DR. ROOPAM JAIN PROFESSOR & HOD DEPARTMENT OF PATHOLOGY & BLOOD BANK

1. NEOPLASIA
Clinical Features of Tumors,
Grading and Staging
&
Laboratory Diagnosis of Cancer
Dr. Roopam Jain
Professor & Head

2. NEOPLASIA
Clinical Features
of Tumors

3. The effects of a tumor on the host
A. LOCAL EFFECTS
 i) Compression - e.g. pituitary adenoma may lead to
serious endocrinopathy; a small benign tumour in ampulla of
Vater may lead to biliary obstruction.
 ii) Mechanical obstruction - Benign and malignant
tumours in the gut may produce intestinal obstruction.
 iii) Tissue destruction Malignant tumours, both
primary and metastatic, infiltrate and destroy the vital
structures.
 iv) Infarction, ulceration, haemorrhage -
infarction, surface ulceration, haemorrhage , torsion and
produce infarction and haemorrhage.

4. B. SYSTEMIC MANIFESTATIONS
 1. CANCER CACHEXIA
 2. FEVER
 3. TUMOUR LYSIS SYNDROME
 4. PARANEOPLASTIC SYNDROMES

5. 5
Clinical manifestations of Cancer
Cachexia – wasting
anorexia
early satiety
weight loss
anemia
marked weakness
taste alterations
altered metabolism

6. 1. Cancer Cachexia
 The causes of cachexia are obscure but cachexia is NOT caused
by the nutritional demands of the neoplasm
 results from the action of soluble factors such as cytokines
(TNF-alpha and IL-1) either produced by the tumor or the
host
 Various other causes of cancer cachexia include necrosis,
ulceration, haemorrhage, infection, malabsorption,
anxiety, pain, insomnia, hypermetabolism and pyrexia.

7. 2. FEVER
 Fever of unexplained origin
 Hodgkin’s disease, adenocarcinoma kidney,
osteogenic sarcoma
 The exact mechanism – Unknown (tumour cells
themselves elaborate pyrogens).

8. 3. TUMOUR LYSIS SYNDROME
 caused by extensive destruction of a large number of
rapidly proliferating tumour cells.
 lymphomas and leukaemias, chemotherapy,
administration of glucocorticoids or certain hormonal
agents (e.g. tamoxifen).
 It is characterized by hyperuricaemia, hyperkalaemia,
hyperphosphataemia and hypocalcaemia, all of which
may result in acidosis and renal failure.

9. Effects of Tumor on Host:
4. Paraneoplastic Syndromes
 group of conditions developing in patients with
advanced cancer,
 either by the local or distant spread of the tumor
or by the elaboration of hormones indigenous to
the tissue from which the tumor arose, are known
as PARANEOPLASTIC SYNDROMES
 About 10 to 15% of the patients with advanced
cancer develop one or more of the syndromes
included in the PNS

10. Paraneoplastic Syndromes
 Paraneoplastic syndromes are important for
three reasons:
 1) they may represent the earliest
manifestation of an occult tumor
 2) they may represent significant clinical
problems and may even be lethal
 3) they may mimic metastatic disease and
therefore confound treatment

11. Paraneoplastic Syndromes
(Endocrinopathies)
Cushing Syndrome Small cell
carcinoma-lung;
pancreatic
carcinoma; neural
tumors
ACTH or ACTH-
like substance
Syndrome of
inappropriate ADH
secretion
Small cell
carcinoma-lung;
intracranial
neoplasms
ADH or Atrial
natriuretic
hormones

12. Paraneoplastic Syndromes
(Endocrinopathies)
Hypercalcemia Lung (sq. cell),
breast, ovarian, renal
carcinoma; T-cell
leukemia/
lymphoma
PTH-related
peptide, TGF-alpha,
TNF-alpha, IL-1
Carcinoid Syndrome Bronchial adenoma;
pancreatic & gastric
carcinomas
Serotonin,
bradykinin, ?
Histamine

13. Paraneoplastic Syndromes
(Endocrinopathies)
Hypoglycemia Fibrosarcoma &
other sarcomas;
hepatocellular
carcinoma
Insulin or insulin-
like substances
Polycythemia Renal &
hepatocellular
carcinomas;
cerebellar
hemangioma
Erythropoietin

