The WHO classification of endocrine tumors [5] describes several variants of PTC, including the papillary microcarcinoma, encapsulated variant, follicular variant, DSV, tall cell variant (TCV), cribriform-morular variant, hobnail variant, PTC with fibromatosis/fasciitis-like stroma, solid/trabecular variant, oncocytic variant, spindle cell variant and clear cell variant. DSV-PTC occurs more commonly in women, most frequently in the second or third decade of life [1, 6]. The clinical presentation typically includes diffuse enlargement of the thyroid gland. Elevated serum anti-thyroglobulin and anti-microsomal antibodies may mimic Hashimoto’s thyroiditis [7]. Histologically, DSV-PTC is characterized by dene sclerosis, numerous psammoma bodies, and background changes of chronic lymphocytic thyroiditis. Tumor nests appear solid, with associated squamous metaplasia, including squamous morules. Tumor cells have a propensity to invade the intrathyroidal lymphatic spaces and tendency to show extrathyroidal extension [5]. Compared to C-PTC, DSV-PTC is associated with higher incidences of extrathyroidal extension, cervical lymph node involvement, and distant metastasis, primarily to the lung [8]. However because of its rarity, the clinicopathological characteristics, probability of prognostic significance after thyroidectomy and adjuvant modalities (radioiodine-131 therapy and neck irradiation) are not well characterized. Al-Qahtani et al. [2], in a study of 44 cases of DSV-PTC, suggested that it is more aggressive variant compared to C-PTC and shows an inferior DSS rate.
Several studies have reported an aggressive behaviors and a poor prognosis [2, 9–11]. Akaishi et al.[9] described that most patients with DSV-PTC were young and had a background of chronic thyroiditis. Outcomes for DSV were good, but recurrence was more common than in classical PTC. Moreover, according to Moreno et al. [12], DSV-PTC has the following features: (a) younger age of presentation (b) greater affinity for men (c) greater frequency of extrathyroidal extension and (d) greater frequency of recurrences. They suggested that the clinical importance of recognizing this variant is based on the need to apply a more aggressive treatment and more exhaustive follow-up for such patients. Kazaure et al. [13] reported that although DSV and TCV are rare, they are increasing in incidence and have a worse prognosis compared to C-PTC. Patients with these variants were treated aggressively with thyroidectomy and radioiodine, regardless of the tumor size in a large-scale study of 43,738 patients. Recently, a systemic review and meta-analysis of DSV-PTC by Vuong et al. [14] concluded that high-risk PTC should be considered because of the high propensities for tumor invasion, metastasis, relapse, and mortality. The aggressiveness of DSV-PTCs might be related to a different molecular pathway than that of C-PTC.
Although it is controversial, in a study of the clinical behavior and prognosis of DSV-PTC and insular carcinoma, Albareda et al. [15] proposed that patients with DSV-PTC do not require a different treatment than that given to C-PTC patients, and in contrast, insular carcinoma cases require a more aggressive therapeutic approach. Lam et al. [16] also found that the prognosis of DSV-PTC was similar to that of C-PTC. Yamashita et al. [17] reported that the overall mortality and disease-specific mortality rates showed no significant difference between the DSV-PTC and non-DSV-PTC groups; therefore, they proposed that DSV-PTC is not an aggressive subtype of PTC and that patients with DSV-PTC do not require a more aggressive therapy than those with non-DSV-PTC in the same stage. In the WHO classification of Tumors of the endocrine organs, the authors concluded that DSV-PTC is associated with a shorter DFS. However, the mortality rates are comparable to those of C-PTC, possibly due to the favorable effect of young age, with 93% of the 10–year DSS. [5]
Genetic alterations in DSV-PTC are also different from those in C-PTC. While BRAF mutation is the most common mutation in C-PTC, in DSV-PTC, the RET/PTC rearrangement is frequently found in DSV-PTC and BRAF mutations are rare [18–20]. According to Li et al. [21], their meta-analysis of BRAF V600E mutation and its association with clinicopathological features of PTC identified that unlike RET/PTC rearrangement, BRAF mutations are associated with aggressive clinical manifestations and poor outcomes. This result suggests that the biological aggressiveness of DSVPTCs might be related to a different molecular pathway than the RET/PTC rearrangement. However, Joung et al. [19] analyzed the subtype of the RET/PTC rearrangement. They demonstrated that the RET/PTC rearrangement was the major genetic alteration in patients with DSV-PTC. The RET/PTC1 rearrangement was the most common genetic alteration in DSV-PTC patients and was associated with favorable outcomes. The RET/PTC3 rearrangement was associated with an advanced stage at the diagnosis and poor clinical outcomes, including poor response to therapy.
The present patient had a history of breast and thyroid cancers. Regular inspection, including radiologic studies, is essential for the cancer follow-up. Calcified/osseous images of the cervical area may suggest an osseous metastatic lesion in the cervical area. Awareness of this category showing marked dystrophic calcification may guide the treatment strategies and prevent misdiagnoses.