Close margin of adverse histologic factors with a negative primary tumor margin is not associated with increased locoregional recurrence in colon cancer.

PURPOSE: Locoregional recurrence after resection of colon cancer is increased when primary tumor margin is positive (<1 â€‹mm). Data is limited regarding the risk of locoregional recurrence with close margin (<1 â€‹mm) of histologic factors, such as intravascular tumor, intranodal tumor, tumor deposits, or extranodal extension. We hypothesized that close margin of these factors doesn't affect locoregional recurrence. METHODS: A retrospective review of all colon cancer surgical resections for adenocarcinoma from 2007 to 2020 was performed. Inclusion criteria were specimens with a negative primary tumor margin but a close margin of adverse histologic factors, defined as intravascular tumor, intranodal tumor, tumor deposits, or extranodal extension within 1 â€‹mm of a mesenteric or circumferential margin. RESULTS: Among 4435 pathology reports reviewed, 45 (1 â€‹%) of cases met inclusion criteria. Average follow-up was 38 months. The adverse histologic factor was identified as intranodal tumor in 24 (53 â€‹%) cases, intravascular tumor in 8 (17.8 â€‹%), tumor deposits in 5 (11.1 â€‹%), and more than one pathologic feature in 6 (13.3 â€‹%). There were 9 (20 â€‹%) recurrences; 6 (13 â€‹%) had distant recurrences only, 2 (4 â€‹%) patients had locoregional recurrences only, and 1 (2 â€‹%) patient had both locoregional and distant recurrence. The adverse histologic factor in these three patients was intravascular in two and both intravascular and intranodal in one. CONCLUSION: Based on our results, we do not have evidence that the presence of intravascular tumor, intranodal tumor, tumor deposits, or extranodal extension within 1 â€‹mm of a mesenteric or circumferential margin is associated with increased risk of locoregional recurrence.

Overview of histologic variants of urothelial carcinoma: current trends and narrative review on treatment outcomes.

Background and Objective: The histologic variants of urothelial carcinoma (UC) are tumors arising from within the urothelium in which some component of the tumor morphology is other than urothelial. They are underdiagnosed, aggressive and have varying pathologic response rates to systemic chemotherapy. There are no consensus guidelines on the use of systemic chemotherapy in variant histology (VH) of UC. We performed a contemporary review on pathologic response rates to neoadjuvant systemic therapy and survival outcomes following radical cystectomy in order to provide a rationale for clinical practice recommendations on the management of UC with VH. Methods: A PubMed literature search was conducted for all English articles from inception reporting either pathological response rates to neoadjuvant treatment or survival outcomes after radical cystectomy in non-metastatic VH of UC. Key Content and Findings: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy was shown to be a beneficial treatment strategy in UC with VH. The micropapillary, plasmacytoid, nested and sarcomatoid histologic variants were associated with worse survival outcomes compared to conventional UC and UC with squamous or glandular differentiation despite initial downstaging with chemotherapy. There is evidence of improved survival in patients with sarcomatoid differentiation receiving NAC compared to RC alone. The major prognostic factors that affect survival outcomes in VH of UC include histologic variant subtype, patient age, presence of lymphovascular invasion, hydronephrosis, nodal metastasis and advanced T stage at diagnosis. Recent studies demonstrate that VH of UC are heterogenous tumors and responsiveness to NAC may be a function of the molecular subtypes present. Conclusions: Based on these findings, NAC to achieve pathologic downstaging prior to radical cystectomy is recommended for MIBC with VH. Biomarkers identified by molecular profiling with immunohistochemistry will need to be validated as predictors of response to NAC in future trials.

Acellular mucin in lymph nodes isolated from treatment-naïve colorectal cancer resections: a clinicopathologic analysis of 16 cases.

