A Case of Primary Signet-Ring Cell/Histiocytoid Carcinoma of the Eyelid: Immunohistochemical Comparison With the Normal Sweat Gland and Review of the Literature

Primary signet-ring cell/histiocytoid carcinomas of the eyelid are extremely rare tumors considered to originate from sweat glands. Here, we report the case of a 72-year-old man diagnosed with primary signet-ring cell/histiocytoid carcinoma of the eyelid and present immunohistochemical analyses of the eyelid apocrine gland (Moll gland) and apocrine and eccrine sweat glands of perineum and axilla. Widespread infiltration of tumor cells with signet-ring cell or histiocytoid appearance was observed in his left eyelid, orbit, and periocular lesion. Tumor cells expressed mucins and showed immunoreactivity that was similar to that of the Moll gland: MUC6 (+), GlcNAc alpha 1 -> 4Gal -> R(-), MUC2(-), MUC5AC(-), GCDFP15(+), CD15(+), S100(-), CK7(+), CK20(-), ER(+), PgR (+), HER2(-), E-cadherin(+), p63(-), PSA(-), and TTF-1(-). The tumor cells differed from those of perineal and axillary apocrine and eccrine sweat glands, which were MUC6(-). The Moll gland was ER(-) and PgR(-), whereas perineal and axillar apocrine sweat glands were ER(+) and PgR(+), and perineal and axillary eccrine sweat glands were ER(+) and PgR(-). The tumor showed characteristics similar to that of the eyelid Moll gland, which is demonstrated to be an apocrine gland with a protein expression distinct from that of other apocrine glands. MUC6 and GCDFP15 expression are useful in identifying the Moll gland immunophenotype and GCDFP15, ER and PgR expression are useful in distinguishing primary eyelid signet-ring/histocytoid carcinoma from gastrointestinal malignancies.ArticleAMERICAN JOURNAL OF DERMATOPATHOLOGY. 34(8):E139-E145 (2012)journal articl

Intestinal microbiota in human health and disease: the impact of probiotics

The complex communities of microorganisms that colonise the human gastrointestinal tract play an important role in human health. The development of culture-independent molecular techniques has provided new insights in the composition and diversity of the intestinal microbiota. Here, we summarise the present state of the art on the intestinal microbiota with specific attention for the application of high-throughput functional microbiomic approaches to determine the contribution of the intestinal microbiota to human health. Moreover, we review the association between dysbiosis of the microbiota and both intestinal and extra-intestinal diseases. Finally, we discuss the potential of probiotic microorganism to modulate the intestinal microbiota and thereby contribute to health and well-being. The effects of probiotic consumption on the intestinal microbiota are addressed, as well as the development of tailor-made probiotics designed for specific aberrations that are associated with microbial dysbiosis

Most colitis associated carcinomas lack expression of LGR5: a preliminary study with implications for unique pathways of carcinogenesis compared to sporadic colorectal carcinoma

Abstract Background Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a component of the Wnt receptor complex, is thought to lineage label gastric and intestinal stem cells. LGR5 expression is increased in colorectal carcinoma (CRC) compared to normal tissue. Colitis associated colorectal adenocarcinoma (CAC) often shows distinct morphologic and molecular phenotypes compared to sporadic cases. However, the expression profile of LGR5, and by extension the potential role of an intestinal stem cell phenotype, has not been well described in a series of human CAC. Method RNA in situ hybridization (ISH) for LGR5 expression on 30 CACs (12 cases with conventional morphology and 18 cases with non-conventional type morphology) from 29 inflammatory bowel disease (IBD) patients was performed and compared the expression profile to a control group of 10 sporadic CRCs. Immunohistochemistry for beta-catenin and SATB2 was performed on the 30 CACs. Result LGR5 was positive in 30% (9/30) of CAC cases and 90% (9/10) of sporadic CRCs (p = 0.002). A large majority (89%) of LGR5 positive CACs were of the conventional histologic type, and conventional type CAC showed a significantly higher LGR5 score (median 3.0; interquartile range 1.75–3.25) than non-conventional type CAC (median 1.5; interquartile range 1.00–2.00) (p = 0.034). CAC with conventional morphology did have a lower level of LGR5 expression than sporadic CRC. Sporadic CRCs showed a significantly higher LGR5 level score than non-conventional type CACs (p < 0.001). Nuclear translocation of beta-catenin was strongly associated with LGR5 expression (p = 0.003), however no significant association was identified between SATB2 expression and LGR5 expression status in CACs. Conclusion These findings suggest that the wider spectrum of tumor morphology in CAC may be associated with absence of a LGR5-expressing intestinal stem cell phenotype

