Dermatologica Sinica

: 2021  |  Volume : 39  |  Issue : 1  |  Page : 49--50

Squamous cell carcinoma in a Taiwanese mal de Meleda family with SLURP-1 mutation: A case report

Hao- Jui Weng1, Yi- Hua Liao2, Pei- Jung Lin3, Jau- Shiuh Chen2, Yu- Ping Cheng4, Woan- Ruoh Lee5, Shiou- Hwa Jee4,  
1 Departments of Dermatology, Taipei Medical University- Shuang Ho Hospital, New Taipei City; School of Medicine, College of Medicine, Taipei Medical University; Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan
2 Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan
3 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
4 Department of Dermatology, National Taiwan University Hospital; Department of Dermatology, Cathay General Hospital, Taipei, Taiwan
5 Departments of Dermatology, Taipei Medical University- Shuang Ho Hospital, New Taipei City; School of Medicine, College of Medicine, Taipei Medical University; Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan

Correspondence Address:
Dr. Shiou- Hwa Jee
Department of Dermatology, Cathay General Hospital, No. 280, Renai Rd. Sec. 4, Taipei 106

How to cite this article:
Weng HJ, Liao YH, Lin PJ, Chen JS, Cheng YP, Lee WR, Jee SH. Squamous cell carcinoma in a Taiwanese mal de Meleda family with SLURP-1 mutation: A case report.Dermatol Sin 2021;39:49-50

How to cite this URL:
Weng HJ, Liao YH, Lin PJ, Chen JS, Cheng YP, Lee WR, Jee SH. Squamous cell carcinoma in a Taiwanese mal de Meleda family with SLURP-1 mutation: A case report. Dermatol Sin [serial online] 2021 [cited 2023 Jan 30 ];39:49-50
Available from:

Full Text

Dear Editor,

This is a report of one 68-year-old male patient in a Taiwanese family of mal de Meleda (MDM, OMIM 248300) in which two of his siblings were affected with acral lentiginous melanoma (ALM). Since childhood, he started to present with progressive stock-and-glove-like acral erythrokeratoderma on the palms and soles [Figure 1]a. Later on in his fifties, he developed a painful giant verrucous lesion on his right 5th fingertip. Pustular discharge was noted and the patient attempted to manipulate the lesion by himself without improvement. X-ray revealed bony erosions over the distal phalanx. The finger was thus amputated at the age of 59 in 2010 due to poor wound healing. The pathology and detectable type 71 human papillomavirus (HPV) DNA confirmed verruca vulgaris [Figure 1]b. In 2017, he noted poor wound healing on the distal end of the right index finger and biopsy revealed squamous cell carcinoma (SCC) [Figure 1]c and [Figure 1]d. In 2018, the right index finger was amputated. The pathology showed moderately differentiated SCC with tendon invasion [Figure 1]e. HPV DNA was negative. Currently, he has been under regular evaluation and there has been no sign of recurrence for SCC or evidence of ALM.{Figure 1}

MDM is a rare disease of autosomal recessive heritance first described in 1826 by Stulli on the island of Mljet. It is manifested by transgredient hyperkeratosis of palms and soles with the prevalence of 1:100,000.[1] This disorder is also progredient in nature as its severity increases with aging. Other associated features include hyperhidrosis, nail anomalies, perioral erythema, subungual hyperkeratosis, koilonychia, and high-arched palate. Histologically, the affected regions show hyperkeratosis and acanthosis. Notably, it is well known that MDM patients suffer high incidence of ALM. In fact, one of this patient's elder brothers with MDM was diagnosed with ALM and one of his younger sister with MDM was diagnosed with breast cancer and ALM [Figure 1f].

Mutations in SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1) have been reported in different MDM families of various ethnicity groups.[2],[3] SLURP-1 is an allosteric modulator for the alpha-7 subunit of nicotinic acetylcholine receptors with the proposed function for pro-apoptosis and inhibition of tumor necrosis factor (TNF)-alpha release.[4],[5] In vitro assays showed that SLURP-1 binds to the alpha-7 subunit of nicotinic acetylcholine receptors and addition of recombinant SLURP-1 protein exerts its effects of modulating activities of nicotinic acetylcholine receptors.[4] SLURP-1 gene consists of 3 exons and mutations at various loci of each exon and its introns have been identified in the patients worldwide.[1] In the previous study, we identified a homozygous mutation of G86R in SLURP-1 within a Taiwanese family.[6] This patient also came from the same Taiwanese MDM family and all of his five family members affected with MDM had A/A homozygous G86R mutation of SLURP-1. Furthermore, all the family members with A/A homozygous mutation or A/G heterozygous mutation have had impaired T-cell activation by anti-CD3/28 antibodies. The T-cell function impairment could be restored by addition of recombinant wild type SLURP-1 protein.[6] So far two of five members in this MDM family developed ALM. This patient does not have melanoma; however, SCC developed on his right index finger.

