From the archives of MD Anderson Cancer Center: Plasmablastic lymphoma presenting as a kidney mass in an immunocompetent patient: Case report and literature review.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare, aggressive large B-cell lymphoma with plasmablastic or immunoblastic morphology and a terminally differentiated B-cell immunophenotype. PBL often presents at extranodal sites, commonly the oral cavity of immunocompromised patients with human immunodeficiency virus (HIV) and/or Epstein-Barr virus (EBV) infection. Cases of PBL arising outside the oral cavity in previously healthy immunocompetent patients are rare. CASE REPORT: We report a 65-year-old HIV- and EBV-negative man who presented with abdominal pain, fatigue, and vomiting. Imaging studies showed a 30 × 18 cm bulky lobulated mass located within the left kidney with surrounding para-aortic lymphadenopathy. Serum and urine protein electrophoresis revealed a monoclonal gammopathy of IgA lambda type. Biopsy of the mass showed PBL. Bone marrow lumbar puncture evaluations also showed evidence of PBL. The patient was treated with chemotherapy and radiation with initial improvement; however, he died 14 months after initial diagnosis. CONCLUSIONS: Based on our literature review, this case of PBL is one of the few reported to present as a kidney mass in immunocompetent, HIV- and EBV-negative patient. Distinguishing PBL from plasma cell myeloma (PCM) can be challenging. Knowledge of clinical features including presence of CRAB (hypercalcemia, renal failure, anemia, bone lesions) or bone marrow infiltration by mature clonal plasma cells is helpful to establish a diagnosis of PCM. Genetic features of PCM (typical translocations or mutations) also can be helpful in distinguishing plasmablastic transformation of PCM and from PBL. The case we report also highlights the need for more studies to identify specific immunohistochemical and molecular markers to improve PBL diagnosis in immunocompetent patients.

Recognition of a novel variant of phosphoglycerate kinase 1 deficiency PGK1 Galveston (c.472G > C) in a child with hemolytic anemia, neurologic dysfunction and myopathy.

The enzyme phosphoglycerate kinase 1 (PGK1) catalyzes the first ATP producing reaction in the glycolysis pathway. Certain mutations to the coding gene of PGK1 present clinically with varying manifestations including hemolytic anemia, central nervous system (CNS) dysfunction and myopathy. Various PGK1 mutations have been described in the literature at the clinical and molecular level. Herein, we describe a novel case PGK1 mutation (PGK1 Galveston) in a 4-year-old boy who presented with all three manifestations. We discuss the characteristic hematopathology findings from this patient as well as provide a comparison with previously described neuroimaging findings. The variable clinical presentation of this condition along with its inherent uniqueness provide a diagnostic challenge for physicians. This presentation will add to the current body of knowledge for this condition and help guide future investigation and management.

MALT lymphoma of the tongue: An unusual site that may present a diagnostic challenge.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-grade B cell lymphoma that can affect any organ, usually preceded by acquisition of MALT in response to antigenic stimulus provided by infections or autoimmune diseases. Most often, MALT lymphoma involves the stomach (about 35% of cases), followed by the ocular adnexal region, skin, lungs, and salivary glands, but virtually any extranodal site can be involved. MALT lymphomas are less common at sites of normal MALT tissue, such as Waldeyer ring and the ileocecal region of the gastrointestinal tract. Lymphomas involving the tongue are extremely rare and represent approximately 3% of all lymphomas involving the head and neck region. In this study, we discuss potentially challenging diagnostic aspects of MALT lymphoma involving the tongue and review and summarize the available literature about this topic.

Next-Generation Scholarship: Rebranding Hematopathology Using Twitter: The MD Anderson Experience.

