Not all myeloid sarcomas have a liquid friend! Myelosarcoma of the sacrum accompanied by severe myelofibrosis

Manuscript type : Case Report | Article Date : 2015/06/22

  • Autors

    1. Duma Narjust
    2. Wang Zhen
    3. R Woytanowski John
    4. Canning Andrew
  • Abstract

    Myeloid sarcoma is a rare disease with poor prognosis. It is characterized by tumor masses composed of myeloblastic cells and usually occurs in association with acute myeloid leukemia. A 71 year old female with past medical history of essential thrombocytosis for 15 years. She was asymptomatic at diagnosis, but began experiencing early satiety 1 year prior and was found to have splenomegaly and was started on hydroxyurea without improvement of her symptoms. This time, she presents to the emergency department with severe painless vaginal bleeding for 2 days. A complete blood count revealed severe thrombocytopenia (14,000/µL). Patient reported she was started on ruxolitinib for four months prior but denied any prior bleeding episodes. CT scan was obtained due to concern for a gynecologic malignancy; which revealed a para-spinous soft tissue mass around L4 level protruding into the psoas muscle. CT-guided biopsy of the sacrum was subsequently performed. Histology reported myeloid myeloperoxidase-positive elements. Immunohistochemical stains showed CD34-positive myeloblasts and CD-117-positive immature myeloid elements accounted for 20% of nucleated elements, compatible with the diagnosis of myeloid sarcoma. Bone marrow biopsy showed extensive fibrosis with no significant hematopoiesis and only 1% of myeloblasts. Bleeding resolved after several platelets transfusions and she was discharged with plans to start chemotherapy as outpatient. Her clinical course was complicated with septic shock during chemotherapy; she expired four months after her initial visit to the ED.
  • Description

    INTRODUCTION

    Myeloid sarcoma is a relatively uncommon ex-tra-medullary neoplasm of immature myeloid pre-cursors that are morphologically composed of my-eloblasts, monoblasts/promonocytes, and rarely promyelocytes.1-4 They can present anywhere in the body but have predilection for lymph nodes, bone, soft tissues and skin. This neoplasm typically devel-ops in concurrence with acute myelogenous leukemia or myelodysplastic disorders but could also present as an isolated soft tissue mass without peripheral blood involvement.1 Isolated myeloid sarcomas can some-times be seen as relapse in allogenic bone marrow transplantation or the first manifestation of acute my-elogenous leukemia.3-4

    CASE REPORT

    Our case is a 71-year-old female with past medical history of essential thrombocytosis for 15 years with an average platelet count of 550.000 and Janus As-sociated Kinase 2 (JAK) V617F positive. She was asymptomatic at diagnosis and did not require treat-ment until she started experiencing early satiety and left upper quadrant pain one year prior and found to have new onset splenomegaly by ultrasound. She was treated with hydroxyurea for a six month interval without improvement of symptoms for which reason she was started on ruxolinib. After two months, her symptoms improved and platelets were within normal limits. Four months later, she presented to our emer-gency department complaining of severe painless vaginal bleeding for 2 days. She denied any history of irregular vaginal bleeding or hormonal treatment. On physical examination, she was a well-developed female, with conjunctival pallor; diffuse petechial rash was noted in upper and lower extremities. Complete blood count revealed a white cell count of 4.3 x 10³/µL, hemoglobin of 6.3 g/dL, hematocrit of 25%, platelets 14.000/µL. During further question-ing patient reported she had been experiencing lower back pain for the past five months. Pain was located in the lumbar region and was radiating to lower extremities. Computed tomography (CT) of abdomen and pelvis was obtained due to concern for a gyne-cologic malignancy. This revealed a paraspinous soft tissue mass at the L4 level on both sides of the verte-bral body, protruding into the psoas muscle (Fig. 1-2). No pathologic lymphadenopathy was seen. Follow up magnetic resonance imaging showed, abnormal soft tissue within the neural foramina and epidural space of the upper and mid sacrum, with extensive infiltration of the sacral and iliac bone marrow. There was also infiltration of the lower lumbar spine and extension of the soft tissue mass at the sacral-lumbar junction. CT-guided biopsy of the sacrum soft tissue mass was performed (Fig. 3-4). Histology reported myeloid myeloperoxidase-positive elements and Immunohis-tochemical stains showed CD34-positive myeloblasts and CD-117-positive immature myeloid elements compatible with the diagnosis of myeloid sarcoma, the sample was not tested for JAK mutation on the basis of prior peripheral blood study confirming the mutation. Peripheral blood leukemia and lympho-ma profiles were within normal limits. A normal fe-male karyotype was observed. Bone marrow biopsy showed extensive fibrosis with no significant hemato-poiesis and minute population of myeloblasts (

