Thyroid gland
Papillary thyroid carcinoma
Hobnail variant

Author: Andrey Bychkov, M.D., Ph.D. (see Authors page)

Revised: 2 March 2017, last major update February 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: thyroid gland hobnail variant
Cite this page: Hobnail variant. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidpapillaryhobnail.html. Accessed March 30th, 2017.
Definition / General
Essential Features
  • 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
Terminology
  • Hobnail variant of PTC = Hobnail PTC = PTC with prominent hobnail features
  • Previously described as PTC with micropapillary features, micropapillary carcinoma, micropapillary-hobnail variant and loss of cellular polarity / cohesiveness variant
Epidemiology
Pathophysiology
Diagrams / Tables

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Summary of patients

Clinical Features
  • Neck mass, sometimes with compressive symptoms (dyspnea, dysphagia, hoarseness) (Am J Surg Pathol 2010;34:44)
  • Almost half are incidental findings (Int J Clin Exp Pathol 2015;8:7988)
  • Aggressive tumor with relatively poor prognosis (Thyroid 2014;24:958):
    • Extrathyroidal extension
    • Lymph node metastasis in up to 75%
    • Distant metastases in up to 40% (lung, brain, bones)
    • Local recurrence
    • Progression to poorly differentiated thyroid cancer
    • Advanced clinical stage (AJCC Stage III or IV) at presentation
    • Increased mortality rates compared to classic PTC in most but not all cases
Diagnosis
  • 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)
Radiology Description
Prognostic Factors
  • Hobnail PTC itself indicates propensity for higher grade transformation (Am J Surg Pathol 2015;39:260)
  • Local recurrence rate is 23%, lymph node metastasis 60% - 75%, distant metastasis 25% - 40%
  • Disease specific survival rates are 83%, 71% and 54% at 5, 10 and 20 years after surgery, respectively (Int J Clin Exp Pathol 2015;8:7988)
  • Overall survival rates are 69% and 64% at 5 and 10 years, respectively (Endocr Relat Cancer 2017;24:107)
  • Increased mortality risk in patients harboring multiple mutations, usually BRAF with TP53 or PIK3CA (Thyroid 2014;24:958)
Case Reports
Treatment
  • Total thyroidectomy with neck lymph node dissection followed by TSH suppression therapy and radioactive iodine treatment (J Basic Clin Med 2014;3:12)
Gross Description
Micro Description
  • Histologically, this variant has 3 distinctive features (Am J Surg Pathol 2015;39:260):
    • Micropapillae lacking true fibrovascular cores
    • Hobnail cells with apically placed protruding nuclei and eosinophilic cytoplasm
    • Marked loss of cellular cohesion
  • Main architectural patterns (Am J Surg Pathol 2010;34:44):
    • Papillary pattern is the most common, with variably sized edematous papillae having vascular cores, rare psammoma bodies and lined by discohesive hobnail epithelium 1 - 4 cells thick
    • Clustered pattern represented by micropapillary structures without fibrovascular cores, lined by hobnail cells
    • Follicular pattern is rare with variably sized follicles lined by hobnail cells and little to no colloid
  • Hobnail cells:
    • Cells with apically placed nuclei and protrusion of the apical surface that gives a hobnail appearance
      • Synonyms of hobnailing: tufting, bulging, apocrine snouting; also matchstick, comet tail, teardrop appearance
    • Increased N:C ratio
    • Characteristic PTC nuclear features are less prominent compared to classic variant
    • Dense eosinophilic cytoplasm with well defined cell borders, similar to oncocytes
    • Apical position of nuclei (inversion or loss of polarity) is often accompanied by discohesiveness of the epithelial layer with cell shedding
  • Aggressive morphology:
  • Proportion of hobnail component:
    • Presence of at least 30% of cells with hobnail-micropapillary features is required to entitle a tumor as PTC hobnail variant
    • In original series, most had 50% - 100% of hobnail component (Am J Surg Pathol 2010;34:44)
    • If present, minor hobnail-micropapillary component (5% - 30%) should be correctly identified and stated in the pathology report, because it has adverse prognostic significance (Hum Pathol 2012;43:1596, Hum Pathol 2013;44:320, Endocrine Abstracts 2013;32:P1105, Am J Surg Pathol 2015;39:260, Thyroid 2016;26:129, Poster 198)
    • Concomitant patterns are usually represented by classic, tall cell and oncocytic PTC, rarely by PTC follicular and solid variants; all of them can be considered as precursor lesions
    • Number of sections studied is critical for evaluation of PTC with hobnail cells, thus increase in the number of sections routinely studied, especially sampling at the tumor infiltrating edge, can likely result in a higher incidence of detection of the hobnail PTC (Hum Pathol 2013;44:320)
  • Background: often multinodular goiter or chronic thyroiditis (Rev Endocr Metab Disord 2016 Nov 28 [Epub ahead of print]), rarely microcarcinoma (Diagn Cytopathol 2015;43:990)
  • Nodal and distant metastases usually preserve hobnail pattern, sometimes may progress toward anaplastic carcinoma (Am J Surg Pathol. 2016 Dec 22 [Epub ahead of print])
Micro Images

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Edematous papillae lined by discohesive epithelium

Oncocytic epithelium with loss of cohesiveness

Hobnail cells with apically placed nuclei



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Main patterns


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PTC hobnail variant on different magnifications


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Group 2 papillary carcinoma of the thyroid


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Figure 2 - similar appearing tumors

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IHC

Cytology Description
  • Aspirate is highly cellular with scant colloid and bloody background (Hum Pathol 2013;44:320)
  • Patterns:
    • Papillary-like clusters with vascular cores, sometimes with central psammoma calciļ¬cations (Diagn Cytopathol 2015;43:990)
    • Micropapillary groups without fibrovascular cores
    • Rarely follicular structures
    • Proportion of isolated cells versus clusters can vary
  • Hobnail cells:
    • Medium sized cells with apically placed nuclei, producing surface bulge resulting in hobnail appearance
    • Tapered cytoplasm provides "teardrop" or "comet-like" appearance of hobnail cells (Acta Cytol 2012;56:560)
    • Severe crowding, high N:C ratio, dense eosinophilic cytoplasm
    • Often more than 50% of tumor cells in smear have hobnail morphology
  • Additional nuclear features:
    • Multiple soap bubble-like intranuclear inclusions
    • Occasional grooves and pseudoinclusions (J Clin Exp Pathol 2013;4:152)
    • Variable degree of atypia
    • Sometimes mitotic figures
  • LBP (liquid based preparation) cytology (Int J Clin Exp Pathol 2015;8:7988):
    • Frequent syncytial cell clusters with eccentric nuclei
    • Papillary and micropapillary structures are rare than in conventional smears
    • Comet-like hobnail cells and multiple soap bubble-like intranuclear inclusions
    • Typical nuclear features of PTC
  • Most of the cases correspond to the Bethesda VI category (Thyroid 2014;24:958)
Cytology Images

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Conventional smear


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LBP

Positive Stains
Electron Microscopy Description
Molecular / Cytogenetics Description
  • 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
Differential Diagnosis