Neoplasm

Neoplasm
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Synapse Medical Academy 1
Neoplasm

Neoplasm

Published By:
Synapse Medical Academy

Edited By:
Synapse Publication Team

ISBN No:
978-984-34-4631-2

3rd Edition, 2022

July 2021
For Contact:
Synapse Medical Academy
4A, (1st Lift 3rd Floor), Dilara Tower
77 Bir Uttam C.R Dutta Road, Hatirpool, Dhaka.
Phone: 01978303381, 01968206771

Copyright © 2022. All rights reserved by the publisher. No part of this book may be
reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic
or mechanical including photocopying without prior permission from author.

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Contents

Sl. No. Topic Page No.

1. Neoplasm 05
2. Cells According to Proliferative Capacity 06
3. Stem Cell 07
4. Cell Cycle 08
5. Benign & malignant tumors 09
6. Locally malignant tumors 11
7. Ameloblastoma 12
8. Basal cell carcinoma 12
9. Criteria of a malignant tumor 13
10. Difference between Benign & malignant tumor 13
11. Carcinoma & Sarcoma 14
12. Hormone secreting or Producing Tumor 14
13. Hormone Dependent or Sensitive Tumor 15
14. Dysplasia 15
15. Carcinoma in situ 17
16. Metastasis 17
17. Proto-oncogene 20
18. Inherited & Familial Cancer Syndrome 21
19. Molecular basis of cancer 22
20. Carcinogens 23
21. Tumor Suppressor Gene 25
22. Carcinoma associated with AIDS 26
23. Occupational cancer 26
24. Chronic inflammatory states and cancer 27
25. Grading & staging of a tumor 27
26. Paraneoplastic syndrome 29
27. Tumor Marker 31
28. Pre-cancerous conditions 32
29. Carcinoid syndrome 34
30. Krukenberg Tumor 34
31. Radio & Chemo Sensitivity & Resistance 35
32. Spontaneous Regression of Tumor 36
33. Childhood tumors 37
34. Diagnosis of tumor: Cytology 37
35. Frozen section Biopsy 39
36. Fixatives 40
37. Immunohistochemistry 42
38. Environmental Pollution 42
39. Amyloidosis 43
40. Summary Box 44

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1. Neoplasm

 Neoplasia means new growth. And collection of Cells and stroma composing new growth
are referred to as Neoplasm.
 Tumor usually denotes swelling caused by inflammation. But now equated with neoplasm.
 Oncology (greek oncos = tumor ) study of tumor or neoplasm.

Neoplasm is defined as
“A neoplasia is a new growth, comprising an abnormal collection of cells the growth of
which exceeds and is uncoordinated with that of the normal tissue.” 

General phenomena associated with neoplasia:

 Fever
 Cachexia
 Thrombotic episode
 Polycythaemia
 Dermatomyositis

Cancer cachexia
 Equal loss of both fat & lean muscle mass
 Increased BMR
 Evidence of systemic inflammation ( eg. acute phase reactant)
 Mediator – TNF alpha, IL 1, PIF, IFN gamma

Local Features of Malignant Disease

Symptom
Haemorrhage
Lump
Bone pain or fracture
Skin abnormality
Ulcer
Dysphagia
Increasing constipation,
abdominal discomfort or pain
Airway obstruction, stridor,
cough, recurrent infection
Odynophagia, early satiety,
vomiting
Abdominal swelling (ascites)
Typical site or possible tumour
Stomach, colon, bronchus, endometrium, bladder, kidney
Breast, lymph node (any site), testicle
Bone (primary sarcoma, secondary metastasis from
breast, prostate, bronchus, thyroid, kidney)
Melanoma, basal cell carcinoma (rodent ulcer)
Oesophagus, stomach, anus, skin
Oesophagus, bronchus, gastric
Colon, rectum, ovary
Bronchus, thyroid
Bronchus, stomach, oesophagus, colon, rectum
Ovary, stomach, pancreas

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2. Cells According to Proliferative Capacity

Types of cell according to proliferative capacity:

 The ability of tissue to repair themselves is determined by their intrinsic proliferative
capacity And presence of tissue stem cells. Divided into 3 types.
 Labile tissue: Cells of this type continuously being lost and replaced by maturation from
tissue stem cell and proliferation of mature cells.
 Regenerate as long as pool of stem cell preserved.

Example:
 Haematopoietic cell of bone marrow
 Surface epithelial cells eg. Stratified sq cell of skin, oral cavity, vagina and cervix.
 Cuboidal epithelial of ducts of draining exocrine organs: Salivary gland, Pancreas, biliary
tract.
 The columnar epithelia of GI tract, uterus, fallopian tube.
 Transitional epithelium of urinary tract.

Stable Tissue: Cells of these tissue are in quiescent stage (Go stage of cell cycle) and have
minimal proliferative activity in normal state.
 They have limited regenerative capacity in response to injury. Except Liver.
 Proliferation of these cells particularly important in wound healing.

Example:
 Parenchyma of most solid tissues eg Liver, kidney and pancreas.
 Endothelial cell
 Fibroblast
 Smooth muscle cell

Permanent tissue: cells of these tissues considered to be terminally differentiated and non
proliferative in post natal life.
 Injury to brain and cardiac muscle is irriversible and reaults in scar. ( Scar formation)
 Limited cell replication and differentiation occurs in some areas of adult brain.

Example:
 Majority of neurons. ( Neuron)
 Cardiac muscle
 Skeletal muscle (Satellite cell attached to endomyseal sheath may show some
regenerative capacity)

Q. Example of stables tissue includes -

a) Liver
b) Heart
c) Epithelia of oral cavity
d) Pancreas
e) Transitional epithelium of urinary tract
TFFTF

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3. Stem Cell

 Stem cells: have dual property of being able to self-renew and give rise to differentiated
cells and tissues.
 Stem cells have two types of self-division –

Asymmetric division:
One daughter cell enters a differentiation pathway and give rise matures cell, while other
remains undifferentiated and remains its self-renewal capacity.

Symmetric division:
Both daughter cell retain self-renewal capacity. Such replication occurs early in
embryogenesis and stressed condition like bone marrow repopulation after ablative
chemotherapy

Fundamentally two variety

 Embryonic stem cell: Most undifferentiated. They present in inner cell mass of blastocyst.
Have virtually limitless self-renewal capacity and can give rise to every cell of the body. So
they are said totipotent.
 Tissue stem cell (also called adult stem cell): They are protected within tissue
microenvironment called stem cell niches, located in Bone marrow (Haematopoietic stem
cell), intestine (Crypts), Buldge region of hair follicle, limbus of cornea and sub ventricular
zone in brain.

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Q. Example of tissue stem cell

a) Embryo
b) Placenta
c) Hematopoietic stem cell
d) Crypts of intestine
e) Buldge region of hair follicle
FFTTT

4. Cell Cycle

Cell cycle
 Cell Cycle is a series of events that takes place in a cell as it grows and divides.
 Phase:
1. Interphase: cell spends most of its time in what is called interphase, and during this
time it grows, replicates its chromosomes, and prepares for cell division.
2. Cell division
 Checkpoint :
1. Cell growth checkpoint
2. DNA synthesis checkpoint
3. Mitosis Checkpoint
 Significance: Cancers occurs when cell cycle regulation is lost.

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5. Benign & Malignant Tumours

Classification of tumors on histological basis

Tissue Benign Malignant
Composed of One Parenchymal Cell Type
Connective tissue and Derivatives Fibroma Fibrosarcoma
Lipoma Liposarcoma
Chordoma Chondrosarcoma
Osteoma Osteogenic sarcoma
Endothelial and related tissues
Blood vessels Hemangioma Angiosarcoma
Lymph vessels Lymphangioma Lymphangiosarcoma
Mesothelium Mesothelioma
Brain coverings Meningioma Invasive meningioma
Blood cells and related cells Leukemias
Hematopoietic cells Lymphomas
Lymphoid tissue
Smooth Muscle Leiomyoma Leiomyosarcoma
Striated muscle Rhabdomyoma Rhabdomyosarcoma
Tumors of epithelial origin Squamous cell papilloma Squamous cell or epidermoid
Stratified squamous carcinoma
Basal cells of skin or adnexa Basal cell carcinoma
Epithelial lining of glands or ducts Adenoma Adenocarcinoma
Respiratory passages Papilloma Papillary carcinomas
Renal epithelium Cystadenoma Cystadenocarcinoma
Lover cells Bronchial adenoma Bronchogenic carcinoma
Urinary tract epithelium Renall tubular adenoma Renal cell carcinoma
(transitional) Liver cell adenoma Hepatocellular carcinoma
Urothelial papilloma Urothelial carcinoma
Hydatidiform mole Choriocarcinoma
Seminoma

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Embryonal carcinoma
Tumors of melanocytes Nevus Malignant melanoma

More than one neoplastic cell Type -Mixed tumors, Usually derived from one germ cell layer
Salivary glands Pleomorphic adenoma (mixed Malignant mixed tumor of
tumor of salivary gland salivary gland
Renal angle Wilms tumor
More than one neoplastic cell type derived from more than one germ cell layer – teratogenous
Totipotential cells in gonads or in mature teratoma ,dermoid cyst Immature teratoma,
embryonic rests teratocarcinoma