    DISCUSSION

    Myeloid sarcoma also known as granulocytic sarco-ma, myeloblastoma or extramedullary myeloid cell tumor is the pathological diagnosis of a proliferation of myeloblastic cells at an extramedullary site that disrupts the surrounding architecture of its respective location 5-7 Originally called a “chloroma” due to its green color, myeloid sarcoma (MS) most often pres-ents in conjunction with acute myelogenous leukemia (AML), myeloproliferative neoplasms or myelodys-plasia [8].Myeloid sarcoma occurs in four different clinical settings: (a) as a localized tissue manifesta-tion in patients who already have AML; (b) as a sign of impending blast crisis in chronic myelogenous leukemia or leukemic transformation in patients with myelodysplastic syndrome; (c) as a forerunner of AML in non-leukemic patients; and (d) as an isolated neoplasm without progression to AML (least com-mon) [9-10]. MS rarely present with the absence of systemic disease. Moreover, 66–88% of patients with an isolated MS will develop AML at a mean of 9–11 months after diagnosis.8 Isolated MS occurs most often in males with a mean age of 47 years (range: 29 -72 years).11 Besides its most common locations on the skin, soft tissue, lymph nodes, and gastrointestinal tract, MS may involve any organ or system in the body.5 The symptoms are sub-stantially related with the anatomic location that is involved. MS is usually not included in the differential diagno-sis of a soft tissue masses due to its rarity. In a review of 154 patients with MS, 47% were initially misdiag-nosed as soft tissue sarcomas, non-Hodgkin lympho-mas or malignant melanomas.10 In order to prevent misdiagnosis, histologic examination is obligatory. Microscopically, myeloid cells are identified by a characteristic growth pattern: either diffuse or Indian file. MS is further classified into granulocytic, monoblastic or myelomonocytic based on the predominant cell type found.12 Immunophenotyping also guides the process; the most common positive markers of MS are CD30, CD34, CD56, CD61, CD68/PG-M1, CD99 and CD117. Cytogenetic abnormalities, particularly monosomy 7, trisomy 8, MLL rearrangement, and inv (16), can be seen in about 55% of MS cases.13 Bone marrow sampling is also necessary for the diagnosis of MS to assess the absence of AML or the presence of other myelodysplastic disorders. The prognosis of isolated MS is not well examined in large prospective studies but it has a poor prognosis overall. In some series with subgroup analysis of iso-lated MS performed in children, it was demonstrat-ed that it had a better prognosis than children with AML.14 Tsimberidou et al have demonstrated that isolated MS patients with chromosome 8 abnormali-ties had a worse prognosis and intensive chemothera-pies were needed in this group.15 Optimal therapy for MS has not been fully defined, in part due to a variety of different clinical presenta-tions. Chemotherapy (both systemic and intrathecal), bone marrow transplant, radiation therapy, surgi-cal resection, or a combination of these approaches is employed on a case by case basis.10 Success in therapy in the long term is very low (10%), and the mortality associated with therapy is high (>60%). In our case, the patient had concomitant myelofibrosis delayed the possibility of induction therapy prior to bone marrow transplant. Her disease progressed in-volving the neural foramina and required radiation therapy, showing that each case of MS represents a unique scenario. Several reports have summarized the outcome of rel-atively large cohorts of patients with MS. Yamauchi and Yasuda [16] investigated the association between therapeutic regimens and disease-free survival (DFS) in a group of 74 patients with MS. DFS was signifi-cantly longer in patients treated with systemic chemo-therapy (median 12 months) than in those treated with surgery (3 months) or local irradiation (6 months). In the same page, Pileri et al.13 reported outcome on 67 patients with MS, of which 25 (27%) presented as non-leukemic MS. Among them 47 received che-motherapy (70.1%), six allogeneic BMT (allo-BMT) (9.0%), and four autologous BMT (auto-BMT) (6.0%). At a median follow up of 150 months, only seven were still alive (10.5%) and were in CR; six of them underwent allo-BMT.

    CONCLUSION

    Myeloid sarcomas can present in conjunction with AML, myelodysplastic disorders or as isolated tu-mors in aleukemic patients. These tumors can present in any anatomic location with variable morphological and phenotypic features representing a real diagnostic challenge. Careful histopathological review of these tumors along with an expanded panel of immunohis-tochemistry is mandatory as a misdiagnosis can lead to unnecessary surgery and inappropriate therapy. The importance of our case report is centered in the unique presentation of our patient, having a previous history of essential thrombocytosis, later developing an MS accompanied of severe myelofibrosis. To our knowledge this is the first case reported of this com-bined presentation. Our patient prognosis was direct-ly associated with her myelofibrosis requiring multi-ple blood transfusions and subsequently developing leukopenia and septic shock. There is no consensus on the treatment of MS as there have not been many randomized prospective trials. As per expert review, MS should be treated as AML even in the absence of clinically detectable leukemia. These patients carry an overall poor prognosis despite the use of combined therapy.
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