Rapidly progressing giant invasive prolactinoma.

OBJECTIVE: We report an extremely rare case of a giant invasive prolactinoma presenting as a nasopharyngeal tumour. METHOD: Case report and literature review regarding giant prolactinoma. RESULTS: Giant prolactinoma is a rare form of prolactinoma which accounts for 0.5-4.4 per cent of all pituitary tumours. It is more common in men and generally presents with symptoms of endocrine disturbance or neurological deficit. CONCLUSION: To our knowledge, this is the first report of giant prolactinoma presenting with symptoms of sinusitis and nasopharyngeal tumour.

Ossifying fibromyxoid tumour of the sphenoid sinus.

INTRODUCTION: Ossifying fibromyxoid tumour is a recently described, rare but morphologically distinctive soft tissue neoplasm characterised by a combination of myxoid and/or fibrous stroma with areas of ossification. Although most authors postulate a neuroectodermal origin for this peculiar tumour, there is no agreement in the literature regarding its histopathogenesis. To our knowledge, this is the first reported case of ossifying fibromyxoid tumour involving the sphenoid sinus. HISTOLOGICAL FINDINGS: Tumour of low cell density, composed of small, spindle-shaped or stellate cells with small, irregular nuclei set in a fibromyxoid stroma. MANAGEMENT: Following discussion at the skull base multidisciplinary team meeting, a combined surgical team including an otorhinolaryngologist and a neurosurgeon carried out resection of the lesion, using an endoscopic transnasal approach, followed by reconstruction of the defect. CONCLUSIONS: An awareness of the distinctive histopathological features of ossifying fibromyxoid tumour, and of its clinical effects, is crucial to establishing a definitive diagnosis and thereby instituting appropriate management. This case report also reinforces the evolving role of the endoscopic transnasal approach in the management of inflammatory and neoplastic disease involving the skull base. This is increasingly being made possible by close collaboration between multiple surgical specialties, including otorhinolaryngology and neurosurgery.

Sex cord stromal testicular tumors: a clinical series--uniformly stage I disease.

PURPOSE: Sex cord stromal testicular tumors are rare. Historically 10% of lesions are said to be malignant but to our knowledge there are no clinical or histological features that can accurately predict potential malignant behavior. Because of this, groups at some centers have advocated prophylactic retroperitoneal lymph node dissection in patients with clinical stage I disease. We reviewed our experience with these tumors to determine whether this policy is justified. MATERIALS AND METHODS: We retrospectively reviewed the records of all 38 men older than 18 years with sex cord stromal testicular tumors who were referred to the Wessex regional cancer center for treatment or pathological review during the 25-year period of 1982 to 2006. We then compared our series with a malignant sex cord stromal testicular tumor database generated from the world literature. RESULTS: All Wessex patients were treated with excision of the primary tumor alone and metastatic disease developed in none. All remained disease-free with an overall median survival of 6.8 years (range 1.4 to 25). Features in the literature favoring malignant behavior, ie metastatic disease, included larger tumors (mean 6.43 vs 1.71 cm), a high mitotic rate, tumor necrosis, angiolymphatic invasion, infiltrative margins and extratesticular extension (each p <0.0001). The malignant group had an overall median survival of 2.3 years (range 0.02 to 17.3). CONCLUSIONS: No patient had disease progression in our study, which is to our knowledge the largest reported United Kingdom series of sex cord stromal testicular tumors. Our data suggest that malignancy is uncommon and prophylactic retroperitoneal lymph node dissection is unjustified for clinical stage I disease.

Necrobiotic xanthogranuloma occurring in an eyelid scar.

We present a case report of necrobiotic xanthogranuloma (NXG) in a 76-year-old Caucasian lady occurring as a nodule in a blepharoplasty scar. NXG is a rare histiocytic disease with progressive orbital and systemic features. Management options of excision biopsy or chemotherapy are discussed.

'Lambing ears': a blistering disorder affecting farmers at lambing time.

