Detailed cadaveric analysis of perivesical lymph nodes in cystectomy specimens.

INTRODUCTION: Perivesical lymph nodes were added to the 8th edition of American Joint Committee on Cancer (AJCC) staging for bladder cancer. Currently, these nodes are inconsistently evaluated at the time of radical cystectomy. The objective of this study was to provide a detailed anatomic evaluation of perivesical lymph nodes. MATERIALS AND METHODS: A radical cystectomy was performed on six un-embalmed cadavers with wide resection of perivesical tissue and meticulous care to separate the pelvic sidewall lymph nodes (e.g. obturator, external iliac) from the bladder and perivesical en-bloc specimen. Perivesical tissue dissection in 2 mm slices was performed with a board-certified pathologist. Lymph node size and location were recorded. RESULTS: Gross tissue resembling lymph nodes were identified in the perivesical tissue in 50% (3/6) of the specimens, with a total of six grossly identified lymph nodes. The mean size was 7.5 mm (2-16 mm). On histologic analysis, 4 of 6 (66%) putative gross lymph nodes had confirmed lymphoid tissue. The mean distance of the lymph nodes from bladder wall was 9 mm (3-15 mm). Eight anatomic locations for perivesical nodes were developed: urachal, anterior bladder wall, posterior peritoneum, bladder neck, bilateral pedicle, bilateral lateral bladder wall. CONCLUSION: This cadaveric study with meticulous dissection of the perivesical space confirms that perivesical lymph nodes are a distinct entity and separate from other lymph nodes in the true pelvis. Perivesical lymph nodes are not present in all subjects and pathologic evaluation is more difficult owing to the surrounding fat. We herein propose perivesical regions for evaluation which can serve as a foundation for future studies and anatomic grossing techniques.

AhR ligand aminoflavone suppresses α6-integrin-Src-Akt signaling to attenuate tamoxifen resistance in breast cancer cells.

More than 40% of patients with luminal breast cancer treated with endocrine therapy agent tamoxifen demonstrate resistance. Emerging evidence suggests tumor initiating cells (TICs) and aberrant activation of Src and Akt signaling drive tamoxifen resistance and relapse. We previously demonstrated that aryl hydrocarbon receptor ligand aminoflavone (AF) inhibits the expression of TIC gene α6-integrin and disrupts mammospheres derived from tamoxifen-sensitive breast cancer cells. In the current study, we hypothesize that tamoxifen-resistant (TamR) cells exhibit higher levels of α6-integrin than tamoxifen-sensitive cells and that AF inhibits the growth of TamR cells by suppressing α6-integrin-Src-Akt signaling. In support of our hypothesis, TamR cells and associated mammospheres were found to exhibit elevated α6-integrin expression compared with their tamoxifen-sensitive counterparts. Furthermore, tumor sections from patients who relapsed on tamoxifen showed enhanced α6-integrin expression. Gene expression profiling from the TCGA database further revealed that basal-like breast cancer samples, known to be largely unresponsive to tamoxifen, demonstrated higher α6-integrin levels than luminal breast cancer samples. Importantly, AF reduced TamR cell viability and disrupted TamR mammospheres while concomitantly reducing α6-integrin messenger RNA and protein levels. In addition, AF and small interfering RNA against α6-integrin blocked tamoxifen-stimulated proliferation of TamR MCF-7 cells and further sensitized these cells to tamoxifen. Moreover, AF reduced Src and Akt signaling activation in TamR MCF-7 cells. Our findings suggest elevated α6-integrin expression is associated with tamoxifen resistance and AF suppresses α6-integrin-Src-Akt signaling activation to confer activity against TamR breast cancer.

Trends in the Diagnosis of Phyllodes Tumors and Fibroadenomas Before and After Release of WHO Classification Standards.

