Pathology Color Atlas - Tumor Pathology

Front 1

difference between solid and nonsolid tumors?

Back 1

– Solid tumors are circumscribed tumors such as
carcinomas and sarcomas.
– Non-solid tumors are systemic autonomous prolif-
erations of noncohesive individual cells, such as
occur in leukemias (p. 358).

Front 2

define "tumors of limited malignancy"?

Back 2

These include epithelial and nonepithelial tu-
mors that invade and destroy surrounding tis-
sue but rarely if ever metastasize.

Front 3

Tumor-like Lesions?

Back 3

These are neoplasms that tend to regress spon-
taneously and completely.

Front 4

examples of conditions with defects in nuclear excision repair?

Back 4

Nucleotide excision repair (p. 290) in xeroderma
pigmentosum, ataxia teleangiectatica, Bloom’s syn-
drome, Fanconi’s anemia.

Front 5

examples of conditions wiht defects in DNA mismatch repair?

Back 5

DNA mismatch repair: in hereditary nonpolyosis
colon cancer (p. 380).

Front 6

examples of tumors with RB gene inactivation?

Back 6

RB-gene inactivation occurs in extremely aggressive
rapidly proliferating carcinomas (breast carcinomas,
small-cell bronchogenic carcinomas, and glioblastomas)
and sarcomas (osteosarcoma).

Front 7

what are oncofetal antigens?

examples?

Back 7

Definition: These are surface antigens that are
hardly ever expressed after the fetal period
but can occur again in larger quantities in im-
mature tumors.

These antigens are not specific to any one tumor and do
not trigger a tumor suppressive immune reaction. These
are the most common ones:
— a-Fetoprotein (AFP) is a glycoprotein detectable in
serum and liver cells ( A). It is expressed in hepa-
tocellular carcinoma (p. 322) and yolk sac tumor 1
( B), which release AFP into serum.
— Carcinoembryonic antigen (CEA) is a glycoprotein of
the immunoglobulin superfamily. It is expressed in
fetal intestinal tissue and again in gastrointestinal
tumors ( C), which release CEA into serum.
— Chorionic gonadotropin (b-HCG) is a glycoprotein
that suppresses T cells. It is expressed in chorionic
cells and again in choriocarcinoma 2 cells ( D) and
in aggressive carcinomas of the gastrointestinal
tract, respiratory tract, and breast, which release
b-HCG into serum.

Front 8

what are differentiation antigens?

examples?

Back 8

Definition: These are membrane antigens that
regulate intercellular communication and
therefore the interaction of cells. These anti-
gens are also expressed by tumor cells, some
of them in altered form.

In addition to the clusters of differentiation of the leu-
kocytes, these antigens include:
— prostate-specific antigen (PSA), detectable in the
prostate gland and in prostate tumors (p. 374), and
— S-100 antigen, which controls the cell cycle and
binds Ca 2 . S-100 is detectable in Schwann cells
( F), melanocytes, melanomas (p. 366), tumors
of the neural crest, lipocytes (p. 356), and in liposar-
comas.

Front 9

what sort of antigens are formed by tumor cells?

Back 9

Cancer cells form two types of antigens.
Tumor-specific antigens occur in certain tumors (usually
experimentally induced tumors) and not in normal
cells; they can trigger a humoral or cellular immune re-
action. Autoreactive antibodies formed against them or
cytotoxic lymphocytes also attack other endogenous
antigens, triggering cell destruction in remote body tis-
sues and leading to what is known as paraneoplastic
syndrome (p. 350).
Tumor-associated antigens occur in tumors and in nor-
mal cells. These include oncofetal and differentiation
antigens

Front 10

describe immune reactivity againt tumors

Back 10

Most tumor disorders involve immune reac-
tions to a certain extent.
— Humoral immune reactions: Antibodies
against tumor-associated surface antigens
occur as part of the immune response to tu-
mors. In a few cases, they inhibit tumor
growth to a certain extent, or kill tumors
by antibody-dependent cellular cytotoxi-
city. However, they often have just the op-
posite effect: They cover tumor-specific
antigens, masking them for cytotoxic T cells,
which then do not kill them.
— Cell-mediated immunity: The T-cell system
can destroy tumor cells after detecting
the tumor-specific antigen. Tumor cells
may be destroyed
— Directly by cytotoxic effector cells, and
— Indirectly by release of certain cytokines (IL-2
and TNF-a) which transforms macrophages
into “tumor eaters” and activates natural killer
cells. This leads to an inflammatory reaction
with formation of epithelioid granulomas in
the contributory lymph nodes of a tumor,
creating a sarcoid-like lesion and destroying
some of the tumor cells.

