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Colonic adenomas with extramedullary myeloid tumor (granulocytic sarcoma).

Extramedullary myeloid tumor (EMT) is an accumulation of malignant immature cells of the granulocytic series that is usually green in appearance due to the presence of myeloperoxidase. These invasive and destructive tumors occur most commonly in the skull and surrounding tissues, lymph nodes, skin and soft tissues. Regardless of the site, EMTs are difficult to recognize and may be easily overlooked or diagnosed as malignant lymphoma. EMTs may precede the diagnosis of a chronic myeloproliferative disorder or acute myeloid leukemia, may present coincident with the hematologic diagnosis, or may herald a relapse after therapy. An accurate diagnosis of EMT is of great clinical importance in the ongoing management of hematologic malignancies. We report here two unusual cases of EMT of the colon, which infiltrated adenomatous polyps. We conclude that increased cellularity within the lamina propria of polyps and mucosal surfaces in general should be carefully examined.

Adenomatous Polyps↗

Extramedullary tumors of lymphoid or myeloid blasts. The role of immunohistology in diagnosis and classification.

The diagnosis of primitive hematologic malignancies in extramedullary sites (lymphoblastic lymphoma of T- or B-cell type and myeloid sarcoma) on paraffin-embedded tissue sections is difficult and often impossible because of the primitive morphology of the neoplastic cells. The authors studied 21 extramedullary tumors of lymphoid or myeloid blasts. They used a panel of 22 antibodies on frozen sections and 9 antibodies on paraffin sections to determine the spectrum of immunophenotypes and to develop a practical panel for diagnosis. All but two of the cases could be classified as lymphoid or myeloid using immunohistologic analysis. Thirteen cases were classified as lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL); 10 were classified as precursor T (CD7+, CD3+/-, CD45+) and 3 as precursor B-cell (CD19+/-CD10+CD45-) type. Five cases were classified as myeloid sarcoma (CD13+ myeloperoxidase+, lysozyme+). Two LBL/ALL coexpressed either CD33 (1 case) or CD15 (1 case), and one myeloid sarcoma coexpressed TdT and CD7. One case appeared to be truly mixed lineage, coexpressing CD3 with myeloperoxidase and lysozyme, and two cases expressed no lineage-specific antigens. There were clinical differences between the three major tumor types, and within the category of T-precursor LBL/ALL, classification according to stage of thymocyte differentiation was associated with distinctive clinical features. In conclusion, the spectrum of immunophenotypes detected on frozen section was similar to that reported by flow cytometry on peripheral blood and bone marrow specimens. The most useful antigens on frozen sections were CD7 and CD3 (T cell), CD10 and CD19 (B cell), and CD13 (myeloid). TdT was coexpressed by one myeloid sarcoma and was undetectable in 40% of LBL/ALL. On paraffin sections, myeloperoxidase and lysozyme were reliable markers of myeloid lineage, but none of the markers used on paraffin sections distinguished between LBL/ALL of T- and B-precursor types. Both B-LBL/ALL and myeloid sarcomas were often CD45- on paraffin sections, which may be a obstacle in determining the diagnosis. These distinctions appear to have clinical relevance.

Adolescent↗

Extramedullary tumors of myeloid blasts in adults as a pattern of relapse following allogeneic bone marrow transplantation.

