Pediatric acute myeloid leukemia with breast chloromas

Myeloid sarcoma (MS; also known as granulocytic sarcoma or chloroma) is a solid extramedullary mass composed of primitive myeloid cells that disrupts the normal architecture of the tissue in which it is found. MS can present concurrently with acute myeloid leukemia (AML), precede the diagnosis of AML without evidence of leukemia in the blood or bone marrow or as a relapse in a patient with previously treated AML [1–3]. In children, the overall incidence of MS in association with AML varies, but has been reported to be as high as 24% [4–8]. The most frequently involved anatomic sites are the skin, lymph node, testis, gastrointestinal tract, bone, and central nervous system (CNS) [1–3, 9, 10].

Myeloid sarcoma (MS; also known as granulocytic sarcoma or chloroma) is a solid extramedullary mass composed of primitive myeloid cells that disrupts the normal architecture of the tissue in which it is found. MS can present concurrently with acute myeloid leukemia (AML), precede the diagnosis of AML without evidence of leukemia in the blood or bone marrow or as a relapse in a patient with previously treated AML [1][2][3]. In children, the overall incidence of MS in association with AML varies, but has been reported to be as high as 24% [4][5][6][7][8]. The most frequently involved anatomic sites are the skin, lymph node, testis, gastrointestinal tract, bone, and central nervous system (CNS) [1-3, 9, 10].
Breast MS is very rare and only accounts for approximately 8% of MS cases [1,10], with the majority of cases of breast MS diagnosed in adults [11][12][13][14][15][16][17][18][19][20][21]. There have been three reported cases in adolescents with previously treated AML [22][23][24] and only one case of concurrent diagnosis of a breast MS at the time of AML diagnosis [25]. We report a case of bilateral breast MS in a teenage Asian American patient diagnosed concurrently with AML.
An 11-year-old teenage female patient (Asian-Indian descent) presented with a 1-2-month history of generalized pallor and fatigue. She was also noted to have a 1-month history of bilateral breast masses. On presentation, her complete blood count demonstrated a white blood cell count of 24,800/mm 3 , hemoglobin level of 3.9 g/dL, and platelet count of 19,000/mm 3  MS clinical features of breast granulocytic sarcoma (GS) are nonspecific, which can present as a unilateral or bilateral palpable, painful, or painless breast mass/nodules and often can be indistinguishable from benign tumors or lymphoma [2,10], making the diagnosis challenging. A tissue biopsy with immunohistochemical stains for the antigens most frequently expressed by MS, including CD34, CD43, CD56, MPO, CD117, CD13, and CD33 [2,3] is important. PET/CT imaging appears to be the best imaging modality to assess the presence of extramedullary AML, which has ability to both detect MS and monitor its response to therapy [26,27].
There is no consensus about the optimal treatment of MS. Highdose chemotherapy, radiation, surgical resection, and allogeneic stem cell transplantation are all modalities that can be incorporated into the therapy of MS [1,27]. It appears appropriate to treat chloroma with AML-type chemotherapy protocols even in the absence of systemic manifestations since AML is almost always present [28].
The prognostic significance of MS in childhood AML is still controversial. Several groups have reported that complete remission rates were lower in patients with extramedullary infiltration following induction chemotherapy [7,8,29], while others reported that overall survival and event-free survival rates were better among patients with AML and MS [4,5,30].
The characteristics of our patient are similar to those of the Tyagi study [6] who reported an increased frequency of t(8;21), 29.9% of 472 Indian children studied were positive for t (8;21). Additionally, a significant association of t(8;21) with chloromas (p < 0.01) was observed in northern Indian children with AML. This compares well with one study which reported a similar frequency (26%) of positive t(8;21) among their 567 pediatric patients from a tertiary care cancer center from western India [31].
Chloromas involving the breast in an adolescent female patient as initial presentation for AML is highly unusual and remains a diagnostic challenge; therefore, it must be included in the differential diagnosis of a breast mass in children and adolescents with or without a previous history of leukemia.

AUTHOR CONTRIBUTIONS
Maria S. Gallardo drafted and edited the manuscript. Richard Joyrich edited the manuscript. Jeffrey W. Taub planned the report and edited the manuscript.

ACKNOWLEDGEMENT
We would like to acknowledge Dr. Jeffrey Rubnitz (St. Jude Children's Reseach Hospital Hospital), protocol chair of the AML16 clinical trial.

CONFLICT OF INTEREST STATEMENT
The authors have no conflicts of interest.

FUNDING INFORMATION
The authors received no specific funding for this work.

DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.

PATIENT CONSENT STATEMENT
Verbal consent was obtained from patient and family.