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PARANEOPLASTIC

DERMATOSES
P.ARUN PRASATH

CURTHS CRITERIA

1.

2.
3.

In 1976, Hellen ollendorf Curth proposed criteria for


diagnosis of paraneoplastic dermatoses
Both skin and malignant conditions start at approximately
the same time
Both conditions follow a parallel course
In syndromes, neither the onset nor the course of either
condition is dependent on the other

4.

A specific tumour occurs with a specific skin manifestation

5.

The dermatosis is not common in the general population

6.

A high degree of association between the two conditions is


noted
2 of the 6 criteria are needed to declare that a skin condition

CLASSIFICATION
1.

2.

3.
4.
5.

Acanthotic,
epidermal and
icthyotic conditions
CALM and
lentigines
Pigmentation
Pruritus
Hair, nail and skin
appendageal
involvement

6. Dermatoses
7.

Connective tissue and


rheumatological disorders

8.

Vascular disorders

9.

Deposition disorders

10.

Bullous disorders

1) ACANTHOTIC, EPIDERMAL AND


ICTHYOTIC CONDITIONS
1.

Acanthosis nigricans:

Malignancy associated AN have


.
Rapid onset
.
Symmetrical, hyperpigmented, rugose velvety plaques
.
Involving axilla, flexures, nape of neck, areola
.
Mucosal involvement point to paraneoplastic AN
.
Genesis: production by tumour cells of TGF-B,
cytokines activate insulin like growth factor or their
cutaneous receptors
.
Neoplasm associated: gastric adenocarcinoma most
common

Others: solid organ tumours, rarely lymphomas


and sarcomas

Association: with other paraneoplastic conditions


like
tripe palms,
leser-trelat sign,
pachydermoperiostosis,
paraneoplastic pemphigus,
malignant down.

Acanthosis nigricans:

2.

Acanthosis palmaris ( Tripe palms,


pachydermatoglyphy)

The name stems from its similar appearance to the gut


lining of bovine species, so-called tripe.
. It presents as a corrugate, rugose thickening of the
palms.
. The most common cancers associated: Gastric and lung
carcinoma.
. Tripe palms may be associated with AN, the sign of
Leser-Trelat, and early-stage ovarian cancer
. when not associated with AN, the most likely cancer is
lung adenocarcinoma.
.

TRIPE PALMS

3. The sign of Leser-Trelat:

Sudden eruption of multiple seborrheic keratoses


in association with malignant disease.
association with palmoplantar hyperkeratosis and
AN.
The most frequently reported malignancy is
adenocarcinoma of the stomach or colon.
Rare associations: malignant melanoma, renal
carcinoma, TCC of bladder, lymphoproliferative
disorders, malignant hemangiopericytoma

The sign of Leser-Trelat:

65-year-old man presented with a 4-month history of left flank pain and
nocturia.
Dermatologic examination revealed multiple eruptive seborrheic keratoses,
(Panels A & B). Abdominal USG and CT revealed a localized mass (7 cm by 5
cm in diameter) of the
left lower renal pole with central necrosis.

4. Acquired icthyosis:

presents as rhomboidal scales with free, slightly elevated


margins on extensor surfaces, sparing the flexural folds.
An abrupt onset in an older patient is suspicious for
malignancy.
most common: Hodgkin disease, lymphoreticular tumours
Rare: solid organ tumours, leiomyosarcoma

5. Pityriasis rotunda:
Fixed, annular, scaling, dry-skin associated with HCC
Also seen in leprosy and other systemic diseases

Acquired icthyosis
rotunda

Pityriasis

2 CALM AND LENTIGINES


CALM

LENTIGINES(L) &
FRECKLES(F)

1.

Neurofibromatosis

1.

Peutz-jeghers syndrome(L)

2.

Epiloia

2.

Carney complex (L)

3.

Blooms syndrome

3.

Cowdens disease(gL)

4.

MEN T I & II B

4.

5.

Fanconis anaemia

6.

VHL disease

7.

