Brian Quigley

Leiomyosarcoma Arising in the Pancreatic Duct: A Case Report and Review of the Current Literature

Context. Leiomyosarcomas are rare malignant smooth muscle tumors that may arise in any organ or tissue that contains smooth muscle, commonly within the gastrointestinal tract. They are most often found in the stomach, large and small intestines, and retroperitoneum. Primary pancreatic leiomyosarcoma is extremely rare, and to the best of our knowledge only 30 cases have been reported in the world literature since 1951. Our case represents the first to have a clear origin from the main pancreatic duct. Case Report. This case was diagnosed in a large, tertiary care center in Tampa, Florida. Pertinent information was obtained from chart review and interdepartmental collaboration. A mass in the tail of the pancreas was identified with large pleomorphic and spindle-shaped cells. Immunohistochemistry for vimentin, smooth muscle actin, and desmin was positive. All remaining immunohistochemical markers performed were negative. The tumor clearly originated from the pancreatic duct wall, filled and expanded the duct lumen, and was covered with a layer of benign biliary epithelium. Conclusion. Leiomyosarcoma of the pancreas is an extremely rare malignancy with few reported cases in the literature. The prognosis is poor, and treatment consists of alleviating symptoms and pain management. To our knowledge, this represents the first reported case demonstrating clear origin of a leiomyosarcoma from the pancreatic duct.

Primary biliary tract malignancies: MRI spectrum and mimics with histopathological correlation

Contrast-enhanced magnetic resonance imaging and magnetic resonance cholangiopancreatography (MRCP), due to their excellent soft tissue contrasts, have become first-line noninvasive tests in the characterization and detection of both hepatic and pancreaticobiliary pathologies. MRCP is also helpful in detecting the level and cause of obstruction in patients presenting with jaundice. Cholangiocarcinoma (CCA) is the most common primary malignant tumor arising from the bile duct epithelium, with extrahepatic tumors presenting more often than with intrahepatic ones. However, the diagnosis and management of CCA is made more complex by a variety of malignant and benign conditions that resemble CCA, including hepatocellular carcinoma variants such as the fibrolamellar variant of hepatocellular carcinoma, cholangiocellular carcinoma, biliary metastases, hepatic inflammatory pseudotumor, lymphoepithelioma-like carcinoma, confluent fibrosis, primary sclerosis cholangitis, and the secondary sclerosing cholangitis complex. Consequently, knowledge of the underlying risk factors and imaging characteristics of these conditions is important in differentiating between neoplastic and non-neoplastic conditions in order to reach a definite diagnosis. Endoscopic retrograde cholangiopancreatography should be reserved for those patients who require intervention or biopsy for histopathological diagnosis.

Nonmucinous Biliary Epithelium Is a Frequent Finding and Is Often the Predominant Epithelial Type in Mucinous Cystic Neoplasms of the Pancreas and Liver.

Mucinous cystic neoplasms (MCNs) can occur in the pancreas and liver. Classically, these cystic lesions are lined by columnar mucinous epithelium with underlying ovarian-type stroma. It has been proposed that cysts with ovarian-type stroma and nonmucinous epithelium be considered separate entities in both the pancreas and liver. Using a series of 104 pancreatic and 32 hepatic cases, we aimed to further characterize the epithelium present in MCNs. Mucinous epithelium was defined as pancreatic intraepithelial neoplasia–like columnar cells with pale pink/clear apical mucin. Epithelial cells ranging from flat to cuboidal to short columnar without obvious mucin or goblet cells were classified as nonmucinous/biliary epithelium. A mixture (at least 5%) of mucinous and nonmucinous/biliary epithelium was noted in 81%. Almost half (47%) of the cases had abundant (>50%) nonmucinous/biliary epithelium. Of the 71 cases with ⩽50% nonmucinous/biliary epithelium, 8 cases demonstrated high-grade dysplasia (7 pancreas, 1 liver) and 14 demonstrated invasive adenocarcinoma (11 pancreas, 3 liver). Conversely, of the 58 cases with >50% nonmucinous/biliary epithelium, not a single case of high-grade dysplasia (P=0.007) or invasive carcinoma (P<0.001) was identified. In summary, nonmucinous/biliary epithelium frequently occurs in MCNs of the pancreas and liver. As mucinous and nonmucinous/biliary epithelia often occur together, there does not appear to be enough evidence to regard cases with predominantly nonmucinous/biliary epithelium as separate entities. Our findings suggest that mucinous change is a “progression” phenomenon in MCNs of the pancreas and liver, and only when abundant mucinous epithelium is present is there a risk of progression to malignancy.

