Multiple Lytic Bone Lesions Research Articles

Multiple myeloma presenting with unilateral abducens and trigeminal nerve palsies

Petrous apex masses can manifest with neurologic symptoms due to their involvement of various structures, including cranial nerves (CN) V and VI. The differential diagnosis of petrous masses is broad and includes a variety of both non-neoplastic and neoplastic lesions. We report a rare case of multiple myeloma confined to the right petrous apex, presenting with ipsilateral abducens and trigeminal nerve palsies. A 63-year-old woman presented with a 6–8week history of facial numbness and a 2week history of diplopia, with examination showing right-sided facial hypoesthesia in the CN V1–V3 region and right-sided lateral rectus palsy. MRI of the brain showed a solitary 2.0cm lesion confined to the right petrous apex involving the right cavernous internal carotid artery and Meckel’s cave. A transnasal biopsy showed a proliferation of plasmacytoid cells, which showed diffuse immunoreactivity with antibodies to CD138 and kappa, consistent with a plasma cell dyscrasia. A bone scan subsequently revealed multiple lytic bone lesions involving the skull, left humerus, bilateral femurs and possibly the L4 vertebral body. Bone marrow biopsy and serum laboratory results confirmed the diagnosis of kappa-type multiple myeloma. Although rare, multiple myeloma may initially present with petrous involvement and associated cranial nerve deficits.

THE WIDENING SPECTRUM OF PARANEOPLASTIC DISORDERS: TWO CASES

Paraneoplastic neurological syndromes are non-metastatic disorders triggered by an altered immune response to a neoplasm. Uncommon presentations are increasingly reported, widening the recognised spectrum of these disorders. We present two patients with atypical neurological manifestations that heralded malignancy. <b>Case 1</b> A 79 year old woman presented with progressive asymmetrical (R&gt;L) leg weakness. Examination confirmed significant paraparesis (MRC 2/5 bilaterally) with normal muscle bulk and tone, normal sensation and sphincter control, hyporeflexia and downgoing plantars. MRI of the lumbosacral spine was normal. Nerve conduction studies showed an axonal and demyelinating motor neuropathy. CSF was acellular with high protein (2.5 gr/dl) and normal glucose. Body CT revealed a large retrosternal mass consistent with thymoma. Her paraneoplastic motor neuropathy was treated with intravenous immunoglobulin, which clinically stabilised her progression, and referred for surgical removal. <b>Case 2</b> A 72 year old woman presented with painless, progressive left-sided visual loss. Fundoscopy excluded arterial occlusion or vasculitis. Investigations for autoimmune or infective causes were normal. Chest X-ray, echocardiogram, lumbar puncture and a temporal artery biopsy were diagnostically non-contributory. Body CT showed multiple lytic and sclerotic bone lesions, with abnormal lymphadenopathy in the left axilla. Fine needle aspiration of a node showed adenocarcinoma consistent with metastatic oestrogen receptor positive breast cancer. The final diagnosis was non-metastatic paraneoplastic optic neuropathy.

Nasu-Hakola Disease as Suspected Cause for Bone Disease and Dementia

Progressive dementia in conjunction with multiple bone fractures in a previously healthy young man led to the investigation of the underlying cause. The differential diagnoses (most importantly hypoparathyroidism) were limited given basal ganglia calcifications on the brain computed tomographic scan. Electronic search of the key words basal ganglia calcification, osteoporosis, and dementia revealed a rare condition termed Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. This very rare and potentially fatal genetic disease is characterized by pathological fractures, multiple lytic bone lesions, and presenile dementia. We report an Iranian patient with this disease and a review of the literature.

3:46 PM Abstract No. 47 - Imaging of the thoracic duct using C-arm CT lymphangiography (CTL) following ultrasound guided inguinal nodal injection in children with right to left shunts

