Extramedullary Hematopoiesis in a Sentinel Lymph Node as an Early Sign of Chronic Myelomonocytic Leukemia

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy with features of both a myeloproliferative neoplasm and a myelodysplastic syndrome. Even though extramedullary leukemic infiltration is common in CMML patients, lymph node involvement has rarely been reported in the literature. We present an unusual case of a 72-year-old female who was found to have extramedullary hematopoiesis (EMH) in a sentinel lymph node that was excised during mastectomy for lobular breast carcinoma. One year later bone marrow biopsy was performed due to persistent anemia, thrombocytopenia, and monocytosis and the patient was diagnosed with CMML. Our case illustrates the importance of recognizing EMH in a lymph node during routine histological examination, especially in adults. Proliferation of bone marrow elements in a lymph node, in a patient with no known hematologic disorder, should trigger immediate bone marrow evaluation, as this could be the first clue in diagnosing underlying bone marrow disorder.

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Chronic myelomonocytic leukemia genomic signature correlates with the degree of bone marrow fibrosis: A single-institutional retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.7559 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 7559-7559

Author(s):

Feras Ally ◽

Amar Jariwala ◽

Patricia A. Aoun ◽

Milhan Telatar ◽

Raju K. Pillai ◽

...

Keyword(s):

Bone Marrow ◽

Genomic Dna ◽

Myeloproliferative Neoplasm ◽

Progression Free Survival ◽

Chronic Myelomonocytic Leukemia ◽

Low Grade ◽

Bone Marrow Fibrosis ◽

Targeted Mutation ◽

Myelomonocytic Leukemia ◽

Marrow Fibrosis

7559 Background: Chronic myelomonocytic leukemia (CMML) has features of both a myeloproliferative neoplasm and a myelodysplastic syndrome. The median overall survival (OS) in most series is 20-40 months. CMML is a relatively rare entity, and there is limited understanding of prognostic molecular markers. CMML associated with bone marrow fibrosis grade 1, appear to have shorter progression free survival. In this study we investigated the correlation of mutations with bone marrow reticulin fibrosis in patients with CMML. Methods: We investigated a cohort of 41 consecutive patients diagnosed with CMML 0, 1, 2, and CMML-AML from 2014 to 2019 at our institute. The median age of 41 patients was 68 years (range, 34-82). 27% were females and 73% were males. This cohort consists of 8 (20%) patients with CMML0, 19 (46%) with CMML1, 8 (20%) with CMML2 and 6 (15%) with CMML-AML. Genomic DNA was extracted from the bone marrow aspirates and targeted mutation NGS libraries were prepared from 200 ng of genomic DNA using the SureSelect target enrichment system (Agilent Technologies Inc.). The gene panel consists of 73 genes focused on myeloid neoplasms. The data were curated on the basis of our molecular pathology and national databases. Additionally, clinical data and bone marrow (BM) reticulin fibrosis grades (n = 27 available) were retrieved from the patient’s medical record. Results: The mutational profile frequency in our cohort showed that the most common mutations were TET2 (31%), ASXL1 (31%), and SRSF2 (23%), with frequencies very similar to those reported in the literature. Of the 27 cases with an available reticulin stain, only low grade fibrosis (MF-0, n = 18. MF-1, n = 9) were identified in our cohort. The frequencies of mutations in ASXL1, U2AF1, TP53, JAK2 and RUNX1, positively correlated with low grade fibrosis (MF-1). Additionally, patients with higher frequencies of SRSF2, TET2, and SETBP1 mutations showed no fibrosis (MF-0). Conclusions: This study is the first to correlate the degree of fibrosis with the frequency of mutations in CMML. We found similar mutations spectrum reported in the literature in patients with CMML. The mutational profile associated with CMML cases appears to affect the degree of the bone marrow fibrosis at the time of diagnosis.

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Next-Generation Sequencing Technology Reveals a Characteristic Pattern of Molecular Mutations in 72.8% of Chronic Myelomonocytic Leukemia by Detecting Frequent Alterations in TET2, CBL, RAS, and RUNX1

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.1361 ◽

2010 ◽

Vol 28 (24) ◽

pp. 3858-3865 ◽

Cited By ~ 219

Author(s):

Alexander Kohlmann ◽

Vera Grossmann ◽

Hans-Ulrich Klein ◽

Sonja Schindela ◽

Tamara Weiss ◽

...

