Lecture | Neoplasms (part 1) Flashcards
Uncontrolled proliferation of cells
Neoplasia
Neoplasma are reversible. T/F
T
Neoplasms’ growth is
Autonomous
Neoplasms are ______ even if the stimulus that produce it is removed
Persistent
“Neo” means ______ and “plasia” means ______
New ; growth
A space occupying lesion
Tumor/s
In neoplasms, the growth will now occupy space, it will become a
Mass lesion
Overall biological behavior of tumor rather than its morphological characteristics
Benign versus malignant
Lesion does not penetrate/invade to adjacent tissues nor spread/metastasize to distant sites; more differentiated
Benign
Tumor invade and metastasizes
Malignant
“Benign and malignant” refers to the behavior of the lesion not primarily to how this tumor looks like. T/F
T
Rate of growth in benign tumors
Progressive but slow. Mitoses few & normal
Rate of growth in malignant tumors
Variable. Mitoses more frequent & may be abnormal
Differentiation of benign tumors, and malignant tumors
Benign: well differentiated
Malignant: some degree of anaplasia
Does not invade to surrounding structures; the growth is cohesive; Capsule & BM not breached, may or may not have a capsule
Benign tumor
Poorly cohesive and infiltrative
Malignant tumors
____ tumors are not expected to metastasize (ABSENT) while _____ tumors is characteristic to spread to distant organs (MAY OCCUR)
Benign ; Malignant
Resemblance of cells to its tissue of origin
Differentiation
Resembles mature cells of tissue of origin
Well-differentiated neoplasm
Composed or primitive cells with little differentiation
Poorly-differentiated neoplasm
In between poorly and well differentiated
Moderate differentiation
Composed of cells that are very primitive; a.k.a. Anaplastic tumors because they do not resemble their cells of origin
Undifferentiated tumors
The poorly differentiated the tumor, the more better it is, and the better the prognosis. T/F
F. … the more aggressive it is, and the poorer the prognosis
Primary descriptor of any tumor
Cell or tissue of origin
Benign tumors identified by the suffix
Oma
Benign tumor of cartilage
Chondroma
Benign tumor of glands
Adenoma
Localized disordered differentiation of normal tissues; cells are poorly organized
Hamartoma
Ectopic islands of normal tissue; normal tissues found in a different location
Choristoma
Hamartoma and choristoma are ____
Space occupying lesions but are not neoplasm
Malignant tumors have a suffix if it arises from epithelial cell
Carcinoma
Malignant tumors have a suffix if it arises from the mesenchymal origin (e.g., bone, fibrous tissue, cartilage)
Sarcoma
Fibrous tissue is called __ for benign or ___ for malignant
Fibroma; fibrosarcoma
Leiomyoma ; leiomyosarcoma
Benign and malignant tumor in the smooth muscle
Benign and malignant tumor in the striated muscle
Rhabdomyoma ; rhabdomyosarcoma
Benign and malignant tumor in fat
Lipoma ; liposarcoma
Benign and malignant tumor in the blood vessels
Hemangioma ; angioma
Lymphangioma ; lymphangiosarcoma
Benign and malignant tumor in the lymphatic vessels
Suffix “__” relationship to blood
Emia
Tumors with poorly understood histiogenesis
Eponym/s
There are different exceptions to the rule of classifying neoplasms by their identified suffix. T/F
T
Hepatoma (historical term)
Malignant tumor in the liver
Melanoma (historical term)
Type of skin cancer that is malignant
Malignant tumor in the lymph nodes
Lymphoma (historical term)
Malignant tumor in the testis
Seminoma (historical term)
Reason why some terms ends in “oma” but are not benign
Way back when tumor pathologies started out, they mistakenly termed this lesion as “oma” despite its infiltrative nature
Better term for hepatoma and melanoma
Hepatoma is hepatocellular carcinoma
Melanoma is malignant melanoma or melanocarcinoma
These historical terms remain their terms despite that is is malignant because
Seminoma and lymphoma ; historical ingrained in their literature
Named after the primary investigator; tumors that are poorly understood; cell of origin is not well defined.
Give example
Eponym/s ; ex: Hodgkin’s disease/lymphoma or Ewing sarcoma
Secondary descriptors of a tumor
Morphological and functional characteristics
___ - frondlike structures
___ - soft cellular tumor with little connective tissue
___ - dense fibrous stroma
___ - secrete abundant mucus
___ - necrotic material expressed from ducts
All are examples of an
Papillary carcinoma
Medullary
Scirrhous
Colloid or mucinous carcinoma
Comedocarcinoma
Examples of an eponym
Generally resemble their parent tissues histologically and cytologically; definition resides above all in an inability to invade adjacent tissue and to metastasize
Benign tumors
Behavior is apparent in all stages. T/F
F.
In the initial phase, the behavior is not apparent that is why the recognition whether its benign or malignant falls back to its morphological features.
Tumor cells that arise from smooth muscles of the uterine well; very common tumor in the uterus
Leiomyoma
(tumor [benign] that really looks like a smooth muscle composed of cells that look like smooth muscles)
Depart from parent tissue morphologically and functionally but diagnosis depends on resemblance to normal tissue
Malignant tumors
Lack of differentiated featured in a cancer cell - degree correlates with aggressiveness.
