General principles

Gastric cancer findings are categorized and recorded using the upper case letters T, H, etc. The extent of disease for each parameter is expressed by Arabic numerals following the letter (e.g., T3 H1); where the extent of disease is unknown, X is used. The clinical and pathological classifications are derived from information acquired from various clinical, imaging, and pathological sources (listed in Table 1). The clinical classification (c) is derived at the conclusion of pretreatment assessment before a decision is made regarding the appropriateness of surgery. This classification is an essential guide to treatment selection and enables the evaluation of therapeutic options. The pathological classification (p) is based on the clinical classification supplemented or modified by additional evidence acquired from pathological examination. This informs decision-making regarding additional therapy and provides prognostic information. Where there is doubt regarding the T, N, or M category, the less advanced category should be used.

Table 1 Clinical and pathological classification

Histological tumor findings are recorded in the following order: tumor location, macroscopic type, size, histological type, depth of invasion, cancer–stroma relationship, pattern of infiltration, lymphatic invasion, venous invasion, lymph node metastasis, and resection margins. For example: L, Less, Type 2, 50 × 20 mm, tub1 > tub2, pT2, int, INFb, ly1, v1, pN1 (2/13), pPM0, pDM0 (see subsequent text for an explanation of the abbreviations).

Anatomical extent and stage of gastric carcinoma

Description of the primary tumor

Size and number of lesions

The two greatest dimensions should be recorded for each lesion. Where there are multiple lesions, the tumor with the most advanced T category (or the largest lesion where the T stage is identical) is classified.

Tumor location

The three gastric regions and the esophagogastric junction

The stomach is anatomically divided into three portions, the upper (U), middle (M), and lower (L) parts, by the lines connecting the trisected points on the lesser and greater curvatures (Fig. 1). Gastric tumors are described by the parts involved. If more than one part is involved, all involved portions should be recorded in descending order of degree of involvement, with the part containing the bulk of tumor first, e.g., LM or UML. Tumor extension into the esophagus or duodenum is recorded as E or D, respectively.

Fig. 1
figure 1

The three portions of the stomach. U upper third, M middle third, L lower third, E esophagus, D duodenum

The area extending 2 cm above to 2 cm below the esophagogastric junction (EGJ) is designated the EGJ area. Tumors having their epicenter in this area are designated EGJ carcinomas irrespective of histological type. The location of an EGJ carcinoma is described using the symbols E (proximal 2 cm segment) and G (distal 2 cm segment), with the dominant area of invasion described first, i.e., E, EG, E=G (both areas equally involved), GE, or G. The distance between the tumor center and the EGJ is recorded.

The EGJ is defined as the border between the esophageal and gastric muscles. Clinically this is identified by one of the following: (a) the distal end of the longitudinal palisading small vessels in the lower esophagus at endoscopy; (b) the horizontal level of the angle of His shown by barium meal examination; (c) the proximal end of the longitudinal folds of the greater curve of the stomach shown at endoscopy or barium meal study; or (d) the level of the macroscopic caliber change of the resected esophagus and stomach. It is important to note that the squamocolumnar junction (SCJ) does not always coincide with the EGJ.

Clinically, the tumor location is often expressed as cardia, fundus, body, incisura, and antrum.

Cross-sectional parts of the stomach

The stomach’s cross-sectional circumference is divided into four equal parts: the lesser (Less) and greater (Gre) curvatures, and the anterior (Ant) and posterior (Post) walls (Fig. 2). Circumferential involvement is recorded as Circ.

Fig. 2
figure 2

The four equal parts of the gastric circumference. Less lesser curvature, Gre greater curvature, Ant anterior wall, Post posterior wall

Carcinoma in the remnant stomach

Carcinoma in the remnant stomach encompasses all carcinomas arising in the remnant stomach following a gastrectomy, irrespective of the histology of the primary lesion (benign or malignant) or its risk of recurrence, the extent of resection, or method of reconstruction. The following information should be recorded, as well as, if available, information on the extent of resection and type of reconstruction of the previous gastrectomy.

