Publications by authors named "Luca Muscardin"

36 Publications

Recurrent lentigo maligna in a young patient.

Ital J Dermatol Venerol 2021 Feb;156(1):89-91

Dermatopathological Laboratory, San Gallicano Dermatology Institute, Rome, Italy.

Lentigo maligna (LM) is usually diagnosed in sun-damaged skin of elderly patients and a correct excision of the lesion determines a complete healing from the disease. LM is very rare in young patients and, for this reason, it can be commonly misdiagnosed. We describe the case of a locally recurrent LM in a 19-year-old male patient, which initially arose at the age of 17 years. In order to avoid diagnostic pitfalls, clinicians have to put more emphasis on diseases which previously were prerogative only of elderly patients and that now could begin to engage a younger age, according to climate and behavior changes.
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http://dx.doi.org/10.23736/S2784-8671.16.05222-6DOI Listing
February 2021

Beta HPV Type 15 Can Interfere With NF-κB Activity and Apoptosis in Human Keratinocytes.

Front Cell Infect Microbiol 2020 18;10:111. Epub 2020 Mar 18.

HPV-Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

E7 protein from cutaneous as well as mucosal HPV types can alter NF-κB activity. Conflicting literature data show a HPV-induced up- or down-regulation of the NF-κB pathway in different cell lines. In a previous study we detected the expression of E7 gene of HPV15 in a subungual tumor of a patient affected by incontinentia pigmenti (IP). IP is a rare X-linked genodermatosis in which the IKKγ gene is altered. From observations in transgenic IKKγ defective mice, it was suggested that IKK-deficient cells may undergo rapid hyper-proliferation and apoptosis/necrosis, leading to increased pro-inflammatory cytokine production in the neighboring IKK-positive cells. The objective of this study was to ascertain if beta HPV 15 can alter apoptosis and NF-κB pathway in normal and IKKγ-deficient keratinocytes. The human immortalized keratinocyte cell line (HaCaT), and human primary keratinocyte (HPK) cells were transduced with a retrovirus expressing E6-E7 proteins of HPV 15 and IKKγ was successful silenced mimicking the HPV15 infection and IP. HPV15 E6-E7 gene expression improved NF-κB activity in human keratinocytes even when IKKγ was silenced by siRNA. In IKKγ silenced keratinocyte cells, TNF-α-induced apoptosis was strongly reduced by the expression of HPV15 E6-E7 genes. Beta HPV15 exerted this anti-apoptotic activity by decreasing pro-apoptotic BAK and cleaved Caspase 3 proteins. In conclusion, we can speculate that presence of persistent infection by beta papillomavirus might influence the biological fate of IP by altering NF-κB activation and apoptosis in IKKγ mutated cells, favoring their survival and possibly the development of tumors in the late stage of disease. Taken together, our data reinforce the importance of host genetic background in the pathogenesis of HPV-associated skin lesions.
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http://dx.doi.org/10.3389/fcimb.2020.00111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093591PMC
June 2021

Pigmented porokeratosis with dermal deposits of amyloid: the different chromatic features.

G Ital Dermatol Venereol 2020 Apr 10;155(2):240-241. Epub 2018 Jul 10.

Laboratory of Dermatopathology, San Gallicano Institute of Rome, Rome, Italy.

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http://dx.doi.org/10.23736/S0392-0488.18.05935-7DOI Listing
April 2020

Angiomatoid melanoma: a dermoscopic and pathologic challenge.

G Ital Dermatol Venereol 2019 Dec 7;154(6):718-719. Epub 2018 Feb 7.

Dermatopathological Laboratory, San Gallicano Institute, Rome, Italy.

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http://dx.doi.org/10.23736/S0392-0488.18.05828-5DOI Listing
December 2019

Eosinophilic dermatoses (exaggerated insect bite-like reaction) associated with hematological malignancy: Report of three cases.

Indian J Dermatol Venereol Leprol 2018 Jan-Feb;84(1):93-95

Department of Dermatology, San Gallicano Institute, IRCCS, Rome, Italy.

