Medical Oncology


*Discuss the ways in which pathology can aid in defining cancer and determining treatment.


Prognostic:  estimating likelihood of cancer recurrence and death

Predictive:  likelihood of response to a given therapy

Type of cancer:  Ancillary Pathology Testing:  can help determine origin of cancer cells, sub-classification of cancer (leukemias), aggressiveness of tumor, possible treatment options (HER-2 expression suggests aggressive breast cancer)  Histochemistry, Flow cytometry, In situ hybridization

Tumor stage:  tumor size, invasion into surrounding tissues, spread to regional lymph nodes, metastasis

Tumor grade:  microscopic assessment of tumor cells vs. normal cells.  Abnormal cell appearance, number of mitosis etc.  High grade, poorer recurrence and survival rates.

Surgical margins:

*Explain the difference in treatment goals in the adjuvavnt and metastatic treatment setting.

Goals of treatment include: prevention/risk reduction, adjuvant (after surgery) therapy, metastatic therapy (mostly palliative, quality control) and survivorship (most people with one cancer are at risk for reoccurrences and new cancers, plus treatment toxicity can cause other conditions/malignancies.)

Adjuvant Cancer Therapy:

Given even if no evidence of disease, but at risk for reoccurrence from micrometastases. 

Prolongs both overall and disease-free survival.

Neoadjuvant:  shrink tumor before surgery (breast cancer)

Metastatic therapy:

Generally incurable, treatment given with palliative intent.  Goals include 1)improvement of quality of life and 2)prolongation of life

Exceptions:  Testicular CA is chemosensitive and is curable when even metastatic


*Describe the major categories of cancer chemotherapy drugs and their general mechanism of action.

Al cytotoxic, affect cell replication (DNA synthesis, function and mitosis).

Alkylating agents:  directly attack  nucleophilic sites on DNA, covalent cross-linking of DNA strands.

--Cyclophosphamide, ifosphamide, busulfan, melphalan, chlorambucil, nitrosoureas (carmustine, lomustine--cross blood/brain barrier), cisplatin, carboplatin

Antimetabolites:  fraudulent substrates for biochemical reactions--inhibit cell function or replication

--Purine antagonists:  6-mercaptopurine, fludarabine

--Pyrimidine antagonist:  5-fluorouracil, capecitabine, cytarabine (ara-C), gemcitabine

--Folate antagonist:  Methotrexate (MTX)

Plant alkaloids:  blocks cell division during mitosis (spindle interference)

--Vinca alkaloids:  vinblastine, vincristine, vinorelbine

--Taxanes:  paclitaxel, docetaxel

Anti-tumor antibiotics:  bind with DNA and prevent RNA synthesis

--Anthracyclines:  doxorubicin, epirubicin, daunorubicin all inhibit topoisomerase II enzymes


--Mitomycin C

*Know the common toxicities of cancer chemotherapy:

Depends on dose given and patient's response

General rule:  cells that divide rapidly usually get dead faster

Hematopoetic cells:  infections, bruising, anemia

Hair roots:  alopecia

GI mucosal cells:  anorexia, nausea, vomiting, diarrhea, mucositis, stomitis

Repro organs:  temporary or permanent loss of fertility (advise to freeze egg/sperm, watch out for early menopause)

CHF:  anthracycline

Neuropathy:  taxanes, vinco alkaloids, cisplatin

Hemorrhagic cystitis:  cyclophosphamide, ifosphamide

Renal toxicity:  cisplatin, methotrexate

Hand-foot syndrome (irritation of the lining of palms/soles):  5-fluorouracil

Pulmonary fibrosis:  bleomycin, busulfan

Secondary leukemias/myelodysplasia:  alkylating agents

*List mechanisms of development of chemotherapy drug resistance.  Resist through mutations (intrinsic rate 1 mutation/106 cell divisions)

Mechanisms of drug resistance:  intracellular inactivation of drug, increased drug efflux (MDR), increases in target enzymes, increases DNA repair.

*Describe the major categories of cancer hormonal therapies:

"Cytostatic":  decrease cell growth

Sex hormones effective in breast cancer, and prostate cancer

Corticosteroids effective in lymphomas and leukemias

Anti-estrogen:  Selective estrogen receptor modulators include tamoxifen, raloxifine.  Antagonists include fulvesetrant

Anti-androgens:  flutamide, nilutamide, bicalutamide

Progestins:  megesterol acetate

Suppression of hormone synthesis:  oophorectomy, orchiectomy, LHRH analogs (leuprolide, goserelin), aromatase inhibitors (anastrozole, letrozole, exemestane) and corticosteroids (prednisone, dexamethasone)   Toxicities:  hot flashes, weight gain, impotence, loss of fertility, change in appetite, disruption of menses


*The rationale for the development of biological therapy in cancer, including specific targets of molecularly-targeted cancer therapy.

Rationale:  Stop the normal cell from becoming atypical and then cancerous and then metastatic due to excess stimulation, and cure cancer?!  Or maybe not?

Some approved biological therapies:

*Non-specific immune stimulators:  Interferon (CML, lymphoma, melanoma), IL-2 (melanoma, renal cell), BCG (bladder cancer)

*Molecularly targeted therapy:

Trastuzumab (Herceptin):  anti-HER-2 Ab's (25% of breast CA)

Rituximab:  anti-CD20 Ab (lymphomas)

Imatinib mesylate (Gleevac):  inhibit bcr-abl tyrosine kinase (CML, GIST)

*Methods aimed at blocking growth and invasion of cancer:

Invasion:  direct migration, penetration in neighboring tissues (past BM in epithelium)

Metastasis:  penetrate lymph and blood vessels, and invade normal tissues elsewhere.  Bisphosphates can interfere with bone metastasis (stops osteoclast activity seen bone mets and osteoperosis)

Angiogenesis:  growth of a new network of blood vessels.  Critical for tumor growth and metastasis.


Pathology of Infectious Diseases in Immunodeficient Patients:


*Know the major categories of patients with primary (congenital) immunodeficiencies, the nature of their immune defects, and the primary infection which they experience.

Phagocytic Cell Defects:  Chronic granulomatous disease-- defect in cytochrome oxidase system, defective respiratory burst (not enuf reactive oxygen intermediates).  Susceptible to Staph aureus, Aspergillus fumigatus and Candida albicans. 

Complement Defects:  Messed up C1, C2, C4, mild bacterial infections and lupus-like syndromes

Primary B-Cell deficiency:  Bruton’s congenital agammaglobulinemia:--genetic, x-linked.  In males, get otitis media, pharyngitis, conjunctivitis by pyogenic Staph aureus, Strep pyogenes, Neisseria meningitides, H. flu, and PCP.  Few or no circulating B-cells, decreased lymphoid follicles, plasma cells in lymph nodes, decreased total immnoglobulin.  Normal T-cells, tx: give lots of gamma-globulin.

T-Cell deficiency:  Di-George:  no thymus or parathyroids form (3rd and 4th pouch).  Stem cells do not differentiate to become T-lymphocytes, less function, cell-mediated response.  Lots of oral infections (candida), chronic diarrhea, skin rashes, and generalized failure to thrive.  Watch out with vaccines (smallpox, measles, BCG—can cause infection).  Can also get hypocalcemia with tetany and rigid contractions because kids don't got parathyroids.

SCID:  defective hematopoietic stem cells.

Reticular dysgenesis: no WBC!  Affected children often die in utero or as neonates. 

Others:  defect in stem cells giving rise to lymphocytes (no T or B cells).  Underdeveloped thymus, and IgG’s.  Diarrhea, oral and skin candidiasis, PCP.  PLEASE DON’T VACCINATE.


