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Q. Neoplasm
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C hapter Outline
·
Dysplasia
·
Carcinoma In Situ
·
Aetiologic Factors
·
Spread of Malignant
Tumours
·
Grading of Tumour
·
Staging of the Tumour
DEFINITION
Willis defined neoplasm as “it 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
even after cessation of the stimuli.”
Neoplasia is:
x Progressive x Persistent
x Purposeless x Pervasive
x Perverted x Proliferative mass of tissue.
·
Paraneoplastic
Syndromes
·
Investigations for
Neoplasm
·
Management Strategy
for Cancers
Sarcoma Carcinoma
Arising from mesenchymal
tissues
‘Sar’ means flesh (Greek), Oma
means tumour
Smooth, firm or hard swelling Hard, proliferative, with everted
Warm and vascular with dilated
veins over the surface
Spreads mainly through blood
commonly to lungs, e.g.
liposarcoma, fibrosarcoma,
x Neoplasms which are only locally malignant: No blood spread.
No lymph node spread—Marjolin’s ulcer, Rodent ulcer, Verrucous
carcinoma, Adamantinoma.
x Neoplasms which are loco-regionally malignant: Spread only
to regional lymph nodes is observed—Squamous cell carcinoma,
Papillary carcinoma thyroid.
x Neoplasms which are systemic and spreads through blood and
often also to lymph nodes.
x Melanoma, carcinoma breast.
Arising from epithelial cells
derived from any of the three
germ layers
Carc means crab like
edge
Spreads through lymphatics as
well as blood, e.g. squamous
cell carcinoma, renal cell
carcinoma, adenocarcinoma
Classications
Benign Malignant
Well-differentiated Lack of differentiation
Structures are typical of tissue/
cell of origin
Smooth, slow, progressive rate
of growth
Normal mitotic figures Abnormal mitotic activity
Well localised and capsulated Not localised. Not capsulated
Do not infiltrate surrounding
normal tissues
No metastasis Metastasise through
Curable May not be completely curable
Few benign tumours after a long
time may turn into malignancy
Treatment is simple Treatment is complex and
No recurrence Recurrence can occur
Atypical structure with
anaplasia
Erratic, rapid growth
Infiltrate the surrounding
tissues
lymphatics or blood
complicated
Components
Parenchyma: It contains proliferating neoplastic cells.
Stroma: It contains supporting connective tissues and blood
vessels.
FEATURES OF ANAPLASIA
B
x Lack of cellular differentiation
x Pleomorphism—variation in size and shape
x Hyperchromatism—dark staining nuclei
x Anisocytosis
x Anisonucleosis
x Abnormal mitotic activity
FEATURES OF MALIGNANT TISSUES
B
x Altered differentiation, anaplasia
x Rapid rate of growth
x Local invasion—locally, lymphatic, vascular and perineural
x Metastasis
x Not capsulated
x Increased vascularity
x Microscopic changes—necrosis, numerous atypical mitotic
activities, nuclear changes like pleomorphism/enlargement/
hyperchromatism/clumping of chromatin/enlargement and
multiplication of nucleoli
Fig. 1.473: Soft tissue sarcoma thigh. Note the dilated
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vessels on the surface.
Fig. 1.475: Squamous cell carcinoma scalp. Note the everted edge.
It is ulceroproliferative lesion.
GENETIC
B
x Xeroderma pigmentosa
x Ataxia telangiectasia
x Fanconi anaemia, Bloom syndrome
It is more common in elderly. But it is variable.
Tumour suppressor gene p53 plays important role in prevention of the cancers. Its function is prevention of replication of
damaged DNA. If damaged DNA replicates there is high chances
of abnormal mitotic activity and cancer transformation of the
tissue. Loss or reduction of ability/function of p53 suppressor
gene can lead into cancers. Common cancers associated with
p53 loss are cancers of breast, colorectum, retina, bone, brain,
soft tissues, blood and familial related type.
267
CHAPTER 1Q General Surgery: Neoplasm
Fig. 1.474: Carcinoma heel region. Note the everted edge with
proliferative cauliflower like look.
DYSPLASIA
It means “disordered growth”. There is loss in the uniformity of
the cells with pleomorphism and hyperchromatism, as well as
loss in their architectural orientation.
CARCINOMA IN SITU
Here dysplasia involves the entire thickness of the epithelium,
and is preinvasive. Basement membrane is intact in carcinoma
in situ.
