Minimal Bone Marrow Involvement Research Articles

Utility of leukocyte-associated immunoglobulin-like receptor-1 (CD305) in flow cytometric detection of minimal bone marrow involvement by B-cell non-Hodgkin lymphoma.

Multicolor flow cytometry (MFC) is crucial in detecting occult or minimal bone marrow (BM) involvement by non-Hodgkin lymphomas (NHL), which may not be detected using trephine biopsy or imaging studies. Detection of low-level BM involvement can be challenging without definite immunophenotypic aberrancies. We studied the utility of CD305 in MFC detection of minimal BM involvement by B-NHL, especially in the absence of aberrancies by commonly used markers. The study included 1084 consecutive BM samples submitted for the staging of B-NHLs (excluding CLL) over two years. Samples were studied for morphological, immunophenotypic, and histopathological assessment. MFC studies were performed using 10-13 color MFC, including CD305-antibody (clone, DX26). Minimal BM involvement was defined with a cutoff of ≤10% lymphoma cells in viable cells on MFC assessment. Of 1084, 148 samples revealed overt morphological involvement by B-NHL and were excluded from analysis. BM samples of 172/936 patients were morphologically negative but revealed involvement using MFC independently. Corresponding trephine biopsy involvement was detected in only 79/172 (45.9%) patients. On MFC, 23/172 samples showed BM involvement with >10% lymphoma cells, and 149/172 (86.6%) samples revealed minimal involvement. In 54/149 (36.24%) samples, lymphoma cells were detected only with aberrant loss of CD305 expression. In 78 of the remaining 95 samples (82.1%), it provided an immunophenotypic aberrancy addition to other markers and supported the results. CD305 is a highly useful marker in the flow cytometric assessment of minimal BM involvement by B-NHL. MFC is a superior modality to trephine biopsy in detecting low-level BM involvement.

Assessment of Bone Marrow Involvement in Extranodal NK/T-Cell Lymphoma: Positron Emission Tomography versus Bone Marrow Biopsy, and the Significance of Minimal Involvement by EBV+ Cells (KROG 18-09).

This study aims to investigate the diagnostic significance of positron emission tomography/computed tomography (PET/CT) in assessing bone marrow (BM) involvement through a comparison of PET/CT findings with BM biopsy in extranodal natural killer/T-cell lymphoma. The medical records of 193 patients were retrospectively reviewed. Patients were categorized as having early-stage (PET-ES) or advanced-stage (PET-AS) disease based on PET/CT results. The BM involvement was classified into three groups according to BM biopsy: gross BM involvement, minimal BM involvement (defined as the presence of a limited number of Epstein-Barr virus-positive cells in BM), and no involvement. Calculations of the accuracy of PET/CT in detecting BM involvement and analysis of the clinical outcomes (progression-free survival [PFS] and overall survival [OS]) according to the BM biopsy status were performed. PET/CT exhibited a sensitivity of 64.7% and a specificity of 96.0% in detecting gross BM involvement. For detecting any (both gross and minimal) BM involvement, the sensitivity was 30.4%, while the specificity was 99.0%. Only one patient (0.7%) demonstrated gross BM involvement among the PET-ES group. Survival outcomes of the PET-ES group with minimal BM involvement (3-year PFS, 55.6%; OS, 77.0%) were closer to those of the PET-ES group with no BM involvement (3-year PFS, 62.2%; OS, 80.6%) than to those of the PET-AS group (3-year PFS, 20.1%; OS, 29.9%). PET/CT exhibits high specificity, but moderate and low sensitivity in detecting gross and minimal BM involvement, respectively. The clinical significance of minimal BM involvement for patients in the PET-ES group may be limited.

