Neoplasia‐related spiny keratoderma: Dermoscopic findings of two cases and a literature review

INTRODUCTION

Spiny keratoderma (SK) of the palms and soles is an infrequent palmoplantar keratoderma, of unknown aetiology, characterised by multiple isolated keratotic plugs, arising from the palms, soles, or both.¹, ², ³ It is distinct in two different types: an autosomal dominant benign form, with onset in childhood, and an acquired form, typically starting in the second half of life. This latter variant has been reported associated with the exposure to asbestos and arsenic, to non‐neoplastic systemic conditions (e.g. Darier’s disease, hypertension, hyperlipidemia, diabetes, polycystic kidney disease) or internal malignancies. However, these correlations are still unclear because the likelihood of developing chronic diseases or malignancies is generally higher in patients above the age of 50.¹, ², ³, ⁴

The clinical diagnosis of SK could pose a diagnostic challenge. The filiform keratotic spikes could resemble several other skin lesions such as warts, pitted keratolysis, palmar pits of the nevoid basal cell carcinoma syndrome; moreover, SK must be distinguished from other forms of punctate‐type palmoplantar keratodermas, both acquired (e.g. arsenical keratoses) and genetically determined (e.g. Brauer–Buschke–Fischer keratoderma and acrokeratoelastoidosis lichenoides).¹, ², ³

Histopathological examination of SK usually shows peculiar characteristics that make the diagnosis easy for the pathologist: acanthotic acral epidermis, hypogranulosis, a chimney‐like parakeratotic column and dilated dermal capillary vessels; within the spine, a compact orthohyperkeratosis interspersed with parakeratotic corneocytes with nonspecific inclusions could be observed.³ Anyhow, skin biopsy of the palmoplantar regions represents an invasive diagnostic procedure, which, when possible, should be avoided. For this purpose, dermoscopy can be of great help, as well as in a wide range of neoplastic, inflammatory and infectious cutaneous diseases. Unfortunately, available data concerning the dermoscopic aspects of SK are very poor, probably due to the rarity of this condition.⁵, ⁶

We describe dermoscopic and clinical aspects of two acquired cases of SK in adult Caucasian men, both affected by cancers.

MAIN TEXT

Case 1 was a 78‐year‐old Caucasian man of Italian origin (Fitzpatrick skin type III) with on the palms and, although less numerous, on the soles, multiple small, firm, keratotic papules of 0.5–1 mm in diameter, 1–2 mm in length and skin‐coloured (Fig. 1a‐c). These lesions, present for over 7 years, were asymptomatic but the patient was uneasy for their presence and appearance. About 1 year after the appearance of skin lesions, he was diagnosed with small lymphocytic lymphoma/chronic lymphocytic leukaemia, localised in the palatine tonsils and treated with bendamustine and rituximab. His medical history was also remarkable for Parkinson’s disease, mellitus diabetes, hypertension, hypercholesterinaemia, surgically treated benign prostatic hyperplasia and HBV infection treated with Tenofovir.

Figure 1.

Clinical and dermoscopic findings of the Case 1. (a‐c) Close up views showing multiple yellowish filiform keratotic spikes on the palm and finger of the hands. (d‐f) Dermoscopy of the lesions revealed multiple minute keratotic exophytic projections cylindrical in shape that resembled tiny spines.

Case 2 was a 72‐year‐old Caucasian man of Italian origin (Fitzpatrick skin type II) referred to our Department for multiple non‐melanoma skin cancers (NMSCs) and actinic keratoses at the head and neck, trunk, upper and lower limbs, which developed over the past three years and had never been treated. Finally, we surgically removed five primary squamous cell carcinomas of the head and neck region, obtaining complete resection with histological confirmation, whilst cutaneous precancers have been successfully treated with cryotherapy and topical imiquimod. He also had a history of hyperuricemia and hypertension in therapy with allopurinol and amlodipine. The dermatological examination revealed also some small, millimetre, hyperkeratotic projections of the palms and soles, with dermoscopic aspects similar to case 1 (Fig. 2, a‐c). These lesions had appeared more than 8 years earlier; given their asymptomaticity, he had never felt the need to request a dermatological examination for this reason.

Figure 2.

Clinical and dermoscopic features of the Case 2. (a‐c) Multiple small hyperkeratotic papules on the palms and the soles. As could be noted from the macroscopic images, the spiny lesions can be so tiny as to be unnoticed at the clinical visit. (d‐f) Skin surface microscopy of the palmoplantar areas can highlight lesions significantly better: multiple white‐yellowish punctate structures, which appear as well‐defined, firm and tiny millimetre spicules.

Dermoscopic examination revealed several white‐yellowish keratotic punctate spicules in both patients; in case of detachment from the skin surface, a punctate rounding area (similar to keratolysis) remains, which is then pigmented brown, probably due to the superimposition of pigment of exogenous origin (Figs 1 and 2d‐f). Based on the clinical and dermoscopic findings, we made the diagnosis of acquired SK which developed about one year before the onset of haematological malignancy in Case 1 and about 5 years before the multiple primary squamous cell carcinomas in Case 2.

