Colesevelam and colestipol: novel medication resins in the gastrointestinal tract.

We report the morphologic description of the bile acid sequestrants (BAS) colesevelam and colestipol, as well as the largest series of cholestyramine. Histologically similar medication resins from 4 institutions were prospectively collected over 1 year (26 specimens, 15 patients). Comorbidities included hyperlipidemia (4/15), hypertension (4/15), inflammatory bowel disease (4/15), coronary artery disease (3/15), diarrhea (7/15), hypothyroidism (2/15), and ischemic bowel (1/15). Sites of involvement included the esophagus (1/26), stomach (1/26), small intestine (1/26), ileocecal valve (1/26), and colorectum (22/26). Associated histologic diagnoses included normal (8/26), chronic mucosal injury (11/26), acute inflammation (9/26), erosion/ulceration (6/26), and cytomegalovirus (2/26). The BAS resins were histologically indistinguishable from each other; they were all eosinophilic on hematoxylin and eosin (H&E) and lacked internal "fish-scales." To validate these observations, respective medications were submitted for histologic processing; the processed medications were identical to those in the patient specimens. Rare, irregular "fracture" lines presented diagnostic pitfalls by mimicking the true "fish-scales" of Kayexalate and sevelamer. Clues to the correct identification of BAS include recognition that the "fracture" lines were subtle, irregular, and restricted to large fragments or thick sections, likely representing a processing artifact. Moreover, Kayexalate is violet on H&E and black on acid fast bacillus, and sevelamer characteristically displays a 2-tone color on H&E and is magenta on acid fast bacillus. An association with inflammatory injury was seen (15/26). We believe that the BAS are innocent bystanders in complicated patients, although we cannot exclude their ability to cause mucosal injury in specific settings.

Esophageal leukoplakia or epidermoid metaplasia: a clinicopathological study of 18 patients.

Oral leukoplakia is a relatively common, painless disorder of the oral mucosa. It predominantly affects middle-aged to elderly men and has a strong association with tobacco smoking and alcohol intake. Concomitant histological findings of hyperorthokeratosis and a well-developed granular cell layer, termed orthokeratotic dysplasia, are often associated with oral squamous cell carcinoma. In contrast, analogous lesions within the esophagus, termed esophageal epidermoid metaplasia, are rarely encountered and poorly described in the literature. To better characterize the clinicopathological features of this entity, we have collected 25 cases from 18 patients. Patients ranged in age from 37 to 81 years (mean, 61.5 years), with a slight female predominance (10/18, 56%). On presentation, a majority of patients complained of dysphagia (10/18, 56%). Past medical history was significant for tobacco smoking or long history of second-hand smoke in 11 (61%) patients and alcohol intake in 7 (39%) patients. Seventeen (94%) patients with esophageal epidermoid metaplasia were located within the middle-to-distal esophagus. Histologically, all cases were sharply demarcated and characterized by epithelial hyperplasia, a thickened basal layer, acanthotic midzone, a prominent granular cell layer, and superficial hyperorthokeratosis. Adjacent high-grade squamous dysplasia and/or squamous cell carcinoma were seen in 3 out of 18 (17%) patients. Follow-up information was available for 13 out of 18 (72%) patients and ranged from 2 to 8.3 years (mean, 2.3 years). Seven of the 13 (54%) patients had persistent disease; however, none of them developed squamous dysplasia or squamous cell carcinoma. In an effort to assess the incidence of esophageal epidermoid metaplasia, 198 consecutive esophageal biopsies were prospectively surveyed over a 6-month period at three academic institutions. No cases were identified within this time frame. In summary, esophageal epidermoid metaplasia is a rare condition affecting the middle-to-distal esophagus in middle-aged to elderly females. The occurrence of adjacent high-grade squamous dysplasia and/or squamous cell carcinoma warrants close follow-up.

Serrated polyposis is an underdiagnosed and unclear syndrome: the surgical pathologist has a role in improving detection.