Lymph nodes with acellular mucin harvested from treated colorectal cancers (CRC) are staged as pN0. However, there is variability among pathologists while reporting the pN stage when acellular mucin is found within nodes of untreated CRCs. While the UICC guidelines suggest staging them as pN1, the AJCC and CAP do not offer any recommendations. In order to characterize their clinicopathologic features and outcome, we compared 16 untreated CRCs (study group; mean age: 68 years) harboring nodes with acellular mucin with 34 pN0 and 25 pN1 untreated CRC controls. All tumors were unifocal; 12 (75%) were right-sided lesions. Most cases (75%) showed one node with acellular mucin (range: 1-3). MMR-deficient tumors were significantly more common in the study group (83%) compared to pN0 (33%; p = 0.006) and pN1 controls (8%; p < 0.001). The overall survival of study group patients was closer to pN0 compared to pN1 controls; however, this difference was not statistically significant. In conclusion, untreated CRC that harbor acellular mucin within lymph nodes commonly present as right-sided, MMR-deficient tumors in older women that show a non-mucinous phenotype. While the limited number of cases precludes us from making any formal recommendations about staging, we suggest that the finding of acellular mucin in a node should prompt evaluation of deeper levels (with or without cytokeratin immunohistochemistry) and submission of all pericolonic fat for additional lymph node harvest. Whether acellular mucin in nodes of untreated CRCs is related to the indolent biology of the disease, a robust local immune response or MMR deficiency requires further investigation.

Allaying uncertainty in diagnosing buried Barrett's esophagus.

Subsquamous intestinal metaplasia (SSIM) in the setting of Barrett's esophagus (BE) is a technically challenging diagnosis. While the risk for progression of BE involving the surface mucosa is well documented, the potential risk for development of advanced neoplasia associated with SSIM has been controversial. This study aimed to determine the effects of specimen adequacy, presence of dysplasia, and interobserver agreement for SSIM interpretation. Adult patients (n = 28) who underwent endoscopic therapy for BE with high-grade dysplasia or intramucosal carcinoma (HGD/IMC) between October 2005 and June 2013 were included. Initial evaluation (n = 140 slides) by an experienced gastrointestinal pathologist was followed by an interobserver study by 8 pathologists. Forty-seven (34%) slides had insufficient subsquamous tissue to assess for SSIM. SSIM was found in 19% of all slides and 29% of slides with sufficient subsquamous tissue. At least one slide had SSIM in 54% to 64% of patients. Subsquamous low grade dysplasia (LGD) was found in 4 (15%) slides with SSIM and subsquamous HGD/IMC was found in 5 (19%) slides with SSIM. At the patient level, 8 (53%) had no dysplasia, 4 (27%) had LGD and 3 (20%) had HGD/IMC. Overall agreement for SSIM by slide was 92% to 94% (κ = 0.73 to κ = 0.82, moderate to strong agreement), and by patient was 82% to 94% (κ = 0.65 to κ = 0.87, moderate to strong agreement). This study confirms the need for assessing specimen adequacy and assessing the prevalence of SSIM and is the first to assess interobserver agreement for SSIM and dysplasia within SSIM.

BEARING DOWN ON TREPONEMES: AN ATYPICAL PRESENTATION OF SYPHILITIC UVEITIS.

PURPOSE: To present an atypical case of syphilis that presented with findings concerning for endocarditis and valsalva retinopathy. METHODS: History and clinical examination of 42-year-old white man who presented to the emergency department with acute onset vision changes associated with gastrointestinal symptoms, otalgia, and constitutional symptoms. RESULTS: The review of this case highlights the atypical nature in which syphilis can present and can remain undiagnosed even in the face of extensive workups for other systemic conditions. CONCLUSION: We present a case of syphilis in a patient with multiorgan involvement in whom the diagnosis was made based on atypical ocular examination findings.

Severe Small Bowel Bleeding Associated With Metastatic Clear Cell Renal Cell Carcinoma to the Jejunum.

