General Pathology Neoplasia 2024 -2025

Neoplasia
֎ Definition:
 it is formation of mass due to multiplication of cells. This multiplication is without
cause, without limit, without function and without control.
 Tumors are named by adding the suffix “-oma” to the Latin name of its origin
o Fibroma o Osteoma o Adenoma
o Chondroma o Neuroma
o Lipoma o Lymphoma

֎ Classification of tumors
 Tumors can be classified according to:

Histological origin Clinical behavior

o Epithelial Tumors o Benign Tumors
o Mesenchymal Tumors o Malignant Tumors

Histological Origin
May arise from any tissue in the body as
1. Epithelia: surface epithelium or glandular epithelium
2. Mesenchymal tissues: fibrous tissue, bone, cartilage and vessels
3. Neuroectoderm
4. Haemopoietic and lymphoid cells
5. Germ cells

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 General Pathology Neoplasia 2024 -2025

Clinical behavior

LOCALLY MALIGNANT TUMOURS

o They are malignant tumors that may grow and spread locally and invade the
surrounding normal tissues but never produce distant metastases.
o Examples:
1. Basal cell carcinoma Rodent Ulcer
2. Osteoclastoma
3. Adamantinoma

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 General Pathology Neoplasia 2024 -2025

BENIGN TUMORS
 CHARACTERISTICS OF BENIGN TUMORS:
 Origin: From the normal cells of the tissue (de novo)
 Size: Usually smaller than malignant, but some are huge as uterine tumors
 Rate of growth: Less rapid than malignant ones
 Mode of growth: By expansion They grow as cohesive expansile masses that
compress the surroundings

 Gross Appearance:
1) Usually, solitary
2) Well circumscribed
3) The margins are usually well defined
4) The cut surface is smooth
5) Usually no hemorrhage or necrosis
6) It is usually firm or soft in consistency and not hard
7) Capsule usually encapsulated except for those of surface epithelium
8) Show function.

 Microscopic Picture
1) Mimic Usually resemble the tissue origin.
2) Mitotic figures are absent or few (if present they are
3) The stroma is well formed.
4) No hemorrhage or necrosis.
5) Distant spread (metastasis): Benign tumors do not metastasize.
6) Recurrence after removal: do not recur if completely removed

➢ In General, the cells of benign tumors are well differentiated

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 General Pathology Neoplasia 2024 -2025

Benign Epithelial Tumor

Surface Epithelium → Papilloma

 It is a finger like projection with a surface covered all around with epithelial cells and it is
thrown into folds which become increasingly complex.
 It is accompanied by a corresponding growth of supporting connective tissue and blood
vessels forming the core
 It may be: sessile or pedunculated
 Example:
 Duct papilloma of the breast

Glandular Epithelium → Adenoma

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 General Pathology Neoplasia 2024 -2025

 Special types of adenomas:

1) Cystadenoma: In cases in which retention of
secretion is marked, a cyst forms, which may
reach an enormous size, e.g. some
cystadenomas of the ovary may be 30-40 cm
in diameter, particularly those which secrete
mucus.

2) Fibroadenoma:
 In the breast, the term is clinically useful for a small nodule consisting of a mixture
of acinar elements and prominent supporting fibrous tissue.
 The histological appearances are
variable depending on the
distribution of the fibrous tissue.
 It may be small in size & mobile →
“Breast Mouse”. Or very large in size
→ “Giant Fibroadenoma”

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 General Pathology Neoplasia 2024 -2025

Benign mesenchymal tumor

Lipoma
 A circumscribed mass of fat are commonly
found in the subcutaneous tissue of the arms,
shoulders and buttocks.
 They occur Less commonly in the deep soft
tissues, as they must be carefully distinguished
from low grade liposarcomas

Chondroma
 A chondroma usually arises within the
medullary cavity of the tubular bones of the
hands and feet. It grows slowly, causing
gradual expansion of the bone.
 Rarely multiple enchondromas appear in
children and are associated with deformity.
They occasionally become malignant.

Osteoma
 This tumor is mainly found in the bones of the skull,
although it may occur in long bones.
 Osteomas are relatively small but may produce severe
symptoms because of their situation

Leiomyoma
 The majority of benign smooth muscle tumors
occur in the wall of the uterus where they are
extremely common
 May lie within the uterine cavity or attached
to the serosa. They are firm, rounded masses
which usually begin in the myometrium.