Ataxia telangiectasia

8.

Lynch syndrone

Paraneoplastic acral
lentiginosis

5.

XP(F)

6.

NF(F)

7.

Gardners syndrome(F)

3 PIGMENTATION
HYPERPIGMENTATION

1.
2.
3.

4.
5.

DIFFUSE:

Melanoma
PCC
Ectopic ACTH
syndrome
POEMS syndrome
Mastocytosis

6.

Lymphomas

7.

Werners syndrome

PATCHY/RETICULATED:

1.

Fanconis anaemia

2.

Dyskeratosis congenita

OTHERS:

1.

2.

Carcinoid syndrome
photodistribution
Pancratic, gastric, renal
tumours erythema ab igne
due to local heat application

Mixed hypo and hyper


pigmentation

Hypopigmentation

1.

Poikilodermatous:

Generalised:

Chediak-higashi
syndrome

1.

Dermatomyositis

Localised

2.

R-T syndrome

1.

TSC

2.

MF (Hypopigmented
variant)

4 PRURITUS

Pruritus is a nonspecific marker of malignant


disease. It occurs in apparently normal skin;
Generalized : most commonly associated with
lymphoma or leukemia.
In Hodgkins disease, pruritus begins on the legs
as a continuous burning.
Pruritus is usually a late sign and severe pruritus
signifies a poor prognosis.
Severe pruritus is also seen in Fanconis anemia,
myeloma, pancreatic, gastric tumours, carcinoid
syndrome, polycythemia rubra vera.

Localised pruritus:
Brachioradial pruritus: affects lateral upper arm
or dorsum of forearm due to spinal tumour and
mostly bony abnormalities
Facial or nasal pruritus: brain tumours, tumours
involving floor of fourth ventricle, trigeminal
neuralgia produce this distribution of pruritus

5 HAIR, NAIL AND SKIN APPENDAGES


1.

Hypertrichosis lanuginosa
acquisita(malignant down):

Rare, acquired, excessive growth of lanugo hair.


. The skin, especially on the face and ears, is covered
with soft,downy hairs.
. Prolongation of anagen phase
. The malignant type has a rapid onset and
progression.
. Causative tumours are found in the lung (most
commonly), colon, rectum, bladder, pancreas,
gallbladder, uterus, breast, and lymphatic tissues.
.

Hypertrichosis lanuginosa acquisita(malignant down):

68-year-old woman presented with a sudden increase in hair growth.


Physical examination revealed fine lanugo hair all over her face (Panel A)
and body (Panel B)
A diagnosis of acquired hypertrichosis lanuginosa was made.
increased serum level of carcinoembryonic antigen. Advanced rectal

2. Clubbing of nails:
Clubbing involves an increased convexity of the nail
and soft tissue enlargement of the tips of the
fingers and toes.
There is a loss of the 15 to 20 angle between the
downward curve of the proximal nail and the
adjacent proximal nail fold.
It is associated with neoplasms of the chest, such
as bronchogenic carcinoma, mesothelioma,
Hodgkins disease of the lung, intestinal lymphoma,
and solid tumours metastatic to the thorax.

New-Onset Clubbing Associated


with Lung Cancer

http://www.nejm.org/doi/full/10.105
6/NEJMicm066228

HOA:

Clubbing accompanied by subperiosteal new bone


formation is called hypertrophic osteoarthropathy.
Affected patients complain of bone pain, especially at
wrists, elbows, knees, and ankles, with associated
symmetrical and firm swelling and tenderness.
Epiphyses are spared in the malignant form.
90% of the cases of hypertrophic osteoarthopathy in
adults occur in patients who have or will develop a
malignancy.
The most frequent tumour is non-small-cell lung
cancer, mesothelioma.