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http://dx.doi.org/10.4103/ijdvl.IJDVL_115_17DOI Listing
November 2018

Complete regression of keratoacanthoma with topical tazarotene gel 0.1%: therapeutic and pathophysiological perspectives.

G Ital Dermatol Venereol 2019 Apr 8;154(2):220-221. Epub 2017 Sep 8.

Laboratory of Dermatopathology, San Gallicano Institute, Rome, Italy.

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http://dx.doi.org/10.23736/S0392-0488.17.05718-2DOI Listing
April 2019

Indeterminate cell histiocytosis: A case treated with ultraviolet B narrow band phototherapy (NB UVB).

Photodermatol Photoimmunol Photomed 2017 Nov 1;33(6):329-333. Epub 2017 Aug 1.

San Gallicano Dermatological Institute, IRCCS, Rome, Italy.

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http://dx.doi.org/10.1111/phpp.12327DOI Listing
November 2017

Concurrent Sweet's Syndrome and erythema nodosum in a patient with bilio-pancreatic diversion.

G Ital Dermatol Venereol 2017 08;152(4):392-394

Dermatopathological Laboratory, San Gallicano Institute of Rome, Rome, Italy.

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http://dx.doi.org/10.23736/S0392-0488.16.05330-XDOI Listing
August 2017

Two Cases of Gnatophyma, an Unusual Form of Rosacea.

Skin Appendage Disord 2017 Jan 8;2(3-4):180-182. Epub 2016 Dec 8.

Department of Dermatology, San Gallicano Institute IRCCS, Rome, Italy.

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http://dx.doi.org/10.1159/000453004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264367PMC
January 2017

Melanosis of the lower lip subverted by filler injection: a simulator of early mucosal melanoma.

Australas J Dermatol 2017 Feb;58(1):71-72

Dermatopathological Laboratory, San Gallicano Institute of Rome, Rome, Italy.

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http://dx.doi.org/10.1111/ajd.12475DOI Listing
February 2017

Linear ectopic sebaceous hyperplasia of the penis: the last memory of Tyson's glands.

G Ital Dermatol Venereol 2018 Jun 6;153(3):429-431. Epub 2016 Sep 6.

Laboratory of Dermatopathology, San Gallicano Institute, Rome, Italy.

Pathologists who find ectopic glands on the glans and/or on the prepuce, often describe them as Tyson's glands. In this regard, the term Tyson's glands can be replaced by two different descriptive expressions: papillomatosis corona penis and ectopic sebaceous glands. A 15-year-old Caucasian male patient presented to our Institute with multiple and asymptomatic circular skin colored-to-yellowish papules at the level of the foreskin, also affecting the shaft of the penis, where they assumed a linear feature. The histological examination revealed hyperplastic and dilated sebaceous glands, while in some areas these glands showed also a direct attachment with the epidermis. A lymphocytic infiltrate was also observed in one of the two specimens. A final diagnosis of linear ectopic sebaceous hyperplasia of the penis was made. According to the current report, the ectopic sebaceous hyperplasia of the penis can have a circular and a linear patter, as well as the presence and the absence of a lymphoid infiltrate. A correct clinical and pathological diagnosis are necessary to avoid unnecessary treatments and worries in the patients. In fact, not infrequently, this condition is confused with dermatological diseases as molluscum contagiosum, epithelioid granuloma, lymphangioma circumscriptum, multiple syringomas, lichen planus, and bowenoid papulosis.
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http://dx.doi.org/10.23736/S0392-0488.16.05129-4DOI Listing
June 2018

Resolution of nodulocystic acne with oral dapsone.

Dermatol Ther 2017 Jan 23;30(1). Epub 2016 Aug 23.

Dermatopathological Laboratory Institute "San Gallicano Institute of Rome", Roma, Italy.

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http://dx.doi.org/10.1111/dth.12406DOI Listing
January 2017

Early Angiosarcoma of the Scalp: A Clinicopathological Pitfall.