  1. a.

    The primary lesion at the previous gastrectomy: benign (B), malignant (M), or unknown (X).

  2. b.

    The time interval elapsed between the previous gastrectomy and the current diagnosis, in years (unknown: X).

  3. c.

    Tumor location in the remnant stomach: anastomotic site (A), gastric suture line (S), other gastric site (O), or total remnant stomach (T). Extension into the esophagus (E), duodenum (D), or jejunum (J) is recorded.

Examples: B-20-S, M-09-AJ.

Macroscopic types

Basic classification

Gross tumor morphology is categorized as either superficial or advanced type. Superficial type is typical of T1 tumors while T2–4 tumors usually manifest as advanced types (Fig. 3). Viewed from the mucosal surface, gross tumor appearance is categorized into six types (Table 2). Type 0 is subdivided according to the Macroscopic Classification of Early Gastric Cancer (Sect. 2.1.3.2). Although macroscopic type is determined regardless of the depth of tumor invasion, the T category should also be recorded.

Fig. 3
figure 3

Macroscopic types of advanced gastric cancer

Table 2 Macroscopic types
Subclassification of Type 0 (Fig. 4, modified from the Japanese Endoscopy Society Classification of 1962)
Fig. 4
figure 4

Subclassification of Type 0

Superficial tumors with two or more components should have all components recorded in order of the surface area occupied, e.g. 0-IIc + III (Table 3).

Table 3 Subclassification of Type 0
Description of macroscopic type

The macroscopic tumor type should be recorded in both the clinical and pathological classifications.

Histological classification (Table 4)

Where a malignant epithelial tumor consists of more than one histological subtype, the different histological components should be recorded in descending order of the surface area occupied, e.g., tub 1 > pap (see table below).

Table 4 Histological classification of gastric tumors

Depth of tumor invasion (T)

The depth of tumor invasion is recorded as the T-category. Conventional characters denoting depth of tumor invasion are also recorded: M, SM, MP, SS, SE, SI (see below). The prefixes “c” and “p” are used in conjunction with the T-category and not with the characters M, SM, etc. (e.g., a pathologically diagnosed mucosal tumor should be recorded as pT1a, not pM). Tumor invasion into the muscularis mucosa is included in the M category. Early gastric cancer comprises of T1 tumors irrespective of lymph node metastasis.

TX:

Depth of tumor unknown

T0:

No evidence of primary tumor

T1:

Tumor confined to the mucosa (M) or submucosa (SM)

T1a:

Tumor confined to the mucosa (M)

T1b:

Tumor confined to the submucosa (SM)Footnote 1

T2:

Tumor invades the muscularis propria (MP)

T3:

Tumor invades the subserosa (SS)

T4:

Tumor invasion is contiguous to or exposed beyond the serosa (SE) or tumor invades adjacent structures (SI)

T4a:

Tumor invasion is contiguous to the serosa or penetrates the serosa and is exposed to the peritoneal cavity (SE)Footnote 2

T4b:

Tumor invades adjacent structures (SI).Footnote 3

Cancer stromal volume, infiltrative pattern, and capillary invasion

Cancer stromal volume (to be recorded for T1b or deeper tumors)
  • Medullary type (med): Scanty stroma

  • Scirrhous type (sci): Abundant stroma

  • Intermediate type (int): The quantity of stroma is intermediate between the two above types.

Tumor infiltrative (INF) pattern into the surrounding tissues (to be recorded in T1b or deeper tumors; Fig. 5)
Fig. 5
figure 5

Tumor infiltrative (INF) pattern

INFa:

Tumor displays expanding growth with a distinct border from the surrounding tissue

INFb:

Tumor shows an intermediate pattern between INFa and INFc

INFc:

Tumor displays infiltrative growth with no distinct border with the surrounding tissue.

