Pathological aspects of the assessment of head and neck cancers: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It introduces the current best practice in histopathology and cytopathology as it pertains to head and neck and thyroid cancers. Recommendations • Accurate diagnosis of the type of malignancy is a key component of effective management. (R) • Surgeons and oncologists should understand the scope and limitations of cellular pathology in order to inform multidisciplinary discussions. (R) • A clinically suspected diagnosis of malignancy should be confirmed by biopsy or cytology before operation. (R) • Cytopathological diagnoses should be discussed with surgeons and radiologists to maximise the information gained from each modality of investigation. (R) • Pathological investigations are the basis for accurate cancer staging and stratification of clinical outcomes. (R).

Calculi and intracellular ochronosis in the submandibular tissues from a patient with alkaptonuria.

Alkaptonuria (AKU) is a rare autosomal recessive condition caused by deficiency of the enzyme homogentisate 1,2 dioxygenase, resulting in widespread deposition of oxidised homogentisic acid (HGA) polymer, primarily in joint tissues but also in other connective tissues. Macroscopic pigmentation of connective tissues in AKU is well documented and is the end point of a process that is not understood. Deposition in less common regions may provide clues to the pigment formation process. This is the first report of detection of ochronotic pigment in acinar cells and lumina in the submandibular gland of a patient with AKU. Deposition was noted in the apical region of the cells. A lobar duct presented a large calculus with unusual deposits possibly associated with calcium salts. This report highlights the effect that local and intracellular factors may have on converting HGA into polymeric derivatives in the absence of an extracellular matrix.

Expression of cell cycle associated proteins influences radiocurability of T2N0 squamous cell carcinoma of the larynx.

Cell cycle modulators are important in carcinogenesis and may be of prognostic and therapeutic relevance. This study has examined the influence of the proliferation index (Ki-67) and immunocytochemical expression of epidermal growth factor receptor (EGFR), cyclin D1, and retinoblastoma protein on recurrence rates at the primary site in 50 patients with T2N0 laryngeal carcinomas treated with radical irradiation. Pre-treatment biopsies were retrieved and sections scored for the four immunocytochemical markers. Statistical analysis for association, interaction and survival was performed. Five cases showed loss of expression of Rb protein. The median Ki-67 index was 50%, the median cyclin D1 index 21% and the median EGFR index 47% of cells. EGFR and cyclin D1 expression were positively correlated and, whilst local recurrence tended to occur with a Ki-67 labelling index of <50%, this was not statistically significant. When interactions were examined using Multiple Logistic Regression it was found that there was a direct relationship between EGFR and cyclin D1 expression. If the EGFR index was >20% and the cyclin D1 index >10%, then the odds ratio in favour of a primary site recurrence was very high (5.32 +/-0.41). This study demonstrates that the relationship between EGFR index and cyclin D1 index has a very strong association with primary site recurrence for T2 N0 laryngeal carcinomas treated by irradiation.

Alkaptonuria--a review of surgical and autopsy pathology.

Alkaptonuria is a rare, inherited defect of homogentisic acid 1,2-dioxygenase that leads to the widespread deposition of polymeric homogentisic acid, and clinical symptoms from degeneration of joints and the aortic valve. Pathological descriptions are few and mainly those of late-stage changes related to joint or valve failure. In this review, the macroscopic and histopathological changes in the tissues in alkaptonuria are illustrated by the detailed autopsy study of a 74-year-old female who died from disseminated ovarian carcinoma. The pathology is discussed in the context of the literature and in relation to potential pathogenic mechanisms of tissue damage. This review highlights the heterogeneity of some of the manifestations. In symptomatic patients, degenerative changes in synovial and intervertebral joints are usually well advanced, while early changes include diffuse cartilage pigmentation and chondrocyte necrosis. The initial stage of pigment deposition in the cardiovascular system may be influenced by intravascular pressure and flow disturbances, whereas more intense pigmentation affects fibrolipid components of atheromatous plaques. Pigmentation of the aortic and mitral valve cusps and valve rings is a result of intracellular and extracellular pigment deposition and is associated with calcification and clinically significant aortic stenosis.

Hibernoma--correlation of histopathology and magnetic-resonance-imaging features in 10 cases.

