Neonatal Sweet syndrome: a potential marker of serious systemic illness.

Sweet syndrome is an inflammatory disease characterized by fever and painful erythematous plaques with a dermal neutrophilic infiltrate. It is most common in adults, where it is often parainflammatory or paraneoplastic, but is rare in children. We describe 3 cases of neonatal Sweet syndrome, including 1 patient who had myelodysplastic syndrome and immunodeficiency, the first report of a premalignancy underlying infantile Sweet syndrome. We reviewed the literature on patients presenting with neutrophilic dermatosis in the first 6 months of life. Of 20 cases, 6 had a probable viral etiology, 4 primary immunodeficiencies, 3 neonatal lupus syndrome, 1 gastrointestinal involvement, 1 HIV, and 5 probable genetic cases. Three of these had chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome, caused by mutations in the PSMB8 gene. Most children who presented within the first 6 weeks of life had either a serious underlying condition, such as primary immunodeficiency, or a genetic Sweet syndrome, with 2 fatalities among this latter group. The outcome of postinfective cases was good. Extracutaneous involvement was unusual, whereas postinflammatory scarring and cutis laxa occurred in a minority of patients. In conclusion, Sweet syndrome in the neonatal period often heralds a serious underlying disorder and requires thorough investigation.

Biphenotypic hematologic malignancy: a case report of the 8p11 myeloproliferative syndrome in a child.

SUMMARY: The 8p11 myeloproliferative syndrome, also known as stem cell leukemia/lymphoma, is a rare, atypical, myeloproliferative disorder and lymphoid malignancy associated with chromosomal abnormalities involving the 8p11 chromosomal band. Translocations associated with this syndrome result in the fusion of the fibroblast growth factor receptor 1 (FGFR 1) gene with various partners, resulting in ligand-independent FGFR activity. To date, 8 partner genes have been identified in association with FGFR1 rearrangements. The most frequent FGFR1 translocation partner is the zinc finger gene ZNF198 located at 13q11. Disease phenotypes associated with this translocation include poor prognosis and transformation to acute leukemia and non-Hodgkin lymphoma. In common with a T-cell phenotype, obtaining and maintaining remission is difficult by conventional chemotherapy. This study describes an illustrative case of 8p11 myeloproliferative syndrome/stem cell leukemia/lymphoma outlining its chief features and historical developments.

[Congenital unilateral linear porokeratosis]. / Kongenitale lineare unilaterale Porokeratose.

Porokeratosis is a disorder of epidermal keratinization. A 27-year-old woman had papular, linearly arranged, hyperkeratotic lesions on the right foot since birth. Over the course of her life, the lesions progressed to involve the entire right leg and extended to the right side of her trunk, the right arm and chin. The clinical diagnosis of unilateral linear porokeratosis was confirmed by histopathology.

Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia.

Severe congenital neutropenia (SCN) is a heterogeneous bone marrow failure syndrome predisposing to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We studied 82 North American and Australian SCN patients enrolled in the Severe Chronic Neutropenia International Registry who were on long-term treatment with granulocyte colony-stimulating factor and for whom the neutrophil elastase (ELA2) gene was sequenced. There was no significant difference in the risk of MDS/AML in patients with mutant versus wild-type ELA2: the respective cumulative incidences at 15 years were 36% and 25% (P = 0.96). Patients with either mutant or wild-type ELA2 should be followed closely for leukaemic transformation.

Hemihypertrophy, renal dysplasia and benign nephromegaly.

Hemihypertrophy is associated with malignant visceral abdominal neoplasms in childhood. Benign nephromegaly and nephroblastomas are both known to occur with hemihypertrophy; however, association with renal dysplasia has not previously reported. We describe an infant presenting with recurrent haematuria who had segmental hemihypertrophy, ipsilateral renal dysplasia and contralateral benign nephromegaly. Although debated, renal dysplasia may predispose to and predate malignant change. Rational management and optimal surveillance of renal dysplasia and benign nephromegaly in hemihypertrophy is discussed.

Proliferative nodules in congenital melanocytic nevi: a clinicopathologic and immunohistochemical analysis.

