CHAPTER 19
DERMADROME IN INTERNAL MALIGNANCY
・ The skin often reflects abnormal internal processes, i.e, dermadrome（デルマドローム）, and recognition of this leads to find early presence of internal organ diseases and to realize the prognostic aspects.
・ Because of the immunologic, metabolic, hereditary, and metastatic consequences and interrelationships involving malignant disorders, there is a wide variety of skin manifestations associated with internal malignant diseases.
I. Criteria
・ In a causal relationship between the skin manifestation and internal malignancy, the following criteria are considered.
1. The dermatosis and the internal malignancy start at the same time, or there is only a short interval between the onset of each [ex., dermatomyositis].
2. The malignant process and the dermatosis (unless it is self-limited, for instance, herpes zoster) run a parallel course [ex., malignant acanthosis nigricans].
3. If one is dealing with a tumor, the type of the neoplasm associated with the dermatosis is uniform [ex., adenocarcinoma in malignant acanthosis nigricans（黒色表皮腫）] or distinctive, that is, it's mechanical, toxic, or biochemical actions have specific effects on the skin [ex., flushing in malignant carcinoid].
4. The dermatosis is not common, but specific [ex., erythema gyratum repens（匍行性花環状紅斑）].
5. If the association between dermatosis and malignancy is based on a genetic relationship, the internd disease and the dermatosis develop independently of each other [ex., Peutz-Jeghers-Tourain syndrome] and postulates 1 and 2 need not be fulfilled.
6. The incidence of the association between dermatosis and internal malignancy is statistically important [ex., reticulohistiocytoma（細網組織球腫）, acquired ichthyosis（後天性魚鱗癬）].
II. Classification of Cutaneous Signs of Internal Malignancy
1. Skin infiltration by an internal malignancy
a. Metastatic: lymphatic, hematogenous, or by surgical implantation
1) carcinoma
2) leukemia
b. Metastatic: intreapidermal
1) Paget's disease of the breast （乳房ぺージェット病）
2) extramammary Paget's disease（乳房外ぺージェット病）
c. Autochthonous or metastatic (?)
1) lymphoma
2) malignant histiocytosis
2. Skin changes due to exposure to a carcinogen that also induces internal malignancy.
a. Arsenical keratoses（砒素角化症）
b. Bowen's disease（ボーエン病）
3. Skin malignancies associated with increased risk of separate primary internal malignancy
a. Bowen's disease
b. Kaposi's sarcoma（カポジ肉腫）
4. in changes due to metabolic products of malignancies
a. Malignant carcinoid syndrome
b. Addisonian hyperpigmentation with Cushing's syndrome, from carcinomas producing MSH-and ACTH-like peptides
c. Generalized dermal melanosis (slate-gray). from malignant melanoma
d. Nodular fat necrosis, due to lipases from pancreatic carcinoma
e. Raynaud's syndrome（レイノー症候群）with cryoproteinemia, from multiple myeloma
f. Amyloidosis, from multiple myeloma
g. Necrolytic migrating erythema（壊死性遊走性紅斑）, from functioning glucagonoma
5 Skin changes due to functional disturbances in other systems induced by nonendocrine malignancies
a. Jaundice, obstructive
b. Addisonian hyperpigmentation, from adrenal infiltration by a tumor
c. Purpura, thrombacytopenic
d. Pallor, from anemia
e. Herpes zoster
f. Herpes simplex, severe, protracted
g. Pyoderma（膿皮症）, recurrent
h. Delayed hypersensitivity, exaggerated response to mosquito bites
6 Skin changes, idiopathic
a. Changes frequently related to internal malignancy
1) dermatomyositis, adult-onset（皮膚筋炎，成人発症）
2) acanthosis nigricans（黒色表皮腫）
3) thrombophlebitis, migratory（遊走性血栓性静脈炎）
4) ichthyosis, adult-onset（魚鱗癬，成人発症）
5) alopecia mucinosa. adult（ムチン沈着性脱毛症，成人発症）
6) pachydermoperiostosis, acquired
7) hypertrichosis lanuginosa, acquired "malignant down"
