Marrow Granulomas Research Articles

Clinical and immune aspects of idiopathic acute tubulointerstitial nephritis and uveitis syndrome.

Five patients with idiopathic interstitial nephritis and uveitis without bone marrow granulomas were followed-up for 1 year. Ophthalmological examination revealed bilateral anterior uveitis. Light microscopy of the renal tissue revealed predominant lymphocyte infiltration of the interstitium. Immunohistochemical analysis revealed a clear predominance of memory T lymphocytes (CD45RO+) in the interstitial and tubular infiltration. HLA typing, and immunophenotypic studies of peripheral blood mononuclear cells including absolute lymphocyte and monocyte counts were assessed. The patients' peripheral T-cell subpopulation did not significantly differ from control studies. With steroid treatment maintained during a period of 6-9 months renal function and uveitis responded dramatically in all patients. After 1-year follow-up, only 1 patient showed a relapse of uveitis, but there was complete clinical recovery of the nephritis in all 5 patients. The aim of this study was to describe the 1-year follow-up of 5 new cases of acute tubulointerstitial nephritis and uveitis syndrome, and assess some aspects of their cellular immunity.

Bone Marrow Granulomas, Fever, Pancytopenia, and Lupus-like Syndrome Due to Tocainide

We describe the case of a patient in whom a syndrome of fever, pancytopenia, pleural effusion, hepatosplenomegaly, positive ANA antibodies, and bone marrow granulomas developed in association with tocainide therapy. Tocainide, a recognized, albeit rare, cause of fever, lupus-like syndrome, and cytopenias, should be added to the list of medications that can cause bone marrow granulomas.

Bone marrow granulomas in hairy cell leukaemia following 2‐chlorodeoxyadenosine therapy

Bone marrow granulomas in hairy cell leukaemia following 2‐chlorodeoxyadenosine therapy

Disseminated Mycobacterium malmoense infection in a patient with chronic granulocytic leukaemia

Mycobacterium malmoense is an atypical mycobacterium previously isolated from lymph nodes in children and from adults with pulmonary disease. Disseminated infection is extremely rare and bone marrow involvement has never previously been described. We report a patient with chronic granulocytic leukaemia and persistent fever with granuloma in the bone marrow due to disseminated M. malmoense infection. The patient initially received treatment with isoniazid, ethambutol and rifampicin with clearance of mycobacteria in the bone marrow and clinical improvement. Sensitivity in vitro was established for streptomycin, amikacin, ethambutol and rifabutin. The patient eventually expired as a result of progressive respiratory failure from other opportunistic infections. At autopsy staining of samples from lung parenchyma revealed fungal hyphi but staining for Pneumocystis carinii and myobacteria were negative.

Human ehrlichiosis: Hematopathology and immunohistologic detection of Ehrlichia chaffeensis

Human ehrlichiosis is a recently described zoonosis caused by a rickettsia that infects leukocytes. Most patients have fever, headache, chills, and myalgias and develop leukopenia, thrombocytopenia, anemia, and elevations in serum hepatic aminotransferases. The cause of the peripheral leukopenia and thrombocytopenia is not known. We studied peripheral blood smears, bone marrow aspirates, and bone marrow biopsy specimens from patients with serologically proven ehrlichiosis to characterize the pathologic changes associated with leukopenia or thrombocytopenia, to detect the presence of immunohistologically demonstrable ehrlichiae, and to establish the infected host target cell(s). Specimens were obtained from 12 patients, and immunohistology for Ehrlichia chaffeensis was performed on tissue sections, aspirated bone marrow, and peripheral blood smears. Mean leukocyte and platelet counts available for nine patients were white blood cell count 3,300/μL (range, 1,100 to 10,300/μL) and platelets 61,000/μL (range, 40,000 to 82,000/μL). Findings included myeloid hyperplasia (eight cases), megakaryocytosis (seven cases), granulomas (eight cases), marrow histiocytosis (one case), myeloid hypoplasia (one case), pancellular hypoplasia (one case), and normocellular marrow (two cases). Morulae of E chaffeensis were detected in four of 10 cases examined by immunohistology. Most ehrlichiae were detected within histiocytes, although morulae were rarely present within lymphocytes. Leukopenia, thrombocytopenia, or pancytopenia apparently most often results from peripheral sequestration or destruction; however, hypoplasia of marrow elements is present occasionally. Immunohistologic demonstration of E chaffeensis offers a direct means for establishing the etiologic diagnosis. These observations show the relatively frequent occurrence of bone marrow granulomas and suggest that infection of cells of the reticuloendothelial system may participate in the pathogenesis of human ehrlichiosis.

