Histiocytic Disorder Mimicking a Brain Tumor: A Report of 2 Rare Cases.

BACKGROUND Histiocytic disorders, a group of disorders with heterogeneous pathogenesis, morphology, and clinical presentation, include Rosai-Dorfman disease, Langerhans cell histiocytosis, and Erdheim-Chester disease. They can mimic primary or metastatic tumors, both clinically and radiologically, when involving the brain. Therefore, it is crucial to present and discuss cases of histiocytic disorder involving the central nervous system (CNS) to provide new information on disease presentation and diagnosis more. In this paper, we present 2 cases of histiocytic lesions involving the brain and mimicking primary brain tumors. CASE REPORT Case 1: A 65-year-old man presented with increasing memory loss, confusion, and depression. CT scans showed an isolated 2.9×2.0×0.6 cm intracranial hypothalamic lesion. Case 2: A 61-year-old woman presented with dizziness and confusion for 3 weeks and headaches for 1 day. MRI showed a single 5.0×4.0×3.3 cm extra-axial, dural-based, avidly enhancing, well-defined lesion along the left parietal convexity causing mass effect upon the underlying brain parenchyma, left atrial effacement, and minimal vasogenic edema. CONCLUSIONS Histiocytic disorders are relatively rare in the CNS compared with other locations and mimic more common entities in the brain, such as glioma or metastatic tumors. Despite its rarity, one should remain aware of the condition and consider it in the differential diagnosis. This article provides a brief review and adds pivotal data to the literature.

Karyopyknotic cytoplasmic inclusions in neutrophils.

Karyopyknotic cytoplasmic inclusions in neutrophils (KPCI) have been previously called "Howell-Jolly" like inclusions and identified in immunosuppressed patients with human immunodeficiency virus (HIV) and in patients with various malignancies who have undergone chemotherapy. Attempts to characterize these inclusions have included the Grocott's methenamine silver (GMS), periodic acid Schiff (PAS), Gram, and Feulgen stains. Previous authors have concluded that these inclusions are of deoxyribonucleic acid (DNA) origin. We present a case describing an additional method to confirm this observation and to document previously undescribed curvilinear forms.

Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors.

Acquired imatinib resistance in chronic myelogenous leukemia (CML) can be the consequence of mutations in the kinase domain of BCR-ABL or increased protein levels. However, as in other malignancies, acquired resistance to cytostatic drugs is a common reason for treatment failure or disease progression. As a model for drug resistance, we developed a CML cell line resistant to cyclophosphamide (CP). Using oligonucleotide arrays, we examined changes in global gene expression. Selected genes were also examined by real-time PCR and flow cytometry. Neither the parent nor the resistant lines had mutations in their ATP binding domain. Filtering genes with a low-base line expression, a total of 239 genes showed significant changes (162 up- and 77 down-regulated) in the resistant clone. Most of the up-regulated genes were associated with metabolism, signal transduction, or encoded enzymes. The gene for aldehyde dehydrogenase 1 was over-expressed more than 2000-fold in the resistant clone. BCR-ABL was expressed in both cell lines to a comparable extent. When exposed to the tyrosine kinase inhibitors imatinib and nilotinib, both lines were sensitive. In conclusion, we found multiple genetic changes in a CML cell line resistant to CP related to metabolism, signal transduction or apoptosis. Despite these changes, the resistant cells retained sensitivity to tyrosine kinase inhibitors.

γδ T-Cell Acute Lymphoblastic Leukemia/Lymphoma: Discussion of Two Pediatric Cases and Its Distinction from Other Mature γδ T-Cell Malignancies.

Gamma delta (γδ) T-cell antigen receptor (TCR) expression and its related T-cell differentiation are not commonly reported in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Here we report two pediatric T-ALL cases and present their clinical features, histology, immunophenotypes, cytogenetics, and molecular diagnostic findings. The first patient is a two-year-old girl with leukocytosis, circulating lymphoblasts, and a cryptic insertion of a short-arm segment at 10p12 into the long-arm segment of 11q23 resulting in an MLL and AF10 fusion transcript, which may be the first reported in γδ T-ALL. She responded to the chemotherapy protocol poorly and had persistent diseases. Following an allogeneic bone marrow transplant, she went into remission. The second patient is an eleven-year-old boy with a normal white cell count, circulating blasts, and a normal karyotype, but without any immature cellular markers by flow cytometric analysis. He responded to the chemotherapy well and achieved a complete remission. These cases demonstrate the diverse phenotypic, cytogenetic, and molecular aspects of γδ T-ALL. Early T-precursor- (ETP-) ALL and their differential diagnosis from other mature γδ T-cell leukemia/lymphomas are also discussed.

Increased transferrin receptor expression following 11q23 deletion as a mechanism of malignant progression in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a common adult leukemia characterized by the accumulation of mature neoplastic B-lymphocytes. Typically, CLL follows an indolent course, with most patients surviving for many years. However, 10-20% of CLL patients carry 11q23 chromosomal deletions and often exhibit a more severe disease course, with earlier onset of symptoms, shortened lymphocyte doubling time, poor response to therapy, and shortened survival. The molecular basis for 11q23 deletions resulting in a poor prognosis is currently poorly understood. The tumor suppressor gene, ataxia-telangiectasia mutated (ATM, 11q22.3-23.1), is considered a likely candidate gene whose loss could result in the poor prognosis associated with 11q23 deletion and is mutated in a significant percentage of CLL cases. Recently, recombinant ATM expression in ATM-deficient cells was found to decrease transferrin receptor (TfR) expression, suggesting that deletion of the chromosomal region carrying ATM results in increased TfR expression. TfR imports iron into cells, an event necessary for DNA synthesis and cell growth. Additionally, rapidly growing malignant cells, including lymphomas and CLL, often express high TfR levels. Based on this, we propose that one molecular mechanism by which 11q23 deletions confer a poor prognosis in CLL is via increased TfR expression secondary to ATM loss, resulting in the increased cellular iron import, and hence increased capacity for malignant growth. Our hypothesis may also partially explain why gallium, an atomically iron-like toxic metal that binds to transferrin and the TfR is incorporated into cells and was previously demonstrated to have anti-tumor activity in patients with lymphomas refractory to other chemotherapeutic treatments.