UNLABELLED: OBJECTIVE, DESIGN AND PATIENTS: Hibernoma is an uncommon, slow-growing, benign soft-tissue tumour resembling brown adipose tissue. The histological appearances are well-documented, but there are relatively few descriptions of the magnetic resonance (MR) imaging features. We report a retrospective comparison of the histological and MR appearances of ten hibernomas of the extremities, classified histologically into lipoma-like [<70% multivacuolated adipocytes (MVAs)] and non-lipoma-like hibernomas (>70% MVAs). RESULTS: The lipoma-like hibernomas measured 4-27 cm in maximum size. All were well-defined on MR imaging and histology except for one subcutaneous lesion that blended in with surrounding fat histologically. All lesions were isointense with subcutaneous fat on T1- and T2-weighting apart from one lesion that was predominantly slightly hypointense on T1-weighting and predominantly slightly hyperintense on T2-weighting and STIR. Two slightly inhomogeneous lesions contained thin (<5 mm thickness) tortuous vessels. One patient received intravenous contrast, but the lesion did not enhance. The six non-lipoma-like hibernomas measured 2.5-15.5 cm in maximum size and all were unencapsulated. Three were well-defined and three partly ill-defined on MR imaging. There were no significant differences in the MR characteristics of the non-lipoma-like variants. On T1-weighting, the non-lipoma-like hibernomas that contained >90% MVAs were predominantly slightly hypointense to subcutaneous fat. One lesion was isointense with subcutaneous fat, but this lesion only contained from 80-90% MVAs. All non-lipoma-like lesions were slightly hyperintense on STIR but so too were two of the four lipoma-like lesions. Four of the six non-lipoma-like lesions showed marked or moderate inhomogeneity due to thick septa and prominent vessels. Of the two cases that received intravenous contrast, both showed enhancement corresponding to regions of >90% MVAs or prominent vessels within fibrous septa. CONCLUSIONS: MR imaging has shown some distinguishing features between lipoma-like and non-lipoma-like hibernomas. Lipoma-like hibernomas are usually isointense with subcutaneous fat on T1-weighting, are either homogeneous or slightly inhomogeneous and may contain thin tortuous vascular structures. Non-lipoma-like hibernomas are pre-dominantly slightly hypointense to subcutaneous fat on T1-weighting, often display marked or moderate inhomogeneity with prominent septa and vessels and enhancement is typical. The appearances of non-lipoma-like hibernomas are not diagnostic and may be mimicked by lipoma variants and by well-differentiated liposarcoma or atypical lipoma.

Marsh stars in Liverpool.

INTRODUCTION/METHODS: After the recognition of contaminating algae on histopathological sections stained by periodic acid Schiff (PAS) and Grocott methods, a detailed audit was undertaken to assess the extent of contamination and its possible source. RESULTS: The contaminating organism was a member of the staurastrum genus of Chlorophyta, star shaped organisms commonly found in fresh water marshes. The organisms were seen on sections stained by the diastase-PAS, PAS, or Grocott methods and on cytological preparations between July 2003 and May 2004. It is unlikely that contamination of water baths or concentrated staining solutions was to blame, and a more general contamination of the laboratory water supply is the most likely source. CONCLUSIONS: Contaminating organisms may appear on histological and cytological material and their nature and source should be investigated. Although in this instance, confusion with pathologically important organisms was minimal, algae may occasionally cause significant disease.

acp Best Practice No 169. Evidence based pathology: squamous carcinoma of the hypopharynx.

This best practice article reviews the published evidence on the pathology and patterns of spread of carcinomas of the hypopharynx, and the relevance of pathological features to prognosis. Medline (1966-2001) was searched using a combination of head and neck neoplasms and prognosis, focusing on hypopharynx and pathology. Other relevant publications were identified from the bibliographies of these papers, and from those obtained opportunistically. There is relatively little pathological literature devoted specifically to squamous carcinomas of the hypopharynx and most information comes from large series of patients with head and neck cancers at a range at sites. Lack of consistency in reporting and shifts in terminology make comparisons between series difficult. The most important features determining prognosis are size and extent of local spread of the primary carcinoma and extent of involvement of regional lymph nodes. There is evidence to support the use of the minimum dataset criteria for head and neck carcinomas at this site. Within the hypopharynx, subsite related differences in aetiology and biology may become important.

The management of retroperitoneal soft tissue sarcoma: a single institution experience with a review of the literature.

