Human papilloma virus in squamous carcinoma of the head and neck: a study of cases in south east Scotland.

Several studies have found human papillomavirus virus (HPV) in tissue from head and neck squamous cell carcinomas (HNSCCs), although the number of positive cases varies greatly from study to study. The extent and molecular epidemiology of HPV in HNSCC were assessed within cases drawn from southeast Scotland by performing broad-spectrum, real-time HPV polymerase chain reaction (PCR) on DNA extracted from 100 cases of HNSCC in formalin-fixed, paraffin wax-embedded material. All HPV-positive specimens were genotyped and sampled by laser capture microdissection. Pure samples of tumour, and, where possible, dysplastic and normal epithelium were then submitted for further HPV PCR and genotyping to investigate the sensitivity of the technique in small tissue samples. 10 of 100 cases tested positive for HPV, with 8 of these being derived from Waldeyer's ring. HPV DNA was found in adjacent epithelium in two of four cases where this was available. These findings confirm that HPV is likely to be involved in a subset of HNSCC in this population and that successful amplification of HPV nucleic acid is possible even using small amounts of paraffin wax-embedded tissue.

Embryonal rhabdomyosarcoma of adult nasopharynx.

Adult rhabdomyosarcomas in the head and neck are extremely rare and carry a poor prognosis. They should be considered as a distinct clinical entity. The authors report a case of embryonal rhabdomyosarcoma in an adult nasopharynx treated with a combined modality treatment of chemotherapy and radiotherapy as per the European International Society of Paediatric Oncology (SIOP) MMT 89 study, group D. The patient responded to treatment and 10 years later, he is still alive with no signs of metastatic disease.

Factitious panniculitis masquerading as pyoderma gangrenosum.

We report a case of factitious panniculitis masquerading as florid pyoderma gangrenosum in a 35-year-old woman. At presentation, she had tender, ecchymotic plaques over the lower trunk and limbs, and several biopsies showed active lobular panniculitis. However, the extensive ulceration that ensued was clinically persuasive for pyoderma gangrenosum. We elected to treat the inflammatory element symptomatically with a range of topical and systemic medications including clobetasol propionate, tacrolimus 0.1% ointment, prednisolone, dapsone, cyclosporin A and mycophenolate mofetil, none of which effected an improvement. The possibility of a factitious aetiology had been suspected from the outset, and when signs of clinical depression emerged, antidepressant therapy was initiated and the ulcers were encased in fibreglass casts. Within a short period, healing commenced and slowly progressed with scar formation. In retrospect, we consider the diagnosis to have been factitious panniculitis on the basis of strong circumstantial evidence and the disparity between the histological and clinical features.

Level of agreement and biopsy correlation using two- and three-tier systems to grade cervical dyskaryosis.

At present, a three-tier system is used to grade cervical dyskaryosis in the UK, although the two-tier Bethesda system is used in the United States, and the British Society for Clinical Cytology has recommended that a two-tier system be implemented here. In this study, we have retrospectively re-graded 117 conventional cervical smears using both systems to determine the intra- and interobserver variation and compare the cytology grading in both systems with the final histology. The intra and interobserver agreement was moderate using both grading systems, but the agreement between cytology grade and final histology was poor in both the two- and three-tier systems, and slightly worse using two-tier grading. However, when each of the three histological categories is considered separately the two-tier system appears to work better. Therefore, changing the way in which cervical dyskaryosis is graded in the UK may result in poorer agreement between the cervical smear result and the final histological diagnosis if introduced without proper training, monitoring and assessment.

Best practice in thyroid pathology.

Thyroid pathology is a specialist area but is often encountered by the general pathologist in a variety of forms including cytology, frozen sections, and resection specimens. In the thyroid gland, as for other endocrine organs, many aspects of diagnosis are unique to this area of histopathology; thus, the aims of this paper are to set out best practice guidelines which, although not entirely comprehensive, will be of practical use.

