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