Uremic Tumoral Calcinosis: Preliminary Observations Suggesting an Association With Aberrant Vitamin D Homeostasis

Periarticular tumoral calcification is a unique form of soft tissue calcification that occurs infrequently in patients with end-stage renal disease. The mechanism underlying such massive periarticular calcifications is unknown. The radiographic similarity between uremic tumoral calcifications and those found in hereditary tumoral calcinosis, a disorder of calcitriol and phosphorus homeostasis, caused us to examine whether abnormalities in vitamin D metabolism were associated with uremic calcinosis as well. We examined two uremic subjects with massive periarticular tumoral calcifications and found that they had inappropriately high serum calcitriol levels for the degree of renal function, hyperparathyroidism, and hyperphosphatemia. The source of calcitriol could not be identified in one subject, but likely was derived from granulomatous tissue in the other. In the subject with marrow granulomas, we found that calcitonin administration further stimulated calcitriol production. Although epidemiological studies are needed to confirm this preliminary association between calcitriol and uremic tumoral calcinosis, our observations suggest that normal serum calcitriol levels in association with hyperphosphatemia may be a contributing factor in the development of this rare disorder.

ラットに自然発生する骨髄肉芽腫

Spontaneous granulomas developed frequently in the bone marrow of Slc: Wistar female rats over 19 weeks of age, whereas none did in JCL: SD and Slc: SD rats of either sex. These granulomas were composed histologically of epithelioid cells and macrophages clustered mostly in the center and lymphocytes and plasma cells located in the periphery, and they contained neither microorganisms nor foreign bodies. Ovariectomy of Slc: Wistar rats at 6 weeks of age resulted in a significant decrease in the incidence and size of bone marrow granulomas at 20 and 24 weeks of age. It is concluded that two factors, the strain of rats and female sex hormone, contribute to the pathogenesis of bone marrow granulomas--the former as a hereditary disposition and the latter as a promoter.

Macrophage progenitor cell and colony-stimulating factor production during granulomatous schistosomiasis mansoni in mice.

Schistosoma mansoni worm eggs stimulate a T-cell-mediated granulomatous response in which macrophages play important inflammatory and regulatory roles. Although much has been learned about the functions of the schistosome granuloma macrophages, their origin and replicative ability are unknown. In the present sequential study, macrophage progenitor cells in the bone marrow (GM-CFC) and liver granulomas (M-CFC) were enumerated, and macrophage colony-stimulating factor (CSF-1) in the circulation and culture fluid of explanted granulomas of infected mice was assayed. During the acute phase of the infection, when the granulomatous response was vigorous (weeks 8 to 12) GM-CFC numbers were high in the bone marrow and M-CFC numbers were low within granulomas. Circulating CSF-1 levels were elevated, but the vigorous granuloma-secreted CSF-1 level was low. During the chronic phase of the infection, the number of GM-CFC within the bone marrow and levels of circulating CSF-1 returned to normal. Conversely, a sharp increase in the number of M-CFC occurred within the small immunomodulated granulomas that also secreted high levels of CSF-1. The frequency of M-CFC that proliferated under exogenously added CSF-1 within the immunomodulated granulomas was significantly higher than that of cells in the vigorous granulomas. Adherent macrophage-rich cells obtained after dispersal of the granulomas appeared to be one source of CSF-1 production. These data indicate that during the infection the macrophage supply to and replicative ability within the granulomas is influenced by systemically and/or locally produced CSF-1.

