Jose D. Sandoval-Sus

Rosai-Dorfman Disease of the Central Nervous System: Report of 6 Cases and Review of the Literature

AbstractRosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is an uncommon benign idiopathic lymphoproliferative disorder. The histologic hallmark of RDD is the finding of emperipolesis displayed by lesional histiocytes. While RDD most commonly affects lymph nodes, extranodal involvement of multiple organs has been reported, including the central nervous system (CNS). However, CNS involvement in RDD is rare and is not well characterized. As a result, therapeutic approaches to CNS involvement in RDD are not well established. Herein we report 6 cases of RDD with isolated CNS involvement and review the literature on RDD with CNS involvement. One of the presented cases exhibited intramedullary involvement of the spinal cord—a very rare form of RDD with CNS involvement.

Progressive leukemic non-nodal mantle cell lymphoma associated with deletions of TP53, ATM, and/or 13q14☆ , ☆☆

Leukemic, non-nodal mantle cell lymphoma (MCL) is a relatively indolent disease characterized by asymptomatic leukemic presentation, non-nodal disease distribution, and slow disease progression, particularly in comparison to that of classic nodal MCL. We studied 3 cases of leukemic, non-nodal MCL in which TP53, ATM, and/or 13q14 deletions were identified. All three patients had disease progression leading to treatment requirements in two of the patients at 5 and 18 months after initial diagnosis. The third patient also clinically progressed 25 months after initial diagnosis but was lost to follow up despite recommendation for initiation of therapy. We present these cases as potential evidence that while leukemic non-nodal MCL is typically an indolent disease compared to classically defined mantle cell lymphoma, cytogenetic heterogeneity exists and cases with TP53, ATM, and/or 13q14 deletions may have a relatively aggressive clinical course.

The role of anti-PD-1 and anti-PD-L1 agents in the treatment of diffuse large B-cell lymphoma: The future is now

Immune checkpoints inhibitors have been incorporated into standard treatment protocols for advanced solid tumors. The aim of T-cell-based immune therapy in cancer has been to generate durable clinical benefits for patients, paired with enhanced side effect profiles. The beneficial antitumoral activity of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has been thoroughly demonstrated in certain metastatic malignancies (e.g. melanoma, non-small cell lung cancer, renal cell carcinoma); however, the therapeutic role in lymphoid cancers is complex. Nonetheless, the striking clinical activity seen in early clinical trials of various subtypes of relapsed lymphoma have paved the way for these exciting innovative therapeutic alternatives in these tumors. In this article we assess the literature on the role of the PD-1/PD-L1 pathway in Diffuse Large B-cell lymphoma (DLBCL), and describe future strategies involving these new anticancer agents in this lymphoid neoplasm.

A New Therapeutic Era in GCB and ABC Diffuse Large B-cell Lymphom a Molecular Subtypes: A Cell of Origin-Driven Review.

In the past 15 years, advances in molecular biology have exposed the genetic and physiopathologic heterogeneity of diffuse large B-cell lymphoma (DLBCL). Subsets of patients have been identified in which current chemoimmunotherapies may not be as efficacious, such as the activated B-cell subtype (ABC). In this review, we present an in-depth study of the differences between the two main DLBCL subsets (germinal center B cell [GCB] and ABC), focusing specifically on their different genetic features, active tumoral pathways, and pathologic features. We also discuss the bridges that have been built from the bench to the forefront of patient care through translational research, including the use of immunohistochemistry versus gene profiling to categorize patients with DLBCL and current clinical trial data pertaining to new possible targeted therapies for patients with these two subtypes of DLBCL. We hope that clinicians use this review as a tool to better understand the complexity of the two more prevalent DLBCL subtypes seen in the day to day practice and update their knowledge in both current and upcoming novel treatment options that can potentially change the outcomes of this population.

Usefulness of HGAL and LMO2 immunohistochemistry in the identification of follicular lymphomas of the non-gastric gastrointestinal tract.

Background:We studied the sensitivity of 2 relatively new markers of germinal center B-cell origin, namely human germinal center-associated lymphoma (HGAL) and Lim-only transcription factor 2 (LMO2), in the identification of follicular lymphomas (FLs) of the nongastric gastrointestinal (GI) tract. Materials and Methods:We retrospectively reviewed cases of endoscopically derived primary, nongastric GI lymphomas including FL, grade 1 or 2, and extranodal marginal zone lymphoma (ENMZL) of mucosa-associated lymphoid tissue, classified based on morphologic features and immunohistochemical analysis. HGAL and LMO2 immunohistochemical stains were then prospectively performed in each case. When discrepant immunohistochemical results were obtained, fluorescent in situ hybridization was performed for t(14;18) IGH/BCL2 and IGH rearrangement using a dual color fusion and a dual color break-apart probe, respectively. Results:All but one of the CD10-negative ENMZL cases were negative for both HGAL and LMO2. One case originally classified as ENMZL was positive for both HGAL and LMO2. Fluorescent in situ hybridization did not detect either t(14;18) IGH/BCL2 or IGH rearrangement in this case. It is likely, based on positivity of 2 established germinal center B-cell markers, that this represents a FL which was originally misclassified as an ENMZL based on CD10 negativity. Of the cases of FL (all CD10 and/or BCL-6 positive), 8 (80%) were positive for both HGAL and LMO2. Conclusions:Although HGAL and LMO2 did not demonstrate an increased sensitivity in the identification of FL of the nongastric GI tract in this series, they still were helpful in the reclassification of one of our cases, and may therefore be useful adjuncts in the identification of FL of the nongastric GI tract.

