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Neoplasia Lecture 1:

Identification and classification of tumours,

Benign versus malignant tumours
and
Features of tumour cells

Brett Hambly
Pathology Department

IDENTIFICATION and CLASSIFICATION

‘Definition’ of a ‘tumour’ (neoplasm).

Lay Definition
- a "lump" or swelling

Better Lay Definition

- a "lump" or swelling
which continues to grow

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Pathologist's Definition of a “tumour”

(Willis, 1973)
- An abnormal mass of tissue, the growth of
which exceeds and is uncoordinated with
that of normal tissue and persists in the
same uncoordinated manner after cessation
of the stimulus which evoked the change

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What is meant by the word “CANCER”?
Galen - 2nd century Greek ‘karkinos’ for CRAB
- became ‘cancer’ in Latin

Common usage has degenerated

meaning in the vernacular to ‘any
neoplasm that can result in death’

Cancer = malignant tumour = a tumour capable of metastasis (spread)

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Is this CANCER?
- Cancer? NO
- Is it a Neoplasm?
NO
IT IS:
- A swelling due to a
localised collection of
blood from a ruptured
blood vessel.

HAEMATOMA
BUT the misuse of the suffix
‘-oma’ persists to this day

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Is this CANCER?
NO. This is a lipoma, a
common benign, slowly
growing neoplasm

The lipoma can be

totally excised and
will not recur in
this site

Histologically, it is
almost identical to
normal adipose
tissue

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Is this CANCER?
NO. This is a benign,
but expansive
neoplasm of
connective tissue
origin that has caused
resorption of adjacent
bone.

Histologically, the
neoplasm was
composed of a mass
of differentiated but
disordered fibroblasts
and had well-defined
margins

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Is this CANCER?
NO. This is a benign
neoplasm of the breast - a
fibroadenoma that has
grown to form a large
mass.
Histologically, it has a
characteristic morphology with
differentiated epithelial cells
arranged in distinctive glandular
patterns embedded in a dense
fibrous connective tissue stroma.
It is demarcated from the
surrounding tissues

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 NO. These are colonic polyps. 9
Histologically, these are benign adenomatous
papillomas but they have a potential to progress to
Is this CANCER? malignancy and are considered to be pre-malignant

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Is this CANCER?
NO. This is a Giant Cell
Tumour of Bone.
This neoplasm clearly grows
expansively and causes reactive
resorption of surrounding bone
and this can lead to pathological
fracture.

Histologically, the neoplasm consists

of large numbers of prominent
multinucleated giant cells embedded
in a haemorrhagic stroma containing
characteristic elongated cells with
large nuclei.

The Giant Cell Tumour of bone

is not considered to be a
malignant neoplasm

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 Is this CANCER? 11

Well, almost but not really!

This is a Basal Cell Carcinoma (BCC)

The BCC is slowly growing and destructive

(rodent ulcer) but does not metastasise.
Histologically, this neoplasm has a
characteristic morphology with pallisaded
basal epithelial cells invading slowly with a
‘pushing margin’.
The BCC is very common, easily treated,
rarely biopsied and is NOT RECORDED in
official statistics for cancer.

Is this CANCER? 12

YES. This is a SQUAMOUS CELL CARCINOMA (SCC)

The SCC in this site is actively invasive and actively metastasises to
draining lymph nodes.

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Histogenesis BENIGN MALIGNANT

(Tissue of Origin?)
ONE CELL TYPE
Epithelial carcinoma
Papilloma Squamous cell carcinoma
( > 90% of neoplasms ) Adenoma Adenocarcinoma
• Neuroectoderm Naevus* Malignant Melanoma

Mesenchymal sarcoma
Lipoma Liposarcoma
• Connective Tissue Chondroma Chondrosarcoma
• Endothelial & related Haemangioma* Angiosarcoma
• Haemo(lympho)poeitic Leukaemia / Lymphoma
• Muscle Leio / Rhabdomyoma Leio / Rhabdomyosarcoma

MIXED - more than one cell type Pleomorphic Adenoma

Fibroadenoma
Nephroblastoma (Wilm’s Tumour)

TERATOGENOUS Mature Teratoma Teratocarcinoma

- totipotent cells in gonads or
embryonic cell rests

* Hamartomas: aberrant differentiation of cells that results in a mass of disorganised but mature
specialised cells or tissue indigenous to the particular site. Completely benign.

