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.

The Need for Cultural Awareness Training: A Medical Student Perspective.

Inpatient training is a fundamental aspect of undergraduate and graduate medi- cal education. Physicians in training spend considerable time interacting with patients in a hospital setting during their time in medical school, residency, and fellowship. This time is crucial not only for the trainees to develop their techni- cal and diagnostic abilities, but also to improve their interpersonal communica- tion skills. The need to improve the nontechnical skills of trainees has already been recognized at the graduate medical education level. Our study aimed to examine medical student perspectives on certain nontechnical aspects of the patient-physician interaction and the effect of student demographics and cul- tural and religious preferences on their opinions. The study found that two-thirds of students had never had their teachers discuss how posture could be used to facilitate the medical interview, and 85% of the students agreed that their cur- riculum should include discussions on the appropriate posture for patient com- munication in an inpatient setting. We believe integrating some form of cultural awareness and competency training into the curriculum at the undergraduate medical education level would help prepare future physicians for an increasingly diverse patient population.

To Sit or Stand During the Medical Interview: A Poll of Caucasian Patients.

Nonverbal communication is an important component of the interaction between physician and patient. Multiple studies have revealed that patients perceive physicians who are seated during the medical interview as more compassionate and caring and as spending more time with patients. However, sitting on patient beds without permission may be culturally inappropriate and also may enhance nosocomial infection transmission. We interviewed 127 patients using a 14-item questionnaire soliciting patient demographics and their opinions regarding physician's nonverbal behaviors. One fifth of those surveyed reported having had a physician sit on their bed without permission, and more than 80% of patients preferred their physician adopt a position other than on the patient's bed during the medical interview. Asking patients about their preferences regarding physician posture demonstrates respect, and honoring patient's wishes could improve physician-patient communication. Although a sitting posture alone is unlikely to compensate for poor communication skills, asking patients about their preference regarding physician posture, and then following that preference, can be a simple, practical, and inexpensive way of improving communication, and, as a result, patient outcomes. This strategy should be taught in the medical curriculum.

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.