Congenital pulmonary airway malformation.

BACKGROUND: Congenital cystic adenomatoid malformations (CCAMs) are considered rare developmental anomalies of the lower respiratory tract. These are hamartomatous abnormalities of the lung with adenomatoid proliferation of cysts resembling bronchioles and ususally occur sporadically occur and unilaterally with single lobe involvement. METHOD: A 6-year-old girl was admitted to our center because of prolonged fever and non-productive cough lasting3 months before admission. RESULTS: The only other complaint was night sweating. She did not have dyspnea and did not mention any respiratory symptoms. On examination, coarse crackle and decreased lung sounds in the left side were detected. White blood cell count was 9.100 /µL, hemoglobin was 11.2 g/dL, erythrocyte sedimentation rate was 50 and C-reactive protein was 1+. IgA and IgM for hydatid cyst were tested and both were raised (14 and 1.4, respectively). CONCLUSION: The patient underwent surgery, with the probable diagnosis of hydatid cyst but in operating room diagnosis was changed and it was adenomatoid cystic malformation. In follow-up, she was in good general condition without any post-surgical complaints (Fig. 3, Ref. 11).

Relation between serum ferritin and liver and heart MRI T2* in beta thalassaemia major patients.

There is a need for higly accurate non-invasive methods for assessing organ iron content in thalassaemia patients. This study evaluated the relation between serum ferritin level, liver enzyme levels and hepatitis C antibody and liver and heart iron deposition assessed by MRI T2*. Data were obtained from the medical records of 156 thalassemia major patients in Tehran. There was a moderate negative correlation between serum ferritin and liver MRI T2* relaxation time (r = -0.535) and a weak negative correlation between serum ferritin and heart MRI T2* relaxation time (r = -0.361). Hepatitis C infection and liver enzyme levels did not confound or modify the relation between ferritin and liver or heart MRI T2*. Liver and heart MRI T2* readings were poorly correlated (r = 0.281). Routine evaluation of liver and heart iron content using MRI T2* is suggested to better evaluate the haemosiderosis status in thalassemia patients.

Relation between serum ferritin and liver and heart MRI T2 in beta thalassaemia major patients

There is a need for higly accurate non-invasive methods for assessing organ iron content in thalassaemia patients. This study evaluated the relation between serum ferritin level, liver enzyme levels and hepatitis C antibody and liver and heart iron deposition assessed by MRI T2 Data were obtained from the medical records of 156 thalassemia major patients in Tehran. There was a moderate negative correlation between serum ferritin and liver MRI T2 relaxation time [r= -0.535] and a weak negative correlation between serum ferritin and heart MRI T2 relaxation time [r= -0.361]. Hepatitis C infection and liver enzyme levels did not confound or modify the relation between ferritin and liver or heart MRI T2. Liver and heart MRI T2* readings were poorly correlated [r= 0. 281]. Routine evaluation of liver and heart iron content using MRI T2 is suggested to better evaluate the haemosiderosis status in thalassemia patients

Lipid profile in minor thalassemic patients: a historical cohort study.

Minor beta thalassemia is a disorder without any special symptom which only causes mild anemia. In thalassemic patients accelerated erythropoiesis and enhanced cholesterol consumption have been suggested as the dominant mechanism for low level of lipoproteins. Hyperlipidemia is a risk factor for cardiovascular diseases and hence, low level of serum lipids can act as a protective factor. Because of the differences between social, economic, cultural conditions, dietary habits and genetics patterns among Iranians with other nations, this survey was conducted to verify these parameters among our thalassemia minor subjects. This study was carried out on 100 thalassemia carriers and 200 normal controls. Blood samples were collected and the biochemical evaluation was performed for measuring serum total cholesterol, LDL, HDL, TG, VLD. Descriptive statistical tables, independent t-test, Mann-Whitney and Chi-square were used for analyzing the data. The average values of serum total cholesterol, TG, LDL, HDL and VLDL in thalassemia minor subjects were 163.63 +/- 34.28, 159.74 +/- 157.54, 90.97 +/- 23.94, 34.97 +/- 8.07 and 73.44 +/- 72.43 mg/dl respectively. Moreover, the mean levels of total cholesterol, TG, LDL, HDL and VLDL in normal subjects were 192.77 +/- 37.27, 155.67 +/- 109.58, 123.42 +/- 33.57, 38.02 +/- 15.6 and 71.57 +/- 50.5 mg/dl respectively. The amount of serum total cholesterol and LDL in thalassemia carriers was significantly lower than normal subjects that shows the potential decline of cardiovascular and brain vessels diseases among thalassemia minor subjects compared to control group while other factors between the two groups did not show any significant difference.

