The document discusses tumor lysis syndrome, which occurs when large numbers of tumor cells are destroyed rapidly, releasing their contents into the bloodstream. This can cause hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, potentially leading to acidosis and renal failure. It also summarizes paraneoplastic syndromes, which are symptom complexes not directly caused by the tumor's location or metastasis. Common types include endocrine, neurological, mucocutaneous, and hematological syndromes. The grading and staging of cancers is also summarized, with grading based on differentiation and growth rate, and staging assessing tumor size, lymph node involvement, and metastasis.

1. CLINICAL ASPECTS OF
NEOPLASIA

2. TUMOUR LYSIS SYNDROME:
CHEMOTHERAPY, ADMINISTRATION OF GLUCOCORTICOIDS
OR CERTAIN HORMONALAGENTS (E.G.TAMOXIFEN)
EXTENSIVE DESTRUCTION OF A LARGE NUMBEROF
TUMOUR CELLS
HYPERURICAEMIA, HYPERKALAEMIA,
HYPERPHOSPHATAEMIAANDHYPOCALCAEMIA
ACIDOSIS AND RENALFAILURE.

3. • Definition: Symptom complexes that cannot readily be explained
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.
• 10% of patients with cancer
• Important because they can be 1st manifestation of cancer, and in
some patients can be major cause of morbidity or even death.
• These phenomena are mediated by humoral factors excreted by tumor
cells or by an immune response against the tumor. Some are better
understood than others.
Paraneoplastic
Syndromes
Acromegaly as a result of GH expression
from a pituitary tumor would NOT be a
paraneoplastic syndrome, because pituitary
cells normally express GH

4. CLINICAL SYNDROMES INCLUDED IN THE PNS
1. ENDOCRINE SYNDROME
2. NEUROLOGICALSYNDROME
3. MUCOCUTANEOUS SYNDROME
4. HEMATOLOGICALSYNDROME

5. • Endocrinopathies
Cushings Syndrome (excess cortisol)
• Secretion of ACTH, lung cancers
• Hypercalcemia—most common
protein, TGF-alpha, TNF
• Polycythemia (too many red cells)
• Secretion of erythropoietin
ectopic hormone expression
Again, a tumor of the
adrenal cortex that
•
caused Cushing's
syndrome would NOT
be a paraneoplastic
syndrome
PTH-RP is not exactly PTH, but it has
a similar function
Hypercalcemia results in metastatic
calcification.
Dystrophic calcification occurs in
degenerated or necrotic tissue
• Secretion of parathyroid hormaosns
c
a
er
s
-.related
Kidney cancers are particularly
known for this

6. NEUROLOGICAL SYNDROME:
• Neurological syndromes arise due to altered
immune system.
• Inflammatory cells like T-cells/Antibodies
(abnormally produced/activated in cancers)
react with the nervous tissue and cause
neurological diseases.

7. 1. Polymyositis:
- Inflammation of multiple muscles is called
polymyositis.
- Seen in cancers like Non-Hodgkin lymphoma.
- Mediated by cytotoxic-T cells.

9. 2. Lambert-Eaton myasthenic syndrome:
- Characterized by muscle weakness caused by
pathogenic autoantibodies directed against voltage-
gated calcium channels (VGCC) present on the
presynaptic nerve terminal.
- VGCC antibodies block calcium influx, leading to
reduced ACh vesicle release from the presynaptic
membrane.
- Seen in small cell carcinoma of lungs

11. • Nerve and Muscle Disorders
• Peripheral neuropathies, cerebellar
degeneration, polymyositis—autoimmune
etiology
• Myasthenia
• Autoantibody inhibits function of
neuromuscular junction—profound weakness
Autoimmune, rather than
hormonal, in etiology
Mimics myasthenia gravis (autoimmune attack against nAChR)

12. • Bone and soft tissue
• Hyerptrophic osteoarthropathy and clubbing of
the fingers.
Common in some cancers, but also a
presentation of chronic hypoxia

13. Acanthosis nigricans
Can happen in patients with gastric, lung and uterine
carcinomas
Immunologic, secretion of EGF
Skin changes can appear before discovery of cancer
DERMATOLOGIC PARANEOPLASTIC SYNDROME

14. • Vascular disorders
• Trousseau syndrome
• Venous thrombi--Hypercoagulability, uncertain
cause.
• Non-bacterial thrombotic endocarditis
• Unknown mechanism.

