Skin Signs Of Systemic Cancers

Skin Signs Of
Systemic Cancers

Mucocutaneous Signs Of Systemic
Cancers
• Mucocutaneous findings may suggest systemic
cancers in several ways.
• Associations of heritable mucocutaneous
disorders with systemic cancers.
• By action at a distance, i.e., paraneoplastic
syndromes.

Classification Of Skin Signs Of
Systemic Cancer
METASTATIC CANCERS
• Persistent tumor. Lymphatic extension,
hematogenous spread
• Direct extension. Paget disease,
extramammary Paget disease
• Lymphomas with secondary skin
involvement

HERITABLE DISORDERS
• Cowden syndrome
• Peutz-Jeghers syndrome
• Neurofibromatosis
• Tuberous sclerosis
• Multiple endocrine neoplasia (MEN) (types
1 and 2b)

PARANEOPLASTIC SYNDROMES
• Acanthosis nigricans, malignant, tripe palms
• Acquired ichthyosis
• Bazex syndrome
• Carcinoid syndrome
• Dermatomyositis (p. 14)
• Ectopic ACTH syndrome
• Erythema gyratum repens
• Gardner syndrome
• Glucagonoma syndrome
• Hypertrichosis lanuginosa
• Muir-Torre syndrome
• Palmar keratoses
• Paraneoplastic pemphigus
• Pruritus (p. 7)
• Pyoderma gangrenosum (p. 7)
• Sweet syndrome (p. 14)
• Vasculitis (p. 397)

Metastatic Cancer To The
Skin
• Metastatic cancer to the skin is
characterized by:
solitary or multiple dermal or subcutaneous
nodules, occurring as metastatic cells from a
distant noncontiguous primary malignant
neoplasm.

They are transported to and deposited in
the skin or subcutaneous tissue by one
of the following routes:
▪ Lymphatic routes.
▪ Hematogeneous spread.
▪ Contiguous spread across the peritoneal
cavity or other tissues

EPIDEMIOLOGY
• Age of Onset Any age, but usually older.
• Sex Frequency of primary tumors varies
with sex.
• Incidence In principle almost any cancer
can metastasize to skin. Skin metastases
occur in up to 10% of all patients with
cancer. The frequency of metastases
according to type of tumor are shown in
Table

• Melanoma 44.8
• Breast 30.0
• Nasal sinuses 20.0
• Larynx 16.3
• Endocrine glands 12.5
• Oral cavity 11.5
• Esophagus 8.6
• Kidney 4.6
• Stomach 2.0
Type of Primary Malignancy Patients with Cutaneous
Metastases, %

PATHOGENESIS
Includes detachment of cancer cells from
primary tumor,  invasion,  intravasation
into blood or lymphatic vessel, → circulation,
stasis within vessel,  attachment to
endothelium,  migration across vessel
wall,  invasion into tissue,  proliferation
at metastatic site.

The growth of metastases depends on:
proliferation of metastatic cells,
 cytokine and growth factor release from
cancer and stromal cells,
 angiogenesis,
and immune reactions.

Three patterns of metastases are
observed:
• mechanical tumor stasis (anatomic
proximity and lymphatic draining),
• site-specific (selective attachment of
tumor cells to specific organ),
• nonselective (independent of mechanical
or organ-specific factors).

Clinical Manifestation
• Prior history of primary internal cancer or
cancer chemotherapy or may be first sign
of visceral cancer.

Skin Lesions
• Nodule , raised plaque, thickened fibrotic area.
First detected when <5 mm. Fibrotic area may
resemble morphea; occurring on scalp, may
produce alopecia. Initially, epidermis is intact,
stretched over nodule; in time, surface may
become ulcerated or hyperkeratotic
• May appear inflammatory, i.e., pink to red or
hemorrhagic

Metastatic cancer to the skin:
bronchogenic cancer

Distribution
• Anywhere; specific sites :
Special Patterns of Cutaneous
Involvement:
1.Breast:
• I nflammatory metastatic carcinoma:
erythematous patch or plaque with an
active spreading border

Metastatic cancer of the skin:
inflammatory breast cancer (carcinoma
erysipelatoides) A large erythematous

2-Telangiectatic metastatic carcinoma (
carcinoma telangiectaticum ):
• breast cancer appearing as pinpoint
telangiectases with dilated capillaries within
carcinoma erysipelatoides. Violaceous papules
or papulovesicles resembling lymphangioma
circumscriptum.

