Lect 4-gastric tumors


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Lect 4-gastric tumors

  1. 1. Gastric Tumors SMS 2044
  2. 2. GASTRIC CANCER <ul><li>Gastric cancer is the second most common fatal cancer in the world with high frequency in Japan. </li></ul><ul><li>(after lung cancer) </li></ul><ul><li>The disease presents most commonly in the 5 th and 6 th decades of life and affect males twice as often as females. </li></ul>Contn…
  3. 3. Gastric Cancer Epidemiology Forth common types of cancer Second most common cancer related death Geographic variations (ten times) Continuing decline Primarily a decline of distal GC (2000) (2000)
  4. 4. TUMORS <ul><li>The gastrointestinal tract tumors arising from the mucosa predominate over mesenchymal tumors. </li></ul><ul><li>Parenchyma is a term used to describe a bulk of a substance and it is the functional part of an organ in the body. </li></ul><ul><li>This is in contrast to the stroma, which refers to the structural tissue of organs, being exactly, connective tissues. </li></ul>
  5. 5. <ul><li> The cause of the disease multistep process but several predisposing factors attributed to cause the disease : </li></ul><ul><li>a. Environment e. Atrophic gastritis </li></ul><ul><li>b. Diet f. Chronic gastric ulcer </li></ul><ul><li>c. Heredity g. Adenomatous polyps </li></ul><ul><li>d. Achlorhydria i. H. Pyloric colonisation </li></ul>
  6. 6. Gastric Cancer Environmental factors H. pylori Genetic factors Etiological Factors of Gastric Cancer Precancerous changes
  7. 7. TYPES OF GASTRIC CANCER: <ul><li>A . Benign Tumours </li></ul><ul><li>B . Malignant Tumours </li></ul>
  8. 8. <ul><li> The benign groups includes:- </li></ul><ul><li>1. Non-neoplastic gastric polyps </li></ul><ul><li>2. Adenomas </li></ul><ul><li>3. Neoplastic gastric polyps </li></ul><ul><li>4. Smooth muscles tumours benign </li></ul><ul><li>(Leiomyomas) </li></ul><ul><li>5 . Polyposis Syndrome (eg:- Polyposis coli, </li></ul><ul><li>Juvenile polyps and P.J. Syndrome) </li></ul><ul><li>6. Other benign tumours are fibromas, neurofibromas, aberrat pancreas and </li></ul><ul><li>angiomas. </li></ul>
  9. 9. <ul><li>Gastric Tumors </li></ul><ul><li>These are broadly classified into polyps and carcinoma. </li></ul><ul><li>Gastric Polyps </li></ul><ul><li>The term &quot;polyp&quot; is applied to any nodule or mass that projects above the level of the surrounding mucosa. </li></ul><ul><li>Occasionally, a lipoma or leiomyoma arising in the wall of the stomach may protrude from under the mucosa to produce an apparent polypoid lesion. </li></ul><ul><li>However, the use of the term &quot;polyp&quot; in the gastrointestinal tract is generally restricted to mass lesions arising in the mucosa. </li></ul>
  10. 10. <ul><li>Hyperplastic polyps arise from an exuberant reparative response to chronic mucosal damage and hence are composed of a hyperplastic mucosal epithelium and an inflamed edematous stroma . </li></ul><ul><li>They are not true neoplasms. </li></ul><ul><li>Fundic gland polyps are small collections of dilated corpus-type glands thought to be small hamartomas. </li></ul><ul><li>On the other hand, the less common adenomas contain dysplastic epithelium . </li></ul><ul><li>As with colonic adenomas, adenomas are true neoplasms. </li></ul>MORPHOLOGY
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  12. 12. Histoology <ul><li>Histopathology report of a gastric polyp should comment on the following: </li></ul><ul><li>Histological features of the polyp: </li></ul><ul><li>Presence of cystic dilatation </li></ul><ul><li>Lining epithelium of the cyst </li></ul><ul><li>Presence of muscle fibres in the lamina propria </li></ul><ul><li>Inflammatory inflltrate ( Eg. presence of eosinophils). </li></ul><ul><li>Presence of muscle fibres in the lamina propria. </li></ul><ul><li>Presence or absence of dysplasia or malignancy in case of Neoplastic. </li></ul>
