Unusual Presentation of Lipofibromatosis-Like Neural Tumor in an Adult: A Case Report.

Lipofibromatosis-like neural tumor (LPF-NT) is a rare variant of lipofibromatosis. Standard lipofibromatosis tumors show a predilection for the distal extremities of male children or young adults and are typically painless, slow-growing, subcutaneous or deep soft tissue masses. We present a case of a 50-year-old male with a slowly expanding, right foot mass. Physical examination revealed a painful, non-tender firm mass on the right medial foot. Magnetic imaging studies revealed a poorly defined soft tissue mass extending through subcutaneous tissue up to the dermis. Histologic examination revealed a spindle cell neoplasm. Immunohistochemistry showed co-expression of S100 protein, CD34 and TRK. In addition, the lesion was found to be positive for the LMNA-NTRK1 fusion by next-generation sequencing. These findings were supportive of a diagnosis of LPF-NT. At 3-month post-excision, the patient had no pain and repeat imaging indicated no evidence of tumor. The authors recommended including LPF-NT in the differential diagnosis of masses or lesions that are fibro-fatty tumors.

Eosinophilic Mucin: A Predictor for Disease Severity in Chronic Rhinosinusitis.

OBJECTIVE: The presence of tissue eosinophilia is a determinate of disease severity in patients with chronic rhinosinusitis (CRS). The impact of eosinophilic mucin (EM) as an independent variable has not yet been elucidated. STUDY DESIGN: Retrospective review. SETTING: Tertiary academic clinic.Subjects Methods: CRS patients who failed medical therapy were classified by tissue eosinophilia, presence of polyps and EM. Tissue eosinophilia count per high power field (HPF) as well as the presence of EM were determined by pathologic examination of sinus tissue removed during surgery. Sinonasal Outcomes Test (SNOT-22), Lund-Mackay (LM), and Lund-Kennedy (LK) scores were compared between all groups preoperatively and postoperatively up to two and a half years (30 months). RESULTS: 192 patients with CRS were included in the study. 87 were diagnosed with eosinophilic CRS with polyps, 58 with eosinophilic CRS without polyps, 14 with noneosinophilic CRS with polyps, and 33 with noneosinophilic CRS without polyps. Only patients with eosinophilia had EM on pathology. Of eosinophilic CRS, 50% of patients with polyps and 12% of cases without polyps demonstrated EM, respectively. EM presence portended more severe disease in patients with eosinophilia on subjective and objective scores preoperatively (P < 0.005). Postoperatively, EM patients experienced a greater improvement of symptoms, but continued to have worse endoscopy scores until 1.5 years. A tissue eosinophil count of 30 or greater per HPF was identified as a potential marker for the development of EM. CONCLUSIONS: The presence of eosinophilic mucin predicts overall worse disease severity in patients with eosinophilic CRS.

Paraneoplastic Limbic Encephalitis in a Patient with Primary Well-differentiated Teratoma and Metastatic Poorly Differentiated Embryonal Carcinoma.

Testicular tumors account for 1-2% of all tumors in men, with 95% of these being germ cell tumors. Paraneoplastic limbic encephalitis is a rare sequela of testicular tumors associated with anti-Ma2 and KLH11 antibodies. The most effective treatment for paraneoplastic limbic encephalitis is treatment of the primary malignancy. We report a 41-year-old male that presented to the emergency department with episodic alteration of consciousness and memory disturbances. Negative neurologic evaluation and imaging led to concern for a paraneoplastic process from a distant malignancy. CT imaging revealed an enlarged, necrotic para-aortic lymph node and subsequent ultrasound demonstrated a right-sided testicular mass. Right radical orchiectomy was performed. Microscopically, the mass consisted of mixed respiratory epithelium, gastrointestinal glands, and squamous epithelium with keratinization consistent with a post-pubertal testicular teratoma with associated in situ germ cell neoplasia. Resection of the para-aortic mass revealed large anaplastic cells with epithelioid features, nuclear pleomorphism and frequent mitoses. Immunostaining was positive for Pan-Keratin and OCT4, consistent with poorly differentiated embryonal carcinoma. Resection of the primary and metastatic disease, as well as treatment with corticosteroids, resulted in resolution of the encephalitis. This presentation of severe neurological disturbances in the setting of a metastatic mixed non-seminomatous germ cell tumor represents a rare presentation of paraneoplastic limbic encephalitis.