• Metastatic ovarian cancer Manifesting as carcinoma
erysipelatoides on the lower abdomen and inguinal region. Workup
disclosed ovarian cancer with peritoneal carcinomatosis.

3-Breast carcinoma of inframammary
crease :
cutaneous exophytic nodule resembling
primary squamous cell carcinoma (SCC) or
basal cell carcinoma of skin

• Paget disease : sharply demarcated
plaque or patch of erythema and scaling
occurring on nipple or areola associated
with underlying breast cancer (see
below).

Multiple smooth nodules on scalp:
prostate adenocarcinoma, lung cancer,
breast cancer

2-Large Intestine :
Often presents on skin of abdomen or perineal
regions; also, scalp or face.
3-Lung Carcinoma:
May produce a large number of metastatic
nodules in a short period. Most commonly, reddish
nodule(s) on scalp

• Bronchogenic carcinoma. Large ulcerated,
crusted nodule on the scalp (((DDX)))

5-Hypernephroma:
Can produce solitary lesion; also
widespread. Usually appear vascular, ±
pulsatile, ± pedunculated ; can resemble
pyogenic granuloma. Most common on head
(scalp) and neck; also trunk and extremities.

Metastatic cancer to the skin,
hypernephroma
Hypernephroma metastases
often localize to the head and
have an angiomatous
appearance mimicking pyogenic
granuloma, as in this
lesion on the upper lip of a 66-
year-old man. This was
the first indication that the patient
had cancer of the
kidney.

6-Carcinoma of Bladder, Ovary:
Can spread contiguously to abdominal and
inguinal skin similarly to breast cancer, as
described above, and look like erysipelas
Metastatic breast cancer: cancer en
cuirasse Both breasts are hard upon
palpation—like
an armor plate. There are multiple small
and large, ulcerated nodules and there
is a background of erysipelas-like
erythema (carcinoma erysipelatoides)

• Metastatic cancer to the skin
Adenocarcinoma of the GI tract. This
fungating mass was just the tip of the
iceberg: a much larger mass was in the
subcutis.

• Metastatic cancer to the skin
Adenocarcinoma of the colon. Two
coalescent smooth firm nodules on the
abdomen.

Laboratory Examination
• Dermatopathology :
At times, cell differentiation and architectural
structure sufficient to predict primary site; however,
many times cells anaplastic. Employ monoclonal
antibodies to differentiate solid carcinoma
metastases from lymphoma, neuroendocrine
carcinoma, melanoma, anaplastic angiosarcoma,
and sarcomas.

Management
• With solitary or few lesions and if patient
not terminal, excision may be indicated.

Paget Disease
• Mammary Paget disease (MPD) is a malignant
neoplasm that unilaterally involves the nipple or
areola and simulates a chronic eczematous
dermatitis.
• It represents contiguous spread of underlying
intraductal carcinoma of the breast (1–4% of
breast cancers).
1- MAMMARY PAGET DISEASE

• Usually occurring in females (>50 years),
there are rare examples in males.
• Onset is insidious over several months or
years. May be asymptomatic or there may
be pruritus, pain, burning, discharge,
bleeding, ulceration, nipple invagination.

• Skin lesion presents as red, scaling
plaque, rather sharply marginated, oval
with irregular borders. When scale is
removed, the surface is moist and oozing

• Lesions range in size from 0.3–15 cm
• Mammary Paget disease A sharply defined
psoriasiform plaque that has obliterated the areola and
nipple. There was a lump in the breast and a small
axillary mass.