BACKGROUND: Extramedullary tumors of lymphoid and myeloid blasts outside the well-defined sanctuaries following allogeneic bone marrow transplantation (allo-BMT) are rare. Little is known about the biology, treatment, and outcome of these tumors in this setting. METHODS: In this retrospective analysis, 134 consecutive patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) who underwent allo-BMT at a single institution between 1990 and 1998 were reviewed. Five cases of isolated extramedullary myeloid sarcoma that occurred as patterns of recurrence following allo-BMT between 1990 and 1998 are reported. These patients were treated with radiotherapy, systemic chemotherapy, or a second allo-BMT. Clinical outcome is compared with posttransplantation bone marrow relapses observed during the same period at the same institution. The literature on the clinical characteristics, currently available treatment, and outcome of posttransplantation myeloid sarcoma patients was reviewed. RESULTS: Excluding isolated skin and central nervous system recurrences, the frequency of extramedullary myeloid sarcoma encountered as a relapse pattern following allo-BMT was determined to be 3.7% among patients with acute or chronic leukemia of myeloid origin. The survival of patients who were managed with radiotherapy and systemic chemotherapy was less than 4 months. A patient who underwent a second allo-BMT following local radiotherapy is alive and in complete remission more than 33 months after the diagnosis of myeloid sarcoma. The median survival of 17 patients with posttransplantation bone marrow relapse following allo-BMT was 2.2 months. When posttransplantation medullary recurrences are analyzed, patients with CML had a median survival of 12 months, with a significantly better 5-year survival rate than patients with AML (0 vs. 60%, P = 0.015; median survival, 12 months). CONCLUSIONS: The clinical outcomes of patients with recurrent isolated extramedullary myeloid sarcoma following allo-BMT are poor, as in any leukemic relapse, with the exception of patients with CML in this setting.

Adult↗

Cytology of ascitic fluid in a patient with granulocytic sarcoma (extramedullary myeloid tumor). A case report.

BACKGROUND: Granulocytic sarcoma (GS) is the rare extramedullary manifestation of acute myeloid leukemia that may precede or be concurrent with leukemic infiltration of bone marrow or herald blastic transformation of a chronic myeloproliferative disorder. It has been found in most body sites and shows no age or sex predilection, necessitating its inclusion in the differential diagnosis of undifferentiated neoplasms. CASE: A 36-year-old female presented with a three-year history of abdominal pain, jaundice and fluctuating abdominal girth. Cytology of the ascitic fluid revealed myeloid cells of eosinophilic lineage at all stages of differentiation, with many undifferentiated cells. Immunohistochemical studies on a cell block confirmed the diagnosis of granulocytic sarcoma, which excluded the differential diagnoses of Hodgkin's disease, non-Hodgkin's lymphoma and Langerhans histiocytosis. CONCLUSION: Granulocytic sarcoma may present as a serous effusion and can be diagnosed on a cytologic specimen.

Abdominal Neoplasms↗

Fine-needle aspiration cytology of granulocytic sarcoma and myeloid metaplasia.

The fine-needle aspiration (FNA) cytology of two cases of granulocytic sarcoma involving the breast is reported along with the FNA cytology of one case of myeloid metaplasia (extramedullary hematopoiesis) involving an axillary lymph node. Two patients had known myeloproliferative disorders, while granulocytic sarcoma of the breast was the initial presentation of an unsuspected acute granulocytic leukemia in the other patient. Diff-Quik-stained preparations aided in the diagnosis of all three cases. Immunoperoxidase stains for factor VIII-related antigen helped confirm the megakaryocytic differentiation of the cells in the FNA cytology of myeloid metaplasia. Electron microscopic (EM) examination performed on the aspirated material also showed megakaryocytic differentiation of the bizarre cells. FNA cytology can make a specific diagnosis of granulocytic sarcoma and myeloid metaplasia. The workup of these unusual extramedullary myeloproliferative masses was aided when immunocytochemistry and EM were performed on the aspirated material.

Adult↗

CD163: a specific marker of macrophages in paraffin-embedded tissue samples.

Paraffin-section immunohistochemical analysis was performed using a monoclonal antibody against CD163 to evaluate the antibody's usefulness in identifying cells of monocyte/macrophage lineage in normal and neoplastic conditions. Normal human tissue samples and samples from 211 hematopoietic disorders and 115 nonhematopoietic neoplasms were examined. The distribution of KP1 and PG-M1, monoclonal antibodies to the macrophage-associated CD68 antigen, also were evaluated for comparison. CD163 immunoreactivity was observed in resident macrophages of all normal tissue samples except splenic white pulp macrophages and germinal center tingible body macrophages. Among hematopoietic disorders and nonhematopoietic neoplasms, CD163 expression was restricted largely to cases of chronic myelomonocytic leukemia, histiocytic sarcoma, sinus histiocytosis with massive lymphadenopathy, and littoral cell angioma. Acute myeloid leukemias (AMLs) with monocytic differentiation were CD163- with the exception of 1 case of acute monoblastic leukemia. Most myeloid sarcomas also were CD163-. Compared with the CD68 antibodies, CD163 demonstrated greater specificity as a marker of disorders of monocyte/macrophage origin. However, immunohistochemical evaluation of CD163 expression does not seem to be a sensitive means of determining monocytic differentiation in AMLs in paraffin sections or establishing a diagnosis of myeloid sarcoma.

