Cyberfriends: The help you're looking for is probably here.

Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected.

DoctorGeorge.com is a larger, full-time service. There is also a fee site at myphysicians.com, and another at www.afraidtoask.com.

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With one of four large boxes of "Pathguy" replies.

I'm still doing my best to answer everybody. Sometimes I get backlogged, sometimes my E-mail crashes, and sometimes my literature search software crashes. If you've not heard from me in a week, post me again. I send my most challenging questions to the medical student pathology interest group, minus the name, but with your E-mail where you can receive a reply.

Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource. Someday you may be able to access these pictures directly from this page.

My home page
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Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.

Clinical Queries -- PubMed from the National Institutes of Health. Take your questions here first.
HealthWorld
Yahoo! Medline lists other sites that may work well for you

Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review linked below. If you are interested in complementary medicine, then I would urge you to visit my new 8Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.

I cannot examine every claim that my correspondents share with me. Sometimes the independent thinkers prove to be correct, and paradigms shift as a result. You also know that extraordinary claims require extraordinary evidence. When a discovery proves to square with the observable world, scientists make reputations by confirming it, and corporations are soon making profits from it. When a decades-old claim by a "persecuted genius" finds no acceptance from mainstream science, it probably failed some basic experimental tests designed to eliminate self-deception. If you ask me about something like this, I will simply invite you to do some tests yourself, perhaps as a high-school science project. Who knows? Perhaps it'll be you who makes the next great discovery!

Our world is full of people who have found peace, fulfillment, and friendship by suspending their own reasoning and simply accepting a single authority that seems wise and good. I've learned that they leave the movements when, and only when, they discover they have been maliciously deceived. In the meantime, nothing that I can say or do will convince such people that I am a decent human being. I no longer answer my crank mail.

This site is my hobby, and I presently have no sponsor.

This page was last updated February 6, 2006.

During the ten years my site has been online, it's proved to be one of the most popular of all internet sites for undergraduate physician and allied-health education. It is so well-known that I'm not worried about borrowers. I never refuse requests from colleagues for permission to adapt or duplicate it for their own courses... and many do. So, fellow-teachers, help yourselves. Don't sell it for a profit, don't use it for a bad purpose, and at some time in your course, mention me as author and KCUMB as my institution. Drop me a note about your successes. And special thanks to everyone who's helped and encouraged me, and especially the people at KCUMB for making it possible, and my teaching assistants over the years.

Whatever you're looking for on the web, I hope you find it, here or elsewhere. Health and friendship!

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Define "tumors" and "neoplasms". Tell why they are important. Define "oncology". Tell how tumors are like organs, and how they are different.

Distinguish "benign tumors" and "malignant tumors" by their gross and microscopic appearances and their behaviors. Tell what "well-differentiated" and "poorly differentiated" mean. Tell how benign tumors can cause problems.

Define "cancer", "malignant", and "metastasis". Tell what any cancer will ultimately do to the patient if it is not cured. Recognize the typical appearances of cancers. Distinguish "carcinomas" and "sarcomas".

Tell how and where various cancers tend to metastasize. Describe patterns for invasion and metastasis by various malignant tumors.

List the three most common cancers in men and in women, and the three most common fatal ones.

Given a tumor name, name the cell of origin and describe the behavior. Given the cell of origin (or a hint) and the behavior (or a hint), name the tumor.

Distinguish "grade" and "stage" of a cancer. Tell why these numbers are important.

Recognize, under the microscope, a squamous cell carcinoma, an adenoma, an adenocarcinoma, a tumor of hematologic origin, and a spindle cell sarcoma. Recognize anaplasia, and generally tell benign from malignant tumors.

Critique the following statement, overheard on a cancer ward: "Cancer cells grow faster than normal cells and are not under the body's control. Therefore, the treatment for cancer involves giving anti-mitotic drugs that kill fast-growing cells."

LEARN FIRST

Tumors (neoplasms) may be considered new, useless organs.

Cancers (malignant neoplasms) invade and spread to remote sites (metastasize). Benign tumors cannot invade or spread to remote sites, but they can cause problems by compressing local structures.