BACKGROUND: At lambing time some farmers experience blistering and crusting of the pinnae. This occupational disease, termed 'lambing ears', does not feature in the medical literature. OBJECTIVES: To define the condition and explore its pathogenesis. METHODS: We obtained five biopsies from affected individuals and sent questionnaires to 69 farmers in the U.K. Farming communities abroad were also contacted. RESULTS: The eruption lasts for the duration of the lambing practice. The histological features are dominated by a pandermal perivascular and diffuse, predominantly T-cell lymphocytic infiltrate. Only the pinnae are affected and its incidence is related to the degree of involvement a farmer has with the animals around parturition. The condition also occurs, but less frequently, in farmers who are calving. CONCLUSIONS: This occupational disease occurs with close contact to lambing ewes or calving cows. The histology and distribution are comparable with the juvenile spring eruption variant of polymorphic light eruption, but its demographics are unique.

Case series: adult testicular dermoid tumours--mature teratoma or pre-pubertal teratoma?

Adult testicular dermoid tumours are rare tumours with no reported potential for recurrent or metastatic spread. Despite this they are currently classified as mature teratoma and managed as if they have equivalent malignant potential. This report describes two cases of adult mature teratoma of dermoid type and questions the classification and pathogenesis of this disease. In one of the cases there was a clear history of a testicular lump arising pre-pubertally, raising the possibility that some adult dermoid tumours may in fact be pre-pubertal teratomas that have persisted into adulthood. Classification as a mature teratoma carries with it a follow-up regimen that includes numerous radiological investigations with their attendant radiation exposure. A positive histological diagnosis and separate classification of adult dermoid tumours would allay clinical fears of recurrence and metastasis and negate the need for repeated radiological investigations.

Characterization of a selective and potent antagonist of human P2X(7) receptors, AZ11645373.

BACKGROUND AND PURPOSE: The ATP-gated P2X(7) receptor has been shown to play a role in several inflammatory processes, making it an attractive target for anti-inflammatory drug discovery. We have recently identified a novel set of cyclic imide compounds that inhibited P2X(7) receptor-mediated dye uptake in human macrophage THP-1 cells. In this study the actions and selectivity of one of these compounds, AZ11645373, were characterized. EXPERIMENTAL APPROACH: We measured membrane currents, calcium influx, and YOPRO-1 uptake from HEK cells expressing individual P2X receptors, and YOPRO1 uptake and interleukin-1beta release from THP-1 cells in response to ATP and the ATP analogue benzoylbenzoyl ATP (BzATP). KEY RESULTS: AZ11645373 up to 10 microM, had no agonist or antagonist actions on membrane currents due to P2X receptor activation at human P2X(1), rat P2X(2), human P2X(3), rat P2X(2/3), human P2X(4), or human P2X(5) receptors expressed in HEK cells. AZ11645373 inhibited human P2X(7) receptor responses in HEK cells in a non-surmountable manner with K (B) values ranging from 5 - 20 nM, with mean values not significantly different between assays. K (B) values were not altered by removing extracellular calcium and magnesium. ATP-evoked IL-1beta release from lipopolysaccharide-activated THP-1 cells was inhibited by AZ11645373, IC(50) = 90 nM. AZ11645373 was > 500-fold less effective at inhibiting rat P2X(7) receptor-mediated currents with less than 50% inhibition occurring at 10 microM. CONCLUSIONS AND IMPLICATIONS: AZ11645373 is a highly selective and potent antagonist at human but not rat P2X(7) receptors and will have much practical value in studies of human cells.

Screen detected sclerosing lymphocytic lobulitis and amyloid of the breast in the same patient--a possible causal link.

Sclerosing lymphocytic lobulitis (SLL) and amyloidosis of the breast are both rare. We report the case of a 59 year old woman who presented with suspicious microcalcifications on routine screening mammography. Wire-guided excision biopsy showed features typical of SLL but also localised amyloid deposits within the specimen. Amyloidosis and SLL may have similar immunological causes. This patient represents the first documented association of these two disorders.

ICAM-1 polymorphisms and development of cutaneous malignant melanoma.

