Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved.

The World Health Organization classification and definition of "myeloid sarcoma" is imprecise and misleading. A more accurate term is "extramedullary acute myeloid leukemia tumor (eAML)." The pathogenesis of eAML has been associated with aberrancy of cellular adhesion molecules, chemokine receptors/ligands and RAS-MAPK/ERK signaling. eAML can present with or without synchronous or metachronous intramedullary acute myeloid leukemia (AML) so a bone marrow evaluation is always recommended. Accurate diagnosis of eAML requires tissue biopsy. eAML confined to one or a few sites is frequently treated with local therapy such as radiotherapy. About 75-90% of patients with isolated eAML will develop metachronous intramedullary AML with a median latency period ranging from 4 to 12 months; thus, patients with isolated eAML may also be treated with systemic anti-leukemia therapy. eAML does not appear to have an independent prognostic impact; selection of post-remission therapy including allogeneic hematopoietic cell transplant (alloHCT) is typically guided by intramedullary disease risk. Management of isolated eAML should be individualized based on patient characteristics as well as eAML location and cytogenetic/molecular features. The role of PET/CT in eAML is also currently being elucidated. Improving outcomes of patients with eAML requires further knowledge of its etiology and mechanism(s) as well as therapeutic approaches beyond conventional chemotherapy, ideally in the context of controlled trials.

Hematolymphoid Neoplasms Rarely Mimic Undifferentiated Pleomorphic Sarcoma of Soft Tissue.

CONTEXT.­: Undifferentiated pleomorphic sarcoma (UPS) of soft tissue is defined as a sarcoma with no recognizable line of differentiation. During the past few decades, advances in ancillary studies and review of prior UPS diagnoses have narrowed the category of UPS by excluding more-specific malignancies. However, few of those studies have specifically targeted pleomorphic hematolymphoid neoplasms. OBJECTIVE.­: To determine what fraction of UPS cases are misclassified pleomorphic hematolymphoid neoplasms, such as anaplastic large cell lymphoma, diffuse large B-cell lymphoma, histiocytic sarcoma (HS), myeloid sarcoma, and follicular dendritic cell sarcoma. DESIGN.­: Sixty-one UPS cases were screened by tissue microarray and an immunostain panel with subsequent analysis on whole block sections for suspicious cases. RESULTS.­: Five of 61 tumors (8%) were suggestive of HS based on the screening panel and were further evaluated with additional immunostains (PU.1, CD45, CD163) using whole sections. The 5 candidate HS cases were only focally positive for at most one stain with most staining in smaller, less-pleomorphic cells. Ultimately, no UPS met criteria for anaplastic large cell lymphoma, diffuse large B-cell lymphoma, myeloid sarcoma, follicular dendritic cell sarcoma, or HS. CONCLUSIONS.­: Our results suggest that a UPS of somatic soft tissue is unlikely to represent a misclassified hematopoietic malignancy. Exclusion of HS is most challenging, but immunostaining for PU.1, a nuclear transcription factor, may be easier to interpret in this context.

Superior outcome of pediatric acute myeloid leukemia patients with orbital and CNS myeloid sarcoma: a report from the Children's Oncology Group.

BACKGROUND: Extramedullary leukemia (EML) is common in pediatric acute myeloid leukemia (AML) and occurs as leukemia cells within the cerebrospinal fluid (CSF) or as a solid tumor (myeloid sarcoma-MS). The effect of MS on survival is unknown. METHODS: Patients on CCG protocols 2861, 2891, 2941, and 2961 being treated for AML with intensive-timing chemotherapy were classified for the presence of EML (CSF leukemia, CNS-MS, orbital-MS, or non-CNS MS). CSF leukemia was classified as CNS3 (>5 WBC in the CSF with blasts) and non-CSF leukemia as CNS1/2 (<5 WBC in the CSF with or without blasts). Characteristics and outcomes of these patients were compared. RESULTS: Of the 1,459 total patients, 1,206 (82%) had no EML, 154 (11%) had CSF leukemia, 19 (1%) had CNS-MS, 23 (2%) had orbital-MS, and 57 (4%) had non-CNS MS. The CR rate was significantly higher in patients with orbital-MS and CNS-MS than in those with non-MS and non-CNS MS (96% and 95% vs. 78% and 78%, P = 0.034). Patients with orbital-MS and CNS-MS had significantly higher overall survival than patients with non-CNS MS (92% and 73% vs. 38%, P < 0.001), CNS3 patients (92% and 73% vs. 51, P < 0.001), and CNS1/2 patients (92% and 73% vs. 50%, P < 0.001). Patients with orbital-MS had a significantly lower relapse rate. CONCLUSION: Patients with MS involving orbital and CNS sites had a significantly better survival than patients with non-CNS MS, with CSF leukemia, or with no EML.

Granulocytic sarcomas: difficulties in diagnosis.

