Subcutaneous scalp nodule as the presenting symptom of systemic light-chain amyloidosis

We present a case of subcutaneous nodular amyloidosis mimicking a pilar cyst. Further evaluation led to the diagnosis of malignant systemic light-chain amyloidosis. The epidemiology and histopathological features of light-chain amyloidosis with cutaneous involvement are reviewed, as well as current recommendations for initial evaluation.

suspected and an excisional biopsy was performed. Microscopic examination revealed extensive dermal infiltration by amorphous hyaline and fibrillary material (Figures 1-3) revealing the diagnosis of amyloidosis.

Discussion
Amyloidosis is not just one disease but a rare group of diseases resulting from the extracellular deposition of misfolded proteins in various tissues as toxic amyloid aggregates. Amyloidosis is characterized based on the subtype of amyloid fibril protein as well as the mechanism of deposition. Cutaneous amyloidosis may be organized into one of 3 groups: primary localized cutaneous amyloidosis (PLCA), secondary localized cutaneous amyloidosis, or systemic AL amyloidosis with cutaneous involvement [1]. Among the PLCA group, lichen, macular, biphasic, and nodular forms are recognized.
The most encountered type of PLCA, lichen amyloidosis, presents clinically as multiple hyperpigmented, clustered, pruritic papules on the lower extremities [2]. Macular amyloidosis presents darkly pigmented macules with a rippled surface.
Both lichen and macular types are derived from cytokeratins [2]. The biphasic form is simply a mix of the macular and lichen amyloidoses. Nodular amyloidosis, accounting for 1.5% of PLCA cases, presents as either single or multiple lesions and is derived from immunoglobulins, commonly lambda light chain. There have been less than 100 cases of primary localized nodular amyloidosis reported to date [2][3][4][5]. Some studies suggest that nodular amyloidosis may be associated with systemic disease in 7% to 50% of patients [6,7]. However, a literature review conducted by Biewend et al found that   biopsy is done to monitor for monoclonal plasma cells and if present, requires further evaluation to determine whether the patient has active multiple myeloma [15]. Aspiration of subcutaneous tissues of the abdominal wall or of an involved organ (in our patient, the skin) is required to definitively confirm the diagnosis of systemic amyloidosis [16]. Because primary nodular amyloidosis has a significant association with Sjögren syndrome, serology for ANA, anti-Ro/SSA, and anti-La/SSB may also be considered, which in this case were unremarkable [17][18][19]. lary and reticular dermis as well as in the subcutaneous fat [11]. Flattened rete ridges may be observed in the overlying epidermis. Amyloids stained with Congo red display applegreen birefringence under polarized light. Because nodular amyloid is produced by plasma cell infiltration, specimens may stain with immunohistochemical stains for kappa or lambda chains [11].

Conclusions
It is common for cysts to be falsely diagnosed based on appearance alone. One retrospective analysis aimed to see if histological findings correlated with clinical diagnosis. The authors found that 13 of 295 cases were positive for calcium deposition, described as calcinosis cutis, on histology [12]. GI involvement by nausea, vomiting, or diarrhea; autonomic dysfunction by symptoms of orthostasis or GI dysmolity; and neurologic involvement by peripheral neuropathy. Initial workup for systemic amyloidosis may include CBC, chemistries, serum free light chains, serum and urine protein electrophoresis with immunofixation, and urinary Bence-Jones protein [14]. The presence of a monoclonal protein is found in 80% to 90% of serum and urine immunochemistry studies in patients with primary amyloidosis [15]. Bone marrow