15. GRADING AND STAGING OF CANCER:
• Grading is defined as the gross appearance and
microscopic degree of differentiation of the
tumour.
• Staging means extent of spread of the tumour
within the patient.

16. After a malignant tumour is detected, ‘Grading’ and
‘staging’ helps in:
- Predicting tumour behaviour (what could be
the prognosis?)
- Guiding the therapy.

17. GRADING:
Cancer may be graded grossly and microscopically.
Grading is largely based on 2 important histological
features:
1. The degree of anaplasia.
2. The rate of growth

18. features, cancers are
• Based on these
categorized as:
Grade I & Grade II: as the MOST
DIFFERENTIATED.
Grade III to IV: as the MOST
UNDIFFERENTIATED OR ANAPLASTIC.

19. • Many systems of grading have been proposed but
the one described by Broders for dividing
squamous cell carcinoma into 4 grades depending
upon the degree of differentiation is followed for
other malignant tumours as well.

20. Broders’ grading is asunder:
GRADE DEGREE OF DIFFERENTIATION
GRADE I Well-differentiated (less than 25% anaplastic cells)
GRADE II Moderately-differentiated (25-50% anaplastic cells)
GRADE III Moderately-differentiated (50-75% anaplastic cells)
GRADE IV Poorly-differentiated or anaplastic (more than 75% anaplastic cells)

21. • The degree of differentiation may vary from one
area of tumour to the other.
• Therefore, it is common practice with pathologists
to grade cancers in descriptive terms i.e., well-
differentiated, undifferentiated rather than giving
the tumours grade numbers.

22. STAGING:
• The extent of spread of cancers can be
assessed by 3 ways:
– by Clinical examination (by physicians)
– by Investigations (by PET scan, USG etc)
– by Pathologic examination of the tissue
removed. (by FNAC, Tissue biopsy)

23. Clinical examination Investigations
FNAC, Tissue biopsy

24. • Two important staging systems currently
followed are:
1. TNM staging (T- tumour, N for nodal and M
metastases)
2. AJCC staging (American Joint Committee
On Cancer.)

25. TNM staging
TNM staging:
T: describes
(primary) tumor and
the size of
whether it
the original
has invaded
nearby tissue.
N: describes nearby (regional) lymph nodes that are
involved
M: describes distant metastasis (spread of cancer
from one part of the body to another).

27. • T: size or direct extent of the primary tumor
– Tx: Tumor cannot be assessed
– T0: No evidence of tumor
– Tis: Carcinoma in situ
– Ta: Non- Invasive
– T1, T2, T3, T4: Size and/or Extension of the
primary tumor

29. • N: Degree of spread to regional lymph
nodes
–Nx: Lymph nodes cannot be assessed
–N0:No regional lymph nodes metastasis
–N1: Regional lymph node metastasis.
–N2: Tumor spread to an extent between N1
and N3
–N3: Tumor spread to more distant or
numerous regional lymph nodes.

30. • M: Presence of Distant Metastasis
organs
–M0: No distant metastasis
–M1: Metastasis to distant
(beyond regional lymph nodes)

31. Stage grouping:

32. AJCC Staging.
• AJCC staging divides all cancers into stage 0
to IV, and takes into account all the 3
components of the TNM staging (primary
tumour, nodal involvement and distant
metastases) in each stage.

33. MORPHOLOGIC METHODS IN THE DIAGNOSIS OF
CANCER
The specimen must be adequate, representative, and
properly fixed.
•Core biopsy
•Final needle aspiration biopsy
•Cytologic (Papanicolaou) smears – neoplastic cells are
less cohesive than others and so are shed into fluids or
secretions – cervical cc, endometrial cc, bladder cc,
bronchogenic cc; effusions in the abdominal cavity, pleural
cavity

34. • Immunohistochemistry – a powerful adjunct to
routine histology
• Flow cytometry – in the classification of leukemias
• Molecular methods to detect gene
rearrangement, translocations, amplification of
oncogens, to guide therapy, etc.,
• PCR, FISH, DNA microarray analysis

35. SURGICAL PATHOLOGY REPORT OF CANCERS
Should include:
histopathological diagnosis + prognostic indicators:
• grade
• stage
• excision margins (tumor-positive or negative)
• presence or absence of invasion of lymphatics or
venules