Acquired Elliptocytosis as a Manifestation of Myelodysplastic Syndrome Associated with Deletion of Chromosome 20q

Elliptocytosis is commonly seen as a hereditary condition. We present a case of myelodysplastic syndrome (MDS) del(q20) variant with concomitant acquired elliptocytosis. A 73-year-old male with a history of prostate cancer presented to the hospital for evaluation of bleeding gums. Initial evaluation showed Hgb of 9.3 gm/dl, hematocrit of 28%, platelet count of 36,000 K/cmm, and WBC of 1.8 K/cmm with an ANC of 0.8 K/cmm. A slightly elevated bilirubin of 1.2 mg/dl spurred a hemolytic workup. Peripheral smear showed frequent elliptocytes, teardrop cells, schistocytes, and occasional spherocytes. Bone marrow biopsy did not show significant fibrosis to explain the elliptocytosis. Cytogenetics showed 20q deletion, and later, he was started on therapy for intermediate risk MDS. Bone marrow biopsy after completion of 6 cycles showed complete cytogenetic remission with significant improvement in elliptocytosis. Elliptocytosis in the setting of MDS has rarely been reported, and association with 20q deletion is even rarer. Animal studies have shown that haploinsufficiency ofL3MBTL1contributes to some (20q−) myeloproliferative neoplasms and myelodysplastic syndromes by affecting erythroid differentiation. Our case report raises interesting questions: Does MDS with rarely reported elliptocytosis indicate a disease process that is different from the usual 20q deletion? Is haploinsufficiency ofL3MBTL1responsible for this manifestation?

Download Full-text

Audit of bone marrow biopsy reports submitted to a myelodysplastic syndrome registry

Pathology ◽

10.1016/j.pathol.2021.06.094 ◽

2021 ◽

Vol 53 ◽

pp. S45-S46

Author(s):

Marsali Maclean ◽

Linda Saravanan

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndrome ◽

Bone Marrow Biopsy

Download Full-text

Indolent Neuroendocrine Tumor Involving the Bone Marrow

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-0488-intitb ◽

2003 ◽

Vol 127 (4) ◽

pp. 488-491

Author(s):

Ellen Schlette ◽

L. Jeffrey Medeiros ◽

Miloslav Beran ◽

Carlos E. Bueso-Ramos

Keyword(s):

Bone Marrow ◽

Neuroendocrine Tumor ◽

Bone Marrow Biopsy ◽

Clinical Symptoms ◽

Eosinophilic Cytoplasm ◽

Hydroxyindoleacetic Acid ◽

History Of ◽

Cardiac Valve Disease ◽

Immunohistochemical Studies

Abstract We report a unique case of a patient with a neuroendocrine tumor localized to the bone marrow. The patient had a history of hairy cell leukemia, and the neuroendocrine tumor was detected in a bone marrow biopsy specimen obtained to assess response to 2-chlorodeoxyadenosine therapy. The neuroendocrine tumor was present as nodules that replaced approximately 15% of the bone marrow medullary space and was composed of round cells with fine chromatin, indistinct nucleoli, and relatively abundant, granular, eosinophilic cytoplasm. Histochemical stains showed cytoplasmic reactivity with Grimelius and Fontana-Masson stains, and immunohistochemical studies showed positivity for keratin and chromogranin. The histologic, cytochemical, and immunohistochemical features resembled a carcinoid tumor, and metastasis to the bone marrow was considered initially. The patient was asymptomatic without diarrhea, flushing, or cardiac valve disease. Serotonin production, assessed by the measurement of serum 5-hydroxyindoleacetic acid and substance P levels, was normal. Extensive clinical and radiologic work-up and endoscopy of the gastrointestinal tract to detect a primary site other than the bone marrow were negative. Follow-up bone marrow biopsy 7 years after the initial diagnosis was positive for persistent neuroendocrine tumor. The patient has not received any therapy specific for the neuroendocrine tumor and has had no clinical symptoms or evidence of progression after 9 years of clinical follow-up. We suggest that this neuroendocrine tumor may have arisen in the bone marrow.