8) erythema gyratum repens（匍行性花環状紅斑）
b. Changes occasionally related to internal malignancy
1) pruritus, without causative skin lesions
2) clubbing, with and without hypertrophic osteoarthropathy
3) erythroderma
4) normolipemic（正脂血性） xanthomatosis（黄色腫症）
5) erythema multiforme（多型紅斑）
6) urticaria and erythema annulare centrifugum（蕁麻疹，遠心性環状紅斑）
7) pyoderma gangrenosum, atypical（壊疸性膿皮症，異型）
8) bullous disease and dermatitis herpetiformis（水疱性疾患，疱疹状皮膚炎）
9) dermatoses, bizarre
III. Heritable Diseases with Skin Manifestations and the Propensity to Develop Internal Malignancy.
A. Dominant inheritance:
1. Multiple hamartoma（奇形腫） syndrome (Cowden's disease)
a. Skin signs
1) acral verrucous papules
2) trichilemmomas of face
3) fibromas of oral mucosa
b. Alterations of other system
1) multiple hamartomas
2) lipomas
3) hemangiomas
4) fibrocystic disease of breast
5) thyroid adenomas
6) neuromas
c. Predominant malignancy
1) thyroid carcinoma
2) breast carcinoma
2. Gardner's syndrome
a. Skin signs
1) epidermal cysts
2) dermoid tumors
3) lipomas
4) fibromas
b. Alterations of other system
1) polyposis of colon
2) osteomas
c. Predominant malignancy
colonic adenocarcinomas (very high incidence, unless colectomy done)
3. Multiple mucosal neuromas
a. Skin signs
neuromas on eyelids, lips, tongue, nasal or laryngeal mucosae
b. Alterations of other system
1) parathyroid adenomas
2) hypertension
c. Predominant malignancy
1) pheochromocytoma
2) medullary carcinoma of thyroid (high incidence)
4. Neurofibromatosis（神経線維腫症）(von Recklinghausen's disease)
a. Skin signs
1) neurofibromas
2) cafe au lait spots
3) axillary "freckles"
4) giant nevi
b. Alterations of other system
1) acoustic and spinal neuromas
2) meningiomas
3) osseous fibrous dysplasia
c. Predominant malignancy
1) malignant neurilemmoma (5% incidence)
2) pheochromocytoma (uncommon)
3) astrocytoma, glioma (uncommon)
5. Nevoid basal cell carcinoma syndrome（基底細胞母斑症候群）
a. Skin signs
1) multiple basal cell carcinomas
2) epidermoid cysts
3) "pits" on palms and soles
b. Alterations of other system
1) jaw cysts
2) rib and vertebral abnormalities
3) short metacarpals
4) ovarian fibromas
5) hypertelorism
c. Predominant malignancy
1) medulloblastoma
2) fibrosarcoma of jaw (low incidence)
6. Palmar-plantar hyperkeratosis (tylosis)
a. Skin signs
hyperkeratosis of palms and soles (onset usually after age 10)
b. Alterations of other system
none
c. Predominant malignancy
Esophageal carcinoma (95% incidence)
7. Peutz-Jeghers syndrome（ポイツ・イェガース症候群）
a. Skin signs
pigmented macules on lips, oral mucosa, digits
b. Alterations of other system
intestinal polyposis (predominantly small intestine)
c. Predominant malignancy
gastric, duodenal, and colonic adenocarcinomas (low incidence, 2〜3%)
8. Tuberous sclerosis（結節性硬化症）
a. Skin signs
1) hypopigmented macules
2) shagreen patches
3) adenoma sebaceum
4) subungual fibromas
b. Alterations of other system
1) epilepsy
2) mental retardation
3) hamartomas in brain, kidneys, heart
c. Predominant malignancy
1) strocytomas
2) glioblastomas (low incidence)
B. Autosomal recessive:
1. Ataxia telangiectasia（毛細血管拡張性失調症）
a. Skin signs
telangiectasIa (neck, malar, antecubital fossae, popliteal fossae, ears)
b. Alterations of other system
1) cerabellar ataxia
2) sinopulmonary infections
3) IgA deficiency, ±IgE deficiency
c. Predominant malignancy
lymphoma, leukemia (10% incidence)
2. Bloom's syndrome（ブルーム症候群）
a. Skin signs
1) telangiectasia of sun exposed skin
2) photosensitivity
b. Alterations of other system
1) short stature
2) fine features
3) dolichocephaly
c. Predominant malignancy
Leukemia (high incidence)
4. Chediak-Higashi syndrome
a. Skin signs
1) dilution of skin and hair color
2) recurrent pyoderma
3) giant melanosomes
b. Alterations of other system
1) recurrent infections
2) azurophilic leukocytic infusions
3) nystagmus, iris translucence, photophobia, pacytopenia
c. Predominant malignancy
lymphoma (high incidence)
5. Fanconi's anemia（ファンコニ貧血）
a. Skin signs
patchy hyperpigmentation
b. Alterations of other system
1) bone anomalies
2) chromosomal aberrations
c. Predominant malignancy
leukemia (high incidence)
6. Werner's syndrome (adult progeria)（ウェルナー症候群）
a. Skin signs
1) premature aging
2) scleroderma-like changes
3) graying hair and baldness,
4) leg ulcers
b. Alterations of other system
1) arteriosclerosis
2) cataracts
c. Predominant malignancy
1) sarcoma,
2) meningiomas
C. Sex-linked recessive:
1. Bruton's sex-linked agammaglobulinemia
a. Skin signs
recurrent infections
b. Alterations of other system
1) recurrent infections
2) agammaglobulinemia
c. Predominant malignancy
leukemia, lymphoma (5% incidence)
2. Dyskeratosis congenita
a. Skin signs
1) reticulate hyperpigmentation
2) leukoplakia of mucosae
3) loss of nails
4) hyperkeratosis of palms of and soles
5) atrophy of skin of extensor surfaces
b. Alterations of other system
pancytopenia
c. Predominant malignancy
1) carcinomas ( high incidence)
2) leukemia (occasional)
3. Wiskott-Aldich syndrome
a. Skin signs
1) eczematous dermatitis
2) petechial purpura
3) recurrent pyoderma
b. Alterations of other system
decreased lgM, thrombocytopenia
c. Predominant malignancy
leukemia, lymphoma (10% incidence)