Cutaneous Metastasis of a Mucoepidermoid Carcinoma of the Pancreas: First Reported Case.

BACKGROUND: Mucoepidermoid pancreatic cancer is a rare entity with only 8 cases reported in the literature. On review of the literature, the authors found that cutaneous metastases in pancreatic cancer are rare and have not been associated with the mucoepidermoid subtype. The authors present the first reported case of cutaneous metastasis in a patient with mucoepidermoid carcinoma of the pancreas. CASE PRESENTATION: A 50-year old white male with a metastatic invasive poorly differentiated mucoepidermoid carcinoma of the pancreas was found to have a slow growing lesion in the skin over his left upper quadrant while undergoing active therapy. The lesion was biopsied and the pathology was consistent with pancreatic origin sharing similar morphologic features when compared with the primary pancreactectomy specimen. CONCLUSIONS: Mucoepidermoid pancreatic cancer is an exceedingly rare subtype of pancreatic cancer, with very little information regarding its diagnosis, treatment, and patterns of metastases. Here, the authors present the first reported case of cutaneous metastases of mucoepidermoid pancreatic cancer.

Benign glandular downgrowth in gastric neuroendocrine neoplasms: a potential mimic of composite tumour.

AIMS: We have observed glandular downgrowth in some gastric neuroendocrine tumours (NETs), in which nonneoplastic appearing gastric glands are admixed with submucosal neuroendocrine nests, that could potentially be confused with composite tumours. METHODS AND RESULTS: We reviewed 68 gastric NETs with at least submucosal invasion, and evaluated associations between glandular downgrowth, clinical parameters (age, gender, NET setting) and tumour characteristics (size, depth of invasion, grade). Controls included 45 duodenal NETs. Glandular downgrowth was present in 28 (41%) gastric NETs but only 2 (4.4%) duodenal NETs (P < 0.0001). It was not related to age, gender, hypergastrinemia (downgrowth present in 43% of NETs arising in autoimmune gastritis, 41% of Zollinger-Ellison syndrome, 36% of sporadic NETs), tumour size, depth of invasion, or grade. Glandular downgrowth was confined to the submucosa even though 12 (18%) gastric NETs invaded muscularis propria. Submucosal gastric glands (pyloric type in 79%, intestinal in 50%, fundic in 29%) showed metaplastic changes similar to overlying mucosa, were usually mitotically inactive (64% of cases lacked mitotic figures), were geographically restricted to the NET, and never metastasized. CONCLUSIONS: Our findings support the frequent occurrence and nonneoplastic nature of glandular downgrowth in gastric NETs, which should not be mistaken for composite tumours.

Invasive neuroendocrine carcinoma of the breast: a population-based study from the surveillance, epidemiology and end results (SEER) database.

BACKGROUND: Neuroendocrine carcinoma (NEC) of the breast is a rare type of carcinoma that has not been well studied or characterized. Of the limited number of studies reported in the literature, most are case reports. A few small retrospective series studies have been reported. METHODS: We reviewed data on 142 cases of mammary NEC recorded in the surveillance, epidemiology, and end results (SEER) database during 2003-2009 and evaluated disease incidence and patient age, sex, and race/ethnicity; clinicopathologic characteristics; and survival in comparison to invasive mammary carcinoma, not otherwise specified. We also performed univariate and multivariate analyses to identify prognostic factors in this disease. RESULTS: Review of the 142 SEER cases revealed that NEC is an aggressive variant of invasive mammary carcinoma. It generally occurred in older women (>60 years); present with larger tumor size (>20 mm), higher histologic grade, and higher clinical stage; and result in shorter overall survival and disease-specific survival than invasive mammary carcinoma, not otherwise specified (IMC-NOS). Overall survival and disease-specific survival were shorter in NEC at each stage than in IMC-NOS of the same stage. Furthermore, when all NEC and IMC-NOS cases were pooled together, neuroendocrine differentiation itself was an adverse prognostic factor independent of other known prognostic factors, including age, tumor size, nodal status, histologic grade, estrogen/progesterone receptor status, and therapy. CONCLUSIONS: NEC is a rare but aggressive type of mammary carcinoma. Novel therapeutic approaches should be explored for this uniquely clinical entity.

Viral Hepatitis B Reactivation With Delayed Cholestatic Effect Secondary to Acalabrutinib.

