Case RAC7783. M46. Ear. Mole. r/o MM.Blue naevus · blue [nevus-like] tumour' (a kind of dendritic...
Transcript of Case RAC7783. M46. Ear. Mole. r/o MM.Blue naevus · blue [nevus-like] tumour' (a kind of dendritic...
Case RAC7783. M46. Ear. Mole. r/o MM. ?Blue naevus
RAC7783
Pie Chart Participants
N=74
Benign: 48
Blue naevus: 38
Intradermal: 12
DPN: 10
Compound 3
Clonal: 3;
Spitz 2; Special Site: 1; Congenital: 1
Benign unclassifiable: 1
Uncertain favour benign 10
Uncertain favour malignant 4
Malignant 11 Nodular: 5
Malignant blue: 3
SSMM: 1, Naevoid: 1
N=74
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=49
Combined naevus - intradermal naevus and cellular blue naevus
– several
Combined naevus with naevocellular and DPN like elements
Differential diagnosis is deep penetrating naevus or blue naevus
Sub 5mm reasonably symmetrical combined lesion with
conventional nevus and deep penetrating nevus like
components. Mitotically active, but DPN component cells
uniform and I see no atypical mitoses. Patient on edge of age
range for new presentations of this lesion, so worth getting
history of lesional behaviour at MDT prior to sign out.
Epithelioid cellular blue naevus – x4
Depending on Beta-Catenin and Cyclin D1; DPN or Cellular blue
naevus
EQA Participants: Uncertain favour benign N=10
A pigmented melanocytic lesion which is very cellulra and dual
cell population in keeping with cellular blue naevus. However
there are clearly some cells that show atypia and some mitoses
are located in the deep part of the lesion.I do not think the
features are of melanoma arising in blue naevus or a blue
naevus -like melanoma. On balance I favour cellular bleu
naevus with atypia
Need BAP1 staining
DPN-like but with reverse wedge shape and slightly older age
than usual.
A combined naevus with superficial ordinary intradermal naevus
and deeper DPN component. Could do Beta-catenin to help
confirm this. One mitosis identified in DPN component but no
atypical forms seen.
EQA Participants: Uncertain favour malignant N=4
Combined naevus - compound melanocytic and epithelioid blue.
The blue component is atypical with deep mitoses and extends
into subcutis. Unceratin malignant potential, but would treat as
malignant.
EQA Participants: Malignant N=11
Superficial spreading melanoma arising on intradermal naevus
spitzoid, but several mid/deep mitoses, 2 very close together ( 3
in 1mm2.some atypical junctional nests
Deep mitotic figures (up to 2/mm2 ), infiltrating edge. No
necrosis. ?nevoid melanoma ?atypical CBN
Mitoses: “Can’t see on digital slide”
Pie Chart Slide Club
N=23
SLIDE CLUB RESPONSES
combined banal and epithelioid blue
Combined naevus with a cellular blue naevus component.
Heavily pigmented compound melanocytic proliferation which I think is benign and belongs to the
deep penetrating naevus / combined naevus spectrum. I would recommend conservative re-
excision given the very close deep margin.
Combined melanocytic dermal tumor with a common nevus component at the sides and
superficially. Centrally a DPN-like component but growing less nested than usual and with a
more compact/expansile base. I do not see mitoses or necrosis. Fat cells in the deeper part. I
would prefer a benign lesion, in the spectrum of combined nevus, common & DPN. I would
perform additional MIB, HMB,beta-catenin and BAP1 stain. I would comment on the unusual
growth and I would like clear margins (seems very close to the margin), otherwise advise a (small)
re-excision.
Combined congenital-like cellular naevus with deep penetrating-like pigmented clone. The
latter shows mild cellular pleomorphic and scanty mitotic activity.Given the diagnosis challenges in
these cases, excision with clear margins may be advisable.
Favor benign based on silhouette, absence of junctional component, and relatively regular
distribution of melanin pigment / melanophages. Biphenotypic pattern with smaller nevus cell
aggregates at periphery of larger DPN-like lesion is common presentation of a combined nevus,
however, given patient age, ctyologic atypia, and a possible (deep) mitotic figure, re-excision
seems warranted.
Cellular blue naevus, benign.
