Nevoid acanthosis nigricans: Report of four cases localized to the umbilicus
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
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.
|Patient||Sex||Age (years)||Evolution (years)||Treatment|
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].
|Case||Years||Sex age||Evolution (years)||Localization||Associations||Treatment||Result|
|1||19763||Male 32||Puberty||Abdomen||Epidermal nevus Parotid cancer||Not specified||Not specified|
|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
|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|
|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,
|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|
|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
|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|
|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.|
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 consentThe 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 sponsorshipNil.
Conflicts of interestThere are no conflicts of interest.
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