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doi:
10.4103/ijdvl.IJDVL_1016_18
pmid:
32719198
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Nevoid acanthosis nigricans: Report of four cases localized to the umbilicus

Clinical Dermatology Department, Dermatology Institute of Jalisco, “Dr. José Barba Rubio,” Secretary of Health of Jalisco, Zapopan, Jalisco
Medical Research Division, UMAE Pediatric Hospital, CMNO, IMSS, Guadalajara, Mexico
Corresponding author: Dr. Elizabeth Guevara-Gutiérrez, Monte Olimpo 1413, Colonia Independencia, CP 44340, Guadalajara, Jalisco, México. albtlacuilo@yahoo.com
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This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Reyes-Meza SE, Guevara-Gutiérrez E, Villanueva-Quintero G, Hernández-Arana S, Tlacuilo-Parra A. Nevoid acanthosis nigricans: Report of four cases localized to the umbilicus. Indian J Dermatol Venereol Leprol 2020;1-7.

Abstract

Nevoid acanthosis nigricans is a rare, benign form of acanthosis nigricans. Of the 24 cases documented in the literature, only two are exclusively localized to the umbilicus. We present four cases of nevoid acanthosis nigricans localized to the umbilicus; in patients less than 25 years of age, with no known co-morbidities, three of whom were females. Two of the cases received, with good response, treatment based on topical calcipotriol, a medication not previously reported to be used for this indication. Contrary to other types of acanthosis nigricans, the nevoid acanthosis nigricans is not associated with any syndrome, endocrinopathy, obesity, medication, or neoplasia and it can be confused with other pathologies such as epidermal nevus or dermatosis neglecta.

Keywords

Acanthosis nigricans
nevoid
umbilicus
vitamin D analogs

Introduction

Acanthosis nigricans is a mucocutaneous disorder of keratinization that presents as hyperpigmented plaques with a keratotic surface and velvety appearance. Generally, it is distributed symmetrically in the folds of the neck, axillae, and/or groins and is considered a common dermatological manifestation of systemic illnesses or a reaction to certain medications.1,2 On the other hand, nevoid acanthosis nigricans is a rare and benign form of acanthosis nigricans with only 24 cases documented in indexed literature.3-21 Of these, only 2 are localized exclusively to the umbilicus.6,8

Case Reports

Four patients attended the Dermatology Institute of Jalisco, “Dr. José Barba Rubio.” Three of them were females, with a median age of 19 years. The condition was present a while before presentation, with a median evolution time of 2.5 years [Table 1]. All the patients presented with the characteristic features of well- defined hyperpigmented-brownish plaques with verrucous, scaly surface, localized to the umbilicus [Figures 1a, 1b, 1c, 1d (×40)]. In all cases, the lesions were vigorously rubbed with alcohol swab, to test if they could be removed by doing so, and none could be removed. Thereafter, skin biopsies were performed. The histopathology studies in all the four cases showed similar features characterized by the presence of hyperkeratosis, mild and irregular acanthosis and papillomatosis [Figures 2a, 2b, 2c, 2d]. None had any associated symptoms or had received previous treatments. There was no family history of similar dermatosis or other disturbances of keratinization. They were not overweight or obese, and did not have similar lesions elsewhere. A diagnosis of nevoid acanthosis nigricans was established through clinical and histopathological data. Two patients, whose fasting insulin and glucose levels were within normal limits, received treatment with calcipotriol cream (50 μg/g) two times per day for 3 weeks, with remission of the lesions and without relapse at 3 years of follow-up. The other two patients did not agree to having diagnostic tests performed and declined treatment when they were informed about the benign nature of their condition. Figures 3a and 3b illustrates the improvement observed in patient number 2.