SLIDE CLUB RESPONSES
Uncertain favour benign. Combined naevus with intradermal naevus and component with some
features of deep penetrating naevus
Combined common acquired naevus which merges with a more cellular, pigmented clone of larger
melanoytes.Differential diangosis deep penetrating naevus (so do beta catenin), and an atypical
cellular blue naevus - would do FISH..
Combined nevus with components of congenital pattern nevus and melanocytoma c/w deep
penetrating nevus with atypical features (confluence of nests and fascicles but without severe
atypia or mitoses)
compound melanocytic lesion with modest component of usual type naevus. Admixed and
dominating the coventional naevus is a heavily pigmented and cellular component of short spindle
cells. It is difficult to define mitotic activity (I have found just one in the lower third). There is no
thinning of the epidermis and although the lesion pushes out into subcutis it stops rather abruptly.
On balance I favour a combined naevus with usual and cellular blue types although a combined
lesion with DPN component is a further consideration but one I think less likely.
Atypical DPN ( with some worrying features such as the patients age, few mitotic figures,
asymmetry, increased cellularity and somewhat unusual location on the ear which is a special and
UV exposed site). There are remnants of the conventional dermal naevus in papillary dermis.
Complete excision with 5 mm margin and surveillance should be a sufficient treatment. BRAF and
Beta catenin immunostains could confirm the diagnosis.
SLIDE CLUB RESPONSES
1st: [Uncertain favour benign] This is a very difficult-to-diagnose case. There is a fascicular and
sheet-like growth of pigmented spindle melanocytes which merge with a banal-appearing
naevocytic component close to the surface. The tumor bulges into the subcutis more or less like a
cellular blue naevus; I see no relevant mitotic activity and no foci of necrosis (on the digital slide). I
would sign out a provisional diagnosis of atypical (cellular blue naevus-like) dendritic cell
melanocytic tumor. My gut feeling is that this lesion will behave in a benign fashion. PS - Funny
that the ear is considered as a special site for naevi, because melanomas are even commoner
than naevi in such a location
2nd: This is a combined tumor with a good merging between a banal nevus and a cellular blue
nevus-like melanocytic tumor. I don't know how to correctly call the latter if not 'atypical cellular
blue [nevus-like] tumour' (a kind of dendritic cell counterpart of atypical Spitz tumour). In my
experience, the rule of 'merging' as a criterion for benignity has some exceptions. And this case
may be an exception. I think that this tumour is a low-grade melanocytic malignancy.
a peculiar form of blue nevus of the face. I suggest serial sections to rule out intralesional
malignant evolution. I saw 3 similar lesions with limited follow up of the patients (all consultation
cases). All lesions were on the face of adults or elderly. Two had negative 4-6 years long follow-up.
The third lesion had an obvious melanoma nodule in the middle (but without metastasis, at least
until I could follow up the case).
Two types of cell in the dermis. One ordinary type naevus, the other lager pigmented plump
spindle cell. Mininal junctional component. Minimal variation in cell size/ shape. No mitoses.
Favour Deep penetrating naevus. Would be interesting to see Beta-catenin
benign compound with deep penetrating component
SLIDE CLUB RESPONSES
favour the idea of a combined naevus, with a small superficial / peripheral common acquired
naevus component, and a rather massively cellular but monomorphic plump-spindle cell
component that does not ‘mature’ and is and apparently devoid of mitotic figures. I wonder
whether that component could be related to DPN, even though it looks rather different; I would
ask for a beta-catenin stain all the same. Of course, if I could lay may hands on the materials, I
would study it more extensively for absence of mitotic figures &c.
Combined nevus: Conventional intradermal melanocytic nevus + cellular blue nevus (digital).
Combined melanocytic nevus (glass)
[Uncertain favour malignant] A blue/cellular blue lesion, albeit with an admixed common
acquired component, arising on sun-damaged skin, with readily identifiable mitoses. No necrosis,
but there is some cytological atypia. Recommend NGS.
[Uncertain favour benign] Common naevus and spindle and epithelioid cells but low mitotic rate
and little pleomorphism, some form of combined phenotype. Worrying size and close margin, so
would like wider excision because of uncertainty
favour a combined melanocytic naevus with dysplastic compound naevus and (atypical) deep
penetrating naevus components (glass).
Combined naevus: classic acquired and cellular blue
Deep penetrating naevus; to confirm with Beta-Catenin stain. Advise complete excision
There are nests of small round melanocytes in the superficial dermis. The cytologic features of the
melanocytes are reminiscent of those in deep penetrating nevus, or tumors with PRKCA fusion.