One significant complication of hepatitis B virus includes reactivation (HBVr) in the context of the use of immunosuppressive agents, such as corticosteroids and rituximab, among others. Limited data exist on the topic of HBVr risk in the context of tyrosine kinase inhibitors for which there is no strong guidance recommendation. We describe the clinical characteristics, diagnostic challenges, and the clinical course of a single patient with recurrent mantle cell lymphoma who developed HBVr after treatment with acalabrutinib, a Bruton tyrosine kinase inhibitor.

Oesophageal hyperkeratosis: clinicopathological associations.

AIMS: Oesophageal hyperkeratosis is rarely described. In contrast to hyperkeratosis of orolaryngeal mucosa, where its risk factors and association with squamous neoplasia are well-studied, the prevalence and clinicopathological features of oesophageal hyperkeratosis are unknown. METHODS AND RESULTS: We reviewed prospectively 1845 oesophageal biopsies and found hyperkeratosis in 37 (2.0%). Among 98 patients studied, hyperkeratosis occurred in two distinct settings: group 1 [within Barrett's oesophagus (BO)/adenocarcinoma, n = 61, 62%] and group 2 (outside BO/adenocarcinoma, n = 37, 38%). In contrast to group 1, hyperkeratosis in group 2 was more often multifocal (>3 foci in 51% versus 16%, P = 0.0001), involved mid-oesophagus (51% versus 2%, P < 0.0001), showed endoscopic leucoplakia (24% versus 3%, P = 0.003) and involved current/former alcohol users (51% versus 19%, P = 0.0012). Importantly, invasive squamous carcinoma and squamous dysplasia were seen only in group 2 (47% and 19% versus 0%, P < 0.0001). Further, 42% of group 2, but none of group 1, had benign or malignant squamous lesions of the oral cavity/larynx (P < 0.0001). CONCLUSION: Hyperkeratosis involves ~2% of oesophageal biopsies and can be divided into cases occurring within BO/adenocarcinoma and those occurring outside BO/adenocarcinoma. The former lack clinical significance, whereas the latter are associated frequently with oesophageal squamous neoplasia and squamous pathology of the head and neck region.

Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.

The physiological role of the mitotic checkpoint protein Bub1 is unknown. To study this role, we generated a series of mutant mice with a gradient of reduced Bub1 expression using wild-type, hypomorphic, and knockout alleles. Bub1 hypomorphic mice are viable, fertile, and overtly normal despite weakened mitotic checkpoint activity and high percentages of aneuploid cells. Bub1 haploinsufficient mice, which have a milder reduction in Bub1 protein than Bub1 hypomorphic mice, also exhibit reduced checkpoint activity and increased aneuploidy, but to a lesser extent. Although cells from Bub1 hypomorphic and haploinsufficient mice have similar rates of chromosome missegregation, cell death after an aberrant separation decreases dramatically with declining Bub1 levels. Importantly, Bub1 hypomorphic mice are highly susceptible to spontaneous tumors, whereas Bub1 haploinsufficient mice are not. These findings demonstrate that loss of Bub1 below a critical threshold drives spontaneous tumorigenesis and suggest that in addition to ensuring proper chromosome segregation, Bub1 is important for mediating cell death when chromosomes missegregate.

Metastatic nonhematopoietic neoplasms to the breast: a study of 238 cases.

The aim of this study was to review the clinicopathologic characteristics of metastatic nonhematopoietic malignancies to the breast, in order to identify salient features for practicing pathologists that are useful in distinguishing metastatic lesions from primary breast neoplasms. A total of 238 cases were identified during the period from January 2005 to January 2015. Clinicopathologic features of these cases were retrospectively reviewed. Primary tumors included melanoma (99, 42%), serous carcinoma (35, 15%), neuroendocrine neoplasm (32, 13%), sarcoma (23, 10%), and adenocarcinoma from various organs (47, 20%), and 2 others. Most metastases were unilateral (223, 94%) and unifocal (206, 87%) and were detected radiographically (167, 70%). Concurrent ipsilateral axillary metastasis occurred in 33 (14%) patients. Among 238 cases, 41 had metastatic disease to the breast concurrently or preceding the primary cancer diagnosis. Notably, in 39 (16%) cases, breast metastasis was the first clinical presentation of disease, and 16 (41%) of these cases were initially misdiagnosed as breast primaries. In contrast, with a known history of nonmammary primary tumors, only 4 of 197 (2%) cases were misdiagnosed (p < 0.0001). Metastatic tumors share many overlapping features with breast primary carcinomas. However, cases with a well-circumscribed tumor, lack of in situ component, estrogen receptor/progesterone receptor negativity, and unusual morphologic features should raise the consideration of metastatic disease. While clinical history is paramount for correct diagnosis, metastasis to the breast as the first clinical presentation is not uncommon.

