PATH FALL Neoplasia 1

I bet I will fill through most of these later, but go through and make sure.

Swelling. Currently used as if synonymous with neoplasm.

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epithelial tumors

often used imprecisely to mean any/all tumors

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Benign Neoplasia

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

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‐oma

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

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Benign Glandular Tumor

Either From Glandular Origin

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

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Adenoma

Either From Glandular Origin

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

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cystic masses created by adenomas benign neoplastic glandular cells

Cyst: closed cavity or sac lined by epithelium

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Benign epithelial neoplasms which form finger‐like projections

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Papillomas (benign epithelial neoplasms which form finger‐like projections) protruding into cystic spaces (closed cavity or sac lined by epithelium)

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Growth pattern projects above the skin or mucosal surface

may be neoplastic or nonneoplastic (eg inflam)

3 forms: sessile, pedunculated, papillary

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Sessile Polyp

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

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Pedunculated Polyp

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

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Papillary Polyp

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

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Benign Tumor from Smm

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Benign Tumor from Skm

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Benign Tumor from Blood Vasculature

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Benign Tumor from Lymphatic Vasculature

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will cause death

grows rapidly
invades and destroys surrounding areas
may metastasize

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tumors derived from mesenchyme

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Malignant tumor of basal cells of skin or adnexa (hair, sweat glands, etc)

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Malignant tumor of glandular, duct or columnar cell origin

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Squamous cell carcinoma

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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

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Malignant Neurecotodermal Neoplasm in the skin/conjunctiva/iris

Enlarging; may ulcerate; outline irregular

Compare to Nevus: mole

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benign tumor of placental epithelium

compare to choriocarcinoma

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malignant tumor of placental epithelium

compare to hydatiform mole

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Malignant tumor of male Germ cell epithelium
---dysgerminoma in females

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Malignant tumor of female Germ cell epithelium
---Seminoma in males

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a malignant tumor of germ cell epithelium

See also seminoma and dysgerminoma

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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

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pleomorphic adenoma- one cell gives rise to multiple lineages

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pleomorphic adenoma- one cell gives rise to multiple lineages


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fibroadenoma (fibrous tissue + glands)

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aka Wilm's (Childhood) Tumor: Nephroblastoma

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

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"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

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teratocarcinoma

possible if teratoma immature (not fully differentiated)

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Ovarian Cytic Teratoma

Mature (differentiated, benign) teratoma.

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

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mucous in appearance/mucoid

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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

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myxoma
benign tumor of mesenchyme (stroma/matrix) with a mucoid appearance
---may kill the patient by virtue of location

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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

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hepatocellular carcinoma

sounds benign, but always malignant

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should be called malignant melanoma

sounds benign, but always malignant

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always malignant lymphoma

sounds benign, but always malignant

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plasma cell malignancy

sounds benign, but always malignant

(myelo = bone marrow)

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Malignant Tumor from pleura; peritoneum

sounds benign, but always malignant

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Malignant Brain Tumor

sounds benign, but always malignant

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Malignant Testicular Tumor

sounds benign, but always malignant

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Malignant neoplastic masses of lymphocytes

Compare to Leukemia

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Malignancy of blood forming cells which do not form masses (Compare to Lymphoma);

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

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Benign neoplasm of meninges
---possibly fatal due to location

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benign tumor of nerve origin

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aka Choristopia or Ectopic [tissue] or [tissue] rests

Normal, mature tissue present at an abnormal site.

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aka Heterotopia or Ectopic [tissue] or [tissue] rests

Normal, mature tissue present at an abnormal site.

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aka Heterotopia, Choristoma, Ectopic [tissue] or [tissue] rests

Normal, mature tissue present at an abnormal site.

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--Pancreatic or gastric tissue in a Meckel’s diverticulum
--Lingual thyroid (thyroid in tongue)
--Endometriosis--not a developmental anomaly
--Lacrimal gland tissue in conjunctiva

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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

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1) Transformation: malignant change
2) Growth of the transformed cells
3) Local invasion
4) Distant metastases

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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

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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

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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

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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

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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

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Latent Period: 30 doublings to 1cm3, months-years

Smallest discoverable: 1 cm3

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

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more cells are in the growth fraction

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

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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

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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

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Cancer is monoclonal in origin

progresses from monoclonal cell of origin

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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

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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

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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

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the top one is malignant

the bottom one is encapsulated

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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)

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direct tumor invasion of adjacent tissue or organ

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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

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Gliomas (glial cell tumors) of the CNS

&

Basal cell carcinomas of the skin

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Seeding
Lymphatic metastases
Blood borne metastases

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based upon how far cancer has spread by extension and metastasis

Stage is the most important determinant of prognosis for most cancers

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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

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Peritoneal Seeding:

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

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Peritoneal Seeding:

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

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Peritoneal Seeding:

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

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Peritoneal Seeding:

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

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To Perihilar Lymph Nodes

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

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Carcinomas will metastasize initially via lymphatic channels at periphery of tumor

Carcinomas = Epithelial Tumors

Commonly Oral. Breast, Lung, Colon

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Via cervical lymph nodes

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Via axillary and other nodes

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Via paracolic lymph nodes

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Increases chances of more distant metastases

Regional lymphadenectomy indicated for carcinoma tumor staging

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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

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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

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Arterial exclusively from or via the lungs

Most travel via veins to lungs or liver

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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)

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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

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nodal Involvement

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

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M= Blood Borne Metastases

0 or 1

M1 always stage 4

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Tis-N0-M0

in situ carcinoma

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T1-N0-M0

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

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Increasing Tumor Size, extension, possible lypmh nodes

But no blood borne metasteses (M0)

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Any blood borne metasteses (M1)

or

Extensive Inoperable Local Tumor (T4)

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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

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