Intraocular solitary extramedullary plasmacytoma presenting as unilateral anterior and intermediate uveitis preceded by refractory glaucoma

BackgroundSolitary extramedullary plasmacytoma (SEP) is a localised proliferation of monoclonal plasma cells involving soft tissue with no or minimal bone marrow involvement and no other systemic evidence of multiple myeloma. Intraocular involvement is exceedingly rare.Case presentationWe report a 78-year-old man who was referred with glaucoma in the right eye. He subsequently developed anterior chamber (AC) inflammation and refractory glaucoma then dense vitritis. A vitrectomy was performed with the biopsy revealing numerous plasma cells with atypical findings. In conjunction with the flow cytometry results, and a systemic work up excluding multiple myeloma, a diagnosis of SEP was made. The patient was treated with ocular external beam radiotherapy with resolution of the intraocular inflammation and control of the intraocular pressure. He remains well with no local recurrence and no development of multiple myeloma over a follow up period of 2.5 years.ConclusionsThis is the first case report of SEP presenting as intraocular inflammation without a uveal tract mass.

Prognostically significant bone marrow cellular content changes in diffuse large B-cell lymphoma

Introduction. Increasing of blast cell percentage in bone marrow of diffuse large B-cell lymphoma patients is a sign of unfavourable prognosis. We estimated the frequency of this phenomenon and made attempts to idenify minimal bone marrow involvement in DLBCL by flow cytometry.Materials and methods. Study has been done in 60 DLBCL patients. Diagnosis in all cases was done according to WHO (2008) criteria. Bone marrow study was done on smears (myelogram). Immunophenotypic study was done with a large panel of B-lineage monoclonal antibodies as well as kappa and lambda light chains to membrane immunoglobulins.Results. Increase in blast cell content in bone marrow was noted in 73.3 % of DLBCL patients. That group of patients had lower surviv al. We used the following methods for identification of monoclonal B-lymphocytes: monoclonality according to membrane light immu noglobuline chains within mature B-lymphocytes and aberrancy of immunophenotype. Levels of different B-cell antigen expression – CD20, CD21, CD22, CD24. It was identified B-lymphocytes with aberrant expression of СD21.Conclusion. The most informative methods of identification of minimal bone marrow involvement in DLBCL are estimation of clonality according to light chain expression of mature B-lymphocytes (CD45++CD20+CD5–), as well as assessement of aberrancy of CD21 expression of mature B-lymphocytes.

Epidermotropic CXCR3 positive marginal zone lymphoma: a distinctive clinical histopathological entity potentially originating in the skin; it does not always indicate splenic marginal zone lymphoma

Epidermotropic B cell lymphoma represents a rare form of marginal zone lymphoma presenting as a disseminated skin rash resembling pityriasis rosea. To date there are 8 reported cases. In addition to the widespread nature of the skin rash, there is a proclivity for spleen and bone marrow involvement raising consideration regarding its categorization as a systemic lymphoma. We present an 89-year-old man with epidermotropic B cell lymphoma, who presented with a pityriasis rosea-like skin rash. An initial diagnosis of diffuse large cell B cell lymphoma was made based on the extent of dermal-based large cell infiltration. However, after recognizing the epidermotropic component and the distinctive clinical presentation, a diagnosis of epidermotropic B cell lymphoma was rendered. There was minimal bone marrow involvement based only on flow cytometric analysis, but there was no apparent bone marrow or splenic involvement on routine light microscopic assessment. Remission was = achieved with single agent rituximab chemotherapy and the patient remained symptom free. The neoplastic CD20 positive epidermotropic B lymphocytes expressed CXCR3. Similar to the prior reported cases by the authors, the neoplastic cells expressed CXCR3, a chemokine whose organ and tissue specific ligands could contribute to its relatively indolent clinicalcourse.

How We Manage Patients with Plasmacytomas.