Immunohistochemical Classification of Ampullary Carcinomas: Critical Reappraisal Fails to Confirm Prognostic Relevance for Recently Proposed Panels, and Highlights Muc5ac as a Strong Prognosticator

Recently, immunohistochemistry-based classifications of ampullary carcinomas have been proposed (Ang and colleagues [PMID: 24832159]; Chang and colleagues [PMID: 23439753]). In this study, the prognostic value of Ang/Chang panel markers (CK20, MUC1, MUC2, CDX2) as well as other markers (CK7, MUC5AC, and MUC6) were tested on full-faced sections of 136 ampullary carcinoma resections with substantial (>5 mm) invasion. Immunohistochemistry was correlated with both histologic classification (intestinal [INT], pancreatobiliary [PB], or nontubular based on ≥3/5 observer agreement) and clinical outcome. No prognostic correlation was found with MUC1, CDX2, MUC2 or CK20 despite testing with different quantitative cutoffs. CK7 and CK20 were nonspecific. Ang classification had reasonable correlation with histologic subclassification of tubular cases as INT versus PB with high specificity but low sensitivity and ambiguous category was large (29%) and included also some classical cases. Prognostically, Ang classification approached but did not reach statistical significance, even when their large “ambiguous” group was eliminated and only tubular cases were analyzed (Ang-INT vs. Ang-PB; P=0.08). The Chang panel, in which the definition of the INT subcategory is not clearly defined, only marginally reached prognostic significance when tested as MUC1+/CDX2− versus MUC1−/CDX2+ and only by Wilcoxon test (P=0.0485) but 31% of the cases were “unclassifiable.” The only individual marker that was found to have direct and strong correlation with the clinical outcome was MUC5AC (not used in the Ang or Chang panels), with statistically significant survival differences found with various cutoffs tested (for 20% cutoff, 5-y survival, 68% vs. 31%; P=0.0002). In addition, MUC5AC significantly stratified the histologically PB and INT cases (P=0.01 and 0.03, respectively), as well as Ang’s ambiguous and Chang’s unclassified cases (P=0.006 and 0.007, respectively). In conclusion, the widely used putative lineage markers, MUC1/MUC2/CK7/CK20/CDX2, do not seem to have direct/significant prognostic correlation either individually or in combination of Ang and Chang panels. Ang panel is helpful as an adjunct in determining the cell lineage with a few caveats. MUC5AC proves to be a significant independent prognosticator and should be incorporated into evaluation of ampullary carcinomas.

Non-ampullary-duodenal carcinomas: clinicopathologic analysis of 47 cases and comparison with ampullary and pancreatic adenocarcinomas.

Literature on non-ampullary–duodenal carcinomas is limited. We analyzed 47 resected non-ampullary–duodenal carcinomas. Histologically, 78% were tubular-type adenocarcinomas mostly gastro-pancreatobiliary type and only 19% pure intestinal. Immunohistochemistry (n=38) revealed commonness of ‘gastro-pancreatobiliary markers’ (CK7 55, MUC1 50, MUC5AC 50, and MUC6 34%), whereas ‘intestinal markers’ were relatively less common (MUC2 36, CK20 42, and CDX2 44%). Squamous and mucinous differentiation were rare (in five each); previously, unrecognized adenocarcinoma patterns were noted (three microcystic/vacuolated, two cribriform, one of comedo-like, oncocytic papillary, and goblet-cell-carcinoid-like). An adenoma component common in ampullary–duodenal cancers was noted in only about a third. Most had plaque-like or ulcerating growth. Mismatch repair protein alterations were detected in 13% (all with plaque-like growth and pushing-border infiltration). When compared with ampullary (n=355) and pancreatic ductal (n=227) carcinomas, non-ampullary–duodenal carcinomas had intermediary pathologic features with mean invasive size of 2.9 cm (vs 1.9, and 3.3) and 59% nodal metastasis (vs 45, and 77%). Its survival (3-, 5-year rates of 57 and 57%) was similar to that of ampullary–duodenal carcinomas (59 and 52%; P=0.78), but was significantly better than the ampullary ductal (41 and 29%, P<0.001) and pancreatic (28 and 18%, P<0.001) carcinomas. In conclusion, non-ampullary–duodenal carcinomas are more histologically heterogeneous than previously appreciated. Their morphologic versatility (commonly showing gastro-pancreatobiliary lineage and hitherto unrecognized patterns), frequent plaque-like growth minus an adenoma component, and frequent expression of gastro-pancreatobiliary markers suggest that many non-ampullary–duodenal carcinomas may arise from Brunner glands or gastric metaplasia or heterotopic pancreatobiliary epithelium. The clinical behavior of non-ampullary–duodenal carcinoma is closer to that of ampullary–duodenal subset of ampullary carcinomas, but is significantly better than that of ampullary ductal and pancreatic cancers. The frequency of mismatch repair protein alterations suggest that routine testing should be considered, especially in the non-ampullary-duodenal carcinomas with plaque-like growth and pushing-border infiltration.

