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Thyroid carcinoma other than papillary carcinoma

 

Papillary carcinoma being the most common one constituting 85% of all thyroid cancers is usually the one discussed in detail. But the other tumors occurring in thyroid gland carry an equal importance and thus discussed here.

Follicular carcinoma:

It is the second common carcinoma of thyroid constituting about 5-15%. These tumors have little propensity for lymphatic invasion therefore correlating with negative regional lymph nodes. Hematogenous spread is common and so lung, liver and bone metastases are common.

Risk factors:

    • Associated with dietary iodine deficiency
    • More common in women
    • Common in older individuals ranging between 40-60 years
    • Radiation exposure

Clinical presentation:

Slowly enlarging painless nodules. Usually these are cold nodules.

Gross features:

    • Single nodules
    • May be well-circumscribed or widely infiltrative
    • Gray, tan or pink on cut-section

Microscopic features:

    • Microfollicular or trabecular pattern
    • Round, regular small follicles
    • Hemorrhage, necrosis or tumor infarction may be present
    • Circumscription or invasion: this feature classifies the follicular carcinoma into the following types

WHO classification:

    • Minimally invasive follicular carcinoma (capsular invasion only)
    • Encapsulated angioinvasive follicular carcinoma
    • Widely invasive follicular carcinoma (worse prognosis)

Variants of follicular carcinoma:

    • Clear cell carcinoma: >50% of clear cells
    • Signet ring cell type
    • Spindle cell follicular carcinoma
    • Follicular carcinoma with glomeruloid pattern

Prognostic factors:

Following factors are associated with poor prognosis.

    • Presence of metastasis
    • Multiple site of metastasis
    • Age over 50 years
    • Poorly differentiated areas of tumor
    • Widely invasive tumor
    • Extensive vascular involvement

Genetic features of follicular carcinoma:

    • PPARG gene fusion
    • PI3K/AKT/PTEN pathway
    • RAS mutations
    • THSR mutations
    • TERT mutations
    1. Poorly differentiated carcinoma:

It constitutes around 5% of primary thyroid tumors. These are follicular-derived carcinomas with prognosis between well-differentiated carcinomas and anaplastic carcinomas. Its response to radioiodine is poor.

Clinical presentation:

It constitutes around 5% of primary thyroid tumors. These are follicular-derived carcinomas with prognosis between well-differentiated carcinomas and anaplastic carcinomas. Its response to radioiodine is poor.

Gross features:                                                      

    • Large tumors with infiltrative borders
    • Gray-white cut surface
    • Extensive necrosis

Microscopic features:

It is defined by following features;

    • Solid, trabecular or insular growth pattern
    • Absence of classic nuclear features of papillary carcinoma
    • Presence of at least one of the following features
      • Presence of convoluted nuclei
      • Necrosis
      • Mitotic activity>3/10HPF

Immunohistochemistry:

    • Thyroglobulin is positive
    • TTF and Calcitonin is negative

Genetic features:

    • RAS mutations

 

    1. Anaplastic carcinoma:

These are undifferentiated tumors of thyroid follicular epithelium accounting for less than 5% of thyroid tumors. These have extremely poor prognosis  with a mortality rate of 100%. Patients survive for less than six months after diagnosis.

Risk factors:

Are unknown but history of radiation and iodine deficiency may have some association.

Clinical presentation:

    • Rapidly enlarging bulky neck masses usually in older women
    • Symptoms related to compression and invasion are seen commonly including dysnea, dysphagia and hoarseness.

Gross features:

    • Large tumors with intra and extra-thyroidal tissue involvement and parenchymal destruction

Microscopic features:

    • Highly anaplastic cells
    • Necrosis and vascular invasion
    • Prominent mitotic figures

Variants:

    • Sarcomatoid variant
    • Giant cell variant
    • Epithelial variant
    • Pauci-cellular variant

Immunohistochemistry:

    • PAX8 and CK positive
    • Thyroglobulin is negative
    • TTF1 is focal positive

Genetic studies:

    • P53 mutations most common
    • BRAF mutations
    • RAS mutations

 

Dr Saadia Hafeez

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