Abstract
Context
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, generally associated with a favorable prognosis. However, variants such as the hobnail subtype exhibit more aggressive pathological and clinical features.
Objective
The 2022 WHO classification defines hobnail PTC (HPTC) as tumors with at least 30% hobnail cell morphology, yet the prognostic impact of varying hobnail cell proportions remains unclear.
Design
This study aimed to evaluate the clinicopathological characteristics and prognostic significance of PTC with different degrees of hobnail features, contributing to improved risk stratification and management strategies.
Subjects and Methods
A comprehensive analysis was conducted on PTC cases exhibiting hobnail features at varying proportions. Pathological characteristics, including vascular and lymphatic invasion, calcification, lymph node metastasis, and capsule involvement, were assessed. Logistic regression analysis was performed to determine associations between hobnail morphology and aggressive disease behavior.
Results
Tumors with ≥30% hobnail features exhibited significantly (p< 0.05) higher rates of vascular invasion, lymphatic invasion, calcification, and lymph node metastasis compared to tumors with fewer hobnail features and classic PTC. Logistic regression confirmed a strong association between hobnail morphology and lymphatic invasion/metastatic lymph nodes (p = 0.026). However, no significant correlation (p>0.05) was observed with extrathyroidal invasion, bilaterality, or the necessity of radioactive iodine (RAI) treatment.
Conclusion
The findings emphasize the aggressive nature of PTC with prominent hobnail features, underscoring the need for tailored therapeutic strategies and close monitoring in affected patients. Further research is warranted to refine prognostic models and optimize treatment approaches.
Keywords: hobnail, papillary thyroid carcinoma, prognosis, pathological and clinical features, hobnail subtype of papillary thyroid carcinoma, classic papillary thyroid carcinoma
INTRODUCTION
Papillary thyroid carcinoma (PTC) constitutes approximately 85% of all thyroid malignancies (1). While it is associated with an excellent prognosis, characterised by a 5-year relative survival rate of 98.5% (2), specific subtypes, including the tall cell, columnar cell, and hobnail subtype, exhibit markedly aggressive clinicopathological features in comparison to the classic subtype of PTC (3).
The hobnail subtype of PTC was first described in 2010 as a moderately differentiated subtype within a case series. Histologically, this subtype is characterised by papillary and micropapillary structures lined by cells exhibiting eosinophilic cytoplasm and apically positioned nuclei with prominent nucleoli. These lining cells demonstrate a high nuclear-to-cytoplasmic ratio, with apically located nuclei that form distinct surface projections resembling hobnails (4, 5).
The 2022 WHO classification defines the hobnail subtype of papillary thyroid carcinoma (HPTC) as having at least 30% of cells with hobnail features (5). This subtype is notable for its aggressive clinical behaviour, including higher rates of metastasis and poorer prognosis compared to classic PTC (4, 6). The classification underscores the importance of histological subtyping for accurate prognostic evaluation and effective clinical management of thyroid cancer. Notably, studies have demonstrated that PTCs containing a hobnail component—regardless of whether it constitutes ≥30% or <30%—exhibit greater aggressiveness than classic PTC (6, 7).
Studies in the literature remain limited and are predominantly based on small case series. While the presence of hobnail features is generally associated with a poor prognosis, the correlation between the percentage of hobnail burden and adverse clinical outcomes has yet to be clearly elucidated. The primary aim was to highlight the clinicopathological features of hobnail and classic PTC subtypes and assess their prognostic significance, contributing to the optimisation of treatment and follow-up strategies for patients with this diagnosis.
MATERIALS AND METHODS
This retrospective study analysed 116 patients who underwent thyroid surgery and follow-up at Ondokuz Mayıs University Hospital between 2012 and 2022. The primary inclusion criterion was a diagnosis of PTC with hobnail features. A total of 58 cases with hobnail characteristics were identified, and 58 classic PTC cases from the same period were selected consecutively for comparison, ensuring matched tumour sizes. Only patients with complete clinical and follow-up data were included in the analysis. The pathological evaluations were performed by an endocrine pathologist.
The study was approved by the Institutional Review Board (reference: 2023/379), and data were collected from the hospital’s electronic medical record system. Statistical analyses were performed using SPSS v26, employing appropriate tests (Chi-Square, Fisher’s Exact, T-tests, ANOVA, logistic regression) with significance set at p < 0.05.
Classification of Cases:
- PTC with <10% hobnail features (n=17)
- PTC with 10–30% hobnail features (n=25)
- PTC with Hobnail subtype PTC (≥30% hobnail features) (n=16)
- Classic subtype PTC (n=58).
Figure 1 demonstrates microscopic pictures of hobnail and classic subtypes of PTC.
Figure 1.
