Relapsed chronic lymphocytic leukemia with a cardiac mass: A case report.

Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in the USA. Extra-medullary disease is very rare and is not well characterized. In practice, clinically significant cardiac or pericardial involvement by CLL is extremely rare with only a few case reports in literature. We report a 51-year-old male patient with a past medical history of CLL in remission, who presented with fatigue, dyspnea on exertion, night sweats and left supraclavicular lymphadenopathy. Laboratory investigations were notable for leukopenia and thrombocytopenia. Due to high suspicion of an underlying malignant process, a full body computerized tomography (CT) scan was obtained and showed an 8.8 cm soft tissue mass-like lesion occupying the majority of the right atrium and extending into the right ventricle, with probable pericardial involvement. Enlarged left supraclavicular and mediastinal lymph nodes were also present and had a mild mass effect on the traversing left internal thoracic artery and left pulmonary artery. A transesophageal echocardiogram and cardiac magnetic resonance imaging (MRI) were done to better characterize the cardiac mass. They confirmed a large infiltrating mass (measuring 10 × 7.4 cm) in the right atrium and ventricle, extending into the inferior vena cava inferiorly and coronary sinus posteriorly. A left supraclavicular excisional lymph node biopsy was performed and histopathology was consistent with Small Lymphocytic Lymphoma (SLL)/CLL. This case represents one of the few known cases of cardiac extramedullary-CLL presenting with an isolated cardiac mass. Further studies are needed to characterize the course of the disease, prognosis and optimum management along with the role of surgery.

Outpatient administration of BEAM conditioning prior to autologous stem cell transplantation for lymphoma is safe, feasible, and cost-effective.

High-dose BEAM chemotherapy (BCNU, etoposide, Ara-C, and melphalan) followed by autologous hematopoietic stem cell transplantation is frequently used as consolidative therapy for patients with recurrent or refractory Hodgkin or non-Hodgkin lymphoma. The BEAM regimen has traditionally been administered over 6 days in the hospital, with patients remaining hospitalized until hematologic recovery and clinical stability. In an effort to reduce the length of hospitalization for these patients, our institution has transitioned from inpatient (IP) to outpatient (OP) administration of BEAM conditioning. Here, we report the results of an analysis of the feasibility, cost, complications, and outcomes for the initial group of patients who received OP BEAM compared to a prior cohort of patients who received IP BEAM. Patient and disease characteristics were comparable for the two cohorts, as were engraftment kinetics. Length of hospital stay was reduced by 6 days for the OP cohort (P < 0.001), resulting in a cost savings of more than $17,000 per patient. Fewer complications occurred in the OP cohort, including severe enteritis (P = 0.01), organ toxicities (P = 0.01), and infections (P = 0.04). Overall survival rate up to 3 years posttransplant was better for the OP cohort (P = 0.02), likely due to differences in posttransplant therapies. We conclude that OP administration of BEAM conditioning is safe and may offer significant advantages, including decreased length of hospitalization, reduced costs, decreased risks for severe toxicities and infectious complications, and likely improvement in patient satisfaction and quality of life.

Aneurysmal bone cysts of the vertebrae.

PURPOSE: To review records of 14 patients with aneurysmal bone cysts (ABCs) of the spine. METHODS: Using the Scottish Bone Tumour Registry for the period of October 1952 to November 2005, records of 9 females and 5 males aged 8 to 63 (mean, 25.3) years who had ABCs of the spine and were followed up for a mean of 7.1 years were reviewed. RESULTS: The most commonly involved site was the lumbar vertebrae (n=6), followed by the thoracic (n=4), cervical (n=3), and sacral (n=1) vertebrae. The mean duration of symptoms at presentation was 8.8 (range, 0.3-24) months. The symptoms included gradually increasing pain in the back (n=14), a palpable spinal mass (n=4), spinal deformity (n=2), and neurological deficits (n=5). All the patients underwent surgery: intra-lesional excision (curettage) without bone grafting (n=3), excision (n=7, 2 of whom had adjuvant radiotherapy), and open excisional biopsy (n=4, 2 of whom had iliac crest bone grafting). One patient with a cervical ABC underwent preoperative angiographic embolisation. Another patient with a sacral ABC underwent percutaneous sclerotherapy. Two patients had recurrence. One had recurrence within 4 months and underwent adjuvant radiotherapy; another had recurrence 16.8 years later and underwent repeat curettage. No major complications were encountered. CONCLUSION: Most ABCs of the spine occurred in young females. Intra-lesional excision was an effective treatment.

