Editing Myeloid sarcoma

{{Infobox medical condition
| name            = Myeloid sarcoma
| image           = Chloroma - very high mag.jpg
| caption         = [[Micrograph]] of a myeloid sarcoma within muscle. [[H&E stain]].
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[[File:Chloroma CMUJ.jpg|thumb|right|Chloroma]]
A '''myeloid sarcoma''' ('''chloroma''', '''granulocytic sarcoma''',<ref name="Andrews">{{cite book |author1=James, William D. |author2=Berger, Timothy G. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |display-authors=etal}}</ref>{{rp|744}} '''extramedullary myeloid tumor''') is a solid [[tumor]] composed of immature [[white blood cell]]s<ref name="pmid17194660">{{cite journal  |vauthors=Karlin L, Itti E, Pautas C, etal |title=PET-imaging as a useful tool for early detection of the relapse site in the management of primary myeloid sarcoma |journal=Haematologica |volume=91 |issue=12 Suppl |pages=ECR54 |date=December 2006 |pmid=17194660 |url=http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=17194660}}</ref> called [[myeloblast]]s. A chloroma is an [[extramedullary]] manifestation of [[acute myeloid leukemia]]; in other words, it is a solid collection of leukemic cells occurring outside of the [[bone marrow]].

== Types ==

=== In acute leukemia ===
Chloromas are rare; exact estimates of their prevalence are lacking, but they are uncommonly seen even by physicians specializing in the treatment of [[leukemia]]. Chloromas may be somewhat more common in patients with the following disease features:<ref name="review">{{cite journal |vauthors=Byrd JC, Edenfield WJ, Shields DJ, Dawson NA |title=Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review |journal=J. Clin. Oncol. |volume=13 |issue=7 |pages=1800–16 |date=July 1995 |pmid=7602369 |doi=10.1200/JCO.1995.13.7.1800 }}</ref>
* [[French–American–British classification|French–American–British (FAB) classification]] class M2
* WHO Classification (2016 revision) is a separate entity under the "Acute myeloid leukemia (AML) and related neoplasms"
* those with specific [[cytogenetics|cytogenetic]] abnormalities (e.g. t(8;21) or inv(16))
* those whose [[myeloblast]]s express [[T-cell]] surface markers, [[CD13]], or [[CD14]]
* those with high peripheral [[white blood cell]] counts

However, even in patients with the above risk factors, chloroma remains an uncommon complication of acute myeloid leukemia.

Rarely, a chloroma can develop as the sole manifestation of relapse after apparently successful treatment of acute myeloid leukemia. In keeping with the general behavior of chloromas, such an event must be regarded as an early herald of a systemic relapse, rather than as a localized process. In one review of 24 patients who developed isolated chloromas after treatment for acute myeloid leukemia, the mean interval until bone marrow relapse was 7 months (range, 1 to 19 months).<ref>{{cite journal |vauthors=Byrd JC, Weiss RB |title=Recurrent granulocytic sarcoma. An unusual variation of acute myelogenous leukemia associated with 8;21 chromosomal translocation and blast expression of the neural cell adhesion molecule |journal=Cancer |volume=73 |issue=8 |pages=2107–12 |date=April 1994 |pmid=7512442 |doi=10.1002/1097-0142(19940415)73:8<2107::AID-CNCR2820730815>3.0.CO;2-W|doi-access=free }}</ref>

=== In myeloproliferative or myelodysplastic syndromes ===
Chloromas may occur in patients with a diagnosis of [[myelodysplastic syndrome]] (MDS) or [[myeloproliferative syndrome]]s (MPS) (e.g. [[chronic myelogenous leukemia]] (CML), [[polycythemia vera]], [[essential thrombocytosis]], or [[myelofibrosis]]). The detection of a chloroma is considered ''de facto'' evidence these premalignant conditions have transformed into an acute leukemia requiring appropriate treatment. For example, presence of a chloroma is sufficient to indicate chronic myelogenous leukemia has entered its 'blast crisis' phase.

