Mucinous cystic neoplasms of the liver with biliary prolapse.

OBJECTIVES: To describe the prevalence, clinical and radiological findings of biliary prolapse in pathologically proven mucinous cystic neoplasm of the liver (MCN-L). METHODS: Thirty-four patients, all female with median age 50 years (range, 14-82), with histologically confirmed MCN-L were enrolled. Median tumor size was 9 cm (range, 2-21 cm). Fifty-seven examinations (17 ultrasound, 25 CT, and 15 MR) among 34 MCN-Ls were reviewed. Two radiologists retrospectively assessed images for tumor location, size and other morphological features of the tumor, presence of biliary prolapse and upstream bile duct dilatation. Ultrasound, CT, and MR were assessed separately. Clinical features were evaluated. Clinical and radiological characteristics of MCN-L with and without biliary prolapse were compared. RESULTS: 15% (5/34) of MCN-Ls showed biliary prolapse confirmed at pathology. None of MCN-Ls were associated with invasive carcinoma. Patients with biliary prolapse were significantly younger than those without (median 27 years [22-56] vs. median 51 years [14-82], p = 0.03). MCN-Ls with biliary prolapse were significantly smaller than those without (median 6.4 cm [2.2-7.5] vs. median 9.6 cm [3.1-21], p = 0.01). The upstream bile duct was dilated more frequently in MCN-Ls with biliary prolapse (100% vs. 38%, p = 0.02). Jaundice was significantly more common in MCN-Ls with biliary prolapse (80 vs 3%, p = 0.0005). Other clinical or radiological features were not significantly different between two groups. CONCLUSIONS: Biliary prolapse was found in 15% of MCN-Ls. MCN-Ls with biliary prolapse were significantly smaller and were more commonly associated with upstream bile duct dilation and jaundice than those without biliary prolapse.

Isolated IgG4-related sclerosing cholangitis: a report of 9 cases.

Extrahepatic bile ducts are the most commonly involved extrapancreatic organ site in patients with type 1 autoimmune pancreatitis. IgG4-related sclerosing cholangitis (IgG4-SC) alone, without evidence of pancreatic or other organ involvement, is uncommon and is difficult to distinguish from cholangiocarcinoma preoperatively. We describe 9 patients with isolated IgG4-SC over an approximate 10-year period, each clinically suspected to have cholangiocarcinoma. We examined the clinical, radiological, cytologic (including fluorescence in situ hybridization results), and histologic features. IgG and IgG4 immunohistochemistry were performed. All 9 patients were middle-aged men who presented with obstructive jaundice. The biliary strictures involved all parts of the extrahepatic biliary tree. Serum IgG4 was slightly elevated in three of eight patients. Cytologic findings were interpreted as negative in six, atypical in one, and suspicious for adenocarcinoma in one. Fluorescence in situ hybridization revealed aneuploidy in one and was equivocal (trisomy 7) in 2. Eight of 9 patients underwent radical resection for suspected cholangiocarcinoma. There was only one case diagnosed with IgG4-SC preoperatively based on biopsy. Histologic sections revealed a prominent lymphoplasmacytic infiltrate with storiform fibrosis and marked increased IgG4-positive plasma cells (≥30/high-power field) in all specimens. Fifty percent of cases (4/8) had IgG4/IgG plasma cell ratio >40%. On median follow-up of 2.8 years, no relapse has occurred in any patient. Extrahepatic IgG4-SC may present as an isolated lesion mimicking cholangiocarcinoma. The diagnosis can be challenging. Clinicians and pathologists should recognize this to avoid major surgery.

Rare ALK expression but no ALK rearrangement in pancreatic ductal adenocarcinoma and neuroendocrine tumors.

OBJECTIVES: Anaplastic lymphoma kinase (ALK) gene rearrangements were first identified in anaplastic large cell lymphomas. Subsequently, they have been observed in other tumor types with ALK-rearranged tumors demonstrating responsiveness to ALK inhibitors. The aggressiveness of pancreatic ductal adenocarcinoma warrants the examination of ALK rearrangements in pancreatic cancer as a potential therapeutic target. Immunohistochemical expression of ALK1 correlates with ALK rearrangements in other tumors. We performed ALK immunohistochemistry on samples of pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors using 2 tissue microarrays. METHODS: ALK1 expression was scored for each case as 0, 1+, 2+, or 3+ using established criteria. Fluorescence in situ hybridization using a break-apart assay with probes for ALK was performed to detect ALK rearrangement in ALK1-positive cases. RESULTS: All 46 neuroendocrine tumors were negative for ALK1. Of 140 ductal adenocarcinoma cases, 5 showed immunoreactivity for ALK1: 1 was 3+, 2 were 2+, and 2 were 1+. However, fluorescence in situ hybridization for ALK rearrangement was negative in all 5 cases. CONCLUSIONS: The results demonstrate that ALK1 expression is uncommon in both pancreatic ductal adenocarcinoma and neuroendocrine tumors. Rare ALK1 expression is not induced by ALK translocation, and ALK is unlikely to be a therapeutic target in pancreatic tumors.

