The presence of antibody in patients with malignant melanoma is well established if one examines the serum. In this report we have attempted to identify antibody within solid tumours showing that they are rarely present in any appreciable quantity on the surface of tumour cells but can be seen frequently on a number of different types of host cell within the tumours. This is discussed in the light of the role of antibody in the circulation and the possibility of antibody behaving as a blocking factor in vivo.
AIMS: To assess the incidence of foreign body giant cell reactions and ossification in benign/melanocytic naevi; and to examine their pathological features to gain an insight into their pathogenesis. METHODS: Intradermal (n = 185) and compound naevi (n = 110) from a routine histology service, together with 60 naevi submitted to an ophthalmic pathologist, were examined for foreign body reactions and ossification. Additional cases were identified prospectively in the course of routine reporting. The clinical and pathological features of positive cases were assessed. RESULTS: Foreign body reactions were identified in nine (4.9%) intradermal and four (3.6%) compound naevi, but in none of the naevi from around the eye. One intradermal naevus showed ossification. A further 11 naevi showing foreign body reaction and five showing ossification alone were identified prospectively. The 24 naevi showing a foreign body reaction had a similar age and sex distribution to controls but were more likely to occur on the head and neck. The reaction usually occurred deep to the naevus, sometimes in relation to a hair follicle, and fragments of hair or keratin were identified in most. Osteoid or bone was present within the reaction in five. In six other naevi, all from the head and neck of women, osteoid or mature bone was present deep to the naevus in the absence of a giant cell reaction. CONCLUSIONS: Foreign body giant cell reactions occur not uncommonly in relation to benign naevi, as a result of follicular damage, possibly due to trauma. The similar siting of foci of bone suggests that ossification occurs as a secondary phenomenon in these cases.
In the course of an investigation of melanocytic naevus development in Queensland, Australia, whole-body naevus counts of 66 adolescents were performed separately by two nurse examiners on two occasions on average 4 weeks apart. There was good agreement between the two examiners for counts of total naevi on the whole body (intra-class correlation coefficient = 0.96) and at selected subsites (face, neck, back, upper arms, lower arms). Agreement was lower when raised naevi only were counted (0.83). Intra-examiner repeatability was high for both nurses, particularly for the more experienced examiner (intra-class correlation coefficients = 0.98 and 0.91 for total naevi on the whole body), and was consistently better when all naevi were counted rather than naevi of a particular size. Independent counts of naevi on the back using a computer imaging technique were reproducible (intra-class correlation coefficient = 0.92), but showed only moderate agreement with counts by the nurse examiners. Overall, these results demonstrate high comparability of naevus counts between and within similarly trained examiners. They do not support the common practice in epidemiological studies of restricting counts to naevi larger than 2 mm, or of counting raised naevi only.
Melanocytes in melanocytic naevi and melanomas can display great variation. The presence of nuclear pseudoinclusions (NPI) is said to be useful in the histological and cytological differential diagnosis of malignant melanoma. The prevalence and characteristics of NPI in a series of 493 naevi and 50 melanomas are described. NPI were found in 31% of adult naevi, 30% of congenital naevi from children, 42% of Spitz naevi, 20% of dysplastic naevi, and 56% of melanomas. The presence of NPI is not a reliable criterion for differentiating melanoma from benign melanocytic lesions, although it is useful in distinguishing melanocytic from non-melanocytic tumours.
The monoclonal antibody NK1 C3, synthesised by the Netherlands Cancer Institute, has been used to assess its value in the diagnosis of melanocytic lesions. The antigen recognised by this antibody is not denatured by formalin fixation, with the result that the antibody can be used for retrospective studies on conventionally processed material. Positive results were obtained in primary melanoma (18/18), secondary melanoma (21/21), junctional and compound naevi (32/32), intradermal naevi (9/12), congenital naevi (3/3), so called dysplastic naevi (13/13), blue naevi (5/5), and Spitz tumours (3/14). Non-melanocytic tumours were tested for comparison. The results showed relative but not complete specificity of the antibody for melanocytic tumours, with positive results only in breast and prostate tumours (2/6 and 2/5 respectively). Negative results were obtained with basal and squamous cell carcinoma, appendage tumours, neural tumours, and apudomas. The staining pattern of NK1 C3 was compared with that of antibodies to S100 protein and to neurone specific enolase. Compared with S100 protein NK1 C3 gave stronger staining of a higher percentage of cells in the 12 specimens in which a direct comparison was made. Antibody raised against neurone specific enolase in sheep gave very poor results with heavy background staining. We suggest that NK1 C3 is a useful addition to the battery of monoclonal antibodies of value to the diagnostic histopathologist.
