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Acute erythroleukemia is an aggressive leukemia derived from a multipotential stem cell. Three subtypes have been described: (1) M6a with greater than or equal to 30% blasts of the nonerythrocytic component, (2) M6b with greater than or equal to 30% pronormoblasts of the erythrocytic elements, and (3) M6c with greater than or equal to 30% blasts and greater than or equal to 30% pronormoblasts by the aforementioned exclusion criteria. The poor prognosis associated with this disorder positively correlates with a high pronormoblast:myeloblast ratio; unfavorable cytogenetic aberrations; a high proliferative index; and the presence of P-glycoprotein expression (multidrug resistance phenotype). Chemotherapeutic regimens directed toward these specific parameters should be devised in order to improve the characteristically poor outcome of this patient population.

Acute erythroleukemia (FAB M6) is a rare heterogeneous disease with an increase in red cell precursors and myeloblasts. Three subsets have been described: M6A (myeloblast-rich erythroleukemia); M6B (proerythroblast-rich erythroleukemia); and M6C (myeloblast- and proerythroblast-rich mixed variant). This study was undertaken to define and compare the clinical courses and survival outcomes among M6A, M6B, and M6C variants of erythroleukemia. Sixty-nine cases of M6 leukemia were categorized as consisting of ≥50% erythroid of all nucleated cells and M6A with ≥30% myeloblasts/nonerythroid component; M6B with ≥30% proerythroblasts/erythroid component; and M6C with ≥30% myeloblasts and ≥30% proerythroblasts. The demographics, cell type distribution, and survival (mean ± sd) of these groups were compared. There were 32 M6A, 26 M6B, and 11 M6C patients. No significant difference was seen among the groups in age, sex, or treatment. Compared to M6A, both the M6B (P< 0.0001) and M6C (P< 0.0001) variants showed a statistically significant increase in the percentage of bone marrow erythroid cells, proerythroblasts, and the proerythroblasts/erythroid ratios. Comparing the groups for survival, M6B (3 ± 3.6 months) versus M6A (25 ± 28 months), P< 0.002, and M6C (10 ± 13 months) versus M6A, P< 0.01 had a poorer prognosis. Calculating the proerythroblasts as a component of total bone marrow erythroids provides a complimentary method for delineating the pure red cell erythroleukemia (M6B) and mixed variant (M6C), similar to that for the myeloid/erythroid (M6A) leukemia. Now that it is possible to delineate erythroleukemia subtypes, innovative treatments are indicated to target the malignant erythroid population, which is resistant to myeloid-based therapies. Am. J. Hematol. 65:5–13, 2000. © 2000 Wiley-Liss, Inc.

The diagnosis of granular acute lymphoblastic leukemia (ALL) can be problematic as the cytoplasmic granules found in many blast cells may mimic those seen in acute myelogenous leukemia (AML). This rare variant of B-cell ALL is more commonly diagnosed in children, but may occur in adults. We report a case of granular B-ALL in a 56-year-old female and review the literature.

Recent studies of acute erythroleukemias have reaffirmed DiGuglielmo's syndrome (M6a, myeloblast-predominant) and disease (M6b, pronormoblast-predominant). M6c (mixed myeloblast/pronormoblast) has also been described. However, MDS is still defined according to the percentage of myeloblasts (% myeloblasts) without including the pronormoblast count. A 20-year retrospective study was performed to identify cases demonstrating >or=50% erythrocytic component and

The mechanism by which the immune system of a tumor-bearing host acquires tolerance toward tumor antigens is still elusive. Antigen-presenting cells (APCs) are critical regulators of the decision between immune response and tolerance. APCs that express the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) have been found to inhibit T-cell responses both in vitro and in vivo. We hypothesized that malignant tumors exploit this mechanism by recruiting IDO-expressing APCs to the tumor-draining lymph nodes. To test this hypothesis, archival tissues and records of 26 cases of lymph node dissection for invasive cutaneous melanoma were obtained. IDO immunohistochemistry was performed on 14 cutaneous tumors and 328 regional lymph nodes. Abnormal accumulations of IDO-positive cells with a monocytoid or plasmacytoid morphology were identified in the perisinusoidal regions of draining lymph nodes in 45% of nodes studied. Recruitment of IDO-positive cells was seen in nodes with and without malignancy. We hypothesize that these IDO-positive APCs may contribute mechanistically to acquired tolerance to tumor antigens. Immunostaining of tumor-draining lymph nodes for abnormal accumulation of IDO-expressing cells might thus constitute an adverse prognostic factor and could contribute to the decision process and the appropriate care of patients with this deadly disease.

