Segmental hypomelanosis and hypermelanosis arranged in a checkerboard pattern are distinct naevi: flag‐like hypomelanotic naevus and flag‐like hypermelanotic naevus

The categorization of congenital hypo‐ or hyperpigmented skin lesions following a segmental pattern has been a long‐lasting matter of debate and have been reported under various and often incorrect terms. To reassess published hypomelanotic and hypermelanotic lesions that did not follow Blaschko lines nor a phylloid pattern of mosaicism, we carried out an extensive and critical review of the worldwide literature. Seventy‐four retrieved cases consisted of lateralized hypomelanotic lesions arranged in a flag‐like pattern or appearing as large patches of grossly oval or angulated shape and sharp, serrated margins. Sometimes lesions harboured maculopapular melanocytic naevi or cooccurred with other segmentally arranged naevi. A probably non‐random association with extracutaneous anomalies was also reported on rare occasions. In 70 cases, lateralized hypermelanotic patches were arranged in a flag‐like pattern that often appeared as large quadrangular patches. Sometimes lesions harboured Spitz naevi. Ten cases belonged to phacomatosis melanorosea, whereas several others were part of so far uncategorized cases of phacomatosis pigmentovascularis. Flag‐like hypomelanosis is a distinct naevus type, for which the term ‘flag‐like hypomelanotic naevus’ is suggested. Its cooccurrence with extracutaneous abnormalities might represent a specific syndrome. Flag‐like hypermelanosis is a distinct naevus type, for which the term ‘flag‐like hypermelanotic naevus’ is suggested. Its co‐occurrence with naevus roseus defines phacomatosis melanorosea. Flag‐like hypermelanotic naevus should be distinguished from the checkerboard‐like areas of darker skin as observed in chimaeras.     

Spitz naevi misdiagnosed histologically as melanoma: Prevalence and clinical profile

A Spitz naevus is a benign melanocytic tumour that may histologically resemble a malignant melanoma. Data was retrospectively gathered from patients who attended the Victorian Melanoma Service to determine the prevalence of Spitz naevi pathologically misdiagnosed as melanoma. Assessment of the clinical characteristics of these patients was also performed and compared to those with correctly diagnosed melanoma. It was found that 6.5% of all melanomas referred were in fact Spitz naevi and that Spitz naevi represented the majority of pathologically misdiagnosed melanomas. The Spitz naevi were more likely to be on the lower extremities and were on average, considerably smaller than the melanomas. Patients with Spitz naevi were more likely to be younger, female, have fewer dysplastic naevi and have brown eyes. One hundred per cent of the Spitz naevi were brought to the attention of the initial doctor by the patient compared to 72% of the melanomas. This study concludes that Spitz naevi that are pathologically misdiagnosed as melanomas retain the clinical characteristics of other Spitz naevi and mat greater clinicopathological communication may reduce the frequency of diagnostic error.     

Segmental acne versus mosaic conditions with acne lesions

Acne rarely presents in segmental patterns, which are encountered only in cutaneous mosaicism. We report herein two cases of segmentally arranged acne and systematically review the literature on the topic. Beside already known mosaic conditions which may show primary lesions typical of acne, i.e. nevus comedonicus, Happle-Tinschert syndrome, acne superimposed on epidermal nevi and mosaic Apert syndrome, we introduce the possibility that acne itself may present in a mosaic form. As from the extremely small casuistics retrieved, segmental acne is not present at birth, follows Blaschko lines, is polymorphous in nature and occurs on locations typical of common acne.     

Multiple agminate Spitz naevi: Review of the literature and report of a case with distinctive immunohistological features

We describe a 13-year-old girl with multiple pigmented nodules and plaques arranged in a cluster in the right lumbar region, which had developed since infancy. Eleven of 15 lesions which were examined histologically were found to be Spitz naevi. The remaining four lesions were compound naevocellular naevi, and two of them showed focal dysplasia. Eight Spitz naevi were investigated immunohistologically with monoclonal antibodies against HLA-antigens and malignancy-associated melanocytic antigens which are rarely present in common naevi. Naevus cells in all lesions expressed HLA-ABC antigens, but lacked HLA-DR antigens in seven of the eight lesions. All naevi were positive for 'constitutive' (KG-6-56) and 'early' (K-1-2) markers of naevomelanocytic cells. In five of the eight Spitz naevi, at least one of the three malignancy-associated melanocytic antigens PAL-M1, A-1-43 and A-10-33 was found. The expression of malignancy-associated antigens in multiple agminate Spitz naevi is at variance with their benign clinical course.     

