Clinical and Sonographic Classification of Neurofibromas in Children with Neurofibromatosis Type 1 - A Cluster Analysis.

PURPOSE: High-frequency ultrasound allows the accurate identification of neurofibromas in neurofibromatosis type 1 (NF1). This study aimed to analyze the ultrasound features of neurofibromas in children with NF1, to establish a classification based on the clinical and sonographic patterns of the different types of neurofibromas, and to evaluate the interobserver correlation coefficient (κ) of this classification. MATERIALS AND METHODS: In this prospective, single referral center observational study, clinical and ultrasound findings of neurofibromas in children diagnosed with NF 1 were analyzed. To identify the ultrasound patterns, a cluster analysis allowing the inclusion of both clinical and ultrasound data was designed. The κ coefficient was calculated using 9 external evaluators. RESULTS: 265 ultrasound scans were performed on a total of 242 neurofibromas from 108 children diagnosed with NF1. Cluster analysis allowed the identification of 9 patterns (Snedecor's F, P < 0.001) classified as "classic" cutaneous neurofibroma, blue-red neurofibroma, pseudoatrophic neurofibroma, nodular subcutaneous neurofibroma, diffuse subcutaneous neurofibroma, congenital cutaneous neurofibroma, congenital plexiform neurofibroma, congenital diffuse and plexiform neurofibroma, and subfascial neurofibroma. The κ coefficient of the interobserver ratings was 0.82. CONCLUSION: Patterns identified in the cluster analysis allow neurofibromas to be classified with a very high interobserver correlation.

Congenital cutaneous neurofibromas in neurofibromatosis type 1: Clinicopathological features in early infancy.

BACKGROUND AND OBJECTIVE: Clinicopathological features of cutaneous neurofibromas presenting as large irregularly shaped congenital café-au-lait macules (CALM) in Neurofibromatosis type 1 (NF1) patients have not been well characterized. We aimed to analyze the histopathological findings of large "atypical" CALM in children with NF1. PATIENTS AND METHODS: In this retrospective observational study we analyzed histopathological and immunostaining features of 21 biopsy specimens from 18 large hyperpigmented macules with irregular borders with or without hypertrichosis present during the first months of life in NF1 diagnosed children. RESULTS: Of the 21 biopsies, ten showed a diffuse neurofibroma pattern and four exhibited characteristics of plexiform neurofibroma (PNF). In twelve specimens we observed groups of fusiform cells arranged linearly mimicking a small caliber nerve trunk with abnormal morphology. Repeated biopsies from two of these lesions performed at different ages showed transformation to a plexiform pattern. An increased interstitial cellularity was observed in 17 samples that was more evident around eccrine glands in 16 or accompanying hair follicles and vascular structures in twelve samples. All these cells had immunoreactivity for S100-protein, CD68 and were Melan-A positive in 15 samples. CONCLUSION: Clinicopathological findings of congenital cutaneous neurofibromas provide early diagnostic clues of NF1 with high relevance for monitoring of these patients.

Cutaneous and Systemic Findings in Mosaic Neurofibromatosis Type 1.

BACKGROUND/OBJECTIVES: Mosaic neurofibromatosis type 1 (MNF1) is a variant of neurofibromatosis type 1 (NF1) in which clinical manifestations are limited to one or several body segments. The objective was to characterize the cutaneous features and associated systemic findings in a cohort of children with MNF1. METHODS: We performed a retrospective study of 40 children diagnosed with MNF1 at the Department of Dermatology, Hospital Infantil Niño Jesús, Madrid, Spain, from January 1, 1986, to October 31, 2015. RESULTS: All patients had pigmentary changes, alone (n = 39) or in combination with neurofibromas (n = 1). Twenty-four cases fulfilling the definition of MNF1 had six or more café au lait spots with or without freckling within the affected segment. They all lacked any other National Institutes of Health criteria of NF1. No patient had juvenile xanthogranuloma (JXG) or nevus anemicus (NA). Two children with MNF1 had epilepsy and two others developed malignancy (Hodgkin's lymphoma and ganglioneuroblastoma). CONCLUSIONS: Pigmentary changes are the most frequent presentation of MNF1 in children. MNF1 must be considered with segmentary distribution of freckling and café au lait spots. Other frequent cutaneous findings in NF1, such as JXG or NA, seem to be exceptional in MNF1. Although the possibility of systemic complications and cancer risk seem to be low, patients must be followed up.

Is it just a psoriasiform dermatitis?

Bazex syndrome (BS) is a rare paraneoplastic syndrome most frequently associated with squamous cell carcinomas of the upper aerodigestive tractand other tumours. Characteristically, cutaneous lesions precede the diagnosis of malignancy. We report a 72-year-old patient with 1-year history of acral dermatitis. The diagnosis of BS was based on the presence of psoriasiform acral dermatitis and the evidence of two simultaneous tumors (prostate adenocarcinoma and undifferentiated carcinoma ofthe submandibular gland). It is important to have this syndrome in mind since cutaneous features usually precede an underlying neoplasm.

Nevus anemicus: a distinctive cutaneous finding in neurofibromatosis type 1.

