Prognostic performance of microscopic size measurements in small invasive carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas

M Lisa Zhang; Yuko Omori; Seung-Mo Hong; Noboru Ideno; Kenjiro Date; Dario M Rocha Castellanos; Stuti G Shroff; Giuseppe Zamboni; Raul S Gonzalez; Toru Furukawa; Carlos Fernandez-Del Castillo; Mari Mino-Kenudson

doi:10.1111/his.15198

Prognostic performance of microscopic size measurements in small invasive carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas

Histopathology. 2024 Apr 25. doi: 10.1111/his.15198. Online ahead of print.

Authors

M Lisa Zhang^{1

2}, Yuko Omori^{3

4}, Seung-Mo Hong⁵, Noboru Ideno⁶, Kenjiro Date⁶, Dario M Rocha Castellanos⁷, Stuti G Shroff^{1

2}, Giuseppe Zamboni^{8

9}, Raul S Gonzalez¹⁰, Toru Furukawa^{3

11}, Carlos Fernandez-Del Castillo^{2

7}, Mari Mino-Kenudson^{1

2}

Affiliations

¹ Department of Pathology, Massachusetts General Hospital, Boston, USA.
² Harvard Medical School, Boston, USA.
³ Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
⁴ Department of Pathology, Teine-Keijinkai Hospital, Sapporo, Japan.
⁵ Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁶ Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁷ Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
⁸ Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
⁹ IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy.
¹⁰ Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, USA.
¹¹ Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan.

PMID: 38660970
DOI: 10.1111/his.15198

Abstract

Aims: Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement method for determining the invasive size for tumour staging and prognostication.

Methods: In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000-2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes.

Results: The cohort comprised IPMNs with invasive tubular-type (n = 82, 70%) and colloid-type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS-, AS-, and TS-based pT stages were not significantly associated with recurrence-free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular-type carcinomas, higher LS-, AS-, and TS-based pT stages trended with lower RFS (based on 1-, 3-, and 5-year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5-cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis.

Conclusions: For invasive tubular-type carcinomas arising in IPMN, microscopic size-based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid-type histology that generally portend a more favourable prognosis.

Keywords: IPMN; invasive carcinoma; pancreatic neoplasia; tumour size; tumour staging.