Showing papers by "Geraldine S. Pinkus published in 2017"

Cyclin D1 Is Expressed in Neoplastic Cells of Langerhans Cell Histiocytosis but Not Reactive Langerhans Cell Proliferations.

Abstract: Langerhans cell histiocytosis (LCH) is characterized by frequent activating mutations involving the mitogen-activated protein kinase (MAPK) pathway. Therefore, downstream markers of MAPK pathway activation such as cyclin D1 may be useful as novel diagnostic markers of neoplasia in LCH. The goal of this study was to investigate cyclin D1 expression in LCH and reactive Langerhans cell accumulations using immunohistochemistry on archival tissue. All LCH cases tested (39/39) showed cyclin D1 expression in CD1a/Langerin cells. Most cases (22/39; 56%) showed strong cyclin D1 expression in the majority (≥50%) of lesional cells. Only a few cases (6/39; 15%) showed cyclin D1 expression in a small subset (<20%). Nearly all LCH cases (26/27; 96%) showed p-ERK expression by immunohistochemistry, parallel to cyclin D1 expression. CD1a Langerhans cells in all cases of florid dermatopathic lymphadenopathy and normal skin were negative for cyclin D1, as demonstrated by CD1a/cyclin D1 double staining. The majority of skin specimens (14/18; 78%) with dermatitis-related changes did not show cyclin D1 expression in the CD1a epidermal Langerhans cell aggregates. A minority (4/18; 22%) showed weak cyclin D1 staining in a small subset (5% to 10%) of CD1a Langerhans cells. We conclude that cyclin D1 is ubiquitously expressed in LCH, in keeping with the known near universal MAPK activation in this disease. Further, it is not significantly expressed in reactive Langerhans cell proliferations in lymph node or skin. Therefore, cyclin D1 immunohistochemistry may be useful in excluding non-neoplastic mimics of LCH.

Detection of activating MAP2K1 mutations in atypical hairy cell leukemia and hairy cell leukemia variant.

Abstract: Hairy cell leukemia variant (HCLv) is a rare B-cell lymphoproliferative disorder that resembles classical hairy cell leukemia (HCLc) histologically but is immunophenotypically and clinically distin...

GATA1 Is a Sensitive and Specific Nuclear Marker for Erythroid and Megakaryocytic Lineages.

Abstract: Objectives GATA binding factor 1 (GATA1) is a transcription factor essential for erythromegakaryocytic differentiation. Given its function in lineage specification, we sought to evaluate the immunohistochemical profile of GATA1 in normal marrow and acute leukemia and assess the use of GATA1 as a specific erythromegakaryocytic immunohistochemical marker. Methods Immunohistochemical studies for GATA1 expression were performed on bone marrow biopsy specimens to define its role in the evaluation of acute leukemia and other hematologic disorders. Results In normal marrows, intense nuclear reactivity is seen in immature erythroid precursors and megakaryocytes. Weak to moderate nuclear positivity is seen in eosinophils and mast cells. In marrows involved by acute leukemia, blasts of pure erythroleukemia and acute megakaryoblastic leukemia exhibit intense nuclear GATA1 positivity, while blasts of acute myeloid leukemia of other categories are negative. GATA1 is also absent in the blasts of acute lymphoblastic leukemia/lymphoma and in the neoplastic cells of metastatic carcinoma and plasma cell neoplasms. Conclusions Intense GATA1 nuclear expression is a sensitive and specific marker for cells of erythroid and megakaryocytic lineages and is an excellent marker for neoplastic cells of pure erythroleukemia and acute megakaryoblastic leukemia.

JAK2, CALR, MPL and ASXL1 mutational status correlates with distinct histological features in Philadelphia chromosome-negative myeloproliferative neoplasms.

Abstract: Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPN) [essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF)] vary in morphological features, disease presentation, and, most importantly, clinical outcome.[1][1] The World Health Organization (WHO)

Morphological and immunophenotypical features of hairy cell leukaemia involving lymph nodes and extranodal tissues.

Abstract: Aims Hairy cell leukaemia (HCL) is a rare B cell neoplasm that mainly affects bone marrow (BM), peripheral blood (PB) and spleen. Involvement of lymph nodes and extranodal structures is considered infrequent. Herein we describe our institutional experience of nodal (n = 10) and extranodal (n = 3) HCL during a 30-year period. Methods and results Ten patients had prior evidence of HCL within the BM or PB at a median 35.8 months before nodal/extranodal diagnosis (range: Conclusions Although uncommon, HCL should be considered in the differential diagnosis of small B cell neoplasms involving nodal/extranodal sites, given the therapeutic implications. In particular, recent discoveries including detection of the BRAFV600E mutation in nearly all cases of HCL and the availability of an antibody to CD103 for use in paraffin-embedded tissues will facilitate the distinction of HCL from other small B cell lymphomas in the nodal/extranodal setting.

Fingolimod-Associated Intracerebral Lymphoproliferative Disorder.

Abstract: Most epidemiological studies indicate that incidence of cancer in multiple sclerosis patients is lower than general population. However these studies were performed prior to the emergence of disease-modifying therapies (DMTs). The incidence of cancer may be influenced by newer generation DMTs which are immunomodulatory or immunosuppressant. We describe an atypical case of intracerebral plasmacytic lymphoproliferative disorder in a 47 years old patient on fingolimod. As worldwide usage of oral and infusion DMTs increases, heightened clinical suspicion and early recognition of these serious adverse events remain crucial.

Cost‐effective approach to the diagnostic workup of B cell lymphoproliferative disorders via optimal integration of flow cytometric data

Abstract: SummaryIntroduction The workup of lymphoproliferative disorders (LPDs) involves the combined use of flow cytometry (FC) and immunohistochemistry (IHC). This often results in duplicate immunophenotypic testing and adds costs that may not be eligible for reimbursement based on the Medicare National Correct Coding Initiative. We aimed to establish a cost-effective diagnostic algorithm based on initial FC categorization to reduce repetitive immunophenotyping. Methods We retrospectively reviewed 242 cases of suspected LPDs with concurrent FC and IHC testing over a 12-month period. We correlated FC with surgical diagnoses and evaluated the frequency of repeat IHC testing. Results Repetitive immunophenotyping was common; overall, 85% of cases had at least one marker repeated. Concordant cases were significantly less likely to have markers repeated than discordant cases. Of concordant B cell malignancies, 57% represented recurrent disease; however, repeat marker usage was not decreased as compared to new diagnoses. The most frequently repeated markers were CD3, CD5, CD10, and CD20. Conclusions We propose that in concordant cases, CD5 and CD10 should not be repeated by IHC; this would decrease the use of these markers by 80% and 76%, respectively. We developed an algorithmic approach to IHC usage that has improved incorporation of FC data at our institution and may reduce healthcare costs.

A Woman in Her 40s With Headache and New-Onset Seizures.

Abstract: A woman in her 40s with a history of plasma cell leukemia presented with 1 month of intermittent headaches followed by a seizure. Results from laboratory studies were notable for a cerebrospinal fluid opening pressure of 28 mm H2O and 8 white blood cells, including 1 atypical plasma cell. Imaging studies revealed confluent bifrontal white matter fluid-attenuated inversion recovery hyperintensities, as well as a contrast-enhancing sellar lesion. The patient underwent a stereotactic biopsy. The differential diagnosis, pathologic findings, and diagnosis are discussed.