October 2001: 40-year-old Xhosa male with back pain and leg weakness

A 40-year-old Xhosa male presented with progressive upper lumbar back pain and weakness At examination he was emaciated and had enlarged lymph nodes in the groin and axilla. Both lower limbs were severely atrophic and weak. Sensation to touch and pain was decreased below L3 bilaterally. MR of the spine showed a discrete, contrast-enhancing epidural mass. A T10-T12 laminectomy revealed an soft, vascular extradural tumor dorsal to the cord. The mass was loosely applied to the dura and easy to remove. The operative specimen consisted of a sausage-shaped (3.5 x 2.0 x 1.2 cm), thinly-encapsulated mass of reddish-brown tissue. The cut surface had a mottled, vaguely nodular, yellowish-brown appearance. Microscopic examination revealed sheets of hematopoeitic elements, including myeloid, red cell and megakaryocytic lines, the latter showing Factor 8-related positivity. The final diagnosis was extramedullary hematopoiesis (EMH). A bone marrow biopsy performed as a result of the diagnosis showed a myeloproliferative disease and polycythemia vera. EMH in the spinal epidural space is a rare but treatable cause of progressive paraparesis in patients with a variety of hematological disorders. Since 1956 there have been more than 50 reported cases, most of which occurred in association with thalassaemia. In spinal cord compression secondary to EMH, the lesions are commonly localized to the mid-lower thoracic region.     

Pleural fluid extramedullary hematopoiesis case report with review of the literature

Extramedullary hematopoiesis (EMH) is the trilineage formation of normal blood cells outside of the bone marrow. While predominantly seen in the spleen and liver, EMH rarely occurs in serous effusions. Accurate diagnosis requires recognition of megakaryocytes and other precursor hematopoietic elements. We present a case of pleural fluid EMH in a patient with primary myelofibrosis and developing leukemia, with a review of the literature, prognostic implications and diagnostic challenges. Diagn. Cytopathol. 2016;44:41–44. © 2015 Wiley Periodicals, Inc.     

Secondary myelofibrosis in visceral leishmaniasis--case report

A 39-year-old woman with a history of travel to the Montenegrin coast presented with a 9-month long history of fever and weakness, and on examination was found to be emaciated with hepatosplenomegaly and pancytopenia. Marrow aspiration showed poor cellularity with abundant Leishman Donovan (LD) bodies in the macrophages. Bone marrow trephine biopsy revealed a marked myelofibrosis (Manoharan classification: grade III) with osteosclerosis. The impression smears of a trephine biopsy stained with Güiemsa also showed LD bodies. The patient did not exhibit evidence of any risk factors for visceral leishmaniasis (VL). She was treated with meglumine antimoniate (Glucantime) without any adverse effect. The spleen returned to a normal volume after 4 months and bone marrow trephine biopsy performed 6 months after initiation of the therapy had returned to normal. A diagnosis was difficult to establish as VL is rarely encountered in the continental parts of Yugoslavia, and with the presence of associated myelofibrosis it could easily have been mistaken for chronic idiopathic myelofibrosis. The association of myelofibrosis with visceral leishmaniasis has been reported in the literature only three times; we thus feel that documentation of this case is merited.     

Sclerosing extramedullary hematopoietic tumor involving lesser omentum and ligamentumteres in liver explant

A 47-year-old patient who presented with a 2-year history of hepatitis B virus-associated liver cirrhosis underwent a liver transplantation. The explanted liver was grossly enlarged and diffusely cirrhotic. The lesser omentum and ligamentum teres revealed a 4 cm ill-defined mass that, on sectioning, showed a gray-white appearance. Extramedullary hematopoiesis on a fibrosclerotic background constituted this mass, but there was also extramedullary hematopoiesis within the liver cords and possibly within the omentum. A bone marrow study also showed chronic idiopathic myelofibrosis. Acute rejection ensued despite immunosuppression and the patient continued to deteriorate and expired. Sclerotic extramedullary hematopoietic tumor is rare, has an unfavorable prognosis, and may mark the end stage of chronic myeloproliferative disorder.     

