Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study.

Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Depending on the type of protocol, different histopathological features, in terms of inflammation, glandular abnormalities and endocrine differentiation were seen in the non-neoplastic mucosa within the irradiated volume. Of note, features mimicking dysplasia, such as crypt distortion, nuclear and cytoplasmic atypia of glandular epithelium, were identified only in the short-course group. DNA mutation analysis, using a panel of 56 genes frequently mutated in cancer, and p53 immunostaining were performed on both tumor and radiation-damaged mucosa in a subset of short course cases. Somatic mutations were identified only in tumors, supporting the concept that tissues with radiation-induced "dysplastic-like" features are not genetically transformed. Pathologists should be aware of the characteristic morphological changes induced by radiation. The presence of features simulating dysplasia in the group treated with short-course radiotherapy may lead to serious diagnostic mistakes, if erroneously interpreted. Next generation sequencing (NGS) analysis further validated the morphological concept that radiation-induced abnormalities do not represent pre-neoplastic lesions.

Common and uncommon features of nephrogenic adenoma revisited.

Nephrogenic adenoma is a common diagnosis in urological pathology that may be challenging for general pathologists. Due to its polymorphic appearance under the microscope, some cases can be misdiagnosed as malignancy and then unnecessarily overtreated. Aside from the typical tubules, cysts and papillae, nephrogenic adenoma may display a broad spectrum of histologic appearances and locations, some of them atypical or unexpected. These unusual and concerning features will have special consideration in this description. The goal of the review is to increase awareness of general pathologists of the varied histology of nephrogenic adenoma.

Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis.

BACKGROUND: In ulcerative colitis (UC), the majority of colorectal carcinomas (CRC) arise in the vast colorectal mucosal domain built with mucus-producing goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny, spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the four reported cases of colonic carcinoma developing in GALT mucosa in UC, searching for possible precursor lesions connected with the evolution of these tumours. MATERIALS AND METHODS: The clinical history, age, gender, endoscopic descriptions, and the pathology (localization, gross and histological descriptions of the luminal surface) of the four UC-GALT carcinomas reported in the literature were reviewed. RESULTS: The luminal surface in three out of the four carcinomas revealed conventional (tubular/villous) adenomas or high-grade dysplasia. All four UC-GALT-carcinomas were detected at an early stage (T1N0). CONCLUSION: GALT carcinomas do occur, albeit infrequently, in patients with UC. The finding that three out of the four GALT carcinomas on record were covered by conventional adenomas or by high-grade dysplasia strongly suggests that non-invasive conventional neoplasias might often precede GALT carcinomas in UC.

The third pathway of colorectal carcinogenesis.

AIMS: The majority of the colorectal carcinomas (CRC) arise in a vast mucosal area built with columnar cells and mucus-producing goblet cells. These carcinomas evolve via the conventional (tubular/villous) adenoma-carcinoma pathway, or the serrated adenoma-carcinoma pathway. Much less frequently CRC arise in the gut-associated lymphoid tissue (GALT) mucosal domain via the third pathway of colorectal carcinogenesis. METHODS: All publications on human colorectal GALT carcinomas in the literature were reviewed. RESULTS: Only 23 GALT-carcinomas found in 20 patients are in record. The GALT carcinomas were detected at surveillance colonoscopic biopsy in 11 patients (four had ulcerative colitis, two were members of a Lynch syndrome family, two of a CRC family, one had familial adenomatous polyposis (FAP), one prior colon adenomas and one a submucosal tumour), or at diagnostic colonoscopic biopsy in the remaining nine patients (three had rectal bleedings, two abdominal pains, one diverticular disease and one protracted constipation. In three, no ground disease or symptoms were provided). In six of the 23 GALT carcinomas, the luminal surface showed tumour cells, ulcerations or no descriptions were given. Ten (66.7%) of the remaining 15 GALT carcinomas showed on top, adenomas (n=8) or high-grade dysplasia (n=2). CONCLUSIONS: The low frequency of GALT carcinomas might be explained by the fact that the colorectal mucosal areas occupied by GALT domains are minute. The finding that two-thirds of the 15 remaining GALT carcinomas (vide supra) were covered by high-grade dysplasia or by conventional adenomas strongly suggest that conventional non-invasive neoplasias might have preceded the majority of the GALT carcinomas in record.

