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PubMed2005

Agnogenic myeloid metaplasia with pulmonary hematopoiesis.

Agnogenic myeloid metaplasia (AMM) is characterized by bone marrow fibrosis, splenomegaly and leukoerythroblastic anemia and is frequently accompanied by extramedullary hematopoiesis (EMH). Pulmonary interstitial EMH associated with myelofibrosis has rarely been described in the medical literature and is usually fatal. We report the case of a 77-year-old man with agnogenic myeloid metaplasia (AMM) treated with hydroxyurea, who seven years after diagnosis presented with dyspnea and severe hypoxemia. Radionuclide bone marrow scanning demonstrated increased tracer activity on the bases of both lungs, consistent with non-hepatosplenic EMH. Pulmonary EMH is rare in patients with AMM, but should be considered in patients with hypoxemia and respiratory distress.

Aged↗
PubMed2004

Agnogenic myeloid metaplasia with pleural extramedullary leukemic transformation.

Agnogenic myeloid metaplasia (AMM) is one of the myeloproliferative disorders, and is usually accompanied by extramedullary hematopoiesis (EMH) in various organs, mainly in the liver, spleen and lymph nodes. Extramedullary hematopoiesis and/or leukemic transformation of EMH in the pleura is a rare occurrence and is usually asymptomatic. Pleural involvement is usually diagnosed on postmortem examination. Herein we describe a 71-year-old man with newly diagnosed agnogenic myeloid metaplasia who was evaluated for progressively worsening dyspnea, pulmonary hypertension and bilateral pleural effusions. EMH involving the lungs and pleura was suspected. A sulfur colloid technetium 99m bone marrow scan performed to detect extramedullary hematopoiesis was negative. The diagnostic thoracentesis yielded bloody fluid that contained a large population of myeloblasts, indicating pleural leukemic transformation. The patient received 100 cGy to the whole lung for treatment of pulmonary hypertension due to EMH. This was followed by 1500 cGy total dose of radiation to the left lung for pleural extramedullary leukemic transformation. Pleural effusions resolved and repeat echocardiography showed reduction of the pulmonary artery pressure. Three months later he had leukemic transformation involving the skin and lymph nodes. Four months after radiation therapy, he had full-blown acute myeloid leukemia. He received 2 cycles of Gemtuzumab ozogamicin (Mylotarg), allopurinol and hydroxyurea. Three months after initiation of chemotherapy, he deteriorated and received salvage chemotherapy of prednisone, VP-16 and imatinib mesylate (Gleevec). He was hospitalized for neutropenic fever and was diagnosed to have pulmonary aspergillosis. He died of multisystem failure 8 1/2 months after being diagnosed with AMM.

Aged↗
PubMed1978

Myeloid metaplasia and osteolytic lesions.

The case of a patient with myelofibrosis and painful osteolytic lesions is described. Biopsy of the involved bone demonstrated myeloid proliferation. Foci of myeloid metaplasia may occasionally result in clinical disability, with bone pain and rarefaction. Myeloid metaplasia should be considered when these symptoms and signs occur in the setting of myelofibrosis. The role of radiation therapy as a palliative maneuver remains uncertain.

Bone Resorption↗
PubMed1978

Splenectomy in myeloid metaplasia.

A retrospective review of 19 patients with documented myeloid metaplasia undergoing, elective splenectomy during the past ten years at the Peter Bent Brigham Hospital is presented. The primary indications for splenectomy in 17 of these 19 were either hypersplenism or symptomatic splenomegaly. Eighteen of the 19 underwent both 59Fe-ferrokinetic studies and 51Cr-sequestration studies or, alternatively, 111In-marrow scintigraphy as a part of their routine preoperative evaluation. The death from sepsis of one patient six weeks post-operatively, whose marrow function was poor and whose level of splenic sequestration was minimal, confirms the efficacy of these studies in the preoperative prediction of hematologic response to splenectomy. Eighteen of the 19 patients benefited from the operation in terms of symptomatic relief and/or hematologic improvement, although surgery presumably did nothing to prolong survival in these patients. We conclude that splenectomy is indicated as a palliative maneuver for carefully selected patients with myeloid metaplasia without prohibitive operative risk, provided the criteria for selection of patients are adhered to and the surgeon and hematologist work together as a team.

