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MORPHOLOGICAL REACTIONS TO ACUTE AND
PERSISTENT STRESS HEALING REPAIRREGENERATION
NEOPLASIA  
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Cellular reaction varies depending on the
type duration and severity of injury
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Adaptation atrophy hypertrophy hyperplasia met
aplasia dysplasia
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HYPERTROPHY HYPERPLASIA
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HYPERPLASIA and HYPERTROPHY are two distinct
processes but frequently both occur together
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HYPERPLASIA takes place by contrast HYPERTROP
HY involves _____________________________________
__
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HYPERTROPHY   The increased size of the cells is
due not to cellular swelling but to the
synthesis of more structural components.
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HYPERTROPHY   -physiologic -pathologic ___________
_______________________ caused by increased
functional demand or by specific hormonal
stimulation
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- increased workload -hormonal stimulation
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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
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• MECHANISMS OF HYPERTROPHY
• (cardiac muscle hypertrophy)
• many signal transduction pathways
• induction of a number of genes
• stimulation of synthesis of cellular proteins

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GENES INDUCED DURING HYPERTROPHY
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- 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
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TRIGGERS FOR HYPERTROPHY IN THE
HEART -mechanical triggers -trophic trigger
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HYPERTROPHY eventually reaches a limit
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The limiting factors for continued
hypertrophy and the causes of the cardiac
dysfunction are poorly understood
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HYPERPLASIA increase in the number of cells
in an organ or tissue, usually resulting in
increased volume of the organ or tissue
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PHYSIOLOGIC HYPERPLASIA hormonal
hyperplasia compensatory hyperplasia   wound
healing s
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MECHANISMS OF HYPERPLASIA
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In hormonal hyperplasia,   In compensatory
hyperplasia
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PATHOLOGIC HYPERPLASIA
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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.
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PATHOLOGIC HYPERPLASIA constitutes a fertile
soil in which cancerous proliferation may
eventually arise.
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METAPLASIA a reversible change in which one
adult cell type (epithelial or mesenchymal) is
replaced by another adult cell
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epithelial metaplasia columnar to squamous
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the influences that predispose to metaplasia if
persistent, may induce malignant transformation
of metaplastic epithelium
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epithelial metaplasia squamous to columnar
type Barrett esophagus
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connective tissue metaplasia
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MECHANISMS OF METAPLASIA    
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precursor cells differentiate along a new pathway
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Certain cytostatic drugs cause a disruption of
DNA methylation patterns and can transform
mesenchymal cells from one type to another
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NEOPLASIA
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what does it mean tumour neoplasm cancer carcino
ma
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TUMOR originally - swelling caused by
inflammation tumor neoplasm (leukemia is not
a tumor )
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ONCOLOGY CANCER
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"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."
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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
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desmoplasia scirrhous
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NOMENCLATURE OF TUMORS is based on the
parenchymal component ____________________________
___ tumors are designated by attaching the
suffix -oma to the cell of origin
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Benign Malignant
fibroma chondroma osteoma lipoma
fibrosarcoma chondrosarcoma osteosarcoma liposarco
ma
Epithelial Non-epithelial
adenocarcinoma squamous cells carcinoma
adenoma papilloma
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BENIGN TUMORS e.g.
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MALIGNANT TUMORS sarcomas malignant tumors
arising in mesenchymal tissue
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carcinomas malignant neoplasms of epithelial
cell origin
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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
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TERATOMAS  
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polyp macroscopically visible projection above a
mucosal surface
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look at the following slides, recognise the
tissue of origin and name the neoplasms
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DIFFERENTIATION the extent to which neoplastic
cells resemble comparable normal cells, both
morphologically and functionally
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well-differentiated tumors poorly
differentiated or undifferentiated tumors
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benign tumors are well differentiated  
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malignant neoplasms range from well
differentiated to undifferentiated
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ANAPLASIA the lack of differentiation
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Lack of differentiation, or anaplasia is marked
by a number of morphologic changes PLEOMORPHISM
- variation in size and shape -abnormal
nuclear morphology
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MITOSES -large numbers of mitoses reflecting
the higher proliferative activity -
atypical, bizarre mitotic figures
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LOSS OF POLARITY -disturbed orientation of
anaplastic cells OTHER CHANGES e.g. -formation
of tumor giant cells
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benign neoplasms and well-differentiated
carcinomas of endocrine glands frequently
elaborate the hormones characteristic of their
origin
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well-differentiated squamous cell carcinomas
elaborate .... well-differentiated
hepatocellular carcinomas elaborate ....