Am J Dermatopathol 2016 Sep;38(9):690-4

*Clinica Dermatologica, La Sapienza University of Rome, Rome, Italy; †Clinical Department, San Gallicano Institute of Rome, Rome, Italy; and ‡Dermatopathological Laboratory, San Gallicano Institute of Rome, Rome, Italy.

Angiosarcoma (AS) is a rare malignant vascular tumor, which affects mainly elderly patients. After the diagnosis, the mean overall survival of patients is 30 months. The variable presentation of the malignancy, the benign appearance of the cutaneous lesions, and the minimal histological changes in early lesions can sometimes delay the correct diagnosis. The authors report a case of an 80-year-old white male patient, with a painless and ecchymotic lesion of the scalp, which histologically showed minimal pathological atypia, conclusive for a diagnosis of AS with minimal histological changes. The authors discuss the main and most emblematic cases of AS initially misdiagnosed for other cutaneous diseases reported in the literature, noting that in some cases, also the histology can be treacherous and a trap for the dermatopathologist. The recent findings on MYC, FLT4 and KDR amplification, and the relative therapeutic perspectives are also discussed. Finally, the authors draw up some pathological cornerstones, which could improve the diagnosis, above all in early lesions with minimal atypia.
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http://dx.doi.org/10.1097/DAD.0000000000000677DOI Listing
September 2016

Gray color in Berloque dermatitis of the face: dermoscopic pitfall.

G Ital Dermatol Venereol 2016 Aug;151(4):451-2

San Gallicano Dermatologic Institute, IRCCS, Oncologic Dermatologic Department, Rome, Italy -

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August 2016

The role of Wnt/β-catenin signaling pathway in melanoma epithelial-to-mesenchymal-like switching: evidences from patients-derived cell lines.

Oncotarget 2016 Jul;7(28):43295-43314

Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy.

Deregulations or mutations of WNT/β-catenin signaling have been associated to both tumour formation and progression. However, contradictory results concerning the role of β-catenin in human melanoma address an open question on its oncogenic nature and prognostic value in this tumour. Changes in WNT signaling pathways have been linked to phenotype switching of melanoma cells between a highly proliferative/non-invasive and a slow proliferative/metastatic condition. We used a novel panel of cell lines isolated from melanoma specimens, at initial passages, to investigate phenotype differences related to the levels and activity of WNT/β-catenin signaling pathway. This in vitro cell system revealed a marked heterogeneity that comprises, in some cases, two distinct tumour-derived subpopulations of cells presenting a different activation level and cellular distribution of β-catenin. In cells derived from the same tumor, we demonstrated that the prevalence of LEF1 (high β-catenin expressing cells) or TCF4 (low β-catenin expressing cells) as β-catenin partner for DNA binding, is associated to the expression of two distinct profiles of WNT-responsive genes. Interestingly, melanoma cells expressing relative low level of β-catenin and an invasive markers signature were associated to the TNF-α-induced pro-inflammatory pathway and to the chemotherapy resistance, suggesting that the co-existence of melanoma subpopulations with distinct biological properties could influence the impact of chemo- and immunotherapy.
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http://dx.doi.org/10.18632/oncotarget.9232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190024PMC
July 2016

Electrochemotherapy of a Multirecurrent Dermatofibrosarcoma Protuberans of the Orbital Margin: A Case Report.

Anticancer Res 2015 Nov;35(11):6121-6

Department of Plastic and Reconstructive Surgery, San Gallicano, Dermatologic Institute for Research and Care, Rome, Italy.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous sarcoma with high recurrence rate. Radical surgery is the treatment of choice, although in cosmetically-sensitive areas such as the head and neck, this option is often not pursued. Electrochemotherapy (ECT) is a minimal invasive anti-tumor modality which is increasingly being used to treat skin metastases from different malignancies. A 31-year-old woman presented with subcutaneous local multirecurring DFSP located at the proximal end of the left eyebrow. ECT was offered as a palliative treatment to avoid radical disfiguring surgery. Two days following ECT, the patient was discharged in good general health. Partial tumor regression was appreciable at two months' follow-up by ultrasound and magnetic resonance imaging. At six months, residual fibrotic tissue was observed; at three years, no evidence of the tumour was detected. In our case, ECT achieved good local tumor control with excellent cosmetic results, preserving the patient's quality of life.
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November 2015

Purely cutaneous sclerosing IgG4-related disease of the cephalic region: case report and a mini-review of the clinical and pathological aspects.