Clear cell renal cell carcinoma is a malignancy of the kidneys that most commonly metastasizes to lung, bone, lymph nodes, liver, adrenal glands, and brain. We present a 75-year-old man with severe and chronic gastrointestinal bleeding who was eventually discovered to have clear cell renal cell carcinoma metastatic to his jejunum as the source of his bleed. This is a rare phenomenon and an unusual cause of gastrointestinal bleeding.

Case report: multiple gastrointestinal stroma tumors in the background of neurofibromatosis type 1.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies of the gastrointestinal tract. GISTs can occur in the background of neurofibromatosis 1 (NF-1), where chemotherapeutic treatment is not optimal and surgical intervention is the only management option. In this case report, we present a case involving a 61-year-old gentleman with NF-1. The patient presented with acute blood loss anemia that was initially controlled with embolization of a hyper-vascular mass abutting the distal jejunum. The patient was taken to the operating room for excision of the mass. All macroscopic disease was excised and the pathology noted GISTs. Surgical decision making is not clearly delineated in the literature for GISTs in patients with NF-1, where targeted therapy is not a treatment option. Resection of all disease should be considered, since NF-1 associated GISTs generally do not have harbor mutations that can be targeted.

Extraosseous Calcification of the Esophagus: Clinicopathologic Correlates of Esophageal Mucosal Calcinosis.

Esophageal mucosal calcinosis (EMC) is a rare cause of dysphagia with high morbidity. We present a patient who experienced melena and 3 months of solid and liquid dysphagia along with bilateral lower extremity pain, erythema, and edema later determined to be calcific uremic arteriolopathy (CUA), or calciphylaxis. An esophagogastroduodenoscopy revealed nodularity and linear ulcerations in the upper third of the esophagus. Histology showed active inflammation and ulceration with small foci of subepithelial and intraepithelial calcification consistent with EMC. There is no known treatment for this disorder. Sodium thiosulfate, typically used to treat CUA, did not improve her dysphagia.

Interobserver Variability in Scoring Liver Biopsies with a Diagnosis of Alcoholic Hepatitis.

BACKGROUND: Alcoholic hepatitis (AH) is one of the most severe forms of alcoholic liver disease. Recently, a histologic scoring system for predicting prognosis in this patient cohort was proposed as Alcoholic Hepatitis Histologic Score (AHHS). We aimed to assess interobserver variability in recognizing histologic features of AH and the effect of this variability on the proposed AHHS categories. METHODS: Hematoxylin-eosin- and trichrome-stained slides from 32 patients diagnosed with AH with liver biopsies within 1 month of presentation (2000 to 2015) were reviewed by 5 pathologists including 3 liver pathologists and 2 gastrointestinal (GI) pathologists masked to the clinical findings or outcome. Histologic features of AH were assessed, the AHHS was calculated, and an AHHS category (mild, moderate, severe) was assigned. The Fleiss' kappa coefficient (κ) analysis was performed to determine the interobserver agreement. RESULTS: A slight-to-moderate level of interobserver agreement existed among 5 reviewers on histopathologic features of AH with κ value ranging from 0.20 (95% confidence interval (CI): 0.03 to 0.46, megamitochondria) to 0.52 [95% CI: 0.40 to 0.68, polymorphonuclear leukocyte (PMN) infiltration]. There was only a fair level of agreement in assigning AHHS category (κ = 0.33, 95% CI: 0.20 to 0.51). While overall fibrosis and neutrophilic inflammation were comparably evaluated by 3 liver pathologists and 2 GI pathologists, bilirubinostasis and megamitochondria were more consistently diagnosed by liver pathologists. Overall, 18 of 32 (56%) were uniformly assigned to an AHHS category by all liver pathologists with a κ value of 0.40 (95% CI: 0.22 to 0.60). CONCLUSIONS: In general, features of AH can be recognized with a slight-to-moderate level of interobserver agreement and there was fair interobserver agreement on assigning an AHHS category. Significant interobserver variability among pathologists revealed by the current study can limit its usefulness in everyday clinical practice.

