Relationship of surgery with Pathology

Dr G K Swethadri.
Prof. Deaprtemnt of Pathology
Fr. Muller Homeopathic Medical College
Mangalore.

As is your pathology so is your practice. sir william Osler
Historical aspects
Philosophy.
Renaissance
Clean water, asepsis, immunization
Rapid developments in the 20^th century
Super-specializations

Fast pace of life is demanding early detection and cure. Fortunately the role of pathologist is well defined and needed and accepted by the surgeon.

Relevance of pathology to surgeons is immense.let me try to analyse these aspects.

All organs can suffer.

Inflammation
Degeneration
Immune insult
Hemodynamic derangements
Nutritional ,chemical,radiation injury
Trauma
Neoplasia
Genetic defects.

Consequence.

Changes in the organ and body as a whole.
Changes are either gross or microscopic .they are called morphological changes.The changes all begin in the cell.
’it is called THE CELLULAR BASIS OF DISEASE”by Virchow.
Briefly Inflammation,degeneration,vascular changes and neoplasia are the features one looks for.
THE MICROSCOPE helps seek these changes
acute appendicitis-neutrophils
parkinsonism-lewy body
thrombus in a vessel in gangrene
cancer cells in a tumour

SURGEON WANTS THE PATHOLOGIST TO IDENTIFY THE CELLULAR/TISSUE CHANGES.that forms the clinicopathlogical correlation.

Some basic aspects

Hypertrophy of the left ventricle
Hypertrophy (micro)
Hyperplasia of endometrium
Atrophy of thymus gland
Morphology of cell injury
Protein accumulation – Hyaline
Hyaline degeneration – structureless, glassy, extra or intracellular material.
Lipids accumulation
Fatty change – intracellular accumulation of droplets of neutral fat (macro- and microvesicular).
The most common cause is poisoning and hypoxia.
The proteins of the cell are denatured and the cell becomes coagulated or clotted.
Cytoplasm becomes hyper-eosinophilic and the nuclear changes appear.
The cells persist as cell ghosts
Dead tissue appears firm and pale.

Gangrene

Gangrene is necrosis affecting the areas connected with the air and adde putrefaction.
Dry gangrene – ischemia without infection
If infection (clostridial) and oedema – wet gangrene or gas-gangrene.

An understanding pathologic basis must.

Once clinicopathlogical correlation is established then patient management becomes easy and objective.
That is why pathology is needed for the surgeons.
Let us study a few examples of CPC

It took a long time for histopathology to be accepted as a prerequisite for diagnosis

•Well it is easy.if not….

Let us study the example -breast

The expectations have changed.

Earlier we used to see huge cancer,bilateral,late stage.
Now self examination,mammography,needle aspirations have made women seek screening.even obese and those on OCP are seeking early detection.
Expectation of surgeon on pathologist is increasedearly diagnosis is the order of the day.

SCIENTIFIC RETHINKING HALSTEAD RECOMMENDED RADICAL MASTECTOMY,

As histopathologists become aware that lympo-vascular emboli are seen in sections ,they wondered at the possibility of dissemination .Then why radical; save the organ as much as possible.now mastectomy,quadrantectomy are being practiced with radiotherapy

Not only diagnosis but also grading staging ,prognostification, decision making for therapy is coming in the perview of pathologist.

Breast conservation is the order of the day.a precise diagnosis and extent of disease are essential for this.

Steps of diagnosis
Clinical exam
Mammography
Ultra sound
MRI
FNAC
Tru-cut biopsy
Excision
Clinical+cytology+mammography=99.9 accuracy

Nottingham prognostic index

Index=0.2xsize+grade+node.(no=1,1-3 nodes=2,4>=3)
Take for example 6 cm tumour,4 positive lymph nodes and moderate grade(2)
(.2×6)+2+3=6.2.
Look at the prognosis.
Good=<3.4;mod=3-4.5;poor=5.4.
Our example is of a poor prognosis i.e.13%15 yr survival.

Organize your teaching.

