Manifestations of Cancer

Question 1

How is tissue integrity lost during cancer growth?

Answer 1

• tumor growth can compress and erode blood vessels
• tissue ulceration and necrosis:
  blood in stool can be early warning sign of colorectal cancer
  painless hematuria may be only sign of bladder cancer
• cancer can produce tissue destroying toxins and enzymes: tissue damaged by cancer doesn’t heal properly

Question 2

How can tumor growth effect normal tissue?

Answer 2

• massof an abdominal tumor can cause a bowel obstruction
• development of effusions:
  pleural, pericardial, or peritoneal spaces:
  pleural effusion think lung cancer or lymphoma, peritoneal fluid think ovarian cancer

Question 3

Why does anorexia occur secondary to cancer?

Answer 3

• due to decreased caloric intake:
  physical obstruction of GI tract
  pain
  depression
  constipation
  malabsorption
  debility or side effects of tx such as opiates, radiotherapy, or chemotherapy
• wt loss is primarily from fat stores then muscle
• protein loss is equally divided among skeletal muscle and visceral proteins: will have decreased liver mass
• this is reversible with protein and calor supp

Question 4

Why does cachexia occur secondary to cancer?

Answer 4

• involuntary loss of at least 5% of body mass
• not just related to decreased food intake
• secondary to hypermetabolic state and altered nutrient metabolism created by cancer
• tumors consume large amts of glucose and increase lactate formation
• further abnormalities in fat and protein metabolism
• visceral proteins are preserved and liver recycles nutrients and hepatomegaly occurs
• only way to reverse this is tx of cancer

Question 5

What is cancer anorexia-cachexia syndrome?

Answer 5

• common manifestation of solid tumors except breast cancer
• more common in kids and older adults
• wt lost from fat and skeletal muscle
• oral or parenteral nutritional supp. doesn’t reverse cachexia
• involuntary loss of 5% of body wt:
  shorter median survival, doesn’t respond as well to chemo, have problems with toxicity

Question 6

How is fatigue secondary to cancer?

Answer 6

• can be secondary to cancer or it’s tx
• 1/3 of pts present with fatigue
• cancer fatigue is characterized by tiredness, weakness, and lack of energy
• not relieved by sleep or rest like that of normal health persons
• fatigue can preced dx and can last months after cancer tx
• cause is likely mulitfactorial

Question 7

How can fatigue be categorized?

Answer 7

• central or peripheral
• peripheral fatigue occurs in neuromuscular jxns and muscles:
  inability of peripheral neuromuscular appartatus to perform a task in response to stimulus.
  lack of ATP and build up of lactic acid - leads to decreased firing at neuromuscular jxns (abs eating away at jxns)
• central fatigue: arises in CNS
  difficulty in initiating or maintaining voluntary activities.
  May be secondary to dysregulation of serotonin and proinflammatory cytokines
  (have a lot of pain - can’t sleep)

Question 8

Poor sleep secondary to cancer?

Answer 8

• trouble falling asleep, staying asleep, nighttime awakenings and restless sleep
• sometimes secondary to pain or SEs of tx such as nausea and vomiting

Question 9

How does anemia occur secondary to cancer?

Answer 9

• may be related to blood loss, hemolysis, impaired RBC production, or tx effects
• often tx with epogen but may require a transfusion

malignancies can decrease RBC production by:

• nutritional deficiences
• bone marrow failure
• blunted EPO response
• inflammatory cytokines produced by tumors decrease EPO production

Question 10

Most common malignancies to present with a fever?

Answer 10

• lymphoma (Non-hodgkin’s)
• leukemia
• renal cell (20% present with fever)
• hepatocellular carcinoma
• atrial myxomas: uncommon tumor type but MC primary heart tumor: up to 30% present with fever

Question 11

When will these sxs of cancer present?

Answer 11

• may present b/f cancer is dx or may be signs of advanced disease
• careful eval of pts with these presenting complaints may uncover occult malignancies

Question 12

What are paraneoplastic syndromes? Cause? Most common in what cancers? Mechanisms?

