cutaneous manifestations are extremely valuable marker because they may well be the presenting manifestation of an underlying neoplasm. Increased clinician awareness could prove beneficial for the patient by promoting earlier screening and diagnosis, as well as increased intervention measures, thereby significantly affecting the chances of survival and/or improving the quality of life of the patient

1. DR. GAMAL SULTAN

3. INTRODUCTION
cutaneous manifestations are extremely valuable marker because
they may well be the presenting manifestation of an underlying
neoplasm.
Increased clinician awareness could prove beneficial for the patient
by promoting earlier screening and diagnosis, as well as increased
intervention measures, thereby significantly affecting the chances
of survival and/or improving the quality of life of the patient

4. CUTANEOUS
METASTASIS OF
MALIGNANCIES
CUTANEOUS SIGN &
SYMPTOMS OF
MALIGNANCY
CUTANEOUS
PARANEOPLASTIC
SYNDROMES

5. Cutaneous metastases from carcinoma are relatively uncommon in
clinical practice, but they are very important to recognize
The incidence of cutaneous malignancy varies. In some autopsy
studies of patients with metastatic carcinoma, as many as 9% of
individuals were noted to have cutaneous metastases. Other studies
suggest a range of 3-4%.
rarely the presenting sign but their re-appearance may be an
indicator of disease recurrence.

6. The most common metastatic malignancies
In woman
the breasts (69%), the colon (9%), melanomas (5%), the ovaries
(4%), and the lungs (4%).
In men
the lungs (24%), the colon (19%), melanoma (13%), and the oral
cavity (12%).

7. The mechanism for metastasis
Regional spread by way of tissue most often occurs through body
cavities, especially the peritoneal cavity. Transplantation can be
caused by mechanical transport of tumor fragments by instruments
during surgery or other invasive procedures.
Lymphatic and vascular routes are the most common pathways,
Lymphatic spread is the most common pathway for the initial
spread of carcinoma.
Hematogenous spread is commonly associated with metastasis
from sarcomas

8. Clinical Presentation of Cutaneous
Metastases
They present as solitary or multiple
nodules. The nodules are often
nonpainful, round or oval, firm,
mobile, and rubbery in texture. The
nodules are usually flesh colored, (
from flesh colored to brown or blue-
black).
tend to have a predilection for areas
of old surgical scars

9. The scalp is a primary site of
distant tumor metastases,
with lesions that appear
either nodular or as
circumscribed areas of hair
loss, known as alopecia
neoplastica

10. The lymphatic obstruction from
tumor cells leads to extensive
thickening of the skin, and
fibrosis of the dermis and
subcutaneous tissue The term
carcinoma en cuirasse is a hard
and infiltrated plaque with a
characteristic leathery or woody
appearance

11. Sister Mary Joseph’s nodule
is a broad term that refers to any
malignant metastatic nodule near the
umbilical area, with the primary sites
of origin most commonly being
malignancies of the stomach, colon,
ovaries, pancreas, gallbladder, and
lymphomas

12. Common cutaneous sites for metastases and their
probable primary sites
Scalp
breast, lung,kidney
Neck
oral SSC
Face
oral SSC, lung,
kidney
Chest
breast, lung, mela-
noma
Extremities
melanoma, breast,
lung, renal,
intestinal
Umbilicus (Sister Mary
Joseph's nodule)
stomach, colon, ovary,
kidney, breast
Back
lung

13. pruritus
petechiae,
ecchymoses
pallor ichthyosis
urticaria
bullous
eruptions
erythema
nodosum
alopecia
stomatitis phlebitis

14. Generalized pruritus may be the
initial symptom present in patients
with solid tumors .
pruritus origin is complex. It can be
either peripheral or central in origin.
The production of pruritogenic
mediators such as histamine,
serotonin, and cytokines stimulate the
free nerve endings of specialized C
fibers found in the skin

15. The use of corticosteroids or
H2 receptor blockers,, is not
useful in the treatment of
pruritus associated with solid
tumors. Twycross et al.
proposed a treatment ladder
for the management of
pruritus in these patients,
consists of using paroxetine

16. A localized itch may offer a
diagnostic clue to an underlying
malignancy, for example:
(1) scrotal itch may be associated
with prostate cancer;
(2) nostril itching associated with
brain tumors infiltrating the floor
of the fourth ventricle;
(3) vulval itch with cervical cancer;
(4) perianal itch with colon or rectal
cancer

17. They are defined as clinical syndromes involving non-metastatic systemic
effects that accompany malignant disease
disorders that are triggered by an altered immune system response to a
neoplasm. result from substances produced by the tumor, and they occur
remotely from the tumor itself
The symptoms may be endocrine, neuromuscular or musculoskeletal,
cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or
miscellaneous in nature.

