23 research outputs found
Congenital muscular dystrophy, cardiomyopathy, and peripheral neuropathy due to merosin deficiency: Peripheral nerve histology of cauda equina
AbstractPeripheral neuropathy, white matter abnormalities, and cardiomyopathy are associated findings with merosin-deficient congenital muscular dystrophy. Although characterization of the neuropathy with nerve conduction studies has been well documented, limited research has been able to correlate histopathology with nerve biopsy in humans. Our understanding of the mechanism, described as a demyelinating neuropathy, is mainly derived from mouse model studies. We report a 23-year-old male who succumbed to respiratory failure and ultimately cardiac arrhythmia in the setting of an uncharacterized end stage progressive muscular disease complicated by cardiomyopathy and severe scoliosis. Autopsy revealed extensive muscular atrophy and replacement by fibroadipose tissue throughout the skeletal muscle and myocardium. Immunohistochemical analysis of the muscle biopsy showed a complete loss of merosin. Thus, the cause for both his muscular disease and demyelinating neuropathy was established with the diagnosis of merosin-deficient muscular dystrophy. Nerve biopsy obtained from the cauda equina showed clear evidence of segmental demyelination and remyelination, providing a better understanding of the proximal peripheral nerve histopathological changes in this disease entity
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Epithelial-Stromal Polyps of the Colon Are Not Perineuriomas
Objectives: Some colorectal polyps contain serrated or tubular crypts surrounded by whorls of spindle cells that expand the mucosa. 'These epithelial-stromal polyps have been termed benign fibroblastic polyps or, more commonly, perineuriomas. We hypothesized that these lesions are pathogenetically heterogeneous polyps that share in common exuberant fibroblastic proliferations derived from the pericryptal sheath.
Methods: Forty-six epithelial-stromal polyps containing serrated crypts (n = 21) and nonserrated crypts (n = 25) were evaluated with epithelial membrane antigen and BRAF V600E immunohistochemical stains, and a subset was subjected to next-generation sequencing for BRAF mutations. Polyp morphology and immunohistochemical results were correlated with clinical information.
Results: Epithelial-stromal polyps containing serrated crypts were significantly associated with other sessile serrated polyps (43%, P = .01) and hyperplastic polyps (29%, P = .006). They also showed BRAF V600E abnormalities (95%) and strong, patchy epithelial membrane antigen staining of spindle cells (95%). In contrast, polyps with nonserrated crypts lacked BRAF alterations and infrequently showed robust EMA staining of stromal cells (16%, P < .01).
Conclusions: Benign epithelial-stromal polyps with serrated epithelium are biologically similar to sessile serrated polyps and should be classified as such to ensure appropriate clinical surveillance. The nature of polyps without serrated crypts is less clear, but evidence that they are perineuriomas is circumstantial at best
The Frontiers of Appendiceal Controversies
Appendiceal mucinous neoplasms show a range of morphologic features and biological risk. At one end of the spectrum, high-grade adenocarcinomas are cytologically malignant with infiltrative invasion, lymph node metastases, and behavior similar to that of extra-appendiceal mucinous adenocarcinomas. At the other end, mucinous neoplasms confined to the mucosa are uniformly benign. Some cases lying between these extremes have potential risk to metastasize within the abdomen despite a lack of malignant histologic features. They show "diverticulum-like," pushing invasion of mostly low-grade epithelium through the appendix with, or without, concomitant organizing intra-abdominal mucin. The latter condition, widely termed "pseudomyxoma peritonei," tends to pursue a relentless course punctuated by multiple recurrences despite cytoreductive therapy, culminating in death for many patients. The combination of bland histologic features and protracted behavior of peritoneal disease has led some authors to question whether these metastatic tumors even represent malignancies. The World Health Organization and its cadre of experts widely promote usage of "low-grade appendiceal mucinous neoplasm" as an umbrella term to encompass benign and malignant conditions, as well as those that have uncertain biological potential. Although this practice greatly simplifies tumor classification, it causes confusion and consternation among pathologists, clinical colleagues, and patients. It also increases the likelihood that at least some patients will undergo unnecessary surveillance for, and treatment of, benign neoplasms and non-neoplastic conditions. The purpose of this review is to critically evaluate the relevant literature and discuss a practical approach to classifying appendiceal mucinous neoplasms that more closely approximates their biological risk
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Desmoplastic Small Round Cell Tumor Is an Important Mimic of High-Grade Carcinoma in Colonic Biopsy Samples