Tumors arise from single cells, and they recapitulate, more or less, the things that cell did in health. The cell of origin gives its name to the tumor.

Benign tumors are usually round like balls. Cancers look like cauliflowers, ulcers, or else simply expand the organ.

Cancers that arise from epithelium are called "carcinomas". Cancers that arise from mesenchyme/mesoderm are called "sarcomas".

Cells and histologic architecture in benign tumors is similar to normal histology. Cells and microscopic architecture in cancers are bizarre. The grade of a cancer is a function of how bizarre the cells look. The higher the grade, the more likely to cancer is to behave aggressively.

The stage of a cancer is how far the clinician knows it has spread.

Microscopic Neoplasia III Great pathology images Indiana Med School

General Pathology Virginia Commonwealth U. Great pictures

Neoplasia I Introductory Pathology Course University of Texas, Houston

Neoplasia Cornell Class notes with clickable photos

Neoplasia II Introductory Pathology Course University of Texas, Houston

Neoplasia I From Chile In Spanish

Neoplasia II From Chile In Spanish

Neoplasia III From Chile In Spanish

Neoplasia IV From Chile In Spanish

Neoplasia V From Chile In Spanish

Neoplasia VI From Chile In Spanish

Neoplasia VII From Chile In Spanish

Neoplasia VIII From Chile In Spanish

Neoplasia IX From Chile In Spanish

QUIZBANK: See next handout

One out of about every five persons in the US who die this year will die of tumors (about 500,000 total).

* "Tumor"--literally any swelling. Galen distinguished tumors that are:

"natural"--pregnant uterus

"unnatural"--pus, bony callus

"contrary to nature"--what we now know as neoplasms ("new growths")

The ancient medical writings show an awareness of cancer, and Morgagni remarked that by his era, most physicians were aware that tumors were not treatable except by surgery.

"Oncology" is the study of tumors. In current usage, an oncologist is an internist or surgeon who specializes in the administration of cancer chemotherapy.

In modern usage, a tumor/neoplasm may be thought of as an attempt by the body under some stimulus to make some new sort of organ. (It develops in the wrong shape, in the wrong place, and it persists after the initiating stimulus is removed.)

Tumors are like organs:

All have parenchyma and stroma.

Cells usually look similar to cells in the organ where the tumor arose.

Cells will continue to perform some of the functions of the parent organ.

Tumors are different from organs:

They don't contribute to the homeostasis of the body.

They usually grow more rapidly than surrounding tissues.

Some benign and all malignant tumors never cease to grow.

When a benign tumor "ceases to grow", it simply means that the number of cells dying off equals the number of new cells. Since the genome of malignant tumors is by definition destabilized, more-and-more actively-proliferating clones of cells appear, so continued growth is inevitable.

"Spontaneous regression" of a cancer (i.e., massive shrinkage or disappearance without adequate therapy to explain it) is much-discussed phenomenon that occasionally happens. More often than not, the cancer comes back after a few months. Review, emphasizing the ongoing mystery: In Vivo 14: 773, 2000.

Most tumors show some derangement of histologic architecture.

Malignant tumors are locally invasive and have metastatic potential.

We have already learned a few essential terms:

Anaplasia: Ugly cells. A marker for cancer or pre-cancer.

Neoplasia: A new, useless organ produced by cells bearing mutations.

Dysplasia: Ugly cells in an epithelium, without invasion. Near-synonyms are "carcinoma in situ", "intraepithelial neoplasia", "incipient neoplasia", and "precancer".

Malignant: A neoplasm that will invade the surround tissue. A synonym for "malignant neoplasm" is "cancer". Most types of cancer will also eventually spread to remote sites; hence the importance of timely detection and cure.

Benign: (1) A neoplasm that will compress but not invade the surrounding tissue. (2) Loosely, any non-cancer, non-precancer diagnosis.

A tumor is either benign or malignant.