Purpose To study the feasibility of C-arm CTL following ultrasound guided inguinal lymph node injection of water soluble contrast media in children with right to left shunts. Materials and Methods Patient 1 : A 4 year old boy with complex congenital heart disease developed recurrent right sided chylothorax which resolved followed by left chylothorax requiring several chest tubes. A lymphangiogram was performed to look for thoracic duct leak. Patient 2 : A 13 year old girl with multiple cutaneous epidermal nevi, simple renal and splenic cysts, multiple lytic bone lesions, bilateral interstitial lung disease, multiple left lower lobe pulmonary AVM’s developed recurrent chylopericardium. This was managed with pericardial drainage and lymphangiogram was performed to look for leak. Technique : Lipiodol could not be used due to the risk of systemic embolization in the presence of right to left shunts. Under ultrasound guidance bilateral inguinal nodes were accessed using 25G needles followed by slow hand injection of Optiray 320. 2D-fluoroscopic visualization of the pelvic and lumbar lymphatics up to L2 level was possible beyond which dilution of contrast from leakage across the wall of the lymphatics precluded visualization. C-arm CT (syngo Dyna CT®, Siemens Medical Solutions USA Inc.) of the chest was performed using 8s DR-body protocol and images were reconstructed. Results Patient 1 : C-arm CTL showed a lobulated pseudoaneurysm of the thoracic duct at the level of T6 adjacent to a surgical clip with normal course and caliber of the rest of the duct to its insertion into the left subclavian vein and no leak. Patient 2 : C-arm CTL showed reflux of contrast into dilated lymphatics in the mediastinum, left hilum and left lower lobe suggestive of lymphangiectasia with uninterrupted course of the rest of the duct to the left subclavian vein. No leak into the pericardium was seen but the study was limited by artifacts from pericardial drainage catheter and nasogastric tube. Conclusion C-arm CTL can successfully demonstrate thoracic duct anatomy and pathology in combination with ultrasound guided inguinal nodal injection of water soluble contrast agent in children with contraindication for oily contrast media.

Eosinophilia and Bone Lesion as Clinical Manifestations of Aggressive Systemic Mastocytosis

We report a patient with aggressive systemic mastocytosis (SM), who exhibited eosinophilia and unusual destructive bone lesions. A 43-year-old female was referred to our hospital because of a vertebral compression fracture, multiple lytic bone lesions, and eosinophilia in February 2011. A diagnosis of aggressive SM was made on the basis of abnormal mast cells in the bone marrow, high serum tryptase levels, and multiple lytic bone lesions including vertebral compression fractures. Polymerase chain reaction and subsequent sequencing of its products to identify mutations of c-kit yielded negative results and imatinib mesylate failed to improve the SM of the patient. She was then treated with interferon-α, with considerable improvement of the disease, although severe myelosuppression prevented the continued administration of a sufficient dose of this agent. In August 2011, the patient suddenly developed paraplegia of the lower extremities. Magnetic resonance imaging demonstrated epidural mass lesions at the levels from Th9 to Th11, compressing the spinal cord. Emergent laminectomy and subsequent irradiation of the tumors were performed without improvement of the paraplegia. Histopathologic examination of the epidural tumors, from samples obtained intraoperatively, confirmed the diagnosis of SM. She was further treated with dasatinib and then cladribine without obvious improvement, although the latter reduced the eosinophilia to some extent ; however, she died of sepsis in September 2011.

Plasma Cell Myeloma with Unusual Expression of CD19, CD10, CD45 and Surface Light Chain in a Human Immunodeficiency Virus Positive Patient

A 52-year-old male with a history of Human Immunodeficiency Virus (HIV) infection presented with acute renal failure, hypercalcemia, anemia, and cervical lymphadenopathy. Serum protein electrophoresis demonstrated an IgG kappa monoclonal protein and bone scan demonstrated multiple lytic bone lesions. Given patient history/clinical presentation of HIV infection and cervical lymphadenopathy, differential diagnosis includes plasma cell myeloma, B cell lymphoma with extensive plasmacytic differentiation, plasmablastic lymphoma and HHV-8 associated large B cell lymphoma. Flow cytometry of the bone marrow aspirate showed a CD19 positive/CD20 negative population with high side scatter and co expression of CD45, CD10, CD56, and surface kappa light chain. Bone marrow biopsy/clot showed sheets of atypical plasmacytic cells. Immunohistochemical stains showed these atypical plasmacytic cells were positive for CD138, CD79a, CD56, MUM-1, CD19, CD10 and kappa light chain; negative for CD20, PAX-5, HHV-8, EBV and EBER in situ hybridization. Ki-67 demonstrated a low proliferation index in these atypical cells. Cytogenetic study showed a normal male karyotype. All things considered, including clinical presentation, morphologic and immunophenotypic features, it represents a unique case of plasma cell myeloma with unusual expression of CD19, CD10, CD45, and surface light chain.