Nodal monocytoid B-cell lymphoma (nodal marginal-zone B-cell lymphoma).

Benign monocytoid B cells are seen in lymph nodes in different types of lymphadenitis and they occur in the form of clusters within and around sinuses and in the interfollicular areas, but rarely completely surround benign follicles to produce a marginal-zone pattern. The cytologic hallmark of these cells is the presence of abundant pale to clear cytoplasm; these cells usually are of medium size, and they have a rather bland-appearing, irregular nuclei with inconspicuous nucleoli. Malignant monocytoid B-cell proliferations in a lymph node have been classified as monocytoid B-cell lymphomas (MBCL), which are now called nodal marginal-zone B-cell lymphoma (MZL) in the World Health Organization (WHO) classification. In the recently published clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma, 25 of 1,378 cases (1.8%) were classified as primary MZL, whereas four times as many cases (105 or 7.6%) were classified as low-grade mucosa-associated lymphoid tissue (MALT)-type lymphoma. Transformation to large-cell lymphoma at the time of diagnosis was seen in five of 25 (20%) cases of nodal MZL and in 32 of 105 (30%) cases of MALT-type lymphoma. Comparison of the clinical findings at presentation and the survival results indicate that nodal MZL is more aggressive clinically than low-grade MALT-type lymphoma. For example, patients with nodal MZL had a significantly higher incidence of advanced-stage disease, including peripheral and paraaortic lymphadenopathy, than those with MALT-type lymphoma. Moreover, patients with nodal MZL had lower 5-year overall survival and failure-free survival than patients with MALT type lymphoma. When analysis was restricted to those patients with zero to three adverse risk factors in the International Prognostic Index, patients with nodal MZL still had a significantly lower overall and failure-free survival at 5 years than patients with MALT-type lymphoma. We conclude that nodal MZL is a distinctive disease entity and is similar to other low-grade nodal lymphomas, such as the follicular or small lymphocytic lymphomas, but different than MALT-type lymphoma.

Polymyositis as a manifestation of chronic graft-versus-host disease.

A syndrome indistinguishable from idiopathic polymyositis occurred in 11 patients as a manifestation of chronic GVHD. All patients had elevation of creatine phosphokinase (CPK). Immunohistology demonstrated the effector cells in the muscle infiltrates as cytotoxic T cells, a finding similar to idiopathic polymyositis. Polymyositis is a rarely reported complication of chronic graft-versus-host disease (GVHD) with only 8 cases described in the literature. We encountered this syndrome in a small but significant percentage of our patients with chronic GVHD. Polymyositis associated with chronic GVHD does not affect the overall prognosis for the patient. Moreover, polymyositis can be the only manifestation of chronic GVHD. Awareness of this complication is important because it can be confused with other causes of muscle weakness after bone marrow transplantation. Finally, prompt initiation of corticosteroid therapy results in a rapid improvement of the associated symptoms.

Hematopoiesis research in aplastic anaemia induced by accidental protracted radiation.

Over the past few years there have been 2 radiation-related accidents involving a large number of individuals: the April 1986 accident in Chernobyl nuclear power station in the Ukraine and the September 1987 accident in Goiania, Brazil. These 2 radiation-related accidents highlight the major question raised by radiation-induced injury to the haematopoietic system, that is: does a given patient suffer from a reversible or an irreversible haematopoietic stem cell damage? Although about 350 radiation accidents involving several thousand people are known from the literature, in-depth haematopoiesis analyses of individuals after a radiation-related accident have rarely been reported. In this paper we present the case of a young man with radiation-induced aplasia and compare some biological data to those of 16 normal individuals and of 17 patients with acquired aplastic anaemia. Our patient was clinically and biologically (as assessed by long-term bone marrow culture) indistinguishable from patients with idiopathic acquired aplastic anaemia. Furthermore, therapeutic attitudes in this patient are discussed. In-depth study of such radiation-induced aplastic anaemia cases can shed some light in the understanding of this disease and may help in therapeutic decisions.

Immunopathology of malignant mesothelioma.

The pathologic diagnosis of malignant mesothelioma is difficult because the disease is rare and because it has many morphologic variants. This chapter emphasizes practical aspects of the pathologic features and of the differential diagnosis of malignant mesothelioma.

UCL3D3 and UCL4D12 reactivity in small B-cell neoplasms with special emphasis on monocytoid B-cell lymphoma.