Hematopathologists are witnessing very exciting times, as a new era of unsurpassed technological advances is unfolding exponentially, enhancing our understanding of diseases at the genomic and molecular levels. In the evolving field of precision medicine, our contributions as hematopathologists to medical practice are of paramount importance. Social media platforms such as Twitter have helped facilitate and enrich our professional  interactions and collaborations with others in our field and in other medical disciplines leading to a more holistic approach to patient care. These platforms also have created a novel means for instantaneous dissemination of new findings and recent publications, and are proving to be increasingly useful tools that can be harnessed to expand our knowledge and amplify our presence in the medical community. In this Editorial, we share our experience as hematopathologists with Twitter, and how we leveraged this platform to boost scholarly activities within and beyond our subspecialty, and as a powerful medium for worldwide dissemination of educational material and to promote our remote teaching activities during the COVID-19 pandemic.

A proposal for pathologic processing of breast implant capsules in patients with suspected breast implant anaplastic large cell lymphoma.

Breast implant anaplastic large cell lymphoma is an entity recently recognized by the World Health Organization. The tumor arises around textured-surface breast implants and is usually confined to the surrounding fibrous capsule. Currently, there are no recommendations for handling and sampling of capsules from patients with suspected breast implant anaplastic large cell lymphoma without a grossly identifiable tumor. We analyzed complete capsulectomies without distinct gross lesions from patients with breast implant anaplastic large cell lymphoma. The gross appearance of the capsules as well as the presence, extent and depth of tumor cells on the luminal side and number of sections involved by lymphoma were determined by review of routine stains and CD30 immunohistochemistry. We then used a mathematical model that included the extent of tumor cells and number of positive sections to calculate the minimum number of sections required to identify 95% of randomly distributed lesions. We identified 50 patients with breast implant anaplastic large cell lymphoma who had complete capsulectomies. The implants were textured in all 32 (100%) cases with available information. Anaplastic large cell lymphoma was found in 44/50 (88%) capsules; no tumor was found in six (12%) patients who had lymphoma cells only in the effusion. The median number of sections reviewed was 20 (range, 2-240), the median percentage of sections involved by tumor was 6% (range, 0-90%), and the median percentage of sections involved by lymphoma was 10% (range, 0-90%). Invasion deep into or through the capsule was identified in 18/50 (36%) patients. In patients with breast implant anaplastic large cell lymphoma without a grossly identifiable tumor we identified a spectrum of involvement and we propose a protocol for handling, sampling and reporting these cases. The number of sections to exclude the presence of lymphoma with more than 95% certainty was supported by a mathematic rationale.

Immunopathology of Kikuchi-Fujimoto disease: A reappraisal using novel immunohistochemistry markers.

AIMS: Kikuchi-Fujimoto disease (KFD) is a self-limited disease characterised by destruction of the lymph node parenchyma. Few studies have assessed the immunohistological features of KFD, and most employed limited antibody panels that lacked many of the novel immunohistochemistry markers currently available. METHODS AND RESULTS: We used immunohistochemistry to reappraise the microanatomical distribution of plasmacytoid dendritic cells (pDCs), follicular helper T cells and cytotoxic T cells, B cells, follicular dendritic cell (FDC) meshworks, and histiocytes in lymph nodes involved by KFD. The study group consisted of 138 KFD patients (89 women; 64.5%) with a median age of 27 years (range, 3-50 years). Cervical lymph nodes were most commonly involved, in 108 (78.3%) patients. The numbers of pDCs were increased, predominantly around and within apoptotic areas and the paracortex, and tapering off within xanthomatous areas. pDCs formed sizeable tight clusters, most notably around apoptotic/necrotic areas. T cells consisted mostly of CD8-positive cells with predominant expression of T-cell receptor-ß. There were notable increases in the numbers of CD8-positive T cells within lymphoid follicles, and their numbers correlated with alterations in FDC meshworks (P < 0.001). The number of follicular helper T cells was decreased within distorted FDC meshworks. CD21 highlighted frequent distortion of FDC meshworks, even in lymph node tissue that was distant from apoptotic/necrotic areas. Distorted FDC meshworks spanned all morphological patterns, and FDC meshwork characteristics (intact; distorted; remnant/nearly absent) correlated with morphological patterns (P < 0.01). CONCLUSIONS: The immunohistological landscape of KFD is complex and characterised by increased numbers of pDCs that frequently cluster around apoptotic/necrotic foci, increased numbers of cytotoxic T cells, and substantial distortion of FDC meshworks.

