
Gross Pathology:
- Encapsulated looking single nodular swelling around 8.5 cm size (microscopically infiltrative tumor)
- Central grayish-white scar like areas with shrouding pale brownish solid and cystic changes
- Compressed rim of the normal thyroid tissue is seen
- Overall gross findings are not helpful in the diagnosis except only suggest malignant nature of process




















Columnar Cells Variant of Papillary Thyroid Carcinoma
Additional areas like tall cell variant of papillary thyroid carcinoma are also seen
Histopathology:
- Thyroid follicular cells are arranged in papillary, follicular and some trabecular structures (elongated compressed follicles)
- Papillary, follicular, and trabecular structures are lined by cells with nuclear crowding, stratification and hyperchromasia (coarse and dense chromatin) and eosinophilic-to-clear cytoplasm. Some areas also show subnuclear cytoplasmic clearing and vacuoles. Some cells show enlarged vesicular nuclei and distinct nucleoli.
- Few cells show intranuclear grooves and inclusions, however, chromatin clearing is not easy to find out.
- Many follicles are filled with variable amount of colloid. Some cells in colloid material show squamous metaplasia.
- In addition to all above, some areas have tall cells like morphology (height is 2-3 times the width) with abundant eosinophilic cytoplasm and markedly elongated parallel follicles, which are giving appearance of railroad tracks. These areas also lack the nuclear stratification.
- Some areas also show apical location of nuclei (which is one of the features of hobnail variant of PTC, later frequently present in combination with tall cell and columnar cell PTC).
- Mitotic figures and necrosis are not present
Practical Points of Pathoclinics:
- Columnar cells variant of papillary thyroid carcinoma (PTC) is an uncommon variant of PTC. Generally columnar cells PTC present in older individuals with large single or multi-nodular mass (greater than 5 cm in good number of cases), extrathyroidal extension and nodal metastasis in more than 50% of all cases. Lymphatic invasion and vascular invasion are common. Distant metastasis can occur in few cases at the time of presentation.
- Microscopically, columnar cells variant of papillary thyroid carcinoma (PTC) is characterized by predominance of columnar cells with crowded hyperchromatic and stratified nuclei, resembling colorectal adenomas and carcinomas. Tumour cells also exhibit nuclear features of conventional PTC but often focal and not well developed compared to conventional or tall cell PTC. Thyroid follicular cells do not show chromatin clearing. The cytoplasm is eosinophilic or clear with supranuclear and subnuclear vacuoles, reminiscent of those of early secretory endometrium. Quantitative criteria regarding the percentage of columnar cells required for a diagnosis of columnar cell variant of PTC are not specified. Columnar cells PTC may have a variable combination of papillary, follicular and trabecular pattern. Solid, complex glandular or cribriform growth can be seen but uncommon. Areas of squamous metaplasia can be seen but without squamoid morules. Some case may show necrosis and mitoses. Colloid is commonly seen. Dystrophic and psammomatous calcification are uncommon.
- The missense mutation, BRAFV600E mutation is found in one-third of cases especially in older male patients with an aggressive behavior.
- On immunohistochemistry, TTF-1 positivity along with patchy and weak thyroglobulin positivity help to confirm the thyroid origin of tumor. Columnar cells PTC can show diffuse CDX2 and CA19.9 positivity. Intense diffuse expression for p53 can be seen.
- Distinction of relative indolent and aggressive columnar cells PTC cannot be made reliably on basis of cyclin D1, beta-catenin, estrogen and progesterone receptors and Ki-67 index, as cyclin D1 (nuclear expression), Beta-catenin (membranous and some have cytoplasmic positivity), estrogen and progesterone receptors (nuclear expression) and increased Ki-67 index are seen in both indolent and aggressive columnar cells PTC. However, progesterone receptor expression is diffuse and strong in indolent tumor and weak or absent in aggressive columnar cells PTC. Cytoplasmic Bcl-2 expression is mildly decreased in indolent tumors.