Table1:: Epidemiological characteristics of the patients with nevoid acanthosis nigricans of the umbilicus
Patient Sex Age (years) Evolution (years) Treatment
1 Female 20 5 None
2 Female 22 1 Calcipotriol
3 Female 17 3 Calcipotriol
4 Male 18 2 None
Figure 1a:: Patient 1 showing a well defined hyperpigmented brownish plaque with verrucous, scaly surface
Figure 1b:: Patient 2 showing a well defined brownish plaque with hyperkeratosis areas and exophytic appearance
Figure 1c:: Patient 3 showing a verrucous brownish plaque with scaly surface and precise borders
Figure 1d:: Patient 4 showing a verrucous brownish plaque with velvety appearance and precise borders
Figure 2a:: Histopathology of patient 1 showing hyperkeratosis and papillomatosis (H and E, ×400)
Figure 2b:: Histopathology of patient 2 showing hyperkeratosis, mild and irregular acanthosis with papillomatosis (H and E, ×400)
Figure 2c:: Histopathology of patient 3 showing hyperkeratosis and papillomatosis alternating with moderate acanthosis, interpapillary valley filled with keratine (H and E, ×400)
Figure 2d:: Histopathology of patient 4 showing hyperkeratosis and mild papillomatosis of the epidermis with scarce lymphocytic infiltrate on the dermis (H and E, ×400)
Figure 3a:: Brownish hyperkeratotic and exophytic plaque localized to the umbilicus of patient 2 (×40)
Figure 3b:: Clinical image showing clearance of the lesion after three weeks of treatment with topical calcipotriol (×40)

Discussion

Nevoid acanthosis nigricans is a rare and benign form of acanthosis nigricans that can present during infancy or puberty.3-21 It was first described in 1976 by Curth.3 Since that description, there have been 23 cases published.4-21

Nevoid acanthosis nigricans presents slightly more often in males, is localized to bodily areas that differ from the classic acanthosis nigricans, is generally unilateral, and is distributed in segmental form or follow Blaschko’s lines. In published cases, the most frequent localization reported is in the trunk, in 79% cases, followed by extremities in 13%, and the head in 8% cases.3-21 Only two (8%) of the reported cases are localized exclusively to the umbilicus6,8 [Table 2].

Table 2:: Characteristics of patients with nevoid acanthosis nigricans published in the literature
Case Years Sex age Evolution (years) Localization Associations Treatment Result
1 19763 Male 32 Puberty Abdomen Epidermal nevus Parotid cancer Not specified Not specified
2 199114 Male
17
4 Abdomen and umbilicus None Not specified Not specified
3 20039 Female 18 4 Abdomen and umbilicus None Not specified Not specified
4 20058 Female 18 2 Umbilicus None Tretinoin 0.1% Excellent
5 20066 Female 16 4 Umbilicus None Minocycline and
adapalene 0.1%
Improvement
6 200612 Female 18 12 Clavicular region Hashimoto thyroiditis Topical tretinoin 0.025% No improvement
7 200612 Female 16 Childhood Thigh Amenorrhea, obesity, classical acanthosis nigricans Not specified Not specified
8 200612 Male
7
4 Back None Not specified Not specified
9 200612 Male 28 2 Pectoral region None Not specified Not specified
10 200810 Female 18 7 Nape, retroauricular region None Not specified Not specified
11 200815 Male 8 6 Axillary region None Ammonium lactate 12% Mild improvement
12 201011 Male 28 6 Sternal and pectoral region Neurofibromatosis Not specified Not specified
13 20114 Female 19 3 Sternal and submammary region None Tretinoin 0.025% Improvement
14 20127 Female 29 14 Shoulder and arm None Tretinoin, corticosteroids, hydroquinone No improvement
15 20127 Male 18 1.5 Scapular region None Not specified Not specified
16 20127 Male 6 2 Auricular tragus None Not specified Not specified
17 201316 Female 40 25 Leg None Not specified Not specified
18 201417 Male 25 8 Pectoral region None Retinoids Not specified
19 201418 Male 40 25 Axillary and pectoral region None Keratolitic, retinoid,
corticosteroid
No improvement
20 201419 Female 23 9 Axillary region None Laser CO2 Improvement
21 201413 Male 12 6 Scapular region None Tretinoin No improvement
22 201520 Male 18 3 Axillary and pectoral region None Tretinoin 0.05% Not specified
23 20155 Male
17
0.25 Abdomen None Tretinoin 0.05% Improvement
24 201621 Female 9 4 Scapular region None Laser CO2 Very satisfactory

