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A 70-year-old woman presented with itching and skin lesions on her torso, arms, and legs. She had a medical history of hypertension and chronic myelomonocytic leukemia type 1 (CMML-1). Physical examination revealed mixed purpuric and erythematous maculopapular lesions on her trunk and limbs. Laboratory tests showed low platelet and white blood cell counts. A punch biopsy confirmed the presence of myelomonocytic leukemia in the skin. This case highlights the rare occurrence of cutaneous involvement in CMML and the importance of prompt diagnosis and appropriate treatment. [Extracted from the article]

A 32-year-old woman presented to the dermatology clinic with a 3-year history of progressive skin thickening. She had thickened skin on her face and body, with papules and induration. She also experienced tingling and occasional pain in her hands. Tests revealed fibroblast proliferation with collagen and mucin deposition in the skin, as well as monoclonal gammopathy. The diagnosis was scleromyxoedema with smouldering multiple myeloma. Treatment with thalidomide resulted in significant improvement. Scleromyxoedema is a rare condition characterized by skin lesions and is associated with monoclonal gammopathy. It can have diverse internal manifestations and requires a skin biopsy for diagnosis. [Extracted from the article]

Atraumatic splenic rupture is a complex surgical pathology owing to its rarity, non-specificity of symptoms and gravity of possible outcomes. This case outlines the investigation and management of a patient with atraumatic splenic rupture secondary to undiagnosed hairy cell leukaemia. While the patient was initially managed conservatively, they went on to have a splenectomy owing to ongoing transfusion requirements. A review of the literature has also been performed and presented to highlight the potential causes of atraumatic splenic rupture and the various options for confirming diagnosis and definitive management. [ABSTRACT FROM AUTHOR]

Objectives: To assess the efficacy of a method to circumvent CD20-positive antigen masking by rituximab for flow cytometry analysis of B-cell malignancies in hematology patients.Methods: Mononuclear cells (MNCs) from 10 healthy individuals and 5 untreated patients with B-cell malignancies were sensitized with rituximab. Patients' diagnoses included chronic lymphocytic leukemia, hairy cell leukemia, and follicular lymphoma. MNCs were isolated by gradient density centrifugation. An EDTA/glycine acid (EGA) elution method was used to dissociate CD20-rituximab complexes; afterwards, CD20-positive immunoreactivity was assessed by flow cytometry. A saturation curve was built based on serial dilutions of rituximab. Median fluorescent intensities of CD20-positive signals were obtained before sensitization with rituximab and after its elution with EGA.Results: CD20-positive signals were not detectable by flow cytometry after rituximab sensitization of B cells. CD20-sensitized vs CD20-unsensitized, CD20-sensitized vs CD20-eluted, and CD20-eluted vs CD20-negative control (NC) MNC populations exhibited statistical differences (P = .001), while CD20-sensitized vs CD20-NC populations did not (P = .499), confirming CD20 antigen masking by rituximab.Conclusions: Rituximab interfered with the flow cytometry protocol for CD20 determination on normal and neoplastic B cells. The EGA method efficiently eluted rituximab, allowing for accurate identification of CD20-positive B cells. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated efficacy of two dual immunohistochemistry (IHC) staining assays in assessing hairy cell leukemia (HCL) involvement in core biopsies and compared the results with concurrently collected flow cytometric data.Methods: Overall, 148 patients with HCL (123 male, 25 female; mean age: 59.8 years; range: 25-81 years) had multiparameter flow cytometry performed using CD19, CD20, CD22, CD11c, CD25, CD103, CD123, surface light chains, CD5, and CD23. In parallel, bone marrow IHC was done using PAX5/CD103 and PAX5/tartrate-resistant alkaline phosphatase (TRAP) dual IHC stains.Results: Overall sensitivity of dual IHC stains was 81.4%, positive predictive value was 100%, and negative predictive value was 81.7%. All IHC-positive cases concurred with flow cytometry data, even when HCL burden was extremely low in the flow cytometry specimens (as low as 0.02% of all lymphoid cells).Conclusions: Dual IHC stain is a sensitive tool in detecting HCL, even in cases with minimal disease involvement. [ABSTRACT FROM AUTHOR]

