Hematolymphoid Neoplasms in Serous Effusions: Morphological Spectrum, Distribution, and Role of Ancillary Techniques—A Retrospective Analysis of 75 cases

Introduction Involvement of body fluids can occur at the time of diagnosis or during the disease course of hematolymphoid neoplasms. Cytodiagnosis of malignant effusion is important in effective clinical management. Objectives (1) The aims of the study were to determine the frequency of distribution of various hematolymphoid neoplasms involving body fluids, (2) to study the morphology of hematolymphoid neoplasms in fluids, and (3) to assess the role of ancillary techniques in the diagnosis. Materials and Methods In this retrospective study, all cases of hematolymphoid neoplasms involving body fluids diagnosed from January 2016 to December 2018 were evaluated. Results During the 3-year period, there were 75 cases of hematological malignancies involving body fluids. These included 48 male patients and 27 female patients. Pleural fluid was involved in majority of cases (56 cases; 74.67%), followed by ascitic fluid (17 cases; 22.67%), and pericardial fluid (2 cases; 2.67%). High cellularity, monotonous population of cells, high nuclear-cytoplasmic (N/C) ratio, indentation/irregularity of nuclear membrane, immature chromatin/irregular clumping of chromatin, increased mitosis, and karyorrhexis were the key features which helped to differentiate between reactive and neoplastic processes. There were 35 cases of B-cell neoplasms, 33 cases of T-cell neoplasms, and seven cases of myeloid neoplasms involving body cavity fluids. T-lymphoblastic lymphoma was the most common subtype (29 cases; 38.7%), followed by diffuse large B-cell lymphoma (DLBCL) (12 cases; 16%). In 53 cases, effusion was present in the initial presentation itself. Initial diagnosis was made in effusion cytology in 25 cases (33.33% of the total), with the help of flow cytometry in 20 cases, and immunohistochemistry (IHC) in cell blocks in five cases. Conclusion Diagnosis of hematolymphoid neoplasms in body fluids based on correlation with clinical details, critical evaluation of cytology findings, and comparison with previous diagnosis along with the judicious use of ancillary techniques helps in deciding an early treatment plan.

Diagnosis and treatment of mixed phenotype (T-myeloid/lymphoid) acute leukemia with novel ETV6-FGFR2 rearrangement

Key Points Myeloid/lymphoid neoplasms with eosinophilia are driven by aberrant tyrosine kinases in pluripotent cells and display variable phenotypes. FGFR-driven hematolymphoid neoplasms are targetable by TKI inhibitors such as ponatinib; studies of specific FGFR inhibitors are ongoing.

Development of an algorithm for the identification of leukemic hematolymphoid neoplasms in Primary Care patients

BackgroundDiagnosis of hematolymphoid neoplasm (HLN) requires different technologies which are performed on a patient basis instead of per protocol. We hypothesize that integration of hematimetric and cytological analysis along with multiparametric flow cytometry (MFC) provides a framework to evaluate peripheral blood (PB) samples from Primary Care.MethodsSamples from patients with persistent (>3 months) lymphocytosis (>5 × 109/L) and/or monocytosis (>109/L) or the presence of atypical and/or blast cells upon the smear review were analyzed by MFC concurrent to cytological analysis. MFC studies were carried out following standardized procedures.ResultsIn a 3-year period, smear review and MFC were performed simultaneously in 350 samples, demonstrating HLN in 194 cases (55.4%). In 156 cases, reactive cell populations were found. The combination of age, absolute lymphocyte count (ALC), hemoglobin and platelets provided the best correlation with MFC for the presence of a chronic lymphoproliferative disorder (CLPD) in lymphocytosis [area under the curve (AUC) 0.891, p < 0.05]. A model evaluating the probability of CLPD has been proposed and validated in an independent cohort.ConclusionsA strategy to perform MFC studies following standardized procedures has proven to be useful to evaluate samples from patients in Primary Care centers for HLN diagnosis or reactive conditions, providing a sensitive and rapid clinical orientation and avoiding unnecessary consultations in routine clinical practice. The probability for the presence of CLPD in PB can be calculated and help guide decision-making regarding further testing.

Hematolymphoid Neoplasms Rarely Mimic Undifferentiated Pleomorphic Sarcoma of Soft Tissue

Context.— Undifferentiated pleomorphic sarcoma (UPS) of soft tissue is defined as a sarcoma with no recognizable line of differentiation. During the past few decades, advances in ancillary studies and review of prior UPS diagnoses have narrowed the category of UPS by excluding more-specific malignancies. However, few of those studies have specifically targeted pleomorphic hematolymphoid neoplasms. Objective.— To determine what fraction of UPS cases are misclassified pleomorphic hematolymphoid neoplasms, such as anaplastic large cell lymphoma, diffuse large B-cell lymphoma, histiocytic sarcoma (HS), myeloid sarcoma, and follicular dendritic cell sarcoma. Design.— Sixty-one UPS cases were screened by tissue microarray and an immunostain panel with subsequent analysis on whole block sections for suspicious cases. Results.— Five of 61 tumors (8%) were suggestive of HS based on the screening panel and were further evaluated with additional immunostains (PU.1, CD45, CD163) using whole sections. The 5 candidate HS cases were only focally positive for at most one stain with most staining in smaller, less-pleomorphic cells. Ultimately, no UPS met criteria for anaplastic large cell lymphoma, diffuse large B-cell lymphoma, myeloid sarcoma, follicular dendritic cell sarcoma, or HS. Conclusions.— Our results suggest that a UPS of somatic soft tissue is unlikely to represent a misclassified hematopoietic malignancy. Exclusion of HS is most challenging, but immunostaining for PU.1, a nuclear transcription factor, may be easier to interpret in this context.

A Case of Histiocytic Sarcoma Arising from Mycosis Fungoides

Histiocytic sarcoma (HS) is an uncommon malignant neoplasm arising from mature histiocytes and most commonly characterized by the immunophenotypic expression of CD68, CD163, or lysozyme. Although rare, HS arising as a second primary malignancy following hematolymphoid neoplasms has been reported. To our knowledge, this is the first reported case of HS occurring as a second primary malignancy in a patient with mycosis fungoides (MF), with the retained immunophenotype markers CD30 and CD4.

Germline Predisposition to Hematolymphoid Neoplasia

Objectives The 2017 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review clinical cases with germline predisposition to hematolymphoid neoplasms. Methods The Workshop Panel reviewed 51 cases with germline mutations and rendered consensus diagnoses. Of these, six cases were presented at the meeting by the submitting pathologists. Results The cases submitted to the session covering germline predisposition included 16 cases with germline GATA2 mutations, 10 cases with germline RUNX1 mutations, two cases with germline CEBPA mutations, two germline TP53 mutations, and one case of germline DDX41 mutation. The most common diagnoses were acute myeloid leukemia (15 cases) and myelodysplastic syndrome (MDS, 14 cases). Conclusions The majority of the submitted neoplasms occurring in patients with germline predisposition were myeloid neoplasms with germline mutations in GATA2 and RUNX1. The presence of a germline predisposition mutation is not sufficient for a diagnosis of a neoplasm until the appearance of standard diagnostic features of a hematolymphoid malignancy manifest: in general, the diagnostic criteria for neoplasms associated with germline predisposition disorders are the same as those for sporadic cases.