Capillary invasionFootnote 4
  • 2.1.6.3.1 Lymphatic invasion (ly)

    • ly0: No lymphatic invasion

    • ly1: Minimal lymphatic invasion

    • ly2: Moderate lymphatic invasion

    • ly3: Marked lymphatic invasion

  • 2.1.6.3.2 Venous invasion (v)

    • v0: No venous invasion

    • v1: Minimal venous invasion

    • v2: Moderate venous invasion

    • v3: Marked venous invasion

Lymph node metastasis

Anatomical definition of lymph nodes and lymph node regions (Figs. 6, 7)

The lymph nodes (LNs) of the stomach are defined and given station numbers, as shown in Table 5 and Figs. 7, 8, 9. Lymph node stations 1–12 and 14v are defined as regional gastric lymph nodes; metastasis to any other nodes is classified as M1. In tumors invading the esophagus, lymph node numbers 19, 20, 110, and 111 are included as regional lymph nodes. For carcinomas arising in the remnant stomach with a gastrojejunostomy, jejunal lymph nodes adjacent to the anastomosis are included as regional lymph nodes. Please refer to the “Gastric Cancer Treatment Guidelines” [1] for a detailed account of which lymph nodes are to be dissected in gastric resection with curative intent.

Table 5 Anatomical definitions of lymph node stations
Fig. 6
figure 6

Location of lymph node stations

Fig. 7
figure 7

Location of lymph nodes in the esophageal hiatus and in the infradiaphragmatic and paraaortic regions

Fig. 8
figure 8

Histological evaluation criteria of tumor response after preoperative therapy

Fig. 9
figure 9

Measurement of the lesion from the serosal surface

Recording of lymph node metastasis

For surgical resection specimens, the total number of lymph nodes and the number of involved lymph nodes at each nodal station are recorded. When a tumor nodule without histological evidence of lymph node structure is found in the lymphatic drainage area of the primary tumor, it is recorded as extranodal metastasis and counted as a metastatic lymph node in the pN determination.

Lymph node metastasis (N)
  • NX: Regional lymph nodes cannot be assessed

  • N0: No regional lymph node metastasis

  • N1: Metastasis in 1–2 regional lymph nodes

  • N2: Metastasis in 3–6 regional lymph nodes

  • N3: Metastasis in 7 or more regional lymph nodes

  • N3a: Metastasis in 7–15 regional lymph nodes

  • N3b: Metastasis in 16 or more regional lymph nodes

Although it is not a prerequisite, the examination of 16 or more regional lymph nodes is recommended for N status determination.

Metastatic ratio of lymph nodes

The metastatic ratio is the ratio of metastatic nodes to the total number of dissected nodes and is recorded for each nodal station for all regional lymph nodes.

Distant metastasis

Metastasis to sites other than regional lymph nodes (distant metastasis) is M1 disease. In addition, peritoneal metastasis, peritoneal lavage cytology, and hepatic metastasis may be described by the conventional symbols P, CY, and H, respectively (see below). Positive peritoneal lavage cytology is recorded as cy+ by the International Union Against Cancer (UICC)/TNM system.

Presence or absence and sites of distant metastasis (M)

  • MX: Distant metastasis status unknown

  • M0: No distant metastasis

  • M1: Distant metastasis

Sites of metastasis are recorded using the following notation: LYM (lymph nodes), SKI (skin), PUL (lung), MAR (bone marrow), OSS (bone), PLE (pleura), BRA (brain), MEN (meninx), ADR (adrenal), OTH (others)Footnote 5

Peritoneal metastasis (P)

  • PX: Peritoneal metastasis is unknown

  • P0: No peritoneal metastasis

  • P1: Peritoneal metastasis.

Peritoneal lavage cytology (CY)

  • CYX: Peritoneal cytology not performed

  • CY0: Peritoneal cytology negative for carcinoma cells

  • CY1: Peritoneal cytology positive for carcinoma cells

A macroscopically curative resection with CY1 is R1.

