Primary schwannoma of the bone: a clinicopathologic and radiologic study of 17 cases.

Primary schwannoma of the bone, defined as arising within the medullary cavity and radiologically mimicking more common primary bone tumors, is rare. We present 17 tumors, 13 conventional schwannomas, and 4 melanotic type. Collectively, they represented <1% of all primary bone tumors seen at Mayo Clinic over a 33-year period. Most tumors affected long bones. There was a slight female predilection. Fifteen tumors were sporadic, and 2 were syndrome associated (Carney complex). Pain was the most common symptom. Given their rarity, schwannomas of the bone are not usually included in the differential diagnosis of primary osseous spindle cell tumors. Thus, they are prone to misdiagnosis and overtreatment. Similar to their more common extraosseous counterparts, primary schwannomas of the bone behave in a benign manner and are successfully treated by local excision alone.

Benign bone tumors--recent developments.

Benign bone tumors frequently pose a diagnostic challenge for general surgical pathologists. Accurate pathologic diagnosis requires careful clinical and radiological correlation. The most significant recent advances in some benign bone tumors have occurred at the molecular and cytogenetic level. The detection of clonal chromosomal aberrations, various specific molecular genetic events, and the description of the bone cell signaling pathways in the field of osteoimmunology have provided a better understanding of the pathophysiology of certain tumors and an important aid in the diagnostic workup and differential diagnosis of some bone lesions demonstrating overlapping clinical and pathologic features. Future directions include prognostic and therapeutic applications of these findings. Newer less invasive therapeutic techniques and medical management have been developed for the treatment of certain benign bone tumors.

Metastasizing (malignant) ameloblastoma: review of a unique histopathologic entity and report of Mayo Clinic experience.

PURPOSE: To provide a comprehensive review of metastasizing (malignant) ameloblastoma, establish a new baseline of valid cases using histologic criteria and minimum documentation, and report 3 cases from the Mayo Clinic files. PATIENTS AND METHODS: Ninety-eight original reports of "metastasizing," "malignant," or "atypical" ameloblastoma were reviewed. The following data were gathered for reports that demonstrated well-differentiated ameloblastoma at the metastatic site: gender, ethnicity, age at time of primary tumor diagnosis, histologic pattern of primary tumor, anatomic sites of primary and metastatic tumors, interval from diagnosis of primary to diagnosis of metastasis, number of recurrences preceding metastasis, treatment responses to radiation and/or chemotherapy, presence of hypercalcemia, and length of survival after metastasis. RESULTS: Twenty-seven valid reports of metastasizing (malignant) ameloblastoma were identified; 81% originated in the mandible, recurring on average 4 times before metastasis. Lungs were the initial site of metastasis in 78% of reports, of which 71% were bilateral. The average time from diagnosis of primary to metastasis was 18 years. Over half of the patients were alive and had survived an average of 10 years since diagnosis of metastasis. Those patients who had succumbed to their disease had an average survival time of 3 years after diagnosis of metastasis. CONCLUSIONS: Metastasis of well-differentiated ameloblastoma occurs more rarely than previously believed. Metastasis to the lungs bilaterally, by the hematogenous route, usually follows multiple failed attempts at primary tumor control. The absence of malignant cytologic transformation correlates with relatively indolent metastatic site growth. Treatment of metastasizing (malignant) ameloblastoma should include close observation, thoracotomy with wedge resections, or experimental chemotherapeutic combinations.

International collaborative study on ghost cell odontogenic tumours: calcifying cystic odontogenic tumour, dentinogenic ghost cell tumour and ghost cell odontogenic carcinoma.