Hairy cell leukemia (HCL) is an indolent B‐cell malignancy characterized by high initial sensitivity to purine analog chemotherapy, minimal residual disease (MRD) frequently accompanying complete remission (CR), and relapses requiring additional treatment. Repeat chemotherapy shows decreasing efficacy and increasing toxicity with each course. Newer therapies targeting BRAF/MEK or Bruton's tyrosine kinase are effective but generally leave MRD. Rituximab has modest activity as a single agent and can achieve MRD‐negative CR in combination with purine analogs, but there is significant toxicity from the chemotherapy. Moxetumomab pasudotox‐tdfk (Moxe) is a biologic containing an antibody fragment (Fv) binding to CD22, attached to a portion of Pseudomonas exotoxin A. Binding to CD22 enables the toxin to enter and kill cells. Moxe is administered by 30‐minute infusions on days 1, 3, and 5 of up to six cycles spaced 4 weeks apart. In phase I testing, 64% of 33 patients at the highest dose level achieved CR, most without MRD. Lack of MRD correlated with prolonged CR duration; of 11 MRD‐negative CRs, 10 were still in CR after a median of 42 months of observation. In pivotal testing, 75% of 80 patients had a hematologic response, 41% with CR; 82% (27/33) of CRs were MRD‐negative, and only 4 of the 27 MRD‐negative patients relapsed during the follow‐up period. Hemolytic uremic syndrome and capillary leak syndrome were each observed in 9% of patients, all reversible. In September 2018, the U.S. Food and Drug Administration approved Moxe for the treatment of relapsed/refractory HCL after ≥2 prior therapies. Moxe is undergoing further development in combination with rituximab. Implications for Practice: Hairy cell leukemia (HCL) has effective treatments including purine analogs with and without rituximab, and oral inhibitors of BRAF, MEK and Bruton's tyrosine kinase (BTK). Despite these therapies, relapse occurs, and moxetumomab pasudotox has an important role in relapsed and refractory HCL because of its ability to achieve high rates of complete remissions (CRs) without chemotherapy; most of these CRs are without minimal residual disease (MRD). CR duration is enhanced in patients who achieve eradication of MRD. To improve the efficacy of this recombinant immunotoxin, a phase I trial is underway in combination with rituximab to reduce tumor burden and decrease immunogenicity. Despite effective treatments for hairy cell leukemia, relapse occurs. This article focuses on current treatment approaches, including treatment with the recently approved biologic, moxetumomab pasudotox‐tdfk. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosis of central nervous system involvement in acute lymphoblastic leukemia (ALL) requires morphologic expertise; therefore, we evaluated interphase fluorescence in situ hybridization (iFISH) of cerebrospinal fluid (CSF) cytospin preparations as a potential complementary test.Methods: Twenty-three CSF cytospin specimens from 13 pediatric patients with ALL were included. iFISH probes detecting BCR-ABL1, ETV6-RUNX1, and KMT2A rearrangement and CDKN2A deletion, which were present at initial diagnosis, were used on follow-up CSF cytospin specimens and were compared with cytology.Results: Seventeen (73.9%) follow-up specimens showed concordant results between iFISH and cytology. Two (8.7%) samples with discordant results were positive by iFISH but not by cytology; one (4.3%) was positive only by cytology. In the remaining three (13.0%) specimens, too few cells were available for cytology, whereas iFISH interpretation was possible.Conclusions: iFISH of CSF cytospin preparations improves malignant cell detection in pediatric ALL. [ABSTRACT FROM AUTHOR]

The industrial solvents benzene and trichloroethylene (TCE) are known carcinogens, and these solvents contaminated the drinking water at Marine Corps Base Camp Lejeune from the 1950s to 1980s. Benzene and TCE are linked to the hematopoietic cancers acute myelocytic and lymphocytic leukemia and chronic lymphocytic leukemia. We report the case of a veteran stationed at Marine Corps Base Camp Lejeune during this period who developed hairy cell leukemia (HCL), a rare form of lymphocytic leukemia. We review his presentation, medical history, solvent exposure, and literature on the carcinogenicity of benzene and TCE. This patient represents a possible link of TCE or benzene to HCL. The case also informs clinicians of the updated epidemiology with regards to clinical findings for HCL. [ABSTRACT FROM AUTHOR]

Objectives: The importance of distinguishing mature B-cell lymphoproliferative disorders (B-LPDs) is highlighted by the distinct treatments used for and varying prognoses seen in association with these different diseases. Immunophenotyping allows for accurate and efficient differentiation of many B-LPDs. Recently, we showed that CD200 is highly expressed in hairy cell leukemia (HCL) but not in marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), or hairy cell leukemia-variant (HCL-v). Here, we assessed the usefulness of a flow cytometric panel combining CD200 and CD1d with CD25, CD103, and CD11c to distinguish CD10–, CD5– B-LPDs. Methods: We analyzed the expression of CD200 and CD1d by flow cytometric analysis in 79 cases of CD10–, CD5– mature B-LPDs. Results: Distinct patterns of CD200 and CD1d expression were seen in the examined B-LPDs. HCL showed bright positivity for CD200 along with positive staining for CD1d, whereas HCL-v showed low levels of expression for both markers. LPL demonstrated positive staining for CD200 in combination with dim to negative staining for CD1d. In contrast, MZL was commonly positive for CD1d and negative for CD200. Conclusions: Flow cytometric analysis of CD200 and CD1d, along with CD25, CD103, and CD11c, can aid in the diagnosis of CD10–, CD5– mature B-LPDs. [ABSTRACT FROM AUTHOR]

Objectives: Recent reports have used immunohistochemistry (IHC) with a mutation-specific antibody to detect the BRAF V600E mutation, which is found in nearly all cases of hairy cell leukemia (HCL). To date, however, only a small number of non-HCL, splenic B-cell lymphomas have been examined by IHC. Methods: We analyzed 121 cases, including 26 HCLs, 52 non-HCL splenic lymphomas, 22 chronic lymphocytic leukemias/small lymphocytic lymphomas (CLLs/SLLs), and 21 plasma cell neoplasms (PCNs) for BRAF V600E expression by IHC. Molecular testing for BRAF V600E was performed in a subset of cases, using allele-specific polymerase chain reaction and/or Sanger sequencing. Results: Twenty-six (100%) of 26 HCL cases were positive by IHC vs one (1%) of 95 non-HCL cases. Positive staining was identified in one (2%) of 44 splenic marginal zone lymphomas (SMZLs), while each of 22 CLLs/SLLs, 21 PCNs, six unclassifiable splenic lymphomas, and two HCL variants were negative. IHC and molecular results were concordant in all cases examined (21 HCLs and 21 non-HCLs, including the BRAF+ SMZLs). Conclusions: The detection of BRAF V600E by IHC is useful in the distinction of HCLs from other splenic-based lymphomas, although the identification of at least rare SMZLs containing this abnormality illustrates the continuing need for a multiparameter approach to diagnosis. [ABSTRACT FROM AUTHOR]

