Consistent Clinical Features Research Articles

Metastatic Basal Cell Carcinoma: Four Case Reports, Review of Literature, and Immunohistochemical Evaluation

Metastatic basal cell carcinoma (BCC) is relatively rare and is seldom considered a complication in the routine treatment and follow-up of patients with BCC. Although multiple studies have tried to distinguish aggressive from nonaggressive BCCs, to our knowledge, no consistent clinical, histopathologic, or immunohistochemical features have yet been reported. To report 4 cases of metastatic BCCs and to evaluate these in addition to known nonmetastatic BCCs with specific immunostains in an attempt to find distinct morphologic or immunohistochemical patterns that could be helpful in identifying aggressive BCCs. We reviewed 4 cases of metastatic BCCs and recorded the clinical and morphologic findings. We then searched our archives for 14 cases of BCC that followed the usual nonaggressive course. We evaluated these 18 cases with immunohistochemical stains for Ki-67, p53, and bcl-2. In metastasizing BCC, Ki-67 staining was slightly higher in metastatic sites than in primary sites (average 63% and 51%, respectively). p53 was expressed in 3 of 4 primary sites and 2 of 4 metastatic sites. Bcl-2 was positive in both primary and metastatic sites in 3 of 4 cases. In the 14 cases of nonaggressive BCC, staining for Ki-67 averaged 38%, p53 was positive in 11 cases, and Bcl-2 staining was noted in 13 cases. Overall, in the small sample that we evaluated, the immunohistochemical markers for Ki-67, p53, and Bcl-2 did not distinguish between metastatic and nonaggressive BCCs.

Metastatic basal cell carcinoma: four case reports, review of literature, and immunohistochemical evaluation.

Abstract Context.—Metastatic basal cell carcinoma (BCC) is relatively rare and is seldom considered a complication in the routine treatment and follow-up of patients with BCC. Although multiple studies have tried to distinguish aggressive from nonaggressive BCCs, to our knowledge, no consistent clinical, histopathologic, or immunohistochemical features have yet been reported. Objective.—To report 4 cases of metastatic BCCs and to evaluate these in addition to known nonmetastatic BCCs with specific immunostains in an attempt to find distinct morphologic or immunohistochemical patterns that could be helpful in identifying aggressive BCCs. Design.—We reviewed 4 cases of metastatic BCCs and recorded the clinical and morphologic findings. We then searched our archives for 14 cases of BCC that followed the usual nonaggressive course. We evaluated these 18 cases with immunohistochemical stains for Ki-67, p53, and bcl-2. Results.—In metastasizing BCC, Ki-67 staining was slightly higher in metastatic sites than in...

PTU-associated Vasculitis in a Girl With Turner Syndrome and Graves' Disease

Palpable purpura is a concerning clinical finding in pediatric patients and can have many causes, including infectious and autoimmune processes. A rare cause, drug-induced vasculitis, may result from the production of antineutrophil cytoplasmic antibodies (ANCAs) in response to a medication. We report a girl with Turner syndrome and Graves' disease who presented with palpable purpuric lesions. The diagnosis of propylthiouracil (PTU)-associated vasculitis was made by observation of consistent clinical features, the detection of elevated ANA and ANCA in the blood, and the observed clinical resolution of symptoms following withdrawal of PTU. Subsequent treatment of persistent hyperthyroidism with radioablation did not result in an exacerbation of the vasculitis, a complication described in prior case reports.

Plexopathy in a Heroin Addict

Muscle and peripheral nerve disorders are important complications in intravenous heroin abusers. Rhabdomyolysis and acute lumbosacral plexopathy are important in the differential diagnosis of patients developing muscle weakness in an intensive care unit after intravenous overdoses of heroin. A 25-year-old man developed rhabdomyolysis with neuromuscular involvement, and consistent clinical and electrodiagnostic features of lumbar plexus neuropathy after an intravenous injection of heroin. The improvement occured slowly, over months, in spite of intensive physiotherapy.

