This document discusses neoplasia (tumors). It defines neoplasia as new growth forming an abnormal mass caused by autonomous proliferation of cells independent of stimuli. There are two main components of tumors - transformed neoplastic cells and supporting stroma and vessels from the host. Tumors are classified as benign or malignant based on their behavior and prognosis, and by their tissue of origin histologically. Malignant tumors have characteristics of uncontrolled rapid growth, invasion, ability to spread, recurrence, and causing death. Their structure shows irregular margins, necrosis, and cellular anaplasia. Mechanisms of local and distant spread include invasion of surrounding tissue and vessels, as well as migration of tumor cells through lymphatics and blood

1. Neoplasia (tumor)
• New growth forming abnormal mass caused by
autonomous self controlling proliferation of cells
independent of stimuli.
• Oncology: study of tumors.
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2. General characteristics:
– Uncontrolled proliferation:
• Derived from any cells even the non dividing.
• Continue proliferation even the pt. is starved.
• Irreversible & unlimited proliferation (progress even
after stoppage of any evoking stimulus).
– No useful function for proliferation (some with harmful)
– 2 basic components :
• Transformed cells (neoplastic): monoclonal or
polyclonal.
• Supporting stroma & vessels: non-transformed
elements derived from the host due to tumor derived
factors. 2

3. Classification
• biological (according to behavior):
– Benign: good prognosis
– Malignant: poor prognosis
– Intermediate: locally malignant & locally
aggressive.
• Histological (according to tissue of origin):
– Epithelial.
– Mesenchymal.
– Others.
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4. Benign neoplasms
• Tumor behavior:
–Rate of growth: often slow.
–Mode of growth: expansile.
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5. Benign neoplasms
–Prognosis: don’t spread or recur after excision
and are not dangerous unless:
• Arise in vital organ (brain).
• Arise in hollow organ (intestine obstruction).
• Produce hormones.
• Some may change malignant:
– Gross: faster growth rate, changing growth mode
(infiltrative, destructive,metastasizing).
– M/P: capsular invasion, necrosis, hrge, changing
microscopic pattern (loss of cellular & histological
differentiation). 5

6. Benign tumor
• Tumor structure:
– Gross:
• Margin: well defined.
• Cut section: commonly uniform with no hrge or
necrosis.
• If arising inside solid organ: appear globular or
ovoid & surrounded by fibrous capsule (rim of
condensed CT).
• If arising from surface epithelia non
capsulated polyp (papilloma).
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7. Benign tumor
• M/P:
– Cell differentiation (extent to which tumor cells
resemble normal cells): perfectly differentiated
(closely mimic normal cells) & rare mitosis.
– Histological differentiation:
• Cells exhibit a similar structural pattern to normal
tissue.
– Other:
• Has stroma with few vessels.
• 2ry changes (myxoid or hyaline) may occure but hrge or
necrosis are extremely exceptional. 7

8. Malignant tumors
• Tumor behavior:
–Rate of growth: often rapid.
–Mode of growth: invasive (infiltrate &
destroy normal surroundings) with some
degree of expansion.
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9. Malignant tumors
– Prognosis:
• Spread.
• Very commonly Recur after surgical excision.
• Serious & cause death:
– Local & distant organ destruction, Vital centers destruction
(brain tumor), Obstruction of hollow organ lumen, Organ
failure (liver,kidney), Malnutrition, chronic toxaemia (2ry
bact. Infection), anaemia.
– Cachexia: marked wt. loss, weakness, anorexia, anaemia,
low resistence (pnumonia). TNF (suppress appetite &
interfere with fat metabolism).
– Paraneoplastic syndromes : 10% due to abnormal tumor
products.
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10. Malignant tumors
• Tumor structure:
– Gross:
• Margin: irregular & ill-defined.
• Cut section: areas of hrge & necrosis.
• If arising inside solid organ: irregular non capsulated
mass, rarely with capsule (incomplete & microscopic
foci of invasion).
• If arising from surface epithelia non capsulated
masses with different patterns:
– Polypoid fungating cauliflower-like.
– Ulcer: irregular with raised everted edge & rough necrotic floor.
– Infiltrating pattern (below surface in tubular organ & may cause
annular stricture). 10