Microscopic figures of hobnail and classic subtypes of papillary thyroid carcinoma (PTC). Hobnail subtype of PTC showing micropapillary architecture, loss of cell cohesion, and apically placed nuclei protruding into the luminal space, forming the characteristic “hobnail” appearance (A-B). Classic subtype of PTC demonstrating well-formed papillae with fibrovascular cores and characteristic nuclear features, including chromatin clearing, nuclear overlapping and grooves (C-D).
Data Grouping for Analysis:
Study 1. All four categories individually.
Study 2. PTC with <10% hobnail features vs. classic subtype PTC
Study 3. PTC with <30% hobnail features vs. hobnail subtype ( ≥30% hobnail).
Demographics and Clinical Features
Patient age ranged from 23 to 76 years (mean 45.1 ± 13.39), with a diagnosis age range of 17–73 years (mean 40.08 ± 13.20). Females constituted 69% of the cohort.
Total thyroidectomy was performed in nearly all cases (115/116), with only one lobectomy.
Mean tumour size did not differ significantly between subtypes, as the classic PTC tumour cases were matched with those having hobnail features by size (p=0.696):
- <10% hobnail: 19.82 ± 11.42 mm
- 10–30% hobnail: 23.90 ± 13.40 mm
- ≥30% hobnail: 23.06 ± 14.31 mm
- Classic PTC: 21.62 ± 12.71 mm
Mean follow-up durations (in months) were:
- <10% hobnail: 22.65 ± 20.93
- 10–30% hobnail: 37.40 ± 30.68
- ≥30% hobnail: 29.06 ± 25.67
- Classic PTC: 68.83 ± 39.4
There was no significant difference in follow-up duration among groups (p=0.750).
RESULTS
Study 1
PTC with <10% hobnail features, PTC with 10-30% of hobnail features, and PTC showing ≥ 30% of hobnail features were compared to the classic subtype of PTC in terms of pathological characteristics.
Capsule presence was observed in 5 cases (29.4%) with less than 10% hobnail features, 12 cases (48.0%) with 10-30% hobnail features, 8 cases (50.0%) with greater than 30% hobnail features, and 31 cases (53.4%) of the classic subtype. The analysis revealed no statistically significant association between these groups (p=0.386). Capsule invasion was noted in 4 cases (23.5%) with < 10% hobnail features, 12 cases (48.0%) with 10-30% hobnail features, 7 cases (43.8%) with ≥ 30% hobnail features, and 19 cases (32.8%) of the classic subtype. There was no statistically significant association between the groups (p=0.341).
Lymphatic invasion was most frequently observed in tumours with ≥ 30% hobnail features (87.5%), followed by 10–30% hobnail features (52.0%), < 10% hobnail features (29.4%), and the classic subtype (34.5%), with a statistically significant association (p < 0.001). Vascular invasion was noted in 37.5% of tumours with ≥ 30% hobnail features, 36.0% with 10–30% hobnail features, 11.8% with < 10% hobnail features, and 6.9% of the classic subtype, showing a significant association (p = 0.001), with a higher prevalence in tumours containing hobnail features. Perineural invasion was rare, seen in 5.9% of tumours with < 10% hobnail features and 1.7% of the classic subtype, with no cases in the 10–30% or ≥ 30% hobnail groups; the difference was not statistically significant (p = 0.535). Parenchymal invasion was most common in 10–30% hobnail tumours (84.0%), followed by ≥ 30% hobnail features (81.3%), < 10% hobnail features (76.5%), and the classic subtype (48.3%), with a statistically significant association (p = 0.003), indicating a higher prevalence in hobnail subtype.
Tumours with ≥ 30% hobnail features exhibited the highest percentage of calcification presence, observed in 15 cases (93.8%). This was followed by tumours with 10-30% hobnail features, where calcification was present in 20 cases (80.0%), tumours with < 10% hobnail features, observed in 11 cases (64.7%), and the classic subtypes, observed in 34 cases (37.9%). The presence of ≥30% hobnail features was significantly associated with a higher occurrence of calcification (p<0.001).
Multifocality was observed in 41.2% of tumours with <10% hobnail features, 41.7% with 10–30% hobnail features, 43.8% with ≥ 30% hobnail features, and 58.6% of the classic subtype, with no statistically significant difference between the groups (p = 0.378). Bilaterality was present in 29.4% of tumours with <10% hobnail features, 37.5% with 10–30% hobnail features, 25.0% with ≥ 30% hobnail features, and 44.8% of the classic subtype, with no statistically significant association (p = 0.442). Necrosis was absent in tumours with <10% hobnail features, ≥ 30% hobnail features, and the classic subtype, while it was present in 8.0% of tumours with 10–30% hobnail features. The differences were not statistically significant (p = 0.124). Mitosis was observed in 11.8% of tumours with <10% hobnail features, 12.0% with 10–30% hobnail features, 12.5% with ≥ 30% hobnail features, and 3.4% of the classic subtype, with no statistically significant association between the groups (p = 0.216).