Desmoplastic small round cell tumor (DSRCT) is a rare but aggressive malignancy that usually occurs within the intra-abdominal cavities of young adult males. Most DSRCTs can be reliably diagnosed based on the presence of characteristic morphology; coexpression of epithelial, myogenic, and neuralmarkers; and detection of the reciprocal translocation t(11;22)(p13:21) associated with the EWS::WT1 fusion. However, occasional tumors lack classic features, affect older adults, or are located outside the abdominal cavity. Mucosal biopsy samples can pose challenges when both the stromal and epithelial components are not represented. Herein, we present a case of DSRCT that simulated clinical and histologic features of a colonic adenocarcinoma. Biopsy sampling revealed nests of cytokeratin-positive epithelioid cells that simulated a high-grade carcinoma with neuroendocrine features. This case report emphasizes the importance of considering this rare entity when presented with high-grade epithelioid tumors that occur in young patients
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Intraoperative Evaluation of the Gastrointestinal Tract
Intraoperative consultation for diseases of the luminal gut can facilitate the immediate management of surgical patients in several situations. Most of the tubular gut is easily accessible to endoscopic evaluation, and, thus, many patients have an established diagnosis prior to surgery. The most common indication for intraoperative consultation of the tubular gut is evaluation of resection margins in the setting of neoplasia. Frozen sections may also be used to establish a primary diagnosis when lesions are not amenable to endoscopic evaluation, intraoperative findings raise the possibility of malignancy, or incidental peritoneal nodules are detected during cancer operations. Frozen sections are performed in the latter situation to exclude the possibility of metastatic disease; many patients with stage IV disease do not benefit from resection of the primary tumor. Lastly, the intraoperative evaluation of patients with possible Hirschsprung disease relies heavily on pathologists to identify the extent of aganglionosis in order to optimize extent of resection. It is important that pathologists offer timely, accurate diagnoses with full understanding of the specific concerns to be addressed in all of these scenarios. The purpose of this chapter is to discuss the situations in which pathologists may be asked to perform intraoperative consultations for surgeons treating patients with diseases of the tubular gut
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Cytomegalovirus reactivation in inflammatory bowel disease: an uncommon occurrence related to corticosteroid dependence
Cytomegalovirus promotes mucosal injury in patients with inflammatory bowel disease, historically affecting 10-25% of ulcerative colitis patients with refractory disease. Viral reactivation is likely related to long-term corticosteroid therapy, which is no longer central to maintenance of patients with inflammatory bowel disease. We hypothesize that viral detection rates have decreased in the modern era, reflecting widespread use of immunomodulatory agents to control inflammation. We performed this study to evaluate the relationships between medical regimens and cytomegalovirus detection rates among patients with inflammatory bowel disease. We searched our database for all patients with established inflammatory bowel disease and severe flares diagnosed from 2002 to 2017. Patients maintained with corticosteroid therapy were considered to be corticosteroid-dependent and those treated with other agents were classified as corticosteroid-independent, provided they had not received corticosteroids within 6 months of colonoscopy. Biopsy samples were reviewed for viral inclusions and subjected to cytomegalovirus immunohistochemistry, and rates of viral detection were compared between groups. There were 135 corticosteroid-dependent patients; most had ulcerative colitis flares occurring during the 2002-2009 period. Patients with ulcerative colitis and Crohn disease were equally represented in the corticosteroid-independent group (n = 133) and most were evaluated for disease flares during the 2010-2017 interval. Cytomegalovirus was detected in 13 (8%) cases; 9 (69%) were diagnosed from 2002 to 2009 and all were obtained from corticosteroid-dependent patients (p = < 0.001). We conclude that rates of cytomegalovirus-related enterocolitis are declining among inflammatory bowel disease patients, reflecting a shift away from corticosteroid-based maintenance therapy in favor of more effective agents that do not promote viral reactivation
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Histologic Features of Tacrolimus-induced Colonic Injury