To discuss the diagnostic approach, treatment options, and future considerations in the management of plasmacytomas, either solitary or in the context of overt multiple myeloma (MM). Advanced imaging techniques such as whole-body magnetic resonance imaging and positron emission tomography/computerized tomography are essential for the diagnostic workup of solitary plasmacytomas (SP) to rule out the presence of other disease foci. The role of flow cytometry and clonal plasma cell detection is currently under study together with other prognostic factors for the identification of patients with SP at high risk of progression to overt MM. Solitary plasmacytomas are treated effectively with local radiotherapy whereas systemic therapy is required at relapse. Clonal plasma cells that accumulate at extramedullary sites have distinct biological characteristics. Patients with MM and soft tissue involvement have poor outcomes and should be treated as ultra-high risk. A revised definition of SP that distinguishes between true solitary clonal PC accumulations and SP with minimal bone marrow involvement should be considered to guide an appropriate therapeutic and follow-up approach. Future studies should be conducted to determine optimum treatment approaches for patients with MM and paraskeletal or extramedullary disease.

Detection of Minimal Bone Marrow involvement of Blastic Plasmacytoid Dendritic Cell Neoplastic Cells - CD303 immunostaining as a diagnostic tool.

Blastic plasmacytoid dendritic cell (pDC) neoplasm (BPDCN) is a relatively rare hematological malignancy with significantly complex clinicopathological features that are still unclear. This study aimed to analyze the clinicopathological data of BPDCN and evaluate immunohistochemical detection of minimal bone marrow (BM) involvement. In this study, we examined skin and BM lesions from 6 patients with BPDCN. Neoplastic cells tested positive for CD303 (polyclonal, 100%; monoclonal, 40%) in the skin lesions and for CD303 (polyclonal, 100%; monoclonal, 67%) in the BM clots. Although immunostaining of CD4, CD56, CD123, CD303, and TCLl detected minimal BM involvement in 3 patients, morphological identification was challenging in the BM clots stained with hematoxylin-eosin. In conclusion, our results demonstrate the significance of observing BM smears to detect neoplastic cells and that immunohistochemical examination, including CD303 antibodies, is useful to detect minimal BM involvement. This study is the first to report the expression of thymic stromal lymphopoietin (TSLP) and its receptor in BPDCN cells. Therefore, the TSLP/TSLP receptor axis may be associated with the proliferation of BPDCN, and consequently, the survival of patients.

The Clinical Impact of Minimal Bone Marrow Involvement on the Outcome of Patients with Follicular Lymphoma

IntroductionFollicular lymphoma (FL) is the second most common type of non-Hodgkin cell lymphoma, and usually manifests as a disseminated disease. Bone marrow (BM) involvement, which occurs in 40-70% of cases, is often seen in follicular lymphoma and thought to be associated with less favorable prognosis. Diagnosis of BM involvement has traditionally been based on morphological findings, and BM involvement has been determined using histology alone in most clinical trials. Immunocytologic or molecular studies, such as flow cytometry (FCM) and polymerase chain reaction (PCR), have become more readily available, and their usage has clearly documented minimal BM involvement reproducibly. In this study, we evaluated the impact of BM involvement detected by FCM and PCR on the outcome of patients treated for FL. MethodsPatients who were diagnosed with biopsy-proven FL between 2004 and 2015 at our institution were included in the study. All patients had received a staging bone marrow examination before treatment with immunotherapy-based regimen. Immunocytologic [FCM] and/or molecular [PCR] studies were always performed if the patients did not have morphological BM involvement. We used 4- or 6- color FCM, and performed PCR analysis of Bcl-2/IgH rearrangement and/or IgH rearrangement detected by modified BioMed-2 protocol. A total of 90 patients were included, and the median follow-up duration was 36 months (range, 6|122 months). The BM status was classified using into 3 categories: morphological, minimal, and negative BM involvement. Minimal BM involvement was defined as BM involvement detected by FCM or PCR without morphological evidence. Morphological and minimal BM involvements were detected in 37 (41%) and 38 (42%) patients, respectively. The primary outcome measure was progression-free survival (PFS). PFS curves were plotted using the Kaplan-Meier method and compared by the log-rank test. Multivariate analyses were performed using a Cox linear regression model. There were significant differences in gender, LDH levels, stage, nodal sites, and FL International Prognostic Index (FLIPI) between patients with and without morphological BM involvement (Table1). ResultsThe 3-year PFS rate for patients with negative BM involvement was significantly better than that for patients with minimal or morphological BM involvement (84.8% vs. 40.3% vs. 60.5%; p= 0.043) (Figure 1). There was no statistical difference in 3-year PFS between patients with morphological BM involvement and those with minimal BM involvement. The difference of 3-year PFS rate between patients with minimal BM involvement and those with negative BM involvement was significant for patients with FLIPI low-intermediate risk (88.9% vs. 51.5%; p= 0.032) and those with advanced stage disease (90.0% vs. 33.6%; p= 0.027), but there were no significant differences in patients deemed FLIPI high risk and those with limited stage disease. Multivariate analysis revealed that BM involvement, including morphological and minimal involvement, was a significant poor prognostic factor (hazard ratio 4.885 [95% confidence interval 1.16-20.56], p = 0.0305). ConclusionAt the start of treatment, bone marrow involvement was seen in most FL patients. Patients without any BM involvement had an excellent prognosis. Patients with minimal BM involvement had an equally poor prognosis as those with morphologic BM involvement. [Display omitted] [Display omitted] [Display omitted] DisclosuresIshikawa:Mundipharma KK: Research Funding.