Characteristics of benign ("good") tumors:

• Cells resemble normal cells and tumor architecture resembles that of the parent organ ("well-differentiated").

• Usually are spherical and compress the surrounding tissues (giving rise to the appearance of a "capsule").

Benign lipoma Round and smooth WebPath Photo

Benign lipoma WebPath Photo

Benign lipoma WebPath Photo

Benign leiomyomas WebPath Photo

Benign leiomyoma Normal-looking smooth muscle WebPath Photo

Leiomyoma Electron micrographs VCU Pathology

{14165} benign ovarian cystic tumor; it weighed approximately 30 lb
{17488} benign fibroadenoma of breast

• Grow slowly and have few mitotic figures.
• Never metastasize. (If it metastasizes, it has turned malignant.)

Characteristics of malignant ("bad") tumors

Malignant tumors generally grow more rapidly than benign tumors.

However, no malignant tumor grows as rapidly as an embryo, nor do cancer cells divide nearly as fast as cells in normal bone marrow or intestinal epithelium. Today, anyone who thinks of cancer cells growing "without any control" is guilty of willful ignorance

Cells differ morphologically and functionally from normal cells, and tumor architecture is less organized than that of parent tissue.

Tumor cells are locally invasive; the tumor grows into the surrounding tissue and destroys it.

This feature led Dr. Hippocrates to call such tumors karkinoma after karkinos, Greek for "crab." (Cancer is Latin for "crab".)

Bone sarcoma WebPath Photo

Anaplastic cancer cells David Barber MD -- KCUMB

Anaplasia / dysplasia developing in a columnar epithelium David Barber MD -- KCUMB

Cutaneous leiomyosarcoma Pittsburgh Pathology Cases

Metaphase
Cancer cell in division
Dave Barber MD, KCUMB

The tumor will eventually metastasize, spreading to another site remote from the original tumor (exceptions: basal cell carcinomas of skin, cancers of glial origin).

Malignant tumor and cancer are synonyms.

Benign or malignant, each tumor has a "cell of origin" from its tissue.

Old studies proved that women heterozygous for G6PD variants express only one form in each uterine tumor because of lyonization. And we've long known that plasma cell myeloma produces a monoclonal immunoglobulin product. More about "Nowell's law" soon.

Tumor cells almost always mimic one cell type of some normal organ, usually the one in which the tumor arose.

Cells may continue to elaborate keratin, mucus, hormones, immune globulin, etc. And they may show cross-striations (skeletal muscle cells), microvilli (certain glandular cancers), melanosomes (melanocyte cancer)., etc., etc.

The resemblance will be better or worse depending on whether the tumor is "well-differentiated" or "poorly differentiated."

Much of the day-to-day work of a surgical pathologist is figuring out the cell of origin of poorly-differentiated cancers. The main tools are electron microscopy (now mostly passé) and immunoperoxidase stains ("the brown revolution").

Worth learning now:

Squamous cell carcinomas

These arise anywhere there is a stratified squamous epithelium, either healthy (skin, esophagus, mouth, many others) or metaplastic (endocervix, bronchi).

Look for any (or even all) of the following:

• keratin (will stain orange-red on H&E)
• pearls (i.e., whorls that mimic little hairs)
• desmosomes ("intercellular bridges", "prickles")
• tonofilaments (electron microscopy)
• single-cell apoptosis (cells think they're at the top of the epidermis)



The better these things show, the better-differentiated the tumor! (Benign squamous tumors are uninteresting connective tissue covered with almost-normal-looking stratified squamous epithelium.)