T-helper 2 cytokines, transforming growth factor ß1, and eosinophil products induce fibrogenesis and alter muscle motility in patients with eosinophilic esophagitis.

BACKGROUND & AIMS: Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEFs), human esophageal muscle cells (HEMCs), and esophageal muscle strips to eosinophil-derived products. METHODS: Biopsy specimens were collected via endoscopy from the upper, middle, and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls). Primary cultures of esophageal fibroblasts and muscle cells were derived from 12 freshly resected human esophagectomy specimens. Eosinophil distribution was investigated by histologic analyses of full-thickness esophageal tissue. Active secretion of EoE-related mediators was assessed from medium underlying mucosal biopsy cultures. We quantified production of fibronectin and collagen I by HEF and HEMC in response to eosinophil products. We also measured the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by, and adhesion of human eosinophils to, HEFs and HEMCs. Eosinophil products were tested in an esophageal muscle contraction assay. RESULTS: Activated eosinophils were present in all esophageal layers. Significantly higher concentrations of eosinophil-related mediators were secreted spontaneously in mucosal biopsy specimens from patients with EoE than controls. Exposure of HEFs and HEMCs to increasing concentrations of eosinophil products or co-culture with eosinophils caused HEFs and HEMCs to increase secretion of fibronectin and collagen I; this was inhibited by blocking transforming growth factor ß1 and p38 mitogen-activated protein kinase signaling. Eosinophil binding to HEFs and HEMCs increased after incubation of mesenchymal cells with eosinophil-derived products, and decreased after blockade of transforming growth factor ß1 and p38 mitogen-activated protein kinase blockade. Eosinophil products reduced electrical field-induced contraction of esophageal muscle strips, but not acetylcholine-induced contraction. CONCLUSIONS: In an analysis of tissues samples from patients with EoE, we linked the presence and activation state of eosinophils in EoE with altered fibrogenesis and motility of esophageal fibroblasts and muscle cells. This process might contribute to the development of dysphagia.

Distinguishing clear cell renal cell carcinoma, retroperitoneal paraganglioma, and adrenal cortical lesions on limited biopsy material: utility of immunohistochemical markers.

Retroperitoneal recurrence of clear cell renal cell carcinoma (CCRCC) after surgical resection is often investigated by needle biopsy and frequently requires immunohistochemistry to distinguish from other lesions with similar histology. This study explores the diagnostic utility of a panel of immunohistochemical markers and emphasizes potential pitfalls in dealing with this differential diagnosis. A tissue microarray with 1 mm tissue cores was constructed to include 21 CCRCC, 19 adrenocortical lesions, and 15 retroperitoneal or mediastinal paragangliomas. Triplicate cores were used for each case. The tissue microarray was then immunostained with epithelial, RCC, adrenocortical, and neuroendocrine markers. Pancytokeratins AE1/3, CAM5.2, and epithelial membrane antigen were positive in 52.4%, 66.7%, and 61.9% of CCRCC cases. Three (14.2%) CCRCC cases were negative for all 3 epithelial markers. AE1/3 and epithelial membrane antigen were negative in all adrenocortical lesions and paraganglioma cases, whereas CAM5.2 was positive in 78.9% of adrenocortical lesions and 6.7% of paragangliomas. RCC markers, including RCC Ag, CA9, and CD10, were positive in 76.2%, 85.7%, and 100% of CCRCC cases and were negative in all adrenocortical lesions and paragangliomas. Calretinin and Melan-A were positive in 100% and 94.7% of adrenal, 0% and 14.3% of CCRCC, and 26.7% and 26.7% of paragangliomas. Epithelial markers may be entirely negative in CCRCC, whereas pancytokeratin CAM5.2 is often positive in adrenocortical lesions. Furthermore, neuroendocrine markers are frequently positive in adrenocortical lesions. Therefore, a panel of, rather than single, epithelial, "CCRCC-specific," adrenocortical and neuroendocrine markers should be applied in the differential diagnosis of CCRCC, adrenocortical lesions, and paragangliomas.