Microscopic pulmonary embolisation of an indwelling central venous catheter with granulomatous inflammatory response.

Indwelling catheters can disintegrate into tiny fragments and embolise. Once the fragments are detected radiographically, they can be removed using vascular intervention techniques. Rarely, indwelling catheters dwindle into inextricable pieces that embolise into minute pulmonary vessels and lymphatics, causing granulomatous changes microscopically. The present study reports a 54-yr-old female who had received several indwelling central lines during several abdominal surgeries over a 5-yr period. The patient developed a noncaseating granulomatous skin lesion followed by exertional dyspnoea a few months later. Chest radiographs and computed tomography showed diffuse interstitial infiltrates. Open lung biopsy showed two types of granulomas: 1) peri-lymphangitic and peri-bronchiolar non-necrotising granulomas consistent with sarcoidosis; and 2) distinct foreign body granulomas. In some of the foreign body granulomas, confocal Raman spectroscopy identified the presence of bisphenol-A-polycarbonate, a polymer commonly used in biomedical devices. The patient improved following treatment with prednisone followed by methotrexate. The present case illustrates an interesting combination of two causes of granulomatous disease, the importance of examining all biopsy specimens from sarcoidosis patients for foreign particles and the rare occurrence of microscopic embolisation of catheter fragments to the lung with foreign-body giant cell reaction to them.

Clear cell carcinoid tumor of the gallbladder: another distinctive manifestation of von Hippel-Lindau disease.

We describe a morphologically distinctive carcinoid tumor of the gallbladder that occurred in a 38-year-old man with von Hippel-Lindau (VHL) disease. The carcinoid tumor was composed predominantly of lipid-containing clear cells arranged in nests and tubules with pagetoid spread into the biliary epithelium and was interpreted as metastatic renal cell carcinoma. The neoplastic cells showed diffuse immunoreactivity for chromogranin, synaptophysin, cytokeratins (cytokeratin 7 and AE1/AE3) and, unexpectedly, for inhibin, but were negative for monoclonal carcinoembryonic antigen, serotonin and a variety of peptide hormones. This clear cell carcinoid tumor of the gallbladder was histologically similar to the recently described clear cell endocrine pancreatic tumor associated with VHL. Four cases of the latter tumor, which were also inhibin positive showed, in addition, focal and variable reactivity for the pancreatic hormones. Two classical carcinoid tumors of the gallbladder, two renal cell carcinomas associated with VHL and 11 of 13 sporadic endocrine pancreatic tumors (not associated with VHL) did not show immunoreactivity for inhibin. Inhibin appears to be an immunohistochemical marker for gallbladder clear cell carcinoid and clear cell endocrine pancreatic tumors associated with VHL and is a useful tool to distinguish these tumors from metastatic renal cell carcinoma. However, the basis for the inhibin positivity in these endocrine tumors is unknown.

Metaplastic lesions of the extrahepatic bile ducts: a morphologic and immunohistochemical study.

Although metaplastic changes can occur in the extrahepatic bile ducts, a detailed morphologic study of these lesions has not been done. We examined the bile duct mucosa in 42 pancreaticoduodenectomy specimens, 32 with neoplastic lesions and ten with inflammatory lesions of the extrahepatic bile ducts, to assess the prevalence and type of metaplastic lesions. For comparison, the common bile ducts from 10 autopsy cases were reviewed. Twenty of the 42 total cases (48%), 13 of the 32 neoplastic cases (40%), and 7 of the 10 inflammatory cases (70%) had metaplastic changes. Pyloric gland metaplasia was the most common type (16/20 cases; 80%), whereas intestinal metaplasia was seen in 1/20 cases (5%). A combination of pyloric gland and intestinal metaplasia occurred in 2/20 cases (10%), and squamous metaplasia plus the above-mentioned two types of metaplasia was seen in 1/20 cases (5%). None of the normal common bile ducts obtained from ten autopsies had metaplastic changes. Endocrine cells were identified in nine (56%) of 17 metaplastic lesions. In contrast, endocrine cells within the intramural glands were seen in only 2 of the 10 normal common bile ducts. Although a significant proportion of carcinomas (6/13 cases) was in close proximity to areas of metaplasia, we were unable to find dysplastic foci within the metaplastic glands or the metaplastic surface epithelium. Reactive atypical cells involved the surface biliary epithelium and intramural glands and were associated with inflammation and metaplastic changes. The presence of goblet, mucinous, squamous, and reactive atypical cells in association with hyperplasia of intramural glands in frozen sections or small biopsy specimens may be mistaken for malignancy; hence, recognition of these lesions is of diagnostic importance.