Post-neurosurgical nosocomial bacterial meningitis in adults: microbiology, clinical features, and outcomes

The clinical data of 62 adult patients who suffered post-neurosurgical nosocomial bacterial meningitis, retrospectively collected over a 16-year period, were studied. Cases were divided into two groups based on the date of presentation, the first period being 1986-1993 and the second 1994-2001. Fever and progressive consciousness disturbance were the most consistent clinical features - signs that may also be attributed to other postoperative neurosurgical problems. The common pathogens included Staphylococcus aureus, coagulase negative Staphylococcus, Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii. An increase in polymicrobial infections and multi-antibiotic resistance during the second period was identified. In the first half of the study, mortality was 22%, and in the second half 36%. Adult post-neurosurgical nosocomial bacterial meningitis has become an important clinical problem. The choice of appropriate empirical antibiotics is challenging and must be guided by an awareness of the relative frequency of various pathogens and the increasing incidence of resistant strains. Although high mortality rates may, in part, be related to the primary brain pathology, early diagnosis and the timely use of antibiotics based on antimicrobial susceptibility testing are essential for survival.

Hemosiderotic fibrohistiocytic lipomatous lesion: clinical correlation with venous stasis

Hemosiderotic fibrohistiocytic lipomatous lesion (HFLL) is a recently proposed lipomatous entity. HFLL was originally suggested to be a benign reactive lesion arising due to an antecedent trauma. We report two patients with HFLL who also suffered from chronic vein insufficiency due to varicose involving deep veins of the low limbs. Both patients were middle-aged women with solitary, poorly circumscribed subcutaneous lesions on the lower extremities. Histopathological examination revealed typical features of HFLL. We think that the consistent clinical features such as advanced age, female sex predilection, and specific location along with distinctive histopathological features allow the suggestion that impaired blood circulation, to wit, venous stasis is involved in the pathogenesis of HFLL. We hypothesize that the proliferation of spindled fibroblastic and myofibroblastic cells and capillaries, erythrocyte extravasation, and hemosiderin deposition with lipomatous tissue of HFLL may simply represent an exaggerated tissue response to venous stasis in which elevated venous and capillary pressures, oxygen saturation, and edema stimulate the proliferation of the above mentioned elements and lead to erythrocyte extravasation. A similar histopathological pattern is seen in acroangiodermatitis of Mali and vascular transformation of lymph node sinuses, and these conditions are also associated with impaired blood circulation.

Schimke‐immuno‐osseous dysplasia: New mutation with weak genotype–phenotype correlation in siblings

Schimke-immuno-osseous dysplasia (SIOD) is a multisystem disorder with the following consistent clinical features: spondyloepiphyseal dysplasia with disproportional growth deficiency, nephrotic syndrome with focal and segmental glomerulosclerosis, and defective cellular immunity. Transitory ischemic attacks due to vaso-occlusive processes are complications in some patients with severe SIOD. Recently, mutations of SMARCAL1, which encodes a putative chromatin remodelling protein, have been associated with SIOD. Patients with milder disease were observed to harbor a missense mutation on each allele, whereas patients with a severe form of the disease were predicted to have at least one allele with a nonsense, frameshift or splicing mutation. We report two brothers who are both compound heterozygous for the mutations 836 T>C and 2542 G>T detected in exons 4 and 17, respectively. We demonstrate the lack of genotype-phenotype correlation in these patients as one brother shows some features of the severe form while the other does not. Neither clinical nor molecular findings can fully predict the clinical course of SIOD.

Clinical and molecular characterization of lipoid proteinosis in Namaqualand, South Africa.

Lipoid proteinosis (LiP) is a rare autosomal recessive disorder characterized by a hoarse voice, warty skin infiltration and scarring. Mutations within the extracellular matrix protein 1 (ECM1) gene cause LiP. Since the early 1970s it has been recognized that South Africa has one of the largest groups of LiP patients worldwide, suggesting a probable founder effect. As LiP patients present with considerable clinical variability, this group of patients offers a unique opportunity for genotype-phenotype correlation. To assess the clinical features and the molecular basis of LiP in patients from the Namaqualand area of the Northern Cape province of South Africa and to examine molecular evidence for a founder effect. The LiP patient cohort consisted of 29 Coloured patients from Namaqualand and a further seven Caucasoid patients from other areas of South Africa. The control group included 100 healthy geographically and ethnically matched individuals from Namaqualand. Samples were collected after informed consent and with ethics committee approval from the University of the Witwatersrand. LiP patients were examined clinically and a structured recording sheet was completed. A brief neurological evaluation was also performed. The LiP founder effect was investigated at the molecular level by ECM1 mutation detection and haplotype analysis. The most consistent clinical signs for a diagnosis of LiP in this group were a hoarse voice and thickened sublingual frenulum leading to restricted tongue movement. Homozygosity for a nonsense mutation in exon 7 of the ECM1 gene, Q276X, was identified in all patients (Coloured and Caucasoid). Despite this genetic homogeneity, considerable clinical variability in skin presentation and psychiatric involvement was observed. Haplotype analysis using markers from a 9.98-Mb region around the ECM1 locus confirmed the founder effect with a founder core haplotype, 19-Q276X-12 (ND1-ECM1-D1S2343), in all but four LiP-associated alleles (n = 58). A LiP carrier rate of 1 in 9 was observed among the 100 Namaqualand controls, predicting a LiP incidence of 1 in 324 in this community. Although several consistent clinical features in LiP patients homozygous for the Q276X mutation in the ECM1 gene were observed, there remains considerable clinical variability. This suggests the action of genetic and environmental modifiers of disease severity. Strong molecular evidence supports a single founder effect for the high prevalence of LiP in South Africans, both Coloured and Caucasoid.

