Test 2- Neoplasia Flashcards
Neoplasia
The process of tumor formation.
Neoplasia becomes more common as age increases.
Neoplasm or tumor
“New growth” - “composed of cells originally derived from normal tissues that have undergone heritable genetic changes that allows them to become relatively unresponsive to normal growth controls and expand beyond their normal anatomic boundary”
Oncology
Study of tumors or neoplasms.
Neoplasm (tumor): two basic components
- Parenchyma- formed by the neoplasic cells that ma
- Stroma (connective tissue and blood vessels that support the neoplastic cells). Some tumors induce prominent desmoplasia (the formation and development of collagen-rich fibrous connective tissue stroma): e.g.: scirrhous carcinomas (“stony hard consistency”)
Supplies the nurishment for the neoplasa cells
Pre-neoplastic changes
“Because cell replication
is involved in neoplastic transformation, regenerative, hyperplastic and dysplastic proliferations are fertile soil for carcinogenesis to occur”…
- this can be any process that is involved in cell replication
hyperplasia can be a pre- neoplasic change BUT it doesn’t mean that everytime there is hyperplasia that there is a tumor
Papillary ductal hyperplasia,
breast
The image above shows a small lesion , under 1 mm, with severe cytologic atypia, apocrine features and no necrosis. Because the architecture is disorganized, lesions such as these may be classified as “carcinoma in situ”
- epithelial tumors
Hyperplasia
Metaplasia
Reversible change in which one adult cell type is replaced by another adult cell type of the same germ cell line. Usually specialized epithelium is replaced by less specialized epithelium.
Metaplasia is often, but not always an adaptive response.
Epithelial metaplasia is commonly to squamous epithelium and usually due to chronic irritation (not alwayse.g.: Vitamin A deficiency).
In the respiratory epithelium squamous metaplasia leads to impaired function of the mucociliary escalator (picture)chronic heavy cigarette smokers (10-fold greater risk to develop lung cancer in comparison to non-smokers)
Carcinoma in situ. The entire thickness of the epithelium is replaced by dysplastic cells. There is preservation of the basement membrane but no orderly differentiation of squamous cells.
Mesenchymal Tumors:
COMMON TYPE OF TUMOR
Mesenchymal Tumors: Arise from cells of mesodermal origin.
– Benign:suffix“oma”
– Malignant:Suffix“sarcoma”
Epithelial Tumors:
COMMON TYPE OF TUMOR
Epithelial Tumors: Primarily arise from cells of endodermal and ectodermal origin. Benign: papilloma exophytic growth from an epithelial surface; polyp benign epithelial tumor that projects from a mucosal surface.
– _Malignant:_carcinoma;addorganoforigin;addwhetherarisesfrom glandular epithelium or form glandular structures microscopically; add whether induces desmoplasia (scirrhous) or produces mucin (mucinus).
– Carcinoma in situ
Mixed Tumors
Mixed Tumors (multiple cell types derived from a single or multiple germ cell layers – pluripotential or totipotential cell)
– Mixed mammary tumors in dogs
– Teratomas
– Nephroblastoma(Embryonalnephroma,Wilms’tumor)
Teratomas
“Arise from totipotent germ cells. They contain tissues derived from all embryonic cell layers and consist of a bizarre mixture of adult and embryonic tissue types
pic Horse, testicular teratoma
Nephroblastoma, pig
Nephroblastomas are Also known as embryonic Nephromas or Wilms’ tumors
Tissue of origin: metanephric blastema
Epithelial and mesenchymal components- Mixed Tumors
Nephroblastoma, dog
Tissue of origin: metanephric blastema
Epithelial and mesenchymal components
Nephroblastomas are Also known as embryonic Nephromas or Wilms’ tumors
There is a unique tumor reported in thoracolumbar junction of the spinal cord of young dogs(up to 3 years old), mainly German Shepherds, that is now believed to be a nephroblastoma.
