Introduction

Hobnail variant of papillary thyroid carcinoma (HV-PTC) is an unusual entity recently included in WHO classification of endocrine tumors (2017) and proposed as an aggressive variant of PTC. Compared to patients of classical counterparts, HV-PTC frequently has extrathyroidal extension, exhibits nodal or distant metastasis, and responds poorly to radioiodine treatment, leading to increased mortality^.[1] The pathologist is instrumental in the diagnosis of HV-PTC. It is a diagnostic challenge which can be resolved by close attention to morphology, clinicoradiological correlation along with Immunohistochemical and molecular studies in some cases.

Case History

A 68 year old male patient , known case of coronary artery disease, hypertension, aortic aneurysm presented with swelling over the neck and change in voice for last 05 months. CECT neck and chest was done which revealed a large hypodense enhancing nodule measuring 2.9x2.7x.3.7 cm (APxTRxCC) is seen epicentered at superior aspect of right lobe of thyroid gland. FNAC was performed which was opined as Bethesda category V suspicious for Papillary Thyroid Carcinoma (PTC). Considering the strap muscle involvement radiologically and intraoperatively, total thyroidectomy was performed.

Fig 1: A brownish nodule is noted grossly on superior pole of thyroid lobe measuring 3x2 cm. Capsular breach seen. Gross capsular invasion present.

Fig 2: CECT Neck and Chest: In Axial view, a large hypodense enhancing nodule measuring 2.9x2.7x3.7 cm (APxTRcCC) is seen epicentered at superior aspect of right lobe of thyroid gland. Left lobe and isthumus appear normal. A large hypodense enhancing nodule measuring 2.9x2.7x3.7 cm (APxTRcCC) is seen epicentered at superior aspect of right lobe of thyroid gland. Left lobe and isthmus appear normal.

Intraoperatively and on gross findings, there was hard nodule of size 3 x 2 cm involving right superior lobe. Strap muscle involvement was seen. Another nodule was noted measuring 0.7x 0.7x 0.7 cm on superior pole of right thyroid. Left lobe of thyroid and isthmus were normal.

Fig 3: Histopathological sections from right lobe of thyroid show presence of tumour arranged in arborising papillary architecture with fibrovascular cores. Numerous micro papillae seen with hyalinised cores at places >30% of lining cells have nuclei at the surface and show hob nailing.

Microscopically sections from right lobe of thyroid showed presence of tumour arranged in arborising papillary architecture with fibrovascular cores. The cores at places appeared hyalinised. More than 30% of lining cells showed loss of polarity, relatively high N: C ratio with apical nuclei at the surface and showing a surface bulge/ hob nail appearance. Focal areas less than 10 % showed tall cell changes. The tumour is seen to be breaching the thyroid capsule and invading the adjoining strap muscle. Optically clear nuclei with marginated chromatin, nuclear grooving and occasional intranuclear inclusions were seen. Foci of squamoid differentiation were noted. Microscopic strap muscle involvement was noted . Left thyroid showed normal histomorphology and was free from tumor.

Fig 4: Immunohistochemistry shows  (A) Strong nuclear positivity for PAX8 (IHC, 400x); (B) nuclear positivity for TTF-1 (IHC, 400x)

The final opinion rendered was Hobnail variant of papillary thyroid carcinoma (HV-PTC). Stage : pT3b Nx Mx (AJCC 8^th edition)

