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. 2023 Dec 31;44(1):127–172. doi: 10.1002/cac2.12516
Sample type Grade I recommendations Grade II recommendations Grade III recommendations
Gross examination Microscopic assessment
Biopsy specimen* Evaluation of the size and number of samples Confirm the histopathology of the lesion:
  • Cancerous/non‐cancerous

  • Benign/malignant

  • Histological subtype

  • Depth of invasion (if possible)

Immunohistochemical examination for diagnosis if needed j Evaluate the status of Helicobacter pylori infection m (Evidence 1B)
Endoscopic resection specimen a (EMR/ESD)
  • Tumor site b

  • Tumor size (cm3)

Intra‐epithelial neoplasm/adenoma (low grade/high grade)Invasive carcinoma:
  • Histological subtype d /Lauren classification e

  • Histological grade

  • The depth of penetration into the gastric wall

  • The proximal/distal margin and the deep margin

  • Vascular and lymphatic invasion

  • Immunohistochemical examination for diagnosis if needed j

  • Early‐stage gastric cancer

  • Macroscopic appearance k

Evaluate the status of Helicobacter pylori infection m (Evidence 1B)
Surgical resection specimens for those without neoadjuvant therapy#
  • Type of the surgical specimen

  • Tumor site

  • Tumor size (cm3)

  • Distance of tumor from the proximal and distal margin

  • The stations and number and of lymph nodes retrieved (at least 16 lymph nodes and/or preferentially >30 lymph nodes to be retrieved) c

  • Histological subtype/Lauren classification/Histological grade (G1, G2, G3)

  • The depth of penetration into the gastric wall (pT classification)

  • Vascular, lymphatic, and perineural invasion

  • Proximal/distal margin f

  • Involvement of the esophagus/duodenum (if resected)

  • Number of positive lymph nodes and total number of lymph nodes examined (pN classification)

  • Number of lesions g

  • Distant metastasis (pM stage) h

  • pTNM stage (8th AJCC/UICC edition)

  • Immunohistochemical examination for diagnosis if needed j

  • Advanced stage gastric cancer

  • Macroscopic appearance l

Evaluate the status of Helicobacter pylori infection m (Evidence 1B)
Surgical resection specimens for those who had neoadjuvant therapy #
  • Type of the surgical specimen

  • Tumor site

  • Tumor size (cm3)

  • Distance of tumor from the proximal and distal margin

  • Histological subtype/Lauren classification/Histological grade (G1, G2, G3)

  • The depth of penetration into the gastric wall (pT classification)

  • Immunohistochemical examination for diagnosis if needed j Gastric cancer with the advanced stage l

Evaluate the status of Helicobacter pylori infection m (Evidence 1B)
  • The stations and number and of lymph nodes retrieved (at least 16 lymph nodes and/or preferentially >30 lymph nodes to be retrieved) (If lesion is not evident, careful examination and multipoint sampling should be made to avoid misdiagnosis or down staging)

  • Vascular, lymphatic, and perineural invasion

  • Proximal/distal margin f

  • Involvement of the esophagus/duodenum (if resected)

  • Number of positive lymph nodes and total number of lymph nodes examined (pN classification)

  • Number of lesions g

  • Distant metastasis (pM stage) h

  • pTNM stage (8th AJCC/UICC edition)

  • TRG i

  • ypTNM stage (8th AJCC/UICC edition)

Abbreviations: EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; pT, pathological tumor depth invasion classification; pN, pathological nodal classification; pM, pathological distant metastasis classification; ypTNM, post neoadjuvant pathological tumor‐node‐metastasis classification; AJCC/UICC, American Joint Cancer Committee/Union Internationale Contre le Cancer.

*

When a diagnosis cannot be established through biopsy, cytological brushings or lavage fluid may serve to confirm the presence of a tumor. In cases of unresectable advanced gastric cancer, an exfoliative cytological examination of their peritoneal ascites or pleural effusion, along with biopsies from distant metastases, can aid in pathological diagnosis.

#

Institutions are encouraged to adopt a standardized pathological report template, as it streamlines diagnosis and enables consistent clinical analysis. A reference template is provided in section 5.3.

