Plexiform fibromyxoma with cotyledon-like serosal growth: A case report of a rare gastric tumor and review of the literature.

Plexiform fibromyxoma is a rare, benign mesenchymal neoplasm that predilects the gastric antrum and has potential for misdiagnosis as a gastrointestinal stromal tumor (GIST). The histology of the tumor is characterized by interwoven fascicular growth of cytologically bland spindled cells within a variably myxoid stroma. The current study reports the clinicopathological and immunohistochemical findings of a plexiform fibromyxoma resected from a 28-year-old Vietnamese female. The patient presented with acute, severe abdominal pain and worsening anemia. The initial fine-needle aspiration and needle core biopsy of the gastric antral mass led to an initial diagnosis of GIST. The subsequent distal partial gastrectomy revealed a 5.5-cm transmural antral mass that ulcerated the overlying mucosa and grew as variably elongated, myxoedematous, polypoid (cotyledon-like) excrescences from the serosal surface. Microscopically, the tumor demonstrated plexiform and multinodular growth of cytologically bland spindled cells proliferating in an abundant myxocollagenous stroma with a prominent capillary network. Tumor cells immunohistochemically expressed smooth muscle actin and CD10, but did not express CD117, Discovered on GIST-1 or nuclear ß-catenin. Follow-up evaluation 23 months post surgery revealed no evidence of residual tumor. A review the cases of this rare entity reported in the English language literature is also provided.

Peripheral lung adenocarcinomas with KRAS mutations are more likely to invade visceral pleura.

CONTEXT: Kirsten-RAS (KRAS) mutations play an important role in the carcinogenesis of a subset of lung adenocarcinomas and are associated with poorer prognosis. OBJECTIVE: To investigate the relationship of KRAS mutation status to the histologic subtype of adenocarcinoma according to the recent classification, patient demographics, tumor size, predominant histologic subtype, nodal status, and visceral pleural invasion, in an attempt to uncover the reason for the worse prognosis associated with KRAS mutation. DESIGN: A total of 187 consecutive resected lung adenocarcinomas from our institution from 2008 to 2011 that were diagnosed according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification and screened for KRAS mutations were included in the study. RESULTS: A total of 32% of the adenocarcinomas harbored the KRAS mutation. The median age in the KRAS mutation group was 69 years (range, 43-86 years), and male to female ratio was 1:2.3. The proportion of heavy smokers was significantly higher in tumors with KRAS mutation compared with wild type (83% versus 62%; P = .01). A total of 27% of tumors with KRAS mutation had pleural invasion versus 11% of tumors without KRAS mutation (P = .009). A total of 59 tumor samples were positive for KRAS mutation (25 for G12C, 14 for G12A, 8 for G12V, 7 for G12D, 3 for G12S, and 1 for G12T), and only 3 tumors harbored codon 13 mutations (G13C). Two tumors had double mutations. CONCLUSIONS: KRAS mutations are more common in heavy smokers, and lung adenocarcinomas with KRAS mutation are more likely to invade the visceral pleura. Increased frequency of visceral pleural invasion may explain in part the worse prognosis associated with KRAS mutations.

The utility of p63, p40, and GATA-binding protein 3 immunohistochemistry in diagnosing micropapillary urothelial carcinoma.

Micropapillary urothelial carcinoma (MPUC) is an uncommon variant of urothelial carcinoma (UC) with an aggressive clinical course. There have been limited studies on the UC markers GATA-binding protein 3 (GATA3), p63, and p40 in MPUC. Our study investigated the immunoreactivity of these 3 markers in MPUC compared with conventional UC of different grades and stages. Immunohistochemistry was performed on 62 cases of high-grade urothelial carcinoma (HGUC), 16 low-grade urothelial carcinoma (LGUC), and 20 MPUC. p63 expression was strong and diffuse in all LGUC, significantly decreased in high stage and HGUC, and virtually absent in MPUC. p40 expression was decreased in HGUC and markedly decreased in MPUC relative to LGUC. These results suggest that loss of p63 expression in a UC appears to be associated with adverse features--including cases with micropapillary differentiation. Decreased GATA3 expression was seen frequently in high-grade and high-pathologic stage (≥pT2) tumors but was retained in MPUC cases. The findings of retained GATA3 expression in MPUC, which often shows a loss of expression of other urothelial markers such as p63, may be helpful for determining the origin of micropapillary carcinoma of unknown primary. Compared with the traditional markers p63 and p40, GATA3 is the most sensitive marker of conventional UC and MPUC.