Defining the sudden infant death syndrome.

Sudden infant death syndrome (SIDS) is a term that was first proposed in 1969 for a distinctive subgroup of unexpected infant deaths that occur during the postneonatal period with relatively consistent clinical, epidemiological, and pathological features. This term played an important role by focusing attention on a major category of postneonatal infant death, providing support to grieving families, and diminishing the guilt and blame characteristic of these deaths. Unfortunately, the application of this term has become increasingly controversial. Some have applied it too liberally, and others not at all. According to the definition proposed in 1969, despite slight changes suggested in 1989, SIDS remains a diagnosis of exclusion. Although this syndrome has several distinctive features, including age distribution and apparent occurrence during sleep, there has been reluctance to include these features in the definition. The problems created by the lack of an adequate definition are discussed. A 2-tiered approach is suggested, with a more general definition intended primarily for case management and death administration, and a more restrictive one intended primarily for research purposes, which distinguishes those deaths closely fitting the classic SIDS profile from those with one or more less typical features.

The Brugada syndrome: is an implantable cardioverter defibrillator the only therapeutic option?

In 1992 two Spanish cardiologist brothers, Pedro and Josep Brugada reported eight patients with aborted cardiac arrest and no demonstrable heart disease who exhibited in sinus rhythm right bundle branch block (RBBB) with prominent STsegment elevation in precordial leads V 1‐V3. 1 Despite initial controversy about the diagnosis, especially concerning the possibility of a subtle arrhythmogenic right ventricular dysplasia, the repeated lack of right ventricular involvement along with consistent clinical, electrocardiographic (ECG), and electrophysiological features convinced the cardiological community that the Brugada syndrome was actually a new and important cause of sudden cardiac death (SCD) in ostensibly healthy patients. 2 During the last decade an increased awareness among physicians has resulted in a growing number of patients reported worldwide. In 1998, Chen et al. 3 were first to establish that the Brugada syndrome was a genetic disease with an autosomal dominant pattern of transmission. These investigators described mutations all affecting the cardiac sodium channel SCN5A on chromosome 3. More recently, a novel gene locus on chromosome 3, distinct from SCN5A has been identified. 4 The genetic pattern of transmission of the disease has lead to the increased detection of asymptomatic patients affected by the disease among families of cardiac ar

X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings.

X-linked lissencephaly with absent corpus callosum and ambiguous genitalia is a newly recognized syndrome responsible for a severe neurological disorder of neonatal onset in boys. Based on the observations of 3 new cases, we confirm the phenotype in affected boys, describe additional MRI findings, report the neuropathological data, and show that carrier females may exhibit neurological and magnetic resonance imaging abnormalities. In affected boys, consistent clinical features of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia are intractable epilepsy of neonatal onset, severe hypotonia, poor responsiveness, genital abnormalities, and early death. On magnetic resonance imaging, a gyration defect consisting of anterior pachygyria and posterior agyria with a moderately thickened brain cortex, dysplastic basal ganglia and complete agenesis of the corpus callosum are consistently found. Neuropathological examination of the brain shows a trilayered cortex containing exclusively pyramidal neurons, a neuronal migration defect, a disorganization of the basal ganglia, and gliotic and spongy white matter. Finally, females related to affected boys may have mental retardation and epilepsy, and they often display agenesis of the corpus callosum. These findings expand the phenotype of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia, may help in the detection of carrier females in affected families, and give arguments for a semidominant X-linked mode of inheritance.

Turner's syndrome in adulthood.

