a 45-year - old hispanic woman presented to a local hospital with a 2-week history of progressively worsening diffuse back pain , fatigue , a generalized sense of weakness , and daily fevers and sweats . she denied any parasthesias , or dyasthesias , but the pain was severe enough to limit some of her activities of daily living . of note she did have a significant history of von willebrand 's disease diagnosed at the age of 35 and had otherwise been in good health without major medical problems thus far . physical examination revealed a palpable , non - mobile , 22 centimeter mass at the level of the left 10th rib with no overlying cutaneous changes . neurological examination was grossly normal . the complete blood count ( table 1 ) revealed leukocytosis of 33.810/l , 2% blasts with a left shifted differential without thrombocytosis ( 41610/l ) , or anemia ( 9.0 g / dl ) . the chemistry panel was significant for hypercalcemia ( 13.8 mg / dl ) , an elevated lactate dehydrogenase ( ldh ) level ( 4,823 a bone scan demonstrated increased uptake in the left hip felt to be a degenerative left acetabulum ( fig . plain radiographs ( fig . 1 ) and mri imaging of the left hip showed lytic lesions in the left femoral neck . both a marrow biopsy and a tissue sample of the rib mass were non - diagnostic . hip view shows multiple discrete myelomatous lesions in the pelvis and a lucent lesion in the left femoral neck . progression of cbc , ldh , and alkaline phosphatase during hospital stay upper limit of normal 618 iu / l ; upper limit of normal 126 iu / l . wbc , white blood cell count ; hb , hemoglobin ; na , not available ; ldh , lactate dehydrogenase . for the hypercalcemia , broad - spectrum intravenous antibiotics were started since the patient had a low - grade fever of 99.6f . the patient was transferred to our institution suspecting a diagnosis of multiple myeloma . on presentation to our institution , the white blood cell count ( wbc ) was 33.710/l consisting of 80% neutrophils and a left shift including 2% metamyelocytes and 2% blasts . tear drop cells were not identified and there were no schistocytes . the hemoglobin was 9 g / dl and the platelet count was 41610/l . ldh levels were elevated at 4,823 iu / l ( upper limit of normal [ uln ] 618 iu / l ) , corrected calcium was 11.94 mg / dl , and alkaline phosphatase levels were 257 iu / l ( uln 126 ) . a bone survey shortly after transfer showed normal bone mineral content , multiple discrete lytic lesions in the skull , ribs , pelvis , and shoulder girdle and a lytic lesion in the adjacent left supra - acetabular ilium and femoral neck ( fig . 1 ) . a pet / ct scan showed diffuse activity of the marrow spaces throughout the axial skeleton and extending into the appendicular skeleton as well as throughout the spleen . large lytic lesions were also noted within several regions including the left femoral neck and left acetabular roof which corresponded to the lesions seen on the bone survey ( fig . however , serum protein electrophoresis and immunofixation did not show evidence of a monoclonal protein . ( a ) extensive nodular increased activity most evident in long bones such as both humeri and femurs . ( b ) conspicuous foci with intense activity are seen in the medial condyle of the right femur ( suv 3.3 ) and left acetabular roof and femoral neck where a 3 cm lytic lesion is seen with cortical destruction ( suv 15.8 ) . during the course of hospitalization her temperature remained elevated between 99.3f and 102.4f despite the use of broad - spectrum antibiotics . blood and urine cultures remained consistently negative and no source of infection was identified . within 2 weeks of admission , the blood counts deteriorated and the patient became increasingly anemic , thrombocytopenic , and leukopenic ( table 1 ) . a repeat marrow biopsy and curettage of the left femoral neck region ( a ) the lesion is infiltrative and bone destructive ( hematoxylin&eosin , 100 ) . ( b ) a higher power view of the infiltrative tumor cells and admixed megakaryocytes ( hematoxylin&eosin , 500 ) . ( d ) many tumor cells which are positive for factor viii - related antigen . the marrow biopsy was characterized by marked fibrosis with many crushed large cells and diminished hematopoietic elements . immunohistochemical staining was limited with cd34 highlighting a few vessels and cd61 positive in some of the crushed cells . tumor cells were negative for myeloperoxidase ( mpo ) and non - specific esterase ( nse ) . the left femoral neck showed a malignant tumor infiltrate composed of large mononucleated to anaplastic cells with moderate cytoplasm and some multinucleated forms ( fig . the tumor cells were negative for cd138 , cd20 , cd3 , cytokeratin , s-100 , and cd30 . immunohistochemical stains which were positive on subset of cells included factor viii ( megakaryoctyes and some of the mononucleated tumor cells ) , cd61 ( mononucleated tumor cells ) , cd117 and mpo , and cd31 ( some mononucleated cells and some megakaryocytes ) . the infiltrate was associated with marked stromal fibrosis and significant tumor necrosis . in combination , these features suggested a diagnosis of myeloid sarcoma with megakaryocytic differentiation ( aml fabm7 ) . cytogenetic analysis based on the marrow sample revealed translocation t(1;13)(p22;q12 ) in 3 metaphases and del(13)(p12q22 ) in one . the patient received induction chemotherapy consisting of idarubin and intermediate dose cytarabine in combination with clofarabine as part of an investigational induction program for patients younger than 60 years old . on day 4 of chemotherapy an allogenetic stem cell transplant is being considered early in the treatment course for her myeloid sarcoma with megakaryocytic differentiation . acute panmyelosis with myelofibrosis is a rare form of aml which presents acutely with constitutional symptoms , fevers and bone pain , and pancytopenia ( 1 ) . in general , osteolytic lesions are rare in leukemias and lymphomas and are