Definition
Classification
Pathogenesis
Pathology-gross and microscopy
Diagnostic investigations
Differential
Prognosis
Research
the need for precise diagnosis;
verruca v/s Cervix:
Infiltrating Carcinoma Cx:
Squamous Carcinoma:
Melanma

Clark’s levels

1.confine to epidermis and appendages-in situ
2.papillary dermis-microinvasive; between papillary and reticular dermis a few melanoma cells
3.pap dermis and impinge upon ret dermis
4.impinge and invade ret dermis
5.subcutaneus fat invasion

Some examples are illustrated

Mystery and happiness
Intrigue.
The mimic
Let us see how to teach a topic,for example’ BREAST PATHOLOGY”
Given as separate power point presentation.

Intra op diagnosis in CNS.note.described as a separate paper.
Frozen.
Sheets of round to spindle cells
Cartilagenous lobules & spindle cell areas & infiltration to bony trabeculae with destructon
Chondrosarcomatous areas
Pleomorphic cells in chondroid matrix
Distinct chondroid and spindle areas

WHAT IS IT.THE SURGEON ASKS

The mystery is solved to some extent by the pathologist.
Then the larger question;how can we together help people?
Registries;
Large medical force can contribute by educating and screening common man about cancer.
Aspects of curable-treatable cancer and spread of optimism.if detected early it can be cured.

Evolution of screening

One out of 10-13 people in India will be struck by cancer in their lifetime.
Tobacco,alcohol,diet,occupation,occupational disease,sexual hygiene.education and prevention.
NCCP was started in 1975-76. tobacco educaion,small family,18 yrs as marriageble age for female,use of condom
Secondary;cervical pap smear,pre invasive diseae is 100% curable.35% in advanced.
Detection centers in medical colleges(105 colleges),post partum centers,district hospital level is in the experimental stage.
In 1000 females-2.5-13.7 dysplasia was detected
Married ,asymptomatic,<40 yr,<20 yr married life,may be excluded from screeing.
Visual exam.13.7%of 67416 had unhealthy cervix.
FNAC for breast can cancer screen
Yearly occult blood for cancer.
2 yearly videoscopic multiple biopsies for GIT

Chemoprevention.

Premalignant
Head and neck-isotretinoin
NSCLC 13-cis-retinoic acid.
HCC.HEP B VACCINE,INTERFERON
Ca colon-high fibre diet.calcium 1 g.in diet.
Pt with adenoma;folic acid and vit-c.
Anal cancer-homosexuality
Breast;tamoxifen in high risk by 35 yr

Investigations in cancer

Good clinical exam.routine blood tests
BRCA-1 from leucocytes.electrophoresis.MM
Bacterial,viral,parasitic studies
Tumour markers.laparotomy.B.M.biopsy
Tissue biopsy.frozen section.
U.S and CT guided needle biopsy,endoscopic,video assisted biopsy,IHC,EM,Cytogenetics.
Tissue diagnosis,grading,staging

Surgeon looks at pathologist for

Anemia-GIT,Leukemia,MPP,polycythemia,renal bleeding gum-coagulation
Liver-PT,PTT,Platelets,bleeding disorders
Microbiology.H.pylori,AIDS.kaposi,NHL,genital cancer
HPV cervix cancer,schistosoma-bladder tumour.

Serum markers.

PSA,CA-125,HCG,AFP
FOR DIAGNOSIS AND FOLLOW UP.
Hormones
BM aspiration and biopsy.

Different types of tissue biopsy.

Core needle biopsy;cylinder of tissue 3-4 m wide and 1-2 cm long.liver,lung,mediastinum,lung,pancreas,breast,prostate. tru-cut
Do BT,CT,PT,PTT before biopsy.trans jugular 16 gauge 85 cm needle biopsy if bleeding.
Excision.can be diagnostic and curative.skin,sub cutis,breastmelanoma,BCC.
Incision biopsy.if biopsy is difficult or dangerous a part of tissue is taken.ex.soft tissue.
Laparascopic biopsy.intraperitoneal organs.
Frozen section;brain breast to prevent second operation.
Endoscopic biopsy;nasal,pharyngeal,bronchial,esophageal,gastric,bile duct,colon etc.cystoscopy.
Spiral 3d CT can be used to guide fibroptic steriotactic biopsy forceps in glioma paracentesis
A tumour can present as an ascitis.repeat paracentesis is common in malignancy,study of effusion by cytology is of great help to dfferniate,transudate,exudate,tuberculosis,malignant ascitis.
Flow cytometry
Hematolymphoid neoplasms.detection and characterization,clonality,lineage,residual disease.

