Faculty Bibliography

There is a considerable need to identify those individuals with prostate cancer who have indolent disease. We propose that genes that control adult stem cell homeostasis in organs with slow turnover, such as the prostate, control cancer fate. One such gene, KLF4, overexpressed in murine prostate stem cells, regulates their homeostasis, blocks malignant transformation, and controls the self-renewal of tumor-initiating cells. KLF4 loss induces the molecular features of aggressive cancer and converts PIN lesions to invasive sarcomatoid carcinomas; its re-expression in vivo reverses this process. Bioinformatic analysis links these changes to human cancer. KLF4 and its downstream targets make up a gene signature that identifies indolent tumors and predicts recurrence-free survival. This approach may improve prognosis and identify therapeutic targets for advanced cancer.

Objectives: To report a rare recurrent malignant gastrointestinal neuroectodermal tumor in a 36-year-old woman with an upper gastrointestinal obstruction. Clinical History: In January 2017, a 36-year-old female physician with a history of GI tract clear cell sarcoma- like tumor s/p resection (September 2015) had a follow-up PET/CT scan that found a new PDG-avid lesion in the left adnexal region. The TVUS ruled out an adnexal lesion. In September 2017, she presented to the emergency room for abdominal discomfort but no nausea, vomiting fever, or chills. She then underwent laparoscopy small bowel resection with primary anastomosis. Pathologic Findings: The gross specimen showed a segment of small bowel with a thin brown cystic mass (2.9 +/- 2.9 +/- 1.4 cm) arising from the anastomotic site. Sectioning revealed a tan-brown solid and partially cystic mass with thin brown fluid. Microscopy revealed epithelioid and spindle cells arranged in nests and cords, with abundant clear cytoplasm, slightly pleomorphic nuclei with occasionally prominent nucleoli, low mitotic activity, and no necrosis. No positive lymph nodes were identified. Neoplastic cells infiltrated most of the thickness of the gastric wall, sparing the mucosa. Immunohistochemical stains revealed reactivity for S-100 protein and vimentin. Actin, desmin, and CD117 were negative. EWSR1 (22q12) translocation was detected. Final Diagnosis: Recurrent tumor (gastrointestinal-type clear cell sarcoma) similar to a previous one is seen in mesenteric adipose tissue adjacent to the small intestinal anastomotic site. Strong reactivity for neural markers (S-100, SOX10, synatophysin, and vimentin) and negative melanocytic markers (HMB 45, Melanin A) suggest an origin from a gastrointestinal neuroectodermal precursor cell not differentiable along the melanocytic lineage.
Conclusion(s): Malignant gastrointestinal neuroectodermal tumor has frequent local recurrences that are easily misdiagnosed as metastasized melanoma. Clinical history, pathologic morphology, and molecular tests are the best combination for diagnosis

Background: On January 1, 1898, New York City consolidated the five boroughs to create the modern municipal government. This legislation reorganized the borough-based coroner system and death recordkeeping. The previous year, the world-renowned Bellevue Hospital Medical College pathology department lost its morgue in a fire. Among the records saved in the aftermath, recently rediscovered, were log books documenting hundreds of autopsies performed at Bellevue Hospital in 1897. Design: Data from 324 autopsies (n=325, excluding one duplicate entry) performed at Bellevue Hospital between March 16 and December 31, 1897 were collected in a Microsoft Excel 2010 spreadsheet. Each decedent's name, age, race, ethnicity, country of origin, medical division, ward assignment, time of death, time of autopsy, and autopsist(s) were recorded, along with external examination findings, gross findings by organ system, and final anatomic diagnosis. Frequency tables and measures of central tendency were compiled. The final anatomic diagnoses were subcategorized by etiology (chronic disease, malignancy, infectious disease, therapeutic complication, medicolegal, psychiatric). Where possible, patient and physician identifiers were matched to contemporaneous public records, medical journals, and online archives (NYU Health Sciences Library, New York Public Library, National Library of Medicine). Microscope slides and laboratory medicine results were unavailable. Results: Decedents included 222 men, 82 women, and 20 of unknown sex. Age was recorded for 166 adults and 46 children. The adults' average age at death was 42 years (range 19-78 years); children, 17 months (3 days-13 years). The majority (310) were U.S. born, with 11 European-born (Ireland, Germany, Austria, Italy, Sweden), 3 of unknown birthplace. Six U.S.-born were identified as "colored." The combined medical divisions ordered 208 autopsies, and the surgical 21. Other decedents were from the insane pavilion (2), emergency ward (1), prison (1), and found on the street (6). Average turnaround time was 43 hours (1 hour-14 days after death). Thirty-nine autopsies were same-day. Conclusions: The most frequent causes of death in this cohort match those reported by New York State in 1896-8. Average age at death, 42 years, was younger than U.S. life expectancy (46.3 years for men, 48.3 years for women). There was insufficient data to classify decedents' occupations and socioeconomic status. No major diagnostic errors were seen, accounting for changes in nomenclature over time