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Context.— High-grade appendiceal mucinous neoplasm (HAMN) is a relatively recently introduced term describing a rare epithelial neoplasm of the appendix that demonstrates pushing-type invasion but high-grade cytologic atypia. It remains understudied. Objective.— To describe clinicopathologic features of HAMNs. Design.— We identified 35 HAMNs in a multi-institutional retrospective study. Clinical and histologic features were reviewed in all cases, as well as molecular features in 8 cases. Results.— Patients were 57 years of age on average and most commonly presented with abdominal/pelvic pain. Histologically, 57% of the tumors showed widespread high-grade features. Architectural patterns in high-grade areas included flat, undulating, or villous growth, and occasionally micropapillary, cribriform, or multilayered growth. Thirteen cases had intact serosa, and the remaining 22 perforated the serosa, including 7 with peritoneal acellular mucin beyond appendiceal serosa and 10 with grade 2 pseudomyxoma peritonei. Molecular abnormalities included KRAS mutations in 7 cases and TP53 mutations in 4. No tumor confined to the appendix recurred. Two patients without pseudomyxoma peritonei at initial presentation developed pseudomyxoma on follow-up. Among 11 patients who presented with pseudomyxoma peritonei, 5 died of disease and 3 were alive with disease at last follow-up. Conclusions.— HAMNs have a similar presentation to low-grade appendiceal mucinous neoplasm, and similar stage-based prognosis. When they spread to the peritoneum, they typically produce grade 2 pseudomyxoma peritonei, which may be associated with a worse prognosis than classical grade 1 pseudomyxoma peritonei.

Context.—Hepatotoxicity is an important side effect of thiopurine analog treatment for inflammatory bowel disease. A variety of histopathologic findings have been observed in patients with inflammatory bowel disease with thiopurine-induced hepatotoxicity, including nodular regenerative hyperplasia, vascular injury, and cholestasis. Objective.—To describe the histologic features shared by 3 cases of thiopurine-induced hepatotoxicity in patients with inflammatory bowel disease. Design.—We identified 3 patients with inflammatory bowel disease who developed hepatotoxicity due to 6-mercaptopurine from the educational files of the Department of Pathology at Massachusetts General Hospital (Boston). Histology slides (stained with hematoxylin-eosin, trichrome, periodic-acid Schiff with diastase digestion, and iron stains) and patients' medical records were reviewed retrospectively. Results.—All 3 patients were receiving 6-mercaptopurine monotherapy at therapeutic doses, had normal thiopurine metabolite levels, and presented with elevated aminotransferase levels. Biopsies from all 3 cases exhibited a pattern of centrilobular hepatocyte injury characterized by ceroid-laden macrophages, hepatocyte anisonucleosis, and increased lipofuscin pigment, as well as centrilobular steatosis. Aminotransferase levels trended downward and either normalized or remained at borderline elevated levels after 6-mercaptopurine dose was reduced (in 1 patient) or discontinued (in 2 patients). Conclusions.—Recognition of a pattern of centrilobular injury enables pathologists to suggest thiopurine-induced liver injury as the cause of elevated aminotransferases in patients with inflammatory bowel disease.

Mucinous cystic neoplasm and intraductal papillary mucinous neoplasm are 2 types of cystic pancreatic mucinous tumors, each with its own distinct clinicopathologic features and pathogenetic mechanisms. We report here an unusual pancreatic mucinous neoplasm with features of both a mucinous cystic neoplasm and an intraductal papillary mucinous neoplasm in a 40-year-old woman who underwent total pancreatectomy. The endoscopic retrograde cholangiopancreatogram and gross examination demonstrated a mucin-producing intraductal neoplasm involving the length of the main pancreatic duct, typical of main duct intraductal papillary mucinous neoplasm, but histology of the main duct showed involvement by a biphasic tumor composed of columnar epithelium overlying ovarian-type stroma, characteristic of a mucinous cystic neoplasm. Immunohistochemistry confirmed that the stromal cells expressed estrogen and progesterone receptors, inhibin, and calretinin. Pancreatic mucinous cystic neoplasm involving the entire main pancreatic duct has not, to our knowledge, been previously reported.

Low grade appendiceal mucinous neoplasms can spread to the peritoneum as pseudomyxoma peritonei even though they are not obviously invasive in the appendix. During the past several decades, several problematic issues surrounding this enigmatic tumor have been debated in the literature, including appropriate nomenclature for the appendiceal tumors and their peritoneal metastases. In this article, the most contentious issues in the area of appendiceal mucinous tumors are examined. First, the classification systems that have been proposed for these tumors are compared in the context of whether the appendiceal mucinous tumors are ruptured adenomas or invasive carcinomas. The controversy about the nature of pseudomyxoma peritonei and its classification systems is discussed in the following section. A brief discussion follows that examines the issue of localized pseudomyxoma peritonei and its clinical significance. Next reviewed is the largely resolved controversy about whether ovarian mucinous tumors in this setting are separate primaries or are metastases from the appendiceal tumor. Finally, the controversy about the most effective treatment of patients with pseudomyxoma peritonei is discussed.

Context.—Although cervical cancer screening by cytology is successful, the test continues to show relatively poor operating characteristics. Cell cycle markers may enhance detection of high-grade squamous intraepithelial lesions. Objective.—To determine the clinical usefulness of ProExC, an immunocytochemical assay for cell cycle components, performed on routine cervical cytology samples. Design.—Cervical cytology samples were collected using the SurePath method. Residual cells remaining after preparation of the Papanicolaou-stained slide were used to make a second slide for ProExC staining using an indirect polymer-based immunoperoxidase method. Only adequately cellular slides were evaluated for the presence of nuclear staining within cytologically abnormal epithelial cells. Results were correlated with clinical follow-up. Results.—Six hundred twenty-four samples were satisfactorily cellular and stained. Correlation with clinical follow-up for subsequent cervical intraepithelial neoplasia 2+ on biopsy/high-grade squamous intraepithelial lesion on cytology (CIN 2+/HSIL) showed that 434 results were true negative, 78 true positive, 18 false-negative, and 94 false-positive, resulting in a sensitivity/specificity of 81%/82%. When ProExC results were combined with any level of cytologic atypia, sensitivity for CIN 2+/HSIL was 92% and specificity was 84%. Conclusions.—ProExC shows promise as an aid in enhancing the sensitivity and specificity of cervical cytology for subsequent CIN 2+/HSIL and may be useful in identifying those cervical lesions most apt to progress.