2 pathological diagnosis of cancer
-
Upload
sumit-prajapati -
Category
Documents
-
view
4.231 -
download
1
Transcript of 2 pathological diagnosis of cancer
Learning is the beginning of wealth. Learning is the beginning of wealth. Learning is the beginning of health. Learning is the beginning of health. Learning is the beginning of spirituality. Learning is the beginning of spirituality. Learning is where miracles begin. Learning is where miracles begin.
– – Jim RohnJim Rohn
Pathological Diagnosis of Pathological Diagnosis of NeoplasmNeoplasm
Jing-Ping YUN, Jing-Ping YUN, M.D., Ph.D.M.D., Ph.D. 云 径 平云 径 平 Professor in Department of Pathology Professor in Department of Pathology
Cancer Center of Sun Yat-sen University Cancer Center of Sun Yat-sen University
Pathological Diagnosis of NeoplasmPathological Diagnosis of Neoplasm
Recognize: roles of pathological diagnosis applied Recognize: roles of pathological diagnosis applied in clinical oncology in clinical oncology
Understand: definition, morphology, nomenclature, Understand: definition, morphology, nomenclature, differentiation, differences between differentiation, differences between
benign and malignant benign and malignant neoplasm, neoplasm, Grading and Grading and staging, Precancerous staging, Precancerous lesions lesions
Familiar with: principles and technologies Familiar with: principles and technologies of diagnostic pathology of diagnostic pathology
The Key Points of Medical ScienceThe Key Points of Medical Science
Disease
To prevent
To diagnose
To treat
Goals and Tasks Goals and Tasks of Diagnostic Pathologyof Diagnostic Pathology
Determine: Nature and name of Determine: Nature and name of disease (neoplasm)disease (neoplasm)
Determine: grading and stagingDetermine: grading and staging
Report: molecular changes and Report: molecular changes and Biomarkers Biomarkers
Main Contents of Pathological Main Contents of Pathological Diagnostic Report Diagnostic Report
Where: Organ and tissue involved by Where: Organ and tissue involved by the lesion the lesion
Why: morphological characteristics, Why: morphological characteristics, immunophenotypes, immunophenotypes,
molecular molecular changes, biomarkers changes, biomarkers
What: Nature and name of disease, What: Nature and name of disease, Grading and staging, Grading and staging, Comments Comments
Neoplasm: ContentsNeoplasm: Contents
DefinitionDefinition NomenclatureNomenclature Morphologic characteristics Morphologic characteristics Biologic changeBiologic change
Transformation Transformation Growth rateGrowth rate Benign vs Malignant neoplasmBenign vs Malignant neoplasm Invasive and metastasisInvasive and metastasis Molecular basisMolecular basis
Grading and StagingGrading and Staging Precancerous lesionPrecancerous lesion Tumor-like lesionTumor-like lesion
Definition of NeoplasmDefinition of Neoplasm
Dr. DA Willis
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.
Terms for NeoplasmTerms for Neoplasm
Neoplasm — the new growth Neoplasm — the new growth Neoplasia — the process of “new growth”Neoplasia — the process of “new growth”
Tumor — the term was originally applied to the Tumor — the term was originally applied to the swelling caused by inflammation, but by long swelling caused by inflammation, but by long precedent, the term is now equated to neoplasmprecedent, the term is now equated to neoplasm
Cancer — the common term for all malignant Cancer — the common term for all malignant tumorstumors
Oncology — the study of tumors or neoplasmOncology — the study of tumors or neoplasm
More Terms …More Terms … Dysplasia — recognizable morphologic changes in cells that Dysplasia — recognizable morphologic changes in cells that
indicate the presence of genetic mutations beginning the indicate the presence of genetic mutations beginning the development of a neoplasm. Usually grading dysplastic development of a neoplasm. Usually grading dysplastic changes based on the thickness of the involved epithelium: changes based on the thickness of the involved epithelium:
less than 1/3 mild atypical proliferation.less than 1/3 mild atypical proliferation.less than 2/3 moderate atypical proliferation.less than 2/3 moderate atypical proliferation.more than 2/3 severe atypical proliferation.more than 2/3 severe atypical proliferation.