Use of eltrombopag, a thrombopoietin receptor agonist, in post-transplantation thrombocytopenia.

Persistent thrombocytopenia after stem cell transplantation can lead to increased morbidity and mortality [1,2]. The underlying causes are often multifactorial in this patient population [3,4]. In autologous transplantation, thrombocytopenia is usually a result of poor engraftment or a sign of impending disease relapse. In allogeneic stem cell transplantation, the etiology is often more complex with engraftment deficits, medication effects, graft versus host disease (GVHD), and other immunologic processes potentially contributing. Eltrombopag is an orally available nonpeptide thrombopoietin (TPO) receptor agonist which interacts with the transmembrane domain of the receptor on bone marrow megakaryocytes and upstream progenitor/stem cells. It has been studied in patients with chronic idiopathic thrombocytopenic purpura [5] and in patients with thrombocytopenia secondary to hepatitis C infection [6]. Unlike the case with recombinant human TPO, its use has not been associated with anti-platelet antibody production [7]. We report two cases of post-transplantation thrombocytopenia, one allogeneic and one autologous, where eltrombopag was given to treat prolonged thrombocytopenia. The use of eltrombopag in these two cases was effective in elevating platelet counts to levels that eliminated the need for platelet transfusions.

Ewing's Sarcoma of the Zygomatic Arch Presenting in a 69-Year Old: An Unusual Case Report.

Objective. We report a rare case of Ewing's sarcoma of the zygomatic arch presenting in a 69-year-old patient. Method. Case report and a review of the world literature on Ewing's sarcoma incidence and management. Results. Ewing's sarcoma is a malignant round cell tumour of neuroectodermal origin that typically presents in the pelvis and long bones of children and adolescent boys. This report is the first to document the presentation of ewing's sarcoma of the zygomatic arch in a 69-year-old lady. Our patient underwent surgical excision and radiotherapy and at 4-year followup has no signs of recurrence or metastasis. Conclusion. To our knowledge this is the first case report to document Ewing's sarcoma of this location in a 69-year-old patient. This case report highlights the importance of diagnostic investigations in Ewing's sarcoma and discusses the management issues that this rare presentation raises.

Predictive factors for recurrence of simple bone cyst of the proximal humerus.

PURPOSE: To evaluate factors predictive of recurrence following curettage of simple bone cysts (SBCs) in the proximal humerus. METHODS: Records of 29 male and 3 female patients aged 3 to 22 (mean, 11) years who underwent curettage with or without bone grafting for a solitary SBC in the proximal humerus were reviewed. The appearance, size, location, activity level, and fracture pattern of each cyst were recorded. The cyst index indicated the risk of refracture. Recurrence was defined as a refracture or enlargement of the cyst. RESULTS: 31 patients presented with a pathological fracture. The main symptoms were pain (n=30), loss of function (n=22), and mass/swelling (n=15). 25 patients gave a history of trauma. The duration of symptoms was less than one month. 10 patients had recurrence after a mean of 10 (range, 4-27) months; 5 were refractures and another 5 were enlargement of the cysts. Six were treated conservatively and eventually healed, whereas 4 underwent further curettage. Factors predictive of recurrence were patient age 5 years or younger (p=0.014), right-sided cyst (p=0.01), larger cyst (p=0.039), multilocular cyst (p=0.004) and unimpacted fracture (p=0.04). Recurrence was not related to gender, cyst location, or cyst activity level. CONCLUSION: Most SBCs heal even if the fracture is treated expectantly. SBCs should be left alone unless symptomatic. If curettage is performed, grafts or bone substitutes should be used. More aggressive treatment might be necessary for unimpacted fractures to minimise the risk of recurrence.

Osteoclast-like giant cell tumor arising in the soft tissue of the breast: report of a case.

Extraosseous manifestations of osteoclast-like giant cell tumors (OGCTs) in soft tissue are unusual, especially in the breast. However, multinucleated osteoclast-like giant cells have been described in association with epithelial malignancy, as a variant of breast carcinoma. We report a case of OGCT of the soft tissue of the breast, not associated with epithelial elements. To the best of our knowledge, this is only the second such case reported.

