Extensive Skeletal Involvement Research Articles

Lymphangiomatosis with Extensive Skeletal Involvement

Aim : To review a case presentation of systemic lymphangiomatosis- an uncommon medical condition that can be easily misdiagnosed in the clinical setting Abstract : Generalized lymphangiomatosis is a rare condition with characteristic multi-centric angiomatous malformations of the skeletal system, with involvement of surrounding soft tissues and skin. It results from a congenital anomaly and presents predominantly in the paediatric age group. Systemic involvement includes not only the skeletal system, but also the pulmonary and gastrointestinal systems. Its diagnosis can be difficult to ascertain but is hinged on clinical presentation, imaging and histological confirmation. The condition carries a variable prognosis as treatment options are very limited. Pulmonary involvement is usually terminal, however. A case is presented to highlight the difficulties in diagnosing and managing this condition. Conclusion : The diagnosis of lymphangiomatosis involving the skeletal system is highly reliant on imaging studies; that depict well defined osteolytic changes of the bone. Management is supportive and no cure currently exists. Keywords : lymphangiomatosis, systemic, skeletal involvement

Lymphangiomatosis with Extensive Skeletal Involvement

Aim : To review a case presentation of systemic lymphangiomatosis- an uncommon medical condition that can be easily misdiagnosed in the clinical setting Abstract : Generalized lymphangiomatosis is a rare condition with characteristic multi-centric angiomatous malformations of the skeletal system, with involvement of surrounding soft tissues and skin. It results from a congenital anomaly and presents predominantly in the paediatric age group. Systemic involvement includes not only the skeletal system, but also the pulmonary and gastrointestinal systems. Its diagnosis can be difficult to ascertain but is hinged on clinical presentation, imaging and histological confirmation. The condition carries a variable prognosis as treatment options are very limited. Pulmonary involvement is usually terminal, however. A case is presented to highlight the difficulties in diagnosing and managing this condition. Conclusion : The diagnosis of lymphangiomatosis involving the skeletal system is highly reliant on imaging studies; that depict well defined osteolytic changes of the bone. Management is supportive and no cure currently exists. Keywords : lymphangiomatosis, systemic, skeletal involvement

Alkaptonuria: Case report

Alkaptonuria is a rare, autosomal-recessive disorder of phenylalanine/tyrosine metabolism due to congenital deficiency of the enzyme homogentisic acid oxidase. Herein, we are reporting a classical case of alkaptonuria with extensive skin pigmentation and skeletal involvement. Histopathological examination also revealed classical ochre-colored deposits in dermis.

Ultrasound guided nerve block in successful anesthetic management of an achondroplasic dwarf with severe kyphoscoliosis.

Sir, A 23-year-old man (weight = 34 kg, height = 119 cm) presented with a history of pain in the right foot and fever since 5 days. He gave a history of abnormalities of the limbs and trunk since birth. On examination, his pulse rate was 74/min, blood pressure = 130/80 mmHg, and there was an abscess of the right foot with cellulitis extending up to the level of calf. He had a short stature, kyphoscoliosis, abnormal and short lower limbs. Cardiovascular and respiratory systems were normal except for deformity of the chest. Airway examination revealed a broad nasal bridge, adequate mouth opening, modified Mallampati score — 2, and normal neck movements. There was a kyphoscoliotic deformity involving the entire spine. His hemoglobin concentration was 12.3 g/dl and total leucocyte count = 25730 cells/cm3. Electrocardiogram showed incomplete right bundle branch block. A radiograph confirmed the kyphoscoliosis involving the entire spine from cervical to the lumbosacral region [Figure 1]. Figure 1 Radiograph showing severe kyphoscoliosis involving the entire spine from cervical to lumbosacral region After initiating routine monitoring, intravenous fentanyl 50 μg and midazolam 1 mg was administered and the patient was put in left lateral position. The right sciatic nerve block was performed at the subgluteal region using a combined ultrasound (out of plane technique) and a peripheral nerve stimulator technique with a 22G 10 cm insulated needle (Stimuplex® A) after eliciting dorsiflexion of the foot. Then, the patient was turned supine and the right femoral nerve block was performed using similar technique (except the in-plane technique for ultrasound) after eliciting contraction of the quadriceps. The local anesthetic mixture contained 12 ml of lignocaine 2% with adrenaline 5 μg/ml + 10 ml of bupivacaine 0.5% + 3 ml of NaHCO3 + 7 ml normal saline (total volume = 32 ml). There were neither any technical difficulties nor any anatomical variations of the nerves noted during the procedure. Drainage of the abscess with debridement up to a few centimeters below the knee was completed successfully in 30 min. However, analgesia lasted only for about 3 h. Achondroplasia is the most common cause for dwarfism with an approximate incidence of 1.5 in 10,000-1 in 40,000 live newborns with majority (80%) of the cases due to spontaneous mutation.[1,2,3,4] Achondroplasia is caused by a genetic mutation of the fibroblast growth factor receptor-3, which affects bone growth due to change in endochondral ossification and leads to bone malformation.[5] Due to the defective bone growth with extensive skeletal involvement, both general, and neuraxial anesthesia for these patients may be associated with several difficulties including difficult airway, laryngomalacia, technically challenging neuraxial anesthesia, unpredictable spread of local anesthetics in the epidural space and subarachnoid space and compromised pulmonary function.[4,5] Even though, there have been a few cases of successful spinal and epidural anesthesia[3] in such patients undergoing caesarean section, various reports have described technical difficulties during the procedure, increased complications[2] unpredictable spread of local anesthetic,[4] and failure of neuraxial anesthesia. Neurological problems may develop later in life because of compression of the cord due to osteophytes, prolapsed intervertebral discs, and deformed vertebral bodies. Therefore, it has been suggested to avoid neuraxial anesthesia in these patients and anesthesiologists have been reluctant to opt for neuraxial anesthesia.