Two recently described monoclonal antibodies, UCL3D3 and UCL4D12, have been reported to have some specificity for mantle zone B lymphocytes and marginal zone/follicular center B lymphocytes, respectively, in the spleen. Forty-nine B-cell neoplasms, including 20 cases of monocytoid B-cell lymphoma (MBCL), were studied by frozen section immunohistochemistry with these antibodies to evaluate their utility. Tonsil, lymph node, and reactive spleen also were studied with the antibodies. Although a wide overlap was observed among the different lymphomas, a majority of cases of MBCL and half of cases of hairy cell leukemia (HCL) reacted with both markers, suggesting both marginal/follicular and mantle cell antigen expression. None of four cases of mantle cell lymphoma reacted with the proposed mantle cell marker UCL3D3, whereas three of these cases immunoreacted with UCL4D12. This marker is known to react with a subpopulation of follicular center cells and possibly with marginal zone lymphocytes. A comparison of nodal and extranodal neoplasms failed to show a significant difference in the pattern of immunoreactivity with these antibodies. Tonsil and lymph node controls showed some mantle zone staining with both antibodies, and there was a slight overlap in mantle and marginal zone staining of the spleen controls. These findings suggest an immunologic similarity between some cases of HCL and MBCL. However, the findings also would suggest that these antibodies, particularly UCL4D12, have less specificity than has been previously assumed, and UCL4D12 may not have practical utility in the evaluation of low grade B-cell lymphomas.

Reed-Sternberg-like cells in low-grade lymphomas are transformed neoplastic cells of B-cell lineage.

Multinucleated giant cells resembling Reed-Sternberg (RS) cells are occasionally observed in high-grade lymphomas of the large-cell or immunoblastic type, but much less commonly in low-grade lymphomas. This study was conducted to determine whether RS-like cells found in seven B-cell low-grade lymphomas were immunologically similar to the neoplastic cells in the lymphoma or to the true RS cells seen in Hodgkin's disease, and whether they were therefore indicative of a composite lymphoma. Immunohistochemical studies were performed on paraffin sections of the seven low-grade (one small lymphocytic, one mantle zone, and five follicular) lymphomas with a panel of antibodies reactive with leukocyte common antigen (LCA), B-cell, T-cell, and Hodgkin's disease associated antigens. The RS-like cells were reactive with LCA (four of six), L26 (seven of seven), LN1 (five of six), LN2 (two of six), and MB2 (three of six). No positive staining was seen with either Leu-M1 or Ber-H2. The RS-like cells in the mantle zone lymphoma expressed L26, Leu-22, and kappa cytoplasmic light chains. This immunophenotype is similar to that of the neoplastic small lymphocytic cells. One of the low-grade follicular lymphomas progressed to an immunoblastic lymphoma with many RS-like cells. Paraffin immunohistochemistry on both lesions revealed a similar B-cell phenotype for the RS-like cells. Immunogenetic studies revealed B-cell and bcl-2 gene rearrangements in the immunoblastic lymphoma. These results indicate that RS-like cells in low-grade lymphomas are transformed neoplastic cells of B-cell lineage. With careful morphologic examination augmented by immunohistochemical studies, these lesions can be differentiated from Hodgkin's disease and from composite lymphomas of the combined Hodgkin's and non-Hodgkin's type.

Monocytoid B-cell lymphoma.

Monocytoid B-cell lymphoma is a distinct clinicopathologic entity occurring primarily in the lymph nodes of elderly patients. Its unique features compared with other low-grade lymphomas are also its characteristic morphologic features. These are its rare leukemic conversion and infrequent bone marrow involvement, and its relatively common association with autoimmune disease. Although MBCL is believed to be a low-grade, indolent type of lymphoma, its progression to high-grade lymphoma warrants close follow-up of patients.

Immunohistologic studies of bone marrow biopsies on frozen sections: an analysis of 42 cases.

An immunohistologic study of bone marrow biopsy frozen sections from 42 cases involved by a variety of reactive and neoplastic disorders is presented. Thirteen cases also were studied using other methods, including cytochemistry, surface marker analysis of cell suspensions, and/or DNA hybridization. Thirty-four of 42 cases (81%) were adequately phenotyped on frozen tissue using a panel of antibodies for hematolymphoid-associated antigens. The immunostains from the remaining eight cases were unsatisfactory, primarily as a result of heavy background staining. Eighteen cases were lymphoproliferative disorders of B-cell phenotype and 12 of these showed surface monotypic immunoglobulin expression by the frozen section technique. Six cases showed B- or pre-B-cell antigens but no surface immunoglobulins. Of the remaining 16 patients, two cases showed myeloid markers and three showed T-cell phenotype. Nine cases showed a mixture of polyclonal B- and T-cell populations. Keratin was demonstrated in a single case of metastatic carcinoma included in the study. These results indicate that the majority of hematopoietic processes can be successfully phenotyped on bone core frozen sections and demonstrate the usefulness of immunohistologic study of the frozen bone marrow biopsy specimens, especially when the specimens for other modalities are not available or are inadequate. The keys to achieving the best results from the frozen bone marrow immunohistochemistry were the gentle handling of the specimens and the preparation of high-quality, cryostat-cut frozen sections.

