Sequencing of an Undifferentiated Carcinoma with Osteoclast-Like Giant Cells of the Pancreas: A Case Report.

Background: Undifferentiated carcinoma with osteoclast-like giant cells/osteoclast-like giant cell reaction (UC-OGC) is a rare form of pancreatic cancer historically associated with a poor prognosis. Molecular tumor profiling provides new information about tumor origins and a more nuanced understanding of the potential efficacy of different chemotherapeutic agents. Presentation: A 69-year-old man presented with a 13-cm periampullary pancreatic mass. Biopsy of a neighboring lymph node was consistent with adenocarcinoma. After neoadjuvant chemoradiation, the patient underwent resection and the tumor was consistent with UC-OGC. Next-generation sequencing was performed with genomic and proteomic analyses analyzed by a molecular tumor board review. These analyses revealed genetic alterations similar to those seen in pancreatic ductal adenocarcinoma, as well as potential therapeutic targets for the patient's subsequent therapy. Conclusions: Understanding a tumor's genetic changes allows for better understanding of its biology and may improve treatment efficacy. We believe that future study in tumor profiling will improve our understanding of rare cancers such as UC-OGC and also pave the way for the use of novel therapies to specifically target mutations in a broad range of more common tumors.

Isolated Ovarian Metastasis from Pancreatic Cancer Mimicking Primary Ovarian Neoplasia: Role of Molecular Analysis in Determining Diagnosis.

Background and Presentation: In this study, we present the case of a 64-year-old female with a chief complaint of abdominal pain and bloating, which had been persistent over a period of 4 months. Imaging revealed a 6.1-cm left-sided pancreatic mass as well as a 19.1-cm multiloculated cystic lesion in the pelvis, later revealed to be replacing the left ovary. The pancreatic mass was biopsied through endoscopic ultrasound-guided fine needle aspiration, and diagnosed as adenocarcinoma by cytology. The patient was treated with neoadjuvant chemotherapy and radiation before laparotomy for resection of the pancreas and left adnexal mass. Her response to treatment was followed radiologically and biochemically with cancer antigen (CA) 19-9 (114-35 U/mL), carcinoembryonic antigen (12-4.8 ng/mL), and CA-125 (119-15.3 U/mL) levels. She subsequently underwent an Appleby procedure, and resection of left pelvic mass and bilateral oophorectomy. Permanent sections revealed residual pancreatic ductal carcinoma with treatment effect, and a multicystic epithelial neoplasia of the left ovary for which the differential was primary ovarian carcinoma versus metastatic disease. Conclusions: Molecular mutational analysis was performed on sections of both the ovarian tumor and the pancreatic tumor to aid in diagnosis. The ovarian tumor in this case showed exactly the same mutations, KRAS G12R and TP53 G245S, as in the treated pancreatic cancer. This raised the high probability that these tumors originated from the same clonal event. The findings suggested that the ovarian tumor was an isolated metastasis of the pancreatic primary, despite the morphologic ambiguity between the two sites of neoplasia.

Imitators of chronic pancreatitis: diffuse neuroendocrine tumour of the pancreas.