Tumour growth in cutaneous malignant melanoma (CMM) is mediated by cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1). ICAM-1 expression is associated with increasing Breslow thickness of vertical growth-phase tumours and, in patients with stage 1 disease, may be associated with disease free and patient survival. In this study we have investigated whether two single nucleotide polymorphisms (SNPs) in the ICAM-1 gene encoding amino acid substitutions in codons 241 and 469 of the expressed ICAM-1 molecule are associated with susceptibility to and markers of prognosis (including tumour Breslow thickness) in CMM. A total of 164 CMM patients and 264 cancer-free controls were genotyped for these SNPs by the 5' nuclease assay for allelic discrimination (TaqMan). No genotypes showed any significant associations with CMM susceptibility, although there was a non-significant increase in frequency of the ICAM-1 469 AA genotype among CMM patients vs. controls (38.4% vs. 29.9%; P = 0.11). However, the ICAM-1 241 GG genotype was significantly decreased in frequency among patients with primary invasive tumours of greater Breslow thickness (72.5% vs. 91.2%; P = 0.013; OR = 0.25 (0.072-0.85)). These results provide no evidence for a role for the ICAM-1 codon 241 and 469 SNPs in determining susceptibility to CMM, but provide preliminary evidence that the role of ICAM-1 polymorphism in modulating tumour growth in CMM requires further investigation in a larger study group.

The continued value of central histopathological review of testicular tumours.

AIMS: Central histopathological review of testicular tumours prior to definitive treatment can have an important impact on patient management. This study was designed to assess the continued value of central review in the light of increasing subspecialization and increased numbers of consultant histopathologists. MATERIALS AND RESULTS: The original and review reports of 291 testicular cancer specimens from 1998 to 2002 were analysed, looking particularly at major diagnosis, vascular invasion and the tumour elements within non-seminomatous germ cell tumours (NSGCT). When a diagnosis was altered any effect on subsequent patient management was assessed. There was a discrepancy in tumour type in 11 cases (4%) compared with 6% in 1992-1997. The commonest change was from seminoma to NSGCT or combined germ cell tumour (5/11). There was also diagnostic difficulty with spermatocytic seminoma (3/11). The clinical management of all 11 cases was influenced as a result of the review diagnosis. Discrepancies in vascular invasion were noted in 13 of the 126 NSGCTs (10%) compared with 20% in 1992-1997. Differences in NSGCT tumour elements, though clinically less important, were frequent in both groups. CONCLUSIONS: There continues to be a small number of significant and clinically important errors identified following central histopathological review of testicular tumours. This study highlights the value of central review and supports its continued practice in the management of testicular tumours.

Aluminium hydroxide-induced granulomas in pigs.

The effect of intramuscular injection of 40 mg/2 ml aluminium hydroxide in the neck of pigs was examined in a number of ways. The investigation followed repeated slaughterhouse reports, according to which 64.8% of pigs from one particular farm were found at slaughter to have one or more nodules in the muscles of the neck (group slaughtered). The pigs had been injected with a vaccine containing 40 mg/2 ml dose of aluminium hydroxide as adjuvant. Research consisted of two phases: first, an epidemiological study was carried out, aimed at determining the risk factors for the granulomas. The results indicated that the vaccine was to be held responsible for the formation of granulomas. A clinical trial was then performed to further substantiate the initial hypothesis, by comparing pigs, which were aseptically inoculated twice with either the original vaccine or the adjuvant alone (groups vaccine and adjuvant) to pigs inoculated twice with apyrogenic bi-distilled water (group water) and to pigs inoculated once with the adjuvant and once with apyrogenic bi-distilled water (group adjuvant/water). Both studies agreed in their conclusions, which indicate that the high amount of aluminium hydroxide was the cause of the granulomas.

Transitional cell carcinoma of the bladder mimicking lobular carcinoma of the breast: a discohesive variant of urothelial carcinoma.

AIMS: To describe a series of 10 cases of transitional cell carcinoma which show morphological features which mimic lobular carcinoma of the breast and diffuse carcinoma of the stomach. METHODS AND RESULTS: Ten cases were identified from the files at Southampton University Hospitals NHS Trust and from the authors' consultation files. Immunostains were performed and clinical information was obtained. Eight of the patients were male and two female. Ages ranged from 52 to 77 years at presentation. All of the tumours showed areas where the tumour was composed of uniform cells with a discohesive single-cell, diffusely invasive growth pattern. In areas the tumour cells were arranged in linear single-cell files and in separate areas solid sheets of discohesive cells. In all of the cases some tumour cells showed prominent intracytoplasmic vacuoles. In addition to this pattern, four cases showed typical transitional cell carcinoma or carcinoma in situ. The majority of the tumours expressed cytokeratin 20 but not oestrogen receptors. CONCLUSION: This study highlights a pattern of diffusely invasive transitional cell carcinoma not previously described and one which is important to recognize in order to avoid misdiagnosis of metastatic lobular carcinoma of the breast, especially in small biopsies.

Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is particularly problematic in certain patient groups, including patients with dystrophic or junctional epidermolysis bullosa (DEB/JEB). Theoretically, vaccination against a cell surface antigen which is expressed on this type of tumour could prevent SCC development, as well as treat primary and metastatic disease in this patient group. Preliminary studies have suggested that MUC1, a transmembrane glycoprotein, is overexpressed in sporadic cutaneous SCCs, and MUC1 has been used with some success as a target antigen for vaccine development in breast cancer, where it is expressed on > 50% of neoplastic cells in approximately 50-80% of tumours. Furthermore, aberrant glycosylation of MUC1 has been detected in this and other cancer types; however, the glycosylation status of MUC1 in cutaneous SCC is not known. OBJECTIVES: To investigate the expression and glycosylation status of MUC1 in SCCs arising in patients with DEB and JEB, and for comparison in sporadic SCCs and sporadic Bowen's disease. METHODS: Immunohistochemical analysis of MUC1 in 30 SCCs from subjects with DEB/JEB, 55 sporadic SCCs and 30 sporadic lesions of Bowen's disease was carried out using four separate monoclonal antibodies which recognize different isoforms of MUC1. RESULTS: Expression of MUC1 was detected in 100% of SCCs arising in patients with DEB and JEB; > 50% of neoplastic cells stained positive for MUC1 in 57% of DEB/JEB SCCs, with over 95% of tumour cells immunopositive in 33% of cases. MUC1 expression was also observed in 95% of sporadic SCCs and 97% of Bowen's disease, with 36% of sporadic SCCs immunopositive for MUC1 in > 50% of tumour cells. Investigation of the glycosylation status showed that MUC1 was predominantly hyperglycosylated in the DEB/JEB and sporadic tumours. CONCLUSIONS: The results demonstrate that a significant proportion of DEB/JEB and sporadic SCCs express MUC1 in > 50% of tumour cells. Therefore, MUC1 may be a suitable candidate antigen against which to develop a tumour vaccine for these patient groups.

Cytokine gene single nucleotide polymorphisms and susceptibility to and prognosis in cutaneous malignant melanoma.

Cutaneous malignant melanoma (CMM) is a potentially fatal malignancy in which exposure to UV light is the most important risk factor. Several lines of evidence suggest that CMM patients develop an immune response to their tumours, although, in most cases, anti-tumour immune responses are insufficient to abrogate tumour development. Polymorphism in genes regulating the immune response and cell growth may result in increased susceptibility to and/or poorer prognosis in certain individuals. In this study, we addressed whether single nucleotide polymorphisms (SNPs) associated with differential expression of selected pro- and anti-inflammatory cytokines and growth factors [interleukin (IL)-1beta-35 and -511, IL-2 -330, IL-4 -590, IL-6 -174, IL-8 -251, interferon (IFN)-gamma+874 and transforming growth factor (TGF)beta1 +915] or as markers of candidate cytokine genes (IL-12 +1188) are associated with susceptibility to or known prognostic indicators (e.g. initial tumour growth phase, Breslow thickness, mitotic count in vertical growth phase tumours, tumour regression) in CMM. One hundred and sixty-nine British caucasian CMM patients and 261 controls were included in the study and all SNPs were genotyped by ARMS-PCR. No SNP genotypes or alleles showed significant associations with CMM susceptibility and only the IL-1beta-511 TT genotype was associated with thinner invasive tumours at presentation, as assessed by Breslow thickness at the clinically significant cut-off point of 1.5 mm [occurring in 2/51 (3.9%) thicker vs. 14/78 (17.9%) thinner tumours (P = 0.03; relative risk = 0.29 (95% confidence interval 0.05-0.95)]. These findings suggest that - with the possible exception of IL-1beta- genetic variation associated with differential expression of the selected pro- and anti-inflammatory cytokines is unlikely to play a major role in susceptibility to and prognosis in CMM.