Differential diagnosis
• includes eczematous dermatitis, psoriasis,
benign ductal papilloma, nippleareola
retention hyperkeratosis, impetigo, SCC in
situ, familial pemphigus.

• Eczematous dermatitis of the nipples is
usually bilateral; it is without any induration
and responds rapidly to topical
glucocorticoids. Nevertheless, be
suspicious of Paget disease if “eczema”
persists for >3 weeks. Diagnosis verified
by biopsy showing neoplastic cells in
epidermis following a pathognomonic
pattern of spread. Define underlying
intraductal carcinoma by mammography.

Management
• surgery, radiotherapy, and/or
chemotherapy as in any other breast
carcinomas.
• Lymph node dissection if regional nodes
are palpable.

Prognosis
• When breast mass is not palpable, 92% of
patients survive 5 years after excision;
82%, 10 years. When breast mass is
palpable, 38% survive 5 years; 22%, 10
years. Prognosis worse when there is
lymphadenopathy.

Paget Disease
• Extramammary Paget disease (EPD) is a
neoplasm of the anogenital and axillary skin,
histologically identical and clinically similar to
Paget disease of the breast.
2- Extramammary Paget Disease

• Often representing an intraepidermal
extension of a primary adenocarcinoma of
underlying apocrine glands or of the lower
gastrointestinal, urinary, or female genital
tracts.
• Often, however, it is unassociated with
underlying cancer.

• The histogenesis of EPD not uniform.
Occurs as an in situ upward extension of
an in situ adenocarcinoma in deeper
glands (25%). Alternatively, EPD may
have a multifocal primary origin in the
epidermis and its appendages. Primary
tumors in the anorectum can arise within
the rectal mucosa or intramural glands.

• Insidious onset, slow spread, + itching.
The lesion presents as erythematous
plaque, + scaling, +erosion
• + crusting, + exudation; eczematous-
appearing lesions but borders are sharply
defined

• Extramammary Paget disease Moist, well-demarcated,
eroded, oozing, erythematous plaque on the scrotum
and inguinal fold in an older male. The lesion is
commonly mistaken for Candida intertrigo and
unsuccessfully treated as such.

• In perineal/perianal EPD, underlying
carcinoma should be searched for by
rectal examination, proctoscopy,
sigmoidoscopy, barium enema .
• In genital EPD, search for underlying
carcinoma by cystoscopy, intravenous
pyelogram ;
• in vulvar EPD, by pelvic examination

Differential diagnosis
• includes all red plaques: eczematous dermatitis,
lichen simplex chronicus, lichen sclerosus et
atrophicus, lichen planus, intertriginous
psoriasis, Candida intertrigo, SCC in situ
(erythroplasia of Queyrat), human papilloma
virus–induced SCC in situ, (amelanotic)
superficial spreading melanoma.

EPD is usually much larger than is apparent
clinically.
Surgical excision must be controlled histologically
(Mohs micrographic surgery).
If Paget cells are in dermis and regional lymph
nodes are palpable, lymph node dissection may
improve prognosis, which is related to underlying
adenocarcinoma.

Peutz-Jeghers Syndrome
• Peutz-Jeghers syndrome (PJS) is a familial
(autosomal dominant, spontaneous mutation in
40%) polyposis characterized by many small,
pigmented brown macules (lentigines) on the
lips, oral mucous membranes (brown to bluish
black), and on the bridge of the nose, palms,
and soles.

• Macules on the lips may disappear over
time, but not the pigmentation of the
mouth; therefore the mouth pigmentation
is the sine qua non for the diagnosis

The main criteria for clinical
diagnosis are:
• Family history
• Mucocutaneous lesions causing patches
of hyperpigmentation in the mouth and on
the hands and feet.
• Hamartomatous polyps in the
gastrointestinal tract.

• Barium enema
radiograph
showing
multiple polyps

• There are usually, but not always, multiple
hamartomatous polyps in the small bowel,
as well as in the large bowel and stomach,
that cause abdominal symptoms such as
pain, GI bleeding, anemia.
• Whereas pigmented macules are
congenital or develop in infancy and early
childhood, polyps come on in late
childhood or before age 30.

