Module 5.1 Melanocytic nevi

Author Dr Gary Pellizari

The aim of this module is to focus on the common Melanocytic Naevi, their characteristic clinical and dermoscopic features and their variations . It will attempt to correlate these features with the relevant histology.


The reading for this material is contained in:
Handbook or Dermoscopy
An Atlas of Surface Microscopy of Pigmented Skin lesions by Menzies. (McGraw Hill)
Cancer of the Skin. Darrell S Rigel. (Elsevier Saunders)
Skin pathology. 2nd edition. David Weedon. (Churchill Livingston)
Other articles referenced under each subsection.


Melanocytic Naevi
(Naevus = Latin for Birthmark)
Other terms (Nevomelanocytic Naevus, Naevocellular Naevus)
Definition. Chronic benign proliferation of Melanocytes in Nests.

Normal epidermis contains predimonantly Keratinocytes with Melanocytes scattered along the dermoepidermal junction with a Melanocyte:Keratinocyte ratio of 1 in 4-6 cells..

2 step algorithms attempt to differentiate melanocytic lesions from non melanocytic lesions.
Melanocytic lesions are defined as those lesions made up of increased numbers of Melanocytes compared to normal skin.
Dermoscopically this can be difficult because Non Melanocytic lesions can still have basal melanocyte proliferation and hyperpigmentation.
Eg Solar Lentigo. They appear to have a network due to elongation of the rete ridges along with melanocytic proliferation or hyperpigmentation.


Melanocytic Naevi however are differentiated histologicallly from other Melanocytic lesions by 2 features.
1. the presence of Nests of melanocytes.
2. the presence of Naevomelanocytes*


*When Melanocytes become Naevomelanocytes they lose their dendritic processes and are thought to be functionally different to those found in normal skin (eg lose the ability to impart melanin) giving their lesions the title of Naevus. Naevomelanocytes can be difficult to differentiate even for experienced dermatopathologists. Hence epidermal and dermal Naevomelanocytes are often referred to as Melanocytes.




Melanocytic Naevi are either congenital or acquired.

The Life of a Naevus

Melanocytes are derived from the neuroectoderm and migrate to various body sites including skin. Melanocytes which make their way to the skin may develop into naevi.
Most Naevi are Acquired appearing in childhhod or adolescence. Most stop growing by around age 20. They can however continue to appear up until the 4th and 5th decades of life when their numbers are maximal. Thereafter numbers decrease with each successive decade. Therefore a process of involution occurs explaining the paucity of Naevi seen in the elderly.
Maturation of Naevi occurs more slowly on palms, soles and genitals and they remain Junctional for longer.
Sun exposure in childhood is associated with increasing numbers of Naevi.
They are more prevalent in boys than girls and in those with fair skin, blond or red hair.
Less commonly Naevi are present at or just after birth (Congenital Melanocytic Naevi. CMN). Some can be tardive and are thought to be present at birth but initially inconspicuous.
In the 19th Century Unna proposed the “descending Naevus” principle described below.
Naevi generally mature through childhood from Junctional Naevi > Compound Naevi> to Intradermal Naevi. At this point growth of Naevus cells stop and they are all contained within the dermis. Dermal Naevi lose their pigmentation with time.
Some authors suggest that a Lentigo simplex is a precursor to a Junctional Naevus. In between these lesions exists a Junctional Lentiginous Naevus.
Hence the progression could be described as follows.

Acquired Naevi
Lentigo Simplex > (Increased numbers of single basal melanocytes with elongated rete ridges.
>
Junctional Lentiginous Naevus > As seen in a Lentigo Simplex but junctional nests of Melanocytes form with occasional evidence of mature intradermal naevomelanocytes.
>
Junctional Naevus > Discrete nests of Naevomelanocytes at the dermoepidermal junction usually located at the rete ridges. (In Nails this gives rise to longitudinal Melanonychia)
>
Compound Naevus > Nests of junctional and Intradermal Naevomelanocytes.
>
Dermal Naevus >Naevomelanocytes confined to the dermal layer with subsequent Involution.

_____________________________

Recently Zalaudek et al have proposed a dual concept of Naevogenesis.
Endogenous: Globular patterns seen in small Congenital , Compound and Dermal naevi arise from melanocytes which via endogenous genetic mutations “arrest” in the dermis. These persist through life and rarely regress.

Exogenous: True acquired Naevi are characterized by a reticular pattern and develop as a response to intermittent UV exposure and Braf mutations.

I. Zalaudek, R. Hofmann-Wellenhof, H.P. Soyer, G. Ferrara, G. Argenziano (2006) Naevogenesis: new thoughts based on dermoscopy
British Journal of Dermatology 154 (4) , 793–794

_____________________________


The commonly recognized Naevi are as follows.

Junctional Naevi
Compound Naevi
Dermal (Intradermal) Naevi.
Combined Naevi
Congenital Nevi.
Dysplastic Naevi
Recurrent Naevi
Spitz Naevi
Acral Naevi



Junctional Naevus

These are usually tan/ brown macules.
They are found in all ages but peak at age 45.
Found more often in intermittently sun exposed areas.

These are characterized by an increased number of Melanocytes with nests which are confined to the Dermoepidermal junction.