Turner's syndrome is the most common chromosomal abnormality in females, affecting 1:2,500 live female births. It is a result of absence of an X chromosome or the presence of a structurally abnormal X chromosome. Its most consistent clinical features are short stature and ovarian failure. However, it is becoming increasingly evident that adults with Turner's syndrome are also susceptible to a range of disorders, including osteoporosis, hypothyroidism, and renal and gastrointestinal disease. Women with Turner's syndrome have a reduced life expectancy, and recent evidence suggests that this is due to an increased risk of aortic dissection and ischemic heart disease. Up until recently, women with Turner's syndrome did not have access to focused health care, and thus quality of life was reduced in a significant number of women. All adults with Turner's syndrome should therefore be followed up by a multidisciplinary team to improve life expectancy and reduce morbidity.

Management of immune thrombocytopenic purpura in children.

Immune thrombocytopenic purpura (ITP) is the most common acquired bleeding disorder occurring in previously healthy children and can be classified into two major forms. Acute and chronic ITP are benign conditions with a high probability of spontaneous recovery with or without therapy. Rates of 80-90% complete remission can be achieved irrespective of the treatment given. In only 10-20% of children thrombocytopenia persists for more than six months, showing a chronic course, which also has a high probability of remitting over time (up to 80% or more). The variability of the clinical course, and the lack of consistent clinical features, make the decision on whether and how to treat difficult. Most physicians are driven to treat all children with symptoms by concern over life-threatening hemorrhage, although the risk of intracranial hemorrhage (ICH) is only 0.1-0.9%. The commonly used treatment regimens for acute ITP are corticosteroids, intravenous immunoglobulins (IVIgG), or intravenous anti-D immunoglobulin (anti-D). So far, there is no evidence that initial therapy can prevent ICH or a chronic course of the disease. In chronic ITP the same drugs are generally used and it seems that pulses with steroids may be just as effective as IVIgG. Anti-D may also be considered a reliable and cheap alternative for chronic disease. A major problem in the management of chronic ITP is the question of whether repeated infusions of Ig (IVIgG or anti-D) and/or corticosteroids can postpone or ultimately preclude splenectomy, which must be considered only for a small proportion of patients resistant to therapy. In these cases, a laparoscopic approach should be preferred. Children who fail to respond to splenectomy (< 20% of cases) warrant second line treatment with other drugs, like cyclophosphamide or azathioprine and deserve a revisit of diagnosis for exclusion of secondary ITP.

Necrotising fasciitis of a limb

Between January 1992 and December 1998, we treated 24 patients with necrotising fasciitis of a limb. There were 15 men and nine women with a mean age of 59.8 years (5 to 86). The infection was usually confused with cellulitis. Exquisite pain and early systemic toxicity were the most consistent clinical features. Diabetes mellitus and hepatic cirrhosis were the most commonly associated medical diseases. One third of the patients died. Those with involvement of the limbs above the knee or elbow on admission had a significantly higher rate of mortality than those with distal lesions (Fisher’s exact test, p = 0.027). There was no correlation between mortality and advanced age (Student’s t-test, p = 0.22) or between amputation and survival (Fisher’s exact test, p = 0.39).

Necrotising fasciitis of a limb.

Between January 1992 and December 1998, we treated 24 patients with necrotising fasciitis of a limb. There were 15 men and nine women with a mean age of 59.8 years (5 to 86). The infection was usually confused with cellulitis. Exquisite pain and early systemic toxicity were the most consistent clinical features. Diabetes mellitus and hepatic cirrhosis were the most commonly associated medical diseases. One third of the patients died. Those with involvement of the limbs above the knee or elbow on admission had a significantly higher rate of mortality than those with distal lesions (Fisher's exact test, p = 0.027). There was no correlation between mortality and advanced age (Student's t-test, p = 0.22) or between amputation and survival (Fisher's exact test, p = 0.39).

Direct duplication of 8p21.3?p23.1: A cytogenetic anomaly associated with developmental delay without consistent clinical features

We report six cases in two families and a sporadic case with a direct duplication of region 8p21.3→23.1. In one family, the duplication started in the mother and was transmitted to one son and one daughter. In the second family, the father was mosaic for the anomaly that was transmitted to his two daughters. The cytogenetic anomaly was initially described as an 8p+ with banding analysis and then delineated with fluorescence in situ hybridization (FISH) using whole-chromosome 8 painting, 8p specific painting, and 8p or 8p/8q subtelomeric probes. Deletion was not detected in the subtelomeric region of the abnormal chromosome 8 examined in one family and in the sporadic case. The phenotypic picture varies from normal to moderate mental retardation in the affected individuals. No consistent minor anomalies or congenital defects were observed among these cases. After comparing the chromosome region involved in our cases with those in others having direct or inverted duplications of 8p, it is thought that the segment 8p21.1→21.3 might be the critical region for an 8p duplication syndrome. The parental origin of the duplication does not seem to impact its clinical significance. © 2001 Wiley-Liss, Inc.