Potential Treatment of Marginal B-Cell Lymphoma With Antiviral Therapy

Background: The association between hepatitis C (HCV) and subtypes of B-cell lymphomas was initially described in epidemiological studies. These subtypes mainly are marginal zone lymphomas (MZLs) and lymphoplasmacytic lymphomas, both of which are indolent lymphomas. Hence there is a reported association - there is a potential role for antiviral strategies to influence the clinical course of these lymphomas. Case: We present a 39-year-old female patient with past medical history of hepatitis C with cirrhosis who underwent orthotropic liver transplantation. She was found to have periportal lymphadenopathy intraoperatively which were sampled. Pathology revealed marginal zone B-cell lymphoma. An MRI obtained one month postoperatively which showed persistent periportal, portocaval and gastrohepatic lymphadenopathy. She was asymptomatic without symptoms of night sweats, fever or weight loss. A subsequent bone marrow biopsy revealed small atypical lymphoid infiltrates suggestive of minimal bone marrow involvement. Given it was a low-grade B-cell lymphoma; patient was followed up and no treatment was initiated. One month later - she was noticed to have jaundice and worsening transaminases. Subsequently, she underwent liver biopsy, which showed changes consistent with severe recurrent hepatitis C. After thorough evaluation, she was started on Sofosbuvir and Ribavirin. The patient completed 24 weeks of therapy and achieved sustained viral response. Subsequently she had a PET scan, which showed no abnormal FDG uptake in the neck, chest, abdomen and pelvis or osseous structures. She remained in remission through her last follow up. Discussion: We report here the response to antiviral treatment of a liver transplant patient with low grade B-cell lymphoma associated with HCV infection. This further supports the potential link between some sub-types of B-cell lymphoma and HCV infection, and supports the use of antiviral treatment in this setting.

Bone marrow flow cytometry in staging of patients with B-cell non-Hodgkin lymphoma.

BackgroundBone marrow biopsies are routinely performed for staging patients with B-cell non-Hodgkin lymphoma (NHL). In addition to histomorphological studies, ancillary tools may be needed for accurate diagnosis. We investigated the clinical utility of multiparameter flow cytometric examination of bone marrow aspirates.MethodsA total of 248 bone marrow specimens from 232 patients diagnosed with B-cell NHL were examined. Monoclonal antibodies directed against CD19, CD20, CD10 (or CD5), and κ and λ immunoglobulins were used. Multi-stage sequential gating was performed to select specific cells of interest, and the results were compared with bone marrow histology.ResultsThe concordance rate between histomorphology and flow cytometry was 91.5% (n=227). Eight cases (3.2%) were detected by flow cytometry alone and were missed by histomorphology analysis, and 6 of these 8 cases showed minimal bone marrow involvement (0.09-2.2%). The diagnosis in these cases included large cell lymphoma (n=3), mantle cell lymphoma (n=3), and mucosa-associated lymphoid tissue (MALT) lymphoma (n=2). Thirteen cases were histopathologically positive and immunophenotypically negative, and the diagnoses in these cases included diffuse large cell lymphoma (n=7), T-cell/histiocyte-rich large B-cell lymphoma (n=2), anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (n=1), follicular lymphoma (n=1), MALT lymphoma (n=1), and unclassifiable lymphoma (n=1).ConclusionsMulti-color flow cytometry can be a useful method for assessing bone marrow in staging NHL and also plays a complementary role, especially in detecting small numbers of lymphoma cells.