Heard Benign but malignant:

Chordoma : Malignant tumor of spinal cord
Mesothelioma : Malignant tumor of pleura
Melanoma : Malignant tumor of melanocytes
Hepatoma : Malignant tumor of hepatocytes
Lymphoma : Malignant tumor of lymphoid tissue
Synovioma : Malignant tumor of synovial membrane
Glioma : Malignant tumor of glial cell (eg. Astrocytoma, Oligodendrocyte)
Seminoma : Malignant tumor of germ cell of testis
Dysgerminoma : Malignant tumor germ cell of ovary
Medullablastoma : Malignant tumor of CNS

Q. Following tumors are histologically benign -

a) Astrocytoma
b) Meningeoma
c) Scwanoma
d) Medulloblastoma
e) Craniophyringeoma
FTTFT

Classification of bone tumor:

Category and Behavior Tumor Type Common Locations

fraction (%)
Cartilage Benign  Osteochondroma Metaphysis of long bones small
forming (30)  Chondroma bones of hands and feet
 Chondroblastoma Epiphysis of long bones
Chondromyxoid Tibia, pelvis
Fibroma
Malignant Chondrosarcoma Pelvis, Shoulder
(Conventional)
Bone forming Benign Osteoid osteoma Metaphysis of long bones
(26) Osteoblastoma Vertebral column
Malignantt Osteosarcoma Metaphysis of distal femur,
proximal tibia
Unknown Benign Osteoclastroma Epiphysis of long bones
origin (15) Aneurysmal bone cyst Proximal tibia, distal femur,
vertebra
Malignant Ewing sarcoma Diaphysis of long bones
Adamantinoma Tibia

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Q. Benign bone tumors are

a) Osteosarcoma
b) Osteoid osteoma
c) Exostosis
d) Ewing’s sarcoma
e) Osteochondroma
FTFFT

6. Locally Malignant Tumours

Locally malignant tumors are those which show invasion but no metastasis. The term
intermediate tumor is sometimes use for a tumor which behaves as benign. Locally malignant or
even may show metastasis.
Examples:
1) Basal cell carcinoma: Local invasion occurs but rarely metastasize.
2) Giant cell tumor of bone: The tumor is classified as benign, but some are locally
malignant and a small percentage shows metastasis.
3) Ameloblastoma: It arises from enamel organ. It is locally invasive but has a benign
course in most cases.
4) Carcinoid tumor: It is classified as malignant. These tend to infiltrate locally and
sometimes metastasize. Carcinoids of the appendix and rectum almost never
metastasize.
5) Gliomas: Astrocytoma, oligodendroglioma and ependymoma. Distinction between
benign and malignant lesions of gliomas is less evident. Most gliomas are highly
invasive. Malignant gliomas very rarely metastasize outside the central nervous system.
6) Deep-seated fibromatosis (Desmoid tumours): These are infiltrative masses that do
not metastasize.
7) Mixed salivary tumours
Q. Locally malignant tumors are (Residency -20219)
a) Ameloblastoma
b) Basal cell carcinoma
c) Marjolin’s ulcer
d) Melanoma
e) Ewing’s sarcoma
TTTFF

Class Notes:

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7. Ameloblastoma

General Features of Ameloblastoma

 Most common neoplasm of odontogenic  Locally invasive but does not
origin metastasize
 Usually in 3rd – 5th decade  About 80% of Ameloblastoma occur
 Rare in children & elderly in Mandible
 Mostly in posterior region of
mandible
 No specific gender prediction

Fig. Ameloblastoma

08. Basal Cell Carcinoma

 Most common type of skin cancer.

 Most cases are due to long term UV or Sun exposure.
 Most commonly occurs in sun exposed skin.
 Mostly in Elderly Men, 90 % in head neck region, Women, more diverse location
 Rarely metastasize
 Local destruction is major issue.
 Moderately radiosensitive.
 Diagnosed with skin biopsy.

 Subtype :
 Higher risk – infiltrative, micronodular
 Lower risk (Common) – nodular, superficial
 Treatment option :
 Surgical excision
 Moh’s surgery
 Electrodessection and curettage
 Topical creams

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 Radiation

Fig. Basal cell carcinoma

09. Criteria of A Malignant Cell

1. Pleomorphism-Variation in size & shape

2. Abnormal -Nuclear morphology
3. Mitosis - Atypical, bizarre mitotic figure
4. Loss of polarity
5. Haemorrhage & necrosis in center of a tumor

Q. Features of malignancy are- (Residency -2014)

a) Nuclear pleomorphism
b) Cytoplasmic vacuolation
c) Abnormal mitosis
d) Necrosis
e) Foreign body type of giant cell
T F T T (Necrosis often presented in malignancy with other characteristics features but is
not diagnostic features) F (Tumor giant cell present)

10. Difference between Benign & Malignant

Characteristics Benign Malignant

Differentiation/ Well differentiated: structure Some lack of differentiation
anaplasia sometimes typical of tissue origin (anaplasia) structure often atypical
Rate of growth Usually progressive and slow may May be slow to rapid mitotic
come to a standstill or regress figures may be numerous and
mitotic figures rare and normal abnormal
Local invasion Usually cohesive, expansile, well Locally invasive, infiltrating
demarcated masses that do not surrounding tissue, sometimes
invade or infiltrate surrounding may be misleadingly cohesive and
normal tissues expansile
Metastasis Absent Frequent, more likely with large
undifferentiated primary tumors
Capsule Encapsulated Not Capsulated

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11. Carcinoma & Sarcoma

Differences between Carcinoma and Sarcoma D

Carcinoma Sarcoma
Origin Epithelial tissue Mesenchymal tissue
Age More in old More in young
Vascularity Less vascular More vascular
Rate of Growth Less rapid More rapid
Cut section Less haemorrhage More haemorrhage
Spread Early by lymphatics (?) Early by blood (?)
Prognosis Less worse More worse
Microscopic Mostly, cells arranged in groups Mostly, Cells arranged individually
Radiosensitivity Highly radiosensitive More Radioresistant
Ca in situ occurs Dose not occur

Q. True about carcinoma

a) Originating from mesenchymal cell
b) Less vascular
c) Less rapid growth
d) Spread most preferably by blood
e) Highly radiosensitive
FTTFT

12. Hormone Secreting or Producing Tumour

Lock
 Lung – Brachial carcinomas cell carcinoma
 Ovarian ca
 Chromophore tumor of pituitary, Carcinoid tumors, Choricarcinoma
 Kidney - RCC
 Other – Islet cell tumor of pancreas, Seminoma, monodermal teratoma of the ovary.

Hormone producing tumor of ovary:

ABCDGHST
A – Arrhenoblastoma
B – Breer’s tumor
C – Choriocarcinoma
D – Dermoid cyst, Dysgerminoma (though rare)
G – Granulosa cell tumor
H – Hilus cell tumor
S – Struma ovary
T – Theca cell tumor
Q. Hormone producing tumours of the ovary
a) Brener’s tumour
b) Hilus cell tumour
c) Dysgerminoma
d) Theca cell tumour
e) Struma ovary
TTTTT

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Q. The following tumors secret hormone- (Residency-2017)

a) Bronchial carcinoma
b) Choriocarcinoma
c) Carcinoid tumor
d) Craniopharyngioma
e) Myxoma
TTTFF

13. Hormone Dependant or Sensitive Tumour

Testis Ovary
1.Leydig cell (Hilus cell tumor) 1. Sartoli, stroma cell tumor(Androblastoma)
2. Sartoli cell 2. Granulosa cell tumor
3. Granulosa cell 3. Choriocarcinoma
4. Choriocarinoma 4. Breer’s tumour
5.Theca cell tumour
6. Hilus cell tumour
7. Struma ovary
Malignant Melanoma Breast Carcinoma
Prostate Carcinoma Endometrial Carcinoma
Thyroid Carcinoma

Mnemonic: মা ও বাবার পরেই থাকে অন্যরা

Q. Following are hormone dependent tumour-
a) Papillary ca of the thyroid
b) Renal cell ca
c) Carcinoma of breast
d) Ca of pancreas
e) Ca of the prostate
TFTFT
Q. Hormone dependency may be exhibited by the following tumors (Residency-2021)
a) Malignant melanoma
b) Carcinoma of the prostate
c) Follicular carcinoma of the thyroid
d) Bronchial carcinoma
e) Retinoblastomas
TTTFF

14. Dysplasia

Dysplasia is a term that literally means disordered growth It is encountered principally in

epithelia and is characterized by a constellation of changes that include a loss in the uniformity
of the individual cells as well as a loss in their architectural orientation. Dysplastic cells may
exhibit considerable pleomorphism and often contain large hyperchromatic nuclei with a high
nuclear to cytoplasmic ratio.
Dysplasia is particularly common in squamous and transitional epithelia such as
 Cervix of uterus
 Respiratory tract in chronic cigarette smoker.
 Adjacent to foci of cancerous transformation Gall bladder (uncommon)

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 Oral mucosa (uncommon)

 Skin
 Urinary bladder
 Larynx

Characteristics of dysplasia:
1. Dysplastic cells show considerable pleomorphism (variation in size and shape).
2. Hyperchromatic nuclei which are abnormally large for the size of ccli.
3. Mitotic figures are more abundant than usual. Although almost invariably they conform
to normal pattern.
4. Dyskeratosis and diminished cellular polarity.
5. Presence of koilocytosis, i.e. cytoplasmic vacuolation around the nucleus.

