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You need to know all the information in table 7-1 on page 263.
I bet I will fill through most of these later, but go through and make sure.
Define "Tumor"
Swelling. Currently used as if synonymous with neoplasm.

Path-Neo1-ppt-3
Carcinoma
epithelial tumors

often used imprecisely to mean any/all tumors

Path-Neo1-ppt-3
‐oma
Benign Neoplasia

Implies
---Not life threatening (except space occupying meningiomas/myxomas)
---Slow growing
---Won't Met
---Removable

Path-Neo1-ppt-11
Benign Neoplasia
‐oma

Implies
---Not life threatening (except space occupying meningiomas/myxomas)
---Slow growing
---Won't Met
---Removable

Path-Neo1-ppt-3
Adenoma
Benign Glandular Tumor

Either From Glandular Origin

Or creates glandular structure:
---Hepatocellular/Renal Tubular Adenoma

Path-RC-260
Benign Glandular Tumor
Adenoma

Either From Glandular Origin

Or creates glandular structure:
---Hepatocellular/Renal Tubular Adenoma

Path-RC-260
Cystadenoma
cystic masses created by adenomas benign neoplastic glandular cells

Cyst: closed cavity or sac lined by epithelium

Path-Neo1-ppt-13
Papilloma
Benign epithelial neoplasms which form finger‐like projections

Path-Neo1-ppt-13
Papillary Cystadenoma
Papillomas (benign epithelial neoplasms which form finger‐like projections) protruding into cystic spaces (closed cavity or sac lined by epithelium)

Path-RC-261
Polyp
Growth pattern projects above the skin or mucosal surface

may be neoplastic or nonneoplastic (eg inflam)

3 forms: sessile, pedunculated, papillary

Path-Neo1-ppt-14
Sessile Polyp

(Polyp: Growth pattern projects above the skin or mucosal surface; may be neoplastic or nonneoplastic, eg inflam)

Path-Neo1-ppt-14
Pedunculated Polyp

(Polyp: Growth pattern projects above the skin or mucosal surface; may be neoplastic or nonneoplastic, eg inflam)

Path-Neo1-ppt-14
Papillary Polyp

(Polyp: Growth pattern projects above the skin or mucosal surface; may be neoplastic or nonneoplastic, eg inflam)

Path-Neo1-ppt-14
Sessile Polyp
Papillary Polyp
Pedunculated Polyp
Leiomyoma
Benign Tumor from Smm

Path-RC-263
Rhabdomyoma
Benign Tumor from Skm

Path-RC-263
Hemangioma
Benign Tumor from Blood Vasculature

Path-RC-263
Lymphangioma
Benign Tumor from Lymphatic Vasculature

Path-RC-263
Clinical Implications of "Malignant" Neoplasms
will cause death

grows rapidly
invades and destroys surrounding areas
may metastasize

Path-Neo1-ppt-18
sarcoma
tumors derived from mesenchyme

Path-Neo1-ppt-18
Basal cell carcinoma
Malignant tumor of basal cells of skin or adnexa (hair, sweat glands, etc)

Path-Neo1-ppt-34
Adenocarcinoma
Malignant tumor of glandular, duct or columnar cell origin

Path-Neo1-ppt-34
Squamous cell carcinoma
Squamous cell carcinoma

Path-Neo1-ppt-34
Nevus
aka a mole

benign Neuroectodermal neoplasm in the skin/conjunctiva/iris
Common, brown pigmented
Small; usually less than 0.5 mm; circumscribed
Does not enlarge; change significantly over time

compare to melanoma

Path-Neo1-ppt-34
Melanoma
Malignant Neurecotodermal Neoplasm in the skin/conjunctiva/iris

Enlarging; may ulcerate; outline irregular

Compare to Nevus: mole

Path-Neo1-ppt-34
Hydatidiform mole
benign tumor of placental epithelium

compare to choriocarcinoma

Path-Neo1-ppt-63
Choriocarcinoma
malignant tumor of placental epithelium

compare to hydatiform mole

Path-Neo1-ppt-63
Seminoma
Malignant tumor of male Germ cell epithelium
---dysgerminoma in females

Path-Neo1-ppt-63
Dysgerminoma
Malignant tumor of female Germ cell epithelium
---Seminoma in males

Path-Neo1-ppt-63
Embryonal Carcinoma
a malignant tumor of germ cell epithelium

See also seminoma and dysgerminoma

Path-Neo1-ppt-63
Neoplasms of more than one cell type
usually derived from 1 germ layer

Salivary/Lacrimal glands: pleomorphic adenoma- one cell gives rise to multiple lineages
Breast: fibroadenoma (fibrous tissue + glands)
Renal Anlage aka Wilm's (Childhood) Tumor: Nephroblastoma

