Phacomatosis Pigmentokeratotica Research Articles

Optical coherence tomography confirms non-malignant pigmented lesions in phacomatosis pigmentokeratotica using a support vector machine learning algorithm.

Phacomatosis pigmentokeratotica (PPK), an epidermal nevus syndrome, is characterized by the coexistence of nevus spilus and nevus sebaceus. Within the nevus spilus, an extensive range of atypical nevi of different morphologies may manifest. Pigmented lesions may fulfill the ABCDE criteria for melanoma, which may prompt a physician to perform a full-thickness biopsy. Excisions result in pain, mental distress, and physical disfigurement. For patients with a significant number of nevi with morphologic atypia, it may not be physically feasible to biopsy a large number of lesions. Optical coherence tomography (OCT) is a non-invasive imaging modality that may be used to visualize non-melanoma and melanoma skin cancers. In this study, we used OCT to image pigmented lesions with morphologic atypia in a patient with PPK and assessed their quantitative optical properties compared to OCT cases of melanoma. We implement a support vector machine learning algorithm with Gabor wavelet transformation algorithm during post-image processing to extract optical properties and calculate attenuation coefficients. The algorithm was trained and tested to extract and classify textural data. We conclude that implementing this post-imaging machine learning algorithm to OCT images of pigmented lesions in PPK has been able to successfully confirm benign optical properties. Additionally, we identified remarkable differences in attenuation coefficient values and tissue optical characteristics, further defining separating benign features of pigmented lesions in PPK from malignant features.

Noninvasive imaging exploration of phacomatosis pigmentokeratotica using high-frequency ultrasound and optical coherence tomography: Can biopsy of PPK patients be avoided?

Phacomatosis pigmentokeratotica (PPK) is a distinct and rare type of epidermal nevus syndrome characterized by coexisting nonepidermolytic organoid sebaceous nevus (SN) with one or more speckled lentiginous nevi (SLN). Atypical nevi including compound Spitz and compound dysplastic may manifest within regions of SLN. Patients with PPK, or similar atypical nevus syndromes, may be subject to a significant lifetime number of biopsies, leading to pain, scarring, anxiety, financial burden, and decreased quality of life. The current literature includes case reports, genetics, and associated extracutaneous symptoms of PPK, but use of noninvasive imaging techniques have not been explored. We aim to investigate the value of high-frequency ultrasound (HFUS) and optical coherence tomography (OCT) in discriminating morphological features of pigmented lesions and nevus sebaceous within one patient with PPK. Two modalities, (1) HFUS imaging, based on acoustic properties and (2) OCT imaging, based on optical properties, were used to image a patient with PPK. Benign pigmented lesions, which may raise clinical suspicion for significant atypia, and nevus sebaceous, were selected on different areas of the body to be studied. Five pigmented lesions and one area of nevus sebaceous were imaged and analyzed for noninvasive features. Distinct patterns of hypoechoic features were seen on HFUS and OCT. HFUS provides a deep view of the tissue, with ability to differentiate gross structures beneath the skin. OCT provides a smaller penetration depth and a higher resolution. We have described noninvasive features of atypical nevi and nevus sebaceous on HFUS and OCT, which indicate benign etiology.

Phacomatosis pigmentokeratotica.

