Mikhail Lisovsky

Congenital Extrahepatic Portosystemic Shunts (abernethy Malformation): A Histopathologic Evaluation

Congenital extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare malformation in which intestinal and splenic venous blood bypasses the liver and drains into systemic veins. Aside from the complete or near-complete absence of portal veins, other histologic features of Abernethy malformation have not been evaluated in the literature. The goal of this study was to detail the hepatic histopathology in 5 patients with Abernethy malformation diagnosed at our institution. Paraffin-embedded tissue sections from 1 explant, 2 liver tumor resections, and 2 liver biopsies were evaluated using hematoxylin and eosin stains, reticulin, elastic, and trichrome stains, and immunohistochemistry for D2-40. Histologic findings included absence of portal veins in small portal tracts, absent or hypoplastic portal veins in medium-sized and large-sized portal tracts, isolated capillaries and arterioles in the lobules, hypertrophy of hepatic artery branches, remodeling of the liver architecture, and nodular regenerative hyperplasia in 1 case. Two patients had hepatocellular carcinoma without cirrhosis, and 2 had focal nodular hyperplasia. In addition to loss of portal veins, Abernethy malformation is characterized by multiple abnormalities due to remodeling of the hepatic vasculature. Abernethy malformation may also be associated with hepatocellular carcinoma and focal nodular hyperplasia in some patients.

Effect of initiating a multidisciplinary care clinic on access and time to treatment in patients with pancreatic adenocarcinoma.

PURPOSE Neoadjuvant therapy for pancreatic adenocarcinoma requires referral to multiple specialists before initiating therapy. We evaluated the effect of establishing a multidisciplinary clinic (MDC) for patients with newly diagnosed pancreatic adenocarcinoma on treatment access and time to therapy. METHODS Patients with newly diagnosed pancreatic adenocarcinoma diagnosed and treated at our center were included. Two patient groups were defined: preclinic represented those patients diagnosed before 2008 and MDC represented those patients diagnosed since 2009 who were treated in the newly created MDC and were initially candidates for neoadjuvant therapy. The primary outcomes were days from diagnosis to first treatment (initiation of chemotherapy or external beam radiation), days to completion of all required consultations, and number of visits needed before initiation of therapy. RESULTS Ninety-seven patients were diagnosed and treated at our medical center from 2003 to 2008; 22 were treated in 2009 after the implementation of the MDC. Compared with the preclinic group, patients treated in the MDC had shorter times from biopsy to treatment (7.7 days v 29.5 days, P < .001), shorter time to completion of all required pretreatment consultations (7.1 days v 13.9 days, P < .001), and fewer visits to complete all consultations (1.1 v 4.3, P < .001). Thirty-three percent of patients seen in the MDC enrolled onto clinical research trials. CONCLUSION In patients with pancreatic adenocarcinoma undergoing neoadjuvant therapy, the establishment of a multidisciplinary pancreas tumor clinic led to improved patient access to consultations and shorter time to initial treatment.

Lymphocytic Esophagitis With CD4 T-cell-predominant Intraepithelial Lymphocytes and Primary Esophageal Motility Abnormalities: A Potential Novel Clinicopathologic Entity.

Lymphocytic esophagitis (LE) is an uncommon poorly defined histologic pattern. Its significance is largely unknown. The goal of our study was to characterize LE clinically, histologically, and immunophenotypically. Biopsies of 45 patients with LE and no intraepithelial granulocytes were selected throughout a 36-month period during routine diagnostic work. After reevaluation, complete absence of intraepithelial granulocytes was confirmed in 21 patients (LE-NG group), and few granulocytes were found in 24 patients (LE-FG). The control group consisted of 28 patients with active esophagitis consistent with reflux and overtly increased intraepithelial lymphocytes (REIL). The ratio of CD4:CD8 intraepithelial lymphocytes (IEL)>1 indicated predominance of CD4 IEL; the ratio ⩽1 indicated predominance of CD8 IEL. Dysphagia was the primary complaint in 71%, 54%, and 39% of the patients with LE-NG, LE-FG, and REIL, respectively (P=0.04, LE-NG vs. REIL). Importantly, primary esophageal motility abnormalities were found in 10/11 (91%) tested LE-NG patients, 6/10 (60%) LE-FG patients, and 6/11 (54%) REIL patients. CD4 IELs were predominant in 81%, 50%, and 39% of LE-NG, LE-FG, and REIL cases, respectively (P=0.004, LE-NG vs. REIL), and in 90%, 83%, and 88% of the cases with primary motility abnormalities from the same groups. The prevalence of primary motility abnormalities was significantly higher in patients with CD4-predominant esophagitis than in patients with CD8-predominant esophagitis from all groups (21/24 [83%] vs. 2/8 [25%], P=0.005). A distinctive type of LE with predominance of CD4 IEL is associated with primary motility abnormalities suggesting a diagnostic utility of evaluating CD4 and CD8 subpopulations of T cells in LE.