Travel-screening documentation to enable the "Identify-Isolate-Inform" framework for emerging infectious diseases: It's all in the details.

The early phase of the coronavirus disease 2019 (COVID-19) pandemic and ongoing efforts for mitigation underscore the importance of universal travel and symptom screening. We analyzed adherence to documentation of travel and symptom screening through a travel navigator tool with clinical decision support to identify patients at risk for Middle East Respiratory Syndrome.

How Does Age Impact Presentation and Outcomes in Chronic Rhinosinusitis?

OBJECTIVES/HYPOTHESIS: The presence of eosinophilia and nasal polyps are well-established prognostic indicators of chronic rhinosinusitis (CRS). The importance of demographic background, such as age, as independent variables has not been elucidated while taking these factors into account. STUDY DESIGN: Respective review. METHODS: CRS patients who underwent primary surgical treatment were subdivided based on age (young adults = age 18-39, adults = age 40-64, and elderly = age 65+). Groups were then subdivided based on tissue eosinophilia and nasal polyposis. Sinonasal Outcome Test (SNOT-22), Lund-Kennedy (LK) endoscopy scores, and Lund-McKay (LM) CT scores were compared preoperatively, and postoperatively during a 5-year period. RESULTS: A total of 431 CRS patients identified and then subsequently broken down into 63 young adults (YA), 209 adults (A), and 159 elderly (E). There was no statistical difference between tissue eosinophilia and presence of polyps between the groups. All three groups had similar short- and long-term SNOT-22 patterns postoperatively. At presentation, young adults had significantly higher SNOT-22 score (33.2 YA, 25.3 A, 23.5 E, P = .029) and significantly higher rhinologic scores (1.9 YA, 1.3 A, 1.3 E, P = .0012) than the adult and elderly patients. Objective disease severity using LK endoscopy scores were only significantly higher in young adults at 1-year time (P = .0026). There was no statistical difference between the groups in regards to preoperative LM CT scores. CONCLUSIONS: Young adults are more likely to present with overall higher subjective SNOT-22 scores over adults and elderly patients, despite similar objective findings in the groups. Short- and long-term postoperative improvement holds across all age groups. LEVEL OF EVIDENCE: 4.

When Pigs Fly: A Multidisciplinary Approach to Navigating a Critical Heparin Shortage.

A recent outbreak of African swine fever (ASF) in China has claimed the lives of millions of pigs, and although this virus has no health impacts on humans, the disruption of the global pig population has far-reaching negative impacts on economic and pork-derived products, including the creation of the critical drug heparin. The active pharmaceutical ingredient in heparin is derived from pig intestines, and because of the ASF outbreak, the U.S. faces an imminent shortage of heparin. This drug shortage has the potential for profound implications, as heparin is used in a substantial and varied number of medical conditions. In response to notification of the heparin shortage crisis, our institution, Massachusetts General Hospital, activated its Hospital Incident Command System to streamline organization of major stakeholders and oversee operational and clinical activities required to mitigate the potential risks and optimize alternative effective strategies. This article describes the essential elements of our institution's emergency response plan, including detailed clinical algorithms developed by our experts for maximal heparin conservation and waste reduction by promoting safe and effective alternative strategies. Through this practice, we have also identified opportunities to change providers' prescribing and utilization behaviors for the better. As the ASF has not yet been contained and this crisis continues, the strategies and policies employed by our institution can provide a framework for other institutions to tackle this ongoing challenge and future drug shortage crises. IMPLICATIONS FOR PRACTICE: A detailed description of how one institution addressed the current heparin crisis, to support heparin conservation and waste reduction, is provided. The strategies used helped decrease heparin use by 80% in less than 2 months of establishing the task force. This accomplishment can be credited to the development of a task force and strategic plan in which experts and stakeholders were quickly identified, offered a part in the decision-making process, and frequently updated. Furthermore, the response system was dynamic, accessible, and one in which challenges were recognized and acted upon. The key to any crisis management is respect for one another and constant and open communication. Heparin is such a widespread drug that this shortage can potentially affect every patient population and provider. Understanding one's institutional needs and the effect of this crisis on those needs is one of the first steps when developing a strategic plan. Continually evaluating and adjusting that approach in response to the needs of the institution are critical to its success. Moreover, as it did for the authors' institution, a constant appraisal of the strategies can lead to opportunities for improvements in organization and practice that can be sustained well beyond the crisis.