A rare and unique case of aggressive IgE-λ plasma cell myeloma in a 28-year-old woman presented initially as an orbital mass

A 28-year-old African-American woman presented with new onset of left exophthalmos and diplopia. Computed tomography of the head showed a solitary mass in the left orbit. Excisional biopsy revealed a diffuse infiltrate composed of exclusively λ-restricted monotypic plasma cells based on morphology and immunohistochemistry, consistent with a plasma cell neoplasia. A subsequent staging bone marrow biopsy showed involvement of the bone marrow by λ-restricted monotypic plasma cells, consistent with a plasma cell myeloma. Serum protein electrophoresis and immunofixation studies on the peripheral blood showed a monoclonal band of IgE-λ; thus, an IgE-λ plasma cell myeloma was established. Additional clinical and radiologic workups showed multiple lytic bone lesions, diffuse lymphadenopathy, a pelvic mass, multiple mesenteric soft tissue nodules, and multiple pulmonary nodules, although none of the aforementioned sites was biopsied. The patient was treated with a combination of multiple chemotherapeutic agents and localized radiation due to the aggressive nature of the disease. To the best of our knowledge, this is the first case of an IgE plasma cell myeloma in a patient under the age of 30 years old presenting as a mass in an extramedullary site.

Plasma Cell Myeloma Associated with Epstein-Barr Virus Infection in an 11-Year-Old Girl

Multiple myeloma is extremely rare in children and represents fewer than 1% of all patients with myeloma. We report a case of multiple myeloma in an 11-year-old girl, who presented with a well-differentiated immunoglobulin A/kappa plasmacytoma at the base of the skull at 9 years of age; at that time, the bone marrow biopsy was negative. Two years later, the patient experienced generalized bone pain with multiple lytic bone lesions that affected the skull, long bones, ribs, and clavicle. The bone marrow biopsy showed a well-differentiated (Marschalko-type) multiple myeloma that was positive for CD138 and immunoglobulin A, with kappa light chain restriction. Interestingly, the Epstein-Barr virus (EBV) was detected by in situ hybridization for EBV-encoded RNA (EBER) in the majority of the neoplastic cells from both biopsy specimens. The patient responded favorably to treatment with dexamethasone, thalidomide, and zoledronic acid and is scheduled for bone marrow transplantation.

Disseminated Carcinoma Ex Pleomorphic Adenoma in an Adolescent Confirmed by Application of PLAG1 Immunohistochemistry and FISH for PLAG1 Rearrangement

A 16-year-old previously asymptomatic boy presented with complaints of fatigue, weight loss, and back pain for several months. Imaging studies revealed a large superior mediastinal mass, numerous bilateral pulmonary nodules, and multiple lytic bone lesions. A needle biopsy from a sternal lesion showed a poorly differentiated carcinoma, immunoreactive for cytokeratins and EMA and immunonegative for various organ/tissue-specific markers.His past medical history was significant for excision of aparotid gland tumor 5 years earlier. Histologic review of the salivary gland tumor revealed a pleomorphic adenoma containing a microscopic focus of invasive carcinoma(carcinoma ex pleomorphic adenoma). By immunohistochemistry, both the salivary gland tumor and the disseminated carcinoma expressed PLAG1 with a strong nuclear pattern.Fluorescence in situ hybridization (FISH), using dual-color, break-apart probes for PLAG1, showed rearrangement of the gene in both the salivary gland and the disseminated tumors.FISH demonstrated additional cytogenetic aberrations in the carcinoma, including polysomy for chromosome 8 (in both the primary salivary gland and the metastatic tumors) and PLAG1 amplification (in the metastatic tumor). We conclude that in the proper clinicopathologic setting, application of PLAG1 immunohistochemistry and FISH for PLAG1 gene rearrangement may be valuable in establishing the diagnosis of carcinoma ex pleomorphic adenoma as the source of a cancer of unknown primary site.