*Know the major categories of patients with secondary (acquired) immunodeficiencies, the nature of their immune defects, and the primary infection which they experience.

Infancy:  only have mother’s IgG .  At 7 months, have 50% of mother’s IgG.  Lots of IgM deficient infections:  CMV, rubella, Toxo etc. indicates active infection.  Kids get secretory IgA from breast milk which protects against intestinal viruses and bacteria.  IgA is not absorbed, just hangs out in the mucosal surface.

HIV:  see later questions

Malignancy:  see later questions

Malnutrition:  decreased calories and protein decreases T-cell function and numbers, decreases complement, and compromises neutrophil chemotaxis and killing.  Zn (found in legumes, nuts and seeds) deficieny:  decreases T and B cell function, messes up their cofactors

Diabetes: later questions

*Be able to discuss the frequency and types of infection which suggest the presence of a primary immunodeficiency disease.  I think they're kidding.  I guess any of the infections from Q1?

Upper respiratory viral infections, and lots of severe infections like pneumonia, bronchitis, sinusitis, otitis media, or meningitis.  kids who have more than 6-10 infections/yr are suspect, and adults with more than 3-4 infection/yr

*Summarize the pathogenesis of AIDS and discuss the development of its associated immunodeficiency, drawing on the phases of HIV infection

Viral envelope protein gp120 binds avidly to CD4 molecules on T-cells, dendritic cells, macrophages, CNS microglial cells.  Depletion of T-cells leads to PCP, CMV, bacterial, candida, histoplama, coccidioedis, toxoplasma, isospora and other infections.  Increased number of malignancies such as Kaposi sarcoma (red, violaceous papules/nodules, HHV8), lymphoma and invasive cervical cancer, oh my!.

3 phases of infection:

non-specific viral syndrome:  sharp drop in T-cells, have sx of fever, myalgia, arthralgia, nightsweats and fatigue.  Can do a p24 blood test to dx (I guess the other HIV Ab tests don't work so well since you haven't had time to make Ab's).  Viremia peaks midway in this phase, and falls as Ab's increase.    

Asymptomatic:  mild lymphadenopathy, anemia, leukopenia and thrombocytopenia.  Ab's to gp120 and gp41 remain elevated.  Viral particles are trapped in lymphod tissue with hyperplastic follicles becoming the primary site of viral replication.  T-cells remain stably low.

Acquired immunodeficiency syndrome:  PCP, recurrent bacterial pneumonia, toxo, TB, histoplasmosis, candidiasis, CMV.  Involution of lymphoid follicles, and degeneration of follicular dendritic cell network.  Low T-cells, high virus load.  Give antibiotic prophylaxis!

*Discuss the predisposing factors to infection which may exist in patients with malignant disease and relate these factors to specific types of infection.

Pts. (esp leukemia) receiving extensive cytotoxic drug treatment, get lots of sudden, rapidly progressing symptoms with high mortality.  In leukemia’s induction therapy, 16-20 days of severe neutropenia are seen, and 60-80% of patients get infections.  Consolidation therapy leads to 8-12 days of neutropenia, and 35-50%  infection rate.  70% of deaths in acute leukemia are due to infections.

So in essence, don’t want less than 500 neutrophils, don’t want a rapid decrease in neutrophils, and don’t want to be neutropenic for long.  Other predisposing factors include:  humoral immune dysfunction, cellular immune dysfuction, complement and cytokine deficiency, suppression of endogenous flora, and medical procedures and therapy (ablation of immune system, IV cannulae and catheters, corticosteroids, chemo causing GI and resp mucosal damage.)

Fungal infections occur:  neutropenia more than 7 days, corticosteroids, abiotics, previous fungal infection, chemo-induced mucositis.

Can tell it’s fungal when:  fever 5-7 days despite abiotics, progressive debilitation, diffuse pulmonary infiltrates “not respecting natural anatomic barriers” and unexplained renal or liver failure. 

Sites of Infection:  (SLOPpy APE)  Skin, Lung, Oropharynx, Anal area, Peridontium, Esophagus.  Pathogens:  E. coli, Aspergillus, Klebsiella, Pseudomonas, Candida, Staph aureus, weird staph and strep. 

*Explain why elderly people and those with diabetes mellitus are more susceptible to infection. 

Elderly:  atrophy and dryness of skin and mucous membranes, resp stuff (impaired ciliary motion, decreased cough, microaspiration), GI stuff (gastric atrophy, decreased motility), UTI (decreased fluid intake, decreased voiding, anatomic), decreased T-cells, impaired production of cytokines (IL-2—zoster and TB), decreased IgM, decreased response to specific antigens.

Diabetes:  Most common infections are soft tissue and bone problems due to S. aureus, hemolytic strep, and Candida. 

Anatomic:  injection site, neuropathy (foot ulcers), decreased tissue perfusion due to vascular disease

Immunologic:  decreased granulocyte chemtaxis and bacteriocidal activities (Ab and T-cell function is normal.)


Clinical Syndromes in Renal Disease


  1. Be able to define the major clinical syndromes of glomerular disease
  2. Be able to list and explain the common morphological correlates associated with the major clinical syndromes.


Clinical (def)

Lesions(morph correlates)

Nephritic syndrome

Hematuria, proteinuria, often azotemia and hypertension

Inflammation and/or proliferation, subendothelial deposits, low complement, RBC casts

Nephrotic syndrome

Marked proteinuria, edema, hypercoagulable, hyperlipidemia

Noninflammatory injury to epithelial cell or GBM,

Subepithelial deposits

Isolated urinary abnormalities

Micro hematuria/proteinuria

No symptoms, due to Non-inflammatory mesangial deposits

Tubulointerstitial disease

Hereditary GBM abnormality

Acute renal failure

Acute decline in GFR; see oliguria/anuria

ATN, toxins, drugs


Rapid drop in GFR and nephritis

Crescents (severe injury from GBM breaks)

Chronic renal failure

Progressive decrease in GFR to ESRD

Glomerulosclerosis, tubular atrophy, interstitial fibrosis


  1. Be able to distinguish examples of immune complex mediated glomerular disease from diseases not of immune complex origin.  Understand approaches for making these distinctions.

WTF? Immune diseases are SLE, IgA nephropathy, membranous GN and post-strep GN because they leave immune complexes. What more distinction do you need?!?


4.Understand patterns of immune complex deposition , and their possible pathogenesis, in common forms of immune complex mediated glomerulonephritis.


Pattern of deposition


Clinical Features


Subendothelial, then cleared by inflammatory response, ultimately subepithelial

Ab to strep Ag àimmune complex deposition in glomerulià inflam. response

Abrupt; hematuria, RBC casts, oliguria, gever, ASO, fever

IgA (Berger’s)

Mesangiial deposits w/ IgA and C3

?, may occur after Resp, GI or UT infection

Hematuria, leading cause of ESRD in Asia; HSP is systemic form

Membranous nephropathy

IgG/C3 depostis Epithelial side of GBM

Chronic; usually unknown Ag, may occur in congenital syphilis, malria, hepB/C, some drugs(penicillamine, gold)

GBM thickening, nephrotic syndrome, primarily in adults

One of the most common causes of nephrotic syndrome in adults


5.Gain some understanding of the role of the pathologist and of tissue bipsy in diagnosis and prognosis of renal disease and in choice of therapy.


Oh pathologists, stop kidding yourselves; you are not important.

Principals of Surgical Oncology


I.                     Surgical diagnosis







21-25 gauge needle

+/- local

Cytology not architecure

Show malignancy; investigate masses from the lungs up, soft tissue, ascites??

