Osteopetrosis-associated osteomyelitis of the jaws: a report of 4 cases.

Osteopetrosis represents a heterogeneous group of rare, hereditary bone disorders with variable clinical features and an increase in bone density. The common clinical findings that usually lead to the detection of the disease are fractures and osteomyelitis of the mandible. We report 4 cases of osteopetrosis, complicated by osteomyelitis of the jaws. Maxillary bone was involved in 3 of the cases and mandible in 1 of the cases. Osteomyelitis of the maxilla is extremely rare. When it occurs, there is invariably an underlying predisposing condition. All the 4 patients presented with osteomyelitis after dental extraction. Skeletal survey revealed multiple healed fractures of the long bones in all the cases. Two patients presented with myelophthisic anemia and evidence of extraosseous hematopoiesis and 1 patient with osteopetrotic stenosis of optic and auditory nerve exit foramina. All 4 cases were treated with intravenous antibiotic therapy and debridement of necrotic bone.

Bone marrow necrosis and myelophthisis: manifestations of T-cell lymphoma in a horse.

A 14-year-old spayed American Paint mare was evaluated for mild colic, anorexia, pyrexia, and pancytopenia. Physical examination revealed mild tachycardia, tachypnea, and pale mucous membranes. Serial laboratory analyses revealed progressive pancytopenia, hyperfibrinogenemia, and hyperglobulinemia. A few large atypical cells were observed in peripheral blood smears. Results of tests for equine infectious anemia and antipenicillin antibody were negative. Serum protein electrophoresis indicated a polyclonal gammopathy. Smears of bone marrow aspirates contained hypercellular particles, but cell lines could not be identified because the cells were karyolytic, with pale basophilic smudged nuclei and lack of cellular detail. A diagnosis of bone marrow necrosis was made. Treatment consisted of antimicrobials, nonsteroidal anti-inflammatory drugs, and corticosteroids. The pyrexia resolved; however, the pancytopenia progressively worsened and petechiation and epistaxis developed. The horse was humanely euthanized. Postmortem examination revealed a diffuse round cell neoplasm infiltrating the kidneys, spleen, lymph nodes, lungs, and bone marrow. Immunophenotyping results (CD3+, CD79alpha-) indicated the neoplastic cells were of T-cell lineage. Infiltration of lymphoma cells into the bone marrow appeared to have resulted in severe myelophthisis and bone marrow necrosis. Bone marrow necrosis has been associated previously with lymphoma in humans and dogs. To our knowledge, this is the first reported case of lymphoma resulting in bone marrow necrosis in a horse.

Severe vitamin B12 deficiency resulting in pancytopenia, splenomegaly and leukoerythroblastosis.

Deficiency of vitamin B12 is a well known cause of megaloblastic anemia and pancytopenia. Splenomegaly and leukoerythroblastosis are much less well known manifestations of B12 deficiency. We report a B12 deficient female with severe pancytopenia including normocytic anemia who also had enlarged spleen and circulating nucleated red blood cells as well as circulating immature myeloid cells. Although these findings are reported in the earlier literature, more modern reviews of the subject often fail to mention this association. We review the literature on these unusual manifestations of B12 deficiency and remind clinicians that splenomegaly and erythroblastosis can serve as diagnostic clues in cases of severe megaloblastic anemia secondary to B12 deficiency.

Lenalidomide therapy in myelofibrosis with myeloid metaplasia.

We present results of 2 similarly designed but separate phase 2 studies involving single-agent lenalidomide (CC-5013, Revlimid) in a total of 68 patients with symptomatic myelofibrosis with myeloid metaplasia (MMM). Protocol treatment consisted of oral lenalidomide at 10 mg/d (5 mg/d if baseline platelet count < 100 x 10(9)/L) for 3 to 4 months with a plan to continue treatment for either 3 or 24 additional months, in case of response. Overall response rates were 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. Response in anemia was deemed impressive in 8 patients whose hemoglobin level normalized from a baseline of either transfusion dependency or hemoglobin level lower than 100 g/L. Additional treatment effects in these patients included resolution of leukoerythroblastosis (4 patients), a decrease in medullary fibrosis and angiogenesis (2 patients), and del(5)(q13q33) cytogenetic remission accompanied by a reduction in JAK2(V617F) mutation burden (1 patient). Grade 3 or 4 adverse events included neutropenia (31%) and thrombocytopenia (19%). We conclude that lenalidomide engenders an intriguing treatment activity in a subset of patients with MMM that includes an unprecedented effect on peripheral blood and bone marrow abnormalities.

Leucoeritroblastosis de curso agudo secundaria a infiltración de la médula ósea por linfoma difuso de células B grandes / Acute leukoerythrobastosis due to marrow infiltration caused by diffuse large B cell lymphoma

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Osteopetrosis. Current clinical considerations.