Immunohistochemical analysis of CD123, CD56 and CD4 for the diagnosis of minimal bone marrow involvement by blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy derived from plasmacytoid dendritic cell precursors. Almost all patients show cutaneous manifestations, and >60% show bone marrow (BM) involvement at initial presentation. In cases where there is BM involvement by only a small number of tumour cells, such involvement is difficult to ascertain solely on morphological examination. In such situations, immunohistochemistry (IHC) may be useful in revealing minimal BM involvement by BPDCN. We investigated six patients with BPDCN. Initial morphological diagnosis disclosed BM involvement in only one of the six patients. To confirm BM involvement, IHC for CD4, CD56 and CD123 was performed on BM biopsies or clot sections. IHC revealed minimal BM involvement (CD123, 3/3; CD56, 2/3; CD4, 2/3) in three patients with BM that appeared morphologically normal. Our data clearly support the utility of IHC in diagnosing minimal BM involvement by BPDCN. Accordingly, we highly recommend immunohistochemical analyses for CD123, CD56 and CD4 in BPDCN patients, particularly in cases where the initial BM study indicates normal morphology.

Extramedullary Plasmacytoma of the Lung – Rather a Disseminated than a Localized Disease? – A Case Report of a Primary Pulmonary Plasmacytoma Showing Distinct Signs of Systemic Spread

Objective: We report an unusual case of a patient with a plasma cell tumor presenting first as a primary pulmonary plasmacytoma (PPP) but then showing distinct signs of systemic spread. Case Summary: A 58-year-old woman presented with an extramedullary plasma cell tumor of the lung with additional affection of lymph nodes above and underneath the diaphragm, without apparent infiltration of the bone marrow by malignant plasma cells, but with evidence of a small proportion of clonal plasma cells in FACS analysis. Due to the fact that the patient showed excretion of lambda light chains in the urine in addition to the solid manifestations on multiple sites and minimal bone marrow involvement, we verified the systemic spread. This is in contrast to primary extramedullary plasmacytoma presenting as solitaire plasma cell tumors mostly occurring in the upper aerodigestive tract or extramedullary myeloma, which describes relapses or extramedullary progression of multiple myeloma emerging in various organs. We herein present all features of a, to our opinion, systemic disease by means of affection pattern, laboratory values, and bone marrow infiltration. Conclusion: This unusual case demonstrates the presentation of an extramedullary plasma cell tumor that appeared as a PPP but showed distinct signs of dissemination as well as uncommon features such as a monoclonal component of IgM type. This example reveales that extramedullary manifestations of plasma cell dyscrasia should be surveyed carefully as they can conceal an underlying systemic disease.

Effect of Positive Bone Marrow EBV In situ Hybridization in Staging and Survival of Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal-Type