We report a rare case of diffuse replacement of the pancreas with neuroendocrine tumour mimicking chronic pancreatitis. A 55-year-old female with no significant past medical history initially presented with abdominal pain in 2006. A CT of the abdomen and pelvis was performed, revealing diffuse pancreatic parenchymal calcifications with mild pancreatic ductal dilatation and no discrete mass. She was diagnosed with chronic pancreatitis and followed clinically until 2015, where she presented with recurrent abdominal pain. A repeat CT and MRI of the abdomen were performed which revealed new hypoenhancing masses within the pancreas, particularly in the pancreatic tail. There was a persistent background of pancreatic parenchymal calcifications. The possibility of pancreatic neuroendocrine tumour was raised, and an indium-111 Octreotide scan was recommended. Diffuse intense uptake was identified throughout the pancreas on the indium-111 imaging. Given the concern for neuroendocrine tumour, a total pancreatectomy was performed, with histopathology revealing replacement of the pancreas with coalescing well-circumscribed nodules. Many of the nodules had numerous calcifications and localized amyloid deposition. Immunohistochemical stains of the neoplastic cells were strong for neuroendocrine markers chromogranin A and synaptophysin. Overall the findings were consistent with numerous neuroendocrine tumours of the pancreas, Grade II, as per the 2010 WHO criteria for neuroendocrine tumours of the pancreas. Neuroendocrine tumours of the pancreas are lesions that arise from the islet cells, with an approximate incidence of five cases per million people per year. Only one other case report has been documented in the literature by Singh et al demonstrating diffuse pancreatic neuroendocrine tumour replacing the entire pancreas. As diffuse pancreatic neuroendocrine tumour can look similar on imaging to chronic pancreatitis or other infiltrative processes, we wanted to present this case and some of the more specific imaging findings in distinguishing these entities.

An evaluation of invasive fungal sinusitis outcomes with subsite analysis and use of frozen section analysis.

BACKGROUND: Invasive fungal sinusitis (IFS) is an aggressive mycosis of the nasal cavity with frequent extension to adjacent structures. Occurring more commonly in immunocompromised individuals, prognosis is typically poor despite aggressive treatment. This study aims to examine postoperative outcomes and survival of a cohort of fungal sinusitis patients at an academic center, as well as identify causes of death in IFS patients. METHODS: This study was a retrospective chart review of patient charts and departmental records, yielding patient demographics, medical and surgical treatments, pathology records, and outcomes data. RESULTS: Twenty-seven patients were identified from departmental records between 1998 and 2014. Twenty-one patients presented with Mucor infections, whereas the remaining 6 patients had Aspergillus. All patients were immunocompromised: diabetes (n = 14) and hematologic malignancy (n = 13). Three patients had multiple causes of immunosuppression. Most commonly involved subsites were the maxillary, ethmoid, and sphenoid sinuses. Nasal septum involvement was independently associated with mortality (p < 0.01). Overall mortality was 57.7% within 1 year, although 66.7% of fatalities occurred within 1 month of diagnosis. CONCLUSION: Overall survival for IFS remains poor. Widespread disease and nasal septum involvement were associated with a negative clinical course. Early identification and aggressive surgical and antifungal therapy is warranted. Even despite intense therapy, comorbid conditions and drug toxicity increase mortality and complicate the clinical course.

Gastrointestinal Stromal Tumors: A Review.

The understanding of aberrant molecular pathways that result in gastrointestinal stromal tumors (GISTs) and the rapid development of molecular therapies that target these pathways represent one of the great milestones in translational oncology. The story of GIST is unique in that targeted molecular therapy was successfully applied in clinical therapeutics, with dramatic results redefining the management of these traditionally chemotherapy-resistant tumors. We briefly review the molecular biology and clinical presentation of GIST and then discuss the adjuvant and neoadjuvant use of tyrosine kinase inhibitors in early-stage GIST and their use in metastatic disease. Newer therapeutic advances in the rapidly changing field of GIST management are also discussed.

Orbital Compartment Syndrome as the Presenting Sign of Disseminated Intravascular Coagulation From Metastatic Prostatic Cancer to the Orbit.

A 70-year-old man with castrate-resistant metastatic prostate cancer to the lumbar spine presented with sudden onset of left orbital compartment syndrome. Hematologic workup revealed disseminated intravascular coagulation with isolated left orbital hemorrhage. A canthotomy and blood product transfusions failed to control the bleeding and restore vision. Operative intervention found a new left orbital roof metastasis from primary prostatic carcinoma. Acute onset of headache or ocular pain in patients with metastatic prostate cancer warrants further workup to rule out orbital and intracranial metastases, rare but significant clinical entities that can lead to severe complications.