AETIOLOGIC FACTORS
Age
HEREDITY
B
x Familial: Familial polyposis of colon
x MEN syndrome
x Neurofibromatosis
x von-Hippel-Lindau syndrome
x Familial breast and ovarian cancers
ACQUIRED CAUSES
B
x Chronic atrophic gastritis
x Solar keratosis
x Leucoplakia of oral cavity
x Ulcerative colitis
CHEMICAL CARCINOGENS
B
x Alkylating agents
x Hydrocarbons
x Smoking—lung, aerodigestive system, bladder cancer
x Asbestos—lung cancer
x Alcohol—liver cancer
x Amides, Azo dyes—bladder cancer
x Aflatoxin B
x Arecoline, collagenases and tannins (present in Betel nuts)
x Nitrosoamines, vinyl chloride, insecticides
B
Japan—Carcinoma stomach
China, France—Carcinoma oesophagus
Hong Kong—Nasopharyngeal carcinoma
Australia—Melanoma
India—Carcinoma oral cavity, gallbladder carcinoma
New Zealand—Small bowel tumours
1
GEOGRAPHICAL VARIATION
We travel not to nd ourselves in the world, but to remember that we have a world inside us.
268
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RADIATION CARCINOGENS
B
x UV rays, ionising radiation.
MICROBIAL CARCINOGENS
B
x Human papilloma virus—carcinoma cervix
x Epstein-Barr virus—Burkitt’s lymphoma, naso pharyngeal carci-
noma
x Hepatitis ‘B’ virus—liver cancer
x Human T cell leukaemia virus Type I
x Helicobacter pylori can cause carcinoma of sto mach and is
associated with lymphomas [Mucosa Associated with Lymphoid
SRB’s Manual of Surgery
Tissue (MALT)]
SPREAD OF MALIGNANT TUMOURS
1. Local spread: Into adjacent structures like soft tissues,
vessels, bone.
2. Lymphatic spread
¾
By permeation: Here malignant cells proliferate through
lymphatic vessels up to lymph node level. For example,
in carcinoma breast malig
lymph nodes.
¾
By embolisation: Here cells get dislodged from lymphatic
vessels and freely travel to spread into further level of
lymph nodes. In carcinoma breast spread occurs from
axillary lymph node to supraclavicular lymph node by
embolisation.
¾
Retrograde lymphatic spread occurs once lymph vessel
get blocked by malignant infil tration. In carcinoma breast
retrograde spread occurs to opposite breast, opposite
axilla, or to mediasti num. In melanoma, through dermal
lymphatics and retrograde spread ‘in transit nodules’
occur in the skin.
3. Blood spread
¾
Occurs through veins, as veins are thin-walled and infiltration is easier (arteries contain elastic fibres in their wall,
which resist malignant infiltration).
¾
Blood spread is commonly to lungs, bone (upper end
of femur and humerus, ribs, skull), liver, brain, adrenals
and other organs.
–
Both by permeation (e.g. in renal cell carcinoma
permeation through renal vein is common) and by
embolisation (in other malignancies).
–
In carcinoma prostate, due to increased pressure and
venous blockade, retrograde venous spread occurs
through vertebral venous plexus which causes osteo-
blastic secondaries in pelvic bones and vertebrae.
4. Seedling: For example
¾
From lower lip cancer to upper lip as kiss cancer.
KISS CANCER
B
x Lip; Bladder; Cervix; Vocal cord; Vulva
nant cells permeate into axillary
¾
Recurrence in the scar after surgery for malig nancy,
e.g. deposition of malignancy in the scar of SPC from
bladder tumour.
¾
Seedling in the peritoneal cavity from abdo minal malignancy is common causing intra
5.
Transcoelomic spread:
Spillage or dislodge of malignant
ctable ascites.
cells occurs from primary site resulting in seedling on
other organ, e.g. in carcinoma stomach secondaries in
ovary (Krukenberg tumour) occurs due to transcoelomic
spread. Here cells get deposi
ted on the raw surface of
ovary during ovulation (So it occurs in menstruating age
group only).
GRADING OF TUMOUR
It signifies aggressiveness of tumour.
It is based on differentiation of tumour cells and mitotic
activity.
