Sarcomatoid Carcinoma of the Prostate Presenting in a 44 Year Old

We present the case of a 44-year-old man diagnosed with metastatic sarcomatoid carcinoma of the prostate. The pathogenesis and optimal treatment of this rare and aggressive subtype of prostate cancer are not fully clear. The patient was managed using a multimodality approach of chemotherapy, hormonal blockade and radiation therapy, with palliative intent.

Isolated anterior mediastinal tuberculosis in an immunocompetent patient.

BACKGROUND: The differential diagnosis of a mediastinal mass is a common challenge in clinical practice, with a wide range of differential diagnosis to be considered. One of the rarer causes is tuberculosis. Atypical presentations of tuberculosis are well documented in immunocompromised patients, but should also be considered in the immunocompetent. CASE PRESENTATION: This case outlines a previously healthy 22 year-old immunocompetent male presenting with worsening chest pain, positional dyspnea, dry cough and dysphagia. Chest x-ray showed evidence of an isolated anterior mediastinal mass, which was confirmed on computed tomography. A mediastinoscopy was diagnostic as histology revealed necrotizing granulomatous inflammation and the presence of acid-fast bacilli, indicating mediastinal tuberculosis. CONCLUSION: Typically the underlying presentation of mediastinal tuberculosis is mediastinal lymphadenitis. This case was unusual in that we detected an isolated large anterior mediastinal mass accompanied by a relatively small burden of mediastinal lymphadenitis. Cases similar to this have been documented in immunosuppressed patients however in our case no evidence of immunosuppression was found. This case report emphasizes the importance that a detailed and logical pathway of investigation is pursued when encountering a mediastinal mass.

Endoscopic ultrasound and EUS-guided FNA in the diagnosis of rectal endometriosis.

Endometriosis is characterised by the presence of endometrial glands and stroma outside the uterus. The GI tract is the most common site for extra-pelvic endometriosis, in particular the rectum and sigmoid colon. Using endoscopic ultrasound (EUS), which combines endoscopy with real-time ultrasonography, the wall of the GI tract and adjacent structures can be examined. EUS-guided fine needle aspirates can be also obtained during the procedure. We report a case of rectosigmoid endometriosis which was diagnosed using EUS.

Cutaneous T-cell lymphoma presenting as a ten month history of unilateral facial swelling.

A 25-year-old fisherman presented with a ten-month history of unilateral facial swelling involving his lower lip and eyelids. The differential diagnosis for oro-facial swelling is extensive including congenital, infective, inflammatory and neoplastic processes. Biopsies revealed a cutaneous T cell lymphoma.

Diminished Clostridium difficile toxin A sensitivity in newborn rabbit ileum is associated with decreased toxin A receptor.

Human infants are relatively resistant to Clostridium difficile-associated diarrhea and colitis compared to adults. In that toxin A is the major cause of intestinal damage with this organism, we compared toxin A receptor binding and biological effects in newborn vs adult rabbit ileum. Purified toxin A (M(r) 308 kD) was labeled with tritium or biotin with full retention of biologic activity. Appearance of specific toxin A brush border (BB) binding was strongly age dependent with minimal [3H]toxin A specific binding at 2 and 5 d of life, followed by gradual increase in binding to reach adult levels at 90 d. Absence of toxin A binding sites in newborn and presence in adult rabbits was confirmed by immunohistochemical studies using biotinylated toxin A. Toxin A (50 ng to 20 micrograms/ml) inhibited protein synthesis in 90-d-old rabbit ileal loops in a dose-dependent fashion. In contrast, inhibition of protein synthesis in 5-d-old rabbit ileum occurred only at the highest toxin A doses (5 and 20 micrograms/ml) and at all doses tested was significantly less than the adult rabbit ileum. In addition, toxin A (5 micrograms/ml) caused severe mucosal damage in adult rabbit ileal explants but had no discernable morphologic effect on 5-d-old rabbit intestine. Our data indicate that newborn rabbit intestine lacks BB receptors for toxin A. The absence of the high-affinity BB receptor for toxin A in the newborn period may explain lack of biologic responsiveness to purified toxin, and the absence of disease in human infants infected with this pathogen.

Perioperative chemotherapy in the treatment of osteosarcoma: a 26-year single institution review.

