Café-au-lait Research Articles

Hemangiomas and laser therapy: clinical experience

Background Hemangiomas are common benign vascular tumors characterized by a proliferative growth phase followed by very slow and inevitable regression. They are classified as capillary, cavernous, and mixed lesions, 60% are localized on the head and neck but they can be found in all regions of the body. Most of the lesions are focal and solitary, while 15%–20% are multiple with involvement of extracutaneous sites. Although hemangioma is usually benign, its growth is very unpredictable, due to uncontrollable endothelial cell proliferation, and complications are frequent because hemangiomas can evolve in ulceration. We present our clinical experience on the role of lasers to treat port wine stains, superficial hemangiomas, and cafe au lait macules.

Undifferentiated pleomorphic sarcoma in a child with type 1 neurofibromatosis

Conflicts of interest: none declared. Madam, A 10‐year‐old girl without significant past medical history presented with a slightly tender scalp nodule, growing for several months. On examination, there was a 1·5 cm rubbery, mobile, subcutaneous nodule on the left parieto‐occipital scalp. Additionally, she had axillary and inguinal freckling, seven large café‐au‐lait macules (CALMs) ranging in size from 1 to 6·5 cm, and numerous small CALMs less than 1 cm in size. Neurofibromas were not present, and there were no obvious bony abnormalities. Her family history was unremarkable, and she had had a reportedly normal ophthalmological examination at age 6 years. An excision of the scalp lesion was performed. On examination, there was a fragmented, firm tumour with a yellow‐white surface and focal haemorrhage. On cross‐section, the cut surface had a ‘fish flesh‐like’ appearance. Microscopic examination revealed a proliferation of two populations of cells. The first was organized predominantly as storiform fascicles and comprised of cells with plump, spindle‐shaped, hyperchromatic nuclei, and the second was arranged as sheets of cells with enlarged hyperchromatic and pleomorphic nuclei. There were also numerous multinucleated cells, some of which were osteoclast‐like (Figs 1a and 2a). Mitotic figures, some atypical, were readily observed (Fig. 2b). Immunoperoxidase studies revealed that the atypical cells reacted for CD68 (Fig. 1b) but were not reactive for smooth muscle actin, desmin, AE1/AE3, EAB 903 or S100 protein. Following wide local excision, the patient remains disease free to date.

Penile juvenile xanthogranuloma and neurofibromatosis type-1: risk association with juvenile myelomonocytic leukaemia?

Juvenile xanthogranuloma (JXG) is a benign, self-healing, non-Langerhans cell histiocytosis characterized by accumulation of lipid-laden macrophages. It occurs most commonly on the head and neck of infants and young children and resolves spontaneously without treatment [1]. Lesions may be single or multiple, congenital or acquired. Size varies from few millimetres to several centimetres. Two main clinical forms have been described: a small nodular form (60%) and a large nodular form (40%). Mixed forms and JXG “en plaque” have been described [2]. Moreover, different morphological types of JXG and atypical locations have been reported [3,4]. The first case of penile JXG was reported in 1993 [5]. The typical histologic appearance of JXG consists of a dense dermal infiltrate of foamy histiocytes, foreign body and Touton giant cells, the latter being nearly pathognomonic of JXG [1]. Several authors have reported the occurrence of cafe-au-lait macules (CALMs) or neurofibromatosis type-1 (NF-1) in patients with JXG [3,4,6]. In this report we describe a 7-year-old boy with a solitary penile JXG presentation at age of 2 years in association with NF-1. Case report

喉頭に発生した神経線維腫例

We report a rare case of neurofibroma of the larynx. A 65-year-old man suffering from hoarseness from about 2004, that had become severe by the end of 2007 was found in laryngoscopic examination to have a huge polyp bilaterally involving the vocal cords. The tumor, removed in laryngomicrosurgery, pathological by involved humorous spindle cells accompanied by myxomatous components and positive for NSE and vimentin in immunity dyeing. The histopathological diagnosis was neurofibroma. Because no family history or cafe au lait spots or neurogenic tumors were recognized, it was thought to be solitary onset.