Osteopetrosis is an inherited skeletal condition characterized by increased bone radiodensity. There are three clinical groups: infantile-malignant autosomal recessive, fatal within the first few years of life (in the absence of effective therapy); intermediate autosomal recessive, appears during the first decade of life but does not follow a malignant course; and autosomal dominant, with full-life expectancy but many orthopaedic problems. The infantile variant shows a myelophthisic anemia, granulocytopenia, and thrombocytopenia, and patients eventually die from infection or bleeding or both. Neurologic sequelae include cranial nerve compression (optic nerve, blindness; auditory nerve, deafness; facial nerve, paresis), hydrocephalus, convulsions, and mental retardation. Radiographs show uniform bone density without corticomedulary demarcation, broadened metaphyses, "bone within a bone" or endobone phenomena (tarsals, carpals, phalanges, vertebra, ilium), and thickened growth plates if there is superimposed rickets. Transverse pathologic fractures occur, often followed by massive periosteal bone formation. Computed tomographic scans, magnetic resonance imaging, and bone scans provide specific information. Iliac crest bone biopsy is valuable to quantitate osteoclast and marrow changes by light and electron microscopy. Medical treatments involve high-dose calcitriol to stimulate osteoclast differentiation and bone marrow transplantation to provide monocytic osteoclast precursors. Orthopaedic problems in the intermediate and autosomal dominant forms include increased fractures, coxa vara, long-bone bowing, hip and knee degenerative arthritis, and mandibular and long-bone osteomyelitis. Cranial nerve compression also occurs. Osteotomy, plating, intramedullary rodding, and joint arthroplasty can be done, but are difficult because of bone hardness.

Leukoerythroblastic anemia in metastatic prostate cancer. Clinical and prognostic significance in patients with hormone-refractory disease.

BACKGROUND: The clinical and prognostic significance of leukoerythroblastic anemia (LKEA) in patients with metastatic prostate cancer and, in general, patients with disseminated solid tumors is poorly understood. Therefore, the authors studied a population of patients with metastatic prostate cancer refractory to hormonal therapy to assess the incidence, clinical features, and prognostic implications of LKEA. METHODS: The medical records of 106 patients with hormone-refractory prostate cancer metastatic to bone seen at the Tucson Veterans Affairs Medical Center between 1985 and 1991 were reviewed retrospectively. The clinical and laboratory data, number of packed erythrocyte transfusions required, and length of survival from the time of diagnosis of hormone-refractory disease until last follow-up visit or death were investigated in 91 identified patients. RESULTS: Twenty-six of 91 patients (28.6%) were found to have LKEA. LKEA developed before or at the time of diagnosis of hormone-refractory disease in 8 patients and after diagnosis of hormone-refractory disease in 18 patients. The presence of LKEA was associated with significantly lower hemoglobin levels and platelet (Plt) counts and significantly higher total bilirubin, lactic dehydrogenase (LDH), and alkaline phosphatase values (P < 0.05). Leukopenia (< 4.0 x 10(9)/l leukocytes), thrombocytopenia (< 150 x 10(9)/l Plt), elevated LDH levels (> 220 U/l), and laboratory evidence of disseminated intravascular coagulation (DIC) were more common in patients with LKEA than in those without LKEA (P < 0.01). Microangiopathic hemolysis was seen in only 2 of 91 patients (2.1%). Patients with LKEA had significantly greater transfusion requirements compared with patients without LKEA (P < 0.0001), but the median survival length was not significantly different (9 months versus 11 months, respectively). The presence of DIC and LDH levels of 500 U/l or greater in patients with LKEA was associated with a poor prognosis. CONCLUSIONS: LKEA is a relatively common finding in patients with hormone-refractory metastatic prostate cancer and is associated with greater transfusion requirements. Its presence, however, does not affect survival significantly.

[Post-gastrectomized vitamin B12 deficient anemia with marked leukoerythroblastosis and ringed sideroblasts].

A 77 year-old man, who had received total gastrectomy and splenectomy 11 years ago for gastric cancer was transferred to our hospital because of severe macrocytic anemia. He had been treated with vitamin B1, B2, C and iron preparations for several weeks. Ten days before admission numbness developed in his legs. On physical examination he appeared severely anemic. Laboratory findings revealed severe macrocytic anemia with poikilocytosis, anisocytosis, polychromasia, red cell fragmentation, Howell-Jolly bodies, Cabot rings and marked erythroblastosis (421/100 WBC). Hypersegmented neutrophils and immature granulocytes were also seen in the blood. The bone marrow picture showed marked erythroid hyperplasia, but erythroblasts revealed only slight megaloblastic changes. On bone marrow iron staining all erythroblasts were classified as type III sideroblasts and 15% of them were ringed-form. Serum vitamin B12 was low (44 pg/ml). Methylcobalamin given intramuscularly led to the rapid improvement of all hematological abnormalities including leukoerythroblastosis. Two weeks after vitamin B12 administration, ringed sideroblasts could no longer be detected in the bone marrow. Post-gastrectomy vitamin B12 deficiency anemias combined with erythroblastosis and ringed sideroblasts is a rare condition. Splenectomy is thought to play an important role in the pathogenesis of these conditions.