Download Full-text

Tubulointerstitial Nephritis and Uveitis Syndrome with non Caseating Granuloma in Bone Marrow Biopsy

Acta Médica Portuguesa ◽

10.20344/amp.3981 ◽

2014 ◽

Vol 27 (2) ◽

pp. 268 ◽

Cited By ~ 2

Author(s):

Maria Fraga ◽

Maria João Nunes da Silva ◽

Margarida Lucas ◽

Rui M. Victorino

Keyword(s):

Bone Marrow ◽

Weight Loss ◽

Clinical Practice ◽

Bone Marrow Biopsy ◽

Interstitial Nephritis ◽

Tubulointerstitial Nephritis ◽

Rare Condition ◽

Blood Tests ◽

Caseating Granuloma ◽

History Of

<p>The Tubulointerstitial Nephritis and Uveitis syndrome is a very rare condition, probably under-diagnosed in clinical practice. It is<br />characterized by the combination of an interstitial nephritis and uveitis, and is an exclusion diagnosis. Tissue non caseating granuloma can be rarely present, with only 6 cases reported on bone marrow. We present a case of a 55 year old female with a 3-month history of asthenia and weight loss. Blood tests showed anemia and renal insufficiency. Renal biopsy revealed interstitial nephritis and the bone marrow biopsy showed caseating granuloma. One month later anterior uveitis of the left eye appeared. An extensive exclusion of all possible causes allowed a diagnosis of Tubulointerstitial Nephritis and Uveitis syndrome with caseating granuloma in bone marrow. As ocular and renal manifestations may not occur simultaneously, Tubulointerstitial Nephritis and Uveitis Syndrome should be systematically considered in cases of interstitial nephritis and/or uveitis, and tissue granulomas can be part of this rare syndrome.</p>

Download Full-text

Trepanning or trephines: a history of bone marrow biopsy

British Journal of Haematology ◽

10.1111/j.1365-2141.2007.06749.x ◽

2007 ◽

Vol 139 (1) ◽

pp. 14-19 ◽

Cited By ~ 23

Author(s):

Liakat A. Parapia

Keyword(s):

Bone Marrow ◽

Bone Marrow Biopsy ◽

History Of

Download Full-text

Successful Treatment of Concurrently Diagnosed Multiple Myeloma and Myelodysplastic Syndrome with Isolated Del(5q) with Lenalidomide, Bortezomib, and Dexamethasone

Blood ◽

10.1182/blood-2020-140532 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 17-18

Author(s):

