Table 7b.

Suspected Diffuse Gastric and Lobular Breast Cancer Syndrome of Unknown Genetic Cause: 1 Recommended Surveillance

System/ConcernEvaluationFrequency
Diffuse gastric cancer (DGC) Referral to high-risk gastric cancer screening program
Upper endoscopy to incl:
  • Thorough ≥30-minute exam
  • Targeted biopsies of all suspicious lesions
  • Followed by random biopsies from specific anatomic regions using IGCLC Cambridge 2 or Bethesda method 3, 4
Note: Endoscopy permits direct inspection & biopsy of suspicious areas; however, DGC tends to spread in submucosa, where lesions are difficult to identify.
  • Annually for ≥2 yrs, beginning at age 40 yrs or 10 yrs prior to earliest gastric cancer diagnosis in family, w/minimum age of 18 yrs
  • Note: The likelihood of a positive biopsy is highest w/initial endoscopy & surveillance intervals can be extended at discretion of endoscopist after 2 yrs. This decision should be based on individual findings from previous endoscopies & family history. 5, 6
Lobular breast cancer (LBC) Referral to high-risk breast-screening program
Self-breast examsMonthly in females beginning at age 20 yrs in those w/personal or familial history of breast cancer of any type
  • Clinical breast exams
  • Education on clinical features of LBC (e.g., thickening, indrawn nipple, or change in breast skin)
Annually in females beginning at age 30 yrs in those w/personal or familial history of breast cancer of any type
  • Bilateral breast MRI w/contrast 7, 8
  • Bilateral breast MRI combined w/mammography & breast ultrasound
  • Frequency should be based on personalized breast cancer risk assessment by experienced team.
  • Consider MRI in addition to conventional mammography & breast ultrasound for improved results w/LBC diagnosis. 9

DGC = diffuse gastric cancer; IGCLC = International Gastric Cancer Linkage Consortium; LBC = lobular breast cancer

1.

Also referred to as HDGC-like

2.

IGCLC Cambridge method recommends a thorough high-definition white light examination of at least 30 minutes in a center of expertise. The session should begin with targeted biopsies from all suspicious lesions, followed by five random biopsies from six specific anatomic regions (prepyloric, antrum, transitional zone, body, fundus, and cardia) [van der Post et al 2015a].

3.

Bethesda protocol recommends endoscopic examination with a comprehensive assessment of 22 specific anatomic locations, each of which is meticulously photographed. Four non-targeted biopsies are obtained from each of these 22 sites; any abnormal findings are subjected to biopsy.

4.

When comparing the detection rates per endoscopy, the false-negative rates for detection using the Cambridge method and the Bethesda protocol were 80% (12/15) and 37.7% (17/45), respectively [Curtin et al 2021].

5.

Three independent prospective longitudinal studies of endoscopic surveillance with multiple biopsies in individuals with DGLBCS showed that endoscopic surveillance, performed in reference centers, may be a reasonable alternative to prophylactic total gastrectomy [Friedman et al 2021, Asif et al 2023, Lee et al 2023]. Further studies with greater statistical power are needed before this approach is implemented in clinical practice.

6.

Currently, there are ongoing trials to investigate the utility of probe-based confocal laser endomicroscopy (pCLE) for DGC diagnosis, particularly in identifying early signet ring cell carcinoma lesions [Pilonis et al 2023].

7.

Mammography has a low sensitivity for detecting lobular breast cancer (LBC) due to its subtle and slow-growing nature. Breast imaging radiologists must be aware of the atypical and subtle mammographic patterns of invasive LBC, which include spiculated masses, architectural distortion, and poorly defined asymmetric densities. Breast MRI can detect tumor margins, size, and multifocality more accurately than ultrasound and mammography.

8.

A novel diagnostic approach known as contrast-enhanced spectral mammography (CESM) offers accurate detection similar to breast MRI [Corso et al 2023].

9.

From: Diffuse Gastric and Lobular Breast Cancer Syndrome

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