Use of mucosal eosinophil count as a guide in the management of chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a local inflammatory process driven by eosinophils. Mucosal eosinophil count (MEC) has previously been demonstrated to be a reliable indicator of disease severity. We aim to evaluate use of MEC in guiding medical management of CRS after functional endoscopic sinus surgery (FESS). METHODS: We retrospectively reviewed patients with CRS who underwent FESS from 2004 to 2017. Tissue MEC per high-power field (HPF) was determined by pathologic examination. MECs were compared by polyp status, postoperative medication requirements, and revision surgery. Patients received normal saline (NS) nasal irrigations with additional treatment as needed for disease control: 1-drug therapy (1-DT) intranasal steroid spray (ISS), 2-drug therapy (2-DT) ISS plus budesonide nasal irrigations (BNI) or leukotriene receptor antagonist (LRA), or 3-drug therapy (3-DT) ISS plus BNI and LRA. Correlations between MEC and 22-item Sino-Nasal Outcome Test (SNOT-22), preoperative computed tomography (CT), and nasal endoscopy scores were evaluated. RESULTS: A total of 156 patients were included. Fifty-seven were managed with 1-DT, 35 with 2-DT, and 62 with 3-DT. Across all patients, mean postoperative 6-month and 1-year SNOT-22 (18.1 ± 17.0, 18.1 ± 20.2, respectively) and nasal endoscopy (3.6 ± 3.8, 3.6 ± 4.1, respectively) scores were significantly lower than preoperative scores (37.4 ± 22.8, 6.5 ± 4, respectively). With increasing MEC, odds of requiring 2-DT (odds ratio [OR] = 1.1, p = 0.0002), 3-DT (OR = 1.12, p < 0.0001), and revision surgery (OR = 1.11, p < 0.0001) were significantly increased. Preoperative endoscopy (ρ = 0.44, p < 0.0001) and CT scores (ρ = 0.51, p < 0.0001) and postoperative 6-month (ρ = 0.55, p < 0.0001) and 1-year (ρ = 0.4, p < 0.0001) endoscopy scores demonstrated good correlation with MEC. CONCLUSION: MEC correlates with objective clinical disease severity and may guide aggressiveness of management for the individual patient.

Cervical nodal metastasis after malignant conversion of sinonasal inverted papilloma: Report of a rare case and literature review.

Malignant conversion of sinonasal inverted papilloma (SNIP) occurs in approximately ten percent of cases. These tumors are classically described as locally destructive, but without metastatic potential. Only four cases of malignant conversion with cervical nodal metastases have been described in the English literature. We present the rare case of a 61-year-old Caucasian male with a nasopharyngeal recurrence of malignant SNIP with cervical and retropharyngeal nodal metastases. The patient underwent endoscopic transpterygoid with nasoseptal flap reconstruction, followed by staged bilateral and retropharyngeal node dissection. Histopathology of the specimens demonstrated poorly differentiated invasive nonkeratinizing squamous cell carcinoma with inverted-type features. Three months after surgery, the patient suffered from C1-C2 fractures consistent with osteoradionecrosis and expired. Although the rate of malignant conversion of SNIP is low, this case highlights the need for aggressive, definitive treatment and surveillance.