Expression of inhibin-alpha by granular cell tumors of the gallbladder and extrahepatic bile ducts.

This is the first report of inhibin-alpha expression in granular cell tumors. A Medline search of the literature revealed no case reports of granular cell tumors in any location of the body being tested for inhibin-alpha immunohistochemically, by enzyme-linked immunosorbent assay, by radioimmunoassay, or by immunoprecipitation. Seventeen cases of previously diagnosed granular cell tumors of the gallbladder and extrahepatic bile ducts with hematoxylin and eosin-stained sections, and S-100 protein immunostain were retrieved from the archives of the Armed Forces Institute of Pathology. All cases were reviewed for diagnostic accuracy and then immunostained for inhibin-alpha (with endogenous biotin blocking). All 17 (100%) cases were diffusely positive for inhibin-alpha immunostain. Previous studies of inhibin-alpha-positive lesions reported in the literature include sex cord stromal tumors (granulosa cell tumors, luteinized thecomas, Leydig cell tumors), placental and gestational trophoblastic lesions, and adrenal cortical tumors. This study adds the granular cell tumor to the list of inhibin-positive lesions and should prove helpful in differential diagnosis of these lesions.

Atypical bile duct adenoma, clear cell type: a previously undescribed tumor of the liver.

A variable proportion of bile duct adenomas of the liver are still confused with metastatic well-differentiated adenocarcinoma by surgeons and pathologists. We present here three examples of previously undescribed primary hepatic bile duct tumors that were composed almost entirely of clear cells that closely mimicked metastatic renal cell carcinoma. They were interpreted as atypical bile duct adenomas and occurred in two males and one female whose ages ranged from 25 to 64 years. All three tumors were incidental findings and measured from 0.8 to 1.1 cm. The clear neoplastic cells showed mild nuclear atypia and no mitotic activity. They were arranged in tubules and nests that focally infiltrated the hepatic parenchyma. For comparison, a case of clear cell cholangiocarcinoma and 13 conventional bile duct adenomas were examined. The clear cell cholangiocarcinoma was larger (6.0 cm) and had the tubular pattern of conventional cholangiocarcinoma and an abundant desmoplastic stroma. The clear cells of this tumor exhibited greater nuclear atypia and increased mitotic activity. All three atypical bile duct adenomas expressed cytokeratin (CK) 7, p53 protein, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA); they were negative for CK20, vimentin, Hep Par 1, chromogranin, and prostatic specific antigen (PSA) and exhibited less than 10% of Ki-67-positive nuclei. One atypical bile duct adenoma displayed luminal immunoreactivity for villin. With the exception of Ki-67 reactivity, the 13 conventional bile duct adenomas and the clear cell cholangiocarcinoma had essentially a similar immunohistochemical profile as that of the atypical clear cell bile duct adenomas. The absence of an extrahepatic primary tumor, the histologic features, the immunohistochemical profile, and the fact that all patients are symptom-free 2 months to 18 years after wedge liver biopsy support the interpretation of atypical clear cell bile duct adenoma. The differential diagnosis with clear cell hepatocellular carcinoma and metastatic clear cell carcinomas is discussed.

Immunoreactivity for hepatocyte paraffin 1 antibody in hepatoid adenocarcinomas of the gastrointestinal tract.