Hypertrophic Pulmonary Osteoarthropathy


and Tripe Palms

56-year-old male smoker presented with cough, a weight loss, and diffuse
bone pain
.
The palms had a raised velvety texture (Panel A), and there was digital
clubbing (inset).
CT chest showed a mass in the upper lobe of the right lung (Panel B).
bone scan (Panel C) showed areas of diffuse linear uptake in the femoral
and tibial bones, consistent with hypertrophic pulmonary osteoarthropathy

3. Hyperhidrosis:
Generalised: consistent finding in
phaeochromocytoma
Nocturnal: pcc, lymphoma, carcinoid syndrome
Localised: poems syndrome
4. Sebaceous neoplasms:
Strongly associated with muir-torre syndrome

6 DERMATOSES
1.

Acrokeratosis paraneoplastica (Bazex syndrome):

Is a symmetric hyperkeratosis that affects hands, feet,


ears, and nose.
. It has a psoriasiform appearance, but with a more
bluish hue when compared with the pink colour of
typical psoriasis.
. Early and severe nail involvement is seen in 75% of
cases.
. Subungual hyperkeratosis, flanky white nails, and nail
shedding is common;
. Distal digits are red, fissured, and suppurative.
.

Bazex syndrome is seen in males with squamous


cell carcinomas of the upper aerodigestive tract
(pharynx, esophagus, tongue, lungs).
It precedes the cancer in approximately 67% of
patients.
Retinoids can be used successfully to treat the
syndrome
Causation of this hyperkeratosis:
theories include antigen cross-reactivity between
tumour and skin, or tumour-derived keratinocyte
growth factors.

BAZEX SYNDROME

2. Dermatomyositis:

Specific malignant association- lung cancer in men,


breast and gynaecological tumours in women,
colorectal cancers in both sexes
Subjects with myositis specific autoantibody reactive
with 155kDa and 140kDa nuclear antigens had a
much higher risk
High frequency of heliotrope rash, gottrons papules,
and flagellate erythema in this antibody + subjects
Blind CT scan of chest, abdomen, pelvis increased
yield of malignancies

Dermatomyositis

Gottron's papules.
Erythematous to violaceous
raised papules overlying the
metacarpal and
interphalangeal joints in a
patient with dermatomyositis

Heliotrope. Confluent macular


erythema confined to the upper
eyelid, with associated periorbital
edema

3.Migratory erythemas:
i.
.

.
.

Erythema gyratum repens:


Is a figurate erythema demonstrating rapidly migrating
concentric rings of erythema with a trailing scale,
found on the trunk and proximal extremities.
Described as a wood-grain appearance, the bands
move approximately 1 cm/day.
Strong association with lung cancer
others: carcinomas of the breast, lung, bladder,
prostate, cervix, stomach, esophagus, and multiple
myeloma.
Skin changes precede the tumour 80% of the time .

Erythema gyratum repens:

83-year-old man was evaluated for a 1-year history of a pruritic,


progressively worsening migratory rash, with associated weakness and
weight loss
erythematous skin lesions appeared in concentric, raised, serpiginous
bands, with desquamation (Panel A).
A computed tomographic scan revealed a pulmonary mass measuring 59 by
43 mm (Panel B).

ii) Necrolytic migratory erythema:(glucagonoma


syndrome)

Is a reactive erythema that is a marker for an alpha-2glucagon-producing islet cell tumour of the pancreas.
Eruptions begin as erythematous patches in the groin
and spread to the thighs, buttocks, perineum, and face.
This is followed by scaling, vesicles, pustules, and
bullae.
These heal over a period of 1 to 2 weeks, leaving
indurated, hyperpigmented scars. The course waxes
and wanes.