Small cell variant of Ki-1 lymphoma associated with myelofibrosis and a novel constitutional chromosomal translocation t(3;4) (q13;q12).

An unusual case of small cell variant of Ki-1 non-Hodgkin's lymphoma diagnosed one year after an original diagnosis of idiopathic myelofibrosis is reported. On the second occasion, the patient presented with fever, lymphadenopathy and hepatosplenomegaly. A lymph node biopsy specimen confirmed a diagnosis of small cell variant of Ki-1 lymphoma. A repeat bone marrow biopsy specimen showed myelofibrosis with no evidence of lymphomatous infiltration, but cytogenetic studies on blood, bone marrow and skin fibroblasts revealed a novel chromosomal translocation t(3,4)(q13;q12).     

Autopsy case of primary myelofibrosis in which myeloid sarcoma was the initial manifestation of tumor progression

Myeloid sarcoma (MyS) is defined as an extramedullary tumor-forming neoplasm consisting of immature myeloid cells with/without maturation. We experienced a case involving a 68-year-old Japanese male patient who had been followed-up for four years with a diagnosis of chronic idiopathic myelofibrosis/primary myelofibrosis (PMF) and noticed a painful mass in his left axilla. A wedge biopsy characterized the lesion as MyS that displayed megakaryoblastic/megakaryocytic differentiation. As his complete blood count included a few myeloid blasts (1% of WBC) and a bone marrow biopsy detected fibrosis without evidence of acute myelogenous leukemia (AML), a diagnosis of extramedullary blastic transformation of PMF was made, which was confirmed later by V617F mutation in Janus kinase-2 in both initial bone marrow biopsy and axillary tumor biopsy specimens. The patient died of pneumonia eight months after developing the axillary tumor. At autopsy, multiple MyS masses were detected in his soft tissue, but his bone marrow only contained fibrosis. Although MyS rarely develops before the leukemic transformation of PMF, no evidence of AML could be found in the patient's bone marrow at any point during the course of his disease. Thus, it is possible that the blasts in his peripheral blood were derived from the remaining MyS. Furthermore, the present case indicates that extramedullary blastic transformation, which is occasionally seen in CML, can also occur in PMF. Therefore, it is important to recognize that there is a wide variation in the pathogeneses of MyS and PMF.     

以脊髓压迫为首发症状的髓系肉瘤5例临床分析

目的 探讨以脊髓压迫为首发症状脊柱髓系肉瘤患者的临床表现、影像学特征及治疗方法。方法 采用回顾性横断面研究方法。纳入2014年1月—2017年12月长征医院骨肿瘤科收治的经骨髓穿刺及病理证实的脊柱髓系肉瘤患者5例,其中男3例、女2例,年龄15~54岁;肿瘤位于胸椎3例、腰椎2例。4例采取开放性外科手术治疗,出院后根据骨髓穿刺及病理结果,予以化疗及血液系统肿瘤规范化治疗;另1例行内科保守治疗(消炎镇痛、营养支持、化疗等)。分析患者治疗前后各项观察项目。结果 5例患者均有腰背部疼痛,伴下肢无力3例、双下肢不全瘫1例;X线检查均未见异常,CT和MRI表现为椎体骨质破坏或占位性病变。骨髓穿刺及术后肿瘤病理结果显示为急性粒细胞白血病4例,慢性粒细胞白血病1例;5例患者均经治疗后症状有所缓解。5例患者均获随访:1例术后行去甲氧柔红霉素+阿糖胞苷方案化疗5个疗程,并行异基因造血干细胞移植治疗,目前已随访至术后28个月,患者一般状态良好、无肿瘤复发;另外4例经化疗后出现复发,均死于感染,生存期5~26.5个月。结论 以脊髓压迫为首发症状的髓系肉瘤病例临床罕见,其影像学表现缺乏特异性,易出现误诊,骨髓穿刺及病理检查可确诊;当出现脊髓压迫表现时,建议早期行肿瘤切除神经减压术,术后辅以异基因造血干细胞移植和全身化疗。     

Intradural disc herniation at L5-S1 mimicking an intradural extramedullary spinal tumor: a case report