Core needle

12-16 “ “


Cytology and architecture

Masses from nuts(prostate) to neck, soft tissue

Endoscopic biopsy

Probably an endoscope

See pharm (opiate/BZD)


Its gotta have a hole for the endoscope to get to

Incisional biopsy

Scalpels, punch biopsy thingees

Probably local anesthetic.

Part but not all of lesion

Skin, soft tissue masses



“ “


Make sure its fresh, not formalin

Wide excision


“ /maybe more




II.                   Staging

Important points (I guess)

-          the difference between carcinoma (regional nodes +/- hematogenous spread) and sarcoma (hematogenous, nodal spread rare)

-          Regional stagingà lymphatic mapping + sentinel lymph node dissection; no elective lymph node dissection

-          Surgical Staging of Lymphomaàexcisional, laparoscopy(occasional), laparatomy (rarely)


III.                 Treatment

A.      Resection

1.        try to cure and not complicate (early cancers; BCC vs. pancreatic cancer; adjuvants;laryngeal nerves)

2.        try to achieve negative margins

3.        maybe consider regional nodes

B.       Palliation

1.        surgery usually doesn’t help pain, usually worsesns, save painful tumor or nerve impingement

2.        obstruction – (lymphoma) resection, , bypass, drainage (gastrotomy), tracheobronchial stenting


Surgery cannot  help an asymptomatic patient feel better!!

Breast Pathology (no objectives for this one)


Normally 15-25 lactiferous ducts that start in the nipple and end in TDLU.  TDLU is composed of terminal duct and associated acini, where most breast cancer arise.  Remember from Repro that there are cuboidal cells lining the lumen and then myoepithelial cells surround them.


Inflammatory conditions (not emphasized in lecture)

  • Plasma cell mastitis, granulomatous mastitis.  Can clinically mimic carcinoma.
  • Fat necrosis.  Mostly history of trauma, surgery, radiation.  Possible confusion w/ tumor.
  • Duct ectasia.  Sx of nipple discharge.  Dilated ducts w/ inspissated secretions, inflamm.
  • Silicone mastitis.  Skin iduration, mass.  Foreign body rxn.  Associated w/ slceroderma?


Benign Tumors

  • Fibroademona:  most common.  Young women, painless, well circumscribed mass.  Need to be distinguished from Phyllodes.
  • Phyllodes tumor:  Low grade ones often recur locally, high grade behave aggressively.  Excise.
  • Intraductal papilloma:  Peri/Postmenopausal women w/ serous or bloody nipple discharge.


Fibrocystic changes:

                Continuum from hyperplasia (non-proliferative vs. proliferative)®atypical hyperplasia®DCIS.  Clinically produce masses that must be differentiated from carcinomas.  Frequent cause of microcalcifications on mammography, association w/ CA proportional to degree of epithelial hyperplasia and atypia.

  • Hyperplasia (ductal):  RR 1.5-2.0.  Risk/Marker lesion = risk is equal for either breast, any location, removing the mass won’t decrease the risk.
  • Atypical (ductal or lobular):  ADH and ALH are Marker lesions.  RR 4-5.



  • Carcinoma In-Situ (DCIS or LCIS):  DCIS is a Marker and Precursor lesion = increased risk for tumors at the site of the DCIS.  RR 8-10.  LCIS is Marker lesion ONLY RR 8-10.
  • Invasive Carcinoma
    • Invasive ductal carcinoma NOS most common type.  Lobular less common.  Medullary, tubular, adenoid cystic, mucinous have good prognosis.
    • LN status most powerful prognosticator.  No axillary nodes = 90% 5-year survival.
    • Tumor <2cm good.  Presence of estrogen receptor good—responsiveness to tamoxifen.
    • Her-2/neu should be evaluated.  Responds to herceptin. 
    • Rx for small infiltrating is excision +/- LN dissection + post op radiation.  Advanced stage may get rad/chemo before surgery.


Male Breast

                No lobules.  Gynecomastia is most common pathology, must diff. from carcinoma (rare).



Breast Imaging


1)      Know the epidemiology, breast cancer statistics, and review of literature regarding efficacy of screening mammography.


18,000 women diagnosed, 50,000 die per year (but data was from 1983?).  Overall 32% of cancer in women, 19% of all cancer deaths.  Lifetime risk is 1/8 assuming you live to be 85.  75% occur in women w/ NO RISK FACTORS.  Incidence increased b/c of mammography detection?


For mammography screening, two older studies showed reduction in mortality of 30% at 5 yrs, 20% at 18 yrs.  Another determined that 40% of breast ca was detected by mammography ALONE, 10% were not detected by mammography at all.  More recent study in Canada found no evidence for effectiveness in screening at 40-49 years.  Widely publicized and criticized.  Meta-analyses confirmed reduction in mortality via screening.  Detects tumors at small size before LN mets are likely.


2)      Know the current American Cancer Society and American College of Radiology recommendations for screening mammography.


Monthly self-exam beginning @ age 20, exam by professional every 1-3yrs @20-39 and annually thereafter, both suggest annual mammograms @ age 40.  For high risk patients (mother/sister dx before menopause) start 10 years prior to relatives age at diagnosis.


3)      Give a brief overview of mammographic technique.


Lower energy radiation than standard XR.  Dedicated unit w/ special films.  Screening costs $70-100, very low risk from radiation exposure.  There is a mammographic accreditation program (MQSA law).


4)      Describe the guidelines for mammography referral.


Evaluate a problem such as lump, nipple discharge, focal pain, abnormality on screening mammography, lumpectomy follow-up.  Of screening mamm. 5-10% get call back for more views or ultrasound.  One third of those get biopsy, one third of biopsies are malignant.


5)      Explain the difference between screening mammography and diagnostic breast imaging evaluation.




Limited Resources

High tech, expensive

Cost effective

Time consuming

Two views per breast (MLO & CC)

Other views, ultrasound, interventional procedures

Films screened in batches

Ongoing interaction w/ pt

Radiologist on site not necessary

Requires involvement w/ radiologist

Traditional role of radiologist

Radiologist like a consultant

Goal to detect occult breast CA

Goal to solve diagnostic dilemma or specific recc.

“indeterminate” interpretation acceptable

indeterminate” unacceptable. 


6)      Describe additional breast imaging modalities and their indications.


Ultrasound:  determine whether density on mammogram is benign cyst or solid mass (even see characteristics of benign vs malignant mass).  Also for evaluation of lump w/ normal mammogram, guiding fine needle asp or core biopsy.

MRI:  Highly sensitive but <75% specific.  Good for evaluating implant rupture.  Used to evaluate the extent of disease in known malignancy.  Trials to evaluate as a screening technique ongoing.

Ductography:  Evaluate duct when there is spontaneous, unilateral nipple discharge from a duct (they must have discharge @ the time of exam, papiloma is most common cause).  Contract injected retrograde into duct.

Core biopsy:  Instead of excision/open biopsy.  Can be guided by palpation, ultrasound, or mammography (stereotactic guidance).

PET:  for staging.  Sentinel node biopsy


7)      Know what BI-RADS means, know BI-RADS categories and their management.


Breast Imaging and Reporting Data System.  Look for mass, focal asymmetric density, architectural distortion, diffuse increased density, calcifications.


