Paraneoplastic

Syndromes
Krzysztof Ronowski
Clinic of Oncology
Pozna University of Medical Sciences

Elective Course in Oncology for Medical

Students
18.08.2011
Pozna, Poland

Paraneoplastic Syndromes
- Different symptoms or pathological
disorders not directly caused by the
presence of malignant disease
- Distal manifestation from the primary
localization of the neoplasm or its
metastases

Paraneoplastic syndromes are

observed in the course of more
than 15% of all cases of
malignant diseases

Diagnosis of paraneoplastic
syndromes
Different pathological situations, like
chronic organs insufficiency,
infections, endocrine disorders can
give similar symptoms
Diagnosis of paraneoplastic syndromes
is diagnosis of exclusion other
diseases

Clinical appearance of
paraneoplastic syndromes
Symptoms preceding clinical
manifestation of neoplasm
Symptoms co-existing with signs of
active malignancy
Symptoms observed after failure of
treatment, present in late stages of
advanced/metastatic disease

Establishing diagnosis of
paraneoplastic syndromes
appearing before manifestation
of malignant disease could be
essential for early detection of
neoplasm

Therapeutic approach
Effective treatment of malignant
disease
Symptomatic treatment

Classification of paraneoplastic
syndromes
Common classification based on the
most affected tissue, organ or system

Classification according to mechanism

of initiation particular symptoms and
syndromes

Classification of paraneoplastic
syndromes cont.
Two basic mechanisms of appearance of
paraneoplastic syndromes:
- endocrine, as a result of excretion of
hormones, hormone related peptides or
cytokines
- autoimmunological, as a consequence of
antigen similarity between malignant and
normal tissues

Endocrinological manifestations
of neoplasmatic diseases
Inappropriate secretion of antidiuretic hormone
hyponatremia
Ectopic secretion of PTH or PTHrP hypercalcemia
Ectopic secretion of ACTH and ACTH-like
substances Cushings syndrome
Hypoglycemia as a result of ectopic secretion of
insulin-like growth factor t.II
Gonadotropins (example gynecomastia caused by
germ cell tumors secreting beta-hCG)

Hematological paraneoplastic
syndromes
Erythrocytosis due to secretion of
erythrtopoetin or/and cytokines enhancing
its effect (renal carcinoma, hepatoma,
phoechromocytoma)
Anemia the most common is normocytic
anemia of chronic disease, but also observed
autoimmune hemolytic anemia in the course
of limphoid malignances or microangiopatic
anemia

Hematological paraneoplastic
syndromes cont.
Granulocytosis associated with ectopic
secretion of G-CSF and GM-CSF,
observed in lymphoid malignancies
and tumors of digestive tract
Eosinophilia caused by tumorassociated eosinophil-stilmulating
factor (glycoprotein of 45kd) produced
by Hodgkins cells

Hematological paraneoplastic
syndromes cont.
Coagulopathies
Disseminated Intravascular
Coagulation (DIC) as an effect of
thrombocytopenia, hypofibrinogenemia
and activation of fibrinolisis; requiring
both effective anti-cancer therapy and
symptomatic therapy as life-threatening
status

Paraneoplastic syndromes
connected with nutrition and
digestive system
Anorexia misperception of signals in
feeding centre caused by inadequate level of
serotonin due to secretion of different
cytokines (TNF, IL1, IL6) by cancer cells
Protein losing enteropathy
Hypercatabolism stimulated by TNF- alfa, IL1,
IL6 and other cytokines observed mainly in
muscle and fat tissue

Paraneoplastic syndromes
connected with nutrition cont
Cachexia as a result of anorexia and
increased catabolism paraneoplastic
syndrome often observed in advanced
stages of malignant diseases after
failure of anticancer treatment; requires
symptomatic treatment for quality of
life improvement

Nephrological paraneoplastic
syndromes
Acute and chronic glomerulonephritis
as a result of autoimmunological
reaction against elements of kidneys
glomeruli
Renal failure due to precipitation of
ureic acid, pathological proteins or
calcium in the course of paraneoplastic
metabolic disorders

Cutaneous paraneoplastic
syndromes
Effect of autoimmunological reactions
against different dermal and epidermal
structures
Often preceding manifestation of
malignancy
Proper diagnosis may lead to early
detection of cancer

