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Year : 2020  |  Volume : 63  |  Issue : 4  |  Page : 634-636
Generalized type 2 segmental disseminated superficial actinic porokeratosis coexisted with multiple cutaneous squamous cell carcinomas: Analysis of two cases

1 Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China
2 Department of Dermatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China

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Date of Submission17-Dec-2019
Date of Decision15-Apr-2020
Date of Acceptance16-Apr-2020
Date of Web Publication28-Oct-2020


Porokeratosis (PK) is defined as hyperpigmented macules or patches with a distinctive, ridge-like hyperkeratotic border which is histologically characterized by a cornoid lamella. Here, we report two cases of linear porokeratosis which converted to multiple cutaneous squamous cell carcinoma after long history progression. In addition, patient 2 was accompanied by secondary dermal amyloid deposits, which was rare reported.

Keywords: Amyloidosis, cornoid lamella, cutaneous squamous cell carcinoma, dermal amyloid deposit, linear porokeratosis

How to cite this article:
Zhao Q, Yu B, Zhou H, Feng C, Zhang X, Zheng Y, Geng S. Generalized type 2 segmental disseminated superficial actinic porokeratosis coexisted with multiple cutaneous squamous cell carcinomas: Analysis of two cases. Indian J Pathol Microbiol 2020;63:634-6

How to cite this URL:
Zhao Q, Yu B, Zhou H, Feng C, Zhang X, Zheng Y, Geng S. Generalized type 2 segmental disseminated superficial actinic porokeratosis coexisted with multiple cutaneous squamous cell carcinomas: Analysis of two cases. Indian J Pathol Microbiol [serial online] 2020 [cited 2021 Jul 25];63:634-6. Available from: https://www.ijpmonline.org/text.asp?2020/63/4/634/299339

   Introduction Top

Porokeratosis is an uncommon dermatologic disorder. It's characterized by annular lesions with an atrophic centre and an elevated border. The histological finding is an overlying column of parakeratosis (cornoid lamella), which is a column of tightly fitted parakeratotic cells in the upper epidermis.[1] Five main variants of porokeratosis have been described, including porokeratosis of Mibelli (PM), disseminated superficial actinic porokeratosis (DSAP), disseminated superficial porokeratosis (DSP), porokeratosis palmaris et plantaris disseminata, linear porokeratosis (LP). Overlapping variants can occur, but rarely do.[2],[3] So far, a few autosomal dominant cases of type 2 segmental manifestation with both LP and DSAP characteristics have been reported.[4],[5] According to Lihi Atzmony,[6] LP is a mosaic disorder resulted from second-hit postzygotic mutation in the genes encoding enzymes within the mevalonate pathway, that may open new avenues of thinking with the ultimate goal to develop a therapeutic approach to porokeratosis. The event of loss of heterozygosity occurring at an early developmental stage explains why the risk of malignant degeneration is particularly high in LP.[7] In summary, dermatologists and other medical experts should be more familiar with the unique clinical manifestations of segmental mosaicism.

   Case Report Top

Case 1

A 51-year-old male presented with linear keratotic hyperpigmented plaques on the trunk and limbs following Blaschko's lines since childhood [Figure 1]a. In his 20s, multiple, disseminated brown annular lesions spreaded to his face, neck, and other sun-exposed areas. Linear lesions on the dorsal part of his left foot slowly thicken to a verrucous shape [Figure 1]b. The diagnosis of DSAP was confirmed by characteristic histopathology of porokeratosis [Figure 1]c. The patient responded poorly to oral acitretin 30 mg daily. Over the past 3 years, the lesions on his left abdomen became erosive and biopsy revealed squamous cell carcinoma (SCC) formation [Figure 1]d. This uncommon coexistence of LP and DSAP fulfils the clinical criteria of a type 2 segmental DSAP.[8] After family screening, the patient's father and daughter have similar lesions of DSAP without LP, which further suggests potential postzygotic somatic mutations. Photodynamic therapy was given to local malignant transformed lesions and he responded well after 3 months' follow-up.
Figure 1: (a) Linear lesions along the left upper limb, trunk distribution; (b) Thickened warty plaques; (c) Cornoid lamella. (HE, ×400); (d) Left lower abdomen skin visible erosion, scab