Fever, chills, and weakness in a 61-year-old man.

A 61-year-old man presented to the emergency department of a community hospital with a 2-week history of fever, chills, and sudden extreme weakness of his right arm and lower extremities. He also had a cough, shortness of breath, nausea, abdominal pain, diarrhea, and myalgia. Though initially alert and cooperative, he quickly became unresponsive. In addition, he had hyponatremia, renal insufficiency, and compromised cardiopulmonary function. He was admitted to the intensive care unit for suspected bacterial infection and was started on broad-spectrum antibiotics. Chest radiograph revealed miliary infiltrates consistent with infectious emboli or metastatic carcinoma. Despite intensive resuscitation, the patient died 36 hours after admission. At autopsy multiple nodular lesions were observed on gross examination of the lungs, perihilar and paratracheal lymph nodes, and liver. Microscopic sections of the lung (Figure 1) and brain (Figures 2 and 3) are shown.

Spurious automated platelet count. Enumeration of yeast forms as platelets by the cell-DYN 4000.

We recently encountered a patient with thrombocytopenia secondary to multiple drug therapy, disseminated prostatic adenocarcinoma, and sepsis who had a sudden decrease in his platelet count as enumerated by the Cell-DYN 4000 hematology analyzer (Abbott Diagnostics, Santa Clara, CA). A manual platelet count performed thereafter was even lower. The etiology of the spurious platelet count was clarified when numerous yeast forms were observed on routine microscopy of the peripheral blood smear. Subsequently, these organisms were identified as Candida glabrata from a positive blood culture (BACTEC 9240, Becton Dickinson, Cockeysville, MD). To our knowledge, this is the first report of spurious enumeration of yeast forms as platelets in an automated hematology system. The principle underlying platelet enumeration by the Cell-DYN 4000 system and other hematology analyzers and the value of microscopy on peripheral smears with unexpected CBC count results are discussed.

Pathology case of the month. Abdominal pain and weight loss in a young adult. Anaplastic large cell lymphoma.

A 34-year-old black man presented with a three-month history of abdominal pain, anorexia, and weight loss. Physical examination and radiologic studies revealed diffuse lymphadenopathy. Ascites and bilateral pleural effusions were also evident. The patient's condition deteriorated after admission, and he died prior to initiation of therapy. Histologic sections and special studies performed on a cervical lymph node biopsy performed shortly before the patient's death are shown in Figures 1-4. A bone marrow aspirate and biopsy were also performed and revealed no evidence of disease.

Pathology case of the month. 39-year-old woman with abdominal pain and weight loss. Takayasu's arteritis (TA).

A 39-year-old white woman presented with a history of aortoiliac occlusive disease diagnosed in 1992 attributed to oral contraceptive use. Shortly thereafter, aortoiliac replacement was performed. Mild hyperlipidemia was diagnosed in 2001. At the current clinic visit, she presented to her primary care physician with a 3-month history of postprandial midepigastric abdominal pain relieved by vomiting and a 30-pound weight loss. Her evaluation included an esophagogastroduodenoscopy, a colonoscopy, and an abdominal ultrasound, all of which were within normal limits. Because of her medical history, the patient underwent an arteriogram, which revealed brachiocephalic stenosis (Figure 1), occlusion of the left subclavian artery (Figures 2a and 2b), and narrowing of the superior and inferior mesenteric arteries (not shown). Since she had discontinued her oral contraceptives in 1992 and her hyperlipidemia was mild, the rheumatology service was consulted to evaluate this patient. On physical examination, she had decreased left brachial and radial pulses and a right carotid bruit. Laboratory evaluation revealed a normal complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, and C - reactive protein. Subsequent testing included a prothrombin time, activated partial thromboplastin time, protein S, protein C, reptilase time, antithrombin III, anticardiolipin antibody, antiphospholipid antibody, lupus anticoagulant, homocysteine, RPR, and a lipid profile. All test results were within normal limits. Due to the severity of her abdominal pain, the patient underwent superior mesenteric artery (SMA) bypass surgery. Sections from the aorta resected in 1992 are shown in Figures 3 and 4.

CD23 negative chronic lymphocytic leukemia of the tonsil: report of a case.

We present the case of atypical chronic lymphocytic leukemia presenting as a tonsillar mass in an elderly man. Histological examination of the tumor revealed diffuse submucosal infiltration by small lymphocytes. On flow cytometry, a monoclonal B lymphocytic population expressing CD5, CD19, lambda light chain, but not expressing CD10, CD23, or FMC7 activities, was observed. A diagnostic conundrum occurred with the demonstration on molecular cytogenetic analysis of the chromosomal translocation abnormality, t(11;14)(q13;q32). The diagnosis of CD23 negative chronic lymphocytic leukemia was made after further molecular studies failed to detect the bcl-1 gene rearrangement.