Orthotropic Liver Transplantation for Acute Intrahepatic Cholestasis in Sickle Cell Disease: Clinical and Histopathologic Features of a Rare Case.

Sickle cell disease has a wide range of hepatic manifestations, with acute intrahepatic cholestasis being one of the rarest and most fatal, often resulting in acute fulminant hepatic failure. Liver transplantation is an emerging but rarely utilized treatment for hepatic failure in the setting of sickle cell disease. Few such cases have been reported in the literature, with little emphasis on histopathologic correlation. We report a case of acute intrahepatic cholestasis in a patient with sickle cell disease who underwent orthotropic liver transplantation and describe novel correlating histopathologic features. The patient is a 29-year-old man who presented with hyperbilirubinemia, acute kidney injury, and coagulopathy. He was diagnosed clinically with acute intrahepatic cholestasis and received an orthotropic liver transplant. The explanted liver demonstrated marked sinusoidal expansion by sickled erythrocytes, hyperplastic Kupffer cells, and extramedullary hematopoiesis. There was extensive sinusoidal and centrizonal fibrosis with occlusion of central veins reminiscent of chronic sinusoidal obstructive syndrome, a previously undescribed pattern of injury. This case represents one of the few reported cases of sickle cell intrahepatic cholestasis treated by transplantation and demonstrates the rarely reported histopathologic features and gives insight to a potentially new mechanism of injury in these patients. Familiarity with the morphologic features of sickle cell hepatopathy and its clinical manifestations is important as transplantation in sickle cell-related liver injury increases in frequency.

Discrepant HPV/cytology cotesting results: Are there differences between cytology-negative versus HPV-negative cervical intraepithelial neoplasia?

BACKGROUND: The objective of this study was to compare cervical high-grade squamous intraepithelial lesions subcategorized as cervical intraepithelial neoplasia-3 (CIN-3)-positive after a negative cytology result but positive for high-risk human papillomavirus (HR-HPV) testing to those with a negative HR-HPV test but positive cytology (atypical squamous cells of undetermined significance [ASCUS]-positive/HPV-negative) and to assess reasons for discrepancies. METHODS: The authors retrospectively analyzed women who underwent screening with cytology and HPV testing from 2010 through 2013. After a review of surgical specimens and cytology, discrepancies were classified as sampling or interpretation error. Clinical and pathologic findings were compared. RESULTS: In total, 15,173 women (age range, 25-95 years; 7.1% were aged < 30 years) underwent both HPV and cytologic testing, and 1184 (8.4%) underwent biopsy. Cytology was positive in 19.4% of specimens, and HPV was positive in 14.5%. Eighty-four CIN-3-positive specimens were detected, including 55 that tested ASCUS-positive/HPV-positive, 11 that tested negative for intraepithelial lesion or malignancy (NILM)/HPV-positive, 10 that tested ASCUS-positive/HPV-negative, 3 that tested NILM/HPV-negative, and 5 tests that were unsatisfactory. There was no significant difference between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3 in terms of size, time to occurrence, the presence of a cytopathic effect, screening history, race, or age. Six of 11 NILM/HPV-positive cases were reclassified as ASCUS, indicating an interpreting error of 55% and a sampling error of 45%. No ASCUS-positive/HPV-negative cases were reclassified. Seven cases of CIN-3 with positive cytology were HPV-negative. CONCLUSIONS: There are no significant clinical or pathologic differences between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3-positive specimens. Cytologic sampling or interpretation remains the main reason for discrepancies. However, HPV-negative CIN-3 with positive cytology exists and may be missed by primary HPV screening. Cancer Cytopathol 2017;125:795-805. © 2017 American Cancer Society.

Cytologic criteria to reduce error in EUS-FNA of solid pseudopapillary neoplasms of the pancreas.

INTRODUCTION: Standardization of error classification in pathology remains an important issue. This study assesses the extent of error in cytopathologic diagnosis of solid pseudopapillary neoplasms (SPN) of the pancreas. Because of morphologic overlap of SPN and pancreatic neuroendocrine neoplasms (NET), we compared cytologic characteristics to determine which best distinguishes these entities. MATERIALS AND METHODS: We collected cases diagnosed as SPN either by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) by cytology or surgical pathology from January 2000 to March 2013. An equal number of NET cases were randomly selected. Cytology and surgical pathology cases were evaluated for diagnostic errors and patient impact. Cytologic features in SPN and NET were scored based on presence of previously described characteristics. RESULTS: A total of 17 patients with EUS-FNA were diagnosed with SPN by cytology or surgical pathology. Of those, 14 had surgical follow-up and 13 had adequate cell blocks and immunohistochemistry. There were 5 discrepancies between cytology and surgical pathology (5 of 14, 36%). There were no false positives or false negatives, but 5 misclassifications: 4 diagnosed as NET on cytology, and 1 as NET versus SPN. All misclassification errors were associated with no harm. When compared with NET, fine chromatin, nuclear grooves, pseud papillae, pink stroma, and hyaline globules are statistically significantly associated with SPN. CONCLUSIONS: EUS-FNA of pancreatic SPN has excellent positive and negative predictive value, with no false positives or false negatives in this 12-year study. Only misclassification errors as pancreatic NET were made with minimal impact. We suggest that the presence of 3 of 5 major cytologic criteria offer accuracy in diagnosing SPN to prevent misclassification.