Path-Neo1-ppt-65
Tumor of the Salivary Glands
pleomorphic adenoma- one cell gives rise to multiple lineages

Path-Neo1-ppt-65
Tumor of the Lacrimal Gland
pleomorphic adenoma- one cell gives rise to multiple lineages


Path-Neo1-ppt-65
Cell Types of Breast Tumor
fibroadenoma (fibrous tissue + glands)

Path-Neo1-ppt-65
Renal anlage
aka Wilm's (Childhood) Tumor: Nephroblastoma

a tumor with more than one cell type (generally derived from 1 germ layer)

Path-Neo1-ppt-65
Teratoma
"Monster Mass"

Tumor of more than one germ cell.
Orignate from totipotent cells found in ovary, testis, or abnormal embryonic "rests" (depots).

fully differentiated = benign
immature = malignant
malignancy that arises from within teratoma= teratocarcinoma

Path-Neo1-ppt-68
Path-RC-621
Malignancy that Arises from within Teratoma
teratocarcinoma

possible if teratoma immature (not fully differentiated)

Path-Neo1-ppt-68
Path-RC-621
Dermoid Cyst
Ovarian Cytic Teratoma

Mature (differentiated, benign) teratoma.

Differentiates along primarily epitheliod lineage: skin, hair, sabeceous glands, teeth

Path-Neo1-ppt-68
Path-RC-622
Myxo
mucous in appearance/mucoid

Path-Neo1-ppt-72
Myxoma
benign tumor of mesenchyme (stroma/matrix) with a mucoid appearance

---most common tumor of heart in adults
---may kill the patient by virtue of location

Path-Neo1-ppt-72
Most Common Tumor of Heart in Adults
myxoma
benign tumor of mesenchyme (stroma/matrix) with a mucoid appearance
---may kill the patient by virtue of location

Path-Neo1-ppt-72
Tumor names that sound benign
but are always malignant
Hepatoma = hepatocellular carcinoma
Melanoma should be called malignant melanoma
Lymphoma is always malignant lymphoma
Multiple myeloma (myelo = bone marrow): plasma cell malignancy
Mesothelioma, arises from pleura; peritoneum
Gliomas: brain tumor
Seminomas: testicular tumor

Path-Neo1-ppt-72
Hepatoma
hepatocellular carcinoma

sounds benign, but always malignant

Path-Neo1-ppt-72
Melanoma
should be called malignant melanoma

sounds benign, but always malignant

Path-Neo1-ppt-72
Lymphoma
always malignant lymphoma

sounds benign, but always malignant

Path-Neo1-ppt-72
Multiple Myeloma
plasma cell malignancy

sounds benign, but always malignant

(myelo = bone marrow)

Path-Neo1-ppt-72
Mesothelioma
Malignant Tumor from pleura; peritoneum

sounds benign, but always malignant

Path-Neo1-ppt-72
Glioma
Malignant Brain Tumor

sounds benign, but always malignant

Path-Neo1-ppt-72
Seminoma
Malignant Testicular Tumor

sounds benign, but always malignant

Path-Neo1-ppt-72
Lymphoma
Malignant neoplastic masses of lymphocytes

Compare to Leukemia

Path-Neo1-ppt-78
Leukemia
Malignancy of blood forming cells which do not form masses (Compare to Lymphoma);

involves bone marrow diffusely neoplastic cells may circulate in peripheral blood.

Path-Neo1-ppt-78
Meningioma
Benign neoplasm of meninges
---possibly fatal due to location

Path-Neo1-ppt-79
Neuroma
benign tumor of nerve origin

Path-Neo1-ppt-79
Heterotopia
aka Choristopia or Ectopic [tissue] or [tissue] rests

Normal, mature tissue present at an abnormal site.

Path-Neo1-ppt-81
Choristoma
aka Heterotopia or Ectopic [tissue] or [tissue] rests

Normal, mature tissue present at an abnormal site.

Path-Neo1-ppt-81
Ectopia
aka Heterotopia, Choristoma, Ectopic [tissue] or [tissue] rests

Normal, mature tissue present at an abnormal site.

