Case Report Journal of Hematology & Multiple Myeloma Published: 13 Sep, 2018

Cutaneous Myeloid Sarcoma

Wronska M*, Golbari NM, D’Abreo N and Sticco K Department of Medicine and Population Health, NYU School of Medicine, New York

Abstract Introduction: Myeloid Sarcomas (MS) are rare ’s occurring at extramedullary sites. They are typically found in the setting of Acute Myeloid (AML) either concurrently or at relapse. Less often, they may be associated with other hematologic disorders such Myelodysplastic Syndromes (MDS) or Myeloproliferative (MPN). Rarely MS can present as an isolated leukemic tumor, without involvement. The presentation of these isolated cases is greatly variable and can make diagnosis particularly challenging. Case Presentation: A case report of a 79-year old patient with rare and rapidly evolving cutaneous presentation of isolated MS, without bone marrow involvement. Discussion: This case identifies the potential for isolated MS to present as a cutaneous skin infiltration in the absence of AML, MDS or MPN. Given the rarity of this neoplasm and the wide variation in symptomology, it is prudent to be aware of aberrant presentations of isolated MS. This case highlights the need for to consider MS in the differential diagnosis, even in the context of negative bone marrow, as early diagnosis and treatment with has been demonstrated to improve survival outcomes. Keywords: Isolated myeloid sarcoma; Cutaneous infiltration; Skin infiltration

Introduction Myeloid Sarcoma (MS), also known as granulocytic sarcoma, chloroma, or myeloblastoma, is a rare extramedullary proliferation of thought to be a variant of Acute (AML) [1]. The initial manifestation of the disease is highly variable and can present at different stages, such as preceding or coinciding with AML, arising from plastic transformation of a Myelodys plastic Syndrome (MDS), or developing from a chronic Myeloproliferative Neoplasm (MPN) [2]. However, MS rarely occurs in the absence of bone marrow involvement [3], and it is identified as OPEN ACCESS isolated MS.

*Correspondence: Case Presentation Wronska M, Department of Medicine A 79-year old male with past medical history of atrial fibrillation, benign prostatic hyperplasia, and Population Health, NYU School of and resected colon cancer in 2008, presented with new onset of shortness of breath, difficulty Medicine, New York, USA, ambulating and a diffuse progressive skin rash. On initial examination, skin exam revealed E-mail: Marta.Wronska@nyulangone. innumerable, indurated, non-pruritic, non-tender, red and purple papules and nodules on the arms, org chest, back and abdomen (Figure A). By day 6 of admission, the rash had progressed to the neck Received Date: 13 Aug 2018 and face, and the discrete lesions on the arms had coalesced into large indurated plaques (Figure B Accepted Date: 10 Sep 2018 and C). Published Date: 13 Sep 2018 Initial blood work was significant for leukocytosis ( count: 15.2 x 109/L with Citation: normal differential without immature cells), (hemoglobin: 8.4 g/dl MCV: 89),and Wronska M, Golbari NM, D’Abreo N, thrombocytopenia (platelets: 82 x 109/L). Computed Tomography (CT) revealed innumerable Sticco K. Cutaneous Myeloid Sarcoma. skin nodules in the chest, abdomen, and pelvis, splenomegaly (15 cm x 11 cm), and minimally J Hematol Mult Myeloma. 2018; 3(2): enlarged bilateral maxillary and upper abdominal lymph nodes. Patient underwent skin , and 1016. subsequently bone marrow biopsy due to hematologic abnormalities. © 2018 Wronska M. This is Copyright Bone marrow biopsy reveale d a mildly hyper cellular bone marrow for age, with trilineage an open access article distributed under hematopoiesis and erythroid hyperplasia, no increase in blasts was identified. Cytogenetic analysis the Creative Commons Attribution showed abnormal karyotype with trisomy 8 (47, XY, +8(8)/46, XY (12 )). did not License, which permits unrestricted reveal immunophenotypic abnormalities. use, distribution, and reproduction in any medium, provided the original work Skin biopsy showed dermal infiltrate consisting of medium-sized to large atypical cells with is properly cited. evenly dispersed chromatin and variably prom inent nucleoli. Sections were positive for CD4,

Remedy Publications LLC. 1 2018 | Volume 3 | Issue 2 | Article 1016 Wronska M, et al., Journal of Hematology & Multiple Myeloma

Image D: Positive staining for MPO under high power.

