Neoplasia

• Neoplasia


  New growth
• Tumor


  Originally applied to the swelling caused by inflammation, but the non-neoplastic usage has vanished and is now equated with neoplasm
• Oncology


  The study of tumor or neoplasm
• Neoplasia


  An abnormal mass of tissue with uncoordinated growth exceeding that of normal, which persists in the same excessive manner after cessation of the stimuli which evoked the change
• Two components of tumors

  • Parenchyma
  • Reactive stroma
• Parenchyma


  Main cell of the tissue, clonal neoplastic cells
• Reactive stroma


  Made up of connective tissue, blood vessels, and variable number of cells of adaptive and innate immune system
• The classification of tumors and their biologic behavior is based on their parenchymal component, but their growth and spread are critically dependent on their stroma
• In some tumors, connective tissue is scant and so the neoplasm is soft and fleshy. In other cases, the parenchymal cells stimulate the formation of an abundant collagenous stroma, referred to as Desmoplasia
• Classification of tumors


  • Benign tumors
  • Malignant tumors (Cancers)
  • Mixed tumors
• Benign tumors


  Their gross and microscopic appearances are considered relatively innocent; implying that it will remain localized, will not spread to other sites, and is amenable to surgical removal. The patient usually survives, however, benign tumors may cause significant morbidity and sometimes fatal
• Malignant tumors (Cancers)


  Collectively known as Cancers, derived from the Latin word for crab, because they tend to adhere to any part that they seize on in an obstinate manner. They have an aggressive behavior, can invade and destroy adjacent structures and spread to distant sites or metastasize to cause death
• Mixed tumors


  Divergent differentiation of a single neoplastic clone capable of producing cells that do not resemble the parenchyma of the tissue
• Nomenclature of benign tumors

  • Suffix -oma attached to the name of the cell type
  • More complex for benign epithelial tumors based on cells of origin, microscopic pattern, or macroscopic architecture
  • Examples: Adenoma, Papilloma, Cystadenoma, Polyp
• Nomenclature of malignant tumors

  • Sarcoma (malignant tumor from mesenchymal tissues)
  • Leukemia (malignant tumor from blood-forming cells)
  • Lymphoma (malignant tumor from lymphocytes and their precursors)
  • Carcinoma (malignant neoplasm of epithelial cell origin)
• Carcinoma


  Malignant neoplasm of epithelial cell origin, derived from any of the three germ layers (Ectoderm, Mesoderm, and Endoderm)
• Carcinoma subtypes


  • Squamous Cell Carcinoma
  • Adenocarcinoma
  • Renal Cell Carcinoma
  • Bronchogenic Squamous Cell Carcinoma
  • Adenocarcinoma
  • Embryonal
  • Poorly or Undifferentiated Carcinoma
• Pleiomorphic adenoma


  Arises from a single line or germ cell layer, e.g. mixed tumor of the parotid glands
• Teratoma


  Contains recognizable mature or immature cells or tissues belonging to more than one germ cell layer, and sometimes all of the three. Arises from totipotential cells. Contains bone, hair, teeth, skin, glands, brain, etc. Usually found in the ovary and testis
• Choristoma


  Normal tissue in a different location, heterotrophic rest of cells, e.g. well-developed pancreatic tissue in the submucosa of stomach, duodenum, etc.
• Hamartoma


  Benign mass composed of disorganized mature cells belonging to the organ or particular site. Once thought to be a developmental malformation, but many have clonal chromosomal aberrations that are acquired through somatic mutations
• Differentiation


  Refers to the extent to which neoplastic parenchymal cells resemble the corresponding normal parenchymal cells, both morphologically and functionally
• Anaplasia


  Refers to lack of differentiation associated with morphologic changes. Anaplasia is the hallmark of malignant transformation. Cancer cells do not reverse from mature to immature cells; they proliferate from stem cells in the tissue
• Benign tumors are well differentiated, while malignant neoplasms exhibit a wide range of parenchymal cell differentiation, mostly exhibit morphologic alterations that betray their malignant nature
• Anaplastic changes


  • Pleomorphism (variation of shape and sizes)
  • Abnormal nuclear morphology (disproportionally large nuclei, increased nuclear-cytoplasmic ratio, irregular shape, hyperchromatic)
  • Mitoses (many cells in mitosis, bizarre or atypical mitotic figures)
  • Loss of polarity (disorganized growth)
  • Insufficient vascular stroma leading to necrosis
• The better differentiation of the transformed cell, the more completely it retains the functional capabilities of its normal counterpart. In some instances, new and anticipated functions emerge, such as expression of fetal proteins or proteins normally found in other adult cells
• Metaplasia


  Replacement of one cell type with another, nearly always found in association with tissue damage, repair, and regeneration. The replacing cell type is better suited to some alterations in the local environment
• Dysplasia


  Disordered growth, characterized by loss of uniformity of individual cells and their architectural orientation, exhibits pleomorphism. Severe dysplasia is pre-invasive, and once the tumor cells breach the basement membrane it is considered invasive. Dysplasia may be a precursor to malignant transformation but does not always progress to cancer
• Doubling time of tumor cells: One cell can undergo 30 doublings (30 divisions) leading to 10^9 cells, the least detectable size, in 90 days with a 3 day cell cycle. 10 more doublings (30 days) leads to 10^12 cells weighing 1 kg, the maximum size compatible with life
• Fraction of tumor cells in the replicative pool

  Cancers in the breast and colon have low fraction, usually 0.1-2%, while in leukemia, lymphoma, and small cell carcinoma, 20% is in the replicative pool
• Rate of cell shedding or death

  If necrosis and apoptosis is faster than proliferation, there is slow growth. If proliferation is faster than necrosis, there is a faster growth and a larger tumor
• Both malignant and benign tumors have growth rates that are not constant over time, and correlate with the level of differentiation as well as factors like hormone dependence and adequacy of blood supply
• Cancer stem cells and cell lineages

  Could arise from normal tissue stem cells or more differentiated cells that acquire self-renewal property. Tumor initiating cells (T-ICs) allow cells to grow indefinitely in immunodeficient mice and may present 25% of total cellularity in some cancers
• Local invasion


  Cancer growth is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue, unlike benign tumors which grow as cohesive masses that remain localized. Malignant tumors are poorly demarcated and lack a well-defined cleavage plane, while benign tumors usually develop a fibrous capsule separating them from host tissues
• Invasiveness is the most reliable feature that differentiates cancers from benign tumors, next to development of metastases. Most malignant tumors do not recognize anatomic boundaries, making their surgical resection difficult or impossible
• Capsule


  • Pressed fibrous tissue that separates tumors from host tissues
  • Consists of large matrix deposited by stromal cells
  • Fibroblasts are activated by hypoxic damage resulting from the pressure of the expanding tumor
• Hemangiomas lack a well-defined capsule, making them unresectable
• Malignant tumors


  • Poorly demarcated
  • Lack a well-defined cleavage plane
• Slowly expanding tumors


  • May produce an enclosing fibrous capsule
  • May push along a broad front into adjacent normal structures
• Pseudoencapsulated masses


  • Almost always present rows of cells penetrating the margin and infiltrating the adjacent structures, showing a crab-like pattern of growth