Intradural lumbar disc herniation is a rare pathological entity. The pathogenesis of intradural lumbar disc herniation is not known clearly. Intradural disc herniations usually occurred at the L4-L5 levels but have also been reported at other levels. However, intradural disc herniation at L5-S1 is quite rare. There are approximately nine reports in the English literature of intraradicular disc herniation at L5-S1. We described a 61-yr-old man with suspected intradural mass at the level of L5-S1 space. The patient presented with pain in the lower back and both lower legs for 4 months and a sudden exacerbation of the symptoms for 3 days. Gadolinium-enhanced magnetic resonance imaging (MRI) demonstrated a large disc herniation at the L5-S1 level with an intradural component. L5 and S1 laminectomy was performed, and dura was swollen and immobile. Subsequent durotomy was performed and an intradural disc fragment was removed. The patient had full recovery in 3 months. Intradural lumbar disc herniation must be considered in the differential diagnosis of mass lesions in the spinal canal. Contrast-enhanced MRI scans are useful to differentiate a herniated disc from a disc space infection or tumor.     

经皮穿刺椎体后凸成形中骨水泥渗漏入椎管与胸腰椎椎体后壁形态的关系

背景:经皮穿刺椎体后凸成形术(percutaneous kyphoplasty,PKP)是治疗骨质疏松性椎体压缩骨折的有效方法,虽然临床效果满意,但骨水泥渗漏仍然为其主要并发症,既往文献报道骨水泥渗漏进入椎管的因素较多,但由于缺少对于胸、腰椎椎体后壁形态的观察,胸腰椎椎体后壁形态差异可能也是导致骨水泥渗漏进入椎管的重要因素之一。目的:探讨胸、腰椎椎体后壁形态对骨质疏松性椎体压缩骨折患者行PKP术骨水泥渗漏入椎管的影响。方法:选取行PKP术治疗的临床资料完整并同时具有T6-L5的CT平扫及三维重建影像资料的骨质疏松性椎体压缩骨折患者98例。采用CT三维重建及多平面重建技术测量非骨折椎体后壁凹入椎体的深度及相应椎体中矢状径,计算各椎体后壁凹入椎体深度占同一椎体中矢状径百分比。将测量椎体分为胸椎组(T6-T12)和腰椎组(L1-L5)进行比较观察。选择同期内行PKP手术治疗无CT三维重建资料的骨质疏松性椎体压缩骨折患者357例(548个椎体),也分为胸椎组和腰椎组观察比较骨水泥渗漏侵占椎管程度。结果与结论:①测量98例患者椎体后壁参数发现,椎体后壁凹入椎体深度在T6-T12逐渐加深,平均4.6 mm;L1-L5逐渐变浅,平均0.6mm,椎体后壁凹入椎体深度占同一椎体中矢状径百分比T6-T12均为16%(1/6);L1-L5平均为3%,腰椎较胸椎明显小于16%(1/6);②观察同期行PKP手术治疗的357例患者发现:胸椎行PKP术骨水泥脉渗漏入椎管渗漏率为10.2%(31/304),腰椎渗漏率为3.7%(9/244)。胸椎组骨水泥渗漏侵占椎管最大矢状径平均为(3.1±0.2)mm,侵占椎管面积平均为(30.8±0.3)mm2,椎管侵占率为(22.5±0.2)%;腰椎组骨水泥渗漏侵占椎管最大矢状径为(1.4±0.1)mm,侵占椎管面积为(14.9±0.2)mm2,椎管侵占率为(11.4±0.3)%,胸椎组骨水泥渗漏发生率、侵占椎管最大矢状径、面积明显大于腰椎组(P<0.05)。③结果证实,中下胸椎行PKP术应尽量避免骨水泥分布达到椎体后16%(1/6),因中下胸椎、腰椎椎体后壁凹入椎体深度差异会对PKP术骨水泥渗漏进入椎管的观察造成影响,可能是导致中下胸椎椎管内骨水泥渗漏率明显高于腰椎的原因之一。该试验获得西南医科大学附属医院伦理委员会批准(批准号:K2018008)。     