Burkitt Lymphoma Arising From Lymphoplasmacytic Lymphoma Following Acquisition of MYC Translocation and Loss of the ETV6 Tumor Suppressor Gene

Lymphoplasmacytic lymphoma is a mature B-cell lymphoma with variable plasmacytic differentiation that displays an indolent clinical course. Its transformation to a high-grade B-cell lymphoma may occur uncommonly. Although acquisition of a MYC translocation could result in transformation of a low-grade lymphoma into diffuse large B-cell lymphoma, Burkitt lymphoma, or B-lymphoblastic leukemia, to our knowledge the latter 2 transformations have not been well documented in lymphoplasmacytic lymphoma. We report the case of a 70-year-old woman with a 9-year history of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia who presented with rapid enlargement of a left neck mass and pancytopenia, which was diagnosed as Burkitt lymphoma with extensive bone marrow involvement. A series of histopathologic, molecular, and cytogenetic evaluations proved a cytogenetic evolution including t(8;14)(q24;q32)/MYC-IgH and identical clonal B-cell gene rearrangements from the 2 distinct lymphomas, confirming stage 4 aggressive Burkitt lymphoma arising from lymphoplasmacytic lymphoma.

Amyloid light chain deposition associated with dermatofibroma: serendipity or association?

Primary cutaneous amyloidosis, also known as nodular amyloidosis, is defined as deposition of amyloid light chain in the skin in the absence of a systemic cause of amyloidosis. Such amyloid is produced by a localized aggregate of clonal plasma cells. In contrast, secondary cutaneous amyloidosis is related to lesions such as squamous cell carcinoma, Bowen disease, basal cell carcinoma, and discoid lupus erythematosus, and has been shown in most cases to be derived from keratin epithelial elements. Herein, we present a unique case of nodular amyloidosis occurring in association with a cellular dermatofibroma.

Hepatobiliary Mucinous Cystic Neoplasms With Ovarian Type Stroma (So-Called “Hepatobiliary Cystadenoma/Cystadenocarcinoma”): Clinicopathologic Analysis of 36 Cases Illustrates Rarity of Carcinomatous Change

The literature is highly conflicting on hepatobiliary mucinous cystic neoplasms (MCNs), aka “hepatobiliary cystadenoma/cystadenocarcinoma,” largely because ovarian stroma (OS) was not a requirement until WHO-2010 and is not widely applied even today. In this study, MCNs (with OS) accounted for 24 of 229 (11%) resected hepatic cysts in one institution. Eight of the 32 (25%) cysts that had been originally designated as hepatobiliary cystadenoma/cystadenocarcinoma at the time of diagnosis proved not to have an OS during this review and were thus re-classified as non-MCN. In total, 36 MCNs (with OS) were analyzed—24 from the institutional files and 12 consultation cases. All were women. Mean age was 51 (28 to 76 y). Mean size was 11 cm (5 to 23 cm). Most (91%) were intrahepatic and in the left lobe (72%). Preoperative imaging mentioned “neoplasm” in 14 (47%) and carcinoma was a differential in 6 (19%) but only 2 proved to have carcinoma. Microscopically, only 47% demonstrated diffuse OS (>75% of the cyst wall/lining); OS was often focal. The cyst lining was often composed of non-mucinous biliary epithelium, and this was predominant in 50% of the cases. Degenerative changes of variable amount were seen in most cases. In situ and invasive carcinoma was seen in only 2 cases (6%), both with small invasion (7 and 8 mm). Five cases had persistence/recurrence, 2 confirmed operatively (at 7 mo and 15 y). Of the 2 cases with carcinoma, one had “residual cyst or hematoma” by radiology at 4 months, and the other was without disease at 3 years. In conclusion, many cysts (25%) previously reported as hepatobiliary cystadenoma/cystadenocarcinoma are not MCNs. True MCNs are uncommon among resected hepatic cysts (11%), occur exclusively in females, are large, mostly intrahepatic and in the left lobe (72%). Invasive carcinomas are small and uncommon (6%) compared with their pancreatic counterpart (16%). Recurrences are not uncommon following incomplete excision.