Tacrolimus is a common immunosuppressant used in solid organ transplant recipients. Although most patients develop diarrheal symptoms, data regarding patterns of injury in patients taking tacrolimus are limited. We performed this study to characterize tacrolimus-related features of colonic injury. We retrospectively identified colonic samples from 20 patients receiving tacrolimus monotherapy. Records were reviewed for symptoms, endoscopic findings, other medications, and infections. None of the patients had gastrointestinal infections or used other drugs known to cause colonic injury; none had received mycophenolate within 6 months of presentation. Cases were evaluated for the nature and distribution of inflammation and crypt abnormalities, including distortion, destruction, and apoptosis. Eighteen (90%) patients were solid organ transplant recipients. Seventeen (85%) had gastrointestinal symptoms, particularly diarrhea (75%). More than 50% had endoscopic colitis and 15% had ulcers and/or erosions. Most (90%) cases showed regenerative epithelial changes; apoptotic crypt cells were present in 55% and numerous in 10% of cases. Neutrophilic cryptitis was present in 60% of cases; 35% showed crypt destruction. Plasma cell-rich lamina propria inflammation and crypt distortion were observed in 40% and 25% of cases, respectively. There was no correlation between therapy duration and features of chronic injury. We conclude that tacrolimus can cause symptomatic colitis. Histologic abnormalities are often mild, featuring regenerative crypts and scattered apoptotic debris. However, 40% of symptomatic patients have chronic colitis, most likely reflecting drug-induced immune dysregulation. Pathologists should be aware of these associations because colitis often resolves with decreasing drug dosage rather than treatment directed toward inflammatory bowel disease
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Post-inflammatory mucosal hyperplasia and appendiceal diverticula simulate features of low-grade appendiceal mucinous neoplasms
Post-inflammatory mucosal hyperplasia and appendiceal diverticulosis simulate mucinous neoplasms, causing diagnostic confusion. Distinction between neoplasia and its mimics is particularly important since many authorities now consider all appendiceal mucinous neoplasms to be potentially malignant. The purpose of this study was to identify clinicopathologic and molecular features that may distinguish appendiceal mucinous neoplasms from non-neoplastic mimics. We retrospectively identified 92 mucinous lesions confined to the right lower quadrant, including 55 non-neoplastic examples of mucosal hyperplasia and/or diverticulosis and 37 low-grade neoplasms. Presenting symptoms, radiographic findings, appendiceal diameter, appearances of the lamina propria, non-neoplastic crypts, and epithelium, as well as mural changes were recorded. Twenty non-neoplastic lesions were subjected to KRAS mutational testing. Non-neoplastic appendices were smaller (p < 0.05) and more likely to present with symptoms of appendicitis (p < 0.05) than neoplasms. While post-inflammatory mucosal hyperplasia and diverticula often showed goblet cell-rich epithelium, extruded mucin pools, and patchy mural alterations with fibrosis, they always contained non-neoplastic crypts lined by mixed epithelial cell types and separated by lamina propria with predominantly preserved wall architecture. On the other hand, mucinous neoplasms lacked normal crypts (p < 0.05) and showed decreased lamina propria (p < 0.05) with diffusely thickened muscularis mucosae and lymphoid atrophy. Six (30%) non-neoplastic lesions contained KRAS mutations, particularly those containing goblet cell-rich hyperplastic epithelium. We conclude that distinction between neoplastic and non-neoplastic mucinous appendiceal lesions requires recognition of key morphologic features; KRAS mutational testing is an unreliable biomarker that cannot be used to assess biologic risk or confirm a diagnosis of neoplasia
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Lymphocyte-predominant Esophagitis: A Distinct and Likely Immune-mediated Disorder Encompassing Lymphocytic and Lichenoid Esophagitis
Lymphocytic esophagitis is a well-known manifestation of Crohn disease among children but is not considered to be an immune-mediated mucositis in adults. We hypothesize that adult-onset lymphocyte-predominant esophagitis is also an immune-mediated inflammatory pattern, the nature of which has been masked by other conditions that feature esophageal lymphocytosis and occur in older patients. We performed this study to consolidate diagnostic criteria for lymphocyte-predominant esophagitis and determine its clinical significance. We identified 61 patients with lymphocyte-rich inflammation in the mid or proximal esophagus, none of whom had another explanation for esophageal lymphocytosis. Affected patients were usually older adults and 72% were women. Most (56%) presented with dysphagia and 34% had eosinophilic esophagitis-like changes with rings, exudates, and/or edematous mucosa and linear furrows. Intraepithelial lymphocytosis was accompanied by mucosal injury featuring edema, basal zone hyperplasia, and scattered dyskeratotic cells. Some cases displayed occasional neutrophils or even superficial microabscesses; eosinophils were consistently infrequent. Most (67%) patients had at least 1 systemic immune-mediated disorder, particularly Crohn disease (30%) and connective tissue diseases (23%); only 1 had mucocutaneous lichen planus. We conclude that mild mucosal lymphocytosis (ie, ≥20 lymphocytes/HPF) alone is a frequent and nonspecific finding; criteria for lymphocyte-predominant esophagitis should include evidence of mucosal injury and allow for more than the occasional neutrophil. When this diagnosis is limited to cases that feature lymphocytosis unattributed to acid reflux, motility disorders, or infection, lymphocyte-predominant esophagitis may represent an immune-mediated disorder with characteristic clinical manifestations and a predilection for middle-aged women