=== In eosinophilic leukemia ===
At least one case of [[FIP1L1#FIP1L1-PDGFRA|''FIP1L1-PDGFRA'']] fusion gene-induced eosinophilic leukemia presenting with myeloid sarcoma and eosinophilia has been reported. This form of myeloid sarcoma is distinguished by its highly successful treatment with [[imatinib]] (the recommended treatment for ''FIP1L1-PDGRGA'' fusion gene-induced eosinophilic leukemia) rather than more aggressive and toxic therapy.<ref name="pmid26276769">{{cite journal | vauthors = Vega F, Medeiros LJ, Bueso-Ramos CE, Arboleda P, Miranda RN | title = Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1 | journal = American Journal of Clinical Pathology | volume = 144 | issue = 3 | pages = 377–92 | year = 2015 | pmid = 26276769 | doi = 10.1309/AJCPMORR5Z2IKCEM | s2cid = 10435391 | doi-access = free }}</ref>

=== Primary chloroma ===
Very rarely, chloroma can occur without a known pre-existing or concomitant diagnosis of acute leukemia, [[acute promyelocytic leukemia]] or MDS/MPS; this is known as primary chloroma. Diagnosis is particularly challenging in this situation (see below). In almost all reported cases of primary chloroma, acute leukemia has developed shortly afterward (median time to development of acute leukemia 7 months, range 1–25 months).<ref name="review"/> Therefore, primary chloroma could be considered an initial manifestation of acute leukemia, rather than a localized process, and could be treated as such. Where disease development or markers indicate progresses to acute promyleocytic leukemia (AML3) treatment should be tailored to this form of disease.

== Location and symptoms ==
Chloromas may occur in virtually any organ or tissue. The most common areas of involvement are the skin (also known as ''leukemia cutis'') and the gums. Skin involvement typically appears as violaceous, raised, nontender plaques or nodules, which on [[biopsy]] are found to be infiltrated with myeloblasts<ref name="http://www.ncbi.nlm.nih.gov/pubmed/26063639">
{{cite journal |author=Tan BY. |title=Myeloid Sarcoma Masquerading as Granulation Tissue: A Diagnostic Pitfall. |journal=Int J Surg Pathol |volume=23 |issue=7 |pages=553–556 |year=2015 |doi=10.1177/1066896915588931|pmid=26063639 |s2cid=5658954 }}</ref> Note that leukemia cutis differs from [[Sweet syndrome|Sweet's syndrome]], in which the skin is infiltrated by mature neutrophils in a [[paraneoplastic]] process. Gum involvement ([[Gingival enlargement|gingival hypertrophy]]) leads to swollen, sometimes painful gums which bleed easily with tooth brushing and other minor trauma.

Other tissues which can be involved include [[lymph node]]s, the [[small intestine]], the [[mediastinum]], the [[lung]], [[epidural]] sites, the [[uterus]], the [[ovary|ovaries]], and the orbit of the [[eye]]. Symptoms of chloroma at these sites are related to their anatomic location; chloromas may also be [[asymptomatic]] and be discovered incidentally in the course of evaluation of a person with acute myeloid leukemia.

[[Central nervous system]] involvement, as described above, most often takes the form of ''meningeal leukemia'', or invasion of the [[subarachnoid space]] by leukemic cells. This condition is usually considered separately from chloroma, as it requires different treatment modalities. True chloromas (i.e. solid leukemic tumors) of the central nervous system are exceedingly rare, but have been described.