18. (AN) manifests as a
hyperpigmented, velvety
thickening of the skin that
usually occurs in the
intertriginous zones, including
the axillae, groin, neck, and
inframammary folds.

19. Acanthosis nigricans can be classified into three
different subgroups:
the hereditary benign acanthosis nigricans,
Acanthosis nigricans related to obesity
Acanthosis nigricans in an obese patient, it is usually
benign and related to an increase in insulin resistance. A
family history of endocrinopathies,as well as chronic
steroid use.
malignant acanthosis nigricans

20. Malignant Acanthosis Nigricans
 Patients who have AN associated with
malignancies also have skin changes
involving the scalp, areolae, and eyelids.
 Most cases of paraneoplastic AN involve
an adeno-carcinoma, most commonly one
arising in the GIT (stomach or live) and
less commonly in the (lungs, ovaries,
uterus, breasts, kidneys, prostate or
bladder)

21. conditions manifest with small, whitish to
brownish, polygonal scales that lift up at
the free edge and are widely distributed
on the trunk and extensor surfaces of the
extremities.
The palms and soles are usually spared.
This condition is associated with a variety
of chronic illnesses, including
malignancy.

23. Associated noncancerous conditions
Acquired immunodeficiency syndrome (AIDS)
Systemic lupus erythematosus
Sarcoidosis
Autoimmune disease e.g., dermatomyositis and mixed connective-tissue disease
Endocrine abnormalities E.g., hyperparathyroidism and hypothyroidism
Malnutrition
Infectious etiologies - E.g., tuberculosis and leprosy
Use of certain medications - E.g., nicotinic acid, cimetidine, and clofazimine

24. Associated cancers
AI is most strongly associated with Hodgkin lymphoma
Other AI-associated malignancies include Kaposi sarcoma,
cutaneous T-cell lymphoma, non-Hodgkin lymphoma, leukemias,
and solid tumors (including those arising in breasts, lungs, or
bladder).
Rare cases of AI associated with graft versus host disease
(GVHD) have been reported after bone marrow transplantation.

25. symmetrical, scaly, violaceous
plaques on the acral surfaces,
with severe forms progressing to
bullae. The lesions
predominantly occur on the
hands, feet, ear helices, nose tip,
and scalp

26. Skin changes may spread to involve
the knees, elbows, and malar surface
of the face.
Alopecia and nail changes are
common and can be early findings.
Subungual hyperkeratosis, onycho-
dystrophy, and white flaking of the nail
surface.

27. Skin eruptions often precede detection of the cancer, with a
reported median interval of as long as 1 year between the onset of
skin changes and the diagnosis of malignancy.
The development of the lesions also tends to parallel the course
of malignancy
The lesions may regress with successful cancer therapy and
may recur with relapses, thus serving as a marker for status.

28. 3 well characterized stages that parallel
the dissemination of the underlying
cancer
Stage 1: poorly defined psoriasiform plaques
involving the ears, nose, nails, fingers, and
toes; nail folds become dystrophic at this
stage
Stage 2: larger and more proximal regions;
violaceous keratoderma with central clearing
is seen over the cheeks, palms, and/or soles
Stage 3: Characterized by involvement of the
legs, knees, thighs, and arms

29. associated cancers
Bazex syndrome appears to be exclusively associated with malignancy;
therefore, its presence should prompt an extensive search for an occult
cancer.
It is most commonly associated with squamous cell carcinomas of
the upper aerodigestive tract, including the tongue, floor of the mouth,
palate, tonsils, pyriform sinus, larynx, pharynx, esophagus.
Cancers also reportedly; these include adenocarcinoma of the colon
and breast and Hodgkin lymphomas.

30. defined as the rapid
increase in the number
and size of seborrheic
keratoses in patients with
an internal malignancy.

31. Lesions can develop anywhere, but
they are most common in the usual
distribution of seborrheic keratoses;
ie, the chest and back (76% of
cases).
Patients either are asymptomatic or
have symptoms limited to pruritus
(50% of cases).