Imatinib in the management of multiple gastrointestinal stromal tumors associated with a germline KIT K642E mutation.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gut and are distinguished by expression of CD117 (c-Kit). Oncogenic mutations in the KIT or PDGFRA gene are detected in approximately 85% of sporadic GISTs. In recent years, examples of familial GIST have been reported in which germline mutations of KIT or PDGFRA result in multiple GISTs, skin disorders, and other abnormalities. The most common germline mutations are in KIT exon 11, mutations in exons 8 and 17 have also been described, and there are 2 families with germline PDGFRA mutations. We present a case in which a germline KIT exon 13 mutation (K642E) was discovered in a patient with multiple GISTs of rectum, small intestine, and esophagus, as well as diffuse hyperplasia of the interstitial cells of Cajal. To our knowledge, this is only the second germline example of this particular mutation. The patient's esophageal tumors were stabilized with imatinib.

Tumours of the hand presenting as pathological fractures.

Tumours represent one of the important differential diagnoses that need to be considered while investigating fractures of the small bones of the hand, as this can sometimes be the sole or the first presenting complaint. We conducted a retrospective study of the Scottish Bone Tumour Registry, analysing the records of patients with hand tumours which primarily presented as pathological fractures. The registry held records of 233 patients with tumours involving the bones of the hand, of which 53 (22.7%) had pathological fractures as the first presenting complaint. The average age at presentation was 36.9 yrs. The proximal phalanx was the most common bone involved (50.9%). The distal phalanx rarely developed pathological fractures due to tumours (5.3%). Most of the lesions affected the fifth ray (43.9%) Chondroma was the most common tumour seen (43 patients). Malignant lesions were an infrequent cause of pathological fractures (7 chondrosarcomas and 1 Ewing's sarcoma). Tumours are less commonly seen as a cause of fractures in the hand with most such fractures initially treated as minor injuries with buddy strapping and early mobilisation. A carefully obtained history and study of radiographs is essential to diagnose these lesions.

Pigmented villonodular synovitis of the foot and ankle: Forty years of experience from the Scottish bone tumor registry.

Fourteen cases of pigmented villonodular synovitis (PVNS) of the foot and ankle accrued from the Scottish Bone Tumor Registry are presented with an average follow-up of 4.6 years. This study analyzed the clinical, radiological, and histopathological features and investigated their clinical behavior and the factors influencing recurrence. The mean age of the patients was 26.4 years (range, 8-52 years). There were 8 women and 6 men. The mean delay in presentation was 10.3 months. The anatomical sites were phalanges (n = 2), tarso-metatarsal area (n = 3), and hindfoot (n = 9) (6 extraarticular soft tissue swellings around the ankle, 2 ankle, 1 subtalar joint). Eight (57.1%) cases presented with a painless lump, 5 (35.7%) patients had painful masses, and 1 case had a lump associated with toe deformity. Peri-articular tissue invasion and cortical infiltration were found in one third on plain films. Magnetic resonance imaging findings were suggestive of synovial sarcoma in 2 cases because of extensive low-signal soft tissue hypertrophy and bone erosion. Excision of the lump was performed in 4 cases with a complete recovery. Phalangeal lesions were treated with toe amputation through the metatarsophalangeal joint, and no cases had recurrence. There were 2 recurrences affecting the ankle and the subtalar joint. There was a 14.3% recurrence rate, while complete recovery was achieved in 85.7% cases (12/14). A high index of suspicion for PVNS should be observed for cases presenting with a painless or painful mass in the foot and ankle region. Complete recovery can be achieved in the majority by complete excision. Toe amputation may be considered for foot phalangeal PVNS.

Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene.

Low-grade fibromyxoid sarcoma (LGFMS) is an indolent, late-metastasizing malignant soft-tissue tumor that is often mistaken for either more benign or more malignant tumor types. Cytogenetic analyses have identified a recurrent balanced translocation t(7;16) (q32-34;p11), later shown by molecular genetic approaches to result in a FUS/CREB3L2 fusion gene. Whereas preliminary studies suggest that this gene rearrangement is specific for LGFMS, its incidence in this tumor type and the possible existence of variant fusion genes have not yet been addressed. For this purpose, a series of potential LGFMS were obtained from nine different soft-tissue tumor centres and subjected to molecular analysis as well as careful histopathologic review. Reverse transcriptase-polymerase chain reaction analysis disclosed a FUS/CREB3L2 fusion transcript in 22 of the 23 (96%) cases that remained classified as LGFMS after the histologic re-evaluation and from which RNA of sufficient quality could be extracted, whereas none of the cases that were classified as other tumor types was fusion-positive. In one of the tumors with typical LGFMS appearance, we found that FUS was fused to the CREB3L1 gene instead of CREB3L2. The proteins encoded by these genes both belong to the same basic leucine-zipper family of transcription factors, and display extensive sequence homology in their DNA-binding domains. Thus, it is expected that the novel FUS/CREB3L1 chimera will have a similar impact at the cellular level as the much more common FUS/CREB3L2 fusion protein. Taken together, the results indicate that virtually all LGFMS are characterized by a chimeric FUS/CREB3L2 gene, and that rare cases may display a variant FUS/CREB3L1 fusion.

