Transcript Prezentacja programu PowerPoint - Patho

MORPHOLOGICAL REACTIONS
TO
ACUTE AND PERSISTENT
STRESS
HEALING
REPAIR
REGENERATION
NEOPLASIA
Cellular reaction varies
depending on the type
duration
and severity of injury
Adaptation
atrophy
hypertrophy
hyperplasia
metaplasia
dysplasia
HYPERTROPHY
HYPERPLASIA
HYPERPLASIA and HYPERTROPHY
are two distinct processes
but frequently both occur together
HYPERPLASIA
takes place
by contrast
HYPERTROPHY
involves
_______________________________________
HYPERTROPHY
The increased size of the cells is due
not to cellular swelling
but to the synthesis of more structural
components.
HYPERTROPHY
-physiologic
-pathologic
__________________________________
caused by increased functional demand
or
by specific hormonal stimulation
- increased workload
-hormonal stimulation
HYPERPLASIA and HYPERTROPHY
often occur concomitantly
during the responses of tissues and organs
to increased stress and cell loss
even cardiac and skeletal muscles
are capable of limited proliferation
as well as repopulation from precursors
MECHANISMS OF HYPERTROPHY
(cardiac muscle hypertrophy)
many signal transduction pathways
induction of a number of genes
stimulation of synthesis of cellular proteins
GENES INDUCED
DURING HYPERTROPHY
- switch of contractile proteins
from adult to fetal or neonatal forms
- some genes that are expressed
only during early development
are re-expressed in hypertrophic cells
TRIGGERS FOR HYPERTROPHY
IN THE HEART
-mechanical triggers
-trophic trigger
HYPERTROPHY
eventually reaches a limit
The limiting factors for continued hypertrophy
and the causes of the cardiac dysfunction
are poorly understood
HYPERPLASIA
increase in the number of cells
in an organ or tissue,
usually resulting
in increased volume of the organ or tissue
PHYSIOLOGIC HYPERPLASIA
hormonal hyperplasia
compensatory hyperplasia
wound healing
s
MECHANISMS OF HYPERPLASIA
In hormonal hyperplasia,
In compensatory hyperplasia
PATHOLOGIC HYPERPLASIA
Although these forms of hyperplasia are abnormal,
the process remains controlled,
because
the hyperplasia regresses
if the hormonal stimulation is eliminated
That distinguishes
benign pathologic hyperplasias from cancer,
in which the growth control mechanisms
become defective.
PATHOLOGIC HYPERPLASIA
constitutes
„a fertile soil in which cancerous proliferation
may eventually arise.”
METAPLASIA
a reversible change
in which one adult cell type
(epithelial or mesenchymal)
is replaced by another adult cell
epithelial metaplasia
columnar to squamous
the influences that predispose
to metaplasia if persistent,
may induce malignant transformation
of metaplastic epithelium
epithelial metaplasia
squamous to columnar type
Barrett esophagus
connective tissue metaplasia
MECHANISMS OF METAPLASIA
precursor cells differentiate
along a new pathway
Certain cytostatic drugs cause a disruption
of DNA methylation patterns
and can transform
mesenchymal cells
from one type
to another
NEOPLASIA
what does it mean:
tumour
neoplasm
cancer
carcinoma
TUMOR
originally - swelling caused by inflammation
tumor = neoplasm
(leukemia is not a tumor )
ONCOLOGY
CANCER
"A neoplasm
is an abnormal mass of tissue*,
the growth of which exceeds
and is uncoordinated
with that of the normal tissues
and
persists in the same excessive manner
after cessation of the stimuli
which evoked the change."
