Prognostic Implication of Histopathologic Indicators in Salivary Duct Carcinoma: Proposal of a Novel Histologic Risk Stratification Model

Masato Nakaguro, Yukiko Sato, Yuichiro Tada, Daisuke Kawakita, Hideaki Hirai, Makoto Urano, Tomotaka Shimura, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Chihiro Fushimi, Akira Shimizu, Soichiro Takase, Takuro Okada, Hiroki Sato, Yorihisa Imanishi, Kuninori Otsuka, Yoshihiro WatanabeAkihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Natsuki Saigusa, Hideaki Takahashi, Mizuo Ando, Toyoyuki Hanazawa, Toshitaka Nagao

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Salivary duct carcinoma (SDC) is a rare, aggressive malignancy that histologically resembles high-grade mammary duct carcinoma. Because of the rarity of this entity, data verifying the association between histologic features and patient survival are limited. We conducted a comprehensive histologic review of 151 SDC cases and performed an analysis of the association between various histomorphologic parameters and the clinical outcome with the aim of developing a histologic risk stratification model that predicts the prognosis of SDC patients. A multivariate analysis revealed that prominent nuclear pleomorphism (overall survival [OS]: P=0.013; progression-free survival [PFS]: P=0.019), ≥30 mitoses/10 HPF (PFS: P=0.013), high tumor budding (OS: P=0.011; PFS: P<0.001), and high poorly differentiated clusters (OS: P<0.001; PFS: P<0.001) were independent prognostic factors. Patients with vascular invasion demonstrated a marginally significant association with shorter PFS (P=0.064) in a multivariate analysis. We proposed a 3-tier histologic risk stratification model based on the total number of positive factors among 4 prognostically relevant parameters (prominent nuclear pleomorphism, ≥30 mitoses/10 HPF, vascular invasion, and high poorly differentiated clusters). The OS and PFS of patients with low-risk (0 to 1 point) (23% of cases), intermediate-risk (2 to 3 points) (54% of cases), and high-risk (4 points) (23% of cases) tumors progressively deteriorated in this order (hazard ratio, 2.13 and 2.28, and 4.99 and 4.50, respectively; Ptrend<0.001). Our histologic risk stratification model could effectively predict patient survival and may be a useful aid to guide clinical decision-making in relation to the management of patients with SDC.

Original languageEnglish
Pages (from-to)526-535
Number of pages10
JournalAmerican Journal of Surgical Pathology
Issue number4
Publication statusPublished - 2020 Apr 1


  • histologic risk stratification model
  • poorly differentiated clusters
  • prognosis
  • salivary duct carcinoma
  • tumor budding

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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