Nephroblastoma, pig
Biology of tumor growth: Benign versus Malignant
a) Differentiation/ anaplasia
— benign tumors- are very well differentated and they will very closely resemble the cell of the origin
neoplasic cells- look different from the cells of origin
b) Rate of growth
malignant tumors grow extremely fast, but benign tumors grow at a more normal rate
c) Local invasion (expansile/ infiltrative growth)
malignant tumors-infiltrative growth—- they are invasive
d) Presence or absence of metastasis(secondary growths of a tumor)
Differentiation/ Anaplasia
Refers to the extend to which parenchymal cells resemble the correspondent normal parenchymal cells, both morphologically & functionally
Benign tumors are well-differentiated
Malignant neoplasms can be well-differentiated or undifferentiated (the latter are said to be “anaplastic”).
Anaplasia is characterized by
Anaplasia (“cellular atypia”) is characterized by:
—-Pleomorphism- tumor cells have different sizes, the nuclei are different sizes and morphology
—-Abnormal nuclear morphology
—High mitotic rate
—Loss of polarity (disorganization)
Anaplasia is also understood as lack of
Anaplasia is also understood as lack of differentiation“to form backwards”, implying a reversal of differentiation to a more primitive level.
anaplastic cells arise from
The truth is that in most cancers anaplasia does not represent reverse differentiation of mature normal cells; anaplastic cells arise from less differentiated stem cell-like (totipotent cells) present in tissues.
Anaplasia: pleomorphic muscle cells: Rhabdomyosarcoma
maliganant tumor arising from the mesechemyal cells
skeletal muscle
high degree of anaplasia
In general, the growth rate of tumors correlates with
In general, the growth rate of tumors correlates with their level of differentiation, and thus most malignant tumors grow more rapidly than do benign lesions” (Robbins & Cotran)there are of course many exceptions to the rule…
b) Rate of Growth/ cell proliferation
The main mechanisms that regulate tissue growth are:
- Rate of cell proliferation (fraction of cells in the replicative pool adds to cells undergoing mitotic activity)
- Rate of programed cell death (apoptosis)
This is also applicable to neoplasms…
Apoptosis
Non-lethal genetic damage lies at the heart of carcinogenesis.
Genetic damage per se does not constitute mutation, mutation occurs during DNA replication”the alteration in DNA sequence caused by genetic damage needs to be imprinted in the genome.
Neoplasms and Apoptosis
Many neoplasms may present alterations in apoptotic pathways leading to further genomic instability; one of the hallmarks of malignant transformation cells that may have suffered significant DNA damage are allowed to replicate (no cell-cycle arrest), eventually this may lead to the formation of increasingly aggressive subclones.
Local Invasion
PIC: Horse, thyroid adenoma, 10-532, UCVM, Oillanes Note expansile growth.— THIS IS A BENIGN TUMOR- it’s well localized
Benign vs Malignant
a) Differentiation/ anaplasia
b) Rate of growth
c) Local invasion (expansile/ infiltrative
growth)
d) Presence or absence of metastasis
Malignant tumors
Malignant tumors are infiltrative and invade and destroy the surrounding tissue
Malignant tumors have a ______ pattern of growth
“crablike pattern of growth”
Presence or absence of metastasis
“Metastases are tumor implants discontinuous with the primary tumor”.
Metastasis is the hallmark of malignancy since benign neoplasms do not metastasize.
“In general, the more aggressive, the more rapidly growing and the larger the primary neoplasm, the greater the likelihood that it will metastasize or that has already metastasized”
Dog, mammary Ca
maliganant- inducing ulceration
mammary carcincoma
Cat, mammary carcinoma (malignant with some necrosis that has arisen from the epithelial cells)
cat, mammary Ca, AVC – cellular pleomorphism, abnormal mitosis
large nucleaed cells start growing from the inside
Horse, pedunculated peritoneal (mesenteric) lipoma,
benign tumor
Horse, necrotic mesenteric lipoma,
benign
Pancreas, dog
benign
Pancreatic adenoma
benign
Pituitary adenoma, cat
benign- because it’s very well circumscribed
Cat –Meningioma,
benign
Cat, Adult, Meningioma(most common brain tumor in cats and dogs), occipital lobe,
Meningioma- in the meninges on the outside of the brain
Meningioma, cat
dog, Meningioma
Dog, malignant meningioma- This is maligant tumor, even though the nomenclature is not consistent. This tumor is invading the cranial nerves
cat, meningioma
benign tumor, but it was fatal due to compression atrophy of the hemispheres
Pathways of spread (malignant tumors)
- Transcoelomic spread (Seeding or invasion of body cavities and surfaces)—– usually a characterisitic of carsinomas
- Lymphatic spread—- carsinomas often do this
- Hematogenous spread-
Invasion & and mestastasis are biological hallmarks of
“Invasion & and mestastasis are biological hallmarks of malignancy”
desmoplasia
the formation and development of collagen-rich fibrous connective tissue stroma
e.g.: scirrhous carcinomas (“stony hard consistency”)
undifferentiated tumors
Can’t tell the cell of origin
these tumors are very often very malignant
Metastatic Cascade
- Loss of cadherin and catenin function
- Integrin and other receptors bind to ECM components such as fibronectin, laminin, collagen and vitronectin
- Degradation of BM and ECM components occurs by↑protease activity (matrix metalloproteinases such as type IV collagenase, urokinase and serine protease).