11. 11

12. 12

13. Malignant tumors
• M/P:
– Cellular anaplasia :abnormal differentiation of
cells that show grades of atypia (mild to marked):
• Cellular & nuclear pleomorphism.
• Nuclear enlargement & hyperchromatism: DNA
synthesis, dark with > N/C ratio.
• Prominent nucleoli.
• Abundant mitosis with abnormal mitotic figures.
• Tumor giant cells ( single large polypoid or multible n.)
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14. Initial hepatocellular carcinoma
(HE) x 200
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15. Figure 2: Diffuse population of tumor cells with round to pleomorphic nuclei,
horse shoe shaped nuclei, mitotic figures, apoptotic bodies and part of overlying
epidermis can be seen (H and E, x400), Inset showing CD 30 positivity (IHC, x400)15

16. Squamous cell carcinoma
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17. M/P of Malignant tumors
– Histological differentiation:
• Degree of resemblance to the normal tissue (morphologically
& functionally).
• Grades:
– I: well diff.
– II: moderately diff.
– III: poorly diff.
– IV: undiff. (anaplastic)
• Better diff: less marked cellular anaplasia & slow growth.
• undiff. : great cellular anaplasia & faster growth.
– Other:
• Has stroma rich in vessels.
• 2ry changes (myxoid or hyaline) may occure & hrge & necrosis
are common. 17

18. Michanism of Spread of malignant tumors
(locally & distantly)
• Invasion of ECM:
– Loss of cellular cohesion (losening): due to loss of cadherines detach.
– Attachment of tumor cells to matrix component (laminin & fibronectin)
– Degradation of ECM by enzymes as type IV collagenase & cathepsin D
to form passageways.
– Migration by psudopodia by autocrine mobility factor.
• Vascular dissemination & homing of tumor cells:
– Migration contact with bl.vs. Penetration cross BM & reach
blood tumor emboli:
• Destroyed by immune michanism (most)
• Survivors adhere to platelets.
• Impacted in small vs. Adhere to endothelium cross BM
settle proliferate metastatic deposite (2ry)
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19. Michanism of Spread of malignant tumors
• Local (direct) spread:
– In all directions along lines of least resistence.
– Some structures delay direct spread (cartilage,
periostium ).
– michanism (invasion of ECM).
– To surface (skin or mm) malignant ulcer.
– From hollow organ to adjacent one malig. Fistula.
– Some spread along perinural space sever pain
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20. • Distant spread (metastasis):
– Development of 2ry malig. Implants discontineous with the
1ry tumor.
– lymphatic, hematogenous, transcoelomic, others.
– Lymphatic:
• Lymphatic embolism:
– Reach lymph & then to subcapsular sinus of LN, proliferate &
obleterate LN.
– May spread from 1 node to another by efferent lymphatics.
– Gross: large, firm, grey white cut surface, fixed (if the capsule is
invaded).
– M/P: resemble 1ry tumor from which it is derived.
– Progressive spread lead to emboli in the thoracic duct bl.spread.
• Lymphatic permiation:
– malig. Cells grow inside the lumen as solid columns that obstruct
lumen lumphatic edema. 20

21. Metastatic Melanoma in Lymph Node
This 6.5-centimeter mass was removed from the axilla of a middle-aged woman, who
was a longtime resident of a developmental center for the severely disabled. She was
unable to give any history, but there was no medical record of a primary melanoma,
and we were unable to find any biopsy scars at the time of surgery. The dark brown
color of the cut surface provided a clue to the diagnosis, an unusual finding in
metastatic melanomas, which are more typically amelanotic (like the upper right
segment of this specimen). Pigment was easily demonstrated in the tumor cells at
frozen section, allowing a definitive diagnosis intraoperatively.
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22. A liver studded with metastatic cancer. 22

