Matthew Lewin

The optimal number of biopsy fragments to establish a morphologic diagnosis of eosinophilic esophagitis.

OBJECTIVES:Eosinophilic esophagitis (EoE) is characterized clinically by dysphagia, chest pain, and food impaction, and morphologically by increased numbers of intraepithelial eosinophils and marked basal hyperplasia of the squamous mucosa. The consensus criteria for a diagnosis of EoE include the presence of ≥15 eosinophils/HPF in biopsies from both proximal and distal esophagus in the absence of other causes of esophageal eosinophilia, and the lack of clinical response to proton pump inhibitor therapy. Because of the variability in the distribution of intraepithelial eosinophils among biopsy fragments and the lack of standardized biopsy practices, we sought to determine the optimal number of esophageal biopsies from the mid and distal esophagus needed to reach the minimum morphologic criteria of ≥15 eosinophils/HPF.METHODS:From 5 January 2009 to 26 September 2011, 771 patients were diagnosed with EoE at our institution. From that patient population, 102 sequential cases were chosen for further study, all of whom had biopsies taken from the mid and distal esophagus. Cases with only gastric mucosa present and biopsies taken from patients with a previous diagnosis of EoE were excluded. The original H&E-stained slides were reviewed, and the number of biopsy fragments containing squamous mucosa was recorded. By using a × 40 objective and × 10 oculars (field diameter=0.52 mm, field area=0.21 mm2), the number of eosinophils per high power field (EOS/HPF) in up to three HPFs was counted in each biopsy fragment.RESULTS:The EOS/HPF were counted in 1,342 biopsy fragments. The number of biopsy fragments obtained from the mid esophagus ranged from 1 to 20 (mean 7; median 7) and those obtained from the distal esophagus ranged from 1 to 18 (mean 6; median 5). There was no significant difference between the mean number of EOS/HPF from the mid (26) and lower (25) esophagus or between the mean peak number of EOS/HPF from the mid (69.1) and lower (60.4) esophagus. The probability of one, four, five, and six biopsy fragments containing >15 EOS/HPF was 0.63, 0.98, 0.99, and >0.99, respectively.CONCLUSIONS:From these data, at least four biopsy fragments should be submitted from the mid and/or proximal esophagus to optimize the chances of a positive diagnosis of EoE in populations not known to have undergone previous proton pump inhibitor therapy. However, the yield is not increased beyond six biopsy fragments. In order to morphologically exclude a diagnosis of reflux esophagitis as the cause of intraepithelial eosinophilia, distal esophageal biopsies, if obtained, must be accompanied by more proximal biopsies (i.e., mid esophagus or higher).

Angiotensin-II inhibitor (olmesartan)-induced collagenous sprue with resolution following discontinuation of drug

Collagenous sprue (CS) is a pattern of small-bowel injury characterized histologically by marked villous blunting, intraepithelial lymphocytes, and thickened sub-epithelial collagen table. Clinically, patients present with diarrhea, abdominal pain, malabsorption, and weight loss. Gluten intolerance is the most common cause of villous blunting in the duodenum; however, in a recent case series by the Mayo Clinic, it has been reported that olmesartan can have a similar effect. In this case report, a 62-year-old female with a history of hypothyroidism and hypertension managed for several years with olmesartan presented with abdominal pain, weight loss, and nausea. Despite compliance to a gluten-free diet, the patients symptoms worsened, losing 20 pounds in 3 wk. Endoscopy showed thickening, scalloping, and mosaiform changes of the duodenal mucosa. The biopsy showed CS characterized by complete villous atrophy, lymphocytosis, and thickened sub-epithelial collagen table. After 2 mo cessation of olmesartan, the patients symptoms improved, and follow-up endoscopy was normal with complete villous regeneration. These findings suggest that olmesartan was a contributing factor in the etiology of this patients CS. Clinicians should be aware of the possibility of drug-induced CS and potential reversibility after discontinuation of medication.

Sclerosing extramedullary hematopoietic tumor: emphasis on diagnosis by renal biopsy.

Sclerosing extramedullary hematopoietic tumor (SEMHT) is a rare lesion that typically arises in patients with chronic myeloproliferative disorders. Morphologically, it exhibits atypical megakaryocytes, granulocytic precursors, and erythroid precursors set in a background of dense collagen sclerosis. Sclerosing extramedullary hematopoietic tumor may be easily mistaken for other neoplasms, such as sarcoma, carcinoma, or Hodgkin lymphoma, particularly if pertinent clinical history is not provided. Misdiagnosis may occur because of the difficulty in recognizing the megakaryocytic lineage of the atypical cells and because of the paucity of other hematopoietic elements. We report a case of a 72-year-old man with proteinuria and renal insufficiency who underwent renal biopsy to determine the etiology of the proteinuria. The kidney biopsy demonstrated an unusual tumor in which the initial morphological impression that of sclerosing liposarcoma. However, upon learning of the patients previous history of chronic idiopathic myelofibrosis and with the aid of immunohistochemistry, the correct diagnosis of sclerosing extramedullary hematopoietic tumor was made. Sclerosing extramedullary hematopoietic tumor should be considered in the differential diagnosis when percutaneous renal biopsy or other intra-abdominal biopsy reveals a sclerotic lesion with interspersed large atypical cells, especially in a patient with a history of chronic myeloproliferative disorder.