Correlation of EGFR mutation status with predominant histologic subtype of adenocarcinoma according to the new lung adenocarcinoma classification of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society.

CONTEXT: Epidermal growth factor receptor (EGFR) mutations have been identified as predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. OBJECTIVE: To investigate the relationship of EGFR mutation status to the histologic subtype of adenocarcinoma according to the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. DESIGN: We screened EGFR mutation in 200 consecutive lung adenocarcinoma resection specimens diagnosed between 2008 and 2011. RESULTS: Among 200 lung adenocarcinomas, EGFR mutations were identified in 41 tumors (20.5%). The mean age in the EGFR-mutant group was 64.8 years and this group consisted of 78% females and 22% males. Most patients with EGFR-positive lung cancers were never-smokers (51%) as compared to 8% with EGFR-negative cancers (P < .001). The most common mutations identified in our population were deletions in exon 19 (22 patients) and L858R in exon 21 (12 patients). Five patients had double mutations. The predominant pattern of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers as compared to 69% with acinar pattern in EGFR wild-type lung cancers (P < .001). Of 22 minimally invasive adenocarcinomas, 8 (36%) had EGFR mutations, accounting for 20% of adenocarcinomas with EGFR mutations (P < .05). CONCLUSIONS: Based on the new IASLC/ATS/ERS classification, the predominant subtype of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers (P < .001). However, histologic subtype should not be used to exclude patients from tyrosine kinase inhibitor therapy, since EGFR mutations are found in lung adenocarcinomas of other subtypes.

Cytomorphology of intraductal oncocytic papillary neoplasm of the liver.

We describe the first cytology case report of an intraductal oncocytic papillary neoplasm (IOPN) of the liver. A 51-year-old male presented with recurrent cholangitis. Magnetic resonance imaging and endoscopic retrograde cholangiopancreatogram revealed a 1.1 × 0.9 cm polypoid lesion within the left intrahepatic bile duct. Fine-needle aspiration and needle core biopsy (NCB) revealed nests, 3-dimensional or papillary clusters of columnar or cuboidal cells with loss of polarity. The nuclei were uniform with even chromatin, and cytoplasm was granular or vacuolated. No mitosis or necrosis was seen. The cytologic and histologic diagnosis was "consistent with Intraductal Oncocytic Papillary Neoplasm (IOPN), intermediate grade (borderline)." The patient then underwent a left lateral liver segmentectomy. Microscopic examination showed histology similar to the NCB with no stromal invasion identified. Hepatic IOPN poses a diagnostic challenge due to its broad differential diagnoses. Both malignant and non-malignant IOPNs may present with similar clinical symptoms, pathology, histology, cytomorphology, and immunohistochemistry. Hepatic IOPN should be excised as it is a precursor lesion of adenocarcinoma.

Sarcomatoid (spindle cell) carcinoma of the pancreas: A case report and review of the literature.

Sarcomatoid (spindle cell) carcinoma of the pancreas is a rare, high-grade epithelial malignancy composed predominantly or exclusively of spindle cells demonstrating evidence of epithelial derivation, but no features indicative of a specific line of mesenchymal differentiation. The current study presents the case of an 85-year-old Caucasian male with a tumor mass in the body of the pancreas. The individual subsequently underwent a distal pancreatectomy, splenectomy and partial gastrectomy. Microscopic examination of the 3.3-cm mass located in the body of the pancreas revealed a small, but high-grade, adenocarcinomatous component that blended imperceptibly with malignant spindle cells. No light microscopic or immunohistochemical evidence of specific mesenchymal differentiation was identified, and the spindle cells, as in the case of the carcinoma, were diffusely keratin-positive. Sarcomatoid (spindle cell) carcinoma defined in this way rarely presents in the pancreas, with, to the best of our knowledge, only six cases reported in the English literature.