Clinical significance of dysplasia:

Dysplastic changes mild to moderate grade may transform to cancer but this changes are
usually reversible and with the removal of inciting cause the epithelium may revert to
normal. However severe dysplasia may be irreversible.
Dysplasia differs from cancer in three important respects:
i) Lack of invasiveness
ii) Reversibility:
iii) Increased number of Mitosis
Regarding dysplasia and metaplasia:
 Metaplasia means replacement of one type of cells with another type of cells but not
phenotypically change, assoc. with tissue damage, repair, and regeneration.
 Dysplasia:
Cervical intraepithelial neoplasia (CIN-1): when dysplastic epithelium is present in basal
one third.
CIN-2: Basal two third is dysplastic
CIN-3: Whole epithelium is dysplastic but no crossing the basement membrane.
 If crossing the basement membrane, then it is called invasive carcinoma.
 Mutations assoc. with cancers may have mild dysplasia,
 It may be precursors of malignant neoplasm, but not always progress to cancer
 It is always completely reversible, if inciting agents are withdrawn.
 It often occurs in metaplastic epithelium, but all metaplastic epithelium is not
dysplastic.

Q. Dysplasia (Residency-2021)
a) Is always encountered in epithelium
b) Is characterized by presence of mitosis
c) Is characterized by altered nuclear-cytoplasmic ratio
d) Always progress to cancer
e) Of sometimes reverses to normal

T T F increased nucleo-cytoplasmic ratio) F (If inciting agents are withdrawl, it may reverse
back to normal, but anaplasia never back to normal) T

Q. Regarding differentiation and anaplasia of a tumor - (Residency-2013)

a) Malignant tumors are never well differentiated
b) Benign tumors may show features of anaplasia
c) Staging is dependent on above factors
d) Are assessed under microscope
e) Are subjective assessment

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FFFTF

15. Carcinoma in Situ

Carcinoma in situ:
When dysplasia is marked & involve the entire thickness of epithelium, the lesion is
known as carcinoma in situ. It is a epithelial neoplasm which has all the cellular features of
malignancy but has not yet invaded through the epithelial basement membrane. It is a pre-
invasive stage of carcinoma. It may progress to invasive carcinoma. It is every early stage and
its excision causes complete cure of cancer.
Examples:
1. CIN (cervical intraepithelial neoplasm)
2. Carcinoma in situ in the epidermis of skin preceding the formation of invasive sq. cell
carcinoma.
3. In situ cytological atypia in the lining epithelium of the respiratory tract in habitual
smokers. 4. In situ ca of the female breast: a) Ductal ca in situ. b) Lobular ca in situ.
4. Dysplastic leukoplakia of mouth
5. Adenomas of colon
6. Bowen's disease of skin.
7. Actinic keratosis
8. Erythroplasia of Queyrat
9. Paget's disease of skin
10. Carcinoma in situ of the urinary bladder.
11. Bowenoid papulosis of penis
Q. Carcinoma in Situ
a) Is a premalignant condition
b) Usually reverts back to normal state
c) Can metastasize through lymphatics
d) Is common in cervix
e) Is to be diagnosed by biopsy
FFFTT

16. Metastasis

Metastasis:
It is the process whereby primary malignant tumor spread to form secondary tumor at a
distant site discontinuous with the primary tumor.
[All malignant tumor metastasize except tumor of brain 'glioma’ and basal cell carcinoma of
skin.
Methods of metastasis:
1. Seeding of body cavities and surface
2. Lymphatic spread.
3. Hematogenous spread.
Box: Metastasis
 30% of newly diagnosed solid tumours (except melanoma) present with metastasis.
 Lymphatic route: mostly carcinoma but sometimes sarcoma.
 Hematogenous route: typically sarcoma but sometimes carcinoma.
 Skip metastasis: when local lymph nodes are by passed because venous-lymphatic
anastomoses or inflammation or radiation.
 Sentinel lymph node: first lymph node that receive lymph flow from the primary

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tumour.
 Blood borne metastasis commonly occurs in lungs and liver

No metastasis:
 Basal cell carcinoma
 Glial cell carcinoma
 Giant cell tumour of bone
 Ameloblastoma
 Craniopharyngioma
 Carcinoid tumour
 Gliomas
 Deep seated fibromatosis

Tumors commonly metastasize to bone:

 Breast
 Ca of bronchus of lung
 Thyroid ca except papillary ca
 Carcinoma of prostate
 Renal tumor

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May occurs in:

 Testis
 Ovary
 Melanoma
 Cholangio carcinoma

 Lung Cancers main sites for distant metastasis: BLAB

1) B: Bone
2) L: Liver Common site of
3) A: Adrenals bone metastasis:
4) B: Brain  Pelvis
 Gastric cancer main site of metastasis: LLB Pass  RIBS
1) L: Lung
 Upper end of
2) L: Liver
humarous
3) B: Bone marrow
4) Pass: Peritoneum
 Tumour that metastasize to skin: BLOCK
1) B: Breast
2) L: Lung
3) O: Ovary
4) C: Colon
5) K: Kidney
 Tumor that metastasize to Brain
1) Lung: 48%
2) Breast: 15%
3) Melanoma: 9%
4) Colon: 5%
Tumor metastasize to orbit:
 Breast ca
 Bronchogenic ca
 Prostate ca
 Gastrointestinal adeno ca
 Thyroid ca
 RCC
 Neuroblastoma
 Ewing sarcoma
 Wilms tumor
Q. Primary Tumor sites that metastasize to the brain includes [Diploma-18]
a) Lungs
b) Breast
c) Heart
d) Spleen
e) Colon
TTFFT
Q. Haematogenous metastasis occurs in (Residency-2011)
a) Malignant fibrous histiocytoma
b) Angiosarcoma
c) Basal cell carcinoma
d) Fibrosarcoma
e) Leiomyoma
T T F (Locally malignant tumour, no metastasis) T F (Benign tumour, no metastasis)

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(Ref: SRB manual of surgery 5th page 719)

Q. The neoplasms commonly metastasize to bones are (Residency-2021)

a) Papillary thyroid cancer
b) Carcinoma of prostate
c) Renal adenocarcinoma
d) Hepatocellular carcinoma
e) Glioblastoma multiforme
F (Follicular carcinoma of thyroid) T T F F (Locally malignant tumour, GBM is a grade IV
malignant tumour of brain, usually confined to brain, not metastasis)

17. Proto-Oncogenes

Oncogenes, Oncoproteins, and Unregulated Cell Proliferation:

 Proto-oncogenes: normal cellular genes whose products promote cell proliferation
 Oncogenes: mutated or overexpressed versions of proto-oncogenes that function
autonomously, having lost dependence on normal growth promoting signals
 Oncoprotein: a protein encoded by an oncogene that drives increased cell
proliferation through one of several mechanisms

Oncogene Cancer Diagnostic Targeted Therapy

P110α Breast, prostate, endometrial, PCR, sequencing
colorectal, cervical, head and neck,
gastric, lung
EGFR Lung, glioma, colorectal, ovarian, PCR, FISH, IHC Gefitinib, erlotinib,
breast cetuximab
ERBB2 Breast, gastric, ovarian, bladder POCR, Trastuzumab,
(HER2) sequencing lapatinib
B-RAF Melanoma, thyroid, colorectal, PCR, sequencing vemurafenib
ovarian
K-RAS Pancreatic, lung, colorectal, PCR, sequencing
endometrial, ovarian
H-RAS Bladder PCR, sequencing
N-RAS Melanoma, AML PCR, sequencing
MYC Lymphomas, colorectal, breast, prostate, FISH, IHC
melanoma, neuroblastoma, ovarian
BCR-ABL CML, ALL, AML FISH, PCR Imatinib, dasatinib,
nilotinib
IDH1 Glioblastoma, AML PCR, sequencing
IDH2 Glioblastoma, AML PCR, sequencing
JAK2 CML, ALL FISH
KIT Gastrointestinal stromal tumors, IHC, flow
AML, melanoma cytometry
MET Kidney, gastric, lung, head and neck,
colorectal
FLT-3 AML PCR

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P53 (Guardian of the genome)

 P53 is the central monitor of stress in the cell and can be activated be
1) Anorexia
2) Inactivated signaling by mutated Oncoprotein
3) DNA damage
 P53 controls the expression and activity of proteins involved in cell cycle arrest, DNA
repair, cellular senescence and apoptosis.
 If DNA damage cannot be repair,P53 induces additional events that lead to cellular
senescence or apoptosis
 The majority of human cancers demonstrate biallelic loss of function mutation in TP53