Acute Myeloid Leukemia Presenting as Back Pain in a 12-Year-Old Boy

Acute Myeloid Leukemia Presenting as Back Pain in a 12-Year-Old Boy

The isotope bone scan: we can do better

The conventional isotope bone scan using Tc-labelled diphosphonate is perceived as being highly sensitive but non-specific in the detection of skeletal pathology. The poor specificity is a significant clinical issue, as additional investigations are frequently required (X-ray, CT, MRI) to clarify equivocal lesions, such as the presence of degenerative changes, where metastatic involvement is suspected. This inevitably leads to extra cost, heightened concern and frequent delays in management. Where available, specificity (and to a lesser extent sensitivity) has been greatly improved with the use of single photon emission computed tomography (SPECT)/CT [1–3], but can be further significantly improved with the use of F-fluoride positron emission tomography (PET)/CT [4–6]. Further, F-fluoride can on occasion identify early metastatic lesions at a time when the bone scan is normal [7–10]. Nevertheless, F-fluoride is rarely used routinely for bone imaging due to the limited availability of PET, cost and competition for time on the PET scanner. In addition to the above issues there are significant limitations to the use of the bone scan for its most common application, the detection and assessment of metastatic disease. A frequent request is to monitor the effect of treatment, but it is well recognised that even with successful treatment there will be a significant delay before this becomes apparent on the bone scan due to ongoing altered metabolic activity in bone, and there is the possibility of a flare response if the study is performed too early. In the situation where there is such extensive skeletal involvement that lesions coalesce, effectively superficially ‘normalising’ appearances (the ‘superscan’ of malignancy), any change is likely to be difficult to detect and further, it is now apparent there may be significant alterations in the metabolic activity of individual lesions but with no apparent visual difference between studies [11]. In this situation quantitation is required to clarify the issue. Quantitation with a conventional bone scan is problematic and techniques that have been used in the past such as measuring bone to soft tissue or lesion to bone ratios are crude and nowadays rarely, if ever, performed. Quantitation is, however, routine with PET studies, and standardised uptake values (SUVs) are commonly measured using the ‘universal’ tracer F-fluorodeoxyglucose (FDG). As previously stated, F-fluoride is not routinely used for bone scanning, although there are research reports demonstrating that SUVs can detect significant metabolic change in individual metastatic lesions even when visual evaluation reveals little if any difference [11]. In oncology there are a large number of new treatments that are either in development or have recently become available, and evaluating skeletal response is critical with regard to the future of a drug’s development or to decide upon the optimal management of a patient. SUVs are satisfactory in most routine situations, although one must be aware of their limitations. Care must be taken with regard to quality control, for example if there is significant variation in the time when the scan is performed following injection, as this can impact on SUVs (generally there is increased uptake of tracer in a tumour with time). A more important limitation is that SUVs may not be accurate if skeletal involvement is so extensive that the arterial input function is altered, and in such situations I. Fogelman :G. M. Blake King’s College London, Department of Nuclear Medicine, King’s College Academic Health Partners, Guy’s Campus, Ground Floor, Borough Wing, London SE1 9RT, UK

