Outcomes of Papillary Thyroid Microcarcinoma Presenting with Palpable Lateral Lymphadenopathy.

Purpose: Papillary thyroid microcarcinoma (PTMC) is typically indolent in nature, allowing management with active surveillance protocols. Occasionally, a more aggressive phenotype can present and may lead to poor outcomes such as patients presenting with clinically significant lateral lymphadenopathy (cN1b). Prior analysis of the outcomes of this cohort is largely from papillary thyroid cancer (PTC) (>1 cm) or from institutions where use of radioactive iodine (RAI) is limited. Hence, we aim to describe the outcomes of patients with PTMC who presented with palpable cN1b disease, treated with total thyroidectomy and RAI. Methodology: We performed a retrospective cohort study. Outcomes of patients with PTMC who presented with palpable lateral lymph node (LN) metastases (microPTC cN1b) treated between 1997 and 2020 at Royal North Shore Hospital were compared with two control groups' outcomes: patients with clinically detected PTMC without evidence of involved LNs (microPTC cN0) and with larger PTC (>10 mm) who presented with palpable lateral lymphadenopathy (larger PTC cN1b). We assessed clinicopathological variables, postoperative risk stratification, rates of disease recurrence, reoperative surgery, and structural disease-free survival (DFS). Results: In total, 1534 PTMCs were diagnosed following thyroid surgery in the study period; of these, 157 (10%) were clinically detected microPTC cN0 and 26 microPTC cN1b (1.7%). There were 138 patients in the larger PTC cN1b control group. All cN1b patients were treated with total thyroidectomy and adjuvant RAI. Mean size of the largest LN deposit was similar between the microPTC cN1b and larger PTC cN1b groups (23 vs. 27 mm, p = 0.11). Patients with microPTC cN1b were more likely to have biochemical or structural persistence or recurrence compared with microPTC cN0 (19%, 5/26 vs. 3.8%, 6/157, p = 0.002) but less likely than larger PTC cN1b patients (19%, 5/26 vs. 42%, 58/138, p = 0.04). All patients in the microPTC cN1b group who had an excellent response to initial therapy (85%, 22/26) were disease free at last follow-up. The rate of reoperation was similar for the microPTC cN1b and microPTC cN0 groups (4%, 1/26 vs. 2%, 3/157, p = 0.461) and significantly lower than the larger PTC cN1b group (4%, 1/26 vs. 26%, 36/138, p = 0.002). Five-year DFS estimates were significantly better for microPTC cN1b patients than for larger PTC cN1b patients (94% vs. 59%, p = 0.001). Conclusions: MicroPTC cN1b patients treated with thyroidectomy and adjuvant RAI have inferior clinical outcomes compared with microPTC cN0 patients but have better outcomes than their larger PTC cN1b counterparts with respect to disease persistence and recurrence. Response to initial therapy provides valuable prognostication in microPTC cN1b patients: if these patients had an excellent response to initial treatment, they achieved long-term DFS in this series.

Allergic environment enhances airway epithelial pro-inflammatory responses to rhinovirus infection.

Airway epithelial cells (AEC) exhibit a pro-inflammatory phenotype in patients with allergic asthma. We examined the effect of an allergic cytokine environment on the response of AEC to rhinovirus (RV), the most common trigger of acute exacerbations of asthma. Calu-3 cells, a well-differentiated human AEC line, were cultured with or without the T-helper type 2 cytokines interleukin (IL)-4 and IL-13, then stimulated with a toll-like receptor (TLR) 3 agonist (poly I:C, dsRNA) or a TLR7 agonist (imiquimod), or infected with RV 16. Expression of pro-inflammatory and antiviral mediators, and of viral pattern-recognition molecules, was assessed using nCounter assays, quantitative real-time PCR (qRT-PCR) and protein immunoassays. Both dsRNA and imiquimod stimulated expression of mRNA for IL6 and IL8 whereas expression of several chemokines and antiviral response genes was induced only by dsRNA. Conversely, expression of other cytokines and growth factors was induced only by imiquimod. RV infection not only stimulated expression of the inflammation-related genes induced by dsRNA, but also of complement factor B and the novel pro-inflammatory cytokine IL-32. In the T helper type 2 (Th2) cytokine environment, several mediators exhibited significantly enhanced expression, whereas expression of interferons was either unchanged or enhanced. The allergic environment also increased expression of pattern-recognition receptors and of intercellular adhesion molecule 1, the cell surface receptor for RV. We conclude that Th2 cytokines promote increased production of pro-inflammatory mediators by AEC following infection with RV. Increased viral entry or enhanced signalling via pattern-recognition receptors could also contribute to the exaggerated inflammatory response to RV observed in allergic asthmatics.