Front 11

why does the immune response to tumors usually fail?

Back 11

However, immune surveillance usually fails for
these reasons:
— Lack of immunity: The tumor cells’ tumor-specific
antigens exhibit insufficient immunogenicity.
— Lack of T-cell clones: The body’s immune system tol-
erates tumor antigens because of the absence of an
appropriate tumor-induced T-cell clone.
— T-cell inefficiency: The cytotoxic effector cells fail to
detect the tumor antigen due to either ineffective
HLA expression or because peeled-off tumor anti-
gens block their antigen receptors (HLA molecules).

Front 12

muir torre syndrome?

Back 12

— Muir-Torre syndrome involving a “caretaker” gene
mutation (MLH1, MSH2 = mismatch repair); leads
to gastrointestinal and genitourinary tumors, skin
tumors, and breast cancer ( A, breast cancer in
twins).

Note: The rule of thumb for predisposition to cancer
is that multiple carcinomas occurring before the fifth
decade of life suggest a familial predisposition, usual-
ly with autosomal dominant inheritance.

Front 13

Li fraumeni sy.?

Back 13

Li-Fraumeni cancer syndrome involves a mutation of
the p53 suppressor gene. This leads to early cancer
as well as sarcomas, carcinoma of the adrenal cor-
tex, bronchogenic carcinoma (p. 378), colorectal
carcinoma (p. 379), gliomas (p. 368), leukemia,
and lymphomas.

Note: The rule of thumb for predisposition to cancer
is that multiple carcinomas occurring before the fifth
decade of life suggest a familial predisposition, usual-
ly with autosomal dominant inheritance.

Front 14

nutritional and drugs- predisposing factors to cancer?

Back 14

Nutritional Fats: Increased intake of fat
leads to elevated secretion of bile acids that
can be changed into carcinogens by intestinal
bacteria. This increases the risk of colorectal
carcinoma (p. 380).
High Nutritional Fiber Intake: This de-
creases the risk of carcinoma of the colon.
Alcohol Abuse ( B): Alcoholic beverages,
especially distilled fruit spirits, contain nitrosa-
mines (from putrefactive substances). Ethanol
interferes with the mixed function oxidase sys-
tem especially in the liver, impairing its detox-
ification of carcinogens. This leads to cytotoxi-
city and hypovitaminosis (especially of vitamin
A). This interferes with repair of the squamous
epithelium and leads to esophageal carcinoma.
Cigarette Smoke ( C): Smoke contains
substances such as benzpyrene and nitrosa-
mine that cause p53 mutation that leads to
bronchogenic carcinoma (p. 378).

Front 15

leukoplakia? definition?

Back 15

Definition: This is a white patch of altered
superficial epithelium that cannot be wiped
off ( C1, D)

istologic findings include focal squamous tis-
sue changes characterized by:
— Hyperkeratosis, increased cornification with
formation of nonnucleated cornified scales;
— Parakeratosis, excessively rapid cornifica-
tion with formation of nucleated cornified
scales ( B1);
— Basal cell hyperplasia ( B2, C2);
— Inflammation, lymphocytic infiltration of
the stroma (not necessarily present).
The prognosis is favorable. Concurrent presence
of dysplasia represents a precancerous condi-
tion.

Front 16

definition of dysplasia?

Back 16

Definition: This refers to reversible histologic
deviation of epithelial tissue from normal
( A) with deranged differentiation but con-
trolled proliferation. It is a precancerous lesion.

Histologic findings include cells that exhibit
marked variability in the nuclear size (pleo-
morphism) and mitoses with loss of functional
epithelial orientation (loss of polarity; A, B1).
The prognosis is favorable.

