Anthony Mattia

Breast lymphoma. A B-cell spectrum including the low grade B-cell lymphoma of mucosa associated lymphoid tissue.

We studied the morphologic, immunologic, and clinical features of 31 cases of malignant lymphoma involving the breast. Primary breast lymphoma occurred in nine women with a median age of 69 years (range, 51-87 years); median follow-up was 31 months (range, 9-67 months). Eight cases were low grade, one was high grade, and all expressed B-lineage antigens. Four cases had features of lymphoma of mucosa-associated lymphoid tissue (MALT); three were free of disease after excision alone at 10, 12, and 48 months, whereas the fourth relapsed with transition to immunoblastic lymphoma and died at 25 months. Four patients had follicular lymphomas, three of which relapsed, causing death from active disease at a median of 55 months (range, 25-67 months). One case of small noncleaved cell lymphoma relapsed, causing death at 31 months. Lymphoma secondarily involved the breast in 22 patients (21 women, one man) with a median age of 60 years (range, 39-83 years) at breast relapse; these patients were followed for a median of 88 months (range, 2-271 months) from primary diagnosis and 4 months (range, 0-116 months) from breast relapse. Nineteen patients had prior documented lymphomas (10 nodal or splenic, nine extranodal), and breast involvement most commonly occurred as part of widespread, predominantly nodal disease. Three patients had breast involvement by lymphomas that were generalized at diagnosis or staging. Thirteen cases were low grade (nine follicular), seven intermediate grade, and one high grade; 19 of 20 cases expressed B-lineage antigens, and one expressed T-lineage antigens. Four cases had features of MALT-type lymphoma; in these patients, isolated breast relapses were interspersed with other extranodal relapses, with interim resolution of disease after local or systemic therapy; two were free of disease and two were alive with localized disease on treatment at median follow-up of 60 months (range, 9-91 months). In contrast, 15 of 18 non- MALT lymphomas had widespread disease at breast relapse (median, 29 months; range, 0-259 months); 16 of 18 received systemic therapy, 10 died with active disease, and five of eight had disseminated active disease at last follow-up Primary breast lymphomas were commonly low grade. The follicular lymphomas had clinical behavior similar to nodal follicular lymphoma. Primary MALT-type lymphomas were a distinct subset with a potential for diseasefree survival after local therapy. Secondary breast lymphomas were heterogeneous and more commonly higher grade, although follicular lymphoma was the most common subtype. Non-MALT secondary breast lymphoma occurred in a setting of widespread disease in most cases. However, MALT-type lymphomas occurred as isolated relapses from other extranodal sites, with a potential for disease free survival after local therapy

Collagenous colitis associated with lansoprazole

Background: Collagenous colitis is a diarrheal illness of unknown cause. The purpose of this report is to describe a case of collagenous colitis related to lansoprazole exposure. Study: Case report. Results: A patient is described who developed clinical and pathologic findings of collagenous colitis during treatment with lansoprazole and omeprazole. Symptoms of diarrhea and histopathologic abnormalities resolved after drug withdrawal and recurred with re‐exposure to lansoprazole. Conclusions: The observations are compatible with collagenous colitis or lymphocytic colitis associated with exposure to lansoprazole.

Microscopic Colitis Associated With Omeprazole and Esomeprazole Exposure

Goals The aim of this study was to determine whether proton pump inhibitors other than lansoprazole might be associated with microscopic colitis. Background Lansoprazole exposure has been associated with diarrhea and microscopic colitis, but this relationship has not been described with other proton pump inhibitors. Study Cases of microscopic colitis from a consultative gastroenterology practice were collected and reviewed for proton pump inhibitor exposure. Standard clinical, endoscopic, and biopsy findings were analyzed. Results A case series of 4 patients is described in which subjects developed classic symptoms of lymphocytic-collagenous colitis with typical mucosal histopathology during treatment with omeprazole/esomeprazole. Symptoms promptly stopped and mucosal biopsies returned to normal with drug withdrawal. Disease quickly recurred in 2 patients who were reexposed to the drugs, one with biopsy documented recurrent collagenous colitis. Conclusions Some cases of microscopic colitis seem to be associated with omeprazole/esomaprazole exposure. These results have epidemiologic, diagnostic, and therapeutic ramifications, which are discussed.

Diagnostic accuracy of a rural live video telepathology system.

Accuracy of diagnoses rendered using a live video telepathology network was assessed for permanent sections of surgical pathology specimens. To determine accuracy, telepathology diagnoses were compared with those obtained by directly viewing the glass slide using a standard microscope. A total of 294 cases were read via both telepathology and glass slide by attending pathologists at a tertiary care medical center. Overall accuracy was defined as exact concordance between diagnoses. Clinically insignificant differences in diagnoses were excluded to determine clinically significant accuracy. For the 285 cases with complete data, the overall accuracy for telepathology was 0.912 (95% confidence interval [CI], 0.872-0.941), whereas the overall accuracy for glass slide readings was 0.968 (95% CI, 0.939-0.985). This difference is statistically significant (p = 0.009). When focusing on clinically significant discrepancies, where the difference in diagnosis might affect therapeutic decisions, the video accuracy was only slightly less than the glass slide accuracy (0.965 [95% CI, 0.934-0.982] vs. 0.982 [95% CI, 0.957-0.994], respectively), but this difference is not statistically significant (p = 0.302). Most of the cases with clinically significant differences involved lesions with inherently high interobserver variation. Certainty of diagnosis did not differ between video and glass slide readings (p = 0.911), but there was an association between certainty of diagnosis and diagnostic accuracy for video (p = 0.003 for clinically significant accuracies). Based on these findings, we recommend when using this telepathology system that only preliminary diagnoses should be given in the following situations: for diagnostic areas with known high interobserver variability; when the consultant has any degree of uncertainty about the presence or absence of the lesion in question; and when there is insufficient experience using telepathology as a diagnostic medium.