Classification and management


Normal:  screen in 12 mo


Benign:  screen in 12 mo (e.g. lucent mass—lipoma)


Probably Benign: screen in 6 mo (common to have at first mammogram)


Suspicious:  biopsy


Highly Suggestive of Malignancy:  recommend incision, take appropriate action


Incomplete:  additional imaging needed.  (usually for screening pt needing call-back)


8)      Know the correspondence between mammographic interpretation and pathologic diagnosis and the critical nature of mammographic-pathologic correlation.


Shape:  Irregular>Lobular>Oval>Round in likelihood of malignancy.

 Margins:  Spiculated likely to be malignant, Circumscribed likely to be benign (also Microlobulated, Obscured, Indistinct).  Circumscribed usually cysts (age35-50) or fibroadenomas (20-35).  Hyalinized fibroadenomas = Popcorn Calcifications.  Circumscribed mass w/ benign characteristics on spot mag and US have probability <2% malignant.

Density:  In relation to surrounding tissue.  Low density less likely malignant.

Associated findings:  calcifications, architectural distortion, skin retraction, etc.

Focal Assymetric Density

“FAD” termed when the finding persists on extra views.  For first one called BI-RADS 0.  Persistent w/ negative US called BI-RADS 3. 


Malignant:  pleomorphic, heterogeneous, linger dot-dash, clustered, ductal, segmental

Benign:  coarse, round, punctate, lucent-centered, popcorn, rim, milk-of-calcium shape, diffuse distrib.

Malignant calcifications usually DCIS, also seen in infiltrating ductal carcinoma.  Benign calcifications can resemble them in appearance.  Lobular carcinoma, LCIS notorious for escaping detection on mamm.


9)      Explain the limitations of mammography.


Dense fibroglandular tissue in most young nulliparous women is hard to interpret.  Tumors w/ less desmoplastic reaction or lacking calcification may be hidden by the fibrous tissue.  Presence of multiple benign-appearing masses makes it harder to find the malignant one.


Lupus Objectives:

1. Major clinical features of SLE:

fever, fatigue, wt loss, arthritis, skin rash (photosens butterfly rash on cheeks, or discoid lupus rash w/ scarring), GN, pleuritis, pericarditis, pulm inflam, seizures, psychosis, strokes, leukopenia, anemia (inflam-related, or hemolytic), thrombocytopenia, coag problems, impaired fertility, retinal vasculitis, vision loss


2. Epidemiology of SLE:

young women (childbearing age), F:M=9:1, esp common in African-Americans and some Asian pops. (Philippines), onset 2nd-5th decade, overall prev 2-10/100,000 but can be up to 1/250 in 15-64 yo African American women


3. Utility of ANA test and anti-dsDNA test:

ANA is pos in 95-99% of all pts w/SLE (its 95-99% SENSITIVE), but, ~5% of nl people have low-level pos ANA too. Can also have pos ANA in other dzs, exposure to some drugs. ANA can be against:

dsDNA: (pos in 70%, specific/diagnostic for SLE!), also prognostic

RNA/protein complex: “anti-Sm”(pos in 30%, VERY specific)

RNA processing proteins: anti-SS-A (anti-Ro), anti-SS-B (anti-La)


4. Immune complex (IC) model of disease:

                SLE is prototype Type III IC dz

                Neither the Ag or Ab alone causes tissue damage, the COMPLEX does

                In SLE the Ag are nuclear Ags (DNA, nuclear proteins)

                Circulating IC deposit in tissues, or, they may be formed in situ in tissues

Then, classical complement pwy is activated, anaphylotoxins (C5a, C3a) are produced,

                PMNs come, inflamm stuff released, MAC damages tissue


5. Principles of immunofluorescence microscopy of kidney/skin in SLE:

                Biopsy is examined for lumpy deposits of Igs and complement (C3, C1q)


2 types of renal lupus patterns to KNOW!!

-Diffuse proliferative lupus nephritis: glom have many PMNs and many

subendothel immune deposits seen on EM, WORST prognosis

                                -Membranous lupus nephritis: few inflam cells in glom, immune deposits mostly

subepithelial, BETTER prognosis


6. Potential mechs leading to B-cell autoimmunity and Ab production in active SLE:

                -primary B-cell dysfunction

                -deficient suppressor T-cell function causing abnormal B-cell activity

                -normal response to sequestered Ag that have been accidentally exposed to the IS

                -normal immune response to viral/other Ag giving Ab that cross-react w/self Ag

                -response to altered self-Ag (alteration due to infection, toxin, etc)


                May have different ones of the above mechs in different patients, different stages of dz.

It is NORMAL to have some auto-Ab

germline Ig genes code for lots of auto-Ab but these are low affinity and react w/ lots of different Ags. Also, nl people make some auto-Ab after infection but these are random, polyclonal, and mostly IgM.

But in a pt w/SLE…

the auto-Ab are higher affinity, more specific, mostly IgG.

                Sunlight often exacerbates SLE rash & maybe other sx.

                Also—ANAs can be induced in nl people by certain drugs, esp PROCAINAMIDE.

                After 2 yr on procainamide, 90% pts have ANA, and 5-10% get SLE sx (reversible)


7. Levels of C3, C4 and “total hemolytic complement” in active SLE:

                they are low when SLE is active


8. Clinical/pathol. features of:

Scleroderma—“hardened skin,” fibrosis/collagen deposition in skin, also fibrosis and vascular dz of organs:

                kidneys: arteriolar/glomerular sclerosisàsevere HTN, renal failure

                lungs: fibrosis of alveolar septaàdyspnea, hypoxia

                GI: fibrosisàGERD, intest pseudo-obstruction (messed up peristalsis),

                                and diverticuli

                heart: fibrosisàcardiomyopathy, CHF, or heart block


Sjogren’s syndrome—Dry eyes, dry mouth, arthritis

                Lymphocytic infiltrate in exocrine glands.

                Auto-Ab include anti-SSA(Ro) and anti-SSB (La), also in some SLE pts

                Arthritis may be mild or deforming like RA


Polymyositis, Dermatomyositis—chronic inflam in skel muscle

                Weakness, fatigue

                Muscle CK in blood, EMG confirm dx

                W/skin rash=dermatomyositis, w/o rash=polymyositis

                PM/DM pts may have ANA or other auto-Abs

R/O myositis from non-autoimmune stuff—toxins, EtOH, infection



Vasculitis objectives: This chapter sucks…


1. Definition of vasculitis—inflammatory disorder where BV are the primary targets. If there is acute necrosis of vascular wall, then call it “necrotizing vasculitis”, can be local or systemic.


Morphological and clinical classifications:

                1. mostly SMALL BV involved (capillaries, small arterioles/venules)

                                a. Hypersensitivity—serum sickness, drug-ind. “angiitis

                                b. Infection—subacute bact. endocarditis, dissem. GC,

                                     Mixed Cryoglobulinemia (Hep C-related)

                                c. Auto-AgsHenoch-Schonlein purpura, vasculitis assoc w/malignancy,

                                    microscopic polyarteritis

                2. mostly MEDIUM BV involved (small muscular arteries)

                                a. Thromboangiitis obliterans (Buerger’s dz)

                                b. Polyarteritis group—polyarteritis nodosa, vasculitis w/RA or SLE, Kawasaki


                                c. Vasculitis involving lung—Wegener’s granulomatosis, Churg-Strauss synd.

