NEOPLASIA

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NEOPLASIA

• Asima Arslan, M.D.
• Department Of Pathology Laboratory Medicine
• RWJMS-UMDNJ
• January
• 2006

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Facts

• ONE OUT OF FIVE (OR FOUR) PERSONS IN THE US WILL
  DIE OF CANCER ( 500,000 A YEAR)
• 1.5 million NEW cases a year (not including a
  million cases of skin cancers a year and
  pre-cancerous conditions)
• THE SECOND TO IHD ATHEROSCLEROSIS AS A CAUSE OF
  DEATH IN THE US
• 1 in 2 lifetime risk for men, 1 in 3 lifetime
  risk for women
• SOME OF TUMORS ARE PREVENTABLE, SOME ARE EVEN
  CURABLE.
• Skin cancer is the most common human cancer and
  one of the most preventable

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What Is NEOPLASIA

• "A neoplasm is an abnormal mass of tissue, the
  growth of which exceeds and is uncoordinated with
  that of the normal tissues and persists in the
  same excessive manner after cessation of the
  stimuli which evoked the change"

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Benign vs Malignant

• Slow growing
• Encapsulated
• Expansile growth
• No Metastasis
• Well Differentiated

• Rapidly growing
• Non encapsulated
• Infilterative growth
• Metastasis
• Well-Poorly differentiated

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GRADEand STAGE
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• WHY WE CAN NOT USE THE ETIOLOGY TO CLASSIFY
  TUMORS?

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Classification and Nomenclature

• Benign add suffix oma to tissue of origin
• Malignant
• Carcinoma
• Sarcoma
• Leukemia

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Variations in terminology

• Lymphomas
• Skin tumors
• Melanocytes
• Keratinocytes

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Nomenclature

• ADENO CA
• SQUAMOUS CA
• ADENOMA
• LYMPHOMA
• LEUKEMIA
• MULTIPLE MYELOMA
• SARCOMA

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• Adenomatous polyp,
• Colon

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Tubular adenoma, colon
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Squamous cell carcinoma, skin
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SCC
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• Melanoma, skin

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SCC, invasive, cevix
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Osteosarcoma, femur
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SCC, skin
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Acute Myeloid Leukemia
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Pedunculated colon cancer
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Teratoma (Dermoid cyst), Ovary
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Teratoma, ovary
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Teratoma, ovary
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Multiple Myeloma
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Causes of Cancer

• Environmental vs. Hereditary Cancers
• About 85 of cancers are estimated to be
  environmentally induced
• Exposure to environmental carcinogens (chemical,
  radiation, viral)
• Remainder of cancers inherited predisposition
• Mutation??

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HEREDITARY FACTORS AND TUMORS

• Play a small role in some tumors by genetic
  differences in
• Hormones
• Metabolizing capacity
• DNA repair mechanisms
• Immune Systems

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Geographical and Ethnic Differences in Cancer
Incidence
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Pre Cancerous Conditions

• Is Different from the In Situ concept
• Actinic Keratosis
• Lentigo Maligna
• Leukoplakia
• Villous adenoma of the GI

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Why Tumors Are Different From Organs And Normal
Tissue?

• FUNCTION
• RATE OF GROWTH
• PARANEOPLASTIC SYNDROME

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What Are The Final Complications Of Malignancy
(Causes Of Death)

• PNEUMONIA
• PNEUMONIA
• PNEUMONIA
• CACHEXIA
• RENAL FAILURE
• BLEEDING
• SEVERE ANEMIA, THROBOCYTOPEINA
• INFECTIONS
• HYPERCOAGULABILITY
• DIC
• PAIN MORE OF DEVASTATING SYMPTOM THAN A
  COMPLICATIONHAS TO BE CONTROLED

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Paraneoplastic Syndromes

• Remote effects not due to local effects of
  primary tumor or its metastases
• Fever
• Anorexia/weight loss
• Hypercalcemia
• Neurologic
• Hypercoagulable State

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Some Explanation Of Why???

• ONCOGENE ACTIVATION
• Point mutations, translocations, gene
  amplification
• TUMOR SUPRESSOR GENE
• DNA REPAIR GENES
• GENES REGULATING APOPTOSIS
• FAILURE OF IMMUNOLOGICAL DEFENCE MECHANISMS

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Retinoblastoma
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Retinblastoma
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Tumor ANGIOGENESIS

• VEGF, BFGF, TNF

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Tumor Dormancy

• Tumors can recur years after treatment
• Breast cancer is especially noted for long
  periods of dormancy

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Carcinogen

• Chemical carcinogens
• Physical carcinogens (UV, radiation, asbestos)
• Hormones
• Oncogenic microbes (mainly viruses)
• Sometime our weapon to kill the beast is a double
  edge sword

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Viral Carcinogenesis

• Viral infections account for an estimated one in
  seven human cancers worldwide
• Majority of these are due to infection with two
  DNA viruses
• HBV linked to hepatocellular carcinonoma
• HPV linked to cervical carcinoma
• HTLV-1
• Kaposi Sarcoma.. HHV-8

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What Is the Evidence for the Genetic Basis of
Cancer?