Congenital melanocytic nevi (CMN) occur in 1% to 2% of newborns, and the risk of malignant melanoma is increased in patients with large CMN. Appearance at birth or later of a nodular or hyperpigmented area within a CMN simulates malignant melanoma and prompts biopsy. Although their clinical and pathologic features seem ominous, proliferative nodules (PNs) typically are benign and may regress, although atypical features cause greater concern. Here we report clinical and pathologic findings with outcome in 10 children who had multiple biopsies of large CMN with PNs. We reviewed 78 separate samples from the 10 patients and classified the 60 PNs according to published criteria. A subset of 30 samples containing both the CMN and a PNs was analyzed for immunohistochemical reactivity for melanocytic (S-100 protein, HMB45, melan-A), lymphocytic (CD45), cell-cycle/proliferative (Mib-1, p16, p21, p27, c-Myc), apoptotic (p53, Bax, c-kit, CD95), and anti-apoptotic (bcl-2) markers. Both CMN and PNs had similar expression of melanocytic, lymphocytic, and most cell-cycle/proliferative and apoptotic markers, including Mib-1, p16, p21, p27, c-Myc, Bax, CD95, and bcl-2. A greater proportion of PNs than CMN were reactive for p53 (67% vs. 30%, P < 0.0098) and c-kit (97% vs. 3%, P < 0.0001). p53 and p21 expression in CMN and all types of PNs were inversely correlated. When ordinary and atypical PNs were compared, the atypical PNs more frequently expressed p53, Mib-1, Bax, and bcl-2, but less frequently expressed p21. The c-kit expression in nearly all PNs and its absence in nearly all CMN is potentially useful for recognition of PN, suggests a delayed melanocytic maturation process in proliferative nodules, and may be likely indicative of their benign nature. p53 reactivity in concert with a lack of p21 up-regulation by immunohistochemistry suggests that a p53 mutation may be present in PN, although the immunohistochemical findings alone cannot exclude possible overexpression of wild-type p53. Regressive, involutional, or maturational changes were observed in sequential samples from 4 patients. No patient developed malignant melanoma or another melanocytic nevus-associated malignancy during the follow-up period. These findings underscore the similarities between PNs and the underlying CMN and suggest that maturational, proliferative, and apoptotic processes are involved in their clinical evolution.

Congenital melanocytic nevi: treatment modalities and management options.

Congenital melanocytic nevi can be cosmetically disfiguring, give rise to melanoma, and suggest the presence of neurocutaneous melanocytosis. Management decisions must be tailored for each patient and each nevus, taking into consideration the risk for developing malignancy, risk for developing symptomatic neurocutaneous melanocytosis, cosmetic implications of having the nevus, cosmetic implications of any resultant surgical scars from their removal, adverse effects that the nevus may have on psycho-social development, and the adverse effects and long-term sequelae of any surgical intervention. The advantages and disadvantages of different modalities used in the treatment of congenital melanocytic nevi are discussed. Organizational flow diagrams are presented to help clinicians in managing patients with different sized congenital melanocytic nevi.

Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children.

Patients with a giant congenital melanocytic nevus can develop melanotic tumors characterized by central nervous system involvement, termed leptomeningeal melanocytosis or neurocutaneous melanosis. Although symptomatic neurocutaneous melanosis is rare, we previously reported distinct magnetic resonance (MR) findings of T1 shortening, strongly suggestive of neurocutaneous melanosis, in 30 percent (6 of 20) of children with giant congenital melanocytic nevi who presented initially without neurological symptoms. The purpose of this study was to determine the incidence of neurocutaneous melanosis in high-risk patients and its long-term clinical significance. Magnetic resonance imaging was recommended for all 46 patients with "at-risk" giant congenital melanocytic nevi involving the skin overlying the dorsal spine or scalp. The clinical histories and follow-up of these patients were evaluated by retrospective chart review. Forty-two underwent MR imaging of the brain and 11 underwent additional MR scanning of the spinal cord. Abnormalities were identified in 14 of 43 MR studies, and 23 percent (n = 10) had T1 shortening indicative of melanotic rests within the brain or meninges. None had associated masses or leptomeningeal thickening. The most common areas of involvement in these 10 included the amygdala (n = 8), cerebellum (n = 5), and pons (n = 3). In the group of 11 patients with spinal MR scans, a tethered spinal cord was demonstrated in one. Additional abnormalities were detected by MR scanning, including a middle cranial fossa arachnoid cyst, a Chiari type I malformation, and a crescentic enhancement that subsequently resolved. Clinical follow-up averaging 5 years (range, 2 to 8 years) revealed that only one of the 46 patients evaluated developed neurological symptoms, manifested as developmental delay, hypotonia, and questionable seizures but no other signs of neurocutaneous melanosis. No patient has developed a cutaneous or central nervous system melanoma. Magnetic resonance findings of neurocutaneous melanosis are relatively common, even in asymptomatic children with giant congenital melanocytic nevi. Although these findings suggest an increased lifetime risk of central nervous system melanoma, they do not signify the eventual development of symptomatic neurocutaneous melanosis during childhood.

