Case 231: F7. Exophytic naevus over left trapezious. Grown over a few

weeks. Iniitally flat. ?Spitz naevus, ?Malignant

RAC7750 c/o A, B, C

Dermoscopy:

coarse vascular

structures.

c/o D

Case 231: F7. Exophytic naevus over left trapezious. Grown over a few

weeks. Iniitally flat. ?Spitz naevus, ?Malignant

RAC7750

Base

Necrotic foci

Atypical mitotic figure

Deep mitosis

Pie Chart Participants

N=74

Benign: 9

Spitz 30

Uncertain favour benign 16

Uncertain favour malignant 20

Malignant 27

Spitzoid 30

Nodular 8

SSMM 1

Table for Malignant Responses

MPathDx*

*I: Leave as is even if incompletely excised; II: Complete excision <5mm; III: 5mm; IV:

as pT1a, pT1b; 1cm +/-; V: as pT2 or greater e.g. >1cm

EQA Participants: Benign N=9

Symmetrical with collarette and maturation with depth. No

destructive growth. I'd at least be asking a local colleague for a

second opinion, though.

Almost symmetrical compound lesion with epithelioid cells

having promiennt eosinophilic nucleoli and mitotic activity

(9mf/10HPF); focal indvidual cells wrapping around dermal

collagen; no definite pagetoid spread. Overall spitzoid lesion,

favour spitz naevus with atypia (focal ulceration and high

mitoses).

EQA Participants: Uncertain favour benign N=16

Atypical Spitz tumour - low score (according to Barnhill), uncertain malignant

potential. Needs molecular analysis (HRAS mutation or kinase fusion, PTEN,

9p21 deletion, etc); also BRAF, BAP1. I would treat as malignant, but without

SLNB.

Bapoma? Several. DD with Epithelioid spitz

polypoid tumour of large pleomorphic epitheliod naevus cells with big pink

nucleoli, some multinucleated. Some mitoses incl deep ones. Vascular

network and lymphocytes present ? BAPoma

Sheets of mitotically active spitzoid cells forming a wedge shaped but

expansile dermal nodule. Given age group of patient, I would categorise as

atypical Spitz tumour. Need to ensure complete excision (with more sections)

and keep under clinical follow up for 5 years.

Difficult case. On balance I favour atypical spitz, considering the age of the

patient, otherwise could easily be diagnosed as melanoma

EQA Participants: Uncertain favour malignant N=20

I am wary of an outright diagnosis of melanoma in this age

group, and would prefer to call STUMP (but clearly very

worrying), and advise FISH, etc.

Atypical Spitz tumour. STUMP. Favour melanoma, but this is a

young patient

Spitzoid lesion. Young child. Atypia with pleomorphism and deep

mitoses. Do not wish to call MM but worrying features therefore

classify atypical spitz tumour and manage as MM. SNB

questionable.

Looks like a Spitzoid melanoma. STUMP at least. Very mitotic,

but well circumscribed and age 7. Would request FISH before

calling it melanoma

BAPOMA?

EQA Participants: Malignant N=27

Spitzoid lesion but without maturation and several deep mitoses

seen such that despite the patients young age should be

regarded as malignant

Difficult case but I think on balance this is a Spitzoid malignant

melanoma. Pushing deep border and occasional deep mitotic

figures.

Symetrical but consumption of epidermis, variable

pleomorphism, loss of maturation, increased mitotic activity with

deep mitoses.

Pie Chart Slide Club

N=24

*1 STUMP, NOS assigned to Favour Malignant

SLIDE CLUB RESPONSES

Uncertain favour malignant, Spitzoid

Uncertain favour malignant

Spitzoid MM.Highly cellular predominantly dermal tumour with barely any intervening stroma, a

complete lack of architectural and cytological maturation and several deep mitoses.

Nodular severely atypical epithelioid/spitzoid melanocytic tumor; lots of mitoses superficial and

deep, no maturation, no definite ulceration, deep dermal bulky growth. I would prefer a

classification as high risk Spitzoid tumor/STUMP, but melanoma not excluded, based on

histological findings alone. I would definitely do additional immunostainings and molecular analysis

before signing out such a case.

It is a young girl. I have seen such cases in young children with favourable outcome, more than 20

years follow-up without recurrences.

AST, high risk (Spatz et al)

Age is the obvious confounder here, but despite the patient's age, I suspect this is malignant

melanoma, nodular type. While the age definitely prompts consideration of a Spitzoid melanoma,

I see few genuinely 'Spitzoid' histopathologic features here. Ancillary testing might help with

classification.

Spitzoid melanoma of childhood with a comment that these tumours may have a favorable

outcome and that LNSB is unnecessary.

