(14.15) A Rare Case of an Aggressive Hobnail Variant Papillary Thyroid Carcinoma

Hobnail variant papillary thyroid carcinoma (HVPTC) is a rare variant of thyroid cancer and is associated with an increased risk of metastasis, decreased cure rates, and significant mortality.

We present a case of metastatic HVPTC with a rapidly worsening clinical status.

Case(s) Description :

A 43-year-old male presented with an anterior midline fluid-filled neck mass over the thyroid cartilage growing for over a year. Initial FNA biopsy showed atypical squamous cell epithelium and eosinophilic proteinaceous fluid.

CT imagings raised concerns for malignancy, showing a multiloculated complex cystic lesion anterior to the isthmus of the thyroid, hypodense nodules in the right thyroid lobe, necrotic left level V cervical and mediastinal lymph nodes (LN), large bilateral pleural effusions with right mediastinal shift, and intrathoracic dissemination of disease to the lymphatics. A repeat FNA of neck mass and cervical LN revealed a metastatic carcinoma, and thyroid origin was favored. Pleural fluid cytologic analysis revealed cells with apically placed, bulged hyperchromatic nuclei with “hobnail” appearance. PAX-8 and BRAF immunostains were positive. Morphology and immunoprofile were consistent with metastatic HVPTC. The PET scan results were consistent with thyroid cancer with metastasis to the mediastinum, lungs, diaphragm, and bones. The final pathologic stage was T3b N1b M1.

Initial tumor board recommendations were thyroidectomy and cervical and mediastinal LN dissections. However, the patient encountered recurrent hospitalizations from pleural effusions leading to respiratory decompensation that required pleural catheter placements and aspirations of the neck cyst. Due to the progressive nature of the patient’s disease, he was deemed not a surgical candidate by the multidisciplinary team, as surgery would be unlikely curative and would include significant morbidity. Mutational analysis of the tumor cells confirmed BRAF p.V600E somatic mutation, and the patient was started on systemic therapy with lenvatinib initially, which was switched to BRAF mutation target therapy with trametinib and dabrafenib with the intent of treatment being life prolongation. The tumor cells expressed programmed death ligand 1 greater than 80%, suggesting a future role of treatment with immunotherapy.

Discussion :

HVPTC was present in only 0.6% and 1.08% of papillary thyroid carcinoma (PTC) cases in two meta-analyses, respectively, with the former reporting 21.2% of patients dying from it. They usually have larger tumors, more aggressive clinicopathologic features, increased radioactive iodine (RAI) refractoriness, relatively higher locoregional recurrence rates, LN metastases, distant metastases, as well as higher rates of BRAF mutation (73% vs. 45.7%) compared to classic PTC cases. Histologically, the nuclei are apically placed, producing a surface bulge leading to a hobnail appearance. It is suggested that the loss of cellular polarity and cohesiveness observed in HVPTC enhances its metastatic potential.

Conventional treatment strategies such as thyroidectomy, LN dissection, and RAI ablation can be challenging to implement, as in our case.