Broder’s grading of squamous cell carcinoma: Based on keratin/
epithelial pearls
Grade I: Well differentiated—>75% epithelial pearls
Grade II: Moderately differentiated—50–75% epi thelial pearls
Grade III: Poorly differentiated—25–50% epithelial pearls
Grade IV: <25% epithelial pearls
Special Features of Malignant Cells
Independent and autonomous nature without any control
or check.
Normal telomeric shortening is altered. Normal cell divides for
40–60 times. Later telomere gets shortened and cell division
stops. It is altered in malignancy with infinite cell division.
Reduced cellular apoptosis. Normal cell has capacity to die
once its function is over. It is normal programmed death of
a cell. It is activated by tumour suppressor gene p53. If this
gene loses its function, tumour will form.
Tumour has got capacity to create and construct blood supply
called as angiogenic capacity.
Malignant cells invade through the basement membrane and
spread through blood and lymphatics. It is through secretion
of special enzymes, increased interstitial pressure, capacity
to have motility, release of collagenases/proteases/integrins.
Spread occurs by proliferation and permeation as well as
embolisation.
Creation of instability and alteration of existing tissue function
(not obeying normal tissue function of that particular site).
Gompertzian growth—rapid growth of a tumour occurs prior
to its clinically detectable stage. Once it becomes clinically
detectable which needs thirty generation of cell divisions
(1 mm tumour is 109 cells), its growth slows down later. This
late slow growth is due to decreased oxygen to tumour/by
competition between host cells and tumour cells and also
between tumour cells themselves.
Tumour mutation occurs at different generation of divisions
stabilising the tumour further.
Fig. 1.476: Secondaries in neck. FNAC is the
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investigation to diagnose.
Fig. 1.477: Carcinoma ovary specimen. It was malignant teratomas of
ovary. Other ovary was normal. So chemotherapy is used as an adjuvant.
Patient was 23 years young female.
STAGING OF THE TUMOUR
TNM staging system is first designed by Pierre Denoix in 1952.
TNM (UICC)—1st edition came on 1968; eventually TNM—8th
edition has come with effect from 2017. TNM (AJCC) 1st edition
started from 1978; 8th edition stated from 2018. It is used now to
all solid tumours. American Joint Committee on Cancer (AJCC)
and Union for International Cancer Control (UICC) maintains the
TNM systems and alterations.
It allows understanding of the tumour in terms of location,
local extent, nodal spread, distant spread and also designs treatment plan and prognostic outcome. It also provides uniformity
in managing malignant tumours all over the world. It is not used
for lukaemias and CNS tumours.
Mandatory parameters are T, N and M. Other parameters – G
(grading 1–4); S (serum markers 1–3); R (resection status/
completeness R0, R1, R2); L (lymphatic invasion 0–1); V
(venous invasion 0 [no invasion], 1 [microscopic], 2 [macroscopic]). Prefix modifiers are—c (clinical), p (pathological), y
(assessment after chemotherapy and radiotherapy/neoadjuvant
therapy), r (recurrent tumour), a (stage at autopsy).
Staging is based on—clinical; pathological; imaging. Staging is
also done post therapy period; restaging is done during follow
up and recurrence.
T is primary tumour—Tx: Tumour cannot be assessed; Tis:
Carcinoma in situ; T0: No evidence of tumour; T1, T2, T3, T4
extents of primary tumour.
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CHAPTER 1Q General Surgery: Neoplasm
Paraneoplastic syndromes
T
Syndrome Cause Type of tumour
Cushing’s syndrome ACTH or ACTH like
substance
Syndrome of inappropriate ADH Small cell carcinoma lung
ADH secretion Brain tumour
Carcinoid syndrome Serotonin, bradykinin Bronchial adenoma
Hypoglycaemia Insulin Fibrosarcoma
Insulin like substance Hepatoma
Hypercalcaemia PTH related peptide Renal cell carcinoma
Polycythaemia Erythropoietin Renal cell carcinoma, hepatoma
Myasthenia Immunologic Lung cancer
Acanthosis nigricans Epidermal growth factor Lung cancer, uterine cancer, gastric carcinoma
Dermatomyositis Immunologic Lung carcinoma, breast carcinoma
Clubbing and hypertrophic Ca lung
Osteoarthropathy of fingers
Migrating thrombophlebitis Tumour product mucin Ca pancreas, lung
(Trousseau phenomenon) It activates clotting
Small cell carcinoma lung
Neural tumour
Pancreatic tumour
Gastric and pancreatic carcinoma
Carcinoma breast, SCC lung
Ovarian carcinoma, leukaemia
Cerebellar haemangioma
The creation of a thousand forests is in one corn.—Ralph Waldo Emerson
270
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INVESTIGATIONS FOR NEOPLASM
I. BIOPSY
‘Bio’ means life or tissue. Opsis means vision or micro scopy.