{10085} squamous cell carcinoma
{10088} squamous cell carcinoma, sort-of-good desmosomes
{08977} squamous cell carcinoma, sort-of-good pearls
{09157} squamous cell carcinoma, good desmosomes
{09159} squamous cell carcinoma, electron micrograph, tonofilaments in the cell on the right
{10987} squamous cell carcinoma, very good pearls
{12596} squamous cell carcinoma, keratin is very pink, sort-of pearls
{15424} squamous cell carcinoma, good pearls

Squamous cell carcinoma
Good pearl
Dave Barber MD, KCUMB

Squamous cell carcinoma Right cheek Pittsburgh Pathology Cases

Squamous cell carcinoma Good photos Pittsburgh Pathology Cases

Squamous cell carcinoma Eye pathology site

Squamous carcinoma Good pearls WebPath Photo

Squamous cell carcinoma Well-differentiated WebPath Photo

Squamous cell carcinoma Not-so-well differentiated WebPath Photo

Squamous cell carcinoma Nice desmosomes WebPath Photo

Squamous cell carcinoma Electron micrograph -- desmosomes WebPath Photo

Squamous cell carcinoma Electron micrographs VCU Pathology

Invasive squamous carcinoma
Below squamous epithelium
Dave Barber MD, KCUMB

Adenocarcinomas

These arise anywhere there are glands, even single-celled glands (i.e., goblet cells)

Look for any (or even all) of the following:

• lumens (intercellular, intracellular)

Adenocarcinoma Pittsburgh Pathology Cases

Adenocarcinoma Anaplastic cells making clear glands Urbana Atlas of Pathology

Colon adenocarcinoma Not so well differentiated Urbana Atlas of Pathology	Colon adenocarcinoma Fairly well differentiated Urbana Atlas of Pathology

Colon adenocarcinoma Urbana Atlas of Pathology

Breast adenocarcinoma WebPath Photo

• especially, glands-within-glands ("Swiss cheese")

Adenoid cystic carcinoma Breast primary Pittsburgh Pathology Cases

"Glands within glands" Adenocarcinoma Photo by Ed

• or even "inside-out" glands, with the malignant cells growing around a fibrous stalk ("papillary growth")

Adenocarcinoma
Prostate
ERF/KCUMB

Adenocarcinoma
Prostate
ERF/KCUMB

Adenocarcinoma
Prostate
ERF/KCUMB

• mucin (intercellular "lakes", intracellular; "mucicarmine" stain will identify these)
• other secretory products, depending on the gland of origin (immunostain may be required)
• cells forming cohesive nests, or at least sticking to one another

Colon adenocarcinoma Invading glands WebPath Photo

• signet-ring cells containing mucin, alone or in clusters
• microvilli

Microvilli From an adenocarcinoma WebPath Photo

{129} adenocarcinoma, apocrine
{08806} adenocarcinoma of colon; low-power shot shows it arising from the mucosa and pushing toward the muscularis propria
{08852} adenocarcinoma of the pancreas; find some odd glands and some signet-ring cells
{08865} prostate adenocarcinoma; some swiss cheese
{08866} prostate adenocarcinoma; some swiss cheese

Metastatic adenocarcinoma Pittsburgh Pathology Cases

Adenomas exhibit most of the same features (though not glands-within-glands or signet-ring cells), and look benign. (An adenoma may contain dysplasia; in that case, the adenoma is premalignant.) See below.

Spindle-cell sarcomas

These arise anywhere where there is connective tissue.

Look for cells with elongated nuclei running parallel, with at least a modest amount of cytoplasm.

{16671} leiomyosarcoma (smooth muscle cells, slightly high N/C ratio)

Abnormal pap smear
High NC ratio
Dave Barber MD, KCUMB

Sarcoma Trust us. WebPath Photo

Spindle-cell sarcoma WebPath Photo

Spindle-cell sarcoma WebPath Photo

Spindle-cell sarcoma WebPath Photo

Leukemias and lymphomas

Look for cells that resemble blood precursors, not sticking tightly together. (These features distinguish these common cancers from carcinomas and sarcomas.)

{23776} acute leukemia, basophils predominate

Acute Lymphoblastic Leukemia Peripheral smear KU Collection

Lymph node with cancer metastasis
Photo and mini-review
Brown U.