eg: Dysplastic change of cervical epithelium infected by HPVeg: Dysplastic change of cervical epithelium infected by HPV
Anaplasia — recognizable morphologic changes in the tumor Anaplasia — recognizable morphologic changes in the tumor cells lack of differentiation; literally means “to form backward”, cells lack of differentiation; literally means “to form backward”, implying a ‘reverse differentiation’ of mature normal cells. It is implying a ‘reverse differentiation’ of mature normal cells. It is considered a hallmark of malignant transformation.considered a hallmark of malignant transformation.
eg: Anaplastic Rhabdomyosarcomaeg: Anaplastic Rhabdomyosarcoma
DysplasiaDysplasia
Dysplastic change in cervical epithelium
Anaplastic tumor showing cellular Anaplastic tumor showing cellular pleomorphismpleomorphism
Rhabdomyosarcoma: Rhabdomyosarcoma: Anaplastic cellsAnaplastic cells
Proliferative Terms (Not Neoplastic)Proliferative Terms (Not Neoplastic)
• METAPLASIA: One cell type is replaced by another cell type.
eg: cigarette smoking induced change of bronchial epithlelial cells to squamous; Barrett’s esophagitis--where the squamous epithelium of the esophagus is replaced by columnar epithelium.
HYPERPLASIA: An increase in the number of cells in an organ or tissue, which may then have an increased volume.
Physiologic hyperplasia: Proliferation of mammary glandular epithelium at pregnancy, compensatory hyperplasia of the liver after partial hepatectomy
HYPERTROPHY: An increase in size of cells and thus an increase in the size of the organ
eg: physiologic hypertrophy of uterus during pregnancy, hypertrophy of the cardiac muscle in hypertension or valvular disease, hypertrophy of skeletal muscles due to heavy exercise
DifferentiationDifferentiation
Differentiation — refers to the extent which Differentiation — refers to the extent which neoplastic cells resemble comparable normal neoplastic cells resemble comparable normal cells, both morphologically and functionally.cells, both morphologically and functionally.
Tumors are often “Tumors are often “gradedgraded” as to the extent of ” as to the extent of cellular differentiation or how closely they cellular differentiation or how closely they resemble the normal parent tissue that they are resemble the normal parent tissue that they are derived from. derived from.
Grading of DifferentiationGrading of Differentiation
Well-differentiated means the cells are very Well-differentiated means the cells are very similar in appearance and architectural similar in appearance and architectural arrangement to normal tissue of that organarrangement to normal tissue of that organ
““Poorly-differentiated” refers to tumors that show Poorly-differentiated” refers to tumors that show only minimal resemblance to the normal parent only minimal resemblance to the normal parent tissue they are derived from.tissue they are derived from.
““Anaplastic” (undifferentiated) means the tumor Anaplastic” (undifferentiated) means the tumor shows no obvious similarity to it’s parent tissue, shows no obvious similarity to it’s parent tissue, usually associated with aggressive behaviorusually associated with aggressive behavior
Structure of NeoplasmStructure of Neoplasm
Parenchyma:Parenchyma: Neoplastic cells. Neoplastic cells.
Stroma:Stroma: Non-neoplastic (Fibrous connective Non-neoplastic (Fibrous connective tissue and vasculature )tissue and vasculature )
Fast growth Fast growth less stroma less stroma Less stroma Less stroma more necrosis more necrosis
Loss of normal architectural arrangement and polarityLoss of normal architectural arrangement and polarity
LateAdenoma
NormalCrypt
EarlyAdenoma
Adenocarcinoma
Morphological features of tumorsMorphological features of tumors
Pleomorphism – variation in size and shape of Pleomorphism – variation in size and shape of cells and nuclei within the neoplasmcells and nuclei within the neoplasm
Morphological features of tumorsMorphological features of tumors
Mitotic activity - Increased in more malignant Mitotic activity - Increased in more malignant tumors and often abnormal in shapetumors and often abnormal in shape
Morphological features of tumorsMorphological features of tumors
Functional AlterationsFunctional Alterations of Neoplastic cells of Neoplastic cells
Loss of functionsLoss of functions
