title: Differential diagnosis of well-differentiated squamous cell carcinoma from non-neoplastic oral mucosal lesions: New cytopathologic evaluation method dependent on keratinization-related parameters but not nuclear atypism.
abstract: BACKGROUND
  The cytology of oral squamous cell carcinoma (SCC) is challenging because oral SCC cells tend to be well differentiated and lack nuclear atypia, often resulting in a false negative diagnosis. The purpose of this study was to establish practical cytological parameters specific to oral SCCs.
  
  
  METHODS
  We reviewed 123 cases of malignancy and 53 of non-neoplastic lesions of the oral mucosa, which had been diagnosed using both cytology and histopathology specimens. From those, we selected 12 SCC and 4 CIS cases that had initially been categorized as NILM to ASC-H with the Bethesda system, as well as 4 non-neoplastic samples categorized as LSIL or ASC-H as controls, and compared their characteristic findings. After careful examinations, we highlighted five cytological parameters, as described in Results. Those 20 cytology samples were then reevaluated by 4 independent examiners using the Bethesda system as well as the 5 parameters.
  
  
  RESULTS
  Five cytological features, (i) concentric arrangement of orangeophilic cells (indicating keratin pearls), (ii) large number of orangeophilic cells, (iii) bizarre-shaped orangeophilic cells without nuclear atypia, (iv) keratoglobules, and (v) uneven filamentous cytoplasm, were found to be significant parameters. All malignant cases contained at least one of those parameters, while none were observed in the four non-neoplastic cases with nuclear atypia. In reevaluations, the Bethesda system did not help the screeners distinguish oral SCCs from non-neoplastic lesions, while use of the five parameters enabled them to make a diagnosis of SCC.
  
  
  CONCLUSIONS
  Recognition of the present five parameters is useful for oral SCC cytology. Diagn. Cytopathol. 2017;45:406-417. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hara
authors.affiliation: Oral Surgery Division, Yamanashi Prefectural Central Hospital, Kofu, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Misawa
authors.affiliation: Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Ishii
authors.affiliation: Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Koshiishi
authors.affiliation: Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Amemiya
authors.affiliation: Pathology Division, Yamanashi Prefectural Central Hospital, Kofu, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of Oral Pathology, Osaka Dental University, Hirakata, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tominaga
authors.affiliation: Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Oral Pathology, Osaka Dental University, Hirakata, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Oral Pathology, Osaka Dental University, Hirakata, Japan.|Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takashi
authors.identifier: http://orcid.org/0000-0002-7108-8391
authors.initials: T
authors.lastname: Saku
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology; D002467:Cell Nucleus / Q000648:ultrastructure; D003593:Cytoplasm / Q000648:ultrastructure; D003937:Diagnosis, Differential; D005260:Female; D006651:Histocytochemistry / Q000592:standards*; D006801:Humans; D007633:Keratins / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology*; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000473:pathology
chemical_list: D007633:Keratins
keywords: concentric cellular arrangement; filamentous cytoplasm; keratinization; keratoglobules; oral squamous cell carcinoma