Thyroid & parathyroid

• Aggressive variant of papillary thyroid carcinoma (PTC) characterized by predominance of cells with a hobnail appearance often arranged in micropapillary pattern (Am J Surg Pathol 2017;41:854)
  • Hobnail cell appearance designates a peculiar loss of polarity with apically placed bulging nuclei
  • Micropapillary pattern is characterized by cancer cells loosely arranged in small clusters lacking fibrovascular cores, lined by hobnail, cuboidal or flat epithelium often with loss of polarity and cohesiveness
• Micropapillary pattern of tumor is recognized in several organs (bladder, breast, colon, gallbladder, kidney, lung, ovary, pancreas and parotid gland), being associated with poor clinical outcome (Rev Endocr Metab Disord 2016;17:521)
• Originally established as distinct PTC variant by Asioli et al. in 2010 (Am J Surg Pathol 2010;34:44)
  • Hobnail pattern with micropapillary structures was described by Kakudo group as loss of cellular polarity / cohesiveness in early 2000s (Pathol Int 2003;53:204, J Clin Pathol 2004;57:1041, Cancer Sci 2008;99:1908)
  • 70+ cases described (Rev Endocr Metab Disord 2016;17:521)

• Recently described rare variant of PTC with aggressive behavior (extrathyroidal extension, nodal and distant metastasis) and relatively poor prognosis (lower long term survival)
• Microscopically characterized by micropapillary growth pattern and hobnail appearance of cells due to apically placed bulging nuclei
• Diagnosis of PTC hobnail variant requires at least 30% of hobnail-micropapillary pattern in the tumor, although minor hobnail-micropapillary features (5 - 30%) are of significance and should be noted in pathology report

• Rare tumor, < 1% of all PTC
  • Range in PTC series from 0.3% (South Korea) to 2.7% (Southern Italy) (Int J Clin Exp Pathol 2015;8:7988, Rev Endocr Metab Disord 2016;17:521)
• Older patients: mean age 57 years, range 17 - 87 (Rev Endocr Metab Disord 2016;17:521)
• F:M about 3:1, similar to all PTC

• Hobnail PTC is considered a moderately differentiated thyroid carcinoma placed between well differentiated classic PTC and poorly differentiated thyroid cancer (Am J Surg Pathol 2015;39:260, Am J Surg Pathol 2017;41:854)
• BRAF mutation is a likely driver, followed by second hits in TP53, TERT promoter, PIK3CA or CTNNB1 (Endocr Relat Cancer 2017;24:107)
• Associated events are epithelial-mesenchymal transition (Cancer Lett 2009;281:188) and activation of mTOR pathway (J Clin Exp Pathol 2013;4:152), both characteristic for aggressive thyroid cancer

Images hosted on other servers:

• Diagnostic workup is similar to any thyroid mass / nodule:
  • Ultrasound with FNA
  • CT scan may be useful in locally advanced disease to evaluate extrathyroidal extension and lymph node metastases
• Hobnail PTC is a pathological diagnosis rendered on surgical specimens
  • FNAC can suspect hobnail variant and influence surgical tactics
  • PTC hobnail variant requires at least 30% of tumor having hobnail-micropapillary pattern
  • Minor hobnail micropapillary features (5 - 30%) should also be correctly identified and stated in pathology report due to potential aggressive behavior (Hum Pathol 2012;43:1596)

• Sonography: oval, solid or heterogeneous, coarsened hypoechoic and vascular mass with irregular margins, often accompanied by ipsilateral cervical lymphadenopathy (J Clin Exp Pathol 2013;4:152, Diagn Cytopathol 2013;41:757)

Contributed by Andrey Bychkov, M.D., Ph.D.


Images hosted on other servers:

Images hosted on other servers:

• Cytoplasm of oncocytic cancer cells is packed with mitochondria (Am J Surg Pathol 2010;34:913)

• Main: BRAF V600E mutation in most cases (50 - 80%)
• Common: TP53 (55%), TERT promoter (45%), PIK3CA (28%)
• Rare: CTNNB1 (17%), EGFR (11%), AKT1 (6%) and NOTCH1 (6%)
• More than 70% of tumors have concurrent mutations (Endocr Relat Cancer 2017;24:107)
• RET / PTC1 is uncommon, up to 20%, based on one study (Thyroid 2014;24:958)
• No RAS family mutations
• Mutation profile in primary tumor and metastasis is usually maintained

• Nose: Diagnostic Pathology: Endocrine, 2012, Wenig: Atlas of Head and Neck Pathology, 3rd Edition, 2015, Nikiforov: Diagnostic Pathology and Molecular Genetics of the Thyroid, 2nd Edition, 2012

Which statement is incorrect about hobnail PTC?

1. Rare variant of papillary thyroid carcinoma
2. Relatively aggressive clinical behavior
3. Microscopically characterized by hobnail cells and micropapillary pattern
4. Common BRAF V600E, TP53 and TERT promoter mutations
5. High mortality

E. High mortality. Hobnail papillary thyroid carcinoma is an unusual and aggressive variant of PTC characterized by predominance of cells with a hobnail appearance often arranged in micropapillary pattern. Despite multiple mutations and frequent nodal (up 75%) and distant (up to 40%) metastases, mortality is relatively low - disease specific survival rates are 80+% and 70+% at 5 and 10 years after surgery.

Comment Here

Reference: Hobnail

What proportion of a hobnail micropapillary pattern in the tumor is required for a diagnosis of PTC hobnail variant?

1. 5%
2. 10%
3. 25%
4. 30%
5. 50%

D. 30%. The presence of at least 30% of cells with hobnail micropapillary features is mandatory to diagnose a tumor as PTC hobnail variant. Nevertheless, a minor hobnail micropapillary pattern (5 - 30%) has prognostic significance and should be noted in the pathology report.

Comment Here

Reference: Hobnail

What category of the Bethesda System of Reporting Thyroid Cytopathology corresponds best to FNA smears of hobnail PTC with comet-like cells?

1. I (non-diagnostic)
2. III (AUS/FLUS)
3. IV (FN/SFN)
4. V (suspicious for malignancy)
5. VI (malignant)

E. VI (malignant). Cases with diagnostic hobnail cells are easily placed into the Bethesda VI category.

Comment Here

Reference: Hobnail