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Adenocarcinoma of the colon: crude glandular pattern

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Squamous cell carcinoma

• Basal epithelium like cells, very atypical in appearance

• Often exhibit keratin pearls (attempts to differentiate into sq. epith)
• Carcinoma in situ prior to invasion through basement membrane

Naevus: neuroectodermal benign tumour; ? hamartoma 16

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Microcapillary Haemangioma (Port wine stain)
Example of a hamartoma

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Hodgkin’
Hodgkin’s Lymphoma

- solid malignant tumour of white

cells
- Grows initially within lymph
nodes

“Rubbery” lymph nodes

containing tumour

Abdominal Aorta

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Benign Teratoma of the Ovary
Multiple cell types derived from pluripotent stem cell in gonad

Teeth

Hair Skin

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General Features of Benign versus Malignant Neoplasms
Benign Malignant
Evidence of Rate of Growth
Mitoses Normal number & structure Increased number/abnormal
structure
Nuclei Normal Pleomorphic
Nucleoli Normal number & structure Prominent/multiple
Cytoplasm Normal Basophilia
Necrosis/Haemorrhage Absent Prominent

Differentiation
Morphological Near normal Variable to none
resemblance
Functional Near normal Near normal, absent or abnormal
resemblance
Relation to adjacent tissues
Demarcation Readily recognised Poorly defined due to INVASION
Distant spread Never Frequent (including metastasis)

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 Anaplastic carcinoma 1

Note: nuclear pleomorphism Note: ‘near-normal’ tumour entrapped by invasion

Note: mitotic figures (including abnormal)
Note - lack of tissue-specific differentiation and poor cellular differentiation

Anaplastic Sarcoma 2

Note - prominent nucleoli

Note also - nuclear pleomorphism, mitotic figures (including abnormal), lack of cell and
tissue differentiation.

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Anaplastic sarcoma

Mitosis Abnormal mitotic figure

(“caterpillar-like”) Tripolar mitosis Multi-nucleated cell

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Cervical Squamous
Cell Carcinoma Uterus

Tumour Necrotic
cells core

Ulcerated bleeding
cervical cancer

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Macroscopic differences between benign and malignant tumours
(1) Mass
A benign tumour grows by expansion, while a malignant
tumour both expands and invades surrounding tissue.
Benign tumours (generally) are:
(1) well circumscribed and round;
(2) have a capsule;
(3) their size varies enormously;
(4) colour and texture: grey or white and uniform.

Malignant tumours (generally) have:

(1) finger like projections;
(2) irregular margins;
(3) are not circumscribed;
(4) have variable texture and colour, often due to haemorrhage
and necrosis.

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Comparison between tumour margins
Benign fibroadenoma Malignant carcinoma
of Breast of Breast

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Macroscopic differences between benign and malignant tumours

(2) Ulceration
May form on mucosal surfaces or skin.
Benign neoplastic ulcers: rarely occur; tend to have very sharp
edges, are shallow and the floor is
usually not indurated.
Malignant ulcers: tend to have rolled edges and tend to
feel hard; are irregular in shape and
may be irregularly indurated.
(3) Polyps
Neoplastic tissue protruding from the skin or from a mucosal
surface.
Benign polyps: usually pedunculated (have a stalk) and have
a uniform texture.
Malignant polyps: usually sessile (flat); may ulcerate & bleed;
often have an indurated base.