BACKGROUND: Chemotherapy in the multimodality treatment of osteosarcoma has improved survival. Reported outcomes on adult patients are limited. Poor necrosis rates post neoadjuvant chemotherapy (NAC) is considered an adverse prognostic factor and attempts have been made to improve survival in this group. PATIENTS AND METHODS: Adult and young adult patients diagnosed with osteosarcoma between January 1986 and August 2012 were retrospectively reviewed. Patients identified were stratified according to stage (localised or metastatic) and age (≤40 and >40 years). Event free survival (EFS) and overall survival (OS) outcomes were determined. In patients with localised disease ≤40 years, survival was assessed according to necrosis rates post NAC (<90 and ≥90%). NAC consisted of two cycles of methotrexate alternating with doxorubicin/cisplatin (MAP) followed by definitive surgery. Those with ≥90% tumour necrosis continued on MAP. Patients with <90% necrosis received ifosfamide and etoposide (IE) post operatively. RESULTS: A total of 108 patients were reviewed and 97 were included. Median age was 23 years (range 16-75) and 70% of patients were male. Five year EFS and OS across all groups was 57% and 63% respectively. Of the patients with localised disease (N = 81), 5-year overall survival (OS), with a median follow up of 7 years (2-26) was 70% (p < 0.0001). Patients aged 16-40 (N = 68) with localised osteosarcoma had a significantly improved 5-year OS (74%) compared to those >40 years (N = 13) (42%) (p = 0.004). Of the 68 patients with localised osteosarcoma ≤40 years, 62 were evaluated according to necrosis rates post MAP. In 33 patients who achieved ≥90% necrosis and continued MAP, 5-year OS was 82%. In 29 patients who had <90% tumour necrosis and received adjuvant IE, 5-year OS was 68% (p = 0.15). Multivariate analysis confirmed age and stage as prognostic factors but not poor necrosis rates in our treated population. CONCLUSIONS: Long-term survival outcomes in a predominantly adult Irish population are similar to large reported trials. Age and stage at diagnosis are prognostic. Postoperative ifosfamide/etoposide alone in patients with poor necrosis rates is a feasible regimen, but its role in the adjuvant setting remains uncertain.

Malignant phaeochromocytoma metastasising to the breast.

BACKGROUND: Nearly one-quarter of metastatic tumours in the breast are from an occult extramammary tumour, usually a lung carcinoma. AIM: To report on a patient with a history of metastatic malignant phaeochromocytoma and a breast mass. RESULT: A 54-year-old female presented with a right breast mass. At the age of 32, she had presented with a phaeochromocytoma. The staining of the breast mass was comparable with that of her original adrenal tumour. CONCLUSION: This is the first published case of a phaeochromocytoma metastasising to the breast, and demonstrates the challenge that extramammary tumours in the breast can pose for the pathologist.

Linear IgA disease--a review of four patients.

Four cases of Linear IgA Disease (LAD) seen over a five year period are reviewed and our most recent LAD patient is described in detail. We summarise data on our patients and outline clinicopathologic features, aetiology and management of this unusual but important condition.

Primary bone lymphoma: single institution case series.

BACKGROUND: Primary bone lymphoma (PBL) is a rare condition and accounts for less than 2% of adult lymphomas and 3% of all primary bone malignancies. Because of the rarity of this disease, there is a lack of prospective randomised clinical trials and hence optimal treatment is uncertain. AIM: We report on our experience of treating PBL over 20 years. METHODS: Using our hospital database, we identified all patients with PBL, their treatment, and long-term follow-up. RESULTS: From January 1989 to July 2007, we identified 12 patients with PBL. Long extremity bones were the most common presenting sites. Multifocal disease was present in three cases. Treatment modalities included surgery, chemotherapy, and radiotherapy. Median follow-up was 8 years (range 0.5-18.5 years), and overall survival was 100%. CONCLUSIONS: Combined modality therapy, i.e. chemotherapy followed by radiotherapy, is the preferred treatment option unless adverse neurology or an unstable fracture presents first.

Mycosis fungoides--a review of the management of 28 patients and of the recent literature.

BACKGROUND: Mycosis fungoides is an uncommon cutaneous T-cell lymphoma characterized by malignant monoclonal proliferation of T-helper lymphocytes. Its course is variable with a potential for lymphatic and hematogenous involvement. We report the investigations, staging, treatment, follow-up, and outcome of 28 patients. This is the first such study reported from Ireland. METHODS: Twenty-eight patients with mycosis fungoides (14 women, 14 men; average age, 52.5 years) were reviewed over 12 years in the dermatology clinic which assesses an average of 4500 patients per year. All mycosis fungoides patients were referred from their family physicians. The diagnosis was made in all cases from a combination of clinical findings, histology, and immunohistochemistry. TNM staging revealed 11 patients at diagnosis stage IA (T1), 12 at stage IB (T2), four at stage IIB (T3), and one at stage III (T4). RESULTS: The usual male preponderance was not found. Eight patients needed multiple biopsies to establish the diagnosis. Detailed investigations were not useful in the early stages. Patients were followed up over a 12-year period. Thirteen patients died as a result of cutaneous lymphoma. Two patients with stage IA disease progressed rapidly and died, a feature reported in only 10% of patients at this stage. Five patients showed unusual features, including a long history prior to presentation, the development of the rarely reported bullous mycosis fungoides, and aggressive disease beginning at a young age. CONCLUSIONS: Mycosis fungoides is rare; we reviewed 28 patients over 12 years. The prognosis is poor at the later stages; 13 patients died. Two patients who died were unusual in that they rapidly progressed from stage IA disease; however, in the majority of patients with this stage, the prognosis is excellent. Detailed investigations were unhelpful in early stage disease. Close clinical follow-up is essential to identify disease progression.