Metastatic neuroendocrine tumour in the breast: a potential mimic of in-situ and invasive mammary carcinoma.

AIMS: The aim of this study was to review the clinicopathological characteristics of neuroendocrine tumours (NETs) metastasizing to the breast, in order to identify features that could be useful in distinguishing these metastatic lesions from primary breast neoplasms. METHODS AND RESULTS: Eighteen metastatic NETs in the breast were identified from two large hospitals over a 15-year period. Eleven (62%) tumours originated in the gastrointestinal tract, 5 (28%) originated in the lung, and the other two were of indeterminate origin. Eight (44%) cases were initially misdiagnosed as primary mammary carcinomas. In retrospect, all metastatic tumours exhibited architectural and cytological features that would suggest neuroendocrine differentiation. Immunohistochemistry can further aid in the distinction between metastatic neuroendocrine and primary mammary carcinoma. All 11 tumours from the gastrointestinal tract expressed CDX-2, 3 (60%) of five tumours from the lung expressed thyroid transcription factor-1, and only 2 (11%) of 18 showed weak oestrogen receptor positivity. Additionally, unlike primary carcinomas, the majority (82%) of metastatic NETs were negative for cytokeratin 7, and all were negative for gross cystic disease fluid protein 15 and mammoglobin. CONCLUSIONS: There is a high propensity for metastatic NETs to mimic primary breast carcinomas. Careful attention to cytological and architectural features can help to identify cases that require further immunophenotypic workup with a panel of tissue-specific antibodies. However, clinical history is paramount for optimal diagnosis.

Rosai-Dorfman disease confined to the breast.

Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy) is an uncommon, idiopathic, benign histiocytic lesion. It usually involves the cervical lymph nodes and, less commonly, extranodal sites. Involvement of the breast is rare, with only 17 cases reported in the English literature to date. Here we describe 3 new patients with extranodal Rosai-Dorfman disease in the breast. All 3 patients-aged 45, 53, and 54 years-presented with solid breast lesions that were detected on screening mammography and had no clinical history of Rosai-Dorfman disease or radiographic evidence of extramammary involvement. Initial diagnoses were accomplished by needle core biopsy in the one case and excisional biopsy in the other two. We present the histopathologic findings and follow-up of each patient and conduct a literature review of mammary Rosai-Dorfman disease with emphasis on its differential diagnosis. Because Rosai-Dorfman disease frequently mimics invasive breast carcinoma in its clinical presentation and radiographic appearance-and can mimic other benign or malignant histiocytic lesions microscopically-awareness and appropriate diagnosis of this entity are essential for proper treatment.

Idiopathic refractory ascites after allogeneic stem cell transplantation: a previously unrecognized entity.

At our center, we observed a series of patients who developed transudative refractory ascites secondary to noncirrhotic, non-veno-occlusive disease (VOD)-related portal hypertension after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients were considered to have idiopathic portal hypertension-related refractory ascites (IRA) if they developed ascites secondary to intrahepatic portal hypertension (serum ascites albumin gradient ≥1.1 g/dL or hepatic venous pressure gradient [HVPG] >5 mm Hg), but did not meet the clinical criteria for classical VOD/sinusoidal obstructive syndrome (SOS) and did not have any alternate etiology of portal hypertension. From our institutional database, we identified 40 patients who developed IRA after allo-HSCT between 2004 and 2018. The patients' median age at the time of allo-HSCT was 54 years (range, 21-73 years). The median time to development of IRA after allo-HSCT was 80 days (range, 16-576 days). The median number of paracentesis was 3 (range, 1-11), and 15 (38%) patients had an intraperitoneal catheter placed for continued drainage of the rapidly accumulating ascites. Portal pressures were measured in 19 patients; 6 (15%) had moderate portal hypertension (HVPG 6-9 mm Hg), and 13 (33%) had severe portal hypertension (HVPG ≥ 10 mm Hg). Liver biopsy was performed in 24 patients. None of the patients met the criteria for classical VOD/SOS (clinical/histological) or cirrhosis (histological). The cumulative incidence of nonrelapse mortality was 63%, and the median survival duration after the development of the IRA was 7 months (range, 0.8-125.6 months). IRA is a poorly understood and often fatal complication of allo-HSCT.