Our experience, together with the limited data available in the literature, suggests that the dermoscopic findings usually related to SK are represented by multiple millimetre rounded hyperkeratotic white‐yellowish spicules. The tiny plugs can vary in number from a few elements to dozens and arise indifferently along the furrows or the ridges. Although they can be grouped, they show no tendency to confluence, always remaining well delimited from each other.⁵, ⁶

Due to the complex sensory and motor functions of the palmoplantar skin, SK is often associated with symptoms, worsening the life quality of patients. Several treatments have been proposed, including mechanical debridement with shaving or carbon dioxide laser vaporisation, and topical treatments with urea, salicylic acid, 5‐fluorouracil or retinoid cream.¹, ³

Table 1 summarises all published manuscripts reporting SK patients suffering from concomitant malignancies.¹, ², ³, ⁴, ⁵, ⁷, ⁸, ⁹ We performed a systematic review in MEDLINE using the following key words: ‘spiny keratoderma’, ‘music box spine keratoderma’, ‘punctate keratoderma’, ‘filiform hyperkeratosis’ and ‘minute digitate hyperkeratosis’. Every reference cited in all the articles included has also been verified. Every article that met the search criteria was analysed, regardless of language. Gray literature, any document that has not gone through peer review for a publication and conference abstracts were excluded. To date, there have been described fewer than 50 different cases of SK. About a third of these have been reported in patients with personal history of malignancies; 12 of these 18 cancer‐related SK patients (66.6%) were male, with a mean age of 72.4 years (range 54–85). The remaining 6 cases were female, with a mean age of 74 years (range 61–85). Of note, in 9 of 18 (50%) subjects SK preceded the diagnosis of the malignant tumour.¹, ², ³, ⁷ The most frequent related cancers were skin tumours, followed by haematological malignancies (6 and 4 cases, respectively).¹, ², ³, ⁴, ⁵, ⁶, ⁷, ⁸, ⁹ Specifically, about 27.7% of the reported cases (5 among the 18 patients described) had a coexistence of medical history of both melanoma or NMSCs and SK. Although primary cutaneous tumours with metastatic potential are extremely common malignancies, they have been described by different authors in patients with various paraneoplastic signs and symptoms, allowing hypothesising a possible correlation. In addition, other than SK, various types of palmoplantar keratoderma have been described in patients with both cutaneous and non‐cutaneous malignant tumours, including squamous cell carcinoma of the of the head–neck region.¹⁰

Table 1.

Clinical findings of all reported subjects affected with both SK and malignant cancers

Reference	Age (years, y), sex	Associated malignancy
Corral et al. 2020† PMID: 33054945	83 Female	Endometrial carcinoma
Bao et al. 2020 PMID: 32995441	81 Female	Breast cancer
Abadías‐Granado et al. 2020 PMID: 32088157	54 Male	Laryngeal cancer
Campbell EH et al. 2018† PMID: 29693077	74 Male	Non‐melanoma skin cancer and Renal cell carcinoma
Gaiser et al. 2017 PMID: 29693077	83 Male	Non‐melanoma skin cancers (note: professional exposure to asbestos)
Pirmez et al. 2016 PMID: 26871926	72 Male	Multiple myeloma
Texteira et al. 2016† https://doi.org/10.29021/spdv.74.4.683	65 Male	Mycosis fungoides
Poppe et al. 2012† PMID: 22361841	85 Male	Melanoma
Rosina et al. 2012† PMID: 22834644	61 Female	Colon adenocarcinoma
Walsh et al. 2010† PMID: 19755909	71 Female	Lung squamous cell carcinoma and Adenocarcinoma
Bordel‐Gomex et al. 2008 PMID: 18355198	75 Female	Chronic lymphocytic leukaemia
Yukawa et al. 2007† PMID: 17340030	64 Male	Gingival squamous cell carcinoma
Bernal et al. 2000† PMID: 11146361	70 Male	Chronic lymphocytic leukaemia
Handa et al. 2000 PMID: 11056427	85 Female	Esophageal cancer
Mehta et al. 2002 PMID: 12072012	73 Male	Myelofibrosis
Horton et al. 1998 PMID: 9675341	80 Male	Squamous cell carcinoma of the nose
Rault et al. 1997† PMID: 9740869	79 Male	Sigmoid adenocarcinoma
Kaddu et al. 1995 PMID: 7615881	70 Male	Melanoma

^† Cases in which the onset of SK preceded the diagnosis of the tumour.

These data might suggest that SK could be considered a potential cutaneous indicator of malignancy in a genetically predisposed patient.⁵, ⁶, ⁷, ⁸, ⁹

CONCLUSION

In conclusion, this report underlines the crucial rule of an accurate dermatological examination, which also should include non‐invasive epiluminescence microscopy, in the evaluation and differential diagnostics of patients with punctate keratoderma. Furthermore, in consideration of the risk of underlying malignancies in SK patients, it is recommended a routine initial evaluation that should include a general physical examination and complete laboratory studies. Complete personal and family history, regular medical examinations and cancer screenings appropriate for age and gender are also essential for early detection of any associated internal disease.

INFORMED CONSENT

Clinical photographs were performed after proper informed consent.