Net1 and Myeov: computationally identified mediators of gastric cancer.

Gastric adenocarcinoma (GA) is a significant cause of mortality worldwide. The molecular mechanisms of GA remain poorly characterised. Our aim was to characterise the functional activity of the computationally identified genes, NET 1 and MYEOV in GA. Digital Differential Display was used to identify genes altered expression in GA-derived EST libraries. mRNA levels of a subset of genes were quantitated by qPCR in a panel of cell lines and tumour tissue. The effect of pro- and anti-inflammatory stimuli on gene expression was investigated. Cell proliferation and invasion were measured using in an in-vitro GA model following inhibition of expression using siRNA. In all, 23 genes not previously reported in association with GA were identified. Two genes, Net1 and Myeov, were selected for further analysis and increased expression was detected in GA tissue compared to paired normal tissue using quantitative PCR. siRNA-mediated downregulation of Net1 and Myeov resulted in decreased proliferation and invasion of gastric cancer cells in vitro. These functional studies highlight a putative role for NET1 and Myeov in the development and progression of gastric cancer. These genes may provide important targets for intervention in GA, evidenced by their role in promoting invasion and proliferation, key phenotypic hallmarks of cancer cells.

Immunohistochemistry of the Hfe protein in patients with hereditary hemochromatosis, iron deficiency anemia, and normal controls.

In 1996 two mutations in Hfe, the gene affected in hereditary hemochromatosis, were identified as C282Y (c.845G. A) and H63D (c.187C. G). Immunohistochemical studies have localized the protein product of Hfe to the deep crypts of the duodenum, the maximum site of iron absorption. To date, there are no published data on the cellular location and regulation of Hfe in patients with hemochromatosis who are homozygous for C282Y. The aim of this study was to identify the cellular localization of Hfe in genotyped individuals and to study possible regulation of this protein by the mutations described in the Hfe gene locus and iron deficiency. Duodenal biopsy specimens and serum for iron, ferritin, and transferrin saturation were taken from controls (n = 10) and patients with hereditary hemochromatosis (n = 10) and iron deficiency anemia (n = 10). All participants were genotyped for C282Y and H63D mutations. Expression of Hfe in the duodenum was demonstrated by immunohistochemistry. Hfe was expressed in the deep crypts of the duodenum in all three groups in a perinuclear fashion. Hfe staining was weaker in the hemochromatosis and iron deficiency patients (mean transferrin saturation 69.6%, SD 23% and 15%, SD 11%, respectively) when compared to controls (mean transferrin saturation 33.1%, SD 15%). There was no difference in the intensity of Hfe staining within the hemochromatosis group who were iron overloaded when compared to their iron-depleted counterparts. In summary, Hfe is expressed strongly in the deep crypts of the small intestine of normal subjects. Homozygosity for C282Y and conditions of iron deficiency result in a downregulation of Hfe. Furthermore, Hfe is not regulated by therapeutic iron depletion in patients with hemochromatosis who are homozygous for the C282Y mutation.

Hemochromatosis in Ireland and HFE.

Sixty patients diagnosed with hereditary hemochromatosis with grade 3 or 4 hepatic iron overload and 18 patients diagnosed with hereditary hemochromatosis who had less than grade 3 hepatic iron overload were examined for the HFE gene mutations, 845A (C282Y) and 187G (H63D). Control samples were obtained from 109 randomly selected individuals. Fifty-six of 60 unrelated hereditary hemochromatosis patients (93%) with grade 3 or 4 hepatic iron deposition were homozygous for the C282Y mutation. Fourteen of the 18 hereditary hemochromatosis patients with <3+ iron deposition (76%) were homozygous for the C282Y mutation. Three of 8 patients who were heterozygous for the C282Y mutation were also heterozygous for the H63D mutation. Thirty-one of 109 control individuals were heterozygous for the C282Y mutation and 27 were heterozygous for the H63D mutation. Our finding that 93% of hereditary hemochromatosis patients who fulfil standard diagnostic criteria are homozygous for the C282Y mutation provides clear evidence that this mutation is strongly associated with hereditary hemochromatosis. The allele frequency of 14% for the C282Y mutation in our control population is the highest reported and supports the hypothesis of a Celtic origin for the hereditary hemochromatosis gene.

Effect of tumour thickness and other factors on the risk of regional disease and treatment of the N0 neck in early oral squamous carcinoma.