The spectrum of spitzoid tumours: A clinical study

This study explores the relationship between different types of spitzoid tumours, spindle cell naevus of Reed and spitzoid melanomas. Clinical and histopathological data were retrospectively reviewed from our hospital database in Cambridge from January 2006 to July 2009. Clinical images, where available, were recorded. Search headings from our pathology database included ‘spitzoid tumours’, ‘Spitz naevi’, ‘atypical spitzoid tumours’, spitzoid tumours of uncertain malignant potential (‘STUMP’), ‘spindle cell naevus of Reed’ and ‘spitzoid melanomas’. The total number of spitzoid tumours was 118 comprising Spitz naevi (72), atypical spitzoid tumours (30), spitzoid melanomas (eight), and other naevi with spitzoid features (eight). In total, 60% of Spitz naevi were diagnosed clinically and 50% reported a history of change with spitzoid melanoma, compared with 32% with Spitz naevi. In all, 60% of Spitz naevi and atypical spitzoid tumours were pigmented in contrast with spitzoid melanomas (83%). Variegated pigmentation was found in 20% of Spitz naevi and atypical spitzoid tumours, however, no spitzoid melanomas had mixed pigmentation. There were 30 atypical spitzoid tumours (9 M : 21 F); 16 occurred on the lower limbs, peaking in the 20–30‐years age group. There were eight patients with spitzoid melanomas with a 7:1 F : M ratio, 50% of which were diagnosed clinically. Of the 34 spindle cell naevus of Reed (10 M : 24 F), 31 were misdiagnosed, most commonly as melanoma. Reed naevi peaked in the 30–40 year age group and on the upper limbs and lower limbs in the 20–30‐years age group. In summary, age and sex appeared helpful in distinguishing benign from malignant spitzoid tumours, however history was less discriminatory. Spitzoid melanomas, most of which were pigmented occurred more commonly in females. Atypical spitzoid tumours were more common in females and pathologists favoured malignancy in this group beyond 20 years of age.     

An assessment of the value of Ag NOR staining in the identification of dysplastic and other borderline melanocytic naevi

One hundred and six melanocytic lesions were studied to determine the value of the so called Ag NOR technique in differentiating dysplastic naevi, Spitz naevi and spindle cell naevi of Reed from malignant melanoma and from 'banal' compound or intradermal naevi. In 79 cases Ag NOR counts were possible. The banal naevi (36) had a mean count of 1.54, (SD 0.3), and the unequivocally malignant superficial spreading melanomas (13), lentigo maligna melanomas (4) and secondary melanomas (4) had a mean count overall of 3.9 (SD 1.59). For dysplastic naevi (16) the mean Ag NOR count was 1.63 (SD 0.36) and for Spitz and spindle cell naevi (in toto 6) the figure was 1.72 (SD 0.55). The difference in Ag NOR counts between all types of naevi and all types of melanoma was highly statistically significant, but there was no difference between banal naevi and dysplastic, Spitz, and spindle cell naevi. Correlation of Ag NOR counts between three independent observers was good. This technique may, therefore, be a useful adjunct in separating true melanoma from borderline melanocytic naevi.     

Pigmented spindle cell naevus

We report 22 cases of pigmented spindle cell naevus (PSCN). The usual appearance of these naevi is that of a heavily pigmented papule found mostly on the legs of young patients. Histologically, PSCN was characterized by symmetrical proliferation of spindle-shaped pigmented melanocytes grouped in large junctional nests. Pagetoid spread of single cells in the overlying epidermis was frequently found. In our opinion, PSCN is a distinctive benign acquired melanocytic naevus that in the past has been frequently misdiagnosed as atypical Spitz naevi or malignant melanoma.     

Dysplastic naevus in non-familial melanoma. A clinicopathological study of 101 cases

In 101 patients with non-familial cutaneous melanoma (CM), melanocytic naevi were counted and classified according to clinical criteria. Only 8% of the patients had very atypical naevi. These atypical naevi were few in number and only one patient exhibited dysplastic naevus syndrome. An histological study was undertaken on the hypothesis that, in a given individual, if the most clinically atypical naevus is not histologically dysplastic it is unlikely that any of the others are. The most clinically atypical naevus in each patient was biopsied. Estimated in this way the prevalence of dysplastic naevi in patients with non-familial CM was only 18%. Comparison of patients with and without dysplastic naevi did not suggest that they constituted two different subsets. An attempt to correlate clinical diagnosis and histological features in this group of patients showed that the diagnosis of dysplastic naevi on the basis of clinical criteria alone is difficult and not reliable.     