BACKGROUND: In 2012, the World Health Organization (WHO) released diagnostic criteria for grading phyllodes tumors based on histologic features. This study sought to examine the application of the WHO criteria and the changing epidemiology of fibroepithelial tumors. METHODS: A retrospective review of surgically excised fibroepithelial lesions from 2007 to 2017 at a single tertiary care institution was conducted. Data regarding the WHO criteria (tumor border, stromal cellularity, stromal cell atypia, stromal overgrowth, mitotic activity) and traditional descriptors (leaf-like architecture, periductal stromal condensation) were collected. Clinical and pathologic characteristics of cases with diagnoses determined before and after 2012 were compared. RESULTS: During the study period, 305 fibroepithelial tumors were identified. No significant differences were observed in terms of mean age, race/ethnicity, presenting symptoms, or method of diagnosis between cases diagnosed before and after 2012. After 2012, the findings showed statistically significant increases in reporting of WHO and traditional histologic features, a decrease in diagnoses of fibroadenomas (85.9% [116/135] before vs 70.0% [119/170] after 2012), and an increase in benign phyllodes tumors (0% [0/135] before vs 12.9% [22/170] after 2012). Patients with a diagnosis of benign phyllodes tumors were significantly younger than those with a diagnosis of borderline, malignant, or non-graded phyllodes tumors (mean age, 25.7 ± 10.6 vs 52.8 ± 9.9, 40.7 ± 24, 46.3 ± 1.5 years, respectively; p = 0.006). CONCLUSIONS: The expanding use of the 2012 WHO criteria has been accompanied by an increased diagnostic frequency of benign phyllodes tumors and a decrease in fibroadenomas. As fibroepithelial diagnoses become more distinct, evidence-based management recommendations for less virulent phyllodes diagnoses should be developed.

Case Report: An exceptional response to neoadjuvant radiotherapy and chemotherapy in undifferentiated pleomorphic sarcoma following checkpoint inhibitor use.

Undifferentiated pleomorphic sarcoma (UPS), a subtype of soft tissue sarcoma (STS), is an uncommon malignancy associated with a poor prognosis. As with other forms of sarcoma, surgical resection remains the only form of treatment with curative potential. The role of perioperative systemic therapy has not been definitively elucidated. Due to high recurrence rates and metastatic potential, management of UPS can pose a difficult task for clinicians. In cases of unresectable UPS due to anatomic limitations and in patients with comorbidities and poor performance status (PS), management options are limited. We describe a patient with UPS involving the chest wall with poor PS who achieved complete response (CR) following neoadjuvant chemotherapy and radiation in the setting of prior immune-checkpoint inhibitor (ICI) therapy.

Racial and Ethnic Disparities in Gynecologic Carcinosarcoma: A Single-Institution Experience.

We aimed to determine the incidence, treatment regimen, and treatment outcomes (including progression-free survival and overall survival) of gynecologic carcinosarcoma, a rare, aggressive, and understudied gynecologic malignancy. This retrospective review included all patients with gynecologic cancers diagnosed and treated at a single tertiary care comprehensive cancer center between January 2012 and May 2021. A total of 2116 patients were eligible for review, of which 84 cases were identified as carcinosarcoma: 66 were uterine (5.2% of uterine cancers), 17 were ovarian (3.6% of ovarian cancers), 1 was cervical (0.28% of cervical cancers), and 1 was untyped. Of the patients, 76.2% presented advanced-stage disease (stage III/IV) at the time of diagnosis. Minority patients were more likely to present with stage III/IV (p < 0.0001). The majority of patients underwent surgical resection followed by systemic chemotherapy with carboplatin and paclitaxel. The median PFS was 7.5 months. Of the patients, 55% were alive 1 year after diagnosis, and 45% were alive at 5 years. In the studied population, minorities were more likely to present with more advanced disease. The rate of gynecologic carcinosarcomas was consistent with historical reports.

72-year-old man with right homonymous hemianopia and gait instability.

An elderly man presented with right homonymous hemianopia and gait instability. He was found to have a left occipital ring enhancing lesion that was resected. Neuropathologic examination demonstrated a Cladophialophora bantiana brain abscess (cerebral phaeohyphomycosis).

Hemorrhagic pericardial effusion resulting in constriction in hereditary hemorrhagic telangiectasia.