A Case of Malignant Peripheral Nerve Sheath Tumor of the Neck Associated with Neurofibromatosis Type I

Neurofibromatosis is an autosomal dominant hereditary disorder characterized by skin abnormalities such as cafe au-lait spots, and soft tissue legion such as generalized subcutaneous neurofibroma. Malignant peripheral nerve sheath tumor is a spindle cell sarcoma that mostly arises in the soft tissue but rarely arises in the head and neck region. Malignant peripheral nerve sheath tumor can develop from the pre-existing neurofibromas or schwannomas, and from the peripheral nerves. They can also occur after radiation therapy. Malignant peripheral nerve sheath tumor is usually associated with neurofibromatosis type I. The authors recently experienced a case of malignant peripheral nerve sheath tumor associated with neurofibromatosis type I in a 20-year-old female patient who presented with a well marginated oval shape mass in the left neck.

McCune-Albright Syndrome (MAS): Early and Extensive Bone Fibrous Dysplasia Involvement and “Mistaken Identity” Oophorectomy

McCune-Albright syndrome (MAS) is a triad of gonadotropin-independent precocious puberty (GIPP), café-au-lait spots (CALS) and fibrous dysplasia (FD) of bone. The extent of the abnormalities is variable. We report a 3 year old girl with CALS since infancy, FD diagnosed at age of 2.5 years, and at the age of 3 years vaginal bleeding. The ultrasound revealed a cystic mass of the ovary, surgical pathology found ovarian cyst. LHRH stimulation demonstrated GIPP (LH 9.8 mIU/ml and FSH 8.9 mIU/ml; normal LH 1.8-10, FSH 9-26 mIU/ml). Radiographs and bone scans demonstrated FD in multiple bones. Peripheral leucocytes and the ovary were negative for GNAS gene mutations. Treatment with Letrasole interrupted the pubertal development. We conclude that the clinical signs of MAS are telling and that timely MAS diagnosis prevents unnecessary oophorectomy. A close follow up is recommended regarding development of endocrine disorders and spreading of FD.

A 19-year-old-man with a Cafe Au Lait Spot Referred for Suspicion of Acromegary who was Diagnosed with Fibrous Dysplasia in Childhood.

A 19-year-old-man with a Cafe Au Lait Spot Referred for Suspicion of Acromegary who was Diagnosed with Fibrous Dysplasia in Childhood.

A 19-year-old-man with a Cafe Au Lait Spot Referred for Suspicion of Acromegary who was Diagnosed with Fibrous Dysplasia in Childhood.

A 19-year-old-man with a Cafe Au Lait Spot Referred for Suspicion of Acromegary who was Diagnosed with Fibrous Dysplasia in Childhood.

Naevus Lentiginosus Linearis: A Distinct Skin Disorder

© 2010 The Authors. doi: 10.2340/00015555-0810 Journal Compilation © 2010 Acta Dermato-Venereologica. ISSN 0001-5555 Sir, Congenital naevi of the melanocytic system include numerous types, which differ in their clinical appearance, pattern of distribution, and histopathological features (1). Examples are large congenital melanocytic naevus, macular naevus spilus, papular naevus spilus, cafe-aulait macules of neurofibromatosis 1, cafe-au-lait macules arranged in broad bands as noted in McCune-Albright syndrome, partial unilateral lentiginosis, naevus achromicus (naevus depigmentosus), phylloid hypermelanosis, and phylloid hypomelanosis (1–3). We describe here two patients with a systematized pigmentary naevus that differed from all naevi reported so far.