== Diagnosis ==
Definitive diagnosis of a chloroma usually requires a [[biopsy]] of the lesion in question. Historically, even with a tissue biopsy, pathologic misdiagnosis was an important problem, particularly in patients without a clear pre-existing diagnosis of acute myeloid leukemia to guide the pathologist. In one published series on chloroma, the authors stated that 47% of the patients were initially misdiagnosed, most often as having a malignant [[lymphoma]].<ref>{{cite journal |vauthors=Yamauchi K, Yasuda M |title=Comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature |journal=Cancer |volume=94 |issue=6 |pages=1739–46 |date=March 2002 |pmid=11920536 |doi=10.1002/cncr.10399|s2cid=30158836 }}</ref>

However, with advances in diagnostic techniques, the diagnosis of chloromas can be made more reliable. Traweek et al. described the use of a commercially available panel of [[monoclonal antibody|monoclonal antibodies]], against [[myeloperoxidase]], [[CD68]], [[CD43]], and [[CD20]], to accurately diagnose chloroma via [[immunohistochemistry]] and differentiate it from lymphoma.<ref>{{cite journal |vauthors=Traweek ST, Arber DA, Rappaport H, Brynes RK |title=Extramedullary myeloid cell tumors. An immunohistochemical and morphologic study of 28 cases |journal=Am. J. Surg. Pathol. |volume=17 |issue=10 |pages=1011–9 |date=October 1993 |pmid=8372941 |doi=10.1097/00000478-199310000-00006|s2cid=41874263 }}</ref> Nowadays, immunohistochemical staining using [[monoclonal antibodies]] against [[CD33]] and [[CD117]] would be the mainstay of diagnosis. The increasingly refined use of [[flow cytometry]] has also facilitated more accurate diagnosis of these lesions.

== Prognostic significance ==
Evidence is conflicting on the [[prognosis|prognostic]] significance of chloromas in patients with acute myeloid leukemia. In general, they are felt to augur a poorer prognosis, with a poorer response to treatment and worse survival;<ref>{{cite journal |vauthors=Byrd JC, Weiss RB, Arthur DC, etal |title=Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461 |journal=J. Clin. Oncol. |volume=15 |issue=2 |pages=466–75 |date=February 1997 |pmid=9053467|doi=10.1200/JCO.1997.15.2.466   }} </ref> however, others have reported chloromas associate, as a biologic marker, with other poor prognostic factors, and therefore do not have independent prognostic significance.<ref>{{cite journal  |vauthors=Bisschop MM, Révész T, Bierings M, etal |title=Extramedullary infiltrates at diagnosis have no prognostic significance in children with acute myeloid leukaemia |journal=Leukemia |volume=15 |issue=1 |pages=46–9 |date=January 2001 |pmid=11243398 |doi=10.1038/sj.leu.2401971|doi-access=free }}</ref> In case of primary isolated choloroma, prognosis is better <ref>{{cite journal |vauthors=Imrie KR, Kovacs MJ, Selby D, Lipton J, Patterson BJ, Pantalony D, Poldre P, Ngan BY, Keating A etal |title=Isolated chloroma: the effect of early antileukemic therapy |journal=Annals of Internal Medicine |volume=123 |issue=5 |pages=351–3 |date=September 1995 |pmid=7625623 |doi=10.7326/0003-4819-123-5-199509010-00005 |s2cid=20631629 }}</ref>

== Treatment ==
As described above, chloromas should always be considered manifestations of systemic disease, rather than isolated local phenomena, and treated as such. In the patient with newly diagnosed leukemia and an associated chloroma, systemic chemotherapy against the leukemia is typically used as the first-line treatment, unless an indication for local treatment of the chloroma (e.g. compromise of the [[spinal cord]]) emerges. Chloromas are typically quite sensitive to standard antileukemic [[chemotherapy]]. Allogeneic hematopoietic stem cell transplantation should be considered in fit patients with suitable available donor, as long term remissions have been reported.<ref>{{cite journal  |vauthors=Kaur V, Swami A, Alapat D, etal |title=Clinical characteristics, molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years |journal=Hematology |volume=23 |issue=1 |pages=17–24 |pmid=28574302 |doi=10.1080/10245332.2017.1333275|year=2018 |doi-access=free }}</ref>

If the chloroma is persistent after completion of induction chemotherapy, local treatment, such as [[surgery]] or [[radiation therapy]], may be considered, although neither has an effect on survival.<ref>{{cite journal  |vauthors=Imrie KR, Kovacs MJ, Selby D, etal |title=Isolated chloroma: the effect of early antileukemic therapy |journal=Ann. Intern. Med. |volume=123 |issue=5 |pages=351–3 |date=September 1995 |pmid=7625623 |doi=10.7326/0003-4819-123-5-199509010-00005|s2cid=20631629 }}</ref>

Patients presenting with a primary chloroma typically receive systemic chemotherapy, as development of acute leukemia is nearly universal in the short term after detection of the chloroma.