Nyomi Washington ◽

Eugen A Shippey ◽

Michael B Osswald

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Partial Response ◽

Myelodysplastic Syndrome ◽

Bone Marrow Biopsy ◽

Induction Therapy ◽

Successful Treatment ◽

Light Chain ◽

Plasma Cells ◽

Bone Marrow Blasts

Lenalidomide is known to be an effective therapy for multiple myeloma (MM) and for myelodysplastic syndrome with isolated del(5q). However, there have been very few reports of treatment of both conditions using lenalidomide when they are diagnosed concurrently. A review of the literature revealed two reports of MM and del(5q) MDS treated with lenalidomide. We report the case of a patient simultaneously diagnosed with multiple myeloma and myelodysplastic syndrome with isolated del(5q) who was treated successfully with lenalidomide. The patient is a 74 year old female who was referred to hematology for worsening chronic macrocytic anemia with a hemoglobin of 9.4 g/dL. A serum protein electrophoresis (SPEP) was obtained during her workup and demonstrated an IgG kappa monoclonal spike of 4.7 g/dL. Free light chain analysis demonstrated a kappa/lambda ratio of 36.7. The patient was mildly hypercalcemic at 10.6 g/dL but had no renal insufficiency. Platelet and white blood cell counts were normal. There were no osteolytic lesions on skeletal survey and a whole body PET scan identified no bony disease or plasmacytomas. A β-2 microglobulin level was 3.7 mg/L and albumin was 3.3 g/dL. Bone marrow biopsy revealed 60% plasma cells in a 70% cellular marrow. Granulocytic and megakaryocytic dysplasia was identified. Fluorescence in situ hybridization returned showing a 4:14 translocation in 72% of analyzed nuclei and monosomy 13 in 61% of nuclei analyzed consistent with an unfavorable risk profile. Chromosome analysis also revealed a 5q deletion in 15 of 20 analyzed cells. Bone marrow blasts were measured at 1%. Therefore, the patient concurrently met diagnostic criteria for stage II IgG kappa multiple myeloma per the International Staging System and low risk myelodysplastic syndrome with isolated del(5q) per the 2016 WHO classification of MDS with a Revised International Prognostic Scoring System Score (IPSS-R) of 2. She was started on lenalidomide 25 mg daily, bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 and dexamethasone 20 mg on days 1, 8, and 15 of a 21 day cycle. After 3 cycles of therapy, serum immunofixation electrophoresis showed an unquantifiably low IgG kappa monoclonal spike and the patient's kappa/gamma light chain ratio had normalized to 1.1. Hemoglobin and calcium returned to normal. On repeat bone marrow biopsy, there was normocellular marrow with 4% polytypic plasma cells by kappa/lambda immunohistochemistry. No dysplasia was identified and bone marrow blasts were 1.5%. Therefore, the patient achieved a very good partial response (VGPR) to therapy for multiple myeloma according to International Myeloma Working Group criteria within 3 months. She met National Comprehensive Cancer Network criteria for response of her MDS to lenalidomide by normalization of hemoglobin. The patient's case demonstrates successful treatment of concurrently diagnosed multiple myeloma and MDS with isolated del(5q) using lenalidomide. Among the two other similar cases we discovered in the literature, one patient was treated with low-dose lenalidomide and dexamethasone [Nolte, et al. Eur J Haematol. 2017 Mar;98(3):302-310.], and the other patient was treated with high-dose lenalidomide and dexamethasone, achieving a partial response [Ortega, et al. Leuk Res. 2013 Oct;37(10):1248-50.]. Neither patient received a proteasome inhibitor. In our case, the patient was treated with higher intensity induction therapy for multiple myeloma and achieved a VGPR. She did not have worsening cytopenias during therapy, and in fact experienced normalization of her blood counts. Therefore, it is reasonable to treat patients simultaneously diagnosed with MM and MDS with isolated del(5q) with standard three-drug induction therapy for multiple myeloma. While our approach makes sense in the abstract, hematology/oncologists should be aware that it works in practice. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Two Cases of Severe Hypertension in JAK2 Mutation-Positive Myeloproliferative Neoplasms

Case Reports in Vascular Medicine ◽

10.1155/2020/8887423 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Raunak Rao ◽

Spoorthy Kulkarni ◽

Ian B. Wilkinson

Keyword(s):

Bone Marrow ◽

Renal Artery ◽

Renal Artery Stenosis ◽

Bone Marrow Biopsy ◽

Blood Count ◽

Severe Hypertension ◽

Myeloproliferative Neoplasms ◽

Artery Stenosis ◽

Full Blood Count ◽

Jak2 Mutation

Background. Myeloproliferative neoplasms are a heterogeneous group of disorders resulting from the abnormal proliferation of one or more terminal myeloid cells—established complications include thrombosis and haemorrhagic events; however, there is limited evidence to suggest an association with arterial hypertension. Herein, we report two independent cases of severe hypertension in JAK2 mutation-positive myeloproliferative neoplasms. Case Presentations. Case 1: a 39-year-old male was referred to our specialist hypertension unit with high blood pressure (BP) (200/120 mmHg), erythromelalgia, and headaches. We recorded elevated serum creatinine levels (146 μM) and panmyelosis. Bone marrow biopsy confirmed JAK2-mutation-positive polycythaemia vera. Renal imaging revealed renal artery stenosis. Aspirin, long-acting nifedipine, interferon-alpha 2A, and renal artery angioplasty were employed in management. BP reached below target levels to an average of 119/88 mmHg. Renal parameters normalised gradually alongside BP. Case 2: a 45-year-old male presented with high BP (208/131 mmHg), acrocyanosis, (vasculitic) skin rashes, and nonhealing ulcers. Fundoscopy showed optic disc blurring in the left eye and full blood count revealed thrombocytosis. Bone marrow biopsy confirmed JAK2-mutation-positive essential thrombocytosis. No renal artery stenosis was found. Cardiac output was measured at 5 L/min using an inert gas rebreathing method, providing an estimated peripheral vascular resistance of 1840 dynes/s/cm5. BP was well-controlled (reaching 130/70 mmHg) with CCBs. Conclusions. These presentations highlight the utility of full blood count analysis in patients with severe hypertension. Hyperviscosity and constitutive JAK-STAT activation are amongst the proposed pathophysiology linking myeloproliferative neoplasms and hypertension. Further experimental and clinical research is necessary to identify and understand possible interactions between BP and myeloproliferative neoplasms.