A Rare Case of Carcinoma Cuniculatum Involving the Larynx in Association with a Saccular Cyst.

Carcinoma cuniculatum (CC), a rare, well-differentiated variant of squamous cell carcinoma, is uncommon in head and neck sites but when it does occur is most common in the oral cavity. Here we report a rare case of CC involving the larynx. A 49-year-old man presented with 10 months of worsening hoarseness and, despite multiple biopsies, no diagnosis of malignancy could be established. Eventual partial excision of the lesion and histologic review of prior specimens confirmed the diagnosis of CC. Focally, a transition to respiratory epithelium indicated the presence of an associated saccular cyst. Total laryngectomy was performed and 6 months later the patient is free of disease. Only two prior cases of CC have been reported in the larynx. Diagnosis of CC is challenging given the low grade histologic features and awareness of this entity for both treating physicians and the pathologist is important to reach a diagnosis of malignancy. This case highlights the challenges in diagnosis of CC, especially in unusual locations and when associated with other lesions such as a saccular cyst. Awareness of this rare tumor type combined with close communication between treating clinicians, radiologists and pathologists should allow earlier diagnosis and treatment.

Non-neoplastic epithelial cysts of the pancreas: a rare, benign entity.

OBJECTIVES: With the increased use of cross-sectional radiologic imaging in recent years, cystic lesions of the pancreas are being diagnosed with greater frequency. While pseuodocysts have historically accounted for the majority of benign pancreatic cysts, there are a number of rare, benign cystic lesions of the pancreas that can mimic neoplastic cysts. The objective of this study was to review a single institution's experience with these benign cystic lesions of the pancreas. METHODS: We conducted a retrospective analysis of all patients who underwent surgical resection for pancreatic disease from 2005 to 2012 at our institution. Out of a total of 947 pancreatic resections, we identified those cases performed for cystic disease, and focused upon the clinicopathologic data of patients with non-neoplastic pancreatic cysts. RESULTS: Of the 947 pancreatic resections, 256 (27%) were performed for cystic disease. Sixteen cases (6.3%) out of the total of 256 pancreatic operations performed for cystic disease were found to have non-neoplastic cystic lesions of the pancreas. Preoperative imaging revealed primary lesions in all patients, eight of which were found incidentally. Of these lesions, 14 were suspected preoperatively to be mucinous neoplasms and two to harbor pancreatic adenocarcinoma. However, postoperative pathology revealed eight patients with ductal retention cysts, three squamoid cysts, one mucinous non-neoplastic cyst, one congenital ciliated foregut cyst, one lymphoepithelial cyst, and two endometrial cysts. Two patients had complications postoperatively, one pancreatic fistula and one SMV thrombosis. Both complications resolved with conservative management. CONCLUSIONS: Non-neoplastic epithelial pancreatic cysts are rare, benign lesions. In our institutional experience, these lesions are often indistinguishable from cystic neoplasms of the pancreas preoperatively. As such, many of these lesions are resected unknowingly. It is important for the clinician to be well informed of the nature of these lesions, in the hopes to avoid unnecessary resection whenever possible.

Acinar cell cystadenoma of the pancreas: report of three cases and literature review.

INTRODUCTION: Acinar cell cystadenoma (ACC) of the pancreas was first described as a distinct pancreatic cystic neoplasm in 2002. METHODS: We have encountered three cases of ACC at our institution in addition to the 15 cases reported to date in the world literature. The gender distribution in the total cohort of patients with ACC slightly favored females (61 % female), and the median age was 49.5 years. RESULTS: Almost half (53 %) of the cases were identified incidentally, while the remainder presented with abdominal pain. The median tumor diameter was 5 cm in size, and no patients have had documented disease recurrence or progression, even in the setting of an incomplete resection. CONCLUSION: These findings suggest a relatively indolent biology, and that complete resections are curative. As we will show, surgical resection is warranted to treat symptoms and prevent local extension or malignant transformation.