Murali Sundaram

Heterotopic ossification: a review

Heterotopic ossification is the formation of bone in the soft tissues. Soft tissue bone deposition may range from the minimal and inconsequential to massive and clinically significant. In some clinical settings it is a predictable finding with an unpredictable course and in other settings it may be diagnostically confounding. Heterotopic ossification may be encountered in clinically disparate disease processes and circumstances. We review the genetic, neurogenic, post-traumatic, post-surgical and “reactive” causes of heterotopic ossification and discuss some current concepts of its pathogenesis.

Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa.

BACKGROUND Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa. METHODS PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1:1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12. RESULTS We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P<0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences. CONCLUSIONS Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. (Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively.).

Primary Ewing’s sarcoma of the vertebral column

ObjectiveTo determine the demographics, imaging findings, clinical symptoms, and prognosis of primary vertebral Ewing’s sarcoma (PVES).DesignA retrospective review of medical records and radiological studies of patients diagnosed with PVES from 1936 through 2001 in our institution and Department of Pathology consultation files was undertaken. Metastatic and soft tissue Ewing’s sarcoma cases were excluded.ResultsFrom a total of 1,277 cases of Ewing’s sarcoma, 125 (9.8%) had a primary vertebral origin. There were 48 females and 76 males. Patient ages ranged from 4 to 54 (mean 19.3, standard deviation 10.7, median 16) years. Vertebral column distribution was four cervical (3.2%), 13 thoracic (10.5%), 31 lumbar (25%), and 67 sacrum (53.2%). More than one vertebral segment was involved in ten cases (8%). Satisfactory imaging studies were available in 51 patients: 49 radiographs, 27 computerized tomography (CT), and 23 magnetic resonance imaging (MRI) studies. The majority of tumors were lytic (93%). Three cases were mixed lytic and sclerotic (6%) and one sclerotic. In the nonsacral spine, the majority of lesions (12/20) involved the posterior elements with extension into the vertebral body. Five cases were centered in the vertebral body with extension into the posterior elements. Two cases were limited to the posterior elements, and one case solely involved the vertebral body. Ala was the most frequently affected site in the sacrum (18/26). Spinal canal invasion was frequent (91%). Detailed clinical information was available in 53 patients. Duration of symptoms ranged from 1 to 30 (mean 7) months. Local pain was the first symptom and seen in all cases. Neurological deficits were present in 21 (40%) cases. All patients received radiation in various dosages; 70% additionally received chemotherapy. Twenty-five patients had surgery, and two patients received bone marrow transplantation. Forty-five patients had follow-up; the five-year disease-free survival probability is 0.53. Disease-free survival probabilities are 0.60 for sacral tumors and 0.45 for nonsacral tumors.ConclusionPVES is an uncommon tumor, usually seen in the second decade of life (mean age 19.3 years) with a male predilection (62%). An aggressive osteolytic lesion, particularly in the sacrum, should raise suspicion for this tumor in adolescents. Prognosis was similar in sacral and nonsacral tumors.

Magnetic resonance imaging of lesions of synovial origin

Three patients with histologically differing lesions of synovial origin and two with synovial cysts, one of which was a dissecting popliteal cyst, were examined by magnetic resonance imaging (MR) and computerized tomography (CT). The three histologically proven synovial lesions were synovial sarcoma, diffuse giant cell tumor of tendon sheath, and synovial chondromatosis. In two of the five patients MR provided better anatomic and morphologic appreciation than CT, while in the others they were of equal value. CT demonstrated calcification in two of the lesions while on MR calcification could be identified in only one patient where it outlined the mass. MR did not demonstrate calcification in the substance of the diffuse giant cell tumor of tendon sheath. Coronal, transverse, and sagittal images of magnetic resonance graphically demonstrated the extent of the soft tissue masses and their relationship to bone, vessels, and soft tissue structures. Synovial sarcoma had a shorter T1 than diffuse giant cell tumor of tendon sheath (these two lesions being of comparable size) and also had a uniformly longer T2. The dissecting popliteal cyst showed the most intense signals on the T1 weighted images, while the uncomplicated synovial cyst showed a long T1. On the T2 weighted images, each type of cyst showed a long T2. The variance and overlap of intensity of MR signals suggest limited specificity in predicting the histologic nature of the synovial lesion.

Magnetic resonance imaging of soft tissue masses: an evaluation of fifty-three histologically proven tumors.

Fifty-three histologically confirmed soft tissue masses in 48 patients were evaluated by magnetic resonance imaging (MR) and computerized tomography (CT). Twenty-three of these were malignant, twenty-three benign and seven of intermediate malignancy (all aggressive fibromatosis). The two procedures were compared for sensitivity and delineation of masses, their relationship to important neurovascular structures, their potential for histological diagnoses, their relative roles in influencing the surgical approach and the preferred modality in the follow-up for detection of tumor recurrence. Both modalities have their relative strengths and weaknesses. However, the superior contrast resolution of magnetic resonance imaging, its demonstration of lesions not clearly identified by CT, its pluridirectional capabilities and its ability to demonstrate large soft tissue tumors in a single coronal or sagittal plane makes it the preferred initial modality for evaluation of the soft tissue tumor of uncertain etiology and also in the follow-up of these patients. Despite MRs superiority in anatomically staging soft tissue tumors it, like CT, is of limited value in characterizing soft tissue sarcomas.