Image A: Initial presentation.

Image E: Positive staining for lysozyme under high power.

Image B: Expansion of the rash. slight male predominance. Frequent sites of involvement include skin, lymph nodes, as well as subperiosteal bone structures, gastrointestinal tract, bone, soft tissue, testis [3,5,6]. Clinical manifestations differ based on the site of involvement. Research on pathogenesis of MS has shown the predominance of specific ligands and receptors, such as a set of chemokine receptors (CCR5, CXCR4, CXCR7,CX3CR1) was identified to be present only on MS blast cells in the skin, and absent on blasts from bone marrow [7]. Other studies suggested that ability of the blastic cells to migrate of can be attributed to interaction between Matrix Metallo Proteinase (MMP) 9 and leukocyte surface beta (2) integrin [8] and hinted that higher expression of MMP-2, membrane type 1 MMP and tissue inhibitor of MMP-2 play a role in the blast capability to survive and penetrate to other sites [9]. Diagnosis is based on morphological evaluation of tissue from involved sites and bone marrow biopsy. In cases without associated AML, this may be frequently misdiagnosed, Image C: Expansion to the face and neck. most often as non-Hodgkin , undifferentiated cancer, malignant melanoma, extramedullary hematopoiesis and CD33 CD 43, CD56, Myelo Per-Oxidase (MPO) (Figure D), inflammation [6,10,11]. lysozyme (Figure E), and negative for CD2, CD3, CD5, CD7, CD20 Blasts are typically positive on for CD30, CD34, CD117, CD123, and TdT, confirming a clonal myeloid antibodies to MPO and lysozyme. Flow cytometry, essential for population consistent with AML. Cytogenetics revealed trisomy 8. diagnosis, is positive for myeloid-associated antigens such as CD43, Induction chemotherapy for AML was planned, however patient’s CD13, CD33, and CD117, as well as TdT, CD56, CD 61, CD34, but clinical status deteriorated considerably. Patient developed refractory negative for lymphoid antigens such as CD3 and CD20 [5,12] as seen fever, delirium, and concurrently worsening leukocytosis, anemia, in our case. and thrombocytopenia Patient died on day 12 of the hospital stay. Myeloid sarcoma has been associated with several cryptogenic Discussion abnormalities including t (8; 21) and, less often inv (16) (p13; q22) [10, 13, 14]. Fluorescence in situ hybridization analysis has revealed Myeloid Sarcoma (MS) is an extramedullary tumor reported in an array of chromosomal abnormalities including monosomy 5 2% to 8% of patients with AML, or preceding a diagnosis of AML or 7, trisomy 8, trisomy 11, del (5q), and del (20q) [6]. Molecular [1,3]. However there are case reports without overt BM involvement abnormalities reported were NPM1, FLT3 mutation, however the [4]. While cases of MS have been described in all age groups, there is a prognostic significance is unknown [15,16].

Remedy Publications LLC. 2 2018 | Volume 3 | Issue 2 | Article 1016 Wronska M, et al., Journal of Hematology & Multiple Myeloma

