Aberrant immunophenotype

Acute myeloid leukaemia (AML) is a highly heterogeneous disease, exhibiting diverse subtypes according to the characteristics of tumour cells. The immunophenotype is one of the aspects acquired routinely through flow cytometry in the diagnosis of AML. Here, we characterized the antigen expression in paediatric AML cases across both morphological and molecular genetic subgroups. We discovered a subgroup of patients with unfavourable prognosis that can be immunologically characterized, irrespective of morphological FAB results or genetic aberrations...

Cytogenetic karyotypes such as t(4; 14), del(17p), t(14; 16), t(14; 20), and TP53 mutations are associated with high-risk multiple-myeloma (MM) and indicate poor prognosis. Therefore, cytogenetic testing is extremely important for determining prognosis of MM. However, the aberrant karyotypes reported in the current literature are incomplete. The cytogenetic karyotype 17p gain has not received widespread attention, and its relationship with MM prognosis is unknown; additionally, the prognosis of 17p gain associated with t(4; 14) has not been studied in depth...

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (TH 2) cells with co-expression of TCF7 and LEF1, and features of chronic activation. These cells, which we termed TH 2-multipotent progenitors (TH 2-MPP) could self-renew and differentiate into cytokine-producing effector cells, regulatory T (Treg ) cells and follicular helper T (TFH ) cells...

OBJECTIVES: Given that method validation is mandatory for compliance with the International Organization for Standardization (ISO) 15,189 standard requirements, we evaluated the analytical performance of the AQUIOS CL system (Beckman Coulter) and compared it with two bead-based flow cytometry (FCM) protocols (BD FACSCAntoTM- II and Beckman Coulter DxFLEX). There are no comparative literature data on standardized protocols for counting lymphocyte subsets on the new-generation cytometer DxFLEX...

The lack of expression of terminal deoxynucleotidyl transferase (TdT) is frequently associated with KMT2A-rearranged subtype of pediatric acute lymphoblastic leukemia (ALL). However, this association has not been investigated extensively in the Asian population. A retrospective analysis of TdT expression in pediatric B-cell ALL (B-ALL) was performed in patients treated using the Taiwan Pediatric Oncology Group (TPOG) ALL 2002 and 2013 protocols. Among the 331 patients with B-ALL, 12 patients showed TdT negativity at initial diagnosis...

ALK-positive ( +) large B cell lymphoma (ALK + LBCL) is a rare distinct subtype of diffuse large B cell lymphoma presenting with high stage and aggressive behavior. Although B cell markers such as CD20, CD19, and CD22 are generally negative, plasmacytic markers including CD138, CD38, and MUM1 are positive. T cell markers are negative with rare exceptions. We report an unusual case of ALK1 + LBCL in a 58-year-old man with partial expression of CD3 without other T cell antigen expression...

There is no shortage of comprehensive review articles on bone and soft tissue pathology, almost always representing a regurgitation of the literature with little to no guidance on personal "best practices," recommended applications of ancillary testing, and alternative points of view. This special issue of Human Pathology uniquely unites evidence-based medicine, where appropriate, with the collective personal experiences of a wide range of accomplished pathologists from varying institutions and backgrounds, addressing problematic areas, updated and sometimes imperfect classification systems, and their personal preferences for cost-effectively incorporating ancillary testing...

DISEASE OVERVIEW: The eosinophilias encompass a broad range of non-hematologic (secondary or reactive) and hematologic (primary or clonal) disorders with the potential for end-organ damage. DIAGNOSIS: Hypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1.5 × 109 /L, and may be associated with tissue damage. After the exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests...

The diagnosis of lymphoma is based on histopathological and immunophenotypical features. CD5 and CD10 are traditionally considered a T-cell antigen and a germinal center B-cell antigen, respectively. It is very unusual for a low-grade B-cell lymphoma (BCL) to co-express CD5 and CD10. Although the biologic basis or clinical significance of such co-expression is unclear, this rare event may pose a significant diagnostic challenge. Here, we report a case of a 63-year-old male presenting with bilateral cervical lymphadenopathy and lymphocytosis...

GATA3 is a transcription factor involved in T-cell maturation and has been previously shown to be aberrantly overexpressed in malignant Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). However, the immunophenotypes of the cell types expressing GATA3 have not been precisely characterized so far in cHL tissues. In this single-center retrospective cohort study we analyzed the expression patterns of GATA3 alone and in combination with B, T, NK or macrophage-associated markers in 73 cases with newly diagnosed cHL and investigated for a possible correlation with clinical and laboratory parameters...

Bone and soft tissue tumors (BST) are a highly heterogeneous group largely classified by their line of differentiation, based on their resemblance to their normal counterpart in adult tissue. Yet, rendering a specific diagnosis can be challenging, primarily due to their rarity and overlapping histopathologic features or clinical presentations. Over the past few decades, seemingly histogenetic-specific gene fusions/translocations and amplifications have been discovered, aiding in a more nuanced classification, leading to well-established objective diagnostic criteria and the development of specific surrogate ancillary tests targeting these genetic aberrations (e...