Immunostains:



• CEA: endodermal adenocarcinomas ("carcinoembryonic antigen")


• CLA: tumors of white cells ("common leukocyte antigen")


• desmin: myosarcomas


• EMA: adenocarcinomas ("epithelial membrane antigen")


• Factor VIII: endothelium


• GFAP: glial tumors ("glial fibril acid protein")


• NSE: oat cell CA, isletomas, APUDomas ("neuron-specific enolase")


• keratin family: most epithelial neoplasms


• S-100: melanoma, schwannoma, brain, antigen-presenting dendritic macrophages, histiocytosis X, some myoepithelium


• vimentin: mesenchymomas, melanomas, kidney tubule

Carcinoma Keratin stain WebPath Photo

Sarcoma Vimentin stain WebPath Photo

Benign tumors may cause problems:

The tumor may secrete something in excess (typically a hormone).

The tumor may compress surrounding structures.

{221} meningioma compressing brain
{1855} craniopharyngioma

A few benign tumors sometimes transform into malignant tumors. Once this happens, they are no longer benign (so, benign tumors never metastasize).

In some syndromes, benign tumors may be multiple.

Malignant tumors in the U.S:

The most common cancers:

Males (in descending order): prostate, lung, colon

Females (in descending order): breast, lung, colon

The most commonly cancer killers:

Males (in descending order): lung, prostate, colon

Females (in descending order): lung, breast, colon

NOTE: Worldwide, cancer of the cervix is the great killer of women, especially young women.

NOTE: The other great third-world killer is hepatocellular carcinoma, which is primarily a man's tumor (because of hepatitis B carrier status and iron overload).

Thanks to the decline in deaths from atherosclerosis, cancer is now the leading cause of death in U.S. females, and is about tied with atherosclerosis for US males.

What do cancers look like?

You remember that benign tumors are usually round like a ball. (The same can be true of some very tame cancers.)

The Gross appearances of cancers usually fits one of three patterns:

Exophytic ("fungating"): tumor grows as a lump, often with a cauliflower-like surface.

Exophytic cervix cancer WebPath Photo

(Malignant tumors seldom appear "encapsulated.")

{5801} fibrosarcoma; here and below, we'll want microscopy for confirmation
{5831} fibrosarcoma
{5834} liposarcoma
{5958} chondrosarcoma
{08437} uterine adenocarcinoma ("cottage cheese in the uterine cavity")
{08916} uterine adenocarcinoma
{10208} colon adenocarcinoma
{10211} colon adenocarcinoma, in section
{10435} bronchogenic carcinoma
{17511} gastric adenocarcinoma
{11087} squamous cell carcinoma of larynx

Endophytic: tumor grows as an ulcer (i.e., the part that was probably protruding from the surface sloughed).

{09810} esophageal carcinoma
{10436} lip cancer
{12169} lip cancer

Infiltrating: tumor cells invade an organ diffusely without changing its shape.

{1573} brain cancer (glioblastoma)
{1596} same; microscopy
{1599} same; microscopy

Any cancer is likely to exhibit hemorrhage and/or necrosis, grossly and microscopically. These result from the cancer cells invading the tumor's own blood vessels.

Hemorrhage in a high-
grade colon cancer
Dave Barber MD, KCUMB

Microscopic appearance:

Individual cell morphology and tumor architecture may be "well-differentiated" (good prognosis) to "poorly-differentiated" ("anaplastic", bad prognosis).

The malignant-looking cell:

• Increased nuclear DNA, increased nuclear/cytoplasmic ratio, hyperchromatic nucleus, coarsening of chromatin, wrinkled nuclear edges, multinucleation, macronucleoli.
• Numerous and bizarre mitotic figures. Tripolar mitoses are only the most familiar of the many weird patterns you may see. (NOTE: Mitotic figures last longer in cancers than in healthy tissues, so this is not "proof that cancers grow very rapidly".)

Bizarre mitotic figures One is a classic "tripolar" KU Collection

Mitotic figures WebPath Photo

Bizarre mitotic figures WebPath Photo

Cancer cells, smear Urbana Atlas of Pathology

Cancer cells, smear Urbana Atlas of Pathology

Bizarre mitotic figure Ed Lulo's Pathology Gallery

Bizarre mitotic figure Tom Demark's Site

Tripolar mitosis Photomicrograph, nice spindles New England Journal of Medicine

{00132} bizarre mitotic figure

*Better measures of cell division, useful in prognosticating tumors, include immunostaining for PCNA (proliferating cell nuclear antigen) and MIB-1/Ki-67. Many current articles; for example Am. J. Clin. Path. 107: 229, 1997.

