Acute vasculitis resulting in free flap failure: the importance of early recognition and options for management.

Unusual or unexpected medical causes for free flap failure do occur but are uncommon. We present a rare case of a fibula free flap failure due to an acute vasculitis which was undiagnosed until after the flap had failed. In addition to two successful flap salvages and intravenous heparin, an epoprostenol infusion was commenced but a third salvage was not successful. The vasculitis resulted in marked blood vessel wall thickening, and cutaneous manifestations which presented as late signs. High peri-nuclear anti nuclear cytoplasmic antibody (pANCA) and myeloperoxidase (MOP) titres were subsequently found and histology from several blood vessels showed marked inflammation throughout the wall. A diagnosis of microscopic polyangiitis was made and high dose steroids were subsequently commenced. Interestingly, he had vasculitis several years previously treated with oral steroids but had been discharged from the rheumatology clinic. This rare case illustrates the potential hazards of free flap surgery in the vasculitides and discusses the warning signs and various management options to reduce the likelihood of flap failure in these patients.

Primary oral leiomyosarcoma: a clinico-pathologic study and analysis of prognostic factors.

This clinico-pathologic study of primary oral leiomyosarcomas and analysis of potential prognostic factors involved a literature review of 64 cases and a report of four cases treated in the authors' unit. The demographic details, clinical presentation, diagnosis, treatment and outcome were documented for the whole group and clinico-pathologic variables analysed to detect potential prognostic factors. The most common presentation was that of a painless mass, with peak incidence in the 6th decade and a slight male predeliction (M:F=1.3:1). The maxilla was the most frequently involved site, followed by the mandible and tongue. Surgical excision was most commonly employed with radiotherapy and chemotherapy being reserved for recurrent and metastatic tumours. Local recurrence (34%) and metastasis (35%) were not uncommon and occurred most frequently to the lungs and regional lymph nodes (15%). Age, sex, size and mitotic index were not statistically related to recurrence or metastasis. Site (P=0.0125) was a predictor of metastasis. Metastasis (P=0.010) and lesions involving the maxilla and mandible (P=0.019) were associated with decreased survival. The estimated 5 year survival was 55% for the whole group and 43% and 19% for patients with bony involvement and metastasis respectively.

Atypical features in pleomorphic adenoma--a clinicopathologic study and implications for management.

Pleomorphic adenoma is the most common salivary gland neoplasm and infrequently undergoes malignant transformation. Carcinoma ex pleomorphic adenoma is typically an infiltrative neoplasm with features of cellular pleomorphism, high mitotic activity, peri-neural and vascular invasion. More recently, sub-groups of pleomorphic adenoma have been described exhibiting vascular invasion and features of malignancy without evidence of extra-capsular extension. There is little information in the literature regarding how these different histological variants influence clinical presentation and outcome following primary treatment. Following a review of 100 consecutive pleomorphic adenomas removed from the major salivary glands, 4 cases with atypical histological features were found. Three tumours exhibited features of dysplasia/carcinoma without evidence of extra-capsular invasion and a further case demonstrated benign vascular invasion. There were no clinical features suggestive of the atypical nature of these neoplasms, though fine needle aspiration cytology (FNAC) was suspicious of a malignancy in 2 cases and CT scan in 1 case. Patients underwent a superficial parotidectomy or submandibular gland excision based on the location of the lesion. All lesions were completely excised and there were no recurrences in this series.

Can the laboratory affect the investigation and diagnosis of primary biliary cirrhosis?

