PD1/PD-L1 Expressions in Plasmablastic Lymphoma with Clinicopathological Correlation.

The activation of the programmed cell death one (PD1)/PD1 ligand (PD-L1) immune checkpoint pathway is a mechanism of immune evasion characterized by the upregulation of PD-L1 expression by tumor cells and by the tumor microenvironment. This activation leads to the inhibition of PD1-positive T cells and to a decrease in the anti-tumor immune response. Plasmablastic lymphoma (PBL) is an aggressive type of large B-cell lymphoma with limited studies on the frequency of PD1 and PD-L1 expressions and their clinical impact. As PBL is associated with immune suppression in immunocompromised individuals, we hypothesize that the PD1/PD-L1 axis may be relevant in this type of lymphoma. Our study demonstrates a subset of PBL cases with a higher PD-L1 expression by tumor cells [nPD-L1high, in 4 of 21 (19%) cases] and by tumor microenvironment [macrophages/stromal cells, sPD-L1high, in 9 of 21 (43%) cases]. While nPD-L1 expression showed no significant correlation with PD1 expression on tumor-infiltrating lymphocytes, or other clinicopathological parameters, it positively correlated with sPD-L1 expression. Moreover, patients with nPD-L1high had a tendency towards a shorter overall survival (median 9.3 vs. 25.5 months in nPD-L1low patients). In conclusion, our study provides a rationale to identify, by immunohistochemistry, a subset of nPD-L1high patients who may benefit from clinical trials of PD1/PD-L1 checkpoint blockade. Further studies on large cohorts are needed to investigate prognostic and predictive biomarkers for the PD1/PD-L1 pathway in PBL patients.

Management and Outcomes of HIV-Associated Primary Effusion Lymphoma: A Single Center Experience.

BACKGROUND: Primary effusion lymphoma (PEL) is a rare malignancy usually associated with HIV infection. Management and outcomes are poorly understood. METHODS: The medical records of all patients diagnosed with HIV-associated PEL at our institution between 1999 and 2014 were reviewed. Patients were followed till death, treatment failure or loss of follow-up. RESULTS: Twelve patients with PEL were identified during the 15 year study period; 9 had HIV infection. All 9 were male; median age was 45 years. All presented with local symptoms and were diagnosed with PEL a median of 11 years after HIV diagnosis. Location was pleural (3), pericardial (3), peritoneal (1) and extracavitatory (2). By definition, all had Ann Arbor stage 4 at diagnosis. Median follow-up was 34 months. Two patients had poor performance status and were unable to get chemotherapy. Seven patients had a complete remission (CR) and two died within 1 month of diagnosis. The median CD4 levels at PEL diagnosis in patients with poor versus good outcomes were 54 cells/mm3 (range, 26-82 cells/mm3) and 211 cells/mm3 (range, 73-800 cells/mm3). In contrast, the median lactate dehydrogenase (LDH) levels at PEL diagnosis with poor versus good prognosis were 1074 U/L (range, 703-1445 U/L) and 283 U/L (range, 156-760 U/L). CONCLUSIONS: Given its rarity, our knowledge of PEL relies solely on case reports and case series. Prompt HAART and chemotherapy may be effective in HIV- associated PEL and good outcomes are possible. LDH and CD4 may be possible prognostic factors in PEL.

Bilateral Facial Nerve Palsy in Acute B Cell Lymphoblastic Leukemia: A Case Report and Review of the Literature.

Acute lymphoblastic leukemia (ALL) is a haematological malignancy that can involve the central nervous system (CNS). Less than 10 % of patients with ALL have CNS involvement at presentation. The cranial nerve most commonly affected is cranial nerve VII although bilateral involvement is rare. Management and outcomes of these patients are not well understood. Moreover bilateral Bells palsy as a presenting symptom of ALL is extremely uncommon. We report a very unusual presentation of ALL with bilateral facial nerve palsy, and discuss the management strategies and outcomes for patients with ALL that present with cranial nerve palsies.