A 20 yr old female† presented to the department of Dermatology and Sexually Transmitted Diseases, Safdarjung Hospital, New Delhi, India, in February 2019, with progressive asymptomatic brownish-black lesions on the face, neck and chest since birth. Examination revealed yellowish-brown verrucous papules and plaques arranged linearly along the lines of Blaschko on the forehead, nose, right pre-auricular area, neck and chest, suggestive of naevus sebaceous (Fig. 1A and B). Light brown-coloured patch of size 10 × 7 cm with overlying dark brown-to-black macules and papules, suggestive of speckled lentiginous naevus, was present on the left side of the face, extending from forehead to mandibular region (Fig. 2). Biochemical, ophthalmic, neurological and skeletal evaluation revealed no abnormality. Histopathological examination from verrucous plaque showed hyperkeratosis, acanthosis, papillomatosis and follicular plugging in the epidermis. Dermis showed increased number of enlarged sebaceous glands placed abnormally higher, with a few immature hair structures and dilated apocrine glands (Fig. 3). These features were consistent with naevus sebaceous.Fig. 1: (A) Yellowish-brown verrucous papules and plaques arranged linearly along lines of Blaschko, suggestive of naevus sebaceous. (B) Naevus sebaceous over the right pre-auricular area (inset showing similar lesion over anterior chest).Fig. 2: Light brown-coloured patch of size 10 × 7 cm with overlying dark brown-to-black macules and papules, suggestive of speckled lentiginous naevus.Fig. 3: Hyperkeratotic, acanthotic and papillomatous epidermis with follicular plugging. There are an increased number of closely set large sebaceous glands (black arrow) that are placed abnormally higher in the dermis along with a few immature hair structures (yellow arrow). Lower dermis shows dilated apocrine glands (blue arrow) (Hematoxylin and eosin, x100).Phacomatosis pigmentokeratotica (PPK) is a rare form of epidermal naevus syndrome characterized by coexistence of an organoid naevus with sebaceous differentiation along Blaschko’s lines and speckled lentiginous naevus in a checkerboard pattern. Our case represents a rare form of PPK without any extra-cutaneous features. Patients with PPK are at risk of developing basal cell carcinoma and syringocystadenoma papilliferum in naevus sebaceous and malignant melanoma in speckled lentiginous naevus; hence, regular follow up is necessary. The patient was planned for serial surgical excision of naevus sebaceous. Acknowledgment: Authors acknowledge Dr Shruti Sharma, Scientist D, National Institute of Pathology, Indian Council of Medical Research, New Delhi, for providing histopathologic image. Conflicts of Interest: None.

Phacomatosis pigmentokeratotica associated with unilateral toe walking due to short achilles tendon

Phacomatosis pigmentokeratotica (PPK) is characterized by the co-occurrence of speckled lentiginous nevus (nevus spilus) and an organoid nevus with or without extracutaneous involvement. The extracutaneous manifestations may vary widely with musculoskeletal, neurologic, ocular, and vascular findings. The PPK is also associated with an increased risk of cutaneous or extracutaneous tumors. Therefore, the patients with PPK should be followed up regularly for possible malignant transformation. Here, we report a 5-year-old boy with PPK associated with toe walking due to short Achilles tendon, which was not previously reported, to our knowledge.

116 Mosaic RASopathies associated with rhabdomyosarcoma

Rationale: RAS genes are well-established oncogenes known to contribute to the development of cancer. Epidermal, sebaceous, and melanocytic nevi may be triggered by somatic mutations in HRAS, KRAS, and NRAS. The majority of these nevi are not associated with internal malignancies, however, a small subset have been associated with rhabdomyosarcoma (RMS). This calls into question the clinical utility of the anatomic location of the nevi for cancer risk stratification and management. Methods: A retrospective review showed 12 previously reported cases of RAS-driven nevi in conjunction with RMS. 3 additional unreported cases were collected from collaborators through the Pediatric Dermatology Research Alliance (PeDRA). Results: 15 patients with 16 primary RMS were included for analysis. 12/15 were previously reported.1-12 All had RAS-driven birthmarks: 5 patients with epidermal nevi, 4 with congenital melanocytic nevi, 4 with phacomatosis pigmentokeratotica, and 2 with speckled lentiginous nevi/agminated Spitz. Of the 16 RMS: 8 were genitourinary, 3 were pelvic/retroperitoneal, 4 were dermal, and 1 was abdominal. 5/15 tumor-birthmark pairs had genotyping results: 3 had HRAS mutations and 2 had KRAS mutations. Body surface area did not seem to be a contributing risk factor. However, all 15 cases had involvement of the nevus on the trunk. Relevance: Truncal location of mosaic RASopathies may be a risk factor for RMS. Further prospective studies are needed to solidify appropriate monitoring guidelines for patients at risk.