Front 17

define carcinoma in situ?

Back 17

Definition and morphology: Severe epithelial
atypia (for example in the squamous epithe-
lium) and loss of polarity are present with an
intact basement membrane ( E1) and histolo-
gic findings of noninvasive carcinoma ( E2, F).
The prognosis is favorable.

Front 18

microinvasive carcinoma definition?

Back 18

Definition and morphology: Early form of carci-
noma (primarily of the cervix uteri) that pene-
trates the basement membrane and invades tis-
sue to a maximum depth of 3–5 mm.
The prognosis is favorable.

Front 19

pathogenesis of cancer metastasis?

which factors make metastatic neoplasms metastatic?

Back 19

Loss of metastasis-suppressor genes: (e.g. cadherins, TIMPs)

Loss of cohesion: At the beginning of metas-
tasis, the tumor cells lose genes that encode
the adhesion molecules (integrins) that
cling to proteins of the extracellular matrix
(collagen, laminin, and fibronectin) and
those that encode the cell’s “adhesive” re-
ceptors that match the matrix proteins.

Cell motility is brought about by intrinsic
factors in the tumor.

Intravasation and extravasation: Under the
influence of certain growth factors, tumor
cells secrete proteolytic enzymes that de-
grade the extracellular matrix (p. 344).
This allows tumors cells to migrate through
the vessel wall into the lumen of the vessel
and to later leave the vessel and re-enter
tissue (see leukocyte transmigration, p.
200).


Circumvention of immune surveillance: This is
achieved by reduced expression of HLA self-
recognition molecules on the surface of the
tumor cell and by the tumor cell acquiring a
fibrin coating in the blood vessel (tumor
embolus).


Colonization: Tumor cells colonize certain
organs because they detect organ-specific
adhesion molecules and because of the pre-
sence of a target address on the surface of
the tumor cell in the form of lectins.

Front 20

how do tumor cells circumvent immune surveillance?

Back 20

Circumvention of immune surveillance: This is
achieved by reduced expression of HLA self-
recognition molecules on the surface of the
tumor cell and by the tumor cell acquiring a
fibrin coating in the blood vessel (tumor
embolus).

Front 21

symptoms of bone metastasis?

Back 21

Note: Symptoms of bone metastases include:
– Bone pain;
– Pathologic fractures;
– Compression of the spinal cord.

Front 22

which tumors prefer lymphatic metastasis`? which prefer hematogenous metastasis?

Back 22

The rule for metastases is that carcinomas
primarily spread via lymphatic metastases and sarco-
mas primarily via hematogenous metastases.

Front 23

can iatrogenic metastasis occur through needle aspiration biopsies?

Back 23

Yes. Invasive diagnostic and surgical procedures
such as biopsy and exudate aspiration (p. 2)
can lead to iatrogenic dissemination of tumor
cells along the wound canal of the biopsy.

Note: Despite the frequency of fine-needle aspira-
tions, inoculated metastases remain rare.

Front 24

what is canalicular metastasis?

Back 24

This refers to metastasis within a duct system
lined with epithelial tissue. Occurrences of
this rare pattern of metastasis include:
— Breast carcinoma via the lactiferous ducts;
— Carcinoma of the gallbladder via the bile
ducts;
— Carcinoma of the bladder via the ureter.

Front 25

are malignant tumors without necrosis? benign tumors?

Back 25

malignant tumors have a high frequency of associated necrosis, i think it can happen in benign, but USUALLY, benign means there is no necrosis, according to Thieme.

Front 26

pathogenesis and morphology of tumor regression?

Back 26

Pathogenesis: Regressive changes in a malig-
nant tumor, and occasionally in a benign one,
are attributable to the following mechanisms:
— Rapid tumor growth;
— An insufficient vascular network;
— Immune system intervention.
Characteristic morphologic findings occur in
central regression of a tumor.
— Necroses may be spontaneous or iatrogenic.
— Spontaneous hemorrhages may occur due to
tumor necrosis or therapy.
— Scarring may occur, producing crater-like
retraction of the surrounding tissue. Super-
ficial liver metastases produce a typical
“cancer crater” ( A).
— Dystrophic calcification occurs in patients
with certain tumors (see below), where tu-
mor clusters calcify into concrements re-
sembling grains of sand (“psammomatous”
calcification).