Ewing's Sarcoma of the Upper Extremity: Presenting Symptoms, Diagnostic Delay and Outcome.

PURPOSE: To look at the presenting features, Enneking stage, size of primary tumour, method of treatment and patient and doctor delays in upper extremity Ewing's sarcoma to observe the effects on local recurrence, metastasis and survival. PATIENTS AND METHODS: Nineteen patients with upper extremity Ewing's sarcoma were identified using the Scottish Bone Tumour Registry over the past 40 years. RESULTS: With increasing tumour Enneking stage at presentation there was a significantly higher mortality (P=0.02). Patients with a higher Enneking stage also had an increased trend towards local recurrence (P=0.08). Stage did not influence the occurrence of metastasis. Patients with larger tumours tended to have a higher mortality (50 vs. 27% dead at 5 years). All patients presented clinically with pain and all but two complained of some sort of swelling. There was a trend towards a higher Enneking Stage in patients presenting with a longer duration of symptoms (P=0.1). No difference in survival was noted between patients undergoing surgery and chemotherapy and patients undergoing radiotherapy and chemotherapy. Disease-free survival was 100% at both 5 and 10 years for Enneking stage IIA, 56% at 5 and 10 years for stage IIB and 0% at 5 years for stage III. DISCUSSION: This study re-emphasises the potential importance of a diagnostic delay on outcome. Longer symptom duration is associated with a higher Enneking stage at presentation. In turn a higher presenting stage results in a higher mortality. Pain and swelling are prominent clinical findings at first presentation in upper extremity Ewing's.

Management of Skin Toxicity Related to the Use of Imatinib Mesylate (STI571, Glivectrade mark) for Advanced Stage Gastrointestinal Stromal Tumours.

Skin toxicity is a common side-effect of treatment with imatinib mesylate (STI571, Glivectrade mark) in advanced gastrointestinal stromal tumours (GIST) and chronic myeloid leukaemia. The optimal duration of treatment with imatinib mesylate in GIST has not yet been established, as durable remissions have been observed in patients. It is, therefore, important to develop strategies to deal with common side-effects of what may be a long-term treatment. Here we report the case of a patient with advanced GIST who developed a cutaneous drug reaction secondary to imatinib mesylate and the various management options that may be employed depending upon the severity of the toxicity. The case and literature are discussed.

Prognostic factors associated with local recurrence, metastases, and tumor-related death in patients with synovial sarcoma.

Prognostic factors associated with local recurrence, metastases, and tumor-related death in synovial sarcoma were studied in 51 patients in the Scottish Bone Tumor Registry from 1955 to 1999. In a multivariate analysis, the presence of poorly differentiated (PD) areas was the strongest prognostic factor associated with local recurrence (Hazard ratio [HR] = 11.3, 95% CI 2.3, 122.5, p = 0.033), metastases (HR = 16.9, 95% CI 2.3,122.5, p = 0.005), and tumor-related death (HR = 6.9, 95% CI 1.1,41.8, p = 0.036). Other significant independent risk factors included bone invasion (HR = 16.6, 95% CI 1.1, 252.5, p = 0.043) and necrosis (HR = 5.1, 95% CI 1.4, 18.99, p = 0.016) for metastases and bone invasion (HR = 17.6, 95% CI 1.2, 253.2, p = 0.035) for tumor-related death. Increasing percentages of PD areas and necrosis were associated with increasing hazard ratios for metastases and death. In the univariate analysis, PD areas, tumor size, and a mitotic count over 10/10 high-power fields were significantly associated with recurrence, whereas necrosis, vascular invasion, and age more than 25 years were additional risk factors for metastases and death. Local recurrence was significantly associated with increased risks for metastases (OR = 6.8, 95% CI 1.6, 28.7, p = 0.006), and death (all cases). Histologic features such as PD areas, necrosis, vascular invasion, and bone invasion should be considered when deciding about adjuvant therapy.

