BCOR-Rearranged Sarcoma of the Tonsil.

A tonsillar mass in a young patient with no medical issues routinely presents as an infectious process. Practitioners must maintain a broad differential if diagnostic testing does not support an infection. Neoplasm must be excluded. Otolaryngologists must consider malignancies other than squamous cell carcinoma, the most common oropharyngeal malignancy, and lymphoma. Rare tumors, such as sarcomas, must also be considered. Otolaryngologists must be familiar with the proper management of rare oropharyngeal malignancies.

Papillary thyroid carcinoma in struma ovarii: management after surgery.

A woman in her 40s presented with a 3-month history of lower abdominal pain and intermenstrual bleeding. Ultrasound of the pelvis disclosed a 4 cm left adnexal mass. An MRI of the pelvis revealed a 2.2×3.6×2.4 cm solid, enhancing left ovarian mass. Due to high suspicion for malignancy, she underwent laparoscopic left salpingo-oophorectomy and resection of the tumour. Histopathology revealed papillary thyroid carcinoma in the background of struma ovarii as confirmed by thyroglobulin and thyroid transcription factor-1 positivity on immunohistochemistry. BRAF mutation analysis was negative. An ultrasound of the thyroid gland showed two low-risk nodules. An iodine-123 whole-body scan showed normal uptake in the thyroid gland. Thyroid-stimulating hormone (TSH) was 1.070 mcIU/mL (0.450-4.500), and thyroglobulin was 6.8 ng/mL (1.5-38.5). We risk-stratified this patient as low risk for recurrence. Risk stratification of malignant struma ovarii is essential to determine suitable thyroid targeting adjuvant therapy and reduce the risk of recurrence.

A 62-Year-Old Immunocompromised Man With Halo Sign on Chest Imaging.

CASE PRESENTATION: A 62-year-old White man with a history of orthotopic liver transplantation 16 years ago for alcoholic liver cirrhosis on chronic immunosuppression and recurrent decompensated cirrhosis of his graft liver complicated by ascites, hepatic encephalopathy, and esophageal varices presented to the hospital with altered mental status. Over the last few weeks, he had reduced frequency of bowel movements and subsequently developed altered sensorium 3 days before presentation. On arrival to the hospital, he was disoriented and had asterixis consistent with hepatic encephalopathy. He was not in respiratory distress, he was saturating well on room air, and his lungs were clear to auscultation bilaterally. Plain chest radiograph showed multiple ill-defined bilateral airspace opacities. A CT scan of the abdomen and pelvis done on admission incidentally showed bilateral pulmonary nodules with surrounding ground-glass halo in the lower lung zones. Given these findings, a dedicated CT scan of his chest was performed that showed numerous bilateral randomly distributed nodular airspace opacities, many with a central solid component and surrounding ground-glass halo. Antifungal therapy was initiated empirically. Serum aspergillus antigen and 1,3 beta D-glucan were negative. He subsequently underwent a bronchoscopy with BAL and transbronchial biopsy. BAL fluid was negative for bacterial, fungal, and acid-fast bacilli cultures. Pathology from the transbronchial biopsy showed atypical epithelioid cells in intravascular spaces.

Nuclear Expression of ß-Catenin Is Associated with Improved Outcomes in Endometrial Cancer.

Beta-catenin is involved in intercellular adhesion and participates in the Wnt signaling pathway. This study evaluated the expression pattern and prognostic value of ß-catenin in a series of endometrial carcinoma patients. Immunohistochemical analyses were used to assess the expression and subcellular localization of ß-catenin from tissue sections of 74 patients with endometrial carcinoma. No correlation was found between beta-catenin expression and clinicopathological parameters. Patients expressing nuclear ß-catenin (n = 13; 16%) showed a more favorable prognosis than patients expressing membranous ß-catenin; the 5-year disease-related survival rate was 100% for cases expressing nuclear ß-catenin, compared with 73.8% (SE 0.08) of cases expressing membranous ß-catenin (p = 0.04). Although statistical significance was not reached (p = 0.15), cases expressing nuclear ß-catenin showed a 5-year disease-free survival rate of 90.9% (SE 0.08) compared with 67.4% (SE 0.08) of cases expressing membranous ß-catenin. Univariate Cox analysis revealed that membranous ß-catenin expression was found to be associated with a relative risk of death of 33.9 (p = 0.04). The stage of disease (p = 0.0006), histology (p = 0.003), and grading (p = 0.008) were also significantly correlated with disease-free survival according to univariate Cox analyses. Determining ß-catenin expression and localization patterns may predict survival in patients with endometrial cancer and, therefore, should be considered a potential prognostic marker of disease.

