An indurated plantar plaque with surface nodularity

A 65-year-old man presents with the lesions pictured [Figures 1–3].

Figure 1.

Erythematous somewhat pearly indurated plaque on the plantar aspect of the foot. Focal nodularity was noted

Figure 3.

The fissured dermal material staining brick red with a Congo red stain (×40)

Figure 2.

Fissured masses of pale pink material in the dermis (H and E, ×40)

The lesion most likely represents?

1. Lipoid proteinosis

2. Nodular amyloidosis (NA)

3. Lichen amyloidosis (AL)

4. Colloid milium

5. Erythropoietic protoporphyria.

Nodular amyloidosis, also called primary cutaneous NA, is the rarest form of localized cutaneous AL.[1] NA demonstrate AL amyloid deposition usually limited to the skin, differentiating it from systemic AL.[2] The mean age of onset is 60 years,[3] but NA has been found to affect a broad age range and has no predilection for gender or ethnicity;[4,5] NA tends to localize to the legs, hands, feet, trunk, and genitalia,[2,6] Skin lesions appear as pink to red, deep, indurated, asymptomatic nodules. A waxy appearance and shades of yellow or orange may be noted.[7] Individual lesions range from a few millimeters to several centimeters in diameter, with typical lesions being a centimeter or more at the time of presentation.[8] Lesions can occasionally be bullous, anetodermic, or atrophic.[5] NA is classically asymptomatic with little or no pruritis, but hemorrhage may be noted due to capillary weakness from amyloid deposition.[2] The preoperative differential includes xanthoma, lymphoma cutis, cutaneous sarcoidosis, and keloid.[5]

Histopathologic examination reveals diffuse, homogenous, eosinophilic fissured amyloid deposits throughout the dermis.[9] Amyloid may also be noted in dermal blood vessels.[7] Plasma cells are commonly found at the periphery of the deposits.[7] Amyloid deposits characteristically stain brick red with the Congo red stain with apple-green birefringence under polarized microscopy.[6] Thioflavine T is highly sensitive for amyloid and demonstrates yellow-green fluorescence. Crystal violet is more commonly used for epidermally-derived amyloid and stains metachromatically purple.[7] Periodic acid-Schiff (PAS) positivity is also characteristic.

The histological differential diagnosis includes other conditions with eosinophilic deposits within the dermis. Lipoid proteinosis is characterized by deposition of hyaline material in the dermis, mucosa, and viscera.[5] Patients develop characteristic pearly papules at the ciliary margin of the eyelids. Pitted scarring is commonly present on the face, and the voice is gravelly because of infiltration of the vocal chords. Histologically, there is massive basement membrane thickening within the dermis, walls of blood vessels, and surrounding adnexal structures.[5] The deposits typically demonstrate a vertical orientation and are PAS positive and diastase resistant.[5] Macular amyloidosis (MA) and lichenoid amyloidosis (LA) are disorders characterized by deposition of epidermally-derived amyloid within the papillary dermis. The individual deposits are similar in size to civatte bodies and are typically surrounded by a network of melanin incontinence. Amyloid deposits in MA and LA are found only in the papillary dermis with no deeper penetration and no blood vessel involvement.[1] LA presents clinically with rows of discrete, hyperkeratotic brownish-red papules on the shins and lower legs.[1,10] MA presents as a gray-brown, reticulated patch located on the upper back.[5] Both lesions may be pruritic.[2] Colloid millium presents clinically as translucent papules in sun-damaged areas, especially the rims of the auricular pinnae. Pink, fissured masses are noted in the upper dermis, and transition can be identified between elastotic fibers and the pink masses. Erythropoietic protoporphyria presents with indurated erythematous skin in sun-exposed areas, commonly beginning in childhood. Patients complain that their skin burns when exposed to sunlight. Histologically, dense pink mantles of basement membrane material are noted surrounding vessels in the upper third of the dermis.

Immunohistochemical studies have demonstrated that amyloid in NA is of the AL subtype, derived from immunoglobulin light chains.[7] Immunoperoxidase staining shows positivity for both kappa and lambda light chains.[1] Unlike MA and LA, NA amyloid does not label with antikeratin antibodies.[7]

Treatment has proven difficult with recurrence rates ranging from 7% to 50% following surgical excision.[1] Injections with triamcinolone have been noted to produce a paradoxical increase amyloid deposition.[6] Fortunately, the long-term prognosis is good as progression to systemic involvement is rare, but it is important to exclude systemic AL and plasma cell dyscrasia at the time of initial presentation.[2]