal compression
      • dyspnoea, hoarseness
  • Euthyroid (mostly)
    • Sometimes hypothyroid

Gross

  • Cut surface
  • Solid white with fish flesh appearance

Microscopic

  • Mostly diffuse large cell type
  • Sclerosis (focally prominent)
  • Immunoblastic lymphoma
  • Low grade lymphomas
    • small/intermediate cells
  • Diffuse / follicular pattern
  • Packing of follicular lumina of lymphoma

Diagnosis

  • Immunohistochemistry
    • leukocyte common antigen
    • B-cell markers

Hodgkin’s disease of the thyroid gland (lymphoma)

image

Note: Reed-sternberg cell

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Angiosarcoma of the thyroid

image

Tumour is well-differentiated & composed of anastomosing vascular channels lined by epithelioid endothelial cells.

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Staging of cancer

Staging of well-differentiated thyroid cancers is related to age for Stage 1 & 2. But not for Stage 3 & 4.

Younger than 45 years old

  • Stage 1
    • T – any
    • N – any
  • Stage 2
    • T -any
    • N- any
    • M1

Older th
an 45 years old

  • Stage 1
    • T1 (less than 1.5cm)
  • Stage 2
    • T2-3 (more than 1.5cm)
  • Stage 3
    • T4 NO
    • TO N1 (spread to outside thyroid by not outside neck)
  • Stage 4
    • T – any
    • N – any
    • M1

Factors favouring malignancy

  • Age
  • Males
  • Neck irradiation in infancy
  • Solitary nodules (more likely to be malignant)
  • Rate of growth
  • Ipsilateral adenopathy (1 sided)
  • Toxic/got nodules (less likely to be malignant)
  • Cystic nodules (less likely to be malignant than solid ones)

MRI is better than CT for the evaluation of metastatic, retrotracheal or mediastinal lesions

Serum thyroglobulin levels is useful in monitoring patients after removal of a papillary/follicular carcinoma.

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