• Failure to mature along normal functional lines.
• Cells of widely varying sizes.
• Loss of orientation of cells to one another.

There may also be microscopic visible invasion (tumor cells growing into adjacent normal structures where they don't belong), and/or indirect evidence (hemorrhage and/or necrosis; either is important evidence that the tumor in question is malignant).

Today's pathologists have stains to show the laminin in the basement membrane, if there is any doubt as to whether the tumor is "through".

{10478} squamous cell carcinoma invading; be sure you can recognize the tentacles ("tumor cords") cut in cross section

Usually, the more abnormal a tumor appears under the microscope, the more rapidly it grows and the worse the patient's prognosis.

How will I see malignant tumors invading?

Local infiltration

Invasion of surrounding tissues

For some reason, cartilage, tendon, and elastic tissue almost never get invaded.

{08845} cholangiocarcinoma invading around a nerve ("perineural invasion")

Cancer around a nerve WebPath Photo

"Intraepithelial spread" is possible and may take the form of single cells ("Paget's disease" of the nipple from an underlying breast cancer, many melanomas) or of dysplasia / carcinoma in situ, in which an epithelial surface is replaced by a layer of anaplastic cells that has not (yet) penetrated the basement membrane.

What is the difference between dysplasia and carcinoma in situ?
First idea: "Carcinoma in situ is full-thickness dysplasia. Turn the epithelium upside-down. If it looks the same, it is carcinoma in situ. The cells have completely forgotten how to mature." This merely reminds us that going from the mildest dysplasia to the meanest carcinoma in situ is a continuum. The only obvious dividing line is the moment of invasion -- when the first malignant cell penetrates the basement membrane.

Second idea: "Dysplasia is reversible and carcinoma in situ is not." I have been hearing this since I entered medical school without anybody ever showing me any evidence that it is true. How are you going to tell? Nobody has ever made a study to "just watch" either full-thickness or partial-thickness intraepithelial anaplasia.

Third idea: "Who cares? Call them both intraepithelial anaplasia. Mild, moderate, or severe." This made so much sense that Bethesda decided to call them "intraepithelial neoplasia" instead.

{08912} carcinoma in situ, endocervix (junction with normal, i.e., the "carcino-columnar junction")

Carcinoma in situ
Urbana Atlas of Pathology

Metastatic spread:

There are four routes:

(1) Seeding of serosal surfaces (or, in the case of CNS tumors, up and down the neuraxis in the CSF)

(2) Mechanical transplantation (rare, typically iatrogenic; see for example Br. J. Surg. 81: 648, 1994)

(3) Via lymphatics (traditional route for tumors of epithelial origin, i.e., carcinomas)

Tumors spread first to regional lymph nodes, then (because of disruption of directions of lymph flow) to any lymph nodes or organs

{21051} carcinoma in lymphatics (small intestinal mesentery)
{21052} carcinoma in lymphatics

Lymphatic with carcinoma
Uterus
ERF/KCUMB

(4) Via blood vessels (traditional route for tumors of mesenchymal origin, i.e., sarcomas, because the tumor cells are in direct contact with blood vessels from the beginning)

Regardless of the route of metastatic spread, certain tumors have unexplained preference for certain metastatic sites.

Why? Even today, there's no clear molecular explanation.

The common sites for metastatic spread for many common cancers include lymph nodes, lung, liver, bone, and brain.

Most cancers seldom metastasize to the muscles, spleen or gonads.

Requirements for successful metastatic spread:

• Basement membrane and endothelial penetration
• Attachment at metastatic site
• Stromal induction

"Tumor angiogenesis factor" (more about this momentarily...)