Chondrosarcoma of the bones of the feet.

Twelve chondrosarcomas of the bones of the feet from 11 patients in the Scottish Bone Tumor Registry were reviewed. One patient with diaphyseal aclasis (osteochondromatosis) developed 2 chondrosarcomas. The mean age of patients was 52.3 years (range, 17 to 83 years). Men were predominantly affected. Four tumors affected the tarsal bones; the rest involved the short tubular bones. The usual clinical presentation was a painful, progressively enlarging swelling. Radiologically, most showed some bone expansion, cortical destruction with indistinct margins, and soft-tissue extension. Histologically, the majority were middle-grade tumors. Treatment included curettage or local excision for 4 tumors and amputation or ray resection for 8 tumors. Follow-up varied from 6 months to 18 years (average, 5.8 years). Local recurrence after surgery was seen in 3 patients. All 3 died because of metastases to the lungs or brain.

Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes share a common t(7;16)(q34;p11) translocation.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare metastasizing soft tissue tumor with deceptively bland histologic features. The hyalinizing spindle cell tumor with giant rosettes (HSCT) is thought to be a closely related tumor differing only by the presence of collagen rosettes. We report the occurrence of a common t(7;16)(q34;p11) translocation in 2 cases of HSCT and 2 cases of LGFMS, thereby providing the first cytogenetic proof that LGFMS and HSCT are variants of the same entity. The tumors occurred in the thighs of 2 females and in the buttock and supraclavicular fossa of 2 males. One HSCT had a spectrum of unusual histologic features, including the presence of plump epithelioid cells with abundant cytoplasm and strands and nests of clear epithelioid cells separated by eosinophilic hyalinized stroma. Two cases showed a hitherto unreported, focal staining with epithelial membrane antigen, thus adding to the immunohistochemical profile of these tumors. LGFMS and HSCT probably have a wider spectrum of morphologic features than previously thought, the awareness of which will help pathologists to avoid diagnostic pitfalls. Demonstration of the t(7;16)(q34;p11) translocation will help to diagnose difficult cases with unusual histologic features.

Chondroblastoma: varied histologic appearance, potential diagnostic pitfalls, and clinicopathologic features associated with local recurrence.

Chondroblastoma is a rare, benign bone tumor. Although it has distinctive clinicopathologic features, its wide morphologic spectrum may pose diagnostic problems. We present the clinicopathologic features of 42 patients (28 males, 14 females; age range, 8 to 66 years), with emphasis on unusual histologic features, potential diagnostic pitfalls, and factors associated with recurrence. Thirty-four tumors were in long bones, with the most common site being the proximal femur. Unusual histologic features included the presence of atypical, epithelioid, spindle, and foamy cells and necrosis and a diffuse basophilic myxoid matrix. Tumors with focal osteoclast-like giant cell rich areas (n = 11), prominent cystic change (n = 8) and extensive fibromyxoid areas (n = 3) resembled giant cell tumors, aneurysmal bone cysts, and chondromyxoid fibromas, respectively. The diagnosis of referring pathologists was inaccurate in 34% of cases. Six patients (14%) had local recurrence. The only clinical feature significantly associated with increased risk of local recurrence was duration of symptoms for less than 6 months (log rank P =.003). None of the histologic features was significantly associated with recurrence. These included worrisome features such as cellular atypia, necrosis, and mitoses. None of the patients had metastases. An increased awareness of the morphologic spectrum of chondroblastomas will enable pathologists to avoid diagnostic pitfalls. We emphasize the need for a combined clinical, radiologic and histologic approach to the diagnosis of chondroblastomas.

Poorly differentiated extraskeletal myxoid chondrosarcoma with t(9;22)(q22;q11) translocation presenting initially as a solid variant devoid of myxoid areas.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue tumor associated with the translocation t(9;22)(q22;q11-12). Although it has a typical microscopic appearance its morphologic spectrum is wide. We report a case of clinically aggressive, poorly differentiated EMC showing the characteristic translocation, which presented initially as a poorly differentiated sarcoma devoid of myxoid areas in the upper arm of an 85-year-old man. The recurrent tumor contained scattered myxoid areas, which merged imperceptibly with the poorly differentiated areas. Some myxoid areas contained necrotic foci surrounded by viable cells giving rise to a pseudorosette-like arrangement. There were epithelioid foci. This case confirms that solid variants of EMC may exist. Poorly differentiated EMC may have a worse prognosis than classic EMC.