Computed tomography in the diagnosis of blunt thoracic injury

BACKGROUND Computed tomography (CT) is an important diagnostic modality in the evaluation of blunt head and abdominal injuries, but it has not been routinely used to evaluate blunt chest trauma. METHODS One hundred seventy stable patients with blunt thoracic trauma were evaluated with chest x-ray (CXR), and subsequently by CT. RESULTS Of a total of 131 fractures, 53% were identified on initial CXR, 39% on CT, and 26% were not seen on either study. Twenty-one pneumothoraces were seen on CT but not on CXR. Chest tubes were placed in 8 patients and 12 patients were observed without incident. One hemothorax identified by CT scan alone required treatment. Four of 6 diaphragmatic injuries were seen on CT and 2 on CXR. Parenchymal abnormalities were apparent in 189 lung fields on CT and in 66 lung fields on CXR. Most represented atelectasis and did not require treatment. Altogether, CT scanning resulted in changes in management for 11 patients (6%). CONCLUSIONS Although CXR is less sensitive in detecting parenchymal and pleural injuries than CT, the majority of the injuries identified by CT alone are minor and require no treatment. CXR remains the primary modality for diagnostic evaluation of blunt thoracic trauma.

Multicentric giant cell tumor of bone. Clinicopathologic analysis of thirty cases.

BACKGROUND Giant cell tumor of bone accounts for 4% to 5% of primary bone tumors. Approximately 1% of cases present as multiple synchronous or metachronous lesions. In this study, we describe the clinicopathologic features of thirty cases of multicentric giant cell tumor. METHODS Thirty patients who had two or more separate lesions that had been pathologically confirmed to be giant cell tumors were identified. Radiographs were reviewed to evaluate the characteristics and locations of the tumors. Histologic reexamination was performed to document morphologic features. Clinical information and follow-up data were obtained from the medical records. RESULTS The male:female ratio was 1:2, with an average age at presentation of twenty-one years. Fifty-nine percent of the patients were younger than twenty years of age. There were ninety-four tumors in the series, with an average of three (range, two to nine) per patient. Most tumors had arisen in the long bones. Six patients had synchronous ipsilateral involvement of the distal part of the femur and the proximal part of the tibia. Radiographically, the tumors in long bones manifested as expansive lytic lesions involving the metaphysis and extending into the epiphysis. A minority of the tumors were confined to the metaphysis, had features of a fibro-osseous or bone-forming lesion, or arose in skeletally immature patients. Secondary histopathologic changes including fibrohistiocytic regions, reactive bone formation, or aneurysmal bone cyst-like changes were not uncommon. Most tumors were treated with curettage (64%) or resection (22%). The recurrence rate was similar to that of solitary giant cell tumors. Metastatic disease developed in three patients, and two patients had malignant transformation. CONCLUSIONS Multicentric giant cell tumors occur more often in younger patients than do solitary giant cell tumors, and they frequently present as synchronous lesions around the knee. Some tumors appear as bone-forming or fibro-osseous tumors on imaging studies as a result of fibrohistiocytic regions and reactive bone formation. The risk of recurrence depends on the type of surgery that is performed. LEVEL OF EVIDENCE Therapeutic Level IV.

T1-weighted MR imaging for distinguishing large osteolysis of Paget's disease from sarcomatous degeneration

Abstract  Objective. To report five symptomatic patients, four with unequivocal Paget’s disease and large areas of osteolysis and one patient with presumed osteolytic Paget’s disease, evaluated by MR imaging to confirm or exclude a sarcoma.Design and patients. Four men and one woman (median age 74 years) presented with new symptoms of pain. Four of these patients had unequivocal Paget’s disease with large areas of osteolysis; one patient presented with large focal osteolysis and no other finding. MR imaging was performed in each case to exclude malignancy in the area of osteolysis. Results. Two patients whose MR images showed a low signal abnormality on the T1-weighted sequence corresponding to osteolysis on the radiograph were found to have malignant degeneration. Three patients with osteolytic lesions on T1-weighted MR imaging showed preservation of fat signal in the areas of osteolysis, were not biopsied and have been free of malignant disease for from 12 months to 21/2 years. One patient had one area of osteolysis in the iliac bone which showed malignancy and another area of osteolysis which showed preservation of fat signal on the T1-weighted sequence. Conclusions. The information obtained from T1-weighted MR imaging sequences performed on patients with Paget’s disease who have new symptoms and large areas of osteolysis could reliably be used in the clinical decision-making process between conservative follow-up and biopsy.

Magnetic resonance imaging in planning limb-salvage surgery for primary malignant tumors of bone.

In defining the linear extent of a malignant tumor in a long bone, radiographs, computerized tomography, and scintigraphy are routinely employed, especially when non-ablative surgery is being considered. The drawbacks of these modalities in defining the true intracompartmental extent of disease within a bone can largely be overcome with the use of magnetic resonance imaging. We did a prospective analysis of magnetic resonance imaging in sixteen consecutive patients with a primary malignant tumor of a long bone, and it showed that this modality has clinical promise of being more precise than the other modalities in defining the true proximal and distal extent of a tumor in a long bone. Coronal images permit easier planning of surgical techniques for salvage of a limb using an allograft than do a multiplicity of transverse images.

Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment

Quantification of disease severity supports the development of evidence‐based treatments. Assessments to capture clinical improvement in hidradenitis suppurativa (HS) can be improved.