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


Mitotic activity - Increased in more malignant Mitotic activity - Increased in more malignant tumors and often abnormal in shapetumors and often abnormal in shape


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


• 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


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 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


Abnormal mitotic figures often seen in malignant tumor


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


Cytokeratin Vimitin

Adenocarcinoma Sarcoma


Tumor typeTumor type CKCK VIMVIM S-100S-100 CD45CD45

CarcinomaCarcinoma ++ -- -- --

SarcomaSarcoma -- ++ -- --

LymphomaLymphoma -- -- -- ++

MelanomaMelanoma -- -- ++ --

Immunophenotypes of major groups of malignant tumors


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)


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


Fine needle aspiration cytology (FNA)


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


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

MicroscopicMicroscopic appearanceappearance

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