BACKGROUND: We report the first ante-mortem diagnosis of hemorrhagic pericardial effusion in hereditary hemorrhagic telangiectasia resulting in constriction; the case also demonstrates the unusual but well-described complication of right-sided heart failure requiring extracorporeal membrane oxygenation (ECMO) support after pericardiectomy. CASE PRESENTATION: A previously healthy 48 year old man with a strong family history of Osler-Weber-Rendu disease presented to our institution with signs and symptoms of advance heart failure. His workup demonstrated a thickened pericardium and constrictive physiology. He was brought to the operating room where old clot and inflamed tissue were appreciated in the pericardial space and he underwent complete pericardiectomy under cardiopulmonary bypass. Separation from bypass, hampered by the development of right ventricular dysfunction and profound vasoplegia, required significant pressor and inotropic support. The right heart dysfunction and vasoplegia worsened in the early postoperative period requiring a week of ECMO after which his right ventricle recovered and he was successfully de-cannulated. CONCLUSION: Given the poor outcome of severe postoperative right ventricular failure after pericardiectomy, with high central venous pressure, a low gradient between central venous and pulmonary artery pressures and high vasopressor requirements, ECMO should be instituted promptly.

Margin Status Post Cervical Conization Predicts Residual Adenocarcinoma In Situ (AIS) and Occult Adenocarcinoma in a Predominantly Hispanic Population.

Background: Adenocarcinoma in situ (AIS) of the cervix, is increasing in incidence, particularly in women of reproductive age. Fertility preservation is often desired. In a predominantly Hispanic population, we sought to determine the incidence of occult cervical cancer co-existing with AIS, and evaluate how conization margin status correlates with residual disease upon hysterectomy. Methods: A retrospective study utilizing a comprehensive cancer center database was conducted. Data from patients with histologically proven AIS of the cervix were abstracted. Results: Of 47 patients that met the criteria, 23 (49%) were Hispanic, 21 (45%) were White, two (4%) were Asian, and one (2%) was Black. The median age was 37. Forty-two patients underwent cervical conizations; 13/42 (48%) had positive margins upon conization; 28/42 (67%) underwent hysterectomies. Furthermore, 6/13 (46%) patients with positive conization margins had residual disease in hysterectomy specimens, with 2/13 (15%) found to have invasive cancer. In contrast, 0/14 (0%) of patients with negative margins had residual disease (p = 0.036, Chi-squared 4.41, df = 1). In total, 2/27 (7%) patients who underwent hysterectomies had invasive cancer (7%). Conclusions: Positive margins upon cervical conization for AIS of the cervix were correlated with a relatively high rate of residual AIS and occult invasive cancer. Negative conization margins were correlated with no residual disease. Those patients may be candidates for fertility-sparing treatment.

Anthracycline-induced cardiotoxicity: A case report and review of literature.

BACKGROUND: Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment. The use of anthracycline is limited by dose-dependent cardiotoxicity, which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart failure. Despite baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents, there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity (AIC). CASE SUMMARY: A 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70% determined by transthoracic and dobutamine stress echocardiogram. She underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery, and received a total of 450 mg/m2 doxorubicin at the end of her treatment course. She was evaluated regularly during chemotherapy without any cardiac or respiratory symptoms. Approximately two months after her last chemotherapy, the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory failure. Echocardiogram showed an ejection fraction of 5%-10% with severe biventricular failure. Despite attempts to optimize cardiac function, the patient's hemodynamic status continued to decline, and resuscitation was not successful on the seventh day of hospitalization. The autopsy showed no evidence of osteosarcoma, and the likely cause of death was cardiac failure with the evidence of pulmonary congestion, liver congestion, and multiple body cavity effusions. CONCLUSION: We present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m2 doxorubicin over 9 mo. Cardiac monitoring and management of patients receiving anthracycline chemotherapy have been an area of intense research since introduction of these agents in clinical practice. We have reviewed literature and recent advances in the prediction and prevention of AIC. Although risk factors currently identified can help stratify patients who need closer monitoring, there are limitations to our current understanding and further research is needed in this field.

Sarcina Organisms in the Upper Gastrointestinal Tract: A Report of 3 Cases With Varying Presentations.