Gastric hyperplastic polyps: a heterogeneous clinicopathologic group including a distinct subset best categorized as mucosal prolapse polyp.

BackgroundGastric hyperplastic polyps are the second most common subtype of gastric polyps. There has been an ongoing debate about their precise diagnostic criteria and etiological associations. Materials and MethodsA total of 208 gastric polyps that were originally diagnosed as hyperplastic polyps in our department during an 8-year period were reviewed using recently emphasized diagnostic criteria, and their clinicopathologic associations were explored. ResultsOnly 41 cases were confirmed as hyperplastic polyps, whereas 103 cases (49%) were reclassified as polypoid foveolar hyperplasia, and 64 cases (31%) were diagnosed as gastric mucosal prolapse polyps. Gastric mucosal prolapse polyps were distinguished by basal glandular elements, hypertrophic muscle fibers ascending perpendicularly from the muscularis mucosae, and by thick-walled blood vessels. This hitherto undescribed polyp is more commonly sessile than hyperplastic polyps (P=0.0452) and is found more often in the antropyloric region (P: 0.0053). Only 20.6% of hyperplastic polyps were associated with Helicobacter pylori infection. ConclusionsOur findings highlight that gastric polypoid lesions that have morphologic similarities may be related to various mechanisms, including inflammatory and prolapse processes. The predominantly antral location of gastric mucosal prolapse polyps, a zone of pronounced peristalsis, suggests that mucosal prolapse plays a role in the development of these common polyps. Evaluation of the prevalence and clinical associations of these distinctive polyps awaits further studies.

Barrett's esophagus: endoscopic diagnosis.

This collection of summaries on endoscopic diagnosis of Barretts esophagus (BE) includes the best endoscopic markers of the extent of BE; the interpretation of the diagnosis of ultra‐short BE; the criteria for endoscopic grading; the sensitivity and specificity of endoscopic diagnosis; capsule and magnifying endoscopy; narrow band imaging; balloon cytology; the distinction between focal and diffuse dysplasia; the techniques for endoscopic detection of dysplasia and the grading systems; and the difficulty of interpretation of inflammatory or regenerative changes.

Lymphocytic Esophagitis in Nonachalasia Primary Esophageal Motility Disorders: Improved Criteria, Prevalence, Strength of Association, and Natural History.

Lymphocytic esophagitis (LE) is a histologic pattern with no established clinical correlates in the majority of patients. The goal of this study was to evaluate the association between nonachalasia primary esophageal motility disorders (PEMD) and LE. Sixty-nine patients with PEMD and esophageal biopsies, including 22 with nutcracker esophagus, 33 with ineffective motility, and 14 with diffuse spasm, constituted the study group. The control group consisted of 70 patients with severe dysmotility-negative gastroesophageal reflux disease requiring referral for Nissen fundoplication. To improve the criteria for LE, a lymphocyte reference range at different esophageal levels was first established in 17 healthy volunteers. The cutoffs for normal intraepithelial lymphocytes, defined as lymphocyte levels not exceeding mean level±2 SDs, were set at 62, 46, and 41 lymphocytes per high-power field at 0 to 2, 5, and 10 cm above the gastroesophageal junction, respectively. Predominantly focal peripapillary LE was observed in approximately 40% of patients with nutcracker esophagus or diffuse spasm and in 20% of patients with ineffective motility, in comparison with 4% of patients with dysmotility-negative gastroesophageal reflux disease (P<0.035 vs. any subtype of PEMD). Overall, LE was strongly associated with PEMD in multivariate analysis (adjusted odds ratio, 7.93; 95% confidence interval, 2.26-27.9; P=0.001). LE had a chronic course in 56% of the patients with follow-up biopsies. In conclusion, LE has a strong association with PEMD, suggesting the utility of LE in raising the possibility of PEMD.