Alpha-Fetoprotein-Producing Early Gastric Cancer with Intramucosal Hepatoid and Fetal Enteric Differentiation

Alpha-fetoprotein (AFP)-producing gastric carcinomas (AFPGCs) are relatively rare tumors known to have a poor prognosis and commonly found as advanced lesions. Histologically, AFPGCs have been described as having hepatoid and fetal enteric (enteroblastic) morphology and are associated with conventional adenocarcinomas. Prior studies reported a hepatoid component present only in invasive areas and hypothesized that AFPGCs may develop hepatoid features during the process of tumor invasion. We report three cases of AFP-producing early gastric cancer which had an intramucosal hepatoid component. Immunohistochemistry showed that the hepatoid component was diffusely immunoreactive for SALL4, AFP, arginase-1, and HepPar1, and focally for CDX2 and PDX1. An intramucosal transition between the hepatoid component and conventional intramucosal adenocarcinoma was identified. Two patients also had a coexistent fetal enteric component, which was admixed with a hepatoid component. Although at an early stage one patient subsequently developed liver metastasis and a second patient was suspected of having liver metastasis, these were not biopsy-proven. The latter patient had a previous history of hepatocellular carcinoma (HCC) and SALL4 was used on the HCC to distinguish metastatic/further HCC from a gastric metastatic primary with hepatoid differentiation

A preliminary study of IgG4 expression and its prognostic significance in oral squamous cell carcinoma

Abstract Background IgG4, which plays a pivotal role in the progression of phenotypically diverse tumors, serves as a prognostic marker because of its influence on cancer immunity. Nevertheless, the functions of IgG4 in tongue squamous cell carcinoma (TSCC) remained to be identified. Methods To evaluate the significance of IgG4 expression in TSCC, we performed immunohistochemical analysis of patients with TSCC (n = 50) to evaluate the correlation of IgG4 expression with patients’ clinicopathological features and prognoses. Results Higher IgG4 expression detected in TSCC tissues was associated with the less advanced mode of invasion (Yamamoto-Kohama [YK] 1–3) (P = 0.031) and with well-differentiated TSCC (P = 0.077). Kaplan–Meier analyses revealed that the higher IgG4 expression group exhibited better prognosis indicated by overall survival (OS) (P = 0.04) and recurrence-free survival (RFS) (P = 0.016). Univariate analysis of OS indicated that IgG4 expression was associated with longer OS (P = 0.061), and multivariate analysis of RFS revealed that IgG4 expression served as an independent prognostic factor for longer RFS (P = 0.005). Conclusion These results indicate that relatively higher IgG4 levels serve as a favorable prognostic factor for TSCC

IgG4-Related Airway Involvement Which Developed in a Patient Receiving Corticosteroid Therapy for Autoimmune Pancreatitis

A 66-year-old man was diagnosed with autoimmune pancreatitis in February 2009 and started 40 mg of oral prednisolone followed by a maintenance dose of 5 mg daily. The patient developed a cough in October 2010 and visited our division. He had a high serum concentration of immunoglobulin (Ig) G4 and his chest computed tomography showed airway stenosis without bilateral hilar lymphadenopathy (BHL). The bronchial biopsy specimens revealed lymphoplasmacytic infiltrations with IgG4-positive/IgG-positive plasma cells of more than 50%. Thus, we diagnosed the airway lesion with IgG4-related airway involvement. This is the first report of a patient with IgG4-related airway involvement without BHL.ArticleINTERNAL MEDICINE. 50(24):3023-3026 (2011)journal articl