Lymph node metastasis was observed in 29.4% of tumours with <10% hobnail features, 32.0% with 10–30% hobnail features, 62.5% with ≥ 30% hobnail features, and 22.4% of the classic subtype, with the ≥ 30% hobnail group showing the highest risk and a statistically significant difference (p = 0.026). Extrathyroidal spread was absent in tumours with <10% hobnail features, present in 12.0% of tumours with 10–30% hobnail features, 6.3% with ≥ 30% hobnail features, and 5.1% of the classic subtype, with no statistically significant difference between the groups (p = 0.557). Extranodal spread was observed in 33.3% of tumours with <10% hobnail features, 33.3% with 10–30% hobnail features, 16.7% with ≥ 30% hobnail features, and 26.7% of the classic subtype, with no statistically significant association (p = 1.000).
Positive surgical margins were observed in 11.8% of tumours with <10% hobnail features, 8.0% with 10–30% hobnail features, 18.8% with ≥ 30% hobnail features, and 20.7% of the classic subtype, with no statistically significant difference between the groups (p = 0.534). Central lymph node dissection was performed in 52.9% of tumours with <10% hobnail features, 36.0% with 10–30% hobnail features, 31.3% with ≥ 30% hobnail features, and 25.9% of the classic subtype.
Lateral lymph node dissection was conducted in 5.9% of tumours with <10% hobnail features, 6.3% with ≥ 30% hobnail features, 5.2% of the classic subtype, and was not performed in the 10–30% hobnail group.
Both central and lateral lymph node dissection were performed in 11.8% of tumours with <10% hobnail features, 31.3% with 10–30% hobnail features, 31.3% with ≥ 30% hobnail features, and 8.6% of the classic subtype. There was no statistically significant association between the groups (p = 0.097). There was no statistically significant association between the tumour subtypes regarding T-stage (p = 0.487) and N-stage (p = 0.095).
In terms of TNM stage, all cases in the <10% hobnail group were stage 1. In the 10–30% hobnail group, 84.0% (21 cases) were stage 1, while 4 cases were stage 2. In the ≥30% hobnail group, 87.5% (14 cases) were stage 1, and 2 cases were stage 2. In the classic PTC group, 79.3% (46 cases) were stage 1, 3.4% (2 cases) were stage 2, 8.6% (5 cases) were stage 3, and 1 case was stage 4a. No statistically significant difference was found in terms of TNM stage among the groups (p = 0.411).
Chronic lymphocytic thyroiditis (CLT) was present in 29.4% of tumours with <10% hobnail features, 16.0% with 10–30%, 12.5% with ≥30%, and 31.0% of the classic subtype. Follicular nodular disease (FND) was observed in 17.6%, 24.0%, 18.8%, and 24.1% of these groups, respectively. Co-occurrence of CLT and FND was noted in 29.4%, 12.0%, 18.8%, and 6.9%. No statistically significant association was found between groups (p = 0.300).
| Hobnail | classic | P | |
|---|---|---|---|
| Parenchymal invasion | 81.0% | 48.3% | < 0.001 |
| Calcification | 79.3% | 37.9% | <0.001 |
| Vascular invasion | 29.3% | 6.9% | 0.003 |
| Lymphatic invasion | 55.2% | 34.5% | 0.040 |
| Lymph node dissection | 63.8% | 39.7% | |
| Metastatic lymph node presence | 39.7% | 22.4% | 0.07 |
| N stage | 0.164 | ||
| TNM stage | 0.030 |
<10 % of hobnail; 10-30 % of hobnail; > 30% of hobnail; classic type.
RAI treatment was more frequently administered in tumours with a higher percentage of hobnail features (82.4% for <10%, 96.0% for 10–30%, and 100% for ≥30%), compared to 75.9% in the classic subtype, showing a statistically significant difference between groups (p = 0.026).
Treatment response outcomes did not differ significantly between groups (p = 0.856) or regarding relapse (p = 0.534). Total response was achieved in 88.2% of cases with <10% hobnail features, 80.0% with 10–30%, 81.3% with ≥30%, and 87.9% in the classic subtype. Biochemical incomplete response occurred in 5.9%, 8.0%, 6.3%, and 5.2% of these groups, respectively. Structural incomplete response was observed in 8.0% of the 10–30% group and 5.2% of the classic subtype, but was absent in both the <10% and ≥30% groups. Relapse was observed in 3.5% of the classic subtype, with no cases in hobnail groups.