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 General Pathology Neoplasia 2024 -2025

Hemangioma
 Two main varieties exist:

1) Capillary Hemangioma
• These are common in the skin as `birthmarks ',
may be found in internal organs,
• They are well defined, deep red or purple.

2) Cavernous Haemangioma
• This type is usually confined to internal organs and quite often found in the liver.
Like the capillary variety they are well defined and deep purple.
• Similar tumors are found involving the lymphatic system (lymphangioma)

Fibroma
 Fibroma are rare , but tumor like growths are fairly
common.
 An example is Palmar Fibromatosis at first nodular
causes flexion deformities of fingers.

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 General Pathology Neoplasia 2024 -2025

MALIGNANT TUMORS
 CHARACTERISTICS OF MALIGNANT TUMORS:
 Origin: Either de novo or from premalignant lesion as chronic ulcers or as a malignant
transformation of benign tumor.
 Size: Variable but may reach large size in short time.
 Rate of growth: Growth rate correlates with degree of differentiation and thus most
malignant tumors grow more rapidly than benign ones.
 Mode of growth: Grow by progressive infiltration, invasion, and destruction of the
surrounding tissues.

 Gross Appearance
1) Usually ill-defined mass
2) Mostly vague margin
3) Usually hemorrhage and necrosis are present because of rapid cell proliferation
which exceeds the blood supply of the tumor
4) Capsule usually unencapsulated

 Microscopic Picture:
1) Cellular anaplasia in the form of pleomorphism, nuclear enlargement,
hyperchromatic, increased N/C ratio, prominent nucleoli, abundant and irregular
atypical mitoses, abnormal differentiation, and loss of polarity with haphazard
arrangement of the cells
2) Blood vessels are numerous and poorly formed
3) Distant spread (metastasis): With few exceptions all malignant tumors metastasize.
4) Behavior and prognosis: Recurrence is very common. 5 Year survival rate after
treatment without recurrences is curative standard

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 General Pathology Neoplasia 2024 -2025

Malignant Epithelial Tumor

 Definition: Malignant epithelial tumors are known as carcinomas
(Greek karkinos a crab), referring to the typical irregular jagged
shape this is due to invasion into adjacent normal tissues

 Microscopically:
 They are formed of masses, groups, sheets of malignant epithelial cells surrounded by
desmoplasia (fibrosis).

 Types of Carcinoma:
 Like benign epithelial tumors, carcinomas can arise from surface or glandular
epithelium

CARCINOMA OF SURFACE EPITHELIUM

1. SQUAMOUS CELL CARCINOMA

o Definition: malignant tumor of surface epithelium
o Site: This is commonly found on the skin, especially exposed surfaces, but also develops
in other sites covered by stratified squamous epithelium, e.g. lips, tongue, pharynx,
esophagus and vagina.
o Histologically:
 it is composed of irregular strands and columns of invading epithelium which infiltrate
the underlying connective tissue.
 If well differentiated → the central cells show eosinophilic keratin, while the outer
layer consists of basophilic young cells → cell nest (epithelial pearl)

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 General Pathology Neoplasia 2024 -2025

2. BASAL CELL CARCINOMA

o Definition: This is a locally malignant tumor may arise in any part of the skin but is most
common in the face, near the eyes and nose.
o Pathogenesis:
1) First stage:
It starts as a flattened papilloma which slowly enlarges
2) Second stage:
The surface breaks down and a shallow, ragged ulcer with
pearly edges (inverted edges) is formed.

o Histopathology: Usually, It is composed of cells resembling the

basal layer of the skin. It has a characteristic histological
appearance that it doesn’t form nest, no keratin at the center

o Characters:
1) Locally invasive growth which can be extremely destructive
2) Malignant tissue spreads slowly but progressively → (hence
its name: Rodent ulcer).
3) It almost never metastasizes.

CARCINOMA OF GLANDULAR EPITHELIUM

o Definition:
These may take origin from gland acini, ducts or the glandular epithelium of mucous
surfaces. These tumors are named “Adenocarcinomas”.
o Gross picture:
1) Polypoid
2) Ulceration: everted ulcer
3) Invading Crablike structure
4) Cystadenocarcinoma

o Microscopically:
Carcinomas of glandular tissue have three basic forms:
1. Adenocarcinoma: tumor cells are gland-like structure.
2. Signet-Ring Cell Carcinoma: in mucus secreting cells → forms intracellular and
extracellular mucin. This is commonly seen in the stomach.
3. Mucoid Carcinoma: in mucus secreting cells → making lakes of mucin in which cells
float. This is commonly seen in stomach, intestine, breast.