BACKGROUND: Calcifying odontogenic cyst was described first by Gorlin et al. in 1962; since then several hundreds of cases had been reported. In 1981, Praetorius et al. proposed a widely used classification. Afterwards, several authors proposed different classifications and discussed its neoplastic potential. The 2005 WHO Classification of Odontogenic Tumours re-named this entity as calcifying cystic odontogenic tumour (CCOT) and defined the clinico-pathological features of the ghost cell odontogenic tumours, the CCOT, the dentinogenic ghost cell tumour (DGCT) and the ghost cell odontogenic carcinoma (GCOC). METHODS: The aim of this paper was to review the clinical-pathological features of 122 CCOT, DGCT and GCOC cases retrieved from the files of the oral pathology laboratories from 14 institutions in Mexico, South Africa, Denmark, the USA, Brazil, Guatemala and Peru. It attempts to clarify and to group the clinico-pathological features of the analysed cases and to propose an objective, comprehensive and useful classification under the 2005 WHO classification guidelines. RESULTS: CCOT cases were divided into four sub-types: (i) simple cystic; (ii) odontoma associated; (iii) ameloblastomatous proliferating; and (iv) CCOT associated with benign odontogenic tumours other than odontomas. DGCT was separated into a central aggressive DGCT and a peripheral non-aggressive counterpart. For GCOC, three variants were identified. The first reported cases of a recurrent peripheral CCOT and a multiple synchronous, CCOT are included. CONCLUSIONS: Our results suggest that ghost cell odontogenic tumours comprise a heterogeneous group of neoplasms which need further studies to define more precisely their biological behaviour.

Juxtacortical chondromyxoid fibroma of bone: a unique variant: a case study of 20 patients.

BACKGROUND: Chondromyxoid fibroma (CMF) is a rare neoplasm of the appendicular skeleton of young adults. We report 20 cases of a poorly recognized subtype which arises on the surface of long bones and erodes the cortical surface causing a periosteal reaction. This entity should be included in the differential diagnosis of bone surface lesions as it may be mistaken for a more aggressive neoplasm. DESIGN: A retrospective review at the Mayo Clinic identified 259 CMF cases, 13 of which were parosteal. Additionally, 2 cases were diagnosed at the University of Alabama at Birmingham and 5 cases were from one of our authors' files. We reviewed the clinical radiographic and pathologic findings of all 20 cases. RESULTS: Juxtacortical CMF occurred over a large age range (12 to 82 y) with a median age of 40.2 years. A slight male predilection (5:4) was seen. The most common presentation was bone pain. All 20 cases showed solitary, radiolucent surface lesions with sclerotic margins and extension into the overlying soft tissues. Most of the lesions were in the proximal tibial metaphysis. Histologically, the tumors had characteristic features of CMF. Several cases contained distinctive areas of calcification, which is not a feature of conventional CMF. Eleven of 12 cases were cured with simple excision. CONCLUSION: CMF should be included in the differential diagnosis of bone surface lesions. The clinical and radiologic findings must be known. The morphology of this lesion is similar to conventional CMF with the exception of focal exuberant calcification. Conservative therapy is the treatment of choice.

Sonication of removed hip and knee prostheses for diagnosis of infection.

BACKGROUND: Culturing of samples of periprosthetic tissue is the standard method used for the microbiologic diagnosis of prosthetic-joint infection, but this method is neither sensitive nor specific. In prosthetic-joint infection, microorganisms are typically present in a biofilm on the surface of the prosthesis. We hypothesized that culturing of samples obtained from the prosthesis would improve the microbiologic diagnosis of prosthetic-joint infection. METHODS: We performed a prospective trial comparing culture of samples obtained by sonication of explanted hip and knee prostheses to dislodge adherent bacteria from the prosthesis with conventional culture of periprosthetic tissue for the microbiologic diagnosis of prosthetic-joint infection among patients undergoing hip or knee revision or resection arthroplasty. RESULTS: We studied 331 patients with total knee prostheses (207 patients) or hip prostheses (124 patients); 252 patients had aseptic failure, and 79 had prosthetic-joint infection. With the use of standardized nonmicrobiologic criteria to define prosthetic-joint infection, the sensitivities of periprosthetic-tissue and sonicate-fluid cultures were 60.8% and 78.5% (P<0.001), respectively, and the specificities were 99.2% and 98.8%, respectively. Fourteen cases of prosthetic-joint infection were detected by sonicate-fluid culture but not by prosthetic-tissue culture. In patients receiving antimicrobial therapy within 14 days before surgery, the sensitivities of periprosthetic tissue and sonicate-fluid culture were 45.0% and 75.0% (P<0.001), respectively. CONCLUSIONS: In this study, culture of samples obtained by sonication of prostheses was more sensitive than conventional periprosthetic-tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection, especially in patients who had received antimicrobial therapy within 14 days before surgery.