Distant metastasis at the time of diagnosis was observed in 4.0% of cases with 10–30% hobnail features and 1.7% of the classic subtype, with no cases in the <10% or ≥30% hobnail groups. No statistically significant association was found (p = 0.752).
During follow-up, lung metastasis was detected in 4.0% of cases with 10–30% hobnail features and in 1.7% of the classic subtype, with no metastases observed in the other groups. No statistically significant difference was noted (p = 0.752). When comparing tumour subtypes regarding age (p = 0.338), age at diagnosis (p = 0.938), tumour size (p = 0.696), number of metastatic lymph nodes (p = 0.938), and size of metastatic lymph nodes (p = 0.332), no statistically significant associations were found (Table 1).
Table 1.
PTC with any hobnail features. PTC with 10-30 % of hobnail features. PTC showing ≥ 30% of hobnail features and classic type PTC with various pathological characteristicsto the classic variant of PTC
| any of hobnail | 10-30 % of hobnail | > 30% of hobnail | classic type | P | |
|---|---|---|---|---|---|
|
Gender (n. % ) Female |
13 (76.5%) | 14 (56.0%) | 10 (62.5%) | 43 (74.1%) | 0.338 |
| Male | 4 (23.5%) | 11 (44.0%) | 6 (37.5%) | 15 (25.9%) | |
| Age (mean ± SD) | 44.1 ± 13.79 | 45.2 ± 12.7 | 47.2 ± 16.1 | 58 ± 44.7 | 0.746 |
| Age at diagnosis (mean ± SD) | 40.1 ± 12.7 | 25 ± 40.7 | 16 ± 44.2 | 38.6 ± 13.1 | 0.938 |
| Tumour size (mean. mm ± SD) | 19.8 ± 11.4 | 23.9 ± 13.4 | 23.0 ± 14.3 | 21.6 ± 12.7 | 0.696 |
|
Thyroidectomy type (n. %) Lobectomi |
1 (5.9%) | 0 (0 %) | 0 (0 %) | 0 (0 %) | 0.284 |
| Total | 16 (94.1%) | 25 (100%) | 16 (100%) | 58 (100%) | |
|
Capsule precence (n. %) Yes |
5 (29.4 %) | 12 (48.0%) | 8 (50.0%) | 31 (53.4%) | 0.386 |
| No | 12 (70.6%) | 13 (52.0%) | 8 (50.0%) | 27 (46.6%) | |
|
Capsule invasion (n. %) Yes |
4 (23.5 %) | 12 (48.0%) | 7 (43.8%) | 19 (32.8%) | 0.341 |
| No | 13 (76.5%) | 13 (52.0%) | 9 (56.3%) | 39 (67.2%) | |
|
Vascular invasion ( n. % ) Yes |
2 (11.8%) | 9 (36.0%) | 6 (37.5%) | 4 (6.9%) | 0.001 |
| No | 15 (88.2%) | 16 (36.0) | 10 (62.5%) | 54 (93.1%) | |
|
Calcification ( n. % ) Yes |
11 (64.7%) | 20 (80.0%) | 15 (93.8%) | 34 (37.9%) | <0.001 |
| No | 6 (35.3%) | 5 (20.0%) | 1 (6.3%) | 36 (62.1%) | |
|
Lymphatic invasion ( n. % ) Yes |
5 (29.4%) | 13 (52.0%) | 14 (87.5%) | 20 (34.5%) | <0.001 |
| No | 12 (70.6%) | 12 (48.0%) | 2 (12.5%) | 38 (65.5%) | |
|
Perineural invasion ( n. % ) Yes |
1 (5.9%) | 0 (0%) | 0 (0%) | 1 (1.7%) | 0.535 |
| No | 16 (94.1%) | 25 (100%) | 16 (100%) | 57 (98.3%) | |
|
Parenchymal invasion ( n. % ) Yes |
13 (76.5%) | 21 (84.0%) | 13 (81.3%) | 28 (48.3%) | 0.003 |
| No | 4 (23.5%) | 4 (16.0 %) | 3 (18.8%) | 30 (51.7%) | |
|
Lymph node metastasis (n. %) Yes |
5 (29.4 %) | 8 (32.0%) | 10 (62.5%) | 13 (22.4%) | 0.026 |
| No | 12 (70.6%) | 17 (68.0%) | 6 (37.5%) | 45 (77.6%) | |
|
Focality (n. %) Unifocal |
10 (58.8%) | 14 (58.3%) | 9 (56.3%) | 24 (41.2%) | 0.378 |
| Muliyfocal | 7 (41.2%) | 10 (41.7%) | 7 (43.8%) | 34 (58.6%) | |
|
Bilatherality (n. %) Yes |
5 (29.4%) | 9 (37.5%) | 4 (25.0%) | 26 (44.8%) | 0.442 |