Serrated polyposis syndrome (SPS) is poorly defined and patients have an increased but unspecified risk for colorectal carcinoma through the serrated pathway. Despite this association SPS remains relatively obscure and is therefore likely underrecognized. We determined the frequency of SPS among patients with any serrated polyps (SPs) over a 6-month "index" period, and in doing so we assessed the ability of surgical pathologists to improve SPS detection. Particular attention was given to the index procedure to assess the potential predictive value of the findings resulting from a single colonoscopy. A total of 929 patients with at least 1 SP were identified, 17 of whom (1.8%) were determined to meet World Health Organization criteria for SPS. Nine patients met the first criterion (≥ 5 proximal SPs, 2 of which are > 10 mm); 4 met the third criterion (> 20 SPs of any size distributed throughout the colon); and 4 met both criteria. Although no specific SP size or number at the index procedure was clearly superior in its ability to predict SPS, > 50% of cases would be detected if a cutoff of ≥ 3 SPs or a single SP ≥ 15 mm at the index procedure is used. In summary, SPS is rare but more likely underdiagnosed. Additional studies to address the underlying genetic basis for SPS are ongoing in order to shed further light on this syndrome. Surgical pathologists are in a unique position to assist in this endeavor by identifying those patients who either meet or seem to be at high risk of meeting World Health Organization criteria.

Diagnosis of metastatic pancreatic mesenchymal tumors by endoscopic ultrasound-guided fine-needle aspiration.

Involvement of the pancreas by metastatic sarcoma is rare, and can prove challenging to differentiate from sarcomatoid carcinomas which occur more commonly. The endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) technique has been successfully used for the diagnosis of pancreatic carcinomas whether primary or metastatic, and is now considered the most effective noninvasive method for the identification of pancreatic metastases. However, to date very few reports detail the diagnosis of mesenchymal neoplasms by EUS-FNA. Herein, we report a series of four patients who underwent EUS-FNA of the pancreas, where the diagnosis of metastatic sarcoma was made based on morphology and ancillary studies. The cases include metastases of leiomyosarcoma, liposarcoma, alveolar rhabdomyosarcoma, and solitary fibrous tumor. The history of a primary sarcoma of the chest wall, mediastinum, and respectively lower extremity was known for the first three of these patients while in the case of the solitary fibrous tumor a remote history of a paraspinal "hemangiopericytoma" was only elicited after the EUS-FNA diagnosis was made. We conclude that EUS-FNA is efficient and accurate in providing a diagnosis of sarcoma, even in patients without a known primary sarcoma, thus allowing institution of therapy without additional biopsies.

Selective internal radiation therapy-induced extrahepatic injury: an emerging cause of iatrogenic organ damage.

Selective internal radiation therapy (SIRT) using Yttrium microspheres is a novel therapeutic approach to the localized treatment of hepatic tumors. It provides a distinct advantage over conventional external beam radiation in that its targeted nature allows the directed delivery of high doses of radiation to tumors while sparing the surrounding uninvolved hepatic parenchyma. Numerous studies have evaluated the safety and efficacy of SIRT, and it has been used to treat both primary and metastatic hepatic malignancies. However, SIRT is not without risk of complications, and has been known to cause various toxicities due to extrahepatic SIRT microsphere deposition. Reports of such injury have been only sparsely described in the pathology literature to date, and surgical pathologists therefore remain largely unaware of this phenomenon, which can potentially lead to misdiagnosis. Herein, we review the histopathology and pathophysiology of extrahepatic SIRT microsphere migration as a cause of iatrogenic tissue injury, highlighted by 3 examples of gastritis and 1 case of cholecystitis.

Discrepancies in initial death certificate diagnoses in sudden unexpected out-of-hospital deaths: the role of cardiovascular autopsy.

