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Cutaneous Rosai-Dorfman disease (RDD) can be difficult to distinguish from other non-Langerhans cell histiocytoses, particularly xanthogranuloma (XG). Pathologists use S100 immunoreactivity, abundant plasma cells, and the presence of emperipolesis to distinguish RDD from XG. However, S100 expression has been reported in XG and, in practice, we have occasionally observed emperipolesis in cases that were otherwise clinically and pathologically consistent with XG. We present 10 cases of XG with emperipolesis and variable S100 immunoreactivity. Histologically, 7 cases were most in keeping with XG, and a histologic differential of XG versus RDD was raised in the remaining 3 cases. All 10 cases were clinically consistent with XG. Notably, none of these cases showed abundant plasma cells. Nine cases showed variable S100 immunostaining, ranging from focal/weak expression, to focal/strong, diffuse/moderate, and diffuse/strong expression. Histiocytes in all cases were CD68 positive and CD1a negative. We conclude that emperipolesis and S100 expression in a skin biopsy cannot reliably distinguish XG from cutaneous manifestations of RDD. Clinical correlations are essential, as are histologic clues to a diagnosis of classic XG that include an abundance of foamy mononuclear cells, Touton giant cells, and an absence of pale-stained histiocytes, abundant plasma cells, fibrosis, or vascular proliferation.

We report the second case of cutaneous myelofibrosis with a documented JAK2 activating mutation involving the scalp of a 67-year-old woman with primary myelofibrosis in her marrow. In contrast to the previous case, the biopsy revealed extensive lesional collagen deposition and closely mimicked a fibrohistiocytic proliferation. Similar rare lesions occurring in the setting of myeloproliferative neoplasms have been called sclerosing extramedullary hematopoietic tumors. These entities appear histomorphologically and etiologically distinct from extramedullary hematopoiesis, and their diagnosis should prompt the workup for a myeloproliferative neoplasm in the absence of an antecedent diagnosis. The presence of the JAK2 mutation in our case confirmed that the lesions represented skin involvement by a neoplastic myeloid proliferation and not compensatory extramedullary hematopoiesis. Our patient died of disease several months following the appearance of her lesions, which is in keeping with other reports that suggest that cutaneous myelofibrosis may serve as an independent poor prognostic sign in otherwise advanced primary myelofibrosis. A review of the literature further emphasizes the importance of distinguishing this entity from mesenchymal neoplasms and acute myeloid leukemia involving the skin.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and primary cutaneous gamma delta T-cell lymphoma (PCGD-TCL) were initially both classified as subcutaneous panniculitis-like T-cell lymphoma. In 2008, SPTCL with alpha-beta T-cell receptor subtype was separated from primary cutaneous gamma delta T-cell lymphomas (PCGD-TCL). We report four pediatric cases that demonstrate the heterogeneity of each disease and show that PCGD-TCL in children can have an indolent course, whereas SPTCL can behave aggressively. Three patients had spontaneous, durable remissions without treatment, whereas the one patient with disease progression was treated successfully. Watchful waiting may thus be appropriate for initial management of children.

We report a fatal case of invasive fungal sinusitis caused by Cunninghamella echinulata in a febrile, neutropenic 15-year-old male with relapsing acute leukemia. The isolate was recovered from a nasal biopsy from the right middle meatus, and microscopic examination of the tissue revealed angioinvasion and necrosis. Human infection caused by this organism has not been well documented; however, this report alerts us to its life-threatening potential.

Background: Activated Stat3 is an important mediator of oncogenesis in the colon. To test the hypothesis that select Stat activation and/or the pattern of Stat activation serves as a marker for early neoplastic transformation, we examined the distribution of activated Stat1(pStat1), Stat6(pStat6), and Stat3(pStat3) in colitis along the continuum of inactive disease to colitis-associated cancer. Methods: Tissue microarrays were constructed using colonoscopy biopsy and surgical specimens from 67 patients with ulcerative colitis or Crohn's colitis and 11 controls. In all, 111 sets of samples were analyzed representing normal tissue, active disease, low-grade dysplasia, high-grade dysplasia, and colitis-associated cancer. Immunohistochemistry to detect pStat1, pStat6, and pStat3 in colonic epithelial and mucosal immune cells was then correlated with clinical and pathological data (tumor location, histologic type, grade, and lymph node involvement). Results: In 50% of colitis-associated cancer samples, pStat3 was detected prominently in epithelial cells, where it was routinely associated with intense pStat3 staining in surrounding immune cells. Stat3 activation was greater in low-grade tumors than in high-grade ones (P < 0.05). pStat6 expression was more common in normal tissues than in colitis-associated cancer (P < 0.05). pStat1 was detected in a small subset of immune cells in patients with chronic inactive and active colitis, low- and high-grade dysplasia, but not in colitis-associated cancer. Conclusions: pStat3 may be a marker for neoplastic transformation in patients with colitis. A shift from predominant immune cell Stat6 activation to Stat3 activation accompanies the onset of dysplasia with concomitant increased epithelial cell Stat3 activation in a subset of patients. (Inflamm Bowel Dis 2011;)

The authors address a group of loosely associated, characteristically benign soft tissue neoplasms that exhibit partial myoid differentiation. The entities share similarities in morphology and in nomenclature that have historically created confusion. The authors attempt to clarify the distinct architectural patterns and the corresponding immunophenotypic and ultrastructural features that distinguish myofibroma, myopericytoma, myoepithelioma, and myofibroblastoma.