Keyword(s):

Next Generation Sequencing ◽

Molecular Genetic ◽

Myeloproliferative Neoplasm ◽

Chronic Myelomonocytic Leukemia ◽

Next Generation ◽

Hematopoietic Malignancy ◽

Next Generation Sequencing Technology ◽

Cytogenetic Aberrations ◽

Myelomonocytic Leukemia ◽

Generation Sequencing

Purpose Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that is characterized by features of both a myeloproliferative neoplasm and a myelodysplastic syndrome. Thus far, data on a comprehensive cytogenetic or molecular genetic characterization are limited. Patients and Methods Here, we analyzed 81 thoroughly characterized patients with CMML (CMML type 1, n = 45; CMML type 2, n = 36) by applying next-generation sequencing (NGS) technology to investigate CBL, JAK2, MPL, NRAS, and KRAS at known mutational hotspot regions. In addition, complete coding regions were analyzed for RUNX1 (β isoform) and TET2 aberrations. Results Cytogenetic aberrations were found in 18.2% of patients (14 of 77 patients). In contrast, at least one molecular mutation was observed in 72.8% of patients (59 of 81 patients). A mean of 1.6 mutations per patient was observed by this unprecedented screening. In total, 105 variances were detected by this comprehensive molecular screening. After excluding known polymorphisms or silent mutations, 82 distinct mutations remained (CBL, n = 15; JAK2V617F, n = 8; MPL, n = 0; NRAS, n = 10; KRAS, n = 12; RUNX1, n = 7; and TET2, n = 41). With respect to clinical data, a better outcome was seen for patients carrying TET2 mutations (P = .013). Conclusion The number of molecular markers used to categorize myeloid neoplasms is constantly increasing. Here, NGS screening has been demonstrated to support a comprehensive characterization of the molecular background in CMML. A pattern of molecular mutations translates into different biologic and prognostic categories of CMML.

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Bone marrow versus sentinel lymph node involvement in breast cancer: a comparison of early hematogenous and early lymphatic tumor spread

Breast Cancer Research and Treatment ◽

10.1007/s10549-011-1802-x ◽

2011 ◽

Vol 131 (2) ◽

pp. 501-508 ◽

Cited By ~ 11

Author(s):

Andreas D. Hartkopf ◽

Malgorzata Banys ◽

Natalia Krawczyk ◽

Annette Staebler ◽

Sven Becker ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Lymph Node Involvement ◽

Tumor Spread ◽

Node Involvement

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Regional Disease Control in Selected Patients with Sentinel Lymph Node Involvement and Omission of Axillary Lymph Node Dissection

Pathology & Oncology Research ◽

10.1007/s12253-015-9899-6 ◽

2015 ◽

Vol 21 (4) ◽

pp. 861-866 ◽

Cited By ~ 2

Author(s):

Gábor Cserni ◽

Róbert Maráz

Keyword(s):

Lymph Node ◽

Sentinel Lymph Node ◽

Disease Control ◽

Axillary Lymph Node Dissection ◽

Axillary Lymph Node ◽

Lymph Node Involvement ◽

Axillary Lymph ◽

Node Dissection ◽

Node Involvement ◽

Regional Disease

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84P Predictive factors for non-sentinel lymph node involvement in patients with breast cancer and 1-2 positive sentinel lymph nodes treated with breast conservation

Annals of Oncology ◽

10.1093/annonc/mdv519.33 ◽

2015 ◽

Vol 26 ◽

pp. ix16

Author(s):

Y. Tanaka ◽

T. Fujita ◽

Y. Sagara ◽

S. Nishida ◽

S. Shiba ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Lymph Nodes ◽

Predictive Factors ◽

Breast Conservation ◽

Lymph Node Involvement ◽

Sentinel Lymph Nodes ◽

Node Involvement

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Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.2.566 ◽

1997 ◽

Vol 15 (2) ◽

pp. 566-573 ◽

Cited By ~ 77

Author(s):

F Locatelli ◽

C Niemeyer ◽

E Angelucci ◽

C Bender-Götze ◽

S Burdach ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Myelodysplastic Syndrome ◽

Marrow Transplantation ◽

Working Group ◽

Allogeneic Bone Marrow Transplantation ◽

Chronic Myelomonocytic Leukemia ◽

Allogeneic Bone ◽

European Working ◽

Myelomonocytic Leukemia

PURPOSE To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P < .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P < .01). CONCLUSION Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.

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