Detection of Intratumor Heterogeneity in Modern Pathology: A Multisite Tumor Sampling Perspective.

Current sampling protocols of neoplasms along the digestive tract and in the urinary bladder have to be updated, as they do not respond to the necessities of modern personalized medicine. We show here that an adapted version of multisite tumor sampling (MSTS) is a sustainable model to overcome current deficiencies in digestive and bladder tumors when they are large enough so as to make unaffordable a total sampling. The new method is based on the divide-and-conquer algorithm and includes a slight modification of the MSTS, which proved to be useful very recently in clear cell renal cell carcinoma. This in silico analysis confirms the usefulness of MSTS for detecting intratumor heterogeneity (ITH) in tumors arising in hollow viscera. However, MSTS does not seem to improve routine traditional sampling in detecting tumor budding, extramural venous invasion, and perineural invasion. We conclude that (1) MSTS is the best method for tumor sampling to detect ITH balancing high performance and sustainable cost, (2) MSTS must be adapted to tumor shape and tumor location for an optimal performance.

Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis.

BACKGROUND & AIMS: It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS: Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS: Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS: In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.

How do gastroenterologists assess overall activity of eosinophilic esophagitis in adult patients?

OBJECTIVES: There is no "gold standard" for assessing disease activity in patients with eosinophilic esophagitis (EoE). We aimed to compare physicians' judgment of EoE activity with patients' judgment of symptom severity. We also aimed to examine the relative contribution of symptoms as well as endoscopic and histologic findings in shaping physicians' judgment of EoE activity. METHODS: Six gastroenterologists (all EoE experts) assessed EoE-associated symptoms in adult patients. Patients completed a symptom instrument and provided global assessment of EoE symptom severity (PatGA) (Likert scale: 0 (inactive) to 10 (most active)). Following esophagogastroduodenoscopy with biopsy sampling, gastroenterologists provided a global assessment of EoE activity (PhysGA) (Likert scale from 0 to 10) based on patient history and endoscopic and histologic findings. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms and endoscopic and histologic findings explain variations in PhysGA. RESULTS: A total of 149 EoE patients were prospectively included (71.8% male, median age at inclusion 38 years, 71.8% with concomitant allergies). A moderate positive correlation between PhysGA and PatGA (rho=0.442, P<0.001) was observed and the mean difference in the Bland-Altman plot was 1.77. Variations in severity of endoscopic findings, symptoms, and histologic findings alone explained 53%, 49%, and 30%, of the variability in PhysGA, respectively. Together, these findings explained 75% of variability in PhysGA. CONCLUSIONS: Gastroenterologists rate EoE activity mainly on the basis of endoscopic findings and symptoms and, to a lesser extent, on histologic findings.

HPV testing results and histologic follow-up in women with ASC-H cytology in different age groups.

INTRODUCTION: Assessment on human papillomavirus (HPV) testing and disease outcome of atypical squamous cell, cannot exclude high grade squamous intraepithelial lesion (ASC-H) in different age groups is limited in published reports. We reviewed our experience over a 5-year period on ASC-H cytology and correlated age distribution with high-risk HPV (HR-HPV) status and histological follow-up in a large cohort study. MATERIALS AND METHODS: Women with ASC-H cytology were retrieved from the hospital database. HR-HPV status and histological diagnoses on cervical biopsy or loop electrosurgical excisional procedure specimens were reviewed and correlated to 5 age groups. RESULTS: Ages of women with ASC-H ranged from 16 to 88 years, with 42% women <30 years and 58% women >30 years. Among 647 cases diagnosed as ASC-H, 96% (618) had HR-HPV testing results, including 68.2% HR-HPV positive and 31.8% HR-HPV negative. HR-HPV positivity of ASC-H gradually decreased from 95.2% in women <20 years to 40.6% in the age group >51 years. Histologic follow-ups were available for review in 80% (517) of the cases. Cervical intraepithelial neoplasia, grade 2 or higher (CIN2+) lesions were found in 40.3% (208) cases, including 92.9% women with HR-HPV-positive/ASC-H and 7.1% of women with HR-HPV-negative/ASC-H. The detection rate of CIN2+ by ASC-H gradually decreased from 51.2% in women <20 years to 18.2% in women >51 years. The majority of postmenopausal women with HR-HPV-negative/ASC-H had atrophy-related change. CONCLUSIONS: The specificity of ASC-H cytology in detection of cervical CIN2+ lesions is age-dependent: higher in younger women <30 years, but gradually decreased in women >30 years. The vast majority (93%) of CIN2+ lesions were seen women with HR-HPV-positive/ASC-H. HR-HPV testing improves the accuracy and specificity in women with ASC-H in almost all age groups, especially in age groups older than 40 years.

