Precision medicine: Sustained response to erdafitinib in FGFR2-mutant, multiply recurrent ameloblastoma.

BACKGROUND: Ameloblastoma imposes significant morbidity and high-recurrence rates following surgery and radiation therapy. Although 89% of cases harbor oncogenic mutations, the role of targeted therapy is undefined. CASE: We describe a case of a 40-year-old male with multiply recurrent, locally invasive ameloblastoma of the posterior maxillary ridge. The tumor was unresectable for negative margins due to extensive intracranial disease, and the patient suffered severe symptoms including pain. Immune and genomic profiling were obtained to guide systemic treatment, showing a PD-L1 score of 2% and FGFR2V395D and SMOW535L mutations. The patient progressed rapidly on anti-PD1 immunotherapy. He was treated with the FGFR inhibitor, erdafitinib, with excellent partial response including resolution of intracranial disease and cancer-related pain, ongoing 2 years after drug initiation. CONCLUSION: Targeting the FGFR2 mutation resulted in sustained response and improved quality of life. Genomic profiling with targeted therapy for ameloblastoma appears promising, especially when surgery is technically infeasible.

Papillary Mucinous Adenocarcinoma of the Endolymphatic Sac: A Rare Middle Ear Neoplasm.

Glandular neoplasms of the temporal-mastoid region and endolymphatic sac (ELS) are rare, and it is quite challenging to differentiate between an adenoma and an adenocarcinoma. ELS tumors (ELST) usually present with papillary, follicular, or solid patterns and can be further distinguished histologically and through immunohistochemistry. The microscopic features and clinical course of this neoplasm have been comprehensively explained by Heffner, who considered it "low-grade adenocarcinoma of likely ELS origin." The papillary form more commonly affects females, and it is a more aggressive form of ELST that is destructive and exhibits extensive local spread. The tumor usually has a close association with von Hippel-Lindau (VHL) disease, but 11%-30% of the ELST cases develop in individuals without a VHL mutation. ELSTs manifest with headaches, hearing loss, ear discharge, and cranial nerve palsies. Currently, the only available curative therapeutic intervention consists of wide local excision and long-term follow-up. Because of the sensitive location of this tumor, the adjuvant radiotherapy options are still questionable. In this case report, the author presents a 74-year-old woman with a past medical history of Schneiderian papilloma and was diagnosed with papillary mucinous adenocarcinoma of the ELS not associated with VHL disease.

Hypopharyngeal Dedifferentiated Liposarcoma in the MDM2 Era: A Case Report and Short Review.

Pharyngeal liposarcomas are very rare; still more rare are dedifferentiated liposarcomas in the pharynx. An 82-year-old man presented with dysphagia, voice changes, weight loss, nasal regurgitation of liquids, and coughing spells. A 3.5 cm mass was identified in the hypopharynx. The mass was biopsied and diagnosed as a benign fibroepithelial polyp. Continued symptoms and airway obstruction prompted a pharyngectomy, and the mass was then diagnosed as dedifferentiated liposarcoma. Due to infrequency and subtle histological findings, liposarcomas of the head and neck can be misdiagnosed and recur.

Liver transplantation for intrahepatic cholangiocarcinoma.

Although hepatocellular carcinoma (HCC) has become a common indication for liver transplantation (LT), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) are historically contraindicated due to their aggressive behavior. On the basis of recent experiences, some groups have proposed a clinical trial investigating the role of LT for patients with early cholangiocarcinoma (CCA), defined as a single lesion ≤ 2 cm. The purpose of this study is to assess the clinicopathologic features and outcomes following LT for patients who were initially diagnosed with HCC and subsequently found to have either ICC or cHCC-CCA on explant. Patients with the diagnosis of primary liver cancer (PLC) after LT from a single center were retrospectively reviewed. Outcomes for patients with early CCA were compared with patients with HCC within Milan criteria (MC). Out of 618 patients transplanted with PLC, 44 patients were found to have CCA on explant. On the basis of preoperative imaging, 12 patients met criteria for early CCA and were compared with 319 patients who had HCC within MC. The 1- and 5-year overall survival for early CCA versus HCC was 63.6% versus 90.0% and 63.6% versus 70.3% (log-rank, P = 0.25), respectively. Overall recurrence was 33.3% for early CCA versus 11% for HCC. On explant the patients with CCA were more likely understaged with higher tumor grade and vascular invasion. In conclusion, patients with CCA present a diagnostic challenge, which often leads to the finding of more aggressive lesions on explant after LT, higher recurrence rates, and worse post-LT survival. Careful consideration of this diagnostic conundrum needs to be made before a clinical trial is undertaken. Liver Transplantation 24 634-644 2018 AASLD.