Positron emission tomography/computed tomography imaging of brown tumors mimicking multiple skeletal metastases in patient with primary hyperparathyroidism

Brown tumors of bone are highly vascular, lytic bone lesions representing a reparative cellular process rather than a neoplastic process usually seen in patients with hyperparathyroidism. These tumors can behave aggressively and be destructive. We report a 49-year-old male patient who was admitted to our hospital with a long-term history of right shoulder and right hip pain. Multiple lytic and destructive bone lesions were found in X-ray graphy and CT images. These bone lesions mimicked multiple skeletal metastatic lesions and seemed to be those of the terminal stage of malignancy. PET scan was requested for the evaluation of FDG uptake of these lesions and to search the unknown primary tumor site. Positron emission tomography/computed tomography (PET/CT) images showed multiple hypermetabolic malignant or metastatic FDG avid bone lesions in skeletal system. However the biopsy results revealed no signs of malignancy and laboratory data showed elevated serum calcium, alkaline phosphatase, parathyroid hormone, low serum phosphate and parathyroid scintigraphy was performed. Adenoma in the left parathyroid gland was seen with Tc-99m MIBI parathyroid scintigraphy. Pathological results confirmed the diagnosis of parathyroid adenoma. Brown tumor is the potential cause of false-positive result in evaluation of a patient for unknown primary tumor or skeletal metastases with PET/CT imaging.

Dural metastases as a presentation of a Brenner tumor

We present a 56-year-old woman who came to our institution with a 6-month history of intracranial hypertension. Imaging studies showed diffuse dural enhancement, multiple lytic bone lesions and a tumor in the left ovary. A meningeal biopsy was performed; however, during this procedure the patient developed profuse dural hemorrhage and middle cerebral artery territory infarction and died a few hours later. The autopsy revealed a disseminated Brenner tumor that was infiltrating the intracranial dura mater. At this site neovascularization, vascular infiltration by malignant cells and a desmoplastic reaction were all observed, perhaps rendering the patient more susceptible to a dural hemorrhage during the biopsy. To our knowledge, this is the first report of a Brenner tumor presenting as dural metastases.

An unusual presentation of extramedullary plasmacytoma in testis and review of the literature

Extramedullary plasmacytoma is a rare plasma cell neoplasm, and it is extremely uncommon in the testicles. We report a 73-year-old man with multiple myeloma presented with testicular plasmacytoma. He complained of left leg pain and scrotal swelling. Ultrasonography revealed testicular masses. Pathologic examination of the orchiectomy specimen showed plasmocytoma with kappa expression. Multiple lytic bone lesions were seen in bone survey scans, serum immunoelectrophoresis and bone marrow aspiration aided to the diagnosis of multiple myeloma. He received chemotherapy, melphalan and prednisolone, and palliative radiotherapy. He succumbed to disease after 8months.

Altered mental status in a case of multiple myeloma not related to a metabolic cause.