| No | 12 (70.6%) | 15 (62.5%) | 12 (75.0%) | 32 (55.2%) | |
|
Necrosis (n. % ) Yes |
0 (0%) | 2 (8%) | 0 (0%) | 0 (0%) | 0.124 |
| No | 17 (100%) | 23 (92.0%) | 16 (100%) | 58 (100%) | |
|
Mitosis ( n. % ) Yes |
2 (11.8%) | 3 (12.0%) | 2 (12.5%) | 2 (3.4%) | 0.216 |
| No | 15 (88.2%) | 22 (88.0%) | 14 (87.5%) | 56 (96.6%) | |
|
Extrathyroidal spread (n. %) Yes |
0 (0%) | 3 (12.0%) | 1 (6.3%) | 7 (51 %) | 0.557 |
| No | 17 (100%) | 22 (88.0%) | 15 (93.8%) | 51 (87.9%) | |
|
Extranodal spread (n. %) Yes |
1 (33.3%) | 2 (33.3%) | 1 (16.7%) | 4 (26.7%) | 1.000 |
| No | 2 (66.7%) | 4 (66.7%) | 5 (83.3%) | 11 (73.3%) | |
|
Surgical margins (n. %) Yes |
2 (11.8%) | 2 (8.0%) | 3 (18.8%) | 12 (20.7%) | 0.534 |
| No | 15 (88.2%) | 23 (92.0%) | 13 (81.3%) | 46 (79.3%) | |
| Metastatic lymph node number (mean ± SD) | 1.47 ± 3.5 | 2.8 ± 6.6 | 3.7 ± 4.7 | 1.26 ± 3.5 | 0.938 |
| Metastatic lymph node size (mean. mm ± SD) | 10.9 ± 10.0 | 12.0 ± 13.7 | 10.1 ± 9.1 | 18.3 ± 14.2 | 0.332 |
| Lymph node dissection (n. %) | 5 (29.4%) | 11 (44.0 %) | 5 (31.3%) | 35 (60.3%) | 0.097 |
| No | 9 (52.9%) | 9 (36.0%) | 5 (31.3%) | 15 (25.9%) | |
| Central Lateral |
1 (5.9%) | 0 (0.0%) | 1 (6.3 %) | 3 (5.2%) | |
| Central and lateral | 2 (11.8%) | 5 (31.3%) | 5 (31.3%) | 5 (8.6%) | |
|
T stage (n. %) T1a |
5 (29.4%) | 3 (12.0%) | 2 (12.5%) | 0 (0%) | 0.487 |
| T1b | 6 (35.3%) | 10 (40.0%) | 8 (50.0%) | 3 (12.0%) | |
| T2 | 5 (29.4%) | 7 (28.0%) | 3 (18.8%) | 1 (6.3%) | |
| T3a | 1 (5.9%) | 2 (8.0%) | 2 (12.5%) | 0 (0%) | |
| T3b | 0 (0.0%) | 3 (12.0%) | 1 (6.3 %) | 4 (3.4%) | |
| N strage ( n. % ) | 13 (76.5 %) | 17 (68.0%) | 6 (37.5%) | 45 (77.6%) | 0.095 |
| N0 | 3 (17.6 %) | 5 (20.0 %) | 6 (37.5 %) | 7 (12.1%) | |
| N1a N1b |
1 (5.9 %) | 3 (12.0%) | 4 (25.0%) | 6 (10.3%) | |
| Chronic lymphocitic thyroiditis | 5 (29.4%) | 4 (16.0%) | 2 (12.5%) | 18 (31.0%) | 0.300 |
| Folliculary nodular disease | 3 (17.6%) | 6 (24.0%) | 3 (18.8%) | 14 (24.1%) | |
| CLT and FND | 5 (29.4%) | 3 (12.0%) | 3 (18.8%) | 4 (6.9%) | |
| No (n. %) | 14 (23.5%) | 12 (48.0%) | 8 (50.0%) | 22 (37.9%) | |
|
RAI treatment (n. %) Yes |
14 (82.4%) | 24 (96.0%) | 16 (100%) | 44 (75.9%) | 0.026 |
| No | 3 (17.6%) | 1 (4.0%) | 0 (0.0%) | 14 (24.1%) | |
|
Treatment responce ( n. %) Total responce |
15 (88.2%) | 20 (80.0%) | 13 (81.3%) | 51 (87.9%) | 0.856 |
| Biochemical incomplete resp. | 1 (5.9%) | 2 (8.0%) | 1 (6.3%) | 3 (5.2%) | |
| Structural incomplete resp. | 0 (0.0%) | 2 (8.0%) | 0 (0.0%) | 3 (5.2%) | |
| Intermediate response | 1 (5.9%) | 1 (4.0 %) | 2 (12.5%) | 1 (1.7%) | |
|
Relapse ( n. % ) Yes |
0 (0%) | 0 (0.0%) | 0 (0.0%) | 2 (3.5%) | 1.000 |
| No | 17 (100%) | 25 (100%) | 16 (100%) | 55 (96.5%) | |
|
Distant metastasis on diagnosis (n. %) Yes |
0 (0%) | 1 (4.0%) | 0 (0.0%) | 1 (1.7%) | 0.752 |
| No | 1 (4.0%) | 24 (96.0%) | 16 (100%) | 58 (100%) | |
|
Distant metastasis (n. %) Lung |
0 (0%) | 1 (4.0%) | 0 (0%) | 1 (1.7 %) | 0.752 |
| No | 17 (100%) | 24 (96.0%) | 16 (100%) | 57 (98.3%) |
n-number. % - percentage. SD- standart deviation. p- signifficance value.