Due to the rarity of MS and lack of clinical trials, treatment for 7. Faaij CM, Willemze AJ, Revesz T, Balzarolo M, Tensen CP, Hoogeboom new onset myeloid sarcoma usually follows the strategy for AML M, et al. Chemokine/chemokine receptor interactions in extramedullary [17]. Treatment planning takes into consideration, age of the patient, leukaemia of the skin in childhood AML: differential roles for CCR2, CCR5, CXCR4 and CXCR7. Pediatr Blood Cancer. 2010;55(2):344-8. performance status, comorbidities, organ involvement, cytogenetics and molecular abnormalities and involves intensive chemotherapy 8. Stefanidakis M, Karjalainen K, Jaalouk DE, Gahmberg CG, O’Brien S, and radiotherapy if warranted in limited disease. Overall patients Pasqualini R, et al. Role of leukemia cell invadosome in extramedullary with isolated MS, receiving systemic chemotherapy have slower infiltration. Blood. 2009;114(140):3008-17. progression than patients receiving only localized treatment [5]. 9. Wang C, Chen Z, Li Z, Cen J. The essential roles of matrix The utility of hematopoietic stem cell transplant is yet to be studied metalloproteinase-2, membrane type 1 metalloproteinase and tissue prospectively but results from retrospective analyses are promising inhibitor of metalloproteinase-2 in the invasive capacity of acute monocytic [6]. This case highlights an unusual form of MS without bone marrow leukemia SHI-1 cells. Leuk Res. 2010;34(8):1083-90. or obvious organ involvement. Given the rapid progression of disease 10. Byrd JC, Edenfield WJ, Shields DJ, Dawson NA. Extramedullary myeloid and poor prognosis, this case should prompt clinicians to consider cell tumors in acute nonlymphocytic leukemia: a clinical review. J Clin MS early on in the differential. Oncol. 1995;13(7):1800-16. References 11. Suh YK, Shin HJC. Fine-needle aspiration biopsy of granulocytic sarcoma. Cancer. 2000;90:364-72. 1. Roth MJ, Medeiros LJ, Elenitoba-Johnson K, Kuchnio M, Jaffe 12. Traweek ST, Arber DA, Rappaport H, Brynes RK. Extramedlary myeloid E, Stetler-Stevenson M. Extramedullary myeloid cell tumors. An cell tumors. An immunohistochemical and morphlogic study of 28 cases. immunohistochemical study of 29 cases using routinely fixed and Am J Surg Pathol. 1993;17:1011-9. processed paraffinembedded tissue sections. Arch Pathol Lab Med. 1995;119(9):790-8. 13. Dusenbery KE, Howells WB, Arthur DC, Alonzo T, Lee JW, Kobrinsky N, et al. Extramedullary leukemia in children with newly diagnosed acute 2. Rappaport H. Tumours of the Hematopoietic System. Atlas of Tumor myeloid leukemia. J Pediatr Hematol Oncol. 2003;25(10):760-8. Pathology, Section III, Fascicle 8. Washington, DC: Armed Forces Institute of Pathology. 1966;241-3. 14. Tallman MS, Hakimian D, Shaw JM, Lissner GS, Russell EJ, Variakojis D. Granulocytic sarcoma is associated with the 8; 21 translocation in acute 3. Neiman RS, Barcos M, Berard C, Bonner H, Mann R, Rydell RE, et al. myeloid leukemia. J Clin Oncol. 1993;11(4):690-7. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer. 1981;48(6):1426-37. 15. Ansari-Lari MA, Yang CF, Tinawi-Aljundi R, Cooper L, Long P, Allan RH, et al. FLT3 mutations in myeloid sarcoma. Br J Haematol. 2004;126(60:785- 4. Krause JR. Granulocytic sarcoma preceding acute leukemia: a report of six 91. cases. Cancer. 1979;44(3):1017-21. 16. Falini B, Lenze D, Hasserjian R, Coupland S, Jaehne D, Soupir C, et al. 5. Lan TY, Lin DT, Tien HF, Yang RS, Chen CY, Wu K. Prognostic factors of Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status treatment outcomes in patients with granulocytic sarcoma. Acta Haemato. of a significant fraction of myeloid sarcomas. Leukemia. 2007;21(7):1566- 2009;122:238-46. 70. 6. Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M, et al. 17. Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis myeloid leukemia. J Clin Oncol. 2011;29(5):487-94. of 92 adult patients. Leukemia. 2007;21(2):340-50.

Remedy Publications LLC. 3 2018 | Volume 3 | Issue 2 | Article 1016