Epithelioid spitz naevus

SLIDE CLUB RESPONSES

Uncertain favour benign. Requires molecular correlation with FISH. Atypical Spitzoid tumour,

deep and atypical mitotic figures but no necrosis. Malignant rare at this age so more likely benign

although uncertain malignant potential

Spitzoid tumor of uncertain malignant potential. Cannot rule out Spitz melanoma. Would do

HMB45, MelanA/Mart, Ki-67 and p16 stains, also BRAF V600E and available usion genes if BRAF

negative. CGH could be a useful next step. Will be interested in results of these studies.

clearly spitzoid in type. At low power the lesion has a rather dumbell configuration with focal

extension into superficial subcutis. The lesion comprises epithelioid and spindle shaped cells in

compact aggregates with little intervening stroma. There is uniform and severe nuclear atypia,

mitoses at varying levels and also attenuatuion of the epidermis. This lesion is a spitzoid nodular

melanoma.

1st: High-risk atypical Spitz tumor (inflamed, with necrosis)

2nd: This is an atypical Spitz tumour with high-risk features. Pleomorphic epithelioid cells with

inflammation; cells are larger in the depth than close to the surface; there is a group of apoptotic

cells (this is a bad sign).

Atypical Spitz tumor with extension into the deep dermis. Would order immunostains

(Ki67/MelanA, p16, HMB45). The mitotic activity is worrying but could be related to the initial fast

growth phase of the tumor. I would recommend to manage this lesion by complete excision with 5-

10 mm margin and clinical surveillance.

SLIDE CLUB RESPONSES

the combination of deep expansive nodules, pleomorphism and mitoses makes the diagnosis of

benignity impossible. This even though the evolution will probably be favourable. In my own limited

experience only a small fraction of these lesions kills the patient

Very spitzoid in nature, but with severe nuclear atypia with irregular large nucleoli deep, plus

mitoses and pushing margin all point to uncertain malignant potential [favour malignant]

spitzoid nodular melanoma of childhood In view of the large atypical cell type; massiveness of

the dermal architecture associated with ‘epidermal consumption’; mitotic activity at all levels), and

add a note that, although regional lymph node involvement may well occur (be detected at SN),

distant metastasis is relatively unlikely to occur (though can by no means be ruled out).

spitzoid MM with atypical mitoses

Spitzoid melanoma. I thought also in polypoid Spitz nevus, but neoplastic melanocytes are

confluent, there is no maturation and I think that I have seen some mitotic figures in deeper areas

(digital); Polypoid melanoma (glass)

[Spitzoid, Uncertain favour malignant] No obvious pagetoid spread but the epidermis is

considerably thinned and there are intraepidermal melanocytes. The atypia and mitotic activity are

too much to simply ascribe to the young age. However, I would recommend genetic analysis and

make a final report in the light of the findings.

SLIDE CLUB RESPONSES

Melanoma, Spitzoid. Young age gives me a low baseline level of suspicion but histology is very

worrying

high risk atypical Spitzoid tumour and favour a malignant Spitz tumour (normally for a case like

this we would do BRAF & NRAS IHC as well as immunochemistry for assessment of proteins

associated with various chromosomal fusions including ALK, ROS1, NTRK1&3, MET & RET, p16

and FISH) (glass)

Spitz Tumour of uncertain malignant potential (STUMP)

High risk Spitz tumour with numerous mitoses and extends focally into subcutis. Could consider

ABBOTT probe set and p16/C-MYC or aCGH but advise wide local excision.

[Spitzoid, Uncertain favour malignant] Exophytic, symmetric prolieration of spitzoid

melanocytes extending into the reticular dermis. Lesional melanocytes show prominent nucleoli

and pleomorphism. There is associated inflammation. Worrisome features include signficnt mitotic

rate of dermal melanocytes and melanocytes with pyknotic nuclei. Little maturation. However,

given the patient's young age and history of recent growth, this could be a Spitz nevus in its

growth phase.

HMB45 & S100 strong, diffuse

p16 widespread loss

Ki67: lack of maturation, high superficial

& deeper areas

ALK1 negative

Additional Studies: IHC

HMB45

p16

Ki67: lack of maturation, high in superficial & deeper areas

Ki67

MICRO REPORT: Case 231

Nov17

AST, high risk features

Absent Kamino bodies

Pleomorphic, large epithelioid melanocytes

Expansile growth, little intervening stroma

Extending deep, into the subcutaneous fat with a focal pushing deep

margin.