Objectives We tested if modulation of cytosolic K+ levels by ouabain, an inhibitor of Na+/ K+- ATPase, exerts cytoprotection against distinct stressful stimuli in human leukemic cells. Methods The cytosolic K+, Na+ or Ca2+ levels and the cytotoxicity were evaluated by flow cytometry. Key findings Various cytotoxic chemicals and ultraviolet irradiation induced cell death and increased intracellular concentrations of K+, Na+ or Ca2+. Ouabain reduced the cytotoxicity and the elevation of cytosolic levels of K+ but not those of Na+ or Ca2+. Conclusions Our data thus suggest that elevated cytosolic K+ levels are associated with the cytotoxicity in response to distinct stressful stimuli and that ouabain exerts cytoprotection most probably by regulating intracellular K+ levels. [ABSTRACT FROM AUTHOR]

Objectives: BRAF V600E mutation is characteristic of hairy cell leukemia (HCL). A V600E mutation-specific antibody, VE1, has been recently developed. We studied the diagnostic utility of this antibody in HCL and compared it with other B-cell neoplasms. Methods: VE1 activity was assessed using immunohistochemistry in 90 mature B-cell neoplasms, including HCL (n = 17), HCL variant (n = 6), chronic lymphocytic leukemia (CLL) (n = 20), and 47 other B-cell lymphomas. Most (87/90) specimens were formalin-fixed, paraffin-embedded bone marrow (BM) biopsy specimens decalcified in either hydrochloric acid or formic acid. Results: VE1 was positive in 15 (88%) cases of HCL and two (10%) cases of CLL and was negative in all other tumors assessed. The VE1-positive HCL cases showed uniform staining in all tumor cells, but intensity was variable. The two VE1-negative HCL cases had BRAF V600 mutations proven by molecular analysis. The two CLL cases positive with VE1 showed an atypical staining pattern with expression in a minority of lymphoma cells. Immunohistochemistry using the VE1 antibody had a sensitivity of 88% and a specificity of 97% for HCL. Conclusions: VE1 immunohistochemistry is a useful and convenient surrogate for detecting BRAF V600E mutation in BM biopsy specimens decalcified with hydrochloric or formic acid-based solutions. [ABSTRACT FROM AUTHOR]

Objectives: Detection of BRAF V600E mutations in hairy cell leukemia (HCL) has important diagnostic utility. In this study, we sought to compare immunohistochemistry with an antibody specific for this mutation to a sensitive molecular assay. Methods: The performance of the BRAF V600E-specific VE1 antibody was compared with that of allele-specific polymerase chain reaction (PCR) in 22 formalin-fixed, paraffin-embedded (FFPE) specimens with HCL involvement, along with nine splenic marginal zone lymphomas (SMZLs), 10 follicular lymphomas (FLs), 10 mantle cell lymphomas (MCLs), and 10 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLLs). An additional 11 SMZLs, 100 FLs, 20 MCLs, 83 CLL/SLL specimens, and 49 reactive tonsils within tissue microarrays were stained with VE1. Results: A BRAF V600E mutation was detected in 17 (77.3%) of 22 HCL cases by PCR. Immunohistochemistry demonstrated VE1 staining in 20 (90.9%) cases, identifying low-level (~1%) involvement in three HCL cases that were mutation negative by PCR. Evaluation of additional material from these patients confirmed the presence of BRAF V600E. Thirty-nine non-HCL cases were negative by both methods. Within tissue microarrays, weak false-positive staining was observed in two (0.8%) of 263 non-HCL cases. Conclusions: VE1 immunohistochemistry is more sensitive than allele-specific PCR in FFPE bone marrow specimens and can be applied to decalcified core biopsy specimens that are not appropriate for molecular techniques. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate CD200 expression in B-cell proliferative disorders. Methods: We analyzed 180 recent specimens of B-cell neoplasms for CD200 expression by flow cytometric immunophenotypic analysis, which is better able to assess relative intensity of staining than immunohistochemical staining. Results: We found that hairy cell leukemia exhibits a high level of staining for CD200 in comparison to other B-cell lymphoproliferative disorders, including hairy cell leukemia-variant (HCL-V), marginal zone lymphoma, and lymphoplasmacytic lymphoma. We confirmed this observation by semiquantitative immunohistochemical staining. Conclusions: Assessment of the CD200 expression level is helpful to distinguish HCL from HCL-V and other B-cell lymphoproliferative disorders and in the differential diagnosis of B-cell neoplasms in general. [ABSTRACT FROM AUTHOR]

Detection of the integrin subunit CD103 is a useful diagnostic tool in the diagnosis of hairy cell leukemia (HCL). Currently, flow cytometric analysis (FC) and frozen section immunohistochemistry (IHC) represent the only available methods of detection. This study is the first to describe the successful use of a CD103 antibody to identify HCL and HCL-variant in paraffin sections of formalin- or Bouin solution-fixed specimens (n = 68) using an immunoperoxidase technique. In other B-cell lymphoproliferative disorders that morphologically may resemble HCL, including chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 32), mantle cell lymphoma (n = 23), lymphoplasmacytic lymphoma (n = 27), follicular lymphoma (n = 7), and marginal zone lymphoma (n = 13), lymphoid cells are nonreactive for CD103. In HCL, the CD103 staining pattern is predominantly membranous with delineation of delicate cytoplasmic projections. This CD103 antibody is an extremely valuable addition to the IHC panel for the diagnosis of HCL, especially in cases lacking FC analysis. [ABSTRACT FROM AUTHOR]

The presence of the BRAF c.1799T>A V600E mutation was recently described in cases of hairy cell leukemia (HCL) but not in other common lymphomas. However, many uncommon subtypes of lymphoma have not been studied. We designed a BRAF pyrosequencing assay specific for the V600E mutation, which has a sensitivity of 5% and is applicable to paraffin-embedded tissue. DNA was sequenced in 9 cases of HCL; 6 cases of variant HCL; 10 cases each of nodal marginal zone lymphoma (NMZL), extranodal marginal zone lymphoma (ENMZL), posttransplantation lymphoproliferative disorder (PTLD), and large granular lymphocyte (LGL) proliferations; 11 cases of peripheral T-cell lymphoma (PTCL); and 12 cases of anaplastic large cell lymphoma (ALCL). All (100%) cases of HCL were positive for BRAF mutations. No mutations were identified in variant HCL, NMZL, ENMZL, PTLD, PTCL, ALCL, or LGL proliferations. Among lymphoproliferative disorders, BRAF mutations are restricted to HCL. [ABSTRACT FROM AUTHOR]