Cases of SCC arising from palmoplantar keratoderma and subungual regions have been reported in MDM families from Palestine and Turkey with respective SLURP-1 mutations.[7],[8] In our case, a different SLURP-1 mutation of G86R is identified showing similar effects on SCC carcinogenesis. SLURP-1 may play a role in its carcinogenesis with the following hypotheses, including the ability of cancer formation per se and creating an environment favoring carcinogenesis. First, mutations in SLURP-1, a modulator for nicotinic acetylcholine receptors, may render carcinogenicity. Altered calcium signaling has been implicated in tumor progression, including its invasion and proliferation. Nicotinic acetylcholine receptors function as heteropentamers comprised of a combination of different subunits. Currently, 17 subunits in vertebrates have been identified.[9] Among all, alpha-7 subunit possesses the highest permeability for Ca2+ and therefore has been shown to be associated with the progression of various cancers, including gastric cancers, pancreatic cancers, small cell lung carcinoma, colon cancer, and head and neck SCC.[9],[10] Interestingly, alpha-7 subunits of nicotinic acetylcholine receptors also down-regulate SLURP-1 and result in increased proliferation, possibly due to nicotine activation.[9] Second, T-cell dysfunction was reported in the patients with SLURP-1 mutation.[6] The formation of giant verruca can also be partly explained by impaired T-cell function. Thirdly, SLURP-1 may serve as a tumor-suppressor gene in the epidermal lineage while mutated SLURP-1 may lose the function of anti-tumorigenicity.[7] SLURP-1 mRNA levels are downregulated in SCC of various origins in comparison to its benign counterparts.[7] Moreover, the chronic inflammatory status in MDM manifested as marked erythema may induce cancer formation. It is known that inflammation is involved in neoplastic progression, signaling, and chemokine secretion, and there are evidences showing these processes are associated with development of skin cancers. In particular, TNF-α, interleukin (IL)-1, IL-6, IL-17, IL-23, and transforming growth factor-beta are found to be pro-tumorigenic.[11]

In summary, here we presented a case with SCC within a Taiwanese MDM family with G86R mutation in SLURP-1. As SLURP-1 is involved in the carcinogenesis of the malignancy of squamous cell lineage, it is necessary to watch for any malignancy in addition to ALM in the patients with MDM.

Declaration of patient consent

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

Financial support and sponsorship


Conflicts of interest

There are no conflict of interest.


1Perez C, Khachemoune A. Mal de Meleda: A Focused Review. Am J Clin Dermatol 2016;17:63-70.
2Jee SH, Lee YY, Wu YC, Lü YC, Pan CC. Report of a family with mal de Meleda in Taiwan: A clinical, histopathological and immunological study. Dermatologica 1985;171:30-7.
3Fischer J, Bouadjar B, Heilig R, Huber M, Lefèvre C, Jobard F, et al. Mutations in the gene encoding SLURP-1 in Mal de Meleda. Hum Mol Genet 2001;10:875-80.
4Lyukmanova EN, Shulepko MA, Kudryavtsev D, Bychkov ML, Kulbatskii DS, Kasheverov IE, et al. Human secreted Ly-6/uPAR related protein-1 (SLURP-1) is a selective allosteric antagonist of α7 nicotinic acetylcholine receptor. PLoS One 2016;11:e0149733.
5Chimienti F, Hogg RC, Plantard L, Lehmann C, Brakch N, Fischer J, et al. Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda. Hum Mol Genet 2003;12:3017-24.
6Tjiu JW, Lin PJ, Wu WH, Cheng YP, Chiu HC, Thong HY, et al. SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda. Br J Dermatol 2011;164:47-53.
7Bergqvist C, Kadara H, Hamie L, Nemer G, Safi R, Karouni M, et al. SLURP-1 is mutated in Mal de Meleda, a potential molecular signature for melanoma and a putative squamous lineage tumor suppressor gene. Int J Dermatol 2018;57:162-70.
8Baykal C, Sari SO, Uyguner ZO, Ekinci AP, Demir O, Babuna G, et al. Ungual squamous cell carcinoma in a patient with Mal de Meleda. J Dtsch Dermatol Ges 2016;14:514-6.
9Russo P, Cardinale A, Margaritora S, Cesario A. Nicotinic receptor and tobacco-related cancer. Life Sci 2012;91:1087-92.
10Dang N, Meng X, Song H. Nicotinic acetylcholine receptors and cancer. Biomed Rep 2016;4:515-8.
11Tang L, Wang K. Chronic inflammation in skin malignancies. J Mol Signal 2016;11:2.