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Images of the month: A painful nodule arising within chronic necrobiosis lipoidica

Authors:
David McBriar
David McBriar
David McBriar
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Matthew Costley at Belfast Health and Social Care Trust
Matthew Costley
Joseph Houghton
Joseph Houghton
Joseph Houghton
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Donal O’Kane at Belfast Health and Social Care Trust
Donal O’Kane
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© Royal College of Physicians 2020. All rights reserved. e269
Clinical Medicine 2020 Vol 20, No 6: e269–70 IMAGES OF THE MONTH
Images of the month: A painful nodule arising within
chronic necrobiosis lipoidica
Authors: David McBriar,A Matthew Costley,B Joseph HoughtonC and Donal O’KaneD
KEYWORDS: Necrobiosis lipoidica, squamous cell carcinoma
DOI: 10.7861/clinmed.2020-0618
Case presentation
A 77-year-old woman attended clinic for review of longstanding
necrobiosis lipoidica. She reported a tender lesion on the left lower
leg that had developed over 2 months. This had not responded
to treatment with topical steroids, unlike all previous necrobiosis
lipoidica-related ulcerations. On examination, a 15×15 mm tender
ulcerating nodule was evident within an area of clinical chronic
quiescent necrobiosis lipoidica (Fig 1).
This patient originally presented to our department 9 years
previously, with a 3×4 cm well-circumscribed pink-brown plaque
with central atrophy and telangiectasia on the left shin. Histology
demonstrated a palisading and interstitial granulomatous
dermatitis and was supportive of the clinical diagnosis of
necrobiosis lipoidica. Past medical history included hyper tension
and hypothyroidism but not diabetes. Over subsequent years,
the plaque on the left shin enlarged and two smaller plaques
developed on the right shin. Intermittent areas of ulceration were
successfully managed with potent topical steroids (± occlusion).
Topical tacrolimus 0.1% had also been beneficial at reducing
inflammation in non-ulcerated areas.
A 4 mm incisional punch biopsy was performed on the new
nodular lesion. This demonstrated well differentiated squamous
cell carcinoma (Fig 2). The nodule was subsequently excised with
4 mm clinical margins and repaired with a split skin graft.
Discussion
Necrobiosis lipoidica is a rare, chronic granulomatous skin
disorder. Onset is often in middle age, and there is a female
preponderance.1 It is associated with diabetes in 11–65% of
cases.2 The pathogenesis is unclear. Typically, necrobiosis lipoidica
involves the pre-tibial area; but may involve the scalp, face or
upper limbs. Over time, the plaques flatten to form broad, yellow/
Authors: Ainternal medicine training-3, Belfast City Hospital,
Belfast, UK; Bdermatology registrar, Royal Victoria Hospital, Belfast,
UK; Cconsultant histopathologist, Royal Victoria Hospital, Belfast,
UK; Dconsultant dermatologist, Royal Victoria Hospital, Belfast, UK
orange patches, often with ulceration.3 There is no cure, and the
mainstay of treatment is topical corticosteroids.
Marjolin’s ulcer is a term used to describe tumours, classically
squamous cell carcinoma, which arise in the setting of chronic skin
disease. They are more aggressive than primary skin cancer and
have a higher rate of metastatic spread. They may present as an
ulcer which fails to heal, as rapid change or as a tender nodule in
an area of chronic disease.
The development of squamous cell carcinoma in an area
of necrobiosis lipoidica is rare but documented, a review of
Fig 1. Clinical photographs showing chronic necrobiosis lipoidica. a)
Chronic necrobiosis lipoidica in right leg. b) Chronic necrobiosis lipoidica
changes more marked on the left leg. c) Area of chronic necrobiosis on the
left lateral shin containing a 15 mm tender ulcerating nodule.
e270 © Royal College of Physicians 2020. All rights reserved.
