Acinar cystadenoma of the pancreas: a clinicopathologic study of 10 cases including multilocular lesions with mural nodules.

Pancreatic acinar cystadenomas (ACAs) are rare cystic lesions showing acinar differentiation with benign outcome. Although debated, ACAs are favored to be neoplastic and potentially the benign counterpart of acinar cystadenocarcinoma. We present the largest single institution series to date comprising 10 cases. The mean age was 49 years with a female predominance (M:F=1:2.3). Abdominal/flank pain was the most common presentation (n=6). Serum amylase/lipase and cyst fluid amylase were often elevated. All lesions had a benign outcome on follow-up (5 to 67 mo). The lesions were unilocular (n=3) or multilocular (n=7) with mean size of 3.8 cm (range, 2.9 to 5.0 cm) and 5.1 cm (range, 2.0 to 7.5 cm), respectively. Eight lesions were unifocal with locations as follows: head (n=2), head/neck (n=2), body (n=1), tail (n=1), predominantly extrapancreatic with a microscopic intrapancreatic component (n=1), and unspecified location (n=1). Two lesions were multifocal, involving the head/uncinate/body and pancreatic head, respectively. Two aspects of ACAs that may represent a diagnostic pitfall include the propensity for acinar epithelium to appear as nondescript flat/cuboidal epithelium (trypsin/chymotrypsin immunopositive) and epithelial heterogeneity, with focal mucinous and squamous epithelium, the latter particularly in multilocular variants. In addition, 2 cases with intracystic nodules were observed. Array comparative genomic hybridization performed on 1 of these cases showed multiple chromosomal gains involving 1p, 3p, 5q, 6p, 7q, 8, 10q, 11, 14, 20, and X. These findings provide preliminary evidence that ACAs represent a cystic neoplastic lesion.

Acquired activated protein C resistance caused by lupus anticoagulants.

Lupus anticoagulants (LA) can cause acquired activated protein C resistance (APC-R), but the clinical significance is unclear. To investigate thrombosis and acquired APC-R in patients with LA, we enrolled all 132 patients undergoing hypercoagulability testing with positive LA results and in whom APC-R (with factor V-deficient plasma) was performed during a 2.5-year period. Among 121 patients without factor V Leiden, 24.0% had acquired APC-R; retrospective and prospective (mean follow-up, 2.0 years) thrombotic events were analyzed. The distribution of venous vs arterial thrombosis was different for APC-R vs no APC-R (P = .0064). The majority (19/29 [66%]) with acquired APC-R experienced venous thrombosis, whereas a minority experienced arterial thrombosis (9/29 [31%]; P = .017). The opposite pattern occurred among patients without APC-R (arterial thrombi more common than venous thrombi). After excluding thrombotic events more than 5 years from a positive LA test, venous thrombosis occurred in 62% with (18/29) vs 32% without (29/92) APC-R (P = .0045); and arterial thrombosis in 28% with (8/29) vs 51% without (47/92) APC-R (P = .033). Patients with acquired APC-R due to LA had more venous thrombosis than did patients with LA without APC-R and experienced venous more often than arterial thrombosis.

Synchronous follicular lymphoma, kaposi sarcoma, and castleman's disease in a HIV-negative patient with EBV and HHV-8 coinfection.

The authors describe the case of a 65-year-old woman who was HIV negative and had a lymph node biopsy that showed concurrent follicular lymphoma (FL; grade 3A), Kaposi sarcoma (KS), and Castleman's disease (CD) with coinfection by human herpes virus-8 (HHV-8) and Epstein-Barr virus (EBV). The lymphoma was positive for CD20, CD10, and BCL6 and negative for BCL2. Flow cytometry showed a clonal lambda B-cell population, and polymerase chain reaction (PCR) showed a clonal immunoglobulin heavy chain gene rearrangement, confirming a neoplastic B-cell process. Focally, the FL component showed numerous EBER1-positive cells, with rare HHV-8-positive cells. The KS component showed strong HHV-8 expression with rare EBER1-positive cells. The CD component showed scattered HHV-8, viral interleukin-6, and EBER1-positive cells. The simultaneous occurrence of a FL, KS, and CD in an HIV-negative patient expands the spectrum of HHV-8-positive neoplasms and suggests the possibility of HHV-8 rendering mature B-cells hyperresponsive to antigenic stimulation, providing an expanded target for second site mutations or cytokine-driven hyperplasia, culminating in lymphoma.

The role of cytotoxic and regulatory T cells in relapsed/refractory Hodgkin lymphoma.

Recent data suggests the presence of cytotoxic (TIA-1 and granzyme B+) and regulatory T-cells (FOXP3+) in classical Hodgkin lymphoma (cHL) tissues has been shown to correlate with poor overall survival in mainly diagnostic biopsies. By tissue microarray analyses, we extend this observation to a cohort of relapsed/refractory cHL tissue biopsies and analyze immunohistochemical expression of FOXP3, TIA-1, and granzyme B in the inflammatory background and the tumor microenvironment. High expression of TIA-1 (>50%) correlated with poor overall survival (P<0.0001), low expression of FOXP3 (<25%) correlated with poor overall survival (P<0.01), and combined high TIA-1 (>50%) and low FOXP3 (<25%) correlated with poor overall survival (P<0.0001). Expression of cytotoxic and regulatory T-cells shows prognostic significance in the relapsed/refractory clinical setting of cHL.