Anaplasia or cellular atypia
Anaplasia means that the cells have variation in size and shape called
Pleomorphic
Cytological evidence include variation in size and shape, enlarged hyperchromatic nuclei with clumped chromatin pattern and prominent nucleoli, atypical mitosis, bizarre cells
Anaplasia or cellular atypia
Cancer cells tend to be anaplastic and they do not really resemble their cell or tissue of origin. T/F
T
Pleomorphism
Variation in size and shape
Abnormal nuclear morphology of anaplasia
Hyperchromasia
High nuclear cytoplasmic ratio
Chromatin clumping
Prominent nucleoli
Malignant tumor from the smooth muscle cells of the uterus
Leiomyosarcoma
Malignant tumors’ other features that favor malignancy (4)
Mitotic activity
Inavasion-particularly of blood vessels and
Lymphatic
Metastases
Distant metastasis?
Invasion will have a predilection (i.e., preference) towards blood vessels and lymphatics and once they achieve this, these tumor cells can now go to different organs
Features of malignant tumors
Cellular feature: anaplasia
Local invasion: capsule and basement membrane
Metastasis: seeding of body cavities, and lymphatic & hematogenous spread
Metastasis is not apparent in the beginning but in the natural progression of malignancies. T/F
True
What is the most important or unequivocal sign that the neoplasm is malignant?
Metastasis
Benign tumors are apparent because of its rapid in size and its infiltration to surrounding tissues. T/F
False
In breast cancer, the tumor cells appears to form glands, so this is a sarcoma because it arises from the mesenchyme. T/F
False.
Glands are a carcinoma because they are considered epithelial
If the tumor in breast carcinoma appear like glands or like ducts, what is its diagnosis?
Invasive Ductal Carcinoma
If the tumor in breast carcinoma appear like glands or like ducts, what is its diagnosis?
Invasive Ductal Carcinoma
Usual location of metastasis in breast carcinoma
Lymph nodes in the axillary region
Hallmark of malignant lesion
Capacity for involvement outside the area of origin- Invasion- METASTASIS
In breast carcinoma, metastasis in the liver is possible. T/F
True.
Metastasis can be distant, not only in the axillary lymph nodes but it can involve other organs in the body
No specific determinants of malignancy can be detected by light microscopy. T/F
False.
Electron microscopy
It has a significant value in diagnosis of poorly differentiated cancers that are problematic by routine microscopy.
Electron microscopy
Carcinoma is easily distinguishable from sarcoma because the tissue of origin is already apparent. T/F
False.
Hard to distinguish because the tissue/cell of origin is not clr
In the histological diagnosis of malignancy, Carcinoma exhibits _
Desmosomes and junctional complexes (both typically characterizes an epithelial cell),
which are not typical of mesenchymal tumors and absent in lymphomas
In carcinoma, these are short and blunt associated with terminal web
Microvilli
long and slender
Mesothelioma
Microvilli of lymphoid and mesenchymal tumors do not show. T/F
True
Theses are bundles of tonofilaments
Epithelial tumors
Slender microfilaments, terminal web
Mesenchymal tumors
Electron microscopy are readily accessible as all labs operates it. T/F
False.
Only a few laboratories operates an electron microscope as part of its portfolio. Most labs do not incorporate it.
Tumor pathology is the presence of tumor markers, thus all markers allow unequivocal distinction between benign and malignant cells. T/F
False,
No marker allows unequivocal distinction between benign and malignant cells, thus tumor markers should be interpreted AFTER a morphological assessment of the lesion
Uniformly express cytokeratins
Carcinomas
Tumor marker for prostatic cancers
Prostate-associated antigen
(A lineage-associated marker of carcinoma)
Carcinoembryonic antigen (a lineage-associated marker of carcinoma) for _
Colon cancers
Tumor marker for pancreatic and GI cancers
CA 19-9
(A Lineage-associated marker of carcinoma)
CA 125 (a lineage-associated marker of carcinoma) for _
Ovarian cancers
Tumor marker for thyroid carcinomas
Thyroglobulin
(A lineage-associated marker of carcinoma)
Importance of lineage-associated markers
To evaluate if there is a metastasis
To help identify where that tumor is coming from
Importance of lineage-associated markers
To evaluate if there is a metastasis
To help identify where that tumor is coming from
Express chromogranin, neuron-specific enolase, synaptophysin, and leu-7 (CD57)
Neuroendocrine tumors
Positive for vimentin, melanoma-associated antigen, and S-100
Negative for cytokeratin
Malignant melanoma
Soft tissue sarcomas express
Vimentin,
Desmin (for smooth or striated muscle fibers),
Muscle-specific actin (for muscle tissue),
Neurofilament proteins (for neuroblastomas & ganglioneuromas), and
Glial fibrillary acidic protein (for astrocytes)
Generally positive for Leucocyte Common Antigen (CD45)
Malignant lymphoma
A common marker in malignant lymphoma which is true for all leukocytes and lymphocytes and other blood hematolymphoid cell.
This is grouped according to cluster designations.
