Κυριακή 24 Νοεμβρίου 2019

Warthin–Finkeldey-like cells in a lymph node from a child with Li-Fraumeni syndrome

Evolving myelodysplastic syndrome in an HIV patient with history of anal cancer and chemotherapy

Abstract

The incidence of therapy-related myelodysplastic syndromes (t-MDS) has been increasing with the widespread use of highly active antiretroviral therapy (HAART) therapy for HIV and chemotherapy for AIDS-related cancers. The classical dysplastic features in the granulocytes and megakaryocytes may not be easily appreciated. The most reliable distinguishing feature between the hematopoietic dysplasia of t-MDS and that of HIV infection rests on the identification of MDS-related cytogenetic aberrations. Here we report a patient with well-controlled HIV and history of chemotherapy for invasive anal squamous cell carcinoma who developed high-risk t-MDS with complex chromosome abnormalities. Our study emphasizes the importance of diagnosis of MDS in HIV-infected patients, even in the absence of dysplasia, if there are typical cytogenetics changes of MDS. Therefore, the early diagnosis and intervention of t-MDS in HIV-positive patients are critical in the treatment of this aggressiveness disease.

Dual antibody immunohistochemistry: an efficient and sensitive tool for the detection of residual disease in chronic lymphocytic leukemia

Abstract

Highly effective treatments for chronic lymphocytic leukemia (CLL) have the potential to reduce significant tumor burden to single cells and therefore require sensitive tools to assess for minimal residual disease (MRD) in bone marrow (BM) biopsies. Flow cytometry (FC) is the current gold standard for detection of MRD, but requires a specialized facility, specific antibody panels, collecting hundreds of thousands-to-millions of cells, and personnel with expertise in the analysis and interpretation of FC MRD data, which may not be feasible in many small laboratories. Dual-antibody immunohistochemistry (DA-IHC) can identify abnormal populations better than morphology alone, but its correlation with FC assessment is not known. Our aims are to characterize the efficacy of DA-IHC in assessing BM samples post-treatment and to compare results with FC to evaluate for residual disease in CLL. We collected 2-year post-therapy data from 33 CLL patients on two treatment protocols, chemoimmunotherapy (CIT) and single agent ibrutinib (IB), as well as BMs from 10 healthy volunteers as morphologic controls. BM biopsy specimens were examined for the presence or absence of CLL based on morphologic evidence of lymphoid infiltration and aberrant co-expression of CD5 and PAX5 DA-IHC. FC using a standard CLL antibody panel was performed in parallel. All IB patients had residual disease detected by DA-IHC and FC, although five patients (22%) were morphologically negative by routine hematoxylin and eosin (H&E) stain. Those without overt morphologic evidence of disease showed DA-IHC-positive interstitial single cells and were positive for residual disease by FC. The assessments by DA-IHC and FC were significantly correlated (p = 0.004). Four patients (40%) treated with CIT were morphologically negative by H&E, and two of these had no detectable CLL by either DA-IHC or FC. The other two patients had low-level disease detected by both DA-IHC and FC. The MRD levels identified by DA-IHC were correlated with those by FC (p < 0.0001). We characterized the efficacy of DA-IHC in assessing CLL post-treatment and found assessments by DA-IHC and FC were statistically significant in both the IB- and CIT-treated patients. These findings suggest DA-IHC could accurately detect residual disease in cases lacking morphologic evidence by H&E alone. DA-IHC may be a useful tool in current practice as another sensitive and efficient method to assess for MRD in CLL.