Patients treated for acute leukemia who relapse with an isolated chloroma are typically treated with systemic therapy for relapsed leukemia. However, as with any relapsed leukemia, outcomes are unfortunately poor.

Patients with "preleukemic" conditions, such as [[myelodysplastic syndrome]]s or myeloproliferative syndromes, who develop a chloroma are often treated as if they have transformed to acute leukemia.

== History ==
The condition now known as chloroma was first described by the [[British people|British]] [[physician]] A. Burns in 1811,<ref>{{cite book |author=Burns A |title=Observations of surgical anatomy, in Head and Neck |publisher=Royce |location=London |year=1811 |page=364 }}</ref> although the term ''chloroma'' did not appear until 1853.<ref>{{cite journal |author=King A |title=A case of chloroma |journal=Monthly J Med |volume=17 |pages=340–53 |year=1853 |pmid=16693015 |pmc=1315481 }}</ref> This name is derived from the [[Greek language|Greek]] word ''chloros'' (green), as these tumors often have a green tint due to the presence of [[myeloperoxidase]]. The link between chloroma and [[acute leukemia]] was first recognized in 1902 by Dock and Warthin.<ref>{{cite journal |vauthors=Dock G, Warthin AS |title=A new case of chloroma with leukemia |journal=Trans Assoc Am Phys |volume=19 |issue=64 |pages=115 |year=1904 }}</ref> However, because up to 30% of these tumors can be white, gray, or brown rather than green, the more correct term ''granulocytic sarcoma'' was proposed by Rappaport in 1967<ref>{{cite book |author=Rappaport H |chapter=Tumors of the hematopoietic system |title=Atlas of Tumor Pathology, Section III, Fascicle 8 |publisher=Armed Forces Institute of Pathology |location=Washington DC |year=1967 |pages=241–7 }}</ref> and has since become virtually synonymous with the term ''chloroma''.

Currently, any extramedullary manifestation of acute myeloid leukemia can be termed a granulocytic sarcoma or chloroma. Specific terms which overlap with granulocytic sarcoma include:
* '''Leukemia cutis''', describing infiltration of the [[dermis]] (skin) by leukemic cells, which is also referred to as cutaneous granulocytic sarcoma.
* '''Meningeal leukemia''', or invasion of the [[subarachnoid space]] by leukemic cells, is usually considered distinct from chloroma, although very rarely occurring solid [[central nervous system]] tumors composed of leukemic cells can be termed chloromas.

In recent years, the term "myeloid sarcoma" has been favored.<ref name="pmid18606981">{{cite journal |vauthors=Chevallier P, Mohty M, Lioure B, etal |title=Allogeneic Hematopoietic Stem-Cell Transplantation for Myeloid Sarcoma: A Retrospective Study From the SFGM-TC |journal=J. Clin. Oncol. |volume=26 |issue=30 |pages=4940–3 |date=July 2008 |pmid=18606981 |doi=10.1200/JCO.2007.15.6315 }}</ref>

== See also ==
* [[Acute myeloid leukemia]]

== References ==
{{Reflist}}

== External links ==
{{Medical resources
|   ICD10          = {{ICD10|C|92|3|c|81}}
|   ICD9           = {{ICD9|205.3}}
|   ICDO           = 9930/3
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|   MeshID         = D023981
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{{Myeloid malignancy|us=y}}

{{DEFAULTSORT:Chloroma}}
[[Category:Acute myeloid leukemia]]