TRIMODALITY THERAPY FOR STAGE II-III CARCINOMA OF THE ESOPHAGUS: A DOSE-RANGING STUDY OF CONCURRENT CAPECITABINE, DOCETAXEL, AND THORACIC RADIOTHERAPY

Purpose: This dose-escalation study was performed to determine the recommended phase II dose of oral capecitabine to be delivered concurrently with thoracic radiation therapy and weekly docetaxel in patients with locally advanced esophageal carcinoma. Methods: Patients with operable stage II or III esophageal carcinoma were staged by endoscopic ultrasonography and computed tomography. Two cycles of docetaxel (80 mg/m2) and carboplatin (target area under the concentration-time curve: 6 mg/ml × min) were delivered over 6 weeks. This was followed by concurrent weekly docetaxel (15 mg/m2), thoracic radiotherapy (50.4 Gy in 28 fractions), and increasing doses of capecitabine (500–3500 mg) given before each fraction of radiotherapy. After restaging, responding patients continued to esophagectomy within 4 to 8 weeks of completing chemoradiotherapy. Results: Forty-four patients were enrolled, and 40 were assessable for the dose-ranging component of concurrent chemoradiotherapy. Endoscopic ultrasonography stages at enrollment were T3N1 (29 patients), T3N0 (4 patients), T2N1 (6 patients), and T4N0 (one patient). The maximum tolerated dose of capecitabine was 3500 mg. Thirty-six patients had surgery; 83% had R0 resection, and 17% had pathological complete response. Median overall survival was 23.5 months, with 34 and 27% alive at 3 and 5 years. Conclusion: The recommended phase II dose of capecitabine is 3500 mg when given concurrently with 50.4 Gy of thoracic radiotherapy in 28 fractions and weekly docetaxel. This trimodality therapy for operable locally advanced esophageal carcinoma was very well tolerated and remarkably active. This regimen holds promise for the treatment of esophageal carcinoma and warrants further investigation.

Atypical lipomatous tumor mimicking giant fibrovascular polyp of the esophagus: report of a case and a critical review of literature

An 81-year-old man presented to the emergency department with a mass protruding from his mouth after an episode of emesis. A computed tomography scan showed a hypodense, polypoid structure with a fatty component. The long polyp was attached by a narrow stalk to the cervical esophagus. A 14.0-cm slender mass resembling a giant fibrovascular polyp (GFP) of the esophagus was resected. The microscopic, immunohistochemical, and molecular findings were, however, those of an atypical lipomatous tumor (ALT). Atypical lipomatous tumor of the esophagus is a rare, low-grade malignant neoplasm, with a potential for local recurrence and, in most instances, presents as a large intraluminal polyp mimicking a GFP. Cases reported in the literature as primary myxoid liposarcomas of the esophagus are in all likelihood examples of ALT with myxoid change. A recent case reported as a GFP with karyotypic abnormalities on comparative genomic hybridization is also most likely to be an ALT mimicking a GFP. Pathologists need to be aware of the pitfalls in the diagnosis of ALT of the esophagus and should carefully evaluate the adipocytic component of these lesions.

Follicular pancreatitis: a distinct form of chronic pancreatitis—an additional mimic of pancreatic neoplasms

Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis. Immunohistochemistry for Bcl-2, CD21, κ and λ light chains as well as IgG4 and IgG were performed. We found a total of 6 patients (male-female ratio, 2:1; mean age, 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis, while two presented with abdominal pain, fatigue, and elevated liver enzymes. On imaging, 3 patients had a discrete solid mass, whereas 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatic portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2-negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis, or granulocytic epithelial lesions. IgG4-to-IgG ratio was <40% in 5 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers.

Pancreatic PEComa is a novel member of the family of tuberous sclerosis complex-associated tumors: case report and review of the literature

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with variable penetrance and a wide spectrum of disease manifestations even within the same family. Major diagnostic criteria for TSC include several distinct neoplasms, including facial angiofibroma, cardiac rhabdomyoma, lymphangioleiomyomatosis, subependymal giant cell astrocytoma, and renal angiomyolipoma. Germline mutations in either of two genes, TSC1 and TSC2, which code for hamartin and tuberin, respectively, cause TSC. Hamartin and tuberin, along with a third protein, TBC1D7, function as a heterocomplex to regulate activation of mTOR complex 1 (mTORC1) through regulation of the rheb GTPase. [5] Loss-of-function mutations in the TSC1 or TSC2 gene lead to activation of mTORC1, which is a direct contributor to the growth of these tumors, and this abnormal activation can be therapeutically blocked by rapamycin and its analogs, such as everolimus. [3] Although not completely separable clinically, TSC1 mutations are associated with overall milder disease severity than TSC2 mutations. The spectrum of clinical features of TSC continues to evolve. More recently, liver angiomyolipomas and pancreatic neuroendocrine tumors (NETs) have been described as manifestations of TSC. [4], [8] Little is known about other types of pancreatic neoplasms associated with TSC. Here, we describe multiple perivascular epithelioid cell tumors (PEComas) in the pancreas of a patient with TSC and provide proof of TSCrelated origin of these PEComas.