Sir, Altered mental status (AMS) in a patient with multiple myeloma (MM) is generally attributed to uremia, hypercalcemia, hyperviscosity and/or increased serum ammonia. We present an unusual case of altered mental status that could not be attributed to metabolic encephalopathy. Our patient was a 68-year-old African American male who was admitted for AMS. The patient was asymptomatic 1 week prior to admission. On examination, no focal neurologic deficit other than altered sensorium was found. The rest of his physical examination was normal. Routine laboratory analysis revealed elevated BUN of 58 mg/dl (7–25 mg/dl), creatinine of 4.9 mg/dl (0.7–1.4 mg/dl), calcium of 12.1 mg/dl (8.5–10.3 mg/dl), total protein of 9.6 g/ dl (5.5–9 g/dl) and serum ammonia of 65 mcg/dl (35–65 mcg/dl) with normal liver function tests. A toxicology screen was negative. Intravenous hydration with normal saline was initiated. Magnetic resonance imaging (MRI) of brain showed chronic microvascular ischaemic changes with no acute infarct. On cerebrospinal fluid (CSF) analysis, he was found to have elevated protein of 172 g/dl (15–45 g/dl), no pleocytosis and a negative gram stain. Polymerase chain reaction on CSF for herpes simplex was negative. Electroencephalogram (EEG) showed no seizure activity. Though all metabolic parameters normalized by the third day (creatinine of 1.3 mg/dl and calcium of 9.3 mg/dl), there was no improvement in his sensorium. To rule out paraneoplastic syndrome of unknown aetiology, a whole body CT scan was done. It showed a soft tissue mass in the pre-sacral area with multiple diffuse lytic bone lesions. The bone marrow was diagnostic for plasma cell myeloma. Serum immunofixation revealed 5050 mg/dl (700–1600 mg/dl) of monoclonal IgG. The serum viscosity was normal. A repeat lumbar puncture revealed a CSF with negative cytology, but abnormal bands of high intensity in the immunoglobulin region identical to the serum electrophoresis pattern. Four days after the normalization of all his metabolic parameters, there was still no improvement in his sensorium. The patient was started on intravenous dexamethasone for MM. After the first cycle, his sensorium returned to normal. The most common cause of AMS in a patient with MM and acute renal failure (ARF) is metabolic encephalopathy. Though rare, direct invasion of CNS by the myeloma cells has been reported. Currently, 70 cases of leptomeningeal myelomatosis (LMM) and intraparenchymal plasmacytoma have been published [1,2]. Schluterman et.al. published a case series of 23 patients. They were diagnosed up to 29 months (median, 13 months) after the initial diagnosis of MM. The presenting symptom in 65% of the patients was AMS. The CSF analysis revealed pleocytosis and/or increased protein (generally >100 g/dl) similar to our case. CSF cytology showed myeloma cells; however, it was negative in 4 out of the 23 patients at initial presentation. Unlike our patient, cranial leptomeningeal contrast enhancement was seen on MRI in as many as 70% of the cases. Our patient did not fulfil all the diagnostic criteria of LMM but did have a dramatic recovery of his sensorium after the first cycle of dexamethasone therapy. His altered mental sensorium may represent a paraneoplastic manifestation of MM or alternatively, the patient falls into the spectrum of disease activity before fully evolved LMM. He was discharged from the hospital and was referred to an oncologist for further management of MM. In conclusion, altered mental status in a patient with multiple myeloma may be due to a paraneoplastic manifestation of MM or due to direct invasion of the CNS by myeloma cells. Intrathecal chemotherapy should be used for patients that meet the diagnostic criteria of LMM. However, even those who do not may still show a significant improvement in their neurologic status after treatment with intravenous dexamethasone. Conflict of interest statement. None declared.

Thrombocytopenia as first manifestation of splenic angiosarcoma

Dear Editor, Angiosarcoma is a rare mesenchymal neoplasia with an incidence of only 0.14–0.25 cases per million [1]. Most common sites of occurrence are skin and superficial soft tissues, followed by breast, liver, spleen, and bone. Early stage metastases to lung, liver, and lymph nodes are common and overall prognosis is poor [2, 3]. Only approx. 5% of angiosarcomas originate from the spleen, and the existing casuistic reports suggest a dismal clinical prognosis. Here, we describe a rare case of splenic angiosarcoma leading to thrombocytopenia as first manifestation of the disease. A 64-year-old woman presented as hematologic outpatient inMarch 2008 with isolated thrombocytopenia (58/nl) and chronic, slowly progressive fatigue. Thrombocytopenia was first noted in 2006. Pre-existing medical conditions and physical examination were unremarkable. The remaining full blood count was without pathological findings (hemoglobin 12.2 g/dl, normal erythrocyte indices, leukocytes 6.9/nl with normal differential count). Differential diagnosis for moderate thrombocytopenia included various causes for immune destruction of platelets, impaired thrombocyte production, and hypersplenism. However, laboratory screening tests for lymphoma, autoimmune diseases, and virus infections resulted negative. A bone marrow aspirate gave an unspecific picture with unremarkable cellular properties, normal count of megakaryocytes but diffuse infiltration of mature plasma cells up to 15%. A bone marrow biopsy showed hyperplastic left shifted granulopoiesis, left shifted megakaryopoiesis, and erythropoiesis in a hypercellular tissue, partially accompanied with B-cell-rich non-monoclonal lymphocytic aggregates. An abdominal ultrasound showed massive splenomegaly with multiple highly echogenic circular lesions. Multislice computed tomography (MSCT) confirmed splenomegaly (measuring 21 cm craniocaudal) and revealed multiple hypodense lesions with central hyperdense structures (Fig. 1a). In addition, multiple lytic bone lesions in the vertebral column were present. MSCT-guided biopsy of these lytic bone lesions showed infiltrates of a mesenchymal neoplasia containing atypic mitotic bodies, a proliferation fraction of 40% (MIB-1) and negativity for pancytokeratin and S 100. Immunohistochemistry stained positive for vimentin, CD31, CD34, and factor VIII, but negative for desmin, actin, and HHV8, leading to the diagnosis of angiosarcoma (Fig. 2). Meanwhile, the patient suffered from symptomatic splenomegaly (abdominal pain, symptoms of GI tract displacement), and since splenic angiosarcoma may be complicated by splenic rupture [4, 5], an elective splenectomy was performed. Histological examination confirmed the diagnosis of primary splenic angiosarcoma. In addition, the patient was offered palliative chemotherapy and infusions of bisphosphonates; the latter were started immediately. Chemotherapy with paclitaxel (90 mg/m weekly) began with a delay of several weeks (patient’s choice) at a S. Raffel :B. Hildebrandt : I. Sturm (*) Department of Hematology and Oncology, Charite Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany e-mail: isrid.sturm@charite.de

