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Review
. 2015 Jul 1;8(7):7988-97.
eCollection 2015.

Cytologic, clinicopathologic, and molecular features of papillary thyroid carcinoma with prominent hobnail features: 10 case reports and systematic literature review

Young Sub Lee  1 , Yourha Kim  2 , Sora Jeon  2 , Ja Seong Bae  3 , So Lyung Jung  4 , Chan Kwon Jung  1
Affiliations
Review

Cytologic, clinicopathologic, and molecular features of papillary thyroid carcinoma with prominent hobnail features: 10 case reports and systematic literature review

Young Sub Lee et al. Int J Clin Exp Pathol. .

Abstract

The hobnail variant of papillary thyroid carcinoma (PTC) is a rare, aggressive variant in which > 30% of the tumor cells have hobnail features. The clinical behavior and pathologic characteristics of these tumors are still unclear due to the rarity of the entity. The present study aimed to investigate cytologic, clinical, pathological, and molecular features of the hobnail variant from our data and from the literature. We retrospectively retrieved 10 cases of hobnail variant from 2,904 consecutive PTC patients. Cytologic and histopathologic slides from those 10 patients were reviewed. We performed molecular analysis for BRAF, ALK, and TERT promoter mutations on paraffin blocks from surgical specimens, and further analyzed the clinicopathologic characteristics of all case reports published in the literature until now. Cytologically, all tumors were characterized by single cells with eccentric nuclei and tapering cytoplasm (comet-like cells), and syncytial or micropapillary clusters with apically placed nuclei resulting in a hobnail appearance in both conventional smears and liquid-based cytology. The BRAF V600E mutation was found in 8 cases (80%) whereas no cases had ALK fusion or TERT promoter mutations. In the literature review of 55 patients including our cases, most patients presented with advanced stage cancer, and disease-specific survival rates were 83%, 71%, and 54% at 5, 10, and 20 years after the initial surgery, respectively. Characteristic cytologic features can allow a preoperative diagnosis of the hobnail variant of PTC based on cytology specimens. Further studies should be performed to identify the molecular genetics of the variant.

Keywords: ALK; BRAF; TERT; Thyroid cancer; fine needle aspiration; hobnail variant.

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Figures

Figure 1
Figure 1
Cytologic features of hobnail variant of papillary thyroid carcinoma in a conventional smear. A. A papillary fragment lined by hobnail cells (H&E × 200). B. A micropapillary fragment showing hobnail appearance (H&E ×400). C. A comet-like cell (arrow), showing nucleus protruding toward one side and cytoplasm tapering toward the opposite side (H&E × 1000). D. Isolated single cells with multiple soap-bubble-like intranuclear inclusions (arrow) (H&E × 1000). H&E, hematoxylin and eosin.
Figure 2
Figure 2
Cytologic features of hobnail variant of papillary thyroid carcinoma in a liquid-based cytology (ThinPrepTM). A. A syncytial cell cluster showing apically placed nuclei and a surface bulging (Papanicolaou stain × 400). B. A comet-like cell, characterized by eccentric nucleus and tapering cytoplasm (Papanicolaou stain × 1000). C. Multiple soap-bubble-like intranuclear inclusions (Papanicolaou stain × 1000). D. A cell block showing papillary structures with prominent hobnail features (H&E × 200).
Figure 3
Figure 3
A. Histology of hobnail variant of papillary thyroid carcinoma. Thin arborizing papillae are lined by hobnail cells. Single detaching cells (arrow) and tumor necrosis (asterisk) are also noted (H&E × 200). B. Immunohistochemistry reveals positivity for p53 (× 200).
Figure 4
Figure 4
Cumulative survival probabilities of 52 patients with hobnail variant of papillary thyroid carcinoma calculated by the life-table method.
See this image and copyright information in PMC

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