Original Report [Y]:
Combined naevocellular and deep penetrating naevus.
Mitotic rate = low (<1/50hpf).
Depth 4mm
Close to deep (0.5 mm) and focally abutting deep radial margin.
Comment: In view of known challenge for diagnosis in such
cases complete excision with a clear margin may be advisable.
Dear X,
1. ?worth using for slide club
2. Would you recommend a re-excision for a DPN abutting the
margin on someone’s ear?
MICRO REPORT: [X]
That lesion is combined with a superficial common component especially visible in
the junction that it is associated with a deep penetrating component underneath
but that latter presents atypia with hyperdensity and confluent nests into large
sheets. The melanocytes are of large size with enucleated ovular nuclei.
Mitotic activity reaches 2/mm2. There is no inflammatory phenomenon
associated.
The IHC study found a strong nuclear staining with Beta-Catenin and negativity
of antibodies against BRAF V600E. In the deep part, proliferation rate
reaches 20% of stained nuclei.
Mutation by NGS shows the presence of a canonical HRAS mutation and an exon
Beta-Catenine mutation.
The array-CGH could not be performed because of the depletion of
material.
Excision of the ear: Combined melanocytic tumour associating a common nevus
and deep penetrating nevus in the latter atypia with high density and a high
proliferation rate. A complementary resection is advised for this lesion which
reaches 4 mm in depth. These aspects suggest a transformed malignant DPN
component. The resection should be decided in a multidisciplinary meeting
(personal suggestions: complementary resection of at least 1 cm).
The French version of this text prevails.
Lame 10082
1_3
BM18002822 (ABRA)
DLRS = 0,18
Repeat Array CGH: Flat profile
Comment from [X]:
Paper from C Magro described DPN with flat CGH that went malignant if I recall
[Y] Given overwhelming weight of opinion for benign/favour benign would you alter you
opinion of “atypical” and “suggests transformed malignant DPN component”?
Obviously the CGH was a different block but I think it had the DPN component.
I appreciate the lesion could have in the future taken another step.
RAC
[X] I agree this would tend to have me downstage from favor malignant to atypical with
unknown prognosis.
ATYPICAL/”BORDERLINE” DPN
• A small subset of DPN
• Cytologic atypia
• Architectural atypia
• Mitotic activity
SUMMARY: BORDERLINE DPN
• SLN+ve in 1/3
• Cases treated aggressively were free
of dis.
• All 6 examined by CGH showed no
abnormalities
• 7/9 normal by FISH
• 3 cases of progression from
borderline DPN to overt melanoma
SUMMARY: PLEXIFORM MELANOMA
• 4/6 died of disease
CONCLUSION: BORDERLINE
DPN
• Incidence of regional LN
involvement
• Potential progression to over
melanoma
• Management: at least local re-
excision & consideration of SLN
regardless of cytogenetic data
RAC3172
M21. History not available
Diagnosis?
DEEP PENETRATING NAEVUS
DEEP PENETRATING NAEVUS
• Fairly symmetrical wedge-shaped
• Extension in to deep dermis or
subcutis
• Adnexal and neurovascular tropism
• Variable focal junctional component
• Finely pigmented epithelioid cells
• Clear cells, multinucleate cells,
• Spindle cells in deeper areas
• Conspicuous macrophages
• Elongated pigmented dendritic cells
• Mild cytological atypia
• Occassional normal mitotic figures
• Lymphocytic infiltrate
• Often component of combined naevus
RAC3163
M18. Congenital naevus with darker area
Diagnosis?
CONGENTIAL NAEVUS, PIGMENTED
EPITHELIOID CLONE
(possibly DPN-type)
Courtesy of Dr. Pauline Guyot
c/o Dr Arnaud de la Fouchardiere
Combined activation of -catenin signaling and MAP
kinase pathway define DPN
Yeh, Iwei et al. “Combined
Activation of MAP Kinase
Pathway and β-Catenin
Signaling Cause Deep
Penetrating Nevi.” Nature
Communications 8, no. 1
(September 21, 2017): 644.
