Retinoblastoma. The relationship of proliferating cells to blood vessels

In 150 retinoblastomas the authors found a uniform thickness of the cuff of viable retinoblastoma cells that surrounds blood vessels. The mean thickness was 98.7 microns with a standard deviation of 11.9 microns. The cross-sectional area of the cuff was negatively correlated with the mitotic activity in the cuff and positively correlated with the diameter of the central vessel. The mitotic activity in the cuff of cells was inversely related to the distance from the central blood vessel. When the cuff was divided into three concentric rings, the inner ring contained a mean of 6.2 mitotic figures, the middle ring contained a mean of 2.9 mitotic figures, and the outer ring contained a mean of 0.6 mitotic figures. This pattern of growth is similar to that observed in other rapidly growing neoplasms in humans and experimental animals. In these tumors this pattern results from reduction in oxygen tension with increased distance from the central blood vessel.     

Comparison between the prevalence and treatment of wheezing and coughing in Brampton and Mississauga children

An analysis of hospital discharge data showed that Brampton children 4 years and under had higher rates of hospital admissions for asthma, bronchitis and upper respiratory infections than children in the same age group living in Mississauga and other Ontario municipalities. The present study was done to compare the prevalence and treatment of wheezing and coughing between Brampton and Mississauga children 4 and 5 years of age. The study showed that increased use of pediatricians on the part of Mississauga children in comparison to Brampton children resulted in a higher proportion being placed on anti-asthmatic medications even though the underlying prevalence rate of wheezing and coughing was the same in the two samples. Further study is required to determine whether differences in primary care between the two samples can explain a two-fold increase in hospital admission rates for lower respiratory illness among Brampton preschool children in comparison to their counterparts in Mississauga.     

Overexpression/amplification of HER-2/neu is uncommon in hepatocellular carcinoma

BACKGROUND： Hepatocellular carcinoma （HCC） is one of the most prevalent fatal cancers in the world. Despite advances in early diagnosis and improvements in surgical techniques, the survival of patients with HCC even after resection is poor because of the high incidence of recurrences. Therefore, the identification of prognostic factors may be helpful in the development of new treatment protocols. AIMS： To investigate HER-2/neu status in HCC by immunohistochemistry （IHC） and fluorescence in situ hybridisation （FISH）, and to explore the possibility of using trastuzumab in the treatment of HCC. METH ODS： Eight hundred and sixty eight surgical samples from patients with primary HCC were examined for their HER-2/neu status. IHC for HER-2/neu was performed with the HercepTest kit; FISH analysis was performed with the PathVysion HER-2 DNA probe kit. The correlations between HER-2/neu overexpression and clinicopathological characteristics were analysed statistically. RESULTS： HER-2/neu overexpression was detected in 21 （2.42%） of the 868 primary HCCs. Only one specimen showed HER-2/neu gene amplification by FISH. No significant associations were found between HER-2/neu overexpression and the clinicopathological parameters. CONCLUSIONS： There is a low frequency of HER-2/neu overexpression/amplification in HCC. There appears to be no role for HER-2/neu as a prognostic marker and no benefit of anti-HER-2/neu trastuzumab treatment in patients with HCC.     

Acute pustulosis of the legs in diverticulitis with sigmoid stenosis: an overlap between bowel-associated dermatosis–arthritis syndrome and pustular pyoderma gangrenosum

BACKGROUND: Bowel-associated dermatosis-arthritis syndrome denotes the occurrence of diarrhoea with arthritis and skin lesions related to bowel disease with or without bowel bypass. In this condition, the histological finding of cutaneous aseptic neutrophilic cell infiltrate is non-specific and common to a wide spectrum of neutrophilic dermatoses, including pyoderma gangrenosum. OBSERVATION: We describe a 78-year-old woman with fever, abdominal discomfort and arthralgias, who developed grouped pustular lesions on her shins with histologically spongiform pustule formation. Aetiological assessment disclosed diverticular disease with sigmoid stenosis. CONCLUSION: Although clinical and histological features in our case fit the diagnosis of bowel-associated dermatosis-arthritis syndrome, they may also correspond to a pustular variant of pyoderma gangrenosum. Our observation raises the question of the nosological classification of bowel-associated dermatosis-arthritis syndrome within the spectrum of neutrophilic diseases.     

