SMARCA4-Deficient Undifferentiated Tumor: A Rare Malignancy With Distinct Clinicopathological Characteristics.

Switch/sucrose non-fermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4-deficient undifferentiated tumor (SMARCA4-dUT) is a rare malignancy due to inactivating mutations in the SMARCA4 gene of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex. These are aggressive malignancies presenting predominantly in male smokers in their fifth and sixth decades of life with nonspecific respiratory symptoms. Most patients have metastatic disease on presentation. The pattern of metastasis is similar to carcinomas, and the most common metastatic sites are lymph nodes, bones, and adrenal glands. Histologically, these tumors can be either entirely sarcomatoid or with mixed features of sarcoma and carcinoma, with extensive necrosis and high mitotic activity. Immunohistochemistry demonstrates negative expression of keratin and claudin-4, and tumor cell nuclei characteristically lack expression of Brahma-related gene-1 (BRG1). No standard treatment guidelines have been established due to the relative rarity of these tumors, and systemic chemoimmunotherapy has demonstrated benefit in some cases. We report two cases of SMARCA4-dUT with their clinical course and management to provide a perspective on the behavior of these tumors in a Western population cohort.

Clearance of Hepatitis C Virus (HCV) Is Associated With Improved Outcomes in HCV-Associated Lymphoma.

BACKGROUND: Improved hepatitis C virus (HCV) clearance due to directly acting antiviral agents has led to remarkably improved outcomes of indolent HCV-associated non-Hodgkin lymphoma (NHL). The impact of directly acting antivirals on the outcomes of aggressive NHL is still under investigation. Characteristics of HCV-associated NHL in black patients are not well characterized. We report outcomes of HCV-associated NHL compared to their HCV-negative counterparts in a predominantly black population. PATIENTS AND METHODS: Patients with lymphoma between January 2007 and December 2017 were retrospectively studied. Depending on presence or absence of HCV RNA, patients were grouped into HCV positive (HCV+) and HCV negative (HCV-) cohorts. Depending on virologic clearance (VC), HCV+ were classified into HCV+ with VC and HCV+ without VC. Overall response rate (ORR), complete response, overall survival (OS), and progression-free survival (PFS) of HCV+ patients with and without VC were compared to HCV- patients. RESULTS: Of 397 patients with lymphoma, 40 had HCV. Black comprised 90% of HCV+ patients. Diffuse large B-cell lymphoma was most frequent (47%) in the HCV+ group. HCV+ patients without VC had significantly worse OS and PFS compared to HCV- patients. There were no differences in ORR, complete response, PFS, and OS of HCV+ patients with VC and HCV- patients. These results were consistent in subgroups of diffuse large B-cell lymphoma and aggressive lymphoma. CONCLUSION: HCV clearance is positively associated with lymphoma outcomes in black patients. Patients who clear HCV have noninferior outcomes to HCV- patients, while those who fail to clear HCV have significantly worse outcomes.

Lymphoma survivors have an increased long-term risk of chronic kidney disease.

With improving lymphoma survival, late effects of therapy have emerged. Here, we describe pattern of long-term chronic kidney disease (CKD) in lymphoma survivors. Demographics, comorbidities, lymphoma histology, treatment, and outcome were recorded. Glomerular filtration rate (GFR) was recorded at diagnosis, 1, 2, 5, and 10 years. Rate of GFR decline with time and CKD-free survival were recorded. In 397 patients, median age was 55.3 (18-88), 54% were male, 60% were African Americans, 42% had hypertension (HTN), 15% had DM, 13% had hyperuricemia, 86% received chemotherapy, and 14% had baseline CKD. Total 125 (31%) patients developed CKD in 10 years after lymphoma diagnosis. Probability of CKD development increased significantly with time (23% at 1 year to 41% at 10 years). Rate of GFR decline was 4.6 mL/min/per year. Age, HTN, hyperuricemia, and DM (in young patients) predicted risk of CKD. Thus, lymphoma survivors are at substantial long-term risk of CKD development.

Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC).

PURPOSE: Microsatellite instability (MSI) caused by mismatch repair protein (MMRP) deficiency is detected in 15% of sporadic colorectal cancers (CRCs). Our aim is to investigate the frequency of MMRP deficiency in young CRC patients, using immunohistochemical analysis. METHODS: This study targeted cases of CRC at King Hussein Cancer Center from 2004 until 2012 in patients 45 years of age or younger at the time of diagnosis. Clinicopathological data was obtained from 155 patients' records. Immunohistochemistry for MLH1, MSH2, PMS2, and MSH6 proteins was performed on paraffin-embedded tissue containing carcinoma. RESULTS: The median age of patient at diagnosis was 38 years. A total of 29 (19%) cases showed deficient MMRP(dMMRP)expression. Loss of expression of PMS2 was seen in 17 cases, 12 cases of which showed loss of MLH1 expression. Loss of expression of MSH6 was seen in 10 cases, 9 of which showed loss of MSH2 expression. One case (3.4%) showed loss of all four MMR proteins, and another case (3.4%) showed loss of PMS2/MLH1 and MSH6. There was a significant association between abnormal MMR protein expression and tumor location proximal to splenic flexure (p value 0.000), pathologic features suggestive of microsatellite instability (p value 0.000), P53 negativity (p value 0.000), and stage (p value 0.02). Patients with dMMRP CRC appeared to have a significantly better overall survival compared to patients with proficient MMRP(pMMRP)(p value 0.02). Loss of MSH2/MSH6 was significantly associated with positive family history of cancer (p value = 0.020). CONCLUSIONS: The prevalence of dMMRP tumors in this age group appears to be similar to international literature. dMMRP tumors tends to be associated with earlier stages and better outcomes compared to pMMRP cases. dMMRP can serve as a biomarker for better prognosis. These results are of value in directing the clinical management of young patients with CRC.

Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer patients with HIV, hepatitis B, or hepatitis C viral infection.

BACKGROUND: Patients with chronic viral infections including human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) are at increased risk of developing malignancies. The safety and efficacy of ICI therapy in patients with both cancer and chronic viral infections is not well established as most clinical trials of ICIs excluded these patient populations. METHODS: We performed a retrospective analysis of patients with advanced-stage cancers and HIV, HBV, or HCV infection treated with ICI therapy at 5 MedStar Health hospitals from January 2011 to April 2018. RESULTS: We identified 50 patients including 16 HIV, 29 HBV/HCV, and 5 with concurrent HIV and either HBV or HCV. In the HIV cohort (n = 21), any grade immune-related adverse events (irAEs) were 24% with grade ≥ 3 irAEs 14%. Among 5 patients with matched pre/post-treatment results, no significant changes in HIV viral load and CD4+ T-cell counts were observed. RECIST confirmed (n = 18) overall response rate (ORR) was 28% with 2 complete responses (CR) and 3 partial responses (PR). Responders included 2 patients with low baseline CD4+ T-cell counts (40 and 77 cells/ul, respectively). In the HBV/HCV cohort (n = 34), any grade irAEs were 44% with grade ≥ 3 irAEs 29%. RECIST confirmed ORR was 21% (6 PR). Among the 6 patients with known pre/post-treatment viral titers (2 HCV and 4 HBV), there was no evidence of viral reactivation. CONCLUSIONS: Our retrospective series is one of the largest case series to report clinical outcomes among HIV, HBV and HCV patients treated with ICI therapy. Toxicity and efficacy rates were similar to those observed in patients without chronic viral infections. Viral reactivation was not observed. Tumor responses occurred in HIV patients with low CD4 T-cell counts. While prospective studies are needed to validate above findings, these data support not excluding such patients from ICI-based clinical trials or treatment.

Isolated cortical venous thrombosis after fetal demise.

Isolated cortical venous thrombosis (ICVT) occurring in the absence of dural venous thrombosis, constitutes about 2%-5% of all cerebral venous thrombosis. Its vague, non-specific presentation makes it a difficult and challenging diagnosis that needs an extensive workup especially in young patients. Outcome and prognosis depend mainly on early diagnosis and treatment. Here we discuss the clinical presentation, diagnosis and the treatment of a young woman diagnosed with ICVT with acute ischaemic venous stroke, in the setting of eclampsia and family history of coagulation disease.

Usefulness of Malignancy as a Predictor of WorseIn-Hospital Outcomes in Patients With Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TC) is a form of dilated cardiomyopathy often associated with physical or emotional stress. Association with cancer has been reported, however, in-hospital outcomes in TC patients with history of malignancy have not been fully characterized. We conducted a retrospective chart review of hospitalized patients with diagnosis of TC between January 2006 and January 2017. Patients were divided into 2 groups based on the previous history of malignancy. Presenting symptoms, cardiac imaging and short-term events including in-hospital complications and mortality, were compared. Of 318 patients with TC, 81 (25.4%) had a previous diagnosis of cancer. Mean age was 67.5 (SD 12.6), 151 (47.5%) were African American, 122 (38.4%) Caucasian, and 10 (3.1%) of other ethnicities. Patients with history of malignancy were older (70.0 [SD 10.6] vs 66.6 [SD 13.1] years, p = 0.03), had higher heart rate on presentation (93 [SD 19] vs 87 [SD 25] beats/minute, p = 0.03), higher prevalence of severely decreased cardiac function (left ventricular ejection fraction <25%) (29.6% vs 16%, p = 0.01), longer hospitalization (7 (4-13) vs 4 (3-8) days, p = 0.001) and experienced more in-hospital cardiac arrests (6 [7.4%] vs 5 [2.1%], p = 0.035) compared with patients without malignancy history. Higher percentage of longer hospitalization and left ventricular ejection fraction <25% in the cancer group persisted after controlling for sepsis, chemotherapy exposure, and metastatic disease. In conclusion, in a racially diverse hospitalized population of TC, prevalence of cancer history is high, and diagnosis of previous malignancy is associated with adverse in-hospital outcomes.

Acquired Hemophilia A Presenting as Intramuscular Hematoma.

Acquired hemophilia A poses a clinical and diagnostic challenge. Although rare, it is still the most common acquired factor deficiency. We present a case of acquired hemophilia A diagnosed in a 71-year-old female who presented with a right thigh hematoma of acute onset. The diagnosis was established based on the coagulation profile along with factor VIII levels, mixing studies, and inhibitor levels. The patient received multiple lines of therapy including steroids, factor VIIa, Obizur (porcine-derived recombinant factor VIII), followed by multiple cycles of chemotherapy including cyclophosphamide and rituximab.