Hereditary haemorrhagic telangiectasia involving the bone marrow and liver

A 28-year-old Hispanic male presented with a 3-month history of nosebleeds, fatigue, jaundice, easy bruising, weight loss, ascites and lower extremity oedema. Physical examination revealed hepatosplenomegaly, an area of bruising over the left thigh and right buttock and 3–4 telangiectases on the hands but none on the lips or oropharynx. Laboratory studies showed: aspartate transaminase 43 U/l [normal range (NR) 13–40 U/l], alanine transaminase 20 U/l (NR 10–40), gamma glutamyl transferase 203 U/l (NR 8–78), bilirubin 106 lmol/l (NR 3AE4–22AE1), activated partial thromboplastin time 34AE9 s (NR 23AE5–33AE5), prothrombin time 19AE4 s (NR 9AE2–12AE8), and International Normalized Ratio 2AE1 (NR 0AE9–1AE3). All viral and autoimmune hepatitis serologies were negative. The full blood cell count showed haemoglobin concentration 103 g/l, platelets 82 · 10/l, and white blood cells 4AE3 · 10/l with an unremarkable differential. Abdominal computed tomography showed an enlarged, nodular liver with numerous hypervascular masses, a few hypervascular splenic lesions and multiple lytic bone lesions. Bone marrow aspirate and core biopsy showed unremarkable, trilineage haematopoiesis with approximately 10–20% of the marrow space replaced by an anastomosing, benign, vascular lesion infiltrating the cellular marrow (top left, 100·; top right, 400·). Cells lining the vascular network were CD34(+) (bottom left, 200·). Transjugular liver biopsy showed a similar vascular process (bottom right, 200·). It extensively infiltrated throughout a cirrhotic liver, in the parenchymal nodules and in the bands of fibrous tissue encircling them. With the patient’s clinical, radiological, and pathological findings, a diagnosis of hereditary haemorrhagic telangiectasia (HHT) was made. HHT, or Osler-Weber-Rendu syndrome, is an autosomal dominant syndrome that may involve three different genes in the transforming growth factor-b signalling pathway. Defects in this pathway may result in abnormal vessel repair. The syndrome is defined by recurrent, spontaneous epistaxis, telangiectases, visceral arteriovenous malformations (AVMs), and a positive family history. Lung, gastrointestinal tract and liver are the three most common sites for AVMs. In the present case, AVMs involved the liver and bone marrow and probably the spleen. Bone marrow involvement is rare and has not been well reported in the literature.

Lymphangiomatosis: a differential diagnosis of lytic lesions of the temporal bone

We report a histologically proved case of lymphangiomatosis of the skull, involving the temporal bone and presenting as multiple lytic bone lesions. A case report and a review of the literature concerning lymphangiomatosis are presented. Lymphangiomatosis affecting bones is a rare disorder caused by a congenital malformation of the lymphatic system, resulting in diffuse proliferation of the lymphatic channels and involving bones, parenchymal organs and soft tissue. Involved bones show massive osteolysis and progressive, localised bone resorption. Lymphangiomatosis should be kept in mind in the differential diagnosis of lytic lesions of the skull.

