T25 - Tumor Growth Flashcards
What five factors are used to assess tumors?
demarcation
induration
differentation
rate of growth
distant spread (metastasis)
[DIDRM]
Grossly and by palpation, what are the features of benign tumors? (4)
sharp, distinct margins
freely movable by palpation
visible boundary between normal tissue and tumor
encapsulated
Describe how benign tumors grow. (2)
slow expansile growth
compresses surrounding tissue as it grows
Describe the capsule of benign tumors.
consists of dense type I collagen produced by fibroblasts
The capsule of benign tumors is produced in response to
pressure from adjacent masses
The presence of a capsule implies
slow and non-invasive tumor growth
Grossly, what are the features of malignant tumors? (4)
ill-defined margins
indistinct boundary between normal tissue and tumor
jagged/stellate configuration
fixed to surrounding tissue
There are exceptions to the notion that malignant tumors are not well circumscribed. How can malignant tumors be definitively identified on a microscopic scale?
malignant tumors almost always exhibit small foci of penetration through capsule w/ invasive growth into vasculature or surrounding tissue
Define induration.
firmess of tumor on palpation
Fibroblasts in tumors often produce
abnormal, densely collagenous stroma that gives tumor firm/rock-hard/indurated texture
Define desmoplasia. (2)
abnormal stroma production by tumor leading to induration on palpation
“lots of cancer stuff + fiber stuff” [from tutoring]
The finding of induration in a mass suggests
the mass is an invasive cancer.
What is a tumor stroma?
tumor (with neoplastic cells) + recruited “normal” cells such as fibroblasts
Define differentiation.
degree to which a tumor resembles the normal tissue cells from which it arose
What is the relationship between differentiation and malignancy? (2)
benign tumors are very well-differentiated
in other words, degree of differentiation is inversely correlated with tumor aggressiveness
Describe the key architectural indicator of differentiation in epithelial cells. (2)
epithelial cells are polarized → basal and apical have different functions
malignant tumors show loss of polarity → increased stratification of epithelium
What is the key indicator of morphologic differentiation in adenocarcinomas?
loss of ability to make well-formed glands
What is cellularity?
density of cells, seen in tissue section as number of cells per unit area
What is the relationship between cellularity and differentiation? (4)
poorly-differentiated = more malignant → smaller cells → increased cellularity → increased density of nuclei
Describe nuclear morphology in tumors.
greater variability in size/shape = pleomorphism
What causes nuclear pleomorphism?
variations in DNA content (aneuploidy) in tumor cells
How do tumor nuclei stain by H&E?
stain more darkly = hyperchromasia
What is the significance of the nuclear to cytoplasmic ratio?
cytoplasm reduced in poorly-differentiated cells → increased DNA content → higher nuclear to cytoplasmic (NC) ratio
How does abnormal DNA content in tumor cells manifest?
manifested as abnormal mitotic figures, such as tripolar mitoses
Describe the nucleoli of tumor cells.
prominent nucleoli due to need for increased metabolic activity and protein synthesis
What is functional differentiation?
degree to which cells produce normal cellular products
Give four examples of cellular products that can be used to assess functional differentiation.
mucin (glandular cells)
keratin (squamous cells)
hormones (endocrine cells)
extracellular matrix (bone/cartilage cells)
List four key morphologic characteristics that can be used to assess malignancy.
polarity
gland formation
cellularity
pleomorphism
What is anaplasia?
extreme degree of loss of differentiation
What is a synonym for anaplasia?
de-differentiation
What are the four primary features of anaplasia?
total lack of tissue organization
extreme cell/nuclear pleomorphism
large/hyperchromatic/bizzare nuclei
abnormal mitotic figures
[TELA]
What is the relationship between rate of growth and differentiation?
rate of growth inversely correlated with degree of differentiation
Give two examples of tumors that are metastatic at an early stage.
melanoma
small cell carcinoma of the lung
What are the four primary routes of metastasis?
direct seeding
lymphatic spread
hematogenous spread
transplantation
What is direct seeding?
spread within body via detachment and subsequent implantation in physically contiguous manner
What is peritoneal seeding? (2)
when ovarian tumors spread directly into the peritoneal cavity
an example of direct seeding
What is the major mode of spread of carcinomas?