Dermoscopy: These Melanocytes are commonly evenly distributed producing a regular network appearance but can also have some nests of melanocytes producing dots and globules. These are usually distributed regularly or symmetrically through the lesion.


Symmetry in biology is never perfect. The general pattern in this lesion is that of an even regular network interspersed with dots representing nests of melanocytes.
The slightly irregular border here is not significant.



The theme is repeated here. Occasional peripheral dots are not thought to be significant. The presence of dots or globules centrally in lesions is more often associated with benign lesions. The colour is more or less uniformly brown with minor variations.



This variation of the same theme shows some eccentric hyperpigmentation. It is still however considered to be Junctional naevus.



Compound Naevus

Clincal
Tan or dark brown
Most common in children and adolescents.
Often elevated,
Can be dome shaped or elevated.


Histology
These are characterized by an increased number of Melanocytes at both the dermoepidermal junction and in the dermis.

Dermoscopy
They may have features of a network as with Junctional naevi but in addition may have homogenous pigmentation or even depigmentation corresponding to areas of dermal melanocytes. Dots and globules may also be seen.
All of the above features are usually distributed regularly and symmetrically.



Some lesions show little in the way of Junctional features with predominant homogenous or diffuse pigmentation. This diffuse blue/grey colour can sometimes mimic Blue White Veil



Here the central blue colour cannot be mistaken for BW veil.



Combined Naevus

This is defined as a naevus with 2 or more histological patterns of naevus in the same lesion.


The most common form is that of a Compound or Dermal naevus in association with a Blue naevus of “Deep Penetrating Type”

This often raises the possibility of a Melanoma arising in a naevus.
However it is most unusual to develop Melanoma in the dermal component of a naevus without some in situ change.
Hence a lesion of this type should not be considered suspicious in the absence of other features of Melanoma.



DERMAL NAEVI

CLINICAL

Very common.
Mostly found in adults.
Dome shaped, nodular or polypoid lesions.
Flesh coloured or light pigment.

HISTOLOGY

These are characterized by an increased number of Naevomelanocytes contained entirely within the dermis.

DERMOSCOPY

As Menzies states, “Increasing depth of pathology in the skin is associated with a decrease in morphological definition”.
• Hence structureless areas are common.
• They usually have no network but have dots or globules.
• They can have homogenous pigment or be depigmented.
• Common features are a “Cobblestone pattern” ie numerous rhomboid pigmented structures. This feature is often produced by a papillomatous surface.
• They tend to be avascular.
• “Comma” Vessels are commonly seen in Dermal Naevi.



This is a papillomatous dermal naevus showing crypts/fissures and some large comma vessels.

Please Proceed the next part Module 5.2

Module 5.2 Melanocytic nevi

Dermal naevus cont'd

Here is a typical dermal Naevus with a symmetrical pattern. There is no network hence the melanocytes are considered to be completely dermal. Hairs can arise from Dermal Naevi but are also commonly seen in Congenital Naevi.
Small congenital Naevi have many similar features to Dermal Naevi.



Congenital Melanocytic Naevi (CMN)

Congenital Melanocytic Naevi contain Naevomelanocytes which have migrated during embryogenesis from the neural crest to the epidermis via paraspinal ganglia traveling down nerve sheaths. They become evident at birth or shortly thereafter. Some are not visible at birth and develop pigment over time, usually within the first 2 years of life. These are referred to as Tardive Congenital Naevi.

Their presence is usually obtained by history from a parent or clinical examination. Those that cannot be verified by history but bear clinical matching features are called Congenital Naevus Like Naevi. (CNLN).

1-6% of infants are thought to have CMN 1.

They are classified as
• Small < 1.5cm
• Medium 1.5-19.9cm
• Large 20cm or more in greatest diameter.
Some authors use an added category of Giant where Large applies to lesions 10-19.9cm and Giant = 20cm or more.

CMNs are usually benign but the risk of Melanoma in CMNs increases with the size of the Naevus. The lifetime risk of a large/giant Naevus developing Melanoma is 4.5-10% .
A recent review of the subject showed that there is a 465 fold increased relative risk of melanoma in children and adolescents with CMN. ( cf. Risk of melanoma in general population between 10-14 years is 0.5 per 100,000 per year)
It found that 67% of Melanomas arose within the lesion. 2
Melanoma is more likely to develop in childhood or adolescence in large CMN and after puberty in small and medium CMNs.
They can also be associated with Neurocutaneous Melanocytosis with CNS sequelea. 1

Clincally

Usualy round, oval, fairly homogenous, brown, multi-shaded pigmented lesions with well demarcated borders. They often have hair growth. They are usually Macular but can be papular or Mamillated.
Larger Naevi are generally more heterogenous and often have satellite lesions.


Naevi resembling CMN are:
Café au lait macules, Becker’s naevus, Naevus of Ota/Ito, Mongolian Spot, Speckled lentiginous naevus (Naevus Spilus), Dysplastic naevi and Melanoma.


Dermoscopy of these lesions based on a Pattern Analysis model show 4 general patterns.

1. Reticular .
2. Globular
3. Reticuloglobular (with central globules and peripheral network)
4. Diffuse pigment with or without remnant reticuloglobular features

Some points about patterns in CMNs.