G Ital Dermatol Venereol 2016 Jun 4;151(3):296-9. Epub 2015 Sep 4.

Dermatopathological Laboratory, Institute "San Gallicano Institute of Rome", Rome, Italy -

IgG4-related disease is a recently defined emerging entity. Many different organs may be affected by this disease: pancreas, salivary and lacrimal glands, liver, peritoneum and lung. Also the skin may be affected, as secondary localization, while as primary cutaneous localization it has been rarely described. A male patient presented at our Institute with a two-year history of sclerosing erythematous nodules of the scalp. Histological examination showed a T-lymphocyte (CD3+) infiltrate with interspersed plasmacytoid cells and the interposition of a fibrosclerotic tissue. We found numerous IgG4+ cells at the periphery of the nodular structures, while the serum levels of IgG4 and the remaining blood chemistry analysis were normal. Only a few cases of primitive cutaneous pseudo-lymphomatous IgG4-related disease have been described in the literature. Our case showed the same clinical and histologic features of those previously described; the etiology of IgG4-related diseases remains to be elucidated.
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June 2016

Resolution of Benign and Malignant Sebaceous Neoplasms, in a Renal Transplant Patient Treated With Everolimus.

Exp Clin Transplant 2017 Feb 28;15(1):100-102. Epub 2015 Apr 28.

From the Dermatopathological Laboratory "San Gallicano Institute of Rome"; the Via Elio Chianesi, 53, 00158, Roma, Italy.

Nonmelanoma skin cancers are the most common malignancies in transplant recipients under immunosuppression; nevertheless, appendage tumors also may appear. The onset of several cutaneous neoplasms in transplant patients can cause deterioration in quality of life of these patients. A 62-year-old white woman patient developed several malignant and benign sebaceous neoplasms during an immunosuppressive treatment for a renal transplant. The genetic study showed a mutation in MSH6-eson 1 (c116G>A), without mutations in MLH1 gene and MSH2. A final diagnosis of multiple sebaceous tumors in an immunosuppressed patient without Muir -Torre syndrome was made. The spreading of further cutaneous neoplasms led to a change in immunosuppression: namely, that clinicians suspended tacrolimus and add everolimus. After 2 months, all tumor lesions on the face and on the limbs have disappeared, and no further lesions occurred. Everolimus could represent a valid therapeutical treatment for transplant patients at high risk for cutaneous tumors. A genetic consult and a consequent study of the genetic profile should be performed on each of these patients, to avoid risks of recurrent cutaneous tumors and negative effects on the quality of life.
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http://dx.doi.org/10.6002/ect.2014.0208DOI Listing
February 2017

Indolent subtype acral lentiginous melanoma with long radial growth phase: a dermatopathological pitfall.

Am J Dermatopathol 2015 Nov;37(11):873-4

*Dermatopathological laboratory, San Gallicano Institute of Rome, Italy †Department of Dermatology, Dermatologic Clinic, La Sapienza University of Rome, Italy.

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http://dx.doi.org/10.1097/DAD.0000000000000187DOI Listing
November 2015

Another point of view on p16 and Ki67 expression in melanocytic and non-melanocytic cutaneous lesions.