Answer 12

• collection of sxs that result from substances produced by the tumor and occur remotely from the tumor itself
• caused by abnormal increases in hormones secondary to effects of the cancer cells
• MC cancers that these occur:
  lung
  breast
  hematologic
• affects up to 8% of pts with cancer
• Mechanism: immune x-reactivity b/t malignant and normal tissues
• tumor secretion of:
  hormones
  peptides
  cytokines

Question 13

When do paraneoplastic syndromes manifest?

Answer 13

• may be the first or most prominent manifestation
• when a pt w/o a known cancer presents with one of the typical paraneoplastic syndromes, a dx of cancer must be ruled out

Question 14

What systems can paraneoplastic syndromes affect?

Answer 14

• endocrine
• neuro
• heme
• derm
• rheum

Question 15

Endocrine paraneoplastic syndromes?

Answer 15

• SIADH
• hypercalcemia
• cushing syndrome
• hypoglycemia

Question 16

Cause of SIADH?

Answer 16

• secondary to tumor cell production of ADH
• this leads to increased free water reabsorption
• failure of negative feedback system that regulates the release of ADH - ADH production continues despite a decrease in serum osmolality resulting in water retention and dilutional hyponatremia

Question 17

Assoc cancers - SIADH?

Answer 17

• small cell lung cancer (10-45% of pts)
• mesothelioma, bladder, urethral, endometrial, prostate, oropharyngeal, thymoma, lymphoma, ewing sarcoma, brain, GI, breast, adrenal

Question 18

Signs and sxs of SIADH? Clinical manifestations?

Answer 18

• hyponatremia
• increased urine osmolality with decreased urine output
• decreased serum osmolality
• manifestations:
  gait disturbances, falls, HA, nausea, fatigue, muscle cramps, anorexia, confusion, lethargy, seizures, respiratory depression, coma

Question 19

Assoc cancers - manifest with hypercalcemia?

Answer 19

• breast, MM, renal cell, squamous cell cancers (esp lung), lymphoma, ovarian, endometrial
• this is one of MC paraneoplastic syndromes

Question 20

Sxs of hypercalcemia?

Answer 20

• altered mental status
• weakness
• ataxia
• lethargy
• hypertonia
• renal failure
• N/V
• HTN
• bradycardia

Question 21

Hypercalcemia in cancer may be secondary to what?

Answer 21

• secretion of PTH-RP by tumor cells (80% of cases): most commonly from squamous cell cancers (esp lung)
• from osteolytic activity at sites of skeletal mets (2nd MC cause): breast cancer, MM, lymphomas
• tumor secretion of Vit D
• ectopic tumor secretion of PTH

Question 22

How commonly is cushing syndrome a paraneoplastic syndrome?

Assoc cancers?

Answer 22

• 5-10%
• 50-60% from small cell lung cancer or bronchial carcinoid
• thymoma, medullary thyroid cancer, GI, pancreatic, adrenal, ovarian

Question 23

Sxs of cushing syndrome?

lab findings?

Answer 23

• muscle weakness, peripheral edema, HTN, wt gain, centripetal fat distribution
  -lab findings:
  hypokalemia**
  elev. baseline serum cortisol
  normal to elev. midnight serum ACTH
  not suppressed with dexamethasone

Question 24

How common is hypoglycemia as paraneoplastic syndrome? Assoc cancers? Sxs?

Answer 24

• rare to be tumor assoc
• assoc cancers:
  insulin producing islet cell tumors
  non-iselt cell tumors: tumor cell production of IGF-2 or insulin
• sxs:
  recurrent or constant hypoglycemia

Question 25

How do paraneoplastic neuro syndromes occur?

Tx? When are these dx?

Answer 25

• immune cross-reactivity b/t tumor cells and nervous system:
  cause permanent damage
• tx of primary tumor doesn’t always result in neuro improvement
• mainstay of tx: immunosuprressive therapy
• are detected b/f cancer is dx in 80% of cases

Question 26

How common are paraneoplastic neuro syndromes?