Nevus anemicus (NA) is a cutaneous anomaly characterized by pale, well-defined patches with limited vascularization after rubbing. They are largely known to be associated with neurofibromatosis 1 (NF1) and have received little attention in the literature until recently. We sought to characterize the prevalence and clinical features of patients with NA and NF1. We conducted an observational prospective study of 99 children with NF1 at the Hospital Niño Jesús, Madrid, Spain, from January 1, 2012, through July 31, 2013, and reviewed three other series of patients with NF1 and NA recently reported. The prevalence of NA in children with NF1 ranged from 8.8% to 51%, being much more prevalent at younger ages. Prospective studies yielded a higher prevalence than retrospective studies. NA was located most commonly on the trunk, particularly on the anterior chest wall, and was often multiple. Patients with segmental NF1 or isolated café au lait spots rarely had NA, and NA was absent in other genodermatoses. The collection of data was not homogeneous in all studies. NA has a high prevalence in individuals with NF1 patients but seems to be absent in connection with other genodermatoses, therefore its presence can assist in the diagnosis of suspected cases of NF1. The subtle clinical appearance of NA makes its detection difficult, and physicians involved in the care of children with NF1 must be aware of its possible presence and significance.

Cutaneous ultrasound of the nuchal-type fibroma: diagnostic clues and surgery planning.

Nuchal-type fibroma is a rare, benign tumour, arising from the connective tissue and characterized by their usual location in the posterior neck, although extra-nuchal locations may also occur. The excision of nuchal-type fibroma is curative, although it presents as a large poorly circumscribed lesion in the dermal and subcutaneous fat layer, with adipose tissue and muscle fascicles entrapment, what can lead to partial excisions and relapses. Due to its rarity, little is known about the sonographic appearances of nuchal-type fibroma. An early identification and correct extension evaluation is essential to facilitate adequate treatment. Through two clinical cases, we illustrate in this article the utility of cutaneous ultrasound in the early diagnosis of these tumours, highlighting its role in the diagnosis but also in the pre-surgical evaluation improving margins assessment and delimitation.

Annular elastolytic giant cell granuloma associated to late-onset X-linked dominant protoporphyria.

X-linked dominant protoporphyria (XLDPP) is a genetic disorder that affects the synthesis of the heme group due to an increase in delta-aminolaevulinate synthase 2 (ALAS2) enzyme activity. Moreover, annular elastolytic giant-cell granuloma (AEGCG) is a rare reactive granulomatous dermatosis, usually associated with actinic damage. An 86-year-old man presented with edematous-erythematous lesions in photoexposed areas of the face and on the dorsum of both hands. Protoporphyrin levels in serum and feces were significantly elevated and a heterozygous frameshift mutation in the exon 11 of the ALAS2 gene: c.1706-1709del (p.Glu569GlyfsX24) was identified. Concomitantly, we observed an annular plaque with raised borders on the back of his right hand, clinically and histologically compatible with a diagnosis of AEGCG. Skin lesions disappeared only upon use of a physical sunscreen. We report two rare photodermatoses in an elderly patient and discuss the significance of dermal elastic fiber damage induced by the XLDPP as a main triggering factor of AEGCG.

Cutaneous ultrasound: key diagnostic tool for the relapse of a single eccrine spiradenoma.

Eccrine spiradenoma is a rare, benign, adnexal skin tumor of the sweat gland. It is frequently solitary and presents as a small lesion in the dermal or the subcutaneous fat layer. Eccrine spiradenomas rarely progress to malignant transformation but they can relapse. Due to its rarity, there have been few reports about the sonographic appearances of eccrine spiradenoma. Sonographic findings were reported in a relapsing case of an eccrine spiradenoma, located in the deep dermal layers and hypodermis of the preauricular region in a middle-aged man. Ultrasound was very useful to suspect the relapse. Histology was correlated with the sonography and discussed the previously reported imaging findings of eccrine spiradenoma and other sweat gland tumors.

Granuloma annulare subtypes: sonographic features and clinicopathological correlation.

PURPOSE: Diagnosis of granuloma annulare (GA) is based on the clinical and histopathological findings. However, only sporadic case reports of subcutaneous GA sonography have been published to date. The objective of this study was to evaluate the ultrasonographic patterns of the different clinical variants of GA: localized, generalized, subcutaneous, and perforating. METHODS: In this retrospective observational study, we analyzed and correlated the clinical, histopathological, and sonographic features of 15 patients diagnosed with GA. RESULTS: We included 8 women and 7 men with a mean age of 48.4 years (8-77 years). We found three different sonographic patterns depending on the clinical variant of GA: poorly defined hypoechoic band including the dermis (dermal pattern), irregularly shaped hypoechoic hypodermal lumps (hypodermal pattern), and ill-defined hypoechoic dermal and subcutaneous lesions (mixed pattern). Five cases showed increased blood flow signal on Doppler interrogation. CONCLUSION: Although our findings are broadly consistent with the previous reports of subcutaneous GA, the sonographic features in localized, generalized, and perforating GA have not been previously reported.