Hepatic metastasis (H)

  • HX: Hepatic metastasis is unknown

  • H0: No hepatic metastasis

  • H1: Hepatic metastasis.

Stage grouping

figure a

Treatment evaluation

Evaluation after surgical or endoscopic resection

Surgical specimen resection margin

Proximal margin (PM)
PMX:

Involvement of the proximal margin cannot be assessed

PM0:

No involvement of the proximal margin

PM1:

Involvement of the proximal margin.

Distal margin (DM)
DMX:

Involvement of the distal margin cannot be assessed

DM0:

No involvement of the distal margin

DM1:

Involvement of the distal margin.

Resection margin of the endoscopic resection specimen

Horizontal margin (HM)
HMX:

Involvement of the horizontal margin cannot be assessed

HM0:

No involvement of the horizontal margin

HM1:

Involvement of the horizontal margin.

Vertical margin (VM)
VMX:

Involvement of the vertical margin cannot be assessed

VM0:

No involvement of the vertical margin

VM1:

Involvement of the vertical margin.

Residual tumor (R)

The presence or absence of residual tumor after surgery is described as the R status; R0 is a curative resection with negative resection margins; R1 and R2 are non-curative resections.

RX:

Presence of residual tumor cannot be assessed

R0:

No residual tumor

R1:

Microscopic residual tumor (positive resection margin or CY1)

R2:

Macroscopic residual tumor.

Tumor evaluation after preoperative treatment

Description of tumor classification after preoperative treatment

Tumor classification after preoperative chemotherapy or chemoradiotherapy is designated by the prefix ‘y’. The clinical classification following preoperative treatment is designated ycTNM and the pathological classification ypTNM. The ycTNM and ypTNM classification describes the extent of tumor actually present at the time of that examination; it is not an estimate of the extent of tumor prior to preoperative therapy. Only viable tumor cells are taken into account when calculating ypTNM. Signs of tumor regression, including scars, areas of fibrosis, granulation tissue, or mucin lakes are not taken into consideration.

For example: A large adenocarcinoma with computed tomography (CT) evidence of serosal irregularity and lymph node metastasis was classified as cT4aN1M0. Preoperative chemotherapy achieved significant tumor regression, with the tumor being undetectable by endoscopy and CT (ycT0N0M0). Gastrectomy was performed and histological examination revealed viable carcinoma cells in the muscularis propria and in two regional lymph nodes; granulation tissue with mucin lakes was present in five other lymph nodes (ypT2N1M0).

Histological evaluation criteria of tumor response after preoperative therapy (Fig. 8)

The histological response of the primary tumor should be evaluated in the section where the tumor is thought to have been located at the pretreatment assessment and in the sections where tumor cells are likely to remain. Viable tumor cells are defined as cells which are judged to be capable of proliferation.

Grade 0 (no effect):

No evidence of effect

Grade 1:

(slight effect)

Grade 1a (very slight effect):

Viable tumor cells occupy more than 2/3 of the tumorous area

Grade 1b (slight effect):

Viable tumor cells remain in more than 1/3 but less than 2/3 of the tumorous area

Grade 2 (considerable effect):

Viable tumor cells remain in less than 1/3 of the tumorous area

Grade 3 (complete response):

No viable tumor cells remain. It is recommended that the finding is confirmed on additional sectioning.

Response evaluation of chemotherapy and radiotherapy

Tumor response to chemotherapy and/or radiotherapy is assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [2].

The Japanese Gastric Cancer Association (JGCA) developed an original method to evaluate the response of the primary gastric lesion to chemotherapy or radiotherapy [3], but it was not widely used, mainly because of technical difficulties. In the RECIST, primary gastric tumors are regarded as non-target lesions and endoscopic diagnosis is not recommended as an objective evaluation. However, the response of the primary tumor is clinically important and the JGCA methods may provide useful information in future neoadjuvant trials. The results of response evaluation of the primary tumor made by the following methods can be recorded and used as information that is additional to the RECIST results in some trial settings.