Collagenous Sprue, an Enigma in the Spectrum of Celiac Disease

A64-year-old white woman presented to our clinic with bilateral swelling of her hands and feet and an unintentional 50-pound weight loss over the past year. She was having 1 to 2 bowel movements daily with occasional additional watery stools without dietary variation. Laboratory values were as follows: alanine aminotransferase, 35 IU/L; aspartate aminotransferase, 46 IU/ L; alkaline phosphatase, 117 IU/L; total bilirubin, 0.3 mg/dL; albumin, 1.7 g/dL; and hemoglobin, 11.6 g/ dL. Her liver function tests later normalized after discontinuing her statin and meloxicam, but given her weight loss she was evaluated endoscopically. Esophagogastroduodenoscopy showed moderately erythematous mucosa of the entire stomach and blunted duodenal mucosa (Figure A). Her colonoscopy was normal. A biopsy showed almost complete flattening of the duodenal mucosa and subepithelial collagen deposition in the absence of intraepithelial lymphocytosis (Figure B). Collagen was highlighted with a trichrome stain (Figure C). Subepithelial collagen deposition also was seen in the cecum and in the left and right colon (Figure D). Antral and fundic biopsy specimens showed chronic gastritis. Celiac panel and later HLA-DQ2/DQ8 were negative. She was started on 9-mg oral budesonide capsules and initially a gluten-free diet for collagenous sprue. After 16 weeks of treatment she gained 24 pounds, her albumin level increased to 3.3 g/dL, and her edema resolved. She was started on an 8-week budesonide taper and a regular diet without return of symptoms. Collagenous sprue (CS) is a rare cause of severe malabsorption. We present a case of collagenous sprue with concomitant collagenous colitis. Most cases of CS are reported in middle-aged to elderly Caucasian women. CS clinically presents similarly to celiac disease—with chronic diarrhea and weight loss. Our patient had an atypical presentation given her lack of diarrhea. Histopathologically, CS is distinguished by the presence of significant subepithelial collagen deposition entrapping blood vessels and inflammatory cells in addition to distorted villous and crypt architecture in the small bowel. There is ongoing debate regarding whether CS is a separate disease entity or simply part of the celiac spectrum. Some experts believe CS to be a histopathologic variant of celiac disease with a poorer outcome. Biopsy-proven celiac disease and CS both can have concomitant collagenous or lymphocytic gastritis and/or colitis. The prevalence of specific HLA haplotypes has not yet been proven in CS. Corticosteroids have been used increasingly to treat CS. The capsule formulation of oral budesonide has at least equal therapeutic efficacy compared with other steroids, with less first-pass hepatic metabolism, showing benefit with enhanced local colonic absorption; and this formulation has been used successfully to treat refractory sprue as well. Response to dietary gluten removal has been shown to be inconsistent, particularly in HLA-DQ2/DQ8–negative patients. Collagenous sprue is a rare cause of severe malabsorption that may be part of the celiac spectrum. It can

The Impact of New Technologic and Molecular Advances in the Daily Practice of Gastrointestinal and Hepatobiliary Pathology

The practice of anatomic pathology, and of gastrointestinal pathology in particular, has been dramatically transformed in the past decade. In addition to the multitude of diseases, syndromes, and clinical entities encountered in daily clinical practice, the increasing integration of new technologic and molecular advances into the field of gastroenterology is occurring at a fast pace. Application of these advances has challenged pathologists to correlate newer methodologies with existing morphologic criteria, which in many instances still provide the gold standard for diagnosis. This review describes the impact of new technologic and molecular advances on the daily practice of gastrointestinal and hepatobiliary pathology. We discuss new drugs that can affect the gastrointestinal tract and liver, new endoluminal techniques, new molecular tests that are often performed reflexively, new imaging techniques for evaluating hepatocellular carcinoma, and modified approaches to the gross and histologic assessment of tissues that have been exposed to neoadjuvant therapies.