Loss of responsiveness to and dependence Loss of responsiveness to and dependence upon normal regulatory pathwaysupon normal regulatory pathways
Nomenclature of NeoplasmNomenclature of Neoplasm
Cell of origin + SuffixCell of origin + Suffix
Neoplasms are named according to a binomial system Neoplasms are named according to a binomial system denoting their denoting their histogenetic originhistogenetic origin of the parenchymal of the parenchymal component and component and biological behaviorbiological behavior
Histogenetic originHistogenetic origin refers to the tissue or cell type from refers to the tissue or cell type from which the tumor arosewhich the tumor arose
Biological behaviorBiological behavior includes the degree of tumor cell includes the degree of tumor cell deffirentiation and patterm of growth: deffirentiation and patterm of growth: benignbenign and and malignantmalignant
Nomenclature of NeoplasmNomenclature of Neoplasm
Cell of origin + SuffixCell of origin + Suffix
Benign tumors: Cell of origin + ‘Benign tumors: Cell of origin + ‘ ~~ oma’, e.g., adenoma, oma’, e.g., adenoma, osteomaosteoma
Malignant tumors: Cell of origin + ‘Malignant tumors: Cell of origin + ‘ ~~ carcinoma, carcinoma, ~ ~ sarcoma’ , e.g., adenocarcinoma, osteosarcomasarcoma’ , e.g., adenocarcinoma, osteosarcoma
Mixed Tumors – originated from more than one germ layer, Mixed Tumors – originated from more than one germ layer, or created by a divergent differentiation of a single or created by a divergent differentiation of a single pluripotential or totipotential cell into another tissue; benign pluripotential or totipotential cell into another tissue; benign or malignantor malignant e.g., teratoma, pleomorphic adenoma or mixed tumore.g., teratoma, pleomorphic adenoma or mixed tumor
Malignant tumors: suffix ‘Malignant tumors: suffix ‘ ~~ oma’ or othersoma’ or others
e.g., Glioma, Melanoma, Seminoma, Hepatoma, Leukemiae.g., Glioma, Melanoma, Seminoma, Hepatoma, Leukemia
Non-neoplastic lesions: suffix ‘Non-neoplastic lesions: suffix ‘ ~~ oma’oma’
e.g., Granuloma, hamartomae.g., Granuloma, hamartoma
Morphology: e.g., Signet-ring cell carcinomaMorphology: e.g., Signet-ring cell carcinoma
Personal names: e.g., Ewing’s sarcoma, Brenner tumor, Personal names: e.g., Ewing’s sarcoma, Brenner tumor, Hodgkin’s lymphomaHodgkin’s lymphoma
Nomenclature of NeoplasmNomenclature of Neoplasm ExceptionsExceptions
Classification of neoplasmsClassification of neoplasms
Epithelial tumors Epithelial tumors • Benign forms – adenBenign forms – adenoma oma , papill, papillomaoma• Malignant forms – Malignant forms – carcinomacarcinoma, eg , eg
adenocarcinoma, squamous cell carcinomaadenocarcinoma, squamous cell carcinoma
Mesenchymal tumorsMesenchymal tumors• Benign forms – fibrBenign forms – fibromaoma, leiomy, leiomyomaoma, , • Malignant forms – Malignant forms – sarcomasarcoma, eg fibro, eg fibrosarcomasarcoma, ,
leiomyoleiomyosarcomasarcoma
Classification continuedClassification continued
Tumors of lymphocytes are always Tumors of lymphocytes are always malignant malignant –– called called lymphomalymphoma
Tumors of melanocytes Tumors of melanocytes • Benign Benign –– nevus nevus• Malignant - melanomaMalignant - melanoma
Benign vs Malignant TumorBenign vs Malignant Tumor
CharacteristicsCharacteristics BenignBenign MalignantMalignant
Morphology and Morphology and DifferentiationDifferentiation
Well-differentiated appearanceWell-differentiated appearance
Structure similar to tissue originStructure similar to tissue origin
Little or no anaplasiaLittle or no anaplasia
Usually some lack of differentiationUsually some lack of differentiation
Structure often atypicalStructure often atypical
Variable degree of anaplasiaVariable degree of anaplasia
Rate and pattern of Rate and pattern of growthgrowth
Slow, progressive expansionSlow, progressive expansion
Rare mitotic figuresRare mitotic figures
Normal-appearing mitotic Normal-appearing mitotic figuresfigures
Slow to rapid growth; erratic growth Slow to rapid growth; erratic growth raterate
Mitotic figures often numerousMitotic figures often numerous
Mitotic figures sometimes abnormalMitotic figures sometimes abnormal
Local invasionLocal invasion No InvasionNo Invasion
Cohesive and expansile growthCohesive and expansile growth
Capsule often presentCapsule often present
Local InvasionLocal Invasion
Infiltrative growthInfiltrative growth
Usually no capsuleUsually no capsule