From the morphological point of view, though it presents as a hyperpigmented and well-defined velvety-surfaced plaque, its distribution is nevoid.8 The other names that it has been given are -rounded and velvety epidermal nevus,7,18,19 linear acanthosis nigricans,16 unilateral nevoid acanthosis nigricans,4,11,14,17,20,21 or acanthosis nigricans similar to epidermal nevus.3,12

Its clinical course is unpredictable as it can have a short period of activity, to later maintain stability, or it can regress.3,5 Contrary to classical acanthosis nigricans,1,2 nevoid acanthosis nigricans is not associated with insulin resistance, diabetes mellitus type 2, obesity; internal malignant neoplasia, or endocrine diseases.4-10,13-21 In 2006, Ersoy-Evans et al. published four cases of nevoid acanthosis nigricans where one was associated with obesity and amenorrhea, but since the patient also had classical and bilateral acanthosis nigricans lesions; we consider that the said associations were not related to nevoid acanthosis nigricans but rather to the classical acanthosis nigricans.12 Other associations include epidermal nevus,3 neurofibromatosis,11 and Hashimoto thyroiditis,12 although a causal relationship has not been demonstrated between them, and the majority of the published casesdo not refer to any association with systemic illnesses.4-10,13-21

The histopathological features of nevoid acanthosis nigricans do not vary from the classical form; characterized by hyperkeratosis, papillomatosis, mild and irregular acanthosis in the epidermis, with mild perivascular mononuclear inflammatory infiltrate in the superior dermis.3-21 In some cases, hyperpigmentation of the basal layer has been reported.10,13-15,17-19

The differential diagnoses that have been mentioned in published cases include the epidermal nevus,5,6,11,12,16-20 confluent and reticulated papillomatosis,6,12,17 Dowling–Degos disease,6 and seborrheic keratosis.17,18 To this list, we would add dermatosis neglecta and psoriasis [Table 3].22-26

Table 3:: Differential diagnoses of nevoid acanthosis nigricans and their primary characteristics
Diagnosis Age Localization Morphology Histopathology Associations
Epidermal Birth or Any site including Linear plaque Hyperkeratosis, acanthosis, papillomatosis. One-third have involvement of
nevus22 infancy oral mucosa and yellow-brown Can observe nests of nevoid cells. other organ systems
ocular conjunctiva velvety or verrucous, Increase in keratohyalin granules in the
well-defined corneal stratum. Hyperpigmentation of the
basal membrane.
Confluent and 8-32 years Bilateral superior Hyperpigmented Hyperkeratosis in wavy, web form, None
reticulated trunk (primarily the reticulated plaques, papillomatosis, focal acanthosis, increased
papillomatosis23 submammary and brown-colored, melanin in the basal layer
intermammary region) velvety appearance
Dowling-Degos Adult onset Areas of flexion: Mottled and reticular Elongation of the interpapillary Hydradenitis suppurativa;
disease24 (<24 years) axillae, groin, pigmentation, crests, thinning of the suprapapillary multiple keratoacanthomas,
but can occur submammary folds, lesions similar to epithelium, hyperpigmentation of the epidermal, cysts and seborrheic
in infancy and neck comedones and basal layer in filiform pattern. In dermis, keratosis; and perianal
pointed scars lymphohistocytic perivascular infiltrate. squamous cell carcinoma
Seborrheic Adults Usually in areas Brownish plaques Hyperkeratosis, acanthosis, Premalignant and malignant
keratosis25 (>50 years) exposed to slightly elevated, papillomatosis, corneo pseudocysts lesions (24.2%), primarily
sunlight (63.1%) well-demarcated of seborrheic keratosis in
with follicular plugs light-exposed areas
Dermatosis Any age Any area, above Unique plaque, Does not require histopathological study, None
neglecta26 (patients all where there hyperpigmented, but when performed can present yeast
with some was hyperesthesia, verrucous that periodic acid-Schiff positives
disability previous trauma, pain, disappears after
or chronic or immobility cleaning or
illness) scrubbing the skin
Nevoid Infancy or Any localization, Plaque nevoid Hyperkeratosis, papillomatosis, mild None in the majority of
acanthosis puberty primarily trunk (79%) in appearance, acanthosis. In dermis, mild perivascular cases (87.5%)
nigricans3-21 hyperpigmented, mononuclear inflammatory infiltrate.
velvety surface

Clinically, psoriasis could be ruled out on the basis of the following features: 1) patients do not present with lesions in other areas and 2) the lesions are not erythematous plaques with desquamation on the surface. It is well-known that the umbilicus is a habitual localization for psoriasis, but, being a cutaneous fold, the lesions tend to be more erythematous and less desquamative, or in fact do not present scales.27 In a Medline search using the key words “psoriasis,” “localised,” “nevoid,” and “special localisation,” we did not find descriptions of psoriasis with exclusive localization to the umbilicus.

