PARANEOPLASTIC SYNDROME · 2020. 4. 8. · Paraneoplastic syndrome dysfunction is not caused by...
Transcript of PARANEOPLASTIC SYNDROME · 2020. 4. 8. · Paraneoplastic syndrome dysfunction is not caused by...
PARANEOPLASTIC
SYNDROME
Ingrid Dravecká
I.Department of Internal medicine University Hospital, Košice
Paraneoplastic syndrome
Neoplastic cells can produce a variety of
products that can stimulate
o Hormonal
o Hematologic
o Dermatologic
o Neurologic responses
Paraneoplastic syndrome
Disorders that acompany benign or malignant tumors
Not directly related to mass effects or invasion
Every type of tumor has potential to produce
hormones, induce cytokines and immunological
responses
Paraneoplastic syndrome
More common than generally appreciated
Occurs in 7-15% of patients with cancer
Atypical „clinical manifestation“ of cancer
Presenting sign of an unknown neoplasma
Precedes the diagnosis of malignancy
The first sign of recurence
Paraneoplastic syndrome
dysfunction is not caused by invasion of neoplasm (i.e.
not neoplastic) → paraneoplastic
systemic or organic-specific effects
cancers such as small cell carcinoma of the lung
are more likely to cause paraneoplastic syndromes than
others
symptoms develop rapidly over days, weeks or months
Autoimune hypothesis
most paraneoplastic disorders are autoimmunity
diseases
certain protein antigens are sometime expressed in
a cancer
generate an immune response
tumor cells express „onconeural“ antigens that are
identical to molecules normally expressed by neurons
antibodies that react with both the tumor and other
tissue
Hormonal hypothesis
synthesis and secretion of peptide proteins (hormons)
Treatment
to identify the tumor and to treat it effectively
stop progressing of symptoms
immune supression (plasma exchange, i.v.
immunoglobulin)
Distribution
Endocrine system
Cutaneous system
Neurological system
Haematological system
Gastrointestinal system
Common and metabolic
ENDOCRINE SYSTEM
Ectopic production (by neoplastic cells) and expression
of hormones
Aberrant hormone expression
Clinical or biochemical evidence of abnormal endocrine
function in the absence of metastatic tumor spread to
the respective endocrine gland
Defective feedback control
Hypercalcemia caused by ectopic
production of PTHrP - etiology
Common finding in patients with cancer of the lung,
head, neck, skin, breast, lymphomas ...
Ectopic secretion of parathormon related
peptide (PTHrP)
Elevated PTH-like activity (functionally similar but
immunologically different)
Bone metastasis can produce PTHrP
o Cellular proliferation and differentiation in other tissues
o Local osteolysis
Syndrome of a inappropriate antidiuretic
hormone secretion (SIADH)
hyponatremia with plasma hypoosmolality
and innapropriate concentrate urine
absent cardial, renal, adrenal and thyroid
disorders
small cell carcinoma of the lung
elevated level of ADH as possible marker
of response to therapy
Syndrome of a inappropriate antidiuretic
hormone secretion (SIADH)
Laboratory:
hyponatremia (< 120 mmol/l)
elevated levels of ADH
Clinical manifestation
mental status changes, confusion, lethargy,
seizures
Humoral hypercalcemia of malignancy
Clinical manifestation
fatigue, mental status change, weakness
abdominal pain, constipation
nausea, vomiting, anorexia, polyuria
ecg: prolongation of PR and QRS intervals,
shortening of QT interval, bradycardia
Ectopic Cushing´s syndrome (ECS)
uncontrolled secretion of ACTH from
non-pituitary tissue
manifestation of hypercorticolism
12% !!! of all cases of Cushing´s syndrome
(50% - lungs tumors)
aberrant processing of POMC
Ectopic Cushing´s syndrome (ECS)
Clinical manifestation
ECS secondary to small cell carcinoma
rarely shows all the clasic signs of Cushing
syndrome
proximal myopathy, moon faciei,
hypokalemia, hyperglycemia
ECS secondary to bronchial carcinoma is
presented as hypertension and
hypokalemia
Ectopic secretion of gonadotropin
leydig cell hyperplasia