                3. mostly LARGE BV involved          

                                a. Giant cell arteritis (temporal arteritis)

                                b. Takayasu’s arteritis (aortitis)


2. Pathogenic mechs of different types of vasculitis:

                4 types of immune-mediated vasculitis:

                                1. immune complex deposition

                                2. direct tissue damage from Ab

                                3. tissue damage by WBC (WBC activated by Ab binding to WBC Ag)

                                4. tissue damage from cellular immune mechs, often w/granulomas


Some details: results of IC formation are variable and related to:

                1. Size, composition and charge of IC—affects whether complement will be activated

2.Complement activation—can result in clearance of the complex, OR in activation of 

   inflammatory response (activation of PMN, platelets, monos/macros)

3. Release of vasoactive factors—increases vascular perm, C3a and C5a activate mast

    cells and PMNs, MAC is activated and damages vessel wall


3. Vasculitis WITHOUT ICsàAnti-neutrophil cytoplasmic Ab (ANCA)

ANCA have been found in some pts w/ Wegener’s granulomatosis, Microscopic polyangiitis, Polyarteritis nodosa, Churg-Strauss syndrome

2 types of ANCA:


c-ANCA: diffuse, cytoplasmic ANCA, reacts w/ a Ser protease from PMN/macro

lysosome; assoc w/ Wegener’s (95% of active Wegener’s cases). C-ANCA prob pathogenic themselves…c-ANCA titer increases BEFORE relapse!


p-ANCA: perinuclear, against WBC myeloperoxidase; assoc w/ polyarteritis nodosa, microscopic polyangiitis, Churg-Strauss, crescentic GN


4. Clinical/patho features of impt types of vasculitis:


Hypersensitivity (small vessel) vasculitis: ie serum sickness , drug-induced vasculitis.  Most often affects skin. Skin contains lots of PMNs which have nuclear fragmentation. Pt. may have hypocomplementemia , extravasation of RBCs (petechiae) “palpable purpura”. The factors causing the hypersensitivity vasculitis can be microorganisms, meds, tumor/autoAg (“bugs, drugs or self”)


Henoch-Schonlein purpura: a form of hypersens. vasculitis occurring in kids/young adults, 3 key features: purpura on butt/arms/legs; arthritis, and abdominal pain (can have bloody diarrhea). in 30% the kidney is involved (nephrotic OR hematuria!, even RPGN is possible!) Histo: necrotizing vasculitis w/ IgE, sub-epidermal hemorrhages.


Mixed cryoglobulinemia syndrome: vasculitis, poss severe GN; purpura; and arthritis. Cryos are proteins that ppt reversibly in cold…these pts usu have IgM rheumatoid factors (autoAbs that react w/ the Fc portion of IgG) as their cryoglobulins.

Most cases of MCS are in pts w/ Hep C!!!(find HCV mRNA and Abs to HCV in the cryoppt). This syndrome may be present in other conditions like SLE or RA


Giant cell arteritides include:

                1) Temporal arteritis: a systemic vasculitis usu in old people, usu affects

                branches of the carotid, esp temporal branch. Pt has headache/jaw claudication;

                tenderness/palpable nodules along the artery; visual imparment (opthal artery);

                may have polymyalgia rheumatica (a complex of Sx including prox muscle

                pain, morning stiffness, periarticular pain).

                Path: granulomatous arteritis shows focal inflamm in the media, all kinds of

                WBCs, giant cells not always present.


                10-15% of the time, giant cell arteritis involves other (extracranial) vessels

                instead of the temporal artery. This usu gives intermittent claudication, aortic

                regurg, dissection, or aneurysm (???)


                2) Takaysu’s arteritis (pulseless disease): can involve both systemic and

                pulm circ. Usu affects aorta and coronary arteries. Lots of fibromuscular prolif

                in the intimaàgets rigid/stenotic. Usu affects women age 15-45.


Polyarteritis nodosa: Necrotizing immune complex (IC) inflamm of small/medium arteries. peak 40-50, M>F, may be life-threatning (if untreated 5-yr survival <15% and of the fatal cases, half die within 3 months of diagnosis???) ***Treat with steroids/immunosuppressants!!! This lets 80% survive 5 yr or more!!!

Presents w. fever, headache, wt loss, myalgia. Organ involvement: heart, kidney, GI, joints, NS, (skin, lungs less often). Pt gets peripheral neuropathy. Dx. w / biopsyàfibrinoid necrosis” w/ lots of PMNs, fibroblasts and their pdts make the “nodular” appearance.

PA is associated w/ Hep B (and also tumor Ag’s, rarely drugs)



Wegener’s granulomatosis: unknown etiology, necrotizing granulomatous vasculitis of the vessels of resp tract  (upper AND lower) and kidneys (ranges from GN w/ hematuria, on up to RPGN giving renal failure). Can also go to other organs like “skin, joints, nerves and ears” ???

If untreated—almost always fatal w/in 1-2 yrs. BUT immunosuppression (cyclophosphamid plus prednisone, or MTX). Some pts also do well on TMP/sulfa!

Pts present w. URT sx (sinusitis, epistaxis, etc) or LRT sx (cough, hemoptysis) or renal failure.

Dx w/ ANCA, open lung biopsy (multiple round lesions)

Sarcomas (Adult)


  1. Define “sarcoma” and explain how sarcomas are classified


Sarcomas are malignant connective tissue lesions. They have traditionally been classified in terms of histogenesis(cell of origin); now we classify by clinical info, H&E appearance, immunophenotype, ultrastructure (EM), cytogenetic and molecular genetic findings


  1. List and recognize the basic clinical (age of onset, site, clinical behavior) and histopath features of sarcomas listed in this chapter.





Age of onset


Clinical behavior

Histopath features


Peak age <20 yrs; elderly (assoc. w/Pagets)

Metaphyseal region of long bones

- 50% occur around the knee

- death usually due to metastatic disease(hemat. spread)lungs, bone, then brain

Large mass extending beyond boneàpathologic fracture;production of osteiod


Peak 4th-6th decade

Any bone, predilection for axial skel

-High grade are more aggressive, metast.(lungs/skel)

-low grade recur locally

-cause periosteum to stretch and present with pain

Malignant cartilage has radiopath features, nonmalig(enchondroma) àbenign rad. findings


(non-myxoid/myxoid / pleomorphic)

Peak 5th-7th decade /3rd-5th decade/ elderly

Any site in body/ limbs(NEVER retrper.)/limbs

Good prog in extremities, bad in retroper, can dediff, and metast/ can met to soft tissue, retrop., mediastimum, bone/ high rate of local recurrence and mets                                                                                                                                                                                                                               

Similar to mature adipose tissue/round cell/lipoblasts present











Age of onset


Clinical behavior



(cutaneous/vascular / deep)

Young adult/ ?/?

LMS rare in childhood

Any site, most common in uterus, retroper, extremities, large veins

LMS - Insensitive to chemo,, low grade recur locally, high-grade is aggressive, worse prong

Positive for smooth actin/desmin markers; charc. Cytoplasmic filaments


Alveolar RMS- young adults, pleomorphic RMS-older adults, embryonal-pediatric ptx

Skeletal muscle and other soft tissues;most in head/neck/GU tract

Mets via blood and lymph

Pos. for muscle actin, desmin, fast myosin, myogenin, and MyoD1; abortive skeletal muscle filaments


Older adults

Anywhere; most common in face/scalp

Happens idipthc in head/neck, assoc w/lymphedema, epidemic in woman post irradiation of breast CA; super agressive

Endothelial markers CD31/34, factor VII; Weibel-Palade bodies

Malignant periperal nerve sheath tumor (MPNST)

Sporadic in 5th decade; assoc with neurofibromatosis in 3rd-4th decade (30-50%)

Anywhere; common in deep soft tissue of limbs

One of the more common sarcomas, arise in assoc w/large nerves(good for diag)

Spindle cells, S-100 for 50% of cases; Schwannian diff. in EM

Can have heterologous diff.