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  15. 15. PATHOLOGY OF GASTRIC (MALIGNANT) TUMOURS: <ul><li> The gastric cancer may arise in the antrum (50%), the gastric body (30%), the fundus or oesophago-gastric juntion (20%). </li></ul>
  16. 16.  Types of Malignant Tumours : <ul><li>a. Adenocarcinoma </li></ul><ul><li>b. Leiomyosarcoma </li></ul><ul><li>c. Lymphomas </li></ul><ul><li>d. Carcinoid Tumours </li></ul>
  17. 17. Pathohistologic classification Histology Adenocarcinoma 90% Lymphoma 5% Stromal 2% Carcinoid <1% Metastasis <1% Adenosquamous/squamous <1% Miscellaneous <1%
  18. 18. <ul><li> Early Gastric Cancer: Defined as cancer which is confined to the mucosa and submucosa regard- less of lymph nodes status. </li></ul><ul><li> Advanced Gastric Cancer : Defined as tumor that has involved the muscularis propria of the stomach wall . </li></ul>
  19. 19. <ul><li>1. Polypoid or Proliferative </li></ul><ul><li>2. Ulcerating </li></ul><ul><li>3. Ulcerating/Infiltrating </li></ul><ul><li>4. Diffuse Infiltrating (Linnitus- </li></ul><ul><li>Plastica) </li></ul> The macroscopic forms of gastric cancers are classified by (Bormann classification) into:-
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  22. 22. Carcinoma of the stomach Free powerpoint template: www.brainybetty.com
  23. 23. Pathogenesis <ul><li>Vast majority are adenocarcinomas </li></ul><ul><li>Arise on background of chronic gastritis, intestinal metaplasia, dysplasia </li></ul><ul><li>Most cases advanced at presentation </li></ul>
  24. 24. Pathogenesis <ul><li>The major factors thought to affect the genesis of this form of cancer are </li></ul><ul><li>Environmental. </li></ul><ul><li>Risk factors for the increasingly more common diffuse carcinoma are largely unknown, although germ-line mutations in E-cadherin leading to an autosomal dominant inheritance of diffuse gastric carcinoma. </li></ul><ul><li>E-cadherin (epithelial) , also known as CDH1 , is a human gene . CDH1 has also been designated as </li></ul>
  25. 25. <ul><li>Chronic gastritis associated with H. pylori infection remains a major risk factor for gastric carcinoma. </li></ul><ul><li>A recent prospective study from Japan has underscored the relationship between H. pylori infection and gastric cancer. </li></ul><ul><li>The risk is particularly high in those with chronic gastritis limited to the gastric antrum. </li></ul><ul><li>These patients develop severe gastric atrophy, intestinal metaplasia, and ultimately dysplasia and cancer. </li></ul><ul><li>Perhaps chronic inflammation generates DNA-damaging free radicals, and the resulting mutations lead to hyperproliferation that is not balanced by apoptosis. Much remains to be known. </li></ul>
  26. 26. <ul><li>The location of gastric carcinomas within the stomach is as follows: </li></ul><ul><ul><ul><li>pylorus and antrum, 50% to 60%; </li></ul></ul></ul><ul><ul><ul><li>cardia, 25%; </li></ul></ul></ul><ul><ul><ul><li>and the remainder in the body and fundus. </li></ul></ul></ul><ul><li>The lesser curvature is involved in about 40% and the greater curvature in 12%. Thus, a favored location is the lesser curvature of the antropyloric region . </li></ul><ul><li>Although less frequent, an ulcerative lesion on the greater curvature is more likely to be malignant. </li></ul><ul><li>Gastric carcinoma is classified on the basis of depth of invasion, macroscopic growth pattern, and histologic subtype. </li></ul>MORPHOLOGY
  27. 27. <ul><li>The morphologic feature having the greatest impact on clinical outcome is the depth of invasion. </li></ul><ul><li>Early gastric carcinoma is defined as a lesion confined to the mucosa and submucosa, regardless of the presence or absence of perigastric lymph node metastases. </li></ul><ul><li>I. Protruded IIA. Superficial-elevated IIB. Superficial-flat IIC. Superficial-depressed III. Excavated </li></ul><ul><li>Advanced gastric carcinoma is a neoplasm that has extended below the submucosa into the muscular wall and has perhaps spread more widely. </li></ul><ul><li>I. Polypoid or fungating II. Excavating III. Ulcerated and infiltrating IV. Infiltrating (diffuse thickening) </li></ul><ul><li>Gastric mucosal dysplasia is the presumed precursor lesion of early gastric cancer, which then in turn progresses to &quot;advanced&quot; lesions. </li></ul>