Bone scintigraphic patterns in patients of tumor induced osteomalacia

Tumor induced osteomalacia (TIO) or oncogenic osteomalacia is a rare condition associated with small tumor that secretes one of the phosphaturic hormones, i.e., fibroblast growth factor 23, resulting in abnormal phosphate metabolism. Patients may present with non-specific symptoms leading to delay in the diagnosis. Extensive skeletal involvement is frequently seen due to delay in the diagnosis and treatment. The small sized tumor and unexpected location make the identification of tumor difficult even after diagnosis of osteogenic osteomalacia. The bone scan done for the skeletal involvement may show the presence of metabolic features and the scan findings are a sensitive indicator of metabolic bone disorders. We present the bone scan findings in three patients diagnosed to have TIO.

Fibröse Dysplasie versus osteofibröse Dysplasie

Histologically, this lesion, which was first described by Campanacci, is characterized by an osteofibrous stroma replacing normal bone, showing trabeculae which, unlike in FD, are surrounded by a regular rim of prominent cubic osteoblasts, mature lamellar bone and zonal segmentation with newly formed trabeculae mostly in the cortical region. Radiologic features are eccentric, usually diaphyseally localized osteolytic lesions of the tibia with ground glass appearance. Differential diagnosis includes FD and adamantinoma. Just like OFD, the latter occurs almost exclusively in the tibia, its potential malignancy calling for a more radical therapeutical procedure. Being such a rare lesion, there are no clear guidelines regarding formal pathogenesis and therapy of adamantinoma in combination with osteofibrous stromal reaction. The mean age of the eleven patients with OFD was nine years, which is considerably lower than that of patients with FD (30 years). The lesions were found exclusively in the tibia. Surgical therapy is often followed by a recurrence of the tumor (in two cases in the present material), so it should be avoided, where possible. Thus, surgery should only be performed if complications are imminent, such as marked bone deformation or pseudoarthrosis. Unlike in FD, once bone maturation is completed, surgical treatment of OFD is not normally followed by recurrent disease. Thus, the prognosis of OFD with restricted surgical therapy is more favourable than that of FD, which frequently shows extensive skeletal involvement and recurrent disease even after many years. The more aggressive course of OFD reported by other authors must therefore be explained by too early surgical intervention, i.e. during bone maturation.

Is the Prevalence of Paget's Disease of Bone Decreasing?

Secular trends in the severity and prevalence of Paget's disease over a 30-year period are described. Paget's disease has become less prevalent and patients are presenting later, with less severe disease than previously. These data suggest that environmental factors are important in the etiology of Paget's disease. Data from several countries support the view that there are important secular trends in the prevalence and severity of Paget's disease. In this paper, recent trends in the epidemiology of Paget's disease are described. A database of all newly referred patients (n = 1487) with Paget's disease (1973-2002 inclusive, 30 years) was examined. Of these subjects, 56% had scintiscans. Plasma total alkaline phosphatase (total ALP) activity and disease extent on scintiscan were used as indices of severity. A radiographic prevalence survey of 1019 subjects of European origin >55 years of age in Dunedin was undertaken- approximately 20 years after an earlier survey had shown New Zealand to be a high prevalence area. The number of new referrals with Paget's disease declined sharply from 1994 onward, to one half the rate seen 20 years earlier, whereas the mean age at presentation increased by 4 years per decade (p < 0.0001). Total ALP at diagnosis, disease extent on scintiscan, and the number of bones involved were all negatively correlated with both date of birth (p < 0.0001) and year of presentation (p < 0.0001), indicating that more recently born and presenting subjects had substantially less severe bone disease. The radiographic survey showed that the current prevalence was only approximately 50% of that in the 1983 survey (p = 0.012). Although there are a number of potential biases, these data are consistent with a continued secular trend to presentation in older subjects with less extensive skeletal involvement and a declining prevalence of Paget's disease.