Boston↗
PubMed1987

Liver sinusoids and sinusoidal cells in patients with agnogenic myeloid metaplasia.

The origin of sinusoidal portal hypertension often remains unknown in patients with agnogenic myeloid metaplasia. Four consecutive patients with agnogenic myeloid metaplasia had liver biopsies examined under light and electron microscopy. Two of the four had obvious clinical portal hypertension; of these two, only one had portal vein thrombosis. All four cases showed sinusoidal infiltration by myeloid cells (from very mild to obvious) and an increased perisinusoidal collagen network. Under electron microscopy we observed (a) the collagenization of the Disse space, (b) myeloid cells in the lumen and the Disse space, (c) the transformation of perisinusoidal cells into transitional cells, and (d) fragments of basement membrane-like material. It is possible that all these abnormalities, and not only sinusoidal infiltration, contribute to increase vascular resistance, even when there is no clinical evidence of portal hypertension unrelated to vascular thrombosis.

Aged↗
PubMed1989

Intracranial granulocytic sarcoma in postpolycythemia myeloid metaplasia.

A 57-year-old man with a ten-year history of polycythemia vera had myeloid metaplasia, extramedullary hematopoiesis, and terminally, possible leukemic transformation with intracranial granulocytic sarcoma. Radiation therapy produced a partial and temporary beneficial response. Intracranial granulocytic sarcoma is typically associated with acute or chronic myelogenous leukemia and has not been previously associated with postpolycythemia myeloid metaplasia.

Brain Neoplasms↗
PubMed1996

Successful allogeneic bone marrow transplantation for agnogenic myeloid metaplasia in a 3-year-old boy.

PURPOSE: Agnogenic myeloid metaplasia (AMM) is a myeloproliferative disorder characterized by marrow fibrosis, extramedullary hematopoiesis, splenomegaly, and leukoerythroblastosis with abnormalities of red blood cell morphology. This is rarely encountered in children. No conventional curative therapy is known; however, allogeneic bone marrow transplantation (BMT) may eradicate the underlying stem cell abnormality with subsequent normal hematopoiesis. RESULTS: We report a 3-year-old Arab boy who had AMM and who had normal marrow hematopoiesis and markedly reduced fibrosis after high-dose chemotherapy and matched sibling BMT. CONCLUSIONS: Allogeneic BMT offers a potential cure for patients with agnogenic myeloid metaplasia. A preparatory regimen containing busulfan and cyclophosphamide appears promising for patients with the disease.

Bone Marrow Transplantation↗
PubMed1977

Impaired neutrophil function and myeloperoxidase deficiency in myeloid metaplasia.

The ability of neutrophils to phagocytose and kill Candida guilliermondii was investigated in 12 patients with myeloid metaplasia (MM). Following ingestion there was a considerable impairment in the ability of MM neutrophils to kill and digest Candida which was not explained by the very mild impairment in phagocytosis. Quantitative myeloperoxidase measurement revealed an overall deficiency of this enzyme in MM neutrophils and a highly significant correlation between low myeloperoxidase levels and impaired candidacidal activity. Neutrophils from patients with myeloid metaplasia show a pattern of defective microbial killing, high alkaline phosphatase activity and low myeloperoxidase activty which is similar to that seen in severe infections and distinct from chronic granulocytic leukaemia. The cells of one patient with particularly low myeloperoxidase and defective microbial killing were further studied both cytochemically and by electron microscopy. The azurophilic granules of his neutrophils were present in normal numbers and contained normal amounts of acid phosphatase but they lacked myeloperoxidase.

Candida↗
PubMed1991

Increased intraplatelet levels of platelet-derived growth factor and transforming growth factor-beta in patients with myelofibrosis with myeloid metaplasia.