The panda naevus: management of synchronous upper- and lower-eyelid pigmented naevi.

We report four patients presenting with rare synchronous upper- and lower-eyelid naevi. The distributions and appearances of these naevi resemble the distinctive periorbital pigmentation of the panda. The possible embryological origin of this naevus and an approach to management are discussed.

Basal cell carcinoma originating from a nevus sebaceus on the scalp of a 7-year-old boy.

Basal cell carcinoma (BCC) occurs rarely in children and is most often associated with an underlying condition that predisposes patients to the development of malignancy. There have been numerous reports of BCC developing after puberty in nevus sebaceus; however, such occurrences have rarely been described in children. We report a 7-year-old boy with BCC forming in a nevus sebaceus.

Small congenital nevi associated with melanoma: case reports and considerations.

Melanocytic nevi, both congenital and acquired, are considered to be precursors of melanomas. Data about the malignant potential of these nevi are conflicting, particularly with reference to the nevus of the smallest size. Patients with preexisting melanocytic nevi (both congenital and acquired) have risks of developing melanoma that differ from those of subjects without them. The purpose of this study was to verify the presence of melanoma in preexisting nevi both congenital (congenital nevus associated melanoma) (CNAM) and acquired (ANAM). In particular, we investigated melanomas associated with small congenital nevi (SCN). A cohort of 190 patients with primary melanomas was studied. Congenital nevi were called "small" (SCN) when their diameters were less than 1.5 cm. Epiluminescence microscopy (ELM) was performed to further improve the clinical diagnosis and to observe the more subtle changes in the preexisting nevi. Forty of the 190 cases of melanoma were associated with preexisting nevi; of these, 15 had congenital features with a CNAM largest diameter of 1.5 cm. These 15 cases were melanomas of the superficial type with a mean tumor thickness lower than that of ANAM (0.33 vs 1.50). There were no differences between the locations of CNAM and other melanomas. Male patients were significantly more affected. ELM microscopy permitted us to detect the early malignant changes in nevi and thus to improve our diagnosis. A high percentage of small congenital nevi were found to be associated with melanomas. They may be considered as melanomas precursors. Because of their large number and frequency, prophylactic removal of all SCN is not feasible. However, they should be removed as soon as possible when clinical or ELM changes are observed.

Point mutations of the c-Ki-ras gene in carcinoma and atypical epithelium associated with congenital biliary dilation.

OBJECTIVES: Congenital biliary dilation (CBD) may be accompanied later by gallbladder carcinoma or bile duct carcinoma. These cancerous lesions are frequently associated with atypical epithelium that was suspected of being precancerous. To determine whether atypical epithelium may be precancerous, we examined the DNA sequence of the c-Ki-ras gene at codon 12 in nine cases of CBD concurrent with seven gallbladder carcinomas, one bile duct carcinoma, and one bile duct atypical epithelium. METHODS: Tumor specimens were surgically removed from nine patients with CBD at Nagoya University Hospital between 1979 and 1988. Tumor was isolated by microdissection, and DNA was amplified by a two-step polymerase chain reaction which then was directly sequenced. RESULTS: Four of seven gallbladder carcinomas and one bile duct carcinoma contained the c-Ki-ras point mutation at codon 12, and atypical epithelium associated with these carcinomas had the same mutation. One case of atypical bile duct epithelium also contained the mutation. CONCLUSIONS: These results indicate that the c-Ki-ras point mutation at codon 12 may be responsible for either cancer or atypical epithelia associated with CBD.