32. Associated noncancerous conditions
acute drug eruptions
human immunodeficiency virus
(HIV) infection
exfoliative erythroderma
benign neoplasms
pregnancy.

33. Associated cancers
most cases involve adenocarcinomas,
especially those of the
stomach
lungs
colon
rectum
breasts.

34. also known as acanthosis nigricans of the
palms,, and acanthosis palmaris, is
characterized by the appearance of
hypertrophic ("velvety") papillation of the
palms and soles, along with exaggerated
dermatoglyphics and hyperkeratosis.
Tripe palms often occurs simultaneously with
other paraneoplastic syndromes, including AN
and the sign of Leser-Trélat.

35. The skin changes of tripe palms most often
predate (60%) the diagnosis of cancer, but they
may occur at any point in the course of the
malignancy.
23% of lesions occur after the malignancy, and
17% coincide with it.
Lesions respond to successful cancer therapy,
but they may persist for despite remission of
the underlying tumor.

36. Associated cancers
90% of cases are associated with malignancy
gastric and bronchogenic carcinomas are the most
common.
A wide variety of tumor types, including cancers of the
gastrointestinal tract, lungs, head and neck, and
genitourinary (ovarian) system, have been reported;
Tripe palms in the absence of AN is more often
associated with lung neoplasms

37. most commonly seen in the
anogenital region.
Evidence of perianal involvement
has been reported to be associated
with underlying cancer in 25–35% of
patients, whereas only 4–7% of those
with genital involvement are
associated with cancer.

38. If evidence of perianal
involvement is found, the
presence of rectal cancer should
be excluded.
if the genital area is affected,
cancers from the urogenital or
reproductive tracts should then
be excluded .

39. Clinicians may confuse the diagnosis
of extramammary Paget’s disease as
eczema, candidiasis, leukoplakia, or
lichen simplex chronicus. Therefore,
a thorough and pertinent patient
history and assessment of possible
risk factors for the development of
cancer should be obtained.

40. autoimmune paraneoplastic
syndromes. It is characterized by
painful, intractable, erosive ulcerative
stomatitis and a polymorphic
cutaneous eruption consisting of
erythema, papules, iris lesions,
bullae, and erosions

41. 2/3 of cases, paraneoplastic
pemphigus occurs in patients with
a known, preexisting neoplasm.
However,
1/3 of patients develop the
mucocutaneous disease before the
neoplasm is detected.

42. Associated cancers
Paraneoplastic pemphigus is most often
associated with B-cell
lymphoproliferative disorders,
especially non-Hodgkin lymphoma
(80%). also linked to chronic
lymphocytic leukemia, Castleman
disease, thymoma,
An association with solid tumors is
extremely rare

43. DM is an inflammatory proximal myopathy with characteristic skin
changes; it is often associated with an occult malignancy.
The rash is characteristic and diagnostic and usually accompanies
or precedes the onset of the myopathy.

44. Skin manifestations of dermatomyositis
Heliotrope rash and
Periorbital edema
(so named because of the
similarity to the color of
the blue-purple flower, the
heliotrope) on the upper
eyelids

46. Gottron papules
Violaceous, scaly papules over
the interphalangeal and
metacarpophalangeal joints that
evolve into atrophic
telangiectatic macules

47. Gottron sign
Scaling, erythematous to
violaceous plaques over
the elbows, knees and
malleoli with follicular
plugging

48. (poikiloderma)
A macular, red rash on the
face and the V of the upper
trunk that may become shiny
and atrophic, with variable
pigmentation and
telangiectasias

49. The myopathy produces symmetrical
weakness of the limb-girdle muscles and
anterior neck flexors, with or without
muscle tenderness.
This weakness progresses over weeks to
months, with variable involvement of the
pharynx, upper esophagus, or respiratory
muscles.

50. Associated cancers
Most malignancies are detected within 2 ys of onset of DM.
approximately 25% of patients with DM already have or will
develop cancer and risk increase for patients with DM is increased
6-fold over the general population.
The malignancies associated with DM are those common for
ovarian, cervical, lung, and pancreatic and gastric
carcinomas, in addition to non-Hodgkin lymphoma,

51. Lesions consist of dramatic,
erythematous, concentric rings with
scales, which cause the classic
wood-grain appearance.
Lesions may be flat or slightly raised.
They are localized to the trunk and
proximal extremities, sparing the
feet, hands, and face.