BRAF protooncogene is an important mediator of cell proliferation and survival signals. BRAF p.V600E mutation was recently described as a molecular marker of hairy cell leukemia (HCL). We developed and validated a pyrosequencing-based approach that covers BRAF mutational hotspots in exons 11 (codon 468) and 15 (codons 595 to 600). The assay detects BRAF mutations at an analytical sensitivity of 5%. We screened 16 unenriched archived bone marrow aspirate samples from patients with a diagnosis of HCL (n = 12) and hairy cell leukemia--variant (HCL-v) (n = 4) using pyrosequencing. BRAF p.V600E mutation was present in all HCL cases and absent in all HCL-v. Our data support the recent finding that BRAF p.V600E mutation is universally present in HCL. Moreover, our pyrosequencing-based assay provides a convenient, rapid, sensitive, and quantitative tool for the detection of BRAF p.V600E mutations in HCL for clinical diagnostic testing. [ABSTRACT FROM AUTHOR]

CD175 or Tn antigen is a carbohydrate moiety of N-acetylgalactosamine (GalNAc)α1-O- linked to the residue of amino acid serine or threonine in a polypeptide chain. Despite the chemical simplicity of the Tn antigen, its antigenic structure is considered to be complex and the clear determinants of Tn antigenicity remain poorly understood. As a consequence, a broad variety of anti-Tn monoclonal antibodies (mAbs) have been generated. To further investigate the nature and complexity of the Tn antigen, we generated seven different anti-Tn mAbs of IgM and IgG classes raised against human Jurkat T cells, which are Tn-positive due to the low activity of T-synthase and mutation in specific chaperone Cosmc. The binding analysis of anti-Tn mAbs with the array of synthetic saccharides, glycopeptides and O-glycoproteins revealed unexpected differences in specificities of anti-Tn mAbs. IgM mAbs bound the terminal GalNAc residue of the Tn antigen irrespective of the peptide context or with low selectivity to the glycoproteins. In contrast, IgG mAbs recognized the Tn antigen in the context of a specific peptide motif. Particularly, JA3 mAb reacted to the GSPP or GSPAPP, and JA5 mAb recognized specifically the GSP motif (glycosylation sites are underlined). The major O-glycan carrier proteins CD43 and CD162 and isoforms of CD45 expressed on Jurkat cells were precipitated by anti-Tn mAbs with different affinities. In summary, our data suggest that Tn antigen–Ab binding capacity is determined by the peptide context of the Tn antigen, antigenic specificity of the Ab and class of the immunoglobulin. The newly generated anti-Tn IgG mAbs with the strong specificity to glycoprotein CD43 can be particularly interesting for the application in leukemia diagnostics and therapy. [ABSTRACT FROM PUBLISHER]

We describe a case of disseminated Sporothrix schenckii infection in a man with underlying hairy cell leukemia. The immunological defects associated with this malignancy, as well as the management of refractory sporotrichosis are reviewed. [ABSTRACT FROM AUTHOR]

By using flow cytometry, we studied CD103 and CD123 expression by the malignant cells in 300 B-cell lymphoproliferative disorder (BC-LPD) cases, including 114 hairy cell leukemia (HCL), 20 HCL variant (HCLv), 9 splenic marginal zone lymphoma (SMZL; in 5, only CD103 was evaluated), 133 chronic lymphocytic leukemia (CLL), 3 follicular lymphoma (FL), and 21 mantle cell lymphoma (MCL). All HCLs expressed uniform CD103 and bright CD123. Among the 20 HCLv cases, 20 (100%) were CD103+ and 8 (40%) were CD123+ (partial or dim). CD103 was negative in all MCL, FL, CLL, and SMZL cases. CD123 was positive in 1 (25%) of 4 SMZL, 3.8% of CLL (5/133), 7 (33%) of 21 MCL, and 1 (33%) of 3 FL cases. CD103 is specific for HCL and HCLv. CD123 expression is more widespread in BC-LPDs but is useful in conjunction with CD25 to differentiate HCLv from HCL. These findings support the usefulness of CD123 and CD103 to aid in the differential diagnosis of BC-LPDs. [ABSTRACT FROM AUTHOR]

Immunophenotyping is indispensable in the differential diagnosis of B-cell chronic lymphoproliferative disorders (B-CLPDs). However, B-CLPDs often show overlapping immunophenotypic profiles and may be diagnostically challenging. CD1d is an HLA class I-like molecule that presents glycolipids to invariant natural killer T cells. Normal mature B cells constitutively express CD1d, but with the exception of some conflicting data, its expression in B-CLPDs is unknown. We demonstrate that in 222 B-CLPD cases, CD1d expression of less than 45% is strongly predictive of CLL (likelihood ratio, 32.3; specificity, 97.4%; sensitivity, 84.1%). In addition, CD1d showed significantly higher staining intensity in splenic marginal zone lymphoma compared with atypical hairy cell leukemia, lymphoplasmacytic lymphoma, and mantle cell lymphoma, thus allowing the discrimination of the former from the latter immunophenotypically overlapping B-CLPDs. It is important to note that in a given patient, CD1d expression on malignant B cells was similar between tissues and remained unaffected by disease stage and treatment status. Our findings strongly argue for the incorporation of CD1d into routine lymphoma panels. [ABSTRACT FROM AUTHOR]