Hyaline-Vascular Type Castleman's Disease, Sarcoidosis, and Crohns Disease.

Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease.

Acute fibrinous and organising pneumonia: a rare histopathological variant of chemotherapy-induced lung injury.

Bleomycin-induced lung injury is the most common chemotherapy-associated lung disease, and is linked with several histopathological patterns. Acute fibrinous and organising pneumonia (AFOP) is a relatively new and rare histological pattern of diffuse lung injury. We report the first known case of bleomycin-induced AFOP. A 36-year-old man with metastatic testicular cancer received three cycles of bleomycin, etoposide and cisplatin, before being transitioned to paclitaxel, ifosfamide and cisplatin. He subsequently presented with exertional dyspnoea, cough and pleuritic chest pain. CT of the chest demonstrated bilateral ground glass opacities with peribronchovascular distribution and pulmonary function tests demonstrated a restrictive pattern of lung disease with impaired diffusion. Transbronchial biopsy revealed intra-alveolar fibrin deposits with organising pneumonia, consisting of intraluminal loose connective tissue consistent with AFOP. The patient received high-dose corticosteroids with symptomatic and radiographic improvement. AFOP should be recognised as a histopathological variant of bleomycin-induced lung injury.

Discordant intracellular and plasma D-2-hydroxyglutarate levels in a patient with IDH2 mutated angioimmunoblastic T-cell lymphoma.

OBJECTIVES: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma with mutations in genes encoding isocitrate dehydrogenase1 and 2 (IDH1 and IDH2). Mutant IDH generates the oncometabolite D-2-hydroxyglutarate (D-2HG). We report the first case of discordant intracellular and plasma D-2HG levels in a patient with IDH2 R172S mutated AITL. METHODS: An 87-year-old woman was diagnosed with AITL in the groin lymph node by morphologic and immunophenotypic analyses, and molecular studies by DNA sequencing. D-2HG was measured in both tumoral tissue and in pre-treatment plasma by liquid chromatography-tandem mass spectrometry. RESULTS: While D-2HG was markedly elevated in the tissue sample, its level in plasma was normal. We discuss this discordant D-2HG result within the context of previously reported discordant 2HG results in other IDH mutated tumors, and its implication for using circulating D-2HG as a biomarker of IDH mutation. In addition, this case also harbored mutations in RHOA, TET2, and TP53. The molecular pathogenesis is briefly discussed. CONCLUSION: While our case suggests that circulating D-2HG is not a reliable marker of IDH mutation in AITL, more cases need to be studied to arrive at a definite conclusion.

Rhabdomyolysis due to Trimethoprim-Sulfamethoxazole Administration following a Hematopoietic Stem Cell Transplant.

Rhabdomyolysis, a syndrome of muscle necrosis, is a life-threatening event. Here we describe the case of a patient with chronic myeloid leukemia who underwent a haploidentical stem cell transplant and subsequently developed rhabdomyolysis after beginning trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis therapy. Rechallenge with TMP/SMX resulted in a repeat episode of rhabdomyolysis and confirmed the association. Withdrawal of TMP/SMX led to sustained normalization of creatine kinase levels in the patient. A high index of suspicion is necessary to identify TMP/SMX as the cause of rhabdomyolysis in immunocompromised patients.

Rituximab-based therapy and long-term control of autoimmune autonomic ganglionopathy.

We present a patient with autoimmune autonomic ganglionopathy (AAG) who had persistently positive ganglionic nicotinic acetylcholine receptor antibody levels despite immunosuppressive therapy. Rituximab-based therapy for an incidental lymphoma was associated with prolonged symptomatic and serological control of AAG.

Primary dural lymphoma: Complete remission after treatment with radiation therapy.