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Case 2

A 49-year-old male presented with hyperkeratotic plaques, scab and erosion along the Blaschko's lines on the trunk and limbs for more than 4 years. Physical examination, showed disseminated linear hyperpigmented hyperkeratotic papules coalescing into plaques with atrophic central clearance. An incisional skin biopsy across the margin of a typical plaque demonstrated features consistent with porokeratosis. The tender nodule located on the left waist and abdomen was verrucous in appearance and biopsy demonstrated well-differentiated SCC [Figure 2]. Interestingly, crystal violet staining showed deposition of amyloid in the lower field of the cornoid lamella [Figure 3]. A diagnosis of type 2 segmental DSAP associated with malignant squamous transformation and secondary dermal amyloid deposits was made. Patient's all family members are clinically unaffected, in which the condition seems to be a one-off occurrence.
Figure 2: (a) The tender nodule was verrucous in appearance and located on the left waist and abdomen; (b) Biopsy of the tender nodule revealed disordered squamous epithelial cells and typical highly differentiated squamous cells invading the underlying dermis. (hematoxylin and eosin staining, ×200)

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Figure 3: Amyloid deposition stained positively with crystal violet staining can be seen in the lower field of the cornoid lamella. (crystal violet staining, ×400)

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   Discussion Top

LP is thought to represent a mosaic form of DSAP and has an incidence of less than 1 in 200,000. Genetically, the individual should have a germline mutation causing disseminated superficial actinic porokeratosis, and a somatic second mutation or allelic loss in the genes that encode enzymes within the mevalonate biosynthesis pathway.[1] In autosomal dominant skin disorders, two different mosaic manifestations are possible. A type 1 reflects heterozygosity for a postzygotic mutation present in an otherwise healthy embryo. By contrast, a type 2 segmental manifestation originates in a heterozygous embryo from early postzygotic loss of the corresponding wild-type allele, resulting in homozygosity or hemizygosity of the involved area of the body.[8] Our cases consist of a type 2 segmental manifestation, which explains the early onset of severe linear lesions and the presence of non-linear, lentil-sized DSAP lesions.

Mutated genes involved in PK include MVK and 4 additional genes (called SLC17A9, PMVK, MVD and FDPS). MVK, PMVK, and MVD catalyze 3 rate-limiting steps in mevalonate pathway sequentially to produce isopentenyl diphosphate, a fundamental building block for the biosynthesis of isoprenoid compounds such as sterols, including cholesterol, ubiquinone, dolichols, carotenoids, and some classes of isoprenylated proteins.[9] The incidence of various mutations in DSAP/DSP was approximately MVK (27.1%), MVD (58.3%) and FDPS (4.2%). The various mutation rates for PM was 60.5% of MVK and 23.7% of PMVK, respectively. Interestingly, some correlations were found between gene mutations and clinical phenotypes of PK. Giant plaque-type porokeratosis ptychotropica (PPt) and porokeratoma appeared to be unique phenotypes associated with MVK and PMVK mutations, respectively.[10]PMVK and MVD mutations are highly linked to porokeratosis localized to the genitals and around the eyes, respectively.[11],[12] For LP, the percentages of pathogenic mutations in MVK and PMVK were both 10%, while that of MVD is 30%. Moreover, LP with PMVK mutations had large and thickened plaques, while the participant with MVD mutations had thinner plaques, as observed in heritable generalized porokeratosis.[13]

It is estimated that up to 7.5% of patients with porokeratosis will develop a malignancy at the site, and malignant transformation into squamous (61% of cases), bowenoid (30%) or basal cell carcinoma (9%) has been described in all subtypes.[14],[15] The percentage of malignant transformation for the various subtypes is 19% of LP, 9.5% of porokeratosis palmaris and plantaris disseminata, 7.6% of PM, and 3.4% of DSAP/DSP.[14] The allelic loss in LP may explain the higher susceptibility to malignancy.[7] Several risk factors include prolonged duration, larger size, acral involvement, history of undergoing radiation therapy, or lesions in patients that are immunocompromised.[16] Amyloidosis is characterized by extracellular deposition of amyloid, which is soluble autologous protein, in a characteristic abnormal fibrillar form.[17] It consists of primary amyloidosis and secondary amyloidosis. Secondary localized cutaneous amyloidosis may be associated with a pre-existing skin condition or skin tumors, such as basal cell carcinoma, porokeratosis, solar elastosis, Bowen's disease and mycosis fungoides.[18] In patient 2, typical lesions of lichen amyloidosis was not clinically evident. However, histopathology revealed typical amyloid deposition below the cornoid lamella. To our knowledge, DSP with local amyloid deposits were summarized while Linear PK with dermal amyloid deposits has not been reported.