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highly anaplastic undifferentiated cells whatever
their tissue of origin lose their resemblance
to the normal cells from which they have arisen
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sometimes new and unanticipated functions
emerge   - production of fetal proteins
(antigens) - production of ectopic hormones
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The natural history of malignant
tumors malignant change in the target cell-
transformation growth of the transformed
cells local invasion distant metastases
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LOCAL INVASION METASTASES
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LOCAL INVASION benign tumors
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LOCAL INVASION malignant neoplasms
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invasiveness makes surgical resection difficult
even if the tumor appears well circumscribed,
it is necessary to remove a considerable margin
of apparently normal tissues
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METASTASES tumor implants discontinuous with the
primary tumor   
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approximately 30 of newly diagnosed patients
with solid tumors (excluding skin cancers other
than melanomas) present with metastases Metasta
tic spread strongly reduces the possibility of
cure
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pathways of spread
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seeding of body cavities and surfaces
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lymphatic spread   - most common pathway for
the initial dissemination of carcinomas - more
rarely sarcomas   s
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the pattern of lymph node involvement follows
the natural routes of lymphatic drainage  
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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  
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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
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hematogenous spread - typical of sarcomas - also
seen with carcinomas
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cancer cells follow the blood flow draining the
site of the neoplasm the liver and lungs are
most frequently involved secondarily in
hematogenous dissemination
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renal cell carcinoma hepatocellular
carcinomas
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the importance of histologic evidence of
penetration of small vessels at the site of the
primary neoplasm
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from normal epithelium to invasive carcinoma
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normal epithelium dysplasia (old
term) carcinoma in-situ invasive carcinoma
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Dysplasia
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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
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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
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CIN
Squamous Intraepithelial Lesion
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The rate of growth of a tumor is determined by
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the growth fraction
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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
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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
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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
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the growth rate of tumors correlates with their
level of differentiation most malignant tumors
grow more rapidly than do benign
lesions factors affect growth
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leiomyomas rt
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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
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LABORATORY DIAGNOSIS OF CANCER   clinical data
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the laboratory evaluation of a lesion can be
only as good as the specimen made available for
examination  
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appropriate preservation of the specimen
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sampling approaches
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quick-frozen sections
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Immunohistochemistry (specific mono- and
polyclonal antibodies)
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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
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determination of site of origin of metastatic
tumors
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detection of molecules that have prognostic or
therapeutic significance
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cytokeratins - a group comprising at least 29
different proteins - characteristic of epithelial
and trichocytic cells
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vimentin is the major subunit protein of the
intermediate filaments of mesenchymal cells
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S100 protein - localizes in the cytoplasm and
nuclei of astrocytes, Schwann's cells,
ependymomas and astrogliomas - ganglion cells do
not stain for S100 protein
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CD45 is a family of single chain
transmembraneous glycoproteins consisting of at
least four isoforms which share a common large
intracellular domain
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CD68 this antibody detects a 110 kD
glycoprotein and recognizes macrophages in a
wide variety of human tissues, including
Kupffers cells and macrophages in the red pulp
of the spleen, in lamina propria of the gut, in
lung alveoli, and in bone marrow
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HMB-45 reacts with a neuraminidase-sensitive
oligosaccharide side chain of a glycoconjugate
present in immature melanosomes
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CD31 - a superior marker for angiogenesis
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molecular diagnosis   diagnosis of malignant
neoplasms (considerable value in selected cases)
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molecular diagnosis prognosis of malignant
neoplasms certain genetic alterations are
associated with poor prognosis their detection
allows stratification of patients for therapy
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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
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molecular diagnosis diagnosis of hereditary
predisposition to cancer
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flow cytometry
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tumor markers biochemical indicators of the
presence of a tumor - cell-surface antigens -
cytoplasmic proteins - enzymes - hormones  
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CEA - carcinoembryonic antigen
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AFP - ?-fetoprotein
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? -HCG ?-subunit of human chorionic gonadotropin

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prostate-specific antigen (PSA)