Primary synovial sarcoma of the kidney-A case report and literature review.

Primary synovial sarcoma of the kidney is a very rare spindle cell neoplasm that occasionally displays epithelial differentiation. It occurs between 15-60 years of age with a mean of 35 years and a slight male predilection. Most of synovial sarcomas appear as relatively nonspecific soft tissue masses involving the kidney. This rare entity has some overlapping morphologic and immunohistochemical characteristics with other more common renal spindle cell neoplasms. Molecular tools add valuable diagnostic confirmation. We report a 56 year old male who presented to the emergency department with hematuria and abdominal pain. He had an abdominal CT-scan which showed a 6.6 cm enhancing right renal mass. Morphologic and immunohistochemical studies were directed towards synovial sarcoma with confirmation by SYT-SSX gene fusion using RT-PCR molecular technique. We reviewed the literature on the epidemiologic, histologic spectrum, immunophenotypic, clinical significance and prognosis and therapy.

Significance of finding benign endometrial cells in women 40-45 versus 46 years or older on Papanicolaou tests and histologic follow-up.

BACKGROUND: The 2014 Bethesda System recommends reporting the finding of benign-appearing, exfoliated endometrial cells on Papanicolaou (Pap) tests in women aged 45 years and older. We aimed to determine the significance of normal endometrial cells on liquid-based Pap tests in women aged 40 years and older and to correlate this finding with clinical factors and cytologic/histologic follow-up. MATERIALS AND METHODS: We retrospectively identified all women aged 40 years and older who had benign endometrial cells (BECs) on Pap tests at our institution during a 6-year period. Histologic follow-up and outcomes were evaluated. RESULTS: Among 18,850 Pap tests during the study period, 255 (1.4%) had findings of BECs and 159 (62.4%) of these women had follow-up Pap tests or subsequent tissue sampling by surgical procedures. Of the 159 cases, only 4 (2.5%) had significant endometrial pathologic processes, all endometrial endometrioid adenocarcinoma (three women had postmenopausal bleeding and 1 was perimenopausal with menorrhagia). No women between ages 40 and 45 years had significant pathologic findings and only one woman between 46 and 50 years (47 years) had an endometrial endometrioid carcinoma (1.5%). Women older than 47 years have higher odds (5.38) of having a significant endometrial lesion (P = 0.029) than those who are ≤47. CONCLUSION: Clinically significant endometrial lesions occurred predominantly in women older than 50 years (4.6%) and in only one woman between ages 46 and 50 years (1.5%). Therefore, endometrial sampling should be performed in women aged 47 years and older with BECs, especially when additional clinical indicators (e.g., postmenopausal bleeding) are recognized.

Metastatic prostatic stromal sarcoma: A challenging diagnosis on fine-needle aspiration with broad differential diagnosis.

Prostatic stromal sarcomas (PSS) are rare solid organ mesenchymal sarcomas. PSS may pose difficult diagnostic challenges on fine needle aspiration biopsy. We report a 48-year-old man diagnosed with metastatic high grade prostatic stromal sarcoma by a CT-scan guided fine needle aspiration (FNA) biopsy of a right lower lung lobe nodule. We reviewed the literature on the epidemiologic, cyto-histological, and immunophenotypic findings and discussed the differential diagnosis for this rare entity.

EUS-guided fine needle biopsy sampling using a novel fork-tip needle: a case-control study.