Path-Neo1-ppt-81
Common Heterotopias
--Pancreatic or gastric tissue in a Meckel’s diverticulum
--Lingual thyroid (thyroid in tongue)
--Endometriosis--not a developmental anomaly
--Lacrimal gland tissue in conjunctiva

Path-Neo1-ppt-83
Hamartoma 2 common types
disorganized but differentiated proliferation of native tissue

Developmental, Benign: part of a continuum with benign neoplasia

Prominent Examples:
---Pulmonary Chondral Hamartoma: cartilage, bronchi, vasculature
---Clusters Bile Ducts in Liver

Path-Neo1-ppt-89
Path-RC-262
Four phases in the natural history of tumors
1) Transformation: malignant change
2) Growth of the transformed cells
3) Local invasion
4) Distant metastases

Path-Neo1-ppt-89
"Differentiation" of a Neoplasm
The extent to which neoplastic cells resemble comparable normal cells

Benign tumor cells are indistinguishable from non neoplastic cells of same type, may retain functions of the native organ

Anaplasia = lack of differentiation

Path-Neo1-ppt-89
Anaplasia

Morphology of Anaplastic Cells
Lack of Differentiation, the hallmark of malignancy

Morphology:
Pleomorphism‐ variation in size/ shape
Hyperchomatic nuclei‐ increased staining
Increased nuclear/cytoplasmic ratio
Increased mitotic activity; abnormal mitoses
Loss of orientation/polarity of cells
Other: tumor giant cells; necrosis

Path-Neo1-ppt-95
Tumor Grading
Malignant tumors are graded
--Grade 1: well differentiated; low grade>>slow growth
--Grade 2: moderately differentiated
--Grade 3: poorly differentiated; high grade>>rapid growth>>hemorrhage and necrosis

Path-Neo1-ppt-101
Dysplasia
Premalignant Lesions: Disordered Growth

Limited by intact basement membrane;
Does not involve the full thickness of epithelium (contrast with Carcinoma in Situ)
Cells lose polarity; are hyperchromatic and pleomorphic; mitoses increased
Severity based on dysplasia/epithelial thickness
Does not necessarily progress to cancer

Path-Neo1-ppt-106
Carcinoma in situ
Pre-invasive (pre)cancer

Limited by intact basement membrane;
Involves full thickness of epithelium (contrast with Dysplasia)
Cells lose polarity; are hyperchromatic and pleomorphic; mitoses increased
May invade or regress

Path-Neo1-ppt-107
Kinetics of tumor cell growth
Latent Period: 30 doublings to 1cm3, months-years

Smallest discoverable: 1 cm3

10 doublings from 1cm3 to 1kg (maximum life compatible)

Path-Neo1-ppt-112
Why do cancers grow rapidly?
more cells are in the growth fraction

Note: tumor cells take longer to divide than normal cells
(they're not just replicating faster)

Path-Neo1-ppt-114
Growth fraction
proportion of cells in the proliferative pool

MEASURED BY S-PHASE OR PROLIFERATIVE MARKER

Some tumor cells exit cycle

High growth fraction = aggressive behavior, rapid growth, chemotheraputic susceptibility

Path-Neo1-ppt-114
Benign vs Malignant Growth Rate “Exceptions”
Facial hemangiomas of infancy grow rapidly in first weeks after birth

Some malignant tumors may:
--regress (rare)
--grow slowly for years or become dormant
--undergo explosive dissemination over weeks/months after dormancy

Path-Neo1-ppt-115
Origin of Cancer
Cancer is monoclonal in origin

progresses from monoclonal cell of origin

Path-Neo1-ppt-122
Tumor Progression
acquisition of more aggressive behavior, greater malignant potential
---Accelerated growth
---Invasiveness
---Ability to form distant metastases

Incrementally acquired, multiple mutations in different tumor cells:
Produces tumor heterogeneity

Path-Neo1-ppt-122
Tumor Heterogeneity
Tumors are heterogeneous at time of presentation with multiple subclones that differ in invasiveness, karyotype, growth rate, theraputic resistance

Have been honed by selective pressures

Path-Neo1-ppt-123
Benign tumors
cohesive; expansile masses which generally do not invade

Tend be encapsulated: ring of fibrous, host tissue
Tumor is discrete; may be surgically enucleated (shelled out) completely
----Exception: hemangioma is nonencapsulated

Path-Neo1-ppt-123
the top one is malignant

the bottom one is encapsulated

Path-Neo1-ppt-127
Local invasion
Aka infiltration.

invades and destroys surrounding tissue
may produce a desmoplastic stroma
--collagenous; clinically indurated, ‘fixed’

A reliable sign that a tumor is malignant (Second only to metastases)

Path-Neo1-ppt-128
Local extension
direct tumor invasion of adjacent tissue or organ

Path-Neo1-ppt-128
Metastasis
tumor implants discontinuous with the primary tumor

Most reliable sign of malignancy

Almost all cancers can metastesize
----2 exceptions: CNS gliomas and Basal Cell Carcinomas of Skin
Metastatic Potential Tends to Correlated to Local aggressiveness and size

30% of cancers are metastatic at Dx

Path-Neo1-ppt-136
Invasive malignancies
that do not metastasize
Gliomas (glial cell tumors) of the CNS

&

Basal cell carcinomas of the skin

Path-Neo1-ppt-137
What are three pathways of metastases?
Seeding
Lymphatic metastases
Blood borne metastases