CD45
Malignant lymphomas express these markers grouped according to cluster designations
- Blood hematolymphoid cells
- T cell
- B cell
- Langerhan’s histiocytes
Blood hematolymphoid cells - CD45
T cell marker- CD3
B cell markers - CD19, CD20 s
Langerhan’s histiocytes - CD1
Identified by antibodies against factor VIII-related antigen or binding to certain lectins (CD34 or CD31)
Vascular tumors
Proliferating cells display marker/s
Ki67 and Proliferating Cell Nuclear Antigen (PCNA)
Ambivalence to render a specific diagnosis (for a tumor)
Malignant poorly differentiated neoplasm
When this happens, tumor markers are helpful
A high grade malignant tumor located in the nasopharynx of a patient in which the neoplastic cells show positivity to cytokeratin and negative for LCA (or CD45) is most likely diagnosed as?
Undifferentiated carcinoma of the nasopharynx
Negative for cytokeratin and Positive for LCA (CD45)
Large cell malignant lymphoma
Not disease-specific but allow tumor monitoring for recurrence after surgery
Serum tumor markers
Serum tumor markers:
- CEA
- CA125
- PSA
- Alpha fetoprotein
- Human Chorionic Gonadotropin (HCG)
- Human placental alkaline phosphatase
- CEA > colonic cancer
- CA125 > ovarian malignancy
- PSA > prostatic carcinoma
- Alpha fetoprotein > liver cancer or yolk sac tumor in the ovary or testis
- Human Chorionic Gonadotropin (HCG) > trophoblastic tumors
- Human placental alkaline phosphatase > seminomas
Characteristics unique to caner cells; the cause of most cancer deaths
Invasion and metastasis
Before cancer cells invade other organs, the carcinoma may be confined first to the epithelium; No penetration of basement membrane; not defined for connective tissue cells, lymphoid elements, and hepatocytes
carcinoma in situ stage
Growth within tissue of origin then enlarged and infiltrate normal structures causing impairment of function
In situ stage
- Carcinoma found in the cervix
- full thickness of the mucosal surface (squamous epithelium)
- all cells are atypical
- no penetration of the basement membrane
- no invasion to the underlying stroma
Diagnosis?
Carcinoma in-situ (non-invasive stage)
- penetration in the basement membrane
- invasion to the underlying stroma
- tumor may have acquired the capacity for distant metastasis
Diagnosis?
Invasive squamous cell carcinoma / Invasive carcinoma
Refers to the transfer of malignant cells from one site to another not directly connected with it.
Metastatic spread
The metastatic spread is disseminated through the
Vascular and lymphatic channels
(Metastatic spread) Capillaries and venules commonly invaded;
Must lodge in the vascular bed of metastatic site for it to become viable.
Hematogenous metastasis
Appearance of malignant cells in blood is synonymous with metastasis. T/F
False, it is not synonymous.
Favored sites of hematogenous metastasis.
Liver and Lungs
Why does hematogenous metastasis favor the liver and lungs?
Primarily due to the double circulation found in these two organs because these two organs are very vascular which increases the chance that these tumor cells will lodge into this organ
What type of circulation happens in the liver and in the lungs?
Liver - portal circulation, hepatic circulation
Lungs - bronchial circulation, pulmonary circulation
(Metastatic spread) Basement membranes are lacking in lymphatic capillaries; regional lymphatic pattern of spread
Lymphatic metastasis
Metastases found in lymph nodes distant from the site of tumor
Skip metastasis
Steps required for establishment of metastasis
- Invasion of basement membrane
- Movement through the ECM
- Penetration of vascular and lymphatic channels
- Survival and arrest within the circulating blood or lymph
- Exit from circulation into new tissue site (“skip metastasis”)
- Survival and growth as metastasis
Role of adhesion molecules
Invasion
An adhesion molecule that confers metastatic potential; play a role in cell migration, proliferation, and in angiogenesis
Integrins
Expression of adhesion molecule correlates with tumor aggressiveness
Intercellular adhesion molecule-1 (ICAM-1)
An adhesion molecules that is downregulated in highly metastatic clones; decreased expression allows detachment of tumor cells from parent tumor
Vascular cell adhesion molecule-1 (VCAM-1)
Cell-cell adhesion molecules that suppress invasion and metastasis; expression lost or reduced in most carcinomas
Cadherins and Catenins
Tumor cell cytokine that stimulates motility
Autocrine motility factor
Elaboration of proteases (e.g., matrix metalloproteinases) that degrade basement membrane components
Proteolytic enzymes
Needed to establish new colony
Invasion of circulation
Adheres to endothelium causing retraction with exposure of basement membrane and subsequent binding and extravasation
Escape from circulation
Secretion of substances that stimulate angiogenesis
Local growth
Stimulate formation new blood vessels
Angiogenesis
Without a new blood vessel feeding the new colony, these tumors will not grow. T/F
True
Tumors release/secrete growth factors to enhance formation of new blood vessels. T/F
True
The success of the metastatic implant to the distant organs depends on two factors
Favorable environment and vascular anatomy
Depends on surface properties of the cells involved
Proclivity or homing to specific organs