Q. Regarding p53 gene (Residency-2012)

a) It is associated with adult malignant tumors only
b) It arrests cell cycle in G1 phase
c) It is stimulated by lionizing radiation
d) It is located in chromosome 21
e) It is a tumor suppressor gene
FTTFT
Q. Oncogenes – (Residency-2016)
a) Have the ability to promote cell growth in the absence of mitogenic signals
b) Promote autonomous cell growth in cancer cells
c) Product are called Oncoproteins
d) Are physiologic regulators of cell proliferation and differentiation?
e) Are biochemical indicators of the presence of tumor
FTTFF

18. Inherited & Familial Cancer Syndrome

Inherited cancer syndrome (autosomal dominant)

Gene Inherited predisposition
RB Retinoblastoma
P53 Li-fraurmeni syndrome (various tumors)
P161 NK1A Melanoma
APC Familiar adenomatous polyposis / colon cancer
NF1, NF2 Neurofibromatosis 1 and 2
BRCA1, BRCA2 Breast and ovarian tumors
MEN, RET Multiple endocrine neoplasia 1 and 2
MSH2, MLG1 Hereditary non-polyposis colon cancer
MSH6
PATCH Nevoid basal cell carcinoma syndrome
Familial cancers
Familial clustering of cases, but role of inherited predisposition not clear for each individual
Breast cancer
Ovarian cancer
Pancreatic cancer

Inherited autosomal recessive syndromes of defective DNA repair

Xeroderma pigmentosum
Ataxia- telangiectasia
Bloom syndrome

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Fanconi anemia

Familial Cancer Syndrome:

 Early age at onset
 Two or more relatives with cancer
 Multiple or Bilateral tumor
 Most cancers are not inherited but occurs from accumulation of mutation
 Siblings have 2-3 times increased risk.

Example
 Breast Ca
 Ovarian Ca
 Pancreatic Ca
 Malignant Melanoma
 BCC
 NPCC
 Medullary & Papillary ca of thyroid
 Von hipple lindue diseasws
 Li fraumani syndrome
 Pautz Jeghar's syndrome

Q. Following malignant conditions have familial predisposition (Diploma Surgery July

2020)-
a) Carcinoma of the breast
b) Colorectal carcinoma
c) Hepatocellular carcinoma
d) Medullary carcinoma of the thyroid
e) Renal cell carcinoma
TTETT

19. Moclecular Basis of Cancer

Cellular and Molecular Hallmarks of Cancer:

All cancers display eight fundamental changes in cell physiology, which are considered
the hallmarks of cancer. These changes consist of the following:

 Self-sufficiency in growth signals. Tumors have the capacity to proliferate without

external stimuli, usually as a consequence of oncogene activation.

 Insensitivity to growth-inhibitory signals. Tumors may not respond to molecules that

inhibit the proliferation of normal cells, usually because of inactivation of tumor suppressor
genes that encode components of these growth inhibitory pathways.

 Altered cellular metabolism. Tumor cells undergo a metabolic switch to aerobic glycolysis
(called the Warburg effect), which enables the synthesis of the macromolecules and
organelles that are needed for rapid cell growth.

 Evasion of apoptosis. Tumors are resistant to programmed cell death.

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 Limitless replicative potential (immortality). Tumors have unrestricted proliferative

capacity, a stem cell like property that permits tumor cells to avoid cellular senescence and
mitotic catastrophe.

 Sustained angiogenesis. Tumor cells, like normal cells, are not able to grow without a
vascular supply to bring nutrients and oxygen and remove waste products. Hence, tumors
must induce angiogenesis.
 Ability to invade and metastasize. Tumor metastases are the cause of the vast majority of
cancer deaths and arise from the interplay of processes that are intrinsic to tumor cells and
signals that are initiated by the tissue environment.
 Ability to evade the host immune response. You will recall that the cells of the innate and
adaptive immune system can recognize and eliminate cells displaying abnormal antigens
(e.g., a mutated oncoprotein). Cancer cells exhibit a number of alterations that allow them to
evade the host immune response.

20. Carcinogens

Carcinogens:
Definition:
A large number of agents cause genetic damage and induce neoplastic transformation of
cells. These are called carcinogens.
Classification:
1. Chemical carcinogens
2. Radiant energy and
3. Oncogenic viruses and some other microbes.

 Chemical carcinogen:

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1. Direct-acting carcinogens:
i) Alkylating agents: B-propriolactone. Dimethyl sulfate, Diepoxybutane, Anti-cancer
drugs (cyclophosphamide, chlorambucil, nitrosoureas and others)
ii) Acylating agents: 1-acetyl-imidazole, Dimethylcarbamyl chloride

Mnemonics:
 Alkylating agents: NCC PDD
1. N- Nitrosourease
2. C- Chlorumbucil
3. C- Cyclophosphamide
4. P- Propiolactone
5. D- Dimethl sulphate
6. D- Diepoxy butane
Acylating Agents: AD
1) A- Acetyl imidazole
2) D- Dimethyl carbonyl chloride
2. Pro-carcinogens that require metabolic activation:
i) Polycyclic and heterocyclic aromatic hydrocarbons: Benz (a) anthracene, Dibenz
(a, h) anthracene, 3-Methylcholanthrene,7, 12-Dimethylbenz (a) anthracene.
ii) Aromatic amines, amides, azo dyes: 2-Naphthylaminc, benzidine,
2-Acetylaminofluorene, Dimethylaminoazobenzene (butter yellow)

3. Natural plant and microbial products:

Aflatoxin B, griseofulvin, cycasin, safrole, betel nuts.

4) Others: Nitrosamine & amides, vinyl chloride, nickel, chromium, insecticides, fungicides,
polychlorinated biphenyls.

Radiant energy:
a) Ultraviolet rays: Associated with SCC BCC melanoma of skin
 UVA (320-400 nm)
 UVB (280-320 nm)
 UVC (200-280 nm)

b) Ionizing radiation: Associated with leukemia & brain fumoir

 Electromagnetic :X-ray, Y-ray
 Particulate : a- particle, B- particle
Oncogenic microbes:
a) Viruses:
i. DNA oncogenic viruses:
● Human papillomavirus (16,18,33,39)-Cervical and Anal cancer
● Human papillomavirus (5,8,17)-Skin cancer
● Epstein Barr virus-Burkitt’s lymphoma,Nasopharyngeal CA, Hodgkin’s dis.,
Immunoblastic lymphoma
● Hepatitis B virus-HCC
● HHV-8-Kaposi Sarcoma, Body cavity lymphoma
ii. RNA oncogenic virus:
 HTLV-1-T call leukemia/lymphoma
 Hepatitis C virus-HCC

iii. Oncogenic bacteria:

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 H. pylori-Gastric lymphoma(M.A.L.T-omas),Gastric carcinoma

 C. jejuni-Small intestinal MALToma

iv. Oncogenic fungus:

 Spiregillus flavus-Aflatoxin causes HCC

v. Oncogenic parasite:
 Schistosoma haematobium-UB carcinoma
 Chloronsis sinensis-Cholangiocarcinoma
 Opisthrochis vereni(Flukes)-Cholangiocarcinoma

Q. Following are pro carcinogens? [Residency-15]

a) Benzanithracene
b) Cycasin
c) Chlorambucil
d) Benzidine
e) Dimethyl Sulphate
TTFTF

21. Tumor Suppressor Gene

Tumor Cancer Diagnostic Targeted

Suppressor Therapy
P53 Lung, colorectal, bladder, ovarian, IHC, PCR, sequencing
head and neck, gastric, breast,
prostate
PTEN Glioblastoma, melanoma, prostate, IHC, PCR, sequencing
breast, endometrial, thyroid, lung,
colorectal, AML, CLL
P16INK4A Melanoma, pancreatic, lung, bladder, IHC, PCR, sequencing
head and neck, colorectal, breast
P14ARF Lung, bladder, head and neck, IHC, PCR, sequencing
colorectal, breast
BRCA1 Breast, ovarian PCR, sequencing
BRCA2 Breast, ovarian PCR, sequencing
LKB1 Lung, gastrointestinal, pancreatic, PCR, sequencing
cervical, melanoma
VHL Kidney, adrenal, hemangioblastoma PCR, sequencing
APC Colorectal, gastric PCR, sequencing
FBXW7 All, bile duct, colorectal, gastric, PCR, sequencing
endometrial, lung, pancreatic,
prostate, ovarian
Rb Retinoblastoma, lung, bladder, IHC, PCR, sequencing
esophageal, osteosarcoma, glioma,
liver, CML, prostate, breast
NF1 Neurofibroma, neuroblastoma, PCR, sequencing
glioma, colorectal
NF2 Meningioma, schwannoma, glioma PCR, sequencing

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Abbreviations: All, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; CML,
chronic myeloid leukemia; FISH, fluorescent in situ hybridization, IHC,
immunohistochemistry; polymerase chain reaction

22. Carcinoma Associated with AIDS

Neoplasm in HIV infection

 Kaposi’s sarcoma
 Primary lymphoma of brain
 Invasive ca of uterine cervix
 Cervical cancer
 Vulval cancer
 Anal cancer
 Penile cancer
 Hepatocellular ca
 Non Hodgkin & Hodgkin lymphoma
 Sq cell ca