Path-Neo1-ppt-143
Staging of Tumors
based upon how far cancer has spread by extension and metastasis

Stage is the most important determinant of prognosis for most cancers

Path-Neo1-ppt-143
Seeding
One of the three metastatic pathways (along with lymphatics and blood borne)

Cancer breaks through to an “open field” and spreads onto surfaces of space

Peritonal: ovarian, gastric, pancreatic, some intestinal

Pleural/Pericardial: lung cancer

CNS, Urinary Tract

Path-Neo1-ppt-144
How will ovarian cancer metastasize?
Peritoneal Seeding:

Cancer breaks through to an “open field” and spreads onto surfaces of space

Path-Neo1-ppt-144
How will gastric carcinoma metastasize?
Peritoneal Seeding:

Cancer breaks through to an “open field” and spreads onto surfaces of space

Path-Neo1-ppt-144
How will pancreatic carcinoma metastasize?
Peritoneal Seeding:

Cancer breaks through to an “open field” and spreads onto surfaces of space

Path-Neo1-ppt-144
How will intestinal malignancies metastasize?
Peritoneal Seeding:

Cancer breaks through to an “open field” and spreads onto surfaces of space

Path-Neo1-ppt-144
How will lung cancer metastasize?
To Perihilar Lymph Nodes

Plleural/Pericardial Seeding: Cancer breaks through to an “open field” and spreads onto surfaces of space

Path-Neo1-ppt-144
Lymphatic Metastasis
Carcinomas will metastasize initially via lymphatic channels at periphery of tumor

Carcinomas = Epithelial Tumors

Commonly Oral. Breast, Lung, Colon

Path-Neo1-ppt-147
How will oral cancer metastasize?
Via cervical lymph nodes

Path-Neo1-ppt-150
How will breast cancer metastasize?
Via axillary and other nodes

Path-Neo1-ppt-150
How will colon cancer metastasize?
Via paracolic lymph nodes

Path-Neo1-ppt-150
Significance of Lymph Node
Metastases
Increases chances of more distant metastases

Regional lymphadenectomy indicated for carcinoma tumor staging

Path-Neo1-ppt-153
Sentinel Node Biopsy
Sentinel node: first node(s) in the regional basin receives lymph flow from the tumor

Currently used for breast cancer; malignant melanoma

Avoids lymphedema by targetting most likely nodes

Path-Neo1-ppt-154
Hematogenous Metastases
Vessel invasion by tumor emboli

Initial route for sarcomas, Late route of carcinomas

Most commonly
--Via Veins
--To Lungs or Liver

Arterial exclusively from or via the lungs

Path-Neo1-ppt-155
Arterial Hematogenous Metastases
Arterial exclusively from or via the lungs

Most travel via veins to lungs or liver

Path-Neo1-ppt-155
Staging of Cancer
Prediction of Cancer Outcome based on organ-specific statistics

TNM System
T= primary tumor size, invasive depth
N= Nodal Involvement 0 or 1
M= Blood Borne Metastases 0 or 1, M1 always stage 4
If unknown =X (eg MX)

Path-Neo1-ppt-159
TNM System,
evaluating T
Tis = in situ, precancer; no invasion, no risk of metastases

T1‐ invasive but relatively small and confined to primary site

T2‐T4 = tumor increasing in size, and/or invasion at primary site

Path-Neo1-ppt-161
TNM System,
evaluating N
nodal Involvement

N either = 0, no nodes
or =1, any nodes

Path-Neo1-ppt-161
TNM System,
evaluating M
M= Blood Borne Metastases

0 or 1

M1 always stage 4

Path-Neo1-ppt-159
Stage 0
Tis-N0-M0

in situ carcinoma

Path-Neo1-ppt-164
Stage I
T1-N0-M0

small invasive primary tumor, no nodes, no blood‐borne metastases

Path-Neo1-ppt-164
Stages II and III
Increasing Tumor Size, extension, possible lypmh nodes

But no blood borne metasteses (M0)

Path-Neo1-ppt-165
Stage IV
Any blood borne metasteses (M1)

or

Extensive Inoperable Local Tumor (T4)

Path-Neo1-ppt-165
Compare/contrast characteristics of benign vs malignant neoplasms
Benign: Encapsulated, cohesive, well demarcated
Malignant: locally invasive; infiltrating; some may appear cohesive

Benign: ‘Differentiated’
Malignant: Anaplasia

Benign: Low Mitotic Rate, Years of Slow Growth
Malignant: Erratic Growth Rate

Benign: No Mets
Malignant: Freq Mets

Both: Clonal, Autonomous Growth

Path-Neo1-ppt-169
Path-RC-271-Figure 7-20