Study 2
PTC showing any percentage of hobnail features and classic subtype were compared.
The findings indicate that tumours with hobnail features are significantly more likely to exhibit parenchymal invasion (81.0%) compared to classic PTC (48.3%), with a highly significant association (p < 0.001). Similarly, calcification is more prevalent in hobnail PTC (79.3%) than in the classic subtype (37.9%), again with a strong statistical association (p < 0.001). Moreover, vascular invasion is observed in 29.3% of HPTC cases, which is significantly higher than the 6.9% seen in classic HPTC (p = 0.003). Lymphatic invasion also shows a higher incidence in HPTC (55.2%) compared to the classic subtype (34.5%), with a statistically significant difference (p = 0.040).
Although there was a higher rate of lymph node dissection in patients with hobnail PTC (63.8%) compared to those with classic PTC (39.7%), the presence of metastatic lymph nodes did not reach statistical significance between the two groups (39.7% for hobnail versus 22.4% for classic, p = 0.07).
Logistic regression analysis was conducted on these groups. The results suggest that PTC with less than 10% hobnail features has a lower likelihood of capsule presence compared to classic PTC, though this association is not statistically significant (p = 0.295). There is a slight positive relationship with capsule invasion, although not statistically significant (p = 0.118).
Hobnail features are significantly linked to a higher probability of calcification (p = 0.000). However, no significant association was found with bilaterality (p = 0.145) or focality (p = 0.078), nor with the presence of mitosis (p = 0.103). The analysis reveals a strong and statistically significant correlation between hobnail features and vascular invasion (p = 0.004) and lymphatic invasion (p = 0.026).
Hobnail features are associated with an increased likelihood of parenchymal invasion (p < 0.001), but no association was found with perineural invasion (p = 1.000). While extrathyroidal invasion and surgical margin positivity show a slight association, neither is statistically significant (p = 0.347 and p = 0.214, respectively). Hobnail features are significantly associated with a higher likelihood of lymph node metastasis (p = 0.047) (Table 2, Fig. 2).
Table 2.
Logistic regression analysis results for group 2: PTC with Hobnail Features vs. Classic Subtype
| B | S.E. | Exp(B) | 95% CI (Exp(B)) | P | |
|---|---|---|---|---|---|
| Capsule presence | -0.416 | 0.374 | 0.660 | 0.317 -1.372 | 0.295 |
| Capsule invasion | 0.299 | 0.388 | 1.349 | 0.631 -2.884 | 0.118 |
| Parenchymal invasion | 1.521 | 0.426 | 4.578 | 1.987 -10.545 | <0.001 |
| Mitosis | 1.346 | 0.825 | 0.568 | 0.763 -19.354 | 0.103 |
| Calcification | 1.836 | 0.422 | 6.273 | 2.742 -14.351 | <0.001 |
| Vascular invasion | 1.722 | 0.593 | 6.273 | 1.751 -17.899 | 0.400 |
| Lymphatic invasion | 0.299 | 0.382 | 2.338 | 1.106 -4.945 | 0.026 |
| Perineural invasion | 0.000 | 1.427 | 1.000 | 0.061 -16.379 | 1.000 |
| Extrathyroidal invasion | -0.617 | 0.656 | 0.540 | 0.149 -1.954 | 0.347 |
| RAI treatment | 1.458 | 0.602 | 4.295 | 1.319 -13.984 | 0.016 |
| Focality | -0.667 | 0.378 | 0.513 | 0.245 -1.077 | 0.078 |
| Bilaterality | -0.566 | 0.388 | 0.568 | 1.216 -0.773 | 0.145 |
| Metastatic lymph nodes | 0.822 | 0.414 | 2.275 | 0.195 -0.989 | 0.047 |
| Surgical margin | 0.642 | 0.517 | 1.901 | 0.690 -5.238 | 0.214 |
B- unstandardized regression weight. Exp(B) - odds ratio. S.E.- Standard Error. p- significance. CI - confidence intervals 95%.