Muscularis mucosae duplication and the musculo-fibrous anomaly in endoscopic mucosal resections for barrett esophagus: implications for staging of adenocarcinoma.

Endoscopic mucosal resection (EMR) is increasingly used for management of Barrett esophagus (BE)-related neoplasia. Duplication of the muscularis mucosae (MM) has been described in BE esophagectomy specimens, where it can pose difficulties with accurate staging of carcinoma. The frequency, morphologic characteristics, and effect of MM duplication in adenocarcinoma staging in EMRs have not yet been evaluated. We studied 122 EMR specimens from 100 patients from 1999 to 2006. The following histologic features were scored: depth of EMR, presence of MM duplication and its extent, prolapse changes (extension of smooth muscle into lamina propria), gland entrapment, and diagnosis (original and study/final). Carcinomas reaching the level of submucosa were classified as invasive adenocarcinoma (INV); those confined to lamina propria or MM were classified as intramucosal adenocarcinoma (IMAC). Of 122 EMRs, 11 (9%) reached mucosa only, 109 (89%) extended to submucosa, and 2 (2%) extended into muscularis propria. MM duplication was present in 67% (75 of 111 specimens that reached at least submucosa). Prolapse changes were noted in 65 (54%) cases and gland entrapment in 67 (56%). Final pathologic diagnoses were 9 (7%) no specialized Barrett mucosa, 4 (3%) BE without dysplasia, 13 (11%) low-grade dysplasia, 51 (42%) high-grade dysplasia, 33 (27%) IMAC, and 12 (10%) INV. EMRs without BE were less likely to show MM duplication (P = 0.01) and there was a trend toward less frequent prolapse change (P = 0.08) and less gland entrapment (P = 0.08) as compared with EMRs with BE. However, there were no significant differences with respect to MM duplication, prolapse change, or gland entrapment between BE with or without dysplasia, IMAC, or INV. Among 33 cases of IMAC, tumor invaded lamina propria in 10 (30%), inner or single MM in 14 (42%), space between duplicated MM in 5 (15%), and outer MM layer in 4(12%). Lymphatic invasion was seen in 2 (10%) cases in which tumor reached the space between MM layers. Overstaging of carcinomas occurred in the original reports in 8 (7%) cases due to misinterpretation of the muscular anatomy, including one case in which the deep MM was interpreted as muscularis propria. These results show that MM duplication is commonly seen in EMR specimens. It is closely associated with the presence of BE but is not affected by neoplastic progression in the Barrett epithelium. Pathologists need to be aware of this distinctive anatomy of BE for accurate staging of adenocarcinomas, particularly to avoid mistaking a thickened outer MM as muscularis propria. Level of IMAC may be a critical feature because of potential access to lymphatic spaces between duplicated MM layers, and we therefore recommend including an explicit statement about the depth of adenocarcinoma invasion rather than using only broad terms such as IMAC or INV in the diagnostic report.

The prevalence and natural history of untreated isolated central perivenulitis in adult allograft livers.

Central perivenulitis (CP) in the allograft liver can be associated with portal-based acute cellular rejection and autoimmune hepatitis or can occur in isolation (isolated CP). Although several studies have demonstrated the significance of CP, the prevalence and natural history of untreated isolated CP have not been well studied. We examined 100 adult allograft liver recipients who had long-term follow-up, had routine protocol biopsies, and received no treatment for isolated CP. Isolated CP was identified in 28 (28%) patients. It occurred late at a mean of 658 days. Interestingly, patients with late isolated CP (defined as >3 months posttransplant) usually manifested only mildly to modestly elevated liver function tests. However, late isolated CP was associated with prior and subsequent allograft complications. Nearly all (94%) cases of late isolated CP occurred in patients who had early episodes of CP and/or acute cellular rejection. Of 13 patients who developed adverse outcomes in their allografts (zone 3 fibrosis in 10, de novo autoimmune hepatitis in 3, and ductopenia in 3), all experienced episodes of prior CP, and 12 (92%) had late CP; 1 patient required retransplant for chronic rejection, but all were alive within the last year. In summary, "transplant-associated" isolated CP occurs in 28% of adult patients, early CP is predictive of late CP, and late CP (often present as isolated CP) is associated with long-term liver injury in some patients.