Cutaneous paraneoplastic syndromes

cont.
Leser - Trelat syndrome - diffuse seborhoic papillomatosis
affecting mainly trunk; early sign of many malignancies
especially deriving form gastro-intestinal tract; caused by
secretion of TGF and overexpression of EGFR

http://morningreporttgh.blogspot.com/2009/05/less-is-more.html

Cutaneous paraneoplastic syndromes

cont.
Sweet syndrome lupus-like, painful spots localized
on face and neck appearing sometimes few years
before manifestation of lymphoid malignancies

http://dermatology.cdlib.org/DOJvol5num1/therapy/sweets.html

Cutaneous paraneoplastic syndromes

cont.
Paraneoplastic acrokeratosis

Dermatology Online Journal 10 (1): 21

Cutaneous paraneoplastic syndromes

cont.
Pemphigus result of
autoimmunological reaction against
desmosomes

Cutaneous paraneoplastic syndromes

cont.
Dermatitis herpetiformes localized on knees, elbows
and lumbar region early manifestation of small
bowl lymphomas

Pruritis- one of general symptoms of hematological

malignancies as an effect of IL1, IL6 and TNF
secretion by lymphoid malignant cells or/and
activated lymphocytes T infiltrating different solid
tumors

Osteoarticular and muscle systems

paraneoplastic syndromes
Hypertrophic osteoarthropathy digital
clubbing, periostitis of tubular bone, generalized arthritis,
syndrome observed in the course of many solid tumors,
requiring besides primary treatment also effective symptomatic
treatment with steroids and non-steroid anti-inflammatory
drugs

http://cancergrace.org/lung/2009/02/10/hpoa/

Osteoarticular and muscle systems

paraneoplastic syndromes
Palmar Fasciitis and Polyarthritis

From medal.org, the largest collection of medical algorithms,

Institute of Algorithmic Medicine Under License to Medal.org Ltd

Osteoarticular and muscle systems

paraneoplastic syndromes cont.
Myositis
(ovarian cancer, NHL, thyroid cancer

http://www.radiologyassistant.nl/en/4ae30bb452e53

Neurological paraneoplastic
syndromes
Antigen similarity between malignant and nervous
tissue causing autoimmunological reactions e.g.
against myelin associated glycoprotein (MAG)
Acute or subacute inflammations often of
progressive, degenerative and irreversible character
Often preceding manifestation of neoplasm,
diagnosis difficult to establish, resistant for any kind
of therapy; diagnosis of malignant disease is set
often during autopsy after non effective treatment of
neurological disorders

Neurological paraneoplastic
syndromes cont.
Paraneoplastic cerebellar degeneration
subacute inflammatory- degenerative process in Purkynys cells,
leading to ataxia, dysartria, progressing dementia; difficult to
diagnose- MRI and CT scans non specific, sometimes elevated level
of IgG in cerebrospinal fluid; without effective treatment of
underlying malignancy lethal character of this syndrome

Paraneoplastic cerebellar
degeneration

http://www.penncancer.org/pnd/subpage

Neurological paraneoplastic
syndromes cont.
Retinal degeneration
Paraneoplastic opsoclonus-myoclonus
Limbic encephalitis
Sensory and motor neuropathy

Sensimotor peripheral neuropathy

Pseudomiastenic Lambert Eaton syndrome (small cell
lung cancer)

Miscellanenous Paraneoplastic
Syndromes
Fever one of general symptoms of
lymphoid malignances; influence of
interleukines on metabolism of arachidonic
acid leading to increased level of
prostaglandin E2, which stimulates
thermoregulatory centre;
In case of solid tumors the same effect
achieved by elevated level of interferons and
TNF produced by healthy cells as a result of
presence of malignant tissue

Paraneoplastic Syndromes
Knowledge of symptoms and syndromes not directly
connected with primary site of malignant tumor is
important for its early detection
Resolution of paraneoplastic syndromes may be a
prognostic factor in assessment of efficacy of
anticancer treatment
The best mode of treatment of paraneoplastic
syndromes is effective treatment of malignant
disease but for improvement of quality of patients
life, they sometimes require symptomatic treatment