The vary depending on age and site but not sex.


Reticular pattern Globular Pattern
More common in ages >12 More common in ages <12
More common in extremities More common in axial sites, Head, neck, trunk

Homgenouos patterns are also more common in those over 12.

This supports the theory that Melanocytes in CMNs progress from dermal to junctional with age explaining the change from globular to reticular/homogenous patterns.

The most common dermoscopic local features are:
• Globules- shades of brown and black
• Hypertrichosis
• Targets. These are essentially globules with dots in their centre.
Variations on this theme are:
• Target network
(Where the holes in the network contain a tan or brown globule/dot or red dot.)
• Target globules with brown or red dots.
(Where individual target lesions are seen singly or sparsely scattered with tan brown or red dots)

Less common features
• Milia
• Perifollicular hyper/hypopigmentation.
• Blotches, (pigment obscuring dermoscopic features)


Ref.
Rigel. Cancer of the Skin.
L Changchien et al / Age and Site specific variations in the dermoscopic pattern of Congenital Melanocytic Naevi. Arch Dermatol 2007 143(8) 1007-1014

S. Krengel et al. Melanoma Risk in Congenital Melanocytic Naevi: a systematic review. British Journal of Dermatology 2006. 155 pp 1-8
Argenziano. G. Dermoscopy a tutorial. Edra pub.

This table is useful to remember the salient issues regarding CMNs.



This has a central globular pattern and peripheral reticular pattern. It is symmetrical in shape and pattern and hence benign. It is a typical CMN. (photo courtesy of Harald Kittler)



Here is a fairly typical Reticular dermoscopic appearance of a congenital naevus.
It has a patchy network with areas of network thickening. It is not uncommon for the network to appear broken. Central dark areas are common with correspond to heavily pigmented Melanocytes.



Congenital Melanocytic Naevi continued.
This striking lesion in a 12 year old shows blue pigment which is not often seen in CMNs but has a classical peripheral reticulation with central globules.
Photo courtesy of Wynn Hlaing



Dysplastic Naevi (DN)
(Atypical Mole, Clark’s Naevus)

The scientific community has grappled with the term Dysplastic Naevus and its meaning and there is still disagreement amongst experts. The term dysplastic implies a change or process of change from benign to malignant. This case is more convincing for bowel cancer than skin.
Ackerman coined the term Clark’s naevus referring to architectural atypia in a naevus. This is used by some in place of DN.

The National Institure of Health in the US consensus meeting in 1992 recommended the following:

• The term Dysplastic Naevus be replaced with Atypical Mole.
• Histologically they be diagnosed as naevi with architectural disorder.



Dysplastic Naevus Syndrome

Dysplastic Naevus Syndrome (DNS) is used to describe patients with large numbers of atypical naevi. It may be familial or sporadic.

The National Institure of Health in the US consensus meeting in 1992 recommended the following:

• The syndrome for Melanoma prone families be called Familial atypical moe and melanoma syndrome. (FAM-M). (previously Dysplastic Naevus Syndrome)

While in the USA FAM-M is often used Australians and Europeans commonly use Dysplastic Naevus Syndrome.


Various scoring algorithms exist to clinically define DNS. Below is one of many.

Revised dysplastic nevus syndrome score
Each point below scores 1 if present.
A total of 2 or more = dysplastic nevus syndrome

• 100 or more naevi >2mm (50 or more if under 20 or over 50 years of age)
• 2 or more atypical nevi
• 1 or more nei on the buttocks
• 2 or more nevi on dorsal feet

Reproduced from Bishop JA, et al. Genotype/phenotype and
penetrance studies in melanoma families with germline
CDKN2A mutations. J Invest Dermatol 2000; 114(1):28–33.
Blackwell Publishing Ltd.

The risk of Melanoma developing from this syndrome varies from 10-100% depending on the family history.

DN as risk factor for Melanoma

While the risk of Melanoma associated with DNS is well established the risk of Melanoma in the presence of DN in small numbers is less clear.

Various studies have suggested a link between DN and Melanoma.

In 1978 Wallace. H. Clark described an association between subjects with increased numbers of melanocytic naevi and melanoma. Clark described in 1984 the potential evolution from melanocytes in acquired melanocytic lesions from benign >increasing aberration differentiation >nuclear atypia >dysplasia >melanoma.

Shors et al support this notion when they assessed the association of Histologically dysplastic naevi (HDN) as a risk for Melanoma and found that the presence of HDN did in fact confer Melanoma risk.

This has more lately been challenged.

Roesch’s comprehensive review of the current literature shows that there are at present no clinical, histopathological, or molecular criteria to make a distinction between DN and Melanoma. Clinical and Histological Consensus on what defines a DN is difficult to achieve amongst experts and studies show poor concordance of histological opinion when the same histological samples are shown to numerous dermatopathologists. This is due to a lack of commonly accepted and reproducibly measurable criteria.
Marghoob disputes this assertion.

It also finds that
- epidemiological data linking DN with Melanoma shows poor correlation.
- Topographical studies show no association with DN and Melanoma.
- There is also good evidence that 60-75% of Melanoma arise De Novo from apparently normal skin. This lends support to the concept that DN is an entity on its own.
- 9p21 gene is associated with Melanoma but not with DN.