JGCA response evaluation of primary tumor

Tumor response, morphological changes, and efficacy are evaluated by double-contrast barium meal study and/or endoscopic examination of the following three types of primary lesions.

Measurable lesions (a-lesions)

Reduction rate = (longest diameter before therapy − longest diameter after therapy)/longest diameter before therapy.

Evaluable but not measurable lesions (b-lesions)
  1. (i)

    Describe changes in protruded lesions as follows:

    Progression, no change, regression, flattening, or disappearance

  2. (ii)

    Describe changes in excavated lesions as follows:

    • Raised margin: progression, no change, regression, flattening, or disappearance

    • Crater: progression, no change, regression, flattening, or disappearance.

Diffusely infiltrating lesions (c-lesions) [3]

In diffusely infiltrating tumors (type 4), treatment response may be evaluated by expansion of the gastric lumen. In principle, the squares of the lesion shown with standing barium X-ray examination are compared before and after therapy, at the same position with the same volume of barium, and the enlargement rate is calculated.

Enlargement rate = (product calculated before therapy) − (product calculated after therapy)/(product calculated before therapy) × 100%

Definition of response in primary lesion
  • Complete response (CR)

    Disappearance of all tumor lesions and no diagnosis of carcinoma. Biopsy specimens are negative for carcinoma.

  • Partial response (PR)

    • a-lesions: At least a 30% decrease in total size

    • b-lesions: Remarkable regression and flattening of a tumor on X-ray/endoscopic examinations, which roughly corresponds to at least a 50% decrease in tumor size.

    • c-lesions: At least 50% enlargement of the gastric lumen in the area of the lesions by X-ray examination.

  • Stable disease (SD)

    Changes in tumor size or shape are less than PR, but are not progressive disease (PD).

  • Progressive disease (PD)

    Increase in tumor size and/or worsening of the shape (20% or more increase in a-lesions), or new intragastric lesions.

Handling of the resected specimen

Description of findings

Pathological findings are recorded when the following conditions are met.

  1. (a)

    The whole resected stomach is macroscopically observed.

  2. (b)

    The representative sections of the whole resected stomach including the carcinoma are microscopically examined.

Preparation of the resected stomach

After gross inspection and measurement of any serosal tumor involvement (Fig. 9), the stomach is, in principle, opened along the greater curvature. On examination from the mucosal side, the tumor size and the length of the proximal and distal resection margins are measured (Fig. 10).

Fig. 10
figure 10

Measurement of the lesion from the mucosal surface. PM proximal margin, DM distal margin

Fixation of the resected stomach

After dissection of the lymph nodes from the specimen, the stomach is placed on a flat board with the mucosal side up, pinned at the edges with stainless steel pins, and fixed in a 10% buffered formalin solution. A relatively short fixation time (48 h) is recommended for additional immunohistochemical or genetic examinations in the future.

Sectioning of the stomach

Firstly a section is taken along the lesser curvature as a reference line to assess background mucosal changes. In Type 0 superficial tumors, a set of sections parallel to the reference line should be made at 5- to 7-mm intervals (Fig. 11). In advanced tumors, the area of deepest invasion should be sectioned parallel to the reference line. If there is concern about tumor margins, additional sections should be taken (Fig. 12). In multiple tumors or tumors of unusual configuration, suitable sectioning to obtain accurate findings must be devised on a case-by-case basis. The carcinoma in a remnant stomach should be sectioned taking into account its relationship with the suture line and anastomosis.

Fig. 11
figure 11

Sectioning of Type 0 superficial tumors

Fig. 12
figure 12

Sectioning of advanced tumors. A Additional sectioning for decision on T-category. B Sectioning of the largest cross-sectional plane. C Sectioning of the region of deepest invasion. D Sectioning to examine the proximal margin

Sectioning of lymph nodes

Each dissected lymph node should be studied individually. The plane of largest dimension of the node including the hilus should be sectioned.