- Migration: cytoskeleton alterations together with alteration in ECM adhesion structures. Cell migration is stimulated by autocrine growth factors
Tumor-stromal interactions play an important role in
Tumor-stromal interactions play an important role in carcinogenesis
Tumor heterogeneity
• Generated during tumor growth
– By progressive accumulation of heritable changes in tumor cells( remember these are monoclonal, so they arise from the same genetics)
• Generation of
– subclones &
– successful subclones
Successful subclones:
- high proliferative rate
- evasion of host immune response,
- can stimulate development of independent blood supply,
- are independent of exogenous growth factors,
- can spread to distant sites
Cat. Mammary Carcinoma,— malignant tumor- borders are merging with the dermis and the deep dermis
Note the invasive nature of this tumor that readily
infiltrates the deep dermis and subcutis.
Bottom: Clusters of neoplastic epithelial cells are observed in close proximity to a lymphatic vessel (red circle), OI
Cat, metastatic mammary carcinoma, Noah’s Arkive. Lymph node metastases and evidence of transcoelomic spreading (circle).
Horse, gastric carcinoma
Gastric carcinomas, arising from the esophageal region of the gastric mucosa, are common in horses.
Note large ulcerative and proliferative lesions. Gastric carcinomas readily infiltrate the gastric wall and spread throughout the peritoneum. What clinical signs can be observed in affected horses? melanin anemia
Peritoneal carcinomatosis (peritoneal spreading). Horse, Gastric Squamous Cell Carcinoma, Noah’s Arkive
metasize by transcolemic transplanation
Gastric carcinoma – dog, Atlantic Veterinary College.
Note marked thickening of the gastric wall.
Invasive carcinomatous cells have the ability to induce prominent desmoplasia (fibrous connective tissue proliferation). That is the reason why some carcinomas may present a “stony hard” (scirrhous) consistency
row of epithelial cells- with granular cytoplasm- MUCIN secreting cells
increased number on lymphocytes on the surface
Mucous-secreting neoplastic epithelial cells, characterized by bluish foamy cytoplasm, infiltrate the muscle layer of the stomach. Dog, Mucinous gastric carcinoma
Mucinous gastric carcinoma –dog, AVC. In this particular case, special stains like alcian blue can facilitate the visualization of invasive carcinoma cells that originate from the surface gastric epithelium. Mucous contents stain dark-blue. Rows of malignant epithelial cells infiltrate the connective tissue within the muscle layer of the stomach.
Dog,AVC, Mucinous gastric carcinoma – Tumor emboli within a lymphatic vessel.
Stain
Alcian blue/ PAS stain
Mucopolysaccharides present in the cytoplasm of the mucous- secreting neoplastic cells stain blue or red.
Cat, hepatocellular Carcinoma, University of Georgia, Noah’s Arkive. The liver appears diffusely infiltrated by the tumor.
Note peritoneal metastases- Maligniant tumor
Peritoneal implantation (transcoelomic spreadingperitoneal carcinomatosis) – Cat, Hepatocellular Carcinoma-Noah‟s Arkive
Right: Dog, metastases from anal sac carcinoma, TAMU Note: Umbilicated (crateriform) appearance of the lesion is often suggestive of carcinoma.