Abdominal imaging findings in gastrointestinal basidiobolomycosis.

PURPOSE: To describe the abdominal imaging findings of patients with gastrointestinal Basidiobolus ranarum infection. METHODS: A literature search was performed to compile the abdominal imaging findings of all reported worldwide cases of gastrointestinal basidiobolomycosis (GIB). In addition, a retrospective review at our institution was performed to identify GIB cases that had imaging findings. A radiologist aware of the diagnosis reviewed the imaging findings in detail. Additional information was obtained from the medical records. RESULTS: A total of 73 GIB cases have been published in the medical literature. The most common abdominal imaging findings were masses in the colon, the liver, or multiple sites and bowel wall thickening. Initially, many patients were considered to have either a neoplasm or Crohn disease. We identified 7 proven cases of GIB at our institution, of which 4 had imaging studies (4 computed tomography [CT] examinations, 4 abdominal radiographs, and an upper gastrointestinal study). Imaging studies showed abnormalities in all 4 cases. Three-fourths of our study patients had an abdominal mass at CT. Two of 3 masses involved the kidneys and included urinary obstruction. All masses showed an inflammatory component with adjacent soft tissue stranding, with or without abscess formation. CONCLUSIONS: Radiologists should consider GIB when a patient from an arid climate presents with abdominal pain, weight loss, and an inflammatory abdominal mass on CT. Abdominal masses of the colon or liver, bowel wall thickening, and abscesses are the most common imaging findings.

Magnetic resonance elastography can discriminate normal vs. abnormal liver biopsy in candidates for live liver donation.

PURPOSE: The aim of this study was to define liver shear stiffness by magnetic resonance elastography (MRE) that distinguishes normal from abnormal liver biopsy, especially when steatosis ≥20%, among potential live liver donors. METHODS: Baseline clinical, laboratory, imaging, MRE, and liver biopsy results were recorded. Using MRE, hepatic shear stiffness in kilopascals (kPa) was measured and compared to liver biopsy. Comparison between groups was done using χ(2) or Fisher's exact test for categorical variables and Wilcoxon test for continuous variables. Receiver operating characteristic (ROC) curve was calculated to assess diagnostic accuracy. Statistical significance was set at p < 0.05. RESULTS: 38 healthy adults were included. Liver biopsy was normal in 27 and abnormal in 11. ROC curve for MRE defined optimal cutoff at 2.6 kPa (sensitivity 0.72, specificity 0.85, AUC 0.81) to distinguish these 2 groups. Hepatic steatosis ≥20% on biopsy is a contraindication for liver donation in our center. We evaluated the ability of MRE to distinguish this degree of steatosis: 8 persons had steatosis ≥20% and were excluded from donation. ROC curve for MRE defined optimal cutoff at 2.82 kPa (sensitivity 0.88, specificity 1, AUC 0.98) to identify this group. CONCLUSIONS: Liver stiffness measured by MRE, even in the absence of liver fibrosis, can be useful in differentiating normal from abnormal liver histology, and most importantly in patients under evaluation for live liver donation, can very accurately distinguish those with complicated hepatic steatosis ≥20%, our cutoff for donation. In the future, MRE might provide supplementary information to make liver biopsy unnecessary in the donor evaluation process.

Magnetic resonance elastography (MRE) in assessing hepatic fibrosis: performance in a cohort of patients with histological data.

