Histopathologic analysis of bone marrow and bone metastasis in murine neuroblastoma

To elucidate the development of bone metastasis in human neuroblastoma, bone marrow and bone metastases were analysed histologically in a hematogeneous metastasis model of murine neuroblastoma. The bone marrow metastasis occurred initially in the bone marrow sinusoid where tumor cells adhered and extravasated to bone marrow parenchyma, resulting in the formation of nodular lesions in the medullary cavity. The nodular lesions eventually progressed to diffuse lesions segmentally occupying the medullary cavity. During the establishment of the diffuse lesions, tumor cells invaded cancellous bone and/or bone cortex, resulting in bone metastasis. Such nodular or diffuse bone marrow metastatic lesions occurred sporadically in a variety of bones. To improve the results of treatment for neuroblastoma, the characteristics of the bone marrow and the bone metastases demonstrated in this study should be considered in the diagnosis and treatment of this disease.     

Depressed mood and other variables related to bone marrow transplantation survival in acute leukemia

Routine psychiatric evaluations of 100 adult patients undergoing allogeneic bone marrow transplantation for acute leukemia were reviewed to examine the possible relationship of psychiatric and psychosocial factors to duration of survival following the procedure. Three variables were found to independently affect outcome: illness status (first remission vs. other status), presence of depressed mood, and the extent of perceived social support. Patients transplanted while in their first remission had significantly improved survival; patients with depressed mood, regardless of specific psychiatric diagnosis, had poorer outcomes; and patients with a high level of perceived social support had improved survival. The possible mechanisms by which these variables affect outcome are discussed.     

Chronic myeloproliferative disorders in bone marrow biopsies

This Diagnostic Seminar intends to announce that CMPDs can be classified from BMB histologically by a rather simple system, which can be applied by interested histopathologists successfully. The rationale of this classification is to stay within the groups of diseases which are outlined by clinical findings including the peripheral blood and bone marrow smears. The concept of traditional classification as given by the WHO and textbooks, however, has to be revised as follows (1) Primary diseases of CMPDs must be distinguished from advanced disorders. Primary diseases are CML, P. vera, Thrombocythemia, CMGM, and unclassifiable CMPD. (2) Idiopathic, primary myelosclerosis of the bone marrow is a reactive feature consecutive to neoplastic transformation of hematopoiesis, i.e. myeloproliferation. (3) Advanced disorders comprise (3.1.) excess of blasts and blast crisis, and (3.2.) early myelosclerosis, myelosclerosis and myelofibrosis, advanced myelofibrosis. Advanced disorders are designated by a composed term classifying them among the groups of primary disease and specifying the advanced stage by a suffix, so that the underlying disease remains coining the term, even in unclassifiable cases in which only CMPDs can be applied. (4) The CML group must be subtyped into CML of common type versus that with increase or predominance of megakaryocytes. By this system of classification, it seems possible to classify and type the spectrum of variations occurring among CMPDs to a satisfying result.     

Stromal changes in leukaemic and related bone marrow proliferations

The stromal structure of the bone marrow was studied in 96 cases of leukaemia and related disorders.     

Use of peripheral blood blasts vs bone marrow blasts for diagnosis of acute leukemia.

Acute leukemia can be diagnosed when blasts constitute 30% or more of the nucleated cells in a patient's peripheral blood (PB) sample. To determine whether in such cases bone marrow (BM) aspirates are still necessary, we compared the results of diagnostic studies performed on PB samples with blast counts of 30% or more with those performed on the same patients' BM samples. We found no differences in morphologic features, cytochemistry, or immunophenotype between the blasts in PB and BM samples in any of 30 cases studied. However, in 10 (23%) of 44 cases in which cytogenetic analysis was performed, PB but not BM samples were insufficient for analysis. The converse never occurred. Five of the 10 cases had acute lymphoblastic leukemia and 5 had acute myeloid leukemia (41% of the patients with acute lymphoblastic leukemia and 17% of the patients with acute myeloid leukemia). In cases with adequate metaphases, there was strong correlation between the cytogenetic results for PB and BM samples. Some PB samples with blast counts of 30% or more are adequate for diagnosis of acute leukemia, especially when therapy can be delayed until it is known that an adequate number of analyzable metaphases are recovered from the PB samples.     

Pitfalls in bone marrow pathology: avoiding errors in bone marrow trephine biopsy diagnosis

Avoiding errors in the histological interpretation of bone marrow trephine biopsy specimens requires an unprecedented degree of collaboration between histopathologists, haematologists, specimen requesters, specimen takers, laboratory technical staff and other scientific staff. A specimen of good quality, with full, relevant clinical information is the essential starting point. This must then be processed optimally and investigated appropriately, involving immunophenotyping and molecular testing when needed. A wide range of pathologies may involve bone marrow haemopoietic and stromal components, and a systematic approach to analysing each of the components in turn is required to avoid overlooking abnormalities; correlation with bone marrow cells aspirated in parallel is particularly important. Final interpretation should be a synthesis of the histological findings with information from such haematological and other investigations, interpreted with due regard to clinical context.     