A Rare Case of Calciphylaxis in an Orthotopic Liver Transplant Recipient with Acute Kidney Injury.

Calciphylaxis is a rare disease characterized by calcification of small- to medium-sized blood vessels in the dermis and subcutaneous fat, resulting in cutaneous necrosis. Although most commonly shown in patients with end-stage kidney disease, it has also been reported in patients with other diseases, including alcoholic cirrhosis and malignancies. Here, we report an unusual case of calciphylaxis in an orthotopic liver transplant recipient with acute kidney injury. The patient, a 43-year-old white female with a history of type 2 diabetes mellitus, alcoholic cirrhosis, and normal kidney function, presented with decompensated liver disease and hepatorenal syndrome; she no longer responded to medical treatment and required treatment with dialysis. Ten days after admission, she underwent liver transplant, resulting in improved liver function tests. She had acute tubular necrosis (creatinine peak: 325 µmol/L) from sustained hypotension during and after surgery, which required 4 sessions of dialysis over 2weeks. Six weeks after her transplant, she developed painful, nonulcerating, erythematous plaques over her shins and thighs. Skin biopsy of the lesions showed calciphylaxis, calcium deposits, and thrombotic vasculopathy. She also developed severe hypercalcemia (calcium level of 2.75 mmol/L) from immobility, which required treatment with a bisphosphonate and hemodialysis. The lesions improved 6 weeks later, and her renal function returned to normal. Calciphylaxis diagnosed in an orthotopic liver transplant recipient with acute kidney injury has not been previously reported. We hypothesize that her chronic inflammatory state caused down-regulation and low levels of fetuin A and protein C. She also had other risk factors, including hypoalbuminemia, obesity, systemic glucocorticoids, and alcoholic liver disease. Calciphylaxis can occur in patients with alcoholic cirrhosis and acute renal failure even after liver transplant. Further studies into the pathogenesis of this disease may help us understand why it develops in these patients and not others with the same risk factors.

Concomitant Sarcina-Associated Erosive Esophagitis and Refractory Helicobacter pylori Gastritis.

For unclear reasons, there has been an increasing number of reported cases of Sarcina infections in the gastrointestinal tract over the past several years. Associated clinical conditions with the infection most commonly include delayed gastric emptying from diabetes mellitus, a history of previous gastrointestinal surgery, and ulcer disease. The precise pathogenetic role of Sarcina infection in humans remains unclear. Because of the ubiquitous environmental presence of Sarcina and limited previously reported clinical cases, the link between symptoms along with endoscopic findings to Sarcina can be associative at best. When found in the upper GI tract, the decision to treat along with the chosen regimen remains debatable. Sarcina, however, has rarely been seen in the esophagus. We report the third case of Sarcina of the esophagus associated with Helicobacter pylori gastritis.

Incidental early diagnosis of biphasic pulmonary blastoma in a patient with history of stage IV lung adenocarcinoma.

Biphasic pulmonary blastoma is a rare but lethal type of lung malignancy with characteristic histology of both epithelial and mesenchymal components. Previously reported cases have been limited to presentation at advanced stages, suggesting that the clinical course of the disease is usually aggressive. Here, we report a case of incidental diagnosis of biphasic pulmonary blastoma by imaging surveillance in a patient previously treated for adenocarcinoma of the lung. The patient was diagnosed with stage 1 disease and underwent successful resection. Next-generation sequencing (NGS) revealed a high mutation burden, a finding not previously reported in a patient with biphasic pulmonary blastoma.

Effect of complement C1-esterase inhibitor on brain edema and inflammation after mild traumatic brain injury in an animal model.