Sarcina species are anaerobic gram-positive cocci rarely seen in the upper gastrointestinal tract and associated with delayed gastric emptying. We present 3 cases of Sarcina infection with varying clinical presentations including the first reported case of Sarcina in a patient with eosinophilic esophagitis. Although the pathogenesis of Sarcina is unclear, awareness of the bacteria is important as they can usually only be detected on histopathologic examination of upper gastrointestinal biopsies. Treatment in symptomatic patients may prevent severe complications such as emphysematous gastritis and gastric perforation.

Mixed olfactory neuroblastoma and neuroendocrine carcinoma: An unusual case report and literature review.

BACKGROUND: The aim of the study was to present a case of mixed olfactory neuroblastoma (ONB) and carcinoma, an extremely rare tumor with only a few cases in the published literature. CASE DESCRIPTION: An otherwise healthy 27-year-old male presented with sinus complaints, headache, and unilateral eye discharge. Imaging and endoscopy revealed a mass presumed to represent a juvenile nasopharyngeal angiofibroma. Unexpectedly, the final pathology report revealed high grade mixed ONB and carcinoma. This tumor is the sixth and youngest documented patient with mixed ONB and carcinoma. CONCLUSION: Physicians should remain vigilant for the possibility of malignancy in their approach to nasal cavity masses, even in young otherwise healthy patients. Careful review of the immunohistopathology should also be taken, as mixed olfactory tumors such as these are aggressive, rare entities that require multidisciplinary oncologic care.

Does Argininosuccinate Synthase 1 (ASS1) Immunohistochemistry Predict an Increased Risk of Hemorrhage for Hepatocellular Adenomas?

Hepatocellular adenomas (HCAs) often pursue an innocuous clinical course. Recent work has elucidated important subtypes of HCA and biomarkers to identify them, including HCA at an increased risk for malignant transformation. Another key complication of HCAs is the risk of spontaneous tumoral hemorrhage, which may be life-threatening. Identification of a predictive biomarker for this clinical complication would therefore be of clinical value. It has been suggested that Argininosuccinate Synthase 1 (ASS1) immunohistochemistry (IHC) identifies HCA with a high propensity for hemorrhage. The aim of our study was to validate ASS1 IHC as a predictive marker of hemorrhage. Eighty-nine HCAs were collected for ASS1 IHC and subtyped according to published criteria. Clinical records were examined for evidence of tumoral hemorrhage. Twenty-one (23.6%) HCAs were complicated by clinically detected hemorrhage and were more likely to be resected (P=0.0002). Hemorrhage complicated all WHO subtypes of HCA. There was no association between hemorrhage and HCA subtype (P=0.92). Neither the distribution of ASS1 expression nor the intensity of ASS1 expression compared to normal liver showed a significant association with hemorrhage (P=0.051 and 0.34). Interlaboratory comparison of 8 cases showed good agreement regarding the intensity (6/8 and 7/8) and distribution of staining (7/8 and 7/8) across 3 laboratories performing ASS1 IHC. In conclusion, all subtypes of HCA may be complicated by hemorrhage. ASS1 IHC expression did not correlate with hemorrhagic complications. Caution is prudent before routine implementation of ASS1 IHC in clinical practice.

Response to Neoadjuvant Treatment Is Influenced by Grade in Gastric Cancer.

Neoadjuvant therapy is commonly used in the management of gastric cancer. Primary tumor response to treatment correlates with prognosis. Published studies have compared efficacy of neoadjuvant therapy based on stage but not grade. The objective of this study was to determine the change in staging of gastric cancer after neoadjuvant therapy and resection based on grade. A retrospective analysis of gastric cancer patients treated at our institution between 2005 and 2017 was performed. Patient demographics, tumor characteristics, clinical and pathological stage, and microscopic treatment response were analyzed based on grade. Of the 269 patients identified during this period, 82 patients underwent definitive surgical resection, of which 38 patients received neoadjuvant therapy (low grade (grades 1 and 2), n = 17; high grade (grade 3), n = 18; and unknown grade, n = 3). Pathologic downstaging was observed in 52.9 per cent (9/17) of low-grade tumors compared with 22.2 per cent (4/18) of high-grade tumors. Majority of high-grade tumors (77.8%, 14/18) had either upstaging or unchanged stage. High-grade gastric cancers often lack response to neoadjuvant therapy. Novel targeted therapies based on biologic behavior should be evaluated and incorporated into neoadjuvant treatment. Neoadjuvant studies should stratify patients based on grade and report response by grade.