23. • Hematogenous spread:
• Michanism of reaching blood:
– Reach venous circulation through thoracic duct
(carcinoms).
– Direct invasion of bl. Vs within the tumor (sarcoma).
• Course of emboli depend on anatomical factors:
– Systemic veins (vena cava) lung metastasis.
– From lung (pulm. Veins) systemic arterial circulation.
– Portal circulation (GIT) liver metastasis to IVC
through hepatic veins lung.
– To vertebral system of veins (from pelvis, abdomen or
thoracic) to brain, sp.cd & vertebrae (no lung) due to
marked anastomosis. 23

24. Hematogenous spread (cont.):
• Pathology of organ metastasis:
– Most common sites: LLBB
– Rare in ms, spleen,pancreas & intestine.
– Gross: scattered round nodules of variable sizes.
– M/P: resemble 1ry tumor from which it is derived.
• Bone metastases:
– Common in carcinoma thyroid, breast, lung…
– In vascular bone sites as ends of long bone, ribs, sternum,
vertebrae, skull & pelvis.
– Commonly osteolytic but may be osteosclerotic in some prostate
cancer metastasis.
– Effect: path. Fracture, sever pain, BM destruction (pancytopenia).
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25. Bony metastases - adenocarcinoma of prostate:
Metastatic osteoblastic prostatic carcinoma within vertebral
bodies. Primary lesion of any osteoblastic bony metastases
in a male is prostatic
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26. Metastatic prostatic adenocarcinoma (Pulmonary
Pathology) Tags: cancer gross specimen
pathology lung prostate carcinom
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27. • Transcoelomic spread (through body cavities):
– Serosal covering infiltrated cells detach & implanted in
other sites, associated With hrgic effusion.
• Transperitonial: metastatic peritoneal nodules + hrgic acitis.
• Transplural & transpericardial: matastases on diaphragm +
hrgic effusion.
• Trans CSF: matastases within wall of ventricles, base of skull,
sp.cd.
• Others:
– Translumenal: from transitional carcinoma of renal
pelvis.
– Surgical implantation: during management.
– Implantation from carcinoma of lower lip lead to 2ry
tumor on upper lip. 27

28. 28

29. Factors influencing prognosis of
malignancy
• Type.
• Site.
• Differentiation.
• Stage.
• Immune responce against it.
• Efficiency of ttt.
• Tumor hormone receptors.
• Growth fraction.
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30. Aetiological aspects of neoplasia
• Molecular basis of cancer:
– Genetic predesposition of cancer:
• Oncogenes & proto-oncogenes.
• Tumor suppressor genes (antioncogenes).
• Apoptosis genes.
• DNA repair genes.
• Michanism of neoplastic transformation (multistep
theory):
– initiation, promotion, neoplastic transformation.
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31. • Types of carcinogens: chemical, physical,
viruses, hormones.
• Chronic disease predesposition (precancerous
lesions): ch. Inflam. Ds., gall & urinary stones,
hyperplasia & metaplasia, some benign
tumors & others as varicose ulcer.
• Cocarcinogens (helping factors): age, sex, diet,
environmental factors, trauma, blood group &
histocompatibility type.
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32. Spontaneous tumor regression
• Definition:
– Cancer may suddenly regress spontaneously &
permanently.
– regression of metastasis after removal of the 1ry.
– maturation of malignant cells into benign tumor cells
or normal non neoplastic cells.
• Mechanism: unknown (maybe hormonal or
immunological).
• E.g:
– MM, neuroblastoma, choriocarcinoma.
– MM, choriocarcinoma.
– Teratoma of testis & neuroblastoma. 32

33. Laboratory diagnosis of neoplasia
• biopsy.
• FNAB.
• Cytological examination: of fluids.
• DNA flow cytometry.
• Tumor markers:
– Serum tumor markers (in blood): CEA, AFP, PSA.
– Tissue markers (within tumor cells): detected by
IMMUNOHISTOCHEMISTRY in cell memb.,
nucleus, cytoplasm e.g: CK, EMA, LCA, SMA.
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34. Significance of immunohistochemistry
• Diagnostic: to detect cellular origin in
undifferentiated tumors e.g undiff. Tumor +ve
for CK & -ve vimentin,LCA… = carcinoma.
• Prognostic & theraputic: breast cancer with
+ve ER & PR & -ve Her2 (ttt with tamoxifen),
but if the opposite (ttt with chemotherapy as
herceptin).
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