The term "dysplastic" melanocytic naevus has recently been used to describe pigmented naevi with unusual histological and clinical features. There is currently no clear clinical or pathological definition of the term, and this has led to a lack of comparability of material described in reports on these lesions. As a result of careful histological study and a clinicopathological correlation of 100 naevi, we suggest that three distinct groups of histopathological features distinguish so called dysplastic naevi from banal melanocytic naevi. These are architectural atypia, cytological atypia, and a host response. Description of each of these features in routine reports and in published series in place of the loose use of the term "dysplastic" would enable comparisons to be made between series of melanocytic lesions reported from different centres. In the course of this study we observed a considerably increased incidence of naevus type giant cells in the dermal portion of the atypical naevi. These giant cells should not be confused with possibly premalignant cytological atypia.
Dermoscopic patterns of normal-appearing skin have received little scrutiny. We have recently completed an analysis of dermoscopic patterns of naevi in children.
To describe dermoscopic patterns in the normal-appearing skin surrounding naevi and to explore histological features of patterned background skin.
Dermoscopic images of back naevi were obtained from a population-based sample of fifth grade students. The dermoscopic pattern of the background skin around the naevi was analysed. We examined histological features of background skin patterns in a convenience sample of seven specimens from six adult patients.
We observed a dermoscopic pattern in the background of normal-appearing skin in 41% of 1192 dermoscopic images from the backs of the 443 children. The background skin pattern was less frequent in individuals with a fair skin (P < 0.001). A globular pattern was observed in 201 images (17%) and a reticular pattern was seen in 287 images (24%), of which 112 images also showed globules. Inter-rater reliability between the two observers for a random sample of 100 images was excellent (κ = 0.77). In four specimens with a globular background pattern, microscopic melanocytic nests were observed in the normal-appearing skin. No subclinical naevus nests were observed in three reticular pattern specimens.
Dermoscopically recognized patterns are commonly present in clinically normal skin. Microscopic melanocytic nests may be observed in normal-appearing skin with a globular skin pattern.
children; dermoscopy; skin
The early diagnosis of melanoma is critical to achieving reduced mortality and increased survival. Although clinical examination is currently the method of choice for melanocytic lesion assessment, there is a growing interest among clinicians regarding the potential diagnostic utility of computerised image analysis. Recognising that there exist significant shortcomings in currently available algorithms, we are motivated to investigate the utility of lacunarity, a simple statistical measure previously used in geology and other fields for the analysis of fractal and multi-scaled images, in the automated assessment of melanocytic naevi and melanoma. Digitised dermoscopic images of 111 benign melanocytic naevi, 99 dysplastic naevi and 102 melanomas were obtained over the period 2003 to 2008, and subject to lacunarity analysis. We found the lacunarity algorithm could accurately distinguish melanoma from benign melanocytic naevi or non-melanoma without introducing many of the limitations associated with other previously reported diagnostic algorithms. Lacunarity analysis suggests an ordering of irregularity in melanocytic lesions, and we suggest the clinical application of this ordering may have utility in the naked-eye dermoscopic diagnosis of early melanoma.