The Intestinal Absorption of a Prodrug of the mGlu2/3 Receptor Agonist LY354740 is Mediated by PEPT1: In Situ Rat Intestinal Perfusion Studies

LY354740 is a potent mGlu2/3 agonist with a limited oral bioavailability. Its alanyl prodrug, LY544344, showed high affinity to the intestinal peptide transporter PEPT1, and improved the oral bioavailability of LY354740 in various animal models. The aim of the present study was to investigate the mechanism of in vivo absorption of the dipeptidic prodrug LY544344. The permeabilities of LY544344 and LY354740 were examined in the rat in situ single‐pass intestinal perfusion model. The intestinal absorptive flux of LY354740 was shown to be very low in comparison with LY544344. The absorptive flux of LY544344 could best be described by a Michaelis–Menten process in parallel with a linear process. The estimated parameters were: J_max = 26.7 × 10^?5 µmol/(cm²‐s), K_m = 2.6 mM. The absorptive permeability of LY544344 was reduced to approximately 5% of control in the presence of excess Gly‐Sar, a known PEPT1 substrate. Intracellular accumulation of LY354740 and LY544344, estimated postperfusion, showed high levels of LY354740 over LY544344 at all perfusate concentrations studied. However, there was a decline in the intracellular ratio of LY354740 to LY544344 at higher concentrations, suggesting that the metabolic activation to release LY354740 is saturable. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1574–1581, 2010     

Ciliated respiratory-like epithelium forming cystic conjunctival lesions in a patient with Stevens-Johnson syndrome.

A woman with severe cicatricial conjunctival changes secondary to allopurinol-induced Stevens-Johnson syndrome developed bilateral palpebral conjunctival cysts. Pathologic examination of these lesions revealed respiratory-like pseudostratified ciliated epithelium in the walls of several cysts of one eye. To our knowledge, this is the first report of this phenomenon.     

Desmoplastic primitive neuroectodermal tumor with divergent differentiation. Broadening the spectrum of desmoplastic infantile neuroepithelial tumors.

We report an unusual large, multicystic, posterior fossa neuroepithelial neoplasm involving the cerebellum, brain-stem, and quadrigeminal cistern of a 9-month-old girl. The neoplasm consisted of variably sized, sharply demarcated nests of small cells with a high nuclear-cytoplasmic ratio and moderately basophilic nuclei, embedded in a desmoplastic, immature-appearing, mesenchymal stroma. The nests contained mitoses but none were seen in the stroma. Glial fibrillary acidic protein (GFAP), neurofilament protein, synaptophysin, and cytokeratin (AE-1) were expressed in the nests. Mesenchymal cells were negative for neural markers but positive for vimentin and desmin. The neoplasm was interpreted as a mixed mesenchymal and primitive neuroectodermal tumor (PNET) with histologic features reminiscent of a recently described intraabdominal desmoplastic small cell tumor. The tumor responded poorly to chemotherapy and a second operation was performed 1 year later. The second specimen bore no resemblance to the original and consisted of epithelial-like nests and clusters of neoplastic cells frequently interrupted by sinusoidal vessels. Tumor cells had medium-sized vesicular nuclei with small nucleoli, and a granular cytoplasm. Occasional less cellular islands of neuropil-like tissue contained larger cells having eccentric, vesicular nuclei with prominent nucleoli and abundant pink cytoplasm. Mitoses were not conspicuous. Many cells expressed synaptophysin, neurofilament protein, and GFAP. Neurofilament protein was strongly positive in the larger, neuron-like cells and synaptophysin stained the neuropil-like areas strongly but was less prominent in the neuronal perikarya. Unexpectedly, the neuropil-like areas expressed epithelial membrane antigen, whereas the neuronal cells were negative for chromogranin A. The peculiar histologic picture, combination of phenotypic markers, and remarkable biologic behavior of this unusual tumor defies classification according to existing nomenclature and exemplifies the broad range of phenotypes expressed by primitive neuro-epithelial neoplasms.     

Neurofibromatosis type 1: brain stem tumours

We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. Received: 21 November 1996 Accepted: 22 December 1996     

Sebaceous carcinoma of the head and neck. Case report and literature review.

Sebaceous carcinoma is uncommon, with fewer than 400 cases reported. Usually, lesions arise in the meibomian glands of the eyelid; however, extraocular lesions within the head and neck have been reported. Regardless of the location, sebaceous malignancies must be considered aggressive neoplasms with a potential for regional and distant metastasis. Diagnosis may be difficult, given the low incidence and inconsistencies in histopathologic classification. Recently, needle aspiration cytologic characteristics have been delineated, with this procedure becoming increasingly useful in establishing the diagnosis. Treatment requires wide surgical excision with removal of involved regional lymph nodes. Opinions are divided regarding the use of postoperative irradiation or chemotherapy. Records of all patients with sebaceous carcinoma of the head and neck treated at UCLA Medical Center, Los Angeles, over the last 35 years were reviewed. The clinical and pathologic features are discussed, and the literature is summarized.