All* neoplasms have two basic components:
(* almost all)
- proliferating neoplastic cells = parenchyma
- supportive stroma
made up of connective tissue
and blood vessels
neoplasms are critically dependent
on their stroma
desmoplasia
scirrhous
NOMENCLATURE OF TUMORS
is based
on the parenchymal component
_______________________________
tumors are designated
by attaching the suffix -oma
to the cell of origin
Non-epithelial
Epithelial
Benign
Malignant
fibroma
chondroma
osteoma
lipoma
fibrosarcoma
chondrosarcoma
osteosarcoma
liposarcoma
adenoma
papilloma
adenocarcinoma
squamous cells
carcinoma
BENIGN TUMORS
e.g.
MALIGNANT TUMORS
sarcomas
malignant tumors arising
in mesenchymal tissue
carcinomas
malignant neoplasms of epithelial cell origin
Not infrequently a neoplasm
is composed of undifferentiated cells
of unknown tissue origin
and must be designated merely as
„a poorly differentiated”
or
„undifferentiated malignant tumor”
TERATOMAS
polyp
macroscopically visible projection
above a mucosal surface
look at the following slides,
recognise the tissue of origin
and
name the neoplasms
DIFFERENTIATION
the extent to which neoplastic cells
resemble comparable normal cells,
both morphologically and functionally
well-differentiated tumors
poorly differentiated
or
undifferentiated tumors
benign tumors are well differentiated
malignant neoplasms
range from well differentiated
to undifferentiated
ANAPLASIA
the lack of differentiation
Lack of differentiation, or anaplasia
is marked by a number of morphologic changes
PLEOMORPHISM
- variation in size and shape
-abnormal nuclear morphology
MITOSES
-large numbers of mitoses
reflecting the higher proliferative activity
- atypical, bizarre mitotic figures
LOSS OF POLARITY
-disturbed orientation of anaplastic cells
OTHER CHANGES
e.g.
-formation of tumor giant cells
benign neoplasms
and well-differentiated carcinomas
of endocrine glands
frequently elaborate the hormones
characteristic of their origin
well-differentiated
squamous cell carcinomas
elaborate ....
well-differentiated
hepatocellular carcinomas
elaborate ....
highly anaplastic undifferentiated cells
whatever their tissue of origin
lose their resemblance
to the normal cells
from which they have arisen
sometimes new and unanticipated
functions emerge
- production of fetal proteins (antigens)
- production of ectopic hormones
The natural history of malignant tumors
malignant change
in the target cell- transformation
growth of the transformed cells
local invasion
distant metastases
LOCAL INVASION
METASTASES
LOCAL INVASION
benign tumors
LOCAL INVASION
malignant neoplasms
invasiveness makes surgical resection
difficult even if the tumor appears
well circumscribed,
it is necessary to remove a considerable
margin of apparently normal tissues
METASTASES
tumor implants
discontinuous with the primary tumor
approximately 30% of newly diagnosed
patients with solid tumors
(excluding skin cancers other than melanomas)
present with metastases
Metastatic spread strongly reduces
the possibility of cure
pathways of spread
seeding of body cavities and surfaces
lymphatic spread
- most common pathway
for the initial dissemination of carcinomas
- more rarely sarcomas
s
the pattern of lymph node involvement
follows the natural routes of lymphatic drainage
local lymph nodes may be bypassed -"skip metastasis„
because of venous-lymphatic anastomoses
or because inflammation or radiation has obliterated
lymphatic channels
a sentinel lymph node
the regional nodes serve as effective
barriers to further dissemination of the tumor
at least for a time
enlargement of nodes
-the spread and growth of cancer cells
-reactive hyperplasia
so...