Clinical and Mutational Spectrum of Neurofibromatosis Type 1–like Syndrome

Autosomal dominant inactivating sprouty-related EVH1 domain-containing protein 1 (SPRED1) mutations have recently been described in individuals presenting mainly with café au lait macules (CALMs), axillary freckling, and macrocephaly. The extent of the clinical spectrum of this new disorder needs further delineation. To determine the frequency, mutational spectrum, and phenotype of neurofibromatosis type 1-like syndrome (NFLS) in a large cohort of patients. In a cross-sectional study, 23 unrelated probands carrying a SPRED1 mutation identified through clinical testing participated with their families in a genotype-phenotype study (2007-2008). In a second cross-sectional study, 1318 unrelated anonymous samples collected in 2003-2007 from patients with a broad range of signs typically found in neurofibromatosis type 1 (NF1) but no detectable NF1 germline mutation underwent SPRED1 mutation analysis. Comparison of aggregated clinical features in patients with or without a SPRED1 or NF1 mutation. Functional assays were used to evaluate the pathogenicity of missense mutations. Among 42 SPRED1-positive individuals from the clinical cohort, 20 (48%; 95% confidence interval [CI], 32%-64%) fulfilled National Institutes of Health (NIH) NF1 diagnostic criteria based on the presence of more than 5 CALMs with or without freckling or an NF1-compatible family history. None of the 42 SPRED1-positive individuals (0%; 95% CI, 0%-7%) had discrete cutaneous or plexiform neurofibromas, typical NF1 osseous lesions, or symptomatic optic pathway gliomas. In the anonymous cohort of 1318 individuals, 34 different SPRED1 mutations in 43 probands were identified: 27 pathogenic mutations in 34 probands and 7 probable nonpathogenic missense mutations in 9 probands. Of 94 probands with familial CALMs with or without freckling and no other NF1 features, 69 (73%; 95% CI, 63%-80%) had an NF1 mutation and 18 (19%; 95% CI, 12%-29%) had a pathogenic SPRED1 mutation. In the anonymous cohort, 1.9% (95% CI, 1.2%-2.9%) of individuals with the clinical diagnosis of NF1 according to the NIH criteria had NFLS. A high SPRED1 mutation detection rate was found in NF1 mutation-negative families with an autosomal dominant phenotype of CALMs with or without freckling and no other NF1 features. Among individuals in this study, NFLS was not associated with the peripheral and central nervous system tumors seen in NF1.

Efficacy analysis of Q-switched alexandrite laser in the therapy of cafe-au-lait spots

Objective To analyze the factors affecting the therapeutic effect of Q-switched alexan-drite laser on and recurrence of cafe-au-lait spots. Methods A follow up was conducted in patients with cafe-au-lait spots treated with Q-switched alexandrite laser in the Nineth People's Hospital, Shanghai Jiao Tong University School of Medicine from January of 2002 to December of 2006. Groups were classified according to the age, gender, onset age, disease course, treatment interval of patients as well as the number, area, site, shape, color depth, etc, of lesions. Chi-Square test was used to compare the difference in response rate and recurrence rate among different groups. Results A total of 351 valid cases were collected, among which 73 were males, 278 were females, with a total recurrence rate of 84.6% and total response rate of 53.3%. Neither response rate nor recurrence rate significantly correlated with the gender, treatment age or disease course of patients (all P > 0.05). However, the therapeutic effect was significantly affected by the age of ouset (x2 = 6.162, P < 0.05), iesional site (x2 = 14.196, P < 0.001 ), area(x2 = 13.005, P < 0.05), color depth(x2 = 10.063, P < 0.05), shape (x2 = 14.039, P < 0.001 )and treatment interval (x2 = 4.787, P < 0.05). More treatment sessions were associated with a higher efficacy (r = 0.343, P < 0.001 ), and higher treatment energy within a certain range were associated with a better therapeutic effect (r = 0.178, P < 0.01 ) and longer treatment interval (r = 0.157, P < 0.05). Conclusions Q-switched alexandrite laser is an effective approach to the treatment of care -au-lait spots, and its efficacy can be predicted according to different factors that concern. Key words: Laser therapy; low-level; Cafe -an-lait spots; Treatment outcome; Factor analysis; sta-tistical

Clinical analysis of 243 eases of nevus of Ota

Objective To study the clinical features of nevus of Ota in patients from Hubei Province and adjacent areas. Methods A retrospective study was performed to assess the onset age of disease, family history of pigmentary diseases, medication use during pregnancy, etc, of 243 patients with nevus of Ota from Hubei Province and adjacent areas. Results Of the 243 patients, 58% were born with a lesion of nevus of Ota, 42% developed eruptions postnatally (mainly between the age of 5 to 15 years).Family history of pigmentary diseases was observed in 60% of these patients, and in these pigmentary diseases, freckles and cafe-au-lait spots predominated. There was no significant correlation between the development of this disease and history of taking medicine during pregnancy. Conclusions Nevus of Ota may be a hereditary disease, and patients with pigmentary disorders are more likely to have descendants with nevus of Ota. Key words: Nevus of Ota; Clinical analysis; Heredity; Hyperpigmentation

Predictive Value of Café au Lait Macules at Initial Consultation in the Diagnosis of Neurofibromatosis Type 1