Primary diagnosis of Whipple's disease in bone marrow

Whipple's disease (WD) is a chronic systemic inflammatory disease of infectious origin caused by Tropheryma whipplei (TW). Abdominal pain and recurrent diarrhea are usually the main symptoms leading to the suspicion of a primary bowel disease. Systemic manifestations can mimic hematologic disorders. A 49-year-old man presented with fever, weight loss, long-standing arthralgia, and diarrhea. A duodenal biopsy was unremarkable. Bone marrow histology provided no evidence of a malignant hematological disorder but revealed noncaseating granulomas. TW was detected in the bone marrow trephine by polymerase chain reaction. This is the first report to describe TW-associated granulomatous myelitis as the initially recognized organ manifestation of WD, proven at the molecular level. This observation is relevant for the differential diagnosis of patients with systemic symptoms and granulomatous diseases affecting the bone marrow, emphasizing that WD should be considered in cases of unexplained granulomatous myelitis, even when small bowel biopsy specimens are negative.     

Use of the bone marrow imprint in the diagnosis of leukemic reticuloendotheliosis ("hairy cell leukemia").

Leukemic reticuloendotheliosis is a distinct entity, often misdiagnosed as chronic lymphocytic leukemia or lymphoma. The neoplastic cells have a specific tartrate-resistant acid phosphatase isoenzyme by which the diagnosis may be secured. Most individuals are leukopenic, and when, as in our case, rare or no circulating cells with tartrate-resistant acid phosphatase activity are found in the peripheral blood, an alternate site must be sought. Bone marrow aspirations often result in "dry taps," however, and cryostat sections of the bone marrow biopsy necessary to demonstrate tartrate-resistant acid phosphatase activity are involved and impractical to obtain for most laboratories. This report illustrates and recommends the simple technic of imprinting the core biopsy, which yields a satisfactory sample with which the specific cytochemical activity can be demonstrated.     

Molecular diagnosis of leukemia and lymphoma]

Diagnosis of leukemia and lymphoma has been made by morphological, cytochemical, and immunophenotypical methods. Recently molecular biological approaches have been introduced to clarify the cellular lineage of the tumor cells and to demonstrate the monoclonality. Southern blot analysis using immunoglobulin (Ig) and T cell receptor (TcR) genes revealed the presence of monoclonal components in some cases of angioimmunoblastic lymphadenopathy (AILD), in which demonstration of monoclonality was difficult by conventional methods. In preB-ALL, many cases had rearranged IgH and TcR genes simultaneously. These "dual genotype" cases were found to be of accidental involvement of TcR gene in the process of making effective IgH gene rearrangements by the precise analysis of rearranged IgH gene structures. The rearranged TcR gene which was detected in initial lymphoblastic lymphoma cells, was observed in relapsed blasts after lineage conversion to myeloid leukemia, which indicates the same clonal origin. Diagnosis and detection of minimal residual disease by the polymerase chain reaction (PCR) are now recognized as sensitive methods. PCR using oligonucleotides common to each VH and JH gene detects the rearranged IgH gene sensitively. PCR using primers located on the translocation boundary, such as bcr and abl in CML, is very useful in the diagnosis and pursuit of the disease course. PCR study also can be applied to the detection of alteration of some particular genes such as tumor suppressor genes.     

Cost effectiveness of bone marrow transplantation in acute nonlymphocytic leukemia

To compare the cost effectiveness of bone marrow transplantation and conventional chemotherapy, we evaluated the resources used in the care of adult patients with acute nonlymphocytic leukemia who were enrolled in a prospective trial and received induction chemotherapy at a single university hospital. Nineteen patients were subsequently treated with chemotherapy and 17 with transplantation. Cost accounting began with induction chemotherapy and extended over a five-year period. Costs were estimated by means of a resource-based, multivariate prediction model. The transplantation and chemotherapy groups had virtually equivalent use of resources (hospital days, laboratory tests, blood products, and radiologic and operative procedures) over five years, except for a 10-fold increase in the use of the intensive care unit for the patients who underwent transplantation (P less than 0.001). The total costs over five years were estimated at $193,000 per patient for transplantation and $136,000 per patient for chemotherapy (P = 0.02). At five years, the costs per year of life saved ("life-year") were nearly equal ($62,500 per life-year for transplantation vs. $64,000 per life-year for chemotherapy) because of the better rate of disease-free survival in patients who underwent bone marrow transplantation. We conclude that the cost effectiveness of bone marrow transplantation to treat acute nonlymphocytic leukemia compares favorably with that of chemotherapy and could be further enhanced if intensive care resources were used more selectively.