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August 2015

Nodular Amyloidosis of the PenisA Case Demonstrating Keratinocyte Origin

Author Affiliations
  • 1Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
  • 2Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
  • 3Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada
  • 4Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 5Women’s College Hospital, Toronto, Ontario, Canada

Copyright 2015 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Dermatol. 2015;151(8):910-912. doi:10.1001/jamadermatol.2015.0510

Herein we describe the first case to our knowledge of primary nodular amyloidosis of the glans penis, in which the amyloid originates from keratinocytes rather than immunoglobulins.

Report of a Case

A man in his 50s presented with a 6-year history of slowly expanding asymptomatic lesions on the penis that “bruised” after sexual activity and had eluded correct diagnosis for over 6 years. On examination, the patient had painless, raised, firm, translucent-to-yellowish nodules on the glans penis and distal shaft, suggestive of nodular amyloidosis (Figure 1). The biopsy revealed a mixed cellular infiltrate of lymphocytes and plasma cells as well as a few globules of amorphous hyaline-like material in the reticular dermis (Figure 2A). Congo red staining was positive, with birefringence (Figure 2B). Immunohistochemically, the amyloid was positive for 34ßE12 (Figure 2C). No specific staining for either κ or λ light chain was seen. Screen results for systemic amyloidosis with serum immunoglobulin light chains and urinary Bence-Jones proteins were negative. The clinical appearance, the histologic findings, and the absence of systemic involvement were consistent with the diagnosis of primary cutaneous nodular amyloidosis of the glans penis.

Figure 1.
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Primary Cutaneous Nodular Amyloidosis of the Distal Shaft and Glans Penis

This case shows raised, firm, and translucent-to-yellowish nodules on the glans penis and distal shaft.

Figure 2.
Image not available
Histopathologic and Immunohistochemical Images of Amyloid Deposits in Lesional Biopsy Specimens

A, Acanthosis and hyperkeratosis of the epithelial layer, with subepithelial acute and chronic inflammation (hematoxylin-eosin, original magnification ×20). B, Amorphous subepithelial deposits were birefringent on examination under polarized light (main panel) and stained positive with Congo Red (inset), consistent with amyloid deposition (original magnification ×40 for both panels). C, Amyloid deposits were strongly positive for 34ßE12 (original magnification ×40).


Primary cutaneous nodular amyloidosis is typically characterized by single, tan or yellow, waxy nodules or plaques that preferentially occur on acral areas such as the lower extremities, head, trunk, scalp, and genitals.1 To our knowledge, 14 cases of primary cutaneous amyloidosis of the penis have been reported, and all were the nodular type.2,3

In contrast to keratin-derived deposits found in cutaneous macular amyloidosis and lichen amyloidosis, light chain–derived amyloid has historically been the histologic hallmark of nodular amyloidosis.2 Of 14 previous cases of penile nodular amyloidosis, only 1 was tested for high-molecular-weight keratins and stained positive for cytokeratin 5.2 In our case, however, immunohistochemical findings were positive for 34ßE12, a monoclonal antibody against certain high-molecular-weight keratins (cytokeratins 1, 5, 10, 14) that reacts strongly with epidermal keratinocytes4 and also with the amyloid in macular amyloidosis and lichen amyloidosus.5 In addition, there was no specific immunostaining for κ or λ light chains.

Of interest are parallel findings in a case series of primary cutaneous amyloidosis of the auricular concha and external ear reported by Wenson et al.6 All 11 cases in that report showed strong positivity for 34ßE12, while none were positive for cytokeratins 5 or 6 or pancytokeratins AE1 or AE3. These findings suggest that the amyloid in their series was likely derived from the residuum of basal epidermal keratinocyte degeneration. Our case and theirs raise the possibility that cutaneous nodular amyloidosis may not be exclusively of immunoglobulin-light-chain origin.

Our current notion of nodular amyloidosis as immunoglobulin derived is, in fact, based on a small number of individual case reports or case series.2 The accumulating evidence of a keratinocyte origin for at least some cases of nodular amyloidosis suggests that its causes may be more heterogeneous than previously believed.

Management of this condition can be difficult. Previous reports describe 5 cases of penile nodular amyloidosis that were treated surgically, while 9 required no intervention because they were either asymptomatic or not associated with systemic disease.2,3 For asymptomatic nodular amyloidosis, conservative management with regular monitoring for systemic progression has been considered reasonable. For more severe cases, surgery may be appropriate.1

Our findings suggest that biopsy including immunohistochemistry studies to define the nature of the amyloid deposits has merit. If the amyloid appears to arise from keratinocytes rather than immunoglobulins, there may be less need to monitor for systemic disease. This case also highlights the need for clinical vigilance to recognize this rare entity morphologically and institute appropriate investigation and management.

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Article Information

Corresponding Author: Whan B. Kim, BSc, Michael G. DeGroote School of Medicine, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada (

Published Online: May 6, 2015. doi:10.1001/jamadermatol.2015.0510.

Conflict of Interest Disclosures: None reported.

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