• Some individuals show hereditary predisposition
• Individuals with impaired DNA repair systems show
  increased cancer incidence
• Cancer cells contain chromosome
  abnormalities..e.g. translocations in leukemia
  and lymphomas
• Almost all mutagens are carcinogens
• Existence of oncogenes

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Multi-stage Nature of carcinogenesis

• Initiation
• Promotion
• Progression

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The Good, The Bad The.

• DIFFERENTIATION
• SHAPE
• CAPSULE
• RATE OF GROWTH
• MITOSIS
• N/C RATIO
• CHROMASIA
• NUCLEOLUS
• PLEOMORPHISM
• INVASION
• METS

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B Dysplasia pleiomorphic, large N/C ratio,
hyperchromatic nuclei
A normal pap smear. Cells large, well
differentiated, small N/C ratio
C Invasive squamous cell carcinoma
undifferentiated cells, multinucleated,
hyperchromatic nuclei, dense nucleoli. Large N/C
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Signs of malignant process..
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Well differentiated adenocarcinoma of the
endometrium, uterus
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• Leiomyosarcoma, uterus

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Lipoma
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Abnormal mitotic figures
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Tripolar mitotic figure (abnormal)
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Signs of malignant process
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Benign Tumors

• SECRETIONS
• COMPRESSION
• TRANSFORMATION
• LOCALLY INVASIVE!!!

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Meningioma
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The Most Common

• CANCER IN MALE?
• CANCER IN FEMALE?
• KILLER IN MALE?
• KILLER IN FEMALE?
• 50 YS AGO WAS

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Prostatic adenocarcinoma




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Prostatic adenocarcinoma
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Invasive carcinoma of the breast

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Well differentiated ductal carcinoma, breast
Moderate to poorly differentiated ductal
carcinoma, breast

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Bronchogenic carcinoma, lung
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SCC, cervix
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Normal Squamous cells Malignant squamous
cellsnecrosis
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George Nicolas Papanicolaou 1883-1962
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Local Routes, Interstates, Turnpike..Routes Of
Spread

• WHAT EVER THE WAY, SOME LIKE TO GO TO FLORIDA,
  OTHERS WILL PREFER ALASKA BUT SOME WILL GO
  WHEREVER THEY LIKE. WHY?
• STILLLLLLLL .?
• BUT WE KNOW THE MOST COMMON SITESLNS, 2L 2B

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Metastatic carcinoma , liver
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Metastatic carcinoma , liver
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Metastatic carcinoma , lung
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Biology of Invasion and Metastasis

• Invasion of the basement membrane
• Movement through extracellular matrix
• Penetration of vascular or lymphatic channels
• Survival and arrest within the circulating blood
  or lymph
• Exit from the circulation into new site
• Survival and growth as a metastasis

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Carcinoma in situ
Cancer cell becomes capable of invasion
(expresses surface adhesion molecules)
Tumor cells release proteolytic enzymes,
disruption of ECM Invade ECM
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Peritoneal carcinomatosis
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How Do We Get To The Diagnosis Of Malignancy?

• TEAM EFFORT
• CLINICAL ( TUMOR MARKERS, LABS)
• GROSS
• CYTOLOGY
• HISTOLOGY (IHC)
• Molecular pathologist and cytogenetist
• MOST IMPORTANT, EARLY DETECTION.
• LADIESNEVER UNDERESTIMATE THE PAAAAAAAAAAPPPP
  MAMMOGRAMPLEASE

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Why How Do We Grade And Stage Tumors?

• 0-V
• TNM
• Tx, T0, Tis, T1-4
• Nx, N0, N1-3
• Mx, M0, M1

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Lung mass, CT scan
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Immunohistochemistry
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Electron microscopy
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TREATMNT

• SURGERY
• RADIOTHERAPY
• CHEMOTHERAPY
• IMMUNOTHERAPY
• Hormones
• Gene therapyadvancing
• BMT
• CURATIVE VS PALLIATIVE

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References

• This lecture would not be possible except with
  the aid of different textbooks, personal and
  online material
• I am mentioning here some of the web sites I used
  to prepare this lecture
• www.pathguy.com .very useful for students, its
  funny too
• www.mdconsult.com huge amount of everything
  about medicine
• And of course Robbin Cotran Pathologic basis
  of diseases

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• THANK YOU
• WILL HAVE A BREAK FOR 5 MINUTES THEN WE HAVE A
  CASE FOR DISCUSSION..QUICKKKK?