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 General Pathology Neoplasia 2024 -2025

Malignant connective tissue tumors

o Definition: they are referred to as Sarcomas (Greek `sarkoma': flesh). They arise in soft
tissue, in bone and rarely in viscera.
o Characters:
1) Sarcomas are far less common than carcinomas, and second in place to leukemias and
lymphomas in childhood and early adult life.
2) Large well-defined fleshy tumors.
3) Naked eye assessment suggests that they are encapsulated, but histology shows that
this is a false impression.
4) Microscopically: Individually cellular, mostly spindle
cells, separated by matrix secreted by malignant cells
5) They are highly vascular → formation many large
thin-walled blood vessels which are easily invaded
by sarcoma cells.
6) Blood borne metastases is common. while lymph
node involvement is rare

1. LIPOSARCOMA
o Definition: This tumor arises in soft tissues of the limbs and retroperitoneum.
o Microscopic:
 Primitive fat containing cells (lipoblasts), With vascular channels
 Well-differentiated liposarcoma has a good prognosis and
rarely metastasizes.
 Pleomorphic and round cell liposarcomas are highly aggressive
tumors which metastasize early.

2. MYOSARCOMA
a) Leiomyosarcoma
 This is a malignant tumor of smooth muscle.
 These rare tumors arise in deep soft tissues and
particularly in the uterus.

b) Rhabdomyosarcoma
 This is a malignant tumor of skeletal muscle
occurring mainly in children.
 They may occur as polypoid tumors in the bladder,
uterus and vagina, sometimes called sarcoma
botryoides (grape-like).

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3. PLEOMORPHIC OR ANAPLASTIC SARCOMA

o Definition: highly malignant sarcomas that are so poorly
differentiated that their specific type cannot be determined.
o Diagnosis: Immunocytochemistry, electron microscopy and
cytogenetic analysis help in reaching the phenotype (cells of
origin of the tumor).

4. TERATOMA
o Definition: This is a tumor derived from totipotent germ cells.
o Origin: They may also occur at any site in the mid-line where germ cells have stopped in
their migration to the gonads.
o Site:
1) Ovary (usually benign) → mature teratoma (dermoid cyst)
2) Testis (usually malignant).
o Gross picture: It consists mainly of ectodermal structures such
as skin and its appendages and neural tissue. Frequently,
respiratory epithelium, intestinal epithelium, bone and
cartilage are present.

5. PIGMENTED TUMORS
a) MELANOCYTIC NAEVUS OR (MOLE)
• Benign pigmented naevus is extremely common.
• The term `naevus' means a birthmark, but most naevi are acquired in childhood
and adolescence.
• During fetal life melanin-pigment-forming neuroectodermal cells migrate to the
skin and are found in small numbers in the basal layer of the skin.
• A continuous layer of pigmented cells is found adjacent to the basal epidermal
cells.

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 General Pathology Neoplasia 2024 -2025

b) MALIGNANT MELANOMA
o Origin: Malignant proliferation of melanocytes usually arises de novo but some
melanomas arise from pre-existing naevi.
o Cause: Exposure to Sunlight (the UV component) is the most important etiological
factor.
o Sites: Signs Of Malignant Transformation of
1) Skin of: Benign Nevus:
a) face, soles of feet, palms of 1. Color deepness.
hands and nail beds 2. Size changes & induration.
b) legs (in women)
3. Bleeding, itching and enlarged
c) trunk (in men)
regional lymph nodes.
2) Mucous membranes of mouth,
arms and genitalia: rare. 4. Ulceration, infection and microscopic
3) Eye and meninges: rare. evidences of malignancy.

6. LYMPHOMA
o There are no benign tumours of lymph nodes .
o therefore, tumours of lymph nodes are named “MALIGNANT LYMPHOMA”.
o Lymphomas are divided into TWO main types:
1. HODGKIN’S LYMPHOMA
2. NON-HODGKIN’S LYMPHOMA
o They are treated by chemotherapy.

7. LEUKEMIA
o Malignant tumor in bone marrow, leading to production of a huge number of
leukocytes in peripheral blood (300,000 – 500,000/cml.) & deposition in different
organs.

8. HAMARTOMA
o Definition: tumor-like but non-neoplastic malformation
consisting of a mixture of tissues normally found at the
particular site.