Observer variability in the Goseki grouping of gastric adenocarcinoma in resection and biopsy specimens.

AIMS: The Goseki grouping of gastric adenocarcinoma has been suggested as a possible prognostic factor. In those centres where it is used, it may be valuable to assess the Goseki grouping of a tumour on the initial diagnostic biopsy as well as on the resection specimen since it may in theory influence management. We examined the robustness of Goseki grouping of gastric adenocarcinoma in representative sections from resection and biopsy specimens in order to assess the consistency of agreement among a group of pathologists. METHODS: A single representative block from 100 gastric resection specimens was studied using a haematoxylin and eosin and mucin (alcian blue/periodic acid-Schiff) stain. These were circulated in batches to members of a group of 12 pathologists who each completed a simple proforma confirming the presence of carcinoma and assigning a Goseki group. In a second circulation the diagnostic biopsy specimen taken prior to resection was examined in the same way. This allowed comparison of the Goseki group of the biopsy and resection specimens. RESULTS: In both studies kappa statistics showed good agreement on tubular differentiation of the carcinoma, but only moderate agreement for the intracellular mucin production, resulting in moderate agreement for the final Goseki group. Correlation between the Goseki group assigned on the biopsy and resected specimens was seen in 62% of the cases. However, the reproducibility was low (kappa 0.375). CONCLUSIONS: The Goseki grouping of resected gastric adenocarcinoma is reproducible and can be used in prognostication. Goseki grouping of biopsy specimens is of limited value in predicting the Goseki group assigned to the resected carcinoma.

Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules.

AIMS: The immunohistochemical expression of cytokeratin 19 (CK 19) and galectin-3 was evaluated in 69 thyroid lesions to assess their potential as markers in the diagnosis and classification of thyroid malignancy. The following were studied: 26 cases of papillary carcinoma, 12 of follicular carcinoma, 20 follicular adenomas, two medullary carcinomas, one anaplastic carcinoma and eight multinodular goitres. METHODS AND RESULTS: Formalin-fixed paraffin-embedded thyroid tissues were stained immunohistochemically for both CK 19 and galectin-3. CK 19 expression was found in all 26 papillary carcinomas, five of 12 follicular carcinomas, two of two medullary carcinomas and one case of anaplastic carcinoma. Only five of 20 follicular adenomas were positive for CK 19, and this was in a focal distribution. Two of eight multinodular goitres stained focally positive. Galectin-3 expression was found in 22 of 26 papillary carcinomas, 12 of 12 follicular carcinomas and one of two cases of medullary carcinoma. Only two of 20 follicular adenomas were positive. Three of eight multinodular goitres showed focal galectin-3 expression. CONCLUSIONS: Our findings suggest that the immunohistochemical localization of CK 19 and of galectin-3 is a useful adjunct to the histopathological diagnosis of a solitary thyroid lesion. The expression of CK 19 favours a diagnosis of papillary carcinoma in all its variant patterns. Galectin-3 may serve as a marker for the recognition of follicular carcinoma, particularly the minimally invasive form.

Consistency of histopathological reporting of laryngeal dysplasia. The Scottish Pathology Consistency Group.

AIMS: Clinical management of premalignant and malignant lesions of the larynx is dependent on histopathological evaluation. The Scottish Pathology Consistency Group assessed interobserver variation in the evaluation of laryngeal dysplasia. METHODS AND RESULTS: One hundred laryngeal biopsies ranging from normal to invasive carcinoma were assessed. The overall Kappa result of 0.32 was disappointing. However, agreement on those categories which dictate significantly different management was more favourable. The Kappa figure for mild dysplasia versus severe dysplasia/CIS was 0.7, the Kappa figure for mild dysplasia versus severe dysplasia/CIS and invasive carcinoma was 0.77. The Kappa figure for mild and moderate dysplasia versus severe dysplasia/ CIS and invasive carcinoma was 0.57. An attempt to use a two grade system gave a Kappa figure of 0.52. CONCLUSIONS: Our group had a satisfactory agreement on the distinction of mild from severe dysplasia and on microinvasive carcinoma without any discussion as to histopathological criteria to be used. Clinical management--review endoscopy, repeat cord stripping, radiotherapy and laryngectomy--is in general dependent on histological assessment. Thus the agreement on categories which underpin clinical management is reassuring. However, assessment of moderate dysplasia remains problematic. An attempt to utilize a two grade system--low grade from high grade dysplasia/CIS--may have merit. The implications of the terminology used must be agreed among pathologists and clinicians working closely within clinicopathological cancer groups.