Acta Dermatovenerol Croat 2013 ;21(3):149-54

Giovanni Paolino, MD, San Gallicano Institute of Rome, Via Elio Chianesi, 53, 00144 Rome Italy;

The new analysis of the expression of cell cycle regulators (used in various neoplasms) and the nominal immunohistologic assays still represent valid and feasible diagnostic methods in most pathology practice. We examined 114 paraffin-embedded histologic specimens of melanocytic cutaneous lesions. The primary objective of this study was to explore diagnostic potential of the two important cell cycle regulators, p16 and Ki67, also evaluating the variations of expression by use of a semi quantitative graded scale. Another aim was to study the hypothetical correlation between p16 expression (in melanocytic and non-melanocytic lesions) and two independent variables, i.e. patient age and anatomical sites (sun exposed or non-sun exposed) of the lesions. Cell population was considered positive for antibody-specific p16 and Ki67 when at least 33% of the cells showed well-defined nuclear and/or cytoplasmic staining. A special p16 and Ki67 trend was found only in Spitz nevus, atypical Spitz nevus and invasive malignant melanoma (MM). No discriminative values were found regarding other lesions (junctional melanocytic nevus, MM in situ, superficially spreading MM, non-melanoma skin cancers). p16 was over-expressed on sun exposed sites and hypo-expressed on non-sun exposed areas, yielding a statistically significant correlation (p<0.03). According to patient age, p16 was over-expressed in patients aged ≥61 and hypo-expressed in patients aged ≤60 (p=0.09).
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August 2014

Biliopancreatic diversion: when a cure becomes a disease.

Am J Dermatopathol 2014 Mar;36(3):258-9

Dermatopathological Laboratory "San Gallicano Institute of Rome," Roma, Italy.

Phrynoderma is a type of follicular hyperkeratosis located primarily on the extensor surfaces of the extremities. It is most commonly seen in Africa and Southeast Asia, where it is correlated with malnutrition; however, it is rare in developed countries, where it is often the result of malabsorption secondary to pancreatic insufficiency, colectomy, chronic giardiasis, and bariatric surgery. Here, we report a case of a 51-year-old white male patient, who presented to our Institute with a 1-year history of diffuse, reddish-brown asymptomatic papules associated with follicular nodules. In association with cutaneous symptomatology, the patient complained of also having night blindness. The patient, 4 years before, underwent a bariatric surgical treatment, which included a biliopancreatic diversion. Histologic examination of skin biopsy revealed hyperkeratosis and irregular acanthosis of the epidermis in association with dilated follicular infundibulum filled with keratinous material, whereas the laboratory investigations showed hypovitaminosis A. Based on the patient's history and cutaneous biopsy, a final diagnosis of phrynoderma was made. The steady increase of obesity in developed countries results in a relative increase in bariatric surgery. This must involve a multidisciplinary team to manage nutrition deficiencies and prevent possibly important complications, as mentioned in this report.
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http://dx.doi.org/10.1097/DAD.0b013e3182926665DOI Listing
March 2014

Dermo beta brachytherapy with 188-Re in squamous cell carcinoma of the penis: a new therapy.

Eur J Dermatol 2013 Apr;23(2):183-8

Dermatology Department, Tor Vergata University, Rome, Italy.

Background: Squamous cell carcinoma of the penis (SCCP) is the most common penis neoplasia, favoured by phimosis, HPV infection and scleroatrophic lichen. The classic therapy is surgical with anatomic demolition, which often causes important psychological problems. Other non-demolitive therapies can be utilized, such as radiotherapy, brachytherapy and topical medical treatment.

Objectives: We propose a new non-invasive therapy called "Dermo beta brachytherapy (DBBT) with 188-Re" in which a synthetic inert resin-matrix containing a radioactive beta-emitting isotope is applied on the surface of the tumor lesion.

Materials And Methods: A total of 15 patients with a histologically confirmed diagnosis of SCCP were enrolled for treatment (DBBT).

Results: Of the 15 patients, 12 healed, 1 was lost at follow-up and 2 did not respond to therapy.

