Lung Recurrence of Papillary Thyroid Cancer Diagnosed With Antithyroglobulin Antibodies After 10 Years From Initial Treatment

Abstract

Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. More than 98% of patients achieve an excellent response with no evidence of clinical, biochemical, or structural disease after initial treatment. In these patients structural recurrence is rare, more frequently diagnosed in the first 5 years from initial treatment and almost invariably localized in neck lymph nodes. Patient: We report the case of a woman affected by PTC who presented with rapidly rising anti-thyroglobulin antibodies (TgAb) level after 10 years from clinical, morphological and biochemical remission. Diagnosis and Treatment: In 2003, a 56 year old patient was treated with total thyroidectomy and radioiodine remnant ablation (RRA) for a PTC (2 cm) with minimal extrathyroidal extension (T3N1aM0 according to the 6th AJCC TNM staging system) associated with diffuse lymphocytic thyroiditis. In 2004 the patient was free of disease defined as undetectable Tg after recombinant human TSH administration in the absence of TgAb and structural disease. Since February 2012 the appearance and progressive increase of TgAb titer was observed and in 2014 a ¹⁸FDG-PET scan documented three hypermetabolic lesions suggestive of lung micrometastases. The lung lesions were cytologically confirmed as PTC metastases. Both the primary tissue and the lung metastasis were positive for BRAF V600E mutation. The patient was treated with 131-radioiodine that showed radioiodine avid lung lesions that lose the ability to take up iodine at the following treatment. The patient is still alive and the lung lesions are growing slowly. Conclusions: Structural recurrence in patients that demonstrated an excellent response after initial treatment for PTC is extremely rare, and distant metastases exceptional but possible. This case is peculiar because recurrence was early identified after 10 years from initial treatment for the presence of detectable TgAb in a patient that had an histological diagnosis of lymphocytic thyroiditis but with an atypical clinical presentation (normal thyroid at neck ultrasound and undetectable TgAb and anti-thyroid peroxidase antibodies). For this reason TgAb should be tested with Tg in patients with a history of lymphocytic thyroiditis, either histological or humoral, also when TgAb is in the normal range and not suggestive of autoimmune thyroiditis.

Keywords: BRAF mutation; TgAb; lymphocytic thyroiditis; recurrence; thyroid cancer (TC).

Figure 1

(A) Histological slides of primary PTC and lymph node metastasis. (A1) Primary PTC with well-formed papillary structures (20X, hematoxilyn/eosin); (A2) collateral diffuse lymphocytic thyroiditis with lymphoid follicles and germinal centers(5X, hematoxilyn/eosin); (A3) lymph node metastatic lesion of PTC (2.5X, hematoxilyn/eosin). (B) Fine-needle aspiration cytological smears of lung metastastic lesion. (B1) low power magnification showing papillary-like structures with smooth contours and palisading of nuclei (10X, papanicolau stain); (B2) high power magnification showing nuclear characteristics of PTC (finely granular chromatin and one pseudoinclusion) (40X, papanicolau stain); (B3) immunocytochemistry showing cytoplasmatic positivity for thyroglobulin, confirming the thyroid origin of the lung lesion (40X).

Figure 2

(A) ¹⁸FDG-PET scan showing three hypermetabolic nodular lung lesions localized at the medial (1) (SUV max 3.1) and lateral (2) (SUV max 2.7) segment of the right medium lobe and at the apical segment (3) of the left inferior (SUV max 3.9) lobe of the lungs. (B) pWBS showing 131-I uptake corresponding to the hypermetabolic lung lesions localized at the medial segment of the right lobe and at the left inferior lobe.

Figure 3

Graphic representation of the patient's serum Tg values and TgAb titer between 2004 and 2018.