AIMS: To investigate the immunoreactivity of a range of melanocytic lesions, both benign and malignant, with the monoclonal antibody VS38. This was recently described as a marker of reactive/neoplastic plasma cells and, therefore, is useful in the diagnosis of plasmacytoma/myeloma and lymphomas with plasmacytic differentiation. This study was prompted by the recent observation that a plasmacytoid melanoma arising in the nasal cavity was strongly immunoreactive with VS38, which was therefore a potential source of major diagnostic error. METHODS: The Streptavidin-peroxidase complex technique was used on paraffin wax embedded sections of 167 melanocytic lesions. Diaminobenzidine (DAB) was used as chromogen for non-pigmented or lightly pigmented lesions and nickel/DAB for more heavily pigmented lesions. RESULTS: Positive immunostaining for VS38 was seen in 14.5% (10/69) of benign naevi (including 40% (four of 10) of Spitz naevi), 10.5% (two of 19) of dysplastic naevi/in situ melanomas, 92% (35/38) of primary cutaneous melanomas, 100% (four of four) of primary mucosal melanomas, 91.7% (33/36) of recurrent/metastatic melanomas, and 100% (one of one) of clear cell sarcomas of soft tissues. CONCLUSIONS: VS38 immunostaining is frequently positive in primary and recurrent/metastatic malignant melanoma and is also reactive less commonly with benign naevi. These results should be borne in mind when this recently described marker of normal/neoplastic plasma cells is used to identify tumour lineage, particularly in tumours arising at unusual sites, such as in the nasal cavity. The possibility of malignant melanoma should be actively considered and excluded in any undifferentiated tumour which shows VS38 immunoreactivity.
Gorlin syndrome is an autosomal dominant multisystem disorder characterised by multiple basal cell naevi, cysts of the jaw, pits of the palms and soles, skeletal anomalies, and various other defects. Patients with Gorlin syndrome have a predisposition to basal cell carcinomas and other neoplasms. This is the first report to describe the coexistence of Gorlin syndrome and a nasal dermoid cyst. A 4 year old girl was diagnosed with medulloblastoma and treated with surgery and radiation therapy. A genetic evaluation was sought because of the brain tumour, multiple small naevi localised mostly on the upper torso, and rib abnormalities. Biopsies of several naevi showed naevoid basal cell carcinoma. Past medical history was significant for a midline nasal punctum noted at birth. The significance of this finding was unrecognised until the dermoid cyst enlarged, just before the diagnosis of her brain tumour. A common tissue of origin exists between basal cell naevi, cysts of the jaw, and dermoid cysts. We propose that the association of these two rare conditions in one patient is not a chance occurrence.
Background/Aims: The clinical definition of an atypical naevus (“dysplastic naevus” or “naevus with architectural disorder and cytological atypia of melanocytes”) stresses size larger than 5 mm in diameter as a major diagnostic criterion. Because malignant melanomas and their precursors may arise in smaller lesions, a histological study of melanocytic lesions smaller than 4 mm in diameter was conducted to evaluate their histological appearance.
Methods: Two hundred and sixty one naevi smaller than 4 mm in diameter were collected and characterised by histological examination into benign naevi without architectural disorder and naevi with architectural disorder and mild, moderate, and severe atypical melanocytes according to criteria used on larger lesions.
Results: Small melanocytic naevi covered the same complex histological spectrum from benign naevi to severely atypical naevi when compared with larger lesions. A high proportion of small naevi (72%) exhibited features diagnostic for naevi with architectural disorder and cytological atypia.
Conclusion: There is a discrepancy between histological and clinically defined atypical naevi. The same generally accepted criteria for the histological diagnosis of atypical naevi should be used for small melanocytic naevi in addition to large ones. Thus, small naevi exhibiting atypical features on histological examination should be categorised as atypical naevi, regardless of their small diameter.
atypical naevi; dysplastic naevi; naevi with architectural disorder; grading of nuclear atypia
The presence of both laminin and type IV collagen was sought at the dermo-epidermal junction and in the dermis adjacent to benign melanocytic naevi of the junctional, compound, and intradermal types; dysplastic naevi; and both primary and secondary melanoma. In all, 154 lesions were studied, using antibodies to laminin and type IV collagen and an indirect immunoperoxidase technique. The staining patterns seen with the two antibodies were virtually identical, although that of laminin was generally fainter. Breaks in and thinning of the normally continuous line of type IV collagen and laminin at the dermo-epidermal junction were seen in association with the junctional activity of benign naevi, and in malignant melanomas in association with invasive tumour cells. Both benign and malignant cells of the melanocyte series showed relatively light pericellular staining around individual cells and clusters of cells in the papillary dermis. This staining pattern was much stronger in the deeper reticular dermis. It is concluded that the pattern of staining of these two antibodies and in particular the presence of breaks in type IV collagen and laminin at the dermo-epidermal junction are not specific for either benign or malignant melanocytic lesions and cannot be used as a diagnostic marker of invasive malignancy.