T patient was a 47-year-old man whose past medical history was significant for renal transplant, as well as refractory anemia with ringed sideroblasts (Figure 1) diagnosed 1 year previously. He re-presented to his hematologist/oncologist with fatigue and weight loss. The only medications he was taking at the time of presentation were cyclosporine and prednisone. Physical examination was noncontributory. A complete blood count revealed anemia, thrombocytopenia, and rare blasts. A bone marrow aspirate and biopsy were performed and revealed 51% erythrocytic precursors (Figure 2). Characteristic features included the presence of 41% pronormoblasts by FrenchAmerican-British (FAB) exclusion criteria, with marked dysplastic change and ‘‘block-and-blush’’ periodic acid– Schiff positivity (Figure 3) of the erythroid cell lineage. There were 22% myeloblasts by FAB exclusion criteria, with minimal dysplasia of the granulocytic cell line. A diagnosis of acute erythroleukemia, M6b (pure erythroleukemia, Di Guglielmo disease) was established. Cytogenetic analysis demonstrated a complex karyotype with abnormalities of both chromosomes 5 and 7. Review of the previous bone marrow slides confirmed the original diagnosis. The patient underwent 6 cycles of arabinosylcytosine (cytarabine)/daunorubicin therapy. Sequential intrachemotherapy and postchemotherapy bone marrow specimens revealed ablation of all hematopoietic elements, with the exception of the pronormoblasts. The patient died 21⁄2 months after initial diagnosis. A leukemia composed of purely erythrocytic precursors was first described by Di Guglielmo in 1926 and was designated Di Guglielmo disease. Until recently, this fulminant acute leukemia was alternately classified as a myeloproliferative disorder or a myelodysplastic syndrome. Nevertheless, a number of articles and books have described the complex cytogenetics and extremely poor outcome associated with this disease, which represents a distinct leukemic entity.1–4 The overall presentation and outcome of the patient described here are in keeping with previous descriptions of this condition.1,2 Investigators studying this leukemic process proposed that this disorder be renamed

We report a rare case of testicular histiocytoid hemangioma. Pathological features and differential diagnosis of this neoplasm are discussed. Testicular vascular tumors are rare, and include cavernous hemangioma,' capillary hemangioma? papillary endothelial hyperplasia3 and hemangioend~thelioma.~*~ The term histiocytoid hemangioma was proposed by Rosai et a1 to refer to certain vascular proliferations of skin, soft tissue, large blood vessels, bone and heart.6 The microscopic marker of these lesions is the proliferation of plump endothelial cells with bland nuclear features accompanied by a mixed inflammatory cell infiltrate. Histiocytoid hemangioma has rarely been described in the We report an additional case of histiocytoid hemangioma of the testis. CASE REPORT A 33-year-old white man consulted a urologist after palpating a mass in the right testis. The patient had no history of trauma or infection and no other symptoms. Medical and family histories were unremarkable. His wife had recently given birth to their second child. Physical examination was unremarkable except for a hard, approximately 2 cm. mass in the right testis with no significant testicular enlargement. Ultrasound revealed a 1.7 cm. mass in the upper half of the right testis. Findings were most consistent with a neoplastic process and radical inguinal orchiectomy was subsequently performed. Convalescence was uneventful. PATHOLOGICAL FINDINGS

Background Rapid detection of bloodstream infections (BSIs) can be lifesaving. We investigated the sample processing and assay parameters necessary for highly-sensitive detection of bloodstream bacteria, using Staphylococcus aureus as a model pathogen and an automated fluidic sample processing – polymerase chain reaction (PCR) platform as a model diagnostic system. Methodology/Principal Findings We compared a short 128 bp amplicon hemi-nested PCR and a relatively shorter 79 bp amplicon nested PCR targeting the S. aureus nuc and sodA genes, respectively. The sodA nested assay showed an enhanced limit of detection (LOD) of 5 genomic copies per reaction or 10 colony forming units (CFU) per ml blood over 50 copies per reaction or 50 CFU/ml for the nuc assay. To establish optimal extraction protocols, we investigated the relative abundance of the bacteria in different components of the blood (white blood cells (WBCs), plasma or whole blood), using the above assays. The blood samples were obtained from the patients who were culture positive for S. aureus. Whole blood resulted in maximum PCR positives with sodA assay (90% positive) as opposed to cell-associated bacteria (in WBCs) (71% samples positive) or free bacterial DNA in plasma (62.5% samples positive). Both the assays were further tested for direct detection of S. aureus in patient whole blood samples that were contemporaneous culture positive. S. aureus was detected in 40/45 of culture-positive patients (sensitivity 89%, 95% CI 0.75–0.96) and 0/59 negative controls with the sodA assay (specificity 100%, 95% CI 0.92–1). Conclusions We have demonstrated a highly sensitive two-hour assay for detection of sepsis causing bacteria like S. aureus directly in 1 ml of whole blood, without the need for blood culture.