BACKGROUND: The accuracy of death certificates issued for out-of-hospital sudden deaths has been questioned. METHODS: We retrospectively studied a series of consecutive autopsies performed at two community hospitals. RESULTS: Fifty-four autopsies in which the deaths were sudden and that occurred outside the hospital were retained for study. The indication for autopsy was largely driven by the wishes of family or physician who was uncertain about the diagnosis. The overall discrepancy rate was 52%. The death certificate diagnosis, rendered before autopsy, was coronary artery disease in 44/54 autopsies (81%). At autopsy, coronary artery disease was the cause of death in 26 cases (48%), cardiomyopathy in 10 (18%), ruptured aneurysm in 8 (15%), pulmonary embolism in 7 (13%), and valve disease in 3 (6%). The diagnosis of coronary artery disease on the death certificate was accurate only 50% of the time. The discrepancy rate was lowest in patients with a history of cardiovascular disease (33%) and was 60% in patients with no prior medical history. The accuracy rate of death certificates was under one third in cases of cardiomyopathy, valve disease, ruptured aneurysm, pulmonary embolism, and valve disease. CONCLUSIONS: We conclude that in a highly selected group of sudden deaths, in which there was often a question about cause of death, the rate of initial death certificate accuracy is only one half. Furthermore, coronary artery disease as the cause of death is less than 50%, far less than initial death certificate diagnoses would indicate.

Discrepancies between clinical and autopsy diagnoses: a comparison of university, community, and private autopsy practices.

Although it is known that autopsies often disclose unexpected findings, few studies have been published that address the effect of institutional setting, selection bias, and length of hospitalization. Records of medical autopsies from 3 institutional settings were studied for discrepancies between clinical and autopsy findings. The settings were university hospital (n = 85); community hospital (n = 146); and private autopsy (n = 60), which were referred from various community hospitals and paid for by family members. The same prosector performed the autopsies in the community and private settings. The overall rate of major discrepancy that involved the cause of death was 17.2%. Factors that increased the likelihood of missed diagnoses were private setting (P = .0005), community setting (P = .02), and short hospital stay before death (P = .02). Additional major findings were present in 28.5% of autopsies. Length of hospital stay before death, institution, and selection bias all affect the rate of major unexpected findings in hospital-based autopsies.

Successful outcome of progressive multifocal leukoencephalopathy in a renal transplant patient.

We report the case of a 47-year-old man who developed progressive multifocal leukoencephalopathy (PML) after receiving immuno-suppressive therapy for renal transplantation. The patient presented with a focal seizure and cognitive changes 5 months post-transplantation. He was found to have enhancing lesions in the parietal lobe and typical findings of PML in a brain biopsy. Immunosuppression was discontinued and the neurological symptoms gradually resolved over a period of 4 weeks. The patient is free of any neurological symptoms 36 months after the diagnosis of PML and imaging studies demonstrate resolution of the PML lesions. The patient returned to hemodialysis 3 months after immunosuppression was discontinued. We also present a review of the literature on PML in renal transplant recipients.

Histological patterns of polyomavirus nephropathy: correlation with graft outcome and viral load.

Polyomavirus-associated nephropathy (PVAN) is a significant cause of allograft loss. The diagnosis requires allograft biopsy, but the impact of the histological features on diagnosis and outcome has not been described. We studied the distribution and extent of PVAN in 90 patients. Viral cytopathic changes, tubular atrophy/fibrosis and inflammation were semi-quantitatively scored and classified into histological patterns. The histological findings were correlated with viruria, viremia and graft survival. PVAN lesions were random, (multi-)focal and affected both cortex and medulla. Areas with PVAN coexisted with areas of unaffected parenchyma. In 36.5% (15/41) of biopsies with multiple tissue cores, discordant findings with PVAN-positive and -negative cores were observed. However, all patients with PVAN had decoy cells in urine as well as significant viruria and viremia (mean of 2.5 x 10(8) and 2.32 x 10(7) viral copies, respectively). Biopsies showing lesser degrees of renal scarring at the time of diagnosis were associated with, more likely, resolution of the infection, in response to decrease of immunosuppression (p = 0.001). More advanced tubulointerstitial atrophy, active inflammation and higher creatinine level at diagnosis correlated with worse graft outcome (p = 0.0002, 0.0001 and 0.0006). Due to the focal nature of PVAN, correlation of biopsy results with viruria and viremia are required for diagnosis.