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  29. 29. <ul><li>Ulcerative gastric carcinoma. The ulcer is large with irregular, heaped-up margins. </li></ul><ul><li>There is extensive excavation of the gastric mucosa with a necrotic gray area in the deepest portion. Compare with the benign peptic ulcer </li></ul>The three macroscopic growth patterns of gastric carcinoma, which may be evident at both the early and advanced stages, are (1) Exophytic, with protrusion of a tumor mass into the lumen; (2) flat or depressed, in which there is no obvious tumor mass within the mucosa; and (3) Excavated, whereby a shallow or deeply erosive crater is present in the wall of the stomach.
  30. 30. <ul><li>Exophytic tumors may contain portions of an adenoma. </li></ul><ul><li>Flat or depressed malignancy presents only as regional effacement of the normal surface mucosal pattern. </li></ul><ul><li>Excavated cancers may mimic, in size and appearance, chronic peptic ulcers, although more advanced cases exhibit heaped-up margins . </li></ul><ul><li>Uncommonly, a broad region of the gastric wall, or the entire stomach, is extensively infiltrated by malignancy. </li></ul><ul><li>The rigid and thickened stomach is termed a leather bottle stomach, or linitis plastica; </li></ul><ul><li>metastatic carcinoma from the breast and lung may generate a similar picture. </li></ul>
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  33. 33. <ul><li>The Histologic appearances of gastric cancer have been variously subclassified, but the two most important types are the intestinal type and diffuse type . </li></ul><ul><li>The intestinal variant is composed of malignant cells forming neoplastic intestinal glands resembling those of colonic adenocarcinoma. </li></ul><ul><li>The diffuse variant is composed of gastric-type mucous cells that generally do not form glands but rather permeate the mucosa and wall as scattered individual &quot; signet-ring&quot; cells or small clusters in an &quot;infiltrative&quot; growth pattern. </li></ul>Histologic appearances
  34. 34. Microscopy <ul><li>Intestinal type (forms glands – like cancers of colon and oesophagus) </li></ul><ul><li>Diffuse type – dissociated tumour cells often containing a mucinous “blob” – signet ring cells </li></ul>
  35. 35. Histopathology <ul><li>Adenocarcinomas tend to aggressively invade the gastric wall, infiltrating the muscularis mucosae , the submucosa, and thence the muscularis propria. </li></ul><ul><li>Intestinal type adenocarcinoma tumor cells describe irregular tubular structures , harboring pluristratification, multiple lumens, reduced stroma (&quot;back to back&quot; aspect). </li></ul><ul><li>Often, it associates intestinal metaplasia in neighboring mucosa. </li></ul><ul><li>Depending on glandular architecture, cellular pleomorphism and mucosecretion, adenocarcinoma may present 3 degrees of differentiation: well, moderate and poorly differentiated. </li></ul><ul><li>chronic atrophic gastritis , retained glandular structure, little invasiveness, and a sharp margin. </li></ul>
  36. 36. Histopathology <ul><li>Diffuse type adenocarcinoma (mucinous, colloid, linitis plastica, leather-bottle stomach) </li></ul><ul><li>Tumor cells are discohesive and secrete mucus which is delivered in the interstitium producing large pools of mucus/colloid (optically &quot;empty&quot; spaces). </li></ul><ul><li>Margins that appear clear </li></ul><ul><li>It is poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus to the periphery- &quot; signet-ring cell &quot;. </li></ul>08/19/11
  37. 37.