Biopsy means study of tissues using microscopy.
OR life by vision
OR vision for life (to save life).
Biopsy is sent in 10% formaldehyde solution. In special occa-
sions like, to assess receptors/to do histochemistry, biopsy
is sent in low temperature; in normal saline or in specialised
ingredients. Tissues are kept in formalin for 24 hours and
then taken for ‘cut up’ by pathologists. Sections are done after
SRB’s Manual of Surgery
Fig. 1.478: Ethmoidal sinus tumour. Biopsy and CT scan is needed
to confirm and assess the extent.
Fig. 1.479: Carcinoma tongue is more common in lateral margin.
Incision biopsy from the margin is done here.
making tissue blocks using microtome up to 5 microns thickness. These sections are placed on a slide for staining with
haematoxylin and eosin. This is studied under microscopy
by pathologist to give the report. Detailed history, findings,
markings of the specimen should be done by the surgeon
prior to sending the specimen. Bone specimens are decalcified in hydrochloric acid for 7–21 days before sectioning and
staining. So its report will be delayed usually.
Inadequate sampling and improper reports may be due
to—limited tissue sent; tissues are nonviable; too superficial
biopsy done; cautery use on the tissues; crushing effect on
the tissues (gentle meticulous biopsy is important without
rough handling and without over use of cautery on the
required tissues).
Specimens are kept for 6 weeks. Blocks are kept for 30 years.
Slides are kept for 10 years.
Risk of false positivity in malignancy should be remembered.
It is probably due to contamination, interchanged specimens,
wrong interpretation, ulceration, etc. Re-biopsy/reinterpretation/repeat sectioning may be needed in such situations.
Often additional methods like deeper sections; extra blocks;
special stains are needed. Special stains are PAS (Periodic
Acid Schiff) for glycogen, mucin and fungi; D (diastase) PAS
for mucin; Perls Prussian blue for iron in haemochromatosis;
reticulin for fibrous tissue; elastin stains for fibrosis; congo
red for amyloid; Ziehl-Neelsen for mycobacteria; Grocott for
fungi; Giemsa stain for protozoa; Warthin-Starry stain for
spirochaetes.
Fig. 1.480: Typical malignant cachexia observed in GIT
malignancies. It is totally malnourished incapacitated situation.
N is nodal spread - Nx: Nodes cannot be assessed; N0: No nodal
spread; N1: Regional close nodes are involved; N2: Further level
nodes involved; N3: Distant numerous nodes are involved. N1,
N2, N3 varies depends on anatomical location.
M is metastasis (blood) – M0 is no distant spread; M1 is distant
spread is present. Mx is removed from 7th AJCC/UICC systems.
PARANEOPLASTIC SYNDROMES
Certain symptom complexes which are not specifically
explained by the tumour, but are relevant, often problematic
and life-threatening are called as para neoplastic syndromes.
Incidence: Seen in 10% of patients.
TYPES OF BIOPSIES
B
x Incision biopsy—wedge biopsy
x Excision biopsy
x Trucut biopsy
x Pap smear
x FNAC
x Frozen section biopsy
x Punch biopsy
x U/S guided biopsy
x Laparoscopic biopsy
x CT guided biopsy
x Thoracoscopic biopsy
x Endoscopic biopsy (gastroscopic or colonoscopic or through
ERCP or through cystoscopy)
x Proctoscopic biopsy
x Open biopsy either laparotomy or thoracotomy or craniotomy
using Dandy’s brain cannula
A
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B
Figs. 1.481A and B: Carcinoma cheek—advanced. It needs incision
biopsy/orthopantomogram X-ray/CT of the part.
271
CHAPTER 1Q General Surgery: Neoplasm
Fig. 1.484: Soft tissue tumour of buttock. It could be sarcoma.
Fig. 1.482: Secondaries in skull—solitary.
Fig. 1.485: CT head showing secondaries in the brain.
Fig. 1.486: Contrast MRI of spinal column
showing extradural schwannoma.
Fig. 1.483: Carcinoma breast. Note the dilated veins on the surface.
FNAC should be done to confirm the diagnosis.
