Targeted Therapy for BRAF V600E Positive Pancreatic Adenocarcinoma: Two Case Reports.

BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) is a malignancy that typically portends a poor prognosis, with a median overall survival ranging from eight to twelve months in patients with metastatic disease. Novel modalities of therapy, primarily targeted therapy, are now considered for patients with targetable mutations, such as BRAF mutations based on next generation sequencing. BRAF mutations specifically within pancreatic adenocarcinoma remain rare with an incidence of approximately 3%. Previous research on BRAF mutated pancreatic adenocarcinoma is extremely scarce, limited primarily to case reports; therefore, little is known regarding this entity. CASE REPORT: We seek to contribute to prior literature with the presentation of two cases of patients with BRAF V600E + pancreatic adenocarcinoma, who did not have a favorable response to initial systemic chemotherapy and were both subsequently treated with targeted therapy (dabrafenib and trametinib). Each of the patients has sustained a favorable response and there is no evidence of progression thus far on dabrafenib and trametinib, highlighting the potential benefit of targeted therapy in these patients. CONCLUSION: These cases emphasize the importance of early next generation sequencing and the consideration of BRAF targeted treatment in this patient population, especially if a response to initial chemotherapy is not sustained.

A Meningioma Mimic and Distinct Subtype of Primary Central Nervous System Lymphoma: Primary Dural Lymphoma.

Primary central nervous system lymphoma (PCNSL) is an aggressive form of extranodal non-Hodgkin lymphoma that arises in the brain parenchyma, eyes, meninges, or spinal cord in the absence of systemic disease. Primary dural lymphoma (PDL), in contrast, arises from the dura mater of the brain. PDL is usually a low-grade B-cell marginal zone lymphoma (MZL), whereas other types of PCNSL are usually high-grade large B-cell lymphoma. This specific pathological subtype has important therapeutic and prognostic implications, making PDL a distinct subtype of PCNSL. Herein, we report a case of PDL in an African American patient, in her late thirties, who presented to our emergency room with chronic headaches. An emergent magnetic resonance imaging (MRI) of the brain showed a dural-based homogeneously enhancing extra-axial mass along the left hemisphere, which was contained within the anterior and parietal dural mater. A surgical specimen was collected after an emergency debulking procedure. The flow cytometry, done on the surgical specimen obtained, was positive for CD19+, CD20+, and CD22+, but negative for CD5- and CD10-. These findings were consistent with a clonal B-lymphoproliferative disorder. The surgical pathology specimen immunohistochemistry was positive for CD20+ and CD45+, but negative for Bcl-6Cyclin D1- and CD56-. The Ki67 was 10-20%. These findings were consistent with extranodal MZL. Given the location and pathology, the patient was diagnosed with PDL. Due to MZL's indolent nature, location outside the blood-brain barrier, and known efficacy to bendamustine-rituximab (BR), we decided to treat our patient with BR. She completed six cycles without major complications, and her post-therapy brain MRI showed complete remission (CR). Our case adds to the sparse literature about PDL and highlights the efficacy of BR systemic chemotherapy on MZLs.

Primary Testicular Lymphoma: Single Center Experience.

BACKGROUND/AIM: Primary testicular lymphoma (PTL) is an exceedingly rare and aggressive form of non-Hodgkin's lymphoma; the most common subtype is diffuse large B-cell (DLBCL). Standard treatment includes orchiectomy, chemotherapy, central nervous system (CNS) prophylaxis, and prophylactic radiation to the contralateral testis. PTL can reoccur years after complete remission. Treatment to immune sanctuary sites, CNS and contralateral testis, is crucial in preventing relapse. There are limited data characterizing this entity and this study aimed to add to existing literature. PATIENTS AND METHODS: This descriptive retrospective study characterized twelve patients with PTL from years 2010-2021 at Allegheny Health Network. Their demographic data, prognostic factors, treatment regimens, and relapse sites (if any) were tabulated. The mean progression-free survival (PFS) was calculated to describe our experience in treating PTL. RESULTS: Twelve patients were diagnosed with PTL; 10/12 (83.33%) patients were diagnosed with ABC PTL-DLBCL. Median age of diagnosis was 67 years. Eight of the 12 (66.66%) were African American, 4/12 (33.33%) were Caucasian. At the time of diagnosis, 8/12 (66.66%) patients presented with an elevated lactate dehydrogenase (LDH) and 8/12 (66.66%) presented with a left testicular mass. Most were treated with R-CHOP (9/12), intrathecal methotrexate (IT-MTX) (10/12), and radiation to the contralateral testis (9/12). Three of the twelve (25%) patients relapsed. Median time to relapse was 8 months. Mean PFS was 50.417 months. CONCLUSION: We discuss our experience in treating PTL with RCHOP, IT-MTX, and irradiation to the contralateral testis and add to the limited pre-existing data that exist.