MetastasisMetastasis No metastasisNo metastasis Frequent metastasis (definitive criteria Frequent metastasis (definitive criteria for malignancy)for malignancy)
Damage to human bodyDamage to human body Relatively smallerRelatively smaller Relatively biggerRelatively bigger
PrognosisPrognosis GoodGood Bad Bad
Tumor spreadTumor spread
Features of tumor spreadFeatures of tumor spread
invasion and metastasisinvasion and metastasis
Invasion and metastasis are Invasion and metastasis are biologic hallmarks of malignant biologic hallmarks of malignant tumorstumors
Invasion and MetastasisInvasion and Metastasis
Pathways of tumor spreadPathways of tumor spreadDirect SpreadDirect SpreadBody cavitiesBody cavitiesBlood vesselsBlood vesselsLymphaticLymphatic vesselsvessels
Metastatic cascade: two phasesMetastatic cascade: two phases
Invasion of Extracellular MatrixInvasion of Extracellular Matrix Vascular Dissemination and Homing of Tumor CellsVascular Dissemination and Homing of Tumor Cells
Invasion and MetastasisInvasion and Metastasis
• loss of tumor cell-cell adhesion
• invasion of basement membrane and extracellular matrix
• invasion of blood vessels and lymphatics
Steps of invasion
Steps of Extravasation• circulating tumor cells
• formation of tumor clumps
• adhesion to endothelium
• penetration of basement membrane
•Metastatic deposit and growth
Invasion and MetastasisInvasion and Metastasis
Mammary carcinoma in a lymphatic in the lung
Grading & Staging of neoplasmGrading & Staging of neoplasm
GradingGrading – Cellular Differentiation – Cellular Differentiation (Microscopic)(Microscopic)
StagingStaging – Progression or Spread (clinical) – Progression or Spread (clinical)
Grading of neoplasmsGrading of neoplasms
Grade I: Well-differentiated, cells look like normal cells Grade I: Well-differentiated, cells look like normal cells
Grade II: Moderately differentiated Grade II: Moderately differentiated
Grade III: Poorly-differentiatedGrade III: Poorly-differentiated
Grade IV : Nearly anaplasticGrade IV : Nearly anaplastic
Grading of neoplasmsGrading of neoplasms assigned by the pathologist to reflect assigned by the pathologist to reflect the cancer's degree of differentiation, the four grades are the cancer's degree of differentiation, the four grades are generally divided for malignant tumorsgenerally divided for malignant tumors
Staging of neoplasmsStaging of neoplasms
The most common systems for staging employs the TNM The most common systems for staging employs the TNM classification. classification. • "T" - based upon the size and/or extent of invasion. "T" - based upon the size and/or extent of invasion. • "N" -indicates the extent of lymph node involvement. "N" -indicates the extent of lymph node involvement. • "M" - indicates whether distant metastases are present. "M" - indicates whether distant metastases are present.
The TNM forms are filled out using clinical and pathologic The TNM forms are filled out using clinical and pathologic criteria and aid in determination of therapy, estimating the criteria and aid in determination of therapy, estimating the prognosis, and developing statistics useful for determining prognosis, and developing statistics useful for determining outcomes.outcomes.
TNMTNM: Staging of tumor: Staging of tumor
Staging of Malignant Neoplasms
Stage Definition
Tis In situ, non-invasive (confined to epithelium)
T1 Small, minimally invasive within primary organ site
T2 Larger, more invasive within the primary organ site
T3 Larger and/or invasive beyond margins of primary organ site
T4 Very large and/or very invasive, spread to adjacent organs
N0 No lymph node involvement
N1 Regional lymph node involvement
N2 Extensive regional lymph node involvement
N3 More distant lymph node involvement
M0 No distant metastases
M1 Distant metastases present
UICC( 国际抗癌联盟 ) TNM staging system T0 ~ 4 primary tumor size and invasive spectrum
N0 ~ 3 lymph node metastasis
M0 , 1 organ metastasis
I . T1N0M0
II . T2N0M0
T0-2N1M0
III . T3N0M0
T0-3N2M0
V . T4N0M0
T0-4N3M0
T0-4N0-3M1
Tumor-like LesionsTumor-like Lesions HamartomaHamartoma– disorganized but mature mesenchymal or epithelial – disorganized but mature mesenchymal or epithelial
tissues found their normal anatomic location. It represents an tissues found their normal anatomic location. It represents an aberrant differentiation, not a true neoplasia.aberrant differentiation, not a true neoplasia.