Ewing’s /PNET

80% before 20

Any bone; think diaphysis

Bone pain, fever, onion skin cortex; mets to lungs and bone marrow

Round blue cells; CD99













Age of onset


Clinical behav


Synovial carcinoma

Young adults


Aggressive, recurs locally via hemat/lymph spread, most common to lungs

Both epithelial and mesenychymal diff.;spindle cells; pos. for epithelial markers(keratin and epth. Memb antigen)

Malignant fibrous hitocytoma(now known as myofibroblastic sarc)

6th-8th decade

Usually metaphysis of long bones and pelvic flat bones

Path. Fracture; lytic on rad.; may be the most common soft tissue sarcoma

Features of fibroblasts and histiocyts (Macs)







3. Factors that are the basis for grading and staging of sarcomas

Grade- mitotic rate, tumor necorosis, cellularity, differentiation, nuclear pleomorphism


Stageing – depth, size, metastasis


4. Basic similarities/differences between sarcomas, carcinomas, and hematopoeitic neoplasms




Hematopoeitic neo


Chem. Carcinogen cause








In situ lesion




Lymph node mets

-/+(tends to be hematogenous)



Cytogenetic abnormalities





So sarcomas and hematopoeitic neoplasms are closer related to each other than carcinoma


  1. Explain significance of characteristic cytogenetic findings in many sarcomas in terms of pathogenesis, classification, and treatment

Different translocation subtypes are associated with different chemical behavior and are relevant in :

-          tumor classificaton

-          disease surveillance

-          prognosis

-          therapy


Some important genetic aberrations to know (mentioned in lecture)

-          trisomy usually means oncogene

-          non-myxoid liposarcoma àring chromosome 12q 12-15

-          myxoid liposarcoma à t(12;16)(q13;p11) remember the first two #s

-          synovial sarcoma àt(X;18)(p11;q11)                          



Lung Cancer


1.        Compare and contrast the approximate incidence rates and mortality rates for lung cancer with those for breast cancer and prostate cancer.  Know which of the three is preventable given our current knowledge about etiology.



Incidence (2001)

Deaths (2001)

5 yr survival

10 yr
















Of course lung ca is preventable is you don’t smoke (incidence has been declining).  Risk drops to background level 10-20 years after cessation.


2.        Know the current classification scheme for lung cancer.  Be able to explain the value of this scheme in terms of patient prognosis and selection of therapy.


Classified by appearance in light microscopy, which is most powerful predictor of survival.

·         Small cell undifferentiated (20-25% of lung ca)

o        No evidence of differentiation, numerous mitotic figures, rapid DNA synthesis.

·         Non-small cell (about 75% total):  often intermixed, similar prognosis

o        Adenocarcinoma (30-35%) arise in peripheral lung tissue—small bronchioles or pneumocytes.

§         Bronchoalveolar:  spreads in single cell layer over alveolar septa.   Not really invasive, unlikely to spread by lymph/blood.  CXR like pneumonia

o        Squamous cell (25-35%) tend to be along major airways near the hilum, especially at bifurcations of airways.  Keratin pearls.

o        Large cell undifferentiated (10-15%) have lots of cytoplasm and large nuclei.

·         Carcinoid (~5%) arise proximally in bronchi.  Polypoid mass that causes airway obstruction and related symptoms.  Uniform, well-defined arrangements, smooth borders, rich network of blood vessels.   


3.        Be able to correctly classify lung cancers from projected photomicrographs.


4.        Know the general patterns of spread of small cell and non-small cell lung cancer.  Explain how the staging system for each reflects and measures tumor spread.


Spread by invasion of adjacent tissues (SVC syndrome, Horner’s), lymph nodes (peribronchial ® mediastinal  ® cervical, abdominal, supraclavicular), distant metastases (Liver, Adrenals, Bone, Brain).  Small cell also goes to pancreas, kidneys, thyroid, pituitary relatively often.


Non-small cell staging classified by T:  local invasion of chest wall/mediastinum  N:  nodes in or beyond the pleural envelope  M:  distant met’s.  Most non-small cell are stage III/IV, even squamous (57%) which is the most favorable.  Even in stage I non-small cell 5 year survival is only 50-60%.

Carcinoid same staging system.  Most are slow growing and considered benign except for “atypical carcinoids”which are 70-80% likely to metastasize

Small cell staging is either LIMITED (40%): one hemi-thorax or EXTENSIVE (60%).  9 month median survival


5.        Explain how morphologic information is used to diagnose and stage lung cancer.  List the different methods for obtaining biopsy or cytology material and list the diagnostic and staging information that each can provide.











Sputum cytology







Pleural cytology







Fine needle asp.







Bronchial brush/wash







Bronchial biopsy














Open biopsy/resection









6.        Define “paraneoplastic syndrome” and be able to list at least 3 that are associated with lung cancer.


Symptoms not attributable to the local extent or destructiveness of the tumor but rather some humoral factor elaborated by the tumor cells.  Most common = anorexia-cachexia (TNF?). 

Hypercalcemia (PTHrP in squamous cell). 

Migratory thrombophlebitis and non-bacterial thrombotic endocarditis (adenocarcinoma). 

PTH, ADH, or ACTH, and myasthenic syndrome (small cell).


7.        Describe the general treatment options that are most appropriate for each type of lung cancer.


Non-small cell is mainly treated with surgery.  Disease still recurs in more than half of patients.  Radiation may be useful if the tumor is not near to sensitive structures (e.g. spinal cord).  Chemotherapy has had little effect on survival for stage IV disease.

Small cell is combined chemotherapy and radiation, can cure 20% of limited stage.  Surgery only useful as adjunctive therapy for a single nodule.

Neoplasms of URT and Mouth







Nose/Paranasal sinuses


(min. saliv. gl.)









1.Adenoid cystic


Risk Factors

Smoking, Snuff






2.EBV, genetic


Nickel vapors









Dysplasia (biopsy)












vc polyp


Inflam. polyps

Sq. papilloma

Inv. papilloma





Local, LN


Cerv. LN


Cervical LN*


Locally aggressive


1.lung, bone

2.local, met’s




  Rad. Chem.




(1.not as responsive)



Surgical + Rad





2.*LN met’s often

(present w/ mass in post D)

Inverting papillomas-invade locally, need surgery

-Throughout resp. tract

1.Invades nerves

1.Met’s but slow growth



Pulmonary Reactions to Physical Agents

Pneumoconioses and occupational lung diseases


  1. Describe the pulmonary defense mechanisms that remove inhaled dusts.

·         Particles between 3-10 micrometers in diameter are deposited from the trachea on down to the terminal bronchioles, where they are removed by 1) ingestion by macrophages and 2) physical relocation via the mucociliary escalator.  The cilia in the lung epithelium constantly beat upwards, and material is eventually either swallowed or expectorated. 

    • Particles between .3 -3 microns are deposited in the alveoli where they are removed by the processes of chemical dissolution and macrophage action.  Water soluble particles dissolve, and do not accumulate in the lung.  The macrophages either break the material down with enzymes or expose them to the acidic environment of the lysosome.  These two mechanisms can clear 98% of the material that enters the lung, the rest is redistributed.  Macrophages transport the particles to either the mucociliary escalator or the lymphatic system.  The first mech. is very Slow (years), the second is imperfect and leads to accumulation of macrophages at origins of pulmonary lymphatics that cannot be cleared.
    • Particles less than .3 microns in diameter are subject to Brownian motion and do not deposit in the lung.
    • Particles greater than 10 microns deposit in the nose and are likewise removed by a mucociliary process. 
  1. List the pathologic reactions that may ensue when the defense mechanisms are overwhelmed.