Notes:

a

Endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD) have emerged as the new alternative treatment for early‐stage gastric cancer [14, 15]. EMR/ESD specimens should be meticulously resected, collected and prepared according to standardized protocols by the endoscopists or surgeons. It is advised that all samples be sectioned at intervals of 2‐3 mm, perpendicular to the mucosal surface [16, 17, 18].

b

As per the 8th edition of the AJCC/UICC staging system for gastric cancer, esophageal cancer, and EGJ carcinoma [19], the staging criteria for EGJ carcinoma or gastric‐cardia carcinoma are specified as follows: 1) When the tumor infiltrates the gastroesophageal boundary and its epicenter is <2 cm proximal from the EGJ (Siewert I and II), staging criteria for esophageal cancer should be applied; 2) In cases where the tumor invades the gastroesophageal boundary but its epicenter is located ≥2 cm distal from the EGJ (Siewert III), the staging criteria for gastric cancer should be utilized. Thus, accurately determining the location of the gastroesophageal boundary and assessing whether it has been invaded by the tumor are crucial considerations.

c

In patients who have undergone radical gastrectomy without neoadjuvant therapy, it is advisable to pathologically evaluate at least ≥16 lymph nodes for proper staging. However, for a more precise staging evaluation, the ideal number of evaluated lymph nodes should exceed 30. To facilitate an accurate assessment of lymph node metastasis extent, surgeons and pathologists are recommended to systematically collect and categorize peri‐gastric lymph nodes based on their respective stations. These details should be included in the postoperative pathological report along with the total number of metastatic lymph nodes and the total number of lymph nodes examined by clinicians for comprehensive evaluation.

d

The histopathological classification of gastric cancer follows the guidelines outlined in the “World Health Organization (WHO) classification of tumours of the digestive system (2019 edition)” [20]. In instances where achieving a pathological diagnosis poses challenges in lower‐tier hospitals, it is advisable to forward the specimen samples to a specialized center/hospital for further evaluation.

e

As per the Lauren classification [21], gastric adenocarcinoma is classified into intestinal type, diffuse type and mixed type based on its histological growth patterns. The intestinal type typically presents as intestinal metaplasia, predominantly comprising highly to moderately differentiated atypical glands. Occasionally, proximal regions of tumor invasion may exhibit poor differentiation. In contrast, the diffuse type is characterized by loosely adherent cells that extensively infiltrate gastric walls, displaying minimal to no glandular formation. These cells typically appear small, scattered, or clustered, with noticeable interstitial fiber proliferation. The mixed type consists of an approximately equal distribution of intestinal and diffuse type cells.

f

This guideline specifies a positive surgical margin as the detection of cancer cells within a 1 mm distance from the resected margin.

g

The identification of carcinomatous nodules within sub‐serous adipose tissues neighboring the primary tumor site should be considered as regional lymph node metastasis, regardless of the absence of residual lymph node tissues [19]. It is advisable to distinctly document both metastatic lymph nodes and carcinomatous nodules for proper record‐keeping.

h

Tissues confirmed as metastatic and obtained from areas distant to the stomach should be classified as distant metastasis (pM1). This classification encompasses metastatic tissues from remote lymph node stations and cancerous cells identified in other organs, including instances of intraperitoneal washings or peritoneal seedings [19].

i

Assessment of the tumor regression grade (TRG) involves evaluating residual tumor cells and the extent of fibrosis following anti‐cancer treatment, as outlined in the 8th AJCC TNM staging system [19] or the guidelines from National Comprehensive Cancer Network (NCCN) [22]. The 8th edition of the AJCC staging system introduced the post‐neoadjuvant pathological tumor‐node‐metastasis classification (ypTNM) to depict the postoperative pathological staging subsequent to neoadjuvant therapy.

j

In cases where establishing a pathological diagnosis poses challenges, gastric cancer‐related markers can serve for differential diagnosis, prognostic assessment, and guiding treatment or follow‐up [23].

k

Early‐stage gastric cancer is characterized by its confinement within the mucosa and submucosa, regardless of evidence of regional lymph node metastasis.

l

Advanced gastric cancer is delineated by infiltration into the muscularis propria or the deeper layer of the gastric wall. The Borrmann classification consists of four subtypes: Type I represents a nodular polypoid tumor; Type II indicates a local central, bowl‐shaped ulcer with distinct elevated margins; Type III suggests an infiltrating ulcerative tumor with indistinct boundaries; and Type IV depicts a diffuse tumor characterized by poorly demarcated, infiltrative growth (local Borrmann Type IV, diffuse tumor infiltration of the gastric wall [linitis plastica]).

m

The 8th edition of the AJCC/UICC staging system for gastric cancer mandates the documentation of the Helicobacter pylori infection status [19].