ChoristomaChoristoma – normal mature tissue located at an ectopic site – normal mature tissue located at an ectopic site
PolypPolyp– grossly visible nodule or mass projecting from a– grossly visible nodule or mass projecting from amucosal or epidermal surface. It is a hyperplastic response to mucosal or epidermal surface. It is a hyperplastic response to chronic inflammation or irritation. Also it is used to indicate a benign chronic inflammation or irritation. Also it is used to indicate a benign neoplasm in some cases.neoplasm in some cases.
––Nasal polyp, endometrial polyp, vaginal polyp, and Nasal polyp, endometrial polyp, vaginal polyp, and fibroepithelial cutaneous polyp (acrochordon, skin tag) fibroepithelial cutaneous polyp (acrochordon, skin tag) are considered a hyperplastic response to chronic are considered a hyperplastic response to chronic irritationirritation
–– Intestinal polyps are benign neoplasm of mucosal Intestinal polyps are benign neoplasm of mucosal epitheliumepithelium
Colon PolypColon Polyp
Pathogenesis of NeoplasiaPathogenesis of Neoplasia
Normal Cell Neoplastic Cell
DNA Damage
Chemical or physical agents
Normal Normal Hyperplasia Hyperplasia Metaplasia Metaplasia (DNA damage)(DNA damage) Dysplasia Dysplasia (DNA damage)(DNA damage) (DNA damage)(DNA damage) Anaplasia Anaplasia (DNA damage)(DNA damage) Infiltration Infiltration (DNA damage)(DNA damage) Metastasis…. Metastasis….
Progressive DNA Damage – features of neoplasia.Progressive DNA Damage – features of neoplasia.
Pathogenesis of Neoplasia:Pathogenesis of Neoplasia:
LateAdenoma
NormalCrypt
EarlyAdenoma
Adenocarcinoma
Pathogenesis of Neoplasia:Pathogenesis of Neoplasia:
Normal Epithelium
“Proliferative” Epithelium
“Early” Adenoma
“Intermediate” Adenoma
“Late” Adenoma
Invasive Carcinoma
Metastases
APC gene (5q loss or mutation)
Abnormalities Methylation
k-Ras gene (12p mutation)
DCC/SMAD (18q loss)
p53 gene (17p loss)
Additional mutations
Pathogenesis of Neoplasia Pathogenesis of Neoplasia (Colon Cancer)(Colon Cancer)
Development of squmous cell carcinoma in Development of squmous cell carcinoma in the mouse skin, UV radiation (Animal the mouse skin, UV radiation (Animal
Experiments)Experiments)
A
B
C
D
2 weeks
1 months
3 months
Conventional Diagnosis of TumorConventional Diagnosis of Tumor
Signs and symptoms
Palpable lump, pain
Fever, Fatigue, Weight gain or loss
Altered metabolism
Medical imaging: X-ray, CT, ECT,MRI
Gold standard: Surgical biopsy/ pathological diagnosis
direct microscopic examination
Pathological Diagnosis of NeoplasiaPathological Diagnosis of Neoplasia
Recognize: roles of pathological diagnosis applied Recognize: roles of pathological diagnosis applied in clinical oncology in clinical oncology
Understand: definition, morphology, nomenclature, Understand: definition, morphology, nomenclature, differentiation, differences between differentiation, differences between
benign and malignant benign and malignant neoplasm, neoplasm, Grading and staging, Grading and staging, Precancerous Precancerous lesions lesions
Familiar with: Familiar with: principles and technologies of diagnostic pathology
Methodologies of Diagnostic Methodologies of Diagnostic PathologyPathology
Classical MethodologiesClassical Methodologies
Histological diagnosis: Histological diagnosis: Biopsy, Intraoperative consultationBiopsy, Intraoperative consultation Cytological diagnosis: Cytological diagnosis: Fine-needle aspiration; Abrasive Fine-needle aspiration; Abrasive
cytology; cytology; Exfoliative cytology AutopsyAutopsy
Modern TechnologiesModern Technologies HistochemistryHistochemistry ImmunohistochemistryImmunohistochemistry Molecular biological methodsMolecular biological methods Electronic microscopyElectronic microscopy Digital pathology and telepathologyDigital pathology and telepathology
Histopathological DiagnosisHistopathological Diagnosis