AIM: Ten percent of soft tissue sarcomas (STS) arise in the retroperitoneal tissues. The prognosis for patients with retroperitoneal sarcoma is poor with a 5-year survival rate between 12% and 70%. Stage at presentation, high histological grade, unresectable primary tumour and incomplete resection are associated with a less favourable outcome. METHODS: Complete follow-up data were available on 22 patients who underwent surgery for retroperitoneal STS in our institution between 1990 and 2000. Patient, tumour and treatment variables were analysed including use of adjuvant therapy and survival status. RESULTS: Eighteen patients underwent surgery for primary disease, four patients were treated for recurrent disease or metastases. Ten patients presented with pain, seven with an abdominal mass, other presentation included weight loss and haematuria. Thirteen patients presented with tumours larger than 10 cm. The tumours were seven liposarcomas, six leiomyosarcomas, three malignant fibrous histiocytomas, two rhabdomyosarcomas, two malignant schwannomas and two undifferentiated sarcomas. Six primary tumours were completely excised, five patients received radiotherapy and five received chemotherapy. Local recurrence rate was 45% and recurrence-free interval for 10 patients with recurrence was 11 months. Five patients received radiotherapy and five received chemotherapy. The median survival for patients with primary tumours was 36 months, and 5-year survival was 44%. Adjuvant therapy was not associated with higher survival rates. CONCLUSION: This study re-emphasizes the poor outcome of patients with retroperitoneal STS. Adjuvant radiotherapy and chemotherapy do not appear to be any proven benefit and the single most important prognostic factor is aggressive successful en bloc resection of the primary tumour. Our resection rate and 5-year survival rates are comparable with previous reported UK series although lower than large reports from North American centres. This might partly be explained by difficulty in data collection in a retrospective analysis, but may reflect inadequate subspecialization in UK centres.

Molecular markers of metastasis in squamous carcinomas.

The prognosis for patients with squamous carcinomas of the head and neck region is strongly influenced by the presence or absence of cervical lymph node metastases. Biological markers that indicated a high risk of metastasis would have a major role in determining the optimal therapeutic strategy for these patients. This editorial discusses recent studies of molecular and genetic markers of squamous carcinomas in relation to metastatic potential and highlights some of the issues that limit current progress in this field of study.

Bizarre parosteal osteochondromatous proliferation with cortical invasion.

A 15-year-old male presented with an 18-month history of increasing swelling on the radial aspect of his left forearm. Radiographs and MR images showed a partly calcified mass on the lateral border of the radius with erosion of the underlying cortex. Following a CT-guided needle biopsy, the mass was excised by segmental resection of the radial shaft with replacement by a vascularised fibular graft. Histological examination of the resected specimen showed many features typical of a bizarre parosteal osteochondromatous proliferation (BPOP) but with destruction of the underlying cortical bone by cellular spindle cell tissue. Although there were no cytological signs of malignancy, we believe that this unusual disease should be regarded as a particularly aggressive form of BPOP and treated by wide excision. Clinical follow-up of our patient at 2 years shows no sign of local recurrence or metastasis.

Basic fibroblast growth factor and angiogenesis in squamous carcinoma of the tongue.

The relationship between basic fibroblast growth factor (bFGF), receptors for bFGF and neoangiogenesis was investigated in 51 patients with squamous cell carcinoma of the tongue, 26 of whom had metastatic disease in cervical lymph nodes. Vessels were demonstrated by immunocytochemical labelling for CD34 and expressed as raw counts and volume-weighted counts. bFGF protein and its receptors FGFR1(flg) and FGFR2(bek), were demonstrated using immunocytochemical labelling. In situ hybridisation for bFGF mRNA was performed using a 250-bp digoxigenin-labelled RNA probe. In normal epithelium, the expression of bFGF protein and mRNA was more intense in the basal layer, while receptors for bFGF were expressed more strongly in the superficial parts. In carcinomas, expression of bFGF was greater in the more poorly-differentiated cells, but showed no relation to the overall tumour differentiation. There was strong bFGF expression in tumour-infiltrating lymphocytes. The expression of bFGF receptors was variable, with FGFR2 being particularly high in areas of keratinisation. There were no consistent changes in bFGF or receptor expression between primary carcinomas and their lymph node metastases, and there was no correlation with measures of vascularity or tumour growth pattern. bFGF is synthesised by all squamous carcinomas and has the potential to modulate angiogenesis. However, these data suggest that changes in the expression of bFGF and its receptors are not related to the intensity of neoangiogenesis in lingual carcinomas or their nodal metastases.

Dermatomyositis and Whipple's disease.