Lateral ventricle choroid plexus papilloma in childhood: management and complications

BACKGROUND A review of the choroid plexus papilloma of the lateral ventricle in the pediatric age group is presented. The characteristic clinical features, imaging studies, preoperative, and operative approaches, as well as complications, will be included. METHODS Among a group of 24 patients with ventricular choroid plexus papilloma treated by the authors over a 12-year period, seven patients were selected for this study. The selection included patients under the age of 8 years at the time of their presentation with choroid plexus papilloma of the lateral ventricle. Adult patients and children with choroid plexus papilloma at other sites or choroid plexus carcinoma were excluded. At least a 30-month follow-up period was available for all patients except one. Preoperative and postoperative imaging studies confirming total tumor resection were available for all patients. RESULTS Developmental delays and regression were the most consistent clinical features. Magnetic resonance imaging (MRI) proved to be the diagnostic test of choice. The addition of magnetic resonance angiogram (MRA) obviates the need for angiography. Our attempts at tumor embolization failed. CONCLUSION An intersulcal splitting approach to the lateral ventricular trigone, combined with a perioperative external ventricular drainage, may be of value in the avoidance of symptomatic subdural effusions.

Prevalence of Q fever in a rural practice.

Q fever is a world-wide condition caused by the rickettsia Coxiella burnetii. It appears more prevalent in agrarian communities and may have serious sequelae. A descriptive, cross-sectional, observational study using a randomly selected group of the adult working practice population in a rural practice in West Wales was devised. An immunofluorescence test, which identified past infection, was used to look for associations between C. burnetii seropositivity and farm-related or social activities, and to compare the findings with those of other studies. An attempt was made to establish a clinical profile for the illness Q fever. Twenty-one subjects were found to be seropositive to C. burnetii. No definite consistent clinical features were identified. Farming was undoubtedly a risk factor for the disease, maybe with other related factors also important. There was a possibility that alcohol had a protective effect. No sinister sequelae were described. Q fever occurs more frequently in farmers than in non-farmers, but was less common than previously thought. Is Q fever accurately described in medical textbooks? A case is made for a more co-operative approach between primary carers and epidemiologists in the study of illnesses in populations.

Variable clinical expression in a family with OI type IV due to deletion of three base pairs in COL1A1.

We have studied a family with autosomal dominant osteogenesis imperfecta (OI) type IV. Electrophoresis of collagen produced by cultured fibroblasts revealed a slower migrating population of collagen I. Cyanogen bromide peptide mapping localised the structural defect to the area of the alpha 1(1)CB3 peptide. Subsequent sequencing revealed a deletion of nucleotides 1964-1966 in exon 27 of COL1A1. By means of restriction enzyme analysis, the deletion could be detected in all affected family members. This in-frame deletion resulted in the removal of alanine-438 and Glu437Asp substitution in the pro alpha 1(I) collagen chain. Clinical variation was considerable among affected family members. The most consistent clinical features were reduced height and extraosseous manifestations of OI.

Cockayne syndrome: Review of 25 cases

Clinical and laboratory findings of 25 patients with classical Cockayne syndrome (CS) are reviewed. A history of consanguinity was present in 21 patients, and 15 patients had at least 1 affected sibling. Apart from the cardinal features of dwarfism, microcephaly, and mental retardation, the most consistent clinical features included photosensitivity (84%), gait disturbances (84%), progeroid appearance (84%), and ocular abnormalities (88%). The most consistent laboratory findings comprised abnormal nerve conduction (slowed conduction in 13 of the 16 cases with an ENMG), and an abnormal brainstem auditory evoked response (BAER) and/or audiometry (abnormal in 13 of the 17 cases in whom either one of them were available). Cerebral atrophy and calcification of the basal ganglia were the next more common laboratory findings. Clinical criteria are useful in most instances in the diagnosis of CS. In patients in whom the clinical features are controversial for a diagnosis of Cockayne syndrome, studies directed to disorders of myelination involving both peripheral and central nervous systems in conjunction with audiometry may aid in the diagnosis.