Front 27

local tumor complications due to circulatory dysruption?

Back 27

Circulatory Disruption: Tumor growth that
compromises or infiltrates vascular structures
produces a variety of lesions.
— Obstruction of venous drainage is common
and successively leads to varicose changes
in the walls of the veins and thrombosis.
— Vascular thrombosis may result from vascu-
lar stenosis and/or substances produced by
the tumor itself that promote coagulation.
— Bleeding due to erosion of vascular struc-
tures may lead to spitting of blood from
the lungs or bronchi (hemoptysis), vomiting
of blood (hematemesis), passage of bloody
stools (melena), blood in the urine (hema-
turia), acyclic bleeding from the uterus (me-
trorrhagia), and hemorrhagic effusions
( B).

Front 28

local tumor complications due to stenosis?

Back 28

Stenosis: Tumors can lead to several com-
pression syndromes.
— Expansion of the tumor compresses the sur-
rounding tissue ( A) and causes stenosis in
hollow organs ( A2, compression of the
small bowel by a mesenterial liposarcoma;
p. 356). Complications may include difficul-
ties in swallowing, impaired micturition,
disruption of intestinal motility, and also in-
creased intracranial pressure (p. 428).
— Infiltration of the tumor can cause conges-
tion in a hollow organ. Complications may
include prestenotic dilation of the duct, sta-
sis and congestion of secretions or excre-
tions, and bacterial infestation of the con-
gested area.

Front 29

Tumor Necrosis ( C): occurs as a result of
the interplay of several factors. These include:...?

Back 29

— Thrombotic arterial obstruction;
— Vascular compression by the tumor;
— Twisting of the tumor pedicle;
— Cytokines (macrophagic TNF-a);
— Aggressive tumor therapy.

Front 30

complications of tumor necrosis?

Back 30

Ulceration of the inner or outer body surface may
occur, primarily in gastrointestinal, skin, and
breast cancer ( D).
– Perforation of the tumor necrosis may occur into
hollow organs or through the surface of the skin
( E).
– Fistulas may form that communicate with adja-
cent organs.

Front 31

Disruption of Organ Function: occurs espe-
cially in tumors that not only mechanically alter
the organ parenchyma and its supporting tissue
but also destroy them.

examples?

Back 31

Particularly susceptible tissues include:
— Neurovascular structures;
— Urinary tract,
— Intestinal tract;
— Skeletal system, where bone tumors can cause
pathologic fractures ( F).

Front 32

Systemic Complications
Advanced neoplastic disease regularly pro-
duces four types of systemic lesions.

which?

Back 32

metastases
cachexia
tumor anemia
paraneoplastic syndromes

Front 33

causes of cancer cachexia?

Back 33

Cancer Cachexia: involves weight loss in
cancer patients. Causes include:
— Impaired swallowing due to the tumor;
— Impaired digestion due to the tumor;
— Generation of TNF-a by macrophages stimu-
lated by tumor-associated antigens.
— Generation of leptin (fat-cell hormone; p.
84). This results in loss of appetite (anorex-
ia), reduced intake of nutrients, decreased
body fat, and increased energy consump-
tion.

Front 34

causes of tumor anemia?

Back 34

Tumor Anemia: produces the characteristic
pale skin of cancer patients. It is due to several
factors, including:
— Blood loss due to internal bleeding;
— Lack of substances that promote maturation
of blood cells;
— Autoreactive antibodies against erythro-
cytes;
— Displacement of bone marrow by tumorous
infiltrates.

Front 35

definition of paraneoplastic syndromes?

Back 35

DEFINITION: Collective term for a group of gener-
alized pathologic manifestations that are not
attributable to the local effects of a tumor but
are linked to the existence of a tumor and
can regress after the tumor has been removed.

Front 36

pathogenesis of paraneoplastic syndromes?