Grob et al. showed the risk for Melanoma was associated with the sheer number of melanocytic naevi ie 19.6 fold inc with the presence of 120 nevi less than 5mm. While 5 nevi over 5mm diameter increased risk by 10 fold. They did not find an increased risk of Melanoma in patients with DN.
Increased numbers of Naevi on the lower legs have also been shown to increase the risk of Melanoma.

While Histology can confirm the presence of a DN it cannot tell us if a lesion is progressing to Melanoma.

It is a fact that most DN will not become Melanoma but some will. Hence the biology of DN is different to a Melanoma.

This is supported by Roesch et al. who state that DN are in most cases endpoints in the evolution of some Melanocytic Naevi while only some DN are actually Melanoma precursors.

Differentiating which ones are melanoma precursors is the challenge!

Clincal

Kelly has suggested the presence of at least 3 of 5 criteria are needed to clinically define a Dysplastic Naevus.
• Ill defined border
• Irregular border
• Irregularly distributed pigmentation
• Background erythema
• Size over 5mm


They are most commonly found on the trunk but can be found on buttocks and sun protected areas. They appear moreso around puberty than childhood.
They may be solitary or multiple. In the latter case they may be part of DNS.
Clinically and dermoscopically DN are difficult to differentiate from Melanoma and share characteristic features. This often leads to excision to exclude Melanoma.

Dermoscopy

Dermoscopy is useful in identifying these ‘in between’ lesions but has limitations in its ability to detect histologically defined DN. The challenge is how to manage these lesions that ‘appear’ to be dysplastic.
Hence: dermoscopically “Atypical mole” is a more accurate term but one may make a presumption that the histology may be dysplastic.

Marghoob defines DN as any histologically benign naevus that shares ABCD features of Melanoma or could be mistaken for a Melanoma.

For the purpose of this study guide ( from a Dermoscopic point of view) DN will be defined as any Melanocytic lesion which is in between the endpoints of a common benign naevus and Melanoma.

Histology

Weedon describes 4main features:
1.Intraepidermal lentiginous hyperplasia of melanocytes
2. Random cytological atypia of these cells.
3. Stromal response.
4. Architectural atypia

(Concordance studies of these features between different histopathologists is variable)


References.
Clark et al. Hum Pathol. 1984 Dec;15(12):1147-65.
Rigel Cancer of the Skin. El servier Saunders
Weedon. Skin Pathology. 2nd ed. Churchill livingston
Roesch et al. European Journal of Dermatology 2006 16 (5) 479-93
A.Marghoob. Dermoscopy masterclass notes 2007
Shors et al. British Journal of Dermatology 2006 155, 988-993
Ackerman et al, Histopathology 1988 13 (3), 241-56
J Kelly et al. Med J Aust. 1997 Aug 18;167(4):191-4



This reticuloglobular pattern raises suspicion due to its peripherally grouped globules. It is however not a melanoma but a dysplastic naevus.



This lesion is difficult to differentiate from Melanoma as any regression in a naevus must be viewed with suspicion.
This was a regressed dysplastic naevus.
Photo courtesy of Wynn Hylang



This patient has Dysplastic Naevus syndrome and has had a melanoma in the past. He has over 200 naevi on his body and many appear atypical. 2 of the most atypical were excised having features not inconsistent with melanoma. The one on the left was found to be a moderately dysplastic compound naevus while the other mildly dysplastic.

There was no "Ugly duckling sign" in this case and numerous lesions were considered to fit this description. Close monitoring is required in this group of patients.



This lesion had been present for some time on the toe of a 40 year old woman. She felt it had become darker.

It shows irregular border with some irregular peripheral dots. Some blue white colour in the indicated area aroused suspicion. It was however a mildly dysplastic compound naevus. The Blue white area probably represents dermal pigment.

Please Proceed the next part Module 5.3

Module 5.3 Melanocytic nevi

Recurrent Naevi

Pigmentation in scarring creates the diagnostic problem of differentiation between Reactive pigmentation and Recurrence of the initially excised Melanocytic lesion.

In the presence of doubt, initial histology of the excised lesion is vital.
In the case of Atypical Naevi or Melanoma incomplete excision must be considered.

Kornberg and Ackerman coined the term Pseudomelanoma for incompletely excised recurrent melanocytic lesions as they clinically and histologically are difficult to differentiate from Melanoma in situ.

In 2006 R. Botella-Estrada et al studied Melanotic pigmentation in previously excised Melanocytic lesions. Below is a summary of their findings.



Melanotic pigmentation in scars can be grouped as such:

1. Reactive Pigmented Scar - Pigmented lesion arising as a reaction to an excision.
2. Recurrent Naevus- Pigmented lesion arising as a recurrence of the original lesion.
3. Recurrent Melanoma
4. Metastatic Melanoma

1. is differentiated from 2,3 and 4 by the absence of Melanocytic nests.


Clinically they classified the appearance of Pigmentation in scars as:

Macular
Banded
Diffuse Pigmentation.


Of 57 biopsied lesions,
32 were Reactive Pigmented Scars.
25 were Recurrent (Naevi (22), Melanoma (1), or Metastatic Melanoma(2).