Lymphoid enhancer binding factor 1 (LEF1) expression is significantly higher in Hodgkin lymphoma associated with Richter syndrome relative to de novo classic Hodgkin lymphoma.

Lymphoid enhancer binding factor 1 (LEF1) is consistently upregulated in chronic lymphocytic leukemia (CLL) and in a subset of large B cell lymphoma. Knowledge of LEF1 expression in Hodgkin lymphoma is limited. In this study, we used immunohistochemistry to survey LEF1 expression in various subsets of Hodgkin lymphoma, de novo classic Hodgkin lymphoma (CHL) (n = 43), Hodgkin lymphoma associated with Richter syndrome (HL-RS) (n = 20), and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) (n = 9). LEF1 expression was significantly higher in HL-RS compared with de novo CHL (12/20, 60% vs. 12/43, 28%; p = 0.0248). Only a single case (1/9; 11%) of NLPHL showed LEF1 expression. Epstein-Barr virus encoded RNA (EBER) was detected in 17 (40%) cases of de novo CHL and 14 (70%) HL-RS. Notably, we identified a correlation between LEF1 expression and EBER positivity (p = 0.0488). We concluded that LEF1 is commonly positive in CHL but not in NLPHL, and such a distinction may be helpful in this differential diagnosis. The higher frequency of LEF1 upregulation in HL-RS relative to de novo CHL suggests that these neoplasms might have different underlying pathogenic mechanisms and warrants further investigation.

Reconsideration of the first recognition of breast implant-associated anaplastic large cell lymphoma: A critical review of the literature.

The current literature credits Keech and Creech with the first report of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in 1997. Here we discuss what we consider is the first ever description of BIA-ALCL, a recently recognized entity by the WHO. We unearthed the description of a patient that was diagnosed with primary effusion lymphoma (PEL), surrounding a breast implant in 1996. In light of the current state of knowledge, we evaluated the evidence presented in 1996 and consider that BIA-ALCL is a more appropriate diagnosis rather than PEL. We base our proposal on the following features: 1). clinical presentation of effusion around a breast implant, 2). occurring in an HIV negative patient, 3). absence of EBV co-infection, and 4). a historically questionable demonstration of HHV8. In effect we further support that HHV8 is not related with BIA-ALCL based on the following facts: 1). An extensive review of the literature did not disclose a similar case in the next 24 years, 2). Use of state of the art HHV8 by immunohistochemistry did not disclose any positive case among 30 randomly tested cases. We believe this matter is of importance because in the current WHO, the assertion that PEL is a possible complication of breast implants may lead to a diagnosis with poor prognosis and susceptible of morbidity related with aggressive therapy, in contrast with BIA-ALCL that can be cured with surgery alone.

Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury.

Injury to the CNS leads to formation of scar tissue, which is important in sealing the lesion and inhibiting axon regeneration. The fibrotic scar that comprises a dense extracellular matrix is thought to originate from meningeal cells surrounding the CNS. However, using transgenic mice, we demonstrate that perivascular collagen1α1 cells are the main source of the cellular composition of the fibrotic scar after contusive spinal cord injury in which the dura remains intact. Using genetic lineage tracing, light sheet fluorescent microscopy, and antigenic profiling, we identify collagen1α1 cells as perivascular fibroblasts that are distinct from pericytes. Our results identify collagen1α1 cells as a novel source of the fibrotic scar after spinal cord injury and shift the focus from the meninges to the vasculature during scar formation.