BACKGROUND: Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterised by the presence of various laboratory abnormalities but the precise role of laboratory staff in initiating clinical referral and subsequent biopsy is not clear. OBJECTIVE: To examine the impact of laboratory abnormalities in the investigation of PBC. METHODS: In a retrospective study of laboratory results over nine years from 1996, computer records were reviewed to identify how many referrals for biopsy were initiated and subsequent diagnoses made as a result of clinical signs, raised serum alkaline phosphatase activity (ALP), raised IgM concentration, or positive mitochondrial antibodies accompanied by a clinical comment from the laboratory suggesting further action. RESULTS: 22 diagnoses of PBC were confirmed by histopathology. Eleven had high ALP activity which had follow up tests initiated by the laboratory (mitochondrial antibodies or IgM or both) and a comment added suggesting further investigation into the possibility of PBC. Seven had abnormal liver antibodies and one had a high polyclonal IgM concentration which prompted the relevant follow on testing and comments. One had an earlier diagnosis made on serological/clinical grounds and the biopsy was a confirmatory measure. One had no liver related antibodies. One had a request by laboratory staff for follow on tests but these were not asked for in subsequent samples by the requesting clinician. CONCLUSIONS: There is a positive role for laboratory staff in the diagnosis of PBC. Unexplained rises in ALP activity, positive mitochondrial antibodies, or raised IgM concentrations should be investigated more fully by laboratory staff and advice given to prompt a clinical referral for review and biopsy.

Oncofetal fibronectin and oral squamous cell carcinoma.

Fibronectin is a cell matrix glycoprotein, which exists as a number of isoforms that are often found within the cell matrix that surrounds tumours. Collectively these tumour-associated isomers of fibronectin have been termed oncofetal fibronectin (OFFN). We looked for expression of OFFN within oral squamous cell carcinomas (SCC) and related its presence to prognosis. The investigation used a monoclonal antibody (MoAb 5C10) to the glycosylated variant of OFFN, and 100 archival specimens of oral SSC. Immunostaining for OFFN was intense in the adjacent stroma of 43 squamous carcinomas, weak in 27 and absent in 30. Cervical metastases were found in 17/27 (63%) specimens that stained intensely, 6/17 (35%) that stained weakly and 3/13 (23%) that did not stain. Of the 21 cases which had extracapsular lymph node spread, 81% were from those that stained intensely, 19% from those that stained weakly and none from those that did not stain for OFFN expression. Also, 21/44 patients (49%) died in group with intense OFFN staining, 6/26 (23%) in the group with weak staining and 3/30 (10%) in the group that did not stain. The presence of OFFN glycoprotein in oral SCC as evaluated by immunostaining with MoAb 5C10 correlates strongly with the presence of metastatic lymph node involvement, particularly extracapsular involvement, and mortality. We therefore suggest that the degree of expression of OFFN in tumours is a valuable prognostic indicator.

Does type II nitric oxide synthase expression correlate with cellular proliferation in oral squamous cell carcinoma and dysplasia?

BACKGROUND: Nitric oxide (NO) has been implicated both in tumor progression and inhibition. This study investigated whether type II nitric oxide synthase (NOS2) expression correlated with cell proliferation in oral squamous cell carcinoma (OSCC) and dysplasia. METHODS: Paraffin-embedded tissue samples of normal oral mucosa, OSCC, and dysplasia were assessed immunohistochemically using monoclonal antibodies to NOS2 and Ki-67 antigen. We used Western blotting to confirm NOS2 antibody specificity and protein expression in select cases. RESULTS: NOS2 staining was increased in OSCC relative to normal oral mucosa, in which no expression was found. Both NOS2 expression and Ki-67 indices independently correlated with grade of dysplasia (p < .001) but not with the degree of tumor differentiation. A positive correlation was found between NOS2 expression and Ki-67 in cases of mild and moderate dysplasia (p < .001), but not in severe dysplasia and OSCC. CONCLUSIONS: No correlation exists between Ki-67 and NOS2 expression in severe dysplasia and OSCC. The findings suggest that the level of NO produced by NOS2 is insufficient to affect cellular proliferation in these conditions. The mechanism of NOS2 activation and the consequences of its expression remain to be fully explained.

Tongue-base hamartoma in tuberous sclerosis.

This paper describes the case of a 41-year-old female with tuberous sclerosis who presented with a large tongue-base hamartoma. The surgical management of the patient was complicated by the presence of a large thyroid goitre. Awake fibre-optic intubation, thyroidectomy then tracheostomy were necessary before the tongue-base hamartoma could be safely resected. To the best of our knowledge, this is the first reported case of a tongue-base hamartoma in a patient with tuberous sclerosis.