Collagen production by local fibroblasts (if dense, tumor is called "desmoplastic")

Metastatic nodules are called "metastases" or (vulgarly) "mets".

{08443} "liver mets"
{08444} "liver mets"

Cancer of the pancreas Primary and liver metastases KU Collection

Liver metastases WebPath Photo

Lymph node metastasis WebPath Photo

Cancer in pulmonary lymphatics WebPath Photo

Peritoneal metastases WebPath Photo

Pleural metastasis WebPath Photo

Liver Metastases Tom Demark's Site

*There has always been a lot of interest in the basic biology of the metastatic process. It remains an array of tantalizing clues. See, for example, the discovery that the presence of certain blood group antigens on the surfaces of tumor cells seems to increase their mobility and their metastatic potential (NEJM 327: 14, 1992).

Malignant tumors: Grade and Stage:

The grade and stage of a cancer are determined to offer a prognosis and to determine treatment.

Both grade and stage are usually represented by Roman numerals, the best situation by I, the worst by III, IV, or V depending on the tumor type and determined by rules. Do not confuse grade and stage!

Tumor grade: assigned by the pathologist to reflect the cancer's degree of differentiation.

Grade I: Well-differentiated, cells look like normal organ (benign = Grade 0)
Grade II: Not so well-differentiated
Grade III: Worse than that
Grade IV: Even worse
Grade V: Worst of all (most tumor types are graded I-III or I-IV)

Flow cytometry can help measure anaplasia by measuring how much DNA is in each cell.

High-grade carcinoma WebPath Photo

Flow cytometry WebPath Photo

Leave the arcana of grading up to us in pathology. Rules are constantly changing, and new prognostic factors emerging (* for example, a current popular approach is counting argyrophilic nucleolar organizer regions, AgNOR's: Cancer 74: 1658, 1994; bladder J. Urol. 162: 63, 1999; thymoma Chest 115: 1115, 1999; prostate Cancer 79: 1956, 1997; sputum cytology Chest 111: 1591, 1997; Cancer 82: 86, 1998; squamous lung carcinoma Cancer 111: 110, 1997).

Tumor stage: assigned by the clinician on the basis of all available information on the extent of tumor spread.

Stage I might mean the tumor is smaller than 1 cm diameter, without metastases

Stage II might mean the tumor is larger than 1 cm and/or is symptomatic and/or there are metastases to the regional lymph nodes

Stage III might mean the tumor has infiltrated a non-resectable structure and/or there are distant metastases

Rules for assigning stage are quite elaborate and different for each type of tumor.

Alternative system: TNM

"T" for tumor:

T1 might mean primary tumor is smaller than 1 cm in diameter

T2 might mean primary tumor is larger than 1 cm in diameter

T3 might mean primary tumor is invading something non-resectable

"N" for regional lymph nodes:

N0 would mean no tumor in regional lymph nodes

N1 might mean tumor in a few nearby lymph nodes

N2 might mean many nodes, or some nodes farther downstream, are involved

"M" for metastases:

M0 would mean no distant metastases

M1 would imply distant metastases, etc.

*So the TNM stage for a lung cancer that is invading or encasing the superior vena cava but has metastases only in two nearby lymph nodes might be T3 N1 M0.

Memorizing tumor staging systems is not an appropriate pathology learning objective, and I will not test you on it.

Generally tumors of high grade present at high stage, while tumors of low grade present at low stage.

Tumor Nomenclature

I. To assign a name to a tumor that you have examined, begin by writing the suffix -oma. Most tumor names end in this way. (Unfortunately, the suffix simply means "swelling", and some non-neoplasms also use the suffix, i.e., granuloma, hematoma, xanthoma, traumatic neuroma).

II. If the tumor is malignant, write the root carcin- ("crab") if the tumor is of epithelial origin, or sarc- ("flesh") if the tumor is of mesenchymal origin, before -oma. If the tumor is benign, do not write anything.

III. Now choose one or more roots to describe the cell of origin.

If the tumor originated in glandular epithelium, use the root adeno-. (It probably makes little glands and/or mucin.)

