Journal of Hematopathology

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a rare type of lymphoma, which is characterized by distinctive rimming of neoplastic lymphocytes surrounding individual adipocytes in subcutaneous tissue. SPTCL is confined to subcutis and dissemination of SPTCL to extracutaneous sites is extremely rare, if present at all. Here we present a case of SPTCL with mesenteric involvement. The patient initially presented with a solitary skin lesion at the lower extremity. A few months later, he developed new skin lesions at the abdominal wall and mesenteric lesions in the abdominal cavity. Biopsy showed SPTCL in subcutaneous tissue with mesenteric involvement. To our knowledge, this is the first case report of pathologically proven dissemination of SPTCL to other sites.

Multiple myeloma (MM) is a neoplasm characterized by proliferation of clonal plasma cells (PCs) and a combination of clinical manifestations. Flow cytometry is an important method for diagnosing and monitoring of MM. Cytogenetic profiling of neoplastic PCs provides important prognostic information. Although stem cell transplantation (SCT) has significantly improved the overall survival of patients with MM, most SCT recipients relapse. We have studied the immunophenotypic and cytogenetic dissimilarities in the neoplastic PCs before SCT and after relapse in patients with initial complete remission, and investigated a possible influence of such dissimilarities on the patients’ survival. We retrospectively reviewed results of flow cytometric studies of bone marrow specimens from 46 patients with MM who underwent SCT, demonstrated a complete initial response, but subsequently relapsed. In nine of these patients, fluorescence in situ hybridization (FISH) studies were performed both pre-SCT and post-relapse. We have shown a significant flow cytometric and cytogenetic diversity of the neoplastic PCs in relapsed MM post-SCT. Such changes were detected in a considerable number of cases (47.8% and 44.4%, respectively). The most frequent cytogenetic changes indicate an emergence of possibly a more aggressive PC clone, known to be associated with worse prognosis and poorer outcome. Our study has demonstrated that the acquisition of immunophenotypic changes predicts worse overall survival.

Primary central nervous system lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma confined to the central nervous system. Diffuse large B cell lymphoma (DLBCL) is the most common subtype, and it follows a much more aggressive course than its systemic counterpart. Differential diagnosis of PCNSL and systemic DLBCL depends on clinical staging, which is expensive and time consuming. Protein kinase C delta (PKCD) is a protein with proapopitotic properties and has a major role in negative selection of B cells in germinal centers, a regulatory function in B cell receptor (BCR) pathway and MHC II expression. Mutations identified in its gene are reported to be unique for PCNSL and not encountered in systemic DLBCL. Our aim is to evaluate immunohistochemical (IHC) expression and the mutation status of PKCD in PCNSLs and systemic DLBCLs in order to find out whether PKCD could be a novel marker that could be used in differential diagnosis of both entities. A total of 43 cases diagnosed with PCNSL, and 43 cases diagnosed with systemic DLBCL were included in the study. Immunohistochemistry for PKCD antibody and Sanger sequencing targeting exon 16 and exon 18 of PKCD gene were performed. Although immunoreactivity for PKCD was observed in all PCNSL and 95.3% of systemic DLBCL cases, strong and diffuse staining was found to be more frequent in PCNSL than systemic diffuse large B cell lymphomas (p < 0.001). However, mutations defined in literature were not encountered in our cohort. While clinical staging is still the primary way for differential diagnosis of PCNSL and systemic DLBCL, the diffuse and strong PKCD expression can be used as a supportive feature for PCNSL diagnosis.

IgG4-related sclerosing disease is a steroid-responsive syndrome of possible autoimmune origin that can manifest with mass-like lesions in a variety of organ sites. Lymph node involvement may clinically mimic malignant lymphoma, Castleman disease, or infectious lymphadenitis; consequently, accurate diagnosis is necessary to exclude other processes and to initiate steroid therapy appropriately. Histologically, a number of relatively nonspecific features have been associated with IgG4-related lymphadenopathy, mainly increased plasma cells in an interfollicular or intra-germinal center pattern. We describe seven lymph node cases with distinctive perifollicular granulomas, in a concentric or crescent-like arrangement, partially or completely encircling lymphoid follicles. This finding was specifically associated with a marked intra-germinal center increase in IgG4-positive plasma cells, as compared to other patterns of nodal granulomas in a series of control cases. We discuss the clinicopathologic features of these cases, including an unusual presentation in a pediatric patient. This study adds to the morphologic spectrum of IgG4-related lymphadenopathy.