Spitz naevus is rare in Korea

Background. Spitz naevi have not been widely studied in Asians. Aim. To compare the epidemiology and clinicopathological features of Spitz naevi in Koreans with lesions in western countries. Methods. In total, 80 Spitz naevi in 77 patients diagnosed over 10 years at 17 university hospitals in Korea were analysed. Results. The relative incidence of Spitz naevus vs. MM was 1 vs. 10.9. In most patients (75%) the Spitz naevi had been present for > 6 months. The size of the lesion was relatively large. Histologically, most of the lesions (54%) were the dermal type and pigmentation was common (49% of lesions). Immunohistochemical study found that all of the 34 lesions were positive for S‐100 protein but only 14 (47%) were positive for HMB‐45. Conclusion. Spitz naevus is rare in Korea. The lesions were more commonly larger, pigmented, and of the dermal type than reported in western countries.     

Familial melanoma

The presence of large numbers of moles, atypical in appearance and distribution typifies the atypical mole syndrome. The syndrome may occur in one individual alone or in an autosomal-dominant fashion in his/her family. The presence of this phenotype indicates an increased risk of melanoma, although the risk varies according to the presence or absence of a family history. The classification devised by Kraemer et al.¹ works well in estimating the risk of melanomas but is, as yet, not fully evaluated. The diagnosis of the syndrome is essentially clinical, necessitating the consideration of various aspects of phenotype such as total mole count, distribution, clinical appearance of the moles, the age of onset, site, and number of melanomas. It is always helpful to screen first-degree and second-degree relatives if there is a family history of moleyness or melanoma. Small numbers of clinically and, sometimes histologically dysplastic naevi may occur in normal individuals. The vast majority of these probably regress as do totally banal naevi, although a low percentage will result in a melanoma.² Those patients should be questioned to establish the existence of a family history of increased numbers of moles and melanoma. They should also be thoroughly examined for the presence of other signs of the syndrome: increased total mole count, iris freckles etc. In the absence of either a family history or these additional clinical features it is unlikely that these individuals have‘the syndrome'. Common sense advice about sun avoidance and self-examination should be given. It is important to distinguish this from the atypical mole syndrome (AMS). Many authors are unhappy about the use of the term‘dysplastic naevus syndrome’for this condition, partly because the histological appearances of the atypical naevi are not dysplastic in the true sense of the word.³ There has also been considerable uncase amongst pathologists about the implications of reporting a naevus as‘dysplastic’. The situation may be improved if it is recognized that dysplastic naevi can occur normally in the general population and that what is important is the recognition of the full phenotype and family history. Some patients from melanoma families do not have‘classically dysplastic’naevi. It is, therefore, probably better to abandon the term dysplastic naevus syndrome in favour of‘atypical mole syndrome’.     

Atypical lentiginous junctional naevi of the elderly and melanoma

The diagnosis of atypical lentiginous melanocytic naevi in chronic sun-damaged skin is a clinical and pathological challenge. Mottled skin in the elderly is a result of extensive freckling, guttate hypomelanosis, solar lentigines, seborrhoeic keratoses and small dark lentigines. In addition, atypical lentiginous junctional naevi may be seen as isolated lesions and may merge with lesions that are indistinguishable from lentigo maligna. The predominant site distribution of such lesions on the trunk and limbs and the presence of a nested naevoid pattern on biopsy differs from classical lentigo maligna, which develops mainly on the head and neck. Based on case studies combining dermatoscopy with clinical and pathological features, we have found that atypical lentiginous junctional naevi of the elderly may evolve to lentigo maligna and in some cases to small cell (naevoid) melanomas. Such lesions have been previously classified as dysplastic naevi, atypical melanocytic hyperplasia, atypical melanocytic proliferation, atypical lentiginous melanocytic proliferation or premalignant melanosis (McGovern). The current definition of lentigo maligna appears too narrow and the pathway to lentigo maligna in the elderly skin may include a naevoid subset.     

