Metabolic disorders

Published on 08/03/2015 by admin

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Last modified 22/04/2025

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Chapter 14

Metabolic disorders

Tammie Ferringer

Mucinoses

The mucinoses are a group of disorders characterized by mucin deposition in the dermis. The mucin is typically non-sulfated acid mucopolysaccharide (hyaluronic acid) that appears as wispy, faint blue threads on routine sections. It can be better appreciated with colloidal iron, Alcian blue, and toluidine blue staining.

Scleredema (of Buschke)

Key features

• Thickened dermis

• Widened spaces with mucin between normal collagen bundles

• The mucin is most prominent in the deep dermis

• No inflammatory infiltrate or increased fibroblasts

• The histologic features can be subtle and mimic normal skin at scan, but there is increased space between collagen fibers in the deep dermis

Fig 14-1 Scleredema

Fig 14-2 Scleredema

Scleredema most often occurs in the setting of insulin-dependent, adult-onset diabetes on the upper back, an area that normally displays a thick dermis. Scleredema can also occur suddenly following a streptococcal infection or in association with a monoclonal gammopathy.

Pretibial myxedema

Key features

• Large amounts of mucin throughout the dermis

• Collagen bundles separated by mucin and reduced to thin wisps

Pretibial myxedema is found in patients with Graves’ disease, especially those with exophthalmos. It may not develop until after correction of the hyperthyroidism.

Differential Diagnosis

The mucin deposition in pretibial myxedema involves the full thickness of the dermis while the mucin in stasis is restricted to the papillary dermis. Nodular angioplasia and hemosiderin deposition are also features of stasis. Scleredema lacks attenuation of collagen fibers.

Fig 14-3 Pretibial myxedema

Fig 14-4 Pretibial myxedema

Scleromyxedema

Key features

• Increase in dermal fibroblasts, fine collagen fibers, and interstitial mucin

Papular mucinosis (lichen myxedematosus) is composed of linear arrays of waxy papules. Scleromyxedema is a variant in which the papules coalesce with diffuse sclerosis of the skin. An immunoglobulin (Ig) G lambda gammopathy is associated with scleromyxedema and many cases of papular mucinosis.

Differential Diagnosis

Histologically, scleromyxedema resembles nephrogenic systemic fibrosis. The clinical setting varies in that nephrogenic systemic fibrosis occurs in patients with renal failure with involvement of the distal extremities, whereas scleromyxedema is associated with IgG paraproteinemia and typically involves the face.

Fig 14-5 Scleromyxedema

Fig 14-6 Scleromyxedema

Fig 14-7 Nephrogenic systemic fibrosis

Fig 14-8 Nephrogenic systemic fibrosis

Tumid lupus

Key features

• Interface damage is subtle or absent

• Superficial and deep perivascular and periadnexal lymphocytic infiltrate

• Infiltrate typically involves the eccrine coil

• Abundant mucin is present in the reticular dermis

Reticular erythematous mucinosis is indistinguishable histologically from tumid lupus. Many consider it a variant of tumid lupus.

Fig 14-9 Tumid lupus

Fig 14-10 Tumid lupus

Focal mucinosis

Key features

• Dome-shaped papule containing a pool of mucin

Fig 14-11 Focal mucinosis (colloidal iron)

Fig 14-12 Digital myxoid cyst

Digital myxoid cyst resembles focal mucinosis but on acral skin.

Amyloidosis

Primary systemic amyloidosis is due to deposition of light chains. Skin lesions may occur but, in those with no obvious lesions, a blind biopsy of salivary glands or abdominal fat can be examined for the presence of amyloid. Light-chain-derived nodular cutaneous amyloidosis is produced locally by plasma cells and may or may not be associated with systemic amyloidosis. Secondary systemic amyloidosis lacks clinical skin lesions, but may demonstrate amyloid deposits in minor salivary glands or abdominal fat. Epidermal (keratin)-derived forms of amyloidosis include macular and lichen amyloidosis. Amyloid is brick red with Congo red stain and apple green with polarization. The cotton dye pagoda red is most specific for amyloid. Staining with thioflavin T is very sensitive but requires examination with a fluorescent microscope, resulting in yellow-green fluorescence of amyloid deposits. Crystal violet is a metachromatic stain that is very sensitive for epidermal-derived amyloid.

The clinical types of amyloidosis and their associated amyloid protein are listed in Table 14.1. In addition to the specific fibrillar component, amyloid P, a non-fibrillar glycoprotein, binds to all types of amyloid fibrils. Antisera to these proteins can be used immunohistochemically to identify the amyloid deposition.