Annexin-1 and T-bet are recently described immunohistochemical stains that reportedly assist in the diagnosis of hairy cell leukemia (HCL). Our objective was to assess the sensitivity and specificity of a panel of immunohistochemical stains in distinguishing HCL from other B-cell neoplasms, particularly splenic and extranodal marginal zone lymphomas (SMZL and ENMZL, respectively). The study included 234 bone marrow biopsy specimens: 101 HCL, 13 SMZL, and 10 ENMZL cases were assessed with CD20, tartrate-resistant acid phosphatase (TRAP), DBA.44, a-1, T-bet, and cyclin D1, and 110 control cases were assessed with annexin-1 and T-bet. Our study showed that annexin-1 is a specific and sensitive marker for HCL; however, interpretation is limited by positivity within myeloid precursors. T-bet, DBA.44, and TRAP immunohistochemical stains lack sufficient sensitivity and specificity to differentiate HCL from either form of marginal zone lymphoma. However, our data suggest that the addition cyclin D1 to the immunostaining panel will increase the sensitivity and specificity of HCL diagnosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 58-year-old man with fatigue and have past history of diabetes mellitus, hypertension and dyslipidemia and mentions the development of hairy cell leukemia (HCL) in the patient.

We studied CD81 expression by flow cytometry (FC) on benign precursor B cells (hematogones) and leukemic blasts in precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) and established its usefulness in minimal residual disease (MRD) assays. Hematogones showed uniformly bright CD81 expression. In 98 pre-B-ALLs at diagnosis or overt relapse, 80 (82%) showed aberrantly decreased CD81 intensity. We used hematogones in 139 MRD– specimens to set a lower threshold for normal CD81 expression. In 133 specimens positive for residual pre-B-ALL, 87.2% showed increased CD81-dim immature B cells (>10%) and/or a discrete cluster of CD81-dim cells in a background of hematogones. Only 1 of 139 MRD– specimens showed more than 10% CD81-dim cells. Decreased CD81 expression was maintained in 91% of aberrant cases analyzed before and after chemotherapy. Decreased CD81 expression is a sensitive and specific marker for residual pre-B-ALL, even in a background of hematogones, making CD81 a useful addition to a panel for MRD detection by FC. [ABSTRACT FROM AUTHOR]

CD103 is characteristically expressed in hairy cell leukemia (HCL), a B-lymphoproliferative disorder highly responsive to treatment with purine analogs. Other CD103+ diseases are rare and do not respond well to the same therapy, including HCL variant (HCLv) and splenic marginal zone B-cell lymphoma (SMZL) variants. We analyzed 215 cases of CD103+ B-lymphoproliferative disorders to further delineate their immunophenotypic features. Flow cytometric analysis revealed that 78.6% of all cases expressed CD25 and CD103, characteristic of classical HCL. Cases analyzed immunohistochemically were also invariably positive for annexin-A1; a subset coexpressed CD10 (33/169 [19.5%]) or BCL1 (26/65 [36.9%]). In contrast, 21.4% of cases lacked CD25, a subset of which was analyzed and was invariably negative for annexin-A1, CD10, and BCL1. The CD25- cases had variable morphologic features ranging from HCLv and SMZL to prolymphocytic leukemia and diffuse large B-cell lymphoma. Clinically, patients with CD25- disease tended to be older (P= .001), typically had leukocytosis (P= .014), and did not respond well to cladribine or pentostatin. We suggest categorizing CD103+ B-lymphoproliferative disorders into 2 groups. While HCL coexpresses CD25 and annexin-A1, diseases lacking CD25 and annexin-A1 behave clinically differently and can be separated from HCL on diagnosis. [ABSTRACT FROM AUTHOR]

The article discusses the implications of the research success of hairy cell leukemia in the U.S. Accordingly, HCL study has generated key medical applications which include improved survivability of interferon, drug types as well as complete patient remission. In addition, the article notes that HCL become an uncommon cancer that started to lost its essence in medical research. It also cites the developments of HCL research along with the symptoms and treatments.

Background The introduction of new treatments for hairy cell leukemia has resulted in improved patient survival but also engendered increasing concern about the possibility of excess second cancers. The available evidence is conflicting, with most risk estimates based on sparse numbers. To our knowledge, no study has evaluated cause-specific mortality in patients with hairy cell leukemia. Methods We quantified second cancer incidence and cause-specific mortality among 3104 two-month survivors of hairy cell leukemia who were reported to 16 population-based registries in the Surveillance, Epidemiology and End Results (SEER) Program between 1973 and 2002. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were used to quantify the risk of second cancers and causes of death, respectively. The cumulative probability of a second cancer among survivors of hairy cell leukemia was calculated using a competing risk model. All statistical tests were two-sided. Results Mean follow-up of hairy cell leukemia survivors was 6.5 years (range, 2 months-29.3 years). Second cancer risk was statistically significantly elevated (SIR = 1.24, 95% confidence interval [CI] = 1.11 to 1.37) compared with the general population. Survivors had statistically significantly higher risks of Hodgkin lymphoma (SIR = 6.61, 95% CI = 2.13 to 15.42), non-Hodgkin lymphoma (SIR = 5.03, 95% CI = 3.77 to 6.58), and thyroid cancer (SIR = 3.56, 95% CI = 1.30 to 7.74) and a lower risk of lung cancer (SIR = 0.63, 95% CI = 0.42 to 0.90). The cumulative probability of all second cancers was estimated to be 31.9% (95% CI = 26.2 to 37.6) 25 years after hairy cell leukemia diagnosis. Among 10000 hairy cell leukemia patients, a total excess of about 34 cancers, including 21 non-Hodgkin lymphomas, 2 Hodgkin lymphomas, and 7 solid tumors (including 2 thyroid cancers), might be observed per year. Deaths due to solid tumors were not elevated compared with the general population (SMR = 0.9), and there were statistically significant deficits in mortality due to both cardiovascular (SMR = 0.67, 95% CI = 0.56 to 0.80) and cerebrovascular (SMR = 0.61, 95% CI = 0.38 to 0.93) disease. Conclusions Patients with hairy cell leukemia are at increased risk of Hodgkin lymphoma, non-Hodgkin lymphoma, and thyroid cancer. The decrease in lung cancer incidence and smoking-associated vascular mortality may reflect an inverse association of tobacco use with hairy cell leukemia. Future studies should address the roles of immunologic impairment inherent to hairy cell leukemia, treatment modalities, and other factors as codeterminants of morbidity and mortality in hairy cell leukemia survivors. [ABSTRACT FROM AUTHOR]