Necrolytic migratory erythema:


(glucagonoma syndrome)

63-year-old woman with a 41/2-year history of diabetes mellitus presented


with an ulcerating rash, primarily on the shins, groin, and face (Panel A);
cheilitis (Panel B); and glossitis
An enhancing, lobulated mass measuring 7 cm in diameter was found in
the
tail of the pancreas, and the patients fasting glucagon level was
elevated, at 890 pg

Other clinical features : glucose intolerance, high


serum glucagon levels, weight loss, anemia,
diabetes, mental status changes, and venous
thrombosis.
Diagnosis is made by measuring plasma glucagon
levels.
Most patients have metastatic disease at
presentation.
Rx: octreotide that affects the somatostatin
receptors in the skin.

iii) Erythema annulare centrifugum:

Associated with myeloproliferative disorder

iv) Urticaria:

Schnitzlers syndrome: chronic urticaria, bone pain,


hyperostosis, high ESR, monoclonal gammopathy

v)Erythroderma:

Malignant causes include mycosis fungoides or its


leukaemic variant sezary syndrome , other leukemia and
lymphoma, specifically cutaneous T-cell
lymphoma(CTCL).
Solid tumours (late stage) originate from the lung, liver,
prostate, thyroid, colon, pancreas, and stomach .
Ofuji papuloerythroderma associated with peripheral Tcell non-epidermotrophic cutaneous lymphoma

vi)Granuloma annulare:

Associated with lymphomas, haematological


malignancies uncommonly with solid tumours

vii)IBA like reactions :

Haematological malignancies usually CLL

viii)Cutis verticis gyrata:

Occasionally occur as a paraneoplastic syndrome

ix)Mental neuropathy(numb chin syndrome):

Solid organ tumours, lymphoma, melanoma

7 CONNECTIVE TISSUE AND


RHEUMATOLOGICAL DISORDERS
DERMATOSES

TYPE / VARIANT

MALIGNANCY ASSOCIATED
LYMPHOMAS

LUPUS
ERYTHEMATOSUS

SLE
CA - BREAST, LUNG, CERVIX
MONOCLONAL GAMMOPATHY
SCLE

MYELOPROLIFERATIVE

DISORDERS

CA LUNG, LIVER, LARYNX, BREAST,


OESOPHAGUS
LUPUS
ERYTHEMATOSUS
GYRATUM REPENS

SCLERODERMOID
CONDITIONS

EOSINOPHILIC
FASCITIS PANNICULITIS

INCREASED RISK OF INTERNAL


MALIGNANCY
CA OVARY , LUNG

RELAPSING
POLYCHONDRITIS

MYELODYSPLASTIC SYNDROME

SARCOIDOSIS

LYMPHOMA
TESTICULAR TUMOUR, MM, MELANOMA

Contd..
DERMATOSES

NEUTROPHILIC
DERMATOSES

TYPE / VARIANT

PYODERMA
GANGRENOSUM
- SUPERFICIAL
- BULLOUS

SWEETS SYNDROME

MULTICENTRIC RETICULO
HISTIOCYTOSIS

MALIGNANCY
ASSOCIATED
MYELOPROLIFERATIVE
DISORDERS
IgA GAMMOPATHY
SOLID TUMOURS

MYELODYSPLASTIC DISORDERS

SOLID TUMOURS
HEMATOLOGICAL DISORDERS

Pyoderma gangrenosum of the lower leg in a patient with


myelodysplastic syndrome

8 VASCULAR DISORDERS
CONDITION

FEATURES

MALIGNANCY
ASSOCIATED

1. RAYNAUDS

ACROCYANOSIS
CUTANEOUS ISCHAEMIA
DUE TO MICROTHROMBI
DIGITAL INFARCTION AND
GANGRENE

RETICULOENDOTHELIAL
NEOPLASAMS
SOLID TUMOURS
HYPERVISCOSITY
SYNDROMES
(PCV, MYELOMA LINKED
CRYOGLOBULINEMIA)
HYPEREOSINOPHILIC
SYNDROME

