Transcript A paraneoplastic syndrome occurs when a neoplasm

Tumor 2
Pathology
and Histology
A model of neoplastic transformation
(Scientific Truth?)
Mutation in
gene A
Normal Cell
Mutation in
gene B,C, etc.
Increased
proliferation
Increasing
chromosomal aneuploidy
Benign neoplasia
However, this is NOT cancer
Carcinoma
Hepatocellular
Carcinoma
THIS IS CANCER
Renal Cell Carcinoma
Metastatic Carcinoma
to Liver
Cancer is NOT one disease
Deaths 
Incidence 
Germ cell layers
Cancers
are also
classified
according
to what
germ cell
layer they
originate.
Terminology
• Neoplasia – “new growth”
• Tumor – swelling caused by
inflammation, now tumor =
neoplasm
• Cancer – Latin cancer = crab,
malignant tumors
• Oncology – Greek oncos = tumor
Terminology
Neoplasias are classified into two basic types:
• Benign – mass of proliferating cells not subject to
normal physicological controls which can
increase in size but not invade surrounding
tissue or spread to other parts of the body
• Malignant – mass of proliferating cells not
subject to normal physiological control with
capacity to extend (invade) adjacent normal
tissues and to spread (metastasize) to distant
organ sites
CANCER refers to virtually all malignant neoplasias
Mesenchymal – connective tissue & endothelial
related
Benign
•
•
•
•
•
•
Fibroma
Lipoma
Chondroma
Osteoma
Hemangioma
Meningioma
Malignant
•
•
•
•
•
•
Fibrosarcoma
Liposarcoma
Chondrosarcoma
Osteogenic sarcoma
Angiosarcoma
Invasive
meningioma
• Synovial sarcoma
• Mesothelioma
Epithelial origin
Benign
Malignant
• Squamous cell
carcinoma
• Adenoma
• Renal tubular
adenoma
• Liver cell adenoma
•Hydatidiform mole
•
•
•
•
Basal cell carcinoma
Adenocarcinoma
Renal cell carcinoma
Hepatocellular
carcinoma
• Choriocarcinoma
• Seminoma
• Embryonal carcinoma
Macroscopic Criteria for Classification of:
Benign
Malignant
• Structure typical
of tissue of origin
• Encapsulated
• Slow growth
• No metastasis
• Atypical structure
• Locally invasive,
infiltrating
• Rapid & erratic
growth
• Metastasis
Fibroadenoma
Ductal
carcinoma
Microscopic Criteria for Classification of:
Benign
Malignant
•
•
•
•
Well differentiated
Uniform
N:C = 1:4 or 1:6
Rare normal mitotic
figures
• Normal orientation
• Abundant stroma
• Generally less well
differentiated to
undifferentiated
(anaplastic)
• Pleomorphic
• N:C = 1:1
• Hyperchromatic
• More mitoses, abnormal
& bizarre
• Loss of polarity
• Tumor giant cells
Abnormal
mitoses
Pleomorphic,
hyperchromatic,
multinucleated,
giant, “bizarre”
Abnormal mitosis - Here are three abnormal mitoses. Mitoses by
themselves are not indicators of malignancy. However, abnormal mitoses
are highly indicative of malignancy. The marked pleomorphism and
hyperchromatism of surrounding cells also favors malignancy.
Spread of Tumors
• Direct invasion – infiltration &
destruction of surrounding tissue
• Metastasis – noncontiguous spread to
other organ/body locations
– Lymphatics – carcinomas, lymphatic drainage
– Veins & arteries – sarcomas, renal cell carcinoma,
hepatocellular carcinoma
– Implantation – “open field”, ovarian carcinomas,
appendix = pseudomyxoma peritonei
Staging of Malignant
Neoplasms
Stage
Definition
Tis/T0
In situ, non-invasive (confined to epithelium)
T1
Small, minimally invasive within primary organ site
T2
Larger, more invasive within the primary organ site
T3
Larger and/or invasive beyond margins of primary
organ site
T4
Very large and/or very invasive, spread to adjacent
organs
N0
No lymph node involvement
N1
Regional lymph node involvement
N2
Extensive regional lymph node involvement
N3
More distant lymph node involvement
M0
No distant metastases
M1
Distant metastases present
In the diagram
above utilizing a
lung carcinoma as
an example, the
principles of staging
are illustrated:
Grading of Malignant Neoplasms
Grade
Definition
I
Well differentiated
II
Moderately differentiated
III
Poorly differentiated
IV
Nearly anaplastic
Neoplasia • Uncontrolled new growth by cells that are
no longer under complete physiologic
control
• Irreversible
• May be benign or malignant
Lipoma - Of course, neoplasms can be benign as well as malignant,
though it is not always easy to tell how a neoplasm will act. Here is a
benign lipoma on the serosal surface of the small intestine. It has the
characteristics of a benign neoplasm: it is well circumscribed, slow
growing, non-invasive, and closely resembles the tissue of origin (fat).
