W4-L4-Paraneoplasticsyndromes

Question 1

What are paraneoplastic syndromes?

Answer 1

Rare disorders with complex, systemic, non metastatic and atypical manifestations that result from the presence of substances which may alert to the presence of a tumour

Question 2

When do symptoms to paraneoplastic syndromes avail?

Answer 2

Symptoms can manifest before or after the diagnosis of cancer

-These paraneoplastic syndromes accompany benign or malignant tumours.
-They occur remotely from the tumour itself.
-No race, age, gender preference; with a frequency of 2-20% of all malignancies seeing these paraneoplastic syndromes

Question 3

What are the effects of paraneoplastic syndromes?

Answer 3

• Morbidity
• Presenting feature
• Complicate cancer therapy
• Clinical presentation:
  *Headache (very common)
  *Cachexia, pyrexia
  *Endocrine manifestations
  *CNS manifestations
  *Other manifestations

Question 4

Where do paraneoplastic syndromes originate?

Answer 4

1. They can result from aberrant production and release of
   physiologically active substances by the tumour:
   * hormones
   * hormone precursors
   * Enzymes
   * Cytokines
   * from immune cross-reactivity between malignant and
   normal tissues
2. Expression of a gene:
   *In cells where it is not normally expressed (novel expression)
   *that normally occurs in stem cells (during development
3. Suggested molecular mechanisms for ectopic production of hormones (reduced gene expression):
   * Cellular de-differentiation
   * Gene rearrangements
   * DNA methylation

Question 5

List the physical manifestations of paraneoplastic syndromes

Answer 5

• endocrine
• neurological
• dermatological (muco-cutaneous)
• rheumatologic
• haematological
• miscellaneous (cardiovascular, gastrointestinal, renal,
  etc..)

Question 6

The most common paraneoplastic syndrome

Answer 6

endocrine

*A paraneoplastic syndrome that results from Hormones produced from the eutopic or ectopic sources
* Ectopic expression of hormones characterised by:
*High levels
*Abnormal regulation
*Abnormal peptide processing

*Ectopic hormone production: Produced by tissue that is not the hormone’s typical site of synthesis.

Question 7

Name 3 paraneoplastic syndromes associated
with ectopic hormone secretion

Answer 7

• Hypercalcaemia of
  Malignancy
• Hypoglycaemia
• Oncogenic osteomalacia

Question 8

What tumours are associated with hypercalcemia?

Answer 8

Cancers of lung, head and neck H & N, skin, oesophagus,
breast, multiple myeloma and lymphomas

• Causes:
  *PTH-related Peptide (PTHrP) - Humoral Hypercalcaemia of
  Malignancy (HHM)
  *Bone metastasis
  *Vitamin D secretion by tumour
  *Osteolytic cytokines