Biopsy: Biopsy: paraffin-embedded tissue sectionparaffin-embedded tissue section• Incisional biopsyIncisional biopsy• Excisional biopsyExcisional biopsy
Surgical excision: Surgical excision: paraffin-embedded tissue paraffin-embedded tissue sectionsection
• Organs or tissues with the tumorsOrgans or tissues with the tumors• Regional lymph nodesRegional lymph nodes
IIntraoperative consultationntraoperative consultation• Frozen sectionFrozen section
Paraffin-embedded Paraffin-embedded tissue sectiontissue section
Frozen sectionFrozen section
Specimens Specimens Fixed tissues Fixed tissues Fresh tissues Fresh tissues
Making time Making time 24-48 hours 24-48 hours 10-20 minutes10-20 minutes
Saving time Saving time Permanent Permanent Months Months
Morphology under Morphology under
microscopymicroscopy Clarity Clarity Opacity Opacity
Application Application Pathological Pathological Diagnosis Diagnosis
Intraoperative Intraoperative consultationconsultation
Paraffin-embedded tissueParaffin-embedded tissue
vs Frozen sectionFrozen section
Procedure of Paraffin-embedded Section Procedure of Paraffin-embedded Section
and Pathologic Examinationand Pathologic Examination
Specimen of tissues or organs by excision (biopsy or operation)
Cutting
Tissue Treatment Procedure (Dehydration → Paraffin embedding → Section → Staining → Sealing)
Microscopic examination → Reports signed out
Application of modern technologies (IHC, PCR, FISH, EM, etc.) for specific requirement → Reports signed out
Placing on files (Blocks; Slides; Documents, etc.)
Tissue Treatment Procedure
Parameters used in histological Parameters used in histological diagnosis of neoplasmdiagnosis of neoplasm
Gross appearanceGross appearance
Microscopic appearanceMicroscopic appearance• histological patternhistological pattern• tumor cell cytologytumor cell cytology
ImmunohistochemistryImmunohistochemistry
HistochemistryHistochemistry
Cytogenetics /molecular pathologyCytogenetics /molecular pathology
Electron microscopyElectron microscopy
Observe, descript and Observe, descript and record gross appearance record gross appearance of tissues or organs by of tissues or organs by excision, specially excision, specially lesions or tumors in the lesions or tumors in the specimenspecimen
Gross appearanceGross appearance
Gross Appearance of Tumors
Appearance of Tumors---Gross and histological pattern
Benign tumor
--- adenoma of thyroid gland
Appearance of Tumors---Gross and histological pattern
Benign tumor
---Fibroma
Benign tumor
---Lipoma
Microscopic Microscopic Appearance of Tumors---Histological pattern
Carcinoma
---squamous carcinoma
Carcinoma
--- Papillary carcinoma
Microscopic Microscopic Appearance of Tumors---Histological pattern
• Fibrosarcoma• Liposarcoma
Microscopic Microscopic Appearance of Tumors---Tumor Cell Cytology
Normal squamous cells Squamous cell carcinoma
Microscopic Microscopic Appearance of Tumors---Tumor Cell Cytology
Abnormal mitotic figures often seen in malignant tumor
Microscopic Microscopic Appearance of Tumors---Tumor Cell Cytology
Reed-Sternberg cell
Immunohistochemistry (IHC) in Tumor Diagnosis
Diagnosis confirmed in 40%Diagnosis confirmed in 40%
Important diagnostic information gained in Important diagnostic information gained in
50%:narrowing of possibilities, or special diagnosis50%:narrowing of possibilities, or special diagnosis
Tumor phenotypes identifiedTumor phenotypes identified
IHC needed in 10-25% malignant tumors for IHC needed in 10-25% malignant tumors for reclassification, e.g., lymphomareclassification, e.g., lymphoma
New entities and classifications establishedNew entities and classifications established
Epithelium: Keratins— pan-keratin and antibodies to keratins of different molecular weights
Supporting connective tissues: — Vimentin, vWF, CD31 (PECAM)
Hematopoeitic tissues:
— CD45, B220, CD3, F480, Mac-1, Gr-1, CD41 Muscle:
— desmin, smooth muscle actin Neural:
