DERMATOPATHOLOGY OF THE DEGENERATIVE, METABOLIC AND STORAGE DISEASES (Nobody wants this lecture)
Daniel J. Santa Cruz St Louis, MO, USA Thanks to: Dr Franco Rongioletti, Naples, Italy Dr Mario Marini, Buenos Aires, Argentina Dr Susan Mallory, St Louis, MO DERMATOPATHOLOGY OF THE ELASTIC FIBERS
Daniel J. Santa Cruz Cutaneous Pathology St Louis, MO, USA ELASTIC FIBERS
Oxytalan
Elaunin
Elastic fibers
Elastic tendons of the arrectore pilori
ELASTIC TISSUE STAINS
Verhoff-Van Giesson
Orcein (Orcein-Giemsa)
Aldehide fucsin (Gomori)
Iron galein (Churukian)
Fucsin resorcin (Weigert)
AUTOFLUORESCENCE ELASTOTIC PROCESSES
Actinic elastosis
Coloid milium
Elastotic papules of the ear
Linear focal elastosis
Acrokeratoelastoidosis
Elastofibroma
ELASTOSIS Morphea
ELASTOTIC PAPULE OF THE EAR ACROKERATOELASTOIDOSIS
ELASTOFIBROMA ELASTIC NEVUS
Isolated
Multiple
Associated with osteopoikilosis (Buschke-Ollendorf syndrome) BUSCHKE-OLLENDORF SYNDROME University of Miami
. Autosomal dominant . Osteopoikilosis . Dermatofibrosis lenticularis disseminata
TRANSEPIDERMAL MIGRATION OF ELASTIC FIBERS
. Discoid lupus erytemathosus
. Keratoacanthoma
. Scar KERATOACANTHOMA PSEUDOXANTHOMA ELASTICUM
Primary
Acquired
Post treatment
Perforative post pregnancy
Fertilizer (Salt peter)
PSEUDOXANTHOMA ELASTICUM PSEUDOXANTHOMA ELASTICUM PSEUDOXANTHOMA ELASTICUM
ELASTIC DERMATOSES SUI GENERIS
Elastosis perforans serpiginosa
Elastolytic (actinic) granuloma
ELASTOSIS PERFORANS SERPIGINOSA ELASTOSIS PERFORANS SERPIGINOSA ELASTOLYTIC PROCESSES
Stria
Cutis laxa
Anetoderma
Atrophoderma
Middermal elastolysis
Perifollicular elastolysis
Fibroelastolytic papulosis of the neck
Pseudoxanthoma elasticum-like papillar elastolysis
STRIA PXE-like papillary elastolysis ANETODERMA ANETODERMA ATROPHODERMA (PASINI-PIERINI) MIDDERMAL ELASTOLYSIS MIDDERMAL ELASTOLYSIS MIDDERMAL ELASTOLYSIS ELASTIC FIBERS IN TUMORS
Nevi
Keratoacanthoma
Syringoma
Mixed tumor (Chondroid syringoma)
DERMATOFIBROMA Elastic fibers
MUCOUS PSEUDOCYST MUCOUS PSEUDOCYST FOCAL DERMAL MUCINOSIS CUTANEOUS MYXOMA CARNEY’S COMPLEX
Myxoid follicular tumors
Myxoid mammary fibroadenomas
Cardiac myxomas
“Pigmented” nodular adrenocortical adenoma
Hyalinizing trabecular adenoma of the thyroid
Psammamatous melanotic schwannoma
Epithelioid blue nevus
Chromosome locus 17q2 CARNEY’S COMPLEX
The cutaneous myxomas occurred in 22 (54%) of the patients. The cutaneous tumors were detected previously to the cardiac neoplasm in 13 (81%) of the 16 patients that had an atrial myxoma. CARNEY’S COMPLEX Cutaneous myxomas
Clinical characteristics
Early occurrence (average 18 years)
Multicentricity (71%)
Small size (under 1 cm)
Universal distribution, but with preference for eyelids, ears and nipples
Tendency to reccur
Carney JA, Headington, JT and Daniel Su WP. Arch Dermatol 122: 790-798, 1986
CUTANEOUS MYXOMA Carney’s complex CARDIAC MYXOMA Carney’s complex CARNEY’S COMPLEX CARNEY’S COMPLEX
Carney JA, Gordon H Carpenter PC et al. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine 64: 270-283, 1985 Scleromyxedema Patient Presentation
54 WM with 5 year history of waxy yellow coalescing 2- 3 mm papules over the dorsal hands, digits, ears, scalp, axilla, and neck
‘Doughnut sign’ and ‘beads on a string’
Patient Presentation
Woody induration of the facial skin and hands
Glabella invovlement
Histopathology
Deposition of interstitial mucin Mild dermal fibrosis Histopathology
Deposition of interstitial mucin Colloidal Iron Stain
Presence of dermal mucin confirmed by colloidal iron stain Lichen Myxedematosus
Chronic, progressive, idiopathic disorder
Two clinicopathologic subsets
Generalized papular and sclerodermoid form
Generalized papular and sclerodermoid eruption
Histologic triad: Mucin deposition, fibroblast proliferation, fibrosis