Type II nitric oxide synthase (NOS2) expression correlates with lymph node status in oral squamous cell carcinoma.

In tumour biology, nitric oxide (NO) has a complex array of concentration-dependent actions, including both inhibitory and promoting effects. It is thought that the levels of NO found in many human cancers lead to enhanced angiogenesis and tumour dissemination. In the current study, we assessed the immunohistochemical expression of the enzyme type II nitric oxide synthase (NOS2) in 41 cases of oral squamous cell carcinoma and correlated the findings with lymph node status. A significant relationship was found between NOS2 expression and lymph node metastasis (P<0.0002). Furthermore, lymph node metastasis correlated with the degree and intensity of staining seen (P<0.001). No correlation was found between the size of the primary tumour, degree of tumour differentiation or smoking status and NOS2 staining. Western blotting confirmed NOS2 protein expression in select cases. As with many other human tumours, NOS2 is not a ubiquitous finding in oral cancer. Its expression may be of value in assessing lymph node status prior to surgery, and it represents a target for possible therapeutic manipulation.

Correlation between type II nitric oxide synthase and p53 expression in oral squamous cell carcinoma.

Prolonged nitric oxide (NO) production by the enzyme type II nitric oxide synthase (NOS2) has been implicated in angiogenesis and metastasis of human cancers. In animal models, wild-type p53 (but not mutant) protein results in down-regulation of NOS2 expression, which reduces both tumour growth and dissemination. In the current study, we aimed to find out whether a correlation was present in oral squamous cell carcinoma. Fifty-six cases of squamous cell carcinoma were assessed immunohistochemically using antibodies to NOS2 and p53 (clone DO-7). We also confirmed NOS2 protein expression in selected cases using immunoblotting. The results were correlated with clinicopathological findings. Statistical analysis showed a significant relationship between p53 and NOS2 expression (P= 0.001). No relationship was found between size of tumour or histological degree of differentiation, and NOS2 expression in the primary tumour.

Nitric oxide synthase expression is downregulated in basal cell carcinoma of the head and neck.

The small molecule nitric oxide (NO) has many actions, most of which are poorly understood. Recently, NO and related compounds have been implicated in skin damage caused by ultraviolet light although their exact role is not clear. We undertook an immuno histochemical study to assess the expression of type II NO synthase (NOS2) and type III (NOS3) in basal cell carcinomas (BCCs) of the head and neck. In all 48 cases studied, NOS2 was found in the basal cell layer of the skin at the tumour margin but it w as significantly reduced in the tumour epithelial cells (P=0.001). NOS3 was localized to the endothelium of the blood vessels in both skin and tumour in all cases, and it was not seen in the tumour epithelial cells. The results suggest that expression of NOS is down-regulated in basal cell carcinomas.

Expression of inducible nitric oxide synthase and p53 in oral epithelial dysplasia.

AIM: Nitric oxide (NO) has been studied in a variety of human cancers and is implicated in both tumor promotion and inhibition. Downregulation of the enzyme iNOS by wild-type p53 (but not mutant) protein has been shown to occur in normal cells and some tumors, but the relationship has not been reported in oral epithelial dysplasia. METHODS AND RESULTS: An immunohistochemical study was conducted with antibodies to iNOS and p53 (clone DO-7) in 36 cases of oral dysplasia of varying severity. Statistical analysis showed a significant correlation between iNOS staining and grade of dysplasia (P <.001) and between p53 and iNOS staining (P <.001). CONCLUSIONS: This preliminary study has shown that iNOS expression correlates with severity of dysplasia, and it is also increased in those cases showing positive staining for p53. Further research is required to fully establish the relationship between iNOS and p53 in both dysplasia and oral squamous cell carcinoma.

Expression of nitric oxide synthase in pleomorphic adenomas of the parotid.