Back 36

Pathogenesis: Often unclear.
— Cell destruction occurs due to formation of
autoreactive antibodies against tumor anti-
gens and “self” antigens and as a result of
apoptosis caused by certain tumor proteins.
— Dysfunction results from synthesis of pep-
tides with endocrine and enzymatic effects.

Front 37

examples of paraneoplastic endocrinopathies?

Back 37

Endocrinopathies
General pathogenesis: Tumors synthesize ecto-
pic hormones of substances similar to hor-
mones. The most important forms are as fol-
lows:
— Cushing’s syndrome is caused by formation
of ACTH and occurs in patients with bron-
chial cancer.
— Flush’s syndrome is caused by formation of
serotonin and leads to facial erythema, diar-
rhea, colic, and bronchospasm.
It occurs in patients with bronchial or ileal carcinoid
(p. 384).
— Schwartz-Bartter’s syndrome is caused by
formation of proteins resembling ADH
and leads to hyponatremia.
It occurs in patients with small cell bronchogenic
carcinoma (p. 378).
— Hypercalcemia syndrome is caused by for-
mation of parathormone-like protein.
It occurs in patients with squamous cell broncho-
genic carcinoma or renal cell carcinomas.

Front 38

paraneoplastic syndromes; nerve and muscle syndromes ?

Back 38

Nerve and Muscle Syndromes
Pathogenesis: Nerve cells and/or muscle fibers
are destroyed by autoimmune processes and
by tumor-induced apoptosis. The most impor-
tant forms are as follows:
— Myasthenia gravis occurs in patients with
thymus tumors (thymomas).
— Limbic encephalopathy occurs in patients
with small cell bronchogenic carcinoma.
— Degeneration of the cerebellar cortex occurs
in patients with small cell bronchogenic
carcinoma, breast cancer, or ovarian carci-
noma.

Front 39

paraneoplastic syndromes: vascular/hematologic changes?

Back 39

Vascular and Hematologic Changes
Pathogenesis of the most important forms is de-
scribed in the following section.
— Hemolysis: The tumor synthesizes cytotoxic
substances and/or autoreactive antibodies,
damaging the bone marrow and leading
to hemolytic anemia.
This occurs in patients with leukemias or Hodgkin’s
disease’s lymphoma (p. 362).

sizes substances that stimulate erythropoi-
esis (erythropoietin), leading to polyglobu-
lism (an overabundance of erythrocytes).
This occurs in patients with renal cell carcinoma.
— Leukocyte proliferation: The tumor synthe-
sizes substances that stimulate myelopoi-
esis, leading to a leukemoid reaction.
This occurs in patients with stomach cancer or large
cell bronchogenic carcinoma.
— Macroscopic coagulopathy: The tumor
synthesizes thromboplastic substances
that lead to thrombosis (p. 404).
This occurs in patients with pancreatic or adenoid
carcinomas.
— Disseminated intravascular coagulation (p.
402): The tumor synthesizes thromboplas-
tic and fibrinolytic substances that consume
the clotting factors.
This occurs in patients with leukemias.

Note: Coagulopathy is characterized by thrombo-
tic vascular occlusion (primarily in the lung), whereas
disseminated intravascular coagulation is character-
ized by hyalin microthrombi (primarily in the micro-
vasculature of the lung).

Front 40

paraneoplastic syndromes: dermatologic disorders?

Back 40

Dermatologic Disorders
— Acanthosis nigricans manifests itself as
thickening of the skin with clearly discern-
ible papillary lines, hyperpigmentation, and
wart-like papillomas.
It occurs in patients with stomach cancer or squa-
mous cell bronchogenic carcinoma.
— Bazex’s syndrome (paraneoplastic acrokera-
tosis) manifests itself as reddish purple pla-
ques of calcification on the hands, feet,
nose, and ears.
It occurs in patients with carcinoma of the tongue
or tonsils.
— Erythema gyratum repens is a rare skin rash
resembling zebra stripes that changes daily.
It occurs in patients with various carcinomas.
— Hypertrichosis lanuginosa is a rare manifes-
tation involving excessive growth of the
head and body hair.
It occurs in patients with various carcinomas.