The aim of the study was to determine the effect of EBV-encoded RNA-1 in situ hybridization (EBER-1 ISH) in bone marrow specimens on survival outcome in patients with clinical stage I/II natural killer/T-cell lymphoma. We systematically did EBER-1 ISH on 182 archival bone marrow tissues from 91 patients who were diagnosed of stage I/II natural killer/T-cell lymphoma and analyzed the correlation between bone marrow EBER-1 ISH status and survival. We defined minimal bone marrow involvement and definite bone marrow involvement to distinguish the subgroups who revealed EBV-positive cells from normal marrow by EBER-1 ISH from those who showed typical neoplastic cells in bone marrow biopsies. In total, 17 of the 91 (18.7%) patients showed positivity for EBER-1 ISH at least in one of the bilateral bone marrow biopsies with 14 minimal bone marrow involvements and 3 definite bone marrow involvements. Patients with positive bone marrow EBER-1 ISH showed significantly poorer overall survival than those who were negative for bone marrow EBER-1 ISH (median survival, 16.1 months versus not reached; P = 0.045). Considering a high proportion of stage I/II patients (15.4%) with minimal in bone marrow specimens, bone marrow EBER-1 ISH should be routinely done in all patients with localized disease for more accurate staging.

Prevalence and clinical implications of bone marrow involvement in pediatric anaplastic large cell lymphoma

Anaplastic large cell lymphoma (ALCL) harbors the reciprocal chromosomal translocation t(2;5)(p23;q35) in approximately 80% of the cases. The genes involved are nucleophosmin (NPM) and anaplastic lymphoma kinase (ALK) and the resulting chimeric NPM-ALK protein is thought to play a key role in the pathogenesis of t(2;5) positive ALCL. Few data on bone marrow (BM) involvement in ALCL have been published and they mostly rely on morphological examination of BM smears. We studied 52 ALCL for NPM-ALK expression by RT-PCR: 47/52 biopsies were positive. In 41 of the 47 cases we obtained the BM at diagnosis and investigated the prevalence of minimal BM infiltration by RT-PCR and real-time PCR. Minimal disseminated disease was positive in 25/41 patients (61%), of whom six had morphologically infiltrated BM. Survival analysis demonstrated a 5-year progression-free survival of 41 +/- 11% for patients with molecularly positive BM vs 100% for patients with negative BM (P = 0.001). These results suggest that minimal BM involvement at diagnosis is a common event in pediatric ALCL and that minimal BM disease monitoring could identify patients at risk of relapse.

Bone Marrow Biopsies for the Diagnosis of Systemic Mastocytosis

The medical records of 21 patients evaluated for mastocytosis and 2 patients seen for follow-up of known mastocytosis who underwent bilateral iliac crest aspirations and biopsies were reviewed retrospectively to determine whether mastocytosis could be confirmed in each of a patient’s biopsy specimens. In 19 cases (83%), each biopsy specimen showed evidence of mastocytosis; however, in 4 cases (17%), only 1 of 2 biopsy sites revealed mastocytosis. Compared with the 4 patients with only a unilateral positive biopsy result, the bilateral group had significantly higher urinary excretion of 11β-prostaglandin F 2α , higher serum tryptase levels, and higher serum calcitonin values, and a higher percentage had splenomegaly (37% [7/19] vs 0% [0/4]). The 2 groups could not be distinguished by the main initial symptom(s), presence of urticaria pigmentosa, or other laboratory findings (alkaline phosphatase, aspartate transaminase, or hemoglobin concentrations or total WBC, total eosinophil, or platelet counts). Bilateral biopsies might be useful for diagnosing early systemic mastocytosis or detecting minimal bone marrow involvement. The diagnosis of systemic mastocytosis depends partly on finding mast cell infiltration of extracutaneous tissue. The bone marrow commonly is chosen as the site for biopsy. In addition to systemic mastocytosis, an increase in bone marrow mast cells may accompany such hematologic disorders as chronic lymphocytic leukemia, non-Hodgkin lymphoma, 1 dysmyelopoiesis, and myeloproliferative disorders. 2 Hence, in the evaluation of a patient for systemic mastocytosis, bone marrow aspiration and biopsy serve 2 purposes: to confirm the diagnosis of mastocytosis and to evaluate the bone marrow for associated hematologic disorders. The number of mast cells detected in bone marrow samples has been shown to correlate positively with the urinary excretion of tele-methylimidazoleacetic acid, the primary histamine metabolite. 3 Although skeletal scintigraphic findings in mastocytosis might show multifocal or diffuse abnormalities, the radionuclide bone patterns might be normal or show only unifocal involvement. 4 Also, only patchy or focal infiltration patterns involving peritrabecular or perivascular regions or areas around lymphoid aggregates might be evident, rather than diffuse infiltration. 5 To determine whether the presence of mastocytosis could be missed because of sampling error, we retrospectively reviewed the findings in each of the bilateral biopsy sites of 21 patients who had been evaluated for systemic mastocytosis during the previous 5 years and 2 patients with known disease with bilateral biopsies at the time of follow-up.