A 14-year-old boy presented with a 3-year history of a skin rash typical of juvenile dermatomyositis, and a 2-month history of mild proximal weakness, myalgia, and weight loss. A quadriceps biopsy showed perifascicular fibre atrophy, focal necrosis and regeneration, immunohistochemical labelling for HLA-1 on the surface of the fibres, and focal C5-9 deposition in capillaries. Macrophages with diastase-resistant, PAS-positive cytoplasm were present. Ultrastructural studies showed electron dense and membranous debris. The patient's symptoms responded to intravenous immunoglobulin and oral prednisolone. Four months after discontinuing prednisolone, the patient developed cardiac failure, ventricular tachycardia, and a recurrence of his rash. The 16S ribosomal RNA specific for Tropheryma whippelii was identified by polymerase chain reaction (PCR) analysis in skeletal and cardiac muscle. The myalgia and skin rash responded to prednisolone and oral co-trimoxazole, and the tachycardia is controlled by oral verapamil. This patient appears to have a novel association of juvenile dermatomyositis and Whipple's disease.

Neoangiogenesis and squamous cell carcinoma of the tongue.

The relationship between neoangiogenesis and prognosis was investigated in 51 patients with surgically resected squamous carcinomas of the tongue. Twenty-six patients had lymph node metastases treated by radical neck dissection. Potential methodological sources of variation in vascular counts were examined. Vessels were immunolabeled for CD34, and the vessel counts (VC)--as well as the vessel counts adjusted for tumor area (VV)--were obtained in the most vascular parts of the carcinomas. Vascular hot spots were distributed throughout the carcinomas. The VC per hot spot increased with increasing size of carcinoma, and was higher in the resected carcinoma than in the diagnostic biopsy in four of eight cases. VC was not related to the growth pattern of the carcinoma or to metastasis, but patients with nodal metastases tended to have a lower VV than those with no metastases (p = 0.049). The tumor-specific survival of the whole group was 59%, and patients with nodal metastases had a shorter survival than those without metastases (p = 0.008). Cox's proportional hazards model demonstrated that carcinomas with a low VC tended to have a good prognosis (p = 0.023). The results from this relatively small series of cases support the hypothesis that some measures of neoangiogenesis are independent predictors of the spread and prognosis of lingual carcinomas. The variations in methodology among different studies currently preclude an accurate assessment of the prognostic significance of neoangiogenesis.

Effect of propylthiouracil-induced hypothyroidism on the onset of skeletal muscle necrosis in dystrophin-deficient mdx mice.

1. Duchenne and Becker muscular dystrophies are X-linked disorders caused by defects in muscle dystrophin. The mdx mouse is an animal model for Duchenne muscular dystrophy which has a point mutation in the dystrophin gene, resulting in little (<3%) or no expression of dystrophin in muscle. Mdx mice show a characteristic pattern of muscle necrosis and regeneration. Muscles are normal until the third postnatal week when widespread necrosis commences. This is followed by muscle regeneration, with the persistence of centrally nucleated fibres. 2. This work has examined the hypothesis that the onset of this muscle necrosis is associated with postnatal maturation of the thyroid endocrine system and that pharmacological inhibition of thyroid hormone synthesis delays the onset of muscle necrosis. 3. Serum T4 and T3 concentrations of mice were found to rise immediately before the onset of muscle necrosis in the mdx mouse, and induction of hypothyroidism by treatment of animals with propylthiouracil was found to delay the onset of muscle necrosis. 4. The results provide the first demonstration of experimental delay of muscle necrosis by manipulation of the endocrine system in muscle lacking dystrophin, and provide a novel insight into the way in which a lack of dystrophin interacts with postnatal development to precipitate muscle necrosis in the mdx mouse.

Myotubular myopathy: morphological, immunohistochemical and clinical variation.

Myotubular myopathy frequently presents in male infants with severe generalised muscular hypotonia and weakness associated with ventilatory insufficiency, and is diagnosed on biopsy by the presence of many fibres with central nuclei and mitochondrial aggregation. In a 6-year period, we have investigated five unrelated patients with clinical and pathological features suggesting an X-linked myotubular myopathy, including one female patient. In one male infant, a biopsy of vastus lateralis showed less than 2% centrally-nucleated fibres, while biceps brachii showed up to 15% centrally-nucleated fibres. Immunohistochemical expression of the neural cell adhesion molecule (CD56) was more intense in the biceps muscle than in vastus lateralis, while expression of desmin and vimentin was similar. Morphometric evaluation of tissue from each of the patients revealed a wide spread of values for the number of centrally-nucleated fibres per microscopic field, and variation in the extent of immunohistochemical expression of NCAM, utrophin, laminin alpha 5 chain, vimentin and HLA1 antigen. These variations in the manifestations of myotubular myopathy have not been previously described, and will need to be correlated with the increasing knowledge of the mutations in the MTM1 gene coding for myotubularin.