The prognostic value of KRAS mutation in locally advanced rectal cancer.

BACKGROUND: The prognostic value of the KRAS proto-oncogene mutation in colorectal cancer has been debated. Herein, we analyzed the National Cancer Database (NCDB) to assess the role of KRAS mutation as a prognostic marker in patients with locally advanced rectal cancer (LARC). METHODS: We identified LARC patients treated with neoadjuvant chemoradiation from 2004-2015 excluding those with stage I/IV disease and unknown KRAS status. Multivariable logistic regression identified variables associated with KRAS positivity. Propensity adjusted univariable and multivariable analyses identified predictors of survival. RESULTS: Of the 784 eligible patients, 506 were KRAS-negative (KRAS -) and 278 were KRAS-positive (KRAS +). Median survival was 63.6 months and 76.3 months for KRAS + and KRAS - patients respectively, with propensity adjusted 3 and 5-year survival of 79.9% vs. 83.6% and 56.7% vs. 61.9% respectively (HR 1.56, p 1.074-2.272). Male sex, no insurance, and KRAS + disease were associated with poorer survival on unadjusted and propensity adjusted multivariable analyses. CONCLUSIONS: Our analysis of KRAS + LARC suggest that KRAS + disease is associated with poorer overall survival. Given the inherent limitations of retrospective data, prospective validation is warranted.

Racial Disparities with Esophageal Cancer Mortality at a High-Volume University Affiliated Center: An All ACCESS Invitation.

BACKGROUND: Esophageal cancer (EC) has a dismal prognosis with 5-year survival < 19%. Black patients with EC have higher mortality than white patients, but the cause of this disparity is unclear. We sought to investigate the impact of race upon overall mortality (OM) among EC patients at our institution. METHODS: We performed a single-center retrospective review of all patients diagnosed with EC between January 2010 through December 2016 with follow-up through October 2017. We compared the difference among categorical variables and mortality using Fisher's exact test. Odds ratios (OR) and hazard regression (HR) were constructed to analyze treatment options by race. The Kaplan-Meier method was used to plot OM curves by race. We also used a logistic regression analysis to construct a predictive model for mortality based on histology and race. RESULTS: We identified 77 patients (62% male) diagnosed with EC. There was no difference in treatments offered based on race. After adjusting for age, histology and stage, we found mortality was significantly higher in blacks when compared to whites (HR 14.07, 95% CI [2.33-129.70] p < 0.008). Our predictive model revealed that blacks had a higher probability of mortality at all stages of EC. CONCLUSIONS: We found race to be an independent risk factor for OM in EC patients. This likely reflects differences in healthcare utilization or access, as evidenced by higher prevalence of Stage IV EC in black patients. Continued investigation is needed to address this disparity locally and nationally.

A Rare Presentation of Biclonal Gammopathy in Multiple Myeloma with Simultaneous Extramedullary Involvement: A Case Report.

Multiple myeloma is characterized by an abnormal clone of plasma cell infiltration in the bone marrow and presence of a high level monoclonal immunoglobulin (M-protein) in the serum or urine in most cases. The monoclonal protein is usually detected as a discrete band in the gamma globulin region by serum protein electrophoresis. Rarely, it may show a simultaneous presence of two distinct bands, which could be either from a single clone, or two separate clones. We report a very unusual presentation of biclonality with lambda restricted IgG predominant cells from cervical lymph node and kappa restricted IgA cells from the bone marrow simultaneously.