Table 14-1

Clinical types of amyloidosis and their associated amyloid protein

Clinical type	Amyloid fibril protein	Precursor substance
Localized cutaneous
Macular	AK	Altered keratin
Lichenoid	AK	Altered keratin
Nodular	AL (Aλ and Aκ)	Immunoglobulin light chain
Systemic
Primary/myeloma-associated	AL (Aλ and Aκ)	Immunoglobulin light chain
Secondary	AA	Serum amyloid A
Familial Mediterranean fever	AA	Serum amyloid A
Muckle–Wells’ syndrome	AA	Serum amyloid A
Familial amyloid polyneuropathy	Prealbumin (transthyretin)
Hemodialysis-associated	β2-microglobulin

Nodular amyloidosis

Key features

• Large fissured pale pink masses

• Plasma cells usually prominent

Fig 14-13 Nodular amyloid

Fig 14-14 Nodular amyloid (Congo red)

Nodular amyloid consists of light chains (AL) and may be a purely cutaneous lesion or occur in association with primary systemic amyloidosis. Lesions may be a manifestation of a localized plasmacytoma.

Macular amyloid

Key features

• Sparse pink deposits in the papillary dermis

• Amyloid is outlined by a fine network of melanophages

Macular amyloid is a keratin-derived deposition produced by chronic scratching. Clinically, there is mottled hyperpigmentation of the interscapular area. This sparse deposition can be easily overlooked and may mimic normal skin.

Fig 14-15 Macular amyloid

Differential Diagnosis

At scan, some biopsies mimic normal skin and require closer inspection or clinical history to determine the diagnosis. Joe English’s mnemonic “I vacuum dog pus” includes many of these subtle histologic entities:

• Ichthyosis vulgaris

• Urticaria pigmentosa (especially telangiectasia macularis eruptiva perstans)

• Macular amyloid

• Dermatophyte

• Onchocerciasis (microfilaria)

• Gold (chrysiasis)

• Pseudoxanthoma elasticum and psoriasis (guttate)

• Ulerythema ophryogenes

• Seborrheic dermatitis and scleredema

Alternatively, what initially appears to be normal skin at scan can be approached systematically, starting in the stratum corneum looking for organisms, then moving deeper to look for absence of granular layer, followed by the epidermal pattern, alteration in pigmentation, deposition in the dermal papillae, perivascular or interstitial infiltrate, and down to the eccrine glands looking for silver granules.

Lichen amyloid

Key features

• Hyperkeratosis and acanthosis

• Pink amorphous deposits in the papillary dermis outlined by a network of melanophages

Lichen amyloid is a keratin-derived deposition that histologically resembles macular amyloid with superimposed changes of lichen simplex chronicus. Clinically, it presents as intensely pruritic papules in rows, usually on the anterior shins.

Fig 14-16 Lichen amyloid

Cutaneous calcification

The cutaneous deposition of calcium, calcinosis cutis, has been divided into dystrophic, metastatic, and idiopathic forms. Dystrophic calcium deposition occurs in the presence of normal calcium levels, with the deposits forming in damaged tissue as in dermatomyositis, scleroderma, or in scars. Scrotal calcinosis represents calcified epidermoid cysts. Metastatic calcifications occur in normal tissue and are associated with elevated serum calcium or phosphate or both. Calciphylaxis is a unique form of metastatic calcification. Subepidermal calcified nodules are of unknown pathogenesis and belong to the category of idiopathic calcifications. Calcium typically appears basophilic on hematoxylin and eosin-stained sections, and stains black with von Kossa’s silver stain and red with alizarin red.

Calciphylaxis

Key features

• Calcified small vessels in the subcutaneous fat

• Necrosis

Calciphylaxis occurs most frequently in the setting of chronic renal failure and/or hyperparathyroidism, usually in patients with diabetes.

Fig 14-17 Calciphylaxis

Subepidermal calcified nodule

Key features

• Pseudoepitheliomatous hyperplasia with transepidermal elimination of calcium

Fig 14-18 Subepidermal calcified nodule

This is an idiopathic process most common on the chin of a child or heel of a newborn.

Scrotal calcinosis

Key features

• Amorphous masses of calcium

• Smooth muscles scattered through the dermis indicate genital site

Although considered “idiopathic” by some, the condition appears to represent calcification of epidermoid cysts.

Fig 14-19 Scrotal calcinosis

Fig 14-20 Scrotal calcinosis

Gout

Key features

• Palisaded granuloma surrounding amorphous gray material with a feathery appearance

Formalin fixation destroys the uric acid crystals, leaving feathery clefts. Brown crystals that are doubly refractile with polarization are present if the tissue was fixed in ethanol or was incompletely fixed in formalin.

Fig 14-21 Gout

Fig 14-22 Gout

Erythropoietic protoporphyria (EPP)

Key features

• Hyaline cuff (reduplicated basement membrane) around post-capillary venules

• No solar elastosis is present, because patients avoid the burning sensation associated with sun exposure

EPP is associated with a deficiency of ferrochelatase. EPP is the only disorder of porphyrin metabolism with normal urine porphyrins (EPP stands for empty pee pee). There are increased protoporphyrins in the feces and blood.

Differential Diagnosis

The hyaline material in EPP affects the superficial vessels, whereas lipoid proteinosis involves the superficial and deeper vessels as well as eccrine glands. Porphyria cutanea tarda demonstrates much smaller hyaline cuffs around superficial vessels, as well as solar elastosis in the surrounding skin. It often also demonstrates caterpillar bodies, subepidermal bullae, and festooning.