BK Virus–Associated Nephropathy in a Patient With AIDS

The BK virus is a ubiquitous member of the group of human polyoma viruses that commonly is reactivated in the setting of immunosuppression related to renal transplantation, which results in tubulointerstitial nephritis and allograft dysfunction. BK virus-associated nephropathy occurring in association with human immunodeficiency virus infection and acquired immunodeficiency syndrome (AIDS) was reported only rarely. We describe the case of a 43-year-old man with AIDS presenting with nonoliguric renal failure. The renal biopsy specimen showed tubulointerstitial nephritis and renal tubular cell changes consistent with BK viral inclusions. Results of in situ hybridization for BK viral DNA were positive and showed tubular cell intranuclear inclusions. To our knowledge, this represents the third case of AIDS-associated BK virus-associated nephropathy diagnosed by means of biopsy.

Lymphocytic gastritis is not associated with active Helicobacter pylori infection.

Lymphocytic gastritis (LG), characterized by marked intra‐epithelial lymphocytosis in the gastric mucosa, has been frequently associated with both celiac disease (CD) and H. pylori gastritis. The aim of this study was to review and correlate the morphology of LG with the presence of CD and H. pylori.

Marfan Syndrome, MPGN, and Bacterial Endocarditis

D C sethi. s arfan syndrome is an autosomal dominant connective tissue disorder characterized by cular, skeletal, and cardiovascular manifestations. ardiovascular manifestations include dilatation and issection of the proximal aorta and mitral valve rolapse. Marfan syndrome is estimated to have a revalence of 1 case/10,000 people, and at least 5% of cases occur in the absence of a family istory, suggesting parental germ-line defects. Renal complications are uncommon in patients ith Marfan syndrome. We describe a patient with arfan syndrome with proteinuria and renal insufciency. Renal biopsy showed membranoproliferaive glomerulonephritis (MPGN) that led to the etection of an unsuspected systemic disease involvng the kidney. In this report, we discuss one of the mportant secondary causes of MPGN.

Incidence of Diagnostic Change in Colorectal Polyp Specimens After Deeper Sectioning at 2 Different Laboratories Staffed by the Same Pathologists

OBJECTIVES To calculate the incidence of nondiagnostic (ND) colorectal (CR) polyp cases in which deeper tissue sectioning rendered new diagnostic information--particularly adenomas--in 2 laboratories staffed by the same pathologists. METHODS After initial diagnosis, 100 ND CR polyps from each laboratory were reexamined with 3 deeper levels to establish rates of diagnostic conversion based on biopsy specimen location and original observation(s). RESULTS Deeper sectioning rendered new diagnostic information in 43 (21.5%) of 200 biopsy specimens and specifically adenomas in 16 (8.0%) of 200 biopsy specimens. CONCLUSIONS These results support routine ordering of deeper levels on ND CR polyps to improve adenoma detection rates, especially those cases without any histologic abnormality. If another biopsy in the same case already is adenomatous, examination of deeper levels may not be necessary, as it may not have any significant effect on the clinical management of the patient.

Sa1870 Fundic Gland Polyps With Dysplasia

Fundic gland polyps (FGPs) are the most common type of gastric polyp and are seen in up to 5% of patients on endoscopy. Although considered benign, FGPs are more common in patients with familial adenomatous polyposis (FAP). FGPs occur sporadically in up to 1.9% of the general population and in 84% of patients with syndromic FAP. Dysplasia in FGP is reported in 53% of syndromic FGPs and in only 2.3% of sporadic FGPs. The aim of this study is to compare patients with FGPs with dysplasia and those with FGPs without dysplasia. The pathology files from two institutions were searched from 1/1/2009 to 10/1/2013 for FGPs with dysplasia (FGPD). A similar number of control cases of FGP with no dysplasia (FGPND) were also randomly retrieved. All biopsies were reviewed, and diagnoses were agreed upon by three pathologists. Patient demographic data was recorded and included age, gender, race, diagnosis of FAP, and PPI use. Twenty-five patients with FGPD were identified (Male: 15, Female: 10, mean age: 60). Five patients had a confirmed history of FAP (mean age: 36), 9 had a high probability of FAP based on family or personal GI history (mean age: 61), 3 had no indication of FAP (such as family or personal history of colon cancer or polyps) (mean age: 63), and in 8 patients the family or personal history was not recorded (mean age: 62). Seventeen patients (68%) were on a protein pump inhibitor (PPI). The mean age of FGPD patients with FAP is significantly lower than patients without FAP (p< 0.001). The 26 patients with FGPND included 10 males and 16 females (mean age: 60). None of the patients had a history of FAP, 12 had a high probability of FAP based on family or personal GI history (mean age: 61), 6 had no indication of FAP (mean age: 59), and in 8 patients the family or personal history was not recorded (mean age: 55). Eighteen patients (69%) were on a PPI. There were no ethnic/racial differences between the two groups of patients. Of all biopsies from patients with FGPD, 88% of all fragments were smaller than 5 mm2 and 5% were greater than10 mm2. In contrast, of all the biopsies from patients with FGPND, 68% of all fragments were smaller than 5 mm2 and 20% were greater than 10 mm2. These data show no correlation between PPI use and the presence of low grade dysplasia in FGP. FGPND tended to result in larger biopsy fragments than FGPD; however there was no significant difference in the number of polyps described endoscopically between the two groups. Patients who have low-grade dysplasia in FGP are more likely to have FAP or a high probability of FAP than those without dysplasia. Low grade dysplasia in FGP is seen at a younger age in patients with FAP than in those without FAP. Finding low grade dysplasia in FGP, particularly in patients younger than 40 years, should raise a suspicion for FAP.