We analyzed morphological and immunohistochemical features in 174 aggressive B-cell lymphomas of nodal and extranodal origin. Morphological features included presence or absence of a follicular component and cytologic criteria according to the Kiel classification, whereas immunohistochemical studies included expression of CD10, BCL-2, BCL-6, IRF4/MUM1, HLA-DR, p53, Ki-67 and the assessment of plasmacytoid differentiation. Patients were treated with a CHOP-like regimen. While the presence or absence of either CD10, BCL-6 and IRF4/MUM1 reactivity or plasmacytoid differentiation did not identify particular cytomorphologic or site-specific subtypes, we found that expression of CD10 and BCL-6, and a low reactivity for IRF4/MUM1 were favourable prognostic indicators. In contrast, BCL-2 expression and presence of a monotypic cytoplasmic immunoglobulin expression was associated with an unfavourable prognosis in univariate analyses. Meta-analysis of these data resulted in the development of a cumulative immunohistochemical outcome predictor score (CIOPS) enabling the recognition of four distinct prognostic groups. Multivariate analysis proved this score to be independent of the international prognostic index. Such a cumulative immunohistochemical scoring approach might provide a valuable alternative in the recognition of defined risk types of aggressive B-cell lymphomas.

The effect of IgG4, which constitutes the least of the IgG subclasses, on the pathogenesis and prognosis of lymphoma or solid tumors is one of the research topics of interest in recent years. The role of IgG4, which has been reported to suppress antitumor immunity, in classic Hodgkin’s lymphoma (cHL), which is recognized by its pathognomonic microenvironment, is not yet clearly known. The aim of this study was to determine IgG4-positive plasma cell density in the cHL microenvironment and to compare it with histopathological and clinical parameters. In addition, the role of the increase in IgG4-positive cells in the development of relapse after treatment was also investigated. A retrospective cross-sectional study. Ninety-four patients with the initial diagnosis of cHL who had no comorbidity or no treatment history and forty-one reactive lymph nodes with follicular hyperplasia findings were included in the study. Three hot-spot areas were identified with reference to the IgG4 sections. Mean IgG4-positive plasmacyte counts and IgG4/IgG ratios were determined and compared with histopathological characteristics. The mean IgG4 + plasma cell count was 33.57 in cHL cases and 47.04 in the control group (p = 0.233). IgG4/IgG ratio was significantly higher in cHL compared with the control group (0.27 vs. 0.21, p = 0.021). The IgG4/IgG ratio was found to be higher in younger patients with classic Hodgkin lymphoma, with a low correlation (p = 0.028, r =  − 0.226). There was no relationship with gender, lymph node location, histological subtype, EBV positivity and bone marrow infiltration. It was observed that IgG4/IgG ratio was higher in early-stage patients (p = 0.022). No significant IgG4 + cell increase was detected in the initial diagnosis and relapse slides of six patients who developed relapse after standard treatment, resulting in a cure. Novel therapeutic modalities targeting microenvironmental components have been reported to show dramatic effects, particularly in relapsed or refractory patients. Detailed characterization of the cHL inflammatory milieu will be useful for the identification of alternative targets. IgG4 subclass antibodies, which have been described to have anti-inflammatory effects, may have prognostic significance in a proportion of cHL patients.

We report the case of a 75-year-old female presented with lethargy, Hb 93 g/L, WBC 64 x 109/L, platelet 110 x 109/L. Blood film showed blasts, myelocytes, metamyelocytes, neutrophils. Quantitative PCR detected p210 BCR::ABL1 transcript in sorted CD19+ cells, and sorted CD19- cells. Bone marrow smear was packed with blasts. Flow cytometry and bone marrow histology revealed B-lymphoblasts. The patient was diagnosed with CML Blymphoblastic crisis. CML presenting in B-lymphoblastic crisis could resemble features of de novo Ph+ B-ALL, which makes the diagnosis challenging. These patients have inferior outcomes; therefore, it is important to distinguishing CML B -lymphoblastic crisis from de novo Ph+ B-ALL. Positive BCR::ABL1 in both CD19+ and CD19- sorted cell populations support the diagnosis of CML B-lymphoblastic crisis in this case.

High-grade B cell lymphoma (HGBL) is a recently introduced category of aggressive mature B cell lymphoma which is clinically and biologically distinct from diffuse large B cell lymphoma (DLBCL), NOS, and Burkitt Lymphoma. HGBL consists of two categories; the first category includes HGBL with MYC and BCL2 and/or BCL6 rearrangement which is so-called double or triple hit lymphoma. The second category includes HGBL, NOS which lacks genetic double or triple hit; however, its morphology is intermediate between DLBCL and Burkitt lymphoma or appear blastoid. Clinically, patients present with advanced disease, bone marrow involvement, elevated lactate dehydrogenase (LDH), extranodal disease which includes CNS involvement and a high international prognostic index (IPI). Leukemic presentation has been described in various types of B and T cell non-Hodgkin lymphoma; however, peripheral blood involvement as an initial presentation is seldom described in the literature for HGBL with MYC and BCL2 rearrangement. Here, we report two cases of HGBL whose initial presentation was leukocytosis with peripheral blood involvement mimicking acute leukemia.