Janus kinase 2 V617F mutation is detectable in spleen of patients with chronic myeloproliferative diseases suggesting a malignant nature of splenic extramedullary hematopoiesis

Extramedullary hematopoiesis occurs in patients with a variety of hematologic diseases, and the spleen is a common site. Extramedullary hematopoiesis is very common in chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The pathogenesis of extramedullary hematopoiesis is unknown. Using JAK2 V617F mutation as a molecular marker, we assessed paired spleen and bone marrow samples of 15 patients with various types of chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The diagnosis was chronic idiopathic myelofibrosis (n=8), polycythemia vera (n=3), and chronic myelomonocytic leukemia (n=4). DNA was extracted from fixed, paraffin-embedded tissue and assessed for JAK2 V617F by real-time polymerase chain reaction assay followed by melting curve analysis. Concordant JAK2 mutation was detected in the paired samples in 7 patients. A discordant result with JAK2 V617F found in the spleen but not bone marrow was noted in 1 patient. These results indicate that extramedullary hematopoiesis in patients with chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases is a clonal process and lend support to the theory that the cells of extramedullary hematopoiesis are carried from the bone marrow.     

The role of Janus Kinase 2 V617F mutation in extramedullary hematopoiesis of the spleen in neoplastic myeloid disorders.

Extramedullary hematopoiesis (EMH) in the spleen is a characteristic feature of the chronic myeloproliferative disorders (CMPDs) and various other neoplastic or reactive myeloid conditions. However, the origin of these hematopoietic precursor cells and the molecular mechanisms underlying their development in the spleen is uncertain. The V617F mutation in the Janus Kinase 2 gene (JAK2(V617F)) was recently shown to be frequently and preferentially present in the peripheral blood and bone marrow cells of CMPD patients, and the resulting dysregulation of its downstream targets is important to CMPD pathogenesis. To determine the occurrence and potential role of JAK2(V617F) in splenic EMH cells, we studied splenectomy specimens from 47 patients with significant EMH. JAK2(V617F) was detected by real-time PCR melting curve analysis in 22 specimens, including 11/17 chronic idiopathic myelofibrosis, 7/7 polycythemia vera, 1/1 essential thrombocythemia, 1/3 CMPD unclassifiable, 1/5 chronic myelomonocytic leukemia, 0/5 chronic myelogenous leukemia, 1/3 myelodysplastic syndrome and 0/6 acute myeloblastic leukemia cases, whereas only the JAK2 wild-type allele was detected in the other 25. Nineteen of 20 cases with adequate bone marrow samples available for molecular examination demonstrated concordant JAK2 genotypes. Laser-capture microdissection was then used to enrich the EMH and non-EMH splenic cell fractions, confirming that the mutant alleles specifically originated from the EMH cells. Furthermore, megakaryocytes in the JAK2(V617F)-positive splenectomy specimens expressed higher levels of Bcl-xL, an antiapoptotic protein and downstream target of the JAK2/STAT5 pathway. Thus, JAK2(V617F) is frequently present in splenic EMH cells associated with CMPD, but it is rarely identified in splenic EMH cells associated with other myeloid disorders. Our results indicate that the precursor cells leading to extramedullary hematopoietic expansion in CMPD most likely originate from the transformed bone marrow clone. Also, dysregulation of downstream pathways such as Bcl-xL may be important to CMPD disease pathogenesis in the spleen.     

Loss of heterozygosity identifies genetic changes in chronic myeloid disorders, including myeloproliferative disorders, myelodysplastic syndromes and chronic myelomonocytic leukemia.