p53 immunoreactivity in human malignant melanoma and dysplastic naevi

Expression of the tumour suppressor protein, p53, was determined in 77 cutaneous melanocytic lesions, and in five lymph node metastases from malignant melanoma, in an immunohistochemical study employing CM-1, an antiserum raised against recombinant human p53 protein. Because wildtype p53 protein is rapidly degraded in normal cells, p53 immunoreactivity suggests the presence of an abnormally stable p53 protein. This may occur through either post-translational mechanisms or gene mutation. A highly significant correlation was found between p53 immunoreactivity and malignancy in melanocytic lesions (P<0.0001). Overall, p53 immunoreactivity was observed in 63% of tumour specimens examined, but not in benign melanocytic naevi, although occasional foci of weak nuclear p53 immunoreactivity were observed in a minority of dysplastic naevi and a solitary Spitz naevus. A significant correlation was also found between strong p53 immunoreactivity and malignant melanomas associated with a poor prognosis (P=0.008). These data suggest an important role for p53 tumour suppressor protein in the biology of human cutaneous malignant melanoma.     

‘Congenital follicular melanocytic naevi’: a more appropriate term for spotted grouped pigmented naevi

We report two patients with an uncommon form of pigmented naevus consisting of grouped follicular papules. A biopsy taken from the lesions showed multiple naevus cells, predominantly around the hair follicles, with sparing of the eccrine glands. The clinicohistopathological term given for this condition is ‘spotted grouped pigmented naevi type I’, and has rarely been reported. We discuss the unusual morphology and differential diagnosis of this condition, and suggest that the term ‘congenital follicular melanocytic naevi’ is more appropriate for this presentation.     

Segmentally arranged seborrhoeic keratoses with impending atypia and squamous cell carcinoma in an elderly woman

Epidermal naevi (EN) are considered mosaic disorders. Postzygotic mutations are thought to occur during early embryogenesis. They are usually arranged along Blaschko's lines and tend to be noted either at birth or shortly thereafter. Skin tumours arising on EN are occasionally reported, with ongoing discussion as to whether these are collision tumours or a malignant transformation of the EN. We describe a 76‐year‐old woman with segmentally arranged seborrhoeic keratoses that showed impending atypia and, in one lesion, even overt malignant transformation. In biopsies from various lesions we found FGFR3 and PIK3CA hotspot mutations but there was no consistent pattern of mutations explaining the premalignant or malignant growth. So far it is unclear whether the precancerous changes as noted in this elderly patient can be taken as an unusual manifestation of one of the established types of EN, or whether this may represent a separate disorder that could be called ‘SASKIA naevus’. The acronym would stand for s egmentally a rranged s eborrhoeic k eratoses with i mpending a typia.     

Seven-point checklist of dermoscopy revisited

Background Most dermoscopic algorithms to diagnose melanoma were established more than 10 years ago and have been tested primarily on clear‐cut melanomas and excised melanocytic naevi. Objectives To assess the diagnostic performance of pattern analysis and seven‐point checklist on lesions that reflect the current clinical setting, compared with a revised seven‐point checklist with a lower threshold for excision. Methods Eight experienced dermatologists viewed dermoscopic images of 100 excised melanomas, 100 excised naevi and 100 monitored naevi. Each lesion was evaluated by pattern analysis and scored as naevus, melanoma or lesion to be excised. Images were then evaluated using the seven‐point criteria, with both standard and revised thresholds for excision. Results Pooled data using the pattern analysis algorithm showed that 82% of melanomas and 87·5% of monitored naevi were correctly scored as lesion to be excised and benign naevus, respectively. Using the standard and revised thresholds for the seven‐point checklist, excision was recommended for 77·9% and 87·8% of the lesions in the melanoma set, respectively. The standard threshold produced ‘no excision’ recommendations for 85·6% of the monitored naevi, compared with 74·5% using the revised threshold. Pattern analysis, standard seven‐point and revised seven‐point algorithms resulted in recommendations of ‘excision’ for 63·6%, 60·3% and 72·0% of the excised naevi, respectively. Conclusions The diagnostic approach to naevi and melanoma should be adapted to the current clinical setting, in which patients may present with early‐stage melanomas and multiple atypical naevi. To increase sensitivity, a revised seven‐point checklist with a lower threshold for excision should be used.     

Agminate Spitz naevi occurring in an adult after the excision of a solitary Spitz naevus — report of a case and review of the literature

We describe a 21-year-old female who presented with tour agminate Spitz naevi close to the scar from a previously excised solitary Spitz naevus, and review the literature since 1987 on widespread and agminate Spitz naevi. Spitz naevi usually present as solitary firm red or brown popular lesions. Agminate Spitz naevi are unusual and they have been reported mainly in children. It is uncommon for Spitz naevi to recur after surgery and far more unusual for a recurrence to occur in an agminate form. Such lesions may mimic multiple satellite and in-transit metastases which can occur in malignant melanoma, and close follow up of any new lesions occurring in this case is intended.     

