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11 October 2017 - Case of the Week #439

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Case of the Week #439

Clinical history:
A 58 year old woman with hypertension and rheumatoid arthritis presented with a right neck swelling for one month, which had suddenly increased in size and was associated with odynophagia. There was no radiation of pain and no history of weight loss, fever, dysphagia or hoarseness.

Lab investigations revealed a high serum antinuclear antibody, but rheumatoid factor and other serological findings, including antithyroglobulin antibodies, were normal. Liver, kidney and thyroid function tests were normal.

Physical examination revealed a firm to hard nodule in the right thyroid lobe, measuring 4 x 3 cm. Lymph nodes were not enlarged. A hemithyroidectomy was performed.

Grossly, the right lobe measured 4 x 2 x 1.8 cm. Sectioning revealed a firm, gritty and ill-circumscribed white and fibrotic nodule measuring 3.8 x 2 x 1.5 cm. No lymph nodes were identified.

Histopathology images:

Figures 1-4

What is your diagnosis?

Papillary thyroid carcinoma, diffuse sclerosing variant, with lymphovascular invasion and extrathyroidal extension into skeletal muscle.

Special stains:

Figure 5, CK19

Figure 6, EMA

Test question (answer at the end):
Which of the following statements is NOT true about diffuse sclerosing variant of papillary thyroid carcinoma?

A. Aggressive type of papillary thyroid carcinoma
B. Patients are younger than those with classic papillary thyroid carcinoma
C. Histologically characterized by dense sclerosis, squamous metaplasia, numerous psammoma bodies and background Hashimoto thyroiditis
D. Frequent extrathyroidal extension and lymph node metastasis
E. High mortality rate with low 10 year survival (50%)


Microscopic examination revealed an ill-circumscribed tumor composed of scattered, variably sized nodules, nests and clusters of papillary thyroid carcinoma, separated by dense sclerotic stroma with abundant psammoma bodies and lymphoid aggregates, some containing tumor (Figures 1, 2 and 3). Tumor nuclei displayed the classic features of papillary thyroid carcinoma. Foci of squamous metaplasia were also noted (Figure 3). The tumor focally extended into surrounding skeletal muscle and also showed perineural and lymphovascular invasion (Figures 2 and 4). Immunostaining was positive for TTF1, CK19 (Figure 5, which also stained the squamous component), EMA (Figure 6) and BCL2.

Papillary thyroid carcinoma, diffuse sclerosing variant, is a rare variant of PTC, first described by Vickery and colleagues in 1985 (1). It has a prevalence of 0.8% to 1.8% of all PTC (1,2). It most frequently occurs in women in the second to third decades of life (2,3,4). Patients present with diffuse goiter and are mostly clinically euthyroid but can also be hypo- or hyperthyroid. Elevated serum antithyroglobulin and antimicrosomal antibodies may mimic Hashimoto thyroiditis (Coll Antropol 2012;36 Suppl 2:219).

The presence of several characteristic gross and microscopic features is diagnostic – diffuse firm enlargement of the one or both lobes of the thyroid, extensive fibrosis, squamous metaplasia and many psammoma bodies, as well as scattered islands of PTC, lymphatic permeation and background lymphocytic infiltration. There is a higher prevalence of lymphovascular invasion, lymph node and distant metastasis (2,5,6,7).

Preoperative FNA shows PTC cells with typical nuclear features, frequent squamous metaplasia, numerous psammoma bodies and background lymphocytic infiltration.

CK19 is expressed in PTC and in its squamous components, suggesting that squamous metaplasia arises from thyroid follicular epithelial cells (2,9,10). Positive BCL2 and EMA expression are associated with cancer aggressiveness and early recurrence, as well as the lymphovascular invasion and extrathyroidal extension into skeletal muscle present in this case (8,10). The main genetic events are RET/PTC rearrangements, while BRAF and RAS mutations are uncommon (Crit Rev Oncol Hematol 2015;94:64).

Diffuse sclerotic variant of PTC is an aggressive subtype of PTC, or so called “real thyroid cancer” (J Clin Pathol 2013;66:733). It is associated with adverse prognostic features, including frequent extrathyroidal extension, cervical lymph node metastasis, greater incidence of distant metastasis (5-15%) and more frequent recurrence (Crit Rev Oncol Hematol 2015;94:64, Eur J Endocrinol 2017;176:431). However, mortality rates are similar to those of conventional PTC with disease specific survival of 95% and 93% at 5 and 10 years (Endocr Pathol 2005;16:331, Ann Surg Oncol 2006;13:176). Basic treatment includes thyroidectomy with neck dissection followed by radioiodine ablation and TSH suppression therapy (J Clin Endocrinol Metab 2016;101:4603).


1. Vickery Jr AL, Carcangiu ML, Johannessen JV, Sobrinho-Simoes M. Papillary carcinoma (Semin Diagn Pathol 1985;2:90).

2. Lam AK, Lo CY, Lam KS. Papillary carcinoma of thyroid: a 30-yr clinico-pathological review of the histological variants (Endocr Pathol 2005;16:323).

3. Falvo L, Giacomelli L, D'Andrea V, Marzullo A, Guerriero G, de Antoni E. Prognostic importance of sclerosing variant in papillary thyroid carcinoma (Am Surg 2006;72:438).

4. Regalbuto C, Malandrino P, Tumminia A, Le Moli R, Vigneri R, Pezzino V. A diffuse sclerosing variant of papillary thyroid carcinoma: clinical and pathologic features and outcomes of 34 consecutive cases (Thyroid 2011;21:383).

5. Thompson LD, Wieneke JA, Heffess CS. Diffuse sclerosing variant of papillary thyroid carcinoma: a clinico-pathologic and immuno-phenotypic analysis of 22 cases (Endocr Pathol 2005;16:331).

6. LiVolsi VA, Albores-Saavedra J, Asa SL. Papillary carcinoma - in: DeLellis RA, Llyod RV, Heitz PU, Eng C: Pathology and Genetics of Tumours of Endocrine Organs [OP] (IARC WHO Classification of Tumours), 1st ed., 2004, p. 57 – 66.

7. Lam AK, Lo CY. Diffuse sclerosing variant of papillary carcinoma of the thyroid: a 35-year comparative study at a single institution (Ann Surg Oncol 2006;13:176).

8. Koo JS, Shin E, Hong SW. Immuno-histochemical characteristics of diffuse sclerosing variant of papillary carcinoma: comparison with conventional papillary carcinoma (APMIS 2010;118:744).

9. Chan JK, Tsui MS, Tse CH. Diffuse sclerosing variant of papillary carcinoma of the thyroid: a histological and immunohistochemical study of three cases (Histopathology 1987;11:191).

10. Suja P, Gopalan V, Smith RA, Lam AK. Diffuse sclerosing variant of papillary thyroid carcinoma—an update of its clinico-pathological features and molecular biology (Crit Rev Oncol Hematol 2015;94:64)

Test Question Answer:
Despite being an aggressive variant of PTC with some adverse prognostic features, mortality rates are similar to those of classic PTC, with 93% disease specific survival at 10 years.

Image 01 Image 02