Mantle cell lymphoma (MCL) constitutes 3%-10% of non-Hodgkin lymphoma and is characterized by t (11:14)(q13;q32). The common presentation is generalized lymphadenopathy with weight loss, infrequently night sweats, and fever. Among histological subtypes of MCL, the blastoid variant of MCL constitutes 10%-15% of all the cases. It is challenging to diagnose the blastoid variant of MCL based on its morphology alone as it mimics large B-cell lymphoma. Hence, the immunophenotyping and molecular studies aid in its correct diagnosis...

Persistent polyclonal B-cell lymphocytosis is a rare disease with chronic lymphocytosis of polyclonal origin, which is more frequent in mostly asymptomatic middle-aged female smokers. The hallmark of this entity is the presence of bilobed/binucleated B lymphocytes, which are polyclonal as demonstrated by immunophenotyping; an elevated IgM level is common. This disease shows, in most cases, an indolent course over many years and, although controversial, it may rarely convert to malignant lymphoma. In addition to smoking, a genetic predisposition for persistent polyclonal B-cell lymphocytosis is likely...

Two different systems exist for subclassification of acute myeloid leukemia (AML); the World Health Organization (WHO) Classification and the International Consensus Classification (ICC) of myeloid malignancies. The two systems differ in their classification of AML defined by recurrent chromosomal abnormalities. One difference is that the ICC classification defines an AML subset that includes 12 different genetic abnormalities that occur in less than 4% of AML patients. These subtypes exhibit distinct clinical traits and are associated with treatment outcomes, but detailed description of these entities is not easily available and is not described in detail even in the ICC...

SMARCA4 mutation has emerged as a marker of poor prognosis in lung cancer and has potential predictive value in cancer treatment, but recommendations for which patients require its investigation are lacking. We comprehensively studied SMARCA4 alterations and the clinicopathological significance in a large cohort of immunohistochemically-subtyped non-small cell lung cancer (NSCLC). A total of 1416 patients was studied for the presence of SMARCA4 deficiency by immunohistochemistry (IHC). Thereafter, comprehensive sequencing of tumours was performed for 397 of these patients to study the mutational spectrum of SWI/SNF and SMARCA4 aberrations...

Primary pulmonary myxoid sarcoma (PPMS) and thoracic angiomatoid fibrous histiocytoma (AFH) are rare neoplasms with EWSR1 fusions and overlapping morphology. Both tumor types often show epithelial membrane antigen expression, but AFH characteristically co-expresses desmin. We encountered a case of PPMS with the unexpected finding of patchy, strong anaplastic lymphoma kinase (ALK) (previously reported in AFH) and synaptophysin expression. We evaluated a cohort of PPMS and thoracic AFH with systematic morphologic comparison and surveyed for aberrant expression of ALK and synaptophysin...

Flow cytometry-based immunophenotyping is a mainstay of diagnostics in acute myeloid leukaemia (AML). Aberrant CD56 and T-cell antigen expression is observed in a fraction subset of AML cases, but the clinical relevance remains incompletely understood. Here, we retrospectively investigated the association of CD56 and T-cell marker expression with disease-specific characteristics and outcome of 324 AML patients who received intensive induction therapy at our centre between 2011 and 2019. We found that CD2 expression was associated with abnormal non-complex karyotype, NPM1 wild-type status and TP53 mutation...

OBJECTIVES: Flow cytometric immunophenotyping (FCI) is a fast and sensitive method for characterizing hematolymphoid neoplasms. It is not widely used in the workup of systemic mastocytosis (SM), in part because of the technical challenges and in part because the utility of FCI in assessing mast cells is not well understood. The objectives of this study were to assess the diagnostic utility of FCI in establishing a diagnosis of SM and distinguishing SM from nonneoplastic mast cells and to examine the immunophenotypic findings among SM subtypes...

Immune checkpoints (CTLA4 & PD-1) are inhibitory pathways that block aberrant immune activity and maintain self-tolerance. Tumors co-opt these checkpoints to avoid immune destruction. Immune checkpoint inhibitors (ICIs) activate immune cells and restore their tumoricidal potential, making them highly efficacious cancer therapies. However, immunotolerant organs such as the liver depend on these tolerogenic mechanisms, and their disruption with ICI use can trigger the unintended side effect of hepatotoxicity termed immune-mediated liver injury from ICIs (ILICI)...

This study describes a rare case of Burkitt lymphoma with aberrant expression of cytoplasmic terminal deoxynucleotidyl transferase (TdT). Flow cytometry demonstrated a predominantly mature B cell immunophenotype as expected for Burkitt lymphoma, however, the immature marker TdT was also expressed. Immunohistochemistry showed that TdT was localized to the cytoplasm, with absent nuclear localization. The patient received standard intensive chemotherapy for Burkitt lymphoma and has remained in remission for nine years...