Monoclonal gammopathy and systemic manifestations
Absence of thyroid disease
Localized papular form without systemic involvement
Systemic Manifestations
Hematologic - Paraproteinemia 83% - Multiple myeloma 10% - Hematologic malignancies iatrogenic Gastrointestinal 31% - Dysphagia Musculoskeletal - Proximal muscle weakenss due to myositis 27% - Arthritis/arthralgias 10% CNS disturbances 15% - 10 cases of coma have been described - seizures - Peripheral neuropathy - Carpal tunnel syndrome Renal - Scleroderma-like renal disease CR Pulmonary - Restrictive or obstructive lung disease 17%
“Dermato-neuro” Syndrome
Patients can develop serious CNS involvement—etiology unclear and work-up is negative
Flu-like prodrome
Confusion
Dysarthria
Ascending paralysis
Seizures
coma 6 reports of deaths resulting from seizures Other reports of intractable seizures requiring sedation and ventilation >10 reports of associated coma
Associated Gammopathy
Paraproteinemia present in 80% Usually IgG with lambda light chains. Fewer than 10% of cases progress to MM It has been proposed that the PP Ab acts as a direct stimulant of fibroblasts in the skin Paraprotein levels do not correlate with extent, progression, or treatment of the disease. Cutaneous lesions can precede PP
Associated Gammopathy
Patient serum enhances fibroblast proliferation, hyaluronic acid, and prostaglandin-E production in vitro
Isolated Ig from the same patients did not stimulate fibroblasts.
This suggests some other “circulating factor”
1. Harper RA, Rispler J. Lichen myxedematosus serum stimulates human skin fibroblast proliferation. Science 1978;19:545-7. 2. Yaron M, Yaron I, Yust I Brenner S. Lichen myxedematosus (sleromyxedema) serum stimulates hyaluronic acid and prostaglandin E production by human fibroblasts. J Rheumatol 1985;12:171-5. SCLEROMYXEDEMA SCLEROMYXEDEMA SCLEROMYXEDEMA AMYLOIDOSIS
Amyloidosis is a clinical disorder caused by extracellular deposition of insoluble abnormal fibrils, derived from aggregation of misfolded, normally soluble, protein
About 23 different unrelated proteins are known to form amyloid fibrils in vivo, which share a pathognomonic structure although they are associated with clinically distinct conditions.
In local amyloidosis, the amyloid is restricted to a particular organ or tissue.
In systemic amyloidosis, deposits can be present in any or all of the viscera, connective tissue, and blood vessel walls, although intracerebral amyloid deposits are never found.
Acquired amyloidosis is a complication of preexisting primary disease that produces either an inherently amyloidogenic abnormal protein or greatly increased amounts of potentially amyloidogenic normal protein.
Hereditary amyloidosis is caused by mutant genes encoding variant proteins whose structure makes them amyloidogenic. AMYLOIDOSIS Amyloid precursor proteins of dermatological interest
Immunoglobulin light chain-derived (AL)
Serum amyloid A protein (SAA)
β2-microglobulin
Transthyretin ATTR)
Gelsoin (AGel amyloidosis)
Epidermal keratinocyte keratins (amyloid-K) AMYLOIDOSIS
Systemic amyloidosis
Primary and myeloma associated
Secondary
Heredofamilial
Amyloid elastosis
Localized cutaneous amyloidosis
Lichen, papular, and macular
Nodular
Poikilodermatous
Familial cutaneous
Secondary localized PAPULAR AMYLOIDOSIS PAPULAR AMYLOIDOSIS PAPULAR AMYLOIDOSIS PAPULAR AMYLOIDOSIS PAPULAR AMYLOIDOSIS PAPULAR AMYLOIDOSIS
CONGO RED THIOFLAVIN T PAPULAR AMYLOIDOSIS
CONGO RED WITH POLARIZATION
PANKERATIN Kappa Lambda CONGO RED
CONGO RED POLARIZED LIGHT SYSTEMIC AMYLOIDOSIS SYSTEMIC AMYLOIDOSIS AMYLOIDOSIS Secondary localized
Basal cell carcinoma
Bowen’s disease
DSAP
Trichoblastoma
Cylindroma CALCINOSIS CUTIS CALCINOSIS CUTIS CALCINOSIS CUTIS
Derm Atlas. Dr Zirky contribution Calcinosis cutis in scleroderma. Univ of Iowa