14. Paraneoplastic Syndromes
(Nerve and Muscle Syndromes)
Myasthenia Bronchogenic
carcinoma,
Thymoma
Immunologic
Disorders of the
central and
peripheral nervous
systems
Breast,
Carcinoma Lung
(small cell Ca),
Immunologic

15. Paraneoplastic Syndromes
(Dermatologic Syndromes)
Acanthosis nigricans Gastric, lung &
uterine carcinomas
?Immunologic, ?
Secretion of
epidermal growth
factor
Dermato-myositis Bronchogenic &
breast carcinomas
?Immunologic

16. Paraneoplastic Syndromes
(Dermatologic Syndromes)
Seborrheic
dermatitis
Bowel Immunologic

17. Paraneoplastic Syndromes
(Osseous, Articular, Soft Tissue Change)
Hypertrophic
osteoarthropathy and
clubbing of fingers
Bronchogenic
carcinoma
Unknown
Clubbing of fingers Bronchogenic
carcinoma
Unknown

18. Paraneoplastic Syndromes
(Vascular/Hematologic
Changes)
Venous thrombosis
(Trousseau
phenomenon)
Pancreatic &
Bronchogenic
carcinomas; other
neoplasms
Tumor products
(mucins that activate
clotting)
Non-bacterial
thrombotic
endocarditis
Many advanced
cancers
Hyper-coagulability

19. Paraneoplastic Syndromes
(RENAL SYNDROMES)
Nephrotic syndrome UNDERLYING
CANCER :
Various cancers &
Advanced cancers
MECHANISM:
Renal vein
thrombosis, systemic
amyloidosis

20. Paraneoplastic Syndromes
(HAEMATOLOGIC SYNDROMES)
Disseminated
intravascular
coagulation (DIC)
AML,
adenocarcinoma
Mechanism :
Chronic thrombotic
phenomena
Anaemia Thymoma Mechanism :
Unknown

21. Grading and Staging
&
Laboratory Diagnosis of
Cancer

22. Grading and Staging

23. Grading and Staging
 2 System
 To predict tumour behaviour & guide therapy
 Grading = gross appearance & microscopic degree
of differentiation of the tumour.

24. Grading and Staging of
Tumors
 Staging = means extent of spread of tumour within the
patients (clinical)
 Staging is based on clinical, radiological, and surgical
criteria, such as, tumor size, involvement of regional
lymph nodes, and presence of metastases. Staging
usually has more prognostic value.
 Staging is more useful.

25.  Malignant tumors are characterized by a wide
range of cellular differentiation.
 Differentiation is the extent to which tumor cells
resemble their normal cells morphologically and
functionally
 Generally:
 Benign tumors are well differntiated
 Malignant tumors can be well differentiated,
moderately differentiated or poorly
differentiated. They can be “undifferentiated”
Differentiation

26. Differentiation and Anaplasia
 Anaplasia (Anaplasia is lack of differentiation)
 Lack of differentiation, or anaplasia, is
considered a hallmark of malignancy.

27. Features of Anaplasia
1. Loss of polarity and normal arrangement
2. Pleomorphism (variation in size and shape of cells
and nuclei)
3. Hyperchromatism nuclei(nuclei contain abundance
of dark-staining chromatin)
4. Enlarged nucleoli
5. Increased mitosis with abnormal mitotic figures
6. High nuclear to cytoplsmic ratio (High N/C ratio)
7. Formation of tumor giant cells (in some instances)
8. Loss of sturcture

28. Loss of polarity
28

29. Pleomorphism, N:C ratio ,
29

30. N:C ratio
 N:C ratio Generally, the nuclei of malignant
tumour cells show more conspicuous
changes. Nuclei are enlarged
disproportionate to the cell size so that
the nucleocytoplasmic ratio is increased
from normal 1:5 to 1:1
30

31. Anisonucleosis
Just like cellular pleomorphism, the
nuclei too, show variation in
size and shape in malignant
tumour cells
31

32. Nuclear Hyperchromatism
 The nuclear chromatin of malignant cell is
increased and coarsely clumped.
 This is due to increase in the amount of
nucleoprotein resulting in dark-staining
nuclei, referred to as hyperchromatism.
32

33. Mitotic figures
33

34. Multinucleate tumour giant cells
34

35. Differentiation and Anaplasia
 Dysplasia:
 Not neoplstic growth
 Disordered growth and differentiation
 Show mild anaplastic features eg. Nuclear
pleomorphism, hyperchromasia, mitosis….