Evaluation of langerhans cell infiltrate by CD1a immunostain in liver biopsy for the diagnosis of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is characterized by chronic nonsuppurative destructive cholangitis, which is considered to be a cell-mediated immune reaction. Antigen-presenting cells, including Langerhans cells and dendritic cells, have been found in portal tracts and in bile duct epithelium and may play a role in the pathogenesis of PBC, but the importance of identifying these cells for diagnosing PBC has not been studied yet. In this study, we sought to evaluate the importance of identifying Langerhans cells using a CD1a immunostain in the diagnosis of PBC. Liver biopsies from adult patients diagnosed with PBC (n=60), primary sclerosing cholangitis (n=29), obstructive cholangitis (n=13), chronic viral hepatitis B or C (n=19), autoimmune hepatitis (AIH, n=15), acute cellular rejection (n=11), and chronic rejection (n=10) at our institution were retrospectively reviewed. An immunohistochemical stain for CD1a was used to detect Langerhans cells, and the distribution of CD1a-positive Langerhans cell infiltrate was recorded as lobular, portal with bile duct sparing, and intraepithelial. Intraepithelial Langerhans cells were identified in 58% of PBC including antimitochondrial antibody-negative PBC and PBC-AIH overlap cases, 14% of primary sclerosing cholangitis, 15% of obstructive cholangitis, 9% of acute cellular rejection, 6% of AIH, and no cases of chronic viral hepatitis or chronic rejection. The number of intraepithelial Langerhans cells was significantly higher in PBC than in other conditions, with the mean number of CD1a-positive intraepithelial Langerhans cells per bile duct in PBC calculated as 2.2 compared with <1 per duct for the other control cases. Thirty-three of 60 (55%) PBC cases showed at least one bile duct containing ≥2 CD1a-positive Langerhans cells. This was statistically significant (P<0.01) when compared with control groups. The overall sensitivity and specificity of using ≥2 CD1a-positive Langerhans cells per bile duct as the diagnostic criteria for PBC were 55% and 96%. Given the heterogenous nature of liver involvement by PBC, a review of cases with morphologic features of duct damage yielded an increased sensitivity (79%) with no reduction in specificity. In conclusion, the detection of a Langerhans cell infiltrate of ≥2 cells by CD1a in a given bile duct on needle biopsy may be a valuable tool in the diagnosis of PBC.

Handling of radioactive seed localization breast specimens in the pathology laboratory.

Radioactive seed localization (RSL) is an increasingly utilized and effective approach to surgical excision of radiographically identified lesions in the breast. This approach has been reported to be at least as convenient to the patient, radiologist, and surgeon as the standard wire localized approach but with the considerable added benefit of a lower positive margin rate in some studies. To date, there is little information in the published medical literature concerning the optimal handling of these specimens in the pathology laboratory. The US Nuclear Regulatory Commission and its Agreement States oversee the use of radioactive materials in clinical practice and provide guidelines for the performance of RSL procedures, including the safe handling of radioactive seeds. The RSL procedure involves multiple departments, and a robust process should be in place to ensure appropriate accountability, seed tracking, and minimal radiation exposure to staff. This article describes how to properly and safely handle RSL breast specimens, including regulation requirements, specimen labeling and receipt, specimen dissection, protective wear, and seed retrieval, transport, and disposal.

Ossifying fibromyxoid tumor of soft parts: a clinicopathologic, proteomic, and genomic study.

Ossifying fibromyxoid tumor (OFMTs) of soft parts is a rare soft tissue and bone tumor of borderline malignancy displaying an uncertain line of differentiation. The existence of fully malignant OFMT is controversial. To better understand the natural history and line of differentiation taken by OFMT, we studied 46 cases by light microscopic, immunohistochemical (IHC), genomic, proteomic, and fluorescence in situ hybridization (FISH) methods. Cases were classified according to the 2003 Folpe and Weiss system. Clinical and follow-up information was obtained. IHC for S-100 protein, desmin, epithelial membrane antigen (EMA), cytokeratins, smooth muscle actin (SMA), INI-1, neurofilament protein (NFP), CD56d excitatory amino acid transporter-4 (EAAT4), and MUC4 was performed on formalin-fixed, paraffin-embedded (FFPE) tissues. Gene expression profiling and proteomic studies were conducted on FFPE tissues from 13 and 5 cases, respectively. FISH for INI-1 was performed on 10 cases. The 46 tumors arose in 29 men and 17 women (median age, 52 y; range 39 to 63 y) and involved the proximal (N=17) and distal extremities (N=13), head and neck (N=9), and trunk (N=5). Median tumor size was 5.4 cm (range, 1.0 to 21.0 cm). Cases were classified as typical OFMT (26 of 46, 57%), atypical OFMT (5 of 46, 11%), and malignant OFMT (15 of 46 cases, 32%). Clinical follow-up (27 cases, median 55 months' duration) showed all patients with typical and atypical OFMT to be alive without disease. Adverse events, including 3 local recurrences, 3 metastases, and 3 deaths, were seen only in malignant OFMT. IHC results were as follows: S-100 protein (30 of 41, 73%), desmin (15 of 39, 38%), cytokeratin (4 of 35, 11%), EMA (5 of 32, 16%), SMA (2 of 34, 6%), INI-1 (lost in mosaic pattern in 14 of 19, 74%), EAAT4 (31 of 39, 80%), MUC4 (3 of 14, 21%), NFP (8 of 10, 80%) and CD56 (6 of 14, 43%). Gene expression profiling showed typical and malignant OFMTs to cluster together, distinct from schwannian tumors. Proteomic study showed expression of various collagens, S-100 protein, and neuron-related proteins. FISH showed INI-1 deletion in 5 of 7 (71%) cases. We conclude that malignant OFMTs exist and may be recognized by the previously proposed criteria of Folpe and Weiss. Expression of neuron-related markers, in addition to Schwann cell and cartilage-associated markers, suggests a "scrambled" phenotype in OFMTs. Loss of INI-1 or other genes on 22q is likely important in the pathogenesis of these rare tumors.