OBJECTIVE: Traumatic brain injury (TBI) is characterized by damage to the blood-brain barrier, inflammation, and edema formation. In this pilot study, we aimed to investigate the effects of a complement inhibitor, C1-esterase inhibitor (C1 INH), on brain edema and inflammation in a rat model of mild TBI. METHODS: Thirty-six male Sprague Dawley rats were randomly assigned to control, TBI, or TBI plus C1 INH groups. TBI and TBI plus C1 INH rats received an injection of saline or 25 IU/kg C1 INH, respectively, with TBI using a weight drop model. Control rats received saline only. Rats were subsequently euthanized and their brain tissue harvested for analysis. The primary outcome was the extent of edema as assessed by the brain's water content. Secondary outcomes included enzyme-linked immunosorbent assays to determine levels of pro-inflammatory mediators. RESULTS: Tumor necrosis factor-α levels were significantly greater in TBI rats than control rats, indicating that inflammation was generated by the weight drop impact. Brain water content following TBI was significantly different between TBI rats treated with C1-INH (78.7%±0.12), untreated TBI rats (79.3%±0.12), and control rats (78.6%±0.15, P=0.001). There was a significant decrease in C3a and interleukin 2 levels among C1 INH-treated rats compared with untreated TBI rats, but no change in levels of tumor necrosis factor-α and S100ß. CONCLUSION: C1-INH inhibited the complement pathway, suggesting that C1-INH may have a therapeutic benefit in TBI. Further studies are needed to investigate the effect of C1-INH on clinical outcomes.

Simultaneous Pheochromocytoma, Paraganglioma, and Papillary Thyroid Carcinoma without Known Mutation.

BACKGROUND: Pheochromocytoma/paraganglioma is a rare tumor from neuroendocrine cells. 1/3rd of cases have germline mutations. Papillary thyroid carcinoma (PTC) is a common neoplasm from follicular cells of the thyroid. We report a case of pheochromocytoma/paraganglioma and PTC with negative testing for common mutations. CASE: 32-year-old male with incidental liver mass during laparoscopy for acute appendicitis. His symptoms included abdominal pain and profuse axillary hyperhidrosis. MRI showed an 11x12x14 cm cystic and solid mass in right adrenal gland, and 3.4x2.9x3.8 cm mass in porta hepatis. Urine metanephrines was elevated. After preoperative alpha-blockade, patient underwent total right adrenalectomy. Pathology report confirmed diagnosis of pheochromocytoma. According to the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP), tumor's score was 9, indicating poorly differentiated tumor. Ki67 index 5% and S100 were negative. Postoperatively, plasma free metanephrines normalized but plasma free normetanephrines remained elevated. Based on this biochemical profile, presence of paraganglioma was suspected. CT showed 4.2x3.5 cm round soft tissue mass in porta hepatis which increased in size from previous MRI. Simultaneously, PET scan identified a 1.5 cm thyroid mass. Calcitonin level was normal. Fine-needle aspiration was consistent with PTC. Resection of the mass and total thyroidectomy were performed with confirmation of paraganglioma S100 positive and PTC. Normetanephrines decreased to 283 (<148 pg/mL); free metanephrines remained normal. Gene mutation of EGLN1, FH, KIF1B, MEN1, NF1, RET, SDHAF2, SDHC, SDHD, TMEM127, VHL, and SDHA was negative. CONCLUSION: Whether paraganglioma/pheochromocytoma/PTC combination is coincidental or resulted from an underlying unknown mutation cannot be excluded.

Effect of intrasite vancomycin powder on development of epidural fibrosis.

Placement of vancomycin powder into the surgical wound prior to closure has been shown to reduce postoperative infections in spine surgery. This study examines the effect of vancomycin powder on formation of epidural fibrosis (EF). Twenty-two rats underwent a two-level lumbar laminectomy. A control group, a low-dose and a high dose vancomycin powder (applied prior to closure) group was formed. Rats were sacrificed at 30 days and a blinded fellowshiptrained pathologist evaluated the laminectomy segments for EF. 50% of the samples in the high-dose vancomycin group were EF grade 3, compared to 20% of the low-dose and 16.7% of control samples. The average fibrosis grade for the high dose, low dose and control groups were 2.4, 1.4 and 1.8, respectively. There were more grade 3 EF specimens in the high dose vancomycin group. While the average EF grade was also higher in this group, there was not a statistical difference compared with the other groups.