Platelet-derived growth factor (PDGF) is thought to play some role in the genesis of fibrosis associated with myeloproliferative disorders. In addition, transforming growth factor-beta (TGF-beta) has been confirmed to promote fibrotic process. Both PDGF and TGF-beta have been shown to cooperate with epidermal growth factor (EGF) in regulating the growth of human marrow fibroblasts. All three are contained in platelet alpha-granules. We report the results of a study in patients with myelofibrosis with myeloid metaplasia (MMM). We evaluated PDGF, TGF-beta and EGF-like activities in circulating platelets from patients compared to healthy subjects. In contrast to EGF-like intraplatelet levels which were similar in patients and in normal donors (1-4 ng/10(9) platelets), we found constantly higher values for both PDGF and TGF-beta in MMM patients. In both radioimmunoassay (RIA) and assay for mitogenic activity on human bone marrow fibroblasts, PDGF levels were increased on the average 2-3.5-fold over the levels found in normal donors (P less than 0.01 and P less than 0.001, respectively). PDGF serum levels in patients were consistent with those found in platelets. In platelet-poor plasma (PPP), PDGF concentrations were undetectable or congruent to 2 ng/ml in patients and in control donors as well. The total TGF-beta activity in platelet lysates, determined using a competitive radioreceptor binding assay on Swiss 3T3 mouse cells and an inhibition growth assay on CCL64 cells, was found 2-3-fold increased in patients with MMM as compared to control subjects (P less than 0.003). These results emphasize that, not only PDGF, but also TGF-beta are implicated in the myelofibrosis with myeloid metaplasia.

Adult↗
PubMed2005

The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates.

An association between an activating JAK2 mutation (JAK2(V617F)) and BCR/ABL-negative myeloproliferative disorders was recently reported in multiple simultaneous publications. In the current study, mutation analysis for JAK2(V617F) was performed in peripheral blood mononuclear cells (PBMC) from 157 patients with myelofibrosis with myeloid metaplasia (MMM) including 117 with agnogenic (AMM), 22 with postpolycythaemic (PPMM), and 18 with post-thrombocythaemic (PTMM) myeloid metaplasia. The detection rate for JAK2(V617F) was significantly higher in PPMM (91%; homozygous in 18%) compared with either AMM (45.3%; homozygous in 2.6%) or PTMM (38.9%; homozygous in 11.1%). Concomitant analysis in granulocytes (n=57) and CD34(+) cells (n=25) disclosed a higher incidence of homozygous JAK2(V617F) mutation but the overall mutation rate was similar to that obtained from PBMC. JAK2(V617F) was not detected in DNA derived from T cells (n=19). In AMM, the presence of JAK2(V617F) was associated with an older age at diagnosis and a history of thrombosis or pruritus. Multivariate analysis identified only age and the Dupriez prognostic score as independent prognostic factors; JAK2(V617F) had no prognostic significance. In conclusion, JAK2(V617F) is a myeloid lineage-specific event, its incidence in MMM is significantly higher with an antecedent history of polycythaemia vera (PV), and its presence in AMM does not affect prognosis but is associated with PV-characteristic clinical features.

Adolescent↗
PubMed1986

O-acetylated sialic acid variants in intestinal glandular metaplasia of the urinary tract.

Two cases of chronic cystitis, two of chronic ureteritis, one of chronic pyelitis and two transitional cell carcinomas of the urinary tract showed glandular metaplasia or focal mucin production. Positive staining for O-acetylated sialic acid variants (sites 7 and 8) detected by the PB-KOH-PAS method was found in the two cases of cystitis, in one of chronic ureteritis and in one of chronic pyelitis. Positive staining was observed only in areas showing an intestinal type of metaplasia and in which goblet cells and argyrophil cells were also identified. These findings taken together with earlier studies on ovarian cystadenomas lead the authors to believe that O-acetylated variants are markers of an intestinal type of epithelium. Evaluation of O-acetylated sialomucins may be useful in further studies on the histogenesis of primary adenocarcinomas of the bladder.

Adult↗
PubMed1982

Intracranial myeloid metaplasia in myelofibrosis.