A rare phenomenon of twin spotting: Phacomatosis pigmentokeratotica

Phacomatosis pigmentokeratotica is a rare form of cutaneous mosaicism characterized by epidermal nevus usually nevus sebaceous, papular speckled lentiginous nevus, and extracutaneous anomalies. This type of twin-spot phenomenon (didymosis) is due to postzygotic crossing-over resulting in two homozygous daughter cells, representing the stem cells of the two distinct types of nevi and leading to additional extracutaneous defects. We report a case of this rare syndrome in a 4-year-old male child associated with skeletal anomalies.

Phacomatosis pigmentokeratotica: Two cases series of a neurocutaneous rarity from Indonesia

Phacomatosis pigmentokeratotica (PPK) is a distinct epidermal naevus syndrome. The syndrome is characterized by the coexistence of an organoid naevus with sebaceous differentiation arranged along Blaschko's lines, a papular naevus spilus arranged in a checkerboard pattern, in association with other extracutaneous anomalies. We report on two cases of PPK. The first case was an 11-year-old girl with sebaceous naevus on the right side of the body following the lines of Blaschko present since birth, whereas a papular naevus spilus involving the dorsal area of the neck was noted at 8 years of age. The second case was a 15-year old girl presented with sebaceous naevus on her face and neck and papular naevus spilus involving left side of her chest. Electroencephalography (EEG) of both cases revealed abnormal irritative epileptiform waves, and brain mapping showed symmetrical structures and no focus. The diagnoses of our two cases were based on clinical pictures of the coexistence of sebaceous naevus arranged along Blaschko's lines, a papular naevus spilus arranged in a checkerboard pattern, and EEG anomalies. To our knowledge, these cases were first reported in Indonesia. The association with various extracutaneous manifestation is often, as well as the possibility of malignant transformation.Hence a close follow-up of PPK patients is important, which may help in early recognition of the development of extracutaneous anomalies and the possibility of malignant transformation.

Papular nevus spilus syndrome: old and new aspects of a mosaic RASopathy

The co-existence of papular nevus spilus (PNS) and ipsilateral extracutaneous abnormalities involving peripheral nerves of the skin or muscles was originally described as "speckled lentiginous nevus syndrome". To avoid confusion with macular nevus spilus, the condition was recently re-named "papular nevus spilus syndrome". In addition to 14 published cases, we identified six new cases via a search of the worldwide literature. New diagnostic criteria are suggested: (1) presence of a PNS; (2) presence of a neurological or skeletal abnormality which is usually ipsilateral to the nevus; and (3) absence of a nevus sebaceus. According to current knowledge, PNS syndrome is a rather rarely occurring, sporadic disorder that can be considered to be part of a spectrum of mosaic RASopathies, which includes isolated PNS, isolated nevus sebaceus, PNS syndrome, Schimmelpenning syndrome, and phacomatosis pigmentokeratotica.

Phacomatosis Pigmentokeratotica

AbstractIn the group of the epidermal nevus syndromes, Happle defined in 1996 a separate entity characterized by the presence of an organoid epidermal nevus, sometimes showing sebaceous differentiation, and a speckled lentiginous nevus of the papular type, occasionally associated with extracutaneous anomalies including neurological, ophthalmological, and skeletal abnormalities. In particular, the syndrome is associated with mental retardation, epilepsy, deafness, hemiatrophy, dysesthesia, and hyperhidrosis, strabismus, lipodermoid of conjunctiva, coloboma and ptosis, and kyphosis, scoliosis, limb asymmetry, and hypertrophy. Rarely, hypertension, vascular abnormalities, atrioventricular block, hypophosphatemic rickets, and pheochromocytoma may occur. The organoid nevus follows the lines of Blaschko whereas the speckled lentiginous nevus is arranged in a checkerboard pattern. For this syndrome, the term “Phacomatosis Pigmentokeratotica” has been coined and, at the present, it is considered a very rare clinical entity, with less than 20 cases reported in the literature. Recent genetic findings have included this syndrome in the group of the mosaic RASopathies, after the discovery of mutations in the HRAS gene occurring in both sebaceous and vascular nevi, but not in nonaffected tissues.