A man carries success or his failure with him; it does not depend on outside conditions.
Fig. 1.487: CT scan picture of retroperitoneal leiomyosarcoma.
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Trucut Biopsy
It is done using a specialised device wherein gun with trucut tip is
inserted into the surface tissue/organ and gun is fired to close the
punching tip of the needle to catch and cut adequate tissue. It is done
in prostate, breast and surface tumours. It cannot be done to deeper
tissues or tissues which are close to major vessels/structures.
FNAC (Fine Needle Aspiration Cytology)
It is cytological study of tumour cells to find out the disease and
also to confirm whether it is malignant or not.
Procedure: It is done using 23 or 24 gauge needle fixed to
SRB’s Manual of Surgery
Fig. 1.488: Alopecia (hair loss) is common after
chemotherapy for cancers.
specialised syringes which creates negative pressure for
aspiration and contents are smeared on the slides. Dry slides
as well as slides fixed with 100% methanol are used for study.
It is done in parotid, thyroid, lymph node, breast and all other
surface lesions.
In follicular carcinoma of thyroid it is not very useful, as
angioinvasion and capsular invasion which are specific cannot
be detected.
In lymph nodes it is useful for detecting secondaries and
tuberculosis.
U/S guided or CT guided FNAC are popular at present—espe-
cially when it is done from liver, lungs, kidneys, etc. (from
deeper structures/organs).
It is absolutely contraindicated in testicular tumour. Because
tough tunica albugenia usually prevents tumour spread and once
it get disrupted by FNAC, spread can occur.
Cytological study is done after Papanicolaou stain; Giemsa
staining or Romanowsky staining.
Fig. 1.489: Trucut biopsy gun used for trucut biopsy. It gives
histological diagnosis; it is also helpful to assess histochemistry.
Incision Biopsy
It is taken from the edge of the lesion as in ulcer, not from
the centre as there is necrosis.
Usually two biopsies are taken in ulcerative lesion from the
edge—edge/wedge biopsy (edge is a line which limits two
parts; wedge is an area at two meeting parts like thick to
thin, etc).
Incision biopsy is contraindicated in a case of melanoma
where excision biopsy is preferred.
In secondaries in lymph nodes, FNAC is preferred. If it fails
to give information, incision biopsy is done.
Note:
Biopsy taken from the centre of the lesion is only in post-radiation ulcer
and syphilitic gumma. Because of irradiation there is no blood supply in the
margin and tumour proliferates in the centre of the lesion.
Excision Biopsy
In small lesions excision biopsy is done, e.g. lymph node biopsy
is done in case of lymphoma.
Note:
• In 1934, Martin and Ellis did FNAC using 18 G needle with syringe with
local anaesthesia use.
• Kline and Neal in 1973 did syringe needle aspiration using 18 G needle
making dry smears.
• In 1982, A John Webb detailed standard FNAC using 21 G needle. Needle
is passed obliquely into the lesion; constant suction is applied using
Comeco syringe or braced thumb method. With suction persisting
needle is moved in 4 directions. Suction is gently released and needle
is withdrawn. Needle is detached from syringe to draw air which is
reattached to withdrawn needle to blow the content over a dry slide.
• In 1987, A
without aspiration. 25 G needle is used without a syringe. Needle is
moved in various directions to detach the cells by sharp end of the
needle; by capillary force, cells are conducted into the needle lumen.
Air filled syringe is attached to needle to express cells into a glass slide.
Trauma to tissue is said to be less; and feel of tissue consistency is
better through held needle. It is called as Fine Needle Sampling Without
Aspiration/Fine Needle Non-aspirating Cytology (FNNAC)/Fine Needle
Capillary Sampling (FNCS; as capillary action causes conduction of
cells into needle).
• US guided/MRI guided/CT guided/Mammographic guided FNAC are
available now which are more precise versions of localization of lesions
to be aspirated.
• Ether with alcohol in equal proportion is used for wet fixation to stain
Papanicolaou or H&E stains. Grace in 1994 used modified ultra Pap
Zajdello et al fine needle sampling of the tissue in question
Fig. 1.490: Fine needle aspiration cytology (FNAC) of thyroid. It is
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also done in breast, lymph node and other swellings. It is not done for
testicular tumour.