Reactive Pigmented Scars showed one or more of the following histological variations:

Basal Hyperpigmentation
Lentiginous Epidermal Hyperplasia
Melanocytic Hyperplasia

Dermoscopic features to differentiate 1 from 2,3 and 4 were as follows.

Reactive Pigmented Scars	Recurrent Naevi Melanoma Metastatic Melanoma
Regular Pigmented network ^Streaks -thin continuous -Broad Homogenous	Globules *Heterogenous Pigmentation** Irregular prominent network	Strongest correlation with recurrent Naevi
Place text here	Place text here	Place text here

^ Clinically seen as Bands.
* sens 84% spec 97%
**(heterogenous pigmentation = 2 or more colours irregularly distributed)

Reactive hyperpigmentation was more likely to follow 1. Direct closure
2. Shave
While Recurrent lesions were more likely to follow the reverse of that above.

The presence of scar tissue makes prediction of histology difficult and this study showed no correlation between irregular dermoscopic features and atypical histology.

Hence the difficulty in diagnosing these lesions lends support to the policy of completely excising pigmented lesions.


Lesion below:

The above scar results from a lesion with unknown histology.
The bands seen macroscopically and dermoscopic streaking (thin continuous) is more likely to reflect Reactive pigmentation than a recurrent lesion.



The presence of globules in the periphery (pseudopods) make this more likely to be a recurrent Naevus. This in fact is the result after a shave excision.
(Photo by Harald Kittler)



Spitz Naevi
These Naevi first described by Sophie Spitz in 1948 were thought to occur mainly in childhood on the face and lower extremeties. In fact in over 50% of cases they are found over the age of 14 and over 25% are found over the age of 30. 1
In children they are usually not pigmented and are pink/red. Less commonly they are pigmented.

In 1975 Reed et al described a lesion in young adults found in the lower extremities which was darkly pigmented ,known as a Reed Naevus. This is now thought to be a pigmented version of a Spitz Naevus although its cells are almost exclusively Junctional cf other types of Spitz naevi.
Controversy exists as to the histological difference between these.

A more unifying histological concept was created by Ackerman et al where the characteristic cell types noted in Spitz naevi are those of Spindle cell and Epithelioid cells. (ie Melanocytes)

Clinical
-Found in Teenagers, adults and children as acquired lesions and are rarely congenital.
-Are solitary Pink, Red or Brown papules.
-Often less than 6mm.
-Well circumscribed and symmetrical.

Less commonly they can show irregular outline, scaly or eroded surface with variegated colours making differentiation from Melanoma difficult.

Location

Trunk 37%, Lower extremities 28%, Upper extremities 19% Head and Neck 16%


Histology

Most Spitz Naevi are Compound. 5-10% are Junctional and 20% are intradermal.

The Major histological diagnostic criteria include:

*Cell type (Spindle more commonly than Epithelioid)
*Symmetrical appearance
*Maturation of Naevus cells.
*Lack of Pagetoid spread of single Melanocytes.
*Presence of Eosinophilic globules (Kamino Bodies)

Dermoscopy
(of Pigmented Spitz Naevi)

Most Spitz naevi show patterns which are either:

STARBURST (Symmetrically distributed streaks found in the periphery)
Usually seen in the Pigmented Spindle cell Naevus or Reed Naevus.

GLOBULAR(Symmetrically arranged globules or pseudopods in the periphery)
Usually seen in Pigmented Spitz Naevus, Pigmented Spindle and/or Epithelioid Cell Naevus.

ATYPICAL : Features of Starburst or Globular with the following:

• Uneven distribution of colours and structures
• Irregular diffuse pigment resembling Blue White Veil
• Irregular peripheral extensions (black blotches)


Other dermoscopic features of note.

Pseudopods are specific for Melanoma in most lesions but in the case of Spitz naevi their symmetrical distribution creates an exception to the rule.

Central Depigmentation : may be present giving rise to a Negative Network.

Blue White Veil Blue White Veil is usually a highly specific sign for Melanoma but in Spitz naevi can reflect bands of Melanophages in the dermis hence differentiating Melanoma from Spitz Naevi can be difficult

Spitz Naevi with peripheral globules. Some Naevi show symmetrically distributed globules. While they may represent Spitz Naevi they usually represent benign growing Naevi. Kittler studied 1612 Naevi in 385 patients to assess growth. He found that over a median interval of 11months Enlargement was found in 5.3% (n=86) of nevi. The frequency of enlarging nevi was inversely related to age (P<.001), in that enlarging nevi were common in patients younger than 20 years and relatively rare in older age groups. Approximately half of the enlarged naevi showed a peripheral rim of globules. Histologically these were not Spitz Naevi and none were Melanoma. 5

Natural History of Spitz Naevi

While still controversial Argenziano and Pizzichetta have separately followed pigmented Spitz naevi in children and found cases where involution occurs with the suggestion of progression from a globular pattern to starburst to a more homogenous pattern.




