cutaneous menifestion of internal malignancy
DESCRIPTION
Cutaneous menifestion of internal malignancyTRANSCRIPT
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CUTANEOUS MANIFESTATION OF
INTERNAL MALIGNANCIES
TUTORIAL PRESENATATION
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CURTH POSTULATES The malignancy and the skin disease are of concurrent onset
The malignancy and the skin disease run a parallel course. Successful
treatment of the tumor leads to regression of the skin disease, and
recurrence of the tumor leads to a return of cutaneous signs and
symptoms
The relation between the skin disease and the malignancy is uniform. A
specific tumor cell type or site is associated with a characteristic
cutaneous eruption
Based on sound case–control studies, a statistically significant
association exists between the malignancy and a specific cutaneous
disease
A genetic association exists between the malignancy and a specific
cutaneous disease
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INTRODUCTION
The skin often signals systemic changes. Some neoplastic diseases that affect internal
organs may trigger several cutaneous manifestations.
Although these dermatoses are relatively unusual, the recognition of some typical paraneoplastic dermatoses may lead to the early diagnosis of a neoplasm and determine a better prognosis.
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PROLIFERATIVE AND INFLAMMATORY DERMATOSES
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TRIPE PALMS
Refer to a wrinkled or ridged appearance of palmar skin; the soles may occasionally be involved as well
adenocarcinoma of the gastrointestinal tract.
squamous cell carcinoma of the lung
epidermal growth factors
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SIGN OF LESER-TRELAT
describes the sudden appearance and/or rapid increase in size of multiple seborrheic keratoses
adenocarcinoma of the gastrointestinal tract, tumors of the female reproductive system and lymphoproliferative disorders
epidermal growth factors
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ACANTHOSIS NIGRICANS Affected skin has a hyperpigmented, velvety appearance and in
severe cases can become quite verrucous. Flexural areas, especially the axillae, groin, and neck, are most
often involved Papillomatous changes may be noted in the oral cavity, and
hyperkeratosis in a wrinkled or ridged pattern may develop on the palms
90% of all abdominal cancers; 55-61% are of gastric origin, and adenocarcinoma is found in 70-90% of cases Other less associated malignant conditions include uterine, liver, intestine, pancreas, thyroid, ovary, kidney, breast, lung, bladder and gallbladder cancers, mostly consisting of adenocarcinomas.An association with lymphomas and mycosis fungoides has also been reported.
Epidermal growth factors, transforming growth factor alpha (TGF-α), insulin growth factor-like (IGF-1), fibroblast growth factor (FGF) and melanocyte-stimulating hormone (MSHa)
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ACQUIRED HYPERTRICHOSIS LANUGINOSA
extensive growth of silky, nonpigmented lanugo hair on the face, neck, trunk, and sometimes the extremities, particularly in sites previously perceived as hairless by the patient
A painful glossitis, angular cheilitis, and swollen red fungiform papillae on the anterior half of the tongue may accompany the cutaneous changes.
Women are affected more often than men. colorectal cancer is the most frequent association, followed
by lung and breast cancer. Men show greater association with lung cancer, followed by colorectal cancer. Associations with lymphomas, leukemias, and kidney, pancreatic, uterine and ovarian cancer have been reported
fibroblast growth factors (FGF)
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BAZEX SYNDROME (ACROKERATOSIS PARANEOPLASTICA)
erythematous to violaceous psoriasis-like eruption that occurs primarily on acral surfaces
The ears, nose, cheeks, hands, feet, and knees are most often affected.
With time, the palms and soles may develop a keratoderma and the nails may become dystrophic
arcinomas of the upper respiratory and digestive tracts (larynx, pharynx, trachea, bronchus, and/or upper esophagus)
? epidermal growth factors
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ERYTHEMA GYRATUM REPENS
widespread, serpiginous, polycyclic and pruriginous erythema which is desquamative around the edges and fast-growing, about 1 cm/day, producing concentric figures that resemble a wood surface
Hands and feet are often spared
Lung cancer is the most common (32%), followed by cancer of the esophagus (8%) and breast (6%). Other malignancies have been associated with EGR, such as colon, stomach, bladder, prostate, uterine, rectal and pancreatic cancer and multiple myeloma
?