Fig. 1.491: FNAC vacuum creator with loaded syringe [FNAC gun;
Cameco syringe (Sweden) holder]. (Courtesy: Dr Krishna Upadhya,
MD, Nandikoor Laboratory, Mangaluru)
stain 3 changes—by rehydration of air dried smears using normal
saline to cause RBC haemolysis to restore cell transparency; by using
mixture of 4% formaldehyde and 65% ethanol to reduce fixation time
from minutes to few seconds; by using Richard Allen Haematoxylin
2 and cyto stain. Total time of staining in this modification is 90
minutes.
Advantages
Very sensitive.
Done on OP basis.
Least invasive, safer, fast and cheaper.
Anaesthesia is not required.
Tumour dissemination through the track is not present
(except in testicular tumour where it is not done).
Presently DNA study of the cell can detect very early malig-
nancy.
Disadvantages
Negative result cannot rule out malignancy.
Tissue study is not possible.
Further studies not amenable.
Note:
FNNAC—Fine Needle Non-aspirating Cytology is done in some tissues
(in some centres). Here needle is passed into the tissue and material
collected from the needle (without any aspiration) is studied for cytological analysis.
Frozen Section Biopsy
Frozen section is done whenever biopsy report is needed at the
earliest. It is usually done in a pathology set up existing adjacent
to the operation theatre. An unfixed fresh tissue is frozen (using
) in a metal and sections are made and stained. It is techni-
CO
2
cally difficult; processing and staining is of inferior quality and
often it is difficult to give accurate results. But advantage is it is
quick and surgeon can decide the further steps of procedure in
same sitting like nodal clearance/type of resection to be done, etc.
It is done in carcinoma breast or in follicular carcinoma of
thyroid when FNAC fails.
During surgery after resection of the tumour to look for (on
table) the clearance in the margin and depth and also to study
the lymph nodes for their positivity.
II. IMMUNOHISTOCHEMISTRY
It is detection of specific antigen using an antibody. Antibody
labelled with a dye, binds to antigen in a section of tissue causing
specific colours like brown, and determines its presence and
distribution in the tissues. It is safe, specific and quick.
It is used in:
Neoplasia
¾
To confirm, to find differentiation, to detect metastases;
to plan type of therapy.
¾
To categorise leukaemias or lymphomas; either of ‘T’ cell
or of ‘B’ cell type.
¾
To find out site of origin of metastatic tumours, e.g. by
doing prostate specific antigen in prostate cancer or doing
thyroglobulin in thyroid carcinomas or clear cells in the
lung in metastatic renal cell carcinoma.
¾
Detection of receptors or molecules, e.g. estrogen receptors [ER] in breast cancer. ER positive has got better
prognosis. Presence of onco-protein product c—erbB2
in breast cancer signifies poor prognosis.
¾
Gastrointestinal stromal tumour (GIST) can be treated
with imatinib if it shows CD117 expression.
¾
Endocrine tumours are assessed on ki67 proliferative index.
¾
Cytokeratin marker for epithelial tumours like carcinoma;
S100 and actin for glandular malignancy; S100 for melanoma; CD31 and CD34 for vascular malignancy; CA 125
for ovarian tumours; PSA for carcinoma prostate; CD3 and
CD20 for lymphoma.
Infections
¾
Detection of specific antibodies to the antigens of certain
specific infective agents like Epstein-Barr virus, cytomegalovirus, human herpes virus 8, herpes simplex virus, etc.
To identify abnormal accumulation of various proteins like
α′-1-antitrypsin; deposition of amyloid.
Assessment of immunoglobulins.
Screening for mutations.
Note:
Ki-67 (Antigen Ki-67, MKI67): It is a human protein identified by monoclonal
antibody Ki-67. It is originated by immunising mice with HL cell line nuclei.
Ki means Kiel, Germany (city of origin), 67 is number of original clone. It is
a cellular marker of proliferation. During mitosis it is located in chromosome
surface; in interphase it is located in cell nucleus. It is high during active
273
CHAPTER 1Q General Surgery: Neoplasm
The pathological fracture is a transverse one, and although it unites readily, re-fracture is not unusual.
—Max E Lake
274
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phases of cell cycle (G1, S and G2). It is absent in resting (quiescent) phase
of cell cycle. It is useful carcinomas of breast, prostate, brain, neuroendocrine
and urothelial tumours. It is very good marker of growth fraction of the cell.
High Ki-67 predicts higher recurrence and progression. MIB1 is the IgG1
antibody against Ki-67 for formalin fixed, paraffin embedded tissue.
