title: Hobnail variant of papillary thyroid carcinoma: an institutional case series and molecular profile.
abstract: BACKGROUND
  Papillary thyroid carcinoma (PTC) is increasing in incidence while mortality is unchanged. Identifying patients with higher risk of recurrence and death is essential. Case series identify the hobnail variant of PTC (HVPTC), which is characterized by micropapillary architecture, apocrine features, and loss of cellular polarity. Herein, we describe the clinical course, pathologic features, and mutational profile of patients at our institution with HVPTC.
  
  
  METHODS
  A query into the surgical pathologic database (2009-2012) was performed, and clinicopathologic data were collected on all patients carrying the diagnosis of HVPTC. BRAF(V600E) testing was performed on paraffin-embedded blocks using SNaPshot mutational analysis.
  
  
  RESULTS
  Twelve patients with HVPTC were identified, with an average age of 54.1±18.8 years. Seven patients (63.6%) were AJCC Stage III or IV at presentation. Tumors were large (3.7±2.0 cm), some were multifocal (33.3%), and frequently with extrathyroidal extension (58.3%), lymphovascular invasion (41.7%), and lymph node metastasis (75%). Forty percent of the patients had concomitant tall cell features (TCF), and two had small foci of undifferentiated (anaplastic) thyroid carcinoma (ATC). Eighty percent of tumors undergoing mutational analysis had the BRAF(V600E) mutation, and the remaining 20% harbored a RET/PTC1 gene rearrangement. No other known thyroid cancer mutations were identified on SNaPshot analysis. At median follow-up of 26 months, four patients had recurrent or persistent disease, one of whom died from the disease one year after surgery.
  
  
  CONCLUSIONS
  The hobnail variant of PTC has an aggressive behavior, with a high incidence of infiltrative tumors and metastatic disease. Strikingly, all tumors in our series harbored a PTC-associated genetic abnormality, either a BRAF(V600E) mutation (80%) or a RET/PTC1 rearrangement (20%). This histologic variant warrants further study, and patients with this diagnosis should be observed closely for recurrence.
authors.affiliation: 1 Endocrine Surgery Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School , Boston, Massachusetts.
authors.forename: Carrie C
authors.initials: CC
authors.lastname: Lubitz
authors.forename: Konstantinos P
authors.initials: KP
authors.lastname: Economopoulos
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Pawlak
authors.forename: Kerry
authors.initials: K
authors.lastname: Lynch
authors.forename: Dora
authors.initials: D
authors.lastname: Dias-Santagata
authors.forename: William C
authors.initials: WC
authors.lastname: Faquin
authors.forename: Peter M
authors.initials: PM
authors.lastname: Sadow
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002291:Carcinoma, Papillary; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000473:pathology; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D048493:Proto-Oncogene Proteins B-raf