To evaluate the predictive utility of the number and morphologic appearance of isolated café au lait macules (CALMs) in establishing the diagnosis of neurofibromatosis type 1 (NF1) in a cohort of children referred to an NF1 subspecialty clinic. Retrospective study of patients seen between the years 2004 and 2007. Tertiary care neurofibromatosis referral clinic at St Louis Children's Hospital. Patients The study population comprised 110 patients who presented with CALMs and no other diagnostic features of NF1. The median number of CALMs at initial presentation was 6, while the median age of the patients was 33 months. The median age at the last follow-up examination was 76.5 months. Number and morphologic appearance of CALMs and diagnosis of NF1. Thirty-four of the children met diagnostic criteria for NF1 during the study period. Thirty-two children met criteria prior to age 72 months, and 2 children met criteria after 72 months. The mean number of CALMs at presentation in children eventually diagnosed as having NF1 (11.8 CALMs) was significantly higher than the mean number of CALMs in children not diagnosed as having NF1 (4.6 CALMs). Of the 44 children who had 6 or more typical CALMs at presentation, 34 children met criteria for NF1. Sixty-eight patients had CALMs described as "typical," while 42 patients had "atypical" CALMs. Only 2 patients with atypical CALMs met criteria for NF1. Conclusion The majority of patients with 6 or more CALMs will eventually meet diagnostic criteria for NF1, typically by age 6 years, and this likelihood increases with increasing number and typical morphologic appearance of CALMs.

Clinical Overlap Between Mazabraud and McCune-Albright Syndromes

azabraud syndrome (MS) is a rare sporadic disorder, mainly characterized by bone fibrous dysplasia and intramuscular myxomas. We report a new case of MS in a patient who also had cafe au lait spots and precocious puberty suggestive of McCune-Albright syndrome (MAS). To our knowledge, a case of overlap between MS and MAS presenting with monostotic fibrous dysplasia in which the first symptoms were related to multiple intramuscular myxomas has not been reported previously. Sonographers should consider the possibility of a genetic disorder such as MS or MAS when evaluating intramuscular myxomas.

Aphalangia possibly linked to unintended use of finasteride during early pregnancy

Aphalangia possibly linked to unintended use of finasteride during early pregnancy

Clove-transmissibility of Pseudomonas salomonii, the causal agent of ‘Café au lait’ disease of garlic

Bacterial blight of garlic, caused by Pseudomonas salomonii, results in leaf and sheath necrosis and sometimes leads to soft rot and plant death. The epidemiology of this bacterial disease, known as ‘Cafe au lait’ disease, is poorly understood and no resistant cultivars are currently available. To develop control strategies for this disease, we investigated principal sources of inoculum. The pathogen was isolated from bulbs from plants with typical vegetative symptoms of bacterial blight. Subsequent development of typical foliar symptoms on plantlets originating from symptomatic bulbs demonstrated transmission of the pathogen in the planting material. In one of three field experiments the contamination rate of planting stock influenced the disease incidence in field-grown garlic. The importance of planting stock as a source of inoculum was demonstrated here and should be evaluated relative to other potential sources such as crop debris, soil or alternate hosts in order to develop successful control strategies.

Evolving Diagnosis of McCune-Albright Syndrome. Atypical Presentation and Follow up

The diagnosis of McCune-Albright syndrome has classically consisted of the triad of gonadotropin-independent precocious puberty (GIPP), café-au-lait (CAL) spots and fibrous dysplasia of bone. Atypical or incomplete forms of the syndrome have been reported in the literature, with only one or two of the classical symptoms present, and the diagnosis being made after molecular analysis. Therefore not all three classical findings need to be present for the diagnosis to be made. We report a patient who was suspected of having McCune-Albright syndrome after presenting initially with GIPP at age 2 years 10 months. At age 10 years 1 month, a CAL spot appeared and, after reviewing previous imaging studies, a bone cyst was found. Molecular analysis in peripheral leucocytes was negative. We reviewed similar cases described in the literature.

Leopard syndrome

LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. About 200 patients have been reported worldwide but the real incidence of LS has not been assessed. Facial dysmorphism includes ocular hypertelorism, palpebral ptosis and low-set ears. Stature is usually below the 25th centile. Cardiac defects, in particular hypertrophic cardiomyopathy mostly involving the left ventricle, and ECG anomalies are common. The lentigines may be congenital, although more frequently manifest by the age of 4–5 years and increase throughout puberty. Additional common features are café-au-lait spots (CLS), chest anomalies, cryptorchidism, delayed puberty, hypotonia, mild developmental delay, sensorineural deafness and learning difficulties. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. LS is largely overlapping Noonan syndrome and, during childhood, Neurofibromatosis type 1-Noonan syndrome. Diagnostic clues of LS are multiple lentigines and CLS, hypertrophic cardiomyopathy and deafness. Mutation-based differential diagnosis in patients with borderline clinical manifestations is warranted. LS is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, a 50% recurrence risk is appropriate. LS should be suspected in foetuses with severe cardiac hypertrophy and prenatal DNA test may be performed. Clinical management should address growth and motor development and congenital anomalies, in particular cardiac defects that should be monitored annually. Hypertrophic cardiomyopathy needs careful risk assessment and prophylaxis against sudden death in patients at risk. Hearing should be evaluated annually until adulthood. With the only exception of ventricular hypertrophy, adults with LS do not require special medical care and long-term prognosis is favourable.