Hairy cell leukemia (HCL) is a unique chronic lymphoproliferative disorder that can mimic or coexist with other clonal hematologic disorders and has been associated with autoimmune disorders. It should be entertained as an alternative diagnosis in patients with cytopenias being assigned the diagnosis of aplastic anemia, hypoplastic myelodysplastic syndrome, atypical chronic lymphocytic leukemia, B-prolymphocytic leukemia, or idiopathic myelofibrosis. Causative etiology or molecular defects remain unclear, although nonspecific chromosomal and molecular changes have been described. The typical presentation is that of a middle-aged man with an incidental finding of pancytopenia, splenomegaly, and inaspirable bone marrow. Treatment with a purine analogue, cladribine or pentostatin, results in extremely high, durable, overall, and complete response rates, although resistance and relapses do occur. A variant subtype exists and is frequently associated with a poor response. Because of its simplified dosing schedule, cladribine is commonly used as the initial therapy. Treatment of relapsed HCL is dictated by the duration of the preceding remission. Relapsed disease after a prolonged remission can often be successfully retreated with the same initial agent. Resistance in typical HCL is treated with the alternate purine analogue. New agents, such as rituximab and BL22, are actively being evaluated and show promising results in both HCL subtypes. This article uses two patients diagnosed with aplastic anemia and recently seen in consultation at our institution as a springboard to discuss the biology, pathogenesis, clinical presentation, diagnostic evaluation, and treatment options of HCL. [ABSTRACT FROM AUTHOR]

We report the case of a caucasian woman who, between the ages of 49 and 51 years, developed multiple (> 20) basal cell carcinomas (BCC). There was no family history of BCC. No abnormalities in the human homologue of the Drosophila segment polarity gene patched (PTCH), glutathione S-transferases T1 and M1, or cytochrome P450 1A1 were detected by polymerase chain reaction (PCR)-based molecular analysis. There was, however, actinic damage of the skin in sun-exposed areas. The patient was diagnosed as having hairy cell leukaemia (HCL) at the age of 51 years, based upon leucocyte morphology as assessed by light and electron microscopy, tartrate-resistant acid leucocyte phosphatase (TRAP) staining, fluorescence activated cell scanning of peripheral blood leucocytes and bone marrow histology. As the leukaemia slowly progressed over a 3-month period, the patient developed four further BCCs. Given that HCL is characterized by a profound defect in T-cell function, it is conceivable that T-cell immune dysregulation can contribute to the pathogenesis of BCC, possibly enhancing the aetiological effect of ultraviolet irradiation. [ABSTRACT FROM AUTHOR]

The autologous and allogeneic mixed lymphocyte reactions were measured using peripheral blood cells from 13 patients with hairy cell leukaemia (HCL), six of whom had been splenectomized when first studied. T cells from five patients responded to autologous stimulation, and one of these had received splenectomy. Significant alloreactivity was observed in nine patients, of whom three were splenectomized. An absent autologous reaction was associated with ratios of OKT4:OKT8 positive cells < 1.5, and such ratios were more often observed after splenectomy. Non-T cells from 10 of 11 patients stimulated allogeneic normal T cells. The amounts of H LA-DR antigens on hairy cells were similar to those on normal peripheral blood non-T cells. These data suggest that the defects of response in HCL reflect abnormalities at the responder T cell level. Such defects may contribute to the defective host defence frequently observed in HCL. [ABSTRACT FROM AUTHOR]

Mouse-rosette formation was investigated in a variety of leukaemias and lymphomas, and it was found that this phenomenon was restricted to the B lymphocytes of chronic lymphocytic leukaemia and hairy-cell leukaemia. Eighteen of nineteen cases of chronic lymphocytic leukaemia expressed the mouse receptor, but only eight of fifteen cases of hairy-cell leukaemia showed significant mouse rosette formation by peripheral blood cells. A much higher percentage of splenic hairy cells, compared with peripheral blood cells, formed mouse rosettes, but receptor expression was found to be dependent on the surface immunoglobulin (SIg) phenotype. Cases forming mouse rosettes had multiple heavy chain isotypes including IgG on the surface, but the ontogenically more mature SIgG-only cells from other eases failed to form rosettes, whether from peripheral blood or spleen. Cultured hairy cells lost the ability to form mouse rosettes, and receptor expression by peripheral blood hairy cells fluctuated widely in the days following splenectomy. The results suggest that the mouse erythrocyte receptor is an early marker in B cell differentiation and that receptor expression by individual cells may depend on the age of the cell. [ABSTRACT FROM AUTHOR]