Does local recurrence impact survival in low-grade chondrosarcoma of the long bones?

We hypothesized local recurrence of Grade 1 chondrosarcoma in the long bones of the extremity negatively influences survival. To explore that notion, we retrospectively reviewed 164 patients treated surgically for Grade 1 chondrosarcoma of the long bones. Local recurrence occurred in 21 (13%) patients. Four patients had progression of tumor grade on recurrence, and six patients had more than one local recurrence. Seven of the 21 patients with local recurrences had metastasis. Six of the 21 patients with local recurrences died secondary to chondrosarcoma. Local recurrence, progression of grade at recurrence, and distant metastases all were associated with a decrease in overall survival. The difference in survival was not apparent until after 5 years and was more pronounced after 10 years. Recurrence may be regarded as a declaration of an aggressive phenotype and should be treated as such.

Total en bloc spondylectomy of C5 vertebra for chordoma.

STUDY DESIGN: En bloc resection of a chordoma of the C5 vertebra with wide surgical margins. OBJECTIVE: To present the surgical technique of total spondylectomy for a chordoma of the C5 vertebral body. SUMMARY OF BACKGROUND DATA: Malignant bone tumors require wide resection. Wide resection by total en bloc spondylectomy is difficult or not feasible for malignant vertebral tumors of the cervical spine due to the peculiar anatomic complexity of this region, including the vertebral arteries and the neural structures. There are no previous reports of en bloc resection of cervical spine tumors with wide surgical margins. METHODS: Using staged posterior and anterior approaches, a total en bloc spondylectomy and spine arthrodesis was performed. En bloc excision of a C5 chordoma was achieved using a threadwire T-saw (Tomita and Kawahara, Kanazawa, Japan) with surgical margins free of tumor. The patient received postoperative adjuvant proton beam radiation therapy. RESULTS: The patient remains disease-free 9 years after the operation. CONCLUSION: Total en bloc spondylectomy with wide surgical margins is feasible for malignant bone tumors of the cervical spine.

Periosteal osteosarcoma: long-term outcome and risk of late recurrence.

The long-term outcome of periosteal osteosarcoma is not well defined. We sought to examine the disease-specific survival and risk of late recurrence or dedifferentiation in a cohort of 29 patients with average of 15.8 years followup. Disease-free survival was 83%, with five patients dying of disease at an average of 26 months after presentation. Survival was similar with respect to anatomic location, pathologic grade, and limb-salvage resection. All instances of local recurrence, metastatic disease, and death occurred within 3 years after presentation. There were no instances of dedifferentiation. Long-term disease-free survival is possible after resection of the local recurrence. Limb-salvage therapy seems to offer survival equivalent to amputation, and there does not seem to be a substantial risk of late recurrence, dedifferentiation, or disease progression.

Survivorship analysis in patients with periosteal chondrosarcoma.

UNLABELLED: To investigate outcome and identify prognostic factors, we retrospectively reviewed 24 consecutive patients with periosteal chondrosarcomas. There were 17 males and seven females with a mean age of 37.6 years (range, 15-73 years). The femur was involved in 12 patients, the proximal humerus in five, the tibia in two, and the distal fibula, ilium, pubis, metatarsal, and rib in one patient each. The mean greatest dimension of the lesions was 8.1 cm (range, 1.5-27 cm). Based on the histologic pattern, there were 18 Grade 1 tumors and six Grade 2 tumors. All patients were treated surgically. Two patients had intralesional excisions, five patients had marginal excisions, and 17 patients had wide resections. With a mean followup of 17 years (range, 28 months-47 years), seven of 24 patients (29%) had one or more local recurrences. The 5-year local recurrence-free survival was less in patients treated with intralesional or marginal excisions (25%) than for patients treated with wide resections (93%). At the latest followup, six of 24 patients (25%) had died of pulmonary metastases. The overall 5-year metastasis-free survival was 83%. The 5-year metastasis-free survival was less for patients with Grade 2 tumors (50%) than for patients with Grade 1 tumors (94%). LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

Lateral malleolus en bloc resection and ankle reconstruction for malignant tumors.