Antigens, CD↗

Orbital tumor in acute myeloid leukemia associated with karyotype 46,XX,t(8;21)(q22;q22): a case report.

Orbital tumor formation in acute myeloid leukemia (AML) is rare as an initial symptom. Furthermore, orbital granulocytic sarcoma (myeloid sarcoma) in pediatric patients is uncommon. We describe a 5-year-old Japanese girl with a left orbital mass as an initial symptom of AML, the mass revealed by computed tomography. Peripheral blood and bone marrow pictures and a chromosomal analysis disclosing 46,XX,t(8;21)(q22;q22) showed AML (M2 according to the French-American-British classification). She was treated with antileukemic chemotherapy systemically. Three weeks after the initiation of chemotherapy, the orbital tumor regressed markedly. AML as an initial symptom of the orbital mass should be fully considered in a differential diagnosis, even in the absence of typical leukemic symptoms, and chromosomal analysis and immunophenotypical analysis may explain the pathogenesis of the extramedullary leukemic tumor.

Acute Disease↗

c-Kit (CD117) reactivity in extramedullary myeloid tumor/granulocytic sarcoma.

CONTEXT: c-kit, a proto-oncogene, encodes the transmembrane tyrosine kinase receptor CD117 and is detected by flow cytometry in the majority of cases of acute myeloid leukemia. The prognostic significance of the presence of c-Kit in acute myeloid leukemia is debated. Recently, c-kit inhibitors have been studied as possible therapies against hematopoietic malignancies; therefore, c-Kit detection may have important implications for treatment. OBJECTIVES: In this study, we investigated the expression of c-Kit in granulocytic sarcoma (GS) using paraffin-embedded tissue. DESIGN: Routinely formalin-fixed, paraffin-embedded tissues from 30 cases of GS were studied using immunohistochemistry. c-Kit (C-19) (a polyclonal antibody against carboxy terminal domain of c-Kit p145 or CD117) reactivity was compared with myeloperoxidase and lysozyme. The immunohistochemical panel also included CD34, CD68, CD43, Bcl-2, CD45RB, CD20, CD3, CD10, terminal deoxynucleotidyl transferase (TdT), and CD79a. RESULTS: The morphologic patterns included well-differentiated (5 cases), poorly differentiated (19 cases), and blastic forms (6 cases). Clinical data were obtained from 28 of 30 patients. Granulocytic sarcoma presented in lymph nodes in 10 cases, whereas in 20 cases it presented in extranodal sites. c-Kit reactivity was found in 87% (26/30) of the GS cases. There was no significant difference in c-Kit positivity between the nodal (90%, 9/10) and extranodal (85%, 17/20) neoplasms. c-Kit expression was not associated with the degree of the myeloid maturation. Two of 13 lymphoblastic lymphoma control cases and 1 of 28 of the large B-cell lymphomas were weakly immunoreactive with c-Kit. CONCLUSIONS: c-Kit reactivity can be demonstrated in a high percentage of GS cases; its presence may be useful not only in diagnosis, but also in the treatment of GS with new modalities.

Adolescent↗

Disseminated extramedullary myeloid tumor of the gallbladder without involvement of the bone marrow.