Histological features, especially the lack of granular layer and regular papillomatosis could point toward psoriasis. However, these findings are non-specific and can also be present in nevoid acanthosis nigricans and other pathologies such as confluent and reticulated papillomatosis of Gougerot and Carteaud.23 Moreover, our cases lack findings that are observed in 90% of patients with psoriasis (parakeratosis, dermal perivascular lymphocytic inflammatory infiltrate) or in more than 50% of them (Kogoj’s spongiform pustules and Munro micro abscesses).28

Due to the rarity of nevoid acanthosis nigricans, there is no existing consensus for treatment and the results have been variable [Table 2]. We decided to initiate treatment with vitamin D analogs, specifically topical calcipotriol (22-ene-26,27-dehydro1α,25(OH) 2D3), for two reasons: a) for its mechanism of action on keratinocytes: in vitro studies have demonstrated that once vitamin D analogs bind to the intracellular receptor of vitamin D, they act as transcription factors modulating the expression of various genes involved in epidermal proliferation, inflammation, and keratinization.29 In other words, calcipotriol promotes the differentiation of keratinocytes through molecules such as involucrin and transglutaminase-1 and inhibits epidermal proliferation,30 b) For the favorable response observed in patients with nevoid hyperkeratosis of the nipple and areola when treated with calcipotriol31 or with another vitamin D analog, the calcitriol.32 These are the characteristics of the medication explaining the favorable response to treatment in two of the cases mentioned in the present case report, although this response needs to be confirmed in a greater number of cases.