Handling of endoscopically resected specimens

A single resection procedure performed for a single lesion is defined as “en-bloc resection”, and multiple resection procedures for a single lesion are defined as “piecemeal resection”.

Fixation, inspection, and sectioning

The specimen is spread out, pinned on a flat board, and fixed in 10% buffered formalin solution. The size of the specimen, the size and shape of the tumor, and the margins should be recorded on a schematic diagram. The proximal and distal margins are indicated. Fixed materials should be sectioned serially at 2-mm intervals parallel to a line that includes the closest resection margin of the specimen (Fig. 13). When resection margin involvement cannot be denied on a rebuilt diagram such as that shown in Fig. 14, sectioning should be added to examine the true margin.

Fig. 13
figure 13

Sectioning of endoscopic resection material

Fig. 14
figure 14

Rebuilt diagram of endoscopic resection material. The cancerous area is marked with a thick line. SM1 submucosal invasion. A Additional sectioning to examine the true margin

Histological diagnosis

The following should be recorded.

  • The size and number of specimens

  • Macroscopic type of the tumor

  • The size of the tumor (longest and shortest diameters)

  • Histological type of the tumor

    • Different histological types seen in a tumor are recorded according to their quantitative predominance

  • Depth of tumor invasion (pT1a, pT1b1, pT1b2 or M, SM1, SM2)

    • Depth is determined and recorded only when the vertical margin is negative for cancer invasion.

    • When submucosal invasion is present, the actual measured length (in microns) from the lower border of the muscularis mucosae should also be recorded. If the muscularis mucosae is obscure due to ulcerative changes, the length should be measured on the virtual line based on the adjacent normal layer.

    • When the vertical margin is involved, the possibility of deeper invasion should be described.

  • Intratumoral ulcerative findings

    • UL(−): Ulcer or ulcer scar is absent

    • UL(+): Ulcer or ulcer scar is present.

  • Capillary invasion

    • ly(−): Lymphatic invasion is absent

    • ly(+): Lymphatic invasion is present

    • v(−): Venous invasion is absent

    • v(+): Venous invasion is present.

  • Horizontal margin involvement

    • HMX: Horizontal margin involvement is unknown

    • HM0: Horizontal margin is not involved (The length of the margin should be recorded)

    • HM1: Horizontal margin is involved (The number of positive sections should be recorded).

  • Vertical margin involvement

    • VMX: Vertical margin involvement is unknown

    • VM0: Vertical margin is not involved

    • VM1: Vertical margin is involved.

Histological diagnosis of gastric biopsy (“Group Classification”)

Principles

This classification is applied only to endoscopic biopsy materials. Materials obtained by polypectomy, endoscopic resection, or surgery are not included. The “Group Classification” is applied only to epithelial tissue. In principle, the diagnosis is written first, followed by the Group Classification.

Classification

Group X:

Inappropriate material for which histological diagnosis cannot be made

Group 1:

Normal tissue or non-neoplastic lesion

Group 2:

Material for which diagnosis of neoplastic or non-neoplastic lesion is difficult

In such a case, the pathologist should describe the lesion as “indefinite for neoplasia” and add the following reasons for clinicians:

  1. (1)

    Atypical cells exist, but diagnosis of neoplasia based on cellular atypia is difficult because of the small volume.

  2. (2)

    Atypical cells exist, but diagnosis of neoplastic or non-neoplastic lesion is difficult due to remarkable erosion and/or inflammation.

  3. (3)

    Atypical cells exist, but diagnosis of neoplastic or non-neoplastic lesion is difficult due to tissue damage.

Group 3:

Adenoma

Group 4:

Neoplastic lesion that is suspected to be carcinoma

Group 5:

Carcinoma

The histological subtype of carcinoma should be recorded.