A high occult metastatic rate and a high regional recurrence rate are reported among patients with early oral squamous carcinoma; however, considerable controversy exists regarding the merits of elective neck dissection in this group. The purpose of the present study was to examine the influence of various histological factors on the risk of occult neck disease, neck conversion and recurrence among 63 patients with stage I and II oral cancer. Tumour thickness (P = 0.0175) and size (P = 0.023) were both significantly predictive of outcome. Among tumours of a given thickness, those with infiltrative margins also showed a tendency towards a poorer outcome; however, this was not significant (P = 0.0768). Patients undergoing elective neck dissection with pathological evidence of cervical metastases or with subsequent neck recurrence had a better 3-year survival (55%) than those developing neck conversion after primary neck observation (20%). Our data would suggest considering tumours greater than 5 mm in thickness or with infiltrative margins as potential candidates for elective neck treatment.

Imaging of small cell carcinoma of the oesophagus.

Four cases of oesophageal small cell carcinoma are described. Radiological features at presentation included oesophageal strictures in association with bulky intrathoracic and intraabdominal lymphadenopathy. The subject is reviewed and the radiologically relevant features are emphasized.

"Golf ball liver": agent orange hepatitis.

2,4-Dichlorophenoxyacetic acid (2,4-D) is a selective weedkiller which works by uncoupling oxidative phosphorylation and is in widespread use. It is known as "agent orange". A 65 year old man had acute hepatitis, thought to be caused by exposure to 2,4-D. The patient ingested 2,4-D as a result of habitual licking of his golf ball. Clinical and histological data together with a challenge test confirmed the diagnosis of "golf ball liver".

Bronchoscopic diagnosis of sarcoidosis.

Transbronchial lung biopsy (TBLB), transbronchial needle aspiration (TBNA) of mediastinal lymph nodes and bronchoalveolar lavage (BAL) are routinely performed at fibreoptic bronchoscopy. Up to the present time, no data have been available on the efficacy of performing all three of these procedures simultaneously in the bronchoscopic work-up of sarcoidosis. A prospective study was undertaken to compare the diagnostic yield from TBLB, TBNA and BAL in patients presenting with clinical and radiological features typical of sarcoidosis. Thirteen consecutive patients with clinical and radiological features consistent with stage I and II sarcoidosis underwent bronchoscopy with TBLB, TBNA and BAL. Noncaseating granulomata (stain and culture negative for tuberculosis bacilli and fungi) were found in seven of the 13 patients by TBLB, and in six of the 13 patients by TBNA (of which four patients had negative TBLB). Eight of the 13 patients had classical "sarcoid" BAL findings, i.e. >12% lymphocytes, and high CD4+:CD8+ lymphocyte ratio. Combining TBLB, TBNA and BAL gave a diagnostic sensitivity of 100% (12 out of 12 patients) for sarcoidosis. The remaining patient had nondiagnostic bronchoscopic studies and mediastinoscopy biopsy showed a non-Hodgkin's lymphoma. Our data suggest that performing simultaneous transbronchial lung biopsy, transbronchial needle aspiration and bronchoalveolar lavage produces optimal results in the diagnosis of sarcoidosis.

Increased DMT1 but not IREG1 or HFE mRNA following iron depletion therapy in hereditary haemochromatosis.

BACKGROUND AND AIMS: While upregulation of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (IREG1) within duodenal enterocytes is reported in patients with hereditary haemochromatosis (HH), these findings are controversial. Furthermore, the effect of HFE, the gene mutated in HH, on expression of these molecules is unclear. This study examines duodenal expression of these three molecules in HH patients (prior to and following phlebotomy), in patients with iron deficiency (ID), and in controls. METHODS: DMT1, IREG1, and HFE mRNA were measured in duodenal tissue of C282Y homozygous HH patients, in ID patients negative for the C282Y mutation with a serum ferritin concentration less than 20 microg/l, and in controls negative for C282Y and H63D mutations with normal iron indices, using real time polymerase chain reaction. RESULTS: DMT1 and IREG1 mRNA levels were not significantly different in non-phlebotomised (untreated) HH patients compared with controls. DMT1 expression was significantly increased in HH patients who had undergone phlebotomy therapy (treated) and in patients with ID compared with controls. IREG1 was significantly increased in ID patients relative to controls, and while IREG1 expression was 1.8-fold greater in treated HH patients, this was not statistically significant. HFE mRNA expression was not significantly different in any of the groups investigated relative to controls. CONCLUSIONS: These findings demonstrate that untreated HH patients do not have increased duodenal DMT1 and IREG mRNA, but rather phlebotomy increases expression of these molecules, reflecting the effect of phlebotomy induced erythropoiesis. Finally, HFE appears to play a minor role in the regulation of iron absorption by the duodenal enterocyte.