Foci of tumour cell necrosis

Mitotic activity was moderately high at 8/mm2

Atypical mitotic figures

Dec 17: At post-operative review, a palpable ipsilateral

supraclavicular lymph node was noted. A CT PET confirmed an

enlarged 10mm markedly FDG avid lymph node that was highly

metabolically active and suspicious for metastasis

c/o A: Lymph node 1.6cm diameter, grossly involved

Dear Y,

This girl has now come up with a gross (palpated) lymph node deposit 1.6cm in the

neck.

Question is whether at this age she should undergo a full neck dissection.

I’d be tempted to say not if it was my daughter but obviously you might have a view

with the results of CGH still pending.

She’s actually provisionally booked for a neck dissection next Monday.

Kind regards, X

DLRS = 0,20

Initial cytogenetic tests, namely comparative genomic

hybridisation showed multiple segmental gains and

losses on chromosomes 1, 6, 9, 10, 11 and 17.

[Y]:

Preliminary RNA sequencing data revealed mutations in

PIK3CA p.5733F (c.2318C>T), MTOR p.A2416V (c.7247 C>T)

and 3 different mutations on the BRCA 1 gene.

A new analysis we have identified an exon 2 G12S mutation in

KRAS in this child.

There are very few data on KRAS mutated melanocytic

tumors to my knowledge. (But I am working on this topic…)

It is not very good news on the therapeutic options if they

were needed in the future.

Discussion with the adult specialist skin cancer MDT (SSMDT)

highlighted the difficulty in predicting malignant potential from the

clinical, biological and molecular features.

Detailed further discussion with the general paediatricians,

paediatric head and neck and plastic surgeons resulted in the

difficult decision to recommend a therapeutic level 1-3 partial neck

dissection in view of the number of severely atypical

histopathological and molecular features with lymph node

involvement, which suggested a less indolent course despite the

age of the patient.

Following the radical neck dissection, 56/56 lymph nodes were

subsequently negative. The patient made an excellent post-

operative recovery, with minor wound infection and mild

lymphoedema of the ipsilateral jaw post-operatively only.

Clearly age led a significant proportion of EQA responders to

favour benign diagnosis despite worriesome histology

Bapoma mentioned by some participants

Slide Club Panel: More decisively away from benign/favour

benign (<20%)

“Spitzoid”: How can we define today?

Spatz et al: Unfortunately grading AST is based on a now

quite old paper with relatively few cases and little molecular

work-up

Discussion: Slide Club Responses

GENERAL DISCUSSION POINTS

This rare case of a paediatric spitzoid melanoma with lymph node involvement highlights

the challenges in the clinical, histopathological and molecular diagnosis of atypical

spitzoid lesions.

Molecular studies can play a key role in the diagnosis of spitzoid melanomas in

paediatric patients.

KRAS exon 2 mutations, as found in our patient have been rarely described in

melanomas to date. In the Cancer Genome Atlas database only 0.9% (6/666) of

melanomas displayed a KRAS mutation. G12D mutation was the most frequently found

(3/6).

Management of atypical spitzoid tumours is variable, with a lack of evidence of

prognostic benefit for sentinel lymph node biopsy over wide local excision and regular

clinical follow-up (ref).

Managing rare paediatric spitzoid lesions within an adult SSMDT is less than ideal /

remains a challenge and may impact on the provision of optimal holistic and

developmentally appropriate care.

Provision of a paediatric-specific SSMDT at a regional or national level may help tailor

potentially radical treatment decisions in this group of patients.

Melanomas of

childhood.

Am J Pathol.

1948;24:591–609.

“Differentiation

histologically

between juvenile

and adult melanoma

could not be made

with certainty in

most cases” Sophie Spitz

Alan Spatz University of McGill

Canada

Spatz A, Calonje E, Handfield-Jones S, Barnhill RL. Spitz

tumors in children: a grading system for risk stratification.Arch

Dermatol. 1999 Mar;135(3):333-5.

Eduardo Calonje St John’s Institute

UK

Raymond Barnhill Institut Curie

Paris, France

ATYPICAL SPTIZ TUMOUR (AST)

SPITZ TUMOUR OF UNCERTAIN

MALIGNANT POTENTIAL (STUMP)

• GRADING for childhood cases

• May promote better

reproducibility for diagnosis

between observers

• Should be born in mind that not

all cases of metastasis

(especially loco-regional nodes)

indicate a long-term adverse

outcome

• But…even lesions in low risk

category may result in death

from metastatic disease

• Needs validation in a larger

dataset

SPITZ NAEVUS v ATYPICAL SPTIZ TUMOUR

(STUMP)

Spatz A, Calonje E, Handfield-Jones S, Barnhill RL. Spitz tumors in children: a

grading system for risk stratification.Arch Dermatol. 1999 Mar;135(3):333-5.