A new case of hairy-cell leukaemia (HCL) in which the hairy cells (HCs) formed spontaneous sheep erythrocyte (E) rosettes is described, and this E-rosette formation is shown to be an active process independent of surface immunoglobulin (SIg). Sequential studies with a panel of markers of this and of a case of HCL with T-cell features previously described from this laboratory show that both these cases, at certain times of study, possessed combined T- and B-cell features. Extensive follow-up study revealed wide fluctuations in the surface phenotype of peripheral blood (PB) mononuclear cells, while the total leucocyte count remained stable. At various times, the PB mononuclear cells showed the following phenotypes: E+SIg+yFc+C3-E-SIgyFcC3-, E-SIg-yFC+yFc+C3-, E+SIg-yFc+/-C3- and the significance of these phenotypic changes is discussed. The importance of sequential studies with a panel of markers in the characterization of lymphoproliferative disorders is emphasized. [ABSTRACT FROM AUTHOR]

Neoplastic cell preparations from four patients with clinically and morphologically well-defined leukaemic reticuloendotheliosis (LRF,) were investigated for their capacity to synthesize immunoglobulin in vitro. Neoplastic cells from all cases synthesized immunoglobulin of the same light chain class as expressed at their cell surface. Labelled IgM and IgD were identified in cell lysates while free light chain was the predominant labelled immunoglobulin product in the LRE culture supernatants. The capacity of LRE cells to synthesize immunoglobulin and free light chain was similar to that of neoplastic cells from patients with chronic lymphocytic leukaemia, and provides further evidence for the B-lymphocytc origin of the neoplastic cells in LRE. [ABSTRACT FROM AUTHOR]

By the use of a rosette test employing yeast particles coated with C3 activated by the alternative pathway, we have demonstrated that the hairy cells of leukaemic reticuloendotheliosis (LRE) do not possess a receptor for C3. It is also shown that hairy cells display a consistently lower percentage of rosette formation with OXEAC than with ox EA IgM and this is attributed to varying degrees of steric hindrance of IgM or incomplete coating by complement. Blocking with monomeric IgM confirmed this interpretation. These results are used to reconcile previously conflicting reports concerning the presence or absence of a receptor for C3 on the hairy cells of LRE, anti to suggest that the disease is accompanied by a severe reduction of normal B lymphocytes. [ABSTRACT FROM AUTHOR]

Hairy cells from two cases of leukaemic reticuloendotheliosis' were studied for their enzyme content, adherence to nylon wool columns, phagocytosis, and the presence of surface immunoglobulins and lymphocyte-specific surface antigens. The cells reacted negatively for peroxidase, chloroacetate-esterase. alpha-naphthyl-acetate-esterase and naphthol-AS-acetate-esterase. They did not adhere to nylon wool columns nor did they show significant phagocytosis. Most of the hairy cells were found to be positively labelled for surface immunoglobulins of different classes: μ chain-positive hairy cells were predominant in number. In a homogenate of isolated, washed hairy cells from the spleen of one case only IgM could be detected in significant amounts. With peroxidase-coupled anti-thymocyte IgM most of the hairy cells of both cases showed a ring-like labelling very similar to lymphocytes. whereas monocytes and granulocytes showed no labelling. The data suggest that hairy cells are closely related to lymphatic cells of the B-cell type. They exclude with some certains the possibility that hairy cells are directly derived from cells of the myeloid system, particularly monocytes or from classical reticulum cells of the lymphatic tissue. [ABSTRACT FROM AUTHOR]

The present paper describes two new MoAbs, GHI/75 and VMP55, which were raised against a glycoprotein enriched lysate of hairy cell leukaemia. These antibodies recognized a new antigen or 72 kD (unreduced) and 83 kD (reduced) molecular weight. GHI/75 and VMP55 gave very strong staining of plasma cells, moderate labelling of circulating B cells but only weak staining of monocytes., some tissue macrophages and lymphoid cells. Neither antibody reacted with neutrophils or any non-haematopoietic cells. Both antibodies, however, strongly labelled the tumour cells in hairy cell leukaemia, multiple mycloma, plasmacytoma and lymphoplasmacytic lymphomas. No staining was seen of the neoplaslic cells in Hodgkin's disease, myctoid leukaemia or T cell lymphomas. The two antibodies. GHI/75 and VMP55. may be of value in the differential diagnosis of hairy cell leukaemias and plasma cell neoplasms. In addition, the ease with which their antigen can be purified provides the possibility for a detailed study of this molecule. [ABSTRACT FROM AUTHOR]

In the majority of 188 non-Hodgkin lymphomas (NHL) investigated in this study, we found a simultaneous expression of the receptors for c3b and c3d (CR1 & CR2; CCcorr=0.69, P <0.0005). An analysis of the different histological entities of the Kiel classification revealed that this coexpression was most pronounced for germinal center-derived (CCcorr = 0.63, P=0.0004) and immunocytic NHL (CCcorr = 0-86. P=0.0024), whereas in chronic lymphocytic leukaemias there tended to be a more heterogeneotis pattern of complement receptor (CR) expression (CCcorr =0.29, P > 0.10 ) . In contrast to these NHL of mid B cell stage, most of the NHL of early (i.e. acute lymphocytic leukaemia, lymphoblastic NHL) and late B cell stage (i.e. hairy cell leukaemia, immunoblastic NHL, multiple myeloma) did not express either of these receptors. CR positive NHL often showed a follicular arrangement of the neoplastic cells and had higher numbers of T helper/inducer (T4) lymphocytes (PCRI < 0.00005, PCR2 <0.05). Some cases of mid B cell NHL and all cases of hairy cell leukaemia reacted with antibodies against CR3 (i.e. the ic3b receptor). [ABSTRACT FROM AUTHOR]