We report these four patients with nevoid acanthosis nigricans localized to the umbilicus with the aim of familiarizing dermatologists with the clinical characteristics of nevoid acanthosis nigricans, help differentiate it from classical acanthosis nigricans and from other clinical and histopathological differential diagnoses and to consider it among the dermatoses localized to the umbilicus.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. , , , , . Current treatment options for acanthosis nigricans. Clin Cosmet Investig Dermatol. 2018;11:407-13.
    [CrossRef] [PubMed] [Google Scholar]
  2. , , , . Acanthosis nigricans: A fold (intertriginous) dermatosis. Clin Dermatol. 2015;33:466-70.
    [CrossRef] [PubMed] [Google Scholar]
  3. . Unilateral epidermal naevus resembling acanthosis nigricans. Br J Dermatol. 1976;95:433-6.
    [CrossRef] [PubMed] [Google Scholar]
  4. , , . Unilateral nevoid acanthosis nigricans with a submammary location. Ann Dermatol. 2011;23:95-7.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , . Nevoid acanthosis nigricans: A rare case with late onset. Our Dermatol Online. 2015;6:337-8.
    [CrossRef] [Google Scholar]
  6. , . Nevoid acanthosis nigricans localized to the umbilicus. J Dermatol. 2006;33:433-4.
    [CrossRef] [PubMed] [Google Scholar]
  7. , , , , . Nevoid acanthosis nigricans or RAVEN (rounded and velvety epidermal nevus): Three cases. Ann Dermatol Venereol. 2012;139:183-8.
    [CrossRef] [PubMed] [Google Scholar]
  8. , , , . Nevoid acanthosis nigricans localized to the umbilicus: Successful treatment with topical tretinoin. Ann Dermatol. 2005;17:24-6.
    [CrossRef] [Google Scholar]
  9. , , , . A case of nevoid acanthosis nigricans. Acta Derm Venereol. 2004;84:234-5.
    [CrossRef] [PubMed] [Google Scholar]
  10. , , . Nevoid acanthosis nigricans. Indian J Dermatol Venereol Leprol. 2008;74:279-80.
    [CrossRef] [PubMed] [Google Scholar]
  11. . Unilateral nevoid acanthosis nigricans and neurofibromatosis 1: An unusual association. Indian J Dermatol Venereol Leprol. 2010;76:715-7.
    [CrossRef] [PubMed] [Google Scholar]
  12. , , , , . The acanthosis nigricans form of epidermal nevus. J Am Acad Dermatol. 2006;55:696-8.
    [CrossRef] [PubMed] [Google Scholar]
  13. , , . Nevoid akantozis nigrikans. Turk J Dermatol. 2014;3:176-7.
    [CrossRef] [Google Scholar]
  14. . Unilateral nevoid acanthosis nigricans. Int J Dermatol. 1991;30:452-3.
    [CrossRef] [PubMed] [Google Scholar]
  15. , , . Nevoid acanthosis nigricans with subtle melanocyte hyperplasia. J Am Acad Dermatol. 2008;58:S102-3.
    [CrossRef] [PubMed] [Google Scholar]
  16. , . Linear acanthosis nigricans. Egypt Dermatol Online J. 2013;9:8.
    [Google Scholar]
  17. , , , , , , et al. Unilateral nevoid acanthosis nigricans: Uncommon variant of a common disease. Indian Dermatol Online J. 2014;5:S40-3.
    [CrossRef] [PubMed] [Google Scholar]
  18. , . RAVEN: forma particular de nevo epidérmico, Primer caso argentino. Dermatol Argent. 2014;20:268-70.
    [Google Scholar]
  19. , , . Rounded and velvety epidermal naevus, report of a verrucous form in axillary location. BMJ Case Rep. 2014;2014
    [CrossRef] [PubMed] [Google Scholar]
  20. , , . Unilateral nevoid acanthosis nigricans. BMJ Case Rep. 2015;2015
    [CrossRef] [PubMed] [Google Scholar]
  21. , , , . Unilateral nevoid acanthosis nigricans treated with CO2 laser. BMJ Case Rep. 2016;2016
    [CrossRef] [PubMed] [Google Scholar]
  22. , , , . Congenital epidermal nevus. Int J Clin Pediatr Dent. 2014;7:43-6.
    [CrossRef] [PubMed] [Google Scholar]
  23. , , . Confluent and reticulated papillomatosis: Diagnostic and treatment challenges. Clin Cosmet Investig Dermatol. 2016;9:217-23.
    [CrossRef] [PubMed] [Google Scholar]
  24. , , , , . Dowling-degos disease. Rom J Morphol Embryol. 2010;51:181-5.
    [Google Scholar]
  25. , , , , . Clinical and histopathological investigation of seborrheic keratosis. Ann Dermatol. 2016;28:152-8.
    [CrossRef] [PubMed] [Google Scholar]
  26. , , . Dermatitis neglecta. Indian J Dermatol Venereol Leprol. 2011;77:62-3.
    [CrossRef] [PubMed] [Google Scholar]
  27. , , , . Clinical analysis of 48 cases of inverse psoriasis: A hospital-based study. Eur J Dermatol. 2005;15:176-8.
    [Google Scholar]
  28. , , , . Histopathological findings are associated with the clinical types of psoriasis but not with the corresponding lesional psoriasis severity index. Ann Dermatol. 2015;27:26-31.
    [CrossRef] [PubMed] [Google Scholar]
  29. , , . The future of Vitamin D analogs. Front Physiol. 2014;5:122.
    [CrossRef] [PubMed] [Google Scholar]
  30. , . Effects of a novel vitamin D analogue MC903 on cell proliferation and differentiation in vitro and on calcium metabolism in vivo. Biochem Pharmacol. 1988;37:889-95.
    [CrossRef] [Google Scholar]
  31. , , , . Nevoid hyperkeratosis of the nipple and areola: Treatment of two patients with topical calcipotriol. J Am Acad Dermatol. 2002;46:131-3.
    [CrossRef] [PubMed] [Google Scholar]
  32. , , , . Unilateral nevoid hyperkeratosis of the nipple and areola treated with topical calcitriol. Actas Dermosifiliogr. 2008;99:500-1.
    [CrossRef] [Google Scholar]

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