“...currently no IHC or Molecular …that

can be used to make an entirely safe

diagnosis of Spitz nevus or melanoma in

problematic cases.”

• 40% 15y or younger

• H&N commoner location in children

c/w adults

• Compouned (46%); Junctional (33%);

Dermal (21%)

• Epithelioid and/or spindle cells: 100%

• Maturation: 72%

• Inflammation: 70% (rarely dense)

• Epidermal hyperpalsia: 66%

• Melanin: 50%

• Telangiectases: 40%

• Kamino bodies: 34%

• Desmoplastic stroma: 26%

• Mitosis: 23%

• Pagetoid: 13%

• Stromal hyalinisation: 8%

Note: Polypoid SN looks decidedly uncommon!

Am J Dermatopathol. 2009 Apr;31(2):107-16.

Clinical view of a heavily pigmented asymmetric plaque

located on the left arm of a 33-year-old man. B,

Dermoscopically, the lesion exhibits a starburst pattern

typified by pigmented streaks distributed at the periphery in a

regular fashion. Despite the shape, asymmetry, distribution of

color, and structure are rather homogenous in dermoscopy.

C, Histopathologically, the lesion is slightly raised and sharply

circumscribed (hematoxylin–eosin 340); D, there is a

moderate epidermal hyperplasia with hypergranulosis and a

prevailingly nested junctional proliferation of spindle and

epithelioid melanocytes (hematoxylin–eosin 3250). The

overall histopathologic features are quite in between a

PSCSN and a RN.

Ferrara et al Am J

Dermatopathol. 2010

Jun;32(4):410-4.

• Reed / PSCN is recognisable

clincally & dermascopically

• The commonest variant of

Spitz naevus in one large

series

A, Clinical view of a pink nodule located on the right arm of an 11-year-old girl. B, At a first

dermoscopic examination, the lesion exhibits a few red to black hemorrhagic globules over

a pink background. C, The second dermoscopic view refers to the same lesion after 15

days when the planned excision was finally performed. The hemorrhagic globules are no

more appreciated, and the lesion shows a tan pigmentation at the periphery with a few

irregular vessels in the amelanotic central portion. D, Histopathologically, the lesion is

nodular and asymmetric (hematoxylin–eosin 340); E, despite the absence of any pagetoid

spread, there is atrophy of the epidermis, together with some irregular architecture of the

dermal nests, which are notably larger in the depth than close to the surface (hematoxylin–

eosin 3100). The lesion was 4.48 mm in thickness: a sentinel node biopsy showed isolated

tumor cells within the subcapsular sinus.

• “…pink-red

papulonodular lesions,

previously considered

“classical” Spitz nevus,

could be

histopathologically

atypical with a great

probability than tan-

black macules &

plaques of PSCSN/RN”

• The previously “typical”

clinical lesions

associated with Spitz

naevus are probable not

infrequently AST (a

tumour of intermediate

or borderline

malignancy)

Ferrara et al Am

J Dermatopathol.

2010

Jun;32(4):410-4.

Requena et al Am J Dermatopathol. 2012 Jul;34(5):478-86.

• 18 cases

• Mean age 35.2 (15 to 56)

• Mean size 7.27mm

• Mean Breslow 2.51

• High cell density 10/18

• Atypia 9/18 (marked in 1)

• Mitoses 8/18 (atypical & clustered in

4)

• Absent maturation 9/18

• Absent zonation 8/18

SUBTYPES

• Genuine (7)

• Uniform (5)

• Packed (5)

• Polypoid (3)

• Pigmented (2)

BEST PARAMETERS: cell density,

mitosis, zonation, infiltration pattern,

consumption of epidermis

….mitoses in Spitz nevus are scarce, typically in the

superficial areas of the neoplasm. We consider this

criterion very important in the differential diagnosis of

Spitz nevus and spitzoid melanoma; thus, the presence

of mitoses in the lower portion or many grouped in an

area of a spitzoid lesion must be considered highly

indicative of melanoma

Last follow-up: slight keloid scar at the site of her

original surgery and the worrisome moment in April

time when she presented with a changing melanocytic

lesion on her parietal scalp which we excised and

was shown to be a benign melanocytic naevus she

has full mobility and dances and acts and is doing

fantastically. She has slight swelling on the side of the

surgery but not significant lymphoedema.

Acknowledgements:

All EQA and Slide Club responders

Dr Ina Nicklaus

Dr Bella Ganatra

Dr Emma Howard

Dr Claire Bowen

Dr Arnaud de la Fouchardiere