Paget's disease associated
with myelofibrosis and myeloid metaplasia - a common
pathophysiology ?
Cristina João*, Teresa Matias+, João
Sá+
* Serviço de Hematologia &endash; IPOFG, Lisboa;
+Serviço de Medicina, Hospital de S. José, Lisboa,
Portugal
Correspondence: Cristina João, M.D., Hematology Department,
Instituto Português de Oncologia, Lisboa. Telf.: +351 21
7789755. Fax: +351 21 7606495. Email: cristinajoao@yahoo.com
Text
Paget´s disease is a chronic and disabling bone disease of unknown etiology that may represent a global dysfunction of pluripotent hematopoietic stem-cell. It is now believed that a slow paramyxovirus infection in which the pluripotent hematopoietic stem cell might be the reservoir of the virus could be of pathophysiological important.1,2 This observation raised the question whether exists a common pathophysiological pathway for Paget´s disease and haematological disorders with hematopoietic stem cell dysfunction as Myelofibrosis with Myeloid Metaplasia (MMM). We report a case of a 66 year old Caucasian man with a one year history of anemia, loss of weight and localised bone pain (shoulders, knees and dorsal spine). The past history includes a myocardial infarction in 1997 and a cerebral infarction in 1996. The laboratory evaluation showed a normocytic, normocromic anemia (Hb 10,0 g/dl) with a normal % of reticulocytes, normal leucograma and thrombocytopenia (90x109/L), and an elevated alkaline phosphatase (up to 580 µg/L) and lactate dehydrogenate. The serum calcium levels were normal but serum phosphorus was slightly elevated. The examination of the blood film revealed aniso and poikilocytosis, polycromatophilia, tear drop erythrocytes and erythroblasts and immature myeloid cells. The bone marrow examination was a dry tap for two times but the third was able to show a hypocellularity marrow with many areas of bone formation with a pattern of mosaic bone. There was bone lysis and fibrosis but the bone remodelling favored the deposition of new bone. There was any signs of metastases. The imagiological examination showed hepatosplenomegaly and the technetium 99m diphosphonate bone scan showed hot spots all over the spine, omoplats and proximal endings of both umerus. A peripheral blood cell cytogenetic study showed absence of Philadelphia chromosome. All these facts are compatible with MMM3,4 and also Paget´s disease. Several biochemical markers of bone turnover used as Paget´s markers 5 were measured and the results supported the hypothesis of Paget´s disease: urinary hydroxiproline to creatinine ratio 1,5 mg/g (normal value 0,02-0,2); serum osteocalcin 21,30 hg/ml (normal 3-13); serum collagen I cross-links 28,2 hN/hN creat (normal 2,5-5,4), urinary N-telopeptide (NTX) 748 hM (normal 5-65) and urinary D-pyridinoline and deoxypyridinoline 217 hM (normal 8-24). A diagnosis of myelofibrosis and myeloid metaplasia associated with Paget's disease was made 1,6. The patient was considered in the low risk group of the Lille Scoring System of MMM and as having a polyostotic Paget' disease. In conclusion, we present a case of Paget´s disease diagnosed simultaneous with MMM, reinforcing the potential concept of a common pathophysiological mechanism. This observation deserves further investigation on this topic and more fundamental investigation needs to be done in this area.