UNLABELLED: Four children and six adults required en bloc resection of the lateral malleolus for malignant tumors. There were four osteosarcomas, three chondrosarcomas, two Ewing's sarcomas, and one adamantinoma. Surgical margins were wide in seven patients, marginal in two, and intralesional in one. A primary ankle arthrodesis was done in four adults and bracing without any reconstruction was done in four children and two adults. During a mean followup of 14.5 years (range, 3-30 years), there were two local recurrences (two of 10 patients) after a marginal excision and an intralesional excision. One patient had reoperation for a skip osteosarcoma lesion in the proximal fibula. Other complications included chronic osteomyelitis, a lateral talus subluxation and cavovarus deformity, and recurrent ankle instability and degenerative changes of the ankle. At the latest followup, all 10 patients showed no evidence of disease. Five patients who had primary or late ankle arthrodesis had a Musculoskeletal Tumor Society and International Society of Limb Salvage functional score of 28 points (92%), and two adolescents who had postoperative bracing alone had a functional score of 24 points (80%). The three remaining patients had a salvage amputation. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series--no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

Imaging findings in desmoplastic fibroma of bone: distinctive T2 characteristics.

OBJECTIVE: The purpose of this study was to evaluate the imaging features of desmoplastic fibroma of the bone, with an emphasis on MRI signal characteristics. CONCLUSION: Significant T2 shortening of a nonsclerotic fibroosseous lesion should place desmoplastic fibroma high among the diagnostic considerations.

Intratumoral administration of a 1,2-dimyristyloxypropyl-3- dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma.

BACKGROUND: Leuvectin (Vical Inc., San Diego, CA) is a gene transfer product in which a plasmid encoding the human interleukin-2 (IL-2) gene is complexed with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). In the current study, the authors investigated the safety and efficacy of in situ vaccination with Leuvectin in patients with metastatic renal cell carcinoma. METHODS: Thirty-one patients with metastatic renal cell carcinoma were treated with intratumorally administered Leuvectin at doses ranging from 0.75 to 4 mg. These patients subsequently were evaluated for response and for treatment-related toxicity. RESULTS: Treatment was well tolerated: no Grade 3 or 4 toxicities were observed in association with the study agent. Documented side effects included Grade 1 pain at the injection site (20%); mild (i.e., Grade 1 or 2) constitutional symptoms, including malaise/myalgia, low-grade fever, and chills (74%); Grade 1 fatigue (19%); Grade 1 or 2 nausea (10%); and Grade 2 allergy (1 occurrence). Two patients experienced partial responses, which endured for 32 months and 6 years, respectively, and 1 patient currently is experiencing a pathologic complete response, which, to date, has persisted for 50 months; thus, the overall response rate was 10%. In addition, 7 patients (23%) experienced disease stabilization for a median of 8 months (range, 4-48 months). The median duration of survival from the start of Leuvectin treatment was 11 months (range, 2-72 months), with a 1-year survival rate of 48% and a 3-year survival rate of 19%. Laboratory analysis of tumor samples revealed the presence of IL-2 plasmid DNA in six of eight patients posttreatment, increased IL-2 expression in tumor cells in four of eight patients posttreatment, and increased tumor infiltration by CD8-positive lymphocytes in five of eight patients posttreatment. CONCLUSIONS: Immunotherapy with intratumorally administered Leuvectin is safe and can lead to durable objective responses in patients with metastatic renal cell carcinoma.

Traumatic events and symptoms of post-traumatic stress disorder amongst Sudanese nationals, refugees and Ugandans in the West Nile.