The treatment options based on symptom include surgical treatment, cryotherapy, CO2 laser therapy, oral and topical retinoid, topical vitamin D3 analogs, keratolytic agents, etc. Recently, topical 5% imiquimod and topical 3% diclofenac sodium gel have been reported to use on PK, with emphasis on its use in genital or genitogluteal porokeratosis. Photodynamic therapy in our patients has exhibited good outcome in malignant lesions. Some scholars propose that the accumulation of abnormal metabolites or shortage of isoprenoids might predispose patients to idiopathic inflammation of the skin, and that correction of the abnormal isoprenoid biosynthesis might be a novel therapeutic direction for PK.

Declaration of patient consent

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

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Conflicts of interest

There are no conflicts of interest.

   References Top

Sommerlad M, Lock A, Moir G, McGregor J, Bull R, Cerio R,et al. Linear porokeratosis with multiple squamous cell carcinomas successfully treated by electrochemotherapy. Br J Dermatol 2016;175:1342-5.  Back to cited text no. 1
Joshi R, Minni K. Genitogluteal porokeratosis: A clinical review. Clin Cosmet Investig Dermatol 2018;11:219-29.  Back to cited text no. 2
Leow YH, Soon YH, Tham SN. A report of 31 cases of porokeratosis at the National Skin Centre. Ann Acad Med Singapore 1996;25:837-41.  Back to cited text no. 3
Boente M, López-Baró AM, Frontini M, Asial RA. Linear porokeratosis associated with disseminated superfcial actinic porokeratosis: A new example of type II segmental involvement. Pediatr Dermatol 2003;20:514-8.  Back to cited text no. 4
Happle R. A rule concerning the segmental manifestation of autosomal dominant skin disorders. Review of clinical examples providing evidence for dichotomous types of severity. Arch Dermatol 1997;133:1505-9.  Back to cited text no. 5
Atzmony L, Khan HM, Lim YH, Paller AS, Levinsohn JL, Holland KE, et al. Second-hit, postzygotic PMVK and MVD mutations in linear porokeratosis. JAMA Dermatol 2019;155:548-55.  Back to cited text no. 6
Happle R. Cancer proneness of linear porokeratosis may be explained by allelic loss. Dermatology 1997;195:20-5.  Back to cited text no. 7
Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol 1999;41:143-64.  Back to cited text no. 8
Chang Q, Yan XX, Gu SY, Liu JF, Liang DC. Crystal structure of human phosphomevalonate kinase at 1.8 A resolution. Proteins 2008;73:254-8.  Back to cited text no. 9
Walsh SN, Hurt MA, Santa Cruz DJ. Porokeratoma. Am J Surg Pathol 2007;31:1897-901.  Back to cited text no. 10
Chen TJ, Chou YC, Chen CH, Kuo TT, Hong HS. Genital porokeratosis: A series of 10 patients and review of the literature. Br J Dermatol 2006;155:325-9.  Back to cited text no. 11
Sharquie KE, Al-Baghdady BA. Solar facial porokeratosis. J Dermatol 2003;30:216-21.  Back to cited text no. 12
Zhang Z, Li C, Wu F, Ma R, Luan J, Yang F, et al. Genomic variations of the mevalonate pathway in porokeratosis. eLife 2015;4:e06322.  Back to cited text no. 13
Sasson M, Krain AD. Porokeratosis and cutaneous malignancy. A review. Dermatol Surg 1996;22:339-42.  Back to cited text no. 14
Mazori DR, Shvartsbeyn M, Meehan SA, Tarsis SL. Transformation of porokeratosis ptychotropica into invasive squamous cell carcinoma. Int J Dermatol 2017;56:679-80.  Back to cited text no. 15
Silver SG, Crawford RI. Fatal squamous cell carcinoma arising from transplant-associated porokeratosis. J Am Acad Dermatol 2003;49:931-3.  Back to cited text no. 17
Perfetto F, Moggi-Pignone A, Livi R, Tempestini A, Bergesio F, Matucci-Cerinic M, et al. Systemic amyloidosis: A challenge for the rheumatologist. Nat Rev Rheumatol 2010;6:417-29.  Back to cited text no. 18
Nam CH, Park MK, Choi MS, Hong SP, Park BC, Kim MH, et al. Secondary cutaneous amyloidosis in a patient with Mycosis fungoides. Ann Dermatol 2017;29:79-82.  Back to cited text no. 19

Correspondence Address:
Songmei Geng
The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West Fifth Road, Xi'an - 710004, Shaanxi Province
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_987_19

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