10 1 paraneoplastic syndromes (1)

8/10/2019 10 1 Paraneoplastic Syndromes (1)

1/31

Paraneoplastic

Syndromes

Krzysztof RonowskiClinic of Oncology

Pozna University of Medical Sciences

Elective Course in Oncology for Medical

Students

18.08.2011

Pozna, Poland
http://www.ump.edu.pl/pol/?department=12


2/31

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


3/31

Paraneoplastic syndromes are

observed in the course of more

than 15% of all cases ofmalignant diseases


4/31

Diagnosis of paraneoplastic

syndromes

Different pathological situations, like

chronic organs insufficiency,

infections, endocrine disorders cangive similar symptoms

Diagnosis of paraneoplastic syndromesis diagnosis of exclusion other

diseases


5/31

Clinical appearance of

paraneoplastic syndromes

Symptoms preceding clinicalmanifestation of neoplasm

Symptoms co-existing with signs ofactive malignancy

Symptoms observed after failure oftreatment, present in late stages ofadvanced/metastatic disease


6/31

Establishing diagnosis ofparaneoplastic syndromes

appearing before manifestation

of malignant disease could beessential for early detection of

neoplasm


7/31

Therapeutic approach

Effective treatment of malignant

disease

Symptomatic treatment


8/31

Classification of paraneoplastic

syndromes

Common classification based on the

most affected tissue, organ or system

Classification according to mechanism

of initiation particular symptoms andsyndromes


9/31

Classification of paraneoplastic

syndromes cont.

Two basic mechanisms of appearance ofparaneoplastic syndromes:

- endocrine, as a result of excretion ofhormones, hormone related peptides orcytokines

- autoimmunological, as a consequence ofantigen similarity between malignant andnormal tissues


10/31

Endocrinological manifestations

of neoplasmatic diseases Inappropriate secretion of antidiuretic hormone

hyponatremia

Ectopic secretion of PTH or PTHrP hypercalcemia

Ectopic secretion of ACTH and ACTH-likesubstances Cushings syndrome

Hypoglycemia as a result of ectopic secretion ofinsulin-like growth factor t.II

Gonadotropins (example gynecomastia caused by

germ cell tumors secreting beta-hCG)


11/31

Hematological paraneoplastic

syndromes

Erythrocytosis due to secretion oferythrtopoetin or/and cytokines enhancingits effect (renal carcinoma, hepatoma,phoechromocytoma)

Anemia the most common is normocyticanemia of chronic disease, but also observed

autoimmune hemolytic anemia in the courseof limphoid malignances or microangiopaticanemia


12/31


syndromes cont.

Granulocytosis associated with ectopicsecretion of G-CSF and GM-CSF,

observed in lymphoid malignanciesand tumors of digestive tract

Eosinophilia caused by tumor-associated eosinophil-stilmulatingfactor (glycoprotein of 45kd) producedby Hodgkins cells


13/31


syndromes cont.

Coagulopathies

Disseminated IntravascularCoagulation (DIC) as an effect ofthrombocytopenia, hypofibrinogenemiaand activation of fibrinolisis; requiringboth effective anti-cancer therapy andsymptomatic therapy as life-threateningstatus

P l ti d


14/31

Paraneoplastic syndromes

connected with nutrition and

digestive system

Anorexia misperception of signals infeeding centre caused by inadequate level of

serotonin due to secretion of differentcytokines (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


15/31

Paraneoplastic syndromes

connected with nutrition cont

Cachexia as a result of anorexia and

increased catabolism paraneoplasticsyndrome often observed in advanced

stages of malignant diseases after

failure of anticancer treatment; requiressymptomatic treatment for quality of

life improvement


16/31

Nephrological paraneoplastic

syndromes

Acute and chronic glomerulonephritisas a result of autoimmunological

reaction against elements of kidneysglomeruli

Renal failure due to precipitation ofureic acid, pathological proteins orcalcium in the course of paraneoplasticmetabolic disorders


17/31

Cutaneous paraneoplastic

syndromes

Effect of autoimmunological reactionsagainst different dermal and epidermal

structures

Often preceding manifestation ofmalignancy

Proper diagnosis may lead to earlydetection of cancer


18/31

Cutaneous paraneoplastic syndromes

cont.

Leser - Trelat syndrome - diffuse seborhoic papillomatosisaffecting 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


19/31


cont.

Sweet syndrome lupus-like, painful spots localizedon face and neck appearing sometimes few yearsbefore manifestation of lymphoid malignancies

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


20/31


cont.

Dermatology Online Journal 10 (1): 21

Paraneoplastic acrokeratosis


21/31


cont.

Pemphigus result of

autoimmunological reaction against

desmosomes


22/31


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


23/31

Osteoarticular and muscle systems


Hypertrophic osteoarthropathy digitalclubbing, 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/


24/31



Palmar Fasciitis and Polyarthritis

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

Institute of Algorithmic Medicine Under License to Medal.org Ltd
http://www.medal.org/http://www.medal.org/


25/31


paraneoplastic syndromes cont.

Myositis(ovarian cancer, NHL, thyroid cancer

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


26/31

Neurological paraneoplastic

syndromes

Antigen similarity between malignant and nervoustissue causing autoimmunological reactions e.g.against myelin associated glycoprotein (MAG)

Acute or subacute inflammations often ofprogressive, degenerative and irreversible character

Often preceding manifestation of neoplasm,diagnosis difficult to establish, resistant for any kindof therapy; diagnosis of malignant disease is setoften during autopsy after non effective treatment ofneurological disorders


27/31


syndromes cont.

Paraneoplastic cerebellar degeneration

subacute inflammatory- degenerative process in Purkynys cells,

leading to ataxia, dysartria, progressing dementia; difficult todiagnose- 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


28/31

Paraneoplastic cerebellar

degeneration

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


29/31


syndromes cont.

Retinal degeneration

Paraneoplastic opsoclonus-myoclonus

Limbic encephalitis

Sensory and motor neuropathy

Sensimotor peripheral neuropathy

Pseudomiastenic Lambert Eaton syndrome (small celllung cancer)


30/31

Miscellanenous Paraneoplastic

Syndromes

Fever one of general symptoms oflymphoid malignances; influence ofinterleukines on metabolism of arachidonic

acid leading to increased level ofprostaglandin E2, which stimulatesthermoregulatory centre;

In case of solid tumors the same effectachieved by elevated level of interferons andTNF produced by healthy cells as a result ofpresence of malignant tissue


31/31

Paraneoplastic Syndromes

Knowledge of symptoms and syndromes not directlyconnected with primary site of malignant tumor isimportant for its early detection

Resolution of paraneoplastic syndromes may be aprognostic factor in assessment of efficacy ofanticancer treatment

The best mode of treatment of paraneoplasticsyndromes is effective treatment of malignantdisease but for improvement of quality of patientslife, they sometimes require symptomatic treatment

10 1 paraneoplastic syndromes (1)

Documents