A phenotypic and functional analysis of the circulating natural killer (NK) cell population was carried out in a series of patients with hairy ceil leukaemia (HCL). The overall mean NK activity of both the mononuclear and T cell fractions was reduced compared to that of normal controls (466 lytic units (lu) v 573 lu and 226 lu v 381 lu, respectively), though this difference did not reach statistical significance (P < 0.05), individual analysis of the data showed that in five out of 15 and in seven out of 16 cases the K562 killing by the mononuclear and T cells respectively was below the lowest s.d. limit for normal subjects. This reduced NK function was associated with a decreased ability of the effector cells to bind the target. The NK response lo exogenous human leucocyte interferon was also generally depressed in cases with a low basal NK activity. The functional studies were complemented with the evaluation of the membrane expression of NK associated antigens. The percentage of circulating T cells recognized by the monoclonal antibody (MoAb) Leu-7 was significant higher (P <0.001) in HCL than in normal blood (25.2% ± 10.2 v 11.9 ± 5.9 s.d.). However, the reactivity with two other NK-related MoAb, Leu-11 and AB8.28, was significantly lower (7.1% ± 6.9 and 9.8% ± 8.5; P <0.002) than with Leu-7 and moderately reduced compared with that of normal circulating T cells(11.7% +-6.l & 12%,+ 5.5). These findings suggest that in a proportion of patients with HCL there is an Impairment of the NK compartment, which may contribute towards the occurrence of the infective complications which are the primary cause of death in this disease. [ABSTRACT FROM AUTHOR]

Neoplastic B cells from two patients with hyperleucocytic hairy cell leukaemia (HCL) and 19 patients with chronic lymphocytic leukaemia of B cell Type (B-CLL) were investigated to examine the mitogenic responses to the F(ab')2 fraction of anti-human immunoglobulins (anti-Igs) and Staphylococcus aureus Cowan I (STA). Neoplastic cells from both HCL patients lacked surface Tac antigen. Mononuclear cells from the two HCL patients strongly responded to both anti-Igs and STA as measured by 3H-thymidine incorporation in vitro. Although the mononuclear cells from two patients with B-CLL showed high response to STA. cells from none of the patients with B-CLL responded to anti-Igs. Mononuclear cells as well as T-cell-depleted fractions from the two HCL patients showed a strong proliferative response by anti γ chain antibody (anti-γ) and the mononuclear cells from one of the patients were also induced to proliferate by anti-δ, whereas those from normal subjects responded only to a high concentration of anti-μ. Based on the difference in reactivity to anti-Ig, it is suggested that the HCL cells in this study originate from a subset equivalent to 'memory' B cells, whereas the B-CLL cells originate from a subset equivalent to 'virgin' B cells. [ABSTRACT FROM AUTHOR]

Blood from patients with hairy cell leukaemia (HCL) was used to investigate subpopulations of the non-specific activated lymphocyte killer (ALK) cells generated in mixed lymphocyte culture (MLC). Mononuclear cells from four of live patients with HCL had decreased natural killer (NK) cell activity and., of these, all showed a decrease in ALK cell activity against K-562 target cells (NK like cells), but three had normal levels of ALK cells able to kill melanoma cells. One patient who had received splenectomy had normal NK cell activity, and in MLC his cells generated normal levels of both subpopulations of ALK cells. The results support the hypothesis of separate subsets of ALK cells: NK like cells with NK cell precursors and which preferentially lyse the K-562 target cell and a second separate population which arises independent of NK cell precursors and which has strong cytolytic activity against an NK insensitive melanoma cell line. [ABSTRACT FROM AUTHOR]

We describe a 35-year-old woman who presented with proteinuria and microscopic haematuria. Blood tests revealed a low C3 complement level, with no evidence of cryoglobulin. Renal biopsy showed a Type 1 membranoproliferative glomerulonephritis (MPGN) with isolated C3 deposits on immunofluorescence study. Bone marrow aspirate, done for monocytopenia, was consistent with a diagnosis of hairy cell leukaemia (HCL). Both haematological and nephrological diseases completely responded to treatment with cladribine, strongly suggesting that the renal disease was a paraneoplastic syndrome. To our knowledge, this is the first report of a non-cryoglobulinaemic MPGN associated to HCL. [ABSTRACT FROM PUBLISHER]

Leukaemic skin infiltration is uncommon in hairy-cell leukaemia (HCL), a neoplasm characterized by the presence of uniform mononuclear cells with cytoplasmic projections in the blood, bone marrow and spleen. A case is reported in which leukaemia cutis was a transient phenomenon, appearing soon after the onset of a continuous pyrexia associated with marked systemic upset which was subsequently shown to be due to pulmonary tuberculosis. [ABSTRACT FROM AUTHOR]

An eruptive histiocytosis was the presenting feature in a patient who developed acute myelomonocytic leukaemia. The differential diagnosis of the skin lesions is discussed and in the light of a recent similar report we propose that the two disorders are associated. [ABSTRACT FROM AUTHOR]

A case of hairy-cell leukaemia presenting with pyoderma gangrenosum is reported. Alpha interferon did not improve the pyoderma. [ABSTRACT FROM AUTHOR]

This article presents the case study of onset of psoriasis associated with interferon therapy in a patient with hairy cell leukaemia. This patient, an Anglican priest, was diagnosed as having hairy cell leukaemia in March 1983 and a few months later underwent therapeutic splenectomy, Post-operatively, his blood count revealed a persistent neutropenia and the presence of a number of atypical lymphocytes. He was successfully treated with Haelan C cream. Interferons commonly inhibit the growth of keratinocytes in culture and promote terminal differentiation. Hence α and β interferons have been proposed as possible treatments for psoriasis.

A letter to the editor is presented in response to the article "An Assessment of the Usefulness of Immunohistochemical Stains in the Diagnosis of Hairy Cell Leukemia," by M. J. Sherman etal in the 2011 issue.

This section presents abstracts on topics related to scleroderma including a case of paraneoplastic scleroderma related to hairy cell leukemia, weakness of respiratory muscle associated with systemic sclerosis and the cardiac and pulmonary complications of scleroderma.