David McBriar, Matthew Costley, Joseph Houghton and Donal O’Kane
the literature has demonstrated 16 previous cases.4 This case
highlights the need to be vigilant to the development of squamous
cell carcinoma in the setting of chronic, benign skin disease. In
necrobiosis lipoidica, there should be a low threshold for incisional
biopsy of a new nodule, evolving ulcer or area not responding to
recognised treatment. There is currently no specific guidance on
screening or follow-up for non-healing ulceration in patients with
necrobiosis lipoidica.5
Our case displayed a 9-year history of necrobiosis lipoidica
prior to presentation with a squamous cell carcinoma. This is
significantly lower than the average time of necrobiosis lipoidica
prior to presentation with a primary cancer described in the
literature.4 This displays the variety of this rare presentation in
patients with necrobiosis lipoidica; and they should therefore be
counselled in when to seek re-referral and how to self-monitor. ■
References
1 Erfurt-Berge C, Dissemond J, Schwede K et al. Updated results
of 100 patients on clinical features and therapeutic options in
Address for correspondence: Dr David McBriar, Belfast City
Hospital, Lisburn Road, Belfast BT9 7AB, UK.
Email: david.mcbriar@outlook.com
Fig 2. Haematoxylin and eosin stains
showing an abnormal squamous prolif-
eration composed of small islands with
irregular edges infiltrating a chroni-
cally inflamed and fibrotic dermis in
keeping with invasive well differenti-
ated squamous cell carcinoma. a) At
×10 magnification. b) At ×20 magnifica-
tion. c) At ×10 magnification. d) At ×40
magnification.
necrobiosis lipoidica in a retrospective multicentre study. European
Journal of Dermatology 2015;25:595–601.
2 Hammer E, Lilienthal E, Hofer SE et al. Risk factors for necrobiosis
lipoidica in Type 1 diabetes mellitus. Diabetic Medicine 2017;34:
86–92.
3 Kerr-Valentic MA, Samimi K, Rohlen BH, Agarwal JP, Rockwell WB.
Marjolin’s ulcer: modern analysis of an ancient problem. Plast
Reconstr Surg 2009;123:184–91.
4 Lefkovits Y, Adler A. Fatal squamous cell carcinoma from necro-
biosis lipoidica diabeticorum in a diabetic patient. Endocrinol
Diabetes Metab Case Rep 2019;2019:19–0007.
5 Uva L, Freitas J, Soares de Almeida L et al. Squamous cell car-
cinoma arising in ulcerated necrobiosis lipoidica diabeticorum.
International Wound Journal 2015;12:741–3.
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Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy. Learning points PD-1/PD-L1 blockade can induce hypophysitis with a different clinical presentation when compared to CTLA-4 blockade. Diagnosis of PD-1/PD-L1 induced hypophysitis is mainly made on clinical grounds and sellar MRI does not show radiological abnormalities. Hyponatremia due to acute secondary adrenal insufficiency is often the principal sign of PD-1/PD-L1-induced hypophysitis and can be masked by other symptoms due to oncologic disease. PD-1/PD-L1-induced hypophysitis can present as an isolated manifestation of irAEs or be in association with other autoimmune diseases
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Fatal squamous cell carcinoma from necrobiosis lipoidica diabeticorum in a diabetic patient
Article
Full-text available
  • Mar 2019
Necrobiosis lipoidica diabeticorum (NLD) is a chronic granulomatous dermatitis generally involving the anterior aspect of the shin, that arises in 0.3–1.2% of patients with diabetes mellitus (1). The lesions are often yellow or brown with telangiectatic plaque, a central area of atrophy and raised violaceous borders (2). Similar to other conditions with a high risk of scarring including burns, stasis ulcers and lupus vulgaris, NLD provides a favourable environment for squamous cell carcinoma (SCC) formation (3). A number of cases of SCC from NLD have been recorded (3, 4, 5); however, our search of the literature failed to identify any cases of either metastatic or fatal SCC which developed within an area of NLD. This article describes a patient with established type 1 diabetes mellitus who died from SCC which developed from an area of NLD present for over 10 years. Currently, there are a paucity of recommendations in the medical literature for screening people with NLD for the early diagnosis of SCC. We believe that clinicians should regard non-healing ulcers in the setting of NLD with a high index of clinical suspicion for SCC, and an early biopsy of such lesions should be recommended. Learning points Non-healing, recalcitrant ulcers arising from necrobiosis lipoidica diabeticorum, which fail to heal by conservative measures, should be regarded with a high index of clinical suspicion for malignancy. If squamous cell carcinoma is suspected, a biopsy should be performed as soon as possible to prevent metastatic spread, amputation or even death. Our literature search failed to reveal specific recommendations for screening and follow-up of non-healing recalcitrant ulcers in the setting of necrobiosis lipoidica diabeticorum. Further research is required in this field.