Download Full-text

Diagnosis and Treatment of Essential Thrombocythemia: Assessment of Current Clinical Practice.

Blood ◽

10.1182/blood.v114.22.1903.1903 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1903-1903

Author(s):

Vivian H Y Lee ◽

Erica Peterson ◽

Leslie Zypchen ◽

Lynda M Foltz

Keyword(s):

Bone Marrow ◽

Clinical Practice ◽

High Risk ◽

Diagnostic Criteria ◽

Bone Marrow Biopsy ◽

Jak2 V617f ◽

Low Risk ◽

Cytoreductive Treatment ◽

Risk Patients ◽

History Of

Abstract Abstract 1903 Poster Board I-926 Introduction: The discovery of the JAK2 V617F gene mutation has significantly altered the clinical diagnostic approach to the myeloproliferative neoplasms, reflected in the revised 2008 WHO diagnostic criteria. Both the 2001 and 2008 diagnostic criteria for essential thrombocythemia (ET) require a bone marrow biopsy showing megakaryocytic proliferation to make a diagnosis of ET. Published expert opinion based on clinical studies suggests that ET patients > 60 years old or with history of thrombosis should be characterized as high risk and treated with hydroxyurea. It is unclear whether physicians in clinical practice utilize the WHO diagnostic criteria or follow expert treatment recommendations for ET. Methods: We conducted a retrospective chart review of all patients with a clinical diagnosis of ET made by a hematologist who were seen in clinic from 2006 to 2008 at two university teaching hospitals in Vancouver, Canada. Data collected included demographic information, thrombosis history, diagnostic tests performed and treatment administered. Testing for JAK2 V617F became locally available in 2006, so for assessment of diagnostic tests performed, patients were divided into cohorts of diagnosis pre-2006 and 2006–2008. Patients were characterized as high risk if > 60 y or history of thrombosis at the time of diagnosis. All other patients were considered low risk. Results: Diagnostic information was available for 116 patients diagnosed prior to the availability of testing for JAK2 V617F. 65% (75/116) of patients in this cohort had a bone marrow biopsy performed (table 1). 44 patients received a new diagnosis of ET from 2006–2008. Only 48% (21/44) patients in this cohort had a bone marrow biopsy performed, significantly less than in the historical cohort (p = 0.019). 41/44 had JAK2 V617F testing performed: 41% (17/41) were JAK2 V617F negative, 56% (23/41) positive and 1 equivocal. Bone marrow biopsy was performed in 59% (10/17) of JAK2 V617F negative patients and 39% (9/23) of JAK2 V617F positive patients (p = 0.055) (table 1). Bone marrow biopsy was also performed in 1 patient with equivocal JAK2 V617F testing and 1 patient not tested for JAK2 V617F. 170 patients diagnosed with ET were seen in follow up 2006–2008. 64% (109/170) were high risk due to age > 60 y or history of thrombosis. The remaining 36% (61/170) were considered low risk. Hydroxyurea was used preferentially over anagrelide for treatment of ET (table 2). Only 76% of high risk patients were receiving cytoreductive treatment. 23% of low risk patients received cytoreductive treatment. ASA was prescribed to 89% of high risk and 79% of low risk patients. Conclusion: Despite the requirement for a bone marrow biopsy to meet the WHO criteria for ET, hematologists performed a bone marrow biopsy in less than half of patients they diagnosed with ET since 2006. Hematologists performed bone marrow biopsy less frequently after JAK2 V617F testing became available, particularly in JAK2 V617F positive patients. A substantial portion of high risk patients (24%) were receiving no cytoreductive therapy, contrary to expert recommendation. Further study is required to understand the barriers to implementing treatment recommendations in clinical practice. This study highlights the challenges in translating published diagnostic criteria and treatment guidelines into changes in patient care. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

ASXL1 Is a Key Regulator for Erythroid Development and Asxl1 Loss Impairs Erythropoiesis In Vivo

Blood ◽

10.1182/blood.v126.23.3644.3644 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3644-3644

Author(s):

Shohei Yamamoto ◽

Hui Shi ◽

Shi Chen ◽

Peng Zhang ◽

Yuan Zhou ◽

...