Extramedullary myeloid tumors (myeloid sarcomas) are rare neoplasms that are composed of myeloid precursors. They usually arise concurrently with a diagnosis of acute myeloid leukemia, chronic myeloid leukemia, or other myeloproliferative disorders. They may also indicate relapsing disease in a patient with a prior history of leukemia or myeloproliferative disorder. We present our findings of a 63-year-old female diagnosed with extramedullary myeloid tumor first presenting in the gallbladder. She subsequently developed respiratory failure; pre- and postmortem bone marrow studies were negative for leukemia by morphology, flow cytometry, and karyotypic analysis. However, the myeloid neoplasm was disseminated throughout most of her remaining organs. Immunohistochemical stains of the cells indicated a neoplasm of myelomonocytic derivation (CD4, CD43, CD45, CD68, myeloperoxidase, and lysozyme positive). To our knowledge, this is the first report of an extramedullary myeloid neoplasm of the gallbladder with disseminated disease without involvement of the bone marrow.

Antigens, CD↗

Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque.

We report, for the first time, a replication-defective retroviral vector-associated neoplasia in a nonhuman primate. Five years after transplantation with CD34+ cells transduced with a retroviral vector expressing enhanced green fluorescent protein (eGFP) and a drug-resistant variant of the dihydrofolate reductase gene (L22Y), a rhesus macaque developed a fatal myeloid sarcoma, a type of acute myeloid leukemia. Tumor cells contained 2 clonal vector insertions. One insertion was found in BCL2-A1, an antiapoptotic gene. This event suggests that currently available retroviral vectors may have long-term side effects, particularly in hematopoietic stem and progenitor cells.

Animals↗

Electrophoretic mobility profiles of mouse leukemias. II. Electrophoresis of thymic lymphoma, myeloid leukemia and reticulum sarcoma cells.

Electrophoretic mobility of cells from 21 primary mouse leukemias was investigated and compared with that of various normal mouse reference cells. Six thymic lymphomas, nine reticulum cell sarcomas, five myeloid leukemias and one stem-cell leukemia were examined. The mean AEM of cells from the group of primary thymic lymphomas (1.13 microns s-1 V-1 cm) was similar to that of reticulum cell sarcomas (1.15 microns s-1 V-1 cm) and significantly lower than that of the myeloid leukemias (1.20 microns s-1 V-1 cm). Since the examined cell suspensions were prepared from leukemic lymph nodes, the analysis was performed to investigate the possible admixture of normal LNC in the cell populations. Electrophoretograms of normal and leukemic lymph nodes were compared and the AEM of cells from leukemic lymph nodes was considered separately for two cell populations, one corresponding in size to normal LNC (6-9 microns in diameter) and the other to leukemic blast cells (10-16 microns in diameter). In the 6-9 microns cell subpopulations from leukemic lymph nodes, electrophoretically slow cells corresponding to B LNC were almost totally depleted (1%); also electrophoretically fast cells with the mean AEM of T LNC were fewer (45-57%) than in normal LNC populations. The leukemic cells 10-16 microns in diameter displayed mean AEM of 1.09 (thymic lymphomas), 1.12 (reticulum cell sarcomas) and 1.21 (myeloid leukemia) micron s-1 V-1 cm. The mean AEM of blast cells from thymic lymphomas and reticulum cell sarcomas was not significantly different; it was similar to that of blast cells prepared from normal mouse thymus (1.09 microns s-1 V-1 cm) on a density gradient. In contrast, the 10-16 microns cell populations from lymph nodes of mice with myeloid leukemias were significantly faster than blast cells from thymic lymphomas and reticulum cell sarcomas.

Animals↗

Extramedullary acute myeloid leukemia (granulocytic sarcoma) with arm paresis, maculopapular exanthema and organ involvement.

Granulocytic sarcoma (extramedullary myelosarcoma, chloroma) is a rare extramedullary myeloid tumor which can occur at any anatomical site as isolated finding or associated with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). In this case, we describe a 71-year-old man who presented with incomplete paresis of the left arm, periorbital swelling, a maculopapular exanthema and organ involvement including testis and stomach. The tumors responded to combination chemotherapy and the patient fully recovered. However, after five months the patient relapsed and died quickly. This case confirms the importance of including granulocytic sarcoma in the differential diagnoses of a variety of diseases. In AML, the presence of granulocytic sarcoma is associated with worse overall survival. When diagnosed, it should be treated with intensive chemotherapy as soon as possible.

Aged↗