Cutaneous lesions associated to multiple endocrine neoplasia syndrome type 1

Multiple endocrine neoplasia type 1 (MEN1) is a genetic disease that predisposes to endocrine tumour development. Some cutaneous lesions (angiofibromas, collagenomas, melanosis guttaca, lipomas, melanomas, 'cafe au lait macules') have been associated to this syndrome. We compare the prevalence of cutaneous lesion in affected patients with their non-carrier relatives. We studied 9 patients with MEN1 and 20 non-carrier, first-degree relatives. Genetic screening was realized in all of them. Patients were examined by dermatologist, and biopsy was performed when necessary. Patients with MEN1 presented hyperparathyroidism (100%), neuroendocrine tumours of pancreas (66%) and pituitary adenomas (44%); their relatives were free of endocrine features of MEN1. The studied cutaneous lesions were more prevalent in affected patients than in non-carriers (55.5% vs. 25%; P = 0.029). Odds ratio of developing cutaneous lesions in MEN1 patients was 6.6 (95% confidence interval, 1.09-40.43). The frequency of angiofibromas was lower (22.2%) than the reported in other studies (43-88%), and we did not find any collagenoma. MEN1 is associated to some cutaneous lesions and could be useful for detecting MEN1 carriers in an affected family. Cutaneous lesions should be assessed in MEN1 patients.

Managing children with neurofibromatosis type 1: what should we look for?

Neurofibromatosis type 1 (NF1) is one of the most common neurocutaneous disorders. It is an autosomal dominant hereditary condition, although an half of all cases are related with spontaneous mutations. Mutations within NF1 gene (c17q11.2) result in loss of function of the protein neurofibromin leading to increase cell proliferation and tumorigenesis. NF1 is a variable condition concerning its clinical manifestations. It may also present different complications through life--a capital issue to pediatric management. Descriptive, retrospective, study based on clinical notes of patients with NF1 referred to Unidade de Neuropediatria e Desenvolvimento--Hospital Garcia de Orta, between 1992 and June of 2005. Diagnostic criteria were those of National Institute of Health Consensus Development Conference. Thirty-five patients were included (20 male,15 female). Age distribution: <3-year-old--4; 3-6 year-old--3; >6-year-old--28. NF1 diagnosis was proposed at the mean age of 4,7 year-old. Patients were referred for assessment mainly for "café-aulait" spots. Other motives included: first-degree relative with NF1, cutaneous neurofibroma, plexiform neurofibroma, tibia's pseudarthrosis, headaches, seizures, failure to thrive and learning disabilities. Diagnostic criteria included: café-au-lait spots (35/35), first degree relative with NF1 (22/35), axillary or inguinal freckling (9/35), neurofibromas (5/35), iris Lisch nodules (4/35), optic glioma (3/35), dysplastic bony lesions (3/35), plexiform neurofibroma (2/35). Three patients presented short stature and 11/35 macrocephaly. MR imaging revealed unidentified bright signals (UBO's) in 12 cases. Cognitive and psychological evaluation was performed in 12 cases. Mean IQ was 87. Attention-deficit-hyperactivity disorder was present in 40% (14/35) of all cases. Learning disabilities were identified in 48% of cases however only nine children had specifically educational programming. Visuospatial deficits were present in 5/35 children, reading deficits in 4/35, graphomotor deficits in 4/35, language deficits in 3/12 and dyscalculia in 3/12 cases. Three children presented emotional disturbance and other three children social skills deficits. Management of children with NF1 should focus on complications related with its multiple clinical manifestations, some of them age-dependent. It should also involve careful neuropsychological evaluation and observe the development of social skills. A high suspicion and an early intervention are essential to prevent a poor social functioning and outcome.