  38. 38. 08/19/11 Gastric adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the gastric mucosa. According to Lauren classification, gastric adenocarcinoma may be: intestinal type, diffuse type and mixed type
  39. 39. <ul><li>Whatever the histologic variant, all gastric carcinomas eventually penetrate the wall to involve the serosa , spread to regional and more distant lymph nodes, and metastasize widely. </li></ul><ul><li>For obscure reasons, the earliest lymph node metastasis may sometimes involve a supraclavicular lymph node (Virchow's node). </li></ul><ul><li>Another somewhat unusual mode of intraperitoneal spread in females is to both the ovaries, giving rise to the so-called Krukenberg tumor </li></ul>08/19/11 Free template from www.brainybetty.com
  40. 40. Gastric cancer. A, Intestinal type demonstrating gland formation by malignant cells, which are invading the muscular wall of the stomach. (H & E.) B, Diffuse type demonstrating individual red, mucin-containing malignant cells in the lamina propria of an intact mucosa. (Mucicarmine stain.)
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  42. 42. Gastric Carcinoma Malignant Normal Gland
  43. 43. Stages <ul><li>Early stage </li></ul><ul><li>limited in the mucosa and submucosa layers, no matter with or without lymph node metastasis </li></ul><ul><li>Classified by the Japanese Society for Gastric Cancer </li></ul><ul><li><1cm <0.5cm </li></ul><ul><li>Advanced stage </li></ul><ul><li>invaded over submucosa </li></ul><ul><li>According to Bormann’ classification </li></ul>
  44. 44. Morphology---early stage
  45. 45. Morphology---early stage
  46. 46. Morphology---early stage
  47. 47. Morphology ---advanced stage
  48. 48. <ul><li>Gastric adenocarcinoma, intestinal type , infiltrating muscularis propria. (H&E, ob. x10) </li></ul>
  49. 49. <ul><li>Gastric adenocarcinoma, intestinal type . (H&E, ob. X40) </li></ul>
  50. 50. <ul><li>Early gastric carcinoma is generally asymptomatic and can be discovered only by repeated endoscopic examinations in persons at high risk. </li></ul><ul><li>Advanced carcinoma also may be asymptomatic , but it often first comes to light because of abdominal discomfort or weight loss. </li></ul><ul><li>Uncommonly, these neoplasms cause dysphagia when they are located in the cardia or obstructive symptoms when they arise in the pyloric canal. </li></ul><ul><li>The only hope for cure is early detection and surgical removal, because the most important prognostic indicator is stage of the tumor at the time of resection. </li></ul>Clinical Features
  51. 51. Clinical manifestation Signs and Symptoms Early Gastric Cancer Asymptomatic or silent 80% Peptic ulcer symptoms 10% Nausea or vomiting 8% Anorexia 8% Early satiety 5% Abdominal pain 2% Gastrointestinal blood loss <2% Weight loss <2% Dysphagia <1%
  52. 52. Signs and Symptoms Advanced Gastric Cancer Weight loss 60% Abdominal pain 50% Nausea or vomiting 30% Anorexia 30% Dysphagia 25% Gastrointestinal blood loss 20% Early satiety 20% Peptic ulcer symptoms 20% Abdominal mass or fullness 5% Asymptomatic or silent <5% Duration of symptoms Less than 3 month 40% 3-12 months 40% Longer than 12 month 20%