Early changes of the portal tract on microcomputed tomography images in a newly-developed rat model for Budd-Chiari syndrome.

BACKGROUND AND AIM: The effect of increased sinusoidal pressure on the portal tract in Budd-Chiari syndrome (BCS) is as yet not elucidated. Our aim was to investigate portal changes in a newly-developed rat model for BCS. METHODS: We created an outflow obstruction in Sprague-Dawley rats (n = 6) by diameter reduction of the inferior vena cava. Left and right liver lobes with portal vein contrast were scanned using microcomputed tomography, and volumes of the portal tree and liver parenchyma were computed by the ANALYZE software program. RESULTS: Portal branching density was significantly lower in BCS than the shams, and decreased over time (P < 0.01). There was a significant drop in volume of both parenchyma and the portal tree in the left but not right lobes. At 6 weeks post-surgery, the perfusion index (i.e. ratio between both volumes) became equal to (left) or even higher than (right) the shams, suggesting a new equilibrium with preserved portal perfusion. Histological findings were consistent with those observed in humans. CONCLUSION: As early as day 2, a significant loss of peripheral portal branches was seen, which progressed over time. Inter-lobar differences in vascular abnormalities suggest compensatory mechanisms. Despite a decrease in both liver and portal vein volume, relative portal perfusion appeared spared.

Adult autoimmune enteropathy: Mayo Clinic Rochester experience.

BACKGROUND & AIMS: Autoimmune enteropathy is a rare cause of intractable diarrhea associated with circulating gut autoantibodies and a predisposition to autoimmunity. It is rarely observed in adults, with only 11 cases reported to date. METHODS: Fifteen adults with autoimmune enteropathy were identified at the Mayo Clinic, Rochester, from May 2001-June 2006. The demographic, clinical, and treatment data were abstracted from their records. RESULTS: The study population was 87% white, 47% female, with median age of 55 years (interquartile range, 42-67 years). All patients had protracted diarrhea, weight loss, and malnutrition. Celiac disease was excluded by lack of response to gluten-free diet or absence of the celiac disease susceptibility HLA genotypes. Fourteen patients were tested for gut epithelial cell antibodies, and 93% were positive for anti-enterocyte and/or anti-goblet cell antibodies. Predisposition to autoimmune diseases was noted in 80%, as indicated by a variety of circulating autoantibodies. Small intestinal histopathologic findings included subtotal villous atrophy and lymphoplasmacytic infiltration in the lamina propria with relatively few surface intraepithelial lymphocytes. T-cell receptor gene rearrangement studies were negative in all cases. Immunosuppressive therapy was required in 93% of cases. Clinical improvement was noted in 60% after 1-8 weeks of steroid therapy. CONCLUSIONS: Autoimmune enteropathy is a heterogeneous disease and should be considered in the differential diagnosis of malabsorption and small bowel villous atrophy. The presence of gut epithelial cell antibodies can help confirm the diagnosis. No single agent is unequivocally effective in inducing remission, and immunosuppressive therapy is required in most cases.

Bile duct dysplasia in the setting of chronic hepatitis C and alcohol cirrhosis.