FEET COMMONLY INVOLVED


SEVERE BURNING PAIN
ERYTHEMA
MICROVASCULAR
OCCLUSION WITH
PLATELETS @ WHITE
THROMBI

PCV
ESSENTIAL
THROMBOCYTHEMIA

PHENOMENON AND DIGITAL


ISCHAEMIA

2. ERYTHROMELALGIA

3.PALMAR ERYTHEMA

HIGH GRADE

Contd..
CONDITION

FEATURES

MALIGNANCY
ASSOCIATED

4. VASCULITIS

PALPABLE PURPURA,
MACULOPAPULAR,
URTICARIAL
& PETECHIAL LESIONS

HAIRY CELL LEUKAEMIA


MYELOMA
SOLID ORGAN TUMOURS

5.CHILBLAIN LIKE
LESIONS

PERSISTENT RATHER
THAN EPISODIC
RESISTANT TO RX

LEUKAEMIA
MYELOPROLIFERATIVE
DISORDERS
METS FROM BREAST CA

6.FLUSHING

PERSISTENT ERYTHEMA
+_ TELENGIECTASIA
(SCLERODERMA LIKE
CHANGES
PELLAGROID
DERMATITIS

CARCINOID SYNDROME*
MASTOCYTOSIS
PHAEOCHROMOCYTOMA
MCT, RCC, VIPOMAS

Contd..
CONDITION

FEATURES

MALIGNANCY ASSOCIATED

7.CANCER ASSOCIATED
THROMBOSIS
I) MIGRATORY
THROMBOPHLEBITIS
II) DVT

RECURRENT, MULTIPLE,
MIGRATORY
UPPER LIMB

CA PANCREAS, STOMACH,
COLON, LUNG
ADENOCA IN GIT,
UROGENITAL TRACT, BREAST,
LUNG
BREAST CA

III) MONDORS DISEASE

CORD LIKE THROMBOSIS


OF THORACIC &
EPIGASTRIC VEINS

8.OBSTRUCTION
VENOUS

PEMBERTON SIGN

LYMPHATIC

AXILLARY

9.OTHERS
GLOMERULOID ANGIOMA
TELANGIECTASIA
PAINFUL TELANGIEATATIC

RETROSTERNAL THYROID CA
ENLARGEMENT
BREAST CA., LIMB MELANOMA
POEMS SYNDROME
BLOOMS, RT, ADVANCED
CARCINOID
MALIGNANT

9 DEPOSITION DISORDERS
MATERIAL DEPOSITED

DISORDER

ASSOCIATED
INTERNAL
MALIGNANCY

AMYLOID PROTEINS

PRIMARY AND MYELOMA


ASSOCIATED SYSTEMIC
AMYLOIDOSIS (AL
PROTEIN)

PARAPROTEINEMIA,
MYELOMA

SECONDARY
AMYLOIDOSIS
(AA PROTEIN )

HL, HYPERNEPHROMA,
SOLID ORGAN TUMOURS

MUCIN/PROTEOGLYCAN/
FIBROMUCINOSES

SCLEROMYXEDEMA/LICH
EN MYXOEDEMATOUS
PAPULAR MUCINOSES
ALOPECIA MUCINOSA
SCLEREDEMA
POEMS SYNDROME

PARAPROTEINE
MIA

Dermatologic Signs of Multiple Myeloma

87-year-old woman presented for evaluation of progressive, nonpruritic,


waxy papules and ecchymoses in a periorbital (raccoon eyes, ) and
perioral distribution.
HPE revealed hyalinized, amorphous material in the superficial dermis.
Positive Congo red staining and apple-green birefringence under polarized
light confirmed the presence of amyloid fibrils.
Serum and urine electrophoresis with immunofixation revealed monoclonal
kappa light-chain proteins

Scleromyxedema

70-year-old patient presented with a one-year history of progressive


tightening of the skin. examination showed generalized sclerodermoid
induration and discoloration of the skin (Panel A),. Serum electrophoresis
showed a monoclonal gammopathy of the IgG, with lambda light chains.
specimen showed fibrosis, proliferation of fibroblasts, and interstitial deposits
of mucin in the dermis (Panel B).