PURPOSE: The purpose of this study was to compare fibrosis seen on liver biopsy to MR elastography (MRE) stiffness measurements in normal controls and patients with abnormal transaminases and chronic liver disease. METHODS: The control group consisted of 22 healthy liver transplant donors who by definition had normal transaminases. The patient group (32 patients) was recruited from the Mayo Clinic Arizona hepatobiliary clinic over a 3-year span. All subjects underwent a liver biopsy as part of their evaluation and agreed to MRE within 35 days of biopsy. Non-parametric tests were used to compare the MRE-predicted liver fibrosis to the fibrosis noted on liver biopsy. RESULTS: Analysis included 54 subjects (32 patients with chronic liver disease and 22 healthy liver donor candidates). MRE median liver stiffness measurements increased per histologic liver fibrosis stage (one-way ANOVA p = 0.001), with significant correlation between increasing fibrosis stage and stiffness values. Median MRE for control group (2.13 kPa; mean = 2.3 ± 0.6 kPa) was significantly lower than for patient group (3.7 kPa; mean = 4.1 ± 2.1 kPa) (p = 0.003). Significantly, lower median stiffness was seen in zero-to-moderate (F0-2, n = 22) vs. severe fibrosis stages (F3-4, n = 10) 2.80 vs. 5.9 kPa, respectively (p < 0.05). Using a 3.7-kPa cut-off value, the predicted sensitivity and specificity for detecting F0-2 from F3-4 were 91% and 80%, respectively. CONCLUSIONS: Our analysis supports previous findings that MRE is a non-invasive and effective method for detection and assessment of liver fibrosis, particularly for discrimination between F0-2 stages and F3-4 stages. MRE may represent a valuable tool to finely discern hepatic fibrosis non-invasively.

Evolution of microscopic colitis to giant cell colitis without significant intraepithelial lymphocytosis or thickened collagen plate.

Microscopic colitis (MC) is an umbrella term that encompasses lymphocytic colitis (LC) and collagenous colitis (CC). Several histological variants of these 2 entities exist; among them is the uncommon giant cell colitis (GCC), in which histiocytic giant cells (GCs) are present in background of CC or LC. We report the case of a 71-year-old woman complaining of watery diarrhea for several years that was diagnosed with CC. At follow-up, she developed giant cell colitis (GCC). Nine years later, a colectomy revealed a form of microscopic colitis in which significant intraepithelial lymphocytosis and collagen plate thickening have disappeared while GCs persisted with diffuse mononuclear cells inflammation of the lamina propria. Thinning of the collagen plate in association with GCs has been described previously. The case contributes the possibility of further evolution of MC into a pure giant cell colitis in which the prototypical manifestations of MC have all but disappeared.

Gastric adenocarcinoma in common variable immunodeficiency: features of cancer and associated gastritis may be characteristic of the condition.

Common variable immunodeficiency (CVID) is associated with an increased risk of gastric cancer. The aim of the study was to determine the morphological features of CVID-associated gastric adenocarcinoma (CAGA) and of the background gastritis. The population of gastric cancer patients with CVID of Mayo Clinic in the period 2000-2010 was studied; 6 cases of CVID (2 males, 4 females, average age 47 years, age range 26-71 years) were found in 5793 patients with gastric cancer in the study period. Each patient underwent gastric resection for which histology slides were reviewed. Chronic gastritis variables, CVID-related findings, and features of the adenocarcinoma were recorded. CAGA was of intestinal type, with high number of intratumoral lymphocytes (ITLs). Cancer was diagnosed in younger patients than in the overall population of gastric cancer. Severe atrophic metaplastic pangastritis with extensive dysplasia was present in the background in 4 cases, with features of lymphocytic gastritis in 2 cases. Features of CVID (plasma cells paucity in 4 of 6 cases, lymphoid nodules prominent in four cases) could be detected. In summary, gastric adenocarcinoma at young age with ITLs, accompanied by atrophic metaplastic pangastritis, should alert the pathologist of the possibility of CAGA. It follows that, in presence of those characteristics, the search of CVID-associated abnormalities should be undertaken in the nonneoplastic tissues.

Sertoli-Leydig cell tumor with heterologous element: a case report and a review of the literature.