Bone marrow staging of patients with non-Hodgkin lymphoma by flow cytometry

Immunophenotypic analysis is an established tool in the diagnosis and classification of many hematolymphoid disorders; however, the role of flow cytometry (FC) in detecting bone marrow involvement during the staging of non-Hodgkin lymphoma (NHL) has yet to be defined. The authors retrospectively analyzed 157 staging and 70 restaging bone marrow biopsies on which morphologic and FC analyses were performed; these biopsies were taken from 195 consecutive patients. Bone marrow biopsies were blindly and independently reviewed and determined to be positive, negative, or suspicious for morphologic involvement by NHL, with disagreements settled by a third reviewer. A selected panel of monoclonal antibodies was used to determine whether bone marrow involvement was immunophenotypically positive (>5%), minimal (<5%), negative, or nondiagnostic. FC and morphology agreed in 78% of cases (178 of 227: 129 both negative, 49 both positive) and were discrepant in 22% (49 of 227). Seven percent (16 of 227) were morphologically positive but showed no evidence of disease on FC, whereas 12% (27 of 227) were positive by FC but had no morphologic involvement. Of the 162 morphologically negative or suspicious bone marrows, 27 were shown to be involved by FC, resulting in a false-negative detection rate of 17%. Most of these (22 of 27, 81%) had minimal detectable disease. Seven percent of Stage I and 26% of Stage II NHL cases with negative staging bone marrow morphologically were found to be involved by FC. Neither morphologic examination of bone marrow biopsy specimens nor FC alone is adequate to detect all cases of NHL with bone marrow involvement. FC is most sensitive for detecting minimal bone marrow lymphoma, whereas morphology will detect most cases in which involvement is >5%. Cases of early stage NHL with morphologically negative bone marrow could potentially be restaged as Stage IV on the basis of FC results. The clinical importance of minimal bone marrow involvement by NHL needs further evaluation.

9 Hairy cell leukaemia

Hairy cell leukaemia is a rare chronic lymphoproliferative disease, characterized by splenomegaly, pancytopenia and recurrent infection. The characteristic 'hairy cells', present in the peripheral blood and bone marrow, are the hallmark of this leukaemia. The disease has a chronic, progressive course, and the majority of patients afflicted by it require therapy. The most common reason to initiate treatment is neutropenia with or without associated infectious complications, or the development of severe thrombocytopenia. Therapeutic options in hairy cell leukaemia include splenectomy, interferon administration, or the use of chemotherapeutic agents such as pentostatin (2'-deoxycoformycin) and 2-chlorodeoxyadenosine. Splenectomy is still indicated in the treatment of young patients with significant splenomegaly and only minimal bone marrow involvement. Interferon treatment induces remission in approximately 90% of patients with hairy cell leukaemia, but complete remission is obtained in only 5-10%. The development of antibodies against interferon was initially considered a major problem, but longer follow-up of patients who developed antibodies has shown that it is transient and does not have a significant impact on the overall response to treatment. Pentostatin induces complete remission in 60-70% of patients and partial remission in 20-40%. 2-Chlorodeoxyadenosine is a very promising drug in the treatment of this rare leukaemia, inducing long-lasting complete remission in approximately 80% of patients. While interferon does not cure the disease, it is possible that a subset of patients treated with pentostatin or 2-chlorodeoxyadenosine are cured. Longer follow-up of these patients will determine whether this is true.