An academic community hospital experience using commercially available molecular testing in the management of indeterminate thyroid nodules.

INTRODUCTION: Molecular thyroid testing is increasingly being used to further stratify risk of malignancy in cytologically indeterminate thyroid nodules. We report our experience using three commercially available tests in a community hospital setting. MATERIALS AND METHODS: All molecular test reports (Afirma, ThyroSeqV2, and ThyGENX/ThyraMIR) on thyroid nodules from Einstein Medical Center, Philadelphia, between April 2014 to March 2017 were compared with follow-up surgical results as part of a quality assurance exercise. Slides and records of disparities were reviewed. RESULTS: Ninety-five thyroid nodules with molecular testing were identified with surgical follow up available on 19. No benign Afirma results had surgical follow-up. All 7 suspicious Afirma results had surgery, with 3 being benign on follow-up. Ten ThyroseqV2 tested nodules had follow-up surgery and included 2 papillary carcinomas following a completely negative result and another papillary carcinoma following over expression of the NIS gene reported as likely benign. One case with a TP53 mutation was benign on follow-up total thyroidectomy. Follow-up on 1 NRAS point mutation by ThyGenX/ThyraMIR was confirmed malignant although the microRNA portion of the test was negative. CONCLUSIONS: Quality assurance review refined our utilization practices as we better appreciated the limitations of molecular testing and use relative to other factors in managing indeterminate thyroid nodules.

The impact of enoxaparin administration in relationship to hemorrhage in mild traumatic brain injury.

BACKGROUND: Venous thromboembolism prophylaxis in the general trauma population is well established. However, risk of increased intracranial hemorrhage in traumatic brain injury (TBI) population is of concern. The aim for this study is to identify a reproducible model of mild traumatic brain injury (mTBI), evaluated by clinical and histological markers and test the hypothesis that enoxaparin increases the risk of spontaneous brain hemorrhage. METHODS: 40 male Sprague Dawley rats were randomly assigned to 5 groups: group 1 (sham) with no TBI along with 4 groups comparing mTBI with and without pharmacological intervention using enoxaparin at 24 h and 72 h respectively. Mild traumatic brain injury was induced using a weight drop apparatus, with a clinical endpoint of time to right (TTR), along with histological and spectrophotometer analysis for qualitative hemorrhage. RESULTS: There is a statistically significant difference between group 1 (sham) and all other groups with a mean longer time to right of 64 s (p = 0.005) in the mTBI groups. There was a statistically significant difference between group 1 (sham) and all other groups with an increase of 6 g/dL hemoglobin (p < 0.001) in the mTBI groups with no difference in hemorrhage between groups that were treated with enoxaparin. CONCLUSION: The weight drop apparatus is a reproducible model for mTBI that has correlations with clinical and qualitative data. This model was able to produce clinical signs of concussion, as reflected by longer TTR and increased hemoglobin in the mTBI groups. Upon further analysis, there wasno increase in hemorrhage in the pharmacological intervention groups with enoxaparin.

Expression of cell cycle-regulated proteins pRB2/p130, p107, E2F4, p27, and pCNA in salivary gland tumors: prognostic and diagnostic implications.

The retinoblastoma family consists of the tumor suppressor nuclear phosphoprotein pRb/p105 and related proteins p107 and pRb2/p130. Recent immunohistochemical studies of the retinoblastoma family of proteins in lung and endometrial cancer and choroidal melanomas show a tight inverse correlation between the histologic grading in the most aggressive tumor types and pRb2/p130 expression. This led us to investigate the role of pRb2/p130 in salivary tumors. We studied the expression of pRb2/p130, p107, E2F4, p27, and PcNA by immunohistochemistry in a panel of 44 salivary gland tumors. We found a direct correlation between the cytoplasmic expression of pRb2/p130 and tumor grading and the presence of metastasis that was highly statistically significant (P < 0.001). Additionally, increased cytoplasmic pRb2/p130 expression was significantly correlated with a decreased probability of survival (P < 0.001). Interestingly, p107 nuclear expression showed a strong direct correlation when compared with the same variables. pRb2/p130 showed the highest percentage of undetectable nuclear levels in the specimens examined and the tightest inverse correlation (P < 0.0001) with both the histologic grading and pCNA expression in malignant salivary tumors. Additionally, E2F4 showed an identical localization pattern as to that of pRb2/p130. These data suggests an important role for pRb2/p130 in the pathogenesis and progression of certain salivary gland cancers.