Leucine, as an essential amino acid and activator of mTOR (mammalian target of rapamycin), promotes protein synthesis and suppresses protein catabolism. However, the effect of leucine on overall glucose and energy metabolism remains unclear, and whether leucine has beneficial effects as a long-term dietary supplement has not been examined. In the present study, we doubled dietary leucine intake via leucine-containing drinking water in mice with free excess to either a rodent chow or a high-fat diet (HFD). While it produced no major metabolic effects in chow-fed mice, increasing leucine intake resulted in up to 32% reduction of weight gain (P < 0.05) and a 25% decrease in adiposity (P < 0.01) in HFD-fed mice. The reduction of adiposity resulted from increased resting energy expenditure associated with increased expression of uncoupling protein 3 in brown and white adipose tissues and in skeletal muscle, while food intake was not decreased. Increasing leucine intake also prevented HFD-induced hyperglycemia, which was associated with improved insulin sensitivity, decreased plasma concentrations of glucagon and glucogenic amino acids, and downregulation of hepatic glucose-6-phosphatase. Additionally, plasma levels of total and LDL cholesterol were decreased by 27% (P < 0.001) and 53% (P < 0.001), respectively, in leucine supplemented HFD-fed mice compared with the control mice fed the same diet. The reduction in cholesterol levels was largely independent of leucine-induced changes in adiposity. In conclusion, increases in dietary leucine intake substantially decrease diet-induced obesity, hyperglycemia, and hypercholesterolemia in mice with ad libitum consumption of HFD likely via multiple mechanisms.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and primary cutaneous gamma delta T-cell lymphoma (PCGD-TCL) were initially both classified as subcutaneous panniculitis-like T-cell lymphoma. In 2008, SPTCL with alpha-beta T-cell receptor subtype was separated from primary cutaneous gamma delta T-cell lymphomas (PCGD-TCL). We report four pediatric cases that demonstrate the heterogeneity of each disease and show that PCGD-TCL in children can have an indolent course, whereas SPTCL can behave aggressively. Three patients had spontaneous, durable remissions without treatment, whereas the one patient with disease progression was treated successfully. Watchful waiting may thus be appropriate for initial management of children.

Rarely are the viral cytopathic characteristic effects of herpes simplex virus (HSV) encountered in urinary cytopathology (Fig. C-1). In voided urine, such morphology is often attributed to an infection of the external genitalia. In the absence of cutaneous manifestations, however, diagnosis of HSV related pathology can suggest asymptomatic viral shedding and can potentially alert clinicians to the rarer manifestations of HSV urethritis 1,2 and HSV cystitis 3–5 . Presentations of the latter may run the gamut from an unsuspected cause of dysuria or urinary retention to life-threatening hemorrhagic cystitis in an immunocompromised host. 4,5 We present a rare finding of cellular changes consistent with HSV infection in a catheterized urine specimen collected from a 74-year-old woman with hematuria. The patient, who had a history of chronic obstructive pulmonary disease, was presented to the emergency department with dyspnea and was treated for community acquired pneumonia. Over the course of her hospitalization, she developed respiratory failure and required mechanical ventilation with steroid pulse therapy. She subsequently developed hematuria. Urine bacterial cultures were negative and microscopic examination of a catheterized urine specimen revealed frequent atypical urothelial cells amidst a background of acute inflammation and abundant erythrocytes. The abnormal cells exhibited enlarged, ground

The mechanism of epitaxial growth has been investigated by the study of the nucleation process and early growth stages of single-crystal gold and silver films in (100) and (111) orientations. Films were grown by evaporation on vacuum-cleaved NaCl and mica cleavage planes, and on single-crystal NaCl films deposited on fresh mica cleavage surfaces. In the earliest observable period of growth, nuclei have been found to be as small as 5 A in size. These nuclei, which contain 10–20 atoms, strongly indicate that growth proceeds continuously from initial nuclei consisting of only a few atoms. In subsequent stages of growth, coalescence processes occur which are governed by mobility of atoms and clusters on the substrate material. Mobility is highest on the evaporated film substrates, and leads to a decrease in nucleation density as a function of time because of rapid coalescence of the mobile nuclei. Nucleation rates have been measured as a function of substrate temperature and activation energies determined for the nucleation process.