Type 1 Gaucher disease presenting with extensive mandibular lytic lesions: Identification and expression of a novel acid ?-glucosidase mutation

The finding of extensive lytic lesions in the mandible of a 19-year-old Ashkenazi Jewish woman led to the diagnosis of Type 1 Gaucher disease. She had extensive skeletal involvement, marked hepatosplenomegaly, and deficient acid beta-glucosidase activity. Mutation analysis identified heteroallelism for acid beta-glucosidase mutations N370S and P401L, the latter being a novel missense mutation in exon 9. Expression of the P401L allele resulted in an enzyme with a reduced catalytic activity (specific activity based on cross-reacting immunological material approximately 0.21), which was similar to that of the mild N370S mutant enzyme. The expression studies predicted a mild phenotype for the proposita's N370S/P401L genotype which was inconsistent with her severe diffuse skeletal disease and organ involvement. Since lytic mandibular lesions may be complicated by osteomyelitis, pathologic fracture, and tooth loss, regular dental assessments in Type 1 Gaucher patients should be performed.

Severe prenatal infantile cortical hyperostosis (Galley??s disease)

We describe three cases of prenatal infantile cortical hyperostosis (Caffey's disease) from two families, all associated with maternal polyhydramnios. Case 1 (family 1) was an early early neonatal death after delivery at 27 weeks gestation, case 2 (family 2) an intrauterine death at 33 weeks. Case 3 (family 2) had limited skeletal involvement and followed a course typical for Caffey's disease. Only six cases of prenatal Caffey's disease with extensive skeletal involvement have previously been described. Polyhydramnios was reported in all but one and the condition was lethal unless pregnancy reached term. To our knowledge cases 2 and 3 reported here represent the first description of Caffey's disease in which the prenatal lethal form was not sporadic.

Inhibition of mediator release in systemic mastocytosis is associated with reversal of bone changes

A 59-year-old male presented with systemic mastocytosis with extensive skeletal involvement resulting in vertebral compression fractures and bone pain. Histomorphometric analysis of bone revealed increased mast cells, elevated static parameters of bone resorption, and low bone formation. Serum calcium, phosphorus, and alkaline phosphatase were normal; however, serum 1,25-dihydroxyvitamin D3 and osteocalcin levels were low. Histamine levels in plasma and urine were elevated. Following therapy with ketotifen, the patient had resolution of bone pain along with decreased flushing and pruritus. Elevated plasma and urine histamine levels normalized, as did 1,25-dihydroxyvitamin D3 and osteocalcin levels. Indices of low bone formation improved on therapy. Eroded surfaces improved but remained elevated. This case is the first demonstration that bone symptoms and histomorphometric change in systemic mastocytosis are reversed with inhibition of mast cell degranulation. The role of mast cells and their products in bone metabolism is poorly understood, but the therapy of bone disease in systemic mastocytosis should include inhibition of the release of mast cell products along with the use of histamine antagonist.

Incidence of jaw lesions in 193 patients with multiple myeloma

The incidence of alterations of the maxilla and mandible at radiographic screening was evaluated in 193 patients with multiple myeloma, both at the time of diagnosis and after the start of chemotherapy during the course of the disease. Although the study confirms that osteolytic lesions are more frequent in the mandible than in the maxilla, it showed that their incidence was lower than reported in the past. Furthermore, these lesions were mostly asymptomatic and were observed in patients who had extensive skeletal involvement, particularly at the skull level. These findings indicate that systematic radiologic monitoring of the stomatognathic system should be performed, particularly in patients with multiple myeloma at an advanced stage.

Supination-eversion fractures of the ankle joint: changes in incidence over 30 years.

The sex- and age-specific incidence has been calculated for ankle fractures from the first part of the 1950s and compared with the 1980s, a 30-year interval. The fractures were also classified according to Lauge-Hansen. Altogether 1784 fractures were found. During that time interval ankle fractures had become more common, particularly those with extensive skeletal involvement, such as the stage IV supination-eversion fractures, which today have an incidence pattern more typical of a fragility fracture in elderly women.