Molecular profiling in non-small cell lung cancer: a step toward personalized medicine.

CONTEXT: Lung carcinoma is the result of sequential accumulation of genetic and epigenetic changes. Lung adenocarcinoma is a heterogeneous disease with diverse somatic mutations, and several of them include the so-called driver mutations, which may serve as "druggable" therapeutic targets. Thus, development of personalized approaches for the treatment of non-small cell lung carcinoma (NSCLC) mandates that pathologists make a precise histologic classification inclusive of routine molecular analysis of such tumors. OBJECTIVE: To address the molecular mechanisms underlying NSCLC and how this knowledge reflects the multidisciplinary approach in the diagnosis and management of these patients. We will also summarize the current available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, and metastatic NSCLC. DATA SOURCES: Peer-reviewed published literature and personal experience. CONCLUSIONS: There are multiple mechanisms involved in the pathogenesis of lung cancer, which operate in parallel and involve pathways of activation and inhibition of various cellular events. Further research is essential to characterize the histologic and mutational profiles of lung carcinomas, which will ultimately translate into improved and more personalized therapeutic management of patients with lung cancer.

Pediatric vascular injuries: acute management and early outcomes.

BACKGROUND: Although uncommon in children, traumatic vascular injuries have the potential for lifelong disability. We reviewed these injuries, their acute management, and early outcomes at a Level I trauma center. METHODS: Retrospective review of patients identified through trauma registry was query of all noniatrogenic vascular injuries in a pediatric population during a 13-year period. Demographics, injury type and management, concomitant injuries, and inpatient outcomes were analyzed. RESULTS: From 1995 to 2008, 8,247 children with traumatic injuries were admitted. Of which 116 (1.4%) sustained 138 significant vascular injuries; 111 arterial and 27 venous. Mean age was 12.7 years ± 4.1 years. Penetrating mechanism was more frequent (57.8%; 67 of 116) than blunt (42.2%; 49 of 116). The overall mean injury severity score was 17.3, of which 12.3 ± 11.7 was for penetrating trauma and 24.1 ± 19.3 for blunt trauma. Thirteen of the 36 patients with torso injuries and one with carotid/jugular injury died. The surviving 102 patients sustained 118 vascular injuries (102 arterial and 16 venous). Of this group, 15 (14.6%) had multiple vascular injuries. There were 23 (22.5%) with torso injuries, 72 (70.6%) with extremity injuries, and 7 (6.9%) with cerebrovascular injuries. Primary repair was the most common arterial repair technique for survivors (25.5%, 26 of 102) and was used more frequently in penetrating trauma (35.0%, 21 of 60) than blunt trauma (12.0%, 5 of 42). Limb salvage was 97.4% (113 of 116). CONCLUSIONS: Pediatric vascular trauma is uncommon. Penetrating mechanism is more common than blunt. Injuries to the torso carry a high mortality. Limb salvage is almost universal.

Time and degree of glycemic derangement are associated with increased mortality in trauma patients in the setting of tight glycemic control.

BACKGROUND: Tight glucose control (TGC) may reduce mortality in critically ill trauma patients. We hypothesize that euglycemia is beneficial, and a measure considering time and degree of hyperglycemia is most associated with mortality. METHODS: We performed a review of intensive care unit trauma patients admitted for more than 3 days between January 2005 and December 2007 on a TGC protocol with a goal of 80 to 110 mg/dL. Hyperglycemic, hypoglycemic, and euglycemic time ranges, and area of interpolated curves above and below 80 to 110 mg/dL were assessed. Associations with mortality were based on logistic regression models adjusted for age, injury severity score, and admission Glasgow Coma Scale score. RESULTS: A total of 546 patients were identified, and 68 (13%) died. Time spent as hyperglycemic (P = .29) and hyperglycemic area under the curve (P = .58) were not associated with mortality; hyperglycemic area/time (P = .01) was associated with mortality. Regarding hypoglycemia, area over the curve (P = .009) and time spent as hypoglycemic (P = .002) were associated with mortality. CONCLUSIONS: TGC prevents prolonged, high degrees of hyperglycemia; avoiding hypoglycemia likely provides mortality benefit for trauma patients.