Assoc malignancies?

Answer 26

• affects less than 1% of cancer pts overall (rare)
• assoc malignancies:
  up to 5% of pts with small cell lung cancer
  up to 10% of pts with lymphoma or MM

Question 27

What are the neuro syndromes and what cancer are they MC found in?

Answer 27

• limbic encephalitis:
  SCLC*, testicular germ cell, breast
• paraneoplastic cerebellar degeneration: SCLC
• lambert-eaton syndrome: SCLC
• Myasthenia Gravis: thymoma
• autonomic neuropathy: SCLC
• subacute (peripheral) sensory neuropathy: SCLC and other lung cancers

Question 28

Diff b/t Lambert-eaton myasthenic syndrome and Myastehnia gravis?

Answer 28

• Lambert-eaton: 3% of people with SCLC, reverse myasthenia gravis (presents peripherally), weakness of limbs
• myasthenia gravis: presents more centrally, 15% of people with thymoma, presents with eye muscle weakness

Question 29

Derm and Rheum syndromes?

Answer 29

• acanthosis nigricans
• pemphigus
• extramammary paget
• ichthyosis
• dermatomyositis
• erythroderma
• hypertrophic osteoarthropathy
• leukocytoclastic vasculitis
• polymyalgia rheumatica
• sweet syndrome (acute febrile neutrophilic dermatosis)

Question 30

Acanthosis nigricans is assoc with what cancers?

Answer 30

• MC assoc with adenocarcinoma: GI tract MC (gastric carcinoma)
• other adenocarcinomas: lung, breast, ovarian
• also can be assoc with heme cancers

Question 31

Heme syndromes?

Answer 31

• eosinophilia
• granulocytosis
• pure red cell aplasia
• thrombocytosis

Question 32

When are paraneoplastic heme syndromes detected?

Answer 32

• usually detected after cancer dx

- usually seen with advanced disease

Question 33

What is Eosinophilia? Assoc malignancies?

Answer 33

• tumor production of eosinophil growth factors
• assoc malignancies:
  lymphomas and leukemias
  paraneoplastic eosinophilia assoc with:
  lung, GI, and Gyn cancers

Question 34

How common is granulocytosis (neutrophilia)?

Occurs in what cancers?

Answer 34

• occurs approx 15% of pts with solid tumors
• WBC ranges from 12000-30000 (can go as high as 50000) - generally is really high!
• assoc cancers:
  lung cancer (mostly large cell), GI, brain, breast, renal, gyn cancers
• mechanism is poorly understood

Question 35

Pure red cell aplasia is assoc with what cancers?

Answer 35

• MC assoc with thymoma

- may be caused by leukemia, lymphoma, myelodysplastic syndrome

Question 36

How often is thrombocytosis assoc with a malignancy? Cause?

Assoc cancers? Other conditions?

Answer 36

• 35% of pts with platelet ct of greater than 400,000 have a malignancy
• from tumor production of cytokine IL-6
• assoc cancers:
  GI, lung, breast, gyn, lymphoma, renal cell, prostate, mesothelioma, gliobastoma, head and neck cancer
• other commonly assoc conditions:
  infection, post splenectory, acute blood loss, iron deficiency
• usually asx

Question 37

3 most common paraneoplastic syndromes?

Answer 37

• SIADH (increased ADH prod)
• cushing syndrome (increased ACTH production)
• hypercalcemia (PTH-RP): MM or bony mets

Question 38

What malignancies are most commonly assoc with paraneoplastic syndromes?

Answer 38

• SCLC (MC overall)
• breast cancer
• gyn tumors
• hematologic malignancies

Question 39

What may help aid in early dx of cancer?

Answer 39

• recognition of paraneoplastic syndrome

- most likely the neuro paraneoplastic syndromes - they present early in course of cancer