seen more frequently in plasma cell disorders and metastatic solid tumors . however , further work up did not reveal the presence of plasma cells or a population of monoclonal proteins . although non - secretory myeloma was a consideration , it is very rare ( only about 3% of plasma cell disorders ) , involves neoplastic plasma cells ( which could not be detected in this case including by immunohistochemical stains ) , and in up to two - thirds of cases demonstrates abnormal light chain levels or ratio . furthermore , presentation with hypercalcemia is less common in non - secretory myeloma than its more frequent secretory variants ( 2 , 3 ) . the diagnostic procedure which ascertained the diagnosis was a left femoral biopsy pointing strongly toward a diagnosis of a myeloid sarcoma with megakaryocytic differentiation akin to aml fabm7 when taking into consideration the marrow biopsy results as well . skeletal radiological manifestations in patients with myelofibrosis may range from normal to osteoporosis and osteosclerotic changes ( the latter in 30 to 70% of cases ) . osteolytic lesions on the other hand are exceedingly rare ( 4 , 5 ) . in combination with hypercalcemia , occurrence of lytic lesions has been associated with accelerated and blastic phases of myelofibrosis (  acute myelofibrosis ) , a rapid disease course , and poor prognosis ( 6 ) . it typically occurs as de novo and is not preceded by a lengthy prodrome of the clinical manifestations of myelofibrosis . criteria for diagnosis include panmyelosis ( marrow hypercellularity with multilineage involvement ) , severe marrow fibrosis , pancytopenia with absence of tear - drop - shaped red blood cells , and lack of splenomegaly ( 7 , 8) . using a panel of antibodies such as mpo , lysozyme , erythroid markers , and megakaryocytic markers allows demonstration of the multilineage nature of the proliferation . although most patients marrow will show an abnormal karyotype , no specific cytogenetic abnormalities have been described . according to one series of 12 patients with acute panmyelosis structural abnormalities of chromosome 12 were most frequent whereas abnormalities of chromosomes 3 and 13 have been associated with myelofibrosis in previous observations ( 7 , 9 ) . according to who criteria , the diagnosis in this case requires at least 20% blasts of which at least 50% are of megakaryocytic lineage . markers to identify megakaryocytic forms are mainly antibodies with reactivity against platelet glycoproteins ( cd41 , cd42 , cd61 ) or against von willebrand factor viii although not all of them are equally apt for use in routinely processed tissue sections ( 8 , 10 ) . blasts in acute megakaryoblastic leukemia are less heterogeneous than in acute panmyelosis which may reflect a less immature and more committed cell of origin in the former . whereas cd34 is nearly always expressed in panmyelosis , many cases of acute megakaryocytic leukemia lack expression of cd34 and hla - dr . although extensive , marrow fibrosis is less pronounced in the megakaryocytic variant than in panmyelosis . hypercalcemia itself in the absence of osteolytic lesions is a very rare feature as well and has only be described in one previous case report of an 8 month - old non - down syndrome infant with a diagnosis of acute megakaryocytic leukemia and hypercalcemia at presentation ( 11 ) . other diagnoses with overlapping clinical and pathologic features that need to be considered include primary myelofibrosis , fibrotic subtypes of myelodyplastic syndrome , and tumors of other tissues of origin that metastasize to the marrow . these distinctions can usually be reliably made based on the degree of fibrosis , percentage and marker expression of blasts , level of dysplasia , and presence or absence of solid tumor cells in the marrow . the prognosis of patients with either acute megakaryocytic leukemia or acute panmyelosis is nearly equally poor . median survival times following aml type induction therapy are measured in few months and outside use of allogeneic stem cell transplant . only a few long - term survivors have been identified ( 7 , 8 , 12 ) . how alternative treatment modalities and newer drugs may influence future prognosis is unknown and only occasional case reports are described ( 13 ) . in conclusion , this is a 45-year - old patient with progressive constitutional symptoms , osteolytic bone lesions with hypercalcemia , and a rapidly worsening pancytopenia . the final pathological diagnosis is that of an acute megakaryocytic leukemia ( aml m7 ) weighing in identification of megakaryocytic markers in the tissue section and the diffuse and strong staining for cd34 . presentation of patients with osteolytic lesions should not automatically be assumed to be of plasma cell origin and myeloid malignancies should be kept in the differential diagnostic considerations . the authors have not received any funding or benefits from industry or elsewhere to conduct this study . none of the authors have any financial or personal bias that would inappropriately compromise the publication of this work . informed consent was obtained from the patient and her family for educational use of the data and no personal patient information has been disclosed .
acute megakaryocytic leukemia is a rare form of acute myeloid leukemia that carries a poor prognosis . 
 as most cases of osteolytic lesions are due to plasma cell and myeloid malignancies , maintaining a broad differential directly influences clinical course . 
 we document a 45-year - old patient with progressive constitutional symptoms , osteolytic bone lesions in the setting of hypercalcemia , who developed acutely worsening pancytopenia . 
 the diagnosis of myeloid sarcoma with megakaryocytic differentiation was made after obtaining tissue from osteolytic bone that stained strong for cd34 . 
 immunohistochemical testing underscores the importance of how serologic and urine testing remains limited and can delay early diagnosis in this disease .