23. Occupational Cancer

Occupational cancers
Agents or groups of agents
Arsenic and arsenic compounds
Asbestos
Benzene
Beryllium and beryllium
compounds
Cadmium and cadmium
compounds
Chromium compounds
Nickel compounds
Radon and its decay products
Vinyl chloride
Human cancer site for which reasonable evidence is
available
Lung skin hemangiosarcoma
Lung, mesothelioma gastrointestinal tract (esophagus,
stomach, large intestine
Leukemia, (AML)
Lung, Carcinoma
Prostate, carcinoma
Lung carcinoma
Lung & oropharyngeal carcinoma
Lung carcinoma
Hepatic Angiosarcoma

 Lung carcinoma → arsenic, asbestos, beryllium, chromium, nickel, Radon,

uranium, silicon, strontium.
 High incidence of carcinoma is associated with
A. Asbestoses worker
B. Nickel worker

Q. Asbestoses is associated with? [Res-15]

a) Leukemia
b) Mesothelioma
c) Oesophageal ca
d) Colonic ca
e) Angiosarcoma

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FTTTF

24. Chronic Inflammatory States and Cancer

Pathologic condition Associated Neoplasm (s) Etiologic agent

Asbestosis, silicosis
Inflammatory bowel disease
Lichen sclerosis
Pancreatitis
Chronic cholecystitis
Reflux esophagitis, Barrett
esophagus
Sjogren syndrome,
Hashimoto thyroiditis
Opisthorchis, cholangitis
Gastritis/ulcers
Hepatitis
Osteomyelitis
Chronic cervicitis
Chronic cystitis
Mesothelioma, lung
carcinoma
Colorectal carcinoma
Vulvar squamous call
Pancreatic carcinoma
Gallbladder cancer
Esophageal carcinoma
MALT lymphoma
Cholangiocarcinoma, colon
carcinoma
Gastric adenocarcinoma,
colon lymphoma
Hepatocellular carcinoma
Carcinoma in draining
sinuses
Cervical carcinoma
Bladder carcinoma
Asbestos fibers, silica
particles
Alcoholism, germline
mutations (e.g, in the
trypsinogen gene)
Bile acids, bacteria,
gallbladder stones
Gastric acid
Liver flukes (opisthorchis
fellineus)
Helicobacter pylori
Hepatitis B and or C virus
Bacterial infection
Human papillomavirus
schistosomiasis

25. Grading & Staging of a Tumor

Grading:
Grading refers to the level of differentiation of the tumor.

Grading of a tumour is based on:

 The degree of differentiation of the tumour cells.
 The number of mitoses within the or architectural features
Grade I →> 75% cells are differentiated.
Grade II → 75 - 50% cells are differentiated.
Grade III → 50 - 25% cells are differentiated.
Grade IV → 25 % cells are differentiated.
Staging: Staging refers to the extent of spread of a cancer within the pt.
Staging of a tumour is based on:
 The size of the primary lesion,
 It's extent of spread to regional lymphnodes

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 The presence or absence of blood bone metastasis

The major staging systems are -

1. UICC (Union International Centre Cancer) employs TNM system.
2. AJC (American Joint Committee) employs different nomenclature

 TNM system:
T for primary tumor →
TO - Carcinoma in situ
T1
T2 increasing size
T3

N for regional lymph node involvement

NO - No nodal involvement
N1
N2 increasing number & range of nodes
N3

M for metastasis
MO - No metastasis
M1
M2 metastasis present

 AJC system:
This system divides all cancers into
Stage 0
Stage 1 Considering the size of tumors, metastasis present
Stage II nodal involvement & distant metastasis
Stage III
Stage IV

Importance of grading and staging: selection of best form of therapy for the pt.

Q. Grading of the malignant tumour [Residency-19]

a) Depends on differentiation
b) Is also known as pathological staging
c) Is a light microscopic assessment
d) Is same in all organs
e) Correlate with tumour progression
TFTTT

Q. Staging of a Cancer [Residency-16]

a) Number of mitosis
b) Spreading of cancer cells to regional lymphnodes
c) Is based on degree of differentiation of tumour cells
d) Depends on the presence and absence of blood borne metastasis
e) Is based on the size of lesion
FTFTT

Q. Grading of malignant tumor is based in – (Residency-2016)

a) Cellular morphology
b) Regional lymph node metastasis
c) Size of the tumor

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d) Number of mitosis
e) Distant metastasis
TFFTF

26. Paraneoplastic Syndrome

Definition: Some cancer bearing individuals develop signs and symptoms that cannot readily
be explained by the anatomical distribution of the tumour or by the elaboration of hormones
indigenous to tissue from which the tumour arose, these are known as paraneoplastic
syndrome.
 Occurs in 10% of the pt with malignant disease
 May represent the earliest manifestation of an occult cancer
 May even be lethal
 Have the ability to promote cell growth in the absence of mitotic signals
 Biochemical indicators of the presence of a tumour
Clinical syndrome Major forms of Neoplasia Causal
Mechanism(s)Agent (s)
Endocrinopathies
Cushing syndrome  Small cell carcinoma of lung ACTH or ACTH like
(PNS)  pancreatic carcinoma substance
 Neural tumor s
Syndrome of inappropriate Small cell carcinoma of lung, Antidiuretic hormone or
antidiuretic hormone intracranial neoplasms atrial natriuretic hormones
secretion (SIADH)
Hypercalcemia  Squamous cell carcinoma Parathyroid hormone -
(BRAS) of lung related protein, TGF-α,
 Breast carcinoma TNF ,IL -I
 Renal carcinoma
 Adult T cell leukemia
/lymphoma
 Ovarian carcinoma
Hypoglycemia  Fibrosarcoma Insulin or insulin like
 Other mesenchymal substance
sarcomas
 Hepatocellular carcinoma
 Ovarian carcinoma
Carcinoid syndrome  Bronchial adenoma Serotonin, bradykinin
(BGP) (carcinoid)
 Pancreatic carcinoma
 Gastric carcinoma
Polycythemia  Renal carcinoma erythropoietin
 Cerebellar hemagioma
 Hepatocellular carcinoma
NERVE AND MUSCLE SYNDROME
Myasthenia Bronchogenic carcinoma, Immunologic
thymoma
Disorders of the central and Breast carcinoma, teratoma
peripheral nervous systems
Dermatologic disorders
Acanthosis nigricans  Gastric carcinoma Immunologic: secretion of
 Lung carcinoma epidermal growth factor

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 Uterine carcinoma
Dermatomyositis Bronchogenic and breast Unknown
carcinoma

Vascular and hematologic changes

Venous thrombosis Pancreatic carcinoma Tumor products (mucins
(Trousseau phenomenon) Bronchogenic carcinoma that activate clotting)
Others cancers
Nonbacterial thrombotic Advanced cancers Hypercoagulability
endocarditis
Anemia Thymoma Immunologic
Others
Nephrotic syndrome Various cancers Tumor antigens, immune
complex

Paraneoplastic syndrome of lung cancer:

 Hyponatremia
 Hypercalcemia
 Hypocalcemia
 Cushing syndrome
 Gynecomastia
 Carcinoid Syndrome
 Eosinophilia
 Nephrotic Syndrome
 Dermatomyositis

Q. Paraneoplastic syndromes - (Residency-2016)

a) Occur in about 90% of patients with malignant disease
b) May represent the earliest manifestation of an occult neoplasm
c) May even be lethal
d) Can mimic metastatic disease
e) Are relatively frequent in patients with cancer
FTTTF
Explanation:
a) Occurs in 10% patient
e) Relatively infrequent

Q. Hypoglycemia is associated with - (Residency-2017)

a) Fibrosarcoma
b) Pancreatic carcinoma
c) Renal cell carcinoma
d) Hepatocellular carcinoma
e) Papillary serous carcinoma
TFFTF

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27. Tumor Marker

Definition:
Tumor markers are the biochemical indicators of the presence of a tumor selected tumor
makers.
 It can support diagnosis of the cancer.
 Can determine the response to the therapy.
 May indicate relapse during follow ups.