The following abstracts are compiled from Check Sample exercises published in 2008. These peer-reviewed case studies assist laboratory professionals with continuing medical education and are developed in the areas of clinical chemistry, cytopathology, forensic pathology, hematology, microbiology, surgical pathology, and transfusion medicine. Abstracts for all exercises published in the program will appear annually in AJCP. # 1 Fetal Lung Maturity Testing Clinical Chemistry No. CC 08-1 (CC-367) {#article-title-2} Neonatal respiratory distress syndrome (RDS) is a disorder of pulmonary immaturity with a high mortality characterized by low levels of pulmonary surfactant. Gestational age determines risk based on concentration of pulmonary surfactant, ie, as gestation progresses the concentration of pulmonary surfactant increases. As a result, newborns delivered at fewer than 28 weeks have a more than 60% risk of RDS, whereas those delivered at more than 34 weeks have a less than 5% risk of RDS. In situations where gestational age alone is not sufficient to determine RDS risk and preterm delivery is medically needed, amniotic fluid analysis can be performed to determine pulmonary surfactant concentration. Four common methods are the lecithin-sphingomyelin ratio, phosphatidylglycerol measurement, surfactant-albumin ratio, and lamellar body count. All of these tests have excellent negative predictive values but poor positive predictive values, ie, they are great at confirming maturity but poor at confirming immaturity. # 2 Alkaline Phosphatase Isoenzyme Analysis: Guiding the Differential Diagnosis of Elevated Serum Total Alkaline Phosphatase Clinical Chemistry No. CC 08-2 (CC-368) {#article-title-3} The measurement of alkaline phosphatase (ALP) has long been used in clinical medicine, primarily to aid the diagnosis and monitoring of liver and bone diseases. Its diagnostic utility is limited by the enzyme’s wide tissue distribution and by a variety of potential nonpathologic causes. Isoenzyme analysis is one of several tools available to the clinician hoping to further characterize an elevated total ALP. It provides differentiation among liver, bone, intestinal, placental, and tumor-related forms as the cause of an elevation. The case presents a patient with persistent elevated ALP and atypical bands in the isoenzyme electrophoresis gel. An atypical ALP may be the result of a macroenzyme, which, if present, complicates interpretation of the test result and may cause additional, unnecessary testing or procedures. Recognizing and reporting a macroenzyme is an important service the clinical laboratorian can provide a clinician. # 3 Indirect Phlebotomy: Is It Good Practice? Clinical Chemistry No. CC 08-3 (CC-369) {#article-title-4} Indirect phlebotomy, the collection of blood samples through vascular infusion devices, is a common practice adopted to minimize needle-stick pain and discomfort in hospitalized patients. However, this practice can lead to alteration of the specimen and medical errors associated with misrepresentation of the blood test values. Among the possible problems, dilution or concentration of a particular analyte may occur, depending on the contents of the line’s infusate. Although some studies may indicate that blood collection from lines can be acceptable for isolated laboratory tests, there are insufficient data to demonstrate the reliability of line draws as routine practice. Use of lines for specimen collection should be reserved only for those patients with truly poor vascular access or those patients who require multiple phlebotomies in a short time period. Samples should be collected from lines only under a direct physician order, with careful attention to technique and established protocols that take many variables into account, including the analytes, contents of the line, type of line, discard blood volume, time interval between interruption of infusion and sampling, and catheter size. Even with careful attention to these details, clinicians must remain wary of the potential for medical errors related to misinterpretation of laboratory test results based on such samples.

Case: A 73 year old male with no significant past medical history presented with chronic fatigue. A routine CBC revealed an H/H of 6.8/19, MCV 103, WBC 4,100 and platelet count 92,000. Reticulocyte count was 0.6%. Serum iron, B12 and red cell folate studies were within normal limits. A bone marrow aspiration and biopsy were performed. Bone Marrow Findings: The bone marrow aspirate showed an M:E ratio of 1.8:1, with 33% erythrocytic elements. There was markedly left shifted erythropoiesis, with 57% of erythrocytic precursors being pronormoblasts. 1.2% blasts were present. Moderate erythrocytic dysplasia was present, with mild granulocytic and megakaryocytic changes. Vacuolated pronormoblasts were readily identified. No ringed sideroblasts were present. A diagnosis of MDS, NOS was rendered. No cytogenetics were obtained. Follow-up: The patient was transfused 4 units of packed red cells. Due to the patient’s rapidly deteriorating condition, comfort measures only were provided. The patient died 2.5 weeks after the bone marrow procedure. No autopsy was performed. The cause of death was listed as MDS. Discussion: This case is an extremely rare instance of left shifted erythropoiesis in the absence of the requisite number of erythrocytic elements for consideration of acute erythroleukemia (50%). By current definitions, this is an example of a fulminant MDS. However, this case does beg the question of whether or not pronormoblasts should be included in the assessment of malignant disorders of bone marrow.