Granulocytic sarcoma is an uncommon tumor composed of myeloid blasts and/or immature myeloid cells in an extramedullary site which is usually associated with acute or chronic myeloid leukemia. The tumor may also be the initial manifestation of leukemia. The histomorphological diagnosis of granulocytic sarcoma can be challenging to pathologists, especially in the absence of a known hematological disorder. In this case, differentiation of granulocytic sarcoma from malignant lymphomas and other small round cell tumors is very critical. Seven cases of granulocytic sarcoma are reported in this paper. One patient had granulocytic sarcomas at two different sites. Hematoxylin-eosin-stained sections were reexamined. Blastic, poorly differentiated, and well differentiated histopathological variants were found in two, five and one cases, respectively. Immunohistochemical studies were performed on formalin-fixed tissue from all cases using a avidin-biotin-peroxidase complex technique. The panel included antibodies against LCA, CD43, CD34, c-kit, myeloperoxidase, CD68 KP1, CD15, and CD99. All cases stained positively with LCA, CD43, CD34, myeloperoxidase, and CD68. Five cases were positive for c-kit, three cases were positive for CD15, and two cases were positive for CD99. An immunohistochemical panel including at least myeloperoxidase, CD68 and CD34 can be used for detection of myeloid differentiation. It is also important that granulocytic sarcoma be considered in the differential diagnosis of CD99-positive round cell tumors.

Myeloid sarcoma: extramedullary manifestation of myeloid disorders.

Myeloid sarcoma (MS), also termed extramedullary acute myeloid leukemia, extramedullary myeloid tumor, and granulocytic sarcoma or chloroma, is a rare manifestation that is characterized by the occurrence of 1 or more tumor myeloid masses occurring at an extramedullary site. The wide spectrum of this disorder and the conditions that it overlaps diagnostically were well reflected in the 25 cases submitted to the Society for Hematopathology/European Association for Haematopathology Workshop held in Indianapolis, IN, in November 2007. This review, on the one hand, focuses on the definition and most recent achievements on the pathobiology of MS, and on the other, also in the light of the revised World Health Organization classification, summarizes the main features of a representative series of this condition aiming to provide readers a useful document for daily practice.

[Clinicopathologic and immunophenotypic analysis of myeloid sarcoma].

OBJECTIVE: To study the clinicopathologic features of myeloid sarcoma and to evaluate the role of immunohistochemical study in diagnosis of this entity. METHODS: Eighty-two cases of myeloid sarcoma were retrieved from the archives of Department of Pathology, West China Hospital of Sichuan University during the period from January, 1990 to February, 2005. The morphologic features were reviewed and classified according to the 2001 WHO classification for hematopoietic and lymphoid tissue tumors. Immunohistochemical study using a panel of 11 antibodies was performed on 73 cases. The survival data were collected and analyzed by SPSS 10.0. RESULTS: The median age of patients was 35.5 years. The male-to-female ratio was 1.4:1. The sites of occurrence included lymph node (43.1%), skin (16.7%), nose (7.8%), soft tissue (7.8%) and bone (6.9%). Fifty-one cases (62.2%) represented myeloid sarcoma associated with an underlying myeloproliferative disorder and 25 cases (30.5%) represented solitary myeloid sarcoma. As for the morphology, 79 cases (96.3%) were granulocytic sarcoma, including 41 cases (51.9%) blastic type, 25 cases (31.6%) immature type and 13 cases (16.5%) differentiated type. The other 3 cases (3.7%) were monoblastic sarcoma. Immature eosinophils were found in 51 cases (64.6%) of granulocytic sarcoma, among which 13 cases (31.7%) were of blastic type. Immunohistochemical study showed that 95.9% cases (70/73) were positive for myeloperoxidase, 95.5% (63/66) for lysozyme, 95.2% (60/63) for CD68 (KP1), 90.8% (59/65) for leukocyte common antigen, 85.7% (54/63) for CD43, 77.8% (49/63) for CD117, 58.7% (37/63) for CD99, 54.0% (34/63) for CD15, 22.2% (14/63) for CD34, and 4.7% (3/64) for CD68 (PG-M1). Proliferation index, as demonstrated by Ki-67 positivity, was 0.49+/-0.22. Follow-up data was obtained in 59 of the 82 patients. The two- and five-year survival rates were 36.1% and 17.3% respectively. No significant prognostic factors were found in the survival analysis. CONCLUSIONS: Myeloid sarcoma may precede, develop in a background of myeloproliferative disorder or even after remission of the disease. The presence of immature eosinophils is an important morphologic clue and immunohistochemical study plays an essential role in arriving at a correct diagnosis. Immunopositivity for myeloperoxidase is specific for granulocytic differentiation, while CD68 (PG-M1)-positivity suggests monocytic differentiation. Detailed clinicopathologic correlation is also helpful.