— GFAP, NeuN, F480/Mac-1, MBP, NSE, S100 Hormones:
— specific antibodies--insulin, casein, etc. Germ cells:
— alpha-feto protein (teratomas) Proliferation markers
—Ki-67
Classification of Immunophenotype
Immunohistochemistry (IHC) in Tumor Diagnosis
Cytokeratin Vimitin
Adenocarcinoma Sarcoma
Immunohistochemistry (IHC) in Tumor Diagnosis
Tumor typeTumor type CKCK VIMVIM S-100S-100 CD45CD45
CarcinomaCarcinoma ++ -- -- --
SarcomaSarcoma -- ++ -- --
LymphomaLymphoma -- -- -- ++
MelanomaMelanoma -- -- ++ --
Immunophenotypes of major groups of malignant tumors
Immunohistochemistry (IHC) in Tumor Diagnosis
Estrogen Receptor (ER) Her-2 (Cerb B2)
Breast Cancer
Molecular Pathology Molecular Pathology in Tumor Diagnosisin Tumor Diagnosis
Genetic abnormalities of TumorsGenetic abnormalities of Tumors• Changes in chromosome number and Changes in chromosome number and
structure structure • Changes in genes (proto-oncogenes, tumor Changes in genes (proto-oncogenes, tumor
suppressive genes, DNA repair genes)suppressive genes, DNA repair genes)
DiagnosisDiagnosis• Cytogenetic investigationsCytogenetic investigations• Molecular genetic investigationsMolecular genetic investigations
Specific Cytogenetic Abnormalities Specific Cytogenetic Abnormalities Determined in TumorsDetermined in Tumors
Tumor typeTumor type Chromosomal Chromosomal changeschanges
Genes involved Genes involved or fusion genesor fusion genes
Follicular lymphomaFollicular lymphoma t(14;18)(q32;q21) t(14;18)(q32;q21) JH/Bcl-2 JH/Bcl-2
Mantle cell Mantle cell lymphomalymphoma
t(11;14)(q13;q32)t(11;14)(q13;q32) JH/Bcl-1JH/Bcl-1
Synovial sarcomaSynovial sarcoma t(X;18)(p11;q11)t(X;18)(p11;q11) SYT-SSX1SYT-SSX1
EwingEwing’’s sarcomas sarcoma t(11,22)(q24;12)t(11,22)(q24;12) EWS-FL11EWS-FL11
Follicular carcinomaFollicular carcinoma t(2;3)(q13;p25) t(2;3)(q13;p25) PAXPAX88-PPAR-PPARγγ
Cytogenetic investigationsCytogenetic investigations- Fluorescent in situ hybridization (FISH)- Fluorescent in situ hybridization (FISH)
- Identify chromosome rearrangement detecting specific DNA sequences with fluorescently labeled probe
Cytogenetic Changes of Lymphoma Cytogenetic Changes of Lymphoma Determined by FISHDetermined by FISH
FL diagnosed by FISH:IGH/BCL2 t(14;18)(q32;q21)
MCL diagnosed by FISH:IGH/CCND1 t(11;14)(q13;q32)
Diagnostic CytologyDiagnostic Cytology
IntroductionIntroduction
Advantages and disadvantagesAdvantages and disadvantages
Cytopathologic methods and Cytopathologic methods and samplingssamplings
CytopathologyCytopathology refers to diagnostic refers to diagnostic techniques that are used to examine techniques that are used to examine cellscells from various body sites to from various body sites to determine the determine the cause or nature of diseasecause or nature of disease
Advantages Advantages vsvs Disadvantages Disadvantages
AdvantagesAdvantages
• Samples can be collected quickly and easily Samples can be collected quickly and easily • InexpensiveInexpensive• Little or no risk to the patientLittle or no risk to the patient• Examine the cause or nature of diseaseExamine the cause or nature of disease
Specific vs nonspecific inflammation Specific vs nonspecific inflammation Inflammation vs neoplasiaInflammation vs neoplasia
• Direct therapyDirect therapy• Determinate next diagnostic proceduresDeterminate next diagnostic procedures
DisadvantagesDisadvantages
It is not always possible toIt is not always possible to
• Localize neoplastic lesionLocalize neoplastic lesion• Distinguish preinvasive of invasive cancerDistinguish preinvasive of invasive cancer• Distinguish reactive of dysplastic and Distinguish reactive of dysplastic and
neoplastic changesneoplastic changes• Determine tumor typeDetermine tumor type
Advantages Advantages vsvs Disadvantages Disadvantages
Cytopathology MethodsCytopathology Methods
Exfoliative cytology
—spontaneously shed cells in body fluids
Abrasive cytology
—dislodge cells from body surfaces