Hormones
Human chorionic gonadotropin Trophoblastic tumors , nonseminomatous
testicular tumors
Calcitonin Medullary carcinoma of thyroid
Catecholamine and metabolites Pheochromocytoma and related tumors
Ectopic hormones See paraneoplastic syndromes
Oncofetal Antigens
α-fetoprotein Liver cell cancer, nonseminomatous germ
cell tumors of testis
Carcinoembryonic antigen Carcinomas of the colon, pancreas, lung,
stomach, and heart
Isoenzymes
Prostatic acid phosphatase Prostate cancer
Neuron-specific enolase Small-cell cancer of lung, neuroblastoma
Specific Proteins
Immunoglobulins Multiple myeloma and other gammopathies
Prostate cancer
Prostate-specific antigen and prostate- Prostate cancer
specific membrane antigen
Mucins and other Glycoproteins
CA-125 Ovarian cancer
CA-19-9 Colon cancer, pancreatic cancer
CA-15-3 Breast cancer
New Molecular Markers
p53, APC, RAS mutants in stool and serum Colon cancer
p53 and RAS mutants in stool and serum Pancreatic cancer
p53 and RAS mutants in sputum and serum Lung cancer
p53 mutants in urine Bladder cancer

N.B: Elevated α-fetoprotein may also be found in:

1. Spina bifida
2. Anencephaly
3. Omphalocele,Gastrochysis(abd.wall defect)
4. All female nonseminomatous germ cell tumor except dysgerminoma and
choriocarcinoma
5. Viral hepatitis,Liver cirrhosis

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6. Esophageal and deodenal atresia

7. Fetal distress, Twin pregnancy, Cong. nephritic syndrome, IUD
8. Ataxia telengeactasis
Decreased level of alpha-fetoprotein:
1. Down syndrome
2. Trisomy-18
3. DM
Q. Following tumors secretes hormone [Residency- 17]
a) Bronchial ca
b) Choriocarcinoma
c) Carcinoid tumor
d) Craniopharyngioma
e) Myxoma
TTTFF
Q. Tumor markers are (Residency- 13, 16, 17)
a) TSH
b) HbA1C
c) PSA
d) CEA
e) CA-125
FFTTT

28. Pre-Cancerous Conditions

Box: Precursor lesions leads to cancer

 Barret eosophagus
 Squamous metaplasia of bronchial epithelium due to smoking
 UB mucosa due to schistosoma infection.
 Pernicious anemia, chronic atrophic gastritis
 Non inflammatory hyperplasia can lead to cancer, eg: endometrial hyperplasia
 Leukoplakia
 Villous adenoma(leads to cancer in 50 % case)
 Rarely transform to cancer: pleomorphic adenoma, leiomyoma.
 Not at all: lipoma
 T-cell deficient especially oncogenic viruses: increased risk of cancer.

Precancerous disorders:

Organ Diseases
Skin  Xeroderma pigmentosum
 Solar actinic keratosis
 Burn ulcer, varicose ulcer
 Marjolin's ulcer
 Dysplasia naevi
 Leukoplakia
 Radiodermatitis Bowen's disease
Mouth  Leukoplakia
 Erythroplakia
 Plummer Vinson/ Paterson-Kelly syndrome
Oesophagus  Barrett oesophagus
Stomach  Chronic gastritis
 Pernicious anaemia

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 Adenomatous polyp
 Chronic gastric ulcer
Small intestine  Crohn's disease
Colon  Familial adenomatous polyp
 Chronic ulcerative colitis
Hepato-biliary  Cirrhosis of liver
 Cholelithiasis
Lung Bronchial metaplasia & dysplasia
Thyroid gland Autoimmune thyroiditis
Bone Paget's disease
Breast  Intraductal epithelial hyperplasia
 Small duct papilloma
 Sclerosing adenosis
Female genital  Cervical dysplasia
tract  Endometrial hyperplasia
 Dysplasia of vulva
 Leukoplakia
Penis  Leukoplakia

Q. Recognized precancerous condition include?

a) Small intestine polyps in Peutz-Jegher’s syndrome
b) Colonic polyps of familial adenomatous polyposis coli
c) Xeroderma pigmentosum
d) Bowen’s disease
e) Molluscum sebaceoum
FTTTF
Q. Pre-cancerous conditions of oral cavity are?
a) Periodontitis
b) Erythroplakia
c) Leukoplakia
d) Apthous ulcer
e) Erythema multiforme
FTTFF
Table of Non –Precancerous disorders:

Skin  Psoriasis
 Keloid
 Eczema
 Condylomata acuminatum
 Hyperthropic scar
 Nevus
 Blue Nevus
 Moluscusm contagiosum
 Moluscum sebasceum
 Erythema multiformi
Mouth  Apthous ulcer (Canker sore)
Female genitalia  Cervical erosion(Smiddy)
Breast  Fibrocystic disease of the beast
 Hamartomatous polyp
Polyp  Peutz jegher polyp(itself is not
 premalignant)- Smiddy
 Lymphoid polyp

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 Inflammatory nasal polyp

Male reproductive  Nodular hyperplasis of the prostate
system  Bening enlargement of the prostate
 Hemangioma of liver

29. Carcinoid Syndrome

Carcinoid syndrome is associated with:

 Bronchial adenoma
 Gastric carcinoma
 Pancreatic carcinoma

1) Regarding carcinoid syndrome:

 Carcinoid syndrome is due to carcinoid tumor.
 These tumors are commonly seen in the appendix, ileum and the rectum, though they
may occur at any site in the GIT.
 Intestinal carcinoids are of low-grade malignancy. They metastasize to the liver and the
lymph nodes.
 When secretions of the neoplastic enterochromaffin cells of the tumor with liver
metastases are released, patient gets systemic symptoms of carcinoid syndrome.
 Serotonin (5-HT) is released and its metabolite (5-HIAA) is excreted in the urine.
In addition to serotonin, other hormones are also released.
 The cardinal features of the syndrome are flushing and diarrhea (precipitated by
exercise, alcohol or certain foods)
 Symptoms and signs due to local bowel tumors and liver metastases (hepatomegaly)
may be present.
 Right-sided heart valve lesions may be present.
 Diagnosis is confirmed by 24-hour urinary 5-HIAA estimation.

Carcinoid syndrome component: CARCinoid

 C: Cutaneous Flushing
 A: Asthmatic wheezing
 R: Right sided valvular heart disease
 C: Cramping pain & Diarrhea

Q. Carcinoid syndrome is associated with?

a) Bronchial adenoma
b) Pancreatic carcinoma
c) Renal cell carcinoma
d) Fibrosarcoma
e) Gastric carcinoma
TTFFT

30. Krukenberg Tumor

 Primary tumor : Gastric adeno ca

 Route of metastasis : Body seeding, Coelomic spread
 Histology : ‘ Signet ring ‘

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 Nature : Predominantly solid, Lobulated, Enhancing, commonly large > 10 cm

 Marker : CEA
 Secrete : Mucin

31. Radio & Camo Sensitivity & Resistanse

Highly Sensitive:
 Wilm’s tumour
 Ewings sarcom
 Lymphoma
 Seminoma
 Myeloma

Moderately Radio Sensitive:

 Small cell ca of lung
 Breast Ca
 Ovarian ca
 Teratoma
 Skin BCC
 Medulloblastoma
 Plasmocytoma
 Anaplastic thyroid ca
 GI ca

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 Testicular ca
 Head & Neck ca
 SCC of skin

Highly Radio resistant:

 Melanoma
 Osteosarcoma
 Pancreatic ca
Relatively radio resistant:
 Cervical ca
 Bladder ca
 Soft tissue sarcoma
 Sq cell ca of lung
 RCC
 Rectal ca

Highly chemosensitive:
 Wilm’s tumor
 Ewing’s sarcoma
 Lymphoma ( Hodgkin and high grade non hodgkin)
 Teratoma of testis
 Leukemia
 Chorio carcinoma
 Rhabdomyosarcoma

Moderately Sensitive:
 Small cell lung cancer
 Breast cancer
 Ovarian cancer
 Myeloma
 Lymphoma ( low grade non Hodgkin)
 Leukaemia
 Leukaemia
 Advance ca cervix
 Leiomyosarcoma

Highly chemoresistant:
 Melanoma
 Sq cell lung ca
 Large bowel ca

Q. Chemosensitive cancers are?

a) Testicular cancers
b) Melanoma
c) Lymphoma
d) Leiomyosarcoma
e) Rhabdomyosarcoma
TFTTT

32. Spontaneous Regression of Tumor

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Spontaneous regression of cancer commonly occurs:

1. Testicular germ cell tumour, Neuroblastoma,
2. Malignant melanoma, Cutaneous BCC, Breast cancers,
3. Endometrial cancers, Thyroid cancers (Papillary, Follicular carcinoma),
4. Prostate, RCC, Leukemia /Lymphoma).