Tumorigenic potential and disease manifestations of malignant B-cell variants differing in their fibronectin adhesiveness

Microenvironmental interactions of malignant B cells can modulate various in vitro physiological responses, including proliferation, migration, apoptosis, and drug resistance. Disease manifestations of human malignant B-cell variants, isolated based on their differential interactions with fibronectin, were examined in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Disease manifestations were assessed by pathological examinations and skeletal imaging of NOD/SCID mice injected with malignant B-cell variants. Dissemination patterns were analyzed by whole-body real-time imaging of mice injected with fluorescence-labeled malignant cells. Initial dissemination patterns and dynamics of both high (type A) and low (type F)-adherent variants, following intravenous inoculation, were similar. Both cell types reached the spleen and liver within 30 minutes after injection, then increasingly accumulated within the bone marrow. Mice injected with type-A cells developed multiple myeloma-like disease within the bone marrow, with multiple lytic bone lesions. In contrast, type-F cells displayed low tumorigenic capacity in spite of their efficient homing to the bone marrow niche. In addition, type-A cells grew as extramedullary tumors in some of the intravenous-inoculated mice, and formed solid tumors following subcutaneous injection. Both cell variants retained their characteristics surface markers following in vivo outgrowth as tumors, indicating that at least some of their properties are relatively stable. Data suggest that the differential tumorigenicity of B-cell adhesive variants is attributable to the capacity of type-A cells to survive and proliferate within the bone marrow, rather than to different initial dissemination of the two cell populations.

Diffuse Uterine Leiomyomatosis With Uterine Rupture and Benign Metastatic Lesions of the Bone

We report a case of diffuse uterine leiomyomatosis in pregnancy complicated by uterine rupture and dissemination to the bone. A 35-year-old nulliparous woman with a history of uterine leiomyoma presented at term with fetal demise. Failed induction of labor and hemodynamic instability due to uterine rupture resulted in a cesarean hysterectomy. A free-air series performed postoperatively to confirm paralytic ileus revealed multiple lytic bone lesions. The diagnosis of diffuse uterine leiomyomatosis with metastasis was made on histology of the resected uterus and fine-needle aspiration biopsy of the bone. She was managed conservatively, and the lesions are now regressing. Diffuse uterine leiomyomatosis should be considered in pregnant women with a history of uterine fibroids and peripartum hemorrhage.

LYTIC BONE LESIONS IN AN AUSTRALIAN POPULATION: THE RESULTS OF 100 CONSECUTIVE BIOPSIES

The identification of a lytic bone lesion is often perceived as a harbinger of malignancy, especially in an older patient. This study reviews the results of 100 consecutive biopsies of patients who presented with either a solitary lesion or multiple lytic bone lesions in the absence of a history of malignancy. Following preoperative planning, including plain radiographs, bone scan and computed tomography scanning, an open biopsy was carried out. The most common site affected was the pelvis (20 patients), followed by the femur (19) and tibia (15). The lesions were solitary in 88 patients and multiple in 12. The most common diagnosis was a secondary carcinoma presenting as a bone lesion, which was found in 25 patients. The carcinomas were a widely distributed group, but the most common among them were renal cell carcinoma (seven patients), breast carcinoma (five patients) and lung carcinoma (five patients). The most common primary bone tumour was a giant cell tumour (16) followed by myeloma (10). Multiple lesions were not universally an indication of a malignant process. In 14 patients the lesion was not a tumour. This study emphasizes the importance of obtaining a tissue diagnosis.

Macrofocal multiple myeloma in young patients: A distinct entity with favorable prognosis

There are limited reports of young patients with multiple myeloma (MM) who presented with multiple lytic bone lesions but without intervening infiltration of bone marrow, a pattern consisting of macrofocal MM. In order to clearly define the clinical and laboratory features and outcome of such patients, a retrospective analysis was performed of symptomatic patients with MM ≤40 years of age at diagnosis who received primary treatment over a 20-year period. Ten of 51 patients fulfilled the criteria of macrofocal MM. When compared to patients with typical MM, patients with macrofocal pattern were less anemic, none had hypercalcemia, renal impairment, elevated serum LDH or stage 3 according to the International Staging System (ISS). Patients with macrofocal MM usually had preserved the uninvolved immunoglobulins. An objective response to primary treatment was noted in 55% of patients with macrofocal MM and in 50% of patients without this pattern. The median survival of patients with typical MM was 57 months and is projected to exceed 8 years in patients with macrofocal MM (p = 0.087). With macrofocal MM despite multiple lytic bone lesions, patients have features of low tumor burden and improved survival when compared with young patients with typical MM.