Fine needle aspiration cytology (FNA)
— Superficial nodules and organs – easily targeted
— Deep organs – guidance of CT, US
Exfoliative cytology
—spontaneously shed cells in body fluids
• Urine• CSF (cerebrospinal fluid)• Sputum• Effusion in body cavities (pleura, pericardium,
peritoneum)
Cytopathology MethodsCytopathology Methods
Abrasive cytology
—dislodge cells from body surfaces
• ImprintImprint• Scraping and swabbingScraping and swabbing• Endoscropic brushing of mucosal surfacesEndoscropic brushing of mucosal surfaces• Washing of mucosal or serosal surfacesWashing of mucosal or serosal surfaces
Cytopathology MethodsCytopathology Methods
Fine needle aspiration cytology (FNA)
Diagnostic CytologyDiagnostic Cytology
The first important decision for The first important decision for suspicious case is:suspicious case is:
inflammation vs neoplasiainflammation vs neoplasia
Second important decision isSecond important decision is
Benign vs malignantBenign vs malignant
Tumor Cell Types Tumor Cell Types in Diagnostic Cytologyin Diagnostic Cytology
Round to caudate large cells — epithelial tumors
Round large cells Caudate large cells
Diagnostic CytologyDiagnostic Cytology
SummarySummary
• Cytology is diagnostic method to Cytology is diagnostic method to determine cause or nature of diseasedetermine cause or nature of disease
• Cytology is quick, inexpensive and Cytology is quick, inexpensive and accurate method, with a little risk to accurate method, with a little risk to patientpatient
• Cytology has disadvantage in tumor Cytology has disadvantage in tumor diagnosis diagnosis
Case PresentationCase Presentation
HistoryHistory: xxx, M/37y, enlarging painless : xxx, M/37y, enlarging painless preauricular preauricular mass in the left for more mass in the left for more than 6 years.than 6 years.
Physical examinationPhysical examination: preauricular: preauricular mass mass in the left :2x3cm, no tenderness, little in the left :2x3cm, no tenderness, little movable, No other abnormalities. movable, No other abnormalities.
InitialInitial diagnosisdiagnosis: The unknown nature of : The unknown nature of the left parotid gland tumor the left parotid gland tumor
TherapyTherapy: Surgery: Surgery
Gross appearanceGross appearance
MicroscopicMicroscopic appearanceappearance
CK
p63
p53
Pathological DiagnosisPathological Diagnosis
NatureNature: : benign tumorbenign tumor NameName: : keratocystoma of the left parotid keratocystoma of the left parotid
glandgland
Differential diagnosisDifferential diagnosis::Tumor-like diseaseTumor-like disease :: cchoristomahoristomaBenign tumorBenign tumor :: llymphatic cystadenomaymphatic cystadenoma Malignant tumorMalignant tumor :: squamous carcinomasquamous carcinoma
Pathological Diagnosis ReportPathological Diagnosis Report
Gross appearanceGross appearance:: 2x3x1cm, enveloped olive-shaped mass, 2x3x1cm, enveloped olive-shaped mass,
little soft, aspect gray little soft, aspect gray
Microscopic morphologyMicroscopic morphology: consisted of a cystic structure lined : consisted of a cystic structure lined
with keratinized stratified squamous epithelium and solid nests of with keratinized stratified squamous epithelium and solid nests of
parenchymal squamous cells, no mitotic figures, a dense lymphoid parenchymal squamous cells, no mitotic figures, a dense lymphoid
element with follicles in the stroma.element with follicles in the stroma.
ImmunohistochemistryImmunohistochemistry: CK (+), CK5/6(+), p63(+), p53(+): CK (+), CK5/6(+), p63(+), p53(+)
Pathological diagnosis : keratocystoma of parotid gland.
XXX, M/37y,Pathological No: xxxxxx, the left parotid XXX, M/37y,Pathological No: xxxxxx, the left parotid gland massgland mass
Learning without thinking leads to confusion, thinking without learning ends in danger.
学而不思则罔 , 思而不学则殆
-Kong Zi
Learning is like rowing upstream: not to advance is to drop back
学如逆水行舟 , 不进则退