The patient was a 19-year-old female who presented with a chief complaint of progressive pelvic pain. Preoperative ultrasound of the right ovary revealed an ovarian torsion as the cause of the patient's progressive pain. Laparoscopy confirmed the torsion and revealed a right ovary measuring 10 cm in greatest diameter. Intraoperative incision into the ovary revealed a simple ovarian cystic mass measuring 3.0 x 1.5 x 0.8 cm. A solid component within the cyst was identified. Histological sections of the cystic mass demonstrated mononuclear and hyperchromatic Sertoli cells with a trabecular growth pattern. Clusters of medium-sized epithelioid cells with abundant eosinophilic cytoplasm consistent with Leydig cells were also identified between the trabeculae of Sertoli cells. In addition, focal areas of intestinal type mucinous epithelium were identified embedded within the trabeculae of Sertoli cells. Immunohistochemical studies revealed that the Sertoli cells were positive for calretinin (bright) while the Leydig cells were positive for calretinin (dim), inhibin, CAM5.2 and AE1&3. CEA showed positivity mainly of the intraluminal contents of the mucinous type intestinal epithelium. The patient had an uneventful post-operative course and was disease-free for 3 years.

The histopathological approach to inflammatory bowel disease: a practice guide.

Inflammatory bowel diseases (IBDs) are lifelong disorders predominantly present in developed countries. In their pathogenesis, an interaction between genetic and environmental factors is involved. This practice guide, prepared on behalf of the European Society of Pathology and the European Crohn's and Colitis Organisation, intends to provide a thorough basis for the histological evaluation of resection specimens and biopsy samples from patients with ulcerative colitis or Crohn's disease. Histopathologically, these diseases are characterised by the extent and the distribution of mucosal architectural abnormality, the cellularity of the lamina propria and the cell types present, but these features frequently overlap. If a definitive diagnosis is not possible, the term indeterminate colitis is used for resection specimens and the term inflammatory bowel disease unclassified for biopsies. Activity of disease is reflected by neutrophil granulocyte infiltration and epithelial damage. The evolution of the histological features that are useful for diagnosis is time- and disease-activity dependent: early disease and long-standing disease show different microscopic aspects. Likewise, the histopathology of childhood-onset IBD is distinctly different from adult-onset IBD. In the differential diagnosis of severe colitis refractory to immunosuppressive therapy, reactivation of latent cytomegalovirus (CMV) infection should be considered and CMV should be tested for in all patients. Finally, patients with longstanding IBD have an increased risk for the development of adenocarcinoma. Dysplasia is the universally used marker of an increased cancer risk, but inter-observer agreement is poor for the categories low-grade dysplasia and indefinite for dysplasia. A diagnosis of dysplasia should not be made by a single pathologist but needs to be confirmed by a pathologist with expertise in gastrointestinal pathology.

Diaphragm disease of the small bowel: a retrospective review of CT findings.

OBJECTIVE: The purpose of this article is to report the CT findings of pathologically proven diaphragm disease in the small bowel. MATERIALS AND METHODS: A retrospective review identified 12 patients with pathologically proven small-bowel diaphragm disease who underwent CT within 6 months of surgical resection. Two radiologists, who were unblinded to pathologic and clinical findings, evaluated CT examinations for imaging findings of disease extent, appearance, and location. Clinical history and postoperative follow-up were also performed. RESULTS: The most common presenting symptoms were abdominal pain (7/12 [58%]) and anemia (5/12 [42%]). Long-term use of nonsteroidal antiinflammatory drugs was documented in 58% (7/12) of patients. The most common location of small-bowel diaphragms was the ileum (8/12 [67%]). The CT findings were abnormal in 92% (11/12) of patients. The most common CT findings were small-bowel strictures (11/12 [92%]) and focal (median length, 1 cm) bowel wall thickening (8/12 [67%]). Other less common CT findings included mucosal hyperenhancement (6/12 [50%]), small-bowel dilatation (5/12 [42%]), and video capsule retention (6/9 [67%]). Postoperative follow-up in 11 patients found recurrent symptoms in four patients. CONCLUSION: Small-bowel diaphragm disease should be considered in patients with a history of long-term use of nonsteroidal antiinflammatory drugs, chronic abdominal pain, and anemia who present with CT findings of short, symmetric ileal strictures and focal bowel wall thickening.

