A 50-year-old Hispanic man is referred for evaluation of a raised, darkened area on his upper back. He states the site was first noted ~6 months ago and has rapidly enlarged. The lesion is not itchy or painful. He denies a history of recent weight loss, fatigue, swollen glands, and bone pain. He is currently taking medications for control of hypertension and hypertriglyceridemia. Physical examination reveals a hyperpigmented plaque measuring over 3cm; scattered keratoses are noted elsewhere on the body.
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Primary cutaneous amyloidosis is divided into macular, lichenoid, and nodular forms. The infiltrate associated with lichen and macular amyloidosis is derived from epidermal keratinocytes.1 The infiltrate associated with nodular cutaneous amyloidosis (NCA) contains insoluble amyloid fibrils.2
Nodular cutaneous amyloidosis may present either as an asymptomatic, localized cutaneous lesion or more widespread as a manifestation of underlying systemic disease.3 The condition diffusely infiltrates the dermis, subcutis, and blood vessel walls.4 Epidemiologic data is difficult to establish due to a paucity of cases. Nodular cutaneous amyloidosis predominantly affects women in their sixth and seventh decades of life.5 The firm, pink to brown nodules can vary in size from a few millimeters to a few centimeters and may coalesce to form larger plaques.6 These are most commonly found in an acral distribution but have been reported on the scalp, trunk, and genitalia.5,6
Definitive diagnosis is made through biopsy with histopathology demonstrating diffuse amyloid deposits arranged in an abnormal fibrillar form along with plasmacytic infiltration.3 Amyloid appears as an amorphous eosinophilic material by light microscopy and stains positive for Congo red. Specimens stained with Congo red demonstrate apple-green birefringence when viewed under polarized light, a feature considered the gold standard for diagnosis.2
The cause of NCA is not known.6 Skin conditions that can mimic NCA include colloid milium, cutaneous pseudolymphoma, and leiomyoma.6 In over 60% of reported cases, NCA appears in the absence of systemic amyloid deposits, multiple myeloma, or other plasma cell dyscrasias.7 Normal serum protein electrophoresis studies can assist in excluding multiple myeloma.6 The progression of NCA to fatal systemic amyloidosis has been reported, although it is a rare occurrence.8
Asymptomatic cutaneous lesions may not require treatment. Recurrence of the lesion has been noted following shave excision, laser therapy, and radiotherapy.3 Topical and intralesional corticosteroid therapy, as well as cryotherapy, are not effective.6 To prevent further infiltration of surrounding tissue some clinicians advocate the use of wide excision surgery.9
Alexandra Stroia, BS, is a medical student at the Lake Erie College of Osteopathic Medicine in Erie, Pennsylvania. Stephen Schleicher, MD, is director of the DermDox Dermatology Centers, associate professor of medicine at Geisinger Commonwealth Medical College, and clinical instructor of dermatology at Arcadia University and Kings College.
1. Cornejo KM, Lagana FJ, Deng A. Nodular amyloidosis derived from keratinocytes: an unusual type of primary localized cutaneous nodular amyloidosis. Am J Dermatopathol. 2015;37(11):e129-e133. doi:10.1097/DAD.0000000000000307
2. Konopinski JC, Seyfer SJ, Robbins KL, Hsu S. A case of nodular cutaneous amyloidosis and review of the literature. Dermatol Online J. 2013;19(4):10. doi:10.5070/D34x9967k7
3. Khan NAJ, Nellhaus E, Griswold D, Jamil MO. First case of nodular localized primary cutaneous amyloidosis treated with bortezomib and dexamethasone. J Investig Med High Impact Case Rep. 2021;9:23247096211058488. doi:10.1177/23247096211058488
4. Vestey JP, Tidman MJ, Mclaren KM. Primary nodular cutaneous amyloidosis–long-term follow-up and treatment. Clin Exp Dermatol. 1994;19(2):159-162. doi:10.1111/j.1365-2230.1994.tb01148.x
5. Udompaetaikul M, Ophaswongse S, Palungwachira P. Nodular cutaneous amyloidosis involving the glan penis: report of a case. J Med Assoc Thai. 2001;84(7):1065-1068.
6. Nguyen NV. Nodular localized cutaneous amyloidosis. Medscape. Published July 06, 2020. Accessed March 24, 2022. https://emedicine.medscape.com/article/1102770-overview#a1
7. Matsumoto ME, Collins MK, Raptis A, Jedrych J, Patton T. Multifocal primary cutaneous nodular amyloidosis. Dermatol Online J. 2017;23(5):13030/qt9511r6bg.
8. Moon AO, Calamia KT, Walsh JS. Nodular amyloidosis: review and long-term follow-up of 16 cases. Arch Dermatol. 2003;139(9):1157-1159. doi:10.1001/archderm.139.9.1157
9. Stanizzi A, Torresetti M, Barbisan F, Peltristo B, Zavalloni Y, Di Benedetto G. A peculiar case of large and “unresectable” primary localized cutaneous nodular amyloidosis of the ankle. Case Rep Dermatol. 2021;13(3):502-505. doi:10.1159/000519030