Head and Neck Cancer Soft Tissue Radiation Necrosis-Diagnostic Challenge.

A 53-year-old man with T4aN2cM0 tongue base squamous cell carcinoma received definitive chemoradiation. FDG PET/CT at 6 weeks showed partial metabolic response with soft tissue air indicating radiation necrosis at primary site and complete response in the neck. At 9 weeks, contrasted CT showed worsening but nonenhancing ulceration, area biopsied demonstrating a minute carcinoma focus with treatment effect. At 12 weeks, PET/CT showed increased primary site uptake interpreted as disease progression; however, no viable tumor was found at salvage surgery. Because nonenhancing ulceration predicts pure radiation necrosis with no viable tumor, contrasted CT may guide treatment selection in challenging cases.

Interpathologist Diagnostic Agreement for Non-Small Cell Lung Carcinomas Using Current and Recent Classifications.

CONTEXT.­: Measurement of interpathologist diagnostic agreement (IPDA) should allow pathologists to improve current diagnostic criteria and disease classifications. OBJECTIVES.­: To determine how IPDA for pathologists' diagnoses of non-small cell lung carcinoma (NSCLC) is affected by the addition of a set of mucin and immunohistochemical (IHC) stains to hematoxylin-eosin (H&E) alone, by recent NSCLC reclassifications, by simplification of these classifications, and by pathologists' practice location, pulmonary pathology expertise, practice duration, and lung carcinoma case exposure. DESIGN.­: We used a Web-based survey to present core images of 54 NSCLC cases to 22 practicing pathologists for diagnosis, initially as H&E only, then as H&E plus mucin and 4 IHC stains. Each case was diagnosed according to published 2004, 2011, and 2015 NSCLC classifications. Cohen's kappa was calculated for the 231 pathologist pairs as a measure of IPDA. RESULTS.­: Twenty-two pathologists diagnosed 54 NSCLC cases by using 4 published classifications. IPDA is significantly higher for H&E/mucin/IHC diagnoses than for H&E-only diagnoses. IPDA for H&E/mucin/IHC diagnoses is highest with the 2015 classification. IPDA is estimated higher after collapse of stated diagnoses into subhead or dichotomized classes. IPDA for H&E/mucin/IHC diagnoses with the 2015 World Health Organization classification is similar for community and academic pathologists, and is higher when pathologists have pulmonary pathology expertise, have more than 6 years of practice experience, or diagnose more than 100 new lung carcinoma cases per year. CONCLUSIONS.­: Higher IPDA is associated with use of mucin and IHC stains, with the 2015 NSCLC classification, and with pathologists' pulmonary pathology expertise, practice duration, and frequency of lung carcinoma cases.

Cytokeratin-8 in Anaplastic Thyroid Carcinoma: More Than a Simple Structural Cytoskeletal Protein.

Anaplastic thyroid carcinoma (ATC) is almost universally fatal. Elevated keratin-8 (KRT8) protein expression is an established diagnostic cancer biomarker in several epithelial cancers (but not ATC). Several keratins, including KRT8, have been suggested to have a role in cell biology beyond that of structural cytoskeletal proteins. Here, we provide evidence that KRT8 plays a direct role in the growth of ATCs. Genomic and transcriptomic analysis of >5000 patients demonstrates that KRT8 mutation and copy number amplification are frequently evident in epithelial-derived cancers. Carcinomas arising from diverse tissues exhibit KRT8 mRNA and protein overexpression when compared to normal tissue levels. Similarly, in a panel of patient-derived ATC cell lines and patient tumors, KRT8 expression shows a similar pattern. sh-RNA-mediated KRT8 knockdown in these cell lines increases apoptosis, whereas forced overexpression of KRT8 confers resistance to apoptosis under peroxide-induced cell stress conditions. We further show that KRT8 protein binds to annexin A2, a protein known to mediate apoptosis as well as the redox pathway.