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FEATURES/DISEASE PRIMARY SYSTEMIC AMYLODSIS
SCLERMYXEDEMA SWEET SYNDROME
DEFINITION generalized waxy appearance and bleed easily when traumatized (“pinch purpura”). Hemorrhagic lesions are especially common around the eyes
the generalized variant of lichen myxedematosus. generalized eruption of 2-mm to 3-mm waxy lichenoid (flat-topped) papules, often in a linear arrangement; the lichenoid lesions coalesce, leading to induration of the underlying tissue and a resemblance to scleroderma
the acute onset of erythematous, tender papules, plaques, or nodules on the face, extremities, and upper trunk The surface appears vesicular and may be studded with pustules
ASSOCIATED CARCINOMA
myeloma paraproteinaemia hematologic dyscrasia, most commonly acute myelogenous leukemia, and less often in individuals with solid tumors
SPECIAL POINT, IF ANY
Macroglossia is an associated finding. The disease carries a poor prognosis, with the most common causes of mortality being cardiac or renal failure
Longitudnal furrowing The presence of moderate to severe anemia
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PYODERMA GANGREOSUM CLUBBING INFECTIOUS DISEASES
superficial form of pyoderma gangrenosum, known as atypical or bullous pyoderma gangrenosumLesions tend to be more superficial than in the classical form of the disease. Most often, the association is with acute myelogenous leukemia, but several cases of chronic myelogenous leukemia, acute lymphoblastic leukemia, and preleukemic states such as myelofibrosis or agnogenic myeloid metaplasia have also been reported.
lung cancer and tumors metastatic to the lung
Candidiasis, herpes zoster or HPV
classical pyoderma gangrenosum has been associated with a monoclonal gammopathy (and occasionally myeloma), with several solid tumors, and with non-Hodgkin lymphoma.
leukemia and lymphoma
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BLISTERING DISORDERSParaneoplastic pemphigus
Cicatricial pemphigoid
Dermatitis herpetiformis
Epidermolysis bullosa acquisita
severe mucosal erosions and cutaneous blisters and erosions Castleman tumor, non-Hodgkin lymphoma, thymoma, follicular dendritic cell sarcoma, and chronic lymphocytic leukemia are commonly associated neoplasms.
antiepiligrin variant of cicatricial pemphigoid, associated with an increased incidence of malignancy, especially adenocarcinomas
increased relative risk of intestinal lymphoma
lymphoreticular tumors
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OTHERS Generalized pruritus, ichthyosis (noninflamed dry
scaly skin), and exfoliative dermatitis (inflamed dry scaly skin) are nonspecific features of lymphoproliferative disorders ( their association with solid tumors is uncommon.
Pityriasis rotunda may be a variant of acquired
ichthyosis. The eruption consists of geometrically perfect, circular patches of scales. Associated with hepatocellular, gastric and esophageal carcinoma, prostate cancer, chronic lymphocytic leukemia and multiple myeloma
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Coagulopathies with widespread area of purpura is associated with leukemia,
superficial thrombophlebitis and multiple deep venous (and rarely arterial) thromboses also have been noted in cancer patients, especially those with tumors arising in the pancreas, lung, stomach, prostate, or hematopoietic system.The neck, chest, abdominal wall, pelvis, and limbs are affected most frequently.
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Hormone-Secreting Tumors
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ECTOPIC ACTH SYNDROME
Hypokalemic metabolic alkalosis, hypertension, glucose intolerance or frank diabetes, and weight loss are classical clinical features.
Intense hyperpigmentation β-melanocyte stimulating
hormone (MSH) Gene for proopiomelanocortin
(POMC), the precursor peptide for ACTH, is expressed in high levels in the anterior pituitary gland
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CARCINOID SYNDROME A neuroendocrine tumour The most striking cutaneous manifestations are episodes of flushing,
which are caused at least in part by the release of the enzyme kallikrein from tumor cells, with subsequent conversion of kininogen to vasoactive kinin peptides, including bradykinin.
Serotonin may play an important role in the flushing reaction as well. Typical episodes initially last 10 to 30 minutes and involve only the
upper half of the body. As the flushing resolves, gyrate and serpiginous patterns may be noted. With successive attacks, more extensive areas may be affected and the redness takes on a cyanotic quality. This eventually leads to a more permanent facial cyanotic flush with associated telangiectasia
Systemic symptoms associated with the episodic cutaneous flushing may include abdominal pain with explosive watery diarrhea, bronchospasm, hypotension, and tachycardia.
appendix or small intestine; extraintestinal carcinoids may arise in the bile ducts, pancreas, stomach, ovaries, or bronchi.
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GLUCAGONOMA SYNDROME The characteristic cutaneous
eruption, necrolytic migratory erythema, often affects the perioral region and the distal extremities, but may also occur on the abdomen, perineum, thighs, and buttocks, as well as in the groin.
Patches of intense erythema with irregular outlines expand and coalesce to result in circinate or polycyclic configurations
Fragile superficial vesicles on the skin surface rupture quickly to form crusts, although new vesicles may continue to develop along the active margins
?
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Multiple Endocrine Neoplasia Syndrome
The 3 clinical patterns of familial multiple endocrine neoplasia (MEN types 1, 2A, and 2B)
Skin lesions do not characterize MEN 1 A carcinoid-like syndrome has been described in MEN 2A (Sipple
syndrome); otherwise, mucocutaneous lesions occur only in MEN 2B
multiple neuromas appear as whitish nodules mainly on the lips and the anterior one-third of the tongue . Also may be noted on the buccal mucosa, gingivae, palate, pharynx, conjunctivae, and cornea.
