Characteristics of submucosal gastric carcinoma with lymph node metastatic disease

H J Son, S Y Song,1 S Kim,3 J H Noh,2 T S Sohn,2 D S Kim1 & J C Rhee

Presented by intern 張家維

Histopathology 2005, 46, 158–165.

Introduction

2nd most common cause of cancer deaths East Asia and south America Korea and Japan early detection Early Gastric Carcinoma

Mucosa or Submucosa 5-year survival rate Lymph node metastasis

prognosis, submucosal invasion

Introduction

Depth of submucosal layer viaries The depth of submucosal gastric carcinoma

(SMGC) Lymph node metastasis

macroscopic appearance, location, size, tumor area, differentiation, invasion depth, submucosal vascularity, fibrosis near the tumor area

Age- and Sex- matched

Materials and methods

Sampling: 248 patients SMGC Surgical resection Samsung Medical Centre (Seoul, Korea) 1995/Jan.~ 2002/Oct. Total 917 patients SMGC

124 LN metastasis (13.5%) Anticancer therapy X Evidence of metastatic disease X

Materials and methods

124 SMGC with LN metastasis 124 SMGC without LN metastasis Age- and Sex- matched Specimens routinely examined 10% formalin Embedded in paraffin H & E stained

Materials and methods

Macroscopic:

Japanese Endoscopic Society Classification

Elevated, Depressed, Flat Microscopic:

Lauren classification

Materials and methods

Depth of submucosal invasion

1.Ocular lens scale, distance between the

lower edge of the muscularis mucosa and

the deepest invading front of the tumor

cells

2.sm3 method: sm1, sm2, sm3

3.sm2 method: smi , sme

Materials and methods

Tumor size

Longest dimension of the tumor area Tumor area

Longest dimension X its prependicular counterpart

Tumor vessels

vessels with a smooth muscle coat in the submucosa

Materials and methods

Statistical analysis:

Log linear model, McNemar’s test, A paired t-test, Wilcoxon’s signed rank test

P-value < 0.05 statistically significant SAS, version 6.12

Results

Pathological parameters and lymphnode metastatic disease

124 SMGC with lymph node metastasis 69 males (55.6%), 55 females (44.4%) 31~83 y/o, the mean age 56.3 y/o The main locations of the tumors 60 lower, 61 middle, 3 upper 1/3 Tumor size 5~125 mm, the mean = 45 mm Tumor area 0.8~105.0 cm2, the mean = 17.1 cm2

Results

Pathological parameters and lymphnode metastatic disease

The gross types of the tumors

35 elevated (28.2%), 85 depressed (68.5%), 4 flat (3.2%)

The histological differentiations (Lauren’s)

53 intestinal (42.7%), 65 diffuse (52.8), 6 mixed (4.8%)

111 N1 (89.5%), 13 N2 (10.5%)

Results

Pathological parameters and lymphnode metastatic disease

Significantly associated with node-positive SMGC 1. presence of lymphatic tumor emboli 2. a larger tumor area 3. a larger tumor size 4. a non-flat gross type 5. an increased vascularity No significant relationship 1. location 2. Lauren classification 3. tumor related fibrosis

Results

Depth-related parameters and lymph node metastatic disease

Ocular scale-measured depth

1. proved to have a significant correlation

with node-positive SMGC

2. superficial invasive, deeply invasive (2mm) The sm3 method

not well correlated The sm2 method

not well correlated

Results

Multivariate analyses for possible indicators of LN metastatic disease

Multivariate logistic regression analysis location, gross type, Lauren’s classification,

lymphatic tumor emboli, increased vascularity, tumor-related fibrosis, tumor size, depth (sm2 method)

The incidence of lymph node metastatic disease increased in the presence of lymphatic tumor emboli and in the tumors that invaded more than half of the submucosal layer

Discussion

EGC, the “early” horrible disaster curable disease early diagnosis and treatment programs The term of EGC has 2 innate defect 1. lymph node metastatic diseases 2. discriminate submucosal tumor call invasion 5-year survival rate 93~99% for node-negative EGC 73~90% for node-positive EGC 90~100% for intramucosal confinement 73~90% for submucosal invasion

Discussion

The treatment now for EGC

conducting minimally invasive surgical procedures

endoscopic mucosal resection, laparoscopic partial resection

need careful and intensively subclassification Remove all metastatic lymph nodes ?

chance of a cure↓ Factors related to lymph node metastatic disease

Discussion

SMGC lymph node metastasis rate 10~25% 917 SMGC in this tiral 13.5% LN metastasis The parameters related to LN metastasis lymphatic tumor emboli (uni- or multi- variate

analysis) depth-related (accurate invasion depth, sm2

method)

Discussion

The best way to represent a submucosal tumor invasion Tsuchiya et al. = sm3 not appropriate for classifying tumor from endoscopic biopsy specimen Yasuda et al. = accurately the depth submucosal tumor invasion of locally resected tumor > 300μm gastrectomy + LN dissection Japanese Classification of Gastric Cancer criteria (0.5mm) depth of submucosal tumor invasion < 0.5mm sm1 depth of submucosal tumor invasion > 0.5mm sm2

Discussion

Univariate analysis

accurate depth of tumor invasion Multivariate analysis

relative depth of tumor invasion Both accurate depth and relative depth of tumor

invasion are important in predicting LN metastasis of SMGC

A small group of superficial submucosal tumor invasions (even <1mm)

presented LN metasitasis

Discussion

In general, EGC with LN metastasis large, depressed growth (or ulcer), poorly

differentiated adenocarcinoma associated with peptic ulceration

Tumor size contact with submucosal lymphatics and venules Vascularity higher incidence in node-positive SMGCLN metastasis might be associated with tumor cells coming into contact with submucosal lymphatic and venules

Discussion

Lymphatic tumor invasion and deeper tumor invasion into the submucosa

simple and easy parameters for predicting LN metastasis from limited surgery specimens

Small group of superficial involvement of submucosa

LN metastasis Carefully selected patients for minimalizing operation Pathologist should carefully investigate the lymphatic

invasion and the depth of tmor invasion

Characteristics of intramucosal gastric carcinoma with lymph node metastatic disease

S Y Song, S Park,2 S Kim,3 H J Son1 & J C Rhee1

Presented by intern 張家維

Results

macroscopic appearance location size differentiation presence of ulceration vascularity presence of gastritis cystica profunda-like

glandular proliferation disruption of the muscularis mucosae and invasion

into the muscularis mucosae

Results

diffuse type histology (P < 0.001) and deep invasion into the muscularis mucosae (P < 0.05) were indicators of node-positive intramucosal EGCs

Conclusions

These histological indicators are easily accessible and seem to predict lymph node metastatic disease in limited surgical specimens.

Patients should be carefully selected despite the recent trend toward less invasive resection of EGCs, especially for those apparently confined to the mucosa.

Thank you for your attention