If the tumor originated in squamous or transitional epithelium, is benign, and protrudes above the epithelial surface, use the root papillo-.

If the tumor originated in non-glandular epithelium and is malignant, name it for the cell of origin.

Basal cell carcinoma (skin)
Renal cell carcinoma (proximal tubule)
Squamous cell carcinoma (squamous epithelium)
Cholangiocarcinoma (bile ducts)

If the tumor originated from a non-epithelial cell, look for a root in the following list. (We do not consider endothelium and mesothelium to be epithelium for this purpose.)

fibro-: fibroblasts
myxo-: myxoid tissue (Wharton's jelly, etc.)
chondro-: cartilage
osteo-: osteoblasts
lipo-: fat
chordo-: notochord remnants
leiomyo-: smooth muscle
rhabdomyo-: striated muscle
schwanno- / neurilemmo- : nerve sheath (perineurium)
neurofibro-: nerve sheath (endoneurium)
hemangio-: blood vessels
lymphangio-: lymphatics
glomangio-: glomus
synovio-: synovium
mesothelio-: mesothelium
meningio-: arachnoid granulation
lympho-: lymphocytes

There are a few epithelial roots you will have to learn. For example:

chorio- placenta

pheochromocyto-: adrenal medulla

If the neoplastic cell types are mixed, use a compound, for example, fibroadenoma.

Some tumors arise in "totipotential cells" and contain a variety of different mature and/or immature tissues from different germ layers, and these are given names with the root terato- ("monster").

Ovarian Teratoma Australian Pathology Museum High-tech gross photos

Nasopharyngeal teratoma WebPath Photo

Nasopharyngeal teratoma WebPath Photo

Sacrococcygeal teratoma Virtual Hospital

Teratoma of nasal tip Virtual Hospital

Immature skeletal muscle
from a teratoma
ERF/KCUMB

IV. You can add adjectives as appropriate.

papillary
well-differentiated
keratinizing
moderately well-differentiated
mucin-producing
poorly differentiated
follicular
pleomorphic
signet-ring cell
cystic (cysto-)
scirrhus
desmoplastic
medullary
comedo-

V. A handful of tumors that are thoroughly malignant have "benign" names. You will just have to learn these.

lymphoma
mesothelioma
myeloma ("multiple", plasma cell)
astrocytoma
carcinoid (a low-grade cancer of APUD cells)
glioma (micro-, oligodendro-)
ependymoma
seminoma
hepatoma (today, "hepatocellular carcinoma")
melanoma
dysgerminoma
leukemia

VI. A hamartoma is "not a tumor, but is a developmental anomaly" (?) that contains the same tissues as the organ in which it is found, but in the wrong proportions.

Mesenchymal hamartoma

Virtual Hospital

A choristoma ("ectopia") is a mass of normal tissue in an abnormal location.

A tumor that ends in blastoma is composed of cells that resemble those seen in a developing organ. Most blastomas are malignant (but it depends on the site).

A few tumors of uncertain histogenesis are named eponymously: Ewing's sarcoma, Hodgkin's disease, Pindborg tumor, Wilms' tumor, Enzinger's sarcoma.

Visitors to www.pathguy.com reset Jan. 30, 2005:

Drop by and meet Ed

Ed says, "This world would be a sorry place if people like me who call ourselves Christians didn't try to act as good as other good people ." Prayer Request

Teaching Pathology

PathMax -- Shawn E. Cowper MD's pathology education links
Ed's Autopsy Page
Notes for Good Lecturers
Small Group Teaching
Socratic Teaching
Preventing "F"'s
Classroom Control
"I Hate Histology!"
Ed's Physiology Challenge
Pathology Identification Keys ("Kansas City Field Guide to Pathology")
Ed's Basic Science Trivia Quiz -- have a chuckle!
Rudolf Virchow on Pathology Education -- humor
Curriculum Position Paper -- humor
The Pathology Blues
Ed's Pathology Review for USMLE I
Part I
Part II

Pathological Chess

Taser Video 83.4 MB 7:26 min