Discussion

HV-PTC is a rare variant of PTC that comprise of 0.2% to 0.3% of PTC. The diagnosis of this variant has been recently defined by the presence of at least 30% of cells with hobnail features. It has been advocated that with this higher percentage of hobnail/ micropapillary features, the tumours are associated with very aggressive behaviour and significant mortality[2,3]. Tumour with even 10% hobnail features also carry a poor outcome. Eighty percent of tumors undergoing mutational analysis had the BRAF^V600E mutation, and the remaining 20% harbored a RET/PTC1 gene rearrangement. Though HVPTC displays a spectrum of papillary arrangement with predominance of micropapillary structures with hobnail cells, conspicuous nucleoli and intranuclear, cytoplasmic inclusions but the typical nuclear features of papillary thyroid carcinoma is seldom present. HVPTC is associated with aggressive features (old age, lymphovascular invasion, lymph node metastasis, distant metastasis, high stage) along with genetic features of BRAF mutation in 72%, p53 mutation in 56% and h-TERT mutation in 44% but strikingly RET/PTC rearrangement is absent unlike classic variant of PTC. There is lymph node metastasis of 60–75% cases and that of distant spread in 25–40% cases.[1]

The differential diagnosis includes diffuse sclerosing variant of PTC (DS-PTC). However DS-PTC is associated with squamous metaplasia, fibrosis, and abundant psammoma bodies. Medullary thyroid carcinoma with discohesive cells may overlap with cytologic features with HV-PTC. IHC with calcitonin renders a correct diagnosis.

In a recent study HV-PTC showed high rates of extra-thyroidal extension (40.4%), lymph node metastasis (68.1% of patients with lymphadenectomy), and vascular emboli (49.5%), with no differences according to the 30% cutoff. On the other hand, distant metastases were present in HVPTC only (9.4%). Also, advanced age, advanced disease stage, and TERT promoter mutation were associated with HVPTC. More than half of the patients with follow-up had structural or biochemical persistence after 1 year from surgery[4]^. Tumors, such as serous and clear cell carcinoma of ovary, micropapillary breast carcinoma, carcinoma colon, and lung micropapillary adenocarcinoma, which are common mimickers of HV-PTC are differentiated on basis of clinicoradiological input and immunohistochemical markers of WT1, PAX8, GATA3, CDX2, and Napsin-A. Our study showed positivity for TTF1, PAX8 and Beta catenin and negativity for CDX2. This supports the diagnosis of HV-PTC.

Conclusion

Papillary carcinoma thyroid, Hobnail variant (HV-PTC) is a recently described rare variant of PTC . Due to its association with aggressive behaviour and metastasis, appropriate diagnosis, surgical intervention and treatment will improve overall survival of the patient. PTC with even focal hobnail component is characterized by the high frequency of regional metastases at the moment of primary tumor manifestation. The clinicians, pathologists and patients should be aware about this unusual variant and its behaviour so as to enable correct diagnosis, prognostication and treatment.

References

1. Mohapatra D, Naik S, Das P, Agrawala S. Metastatic hobnail variant of papillary thyroid carcinoma: A diagnostic challenge in cell block preparation. Indian J Pathol Microbiol. 2021 Apr-Jun;64(2):358-361. doi: 10.4103/IJPM.IJPM_381_20.
2. Lee YS, Kim Y, Jeon S, Bae JS, Jung SL, Jung CK. Cytologic, clinicopathologic, and molecular features of papillary thyroid carcinoma with prominent hobnail features: 10 case reports and systematic literature review. Int J Clin Exp Pathol. 2015 Jul 1;8(7):7988-97.
3. Asioli S, Erickson LA, Sebo TJ, Zhang J, Jin L, Thompson GB, et al. Papillary thyroid carcinoma with prominent hobnail features: A new aggressive variant of moderately differentiated papillary carcinoma. A clinicopathologic, immunohistochemical, and molecular study of eight cases. Am J Surg Pathol 2010;34:44-52
4. Poma AM, Macerola E, Proietti A, Vignali P, Sparavelli R, Torregrossa L, Matrone A, Basolo A, Elisei R, Santini F, Ugolini C. Clinical-Pathological Features and Treatment Outcome of Patients With Hobnail Variant Papillary Thyroid Carcinoma. Front Endocrinol (Lausanne). 2022 Mar 2;13:842424. doi: 10.3389/fendo.2022.842424.