nodal enlargement in proximity to a cancer
does not necessarily mean dissemination
of the primary lesion
hematogenous spread
- typical of sarcomas
- also seen with carcinomas
cancer cells follow the blood flow draining
the site of the neoplasm
the liver and lungs are most frequently
involved secondarily in hematogenous
dissemination
renal cell carcinoma
hepatocellular carcinomas
the importance
of histologic evidence
of penetration of small vessels
at the site of the primary neoplasm
from
normal epithelium
to
invasive carcinoma
normal epithelium
dysplasia (old term)
carcinoma in-situ
invasive carcinoma
Dysplasia
Dysplasia
does not necessarily progress to cancer
mild to moderate changes may be reversible
and with removal of the inciting causes,
the epithelium may revert to normal
carcinoma in situ
cytologic features of malignancy
without invasion of the basement membrane
neoplastic cells involve the entire thickness
of the epithelium, but the lesion remains
confined to the epithelium
absence of metastases
_______________________________________________________________________
with time, most penetrate the basement membrane
and invade the subepithelial stroma
invasive carcinoma
CIN
Squamous Intraepithelial Lesion
The rate of growth of a tumor
is determined by
the growth fraction
during the early, submicroscopic phase
of tumor growth, the vast majority
of transformed cells are in the proliferative pool
as tumors continue to grow,
cells leave the proliferative pool
the progressive growth of tumors is
deteabrmined
by an excess of cell production over cell loss
The growth fraction of tumor cells
has a profound effect on their susceptibility
to cancer chemotherapy
most anticancer agents act on cells
that are in cycle
a tumor that contains 5% of all cells
in the replicative pool will be slow growing
but relatively refractory to treatment with drugs
that kill dividing cells
One strategy employed in the treatment of tumors
with low growth fraction (e.g., cancer of colon and breast)
is first to shift tumor cells from G0 into the cell cycle
the growth rate of tumors
correlates with their level of differentiation
most malignant tumors grow more rapidly
than do benign lesions
factors affect growth
leiomyomas
rt
Some malignant tumors
grow slowly for years
and then suddenly increase in size,
explosively disseminating
to cause death within a few months
- emergence of an aggressive subclone
of transformed cells
LABORATORY DIAGNOSIS OF CANCER
clinical data
the laboratory evaluation of a lesion
can be only as good
as the specimen made available
for examination
appropriate preservation of the specimen
sampling approaches
quick-frozen sections
Immunohistochemistry
(specific mono- and polyclonal antibodies)
Antibodies against intermediate filaments
have proved to be of value in such cases
because tumor cells often contain
intermediate filaments characteristic
of their cell of origin
determination of site of origin
of metastatic tumors
detection of molecules
that have prognostic or therapeutic
significance
cytokeratins
- a group comprising at least 29 different proteins
- characteristic of epithelial and trichocytic cells
vimentin
is the major subunit protein of the intermediate
filaments of mesenchymal cells
S100 protein
- localizes in the cytoplasm and nuclei
of astrocytes, Schwann's cells,
ependymomas and astrogliomas
- ganglion cells do not stain for S100 protein
CD45
is a family of single chain transmembraneous
glycoproteins consisting of at least four isoforms
which share a common large intracellular domain
CD68
this antibody detects
a 110 kD glycoprotein and recognizes
macrophages in a wide variety of
human tissues, including Kupffer’s cells
and macrophages in the red pulp
of the spleen, in lamina propria of the gut,
in lung alveoli, and in bone marrow
HMB-45
reacts with a neuraminidase-sensitive
oligosaccharide side chain
of a glycoconjugate present
in immature melanosomes
CD31
- a superior marker for angiogenesis
molecular diagnosis
diagnosis of malignant neoplasms
(considerable value in selected cases)
molecular diagnosis
prognosis of malignant neoplasms
certain genetic alterations are associated
with poor prognosis
their detection allows stratification of patients
for therapy
molecular diagnosis
detection of minimal residual disease
after treatment of patients with leukemia
or lymphoma, the presence of minimal disease
or the onset of relapse can be monitored by
PCR-based amplification of nucleic acid
sequences generated by the translocation
molecular diagnosis
diagnosis of hereditary predisposition
to cancer
flow cytometry
tumor markers
biochemical indicators of the presence of a tumor
- cell-surface antigens
- cytoplasmic proteins
- enzymes
- hormones
CEA - carcinoembryonic antigen
AFP - -fetoprotein
 -HCG
-subunit of human chorionic
gonadotropin
prostate-specific antigen (PSA)