Transition from morphologic diagnosis to immunophenotypic diagnosis of acute leukemia—experience of establishing a new flow cytometry laboratory

Abstract

In this era of targeted therapy, traditional reporting of acute leukemia by morphology using French-American-British (FAB) system of classification has limited uses due to lack of standardization and use in risk stratification. Flow cytometry (FCM), cytogenetics, and molecular testing drive the therapeutic decision. However, the lack of high-end testing at all health care strata leaves a general pathologist in a quandary. This study aimed at documenting the leukemia-associated immunophenotype (LAIP) specific for morphologic (FAB) subclasses of acute leukemia (AL). A retrospective case record-based study was carried out including 100 cases of de novo acute leukemia over 1 year to study the association of FCM immunophenotype profile with morphologic FAB classification of acute leukemia. Fourteen cases (14%) were diagnosed as acute leukemia—unclassified by morphology which were accurately classified by FCM into B cell acute lymphoblastic leukemia (ALL) (6), T cell ALL (3), acute myeloid leukemia (AML) (4), and mixed phenotype acute leukemia (MPAL) (1). FCM also differentiated Pre B cell ALL from Burkitt lymphoma, subclassified T cell ALL into thymic categories, diagnosed MPAL, and identified blasts with monocytic differentiation which were not detected by morphology. Although morphologic FAB diagnosis is still widely used to classify acute leukemia, it is imperative that FCM should be used for accurate leukemia diagnosis.

Enteropathy associated T cell lymphoma with Reed-Sternberg-like cells of B cell phenotype and genotype associated with Epstein-Barr virus infection

Abstract

EBV-positive B cell proliferations have been recognized in the setting of some T cell lymphomas. These B cell proliferations often differ to varying degrees in morphology and immunophenotype with a great proportion being Epstein-Barr virus (EBV)-positive with Reed-Sternberg (RS)-like morphology. We describe a case of a 76-year-old Caucasian male who presented to the Emergency Department (ED) with weight loss, abdominal pain, and multiple episodes of vomiting and diarrhea. He underwent a laparotomy with an intraluminal mass seen in the cecum. Histology showed atypical intermediate- to large-sized cells involving the full thickness of the bowel wall with numerous mitotic figures and apoptotic bodies. The adjacent uninvolved mucosa demonstrated villous blunting, increased intraepithelial lymphocytes, crypt elongation, and lamina propria plasmacytosis, consistent with the celiac enteropathy. Rare large transformed cells morphologically consistent with Reed-Sternberg cells (RS cells) were also identified in the mesenteric lymph nodes. Immunophenotyping showed the intermediate- to large-sized cells to be of T cell origin with strongly CD3, CD45, and TIA-1 positive; moderately positive for CD5; and variably positive for CD2, CD25, CD57, perforin, and granzyme B, with an aberrant loss of CD7. The large cells were moderately positive for PAX-5, CD79a, CD20, CD30, and MUM1. They also were positive for EBV latent membrane protein (EBV-LMP) and Epstein-Barr virus-encoded small RNA (EBER). Based on morphology and immunoprofile, a diagnosis of enteropathy associated T cell lymphoma (EATL) with Reed-Sternberg-like cells associated with EBV virus infection was made. This is a rare phenomenon; the presence of large B cell proliferations in EATL, to our knowledge, is yet to be reported.

Primary pulmonary extranodal NK/T cell lymphoma of an elderly adult: a case report and literature review

Abstract

Extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type, is rare and aggressive and often involves the nose, nasopharynx, and upper aerodigestive tract. The non-nasal type can affect the skin, salivary glands, gut, testes, brain, salivary glands, and other sites. Primary ENKTCL of the lung is rare. Here, we report a 68-year-old non-smoking female who presented with fever, dry cough, and night sweats. The chest image showed lung consolidation in the right lower lung field. Pulmonary biopsy showed diffuse abnormal lymphocyte infiltrate in the necrotic exudate. Immunohistochemical data indicated that the tumour cells were positive for CD56, granzyme B, CD3, and TIA. Using in situ hybridization, Epstein–Barr virus-encoded ribonucleic acid (EBER) was detected. There was no evidence to indicate extrathoracic lymphoma involvement. Primary pulmonary ENKTCL was therefore diagnosed. The patient underwent chemotherapy using the P-GEMOX regimen (pegaspargase, gemcitabine, and oxaliplatin) and is still alive.