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 General Pathology Neoplasia 2024 -2025

DIFFERENCES BETWEEN CARCINOMA AND SARCOMA

DIAGNOSIS OF TUMOURS
o Diagnosis of tumors is made by:
1. Gross examination.
2. Conventional histological assessment.
3. Immunocytochemical staining and molecular testing.
 Different immunocytochemical panels used to address specific histological dilemmas
4. For metastatic & anaplastic malignancies of unknown origin, the pathologist may
request immunological markers for exact phenotyping like:
a) Cytokeratin “CK” for epithelial tumours
b) Leucocytic Common Antigen “LCA” for leukocytes,
c) Vimentin for sarcomas.

ENVIRONMENTAL FACTORS CAUSING TUMOURS

o The three major environmental factors which induce tumors are:
1) Chemical Carcinogens
a) Industrial Processes 2) Radiation
b) Social Habits 3) Viruses.
c) Diet.

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ROUTES OF SPREAD
1) Local or Direct Spread:
a) Direct infiltration of the surrounding tissues is common in malignant tumors.
 Microscopic extent of tumor exceeds its macroscopic boundaries (Safety Margin).

2) Distant Spread (Metastasis):

 Metastasis means the development of secondary malignant implants away from the
primary tumor.

1. Lymphatic Spread
o Carcinoma & melanoma show great tendency for early lymphatic invasion than sarcoma
o And it occurs by one of two methods:

a) Lymphatic embolism
 Malignant cells invade the walls of lymphatics ➜Detached tumor cells are carried as
tumor emboli → arrested in the subcapsular sinus of the lymph node ➜The malignant
cells proliferate and gradually destroy and replace the nodal tissue ➜ Capsular
invasion occur and the node become fixed. ➜ Spread of malignancy occurs from
node to another through the efferent lymphatics ➜Tumor emboli reach the main
thoracic duct ➜ reach the venous circulation ➜ causing hematogenous spread.

b) Lymphatic Permeation
o The malignant tumor cells grow inside the lumen of the lymphatics as solid column.
o Groups of cells form emboli in the lymph stream and are carried to the nearest node
(the sentinel node).
o Example:
1) There is marked lymphatic obstruction → tissue edema as in case of breast cancer
→ (Peau d’Orange Appearance).
2) There may be Retrograde tumor embolism in the reverse direction.
3) The best example is involvement of the left supraclavicular lymph node (Virchow’s
node) in carcinoma of the stomach.

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2. Blood Spread
o Common in All Sarcomas
o Some carcinomas may spread early by blood and lymphatics: thyroid, lung, breast,
kidney and prostate.
 Because of their thinner wall, veins are frequently invaded than arteries.
o The most common sites of metastasis: liver, lung, bone and brain. (LLBB)
o Metastases are rare in muscle, spleen, pancreas and intestine.
o Mechanism → ESTINATION OF EMBOLI
 There is formation of thrombus containing malignant cells ➜The thrombus break into
particles which circulate in the blood as emboli containing malignant cells.
 Emboli Destination depends on the anatomical drainage of the vessel invaded:
- Bone secondaries from breasts, lungs, kidneys & thyroid → osteolytic.
- Bone secondaries from prostatic carcinoma → osteosclerotic
- Bone metastases may cause pathologic fracture or bone marrow destruction
causing anemia, leucopoenia and thrombocytopenia.
- Reversal of flow is more likely to happen in certain areas of the body where veins
form a rich plexus and are deficient in valves, e.g. in the pelvis and around
vertebrae, due to Changes in intra-abdominal and intrathoracic pressures

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3. Spread by Implantation

A. Transluminal spread and implantation:

1) Malignant cells may spread along natural passages
from the renal pelvis to be implanted in the mucosa
of the urinary bladder or from the bronchi, to be
implanted in the terminal alveoli.
2) Carcinoma of the lower lip may be implanted over
the opposite upper lip.

B. Surgical implantation:
o Cancer cells may be implanted in the needle track following the
aspiration of malignant ascites or implanted into the surgical wound
causing secondary tumor deposits.

4. Spread by Serous Sacs

(Trans-Coelomic Spread)

o This occurs in tumors that reach the serous sac

surface, like that of the peritoneum, pleura and
pericardium from near-by organs.
o Examples:
1) Transperitoneal spread occurs in carcinomas of
the stomach, colon &pancreas.
2) Carcinoma of the stomach in the females is
usually associated with bilateral ovarian
metastasis termed Krukenberg tumor which is
mainly due to trans-coelomic spread.