DNA ploidy analysis of pleural mesotheliomas: its usefulness for their distinction from lung adenocarcinomas.

The distinction of malignant mesotheliomas from adenocarcinomas with pleural involvement is often difficult, even with electron microscopic and state-of-the-art histochemical and immunologic studies. We evaluated the DNA ploidy and cell cycle of 45 clinically, morphologically, and immunohistochemically well-characterized malignant mesotheliomas to establish their ploidy profile and compared it with that of 41 pulmonary adenocarcinomas. All the cases were mucin negative and had been immunophenotyped with the following monoclonal antibodies: anti-keratin, anti-CEA, anti-Vimentin, anti-HMFG2, Leu M1 (CD15) and B72.3. Single cell suspensions from the paraffin blocks were prepared following Hedley's technique and were analyzed with a Coulter EPICS V flow cytometer. The resulting histograms were interpreted with the Multicycle software program. Five cases were excluded due to their high coefficients of variation. DNA aneuploidy was defined by the presence of more than one G0/G1 peak on the histograms obtained exclusively from the tumor sample. With this criterion, there is a possibility of missing aneuploid cases with a single aneuploid cycling population; however, fixatives and time of fixation produce such a remarkable variation in the fluorochrome uptake that any control, other than normal tissue present in the sample, was rendered unreliable. Five (14%) cases were DNA aneuploid with DNA indexes ranging from 1.2 to 1.9 (mean = 1.5). Three cases had increased S + G2/M values. Of the aneuploid cases, four were epithelial and one sarcomatous. In comparison, aneuploidy was found in 31 (75%) of the lung adenocarcinomas studied (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Monocytoid B-cell lymphomas: an assessment of diagnostic criteria and a perspective on histogenesis.

To determine which morphologic criteria are most useful in distinguishing reactive from malignant monocytoid B cells (MBCs), we compared 16 monoclonal cases (11 nodal, five extranodal) of monocytoid B-cell lymphoma (MBCL) with 12 cases of various reactive diseases in which MBCs were polyclonal. The results of our study showed that in MBCL the MBC component was the predominant architectural finding and that there was confluence of MBCs in all but one case. In contrast, the MBC component did not predominate in the reactive group (P less than .000001) and focal confluence was seen in only one case. A cytologic comparison showed that in MBCL areas there were more large transformed (prominent nucleolated) MBCs (P = .003), a higher mitotic rate (P = .03), and more nuclear irregularities (P = .007) than were present in the reactive group. In addition, evolution to an aggressive histologic type was found in four cases of MBCL. Our results also revealed concomitant multiple, monoclonal, morphologically distinct populations in other compartments (follicular center cells in seven, mantle cells in five, small lymphocytes in five, and plasma cells in 11). These unique findings can be reconciled by postulating (1) that the simultaneous presence of these diverse cytologic types represents morphologic expressions of a B cell whose population is in different phases of its cell cycle and/or its evolution or (2) that the histogenesis of MBCL is possibly from a nodal pluripotent B-stem cell that can differentiate directly into these various cytologic types.

Immunoarchitecture of normal human bone marrow: a study of frozen and fixed tissue sections.