Uncommon Endoscopic Findings in a Tylosis Patient: A Case Report.

Palmoplantar tylosis is a focal non epidermolytic palmoplantar hyperkeratosis and is associated with a very high lifetime risk of developing squamous cell carcinoma of the esophagus (OSCC). It is generally inherited as an autosomal dominant trait with complete penetrance involving the RHBDF2 gene located on 17q25.1. The data regarding endoscopic appearance of the mucosa in patients with tylosis before development of cancer is limited. Surveillance endoscopy is recommended in family members which include annual esophagogastroscopy with biopsy of suspicious lesion with quadratic biopsies from upper, middle and lower esophagus. We describe characteristic endoscopy findings in a tylosis with no evidence of cancer. Prospective documentation of endoscopic findings of similar mucosal changes and disease process to establish a better screening protocol and supplemental intervention with agents like carotenoids (beta-carotene, alpha-carotene, lycopene, beta-cryptoxanthin, lutein, and zeaxanthin) may delay the progression and possibly revert to normal.

Management of Hodgkin Lymphoma in a Sickle Cell Patient: A Case Report.

Sickle cell disease (SCD) is an inherited disorder of hemoglobin mutation in red blood cells, with a patient population that is increasing in age in recent decades due to advances in modern medicine. Hodgkin's lymphoma (HL) is a cancer of white blood cells, and while concomitance of SCD and Hodgkin's has been reported, a discussion of treatment for HL in SCD is lacking from the literature. We present a case of effectively treated HL in SCD and put forth that the regimen used is a practical choice, and as it was completed fully as outpatient, it improved the patient's quality of life compared to an inpatient regimen.

The effect of brain metastasis location on clinical outcomes: A review of the literature.

It is common clinical practice to consider the location of a brain metastasis when making decisions regarding local therapies and, in some scenarios, estimating clinical outcomes, such as local disease control and patient survival. However, the location of a brain metastasis is not included in any validated prognostic nomogram and it is unclear if this is due to a lack of a relationship or a lack of support from published data. We performed a comprehensive review of the literature focusing on studies that have investigated a relationship between brain metastasis location and clinical outcomes, including patient survival. The vast majority of reports anatomically categorized brain metastases as supratentorial or infratentorial whereas some reports also considered other subdivisions of the brain, including different lobes or with particular areas defined as eloquent cortex. Results were variable across studies, with some finding a relationship between metastasis location and survival, but the majority finding either no relationship or a weak correlation that was not significant in the context of multivariable analysis. Here, we highlight the key findings and limitations of many studies, including how neurosurgical resection might influence the relative importance of metastasis location and in what ways future analyses may improve anatomical categorization and resection status.

Paraneoplastic Seronegative Pauci-Immune Glomerulonephritis Associated with Lung Adenocarcinoma Responds to Rituximab: A Case Report.

Anti-neutrophil cytoplasmic antibodies (ANCA) play an important role in the pathogenesis of pauci-immune renal vasculitis. However, in 10% of the cases, ANCA are absent. We present a case of a 64-year-old man with a chronic untreated hepatitis C virus infection and Middle Eastern thalassemia who was ANCA-negative when he was hospitalized due to acute kidney injury and accounts for an uncommon presentation of renal vasculitis. The patient had earlier reported to have undergone local lobectomy and adjuvant chemotherapy (carboplatin/pemetrexed) for lung adenocarcinoma a month prior. IL-6 has been reported to be involved in the pathophysiological cascade causing pauci-immune glomerulonephritis amongst non-small cell lung cancer patients. Previous studies with subgroup analysis have demonstrated that ANCA negativity has been associated with more chronic glomerular lesions and less crescent formation, which tends to have a critical outcome in the renal system. However, our patient underwent kidney biopsy exhibiting active crescentic glomerulonephritis, pauci-immune type with 5 cellular crescents amongst 15 glomeruli. To our knowledge, this is the third reported case of ANCA-negative vasculitis with typical presentation on biopsy in non-small cell lung cancer patients.