Figure 2.
Forest plot of odds ratios (ORs) with 95% confidence intervals from logistic regression comparing papillary thyroid carcinoma (PTC) with any hobnail features versus classic type.
Study 3
PTC with ≥ 30% vs < 30% hobnail features were examined in terms of various pathological outcomes. While the presence of ≥30% hobnail features was associated with a higher likelihood of capsule presence and capsule invasion, neither association reached statistical significance (p= 0.514 and p = 0.694, respectively). No statistically significant associations were found between mitosis presence (p = 0.950), calcification and hobnail features (p = 0.125), vascular invasion and ≥30% hobnail features (p = 0.400), parenchymal invasion (p = 0.979), or extrathyroidal invasion (p = 0.905), despite some suggestive trends. ≥30% hobnail features were significantly associated with an increased likelihood of lymphatic invasion (p = 0.006) and metastatic lymph nodes (p = 0.033). The presence of hobnail features also suggested a slight increase in the odds of focality, although not statistically significant (p = 0.875). For bilaterality and surgical margin positivity, hobnail features were associated with a decrease in the odds; however, the results were not statistically significant (p = 0.506 and p = 0.343, respectively).
The analysis revealed a strong but statistically insignificant association between the presence of ≥30% hobnail features and the need for RAI treatment (p = 0.998). Perineural invasion was excluded from the analysis due to data issues, and wide confidence intervals for many odds ratios suggest caution in interpreting the findings (Table 3, Fig. 3).
Table 3.
Logistic regression analysis results for group 3: PTC with ≥30% vs. <30% Hobnail Features
| B | S.E. | Exp(B) | 95% CI (Exp(B)) | P | |
|---|---|---|---|---|---|
| Capsule presence | 0.386 | 0.591 | 1.471 | 0.462 -4.680 | 0.514 |
| Capsule invasion | 0.234 | 0.596 | 0.694 | 0.393 - 4.063 | 0.694 |
| Parenchymal invasion | 0.019 | 0.751 | 1.020 | 0.234 -0.447 | 0.979 |
| Mitosis | 0.056 | 0.894 | 1.057 | 0.183 -6.092 | 0.950 |
| Calcification | 1.672 | 1.091 | 5.323 | 0.628 -45.145 | 0.125 |
| Vascular invasion | 0.525 | 0.624 | 1.691 | 0.497 -5.749 | 0.400 |
| Lymphatic invasion | 2.234 | 0.818 | 9.333 | 1.879 -46.353 | 0.006 |
| Perineural invasion | -17.48 | 10048.24 | 0.000 | 0.000 | 0.999 |
| Extrathyroidal invasion | -0.143 | 1.194 | 0.867 | 0.083 -8.999 | 0.905 |
| RAI treatment | 18.952 | 10048.2 | 17005 | 0.000 | 0.998 |
| Focality | 0.094 | 0.595 | 1.098 | 0.342 -3.527 | 0.875 |
| Bilaterality | -0.442 | 0.665 | 0.643 | 0.175 -2.365 | 0.506 |
| Metastatic lymph nodes | 1.313 | 0.615 | 3.718 | 1.114 -12.408 | 0.033 |
| Surgical margin | -0.785 | 0.829 | 0.456 | 0.456 -0.090 | 0.343 |
B- unstandardized regression weight. Exp(B) - odds ratio. S.E.- Standard Error. p- significance. CI - confidence intervals 95%.
Figure 3.
Forest plot of adjusted odds ratios (ORs) with 95% confidence intervals from the logistic regression model comparing papillary thyroid carcinoma (PTC) with ≥30% versus <30% hobnail features.
DISCUSSION
The prevalence of PTC is known to be higher in women than in men (8, 9), and female dominance has also been reported in studies on HPTC, regardless of the extent of the hobnail component (≥30% or <30%). Previous studies reported the mean age at diagnosis for HPTC as 51.3 years (range: 14–92) and 52.3 years (range: 21–92)(10-12). In our study, the mean age at diagnosis for HPTC was 45.1 ± 13.4 years, with no significant difference between the groups, aligning with findings from the literature.
Capsular invasion has been identified as an indicator of aggressive behaviour in PTC in certain studies (13, 14). In the present study, no significant association was observed between capsular invasion and the analysed groups. Additionally, a meta-analysis of 94 cases of hobnail subtype PTC reported lymphovascular invasion in approximately 61% of cases, further highlighting its aggressive nature; likewise, other studies reported 41.7% (15, 16).