To provide baseline information on the immunoarchitecture of normal bone marrow, we studied cryostat-cut, frozen, and paraffin-embedded, fixed tissue sections prepared from 21 core biopsies of normal bone marrow obtained during bone marrow harvests for transplantation. A large panel of antibodies was applied that included, for frozen tissue, Leu-6 (CD1), T11 (CD2), Leu-3a (CD4), Leu-1 (CD5), Leu-2a (CD8), J5 (CD10), My7 (CD13), Leu-11 (CD16), B4 (CD19), B1 (CD20), B2 (CD21), Tac (CD25), My9 (CD33), T200 (CD45), NKH-1 (CD56), kappa and lambda chains, beta F1, Ki-67, HLA-DR, TQ1, and keratin, and for fixed tissue, leukocyte common antigen (CD45), L26 (CD20), LN1 (CDw75), LN2 (CD74), LN3, LN4, LN5, MB1 (CD45R), MB2, MT1 (CD43), MT2 (CD45R), UCHL1 (CD45R0), BM1, Ki-1 (CD30), Leu-M1 (CD15), lysozyme, KP1 (CD68), actin, S100, neuron-specific enolase, vimentin, and keratin. On fresh-frozen sections CD19 and CD2 were the most reliable and sensitive markers for B and T cells, staining 5% and 9% of marrow cells, respectively. Immunoglobulins generally showed heavy background staining, which frequently precluded an accurate assessment. The CD4 to CD8 ratio in the bone marrow was reversed from that of peripheral blood. On fixed tissues, leukocyte common antigen was found in 14% of the marrow cells, corresponding roughly to the lymphocyte population. L26, a pan-B-cell marker, stained 3% of the marrow cells. Among the other B-cell markers, LN1 and MB2 stained a large number of cells (40% to 70%), indicating reactivity with cells of the myeloid or erythroid series in addition to lymphocytes. Among the T-cell markers, UCHL1 and MT1 stained 66% and 50% of the cells, respectively, which could be explained by their cross-reactivity with myeloid cells. Nonspecific myelomonocytic markers (Leu-M1, KP1, and lysozyme) also showed reactivity in a high percentage of cells. No particular architectural distribution patterns of B or T lymphocytes were noted in either frozen or fixed bone marrow specimens. The results of this study provide normal baseline data for the immunohistologic application of hematopoietic and lymphoid markers on frozen or fixed bone marrow biopsy specimens.

Monocytoid B-cell lymphoma. The biologic and clinical implications of peripheral blood involvement.

Monocytoid B-cell lymphoma (MBCL) is a newly recognized malignant lymphoma that shares clinical and pathologic features with other low-grade B-cell neoplasms, especially small lymphocytic lymphoma and hairy cell leukemia. However, although circulating malignant cells and bone marrow involvement are relatively common in small lymphocytic lymphoma and are characteristic features of hairy cell leukemia, MBCL in the peripheral blood and bone marrow rarely have been described. From 124 patients entered in the MBCL registry, three cases with peripheral blood involvement are described and the clinical and pathologic features in these patients are compared with those of other low-grade B-cell neoplasms. Monocytoid B-cell lymphoma was confirmed by lymph node biopsy in each case. Two patients had lymphocytosis at the time of presentation; the remaining patient presented with pancytopenia. For each patient, phenotypic studies of lymph node and peripheral blood revealed identical monoclonal surface immunoglobulin expression. The morphologic appearance of the circulating MBCL cells was different in each case, varying from a relatively homogeneous population of small lymphocytes to a heterogeneous collection of large and small lymphoid cells. The two patients with lymphocytosis also had extensive replacement of the bone marrow by MBCL; the third patient had diffuse infiltration by MBCL in a normocellular marrow. All three patients had advanced-stage (Stages III or IV) disease, and all required systemic chemotherapy for disease control. The two patients with lymphocytosis had relentless, progressive infirmity despite relatively aggressive treatment regimens. These patients ultimately died of lymphoma 13 and 18 months after initial diagnosis. The third patient is alive and well with stable disease 30 months after coming to the authors' institution. The clinical and pathologic features of the patients reported here reaffirms the placement of MBCL in the spectrum of low-grade B-cell neoplasms. However, unlike small lymphocytic lymphoma and hairy cell leukemia, MBCL only rarely undergoes leukemic conversion. Furthermore, it appears that peripheralization of MBCL occurs primarily in patients with advanced-stage disease and may be indicative of a relentless course and progressive disease despite aggressive chemotherapeutic intervention.

A novel biotinylated probe specific for hyaluronate. Its diagnostic value in diffuse malignant mesothelioma.

Diffuse malignant mesotheliomas are known to secrete a large amount of hyaluronate, whereas adenocarcinomas produce predominantly neutral mucins. In the present study, we assessed the diagnostic usefulness of a new, highly specific and sensitive hyaluronate binding probe to discriminate between mesotheliomas and adenocarcinomas. We studied 33 mesotheliomas and 37 adenocarcinomas in order to establish specific diagnostic criteria for using the hyaluronate binding probe. Of the adenocarcinomas, only three showed significant positive staining for hyaluronate (8%). By contrast, all the mesotheliomas exhibited positive staining for hyaluronate. Furthermore, the staining reaction was classed as moderate or greater in 26 mesotheliomas (79%), thus suggesting the utility of this probe in the differential diagnosis of malignant mesothelioma versus adenocarcinoma. We conclude that strong cytoplasmic or membranous staining for hyaluronate is highly predictive of malignant mesothelioma. The hyaluronate binding probe should therefore be considered an important adjunct to be used in combination with electron microscopy and immunohistochemistry in the histologic diagnosis of diffuse malignant mesothelioma.