Silicotic lesions of the bone marrow: histopathology and microanalysis.

Silica deposition and characteristic nodular silicotic lesions of the bone marrow, virtually unknown features of silicosis, are described in a case of severe lung silicosis with silicotic granulomas of the liver and spleen. Scanning electron microscopy and X-ray microanalysis confirmed the presence of quartz and feld-spars. The bone marrow lesions included inconspicuous accumulations of silica-containing macrophages, free silica, slight lymphocyte and plasma cell infiltration, and reticulin fibre formation; and development of slightly larger partly fibrous silicotic nodules, comparable to those of the lung, liver, and spleen. Silicosis must therefore be considered in the differential diagnosis of bone marrow granulomas.

Epithelioid granulomas of the bone marrow in non-Hodgkin's lymphoproliferative malignancies.

Ten cases of epithelioid granulomas in the bone marrow of patients with various non-Hodgkin's lymphoproliferative malignancies have been encountered. These included six with non-Hodgkin's lymphoma (three histiocytic and three poorly differentiated lymphocytic types), three with multiple myeloma, and one with acute lymphoblastic leukemia. The bone marrow was not involved by the primary disease in two of the six patients with lymphoma, whereas three with lymphoma showed both granulomatous and lymphomatous lesions in the same marrow specimens, and in one, these lesions were seen in the marrow at different times. The three myeloma patients showed evidence of both myeloma and granulomas in their marrow. In the case of acute lymphoblastic leukemia, the bone marrow showed only granulomas, the leukemic process being in complete remission. Although small numbers of similar cases have been reported before, the authors were unable to find a previous report of acute lymphoblastic leukemia associated with bone marrow granulomas. Although the pathogenesis and the clinical significance of the granulomatous lesion of the bone marrow in non-Hodgkin's lymphoproliferative malignancies are unknown, this lesion should be differentiated from infectious or lipid granulomas as well as from involvement by the primary disease.

Granulomatous Bone Marrow Disease

We have reviewed 58 cases of bone marrow granuloma at a single institution over a 20-year time span, and have summarized the available English literature. We conclude that bone marrow granulomas are an infrequent pathologic finding which, when found, require definition as to an underlying etiology. Undoubtedly, the illnesses associated with marrow granuloma are similar to those causing granulomatous hepatitis. The following additional statements may justifiably be made based on this review. There are no morphologic features which allow reliable differentiation between the causes of bone marrow granuloma. By combining careful histologic, microbiologic, and serologic techniques, an etiology can be documented in most (87%) patients with marrow granulomas. A medication history is an important element of this evaluation. Rocky Mountain spotted fever, cytomegalovirus infection, ibuprofen, acute lymphocytic leukemia, and various collagen vascular diseases should be added to the list of causes of marrow granuloma. The prognostic significance of marrow granuloma in patients without an ascertainable underlying illness remains unclear.

Study on subacute toxicity of intravenous sorbitan trioleate (STO) in Wistar rats.

Subacute toxicity of STO was carried out using Wistar rats. STO was administered intravenously at dose levels of 12.5, 50.0 and 200.0 mg/kg for 35 days. No influence on general symptom, body weight, food and water consumption and urinalysis were observed. In 200.0 mg/kg group, the hematological examination revealed anemia corresponding to the histological findings of the bone marrow. Biochemical analysis displayed the significant increase and/or decrease of enzyme values in 200.0 mg/kg group. Morphology showed the swelling, vacuolization and granuloma of the spleen, hepatic granuloma, the increase of reticulum cells and granuloma in the bone marrow. Embolism and thrombus were also found in the pulmonary and tail veins probably due to an artifact caused by the i.v. injection. The toxicity of the STO were observed only in 200.0 mg/kg group of both sexes and any remarkable change other than physical effects were found in other groups under the above dosage. Accordingly, the maximal no-effect level of the STO in Wistar rats was considered to be 50.0 mg/kg.

