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A case of nodular cutaneous amyloidosis and review of the literature

  • Author(s): Konopinski, Jonathan C
  • Seyfer, Sarah J
  • Robbins, Kerri L
  • Hsu, Sylvia
  • et al.
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A case of nodular cutaneous amyloidosis and review of the literature
Jonathan C Konopinski MD, Sarah J Seyfer MD, Kerri L Robbins MD, Sylvia Hsu MD
Dermatology Online Journal 19 (4): 10

Baylor College of Medicine, Houston, Texas

Abstract

Nodular cutaneous amyloidosis (NCA) is the rarest form of primary cutaneous amyloidosis. The amyloid fibrils of NCA are not unique to NCA but are also the prevailing amyloid component in primary systemic amyloidosis (PSA) and myeloma-associated systemic amyloidosis. Age of presentation in NCA has ranged from 20 to 87 years without a clear gender predilection. Progression from NCA to primary systemic amyloidosis has been reported, with an estimated lifetime risk of approximately 7 percent, prompting the need for appropriate follow up to evaluate for the presence of systemic amyloidosis. We report a case of nodular cutaneous amyloidosis in an otherwise healthy 62-year-old woman and we review the literature.



Introduction

Amyloidosis may affect the skin as part of a systemic infiltration of circulating amyloid or as an isolated disease of the skin resulting from locally produced amyloid, termed primary cutaneous amyloidosis (PCA). Nodular cutaneous amyloidosis is the rarest form of PCA. We report herein a case of nodular cutaneous amyloidosis in an otherwise healthy woman and we review the literature.


Case presentation


Figure 1Figure 2
Figure 1. 1.5 x 1.2 cm yellow-brown plaque on patient’s chest after the punch biopsy was performed.

Figure 2. Faintly eosinophilic, amorphous, fissured masses of amyloid are deposited throughout the dermis.

A 62-year-old woman with no significant past medical history presented with a new lesion on her chest that she first noticed 2 months prior. She denied any recent change in size or color. Exam revealed a 1.5 cm x 1.2 cm yellow-brown plaque on her medial chest (Figure 1). A 4 mm punch biopsy was performed. Microscopic examination showed amorphous, pinkish-gray material between the collagen fibers in the papillary and reticular dermis that stained lightly orange with Congo red (Figure 2). Definitive apple green birefringence was not appreciated. Based on these findings, a diagnosis of nodular cutaneous amyloidosis was made. Serum and urine protein electrophoresis studies were negative. The patient was informed of the results and made aware that regular follow up with her primary care provider was necessary given the possibility for progression of NCA to systemic disease. She later returned for complete excision of the plaque. Both in situ hybridization probes for immunoglobulin mRNA and liquid chromatography tandem mass spectrometry performed on peptides extracted from Congo red-positive areas of the specimen detected a peptide profile consistent with AL (lambda light chains) type amyloid deposition.


Discussion

The amyloidoses are a group of diseases characterized by the extracellular deposition of insoluble aggregates of misfolded proteins, collectively termed amyloid, into various tissues of the body. The amyloid deposits arrange in an abnormal fibrillar form and may disrupt tissue architecture and function. Amyloid appears as an amorphous eosinophilic material by light microscopy and stains positive for Congo red. Additionally, specimens stained with Congo red demonstrate apple green birefringence when viewed under polarized light, a feature that has become the gold standard for diagnosis.

Primary cutaneous amyloidosis is a set of amyloidoses in which amyloid is deposited only into the skin and includes 3 distinct entities: lichen amyloidosis, macular amyloidosis, and nodular cutaneous amyloidosis (NCA). The rarest of these is NCA, in which amyloid diffusely infiltrates the dermis, subcutis, and blood vessel walls [1]. In lichen and macular amyloidosis, the amyloid deposits do not invade blood vessels or extend below the dermis.

The amyloid fibrils in NCA are composed of immunoglobulin light chains, termed “protein AL.” Protein AL is not unique to NCA and is the prevailing amyloid component in several other amyloidosis, including primary systemic amyloidosis (PSA) and myeloma-associated systemic amyloidosis. Immunohistochemical studies have shown that the light chains in NCA may be of the kappa and/or lamba type [2]. Local monoclonal plasma cells produce and secrete the light chains through an unknown mechanism, as demonstrated by light chain restriction and molecular genetics [3, 4]. This is in contrast to the amyloid fibrils in lichen and macular amyloidosis, which are secreted by keratinocytes and comprised chiefly of cytokeratin 5 [5].

Clinically, NCA presents as single or multiple yellow-brown waxy nodules or plaques with well-defined borders, ranging from 0.5 cm to 7 cm in diameter. The overlying epidermis may have an atrophic or anetodermic appearance [6]. Nodules may occur focally and occur most commonly on the trunk and extremities. No clear gender predilection exists, as previous case series have demonstrated male predominance, female predominance, and equal affliction of males and females [3, 7]. Age of presentation has ranged from 20 to 87 years, with the 6th decade of life being the most common [3, 8, 9]. An association of NCA with Sjögren syndrome has been described [3, 10, 11]. Although NCA is rare, it has been estimated that up to 25 percent of NCA cases may be associated with Sjögren syndrome [11]. Serologies including anti-Ro/SSA and anti-La/SSB were evaluated and were negative in this patient.

Therapy aims to improve appearance of the lesions, as no underlying cause for production of amyloid by plasma cells in NCA has been found. No treatment studies have been conducted. Variable cosmetic and histological results have been reported, including surgical excision, cryotherapy, electrodesiccation and curettage, intralesional steroid injection, carbon dioxide (CO2) laser, and dermabrasion. Nodular cutaneous amyloidosis does not respond to intralesional steroid injection and this therapy may actually accelerate amyloid deposition [12]. CO2 laser has been reported to produce excellent cosmetic results but in once case, a recurrent nodule was noted 9 months after treatment [13]. Limitations to other treatment modalities include incomplete cosmetic and histologic eradication.

Progression from NCA to primary systemic amyloidosis has been reported, with a risk of approximately 7 percent [7]. Furthermore, lesions of NCA are histologically indistinguishable from those of primary and myeloma-associated systemic amyloidosis [14]. For these reasons, appropriate laboratory studies and follow up should be coordinated in patients presenting with lesions histologically consistent with NCA in order to evaluate for the presence of systemic amyloidosis.

References

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