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Comparison between benign and
malignant polyps
Benign Transitional cell Malignant squamous cell
“carcinoma” bladder carcinoma bladder
Pedunculated with Sessile, ulcerated, bleeding
uniform texture with indurated base

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Microscopic differences between benign and malignant tumours

(1) Organisation of tumour cells

- Tumour cells may be organised into structures that resemble their tissue of
origin. For example, glandular tumours often form glandular (acinar)
tumour structures.
- The more regular and ordered these structures, the less likely that they are
malignant.
- Glands that are haphazard in size and organisation suggest malignancy.
- Malignant glands may become substantially more anaplastic in more
malignant tumours and lose all glandular organisation.

Microscopic differences between benign and malignant tumours 10

Examples of the arrangement of individual cells in a gland:
Normal: nuclei at base of cells (polarity), single layer of cells of uniform size arranged
around lumen of regular size
Benign: nuclei remain basal but usually enlarged, may be higher density of cells, but
remain regularly related to each other, may be slight increase in mitotic rate with
normal mitoses.
Malignant:
1. Markedly enlarged central nuclei (loss of polarity and increase in
nuclear:cytoplasmic ratio to greater than 50%),
2. Cells variable in size and shape (pleomorphic), and haphazardly arranged "don't
stand up straight" (loss of polarity),
3. Cells may become stratified into two or more layers.
4. Noticeably increased mitotic rate with abnormal mitoses.
5. Cells may become multinucleate.

Benign Malignant
Normal

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Junction between benign colonic polyp 11

and normal mucosa

Crypts of normal Fern-like structure of

colonic mucosa benign colonic polyp

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Adenocarcinoma of the colon

Normal
colonic
mucosa

Pleomorphic cells
↑nuclear/cytopl ratio
Cells “heaped up”
Necrosis

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Microscopic differences between benign and malignant tumours
(2) Cell function and differentiation
Benign and well differentiated malignant tumours tend to retain their function, while an
anaplastic malignant tumour is more likely to loose all function or express bizarre
functions, for example:
(i) Synthesis of mucin: occurs in well differentiated adenocarcinomas but not in
anaplastic.
(ii) Synthesis of keratin: may occur in abnormal locations (keratin pearls) or not at all
in anaplastic tumours.
(iii) Synthesis of melanin: a primary melanoma usually is pigmented but occasionally a
metastasis from a primary lesion may lose its pigmentation, suggesting more
anaplastic change in that subclone of metastatic cells.
(iv) Synthesis of normal or abnormal hormones: the tumour may produce large amounts
of normal or abnormal hormones, e.g.:
(a) phaeochromocytoma produces large amounts of normal catecholamines
(adrenalin and noradrenaline) due to its large bulk; many tumours may produce
abnormal "hormones"
(b) tumour secretion of abnormal parathyroid hormone resulting in hypercalcaemia.

Note: if the hormone is not normally produced by the tissue of origin of the tumour, it
is referred to as a paraneoplastic effect - see later.

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Squamous cell carcinoma

• Basal epithelium like cells, very atypical in appearance

• Often exhibit keratin pearls (attempts to differentiate into sq. epith)
• Carcinoma in situ prior to invasion through basement membrane

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Microscopic differences between benign and malignant tumours
(3) Rate of growth
Benign: slow with low mitotic rate, well demarcated (encapsulated)
expansion.
Malignant: rapid with high mitotic rate & abnormal mitoses; irregular border;
not encapsulated.
Note: After surgery benign tumours are unlikely to recur, while malignant
tumours are.

(4) Secondary changes

Vascularity: benign tumours not very vascular (except a haemangioma!);
malignant tumours are very vascular.
Necrosis/ulceration: not common in benign tumours; common in malignant.
(5) Host responses
• Inflammatory response is common around a malignant tumour (tumour seen
as "foreign" by immune system). May correlate with prognosis e.g. the
greater the lymphocyte infiltration in a melanoma, the better the prognosis.
• Malignant tumours may excite a strong fibrous (collagenous) response
(referred to as desmoplasia).