In a man aged 62 years with a 14-year-history of polycythaemia vera progressing into a myelofibrotic stage symptoms and signs of an intracranial tumour with increased intracranial pressure developed. CT scan as well as angiography of the right internal carotid artery revealed richly vascularized masses within the meninges. The patient died in endocarditis and progressive heart failure and at autopsy the intracranial masses were shown to be due to meningeal myeloid metaplasia. The literature is reviewed and it appears that myeloid metaplasia within the central nervous system might be more common than has been hitherto anticipated. A CT scan is to be recommended in myelofibrosis whenever symptoms and signs suggesting intracranial disease are present.

Brain Diseases↗
PubMed1985

Myeloid metaplasia, perisinusoidal fibrosis, and nodular regenerative hyperplasia of the liver.

We describe two patients with myeloid metaplasia in whom portal hypertension resulted, not from infiltration of the liver sinusoids by myeloid cells, but from perisinusoidal fibrosis and nodular regenerative hyperplasia of the liver. We hypothesize that myeloid metaplasia induced the development of perisinusoidal fibrosis, which resulted in heterogeneous hepatic tissue blood perfusion, with atrophy of the liver cells in the underperfused areas and nodular regenerative hyperplasia in the normally perfused areas.

Aged↗
PubMed1988

Ciliated metaplasia in a gastric adenoma in a Swedish patient.

The second European case of ciliated gastric metaplasia is presented, this time in a Swedish patient. Cilia were found in cystically dilated glands underneath a gastric adenoma. The possibility that cilia represent adaptative metaplasia aimed at expelling the retained mucus within the cysts is discussed.

Adenoma↗
PubMed1983

Arthritis due to synovial involvement by extramedullary haematopoiesis in myelofibrosis with myeloid metaplasia.

A 60-year-old man presented with polyarthralgias, a psoriasiform rash, and severe elbow pain. Peripheral blood smear and bone marrow biopsy established a diagnosis of myelofibrosis with myeloid metaplasia. Biopsy of the skin lesions revealed a nonspecific dermatitis. The clinical presentation was inconsistent with psoriatic arthritis, and there was no evidence for associated gout or collagen-vascular disease. Histological examination of tissue taken at the time of synovectomy indicated elbow arthritis to be due to myeloid metaplasia involving the synovial membrane.

Arthritis↗
PubMed2005

Barrett's oesophagus: from metaplasia to dysplasia and cancer.

Barrett's oesophagus is a premalignant condition that predisposes to the development of oesophageal adenocarcinoma. It is detected on endoscopy and confirmed histologically by the presence in the lower oesophagus of a metaplastic mucosa, the so-called specialised epithelium, which resembles incomplete intestinal metaplasia in the stomach. These similarities with incomplete intestinal metaplasia are present on histology, mucin histochemistry, and immunohistochemistry with various differentiation markers (cytokeratins and MUC antigens). On morphology, the carcinogenetic process of Barrett's mucosa progresses through increasing grades of epithelial dysplasia. Dysplasia, a synonym of intraepithelial neoplasia, is the only marker that can be used at the present time to delineate a population of patients at high risk of cancer. Among the numerous molecular events that have been shown to play a role in the neoplastic transformation of Barrett's mucosa, only changes in DNA ploidy, increased proliferation, and alterations of the p53 gene have been suggested to be of potential help in the surveillance of patients.

Aneuploidy↗
PubMed2005

Myeloid metaplasia in the gall bladder: a case report.

Idiopathic myelofibrosis is often associated with myeloid metaplasia (extramedullary haemopoiesis) in the spleen and liver. However, the gall bladder is an extremely unusual site for it to occur. A 59 year old man with myelofibrosis, who underwent cholecystectomy for chronic cholecystitis, showed myeloid metaplasia in his gall bladder. Pathologically, this may lead to diagnostic difficulties.

Gallbladder Diseases↗
PubMed2001

Bone metaplasia in a case of bilateral renal cell carcinoma.

We present a case of synchronous, bilateral renal cell carcinoma with osseous metaplasia. In renal cell carcinoma, bone can originate through two different processes: osseous differentiation or osseous metaplasia. The case we report here represents the second process. We discuss pathological differential diagnosis and prognosis of the infrequent tumor.

Aged↗