Appropriate use of special stains for identifying helicobacter pylori: Recommendations from the Rodger C. Haggitt gastrointestinal pathology society

Helicobacter pylori is a major cause of gastroduodenal injury, gastric cancer, and lymphoma, and, thus, there is great interest in its detection and eradication. Several detection methods are available, including histochemical and immunohistochemical stains. Application of these stains in clinical practice is heterogenous, to say the least. Although they were developed to enhance H. pylori detection, changing practice models, financial considerations, and a perceived need for rapid case turnaround have led to their widespread use in routine staining studies ordered reflexively on all gastric biopsies. Emerging data suggest that most of these stains are not needed to establish a diagnosis of H. pylori infection, and their added value when biopsies show minimal, or no, inflammation is not clear. In this manuscript, the Rodger C. Haggitt Gastrointestinal Pathology Society puts forth recommendations regarding ancillary stain usage for H. pylori detection based upon critical literature review and collective experience. Pathologists rarely, if ever, detect H. pylori in “normal” biopsies, but readily observe them in optimally stained hematoxylin and eosin sections from infected patients. Therefore, we suggest that use of ancillary stains is appropriate when biopsies show chronic, or chronic active, gastritis without detectable H. pylori in hematoxylin and eosin-stained sections, but performing them “up front” on all gastric biopsies is generally unnecessary. Application of these stains to nongastric biopsies and polyps is appropriate in an extremely limited set of circumstances. It is our hope that recommendations provided herein will provide helpful information to gastroenterologists, pathologists, and others involved in the evaluation of patients for possible H. pylori infection.

Celiac sprue, hyperhomocysteinemia, and MTHFR gene variants.

Goals To describe the association of untreated celiac disease with hyperhomocysteinemia and variants of the methylenetetrahydrofolicacid reductase (MTHFR) gene found in clinical practice. Study Case studies with description of associated clinical, biochemical, and genetic findings and review of literature. Results Five new cases and 7 additional cases found from literature search of hyperhomocysteinemia with celiac sprue are reported. Treatment with gluten-free diet and folic acid led to the variable improvement in homocysteine levels. MTHFR gene variants were present in the each of the new patients described. Conclusions Untreated celiac disease may be associated with hyperhomocysteinemia caused by a combination of vitamin deficiencies and variants in the MTHFR gene. Abnormalities do not consistently improve with gluten-free diet. The abnormal findings could result from vitamin deficiencies or variant MTHFR status. Possible clinical implications for patients with celiac disease and hyperhomocysteinemia are reviewed.

A tailored approach to BRAF and MLH1 methylation testing in a universal screening program for Lynch syndrome

To determine the correlation between BRAF genotype and MLH1 promoter methylation in a screening program for Lynch syndrome (LS), a universal screening program for LS was established in two medical centers. Tumors with abnormal MLH1 staining were evaluated for both BRAF V600E genotype and MLH1 promoter methylation. Tumors positive for both were considered sporadic, and genetic testing was recommended for all others. A total 1011 colorectal cancer cases were screened for Lynch syndrome, and 148 (14.6%) exhibited absent MLH1 immunostaining. Both BRAF and MLH1 methylation testing were completed in 126 cases. Concordant results (both positive or both negative) were obtained in 86 (68.3%) and 16 (12.7%) cases, respectively, with 81% concordance overall. The positive and negative predictive values for a BRAF mutation in predicting MLH1 promoter methylation were 98.9% and 41%, respectively, and the negative predictive value fell to 15% in patients ≥70 years old. Using BRAF genotyping as a sole test to evaluate cases with absent MLH1 staining would have increased referral rates for genetic testing by 2.3-fold compared with MLH1 methylation testing alone (31% vs 13.5%, respectively, P<0.01). However, a hybrid approach that reserves MLH1 methylation testing for BRAF wild-type cases only would significantly decrease the number of methylation assays performed and reduce the referral rate for genetic testing to 12.7%. A BRAF mutation has an excellent positive predictive value but poor negative predictive value in predicting MLH1 promoter methylation. A hybrid use of these tests may reduce the number of low-risk patients referred to genetic counseling and facilitate wider implementation of Lynch syndrome screening programs.

Vascular Injury Characterizes Doxycycline-induced Upper Gastrointestinal Tract Mucosal Injury.

Doxycycline is an oral tetracycline antibiotic that has been associated with upper gastrointestinal (GI) mucosal injury. Recently, characteristic vascular degeneration has been reported in the stomach and duodenum in patients with doxycycline-induced injury. Fourteen patients who underwent upper GI endoscopy for nonspecific symptoms and were found to have doxycycline-induced gastric and esophageal injury are described. Most patients showed characteristic vascular injury. A control group of gastric erosions and esophageal ulcers showed no cases with the characteristic vascular changes. Clinical, endoscopic, and pathologic features of doxycycline-induced upper GI tract injury are reviewed, with an emphasis on vascular injury.