The actions of nitric oxide (NO) in the pathology of solid tumours are complicated and many are poorly understood because NO has both inhibitory and tumour-promoting activities. In the current study we aimed to find out immunohistochemically whether the expression of both the inducible (iNOS) and endothelial (eNOS) forms of the enzyme nitric oxide synthase (NOS) were changed in pleomorphic adenomas of the parotid compared with normal salivary tissue. There was a significant difference in staining for iNOS between the tumour and normal salivary tissue, with tumour epithelial cells being stained in 29 cases of the 30 cases studied (P< 0.0001). The luminal cells of the salivary ducts also stained, but not the normal salivary tissue. Immunohistochemistry for the eNOS isoenzyme showed moderate staining of the tumour epithelium in only three specimens. There was also mild staining in the salivary duct cells of the normal glandular tissue and in endothelium of blood vessels in both tumour and normal glandular tissue in the same 29 cases.

A study to assess inducible nitric oxide synthase expression in oral lichen planus.

Nitric oxide (NO) has been implicated in a variety of diseases but has not been previously studied in oral lichen planus (OLP). Since OLP has a complex immunogenesis with abundant macrophage infiltration, this study determined by immunohistochemistry whether or not the expression of the inducible form of nitric oxide synthase (iNOS) was increased in this condition relative to normal mucosa. Thirty cases of OLP and 10 normal buccal mucosa biopsies were studied utilising primary antibodies to iNOS and CD68, a myelomonocytic marker. iNOS activity was additionally assessed using a [(14-)C]-labelled arginine to citrulline assay. CD68 expression was significantly increased in the cellular infiltrate of all 30 cases of OLP compared with normal mucosa (P<0.009). Although iNOS staining was seen in a minority of cells in nine cases, this was not statistically significant when compared with the absent staining in normal oral mucosa (P=0.26). Furthermore, the minimal iNOS activity found in OLP was similar to that in normal mucosa. We conclude that expression of iNOS by macrophages is downregulated in OLP and discuss the possible reasons for this finding.

Are myoepithelial cells responsible for the widespread expression of inducible nitric oxide synthase in pleomorphic adenoma? An immunohistochemical study.

Many of the actions of nitric oxide (NO) are still poorly understood. Recently, it has been shown that the inducible isoform of the enzyme nitric oxide synthase, iNOS, is expressed in both salivary ducts and pleomorphic adenoma. The current immunohistochemistry study determined whether or not this distribution correlated with smooth muscle actin (SMA) expression, thereby suggesting the expression by myoepithelial cells in both sites. Twenty cases of histologically confirmed pleomorphic adenoma, the sections of which contained adjacent normal salivary gland tissue, were stained for iNOS and smooth muscle actin (clone 1A4). The salivary ducts of all cases were stained intensely by both antibodies, with smooth muscle actin staining also being noted around acini in the normal gland parenchyma. Moderate or heavy staining for iNOS was found in all specimens of pleomorphic adenoma, with smooth muscle actin being distributed in a similar manner in 19 cases. Smooth muscle actin, but not iNOS, was also noted in blood vessels of both normal glands and tumours. The correlation between iNOS and SMA in pleomorphic adenoma was significant (P<0.001). The presence of iNOS in normal salivary ducts and pleomorphic adenoma is most likely due to expression by myoepithelial cells.

Neck mass caused by an intraluminal jugular paraganglioma.

Paragangliomas can develop in a number of head and neck sites, the most common being the carotid body paragangliomas and glomus jugulare tumours. This is a case of a paraganglioma confined entirely within the lumen of the jugular vein.

Does expression of inducible nitric oxide synthase correlate with severity of oral epithelial dysplasia?