Acute Postviral Encephalopathy: Pathologic and Radiologic Correlation in an Atypical Case.

The authors report a case of fatal acute encephalopathy following influenza infection, with slightly atypical pathological and imaging findings. A healthy 8-year-old boy with probable recent influenza A/B infection admitted for refractory seizures was placed on phenobarbital coma and later developed hemodynamic instability. Magnetic resonance imaging revealed bilateral cerebral and cerebellar white matter lesions and microhemorrhages. Following his demise, the autopsy revealed a large area of necrosis in the right centrum semiovale with similar lesions in the temporal and cerebellar regions. Microscopically, there was extensive coagulative necrosis, compatible with necrotizing white matter encephalopathy, and neuronal loss suggesting superimposed hypoxic-ischemia. The acute progressive neurologic deterioration was partly reminiscent on acute necrotizing encephalopathy, a condition recently associated with influenza A. In acute necrotizing encephalopathy, typical brain findings are characterized by bilateral thalamic necrosis/petechiae with variable white matter edema. The somewhat atypical findings in our case can relate to superadded cardiovascular collapse and hypoxic-ischemic effects.

Alcohol fat clearing increases lymph node yield after surgery for colorectal cancer.

Lymph node (LN) yield is associated with oncologic outcome in patients who undergo surgery for colorectal adenocarcinoma (CRC). Standards to maximize LN yield have been initiated to enhance treatment of patients with CRC. This study evaluates the impact of a simple alcohol-based preparation protocol on LN yield. Surgical specimens from patients with CRC were prepared using either the alcohol protocol or standard formalin fixation and LN yield was compared. In total, 80 consecutive patients (n = 40 formalin, n = 40 alcohol) were examined. Overall, median LN yield increased from 17 to 29 (P < 0.01) with the alcohol fat clearance protocol. For patients with rectal adenocarcinoma who underwent proctectomy after neoadjuvant chemoradiotherapy, LN yield increased from 15 to 23 (P = 0.02). The frequency of need for additional sampling to achieve a minimum 12 LN count was also reduced. Initiation of a standardized alcohol fat-clearing protocol increased LN yield after surgery for CRC. This simple, cost-effective measure may improve the efficiency of LN assessment and accurate staging, which may impact oncologic outcomes.

The complexity of the count: considerations regarding lymph node evaluation in colorectal carcinoma.

In patients with colorectal carcinoma, studies have reported improved survival with increasing numbers of retrieved lymph nodes. These findings are puzzling, as increased node sampling was not correlated with significant change in disease staging. Although the physiologic processes underlying this correlation between number of lymph nodes sampled and survival remain unknown, the reported correlation has caused modifications to clinical and non-clinical practices. Herein, we review the literature and discuss potential etiologies responsible for the observed increased survival statistics. Literature regarding colorectal lymph node anatomy, molecular aspects of colorectal cancer, changes in tumor characteristics and utilization of lymph node sample numbers are evaluated. In addition, we present the mathematical concepts available for probabilistic prediction of diagnostic confidence based upon sample size. From evaluation of the aggregate literature, certain facts emerge which are not easily identified within the individual studies. Colorectal carcinoma appears to encompass a number of individual disease entities with different physiologic characteristics and likelihoods of metastasis. In addition, it appears the improved survival is likely multifactorial including effects from intrinsic tumor biology and tumor-host interactions along with ever changing clinical practices. Finally, because lymph node count is dependent on a number of variables and is correlated, but unlikely to be causally associated with survival, use of this number as a quality indicator is unwarranted. Based on statistical considerations, the current recommended goal of 12-15 recovered lymph nodes without evidence of metastatic disease provides approximately 80% negative predictive value for colorectal carcinoma metastasis.