Cardiac size and function in Paget's disease of bone

We performed non-invasive assessment of cardiac size and function by clinical criteria, standard electrocardiography, chest X-ray, systolic time intervals and echocardiography in 27 patients with Paget's disease of bone and in 20 control subjects. The patients were divided into two groups on the basis of the degree of skeletal involvement (< 15% in Group I and > 15% in Group II). No differences in heart size parameters of left ventricular performance were noted between Group I and controls. Cardiomegaly, increased left ventricular diastolic dimension and increased left ventricular mass indicative of ventricular hypertrophy were found in Group II compared to control subjects. In addition, patients with more extensive skeletal involvement had signs of depressed myocardial contractility, increased left ventricular volumes in diastole and systole and enlarged stroke volume, with no differences in echographic cardiac output compared to Group I and controls. The findings show an above normal incidence of cardiac enlargement and disturbed left ventricular performance in patients with Paget's disease and osseous lesions in > 15% of skeleton. The clinical implications of the altered cardiac function in patients with Paget's disease are briefly discussed.

Gastrointestinal Polyposis in Multiple Myeloma

CLINICALLY evident extraskeletal spread of multiple myeloma is a rarity. We report a case of myeloma beginning as solitary plasmacytoma, with progression to extensive skeletal and extraskeletal involvement, in which the major clinical problems were related to involvement of the gastrointestinal tract. Report of a Case The patient was first seen at the age of 69 years, following the diagnosis of plasmacytoma of the right mandible, which had been established by biopsy of a mandibular mass. Except for pain in the area of the excision, she felt well. Her past medical history included hypertension, one episode of diverticulitis, and treated hypothyroidism. Physical examination results showed a healthy-appearing white woman. The blood pressure was 170/84 mm Hg; respiratory rate, 18/min; pulse rate, 85 beats per minute; and temperature, 36.6 °C. There was a somewhat tender 1- to 2-cm firm swelling on the right mandible near the midline. The recent surgical scar

Extraosseous lesions in plasma cell myeloma: A report of six cases

Six cases of multiple myeloma are presented as examples of extensive soft tissue involvement by plasma cell tumors. The sites of tumor infiltration included the skin, subcutaneous tissues, lungs, spleen, liver, lymph nodes, adrenal glands, intrathoracic soft tissues and retroperitoneal space. Some interesting features observed in this group are discussed: long survival in two cases, acute leukemia occurring as a terminal event in one case, excellent therapeutic responses in two cases and an unexpected preponderance of the A-myeloma type of protein. Extraosseous plasmacytomas may be seen in the presence of typical skeletal lesions of multiple myeloma or in the form of disseminated extramedullary disease. The prognosis in these cases may possibly be somewhat better than that in cases with extensive skeletal involvement in which there is minimal or no soft tissue infiltration by plasmacytoma. Extramedullary plasmacytomas, although relatively infrequent, merit consideration in the differential diagnosis of tumors of the skin and subcutaneous tissues, unexplained lymphadenopathy, hepatosplenomegaly, pulmonary, pleural and mediastinal tumors and even abdominal masses.

Polyostotic Fibrous Dysplasia With Thyrotoxicosis

FEW AUTOPSY examinations have been made on patients with polyostotic fibrous dysplasia. The present report is concerned with an individual (Fig 1) with extensive skeletal involvement with this disorder, who had a small area of cutaneous pigmentation and who, during the course of 18 years of observation, developed and was treated for thyrotoxicosis. The patient had generously willed his body to Baylor University College of Medicine and at his death, from extensive cardiopulmonary disease, autopsy was performed and the entire skeleton was reconstructed (Fig 2-4). This skeleton is now in the Anatomy Museum of that institution and is believed to be the only one in this country. The only other known skeleton of an individual with this disorder is (or was) in Berlin.¹ <h3>Report of a Case</h3> D. C. was first seen in the emergency room of the Jefferson Davis Hospital in 1947 at age 37 because of pain

The circulatory dynamics of polyostotic fibrous dysplasia

Six patients with polyostotic fibrous dysplasia were studied clinically and by cardiac catheter technics. Cardiac enlargement was present in three of the six patients. The resting cardiac index exceeded normal values in five of the six patients. Selective venous sampling revealed narrow A-V oxygen differences across areas of extensive skeletal involvement. It is concluded that the osseous lesions of fibrous dysplasia contain functioning A-V fistulas. Polyostotic fibrous dysplasia may be accompanied by high output cardiac failure. It is concluded that polyostotic fibrous dysplasia is accompanied by circulatory changes qualitatively similar to those found in Paget's disease (osteitis deformans).