Cutaneous mucinosis in a patient taking ustekinumab for palmoplantar psoriasis.

Discrete papular lichen myxedematosus (DPLM), asubset of localized lichen myxedematosus, is a rarecutaneous mucinosis of unknown etiology. We reporta case of a 57-year-old woman with palmoplantarpsoriasis who developed DPLM 8 weeks after addingustekinumab to a long-term course of methotrexate.The patient had previously failed 2 prior tumor necrosisfactor (TNF) inhibitors, adalimumab and etanercept.This case demonstrates an association between TNFinhibitor and ustekinumab use in a psoriasis patientand localized lichen myxedematosus for the secondtime in the literature. The presented case is of interestbecause of the rare diagnosis of DPLM, especially inassociation with the start of the anti-IL 12/23 agentustekinumab. The appearance of DPLM in this settingsuggests a possible etiology for the disease.

Anomalous origin of posterior descending artery from left anterior descending in the presence of a diminutive right coronary artery: diagnosed by ECG gated multi-detector CT.

Coronary anomalies are easily detected on ECG gated multi-detector CT which has shown to be superior to conventional angiography is demonstrating their origin and course. We present an unusual case of posterior descending artery arising as the continuation of the left anterior descending artery (LAD) in the presence of a diminutive right coronary artery (RCA). The LAD crossed over the apex and continued its course to the base of the heart in the posterior interventricular groove as PDA. The RCA, although normal in origin, was diminutive and terminated on the lateral wall of the right ventricle. This anomaly has been rarely reported and the previous cases have all been conventional angiographic findings.

Invasive ductal adenocarcinoma arising from pancreatic heterotopia in rectum: case report and review of literature.

Pancreatic heterotopia has been described at several abdominal and intrathoracic locations, most commonly in the stomach and upper part of the small intestine. Its occurrence in the rectum is unusual, and malignant transformation in the rectum has not been reported. We report a case of ductal adenocarcinoma arising in a rectal pancreatic heterotopia in a 42-year-old woman with delayed local recurrence. The tumor was composed of well to moderately differentiated ductal adenocarcinoma infiltrating through the full thickness of the anorectal wall with extension into the vaginal septum. A focus of ectopic pancreas consisting of exocrine acini and small ducts adjacent to the tumor with some ducts showing mild to severe dysplasia reminiscent of pancreatic intraepithelial neoplasia was also observed. Although our literature search found 31 documented reports of tumors arising in the heterotopic pancreas, the present case is the first case of ductal adenocarcinoma arising in a focus of pancreatic heterotopia in the rectum.

Paraganglioma syndrome type 1 in a patient with Carney-Stratakis syndrome.

BACKGROUND: A 33-year-old man was referred to a specialist center with a left neck mass and hypertension. The patient underwent surgery, which confirmed a malignant neck paraganglioma with metastasis to a cervical lymph node. He had no family history of carotid body tumors or pheochromocytoma. INVESTIGATIONS: Measurements of plasma free metanephrines and chromogranin A; radiographic evaluations with CT, (18)F-fluorodeoxyglucose PET and (123)I-labeled metaiodobenzylguanidine scan; gene analysis for mutations in the SDHD and the KIT gene. DIAGNOSIS: Paraganglioma syndrome type 1 in a patient with a paraganglioma, bilateral pheochromocytomas and a gastrointestinal stromal tumor with a somatic Asp579del KIT mutation. MANAGEMENT: The patient underwent surgical excision of all tumors after adequate preparation with alpha and beta blockers. Blood pressure normalized after surgery. The patient is examined regularly with biochemical and radiographic studies, and his follow-up is expected to last throughout life.

Anti-phosphorylated histone H3 expression in Barrett's esophagus, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma.

The high interobserver variability in grading dysplasia in Barrett's esophagus demands a biomarker that can be applied in routine surgical pathology practice. Immunohistochemistry for phosphorylated histone H3 is a reliable marker of identifying mitotic figures and has not been evaluated in Barrett's esophagus-associated neoplastic lesions. We retrospectively studied the expression of phosphorylated histone H3 in 88 endoscopic biopsy samples of Barrett's esophagus without dysplasia (n=19), indefinite for dysplasia (n=11), low-grade dysplasia (n=27), high-grade dysplasia (n=19), or adenocarcinoma (n=12) from a sample of 54 patients. The samples were included after consensus diagnosis of two gastrointestinal pathologists on the hematoxylin-eosin (HE)-stained sections. Anti-phosphorylated histone H3-labeled mitotic figures were counted per 10 consecutive high-power fields (HPFs) in three distinct regions: surface epithelium, upper 2/3, and lower 1/3 of the crypts. Anti-phosphorylated histone H3-labeled mitotic counts for the three compartments of the crypts and the total scores for Barrett's esophagus, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma were compared using the Mann-Whitney U test. For each compartment, the number of anti-phosphorylated histone H3-positive nuclei was higher in low-grade dysplasia than in Barrett's esophagus without dysplasia or indefinite for dysplasia (P<0.001), but no difference was found between Barrett's esophagus without dysplasia and indefinite for dysplasia. High-grade dysplasia biopsies had significantly more anti-phosphorylated histone H3-labeled mitotic figures in the surface epithelium than the low-grade dysplasia (P<0.001). Adenocarcinoma had higher anti-phosphorylated histone H3-labeled mitotic figures than the high-grade dysplasia (P<0.001). Our data support the previous findings of expansion of the proliferative zone and importance of surface mitotic figure in the progression of Barrett's esophagus-low-grade dysplasia-high-grade dysplasia. In addition, phosphorylated histone H3 is a potential supportive marker to histology in differentiating low-grade dysplasia from indefinite for dysplasia and high-grade dysplasia from adenocarcinoma in the mucosal biopsy samples.