33. Childhood Tumours

Common Malignant neoplasms of infancy and childhood:

0 to 4 years 5 to 9 year 10 to 14 year
Leukemia Leukemia
Retinoblastoma Retinoblastoma
Neuroblastoma Neuroblastoma
Wilms tumor
Hepatoblastoma Hepatocellular carcinoma Hepatocellular
carcinoma
Soft – tissue sarcoma (especially Soft-tissue sarcoma Soft-tissue sarcoma
rhabdomyosarcoma)
Teratomas
Central nervous system tumors Central nervous system Osteogenic sarcoma
tumors
Ewing sarcoma Thyroid carcinoma
Lymphoma Hodgkin disease

Q. Common Childhood Solid tumours are?

a) Hemangioma
b) Nephroblastoma
c) Hepatoblastoma
d) Lymphangioma
e) Hamartoma
FTTFF

34. Diagnosis of Tumor: Cytology

Laboratory Diagnosis of Tumors

1. Cytology
2. Histopathology
3. Tumor Markers
4. Immune Cytochemistry
5. Molecular Diagnosis
6. Flow Cytometry

Cytology:
1. Screen for carcinoma of the cervix, often at an in situ stage
2. Endometrial carcinoma
3. Bronchogenic carcinoma
4. Bladder- Malignant urothelial tumors. TCC
5. Prostatic tumors
6. Gastric Carcinomas

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7. Identification of tumor cells in abdominal, pleural, joint and CSF

Sample for cytogical examination

 Sputum
 Scraping from oral ulcer
 Urine

FNAC:
FNAC can be:
1) Imaging Guided: Pelvic lymph node, pancreas.
2) Non-guided: Breast, thyroid, lymph node, prostate, subcutaneous nodule

FNAC cannot differentiate in:

 Follicular Carcinoma
 Benign Follicular Adenoma
Can Differentiate:
 Colloid nodule
 Thyroiditis
 Papillary ca
 Medullary Ca
 Anaplastic Ca
 Lymphoma
Advantage of FNAC:
1. Its less expansive
2. Can be performed outpatient dept.
3. Result is available in 20-30mins
4. Extremely reliable, Rapid & Useful
5. Highly Accurate in experience hand.
Disadvantages:
1. Less invasive
2. Can’t give detailed examination of tissue architecture
3. Inexperienced hands results are not reliable
If suspicious → Biopsy is done

Q. FNAC is done for the diagnosis of (Residency-2019)

a) Tubercular lymphadenitis
b) Hemangioma of liver
c) Papillary carcinoma of thyroid
d) Cystadenocarcinoma of ovary
e) Stromal invasion of a tumor
TTTFF
Explanation:
FNAC cannot differentiate in:
 Thyroid Tumour
 Follicular Carcinoma
 Benign Follicular Adenoma

Can Differentiate:
 Colloid nodule

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 Thyroiditis
 Papillary ca
 Medullary Ca
 Anaplastic Ca
 Lymphoma

Advantage of FNAC:
 Its less expansive
 Can be performed outpatient dept.
 Result is available in 20-30mins
 Extremely reliable, Rapid & Useful
 Highly Accurate in experience hand.

Disadvantages:
 Less invasive
 Can’t give detailed examination of tissue architecture
 Inexperienced hands results are not reliable

Q. Exfoliative cytology is useful for the diagnosis of – (Residency-201)

a) Meningioma
b) Multiple myeloma
c) Bladder cancer
d) Bronchial cancer
e) Cervical cancer
FFTTT
Explanation:
Exfoliative cytology is vaseful for:
1. Lung carcinoma
2) Bladder cancer
3. Cervical cancer
4. Endometrial cancer

35. Frozen Section Biopsy

Uses of Frozen section biopsy:

1. It is commonly used for urgent histological or on table diagnosis of malignancy
2. Depending on result, surgeon can plan next course of operation
3. Determines whether margins are free of malignancy
4. Determine whether the breast nodule is benign or malignant & decide to perform
lumpectomy or mastectomy.
5. Determine presence or absence of ganglion cells in Hirschprung disease in surgical
pathology.
6. Special uses are:
 Used in enzymatic histochemistry
 Used in non enzymatic histochemistry
 Used in immunofluorescence
 In some neuropathology technique: example, for silver (Ag) & Gold (Au)
impregnation.
 Used for detection of amyloid tissue

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Q. Frozen section biopsy is used to-

a) Differentiates benign from malignant
b) Used during surgery to see the extent of the margin
c) Used in non enzymatic histocytochemistry
d) Performed before surgery
e) Presence and absence of ganglionic cell in Hirschprung disease
TTTFT

36. Fixative

Classification of Fixaives:
1.Tissue Fixative:
 Buffered Formalin
(10% formal saline)
 Buffered
Gluteraldehyde
 Zenker’s fluid
 Bouin’s fluid
2.Cytological fixative: 3.Histochemical fixative:
 Formalin solution  Formal saline (10%
alcohol formalin)
 95% Ethanol  Cold acetone
 95% Rectified spirit  Absolute alcohol
 100% Methanol
 Isopropyl
alcohol/propanol
 Alcohol ether

Special Attention: Not Fixatives

1. Xylin
2. Toluin
3. Glycerin
4. Gelatine
5. Normalin (normal saline)
6. Parraffin
7. Chloroform
8. Agar
9. 40% Formaldihyde
Aims of Fixation:
1. It should prevent autolysis & putrefaction of the cell
2. It should penetrate evenly and rapidly
3. It should harden the tissues
4. Increase the optical density
5. Should not cause shrinkage or swelling of the cells
6. Must not react with the receptor sites & thus must not interefere with the staining
procedure
7. It must be cheap and easily available

The Ideal Fixative

So ideal fixative is one which
1. Prevents bacterial decomposition & autolysis
2. Preserves tissue in their natural state & fixes all components (Proteins, carbohydrates,
lipids)
3. Makes cellular components insoluble to liquids encountered in tissue processing
4. Preserves tissue volume
5. Avoids excessive hardening of fixed tissue

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6. Allows enhanced staining of tissues

7. Nontoxic & non allergic

Simple Fixatives

Formalin
 The most commonly used fixative is formalin
 Its is prepared by mixing 40% Formaldehyde gas in 100
w/v of distilled water
 The resultant mixture is 100 % Formalin
 Routinely, 10% formalin is used which is prepared by
mixing 10 ml of 100% formalin in 90 ml of distilled water
Advantages:
1. Rapid penetration
2. Easy availability & cheap
3. Does not over harden the tissue
4. Fixes lipids for frozen sections
5. Ideal for mailing

Disadvantages
1. Irritant to the nose, the eyes and mucous membranes
2. Formation of precipitate of paraformaldehyde which can be prevented by adding 11-
16% methanol
3. Formation of black formalin pigment, Acid formaldehyde hematin
Q. Following are used as fixatives?
a) Xylin
b) Toluin
c) Bouin’s fluid
d) Paraffin
e) 10% formalin saline
FFTFT

Special stains:
1. PAS stain: It colors glycogen (in fungus, hepatocytes) Mucins. Basement membrane-
Magenta color
Use of PAS stain:
A. Demonstration of glycogen and neutral mucin substance.e.g.GIT tumor,mucin
secreting adenocarcinoma
B. To know basement membrane outline
C. Demonstration of fungal hyphae & parasite.e.g.trichomonus,candida
D. Demonstration of intracytoplasmic glycogen in soft tissue sarcoma. Such as-
 Rhabdomyosarcoma
 Malignant melanoma
 Mesothelioma
 Leiomyosarcoma
 Extra skeletal Ewing sarcoma
 Epitheloid sarcoma
 Myxoid chondrosarcoma
 Clear cell sarcoma
E. To identify pituitary basophil granules
2. Perl’s Prussian blue: Iron color-blue (prussian) eg. haemochromatosis
3. Congo red: Use in Amyloidosis

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4. Crystal/gentian violet: It colors amyloid, mucin, renal hyaline, gram (+ve) bacterial
wall use in-Amyloidosis, gram staining

5. Giemsa: Uses-g banding, H. Pylori, Malaria, leishmaniasis, Campylobacter, Chlamydia

6. Masson’s trichrome: Colors keratin, muscle-Red Collagen,Bone-Blue green
7. Fite stain: Uses-Dx of leprosy, TB
8. Warthin: Starry stain: Spirochetes dx

37. Immunohistochemistry

Definitions
Immunohistochemistry
 This is a technique for identifying cellular or tissue constituents (antigens) by means of
antigen antibody interactions, the site of antibody binding being identified either by direct
labeling of the antibody, or by use of a secondary labeling method.
 Immunohistochemistry – using tissue sections
 Immunocytochemistry – cytological preparations

Principle of Immunohistochemistry
 Immunohistochemistry is a method for localizing specific antigen in tissues or cells based
on antigen antibody reaction
 The site of antibody binding is identified either by tagging the antibody, directly or
indirectly with a visible label.
 Fluorescent dye, colloidal metal, hapten, radioactive marker
Advantage: Rapid

Disadvantage:
1) Different batches of biotin and different batches of avidin have differing affinities for
one other → affects the sensitivity
2) Produces non-specific (false-positive) staining

38. Environmental Pollution

Heavy metal toxic to human health:

 Lead
 Mercury
 Cadmium
 Arsenic
Effects of Selected Tobacco Smoke Constituents
Substance Effect
Tar Carcinogenesis
Polycyclic aromatic hydrocarbons Carcinogenesis
Nicotine Ganglionic stimulation and depression; tumor
promotion
Phenol Tumor promotion; mucosal irritation
Benzo [a] pyrene Carcinogenesis
Carbon monoxide Impaired oxygen transport and utilization
Formaldehyde Toxicity to cilia; mucosal irritation
Nitrogen oxides Toxicity to cilia; mucosal irritation
Nitrosamine Carcinogenesis

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39. Amyloidosis

What is amyloidosis?
Amyloidosis (am-uh-loh-sis) is a protein disorder. In this disease, proteins change shape
(Misfold), then bind together and form amyloid fibrils which deposit in organs. As amyloid
fibrils build up, the tissues and organs may not work as well as they should.

Our bodies make several proteins that can cause amyloidosis. To choose the right treatment, it
is very important to know the exact protein that is causing the disease. The two most common
types are light chain (AL) and transthyretin (ATTR) amyloidosis.