This study evaluates changes in genetic loci of chronic myeloid disorders using loss of heterozygosity (LOH) techniques. We present the combined results of three experiments. First, examination of a panel of genetic loci in groups of myeloproliferative disorders was evaluated. The second experiment involved microdissection of megakaryocytes from myeloproliferative disorders and comparison of their genetic changes to surrounding neoplastic marrow elements. Finally, we compared results of LOH studies of myeloproliferative disorders to those of myelodysplastic syndromes and chronic myelomonocytic leukemia. A total of 41 bone marrow biopsies were evaluated. Twenty-seven were myeloproliferative disorders (11 chronic idiopathic myelofibrosis, 11 essential thrombocythemia, 5 polycythemia vera). The remaining cases consisted of myelodysplastic syndromes (total=5; RAEB-1=2; RAEB-2=2; MDS, not otherwise specified=1) and chronic myelomonocytic leukemia (n=8). The abnormalities in myeloproliferative disorders were distributed as follows: D7S2554-4/14 (5/14); D8S263-4/15 (5/15); D9S157-5/15 (5/15); D9S161-7/17 (6/17); D13S319-5/14 (4/14); TP53-5/16 (5/16); D20S108-4/15 (4/15). In 75% cases diagnosed as essential thrombocythemia (6/8), both cases of polycythemia vera (2/2), and 29% cases of chronic idiopathic myelofibrosis (2/7), there were genetic differences between the megakaryocytes and the surrounding marrow. These results suggest that in some cases, megakaryocytes have different clonal abnormalities than surrounding hematopoietic tissue. The genetic profiles of myeloproliferative disorders had several differences from those of myelodysplastic syndromes. Although different from both, chronic myelomonocytic leukemia appeared more similar to myeloproliferative disorders using these techniques.     

37-year-old woman with multiple intracranial masses

Extramedullary hematopoiesis (EMH), defined as the presence of hematopoiesis outside bone marrow and peripheral blood, occurs asa compensatory phenomenon in several hematologic disorders and bone marrow dysfunction. EMH predominantly affects reticuloendothelial system including the spleen, liver and lymph nodes. Here,we report a rare case of multiple intracranial meningeal EMH. A37-year-old woman was anemic with gradually worsening vision for 8 months. Multiple extra-axial masses were found on imaging and the patient underwent the biopsy for the left frontotemporal lesion.Final diagnosis was multiple intracranial meningeal EMH. Treatment of fractionated external beam radiotherapy resulted in marked symptomatic improvement. This case indicates that although the diagnosis of meningeal EMH is difficult, there is a need to consider EMHin the differential diagnosis of anemic patients with tumor-like mass lesions in extramedullary sites.     

Coincidence of chronic idiopathic myelofibrosis and chronic lymphocytic leukaemia. A rare phenomenon?

In 1986 we diagnosed chronic idiopathic myelofibrosis (CIMF) in a 45-year-old asymptomatic patient with hepatosplenomegaly. In 1996 splenectomy was performed because of hypersplenism, and chemotherapy with hydroxyurea was initiated. In 1999 generalised lymphadenopathy of chronic lymphocytic leukaemia (B-CLL) developed. A trephine biopsy showed leukaemic bone marrow infiltration. On heteroduplex analysis we found a clonal rearrangement of IgH in the leukaemic lymphocytes. The coincidence of chronic myeloproliferative and lymphoproliferative diseases in the same patient is a rare phenomenon. According to the relevant literature, seven cases with a combination of CIMF/CLL have been reported. Possible pathomechanisms for the development of such coincidences are: 1) a bilineage manifestation of a pluripotent stem cell proliferation, 2) independent proliferations of two distinct cell lines under a common leukaemogenic stimulus or 3) an accidental association. These coincidence cases often showed a mild clinical course and also in our case, the patient is still alive and in a stable disease condition 16 years after the initial diagnosis.     

Erythrophagocytosis by myeloid cells in a patient with myeloproliferative disorder

This report documents a case of myeloid erythrophagocytosis in a patient with myeloproliferative disorder. The patient had pancytopenia and his marrow was hyperplastic with erythrophagocytosis by myeloid cells of various stages, including myeloblasts. He was diagnosed to have a prefibrotic stage of chronic idiopathic myelofibrosis. The erythrophagocytosis by myeloid cells persisted even after 2 months of treatment for the primary disorder.     