Submandibular Gland Epithelial-Myoepithelial Carcinoma with Osseous Metastasis: A First Reported Case and Review of the Literature.

Epithelial-myoepithelial carcinoma (EMC) is a low grade tumor that comprises 1% of all salivary tumors. Local recurrence is not uncommon, but rarely does this tumor demonstrate distant metastasis. We describe a case of a 53-year old female presenting with an asymptomatic, slowly enlarging left submandibular neck mass. Excision of the left submandibular gland (SMG) revealed epithelial-myoepithelial carcinoma with extensive perineural invasion and microscopically positive margins. A subsequent left supraomohyoid neck dissection demonstrated no residual tumor. The patient was stable for one year until a magnetic resonance imaging (MRI) workup for low back pain revealed multiple sclerotic lesions in the iliac crest and lumbar spine, with an iliac crest biopsy demonstrating metastasis. 2.5 year post-operative positron emission tomography-computed tomography (PET-CT) revealed increased [18F]-fluorodeoxyglucose (FDG) avidity in the right iliac crest, pubic symphysis, thoracic and lumbar spine, 9th rib, and sternum concerning for local recurrence and further osseous metastasis. We report the first known case of a submandibular gland EMC with osseous metastasis and highlight the need for prolonged tumor surveillance.

Frequent loss of pRb2/p130 in human ovarian carcinoma.

PURPOSE: RB2/p130, a member of the retinoblastoma gene family, maps to human chromosome 16q12.2, a region in which deletions have been found in several human neoplasms including breast, prostatic, and ovarian carcinoma. We sought to evaluate pRb2/p130 protein expression and function in ovarian carcinoma. EXPERIMENTAL DESIGN: pRb2/p130 expression was detected by immunohistochemical and Western blot analyses in 45 primary ovarian carcinoma samples. RESULTS: Immunohistochemical analysis revealed loss or decrease of pRb2/p130 expression in 18 cases (40%). pRb2/p130 expression was mostly nuclear and inversely correlated to the tumor grade (P < 0.05). Western blot analysis correlated with immunohistochemical expression. Reverse transcription-PCR followed by Southern blot analysis was performed on a representative set of 20 ovarian carcinomas. RB2/p130 mRNA levels were consistent with protein expression. We found a significant increase in the percentage of G(1)-phase-arrested cells in CAOV3 and A2780 ovarian carcinoma cell lines after transduction with an adenovirus carrying the RB2/p130 gene (Ad-CMV-RB2/p130). CONCLUSIONS: These data indicate that loss or decrease of pRb2/p130 expression is a frequent event in ovarian carcinoma and is regulated mostly at the transcriptional level. Moreover, pRb2/p130 overexpression is able to arrest cell growth in ovarian carcinoma cells, suggesting the putative role of pRb2/p130 as a tumor suppressor in this malignancy.

pRb2/p130, vascular endothelial growth factor, p27(KIP1), and proliferating cell nuclear antigen expression in hepatocellular carcinoma: their clinical significance.

Hepatocarcinoma (HCC) is the fifth most common cancer, with more than one million fatalities occurring annually worldwide. Multiple risk factors are associated with HCC disease etiology, the highest incidence being in patients with chronic hepatitis B virus and hepatitis C virus, although other factors such as genetic makeup and environmental exposure are involved. Multiple genetic alterations including the activation of oncogenes and inactivation of tumor suppressor genes are required for malignancy in human cancers and are correlated with increased stages of carcinogenesis and further tumor progression. In this study of 21 HCC patients, we analyzed pRb2/p130, vascular endothelial growth factor (VEGF), p27((KIP1)), and proliferating cell nuclear antigen as potential HCC molecular biomarkers. In our sample set, we found that p27((KIP1)) was absent. Univariate survival analysis showed that proliferating cell nuclear antigen expression (diffuse staining >50% of positive cells in tumor) was confirmed as a significant HCC prognostic biomarker for determining patient survival agreeing with previous studies (P = 0.0126, log-rank test). Lower pRb2/p130 expression was associated to a borderline P value of inverse correlation with tumor malignancy and to a positive correlation with respect to the time from HCC diagnosis (Spearman coefficient = 0.568; P < 0.05). Conversely, higher VEGF expression was associated with a poor survival (P = 0.0257, log-rank test). We demonstrate for the first time that pRb2/p130 is inversely correlated with VEGF expression and tumor aggressiveness (P < 0.05) in p27((KIP1))-negative HCC patients. pRb2/p130 and VEGF expression are independent from tumor staging, suggesting their possible role as independent prognostic molecular biomarkers in HCC. Furthermore, we have evidence that VEGF together with pRb2/p130 may act as new HCC biomarkers in a p27((KIP1))-independent manner. Additional studies with larger numbers of patient data would allow the use of multivariable techniques and would be able to further identify patients with poorer survival.