BACKGROUND AND AIMS: EUS-guided fine needle biopsy (FNB) sampling and FNA are important methods for obtaining core tissues and cytologic aspirates. To improve the specimen quality for pathologic evaluation, a novel EUS-FNB Shark Core (SC) needle has been designed to acquire core tissue during EUS procedures. We compared the histology yield of EUS-FNB sampling using the SC needle (EUS-FNB-SC) to EUS-FNA in patients who had solid pancreatic and nonpancreatic lesions. METHODS: This was a retrospective case-control study design. Between July 2012 and July 2015 all patients who had EUS-FNB-SC and EUS-FNA were reviewed through a hospital EUS database. Consecutive samples from EUS-FNB-SCs were matched in a 1:3 ratio by lesion site (eg, pancreatic head) and needle gauge (ie, 19 gauge, 22 gauge, 25 gauge) to recent random samples of EUS-FNA. The procedures were performed with rapid onsite evaluation. For study purposes specimen slides were evaluated by 2 cytopathologists for histologic yield using a standard scoring system (0 = no material, 1-2 = cytologic, 3-5 = histologic). The main objectives were to assess the histologic yield of the samples and compare the median number of passes required to obtain core tissue by using EUS-FNB-SC and EUS-FNA needles. RESULTS: Of the 156 patients included in study, 25% patients (n = 39) were in the EUS-FNB-SC group and 75% (n = 117) in the EUS-FNA group. According to standard scoring criteria for histology, the median histology score for EUS-FNA was 2 (sufficient for cytology but not histology) and for EUS-FNB-SC was 4 (sufficient for adequate histology). Ninety-five percent of the specimens obtained from the EUS-FNB-SC group were of sufficient size for histologic screening, compared with 59% from the EUS-FNA group (P = .01). The median number of passes required to achieve a sample was significantly lower in the EUS-FNB-SC group compared with the EUS-FNA group (2 passes vs 4 passes, P = .001). There was significant difference in the median number of passes to all lesion sites and needle gauges. CONCLUSIONS: The histology yield was significantly higher using the EUS-FNB-SC needle compared with the EUS-FNA needle. Additionally, fewer passes were required to obtain histology cores when using EUS-FNB-SC.

Metastatic Chordoma: A Diagnostic Challenge on Fine Needle Aspiration.

Chordomas are primary low grade malignant tumors of bone that usually arise within both ends of axial skeleton. The Notochord is a midline, ectoderm-derived structure that defines the phylum of chordates. Chordomas may pose difficult diagnostic challenges when encountered in secondary locations, such as lungs or other parenchymatous organs. We report the cytologic findings of a metastatic chordoma sampled through CT-scan guided fine needle aspiration (FNA) of lower lobe lung nodule in a 54-year-old man diagnosed with recurrent chordoma involving the lumber spine and paraspinal region.

High diagnostic accuracy of core needle biopsy of soft tissue tumors: An institutional experience.

BACKGROUND: Core needle biopsy (CNB) has been suboptimal in the subclassification and grading of mesenchymal tumors. Recent advances in molecular diagnostics have shown promise in improving this area. The institutional experience with CNBs of soft tissue lesions on cytology cases and correlated histologic follow-up has been evaluated. It also addressed the advantageous use of ancillary techniques, including immunohistochemistry and molecular studies. METHODS: Archived cytologic CNB material and reports of patients with soft tissue lesions were retrieved and CNB results with final resection results were compared. Cases were re-reviewed and data were analyzed with descriptive statistics. RESULTS: From archived data, 215 cases were extracted of 99 female and 116 male patients (mean [range] age, 59.9 [12-95] years). Categories were malignant (n = 157), suspicious (n = 16), and benign (n = 42). In total, 161 (74.9%) had subsequent surgical resection-130 were malignant; 8, suspicious; and 23, benign. Of the malignant or suspicious cases, 138 had follow-up histologic resections, with 97.9% concordance. The most common malignant tumor was liposarcoma (n = 41; 29.7%), followed by undifferentiated pleomorphic sarcoma (30; 21.7%). Of benign tumors, 23 (54.8%) had follow-up surgical resection. Low-grade gastrointestinal stromal tumor was the most common benign tumor (26.1%), followed by fibromatosis (21.7%). Cytohistologic correlation for all categories showed 96.9% concordance. Molecular ancillary studies correctly classified malignant tumors in 37 (26.8%) of the 138 cases. CONCLUSION: CNB is a reliable modality for evaluating soft tissue neoplasms, with high histologic concordance rate.