Conclusion: The results indicate that DBBT is an effective treatment for SCC of the penis, sparing the anatomical integrity of the organ, and allowing normal sexual activity.
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http://dx.doi.org/10.1684/ejd.2013.1927DOI Listing
April 2013

Permanent tattoos: evidence of pseudolymphoma in three patients and metal composition of the dyes.

Eur J Dermatol 2012 Nov-Dec;22(6):776-80

Istituto Dermatologico San Gallicano IRCCS, Via Elio Chianesi 53, 00144 Rome, Italy.

Tattoo-induced pseudolymphoma is a cutaneous inflammatory response, the pathogenesis of which is still unknown. The objective of the present work was to find a possible causal relationship between pseudolymphomatous reactions on the red areas of tattoos and the metals contained in tattoo pigments and skin biopsies. Three individuals with cutaneous lesions on the red areas of tattoos were observed. Clinical and immunohistochemical examinations of the lesions were performed, and the concentrations of Cd, Co, Cr, Hg, Ni and Pb were measured in pigments and biopsy samples. Pseudolymphomas in the red areas were diagnosed in all three cases; one showed the prevalence of B-lymphocytes, whereas the other two showed a prevalence of T cells with a lichenoid pattern. Patch tests were negative. Corticosteroid therapy was ineffective. Cadmium, Co, Hg and Pb in the pigments were probably present as impurities, whereas Cr and Ni were the main components. Chromium and Ni had the highest concentrations, also in the biopsy samples. Permanent tattoos appear to be unsafe, considering the increasing number of diagnosed pseudolymphomas. It can be excluded that Hg was responsible for the reactions, given that the concentration in the red dyes and biopsies was very low. Significant levels of Cr and Ni should be considered as the causes of possible dermal reactions.
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http://dx.doi.org/10.1684/ejd.2012.1844DOI Listing
June 2013

Angiomatous reaction Kaposi-sarcoma-like as a side effect of topical corticosteroid therapy in lichen sclerosus of the penis.

Dermatol Ther 2009 Jul-Aug;22(4):379-82

Department of Dermatology-Oncology, S. Gallicano Institute, IRCCS, Rome, Italy.

Lichen sclerosus (LS) is a chronic inflammatory skin condition usually located in the anogenital area. Topical corticosteroid therapy is the first choice treatment which may arrest or delay the progression of the disorder. We report the case of a 74-year-old man presented with a 6-month history of nodular lesions localized on penis. The man had a previous history of genital lesions that had been diagnosed as LS and treated with long-term topical corticosteroid therapy. After 3 months of corticosteroid therapy, the patient observed the appearance of several nodular erythematous lesions on the penis with progressive disappearance of the clinical symptoms of LS. These purple to red asymptomatic angiomatoid nodules resembled the clinical features of Kaposi sarcoma.
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http://dx.doi.org/10.1111/j.1529-8019.2009.01249.xDOI Listing
September 2009

Detection of HPV-15 in painful subungual tumors of incontinentia pigmenti: successful topical therapy with retinoic acid.

Eur J Dermatol 2009 May-Jun;19(3):243-7. Epub 2009 Feb 12.

Laboratory of Cutaneous Histopathology, Institute of Dermatology S. Maria and San Gallicano, Via Chianesi, 53, 00144 Rome, Italy.

Incontinentia pigmenti (IP) is an X-linked dominant disorder, which occurs in female patients. We present a typical case of IP with subungual tumors (STIP) together with a short review on subungual tumors in IP. The diagnosis was achieved on the basis of the onset in adult life of STIP together with the other specific symptoms like ocular and dental abnormalities and achromic lesions of the legs. In the STIP lesions the presence and, in one of them, the expression, of HPV type 15 were detected. Topical therapy with retinoic acid cured the tumoral lesions. To the best of our knowledge this is the first report of HPV in STIP, opening a new scenario in the pathogenesis and the treatment of STIP. In conclusion, in our opinion, all painful subungual tumors should be considered as a possible late manifestation of IP.
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http://dx.doi.org/10.1684/ejd.2009.0629DOI Listing
July 2009
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