Intestinal Chloroma

Chloromas are an atypical cellular infiltrate of immature granulocytic cells that can occur specially in patients with acute myelogenous leukemia (AML), but can be present in nonleukemic patients. Its clinical course will be dependent on its size and location, from asymptomatic to simulating a malignant gastrointestinal neoplasia. Definitive diagnosis is made upon an immunoprofile that is similar to that present in the blasts and precursor cells of acute myeloid leukemia. Endoscopic and CT images are variable being only part of the protocol panel. Treatment is the same as to AML, but surgery and radiation must be used in order to maintain low relapse and better overall survival.


Introduction
Chloromas, granulocytic sarcoma or myeloid sarcoma (MS) is an extramedullary solid tumor of immature granulocytic cells, known to occur commonly in patients with acute myelogenous leukemia (AML), affecting 2.5%-9.1% of cases, but it can be present in nonleukemic patients [1]. Defined by the World Health Organization (WHO) as a tumor mass consisting of myeloid blasts with or without maturation occurring at an anatomic site other than the bone marrow [2], with only 6.5% of gastrointestinal tract involvement [3].
Described more than two centuries ago by Burns, clinical and pathological diagnosis of chloroma is still highly challenging [4]. Any atypical cellular infiltrate where there was a history of myeloid neoplasia should raise the suspicion for chloroma.
We present the case of an intestinal chloroma.

Case Presentation
A 22-year-old female patient, with no significant medical history, was referred to our hospital because of growing bilateral cervical masses, odinophagy, disphony, unquantified fever, and nocturnal diaphoresis for 40 days. Three days later, petechiae were noted on her limbs, with minor transvaginal bleeding. An out of hospital bone marrow aspiration reported AML.
At physical examination, the only finding was bilateral cervical lymphadenopathy, being painful on the left side. The pulse rate was at 100 bpm, and there were no significant alterations with the rest of the vital signs. Laboratories evidenced anemia with 7 g/dL hemoglobin (range 12-15.5 g/dL), leucopenic with 0.65 x 10⁹/L of leukocytes (range 4.5-11 x 10⁹/L), profound neutropenia with 0 neutrophils (range 2,500-8,000/mm³), thrombocytopenic with platelets 22,000/µL (range 150,000-450,000/µL).
Hyper-CVAD was initiated. She presented fever of 38.5°, cultures were taken as well as antibiotics initiated. She had poor evolution with persisting fever and the need of a platelet concentrate transfusion. As cultures were negative, a thoracoabdominal tomography was done with findings of inflammatory process in peritonsyllar tissue, concentric thickening of 6 mm in ascending colon and slight increase in the density of pericolic fat (Figures 1-2), neutropenic colitis that required only conservative treatment.

Discussion
Chloromas display predominantly green color, due to the presence of MPO, as described earlier (1853) by King [5]. In 1966, Rappaport proposed the term "granulocytic sarcoma" [6], and finally, in 2002, the term myeloid sarcoma was accepted by the WHO [7]. It occurs more commonly in patients with AML (1%), less commonly in those with myelodisplastic syndrome (MDS) and myeloproliferative neoplasm. Chloromas can represent the initial manifestation of relapse in previously treated AML in remission [8]. Infrequently, extramedullary disease is the only site of involvement; the most common sites are skin, bone, soft tissue, lymph nodes. Involvement of gastrointestinal tract is rare up to 6.5% [9]. Isolated chloroma occurs in association with a normal bone marrow biopsy and blood film, in the absence of any history of myeloid neoplasia. In 90% of patients who initially had no hematological disorder, if untreated, AML develops within 10.5-11 months. Incidence of chloroma is unknown and believed to be underestimated.
Clinical presentation is varied and it is highly dependent on tumor size and location. Tumors located in gastrointestinal tract can manifest in several ways like: · Stomach: Epigastralgy, hemorrage, perforation.
The CT features of granulocytic sarcoma of the bowel are variable. Lesions appear as an intraluminal or exophytic polypoid mass, as bowel wall thickening, or as a combination of these manifestations. The enhancement patterns of these lesions are variable. Therefore, leukemic lesions of the bowel itself cannot be differentiated at CT from lymphoma or other neoplastic conditions or inflammatory bowel diseases [1].
In chloroma, several markers have been employed for identification of myeloid origin of tumor infiltration. MPO and chloroacetate immunostaining with antibodies are important for the identification of chloroma, bearing in mind that precursor cells of AML and myeloblasts in chloroma have similar antigen profile [7].
With conventional light microscopy, differential diagnosis of the pathological specimen may be difficult, particularly in the case of lymphoblastic, Burkitt's, or diffuse large B-cell lymphoma or even a nonhematological malignancy [3].
Antic et al. suggested that the minimum panel of immunohistochemical markers should include MPO, CD68, CD43, lysozyme, CD33, CD34, and CD117 in order to establish a definitive diagnosis [7].
There are no consensus guidelines or protocol regarding chloroma treatment. This will depend on several factors including: location of disease, whether it is a relapse or an initial diagnosis, age of patient, and performance status. Current treatment regimen in patients with chloroma or isolated chloroma is conventional AML chemotherapeutic protocols with or without radiotherapy. Surgery can be considered before systemic treatment when rapid debulking, symptomatic relief is needed or to confirm diagnosis. Hematopoietic stem cell transplantation (HSCT) should also be considered in relapsed or refractory patients or even as a consolidation treatment [12].

Conclusions
Although relatively uncommon, chloroma should be suspected in every patient with myeloid neoplasia history with added symptoms. Even though the clinical manifestations are variable, image should always be part of the diagnostic arsenal in order to establish therapeutic regimen that must include surgical, radiation, and chemotherapy. Treatment guidelines based on prospective studies of this rare manifestation are required to determine the best combination of actual therapies, as early detection and treatment will lead to a better overall patient's survival and quality of life.

Additional Information Disclosures
Human subjects: Consent was obtained by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.