52. The rings spread outward in a serpiginous
pattern at a rapid rate; the lesions may advance at
a rate of 1cm daily.
Patients universally report severe pruritus, and
concurrent hyperkeratosis of the palms and soles
has also been reported.
Marked peripheral eosinophilia may occur.

53. Associated noncancerous conditions
EGR without a detectable malignancy, have in rare
cases reported with:
tuberculosis,
CREST (ie, calcinosis cutis, Raynaud phenomenon, bullous
dermatoses, esophageal motility disorder, sclerodactyly, bone marrow
transplantation, telangiectasia) syndrome.
bullous pemphigoid,
pityriasis rubra pilaris,
psoriasis, to be associated with EGR.

54. Associated cancers
EGR is almost always (> 80%) indicative of an underlying
malignancy
Cancers associated with EGR are
transitional cell carcinoma of the kidney
the lungs
esophagus
breasts.

55. The skin and mucous membranes
are affected, with painful, migratory,
erythematous, polycyclic patches or
plaques with superficial pustules,
vesicles, or bullae being present.

56. The lesions are typically widespread, but
they are accentuated in the intertriginous
areas, lower abdomen, and proximal parts of
the lower extremities.
It is often present in a triad with NME,
glucose intolerance, and
hyperglucagonemia.
The typical patient with NME is middle aged,
has diabetes, and has the characteristic rash

57. The diagnosis of NME and glucagonoma syndrome is often
difficult and usually occurs several years after the initial skin
manifestations are noticed.
The most common attempts for treating a presumed benign
inflammatory dermatosis by using topical antifungal agents or
steroids. This approach is unsuccessful, and patients
eventually undergo diagnostic skin biopsy, which reveals NME.
The differential diagnosis of NME includes non-neoplastic
conditions such as acrodermatitis enteropathica, chronic
mucocutaneous candidiasis, pemphigus foliaceus, and
acquired zinc deficiency.

58. Confirming a diagnosis of is achieved by performing specific laboratory tests and
imaging studies to localize the pancreatic tumor.
Elevated serum glucagon levels (and occasionally insulin levels),
an abnormal glucagon response to arginine infusion,
glucose intolerance, and
hypoaminoacidemia
Imaging studies are used to localize the pancreatic tumor.
Celiac arteriography, which reveals the characteristic hypervascularity of the
tumor, is believed to be more sensitive than CT scanning for identifying the primary
lesion.

59. Associated cancers
NME is unique among paraneoplastic syndromes in that it is
almost always associated with a glucagon-secreting alpha-cell
neoplasm of the pancreas,
although it may rarely occur in the presence of jejunal and rectal
adenocarcinomas, villous atrophy of the small intestine, hepatitis
B, or myelodysplastic syndrome.
Of patients with symptomatic glucagonomas, an estimated 67-
90% have NME.

60. Sweet syndrome is characterized
by fever, neutrophilia, and sterile
erythematous plaques or nodules.
Skin lesions most commonly involve
the upper extremities and face and
begin as tender, erythematous
plaques or nodules. The lesions
may evolve into vesicles, bullae, or
pustules.

61. Extracutaneous manifestations are not
infrequent and commonly involve the
eyes, lungs, liver, kidneys, muscles, and
bones.
Laboratory features include
neutrophilia, anemia, and an elevated
erythrocyte sedimentation rate.

62. The diagnosis of Sweet syndrome is based
on the clinical presentation and characteristic
findings at skin biopsy.
Histologic evaluation reveals a neutrophilic
infiltrate in the dermis, without evidence of
infection, vasculitis, or malignant cells.
Patients frequently have a positive
perinuclear antineutrophil cytoplasmic
antibody titer.

63. non-cancerous associasion
Certain drug exposures: imatinib, all- trans -retinoic acid,
granulocyte stimulating factor, and sulfa-based antibiotics
Autoimmune diseases: relapsing polychondritis
Infections: with mycobacteria
Hematologic diseases: myelodysplastic syndrome

64. Associated cancers
Sweet syndrome is associated with an underlying cancer in 20%
of cases.
Approximately 80% of these cases involve hematologic
malignancies; acute myeloid leukemia is most common.
Cases involving solid tumors are also described, usually in
association with adenocarcinomas of the breast or
gastrointestinal and genitourinary tracts

65. DR. GAMAL SULTAN