Intrahepatic cholangiocarcinomas are rare and risk factors remain incompletely understood, but one recently identified potential risk factor is chronic hepatitis C (HCV) infection. To further study this potential association, we searched for dysplasia in the intrahepatic bile ducts in native explanted livers in cases of chronic HCV and control groups. Cases of chronic biliary tract disease were excluded. A total of 1058 explants were reviewed: HCV (511), alcohol alone (112), HCV and alcohol (85), HBV (67), cirrhosis from other causes (149), and noncirrhotic livers, for example, cases transplanted for acute liver failure (134). Dysplasia of the intrahepatic bile ducts was seen in 19/1058 (1.8%) of cases and was associated with chronic HCV infection and alcohol use, P=0.01. Ten out of 19 cases of dysplasia were in the setting of chronic HCV, 5/19 were in the setting of alcohol alone, and the remaining 4/19 were in the setting of combined HCV and alcohol. Seventeen out of 19 cases were classified as low-grade dysplasia and 2/19 as high-grade dysplasia. In all cases of dysplasia, the lesions were multifocal and involved septal-sized bile ducts. In 16/19 cases, the dysplasia was papillary whereas in 3/19 cases the dysplasia was flat. In conclusion, dysplasia can be found within the intrahepatic bile ducts in chronic HCV cirrhosis, supporting recent epidemiologic studies identifying chronic HCV as a major risk factor for intrahepatic cholangiocarcinoma. Alcohol also seems to be a risk factor. The dysplastic changes are multifocal, involve septal sized bile ducts, and are typically papillary.

Globular amyloid deposits isolated to the small bowel: a rare association with AL amyloidosis.

We describe a 55-year-old man with isolated duodenal and jejunal amyloidosis producing rare endoscopic and histologic findings. The patient had no specific gastrointestinal complaints but underwent esophagogastroduodenoscopy and colonoscopy because of progressive microcytic anemia. Endoscopy revealed multiple polyps, some filiform and measuring up to 3 cm in length, in the duodenum and proximal jejunum. Microscopically, the polyps resulted from amyloid deposition, predominantly within the submucosa, but also focally involving muscularis mucosae and lamina propria. The amyloid formed multiple globular submucosal deposits with a lamellated appearance reminiscent of corpora amylacea; linear amyloid deposition was also present in a perivascular distribution and within the overlying mucosa. Immunophenotyping confirmed AL amyloidosis with lambda immunoglobulin light chain restriction. There was no clinical evidence of visceral amyloidosis. The source of lambda light chain production was unclear as bone marrow biopsy and multiple gastrointestinal biopsies revealed normal numbers of polyclonal plasma cells. Further, immunoglobulin-free light chain assay was normal, as were serum and urine protein electrophoreses with immunofixation. This endoscopic presentation of isolated small bowel polyposis is an uncommon association with AL amyloidosis and to our knowledge this represents the first case of globular gastrointestinal amyloidosis resulting from AL amyloid.

Crystal-storing histiocytosis due to massive accumulation of charcot-leyden crystals: a unique association producing colonic polyposis in a 78-year-old woman with eosinophilic colitis.

Crystal-storing histiocytosis is a rare diagnosis that to date has only been associated with 2 conditions: intracytoplasmic accumulation of crystallized immunoglobulins in patients with lymphoproliferative disorders or plasma cell dyscrasias, and histiocytic accumulations of phagocytosed clofazimine, a drug used to treat lepromatous leprosy. We describe a 78-year-old woman with a past medical history of dermatologic mastocytosis and peripheral eosinophilia who presented with diarrhea and weight loss, and was found at colonoscopy to have polyposis limited to the right and transverse colon. She eventually underwent subtotal colectomy to remove the segment of polyposis. At gross examination, the colonic mucosa contained numerous polyps ranging from 1 to 7 mm which on histologic evaluation proved to represent mucosal and submucosal collections of histiocytes whose cytoplasm was distended by numerous brightly eosinophilic crystals. An intense eosinophilic infiltrate surrounded the histiocyte collections and also mildly involved the intervening colonic mucosa and superficial submucosa. Electron microscopy confirmed the presence of intracytoplasmic material identical to Charcot-Leyden crystals within histiocytes, representing the breakdown products of degranulated eosinophils. This is the first reported case of crystal-storing histiocytosis produced by massive accumulation of Charcot-Leyden crystals in eosinophilic colitis.

Prevalence and risk factors for gallbladder neoplasia in patients with primary sclerosing cholangitis: evidence for a metaplasia-dysplasia-carcinoma sequence.