Clinical, pathologic, and molecular features of early-onset colorectal carcinoma.

The incidence of colorectal carcinoma has increased among patients <40 years of age for unclear reasons. In this study, we describe the clinical, pathologic, and molecular features of colorectal carcinomas that developed in young patients. We compiled a study group of 24 patients <40 years of age with colorectal carcinoma, and 45 patients > or =40 years of age served as controls. Cases were evaluated for clinical risk factors of malignancy and pathologic features predictive of outcome. The tumors were immunohistochemically stained for O6-methylguanine methyltransferase, MLH-1, MSH-2, MSH-6, beta-catenin, chemokine (C-X-C motif) receptor 4, epidermal growth factor receptor, TP53, p16, survivin, and alpha-methylacyl-CoA racemase; assessed for microsatellite instability and mutations in beta-catenin, APC, EGFR, PIK3CA, KRAS, and BRAF; evaluated for micro-RNA expression (miR-21, miR-20a, miR-183, miR-192, miR-145, miR-106a, miR-181b, and miR-203); and examined for evidence of human papillomavirus infection. One study patient each had ulcerative colitis and hereditary nonpolyposis colorectal cancer. Ninety-two percent of tumors from young patients occurred in the distal colon (P=0.006), particularly the rectum (58%, P=0.02), and 75% were stage III or IV. Tumors from young patients showed more frequent lymphovascular (81%, P=0.03) and/or venous (48%, P=0.003) invasion, an infiltrative growth pattern (81%, P=0.03), and alpha-methylacyl-CoA racemase expression (83%, P=0.02) compared with controls. Carcinomas in this group showed significantly increased expression of miR-21, miR-20a, miR-145, miR-181b, and miR-203 (P< or =0.005 for all comparisons with controls). These results indicate that early-onset carcinomas commonly show pathologic features associated with aggressive behavior. Posttranslational regulation of mRNA and subsequent protein expression may be particularly important to the development of colorectal carcinomas in young patients.

T cell- and B cell-independent adaptive immunity mediated by natural killer cells.

It is commonly believed that only T lymphocytes and B lymphocytes expressing recombination-dependent antigen-specific receptors mediate contact hypersensitivity responses to haptens. Here we found that mice devoid of T cells and B cells demonstrated substantial contact hypersensitivity responses to 2,4-dinitrofluorobenzene and oxazolone. Those responses were adaptive in nature, as they persisted for at least 4 weeks and were elicited only by haptens to which mice were previously sensitized. No contact hypersensitivity was induced in mice lacking all lymphocytes, including natural killer cells. Contact hypersensitivity responses were acquired by such mice after adoptive transfer of natural killer cells from sensitized donors. Transferable hapten-specific memory resided in a Ly49C-I(+) natural killer subpopulation localized specifically in donor livers. These observations indicate that natural killer cells can mediate long-lived, antigen-specific adaptive recall responses independent of B cells and T cells.

Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues.

Leukotriene B4 (LTB4) is a potent chemoattractant for myeloid leukocytes, which express BLT1, the high-affinity receptor for LTB4. We report here that BLT1 is induced substantially in CD8+ effector T cells and at lower amounts in CD8+ central memory T cells. LTB4 elicited BLT1-dependent chemotaxis in effector cells, but not in naive or central memory cells. Intravital microscopy showed that BLT1 signaling induced rapid integrin-mediated arrest of rolling effector and central memory cells in postcapillary venules. In competitive homing experiments, wild-type effector cells were three times more efficient at migrating to the inflamed peritoneal cavity than were BLT-deficient effector cells. These results identify LTB4-BLT1 as a potent nonchemokine pathway for cytotoxic effector cell traffic.

Naive T cell recruitment to nonlymphoid tissues: a role for endothelium-expressed CC chemokine ligand 21 in autoimmune disease and lymphoid neogenesis.

Naive T cells are usually excluded from nonlymphoid tissues. Only when such tertiary tissues are subjected to chronic inflammation, such as in some (but not all) autoimmune diseases, are naive T cells recruited to these sites. We show that the CCR7 ligand CC chemokine ligand (CCL)21 is sufficient for attracting naive T cells into tertiary organs. We performed intravital microscopy of cremaster muscle venules in T-GFP mice, in which naive T cells express green fluorescent protein (GFP). GFP(+) cells underwent selectin-dependent rolling, but no firm adherence (sticking). Superfusion with CCL21, but not CXC chemokine ligand 12, induced integrin-dependent sticking of GFP(+) cells. Moreover, CCL21 rapidly elicited accumulation of naive T cells into sterile s.c. air pouches. Interestingly, a second CCR7 ligand, CCL19, triggered T cell sticking in cremaster muscle venules, but failed to induce extravasation in air pouches. Immunohistochemistry studies implicate ectopic expression of CCL21 as a mechanism for naive T cell traffic in human autoimmune diseases. Most blood vessels in tissue samples from patients with rheumatoid arthritis (85 +/- 10%) and ulcerative colitis (66 +/- 1%) expressed CCL21, and many perivascular CD45RA(+) naive T cells were found in these tissues, but not in psoriasis, where CCL21(+) vessels were rare (17 +/- 1%). These results identify endothelial CCL21 expression as an important determinant for naive T cell migration to tertiary tissues, and suggest the CCL21/CCR7 pathway as a therapeutic target in diseases that are associated with naive T cell recruitment.