eMedicine Specialties > Dermatology > Metabolic Diseases

Amyloidosis, Nodular Localized Cutaneous: Differential Diagnoses & Workup

Author: Lauren Biesbroeck, Washington University in St Louis School of Medicine
Coauthor(s): Gregory J Raugi, MD, PhD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle
Contributor Information and Disclosures

Updated: Jan 5, 2010

Differential Diagnoses

Colloid Milium
Leiomyoma
Pretibial Myxedema
Pseudolymphoma, Cutaneous

Workup

Laboratory Studies

  • Normal serum protein electrophoresis and urine protein electrophoresis studies help to exclude multiple myeloma, which can also cause amyloid deposits made up of immunoglobulin light chains.
  • Positive antinuclear, anti-Ro, and anti-La antibodies suggest Sjögren syndrome.
  • Laboratory studies, such as CBC, serum chemistry profile, and liver function tests often were part of a general workup in several case reports of patients with nodular localized cutaneous amyloidosis. Nodular localized cutaneous amyloidosis does not cause any abnormal findings in these studies.
  • Urinalysis or 24-hour urine testing can be performed to check for protein. Proteinuria is not a feature of localized cutaneous disease but can be seen in systemic amyloidosis.

Imaging Studies

  • In some patients, imaging studies have included chest radiography, ECG, and abdominal ultrasonography.
  • Screening for amyloid within organs can be accomplished using scintigraphy with radioiodinated serum amyloid P component (ie, SAP scanning). This is a very sensitive test for detecting early systemic amyloidosis.

Procedures

  • Skin biopsy provides the definitive diagnosis. No special tissue preparation or handling is required before delivering the specimen to the laboratory. Special stains and immunohistochemistry are helpful.
  • An optimal biopsy specimen includes the epidermis, papillary dermis, and reticular dermis. The amyloid in nodular localized cutaneous amyloidosis is located in the reticular dermis and subcutaneous fat, and clearly differentiates nodular localized cutaneous amyloidosis from other forms of amyloidosis. A shave biopsy or other superficial sample may not include enough reticular dermis to complete the diagnosis.
  • Consider bone marrow biopsy with gene rearrangement studies (if available) to exclude multiple myeloma.

Histologic Findings

Despite their biochemical heterogeneity, all "amyloid" deposits demonstrate a similar light microscopic appearance. They are eosinophilic and homogeneous when stained with hematoxylin and eosin and viewed with standard optics. When stained with Congo red and viewed with polarized light, deposits exhibit a characteristic green birefringence. In nodular amyloidosis, amyloid is not limited to the papillary dermis but is present in the entire dermis and may extend to subcutaneous fat. Amyloid deposition may be particularly prominent in walls of small blood vessels and surrounding individual lipocytes (see the images).

The bright pink homogeneous-appearing material se...

The bright pink homogeneous-appearing material seen is amyloid stained with Congo red. A distinguishing feature of amyloid in the skin is an affinity to take up Congo red stain.

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The bright pink homogeneous-appearing material se...

The bright pink homogeneous-appearing material seen is amyloid stained with Congo red. A distinguishing feature of amyloid in the skin is an affinity to take up Congo red stain.


Amyloid shows apple green when examined with pola...

Amyloid shows apple green when examined with polarized light.

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Amyloid shows apple green when examined with pola...

Amyloid shows apple green when examined with polarized light.


This transmission electron micrograph of amyloid ...

This transmission electron micrograph of amyloid deposited in the tissue shows loosely interwoven straight filaments.

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This transmission electron micrograph of amyloid ...

This transmission electron micrograph of amyloid deposited in the tissue shows loosely interwoven straight filaments.


Plasma cells, which most likely produce the amyloid, occur within an adjacent and intermingled inflammatory infiltrate. They can be sparse or numerous (similar plasma cell infiltrate occurs in nodular pulmonary amyloidosis but usually is absent in cutaneous lesions of primary systemic amyloidosis). When eosinophilic amyloid material is exposed to potassium permanganate prior to staining with Congo red, the amyloid retains its congophilia, similar to systemic amyloidosis but in contradistinction to secondary amyloidosis. Kappa or lambda light chains (or both) may be present on immunohistochemical staining.13

When viewed with a transmission electron microscope, the apparently homogeneous deposits of amyloid are composed of loosely interwoven 6- to 10-nm–thick straight filaments. The amino acids of the filament proteins are arranged in a characteristic beta-pleated sheet tertiary structure. Amyloid deposits in the skin also contain small amounts of a plasma-derived, nonfibrillar, amyloid-P protein.

More on Amyloidosis, Nodular Localized Cutaneous

Overview: Amyloidosis, Nodular Localized Cutaneous
Differential Diagnoses & Workup: Amyloidosis, Nodular Localized Cutaneous
Treatment & Medication: Amyloidosis, Nodular Localized Cutaneous
Follow-up: Amyloidosis, Nodular Localized Cutaneous
Multimedia: Amyloidosis, Nodular Localized Cutaneous
References
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References

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Further Reading

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Keywords

nodular localized cutaneous amyloidosis, localized cutaneous amyloidosis, NLCA, LCA, amyloidosis cutis nodularis atrophicans, tumefactive amyloid, systemic amyloidosis, Sjogren syndrome, Sjögren syndrome

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Contributor Information and Disclosures

Author

Lauren Biesbroeck, Washington University in St Louis School of Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Gregory J Raugi, MD, PhD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle
Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Catharine Lisa Kauffman, MD, FACP, Georgetown Dermatology and Georgetown Dermpath
Catharine Lisa Kauffman, MD, FACP is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Royal Society of Medicine, Society for Investigative Dermatology, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania
Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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