Bilateral hyperplastic nephromegaly, nephroblastomatosis, and renal dysplasia in a newborn: a variety of universal nephroblastomatosis.

A preterm boy was born at 34 weeks. Prenatal ultrasonography showed oligohydramnios, fetal ascites, large kidneys, and small thorax. He died 21 h after birth of respiratory insufficiency. Autopsy revealed Potter's-like facies, hypoplastic lungs, ascites, and bilateral nephromegaly (renal weight almost 10 times normal). The kidneys were finely nodular externally, solid, and cerebriform on cut section. Histologically, they showed a diffusely distorted architecture of jumbled lobules, hyperplasia of cortical-type tissue with inconspicuous proximal tubules, relative hypoplasia of medullary tissue, tubulointerstitial dysplasia, and perilobar nephrogenic rests. The renal features represent a variety of the universal or panlobar (also called pancortical or infantile) type of nephroblastomatosis. To our knowledge, this is only the third such case reported. In the brain, each lateral ventricle contained a yellow gelatinous mass. Histologically, the masses consisted of a pseudomyxoid matrix with delicate fibers and focal adipocyte clusters, all confined within choroid plexus. We consider these lesions fibrolipomatous hamartomas.

[Congenital nevus cell nevi as precursors of melanomas of the skin]. / Kongenitale Naevuszellnaevi als Melanompraekursoren der Haut.

Based on our observations in 25 patients and on the literature of the last few years, we comment on the clinical findings, genetics, histology, ultrastructure, malignant degeneration and therapy of congenital nevocytic nevi. The differences between large and medium-sized nevi are emphasized.

Histologic patterns of congenital nevocytic nevi and implications for treatment.

The therapeutic problems associated with congenital nevocytic nevi (CNN) have lead to a flurry of interest in neonatal dermabrasion. This is based on the theory that nevus cells at birth are superficial and accessible to dermabrasion and that they later migrate into the deeper dermis. We studied twelve patients with CNN, including seven patients less than 3 months of age, with serial biopsies taken over a period of 15 months. In addition, four neonates with giant CNN underwent dermabrasion, and biopsies were obtained pre- and postoperatively. The histologic features of CNN and the implications for treatment are discussed. Our results are inconsistent with the idea of migration of nevus cells into the dermis during infancy. Dermabrasion of giant CNN at an early age may improve the cosmetic appearance; however, it will not remove most nevus cells and is not recommended as an effective treatment for the prevention of melanoma.

DNA aneuploidy in congenital melanocytic nevi: suggestive evidence for premalignant changes.

Nuclei with abnormal (aneuploid) DNA content were detected by flow cytometric analysis in 4 of 39 congenital melanocytic nevi and in 0 of 62 acquired nevi. Three of the 4 nevi with DNA-aneuploidy were greater than 20 cm in their largest diameter. We suggest that DNA aneuploidy is an indicator of a premalignant condition in congenital nevi in cases where histologic examination does not reveal any evidence for malignant melanoma. Cells with abnormal DNA content (aneuploid cells) are not uniformly distributed in giant congenital nevi: in one lesion we observed an area with a high percentage of cells with DNA aneuploidy, areas with a low percentage of aneuploid cells, and parts that were found to be normal by flow cytometric analysis. Nuclear pleomorphism was found histologically in the area with the high percentage of aneuploid cells while the areas with the low percentage of aneuploid cells were histologically normal. Thus, flow cytometry seems to be an additional sensitive method for the detection of nuclear abnormalities that are not always apparent by conventional histology. Increase in the relative amount of growth phase (S-phase cells), indicating elevated proliferative activity, was detected in 6 of 39 congenital pigmented nevi and in 6 of 62 acquired nevi.