Battling regional (stage III) lung cancer: bumpy road of a cancer survivor in the immunotherapy age.

A 58-year-old woman, a heavy smoker, was diagnosed with stage III squamous cell lung cancer. She was treated with concurrent chemotherapy and radiotherapy, with partial response. 2 months later, she had haemoptysis caused by brisk bleeding from the radiated right upper lobe. Fortunately, her bleed was self-limited. 4 months later, a rapidly enlarging renal mass was discovered and turned out to be metastatic from the lung primary. Second-line chemotherapy with docetaxel and ramucirumab did not have effects on the renal mass after 2 cycles. Despite not being eligible for a durvalumab trial because of lack of PD-L1 expression, she had a meaningful response to nivolumab. Once every 2 weeks, infusion of nivolumab resulted in rapid tumour shrinkage in multiple areas. In the next few months, she experienced a variety of side effects, some of which were potentially life-threatening. She had disease progression 9 months into treatment.

IgG4-Related Disease Presenting as a Solitary Neck Mass.

IgG4-related disease is a newly recognized entity associated with autoimmune conditions involving almost every organ system. It is characterized by elevated serum IgG4 as well as mass like tissue infiltration by IgG4-positive plasma cells. Imaging findings are nonspecific, vary depending on the site of disease, and include mass like enlargement of the salivary or lacrimal glands and enlarged lymph nodes. Radiographic findings often mimic malignancy, necessitating tissue sampling to confirm the diagnosis. Distinguishing IgG4-related disease from malignancy is important as IgG4 responds well to steroids and conservative management.

Nanoscintillator-mediated X-ray inducible photodynamic therapy for in vivo cancer treatment.

Photodynamic therapy is a promising treatment method, but its applications are limited by the shallow penetration of visible light. Here, we report a novel X-ray inducible photodynamic therapy (X-PDT) approach that allows PDT to be regulated by X-rays. Upon X-ray irradiation, the integrated nanosystem, comprised of a core of a nanoscintillator and a mesoporous silica coating loaded with photosensitizers, converts X-ray photons to visible photons to activate the photosensitizers and cause efficient tumor shrinkage.

The initial response to the Boston marathon bombing: lessons learned to prepare for the next disaster.

OBJECTIVE: We discuss the strengths of the medical response to the Boston Marathon bombings that led to the excellent outcomes. Potential shortcomings were recognized, and lessons learned will provide a foundation for further improvements applicable to all institutions. BACKGROUND: Multiple casualty incidents from natural or man-made incidents remain a constant global threat. Adequate preparation and the appropriate alignment of resources with immediate needs remain the key to optimal outcomes. METHODS: A collaborative effort among Boston's trauma centers (2 level I adult, 3 combined level I adult/pediatric, 1 freestanding level I pediatric) examined the details and outcomes of the initial response. Each center entered its respective data into a central database (REDCap), and the data were analyzed to determine various prehospital and early in-hospital clinical and logistical parameters that collectively define the citywide medical response to the terrorist attack. RESULTS: A total of 281 people were injured, and 127 patients received care at the participating trauma centers on that day. There were 3 (1%) immediate fatalities at the scene and no in-hospital mortality. A majority of the patients admitted (66.6%) suffered lower extremity soft tissue and bony injuries, and 31 had evidence for exsanguinating hemorrhage, with field tourniquets in place in 26 patients. Of the 75 patients admitted, 54 underwent urgent surgical intervention and 12 (22%) underwent amputation of a lower extremity. CONCLUSIONS: Adequate preparation, rapid logistical response, short transport times, immediate access to operating rooms, methodical multidisciplinary care delivery, and good fortune contributed to excellent outcomes.