low to normal testosteron
excessive estrogen production
supression of FSH
testicular atrophy
gynecomastia
Glucagonoma syndrome
skin rash
impaired glucose tolerance
weight loss, anemia
GhRH syndrome
acromegaly
Pseudofeochromocytoma
Hypertension, hyperglycemia
Hypoglycemia
ectopic production of IGF-II
Inhib. of glycogenolysis, gluconeogenesis
CUTANEOUS PARANEOPLASTIC
SYNDROMES
Clubbing and hypertrophic
osteoarthropathy
digital clubbing – broadening and
thickening of the distal phalanges of the
fingers or toes, convexity of the nails
symetrical painfull arthropathy
squamous cell and adenocarcinoma of
lung
Pruritus
associated with Hodgkin lymphoma, other
lymphomas
adenocarcinomas of various organs
dissappears with eradication of the tumor
and reappears with reccurence of the
disease
Erythromelalgia
recurrent burning pain, redness and
warmth of the extremities
concomitant Raynaud´s phenomenon
myeloproliferative disorders
Palmar erythema
commonly associated with
hyperestrogenic states, liver disease,
hyperthyroidism, rheumatoid arthritis
18.5% patients with malignant brain
tumors
correlation between intensity of the
erythema and vascularity of the brain
tumor
other tumors: lung cancers, Hodgkin´s
disease, gastric adenocarcinoma
Erythroderma or exfoliative
dermatitis
diffuse erythema involving at least 90% of
the body
lymphoproliferative disorders, cancer of
cervix, lungs..
skin changes precede the diagnosis of
malignancy by several years
Necrolytic migratory erythema
or glucagonoma syndrome
pruritic and painful mucocutaneous
eruption presenting with the weight loss,
anemia, diabetes
lesions fluctuate and migrate on the body
surface
it is characteristic of glucagon secreting
alpha cell pancreatic carcinoma
high glucagon levels
Raynaud´s syndrome
acral ulcerations or digital ischemia,
manifesting as blanching and or cyanosis
of distal fingers after exposure to cold
cancers of all types
Dermatomyositis with or without
polymyositis
15-30% of malignancies
scaly of erythematous eruption affecting
photoexposed areas of the face, neck
Paraneoplastic pemphigus
B-cell lymphoproliferative disorders
mucosal erosions and eruptions
Acquired ichthyosis
lymphoproliferative disorders, solid
tumors
lower portion of the legs as large,
adherent, scaly lesions with pretibial
accentuation
Acanthosis nigricans
common marker for hyperinsulinism and
insulin resistance
asymptomatic hyperpigmented patches
on the neck, axxile, antecubital and
popliteal fossae
paraneoplastic form: sudden onset, rapid
and extensive spread
develops concomitantly with malignancy
Hypertrichosis lanuginosa acquista
sudden appearance of lanugo hair diffusely
on the face, trunk and extremities
women between 40-70 years
NERVOUS SYSTEM
variety of central and peripheral nervous
system syndromes
any cancer has the potential to cause
a paraneoplastic syndrome that will affect
the nervous system
severe nervous system disability
spinal fluid often contains an excess of
white cells and immunoglobulines
NERVOUS SYSTEM
Dementia
Limbic encephalopathy
the progressive change of personality to
dementia
Cellebelar degeneration
NERVOUS SYSTEM
Carcinoma associated retinopathy
Amyotrophic lateral sclerosis
Sensory neuropathy
Sensorimotor polyneuropathy
Myasthenia gravis
autoimmunity disease – antibodies against
ACCH receptors
muscle weakness, fatigue, double vision,
drop of eyelashes, malfunction of eye
muscles
Dermatomyositis
muscle weakness, fatigue, pain – pelvic and
arm muscles, joint disability, dysphagi
Encephalomyelitis
HAEMATOLOGICAL SYSTEM
Erythrocytosis
increased production of erythropoetine
kidney, liver cancer
Thrombocytosis
IL-6 produced by tumor
HAEMATOLOGICAL SYSTEM
Phlebothrombosis
Trousseau´s syndrome (adenocarcinoma
of pancreas + thrombosis)
pulmonary embolism
Intravascular coagulation
release and consuption of procoagulation
factors
GASTROINTESTINAL SYSTEM
Enteropathies
Hepatopathies
Anorexia, cachexy
Thanks for your attention