Hepatocyte paraffin 1 (Hep Par 1) is a monoclonal antibody considered almost specific for normal and neoplastic hepatocytes, that can be used on formalin-fixed paraffin-embedded tissues. Hep Par 1 reactivity has been demonstrated consistently in hepatocellular carcinomas and hepatoblastomas but only rarely in cholangiocarcinomas and metastatic tumors to the liver. Although its role as a marker of hepatocytic differentiation in primary liver tumors has been studied extensively, Hep Par 1 expression has not been explored in extrahepatic lesions, especially rare adenocarcinomas with hepatoid morphologic features. We studied 7 hepatoid adenocarcinomas of the gastrointestinal tract (6 gastric and 1 from the gallbladder) for Hep Par 1 immunoreactivity. Focal Hep Par 1 expression was seen in 6 of 7 tumors. These hepatoid adenocarcinomas also showed reactivity for alpha-fetoprotein and carcinoembryonic antigen. The presence of Hep Par 1 reactivity in extrahepatic hepatoid adenocarcinomas underscores the fact that Hep Par 1 expression is not unique to primary hepatocellular neoplasms. Adenocarcinomas with hepatoid features must be considered in the differential diagnosis of Hep Par 1-positive lesions.

Gallbladder carcinoma: radiologic-pathologic correlation.

Primary carcinoma of the gallbladder is an uncommon, aggressive malignancy that affects women more frequently than men. Older age groups are most often affected, and coexisting gallstones are present in the vast majority of cases. The symptoms at presentation are vague and are most often related to adjacent organ invasion. Therefore, despite advances in cross-sectional imaging, early-stage tumors are not often encountered. Imaging studies may reveal a mass replacing the normal gallbladder, diffuse or focal thickening of the gallbladder wall, or a polypoid mass within the gallbladder lumen. Adjacent organ invasion, most commonly involving the liver, is typically present at diagnosis, as is biliary obstruction. Periportal and peripancreatic lymphadenopathy, hematogenous metastases, and peritoneal metastases may also be seen. The vast majority of gallbladder carcinomas are adenocarcinomas. Because most patients present with advanced disease, the prognosis is poor, with a reported 5-year survival rate of less than 5% in most large series. The radiologic differential diagnosis includes the more frequently encountered inflammatory conditions of the gallbladder, xanthogranulomatous cholecystitis, adenomyomatosis, other hepatobiliary malignancies, and metastatic disease.

Clear cell carcinoma of the liver: a comparative immunohistochemical study with renal clear cell carcinoma.

Morphologic differentiation of clear cell hepatocellular carcinoma (HCC-CC) from clear cell renal carcinoma (RCC-CC) may not be possible without the aid of immunohistochemical stains. We performed a battery of immunohistochemical stains on 10 previously diagnosed HCC-CCs, and 10 RCC-CCs, in order to determine which single or combination of immunostains would be most useful in diagnosis. We concluded that a positive Hepatocyte immunostain (DAKO) is sufficient for a diagnosis of HCC-CC if enough tissue is available. This immunostain distinguishes HCC-CC from other clear cell malignancies with sensitivity of 90% and specificity of 100%, when biopsy material is adequate. Other tests were much less sensitive, although several had specificity of 100%. A negative immunostain does not exclude the diagnosis of HCC-CC (negative predictive value 91%, especially in small biopsy material) and should be followed by additional immunostains such as pCEA for demonstration of tumor canaliculi, ubiquitin for Mallory bodies, and several epithelial cell markers that are typically positive in RCC-CC (epithelial membrane antigen, Leu M-1, pancytokeratin) and negative in HCC-CC.

Noninvasive and minimally invasive papillary carcinomas of the extrahepatic bile ducts.