Nephrogenic systemic fibrosis: a pathologic study of autopsy cases.

CONTEXT: -Nephrogenic systemic fibrosis (NSF) is a rare but serious disorder initially described as a purely dermatologic process. Isolated autopsy reports have described multiorgan involvement by this disease. OBJECTIVE: -To further illustrate the varied and systemic involvement of NSF by describing the autopsy experience at the Massachusetts General Hospital. DESIGN: -We describe the findings in a series of 4 autopsy cases of patients diagnosed with NSF. This report describes the history of renal dysfunction, exposure to gadolinium-containing contrast agents, specific laboratory parameters, and the extent of systemic involvement identified by postmortem examination. RESULTS: -Causes of death included systemic thromboembolic disease (n = 3) and pneumonia (n = 1). Laboratory parameters and type, dose, or timing of gadolinium-containing contrast-agent exposure did not correlate with clinical findings and outcomes. All patients demonstrated cutaneous manifestations of the disease and nephrocalcinosis, with some exhibiting calcification and fibrosis of the dura, thyroid, and heart including the cardiac conduction system, on postmortem examination. Soft tissue calcification was associated with concurrent hyperparathyroidism or high serum parathyroid hormone levels. CONCLUSIONS: -Thromboembolic disease can be a significant clinical complication of NSF. Patients with NSF may also develop characteristic histologic features of fibrosis and calcification in multiple organs, with significant morbidity and mortality. This autopsy series highlights the variability of systemic manifestations of NSF.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen: a report of 3 cases.

The authors describe 3 cases of sclerosing angiomatoid nodular transformation (SANT) of the spleen diagnosed at Memorial Sloan-Kettering Cancer Center within a 1-year period (July 2008 to June 2009). All patients were female, older than 50, with lesions ranging in size from 2 to 4 cm. All were alive and well after splenectomy. All the cases showed characteristic histological and immunophenotypical findings as previously described in the literature, including scattered IgG4positive plasma cells in the fibrosclerotic stroma. Of the 3 patients, 2 had a history of carcinoma, and metastasis was of concern, but a PET scan in one of these patients showed minimal to absent FDG activity suggesting that this process was of a benign indolent nature. However, in 1 patient, a PET scan revealed positive FDG activity, heightening clinical concern for malignancy.

Measurement of a plasma stroke biomarker panel and cardiac troponin T in marathon runners before and after the 2005 Boston marathon.

We report changes in cardiac troponin-T (TnT) and a new plasma stroke biomarker panel (D-dimer, B-natriuretic peptide [BNP], matrix metalloproteinase-9 [MMP-9], S-100 b, Biosite Diagnostics, San Diego, CA) in 30 nonprofessional marathon runners before and immediately after the 2005 Boston Marathon. Following competition, there was a statistically significant increase in MMP-9 (P < .001) and D dimer (P < .001). Nonsignificant changes in S-100 b and BNP were observed. Premarathon and postmarathon values for a multimarker stroke index increased from 0.97 (normal) to 3.5 (low risk or more; P < .001). Two subjects had index values more than the high-risk cutoff value. Mean TnT premarathon and postmarathon levels increased (from <0.01 to 0.03 ng/mL; P < .0001). After the marathon, with a cutoff value of 0.05 ng/mL, 7 runners (23%) had values above the manufacturer's recommended cutoff for myocardial damage. Although biochemical evidence of myocardial damage following strenuous exercise may reflect myocardial stunning or subclinical ischemia, the changes in the stroke index and values for individual stroke markers may reflect a systemic inflammatory response to exertional rhabdomyolysis which is common, but the possibility of subclinical central nervous system damage cannot be excluded.

Analysis of microbial mixtures by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Many different laboratories are currently developing mass-spectrometric techniques to analyze and identify microorganisms. However, minimal work has been done with mixtures of bacteria. To demonstrate that microbial mixtures could be analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), mixed bacterial cultures were analyzed in a double-blind fashion. Nine different bacterial species currently in our MALDI-MS fingerprint library were used to generate 50 different simulated mixed bacterial cultures similar to that done for an initial blind study previously reported (Jarman, K. H.; Cebula, S. T.; Saenz, A. J.; Petersen, C. E.; Valentine, N. B.; Kingsley, M. T.; Wahl, K. L. Anal. Chem. 2000, 72, 1217-1223). The samples were analyzed by MALDI-MS with automated data extraction and analysis algorithms developed in our laboratory. The components present in the sample were identified correctly to the species level in all but one of the samples. However, correctly eliminating closely related organisms was challenging for the current algorithms, especially in differentiating Serratia marcescens, Escherichia coli, and Yersinia enterocolitica, which have some similarities in their MALDI-MS fingerprints. Efforts to improve the specificity of the algorithms are in progress.