Host Defense Against Tumours
– Tumour Immunity
Tumour Antigens
• Products of mutated oncogenes and
tumour suppressor genes,
• Products of other mutated genes,
• Overexpressed or aberrantly expressed
cellular proteins,
• Tumour antigens produced by oncogenic
viruses,
• Others;
Antitumour effector mechanisms
• Cytotoxic T lymphocytes,
• Natural killer (NK) cells
• Macrophages,
• Antibodies;
Immune Surveillance
• Antitumour mechanisms prevent
emergence of neoplasms;
• Immunodeficiencies – cancers,
(Lymphomas),
• Tumour cells escape or evade the
immune system;
TUMOURS PRODUCE:
- MORBIDITY AND MORTALITY,
- ALL MASSES REQUIRE
ANATOMIC EVALUATION
EFFECTS OF TUMOUR ON THE HOST
• LOCATION,
• SIZE,
• LOCAL INVASION,
• FUNCTIONAL ACTIVITY ( HORMONE )
• BLEEDING = Melena, Haematuria, Hematochezia
• SECONDARY INFECTION - ULCERATION,
Clinical features of tumours
• ACUTE SYMPTOMS
= RUPTURE
= INFARCTION
• CANCER CACHEXIA:
… Loss of body fat
… Weakness • TNF
… Anorexia • IL - 1,
• IFN -gamma
… Anemia;
? others
Clinical features of tumours
PARANEOPLASTIC SYNDROMES:
Symptom complexes in cancer-bearing
patients that cannot readily be
explained, either by the local or
distant spread of the tumour or by
the elaboration of hormones
indigenous to the tissue are known as
paraneoplastic syndromes.
Clinical features of tumours
PARANEOPLASTIC SYNDROMES:
10 % of patients with cancer
May be an early manifestation of
occult neoplasm,
May be significant clinical problems,
May mimic metastatic disease;
Clinical features of tumours
PARANEOPLASTIC SYNDROMES:
• Cushing syndrome
-- Small cell carcinoma of lung,
-- Pancreatic carcinoma,
• Inappropriate ADH secretion,
-- Small cell carcinoma of lung,
Clinical features of tumours
PARANEOPLASTIC SYNDROMES:
Hypercalcemia
-- Small cell carcinoma of lung
-- Breast carcinoma
-- Renal cell carcinoma
-- Ovarian carcinoma
Clinical features of tumours
PARANEOPLASTIC SYNDROMES:
• HYPOGLYCEMIA
-- FIBROSARCOMA
-- OTHER MESENCHYMAL SARCOMAS
-- HEPATOCELLULAR CARCINOMA
• CARCINOID SYNDROME
-- BRONCHIAL ADENOMA
-- PANCREATIC CARCINOMA
-- GASTRIC CARCINOMA
Clinical features of tumours
PARANEOPLASTIC SYNDROMES:
POLYCYTHEMIA
-- RENAL CARCINOMA
-- CEREBELLAR HAEMANGIOMA
-- HEPATOCELLULAR CARCINOMA
DERMATOMYOSITIS
-- BRONCHOGENIC CARCINOMA
-- BREAST CARCINOMA
Clinical features of tumours
PARANEOPLASTIC SYNDROMES:
HYPERTROPHIC OSTEORTHROPATHY
-- BRONCHOGENIC CARCINOMA
MIGRATORY THROMBOPHLEBITIS
(Trousseau phenomenon )
-- PANCREATIC CARCINOMA
-- BRONCHOGENIC CARCINOMA
-- OTHERS
Clinical features of tumours
PARANEOPLASTIC SYNDROMES:
NEUROMYOPATHIC SYNDROMES;
.. Peripheral neuropathies,
.. Polymyopathy,
.. Cerebellar degeneration;
.. Myasthenic syndrome
ANEMIA
-- THYMIC NEOPLASMS
NEPHROTIC SYNDROME
-- VARIOUS CANCERS
STAGING OF TUMOURS
* INDICATES THE EXTENT OF
ANATOMICAL SPREAD OF THE
TUMOURS WITH IN THE PATIENT
* USEFUL IN COMPARING THE
NEOPLASMS;
STAGING OF TUMOURS
