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Histology of thyroid cancer

Histologic classification (WHO)

  1. Papillary thyroid carcinoma (about 70%)
  2. Follicular thyroid carcinoma (about 15%)
  3. Poorly differentiated thyroid carcinoma (< 5%)
  4. Udifferentiated (anaplastic) thyroid cacinoma (< 5%)
  5. Medullary thyroid carcinoma (5-10%)
  6. others (lymphoproliferative neoplasias, metastases)

Group 1-4 originate from the follicular epithelium, while group 5 originates from C-cells (calcitonin-producing cells) localized between the follicles. 

Papillary thyroid carcinoma (PTC)

Extirpated thyroid gland with tumor in the right lobe. Click to enlarge. Cut surface from the right lobe in the specimen in the left-hand image. Click to enlarge. Photomicrograph of the same tumor. The tumor is growing in a papillary fashion in a colloid-filled lumen. Click to enlarge.

The microscopic diagnosis is based on evaluation of a combination of different aspects:

  • Growth pattern (papillary structures, solid nests, follicular structures in follicular variant of PTC).
  • Nuclear characteristics: ground glass nuclei, nuclear grooves and inclusions. These changes are, however, not specific for malignancy and are sometimes absent or very difficult to discern.

Papillary thyroid carcinomas (PTC) appear in many variants. To subclassify the tumor, the specific appearance/growth/nuclear features should dominate (>75%).

Grading is not generally recommended, but has been suggested by some investigators. The individual criterias that might indicate worse prognosis is, according to WHO 2004 are:

  • Marked nuclear atypia
  • Necrosis
  • Vascular invasion
  • Increased number of mitotic figures

PTC may be cystic and can then be difficult to diagnose, especially in fine needle aspirates (FNA).

Follicular neoplasia

Cut surface from a thyroid lobe with a follicular carcinoma and easily distinguishable capsule penetration. Click to enlarge. Photomicrograph of the same lobe and demonstrating the capsule penetration. Click to enlarge.

The follicular carcinoma diagnosis is based on detailed histological evaluation of tumor and its relation to the capsule and vessels. Thus, the presence of capsule- and/or vascular invasion is needed to establish the diagnosis, and not the tumor cell appearance.

Follicular carcinoma can be divided into low- and high-grade malignancy based on the extent of capsule- or vascular invasion. Those with focal capsule invasion (minimal invasive) have usually a low malignancy potential.

Follicular benign tumors (adenomas) will sometimes demonstrate nuclear variation and a few mitotic figures, but still they can be considered as benign. Atypical mitotic figures are, however, an indicator of malignancy.

Follicular carcinomas appear in two forms:

  • Minmal invasive
  • Widely invasive  

Carcinomas with oncocytic differentiation

Carcinomas with oncocytic differentiation can be very difficult to evaluate, concerning malignancy and classification.  

Medullary thyroid carcinomas

Photomicrograph showing a medullary thyroid carcinoma. Click to enlarge.

Medullary thyroid carcinoma originates from the calcitonin-producing C-cells in the thyroid gland. Medullary thyroid carcinoma appears as both a spontaneous and a familial variant. The finding of multiple tumors and/or C-cell hyperplasia, indicate a familial variant, while the finding of a solitary tumor frequently is consistent with the spontaneous variant.

Tumor cells are monomorphic with round, oval or spindle shape and a low nuclear/cytoplasmic ratio. These tumors often contain a characteristic amyloid substance.

Poorly differentiated thyroid carcinomas

Photomicrograph demonstrating a thyroid lobe with diffusely infiltrating anaplastic carcinoma. Click to enlarge. Cut surface from a thyroid lobe with diffusely infiltrating anaplastic carcinoma. Click to enlarge.

Poorly differentiated carcinomas are often categorized in two groups of which one is the insular growing carcinoma, and the other one showing features intermediate between differentiated thyroid carcinomas and undifferentiated anaplastic carcinoma. These are usually tumors with solid growth pattern, severe nuclear atypia (no ground glass nuclei), necrosis, mitotic figures and vascular invasion.

Undifferentiated anaplastic carcinomas

These tumors demonstrate severe nuclear atypia, multiple mitotic figures and extensive necrosis and, in addition, often spindle growth pattern eventually with giant cells. In most cases, only biopsy material is available. Differential diagnosis towards poorly differentiated of other origin can be very difficult. 

Papillary micro carcinoma (mPTC)

Papillary micro carcinomas display a diameter ≤10 mm. Tiny papillary carcinomas (2-3 mm) are regularly detected as an incidental finding (incidentaloma) in thyroid glands removed for other reasons. These tumors are, in most cases, considered as a finding of insignificant importance. If, however, the mPTC invades extrathyroidal tissue, the patient should be treated according to the same guidelines as the PTCs of clinical significant dimension.

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