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Risk factors for necrobiosis lipoidica in Type 1 diabetes mellitus
Article
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  • DIABETIC MED
Aims: To compare the clinical and metabolic characteristics of patients with Type 1 diabetes and necrobiosis lipoidica with those of patients with Type 1 diabetes who do not have necrobiosis lipoidica. A multicentre analysis was performed. Methods: Clinical and laboratory data were obtained from 64 133 patients (aged 0-25 years) with Type 1 diabetes with and without necrobiosis lipoidica who were registered in the German/Austrian Diabetes Prospective Documentation Initiative registry. Data were analysed using multivariable regression modelling. Age, diabetes duration, treatment year and sex were considered as confounding factors. Results: Results adjusted for demographic variables are presented. In patients with necrobiosis lipoidica, metabolic control was worse (HbA1c 72 vs. 67 mmol/mol, 8.7% vs. 8.3%; P = 0.0065) and the duration of diabetes was longer [6.24 (3.28-9.97) vs. 5.11 (2.08-8.83) years; P = 0.014; not adjusted]. Patients with necrobiosis lipoidica required higher insulin doses than those without (1.02 vs. 0.92 U/kg/day; P < 0.0001). There was no significant difference in the frequency of microvascular complications (microalbuminuria and retinopathy) between the groups. Furthermore, 24.8% and 17.5% of patients with Type 1 diabetes with and without necrobiosis lipoidica, respectively, had elevated thyroid antibodies (P = 0.051). Necrobiosis lipoidica was correlated with coeliac disease in patients with Type 1 diabetes (3.4% vs. 1.0%; P = 0.0035). Conclusions: Our data indicate a strong correlation between hyperglycaemia and the development of necrobiosis lipoidica. We postulate that the underlying pathogenic processes differ from those leading to microalbuminuria and retinopathy, and additional immunological mechanisms may play a role. This article is protected by copyright. All rights reserved.
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Updated results of 100 patients on clinical features and therapeutic options in necrobiosis lipoidica in a retrospective multicentre study
Article
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Background: Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown aetiology which can manifest in ulcerative skin lesions and is widely recognised in association with diabetes. We evaluated in total 100 patients to improve knowledge about the epidemiology and clinical course of NL. Additionally we focused on treatment options according to evidence level and expert opinion. Objective: To examine the clinical features of patients with necrobiosis lipoidica and to give recommendations for topical and systemic treatment. Materials & methods: This multicentre retrospective study covers data from 100 patients with the diagnosis of NL of the lower leg, treated during the period between 01/2006 and 06/2014. Data from 5 German dermatological centres with 23 men and 77 women with a median age of 52 years were evaluated. We also asked 15 dermatological experts for their opinions about ulceration, associated diseases and their preferences for treatment modalities of NL. Results: Patients' ages ranged from 15 to 95 years (median age 52 years, mean age 49.8 years). NL was significantly more common in women (77%). Ulceration of the NL was observed in 33% of cases, in particular in male patients and in patients with concomitant diabetes mellitus. Thyroidal disorders were found in 15% of all cases. Conclusion: Our data confirm that female sex, middle age and endocrine disorders like diabetes mellitus or thyroid dysfunction are characteristics of patients suffering from NL. Existing therapeutic options were very variable and - according to the opinion of our experts - only a few highly effective.
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Marjolin's ulcer is a rare but highly aggressive squamous cell cancer that is most often associated with chronic burn wounds. Although many individual case reports exist, no thorough evaluation of Marjolin's ulcer patients has been conducted to date. The authors present their experience with 10 patients encountered over a period of 15 years and analyze 25 previous publications, for a total of 443 patients diagnosed with Marjolin's ulcer. Although burn scar represents 76.5 percent of patients in the authors' review, venous stasis ulcers, traumatic wounds, osteomyelitis, and pressure sores are also represented as wound types that can undergo malignant degeneration. The authors' review suggests that there is much variability in the anatomical location of Marjolin's ulcers, with the majority occurring in wounds of the upper and lower extremities. Marjolin's ulcer appears to be preventable if early wound coverage is undertaken. Countries with limited access to medical treatment report a high number of Marjolin's ulcers compared with more developed regions.
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necrobiosis lipoidica in a retrospective multicentre study
  • Jan 2015
  • EUR J DERMATOL
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necrobiosis lipoidica in a retrospective multicentre study. European Journal of Dermatology 2015;25:595-601.