Central nervous system (CNS) involvement in sarcoidosis is rare and typically occurs in 5-10% of patients. Neurological symptoms in a patient with known sarcoidosis can be attributed to neurosarcoidosis without thorough evaluation. Primary Dural Lymphoma (PDL) is an extremely rare form of non-Hodgkin lymphoma. Although PDL is technically a subtype of primary CNS lymphoma, the two entities vary markedly in their histological grade, clinical course, prognosis and treatment. The most common dural- based lesion found on CNS imaging is meningioma. It shares many imaging, clinical and epidemiologic features of PDL which often leads to misdiagnosis of PDL as meningioma. We present a case where a PDL was diagnosed after CNS symptoms failed to resolve after steroid therapy for presumed neurosarcoidosis.

Non-Hodgkin Lymphoma of the Stomach in a Patient Treated with Natalizumab.

A 61-year-old man with relapsing-remitting multiple sclerosis developed extranodal large B-cell lymphoma of the stomach following monthly natalizumab infusions for 6 years. Development of lymphoproliferative disorders increases with chronic use of immunosuppression. Cases of primary central nervous system lymphoma as well as one case of peripheral T-cell lymphoma have previously been reported with natalizumab use. Given the absence of a known association between multiple sclerosis and extranodal presentations of diffuse large B-cell lymphoma, a causal association with natalizumab administration cannot be excluded.

Identification of CREB3L1 as a Biomarker Predicting Doxorubicin Treatment Outcome.

BACKGROUND: Doxorubicin has been shown to inhibit proliferation of cancer cells through proteolytic activation of CREB3L1 (cAMP response element binding protein 3-like 1), a transcription factor synthesized as a membrane-bound precursor. Upon doxorubicin treatment, CREB3L1 is cleaved so that the N-terminal domain of the protein can reach the nucleus where it activates transcription of genes that inhibit cell proliferation. These results suggest that the level of CREB3L1 in cancer cells may determine their sensitivity to doxorubicin. METHODS: Mice transplanted with 6 lines of renal cell carcinoma (RCC) were injected with doxorubicin to observe the effect of the chemotherapy on tumor growth. Immunohistochemistry and bioinformatics analyses were performed to compare CREB3L1 levels in types of cancer known to respond to doxorubicin versus those resistant to doxorubicin. RESULTS: Higher levels of CREB3L1 protein are correlated with increased doxorubicin sensitivity of xenograft RCC tumors (p = 0.017 by Pearson analysis). From patient tumor biopsies we analyzed, CREB3L1 was expressed in 19% of RCC, which is generally resistant to doxorubicin, but in 70% of diffuse large B-cell lymphoma that is sensitive to doxorubicin. Doxorubicin is used as the standard treatment for cancers that express the highest levels of CREB3L1 such as osteosarcoma and malignant fibrous histiocytoma but is not generally used to treat those that express the lowest levels of CREB3L1 such as RCC. CONCLUSION: Identification of CREB3L1 as the biomarker for doxorubicin sensitivity may markedly improve the doxorubicin response rate by applying doxorubicin only to patients with cancers expressing CREB3L1.

The impact of physician posture during oncology patient encounters.

Non-verbal communication is an important component of the physician-patient interaction. Oncology patients face specific emotional and psychological issues requiring additional physician emotional support. Multiple studies in oncology patients have revealed that patients perceive physicians seated during the medical interview to be more compassionate, caring, and likely to spend more time with the patients. These are all associated with improved patient outcomes. Barriers to sitting may be due to those imposed by time, space, and reduced perceived benefit of sitting by the physician. Although a sitting posture alone is unlikely to compensate for poor communication skills, assessing patient preference to physician posture, and following their preference, can be a simple way of improving communication, and thus patient outcomes, especially in oncology patients. The widespread introduction of the electronic medical record (EMR) system over the last decade has added a "third wheel" to the original dyadic physician-patient relationship. Physician posture and eye gaze towards to the EMR and its components has a deleterious effect on communication. Appropriate training and sensitization in this regard should be provided for physicians.