- Sometimes hyperchromatic and stratified nuclei of the columnar cells PTC may mimic a metastatic adenocarcinoma especially colon or endometrial origin. However, presence of primary in other body sites and necrotic background favor metastasis. Expression of TTF-1 and thyroglobulin in case of columnar cells PTC usually resolve the issue. Please take note that PAX8 expression seen in both thyroid and gynecologic neoplasms, so one must rely more on TTF-1 and thyroglobulin. Similarly, CDX2 positivity also seen in columnar cells PTC, so use TTF-1, thyroglobulin and CK20 in appropriate clinical settings.
- Tall cell variant is commonly fall in differential of columnar cells PTC. Tall PTC is defined as cells with two to three times tall than width and with abundant dense eosinophilic cytoplasm. Further at least at least 30% of the total tumor areas show tall cells features. Classic nuclear features of papillary carcinoma including nuclear pseudoinclusions and grooves are easy to appreciate, in contrast to columnar cell PTC. BRAF mutation is seen in about 80% of tall cell PTC. Any PTC with more than 10% of tall cells component should be designated as PTC with areas of tall cell features, as these cases have relative bad prognosis than conventional PTC. In addition, TP53 immunoreactivity is often seen in tall cells PTC in contrast to the classic papillary carcinoma. Tall cell PTC commonly have extrathyroidal extension and increased incidence of metastases. Practically speaking, some clinical features especially aggressive behavior and BRAF V600E mutation of tall cells PTC are similar to columnar cells PTC. Also some scattered reports also mentioned about the combined tall cells and columnar cell morphology in papillary thyroid carcinoma. In present case, combined tall cells and columnar cells PTC are seen.
- Hobnail variant of papillary thyroid carcinoma (PTC) can occur in combination with tall cell and columnar cells variants of PTC. These variants have cuboidal cells with loss of polarity, hobnail features (apical placement of nuclei with surface bulge) and micropapillary architecture. Also, similarity with tall cells variant of PTC in p53 overexpression and BRAF (V600E) mutation. Hobnail variant also has frequent extrathyroidal extension and lympho-vascular invasion. Hobnail pattern in tall cell and columnar cells variants of PTC is associated with worse prognosis.
- Columnar cell variant of PTC may show morphologic overlap with the cribriform morular variant of PTC, especially in presence of elongated follicular structures, slender papillae and cribriform architectural pattern. However, columnar cells of PTC show more nuclear hyperchromasia.
- Columnar cells PTC are treated with thyroidectomy and radioactive iodine. Radiotherapy is reserved for locally advanced disease.
- Columnar cells PTC can be separated into indolent (circumscribed) and aggressive (widely invasive subtypes). Large tumor size, extrathyroidal extension, laryngotracheal invasion, cervical lymph nodal or distant metastasis and anaplastic morphology are associated with poor survival. However, columnar cells PTC with encapsulation and without extrathyroidal extension behave less aggressively. Young female patients also behave batter than old aged male.
References:
- Chen JH, Faquin WC, Lloyd RV, Nosé V. Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma. Mod Pathol. 2011 May;24(5):739-49. doi: 10.1038/modpathol.2011.2. Epub 2011 Feb 25. PMID: 21358618.
- Putti TC, Bhuiya TA. Mixed columnar cell and tall cell variant of papillary carcinoma of thyroid: a case report and review of the literature. Pathology. 2000 Nov;32(4):286-9. PMID: 11186427.
- Putti TC, Bhuiya TA, Wasserman PG. Fine needle aspiration cytology of mixed tall and columnar cell papillary carcinoma of the thyroid. A case report. Acta Cytol. 1998 Mar-Apr;42(2):387-90. doi: 10.1159/000331622. PMID: 9568142.
- Akslen LA, Varhaug JE. Thyroid carcinoma with mixed tall-cell and columnar-cell features. Am J Clin Pathol. 1990 Oct;94(4):442-5. doi: 10.1093/ajcp/94.4.442