primary conjunctival melanomas

Primary conjunctival melanomas.

Patient profile

• 7 patients.

5 females ; 2 males. The female age range was 39-77 (median

age 62). The males were aged 44 and 74.

All patients had unilateral disease.

4 right eyes and 3 left eyes were affected.

14 primary invasive

melanomas in 7 patients

4 patients Solitary mm

3 patients Multiple mm

2 juxta-limbal bulbar conjunctiva;

2 inferior fornix and

inferior tarsal conjunctiva.

1 juxta-limbal bulbar,

1 juxtalimbal bulbar and non-bulbar

1 juxtalimbal bulbar and plica involvement.

Melanoma thickness

• 0.1mm to 1.4 mm

• pT1a to pT2b

• All cases associated with in-situ MM

• One case had vascular invasion.

What’s the big deal?

18 months later………………

8 months later………………

2002

2010

19 nodules overall

7 patients

4 patients solitary 3 patients multiple

1-synchronous 2-metachronous

Location of nodules 19 nodules in 7 patients

8 BULBAR 11 NON-BULBAR

1 patient presented with nodule

6 patientsnodules

after primaryConj mm diag.

Nodule size range 3-9mmMedian-5mm

7 patients

5 free of systemicmets

2 developed systemic mets

Alivelevel 1 and 2

neck lymph nodesintra-parotid lymph node

lung.

DeadBoneLiverBrain

Nodules 3-102 months

after first primaryConj mm

(median 10m)

Systemic mets8-37 m afterFirst nodule

Histology of these nodules?

Local conjunctival metastases

(LCM)

Evidence that nodules are Local METS?

Well defined

Cannon ball

1 nodule-necrosis

Eg. Skin mm

In-transits

Well defined Grenz zone

No overlying in-situ MM

Multiple and synchronous

Nodules-behaviourlike mets.

2 cases Developed

Systemic mets

Argument against mets.• New primaries with once-existent in-situ melanoma,

with the latter regressed in response to Mitomycin C and the nodule having been ‘carved out’

Unlikely

1. In one case, the LCM was the presenting feature with no history of prior topical chemotherapy or surgery.

2. Further primary tumours developed in some cases, while on topical chemotherapy and none of these further primary tumours exhibited a well-defined, nodular morphology.

3. One case, the LCM developed 8 years after the primary tumour had been treated and never received MMC.

Odd distribution of LCMs?• Local factors that promote arrest and growth of the

LCMs.

• Surgery scarring and inflammation -damming up of tumour cells-possible but in 1 case, LCM at presentation and some cases LCM remote from surgery site.

• Seeding by surgery? But 1 case presentation with LCM with no prior surgery history and no nodules at edge of dissection lines.

• Dormant micromets that disseminate early…grow..?

• Circulating stem cells that find niche and expand ?

• All of the LCM extravascular,

• Always extravascular, or whether once intravascular and have exited?

• Intrinsic blood supply

• Associated with a lymphocyte cap. Host reaction?

LCM selected a pre-existing lymphoid niche?

• LCM associated with lymphatic vessels some cases. Intraymphatic spread? Lymphangiogenesis?

Systemic mets.

• 2 cases.

• Is LCM a proxy measure for what is happening systemically?

• Indication for sentinel LN biopsy?

• Should LCMs be regarded as ‘N’ status in pathological TNM classification (like large bowel adenoca)?

Thanks