Frequent loss of expression of the cyclin-dependent kinase inhibitor p27(Kip1) in estrogen-related Endometrial adenocarcinomas.

PURPOSE: p27(Kip1) is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of gynecological tumors, including breast, ovarian, and cervical carcinomas. The role of p27 in endometrial cancer remains controversial. EXPERIMENTAL DESIGN: In the present study, p27 protein expression was investigated by immunohistochemistry in a series of 217 endometrial adenocarcinomas and, where present, in synchronous normal endometrium, simple and complex hyperplasia (with or without atypia), and cystic atrophy. The relationship between p27 expression and clinical outcome was also evaluated. RESULTS: Immunohistochemical analysis revealed a significant loss of p27 expression from normal (33%) through hyperplastic endometrium (50%) to endometrial adenocarcinomas (71%; P

Cytologic findings of malignant vascular neoplasms: a study of twenty-four cases.

Cytologic characterization of malignant vascular neoplasms (MVN) is difficult due to the wide range of differential diagnoses and sampling errors. The objective of this study was to identify criteria helpful in the cytologic diagnosis of MVN. The clinical presentation and cytomorphologic features of 22 angiosarcomas and two hemangioendotheliomas were analyzed. The criteria evaluated included cellularity, cellular arrangement, cell shape and size, pleomorphism, cytoplasmic borders, nuclear shape and number, chromatin pattern, nucleoli, background, and presence of angioformative structures. A previous history of MVN was noted in 18 of 24 patients. Specimens with epithelioid morphology were more cellular and pleomorphic and contained multinucleated cells. Specimens with spindle morphology were usually less cellular and less pleomorphic. Angioformative structures were identified in 11 of 24 cases. Awareness of features suggestive of MVN is necessary to raise the possibility of vascular origin, which can be confirmed with appropriate immunocytochemical studies.

Soft tissue sarcoma at a dialysis access site in a transplant recipient.

Soft tissue sarcomas typically present as soft, painless masses on an extremity. Here, we present a patient with metastatic soft tissue sarcomas at his dialysis access site. This association with dialysis access has not been documented previously. A 62-year-old man presented with a nonhealing wound on his left upper extremity after excision of a pseudoaneurysmal arteriovenous fistula. The patient had received a second kidney transplant that was functioning well. Immunosuppression included tacrolimus, mycophenolate mofetil, and prednisone. He was induced with thymoglobulin twice. A biopsy was performed showing a high-grade pleomorphic sarcoma. A magnetic resonance image of his left upper extremity showed an 11 × 5.5 × 3 cm mass abutting the biceps and brachialis muscles. Also, we discovered several lesions in the axilla and the left side of the neck, which were suspicious for metastases. A positron emission tomography-computed tomography scan confirmed a left upper extremity soft tissue mass, with marked fluorodeoxyglucose uptake, in abnormally enlarged axillary, and supraclavicular lymph nodes of the left thorax, consistent with metastases. The patient underwent chemotherapy and radiation therapy. Soft tissue sarcomas are rare. A high index of suspicion is needed to make a diagnosis. This is the first reported case of a soft tissue sarcoma discovered at a dialysis access site. As with all malignancies, early diagnosis is key to patient survival. Thorough physical examinations and increased vigilance by physicians caring for immunosuppressed patients is invaluable.