Lipoma - At low power
magnification, a lipoma of
the stomach is seen to be
well demarcated from the
mucosa at the lower
center-right. This neoplasm
is so well-differentiated
that, except for its
appearance as a localized
mass, it is impossible to tell
from normal adipose
tissue.
Lipoma - Here is the lipoma at high magnification. This is a good
example of how a benign neoplasm mimics the tissue of origin. These
neoplastic adipocytes are indistinguishable from normal adipocytes.
Liposarcoma - This large mass lesion is a liposarcoma. Common sites are the
retroperitoneum and thigh, and they occur in middle aged to older adults. This
one is yellowish, like adipose tissue, and is well-differentiated. Though indolent,
it continues growing to reach a large size, and following excision, it has a
tendency to recur.
Liposarcoma - This liposarcoma has enough differentiation to
determine the cell of origin (adipocyte), but there is still significant
pleomorphism of these neoplastic cells (lipoblasts).
Liposarcoma - At high magnification, large bizarre lipoblasts are seen in
this liposarcoma. Sarcomas are best treated surgically, because most
respond poorly to chemotherapy or radiation.
The first step toward epithelial neoplasia is cellular
transformation
Traditionally, two forms of cellular transformation have
been recognized that are potentially reversible, but may be
steps toward a neoplasm. These are:
• Metaplasia: the exchange of normal epithelium for
another type of epithelium. Metaplasia is reversible when
the stimulus for it is taken away.
• Dysplasia: a disordered growth and maturation of an
epithelium, which is still reversible if the factors driving it
are eliminated.
However, Hyperplasia: an increase in the number of
phenotypically normal cells, may also reflect an early
stage of transformation.
Metaplasia - The chronic irritation from cigarette smoke has led to an
exchanging of one type of epithelium (the normal respiratory epithelium at
the right) for another (the more resilient squamous epithelium at the left).
Thus, there is metaplasia of normal respiratory laryngeal epithelium to
squamous epithelium in response to chronic irritation of smoking.
Dysplasia
• “disordered growth”
•
•
•
•
•
Loss in uniformity of the individual cells
Loss of architectural orientation
Pleomorphism
Hyperchromatic
Increased mitoses (normal)
Carcinoma in situ
• Dysplastic changes involve entire thickness of epithelium
• If left untreated, will progress to invasive cancer
Dysplasia - This is the next step toward neoplasia. Here, there is normal
cervical squamous epithelium at the left, but dysplastic squamous
epithelium at the right. Dysplasia is a disorderly growth of epithelium, but
still confined to the epithelium. Dysplasia is still reversible.
Dysplasia - When the
entire epithelium is
dysplastic and no
normal epithelial cells
are present, then the
process has gone
beyond dysplasia and is
now neoplasia. If the
basement membrane is
still intact, as shown
here, then the process
is called "carcinoma in
situ" because the
carcinoma is still
confined to the
epithelium. Neoplastic
epithelium is termed
carcinoma.
Carcinoma in situ
Cervical Cancer – neoplastic epithelium has created a gross mass
(tumor) and invaded underlying tissue.
Cervical Cancer –
This is the microscopic
appearance of
neoplasia, or
uncontrolled new
growth. Here, the
neoplasm is infiltrating
into the underlying
cervical stroma.
Squamous Cancer - This is a squamous cell carcinoma. Note the
disorderly growth of the squamous epithelial cells in these large nests
with pink keratin in the centers. Neoplasms may retain characteristics of
their cell of origin. Benign neoplasms mimic the cell of origin very well,
but malignant neoplasms less so.
Adenomatous polyps - Multiple adenomatous polyps (tubulovillous
adenomas) of the cecum are seen here in a case of familial adenomatous
polyposis, a genetic syndrome in which an abnormal genetic mutation
leads to development of multiple neoplasms in the colon.
Differentiation - The concept of differentiation is demonstrated by this
small adenomatous polyp (tubular adenoma) of the colon. Note the
difference in staining quality between the epithelial cells of the adenoma
at the top and the normal glandular epithelium of the colonic mucosa
below.
Adenocarcinoma - micro - The infiltrating glands of this colonic adenocarcinoma
demonstrate less differentiation than the adenomatous polyp, although they still
resemble glands. In general, less differentiation of a neoplasm means a greater
likelihood of malignant behavior. This is the basis for grading. The higher the grade,
the more aggressive the malignant neoplasm. Benign neoplasms are not graded.