Anyloid substance is identified by –

 Methyl violet
 Congored stain (Amyloid)
 Crystal violet
 Lugol’s iodine
 H & E stein

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 Thioflavin T

40. Summary

1. Cancer cachexia
 Equal loss of both fat & lean muscle mass
 Increased BMR
 Evidence of systemic inflammation ( eg acute phase reactant)
 Mediator – TNF alpha, IL 1, PIF, IFN gamma
2. Example of labile Tissue
 Haematopitic cell of bone marrow
 Surface epithelial cells eg stratified sq cell of Skin, oral cavity, vagina and cervix.
 Cuboidal epithelial of ducts of draining exocrine Organs Salivary gland, Pancreas, biliary
tract.
 The columnar epithelia of GI tract, uterus, fallopian tube.
 Transitional epithelium of urinary tract.

3. Variety of Stem cell

 Embryonic stem cell: Most undifferentiated. They present in inner cell mass of
blastocyst. Have virtually limitless self-renewal capacity and can give rise to every cell of
the body. So they are said totipotent.
 Tissue stem cell (also called adult stem cell): They are protected within tissue
microenvironment called stem cell niches, located in Bone marrow (haematopoitic stem
cell), intestine (Crypts), Buldge region of hair follicle, limbus of cornea and sub
ventricular zone in brain.

4.

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5. Heard Benign but malignant:

Chordoma : Malignant tumor of spinal cord
Mesothelioma : Malignant tumor of pleura
Melanoma : Malignant tumor of melanocytes
Hepatoma : Malignant tumor of hepatocytes
Lymphoma : Malignant tumor of lyphoid tissue
Synovioma : Malignant tumor of synovial membrane
Glioma : Malignant tumor of glial cell (eg.Astrocytoma, Oligodendrocytoma)
Seminoma : Malignant tumor of germ cell of testis
Dysgerminoma : Malignant tumor germ cell of ovary
Medullablastoma : Malignant tumor of CNS

6. Hallmark of malignant tumor → Invasion+ metastasis

7. Bone metastasis → usually paired organ
8. BLAB→ Metastatic site of lung carcinoma
9. Block → Metastatic site of skin carcinoma
10. Hormone Secreting Tumor
Lock
 Lung – Bronchial carcinoma,sq cell carcinoma
 Ovarian ca
 Chromophobe tumor of pituitary, Carcinoid tumors, Choricarcinoma
 Kidney - RCC
 Other – Islet cell tumor of pancreas, Seminoma, monodermal teratoma of the ovary.

11. Hormones Sensitive Tumor – মা ও বাবার পরেই থাকে অন্যরা

12. Dysplasia is particularly common in squamous and transitional epithelia such as
 Cervix of uterus
 Respiratory tract in chronic cigarette smoker.
 Adjacent to foci of cancerous transformation Gall bladder (uncommon)
 Oral mucosa (uncommon)
 Skin
 Urinary bladder
 Larynx

13. Chemical carcinogen:

Direct-acting carcinogens:
iii) Alkylating agents: B-propriolactone. Dimethyl sulfate, Diepoxybutane, Anti-cancer
drugs (cyclophosphamide, chlorambucil, nitrosoureas and others)
iv) Acylating agents: 1-acetyl-imidazole, Dimethylcarbamyl chloride

Mnemonics:
 Alkylating agents: NCC PDD
7. N- Nitrosourease
8. C- Chlorumbucil
9. C- Cyclophosphamide
10. P- Propiolactone
11. D- Dimethl sulphate

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12. D- Diepoxy butane

 Acylating Agents: AD
3) A- Acetyl imidazole
4) D- Dimethyl carbonyl chloride
Pro-carcinogens that require metabolic activation:
iii) Polycyclic and heterocyclic aromatic hydrocarbons: Benz (a) Anthracene,
Dibenz (a, h) Anthracene, 3-Methylcholanthrene,7, 12-Dimethylbenz (a)
Anthracene.
ii) Aromatic amines, amides, azo dyes: 2-Naphthylaminc, benzidine,
2-Acetylaminofluorene,
Dimethylaminoazobenzene (butter yellow)

14. Paraneoplastic syndrome of lung cancer:

 Hyponatremia
 Hypercalcemia
 Hypocalcemia
 Cushing syndrome
 Gynecomastia
 Carcinoid Syndrome
 Eosinophillia
 Nephrotic Syndrome
 Dermatomyocitis

15. Krukenberg Tumor

 Primary tumor : gastric adeno ca
 Route of metastasis : body seeding, Coelomic spread
 Histology : ‘ Signet ring ‘
 Nature : predominantly solid, Lobulated, Inhanching, commonly large > 10 cm
 Marker : CEA
 Secrete : mucin

16. Highly Sensitive:

 Wilm’s tumour
 Ewings sarcom
 Lymphoma
 Seminoma
 Myeloma
Moderately Radio Sensitive:
 Small cell ca of lung
 Breast Ca
 Ovarian ca
 Teratoma
 Skin BCC
 Medulloblastoma
 Plasmocytoma
 Anaplastic thyroid ca
 GI ca

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 Testicular ca
 Head & Neck ca
 SCC of skin

Highly Radio resistant:

 Melanoma
 Osteosarcoma
 Pancreatic ca
Relatively radio resistant:
 Cervical ca
 Bladder ca
 Soft tissue sarcoma
 Sq cell ca of lung
 RCC
 Rectal ca
Highly chemosensitive:
 Wilm’s tumor
 Ewing’s sarcoma
 Lymphoma ( Hodgkin and high grade non hodgkin)
 Teratoma of testis
 Leukemia
 Chorio carcinoma
 Rhabdomyosarcoma
Moderately Sensitive:
 Small cell lung cancer
 Breast cancer
 Ovarian cancer
 Myeloma
 Lymphoma ( low grade non hodgkin)
 Leukaemia
 Leukaemia
 Advance ca cervix
 Leomyosarcoma
Highly chemoresistant:
 Melanoma
 Sq cell lung ca
 Large bowel ca

17. Occupational cancers affecting the lung → Arsenic

Asbestos
Beryllium
Chromium
Nickel
Radon
18. CA 15-3 → Breast -cancer
CA 125 → Ovarian cancer
CA 19-9 →Pancreatic cancer.

19. Spontaneous regression of cancer commonly occurs:

1. Testicular germ cell tumour, Neuroblastoma,
2. Malignant melanoma, Cutaneous BCC, Breast cancers,
3. Endometrial cancers, Thyroid cancers (Papillary, Follicular carcinoma),

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4. Prostate, RCC, Leukemia /Lymphoma).

20. FNAC:
FNAC can be:
1) Imaging Guided: Pelvic lymph node,pancreas.
2) Non-guided: Breast, Thyroid, Lymph node, Prostate, Subcutaneous nodule

FNAC cannot differentiate in:

 Follicular Carcinoma
 Bening Follicular Adenoma
Can Differentiate:
 Colloid nodule
 Thyroiditis
 Papillary ca
 Medullary Ca
 Anaplastic Ca
 Lymphoma
Advantage of FNAC:
6. Its less expansive
7. Can be performed outpatient dept.
8. Result is available in 20-30mins
9. Extremely reliable, Rapid & Useful
10. Highly Accurate in experience hand.
Disadvantages:
4. Less invasive
5. Cant give detailed examination of tissue architecture
6. Inexperienced hands results are not reliable
If suspicious → Biopsy is done

21. Uses of Frozen section biopsy:

1. It is commonly used for urgent histological or on table diagnosis of malignancy
2. Depending on result, surgeon can plan next course of operation
3. Determines whether margins are free of malignancy
4. Determine whether the breast nodule is benign or malignant & decide to perform
lumpectomy or mastectomy.
5. Determine presence or absence of ganglion cells in Hirschprung disease in surgical
pathology.
22. Not Fixatives
1. Xylin
2. Toluin
3. Glycerin
4. Gelatine
5. Normalin (normal saline)
6. Paraffin
7. Chloroform
8. Agar
9. 40% Formaldehyde
23. Heavy metal toxic to human health:

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 Lead
 Marcury
 Cadmium
 Arsenic
Exam Night
1) Examples of different stem cell (just do a quick revision)
2) Difference between carcinoma and sarcoma.
3) Environmental factor for neoplasia (specially lung cancer is associated with following
cancers)
4) Major chemical carcinogens.
5) Oncogenic microbials (DNA virus & RNA virus example)
6) Premalignant conditions ( Must revise with special importance to skin)
7) Bony/osseous metastasis commonly occurs in following site (Must revise)
8) Examples of locally malignant tumours.
9) Carcinoid syndrome details
10) Paraneoplastic syndrome (must revise)
11) Grading and staging of tumour.
12) Uses of Frozen section biopsy
13) Tumour markers (special attention to Alpha fetoprotein, carcinoembryonic antigen,
CA- 125, 19-9, 15-3)
14) Examples of fixatives (Must revise)
15) Radio – Chemo sensitive & Resistant tumor
16) Hormone secreting & sensitive tumor
17) Metastasis related

Bibliography
1) Robbin’s pathology 9th edition……
2) Smiddy latest edition……….
3) Khaleque latest edition………..

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