The small molecule nitric oxide (NO) has generated an exponential amount of research since its discovery as a biological messenger in 1987. It has a vast number of actions, many of which are poorly understood. It has been studied in a variety of human cancers and has been implicated both in tumour promotion and inhibition. Although NO is produced by three distinct isoforms of the enzyme nitric oxide synthase (NOS), most cancer research is directed towards the calcium-independent form, iNOS which following induction, produces much higher quantities of NO than the other two. In this study the expression of iNOS is assessed by immunohistochemistry in 26 cases of oral epithelial dysplasia ranging in severity from mild to severe. iNOS staining was found in all 26 cases of dysplasia with the degree of staining correlating to the severity of dysplasia (p < 0.001). There was no iNOS staining seen in adjacent normal epithelium. The possible role of iNOS in the complex transformation from dysplasia to invasive oral cancer and the clinical applications are discussed.

A benign parathyroid cyst presenting with hoarse voice.

Parathyroid tumours and cysts are rare and, when presenting as neck masses, can be clinically misdiagnosed as thyroid lesions. Symptoms may be caused by compression of the surrounding structures or hormonal overactivity. This paper describes a patient with recurrent hoarseness owing to the pressure effects of a parathyroid cyst on the recurrent laryngeal nerve.

Conjunctival impression cytology in the preterm infant and it's relation to outcome.

UNLABELLED: The preterm infant is deficient in vitamin A (retinol) and this has been implicated in the pathogenesis of chronic lung disease of prematurity. Conjunctival impression cytology (CIC) has been used in adults to assess retinol status. We aimed to assess the feasibility of performing CIC in the preterm infant and to determine the significance of abnormal CIC findings. CIC samples were collected during routine retinopathy screening, and classified as inadequate, normal, borderline normal or abnormal. Ninety preterm infants were studied. Seventy-four (82%) CIC specimens produced a positive yield, whereas 16 (18%) were inadequate. Of the 74 adequate samples, 61 (82%) were normal or borderline normal and 13 (18%) abnormal. Seventy-three CIC specimens were assessed by a second histopathologist with complete agreement on 64 (88%) samples and disagreement on 9 (12%) samples. Ten sets of conjunctival impressions, taken from both eyes, gave identical results in all adequate samples. Birth weight was significantly lower in this abnormal group. Four infants (32%) in the abnormal group required treatment for retinopathy compared to two (3%) in the normal/borderline normal group, (P < 0.01). CONCLUSION: Conjunctival impression cytology is simple and reproducible technique which maybe easily applied to the preterm infant. Abnormal CIC is associated with retinopathy of prematurity requiring treatment.

Rosai-Dorfman disease presenting as a parotid mass.

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare, benign disease of unknown aetiology. This disease typically presents with massive, painless cervical lymphadenopathy but may occur in a wide variety of extranodal sites. Our report describes a 71-year-old man who presented with a discrete, unilateral parotid mass which was clinically suggestive of a primary salivary gland tumour. Initial cytological examination of a fine needle aspirate specimen taken from the mass demonstrated a discohesive cell population with nuclear atypia, raising the possibility of malignancy. However, excision of the mass and histological examination enabled a definitive diagnosis to be made.

The value of exfoliative urine cytology in combination with flexible cystoscopy in the diagnosis of recurrent transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To study the value of exfoliative urine cytology in predicting recurrent tumour in patients undergoing surveillance for transitional cell carcinoma (TCC) and to assess the suitability of these patients for flexible cystoscopy. PATIENTS AND METHODS: Specimens of early-morning and freshly voided urine were submitted 2 weeks before surveillance cystoscopy by 111 consecutive patients with known TCC. All patients then underwent cystoscopy under general anaesthesia. The urine specimens were analysed by two pathologists with no knowledge of the patients' history. Cytological findings were correlated with the findings of cystoscopy. RESULTS: Urine cytology predicted 82% of all recurrent tumours found subsequently at cystoscopy; 60% of patients with non-neoplastic pathology had normal cystoscopy. Only 51% of patients with positive urine cytology were shown to have recurrent TCC, but 87% of patients with negative cytology had no recurrent tumours. CONCLUSION: Urine cytology is a good adjunct to assessing the suitability of flexible cystoscopy in the follow-up of patients with transitional cell tumours.