CDKN2A mutation and deletion status in thin and thick primary melanoma.

Human melanoma cell lines and tumor tissue from familial and sporadic melanomas have frequent, nonrandom chromosomal breaks and deletions on chromosome 9p21, a region that includes the tumor suppressor gene CDKN2A/p16INK4A. Germ-line mutations within this gene have been observed in some familial melanoma kindreds, but somatic mutation in sporadic primary melanoma is infrequent. Thirty-nine archival, paraffin-embedded, sporadic, primary cutaneous malignant melanomas (20 >3-mm-thick and 19 <0.75-mm-thick cases) were examined for mutations of the CDKN2A gene using single-strand conformational polymorphism analysis and direct sequencing. No mutations were detected. Loss of heterozygosity for the 9p21 microsatellite marker D9S942 was detected in 6 of 17 informative thick lesions (35%) but 0 of 18 thin lesions (P = 0.006). These results support other studies indicating that intragenic mutation is an infrequent mechanism of CDKN2A inactivation in primary melanoma. The finding of loss of heterozygosity for the 9p21 microsatellite D9S942 in thick but not thin primary melanoma suggests that deletion or inactivation of CDKN2A or other tumor suppressor gene(s) at this locus is involved in the progression rather than initiation of sporadic malignant melanoma.

Malignant melanoma and lymphoproliferative malignancy: is there a shared aetiology?

We report seven patients who developed malignant melanoma either coincident with or before the diagnosis of non-Hodgkin's lymphoma or chronic lymphatic leukaemia. One patient died secondary to leukaemia, and chemotherapy-induced immunosuppression may have contributed to the development of metastatic melanoma in another patient. Immunosuppression, exposure to ultraviolet radiation and genetic factors may result in a host environment that is conducive to the development of both tumours in these patients.

Amelanotic malignant melanoma following cryosurgery for atypical lentigo maligna.

Cryosurgery is an alternative treatment option to surgical excision for lentigo maligna. Clinical evidence of recurrence is usually characterized by repigmentation at the treated site. We report two patients who developed amelanotic malignant melanoma following cryosurgery for a pigmented lentigo maligna. These cases illustrate the potential risk of treating lentigo maligna with cryosurgery.

Aneurysmal fibrous histiocytoma: an unusual variant of cutaneous fibrous histiocytoma.

Aneurysmal fibrous histiocytoma (AFH) (Santa-Cruz DJ, Kyriakos M. Aneurysmal ('Angiomatoid') fibrous histiocytoma of the skin. Cancer 1981;47:2053-2061) is a distinct but poorly recognized clinicopathological variant of cutaneous fibrous histiocytoma (CFH) that may result from the slow extravasation of blood into the tumour. The resulting lesion can have a very different clinicopathological appearance resulting in diagnostic confusion. We describe a patient with an AFH that presented as a pigmented nodule on the foot and discuss clinical recognition and histological differentiation from other tumours.

A rational approach to melanoma follow-up in patients with primary cutaneous melanoma. Scottish Melanoma Group.