Affected individuals have characteristic facies, with thick, protuberant, bumpy lips.
The eyelids are sometimes thickened and slightly everted. Many patients have a “marfanoid” habitus, displaying long, slender
extremities; poor muscle development; sparse body fat; laxity of joints; pectus excavatum; and dorsal kyphosis
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Inherited Syndromes
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COWDEN SYNDROME (MULTIPLE HAMARTOMA SYNDROME) an autosomal dominant condition small (1-4 mm) flesh-colored papules (trichilemmomas) are found
mainly on the head and neck and may assume a wart-like appearance
Similar papules on the tongue and gingiva may coalesce to produce a cobblestone appearance.
Flat wart-like papules may be observed on the dorsum of the hands and feet, and punctate keratoses may be present on the soles, sides of the feet, and palms.
Thyroid tumors f/b endometrial cancer. Cancers of the lung and colon are rare
PTEN/MMAC1 tumor suppressor gene on chromosome 10q22-23, which encodes a tyrosine phosphatase protein that regulates cell proliferation
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GARDNER’S SYNDROME An autosomal dominant condition large, deforming epidermoid cysts fibromas,
lipomas leiomyomas, trichoepitheliomas, and neurofibromas.
A/w extensive adenomatous polyps of the gastrointestinal tract, especially the colon and rectum.
adenomatous polyposis coli (APC) tumor suppressor gene on chromosome 5q21-q22. TheAPC gene product regulates β-catenin, an adherens junction protein, which in turn is involved in cell migration and cell cycle control.
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PEUTZ-JEGHERS SYNDROME
an autosomal dominant disorder The characteristic cutaneous features of this
condition are the freckle-like pigmented macules that occur on the lips, nose, buccal mucosa, fingertips, and under the nails
A/w extensive hamartomatous polyps and carcinomas throughout the gastrointestinal tract, mainly the small intestine
mutations in the STK11/LKB1 gene on chromosome 19p13.3. This tumor suppressor gene encodes a serine/threonine protein kinase that modulates cell cycle progression
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MUIR-TORRE SYNDROME
An autosomal dominant trait the association of visceral carcinoma, usually involving
the gastrointestinal tract, with numerous sebaceous gland tumors (both benign and malignant), occurring primarily on the trunk
Other skin lesions particularly keratoacanthomas can also be seen
Mutations of the DNA mismatch repair (MMR) genes, most often the MSH2 gene located at 2p22-p21, and less commonly the MSH1 gene located at 3p21.3. This mutation leads to microsatellite instability, which may be responsible for the carcinomas observed in these patients.
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HOWEL-EVANS SYNDROME
association between tylosis (thickened skin of the palms and soles) and esophageal cancer.
The keratoderma usually develops during childhood and is accentuated over pressure sites
Oral leukoplakia chromosome 17q25, now
referred to as the tylosis (o)esophageal cancer (TOC) gene, appears to be associated with this syndrome
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BIRT-HOGG-DUBE SYNDROME
an autosomal dominant condition Skin tags and benign hair follicle tumors
(fibrofolliculomas and trichodiscomas) that most often occur on the head and neck
chromophobe and oncocytic types of renal carcinoma is increased, as is the incidence of lung cysts and spontaneous pneumothorax. Medullary carcinoma of the thyroid is also associated
a mutation in the 17p11.2 gene, which encodes folliculin
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HEREDITARY LEIOMYOMATOSIS/RENAL CELL CANCER SYNDROME an autosomal dominant condition The cutaneous leiomyomas may be segmental
or band-like rather than diffuse and symmetric . They are firm, flesh-colored, red or brown, and may be painful. They usually appear by age 25 years
multiple leiomyomas of the uterus and papillary renal cell carcinoma
mutation of the gene 1q42.3-43 encoding fumarate hydratase, an enzyme of the tricarboxylic acid cycle.
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NEUROFIBROMATOSIS TYPE 1 (VON RECKLINGHAUSEN DISEASE) axillary and inguinal freckling, cafe-au-
lait macules, cutaneous neurofibromas, and occasionally, plexiform neuromas
multiple Schwann cell tumors, malignant degeneration of neurofibromas,and pheochromocytomas, which may be bilateral but are usually benign & Gastrointestinal stromal tumors
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CONCLUSION The skin examination can reveal signs of a
predisposition toward malignancy and can yield valuable early clues suggesting an underlying neoplastic process.
Although the skin changes doesn’t guarantee a 100% acurate diagnosis of internal cancer , recognition of these cutaneous signs and symptoms should alert the clinician to initiate appropriate diagnostic measures for a early diagnosis of malignancy