PCR

1.CML,ALL,APL,ALCL
Ph CHROMOSOME-prognostic
Soft tissue.Ewings,PNET,alveolar rhabdo.
Minimal residual diseae.relapse.
FISH.
Down’s,AML,ALL.MDS,small round cell tumour.response to treatment.

PET scan

Using fluorodeoxyglucose.FDG.
Breast cancer for detection of metastasis.
Soft tissue.intralesional change,grade
Lung cancer.coin lesion.determining malignancy.
HD.treatment planning.

Cancer of unknown primary

20%will never know about their primary.detection of primary also depends on history,clinical exam,endoscopy,FNAC,biopsy,
The microscopic feartures may give a clue about the primary.
STAGING-usefulness of biopsy
NSCLC.surgery for stage i,ii,iiiA.
Chemotherapy-III and IV stages
SCLC.TNM staging is not used.
Oesophagus.if adventitia is involved stage iii.
iii and iv-chemotherapy.
Stomach.<6mm endoscopic resection
i,ii,iii with minimal LN.intestinal type give 5 mm margin.if diffuse type give 8 mm margin.
Margin should be free
Role of immunocytochemistry.

HE / IHC

Basic antibody panel

Lymphoma panel

Pan-hematolymphoid marker

•CD45 (CD45RB):
–Leukocyte common antigen
–Positive in all normal lymphoid cells (B, T or NK lineage) except plasma cells
–Reed-Sternberg cells (Hodgkin lymphoma) are CD45-
–But usually not necessary to stain for LCA in a definite lymphoma: can proceed directly to lineage markers (e.g. CD20 + CD3)

Common B cell lymphomas

B lineage markers

•CD20 (e.g. L26):
–Very sensitive (>95% B cell lymphomas positive), although B-CLL may not stain well and B-cell lymphoblastic lymphoma may be negative
–Typically negative in plasma cells, plasmacytomas and plasmablastic lymphomas (thus CD20 negativity is a helpful clue to the diagnosis)
–Nucleolar staining alone should not be considered positive. With heat-induced epitope retrieval, any cell can show this phenomenon

B lineage markers

•CD79a (mb-1):

–B cell receptor complex: sensitive and specific B cell marker (normal plasma cells are positive; germinal center cells are stained weakly)
–~50% plasmacytomas are positive
–But can be positive in T-lymphoblastic lymphoma/leukemia
–Antibody expensive: Use as back-up
•Immunoglobulin (cytoplasmic and/or surface Ig)
•Other B-associated antibodies (LN1, LN2, MB1, MB2, 4KB5) are no longer useful

T-lineage markers

•Cytoplasmic CD3 (polyclonal against CD3e, monoclonal also available, e.g. PS1):

–Highly sensitive and specific for T lineage
–Staining stronger in perinuclear space, often accentuating the nuclear foldings
–Histiocytes may show faint cytoplasmic staining, but with no perinuclear accentuation
–Stains >90% of T and NK cell lymphomas
–May add other T markers (e.g. CD45RO, CD2) if CD3 is negative and yet T-cell lymphoma is suspected

T-lineage markers

CD45RO (e.g. UCHL1, A6):
–Highly sensitive for T lineage; some T cell lymphomas are CD3- CD45RO+
–But also stains histiocytes/myeloid cells and their tumors
•CD43 (e.g. MT1, DFT1, Leu22):
–Highly sensitive for T lineage, but not very specific
–Also stains histiocytes/myeloid cells and their tumors
–Expression in B cells can be upregulated in EBV infection
–More useful for diagnosis of small B-cell lymphomas (looking for aberrant expression)

T lineage markers

•CD4, CD8:
–Infrequently required for study of T cell lymphomas
•CD2:
–Sensitive and specific pan T cell marker
–More expensive than CD3 antibody: use as back-up
CD7:
–Pan T cell marker expressed early in T cell development
–Particularly helpful for demonstrating T lineage in lymphoblastic lymphoma (which can be CD3-)