A British study of 36 Pigmented Spitz Naevi and 3 Spitzoid Melanoma was done in 1999.
They concluded that Atypical features found in Pigmented Spitz naevi do not necessarily correlate with sinister histological changes.
They also noted that in cases of Melanoma simulating Spitz Naevi typical patterns can be seen with no dermoscopic features of Malignancy. 6

Hence the general policy in adults is that Spitz naevi should be removed due to the clinical difficulty in differentiating them from Melanoma.

Argenziano has suggested the following.
Because of difficulties in Histopathological correlation in the case of atypical Spitz naevi, those parts of an atypical lesion should be highlighted or marked so as to allow closer attention by the histopathologist.

The situation in children is more controversial and is not to be dealt with here.

Below are some Spitz examples.

This shows a typical Starburst pattern of a Spitz naevus.
It has some grey blue colour with diffuse pigmentation.
There is central reticular hypopigmentation.
It does not show a true negative network which is sometimes seen in these lesions. Some would refer to this as a Reed Naevus due to its starburst pattern and dark pigmentation.
Photo Courtesy of Stelios Minas.



This lesion was on the abdomen of a 2 year old. Although controversial most would not excise this lesion. Its globular pattern suggests a growing lesion.



They may have central depigmentation giving rise to a Negative Network as seen here.
Courtesy Ian Mccoll



This lesion was found in a 26 year old woman. She felt it had changed. It shows similar features to many benign Spitz Naevi. The central blue area could be considered BW veil but this is subtle. The main clinical feature here is that of change. It is widely agreed that distinguishing Spitz Naevi from Melanoma clinically is very difficult and many practioners will excise any Spitz Naevus in teenagers or adults.
This was in fact a Level II Spitzoid Melanoma.
Courtesy of Ben Cook



This infant was 20 months old. The lesion on the thigh had appeared 6 months ago, and was growing. It had a diameter of 5.5 mm.
The dermoscopic image shows a black structureless centre with peripheral streaks and pseudopods regularly distributed, forming a starbust pattern.
Pathology confirmed the diagnosis of Reed nevus.
Photo courtesy Jean-Yves Gourhant



Acral Naevi

Acral skin has distinctly identifiable features when viewed dermoscopically.

Saida first described dermoscopic features of Acral Naevi in an Asian population.

Three main patterns are seen in Acral Naevi.

1 Parallel Furrow- Pigmented furrow and skin coloured ridges.
2. Lattice Pattern- Pigmented lines crossing furrows.
3. Fibrillar pattern- Filamentous lines usually perpendicular to furrows or at angles.

It is not uncommon for Acral naevi to have combinations of these patterns and can include the less common variations described below.

Histology

Parallel Furrow pattern is caused by melanin pigment produced by
melanocytes residing in the crista profunda limitans, an epidermal rete ridge
underlying the surface sulcus.

Saida has stated that the Parallel Furrow pattern is the prototype pattern from which Lattice and fibrillar arise. Hence Lattice and Fibrillar patterns are variations on the theme of the Parallel Furrow principle.
Lattice Pattern
Lattice lines are simply part of the normal criss-cross skin markings often seen in the arches of soles. They could be considered to be 'Perpendicular Furrows'.
Fibrillar Pattern
This pattern is caused by an oblique arrangement of melanin pigment in the slanting cornified layer. The slanting is considered to be produced by mechanical pressure from body weight. In the fibrillar pattern, the nests of nevus cells are mainly located in the crista profunda limitans, as they are in the parallel furrow pattern. 1

Some authors have noted that a Parallel Furrow pattern can be changed to a Fibrillar pattern pattern when lateral pressure is applied with a dermatoscope. 3.


Pattern Location:

Parallel furrow patterns are more often seen at peri weight bearing areas.
Lattice patterns are often seen on the arch.
Fibrillar patterns are more often seen in weight bearing areas.


Less common dermoscopic variations seen are.

Globular
Homogenous
Reticular



The frequency of the various patterns found were:

Parallel Furrow 50%
Lattice like 16%
Fibrillar 10% (21% in Japanese population)
Atypical 10%
Homgenous 4.8%
Globular 3.5%
Transitional 3.5%
Reticular 2.6%

(Transitional being a combination of features where volar and non glabrous skin meet eg lateral aspect of toe.) 5


Some interesting facts.

Acral Volar skin is the most common site of Melanoma in non white populations.
In a study of 230 acral lesions over 6-24 months 18%changed.
Most changes occur in those aged less than 14.
Parallel Furrow patterns are the most likely to change.
Homogenous pattern is a feature of an involuting lesion.



1. Saida, Toshiaki MD, PhD; Koga, Hiroshi MD
Dermoscopic Patterns of Acral Melanocytic Nevi: Their Variations, Changes, and
Significance. Archives of Dermatology 143(11), November 2007, p 1423-1426

2. Malvehy J, Puig S. Dermoscopic patterns of benign volar melanocytic lesions
in patients with atypical mole syndrome. Arch Dermatol. 2004;140(5):538-544.
3. Clincal and Experimental Dermatology 2006, 32, pg 103.
4. An Atlas of Surface Microscopy of Pigmented Skin Lesions: Dermoscopy. Menzies.s.
5. Zalaudek et al. Arch of Derm 2007 Vol 143, 11 pg 1372



Although a parallel furrow pattern predominates, filamentous areas can be seen. The central area has some blue globules of dermal pigment. When more prominent these are often considered to be combined naevi. Excision may be undertaken to exclude melanoma growing within the lesion.