BACKGROUND: Adenocarcinomas of the extrahepatic bile ducts (EBD) are uncommon neoplasms that are morphologically heterogenous and associated with a poor prognosis. Papillary carcinomas of the EBD, however, appear to follow a much less aggressive clinical course. METHODS: The authors reviewed the clinical records of nine patients with papillary carcinoma of the EBD, analyzed the microscopic features, and selected immunohistochemical reactivity (p53 and MIB-1) that might correlate with patient survival. RESULTS: Six patients were male and three were female, with a mean age of 65 years (range, 48-83 years). The clinical presentation of disease in these patients was similar to that reported for conventional adenocarcinoma of EBD. According to their cell phenotypes, these papillary carcinomas were classified as biliary type (7 cases) and intestinal type (2 cases). Most were located in the common bile duct and were well differentiated (7 cases). Five showed minimal expansile invasion into the ductal wall and four were noninvasive. Five patients were treated with a Whipple operation, three underwent segmental resections, and one underwent a left hepatic lobectomy. One patient died of unrelated causes 16 years after a Whipple operation, and another died of postoperative complications. The remaining 7 patients are alive and disease free 1-13 years after surgery. CONCLUSIONS: Noninvasive and minimally invasive papillary carcinomas of the EBD are associated with excellent long term prognosis regardless of their cytologic features or their immunohistochemical reactivity to p53 and MIB-1. These tumors should be distinguished from biliary papillomatosis, intraductal papillary mucinous carcinomas of the pancreas extending into the bile ducts, papillary adenomas, and papillary hyperplasia.

Expression of proliferating cell nuclear antigen in hyperplastic polyps, adenomas and inflammatory cloacogenic polyps of the large intestine.

AIMS: To compare proliferating cell nuclear antigen (PCNA) immunoexpression in hyperplastic polyps, adenomas, and inflammatory cloacogenic polyps of the human colon and rectum using paraffin wax embedded tissue. METHODS: The monoclonal antibody PC10 was used to demonstrate PCNA immunoreactivity in 88 polypoid lesions from 68 patients. Cases in which immunoexpression was completely absent were excluded, leaving 32 hyperplastic polyps, 31 adenomas, and seven inflammatory cloacogenic polyps for analysis. Labelling indices for the upper and lower third of each lesion and for adjacent normal mucosa were calculated. RESULTS: The upper third labelling indices for adenomas were substantially higher than those for hyperplastic polyps or normal mucosa, whereas those for the upper thirds of hyperplastic polyps and normal mucosa did not differ greatly. The differences between the lower third samples were not significant. In 16 (50%) hyperplastic polyps positive cells persisted onto the luminal surface. Some adenomas showed the most intense staining and the highest labelling indices in the upper third, with strong staining of surface cells; this pattern was not seen in the other lesions. The inflammatory cloacogenic polyps did not show a consistent pattern of immunoexpression. CONCLUSIONS: Differences in cell kinetics between adenomas, hyperplastic polyps, and normal mucosa may be shown in formalin fixed, paraffin wax embedded tissue using PC10 as a marker of proliferative activity. PCNA expression also persists into the upper portions of hyperplastic polyps. Assuming that hyperplastic polyps are hypermature lesions with a slower rate of cell migration, this finding suggests that there may be an alteration in PCNA protein metabolism.

Silicone lymphadenopathy with concomitant malignant lymphoma.

Six cases of axillary lymphadenopathy induced by silicone elastomer following silastic finger joint arthroplasty have been reported; 2 cases had associated malignant lymphoma. This is the 3rd reported case of malignant lymphoma with concomitant silicone lymphadenopathy discovered 8 years after insertion of silastic finger joint arthroplasty for longstanding rheumatoid arthritis. Histology revealed a partially replaced reactive lymph node with immunoblastic lymphoma. Both sides contained single and clusters of multinucleated giant cells with silastic particles, as well as formed asteroid bodies. Malignant lymphoma is associated with rheumatoid disease, but to date, silicone particles have not been linked to malignant lymphoma.

Chondrosarcoma and malignant lymphoma.

We describe two primary malignancies occurring simultaneously. The coexistence of chondrosarcoma and malignant lymphoma, small lymphocytic type (MLSL) (WDLL) is a rare occurrence. In this case, the untreated malignant lymphoma appears to have increased the aggressiveness of the chondrosarcoma through its adverse effect on the host's immune system.