III. TUMOUR MARKERS
Tumour markers are biochemical indicators of presence of a
tumour. They are not used for primary pathological diagnosis.
They are of prognostic value.
Presence of tumour marker signifies recurrence or residual
tumour.
SRB’s Manual of Surgery
IV. OTHER METHODS
Electron Microscopy: It is visualisation of tissue in very high
magnification of 1000 × 500 000 in difficult deciding cases.
But it is time consuming and expensive.
In Situ Hybridisation: It is determination of presence or
absence of a specific gene and its location in a fresh/fixed
tissue sections using an oligonucleotide probe, targeting at
specific DNA or RNA sequence.
Polymerase Chain Reaction (PCR): DNA is amplified using
this special method and detected by technique like electrophoresis. PCR can be done on blood or nontissue samples. It
is highly sensitive, fast and safe. Disadvantages are—expen-
sive and risk of DNA contamination.
Uses
¾
Detection of mutations in congenital conditions like von
Hippel-Lindau disease (vHL gene); haemochromatosis
(HFE gene); colorectal carcinoma (APC gene).
¾
Gene rearrangements in different conditions like lymphoma
or other diseases can be detected by PCR (clonality).
¾
Assessment of loss of heterozygosity in tumours like
oligodendroglioma (1p, 16q).
¾
PCR study for infections like tuberculosis.
Fluorescent In Situ Hybridization (FISH)
¾
It is a type of cytogenetic study (study of chromosomes)
that can be done in fixed or fresh tissues. RNA or DNA
probes are prepared which are tagged with fluorophores
targeted on specific cells or chemicals.
¾
It is used in haematological malignancies, genetic
evaluation like trisomy 23; oligospermia; cancer study,
leukaemias, and in many syndromes.
¾
It is used in assessing the remission and prognosis. It
is safe and quack.
MANAGEMENT STRATEGY FOR CANCERS
Diagnosis is confirmed by biopsy from primary usually.
Evaluations for staging—metastatic work up.
Approaches for primary—surgery/radiotherapy/chemotherapy.
Approaches for secondary.
Palliation in advanced stage—palliation of distressing
symptoms.
TREATMENT OF TUMOURS
B
x Surgery—wide excision/
radical
x Radiotherapy—curative/
palliative
x Chemotherapy
x Immunotherapy
x Gene therapy
Tumour markers
T
Category 1
Hormonal:
Human chorionic gonadotrophin
(HCG)
Calcitonin Medullary carcinoma of thyroid
Catecholamines and VMA Pheochromocytoma
Ectopic hormones In tumours of paraneoplastic syndromes
Category 2
Isoenzymes:
Prostatic acid phosphatase Carcinoma prostate
Neuron specific enolase Small cell carcinoma lung, neuroblastoma
Category 3
Oncofetal antigens:
Alpha fetoprotein Liver cancer, nonseminomatous germ cell tumour
Carcinoembryonic antigen (CEA) Carcinoma colon (common). Carcinoma pancreas, lung, stomach and breast
Category 4
Mucin and other proteins:
CA—125 (Carbohydrate antigen) Ovarian cancer
CA—15-3 Breast cancer
CA—19-9 Pancreatic and colon cancer
Trophoblastic tumour, nonseminomatous testicular tumour
MALIGNANCIES WHICH ARE CURABLE
https://t.me/medicina_free
B
x Basal cell carcinoma
x Adamantinoma
x Verrucous carcinoma
x Marjolin's ulcer
x Papillary carcinoma of thyroid
x Carcinoma colon
SARCOMAS WHICH SPREAD TO LYMPH NODES
B
x Synovial sarcoma
x Ewing’s sarcoma
x Lymphosarcoma
x Kaposi’s sarcoma
x Rhabdomyosarcoma
x Angiosarcoma
275
CHAPTER 1Q General Surgery: Neoplasm
Fig. 1.492: Advanced aggressive malignancy face may be
carcinoma or sarcoma.
Fig. 1.493: Advanced fungating carcinoma of breast.
Fig. 1.495: Secondaries in ovaries—Krukenberg tumour.
Fig. 1.496: Malignant primary nerve sheath tumour (MPNST).
Fig. 1.494: Recurrent secondaries in neck after radical neck
Fig. 1.497: Anal canal carcinoma (SCC).
dissection.
To different minds, the same world is a hell, and a heaven.
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