  53. 53. <ul><li>Gastric adenocarcinoma, intestinal type . Tumor cells describe irregular tubular structures, with stratification, multiple lumens surrounded by a reduced stroma (&quot;back to back&quot; aspect). </li></ul><ul><li>The tumor invades the gastric wall, infiltrating the muscularis mucosae, the submucosa and thence the muscularis propria. </li></ul><ul><li>Often it associates intestinal metaplasia in adjacent mucosa. </li></ul><ul><li>Depending on glandular architecture, cellular pleomorphism and mucosecretion, adenocarcinoma may present 3 degrees of differentiation : well (photo), moderate and poorly differentiate. (H&E, ob. x10) </li></ul>
  54. 54. Spread of gastric carcinoma <ul><li>Local infiltration (through wall of stomach to peritoneum, pancreas etc) </li></ul><ul><li>Lymphatic – local and regional lymph nodes </li></ul><ul><li>Blood – liver, lungs </li></ul><ul><li>Transcoelomic (across peritoneal cavity). Often involves ovaries (esp. signet ring cancer) – Krukenberg tumour. </li></ul>
  55. 55. Less common gastric neoplasms <ul><li>Lymphoma </li></ul><ul><li>Gastrointestinal stromal tumour (GIST) </li></ul><ul><li>Neuroendocrine (carcinoid) tumours </li></ul>
  56. 56. Gastric lymphoma <ul><li>Malignant neoplasm of mucosa associated lymphoid tissue (MALT) </li></ul><ul><li>A (usually) low grade B-cell (marginal cell) lymphoma </li></ul>
  57. 57. Gastric lymphoma (maltoma) <ul><li>Neoplastic cells infiltrate the epithelium (lymphoepithelial lesions) </li></ul><ul><li>Strongly associated with H. pylori and can be cured by eliminating infection. </li></ul>
  58. 58. Gastrointestinal stromal tumours (GIST) <ul><li>Mesenchymal neoplasms </li></ul><ul><li>Derived from interstitial cells of Cajal (pacemaker cells controlling peristalsis) </li></ul><ul><li>Overexpress c-kit oncogene </li></ul><ul><ul><li>Used as diagnostic aid on tissue </li></ul></ul><ul><ul><li>A target for therapy with tyrosine kinase inhibitor imatinib (also used in CML) </li></ul></ul>
  59. 59. GIST-spindle cell neoplasm of GI tract
  60. 60. GIST <ul><li>Larger tumours with high mitotic rate tend to behave malignantly </li></ul><ul><li>Stomach is commonest site </li></ul>
  61. 61. Neuroendocrine tumours <ul><li>Carcinoids are tumours of resident neuroendocrine cells in gastric glands </li></ul><ul><li>Usually seen in context of chronic atrophic gastritis (driven by gastrin) </li></ul><ul><li>Clinical behaviour variable </li></ul>
  62. 62. INVESTIGATIONS : <ul><li>A. Upper gastero intestinal endoscopy </li></ul><ul><li>with multiple biopsy and brush </li></ul><ul><li>cytology </li></ul><ul><li>B. Radiology: </li></ul><ul><li> CT Scan of the chest and abdomen </li></ul><ul><li> USS upper abdomen </li></ul><ul><li> Barium meal </li></ul><ul><li>C. Diagnostic laparoscopy </li></ul>
  63. 63. Treatment Surgical resection EMR = Endoscopic mucosal resection Adjuvant therapy Palliative therapy
  64. 64. TREATMENTS OF GASTRIC CANCER: <ul><li> Surgery (Early or Advanced Cancer) </li></ul><ul><li> Distal tumours which involve the lower ½ (sub-total or partial gasterectomy). </li></ul><ul><li> Proximal tumours which involve the fundus, cardia or body (total gasterectomy). </li></ul>
  65. 65. <ul><li> Chemotherapy for gastric cancer </li></ul><ul><li>(Pre-operatve & post-operative) </li></ul><ul><li>  Radiotherapy </li></ul><ul><li>(Pre-intra & post-operatively) </li></ul>
  66. 66. 08/19/11 Alamak, Finish