This lesion shows a combination of features. The fibrillar pattern indicates probable weight bearing area.

Module 4.1 Algorithms: The Menzies Method

Author Dr Martin Baker

The Menzies Method

Resources
An Atlas of Surface Microcopy of Pigmented Skin Lesions. Menzies,Crotty, Ingvar & McCarthy. The "Self-Test" CD-ROM with this is an invaluable learning aid.
Color Atlas of Melanocytic Lesions of the Skin. Soyer, Argenziano, Hoffmann-Wellenhof & Johr.
An Atlas of Dermoscopy, Marghoob, Braun & Kopf. Another accompanying excellent CDROM with wonderful pictures.
"The Blog" and all our resourceful and inspired contributors!

Introduction

All of the pictures in this presentation are from patients in my practice, (unless otherwise acknowledged), none are enhanced, several are blurred and some show specks and shadows. This is an attempt to recreate the conditions of busy practice, when we often do not have the time to ensure every lesion is looked at for several minutes with perfect equipment and conditions on every occasion.
This algorithm developed in the 1990s through the work of Professor Scott Menzies and others from the Sydney Melanoma Unit. As with other Algorithms, the aim was to develop a standard method of inspecting pigmented lesions dermoscopically to allow novices to understand what they were seeing when they peered at lesions down the barrel of their newly acquired Heine Delta 10s or in many cases when they looked at images on the screen of a mole max.
On the face of it, the Menzies method seems a little more complicated than some of the other approaches. It is in fact very simple once the basics have been grasped and using it on a regular basis will rapidly help the novice user to understand the principles of dermoscopy. No one algorithm is intrinsically better than the others and most experts use a combination with difficult lesions. As with all algorithms the emphasis is on Melanoma diagnosis. Little emphasis is placed on vessels and knowledge of these structures gleaned from other sources should be utilized alongside Menzies criteria when interpreting lesions.


The Menzies method is a 2- step process.

a.Is it melanocytic? If yes go to step 2 to decide if it is a melanoma(module 4.2)

b.If it is not melanocytic is it a seborrhoeic keratosis, a basal cell carcinoma or a vascular lesion.

If the questions are all answered in the negative then the lesion is assumed to be melanocytic. go to step 2 as above.

There are important exceptions to these guidelines which we shall deal with later.

Sometimes the answers are obvious:- Image 1

And sometimes they are not:- Image 2

What do you think these 2 lesions are?

Invasive superficial spreading melanoma 0.9mm thick

Hypomelanotic invasive melanoma 0.6mm thick.



Criteria for Melanocytic Lesions

Pigment network

The pigment network is formed by the differing amounts of pigment containing cells in the rete ridges, which make up the lines of the network and the dermal papillae which constitute the network holes.
Sometimes it is obvious:-



And sometimes it isn’t:-



Describe the features you see in these two lesions and give a diagnosis in each case.
The first one shows a simple lentigo and the second remnant pigment network in an hypomelanotic melanoma. Note also the "negative pigment network in the body of the lesion.



On the face because of the absence of rete ridges, a true network does not appear and pigmentation around follicular openings produces a “pseudonetwork"
Describe the appearances in these two lesions.
The second picture shows a lesion that has recurred at the site of a previous excision of Lentigo Maligna.
Do you think it is a recurrence?

Click on

Lentigo Maligna Melanoma

to see another image from "The Blog"



Aggregated brown or black globules
Brown globules are pigmented cell nests in the region of the dermo-epidermal junction. Whilst regular in size shape and distribution, they become increasingly disordered the further they move along the dysplastic nevus spectrum towards melanoma.

Describe the salient features of lesion 1.

Black dots and globules are localized collections of pigment in the stratum corneum, in benign lesions they tend to be central in position. Location towards the periphery and irregularity in size, shape and distribution indicate an increasing likelihood of malignancy.


Lesion 2 is more ugly looking, describe the salient features

Dermoscopically, lesion 3 ought to be a Melanoma, Histopathologically it wasn’t; it was reported as a severely dysplastic naevus; What margin of excision would you use?



Pseudopods or Radial Streaming
These processes represent the classical radial growth phase of melanoma, although they are often present in other naevi. They represent intraepidermal or junctional confluent nests of melanocytes. An important differentiation is the distribution, if uniformly and symmetrically distributed around the periphery of the lesion then malignancy is unlikely.

Lesion 1 This 0.6mm Superficial spreading melanoma illustrates both pseudopods and radial streaming, with the pseudopods at top right appearing at the end of radially streaming structures. Note that the structures are distributed irregularly around the edge of the lesion, an important pointer to melanoma. The colour of both structures varies from light brown to black.

Lesion 2 is a 2mm melanoma in situ arising in a 5mm dysplastic naevus, the only really significant melanoma feature in a tiny lesion.

Lesion 3 shows a lesion on the dorsum of the foot of a 22 year old which is currently being monitored. Do you think this is wise and why?



Homogenous blue pigmentation

Usually seen in the common blue naevus where it varies in colour from blue gray to blue brown depending on its position in the mid to lower dermis. Homogenous blue pigmentation is always present usually throughout the entire lesion. Networks and brown/black dots and globules are never found.