Front 41

describe the staging system for cancer.

Back 41

Staging: The stage of neoplastic disease is de-
fined according to three criteria. Together,
they comprise what is known internationally
as the TNM system.
— T refers to local tumor growth.
— N refers to spread to regional lymph nodes.
— M refers to distant metastasis.
Several prefixes are used to provide additional informa-
tion.
— TNM refers to initial clinical and radiologic staging.
— pTNM refers to postoperative or pathologic staging.
— yTNM refers staging following chemotherapy.
— rTMN refers staging in the presence of recurrent
cancer.

Front 42

what is grading ?

Back 42

Grading: This involves histologic evaluation of
the extent to which a tumor corresponds to
its tissue of origin.
— G1 indicates a high degree of differentiation
(low malignancy).
— G2 indicates a moderate degree of differen-
tiation (moderate malignancy).
— G3 indicates a low degree of differentiation
(high malignancy).
— G4 indicates no differentiation (very high
malignancy, indicating an anaplastic tu-
mor).

Front 43

which tumors (in general) are more sensitive to radiation therapy?

Back 43

The less differentiated a tumor is,
the greater its malignancy, the more rapid its growth
(mitosis count). Its sensitivity to radiation and spon-
taneous rate of necrosis will also be correspondingly
high.

Front 44

bowen's disease?

Back 44

Bowen's disease (BD) (also known as "squamous cell carcinoma in situ"[1]:655) is a neoplastic skin disease, it can be considered as an early stage or intraepidermal form of squamous cell carcinoma.

Front 45

general pathogenesis of viral tumorigenesis?

Back 45

General pathogenesis: There are several me-
chanisms by which viruses produce tumors.
— Insertional mutagenesis: Viral DNA becomes
integrated into the host genome, triggering
over expression by adjacent host genes.
— Viral oncogenes (v-onc): Viruses contain on-
cogenes that are usually mutated.
— Blockage of apoptosis: Viruses immortalize
their host cells with proteins that inhibit
apoptosis.
— Immunosuppression: Viruses suppress the
body’s immune defenses.

Front 46

examplify some tumors caused by HPV?

Back 46

Human papilloma viruses (HPV): These
cause epidermal viral acanthoma (skin warts)
and laryngeal papillomas ( A) in humans.
They contribute to the development of cervical
carcinomas in women ( B) and anogenital car-
cinomas in homosexual men. The high risk pa-
pilloma viruses (types 16, 18, and 31) contain
the transforming genes E7 and E6.
— E7 bonds to the Rb suppressor gene, causing a loss of
control over the cell cycle with continuous prolif-
eration.
— E6 bonds to and inactivates the p53 suppressor
gene, leading to tolerance of DNA errors and tumor
progression.

Front 47

which 2 groups of RNA tumor viruses have we?

Back 47

— Moderately carcinogenic retroviruses have a com-
plete retroviral genome.
— Highly carcinogenic retroviruses have a deficient re-
troviral genome with an additional control gene (v-
onc). They can only reproduce within the cell with
the aid of “helper viruses”. They induce tumor with-
in a few weeks.

Front 48

examples of DNA tumorviruses?

Back 48

HPV, EBV, adenoviruses, HBV,

Front 49

what is a v-onc? what is a c-onc? how is c-ong transformed to a v-onc?

Back 49

a c-onc is a physiological proto-oncogene.

These v-onc are proto-oncogenes or portions of
proto-oncogenes that the virus has “stolen” on
its way through an infected host cell. Introduc-
tion of a v-onc into the genome of the virus
usually results in damage to or deletion of a vi-
ral structural gene.
After being assimilated by a retrovirus, a c-onc
can be converted into an oncogene in one of
two ways.
— Structural change may occur due modifica-
tion of the c-onc sequence or fusion with
a viral structural gene.
— Over-expression may occur where a c-onc
comes under the control of the virus’s
highly expressive long terminal repeat se-
quences.

Note: Every v-onc in an RNA tumor virus corre-
sponds to a cellular counterpart (c-onc) in the euka-
ryotic cells.