Small orangiophilic squamous-like cells: an underrecognized and useful morphological feature for the diagnosis of malignant mesothelioma in pleural effusion cytology.

BACKGROUND: The cytological diagnosis of malignant mesothelioma (MM) on serous effusion is challenging due to significant morphologic overlap with reactive mesothelial cells and adenocarcinoma. One of the morphologic features of MM in effusion cytology, small orangiophilic squamous-like cells (SOSLC), has received little attention. To the best of the authors' knowledge, the current study is the first to assess the sensitivity and specificity of SOSLC in serous effusion specimens from histology-proven MM cases along with those of reactive mesothelial and adenocarcinoma cases. METHODS: A total of 130 cases of pleural (86 cases) and peritoneal (44 cases) effusion cytology cases (30 with histology-proven MM, 41 with adenocarcinoma, and 59 with reactive mesothelial cells) were studied. The presence or absence of SOSLC was recorded in each case. RESULTS: The cytological diagnoses of the 30 histology-proven MM cases included 1) atypical mesothelial cells, favor reactive (4 cases); 2) atypical mesothelial cells, suspicious for or cannot exclude mesothelioma (18 cases); and 3) positive for MM (8 cases). SOSLC were found in 10 of the 30 MM effusion cases (33.3%), 1 of the 41 adenocarcinoma cases (2.4%), and 5 of the 59 reactive mesothelial cell cases (8.5%). SOSLC were more likely to be present in MM effusions compared with either adenocarcinoma (P<.0001) or reactive mesothelial cell (P<.02) effusions. All 10 cases of MM with SOSLC were from pleural fluids. One case of peritoneal serous adenocarcinoma had SOSLC and 5 cases of reactive mesothelial cells in peritoneal fluid were found to have SOSLC. CONCLUSIONS: Although not sensitive, the presence of SOSLC is quite specific for MM in pleural fluid cytology specimens. Finding this morphological feature in pleural fluid should alert the pathologist to a possible diagnosis of MM.

Histopathological changes in the gastrointestinal tract due to drugs: an update for the surgical pathologist (part I of II).

Abnormalities of the gastrointestinal (GI) tract due to drugs (AGIDs) are numerous and have significant impact. The aim of this narrative review is to help the practicing surgical pathologist recognize selected AGIDs. The adverse drug effects presented were chosen with an emphasis on recent and significant pathological and clinical contributions. The selection was based on a thorough review of the PUBMED-based literature and on the authors' opinions and experience. In the first part of the review, diagnostic abnormalities due to crystals (eg, iron, biphosphonates, nonsystemic drugs), mitosis arresting drugs (colchicine, taxanes), and biological agents, especially ipilimumab, are discussed. Some AGIDs' histopathologic features can be easily recognized. It is however the clinical correlation that in many cases of AGIDs will provide the necessary support for a drug effect diagnosis. The identification of AGIDs requires heightened awareness of the medical team in which close collaboration of pathologists and clinicians cannot be overemphasized.

Histopathological changes in the gastrointestinal tract due to medications: an update for the surgical pathologist (part II of II).

In keeping with the stated goal of providing the surgical pathologist with tools to recognize abnormalities of the gastrointestinal (GI) tract due to drugs (AGIDS), in part II of this review we embark in a more organ-based description of AGIDS. Adequate space is given to the numerous adverse gastrointestinal effects of nonsteroidal anti-inflammatory drugs. Pill esophagitis, esophagitis dissecans, proton pump inhibitors' effects, diaphragm disease, and the recently described effects of drugs such as olmesartan, mycophenolate, and of compounds such as yttrium-90 are highlighted among several others. The inclusion of drug effects in the differential diagnosis of "conventional" diseases (such as gastric antral vascular ectasia, graft-versus-host disease, ischemic colitis, acute colitis, collagenous enteritis, inflammatory bowel disease) is underscored to avoid sometimes significant diagnostic pitfalls. We reiterate the message of the necessary collaboration between pathologist and clinician in the recognition of these entities to provide the best patient care.