Granulocytic fragments in sepsis.

We report here three patients with sepsis and one with acute pancreatitis and possible sepsis who developed granulocytic fragments on blood smears obtained prior to death. In case 1, these fragments were identified cytochemically. In case 3, granulocytic cytoplasmic projections and fragments were identified by electron microscopy of the buffy coat. All patients had leukerythroblastosis. The average corrected white blood count (WBC) was 46 X 10(9)/liter with 34 nucleated red blood cells (nRBC)/100 WBC. Patient 1 had thrombocytosis whereas patients 2, 3, and 4 were thrombocytopenic. Terminal complement levels were decreased in patients 3 and 4 as previously noted in sepsis (Sprung CL, Shultz DR, Marcial E, et al.: Complement activation in septic shock patients. Crit Care Med 14:525, 1986). A general correlation between nRBC and granulocytic fragments/100 hpf (high power field) was observed in patients 3 and 4. Granulocytic fragments were not identified on the blood smears of several patients with leukemoid reactions without erythroblastosis. Although the precise etiology of these fragments is unclear, we believe their recognition is important because all patients died within 32 hours after granulocytic fragments were identified. Furthermore, these fragments can falsely elevate the platelet count. Although myeloid fragments have previously been noted in leukemia and lymphoma, this is the first report of their association with conditions unrelated to hematologic neoplasms. These fragments can easily be recognized by careful examination of the blood smear and represent a newly recognized aspect of the septic shock syndrome.

An unusual case of pycnodysostosis.

A 6 year old boy with clinical and radiological features of pycnodysostosis is described. In addition to pycnodysostosis he had a myelophthisic type of anaemia suggesting an overlap with osteopetrosis.

Familial hypercholesterolemia with unusual foamy histiocytes. Report of a case with myelophthisic anemia and xanthoma of the maxillary sinus.

Accumulation of phagocytic histiocytes with a foam cell morphology has been described in a number of diseases. Familial hypercholesterolemia, one such disease, is characterized by foamy histiocytic accumulation in cutaneous or tendinous xanthomas and within atheromatous lesions. This report describes a patient with familial hypercholesterolemia who had two unusual manifestations of foamy histiocytic accumulation: a maxillary sinus xanthoma, which presented as an expansile mass, and diffuse bone marrow replacement with foamy histiocytes, which was associated with myelophthisic anemia. The accumulation of foamy cells in both locations resembled that seen in many of the storage diseases. The possibility of foamy histiocytic accumulation should be considered in the differential diagnosis of patients with these disease entities who present with space-occupying lesions.

[Neoplastic form of chronic erythromyelosis (erythrosarcoma) with eosinophilia and cardiac lesions]. / Opukholevaia forma khronicheskogo éritromieloza (éritrosarkoma), protekaiushchego s eozinofiliei i porazheniem serdtsa.

The paper is concerned with a case history of a 24-year old man suffering from chronic erythromyelosis with erythrokaryocytic metaplasia of the peripheral lymph nodes, bone marrow, spleen, liver, heart and lungs. The hypereosinophilic syndrome and endocardial fibrosis caused diagnostic difficulties. A short-term effect after injection of the plasma from a patient with erythrocytic aplasia containing antierythroblastic antibodies was obtained, tumor tissue mass reduced. Later on courses of CAMP-therapy were initiated. The progression of disease resulted in the patient's death in 2 years.

Giant basal cell carcinoma with metastases and myelophthisic anemia.

We report a 59-year-old, dark-complexioned black man with a giant basal cell carcinoma infiltrating virtually the entire scalp. Widespread metastatic bone marrow involvement produced a myelophthisic anemia. Basal cell carcinoma is rare in blacks, is rarely this large, and very rarely produces myelophthisic anemia from bone marrow metastases.

Myelofibrosis in neuroblastoma.

Myelofibrosis, a rare childhood disorder, has been reported as an associated complication of certain hematologic malignancies or as an isolated idiopathic process. In this report, we describe a patient with metastatic neuroblastoma whose initial presentation included the findings of myelofibrosis and leukoerythroblastosis. The myelofibrosis regressed with chemotherapy and did not recur when the patient's tumor reappeared.