36. well-differentiated

37. poorly-differentiated

38. Grading and Staging of Tumors
 GRADING of a cancer is based on the degree of
differentiation of the tumor cells and the
number of mitoses within the tumor as presumed
correlates of the neoplasm’s aggressiveness
 Cancers are classified as grades I to IV with
increasing anaplasia

39. GRADING
 Grade 1 – well differentiated
 Grade 2 – Moderately differentiated
 Grade 3 – Moderately differentiated
 Grade 4 – Poorly differentiated

40. Laboratory Diagnosis
of Cancer

41. Laboratory Diagnosis of Cancer
 1) HISTOLOGICAL METHODS – Paraffin-embedding
technique, Frozen section
 2) CYTOLOGICAL METHODS – Exfoliative cytology,
FNAC; Bone marrow aspiration
 3) HISTOCHEMISTRY & CYTOCHEMISTRY
 4) IMMUNOHISTOCHEMISTRY
 5) ELECTRON MICROSCOPY
 6) SERUM TUMOR MARKERS

42. Tumor markers
 Tumor markers sometimes diagnostic or prognostic
 Can be helpful in monitoring effectiveness of
therapy or in detecting relapses/recurrences

43. Tumor Markers
 Tumor markers are biochemical indicators of
the presence of a tumor
 Tumor markers include: cell surface antigens,
cytoplasmic proteins, enzymes and hormones
 Example: Carcinoembryonic antigen (CEA) is
found in carcinomas of colon, pancreas, lung,
stomach and breast

44. Tumor Markers
 CEA assays lack both specificity and the sensitivity
required for the detection of early cancers, but good to
know relapse or as follow up procedure..
 Alpha-fetoprotein (AFP) is associated with liver cell
cancer & nonseminomatous germ cell tumors of the
testis
 AFP can be seen in non-neoplastic conditions such as
cirrhosis and hepatitis

45. TUMOR MARKERS
(Hormones)
MARKERS
Human chorionic
gonadotropin
Calcitonin
CANCERS
Trophoblastic tumors; Non-
seminomatous testicular
tumors
Medullary carcinoma of
thyroid

46. TUMOR MARKERS
(Hormones)
MARKERS
Catecholamine and metabolites
Ectopic hormones production
CANCERS
Neuroblastoma,
Pheochromocytoma and
related tumors
Tumors of the Paraneoplastic
Syndrome

47. TUMOR MARKERS
(Oncofetal Antigens)
MARKERS
Alpha-fetoprotein
Carcinoembryonic antigen
CANCERS
Liver cell cancer; Non-
Seminomatous germ cell
tumors of testis
Carcinomas of colon, pancreas,
lung, stomach & breast

48. TUMOR MARKERS
(Isoenzymes)
MARKERS
Prostatic acid phosphatase
(PAP)
Neuron-specific antigen (NSE)
CANCERS
Prostate cancer
Small cell cancer of lung,
Neuroblastoma

49. TUMOR MARKERS
(Isoenzymes)
MARKERS
Lactic dehydrogenase (LDH)
CANCERS
Lymphoma, Ewings sarcoma

50. TUMOR MARKERS
(Specific Proteins)
MARKERS
Immunoglobulins
Prostate-specific antigen (PSA)
CANCERS
Multiple myeloma and other
Gammopathies
Prostate cancer

51. TUMOR MARKERS
(Mucins & Other Glycoproteins)
MARKERS
CA-125
CA-19-9
CA-15-3
CANCERS
Ovarian cancer
Colon, pancreatic cancer
Breast cancer

52. Summary
The prognosis of a patient with any type of neoplasm
depends on a number of factors including:
 the rate of growth of the tumor,
 the size of the tumor,
 the tumor site,
 the cell type and
 degree of differentiation,
 the presence of metastasis,
 responsiveness to therapy,
 and the general health of the patient.