CANCER INCIDENCE

Most common primary cancers The most common cancer KILLERS

o MALES: Prostate → Lung → colon o MALES: lung → prostate → colon
o FEMALES: Breast → lung → colon o FEMALES: lung → breast → colon
o CHILDREN: leukemia → Gliomas → o CHILDREN: leukemia
Bone sarcoma

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 General Pathology Neoplasia 2024 -2025

GRADING OF MALIGNANT TUMOURS

o Definition: It is the evaluation of the degree of cytological similarity (resemblance) of the
malignant tissue to the tissue origin (degree of differentiation).
o Types:
1) Well Differentiated (Grade I): (75%-100%) are differentiated. It closely. In this grade
more than three fourths of the cells resembles to the tissue of origin
2) Moderately Differentiated (Grade II): (50%-75%) are differentiated and resemble
tissue of origin.
3) Poorly Differentiated (Grade III): (25%-50%) are differentiated.
4) Undifferentiated (Grade IV): (0%-25%) are differentiated and the tumor hardly
resembles the tissue of origin.
5) Anaplastic tumor: Total loss of resemblance to the original tissue.

STAGING OF MALIGNANT TUMOURS

o Definition: It is the evaluation of anatomical extension of the malignant tissue (e.g. in-
situ invasion, local infiltration, regional metastasis, distant metastasis).
o The stage of a malignant tumor is based on:
1) The Size of Tumor “T0, T1, T2, T3, T4”
2) The spread to the regional lymph nodes “N0, N1, N2, N3”
3) The presence or absence of blood-born metastasis “M0, M1”.
o T represents tumor size and extent of local tumor spread.
o N represents the absence or presence of regional lymph node metastasis
o M represents distant metastasis.

 T (tumor size and extent of local tumor spread).

o T0 → no primary tumor
o T1,2,3,4 → indicating the size of tumor
o T(is) → carcinoma in situ

 N (absence or presence of regional lymph node metastasis)

o N0 → no regional lymph node metastasis
o N1,2,3 → extent of regional lymph node metastasis

 M (distant metastasis).
o M0 → no distant metastasis
o M1 → distant metastasis
o M1a for Metastasis In One Site & M1b in multiple sites

o According to this staging tumor estimated as T1 N0 M0 has better prognosis than

other staging as T4 N3 M1

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 General Pathology Neoplasia 2024 -2025

PROGNOSTIC FACTORS OF MALIGNANT TUMORS

1) Age: Poor prognosis in patients with colorectal and lung cancer who are less than 40
years age, while younger age group patient with thyroid carcinoma have favorable
prognosis.
2) Sex: The prognosis of some tumors as colorectal and liver carcinomas is favorable in
females than males. On the other hand the prognosis of lung carcinoma is favorable in
males than females.
3) Tumor Type: e.g. Most sarcomas have poorer prognosis than carcinomas.
4) Tumor Site: e.g. Superficial tumors are diagnosed earlier than deeply seated tumors and
brain tumors.
5) Differentiation or grading: Well differentiated tumors are of favorable prognosis as they
grow slower.
6) Tumor stage: T1 N0 M0 tumors have much better prognosis than other stages, and
tumors assessed as T4 N3 M1 have the worst prognosis.
7) Stromal fibrosis: Associated with a favorable or good prognosis.
8) Efficiency of the immune system: Cancer cells are capable of producing an immune
response. Both cell-mediated and humoral immunity may be involved in the defense
mechanisms against cancer as they have anti-tumor activity. Disturbances of the immune
mechanisms can predispose to cancer.

These prognostic factors accordingly determine the 5-YEAR SURVIVAL RATE

CAUSES OF DEATH & EFFECTS OF MALIGNANT TUMOURS:

Malignant tumors may produce the same effects as benign tumors but they are more serious
owing to their rapid rate of growth and their highly invasive and destructive nature. These
effects include but are not limited to:
1) Anemia: diet deficiency, hemorrhage and bone marrow invasion.
2) Malnutrition due to obstruction of the alimentary tract.
3) Cachexia accompanied by weakness and wasting.
4) Organ failure as C.N.S. failure due to increased intracranial tension and pressure.
Renal, cardiac, liver, or respiratory failure results from compression, invasion,
obstruction or infection.
5) Infections and toxemia, pneumonia, septicemia, and peritonitis
6) Immunologic effects: lymphomas can depress the immune system.
7) Pain in advanced malignancy secondary to invasion of perineural lymphatics.

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