A common complication of myelofibrosis presenting as a rare finding in cerebrospinal fluid cytology

Herein, we present a rare case of intracranial extramedullary hematopoiesis (EMH) diagnosed by cerebrospinal fluid (CSF) cytology and describe the clinical presentation, radiologic, and pathologic findings. A 65 year‐old man with a history of progressing primary myelofibrosis was admitted for headaches and right facial numbness. A brain MRI revealed focal abnormalities that were suspicious for leptomeningeal involvement of acute leukemia. Cytologic examination of CSF demonstrated a hypercellular specimen composed of hematopoietic cells including few blasts, as well as maturing red blood cells and granulocytic cells. The integration of morphologic findings, peripheral blood and bone marrow counts, as well as flow cytometric analysis of CSF and bone marrow, excluded leptomeningeal involvement by leukemic blasts and helped establish the diagnosis of intracranial EMH. Inclusion of EMH in the differential diagnosis of intracranial pathology in patients with known conditions predisposing them to EMH is important because recognizing this rare event has implications for treatment and prognosis.     

Myelofibrosis presenting as spinal cord compression

This report describes a case of myelofibrosis presenting as spinal cord compression on account of extramedullary haemopoietic tissue encroaching upon the spinal cord from a large pelvic mass.     

Regression of myelofibrosis and osteosclerosis following hematopoietic cell transplantation assessed by magnetic resonance imaging and histologic grading.

Myelofibrosis is a reactive, often inhomogeneous process in the marrow cavity, and sampling errors on biopsies obtained to diagnose and monitor the course of myelofibrosis have been a constant problem in hematopathology. We investigated the potential utility of magnetic resonance imaging (MRI) of the lumbar spine, pelvis, and femora as a diagnostic and monitoring technique for assessment of myelofibrosis. Findings on serial marrow biopsies were correlated with T1-weighted spin-echo and short inversion time inversion recovery (STIR) images in patients with chronic idiopathic myelofibrosis or myelofibrosis developing from polycythemia vera or essential thrombocythemia who underwent hematopoietic cell transplantation (HCT). Thirty-five patients were studied before HCT; 11 were followed for 3 months and 10 patients for >/=1 year after HCT with sequential marrow biopsies and MRI studies. MRI allowed direct visualization of the biopsy sites and correlation of histologic and MRI findings. MRI also provided assessment of the extent and degree of myelofibrosis in a large volume of the skeletal marrow. There was good correlation between biopsy results and MRI findings at specific biopsy sites and between successful HCT and resolution of fibrosis and osteosclerosis as determined by MRI. We conclude that in patients with myelofibrosis, MRI of the skeleton provides a comprehensive assessment of the pattern and extent of fibrosis and allows for correlation with biopsy findings. In patients undergoing HCT, MRI accurately reflects response or progression of marrow disease.     

Complete regression of bone marrow fibrosis following allogeneic peripheral blood stem cell transplantation in a patient with idiopathic myelofibrosis

The authors present a case of a 47-year-old man with idiopathic myelofibrosis. The diagnosis of myelofibrosis was made in 1981. Because of progression of the disease and failure of hematopoiesis in 2002, allogeneic peripheral blood stem cell transplantation was performed; the donor was an HLA identical relative. Six months after transplantation, trephin biopsies were made and a complete regression of bone marrow fibrosis was documented. It is the first case of this treatment for idiopathic myelofibrosis in the University Hospital in Hradec Králové.     

Classification of Ph-negative chronic myeloproliferative disorders--morphology as the yardstick of classification.

OBJECTIVE: Histopathology of bone marrow (BM) biopsies plays a crucial role in the interdisciplinary approach to diagnosis and classification of Ph-negative chronic myeloproliferative disorders. Based on careful clinicopathologic studies, BM features are critical determinants that help to predict overall prognosis, to detect complications such as progression to myelofibrosis and blast crisis, and to assess therapy-related changes. METHODS AND RESULTS: A systematic evaluation of BM histopathology allows an objective identification of cases of (true) essential thrombocythemia and their separation from early prefibrotic stages of chronic idiopathic myelofibrosis. By follow-up examinations that include BM biopsies, the progression of the disease process is unveiled, which is especially important for patients with initial polycythemia vera and prefibrotic chronic idiopathic myelofibrosis that may require a different therapeutic approach than the full-blown stages. CONCLUSION: BM biopsy should be considered as major diagnostic tool for evaluation and follow-up of patients enrolled in prospective studies.