217 Phacomatosis Pigmentokeratotica: Mosaic RASopathies as a key to better understand cancer

217 Phacomatosis Pigmentokeratotica: Mosaic RASopathies as a key to better understand cancer

Combined melanocytic and sweat gland neoplasm: cell subsets harbor an identical HRAS mutation in phacomatosis pigmentokeratotica

Phacomatosis pigmentokeratotica (PPK) is characterized by the co-existence of epidermal nevi and large segmental speckled lentiginous nevi of the papulosa type. PPK, previously explained as 'twin spot' mosaicism due to the postzygotic crossing-over of two homozygous recessive mutations, has recently been shown to derive from one postzygotic activating RAS mutation. Epidermal nevi, including those in PPK, are known to give rise to neoplasms such as trichoblastoma and basal cell carcinoma. Within speckled lentiginous nevi, Spitz nevi and melanoma have been well documented. We report a case of PPK with a combined melanocytic and adnexal neoplasm presenting where the nevi conjoined. Using next-generation sequencing techniques, we were able to identify the same HRAS G13R mutation within both components of the tumor, and to show the absence of additional mutated modifier genes in a panel of 300 cancer-related genes. Given the genetic findings in this rare tumor-type, we suggest that this case may be used as a model for understanding the development of biphenotypic neoplasia or intratumoral heterogeneity in some cases.

Photoletter to the editor: A neurocutaneous rarity: phacomatosis pigmentokeratotica.

Phacomatosis pigmentokeratotica is characterized by the coexistence of nevus sebaceus, papular nevus spilus and associated neurologic abnormalities. We report a case of phacomatosis pigmentokeratotica in a 28-year-old male who presented with palmar-plantar dysesthesia and ipsilateral brain hemiatrophy. As a characteristic neuroimaging finding of the disorder, we found multiple hypointense lesions involving the ipsilateral hemisphere.

Phacomatosis Pigmentokeratotica: A Follow-up Report with Fatal Outcome

Phacomatosis Pigmentokeratotica: A Follow-up Report with Fatal Outcome

Phacomatosis pigmento-pigmentaria: the state of art

The term phacomatosis is used to indicate two or more different types of genetically determined cutaneous lesions are contemporarily present, such as phacomatosis pigmentovascularis or phacomatosis pigmentokeratotica. The first observation of a newborn presenting with segmental cafe au lait macules combined with an aberrant Mongolian spot, led some authors to hypothesize that this singular association was not a coincidence, but the result of twin-spotting phenomenon. In the analogy to other similarly named entities, they coined the term ‘phacomatosis pigmento-pigmentalis’.

Phacomatosis Pigmentokeratotica Is Caused by a Postzygotic HRAS Mutation in a Multipotent Progenitor Cell

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome characterized by the co-occurrence of a sebaceous nevus and a speckled lentiginous nevus. The coexistence of an epidermal and a melanocytic nevus has been explained by two homozygous recessive mutations, according to the twin spot hypothesis, of which PPK has become a putative paradigm in humans. However, the underlying gene mutations remained unknown. Multiple tissues of six patients with PPK were analyzed for the presence of RAS, FGFR3, PIK3CA, and BRAF mutations using SNaPshot assays and Sanger sequencing. We identified a heterozygous HRAS c.37G>C (p.Gly13Arg) mutation in four patients and a heterozygous HRAS c.182A>G (p.Gln61Arg) mutation in two patients. In each case, the mutations were present in both the sebaceous and the melanocytic nevus. In the latter lesion, melanocytes were identified to carry the HRAS mutation. Analysis of various nonlesional tissues showed a wild-type sequence of HRAS, consistent with mosaicism. Our data provide no genetic evidence for the previously proposed twin spot hypothesis. In contrast, PPK is best explained by a postzygotic-activating HRAS mutation in a multipotent progenitor cell that gives rise to both a sebaceous and a melanocytic nevus. Therefore, PPK is a mosaic RASopathy.

Phacomatosis Pigmentokeratotica Is a “Pseudodidymosis”

In phacomatosis pigmentokeratotica, papular nevus spilus coexists with nevus sebaceus. The disorder was thought to be a didymosis with early postzygotic recombination. In this issue, however, Groesser and co-workers provide a new concept. Both nevi originate from a single heterozygous HRAS mutation in a pluripotent progenitor cell. This new understanding has implications for other proposed examples of didymosis in humans.