REVERSIBLE BONE MARROW GRANULOMAS WITH OXYPHENBUTAZONE — First report?

REVERSIBLE BONE MARROW GRANULOMAS WITH OXYPHENBUTAZONE — First report?

Acute eosinophilic interstitial nephritis with bone marrow granulomas: Report of a case

A 44-year-old man had renal failure, acute eosinophilic interstitial nephritis, and bone marrow granulomas. There was no anterior uveitis or peripheral lymphadenopathy. No etiologic agents became apparent. This case appears to be an abortive form of the new syndrome reported by Dobrin, Vernier, and Fish ( Amer. J. Med., 59, 325, 1975). Immunofluorescent study did not reveal the known linear or granular pattern along tubular basement membrane, but IgA in the small vessel walls. Steroid treatment led to some improvement of renal function.

PROCAINAMIDE ASSOCIATED WITH BONE MARROW GRANULOMAS — FIRST REPORT

PROCAINAMIDE ASSOCIATED WITH BONE MARROW GRANULOMAS — FIRST REPORT

Bone Marrow Granulomas and Neutropenia Associated With Procainamide

Bone marrow granulomas and neutropenia occurred in a 77-year-old man following the ingestion of procainamide hydrochloride for 50 days. Although neutropenia has occasionally occurred following procainamide therapy, granulomas in the bone marrow have not previously been associated with the use of this drug. There was no other apparent agent that could have been responsible for the granulomas. Eighteen days after administration of the drug had been discontinued, the WBC count returned to normal and there were no granulomas present in the bone marrow.

Bone marrow granulomas and neutropenia associated with procainamide. Report of a case

Bone marrow granulomas and neutropenia associated with procainamide. Report of a case

Acute eosinophilic interstitial nephritis and renal failure with bone marrow-lymph node granulomas and anterior uveitis: A new syndrome

We describe two patients with a unique granulomatous syndrome who presented with renal failure secondary to diffuse eosinophilic interstitial nephritis. Both had bilateral anterior uveltis, bone marrow granulomas, hypergammaglobulinemia and an increased sedimentation rate. One patient had lymph node granulomas and an immunoglobulin G (IgG) rheumatoid factor. An extensive investigation for an etiologic agent was unrewarding, and neither patient could be placed into any existing diagnostic category. Over a period of 2 years both patients have experienced improved renal function and dissolution of their bone marrow granulomas

The superiority of histologic sections of aspirated bone marrow in malignant lymphomas. A review of 1,124 examinations.

Histologic sections on 1,124 consecutive aspirated bone marrow examinations were reviewed. The findings were compared with the reading on smears made from the same aspiration. The result confirms previous studies and indicates that sections are far more valuable than smears in the diagnosis of granuloma, metastatic tumor, and lymphoma in the bone marrow. Only 9 of the 27 cases of malignant lymphomas diagnosed by sections were diagnostic on smears. None of the 5 cases with Hodgkin's disease in this group was apparent on smears. It is concluded that sectioning of the aspirated bone marrow is an important procedure and should be included in the routine examination of bone marrow.

Renal Lesions, Gross Hematuria, and Marrow Granulomas in Infectious Mononucleosis

HEMORRHAGIC manifestations of infectious mononucleosis are not uncommon. Virtually every organ system has been involved. 1 Gross hematuria is quite rare, and renal biopsies have not been done in the few cases reported. Granuloma formation in the bone marrow in infectious mononucleosis is a phenomenon which was first reported less than 20 years ago. 2 This finding, although reported to be quite common, does not yet seem to be within the realm of common medical knowledge. It will be the purpose of this paper to present and discuss the significance of a case of infectious mononucleosis associated with granulomatous changes in the bone marrow, unique renal lesions, and gross hematuria. Report of a Case The patient is a 19-year-old white boy, who had been experiencing confusion, visual hallucinations, chills, fever, sore throat, and grossly bloody urine during the week preceding his hospital admission. The patient was seen by a local