From the Scottish Melanoma Group database for south-east Scotland we evaluated 5-year follow-up in patients with cutaneous malignant melanoma excised between 1979 and 1994 and devised an 'evidence-based' review protocol. Of the 1568 with stage I melanoma, 293 (19%) developed a recurrence, 32 had a second primary melanoma and 97 had an in-situ melanoma. The disease-free interval shortened progressively with increasing tumour thickness. Overall, 80% of recurrences were within the first 3 years, but a few patients (< 8%) had recurrences 5 or 10 years after the initial surgery. In-situ melanomas did not recur. Almost half (47%) the recurrences were noted first by the patient, and only 26% were detected first at a follow-up clinic. One hundred and thirty-nine patients (89%) were still under review when their recurrences were detected, and 102 (65%) had been seen within the previous 3 months. Questionnaires were completed by 120 patients: sun protection and avoidance, and mole examination were more likely after melanoma excision. We recommend 3-monthly review of patients with invasive lesions for the first 3 years. Thereafter, those with lesions >/= 1.0 mm need two further annual reviews. Patients with in-situ lesions should be reviewed once, to confirm adequate excision (0.5 cm margins) and to give appropriate education. Surveillance beyond 5 years is only justified if there are special risk factors.

Hyalinizing clear cell carcinoma of the oral cavity and of the parotid gland.

Hyalinizing clear cell carcinoma (HCCC) is a rare, recently described tumor of salivary gland origin. Differential diagnosis includes benign lesions as clear cell change in a pleomorphic adenoma or in oncocytoma and malignant tumors - i.e. epithelial-myoepithelial carcinoma, polymorphous low-grade adenocarcinoma, mucoepidermoid carcinoma, clear cell acinic carcinoma, clear cell squamous carcinoma, clear cell malignant melanoma, clear cell odontogenic carcinoma, clear cell rhabdomyosarcoma, sebaceous carcinoma and metastasis of renal carcinoma. A favorable prognosis after wide local excision has been evidenced. Three new cases of HCCC (2 in the oral cavity and 1 in the parotid gland) are presented.

Amelanotic lentigo maligna and amelanotic lentigo maligna melanoma: a report of three cases mimicking intraepidermal squamous carcinoma.

The clinical diagnosis of amelanotic melanoma may pose diagnostic difficulties. We report three cases of amelanotic lentigo maligna, two of which developed an invasive component (lentigo maligna melanoma). The clinical appearances in each case mimicked intraepidermal squamous carcinoma.

Observer variability in the histopathological reporting of needle biopsy specimens of the prostate.

The Scottish Pathology Consistency Group has in previous studies examined the consistency of histopathological reporting of biopsies from the cervix, bladder, bronchus, and rectum. In the current study, consisting of 100 needle biopsy specimens of the prostate, a single hematoxylin-eosin (H&E) slide from each case was circulated in batches of 10 to the 12 pathologists, who filled in a simple proforma. This had two sections: a diagnostic category (benign; suspicious or malignant) along with a standard Gleason score for those regarded as malignant. The majority diagnosis of the 100 cases was benign, 53; suspicious, 1; and malignant, 46. The Kappa value for benign cases versus others was 0.86 and for malignant cases versus others was 0.91. Analysis of the data on Gleason scores showed a value of 0.54 when cases were divided into two categories (2 to 6 v 7 to 10) and 0.41 when three categories were used (2 to 4; 5 to 6; 7 to 10). Although not initially part of the design of the study, the majority diagnosis was compared with the original reported diagnosis. In a small subset, examination of further levels, basal cell antibody staining, along with further clinical information, was obtained. With this added information, it appears that there were probably 52 benign and 48 malignant cases. Of the 48 malignant cases, the group majority diagnosis was malignant, 46; suspicious, 1; and benign, 1. The original reported diagnosis was 56 benign, 1 suspicious, and 43 malignant. The group therefore appeared to perform better than the original reporting pathologists. When compared with the results of our previous studies, this study has shown that the diagnosis of carcinoma of the prostate on a needle biopsy is robust.