STAGING SYSTEMS:
1. UNION INTERNATIONALE
CENTRE CANCER ( UICC )
2. AMERICAN JOINT COMMITTEE
ON CANCER STAGING ( AJC )
UICC 1 2 3 4
0 1 2
0 1 2
GRADING OF TUMOURS:
• Indicates the level of differentiation,
• Better differentiation > good prognosis,
• Poor differentiation > poor prognosis;
Grading:
• Degree of Differentiation,
• Grade - I : well differentiated ( > 75% ),
• Grade - II : ( 50 - 75%),
• Grade - III : ( 25 - 50%),
• Grade - IV : Poorly differentiated ( < 25%)
Diagnosis of Cancer
HISTOPATHOLOGY:
• Clinical data - Important,
• Biopsy Adequate,
• Excision Representative,
Properly preserved
• Frozen Section -
Diagnosis of Cancer
2. CYTOLOGIC METHOD:
• Fine Needle Aspiration Cytology ( FNAC )
… Breast, Thyroid gland, Lymph nodes,
… Deeper tissues - Imaging assistance,
• Exfoliative Cytology:
… Pap Smear ( Papanicolaou )
- Vaginal Smear = Carcinoma Cervix,
… Body fluids - Pleural fluid, Ascitic
fluid, Sputum, Aspirate from stomach,
PAP
SMEAR
SHOWING
MILD
DYSPLASIA
Ulcerating Ca Cx:
Pap Smear Results:
HERPES
CANDIDA
ACTINOMYCETES
TRICHOMONAS VAGINALIS
ENDOMETRIAL CELLS
Pap smear - mild dysplasia
SEVERS DYSPLASIA
NON KERATINIZING SCC
Pap smear from squamous
cell carcinoma of cervix
ENDOMETRIAL
ADENOCARCINOMA
CARCINOMA,
BREAST.
( FNAC )
Diagnosis of Cancer
IMMUNOCYTOCHEMISTRY:
• DIAGNOSIS OF UNDIFFERENTIATED
MALIGNANT TUMOURS,
• CATEGORISATION OF LEUKAEMIAS
AND LYMPHOMAS,
• DETECTION OF SITE OF ORIGIN IN
METASTATIC TUMOURS,
• DETECTION OF MOLECULES OF
PROGNOSTIC SIGNIFICANCE
( Estrogen Receptors );
Estrogen Receptor [ER] positivity in Carcinoma, breast
Progesterone Receptor [PR] positivity-Carcinoma, breast
Diagnosis of Cancer
3. MOLECULAR DIAGNOSIS:
• DIAGNOSIS OF MALIGNANT TUMOURS,
• PROGNOSIS OF MALIGNANT TUMOURS,
• DETECTION OF MINIMAL RESIDUAL
DISEASE,
• DETECTION OF HEREDITORY
PREDISPOSITION
4. Tumour Markers:
( Biochemical Indicators of Tumours)
1. Hormones:
… HCG - Trophoblastic tumours,
… Calcitonin - Medullary carcinoma
of thyroid gland,
4. Tumour Markers:
( Biochemical Indicators of Tumours)
2. Oncofetal Antigens:
… Alpha - fetoprotein -
= Hepatocellular carcinoma,
= Testicular tumours;
4. Tumour Markers:
( Biochemical Indicators of Tumours)
3. Isoenzymes:
* Prostatic acid phosphatase -
--- Carcinoma prostate,
* Neuron specific enolase -
--- Neuroblastoma,
--- Carcinoma lung,
4. Tumour Markers:
( Biochemical Indicators of Tumours)
4. Specific Proteins:
* Immunoglobulins -
--- Multiple myeloma,
* Prostate specific antigen
--- Carcinoma prostate,
Tumour Markers: ( contd …)
5. Glycoproteins:
* Ca - 125 - Ovarian tumours,
* Ca - 19-9 - Tumours of colon,
pancreas,
* Ca - 15-3 - Carcinoma Breast;
Blood concentration of tumour marker
Surgery Recurrence
Time [ months ]
Asymptomatic
Clinical Symptomatic
presentation if untreated
Flow Cytometry:
• Rapid and quantitative measurement
of individual cell characteristics,
Eg.: … DNA Content,
… Surface antigens;