Mantle Cell Lymphoma: Contemporary Diagnostic and Treatment Perspectives in the Age of Personalized Medicine

Mantle cell lymphoma is a clinically heterogeneous disease occurring within a heterogeneous patient population, highlighting a need for personalized therapy to ensure optimal outcomes. It is therefore critical to understand the benefits and risks associated with both intensive and deintensified approaches. In the following review we provide a therapeutic roadmap to strategically guide treatment for newly diagnosed and relapsed/refractory patients highlighting pivotal and recently published results involving known and novel therapies.

Updated survival analysis of two sequential prospective trials of R-MACLO-IVAM followed by maintenance for newly diagnosed mantle cell lymphoma

A phase II trial of R‐MACLO‐IVAM followed by thalidomide maintenance for mantle cell lymphoma (MCL) demonstrated promising progression‐free survival (PFS) and overall survival (OS) rates. Thalidomide maintenance was associated with significant toxicity and was subsequently modified to rituximab maintenance. Herein, we present updated results and follow‐up. Two sequential phase II trials included chemotherapy‐naïve patients with MCL up to 75 years old. Four cycles of R‐MACLO‐IVAM chemotherapy were delivered as previously described. Patients who achieved complete responses (CR) were eligible for thalidomide or rituximab maintenance therapy. Among 36 patients enrolled, the MCL International Prognostic Index (MIPI) was low in 53%, intermediate in 36% and high in 11%. Thirty‐five patients completed at least 2 cycles of chemotherapy; 34 (94%) achieved a CR. After a median follow‐up of 74.4 months, the 5‐year PFS was 51% (95% CI 33–68%) and the 5‐year OS was 85% (95% CI 73–97%). Two deaths occurred during the chemotherapy phase due to disease progression and neutropenic sepsis, respectively. One patient developed secondary acute myeloid leukemia after 7 years. R‐MACLO‐IVAM chemotherapy is effective for patients with newly diagnosed MCL. Am. J. Hematol. 90:E111–E116, 2015.

Lymphomatoid Granulomatosis: A Single Institution Experience and Review of the Literature

BACKGROUND Lymphomatoid granulomatosis (LYG) is a rare B-cell lymphoproliferative disorder with frequent extranodal presentation and involvement of the respiratory system. The purpose of this study is to describe the clinical characteristics, pathologic findings, and treatment outcomes of LYG in a single tertiary institution. METHODS This is a retrospective review of series of cases of LYG diagnosed at Moffitt Cancer Center (MCC) between 2000 and 2011. We describe clinical presentation, histopathologic findings, and treatment outcomes. RESULTS We identified 11 cases of biopsy-proven LYG at our institution. All patients presented with lung involvement by LYG. Nine patients were treated with rituximab-based chemotherapy. The overall response rate was 63.6% (complete response rate, 36.44%). Extra-pulmonary involvement was common (central nervous system, kidney, adrenal glands, testicles, and liver). The median overall survival and progression-free survival were 23 and 12.2 months, respectively. CONCLUSIONS LYG is a rare B-cell lymphoproliferative disorder with involvement if the respiratory system. The presentation is heterogeneous, and response to therapy is variable. Although it is considered a poor prognosis disease, long-term survivors in remission have been described.

Excellent outcome of hairy cell leukaemia with extensive mesenteric infiltration following cladribine therapy

A 50-year-old man with no pertinent past medical history presented with worsening abdominal distension and umbilical bulging that had started 4 months previously, associated with weight loss, early satiety, fatigue and generalized abdominal pain. He was evaluated for possible correction of an umbilical hernia; however, his preoperative work-up revealed pancytopenia (white blood cell count 0 91 9 10/l, haemoglobin concentration 96 g/l, haematocrit 0 29 l/l, mean corpuscular volume 107 4 fl, platelet count 74 9 10/l and absolute neutrophil count of 0 29 9 10/l). A computed tomography scan of his abdomen and pelvis showed a confluent mass involving the retroperitoneum and mesentery, which encased the abdominal aorta and inferior vena cava (left). Splenomegaly (17 3 cm) and low volume ascites were also noted. A bone marrow biopsy showed a diffuse, loosely spaced infiltrate of small to intermediate size atypical lymphoid cells, with round to oval nuclei, dense chromatin, abundant cytoplasm and a prominent cell border (“fried-egg appearance”). These cells were positive for CD20 and tartrate-resistant acid phosphatase (TRAP), consistent with hairy cell leukaemia (HCL). Notably, a core needle biopsy of the mesenteric mass revealed a dense cellular infiltrate composed of atypical lymphoid cells with abundant eosinophilic cytoplasm and fine cytoplasmic projections, cytologically similar to those in the bone marrow biopsy. Flow cytometric analysis from the core biopsy of the mesenteric mass demonstrated monoclonal B cells positive for CD19, CD20, CD103, HLA-DR, CD11c and CD25 and negative for CD5, CD10 and CD38, consistent with HCL. The patient was treated with a 7-day course of intravenous cladribine, obtaining a significant improvement of the abdominal distension and blood counts. A bone marrow biopsy and aspirate 4 months after treatment showed normal trilineage haematopoiesis with residual HCL (10%). Restaging imaging showed near resolution of the mesenteric infiltration and retroperitoneal mass, along with complete reversal of splenomegaly (right). At his last follow-up (18 months posttherapy), the patient continues to do well with no evidence of abdominal distension or splenomegaly. HCL associated with abdominal masses, bulky lymphadenopathy and/or mesenteric infiltration is rare. The largest case series (n = 12) showed a response rate of approximately 40% with then available therapies (Mercieca et al, 1992). This case shows that, aside from pancytopenia and splenomegaly, HCL can present with bulky symptomatic intra-abdominal lymphadenopathy and can achieve an excellent response with single-agent cladribine.