Classification of malignant lymphoma subtypes in Korean patients: a report of the 4th nationwide study

Abstract

To determine the relative frequency and change of malignant lymphoma in Korea according to the 4th World Health Organization (WHO) classification and compare with previous reports. Between 2015 and 2016, 7737 new patients with malignant lymphoma were enrolled from 31 institutes, with their clinicopathologic information obtained, and evaluated for the relative frequency of lymphoma subtypes. The relative frequency of non-Hodgkin lymphoma (NHL) was 94.8%, and that of Hodgkin lymphoma (HL) was 5.2%. B cell lymphomas accounted for 83.1% of all NHLs; T/natural killer (NK) cell lymphomas, 16.4%; and immunodeficiency-associated lymphoproliferative disorders, 0.5%. The most common NHL subtypes were diffuse large B cell (41.5%), extranodal marginal zone (MALT, 19.8%), follicular (7.5%), NK/ T cell (4.2%), and peripheral T cell lymphomas, not otherwise specific (PTCL, NOS, 3.4%). Nodular sclerosis was the predominant HL subtype (48.5%), followed by mixed cellularity (28.7%), lymphocyte-rich (6.8%), lymphocyte-depleted (1.5%), lymphocyte-predominant (2.8%), and unclassified HL (11.8%). Compared with a previous report, increased B cell lymphomas (77.6–83.1%) and slightly decreased NK/T cell lymphomas and PTCL were observed. The incidence of follicular lymphoma increased by more than 2.5-fold (2.9–7.5%). Incidence rates of newly diagnosed lymphomas were lower for HL and higher for extranodal NHL, MALT, and nasal type NK/T cell lymphomas in Korea than those in Western countries. A slight increase in the relative frequency of B cell lymphoma and a prominent increase in follicular lymphoma may be attributed to refined diagnostic criteria and Westernized disease patterns.

A case of an unusual lineage switch in late relapse ALL—is it actually a secondary leukemia?

Abstract

Acute lymphoblastic leukemia (ALL) is a malignant disease of lymphoid precursors. According to immunophenotype, it is further subdivided into precursor B cell ALL and precursor T cell ALL, with precursor B cell ALL being much more common both in children and adults. Lineage switch from one lymphoid lineage to another during the course of the disease is extremely rarely reported. Here, we describe a case of a child who initially presented as a precursor B-ALL but 15 years later and after two successfully treated relapses of the original ALL presented with early T cell precursor leukemia. Although it was considered as a relapse, it could be interpreted as a case of secondary leukemia, which can be explained as a consequence of treatment as well as a constitutional feature of an individual. Also, it draws attention to the possibility that hematopoietic cells, and in that context also leukemic cells, are much more plastic and capable of reprogramming than previously thought.

Survey of ERG expression in normal bone marrow and myeloid neoplasms

Abstract

The immunohistochemical stain ERG is a useful diagnostic marker for leukemia cutis. Translocations involving the ERG gene have been identified in acute myeloid leukemia (AML) and it plays critical roles in differentiation of hematopoietic stem cells. However, little is known about ERG expression in the bone marrow or in myeloid neoplasms. The aim of this study is to characterize ERG expression in normal bone marrow specimens, and those with various myeloid neoplasms. We performed immunohistochemical studies assessing ERG expression in bone marrow biopsies obtained over a 1-year period, in which myeloperoxidase (MPO) was used to assess granulocyte populations. Twenty-eight bone marrow biopsies (6 normal, 12 with acute myeloid leukemia (AML), 6 with myeloproliferative neoplasms (MPN), and 4 with myelodysplastic/MPN) were identified. Strong nuclear ERG staining was present within the granulocytes and precursors in near complete concordance with MPO in 26/28 (93%) cases. Fifty-eight percent of AML cases showed more staining for ERG than MPO in the leukemic cells. ERG can be useful for assessing granulocyte populations in bone marrow biopsies, and in many instances of AML, stained a proportion of myeloblasts.

Mummified cells in nodular lymphocyte predominant Hodgkin lymphoma

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