·         Industrial bronchitis--chronic cough and sputum production (with possible chronic airflow obstruction) following chronic exposure to high levels of large dust particles.  Similar histologically to asthma (hypertrophy of bronchial mucus glands, goblet cell metaplasia).

·         Macules--focal collections of dust within the lungs.  Got there both by deposition and macrophage redistribution.  Located (characteristically) adjacent to respiratory bronchioles.   Clincially assymptomatic, just a marker for dust exposure.

·         Peribronchiolar fibrosis--increase in amt. of fibrous tissue encircling respiratory bronchioles (where dust is deposited most heavily).  Mild obstructive deficits.

·         Nodular fibrosis--characteristic of pneumoconioses caused by crystalline silica and coal dust.  Originate adjacent to respiratory bronchioles and nodules grow around dust particles.  Divided into "simple" and "complex" categories.

·         Diffuse interstitial fibrosis--may develop in the backgroud of nodular fibrosis, or on its own.  Usually follows prolonged heavy dust exposure.  Not all exposed individuals develop this disease.  Once dz occurs, death usu. follows due to progressive respiratory failure.

·         Empysema--controversial whether this can arise from dust exposure alone, or whether concommittant cigarette smoking is necessary.  Most prominent in coal workers' pneumoconiosis. 

·         Alveolar lipoproteinosis--architecture of the lung preserved, but alveoli become filled with degenerating Type II pneumocytes, macrophages and surfactant.  Thought that macrophage dysfunction following exposure to silica (or aluminum or kaolin dusts) is basis of disease.  Dz appears several years after exposure and is progressive, death due to hypoxia.

  1. List the 4 main types of occupational lung disease and explain the basic pathogenic mechanism behind each.

* Chemical Pneumonitis is due to direct injury of the lung parenchyma by a toxic agent, usually a gas.  Sx begin within hours of exposure.

*Occupational asthma results when a person inhales an antigen to which he or she has previously been sensititzed.  Interaction of the antigen with the IgE on the surface of mast cells results in the release of histamine + various inflammatory mediators and subsequent bronchoconstriction.  Does not occur on first exposure.  Occurrs in minutes to hours following subsequent exposure.  Inflammation and edema.

*Hypersensitivity pneumonitis  is the result of a complex immunologic reaction involving IgG, IgM, lymphocytes and monocytes.  Months or years of sensitizing exposure are needed before symptoms occur.  Clinical sx may then become evident within 4 to 8 hours following a large exposure to the offending antigen.  Chronic low level exposure results in insidious, slowly progressive sx and may lead to diffuse interstitial fibrosis.

*Pneumoconioses are diseases that follow exposure to inorganic dusts.  The pathogenesis of these disorders do not involve classical immunologic reacations or chemical injury but rather involves poorly understood cellular interactions that become operative when normal host defenses are overwhelmed.  Requires months to years of exposure before dz becomes clinically evident.


  1. Explain why pneumoconiotic lesions are distributed in the lung where they are.

Nodular fibrosis, macules and peribronchioloar fibrosis are located around or adjacent to respiratory bronchioles.  This is because dust particles preferentially deposit distal to the respiratory bronchioles cuz stream of air slows here with the markedly increased cross secional area of lumen.  From there the macrophages injest it and attempt to relocate it to the mucociliary escalator and to the pulmonary lymphatics which have their origins at the respiratory bronchioles (and beneath the pleura).  Also dust likes to accumulate at bifucations, and the respiratory bronchioles are no exception.  

  1. Give examples of two dusts that can induce pulmonary fibrosis and one that causes an asymptomatic reaction that is simply a marker of exposure.

Chronic silicosis and coal dust (coal workers’ pneumoconiosis)

Siderosis refers to exposure to iron dust resulting in macules adjacent to respiratory bronchioles.  This is clinically assymptomatic, though it may be visualized on CXR.

  1. Describe the characteristic pathologic features of siderosis, silicosis, coal workers' pneumoconiosis and asbestosis.

Siderosis:  macules filled with iron dust adjacent to respiratory bronchioles.  May grow to 2 mm in diameter.

Silicosis:  nodular fibrosis (dense, laminated collagen) usu. Apical.  Often partially calcified, visualized by CXR.  Some individuals progress to massive fibrosis in which nodules expand, conglomerate, and cause scarring and retraction of adjacent lung.

Coal Worker’s Pneumoconiosis:  macular and fibrotic lung lesions (CWP) possibly with progressive massive fibrosis (CWP-PMF).  Fibrosis results in “pericicatricial emphysema” of adjacent parenchyma, almost indistinguishable from the centrilobular emphysema associated with cigarette smoking.  Disease arrests upon removal of offending agent, with the exception of PMF.  CWP also causes Caplan’s Syndrome (rheumatoid pneumoconiosis)—granulomatous inflammation (nodules) apparent in individuals with circulating rheumatoid factor.

Asbestosis:  diffuse fibrosis, worst in lower lung zones and near pleura.  Progressive dz.

  1. Explain the difference between "simple" and "complicated" pneumoconiosis.

Simple—nodules less than 1 cm in diameter

Complicated or complex—large conglomerates of nodules or interstitial fibrosis, also known as progressive massive fibrosis.

  1. List the characteristic dose-dependencies and latencies of silicosis and asbestosis.

Silicosis—can occur as a relatively acute process (silicoproteinosis), but more commonly is a chronic, slowly progressive dz, requiring 20 years of exposure to dust containing at least 18% crystalline silica. 

Asbestosis—latency 10-25+ yrs, exposure: high (dose and duration of exposure, though dz has been seen in people with only 9 mo exposure).



Table from class not mentioned in objectives






              Industrial Bronchitis








              Peribronchial fibrosis













              Nodular fibrosis








              Diffuse fibrosis



















              Alveolar lipoproteinosis





Gynecological Pathology


1)      Understand the most common vulvar neoplasms (in-situ and invasive squamous neoplasia, Paget’s disease) and some of their clinical mimics (lichen sclerosis and squamous hyperplasia).

From repro you may remember that vulvar neoplasms are associated with HPV and smoking.  Recurrence is common.  Usu. Squamous in origin, can be melanoma.  In-situ carcinomas are confined to their respective epithelial lining without breaching the basement membrane and have a slew of synonyms:  precancers,” “high grade intraepithelial neoplasia,” “severe dysplasia,” etc.  Invasive carcinomas have crossed the BM.

Paget’s disease—in-situ neoplasm of mucin secreting cells populating the squamous epithelium.  Indolent neoplasm causing “eczema-like weeping erythematous raised plaque.”  Rarely invasive.

Lichen sclerosis:  “atrophic dystrophy”—thin flat epithelium with thick keratin layer.  freq. presents as white patch or with itching or pain. can tear and scar. not cancerous, tx with cream.

Squamous hyperplasia:  also presents as white patch (depigmentation with hyperkeratosis) known as “leukoplakia.”  Leukoplakia is non-specific and may be found in carcinomas (both invasive and in-situ) and with lichen sclerosis.  Slightly increased risk of developing squamous cell CA.  



2)      Understand the clinical significance, concept and grading system of C.I.N. (cervical intraepithelial neoplasia), it’s relationship to cervical carcinoma and PAP screening, and be familiar with synonyms used.