In the present study, tumours with ≥30% hobnail features exhibited the highest likelihood of lymphatic invasion, showing a statistically significant correlation. Similarly, a significant association was found between tumour subtype and the presence of vascular invasion. These findings suggest that PTC subtypes with a higher proportion of hobnail features are more prone to lymphovascular invasion (10, 12). Other studies on aggressive subtypes, such as the tall-cell subtype of PTC, reported a higher prevalence of parenchymal invasion compared to classic PTC cases (18, 19). Consistent with previous data, in our study, parenchymal invasion was significantly more common in cases with hobnail features (20, 21). The prognostic role of calcification remains unclear. Some studies have found that calcification is a parameter that enhances tumour migration and invasion capabilities in PTC (22-25). In our study, it was observed that as hobnail features increased, the percentage of calcification also significantly increased. A Japanese study of 5768 PTC patients with a mean follow-up period of 129 months identified extrathyroidal and extranodal spread as significant prognostic factors for PTC (26).
However, a meta-analysis comparing PTCs with <30% and ≥30% hobnail features found no significant difference in extrathyroidal spread between the groups (10). In our study, no significant difference in extrathyroidal spread was observed between all groups.
Lymph node metastasis is a well-established poor prognostic factor for PTC. In a study comparing 25 cases of HPTC with 165 classic PTC cases, lymph node involvement was found to be 68% in the HPTC group, compared to 38% in the classic PTC group 6. In our study, when comparing HPTC with classic cases, this rate was found to be 62.5% versus 22.4% in favour of HPTC. Additionally, we observed that as hobnail features increased, lymph node involvement also increased in parallel, which is consistent with previous research (27).
HPTC has been reported to be associated with resistance to radioactive iodine therapy in some studies (17). For instance, Morandi et al. analysed HPTC cases and found that only six patients had a favourable response to radioactive iodine treatment (28). However, in our cohort, over 80% of patients in all groups showed a complete response during follow-up after radioactive iodine therapy. This contrasts with previous studies that have indicated a higher rate of structural persistence in HPTC compared to classic PTC (29).
In our study, among the groups that received similar treatment, biochemical incomplete response occurred in 5.9% of cases with <10% hobnail features, 8.0% with 10-30% hobnail features, 6.3% with ≥30% hobnail features, and 5.2% with classic PTC. A structural incomplete response was observed in only two cases, with 10-30% hobnail features (8.0%), and in three cases with classic features (5.2%). Some previous studies report worse outcomes and treatment response for papillary thyroid carcinoma with hobnail features (6). However, similarly to Song et al.’s study, no significant difference in treatment response was found between the groups (30). While a meta-analysis reported a recurrence rate of 36% in HPTC, no recurrence was observed in any cases with hobnail features in our study (10). In contrast, recurrence was detected in two cases of classic PTC (3.5%), without statistical significance.
Although previous studies have reported high rates of distant metastasis in HPTC, ranging from 25% to 43.5% our study found lower rates at the time of diagnosis (7, 31). Distant metastasis was detected in 1 case with hobnail features (4.0%) and 1 case with classic PTC (1.7%). During follow-up, lung metastasis was observed in 1 case with hobnail features (4.0%) and 1 case with classic features (1.7%). While previous studies indicate that approximately 25% of HPTC cases present at stage 2 or higher, all HPTC cases in our study were diagnosed at stage 1 or stage 2, with no significant difference observed compared to the other groups (29).
This study has several limitations. First, the case number is relatively limited because the study is based on a single institution. Second, the ability to assess recurrence, progression, and survival outcomes was limited by the short average follow-up period. Third, molecular analysis could not be conducted, which could have provided valuable insights into the genetic characteristics of the cases. These limitations suggest that further studies with larger cohorts, longer follow-up, and molecular profiling are needed to understand the clinical behaviour of hobnail PTC better.
In conclusion, this study examines the pathological features and clinical outcomes of PTC with varying degrees of hobnail cell cytological features. Tumours with ≥30% hobnail features showed higher rates of vascular and lymphatic invasion, lymph node metastasis, and calcification compared to classic PTC. Logistic regression confirmed a significant link between hobnail features and aggressive disease characteristics. However, no significant associations were found with extrathyroidal invasion, bilaterality, or the need for radioiodine treatment. Although some of the findings are not statistically significant, associative trends in comparisons highlight the aggressive clinical behaviour of PTC with high hobnail cell content and emphasise the need for tailored therapeutic strategies in managing such tumours.
Conflict of Interest
The authors declare that they have no conflict of interest.
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