February 2021 — Dermatopathology

A 23-year-old woman received the following punch biopsy for a tan-yellow pigmented ankle lesion.  

Figure 1
Figure 2

What is the most likely diagnosis?

  • Cutaneous sarcoidosis
  • Necrobiosis lipoidica
  • Necrobiotic xanthogranuloma
  • Granuloma annulare

The correct answer is ...

The diagnosis in this case is: Necrobiosis lipoidica.

Necrobiosis lipoidica (NL) is a poorly understood granulomatous disease of the dermis and subcutaneous tissue that is associated with a variable clinical course. The incidence for this condition is 0.3% of patients with diabetes mellitus with a female predominance, yet it may also present in healthy individuals.1 Additional systemic conditions associated with NL include systemic lupus erythematosus, hypothyroidism, ulcerative colitis, and rheumatoid arthritis.2

To date, the underlying pathogenesis for necrobiosis lipoidica remains unknown, yet numerous theories exist. Some have hypothesized that the pathophysiology of NL involves microangiopathy secondary to glycoprotein deposition in vessel walls; immune complex deposition; development of anti-collagen antibodies; or venous insufficiency.3,4,5

NL is usually characterized by bilateral lower extremity lesions, typically along the pretibial surface that are first visible as either papules or nodules that may progress to waxy yellow-brown plaques. Ulcerations may also develop, particularly following trauma.6 Differential diagnoses based on the clinical presentation and lesion location often include other granulomatous disorders, including necrobiotic xanthogranuloma (NXG), granuloma annulare, sarcoidosis, erythema nodosum, as well as venous stasis ulcers. The need to differentiate amongst these disparate entities underscores the importance of obtaining a biopsy. Histopathologic features of NL biopsy specimens at low magnification exhibit alternating horizontal layers of necrobiosis in a “layer cake” pattern involving the superficial dermis and subcutaneous fat. The epidermis is typically normal but may also demonstrate atrophy, acanthosis, or hyperkeratosis. The palisading necrobiotic granuloma is composed of epithelioid histiocytes and giant cells, occasionally arranged in well-formed granulomas. Additional cell types such as lymphocytes and plasma cells are often present in clusters. Alternating between the granulomas are layers of eosinophilic swollen, degenerative, collagen fibers.


  1. Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum. A clinical and pathological investigation of 171 cases. Arch Dermatol 1966;93:272–81.
  2. Magro CM, Crowson AN, Regauer S. Granuloma annulare and necrobiosis lipoidica tissue reactions as a manifestation of systemic disease. Hum. Pathol. 1996;27:50–6.
  3. Engel M, Smith, G. The pathogenesis of Necrobiosis Lipoidica. Arch Dermatol. 1960; 82:791-797
  4. Evans CD, Perfeira RS, Yuen CT, Holden CA. Anti-collagen antibodies in granuloma annulare and necrobiosis lipoidica. 1988; 13:252-254.
  5. Nakajima T, Tanemura A, Inui S, Katayama I. Venous insufficiency in patients with necrobiosis lipoidica. J Dermatol. 2009; 36:166-9. 
  6. Sibbald C, Reid S, Afsaneh. Necrobiosis Lipoidica. Dermatol Clin. 2015; 33:342-360.
Belinda Galeano profile picture square

Belinda Galeano, M.D., Ph.D.

Resident, Anatomic and Clinical Pathology
Mayo Clinic

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Julia Lehman, M.D.

Consultant, Laboratory of Dermatopathology
Mayo Clinic
Professor of Dermatology and Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

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This post was developed by our Education and Technical Publications Team.