OBJECTIVES: To compare the incidence of traumatic events and its association with symptoms of post-traumatic stress disorder in three population groups in northern Uganda and southern Sudan. METHODS: Household and individual level data collected through a single-round cross-sectional demographic survey. SETTING: The sub-counties of Yivu, Odupi and Midia in the northern Ugandan district of Arua and of Otogo in Yei River district in southern Sudan. PARTICIPANTS: Residents of these Ugandan and Sudanese sub-counties were categorized on the basis of citizenship and refugee status (i.e. as Ugandan nationals, Sudanese nationals or Sudanese refugees). The random sample population consisted of 3,323 adults (mean age: 30 years; 75% female) from 1,831 national and refugee households. RESULTS: Sudanese refugees reported the highest number of violent events experienced or witnessed ever and in the past one year . Witnessing of traumatic events, ever and in the past year , significantly predicted PTSD in surveyed population. Sex, age, education and occupation were also significantly associated with the development of PTSD symptoms. The population prevalence of PTSD was estimated to be 48% for Sudanese stayees, 46% for Sudanese refugees and 18% for Ugandan nationals. CONCLUSIONS: Symptoms of PTSD in war-affected Sudanese populations can be partly explained by traumatic event exposures. The high prevalence of violence and symptoms of PTSD in refugee populations highlight the need for better protection and security in refugee settlements. Humanitarian agencies must consider the provision of mental health services for populations affected by war and forced migration.

Chondroblastoma of the hands and feet.

OBJECTIVE: To review the imaging findings, age and gender distribution of chondroblastoma of the hands and feet. DESIGN AND PATIENTS: Twenty-five cases of pathologically proven chondroblastoma of the hands and feet were reviewed. Available imaging modalities included radiographs (n=24), CT (n=3), MRI (n=5), and radionuclide bone scintigraphy (n=1). The following imaging features for each case were tabulated: location, presence of sclerotic margin, calcification, expansion, presence of fluid/fluid levels on cross-sectional imaging and surrounding edema on MRI. The images were evaluated for skeletal maturity using closure of the physeal plate in the region as a standard. RESULTS: The average age at time of diagnosis was 23 years (range 7-57 years). Eighty-four percent (n=21) of the patients were skeletally mature. Males (20 of 25) outnumbered females by a ratio of 5:1. The bones of the foot accounted for 22 cases: calcaneus (n=8), talus (n=8), metatarsals (n=3), and the cuboid (n=3). The bones of the hand accounted for three cases: phalanx (n=1), triquetrum (n=1), and a metacarpal (n=1). Radiographically all lesions were osteolytic with identifiable calcification in 54% (13 of 24). Fluid/fluid levels were seen in four of five cases on MRI. Edema on MR images was seen in 40% (2 of 5). The size of the lesions ranged from 2 to 41 cm(2). CONCLUSION: Chondroblastomas of the hands and feet share many of the radiographic characteristics seen in the long bones, but manifest in skeletally mature patients with a higher male to female ratio than in long bone chondroblastoma. Talar and calcaneal lesions were encountered only in males. Chondroblastoma of the wrist and hand appears to be exceptionally rare.

Radiographic differentiation of enchondroma from low-grade chondrosarcoma in the fibula.

To evaluate demographic and radiographic features that may differentiate between enchondroma and low-grade chondrosarcoma of the fibula. The radiographs of ninety-three histologically-confirmed cartilaginous tumors of the fibula were retrospectively reviewed along with demographic information as to patient age and gender. Fifty-four enchondromas and thirty-nine low-grade chondrosarcomas were included in the study. Multiple previously-established radiographic features distinguishing enchondroma from chondrosarcoma were evaluated in each fibular tumor in a consensus manner by two experienced, board-certified and fellowship-trained musculoskeletal radiologists. Five radiographic features were shown to statistically favor chondrosarcoma over enchondroma in the fibula. These were soft-tissue mass ( p<0.0001), periosteal reaction ( p=0.008), cortical disruption in the juxta-articular fibula ( p=0.0133), cortical thickening ( p=0.032), and tumor size greater than 4 cm ( p=0.0046). No statistically-significant demographic differences were found between patients with enchondroma and chondrosarcoma of the fibula. When two or more of the identified features of malignancy are identified in the same patient, chondrosarcoma is 2.4 times more likely than in those patients exhibiting none of the features of malignancy. Soft-tissue mass, periosteal reaction, cortical disruption in the juxta-articular fibula, cortical thickening, and tumor size greater than 4 cm indicate chondrosarcoma over enchondroma of the fibula. Radiographs demonstrating more than one of the identified malignant features are more likely to be due to chondrosarcoma than radiographs demonstrating none or only one of the identified features. No unique malignant features of chondrosarcoma in the fibula were observed when compared to previous descriptions of these tumors in the long and short tubular bones of the appendicular skeleton.