lymphatic spread
What is the likely site of lymph node metastasis for the breast?
axillary nodes
What is the likely site of lymph node metastasis for the lung? (2)
hilar nodes
peribronchial nodes
What is the likely site of lymph node metastasis for the testis?
paraaortic nodes
What is the likely site of lymph node metastasis for leg skin?
inguinal lymph nodes
What is the major mode of spread for sarcomas?
hematogenous spread
Hematogenous spread is the major mode of spread for which tumor(s)? (2)
major mode for sarcomas
common mode for carcinomas
Hematogenous spread occurs through which structure?
occurs through venous drainage
How do intestinal tumors metastasize to the liver?
via the portal system
How do prostatic tumors metastasize to the lower spine?
via vertebral plexus
List two tumors that tend to metastasize in an idiosyncratic/noteworthy manner.
lung tumors → adrenals
renal cell carcinoma → renal vein → inferior vena cava → right side of heart
Overall, what are the four most common sites of metastasis?
lymph nodes
lung
liver
bone
Overall, what are the three least common sites of metastasis?
skeleta muscle
heart
GI tract
Why might transplantation of tumor cells be helpful? (2)
give tumor cells access to new territory
rarely done in practice
Why are testicular masses never biopsied?
testis surrounded by tough fibrous capsule, the tunica albuginea, which if broken would give tumor opportunity to spread into scrotal sac and peritoneal cavity
Testicular masses are never biopsied. What is the only option for obtaining diagnostic tissue from a testicular mass?
orchiectomy
Give an example of a neoplasm that is locally aggressive but does not metastasize.
basal cell carcinoma of skin
Give an example of a benign tumor that produces stable deposits at distant sites.
benign metastasizing leiomyomatosis
What are sampling issues?
the idea that only a portion of tumor cells are imaged and visualized with any histologic workup — and that there is therefore an upper theoretical limit on the accuracy of the diagnosis
What is grading?
assessment of level of histologic differentiation
What is the relationship between tumor grading and tumor differentiation?
lesser differentiation = higher grading = more aggressive
What are the tumor grading intervals? (2)
low, intermediate, or high grades
-or-
grades I-IV
What is staging?
assessment of physical extent of disease/tumor spread
What is the most common grading/staging scheme?
TNM system
What is the basis of the TNM system?
T = size of primary (T1, T2, T3, T4)
N = regional lymph node involvement (N1, N2, N3)
M = distant metastasis (M0 [not present] or M1 [present])
TNM combinations correspond to which five stages?
Stage 0
Stage I
Stage II
Stage III
Stage IV
Describe what Stage 0 means.
carcinoma in situ
Describe what Stages I-III mean.
more extensive disease
greater tumor size
spread of cancer to nearby lymph nodes
spread to adjacent organ
[progress from Stage I → II → III as severity increases]
Describe what Stage IV means.
cancer has spread to another organ (distant metastasis)
TNM criteria vary based on the tumor. If grading and staging are discrepant, which parameter is used to assess prognosis?
staging is more important — in other words, stage is a better predictor of clinical progression than grade
Differentiate between embryonic and adult stem cells in terms of potency.
embryonic stem cells are totipotent
adult stem cells are multipotent
What is a niche?
microenvironment composed of adult stem cell + supporting niche cells
What is the recent hypothesis relating cancer stem cells? (2)
tumors harbor cancer stem cells analogous to adult stem cells
the cancer stem cells are rare undifferentiated cells that are capable of replenishing themselves and differentiating to form a tumor
Which three signaling pathways regulate adult stem cells in normal development and tissue homeostasis?
Notch
WNT
hedgehog
What is the limitation of conventional chemotherapy on cancer stem cells?
conventional chemotherapy cannot kill cancer stem cells because cancer stem cells mimic every cell in the body
What is renewal?
formation of two daughter stem cells
What is maintenance?
formation of one daughter stem cell + one differentiated cell
What is differentiation?
formation of 2 differentiated cells
The presence of keratin pearls indicates what kind of malignancy?
keratin pearls = squamous cell carcinoma