Contd..
MATERIAL DEPOSITED

DISORDER

ASSOCIATED
INTERNAL
MALIGNANCIES

LIPIDS

NECROBIOTIC
XANTHOGRANULOMA

PARAPROTEINAEMIA

NOROMOLIPEMIC PLANE
XANTHOMATOSIS

MYELOMA

XANTHOMA
DISSEMINATUM

GAMMOPATHY, BONE
MARROW DYSCRASIAS

METASTATIC
CALCIFICATION

LUNG CA, OTHER


SQUAMOUS CA, MEN
SYNDROME

CALCIUM

PANCREATIC CA
DYSTROPHIC
CALCIFICATION

Contd..
MATERIAL
DEPOSITED

DISORDER

ASSOCIATED INTERNAL
MALIGNANCIES

BILE SALTS AND


PIGMENTS

ICTERUS

INTRHEPATIC BILE DUCT


OBS
EXTRAHEPATIC OBS BY CA
PANCREAS, GB, BILE DUCT,
COLON

IRON

HEMOCHROMATOSIS
(BRONZE DIABETES)

HEPATOCELLULAR CA

MELANIN

MELANOSIS

MALIGNANT PITUITARY
TUMOURS
METASTATIC MALIGNANT
MELANOMA

Cutaneous Melanoma Metastases

55-year-old woman presented with an acral lentiginous melanoma of the left


sole. A radical extirpation of the tumor and an elective dissection of the
inguinal lymph nodes were performed.
Two years later, neoplastic cells had spread to the skin of the lower left leg.
Despite treatment with interleukin-2 and the cytostatic drug dacarbazine,
the metastatic disease involved almost all the skin of the lower left leg

10 BULLOUS DISORDERS
PARANEOPLASTIC PEMPHIGUS

Heterogeneous, multiorgan, autoimmune


syndrome with spectrum of
mucocutaneous manifestations including

pemphigus-like,

pemphigoid-like,

erythema multiforme-like,

graft-versus-host disease-like or

lichen planuslike patterns,

characteristically with intractable oral


ulcers

Associated neoplasms :

Hodgkins lymphoma

Chronic lymphocytic leukaemia

Castlemans tumour, Thymoma

Spindle cell neoplasms and

BULLOUS PEMPHIGOID

Associated Malignancies

Breast, lung, thyroid, larynx,


skin, soft tissue,
Stomach, colon,
lymphoreticular system
prostate, cervix, bladder
kidney and uterus.

PEMPHIGUS VULGARIS

Pemphigus has been linked with


various tumours ,such as
Thymoma and
Castlemanstumour.

Pemphigus foliaceus has been


associated with acanthosis
nigricans-like lesions and
hepatocellular carcinoma .

Pemphigus in Japanese subjects


has been associated with lung
cancer.

OTHER BLISTERING DISORDERS


CONDITION

MALIGNANCY ASSOCIATED

DERMATITIS HERPETIFORMIS

LYMPHOMA- NHL

LIGA

LYMPHOPROLIFERATIVE MALIGNANCY

EBA

MYELOMA, LYMPHOMA

PCT & VARIEGATE PORPHYRIAS

HCC, MYELOMA, VISCERAL CA

A-Z OF CUTANEOUS MANIFESTATIONS


OF INTERNAL MALIGNANCY
A AN, AT

ICTHYOSIS,
INFECTIONS

RAYNAUDS, RT

B BULLOUS D, BLOOMS,
BAZEX,B-K MOLE

JAUNDICE

SK(LT), SWEETS,
SCLERDERMOID SKIN

C CLUBBING, CALM,CVG,
C-H SYN, COWDENS,
CARNEY

K KERATODERMA

TRIPE PALMS, TYLOSIS,


TSC

D DM

L LENTIGINES,
LYMPHODEMA,
LICHENOID D

URTICARIA

E EGR, EMF, ED, EAC

M MIGRATORY TP,
MONDORS D, MT SYN,
MEN SYN

VASCULITIS, VHL

F FLUSHING, FREECKLES,
FANCONI

N NME, NF, NODULE(SMJ)

W-A, WERNER

G GA,GORLINS,GARDNER
S

O OFUJI PE, ORW

XEROSIS, XANTHOMA,
XP

THANK YOU

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