c/o Arnaud de la Fouchardiere. Recent tumour referred as ?Pigmented
epithelioid melanocytoma ?atypical cellular BN
• Atypical Deep
penetrating nevus
• Cellularity (density)
• Inflammatory features
• Mitotic activity: 3/mm²
• Breslow: 5mm
• Diffuse HMB45 positivity
• P16 slightly heterogeneous
• Ki67: 10-20% nuclear
positivity in some areas
• BRAF V600E: negative
• Beta-catenin staining: strong
nuclear staining
• Array CGH
• Exon 3 CTNNB1 G34E
mutation
• No hotspot mutations in
BRAF, NRAS, KIT
Beta-catenin IHC
DEEP PENETRATING NAEVUS MESSAGES
• Recent clarification of genetics: 2 alternations
• 1: MAPK pathway – BRAF, MAPK2, HRAS
• 2: βCatenin pathway – CTNNB1, APC
• «Intermediate tumor» that can progress
towards malignancy
• Beta-catenin IHC is useful in recognizing DPN
c/o Dr Arnaud de la Fouchardiere
Combined PEM: More
Pigment, Low cellularity,
Numerous melanophages
Combined DPN: Less
Pigment, High Cellularity
CTNNB1
PRKAR1A
c/o Arnaud de la Fouchardiere
Many EQA participants and a few panel members (8) did not appreciate
unlikely to be “naevocellular” combined with “blue” as they are mutually
exclusive
Greater proportion of panel favoured DPN (13)
Interesting the MAPK abnormality is in HRAS (present in a proportion of
Spitz, particularly desmoplastic type) but the naevus is naevocellular in
Case 232
However N. spilus is characterised by HRAS mutation (and these lesions
are usually naevocellular)
Of concern 8/17 EQA MPathDx responses were happy to leave a
challening case such as this without re-excision
Even typical DPN should probably be regarded as a “difficult” case for
diagnosis and given possibility for malignant transformation complete
excision with clear margins recommended as for a “melanocytoma”
Discussion
Dutch Master? Without Title, 1986
Prof Wolter Mooi Amsterdam, NL
www.melanocytepathology.com
PS: this might be my last contribution to your excellent
slide club... I plan to quit pathology by the end of this
year, in order to devote my time entirely to some of ‘the
humanities’ (at a modest level of achievement, no
doubt).
THANK YOU WOLTER!
Thank You
Arnaud de la Fouchardiere
All responding EQA members and
panel members
Cases 231 & 232 are dedicated to
Professor Wolter Mooi
REFERENCE
Eur J Dermatol. 2014 Sep-Oct;24(5):594-602. doi: 10.1684/ejd.2014.2393.
Deep penetrating nevus-like borderline tumors: A unique subset of ambiguous melanocytic
tumors with malignant potential and normal cytogenetics.
Magro CM1, Abraham RM2, Guo R3, Li S4, Wang X1, Proper S5, Crowson AN6, Mihm M7.
Author information BACKGROUND:
Deep penetrating nevi (DPN) are a relatively uncommon subtype of melanocytic nevi. A small subset of these lesions exhibit atypical
features (cytologic and architectural atypia, mitotic activity) seen in melanoma. These lesions we term the deep penetrating nevus-
like borderline tumor. Unequivocal melanomas can show overlapping morphologic features of DPN, which have been termed
plexiform melanomas.
PATIENTS AND METHODS:
40 cases of DPN-like borderline tumor were identified along with 6 cases of plexiform melanoma. Clinical follow up was obtained,
along with cytogenetic analysis in the form of fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization
(CGH).
RESULTS:
The DPN-like borderline tumor cases included 24 females and 16 males. Of sentinel lymph node biopsies performed, 1/3 of cases
showed lymph node involvement. All patients where an aggressive clinical approach was adopted remain free of disease. All 6 DPN-
like borderline tumor cases tested by CGH showed normal cytogenetics, as did 7 of 9 cases tested by FISH. Of the plexiform
melanomas, 4/6 patients died of disease. In 3 cases there was morphologic progression from a DPN-like borderline tumor to overt
melanoma. In one case of progression, cytogenetics was normal in the DPN-like borderline tumor and then abnormal in the
progressed melanoma.
CONCLUSION:
DPN-like borderline tumors are melanocytic tumors associated with a high incidence of regional lymph node disease and exhibiting
the potential for melanoma progression despite a normal cytogenetic profile. Patients with these lesions should be aggressively
managed, with at least complete re-excision and consideration of sentinel node biopsy, regardless of cytogenetic data.