• Adenocarcinoma may develop in polyps,
and there is an increased incidence of
breast, ovarian, and pancreatic cancer.
• There is a normal life expectancy unless
carcinoma develops in the GI tract.
Malignant neoplasms may be more
frequent in Japanese patients with this
syndrome, and prophylactic colectomy has
been recommended for these patients.

Malignant Acanthosis
Nigricans
• malignant AN starts as a diffuse, velvety
thickening and hyperpigmentation chiefly on the
neck, axillae and other body folds, as well as on
the perioral and periorbital, umbilical, mamillary,
and genital areas, giving the skin a dirty
appearance

• Hyperpigmentation and hyperkeratosis
soon lead to a rugose, mamillated, and
papillomatous surface.
• Verrucous growths also involve the
vermilion border of the lips . On the oral
mucous membranes there is a velvety
texture with delicate furrows.

• The knuckles and the palms show
maximal accentuation of the palmar ridges
(tripe hands)
Acanthosis nigricans:
tripe palm
The palmar ridges of the
palm show maximal
accentuation, thus
resembling the mucosa of
the stomach of a ruminant
(tripe palm).

• Acanthosis nigricans: malignant Poorly defined, velvety,
verrucous and papillomatous, dark chocolate-brown plaques on the
medial thighs and scrotum. Similar changes were also present in the
axillae and neck, and the vermilion border of the lips was covered
with velvety, raspberry-like growths.

Acanthosis nigricans: malignant Verrucous and
mamillated growths on the vermilion border of the
lips in a patient with carcinoma of the stomach.
The gastric cancer was suspected because of
these raspberry-like growths, acanthosis nigricans
of the major skin folds, and weight loss. There is
still a suture at the site of a biopsy.

Malignant AN differs from other forms of AN
primarily because of :
(1) the more pronounced velvety hyperkeratosis
and hyperpigmentation,
(2) the pronounced mucosal involvement and
involvement of the mucocutaneous junction,
(3) tripe hands, and
(4) weight loss and wasting due to the underlying
malignancy.

• AN may precede by 5 years other
symptoms of a malignancy, usually
adenocarcinoma of the GI or GU tract,
bronchocarcinoma, or, less commonly,
lymphoma. Malignant AN is a truly
paraneoplastic disease, and a search for
underlying malignancies is imperative.
Removal of malignancy is followed by
regression of AN.

Paraneoplastic Pemphigus (PNP)
• Mucous membranes primarily and most
severely involved.
• Lesions combine features of pemphigus
vulgaris and erythema multiforme , clinically,
histologically, and immunopathologically.
• Most prominent clinical findings consist of
severe oral and conjunctival erosions in a
patient with an underlying neoplasm.

• Patients with PNP may also have clinical
and serologic evidence of myasthenia
gravis and autoimmune cytopenia.

• PNP sera contain autoantibodies to plakin
antigens (in the intercellular plaque of
desmosomes), envoplakin and periplakin,
and to desmoplakin I and II. Less
commonly patient sera may also recognize
bullous pemphigoid antigen (230 kDa),
plectin, and plakoglobin, and a unidentified
170- kDa antigen.

• Autoantibodies of PNP cause blistering in
neonatal mice and are detected by indirect
immunofluorescence on rodent urinary
bladder epithelium.

Treatment
is directed toward elimination or suppression
of malignancy but may also require systemic
glucocorticoids.

Paraneoplastic pemphigus -
Severe erosions covering practically the
entire mucosa
of the oral cavity with partial sparing of the
dorsum of
the tongue. Lesions are extremely painful,
interfering
with adequate food intake. This patient had
non-
Hodgkin lymphoma as underlying
malignancy.

• SOURCE: From FITZPATRICK’S COLOR ATLAS
AND SYNOPSIS OF CLINICAL DERMATOLOGY
SIXTH EDITION

Skin Signs Of Systemic Cancers

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