case_images: PMC9792137_01
case_images: (A) fine needle aspiration showing atypical cells forming papillary clusters, diagnosed as TIR5-SIAPEC (Bethesda VI and to Thy5-BTA), compatible with papillary thyroid carcinoma. Histologically the tumor showed complex papillary architecture (B) intranuclear inclusions (C, arrow), mitotic activity (D, arrow), immunohistochemical thyroglobulin (E) and TTF1 expression (F).
case_images: fonc-12-1042525-g001.jpg
case_images: PMC9792137_01_fonc-12-1042525-g001.jpg
case_images: f1
case_images: Thyroid and nodal fine needle aspiration (FNA) cytology identified malignant cells (Bethesda VI) compatible with papillary thyroid carcinoma (Figure 1A). The diagnosis was PTC with high grade features due to the presence of mitotic activity and necrosis (Figures 1B-D). Neoplastic cells were positive for Thyroid Transcription Factor- 1 (TTF-1) and Tg (Figures 1E, F).
case_images: axial (A) and coronal (B) CT-scan showing large inhomogeneous tumor with calcifications of the right thyroid lobe with left tracheal displacement, infiltrating the trachea and esophagus; confluent neck lymph node metastases (maximum diameter of 58 mm) (C); hepatic lesion of 12 mm at V segment (D).
case_images: fonc-12-1042525-g002.jpg
case_images: PMC9792137_01_fonc-12-1042525-g002.jpg
case_images: f2
case_images: CT-scan performed in March 2021, after four months of Lenvatinib, showing a dimensional reduction of latero-cervical lymphadenopathies (maximum diameter of 2 cm) (A), and of left thyroid lobe (3x4,7 cm) (B), and a mild increase of the hepatic lesion (17 mm vs 12 mm) (C).
case_images: fonc-12-1042525-g003.jpg
case_images: PMC9792137_01_fonc-12-1042525-g003.jpg
case_images: f3
case_images: At the first CT-scan evaluation, performed in March 2021, a dimensional reduction of latero-cervical lymphadenopathies (maximum diameter of 2x3 cm), and of left thyroid lobe was obtained, while a mild increase of the hepatic lesion was documented (17 mm vs 12 mm) (Figure 3).
case_images: CT-scan performed in August 2021, after lenvatinib discontinuation, showing a dimensional increase of left thyroid lobe (4,9x3,7 cm) (A), latero-cervical lymphadenopathies (maximum diameter of 3 cm) (B) and multiple brain and cerebellar metastases (C).
case_images: fonc-12-1042525-g004.jpg
case_images: PMC9792137_01_fonc-12-1042525-g004.jpg
case_images: f4
case_images: However, as a consequence of this treatment period-off, in August 2021, a CT-scan was performed due to markedly increased Tg levels (2495 vs 749 ng/ml), reveling disease progression with the onset of at least six bilateral brain and two cerebellar lesions, all with hemorrhagic features (Figure 4).
case_images: (A) basal 18FDG-PET scan showing intense signal in the right thyroid lobe (standardize uptake value, SUV max: 23.7), right neck metastasis (SUV max: 44.5), bilateral supraclavicular lymph nodes (SUV max: 31, right; SUV max: 15., left), lung nodules (Left lower lobe, SUV max: 15.1- Posterior and 17.0-Paravertebral; Right upper lobe, SUV max: 6.5 and 6.2), mediastinal lymph nodes (left pulmonary hilus, SUV max: 10.4; left peribronchial, bilateral tracheo-bronchial and subcarinal, SUV max: 7.3), upper thoracic outlet, paraesophageal, right para-tracheal lymph nodes (SUV max: 18.1); (B) remarkably rapid metabolic response within less than one month of pralsetinib therapy.
case_images: fonc-12-1042525-g005.jpg
case_images: PMC9792137_01_fonc-12-1042525-g005.jpg
case_images: f5
case_images: Subsequent 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) showed high glucose uptake in the right thyroid lobe (SUVmax = 23.7), together with intense uptake at a very large right latero-cervical adenopathy (SUVmax = 44.5), and at several additional lymph nodal and visceral sites, including lung, bone and pancreas (Figure 5A). Noteworthy, the 18F-FDG-PET performed after one month of therapy for early treatment response evaluation, reported a complete metabolic response in almost all sites and a relevant partial response in the others (Figure 5B).
case_images: CT-scan performed in October 2022, 13 months after the beginning of treatment, showing a further tumor volume reduction of left thyroid lobe (2,3x2,7cm) (A), of latero-cervical lymphadenopathies (maximum diameter of 1,3 cm) (B), and a complete radiological response of brain metastases (C).
case_images: fonc-12-1042525-g006.jpg
case_images: PMC9792137_01_fonc-12-1042525-g006.jpg
case_images: f6
case_images: The last CT-scan performed in October 2022, 13 months after the beginning of treatment, showed a further tumor volume reduction and Tg levels have drop to 378 ng/ml (Figure 6).