Diagnosis of high-grade osteosarcoma by radiology and cytology: a retrospective study of 52 cases.

The diagnostic value of combined radiology and fine needle aspiration cytology (FNAC) was retrospectively assessed in a consecutive series of 52 patients with high-grade osteosarcoma. The series was divided into typical and atypical osteosarcomas according to radiological features and site. Thirty-two of 33 radiologically typical osteosarcoma cases were correctly diagnosed by cytology; one lesion was diagnosed as sarcoma NOS. Nineteen osteosarcoma cases were radiographically atypical. Six of these were diagnosed as osteosarcoma and another six as sarcoma NOS. In three cases another type of sarcoma was suggested. One case was falsely classified as benign. FNAC of three cases were non-diagnostic. Overall, the diagnostic difficulties pertained to the radiologically atypical cases. Notably, four of these also posed considerable difficulties in the histopathological assessment prompting external consultation. Our study suggests that open biopsy can be obviated in high-grade osteosarcomas exhibiting typical radiological features, i.e., in two-thirds.

Metastatic chondroblastoma with elevated creatine kinase and paraneoplastic neurologic autoimmunity.

A 17-year-old girl presented with chondroblastoma of the fibula and pulmonary metastases. Serum creatine kinase (CK) was elevated for a decade preoperatively and fell to near normal after tumor excision. An episode of aseptic meningitis 3 months later led to serologic detection of three antibody markers of paraneoplastic neurologic autoimmunity that in adult patients are characteristic of thymoma and lung carcinoma: muscle-type acetylcholine receptor (AChR) autoantibody (Ab), type 2 Purkinje cell cytoplasmic Ab (PCA-2), and collapsin response-mediator protein-5-IgG (CRMP-5-IgG). Locally recurrent chondroblastoma was excised 1 year later. Serum CK was elevated, CRMP-5-IgG was positive, PCA-2 was lower, and AChR Ab was undetectable. Three years after diagnosis she has stable pulmonary metastases, with elevated CK, higher PCA-2, positive CRMP-5-IgG, and undetectable AChR Ab. The association of metastatic chondroblastoma, elevated CK, and an evolving profile of paraneoplastic autoantibodies reveals a previously unrecognized immunobiologic dimension of chondroblastoma.

Dedifferentiation in low-grade mucoepidermoid carcinoma of the parotid gland.

Mucoepidermoid carcinoma (MEC), a common malignant salivary gland neoplasm, is generally divided into low-, intermediate-, and high-grade types according to the histologic features. To our knowledge, the present report describes the first case of dedifferentiation occurring in a low-grade MEC. A 55-year-old man presented with a biphasic neoplasm of the right parotid gland composed of low-grade MEC and dedifferentiated high-grade anaplastic undifferentiated carcinoma. Immunohistochemically, carcinoembryonic antigen expression was restricted to the low-grade MEC portion. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade component. On image cytometric analysis, the low-grade MEC was diploid, whereas the dedifferentiated carcinoma was aneuploid. Although the patient was alive 10 years after the initial diagnosis, the tumor has recurred twice, at 3 months and 7 months after the initial resection. It is important to recognize that dedifferentiation can occur in a low-grade MEC, similar to other low-grade salivary gland carcinomas.