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndrome ◽

Peripheral Blood ◽

Myeloproliferative Neoplasms ◽

Flow Cytometric Analysis ◽

Erythroid Cell ◽

Altered Expression ◽

Erythroid Development

Abstract Objective: Recently, ASXL1 mutations are found in a spectrum of numerous of myeloid malignancies, including myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). ASXL1 mutation is a poor prognostic markers. Recently, we reported that Asxl1+/- mice developed myelodysplastic syndrome (MDS)-like disease and MDS/MPN. Regardless of the existence of defective erythroid lineage maturation and anima in patients with MDS or MPN, the role of ASXL1 in erythropoiesis remains unveiled. Methods: Asxl1+/- mice were utilized for hematopoietic analysis, including peripheral blood counts, blood smear, morphology, flow cytometry and histology. To assess the erythroid phenotypes in vivo, blood smears were subjected to acridine staining for reticulocyte counts. The percentage of reticulocytes and erythroid cell differentiation in peripheral blood and bone marrow were evaluated flow cytometrically following thiazole orange and CD71/Ter119 staining. Colony-forming cells (CFU) and in vitro erythroid differentiation assays were performed with methylcellulose (EPO, SCF) and liquid (EPO, transferrin) cultures of Lin-Kit+ cells of BM, spleen and fetal liver cells. In addition, the nuclear fractions were prepared from cultured erythoblasts of WT and Asxl1+/- mice and subjected to western blotting analyses to determine the histone levels of H3K27me3. RNA-Seq was performed to survey the differentially expressed genes in LK cells of WT and Asxl1+/- mice. Real time PCR was performed to confirm the alteration of erythroid development related gene. Results: Adult Asxl1+/- mice were anemic. High frequencies of immature and dysplastic (tear drop) red blood cells were observed in the peripheral blood of Asxl1+/- mice. Flow cytometric analysis revealed an increased percentage of pro-erythroblasts and basophilic erythroblasts populations in peripheral blood and bone marrow cells compared to that of WT controls, suggesting a blockage of erythroid maturation in Asxl1+/- mice. In vitro methylcellulose cultures showed a dramatic decrease of BFU-E and CFU-GEMM in the bone marrow of Asxl1+/- mice compared to WT controls. Western blot analysis showed that Asxl1+/- erythroblast cells exhibited decreased global levels of H3K27me3 and qPCR of Asxl1+/- erythroblast cells revealed altered expression of genes involved in development and homeostasis of erythroid lineage, including Gata1, Ldb1, Cdc42, and Zfpm1. Conclusion: Our study demonstrates that loss of Asxl1 results in blockage of erythroid cell maturation, indicating that ASXL1 is a key regulator for erythroid development and Asxl1 loss impairs erythropoiesis in vivo. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Myelodysplastic Syndrome with t(1;7) Associated with Marked Dysmegakarypoiesis & Severe Thrombocytopenia: A Case Report and Review of the Literature

Case Reports in Hematology ◽

10.1155/2012/167653 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4

Author(s):

Michael Gilbertson ◽

Annabel Tuckfield ◽

Surender Juneja

Keyword(s):

Bone Marrow ◽

Case Report ◽

Myelodysplastic Syndrome ◽

Diagnostic Criteria ◽

Bone Marrow Examination ◽

Recent History ◽

Severe Thrombocytopenia ◽

Review Of The Literature ◽

Multilineage Dysplasia ◽

History Of

We present the case of a 70-year-old woman who had a bone marrow examination performed to investigate marked thrombocytopenia in the context of a recent history of metastatic glucagonoma. Surprisingly this identified marked dysmegakaryopoiesis and fulfilled diagnostic criteria for refractory cytopenia with multilineage dysplasia, with a relatively uncommon associated cytogenetic lesion t(1;7). We present the case and review the literature of this cytogenetic lesion.

Download Full-text