Prostate Gland - This is the gross
appearance of nodular prostatic
hyperplasia (benign prostatic
hyperplasia, or BPH). The normal
prostate is 3 to 4 cm in cross section,
by comparison
Prostate Gland - The normal
appearance of prostate is shown
at high magnification. Note the
small pink laminated concretion
(these are corpora amylacea) in
the gland lumen to the left of
center. Note the infoldings of the
columnar epithelium.
Prostatic Adenocarcinoma - The gross
appearance of adenocarcinoma of the prostate
is shown here in cross section. The entire
prostate is involved. The yellowish nodules
represent larger foci of carcinoma.
Prostatic Adenocarcinoma - At low
magnification, a needle biopsy of prostate
is seen. The biopsy is filled with back-toback glands with nuclei demonstrating
hyperchromatism and pleomorphism. This
is adenocarcinoma of prostate.
Tumor Invasion
Lung Cancer Malignant neoplasms
are also characterized
by their tendency to
invade surrounding
tissues. Here, the tan
tissue of a lung
cancer is seen to be
spreading along the
bronchi into the
surrounding lung. The
dark round areas are
lymph nodes also
involved by the
neoplasm.
Lung Cancer - This is a squamous cell carcinoma of the lung. It is a
bulky mass that extends into surrounding lung parenchyma.
Breast Cancer - This infiltrating ductal carcinoma of the breast is definitely
infiltrating the surrounding breast. The central white area is very hard
and gritty, because the neoplasm is producing a desmoplastic reaction with
lots of collagen. This is often called a "scirrhous" appearance. There is also
focal dystrophic calcification leading to the gritty areas.
Breast Cancer - At high magnification, the infiltrating ductal carcinoma
of breast has pleomorphic cells infiltrating through the stroma. Note the
abundant pink collagen bands from desmoplasia, making the tumor
feel firmer than normal breast tissue on palpation.
Perineural Invasion - Branches of peripheral nerve are invaded by nests
of malignant cells. This is termed perineural invasion. This is often the
reason why pain associated with cancers is unrelenting.
Metastases
• A primary neoplasm is more likely to appear
within an organ as a solitary mass.
• The presence of metastases are the best
indication that a neoplasm is malignant. The
original clone of cells that developed into a
neoplasm may not have had the ability to
metastasize, but continued proliferation of the
neoplastic cells and acquisition of more genetic
mutations within the neoplastic cells can give
them the ability to metastasize.
Peritoneal Metastases - Neoplasms can spread by seeding within body
cavities such as the pleural cavity or peritoneal cavity. This pattern of spread is
more typical for carcinomas than other neoplasms. Note the multitude of small
tan tumor nodules seen over the peritoneal surface of the mesentery shown
here.
Metastatic Carcinoma within Vessel - Both lymphatic and hematogenous
spread of malignant neoplasms is possible to distant sites. Here, a breast
carcinoma has spread to a lymphatic within the lung.
Metastatic Breast Cancer to Lung Pleura - Here is microscopic evidence of the
spread of a carcinoma via body cavities. A focus of metastatic breast
carcinoma is present along the pleura overlying the lung.
Sarcoma - This large fleshy mass arose in the retroperitoneum and is an example
of a sarcoma. Sarcomas arise within mesenchymal tissues. This one happened to
be a "malignant fibrous histiocytoma" which is a wastebasket term for sarcomas that
do not resemble mesenchymal cells such as striated muscle (rhabdomyosarcoma),
smooth muscle (leiomyosarcoma), fat (liposarcoma), blood vessels (angiosarcoma),
bone (osteosarcoma), or cartilage (chondrosarcoma). Sarcomas tend to be big and
bad.
Examples of Non
Epithelial Cancers
Sarcoma - Sarcomas tend to have a spindle cell pattern. Note that
some of these neoplastic cells are much larger than others, and thus
very pleomorphic.
Osteosarcoma - Here is an osteosarcoma of bone. The large, bulky
mass arises in the cortex of the bone and extends outward.
Osteosarcoma - The osteosarcoma is
composed of spindle cells. The pink
osteoid formation seen here is consistent
with differentiation that suggests
osteosarcoma
Summary
• There is increasing emphasis from funding
agencies for investigators performing cancer
research to demonstrate a ‘Translational’
component between their studies and the clinical
condition.
• In order to make a VALID linkage between the
investigator’s model system and the cancer
being studied by the basic science investigator,
an understanding of the histogenesis and
histopathologic classification of the cancer they
are studying is essential.