Homogenous blue pigment can also be found in regressed lesions, melanoma metastases, and occasional haemangiomata and Bccs.



Parallel Pattern on palms and soles

For a full description.

Acral lesions

part 8.

What we are trying to prevent

Dermoscopy

Exceptions

This section lists the exceptions to the "rules" listed in the previous sections

Exception 1
A delicate, annular pigment network is often seen in dermatofibroma:-


A network can sometimes be seen in Seborrhoeic keratosis:-



Exception 2

Homogenous blue pigmentation (hall mark of blue naevus) is also seen rarely in Some Bccs and Haemangiomas and commonly in Metastatic melanoma as in this image.



Exception 3

Multiple milia like cysts and crypts can occur in occasional dermal naevi.


Exception 4

In some rare cases of seborrhoeic keratoses multiple blue gray globules can be seen. Other features of Seb K help with diagnosis.

Next Section

Module 4.2 Algorithms: The Menzies Method

The Second step

Once the diagnosis of a melanocytic lesion has been made we firstly look for one of the two negative features to decide if the lesion is benign or malignant

a. Symmetrical pigment Pattern

Lesion 1 is obviously symmetrical

Lesion 2 is symmetrical in one axis.

Lesion 3, an obvious melanoma, is asymmetrical in both axes.



b. Is there just a single colour?



Or more than 1 colour



The next step is to look for at least one of the 9 positive features.

These are:-
Blue-white veil
Multiple Brown Dots
Pseudopods
Radial streaming
Scar like depigmentation
Peripheral Black dots and globules
Multiple (5-6) colours
Multiple blue-gray dots
Broadened network

Blue-White Veil

Blue white veil is an indistinct, irregular, confluent blue pigmentation with an overlying white ground-glass haze. This represents histologically aggregated pigmented cells in the dermis (blue) overlaid by compact orthokeratosis. The pigmentation only occupies part of the lesion and is found mainly in papular areas.



Multiple Brown Dots

Dots are small round structures less than 0.1 mm in diameter and brown dots represent focal accumulations of melanin at the dermo-epidermal junction. In melanoma the dots are typically irregularly distributed.



Pseudopods
Are finger like projections of light brown to black pigment, which may terminate in small bulbous structures, at the periphery of the lesion and either connected to the lesion or the pigment network. Typically in melanoma, they are distributed patchily around the circumference of the lesion.

Lesion 1 is an in-situ melanoma; although pseudopods are reported to be uncommon in in-situ melanoma, my experience is that they occur fairly frequently as in the evolving melanoma in-situ shown below:-


Sometimes appearances can be misleading as in this lesion 2:-

SPECIMEN/CLINICAL NOTES: Lesion back. Enlarging lesion with pseudopods.

Sections show a compound melanocytic naevus which has undergone partial
regression of its dermal component with the presence of clumps of deeply
pigmented macrophages within the lesion. These latter features
presumably explain the clinically observed "pseudopods".
The lesions has a symmetrical architecture and exhibits no features of
malignancy or of dysplasia.



Radial streaming
In melanoma radial streaming or streaks as they are known in other algorithms, are distributed irregularly within the lesion. Symmetrical distribution is characteristic of

Reed’s spindle cell naevus.

Radial streaming is histopathologically identical to Pseudopods.

Both radial streaming and a broadened network can be seen in this 0.3mm superficial spreading melanoma on the anterior lower leg.



Scar like depigmentation

This feature indicates regression and appears as white coloured area lighter than the surrounding skin, this is often described as a “reverse network” and histopathologically features fibrosis, loss of pigmentation, epidermal thinning, and effacement of the rete ridges with melanin granules free in the epidermis or in melanophages.


Lesion 1 shows Scar like depigmentation in a 0.7mm superficial spreading melanoma on the back of a 75 year old male. Note the depigmentation is paler than the surrounding skin.
Lesion 2 shows a paler area which still has vessels present representing a hypomelanotic area in a SSM. This area is the same colour as or more commonly, pinker than the surrounding skin.



Peripheral black dots and globules

Represent accumulation of pigment in stratum corneum as a result of pagetoid spread of malignant melanocytes. Characteristically they are peripherally located and intensely black as opposed to brown globules often seen in benign lesions.

Lesion on the scalp of 70 year old noticed after he had a hair cut! 0.3mm SSM.
The blood spots are from the local anaesthetic injections of my over enthusiastic nurse!



Multiple Blue Gray Dots
These structures represent another feature of regression which is very common in Superficial spreading melanoma. Described as “pepper-like” they represent collections of melanin carrying macrophages (melanophages). Large collections of these structures are responsible for the blue white veil appearance. They are often a useful clue for the diagnosis of hypomelanotic melanoma, as in this case of an asymptomatic 0.6 ssm, noticed by the patient's wife.



Multiple (5-6) Colours
The colours in question are red, tan, dark brown, black, gray and blue. Multiple colours indicate increased vasculature in association with melanin distributed from the stratum corneum to the dermis.


Broadened network

Representing expansion of melanocytic nests at the dermo-epidermal junction and manifested by the thickening of the cords or lines in the network of a melanocytic lesion.

Next Section