1. NEOPLASIA 1 Fe A. Bartolome, MD, FPASMAP Department of Pathology Our Lady of Fatima University

4. Composed of cells that grow in a poorly regulated manner

5. Cellular proliferation and growth occur in the absence of any continuing external stimulus

7. Neoplasm Heritable genetic alterations Passed down from progeny of tumor cells Excessive and unregulated proliferation Becomes independent of physiologic growth stimuli (autonomous growth) PERSISTENCE OF TUMOR

9. Fibroma fibroblastic cells

10. Chondroma  cartilage

13. Papilloma – produce papillary patterns that protrude into cystic spacesMacroscopic patterns

16. Arise from mesoderm

20. Tumors that derive from more than one germ cell layer  contain tissue derived from ectoderm, endoderm, and mesoderm

23. Liposarcoma

24. Leiomyosarcoma

27. Squamous cell CA – recognizable squamous cells  oropharynx, larynx, upper/middle esophagus, lung, cervix, skin

34. Determine behavior and pathologic consequences of tumor

37. MALIGNANT NEOPLASMS RANGE FROM WELL-DIFFERENTIATED TO UNDIFFERENTIATED

39. P R O P E R T I E S (a) Normal colonic epithelium. (b) Benign neoplasm of colon. The cells of a benign neoplasm (b) resemble those of the normal epithelium (a), in that they are columnar and have an orderly arrangement. Loss of some degree of differentiation is evident in that the neoplastic cells do not show mucinvacuolation.

40. P R O P E R T I E S (a) Normal colonic epithelium. (c) Well-differentiated malignant neoplasm of colon. Cells of the well differentiated malignant neoplasm (c) have a haphazard arrangement and, although gland lumina (G) are formed, they are architecturally abnormal and irregular. Nuclei vary in shape and size.

41. P R O P E R T I E S (a) Normal colonic epithelium. (d) Poorly differentiated malignant neoplasm of colon. Cells in the poorly differentiated malignant neoplasm (d) have an even more haphazard arrangement, with very poor formation of gland lumina (G).

44. “to form backward”  reversion from a high level of differentiation to a lower level

47. Extremely dark staining (hyperchromatic)

48. Nucleus disproportionately large for the cell  N:C ratio ~ 1:1 (normal = 1:4 or 1:6)

49. Variable nuclear shape; large nucleoli

53. Scant vascular stroma

56. Encountered principally in epithelia

57. Changes include:Loss in uniformity of individual cells with loss of architectural orientation Pleiomorphism Hyperchromatic, abnormally large nuclei Abundant mitotic figures that appear in abnormal locations within the epithelium

59. Often found adjacent to foci of invasive carcinoma

67. If with high growth fraction  greater cell production  more rapid growth (e.g. Small cell CA of lungs)

69. Growth fraction of tumor cells has a profound effect on their susceptibility to cancer chemotherapy

71. Usually > 90 days, up to many years for solid tumors  late diagnosis

72. Growth rate of tumors correlates with their level of differentiation

73. Malignant tumors grow more rapidly than benign tumors

76. A A B Fibroadenoma of the breast. The tan-colored, encapsulated small tumor is sharply demarcated from the whiter breast tissue (A). Microscopic view of fibroadenoma of the breast (B). The fibrous capsule (right) delimits the tumor from the surrounding tissue. (Courtesy of Dr. Trace Worrell, University of Texas Southwestern Medical School, Dallas, TX.)

78. Next to metastasis, invasion is the second most important criterion for malignancy

79. Malignant tumors are poorly demarcated from the surrounding normal tissue.

82. All cancers can metastasize. Major exceptions are: gliomas (glial cells of CNS) and basal cell carcinoma of skin

87. Breast CA usually arise in the upper outer quadrants  spread first to axillary LN

89. Enlargement of nodes may be caused by:Spread and growth of cancer cells Reactive hyperplasia

90. Lymphatic invasion by tumor. (a) Histology of invasion of lymphatic vessel. (b) Tumor in para-aortic lymph nodes. Micrograph (a) shows malignant cells (M) in a small lymphatic vessel. Cells break off from the primary tumor, enter small lymphatics and are carried to lymph nodes, where they frequently grow as metastases. The macroscopic appearance of tumor in nodes is shown in (b); the nodes (N) are enlarged and replaced by tumor which, in this instance, originated from the testis.

92. Arteries less readily penetrated as veins due to thicker walls

94. Gastrointestinal tumors  portal vein  liver metastasis

98. Serous cystadenocarcinoma of ovaries  omentum

99. Peripherally located lung CA  parietal and visceral pleura

103. Comparisons Between Benign & Malignant Tumors

109. CA of the breast 2.5x more common than lung cancer

112. Alcohol abuse  CA of oropharynx, larynx, esophagus, pancreas, liver

113. Cigarette smoking  CA of mouth, pharynx, larynx, esophagus, pancreas, lungs, and bladder

115. Children under 15 y/o

116. 10% of all cancer deaths in the U.S. second only to accidents

117. Acute leukemia & neoplasms of CNS = 60% of all cancer deaths in children

119. E P I D E M I O L O G Y Reported Deaths for the 5 Leading Cancer Types for Females by Age (US, 2000)

120. Average 5-year survival rates for common neoplasms. The chances of surviving for 5 years after diagnosis vary greatly according to the type of neoplasm.

122. Less than 10% of cancer patients have inherited mutations that predispose to cancer.

124. Inherited mutation usually a point mutationoccurring in a single allele of a tumor suppressor gene

125. Childhood retinoblastoma  RBtumor suppressor gene

127. G E N E T I C S Selected Autosomal Dominant Cancer Syndromes

128. G E N E T I C S Inherited Predisposition to Cancer

130. Generally autosomal recessive

136. Seen in virtually all the common types of cancers that occur sporadically

137. Not associated with specific marker phenotypes

138. Features:Early age at onset Tumors arise in 2 or more close relatives of the index case Multiple or bilateral tumors

139. G E N E T I C S Inherited Predisposition to Cancer

141. Chronic gastritis  carcinoma of stomach

142. Chronic colitis  carcinoma of colon

143. Liver cirrhosis  hepatocellular CA

144. Celiac disease  gut lymphoma

147. Villous adenoma  colonic CA (50%)

148. Cervical intraepithelial neoplasia (CIN)  cervical carcinoma

151. Endometrial hyperplasia

154. Increase fiber/decrease dietary saturated fat

155. Reduce alcohol intake

156. Reduce weight

157. Increased adipose tissue  increased aromatase conversion of androgens to estrogen

159. Prevention Modalities in Cancer Treatment of conditions that predispose to cancer: Treatment of Helicobacter pylori infection  decrease risk for developing malignant lymphoma and adenocarcinoma of stomach Treatment of GERD  decrease risk for developing distal adenocarcinomas arising from Barrett’s esophagus

160. E N D of P A R T 1