Phacomatosis pigmento-pigmentaria: Should we add a new type of phacomatosis? Fact and controversies

There are currently five types of recognized phacomatosis pigmentovascularis plus one more, phacomatosis pigmentokeratotica, making six types altogether. Should we stop here and consider the classification as being complete? Or, do we leave room to add more types or, alternatively, lump the ones we have together and shorten the list? We present our reasons for adding one or two new types of phacomatoses to the current classification, in full recognition that it is already complicated and somewhat cumbersome. We consider that the benefits of doing so outweigh any additional strain on the already complicated classification. We expect that this might not sit well with some of our colleagues, but we are prepared to do battle.

Phacomatosis Pigmentokeratotica without Extracutaneous Abnormalities: A Case Study Involving a Preterm Baby

Phacomatosis pigmentokeratotica (PPK) is a rare syndrome defined by the association of an organoid nevus occasionally with sebaceous differentiation, a speckled lentiginous nevus, and other extracutaneous anomalies. A preterm male infant of only 830 g at 27 week gestational age had an organoid nevus showing sebaceous differentiation. Also, he had multiple speckled-lentiginous nevus. Correlating the observed clinical presentation with the histopathological findings, the diagnosis of PPK was established. There have been less than 10 cases of PPK without extracutaneous manifestation. We present an uncommon case of a preterm patient with PPK who had no extracutaneous abnormalities.

Phacomatosis Pigmentokeratotica: A Further Case without Extracutaneous Anomalies and Review of the Condition

Epidermal nevus syndrome is the term for the association of an epidermal nevus and extracutaneous anomalies, including neurologic, ophthalmic, and skeletal defects. Epidermal nevus syndromes include different disorders that share the feature of mosaicism. Phacomatosis pigmentokeratotica (PPK) is a distinctive new epidermal nevus syndrome first described in 1996 characterized by the presence of multiple organoid nevi with sebaceous differentiation, a speckled lentiginous nevus, and skeletal and neurologic abnormalities. Only a handful of cases of PPK without extracutaneous manifestations have been reported. We report here an individual with PPK with only cutaneous signs and confirm this distinctive syndrome has two subtypes according to the presence or absence of extracutaneous involvement.

Verrucous epidermal naevus and naevus spilus associated with lower limb asymmetry and right bundle-branch block: a case of phacomatosis pigmentokeratotica?

Clinical and Experimental DermatologyVolume 37, Issue 1 p. 74-75 Viewpoints in dermatology •Correspondence Verrucous epidermal naevus and naevus spilus associated with lower limb asymmetry and right bundle-branch block: a case of phacomatosis pigmentokeratotica? A. Baroni, A. Baroni Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this authorS. Staibano, S. Staibano Biomophological and Functional Sciences, Section of Anatomical Pathology, University Federico II of Naples, Naples, Italy E-mail: adone.baroni@gmail.comSearch for more papers by this authorT. Russo, T. Russo Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this authorV. Piccolo, V. Piccolo Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this authorR. A. Satriano, R. A. Satriano Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this authorA. Vozza, A. Vozza Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this authorG. Vozza, G. Vozza Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this author A. Baroni, A. Baroni Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this authorS. Staibano, S. Staibano Biomophological and Functional Sciences, Section of Anatomical Pathology, University Federico II of Naples, Naples, Italy E-mail: adone.baroni@gmail.comSearch for more papers by this authorT. Russo, T. Russo Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this authorV. Piccolo, V. Piccolo Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this authorR. A. Satriano, R. A. Satriano Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this authorA. Vozza, A. Vozza Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this authorG. Vozza, G. Vozza Deparment of Dermatology and Venereology, Second University of Naples, Naples, ItalySearch for more papers by this author First published: 25 July 2011 https://doi.org/10.1111/j.1365-2230.2011.04134.xCitations: 7 Conflict of interest: none declared. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume37, Issue1January 2012Pages 74-75 RelatedInformation