CIN is not alarming in and of itself.  It is believed that well under 50% of high grade lesions (CIN III) will progress to carcinoma.  In fact, low grade lesions are not necessarily immediately excised, but rather they are followed for awhile.  (Though it is important to note that high grade lesions are considered more predisposing to invasive cervical carcinoma, and as such are immediately bx/tx.) Progression of the disease was previously viewed as a continuum:

Squamous atypia ® CIN I (LGSIL = low grade squamous intraepithelial lesion) ® CIN II (HGSIL) ® CIN III (HGSIL) ® Invasive carcinoma

However, it is now believed that people can enter into this continuum at any point based upon their environment and which HPV strain(s) they have acquired.  High risk HPV’s: 16,18, 31, 33, 35.  See diagram pg. 236. 

Grading:  low grade CIN has nuclear atypia throughout the thickness of the epithelium, but retains maturation (cells at surface have lower nuclear to cytoplasmic ratio.)  Higher grade lesions have less maturation.  In CIN III (CIS, carcinoma in situ) the entire thickness of the epithelium is comprised of cells with a high N:C ratio reflecting a loss of differentiation control. 

Relationship to PAP screening:  a lack of cervical pap smear screening is considered the single largest risk factor for developing invasive cervical carcinoma.  PAP smears may cry ASCUS too often, but they will catch cancers early and save your a%&.  (ASCUS=atypical squamous cells of undetermined significance).    



3)      Understand the purpose of cervical PAP smear screening, its uses and limitations and why it is effective.

The PAP smear has evolved into a screening for premalignant conditions.  It is highly sensitive, but not very specific (i.e. many women have ‘abnormal’ pap smear results that have no significant pathology).   Its useful cuz it catches stuff early.  It’s limiting because it’s not a diagnostic tool.


4)    Understand the common pattern of spread of cervical carcinoma and know the implications related to staging, prognosis and treatment.


1)       Direct extension into adjacent tissues and organs eventually causing ureteric obstruction, pyelonephritis, uremia and death.

2)       Lymphatic spread to pelvic and paraaortic nodes.

3)       Hematogenous spread in later stages.

Staging, prognosis, and treatment, see table on pg. 235.


5)      Understand endometrial neoplasia and its risk factors and terminology.

Endometrial hyperplasia has three classifications:

1)       Simple, mild, or cystic (“swiss cheese”) – simple hyperplasia with no increased risk of carcinoma.

2)       Adenomatous or “complex” – tissue is more glandular and carries an intermediate risk.

3)       Atypical hyperplasia—thought to be premalignant.  Complex architecture and nuclear abnormalities.  Can be difficult to distinguish between this and well-differentiated carcinoma.

Risk factors: any state of prolonged, unopposed estrogen stimulation—exogenous administration (without progesterone) or obesity.

There were more listed in repro, but not in this class.

        Histologic variants of endometrial carcinoma:

        Adenocarcinoma—“endometrioid” –recapitulates normal endometrial lining

Adenocarcinoma with squamous metaplasia (adenocanthoma)—similar to above but with areas of squamous metaplasia.

Papillary serous and clear cell variants (high grade cytology)-- ?  occur in older patients, no endometrial hyperplasia. (no assoc with estrogen)

Malignant mixed mullerian tumor (carcinoma-sarcoma)—high grade tumor with carcinomatous and sarcomatous elements, older pts, no assoc with estrogen.

Adenosquamous carcinoma—malignant glandular and squamous components and may have a more aggressive course


6)             Define endometriosis, adenomyosis and leiomyoma, and know the most common symptoms associated with each.

Endometriosisectopic endometrial glands and stroma.  Common sx: dysmenorrhea, chronic pelvic pain and infertility (if the fallopian tubes become mechanically obstructed).

Adenomyosis—an extension of endometrial glands and stroma into the myometrium often assoc with hyperplasia of the latter.  can produce sx of : menorrhagia, dysmenorrhea.

Leiomyoma (Fibroid)—benign smooth muscle neoplasm of the endometrium.  Most common of all visceral tumors.  Sx:  assymptomatic abdominal mass, estrogen dep. Can cause variety of sx depending on size and location.


7)      Understand the major categories of ovarian tumors; know their usual clinical presentation, and the pattern of spread of epithelial tumors.

Major categories:

Epithelial neoplasms—derived from serosal (peritoneal) cells, comprise 2/3 of all ovarian tumors and increase in freq. with age.  Presentation not until late.  May present with increasing girth due to ascites.  Spread:  endometrium ® myometrium ® cervix ® vagina, adnexa, peritoneum, paraaortic lymph nodes ® bladder, bowel, distant mets to intra-abdl and/or inguinal (!) lymph nodes   

Germ cell neoplasms—derived from the ovum, typically seen in younger women (2nd and 3rd decade).  Presentation not mentioned. Teratoma = benign, Dysgerminoma = malignant

Sex cord stromal neoplasms—derived from supporting and often hormone producing stromal cells of the ovary.  Most complex, presenting with abnormal hormone production. 


8)      Be familiar with complications of genital tract infections.

Chlamydia in females:  often assymptomatic.  Acute mucopurulent cervicitis presents with yellowish-green discharge; salpingitis is a complication in approx. 10-40%.  Tubal damage and infertility are common sequelae, which predisposes women to ectopic pregnancy.  Also causes premature rupture of membranes via infection of the membranes (chorioamnionitis).

Herpes Genialis: spontaneous abortion or intrapartum transmission to the fetus causing often fatal systemic neonatal herpes.

Hemophilus or “Gardnerellavaginalis—thought to be a factor causing premature rupture of membranes in pregnancy.


Ovaries and GYN infections


Ovarian cancer is < uterus, cervix but more fatal.

Physiological cysts” (follicular or luteal) are more common cause of ovarian mass, but hard to distinguish from carcinoma (also cystic).


Common epithelial neoplasms—from surface serosal (peritoneal) cells, 2/3 of ovarian tumors, older pts

Germ cell neoplasms—2nd/3rd decade

Sex-cord stromal neoplasms—often prd hormones

Usu no sx until metsascites. Or, can be found on routine pelvic exam

Risk factors—family member w/ it, BRCA-1 or 2, Lynch syndrome


Common epithelial tumors:


            Borderline neoplasm—in-situ, no invasion, younger pts, do well even when spreads

                        outside ovary, aka “”low malignant potential”



Grading is less important than stage, cell type is less important than benign/borderline/malignant.

Cell types:

            Serous—mimics fallopian tube lining, most common, papillary architecture

            Mucinous—slow growing, can get huge

            Endometrioid—mimic endometrial carcinoma, may coexist w/ it.

            “Clear cell”—glycogen-rich, very malignant

            Brenner tumor—transitional, usu benign

Germ cell tumors:

Benign cystic teratoma—most common, akadermoid cyst” because of sebaceous stuff

w/ hair in it

            Dysgerminoma (or seminoma)—most common  (or “commonest”) malign. GC tumor.

                        a rare, very malign. form is “yolk sac” or “endodermal sinus” tumor, which

                        makes alpha-fetoprotein

Sex cord tumors

            Fibroma/thecoma—benign, make hormones

            Granulosa tumor—potentially malign, “Call-Exner body” is a space mimicking those

                        seen in maturing graafian follicules

            Sertoli Leydig tumors—usu masculinizing, good prog when differentiated.

Can also have mets TO ovary—usu breast, stomach, colon



Chlamidya—most common, often asymp, complications—ectopic preg, premature ROM.

Herpes—asymp. shedding, complications—SAB, intrapartum transmission to fetus (often fatal)

            see multinucleate giant cell on PAP in acute infec.

Trichomonas vaginalis—often asymp, or foul green discharge

Primary syphilis—chancre 

Non-STD infections include those from IUD insertion, abortion, etc. (see p. 246)