Primary sclerosing cholangitis (PSC) carries an increased risk (10% to 20%) of hepatobiliary malignancy, especially cholangiocarcinoma (CC). Dysplasia, adenomas, and carcinomas of the gallbladder have been described in PSC but are less common than bile duct carcinomas. However, the prevalence and risk factors for gallbladder neoplasia among patients with PSC undergoing orthotopic liver transplantation (OLT) have not been well studied. We evaluated 72 gallbladders from 100 consecutive liver explants for PSC, including 66 cholecystectomies performed at the time of OLT and 6 performed before OLT. All specimens were totally embedded for histologic examination. We evaluated the following histologic features: presence of diffuse lymphoplasmacytic chronic cholecystitis, pyloric metaplasia, intestinal metaplasia, dysplasia (low-grade or high-grade), and adenocarcinoma. Gallbladder dysplasia and adenocarcinoma were correlated with several clinicopathologic parameters using Fisher exact test and t test, including: (1) sex, (2) age, (3) PSC duration, (4) inflammatory bowel disease (IBD) at time of OLT, and (5) concomitant bile duct dysplasia or carcinoma. Lymphoplasmacytic chronic cholecystitis was present in 35 (49%), pyloric metaplasia in 69 (96%), intestinal metaplasia in 36 (50%), dysplasia in 27 (37%; low-grade in 12 and high-grade in 15), and adenocarcinoma in 10 (14%; 2 with lamina propria invasion and 8 with invasion into muscularis or adventitia). Gallbladder carcinoma was associated with intrahepatic bile duct dysplasia (P=0.001), CC (P=0.023), and IBD (P=0.03). Gallbladder dysplasia was associated with hilar/intrahepatic bile duct dysplasia (P=0.0006), CC (P=0.028), IBD (P=0.0014), and older age at OLT (P=0.007). Neither gallbladder carcinoma nor dysplasia had a significant association with sex or PSC duration. These results indicate that complete histologic evaluation of gallbladders in patients undergoing transplantation for PSC yields high frequencies of inflammatory, metaplastic, and neoplastic changes. The strong correlation between gallbladder dysplasia/adenocarcinoma and bile duct dysplasia/CC supports the concept of a neoplastic "field effect" along the intrahepatic and extrahepatic biliary tract in PSC.

"Seedling" mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common incidental tumors of the esophagogastric junction.

Gastrointestinal stromal tumors (GISTs) are the most common nonepithelial neoplasm of the gastrointestinal tract and show a predilection for the stomach. Most are detected because of symptoms, but some are incidental findings at autopsy or surgery for other reasons. Incidental GISTs tend to be smaller at diagnosis, but even small (<1 cm) GISTs have been shown to harbor activating KIT mutations at rates similar to advanced GISTs. However, the prevalence and characteristics of small GISTs in surgical resections of the esophagogastric junction (EGJ) remains unclear. We studied 150 esophagogastric resections for esophageal or EGJ carcinomas (100 with preoperative chemoradiation and 50 untreated cases) that had been extensively embedded for histologic examination (mean 30 sections/case). Number, size, morphology, and location of all GISTs and leiomyomas were recorded. All potential GISTs were evaluated with CD117 and CD34 immunohistochemistry, and a subset (35) leiomyomas with smooth muscle actin, desmin, and CD117. We found 18 incidental GISTs in 15 of 150 (10%) patients; 3 patients harbored 2 separate lesions. Prevalence of GIST was identical in treated (10 of 100) and untreated (5 of 50) cases. All (100%) showed positivity for both CD117 and CD34 and all were of spindle cell morphology. Lesions ranged from 0.2 to 3.0 mm in size (mean 1.3 mm). Eight (44%) were based in the outer muscularis propria, 7 (39%) in inner muscularis, and 3 (17%) between the muscle layers. The lesions tended to cluster near the EGJ, with 8 (44%) on the gastric side, 9 (50%) on the esophageal side, and 1 (6%) undetermined owing to overlying ulceration. Leiomyomas were even more common than GIST, occurring in 47% of patients (44% of treated and 52% of untreated, P=0.39), with a mean of 3 leiomyomas per patient (range 1 to 13) and mean size of 1.7 mm (range 0.2 to 12 mm). Unlike colorectal leiomyomas, most (91%) EGJ leiomyomas were located in the inner muscularis propria and only rarely (1%) in muscularis mucosa. These results suggest that GIST and leiomyoma are common incidental "seedling" lesions of the EGJ, found in 10% and 47% of patients undergoing surgery for esophageal carcinoma. The common occurrence of microscopic GISTs compared with the rarity of clinically manifest and malignant esophagogastric GISTs suggests that additional genetic or epigenetic alterations must happen for neoplastic progression.