Nodular lesions arising in a large congenital melanocytic naevus in a newborn with eruptive disseminated Spitz naevi

Congenital malignant melanoma within a pre‐existing large congenital melanocytic naevus (CMN) is exceedingly rare. Its incidence is difficult to determine due to the small number of reported cases and because of problems associated with diagnosis. Some benign nodular proliferations (called proliferative nodules) arising in CMN, while rare, are significantly more common and can mimic malignant melanoma clinically or histologically. There are no reported cases of congenital melanoma or benign proliferative nodules in CMN in patients who also had eruptive disseminated Spitz naevi. We describe a girl who was noted to have a dark‐brown plaque with several large erythematous nodules affecting the scalp at delivery, in addition to multiple erythematous dome‐shaped papules that developed in a disseminated manner over several months, beginning at 10 days of age. It was difficult, not only clinically but also histologically, to determine the benign or malignant nature of all of these lesions. As primary cutaneous melanoma, atypical proliferative nodules in CMN, bland CMN or CMN with foci of increased cellularity and Spitz naevi show clear differences in the genetic aberration patterns, comparative genomic hybridization (CGH) could be a diagnostic help in ambiguous cases such as this. CGH performed on this patient showed multiple DNA copy number changes in the most atypical nodule, but such alterations could not be found in the remainder of the lesions. CGH showed differences between the nodular lesions that occurred in the CMN and helped us in supporting the diagnosis of this unique case of benign proliferative nodules and a possible congenital melanoma arising in a large CMN, associated with multiple widespread eruptive Spitz naevi.     

LENTINGINOUS DYSPLASTIC NAEVI IN THE ELDERLY: A POTENTIAL PRECURSOR FOR MALIGNANT MELANOMA

Seventy-seven skin biopsies diagnosed histologically as lentiginous junctional naevi from individuals aged over 60 years were reviewed. Seventy-three specimens showed a primarily nested pattern with disordered arthitecture concentrated within the rete ridges conforming to the pathology of a lentiginous dysplastic naevus. In 28 biopsies this was combined with a melanoma in situ. The latter was reflected by a focal loss of the rete ridge system, confluent melanocytic hyperplasia and single cell invasion of the epidermis by atypical malanocytes. Four biopsies showed lentiginous junctional naevi with only isolated naevus cell nests without a disordered architecture or cellular atypia. Thirty-seven of the 57 naevi in men were located on the back in contrast to 5 of the 20 women. In women the lower limb was the most frequent site with 8 of the 20 lesions originating at this site in contrast to 1 of the 57 men. The pathological diagnosis of dysplastic lentiginous naevi in the elderly needs to be recognised as having a high association of melanoma-in-situ changes.     

Understanding spitzoid tumours: new insights from molecular pathology

Spitzoid tumours are a morphologically diverse group of lesions that share histological similarity to the Spitz naevus, a benign melanocytic skin tumour. Distinguishing classic Spitz naevi from cutaneous malignant melanoma is usually achievable on standard histology sections, but occasionally equivocal lesions are encountered that show features intermediate between these two entities and consequently generate considerable clinical and histopathological concern. The nomenclature and diagnostic criteria for spitzoid lesions are not standardized and this article begins by considering the adverse effect this has on our understanding of spitzoid tumour biology. Investigations of some of the hallmark features of cancer and neoplasia in spitzoid tumours are described, and the contribution of these studies to our understanding of spitzoid tumour biology is considered, along with their potential diagnostic utility. These studies compare spitzoid tumours with better-characterized melanocytic lesions, and from such comparisons assumptions concerning the biological nature of different spitzoid tumours can be made. In contrast, investigations of the mitogen-activated protein kinase (MAPK) pathway and DNA gains and losses have suggested that Spitz naevi may be genetically distinct from other melanocytic tumours. The studies that led to this conclusion are reviewed, as well as subsequent work examining whether the same applies to all spitzoid tumours. Possible explanations for the considerable inconsistencies within some of these data are explored. Finally, potential pathways of tumour progression within spitzoid lesions are considered, with an emphasis placed upon insights gained from investigations of MAPK genes and DNA gains and losses.