Clinical Pathological Conference. Malignant Melanoma of the Vulva
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1 Clinical Pathological Conference Malignant Melanoma of the Vulva
2 History F/48 Chinese Married Para 1 Presented in September 2004 Vulval mass for 2 months Associated with watery and blood stained discharge Not painful Consulted TKO Hospital and examination showed 3x1 cm vulval mass at left labia minor near the urethral meatus Biopsy showed malignant melanoma
3 Physical Examination General examination unremarkable No peripheral lymphadenopathy in supraclavicular fossa or groin PV showed a 3.5 x 1.5 cm polypoid growth arising from the inner aspect of left labia minora 1cm from the urethral meatus Vagina and cervix normal Uterus normal size and no adnexal mass felt
4 Right Left Tumour
5 Tumour Urethral Meatus
6 Urethral Meatus Pigmentation Tumour
7 Investigations CXR: No metastasis PET-CT scan: No evidence of regional or distant metastasis
8 Treatment Radical vulvectomy with removal of the distal 1cm urethra (at least 2cm margin) En bloc bilateral groin lymph node dissection performed in November 2004 Post-operative normal micturation, no incontinence, normal stream Wound healing well, no breakdown
9 Pathology Pathology: Malignant melanoma Polypoid growth with surface ulceration No lymphovascular permeation Maximum thickness from the ulcer base 12.5mm Resection margin not involved Bilateral groin lymph nodes no malignancy
10 Malignant Melanoma of Vulval (MMV) % of all melanomas in women 8-11% of all vulval malignancy Second most common malignancy after squamous cell carcinoma Mean age (cutaneous melanoma 30-40) Exposure to UV radiation: unlikely No association with parity or hormones
11 Malignant Melanoma of Vulval (MMV) - 2 Presentation: Mass Bleeding Pruritus Ulceration and discharge Change in pre-existing nevus (de novo) Constitutional symptoms ~70% no clinically detectable LN or distant metastasis DDX: Seborrhoeic keratosis, haemangioma, dermatofibroma, VIN
12 Distribution
13 Staging - 1 Microstaging systems for primary lesion: Clark s (1969) Breslow s (1970) Chung s (1975) Staging systems: AJCC FIGO
14 Staging - 2 Clark s: Level I-V based on dermal connective tissue plane Breslow s: Tumour thickness Chung s: Modified Clark s and Breslow s system due to lack of well defined papillary dermis of vulva
15 Staging - 3 Chung s Clark s Intraepithelial Into papillary dermis Filling papillary dermis Into reticular dermis Into subcutaneous fat
16 Staging - 4 Staging system: AJCC 1992 (American Joint Committee on Cancer) - Stage I-IV Based on microstaging of the primary lesion (including Clark s and Breslow s level) and the status of regional LN and distant sites (TMN concept) Independent prognostic factor by GOG prospective study FIGO Stage I-IV Based on tumour size and extension to adjacent organs as well as regional LN and distant metastasis Not prognostic since more influenced by depth of invasion than by tumour size
17 Prognosis - 1 Overall 5 yr survival 8-55%, mean 36 months (CMM: 72-81%)? Due to advanced stage at presentation? Advanced age of presentation? More aggressive nature? Anatomical constraints prevent proper surgical treatment Local recurrence 30-51% most commonly groin and perineum (poor outcome with median survival 5-6 months) Metastasis: Lung, liver, brain
18 Prognostic Factors - 1 Microstaging (Depth/thickness): Predicts regional node metastasis and correlates with recurrence / survival Risk of occult LN metastasis: <1mm: <5% >4mm: 70% 5 yr survival: Level I/II approaching 100% Level III/IV ~ 30-40% Level V 23-33%
19 Prognostic Factors - 2 AJCC (1992) Stages Independent prognostic factor by GOG 5-yr survival: Stage I 85%, Stage II 40%, Stage III 25% FIGO stage Not prognostic since more influenced by depth of invasion than by tumour size Ulceration, mitotic activity, nodular melanoma, lymphocytic infiltration, LVP, groin LN metastasis, central location, advanced age
20 Treatment - 1 Surgery offers the only effective therapy for control and potential cure Traditionally radical vulvectomy with bilateral groin LN dissection, but considerable morbidity Research on CMM: Treatment should be individualised according to risk factors such as microstaging Because of rarity of MMV, retrospective data only. Therapy based on treatment data of CMM
21 Treatment - 2 Treatment consideration include: Extent of the resection Regional lymph node dissection
22 Extent of Resection - 1 Based on randomised trials for CMM Thickness <1mm: 1cm margin Thickness 1-4mm: 2cm margin (2cm VS 4cm margins same 10 yr local recurrence / survival) Studies on MMV Retrospective studies similar survival associated with radical wide local excision with radical vulvectomy
23 Extent of Resection - 2 Due to morbidity associated with radical vulvectomy Trend towards more conservative resection as for CMM However, radical vulvectomy may sometimes be necessary to achieve adequate margins in bulky central mucosal lesions
24 Regional LN Dissection - 1 For clinically involved LNs without distant metastasis: Therapeutic with better outcome (CMM) For clinically no palpable LN: Controversial Provides prognostic information,? better control of disease and? determine adjuvant treatment Thin tumours <0.76mm (LN metastasis <5% if <1mm): No survival benefit Intermediate thickness (1-4mm) Intergroup Surgical Melanoma Program Better survival for subgroup: 1-2mm, <= 60 yrs, without tumour ulceration Thick tumours >4mm (LN metastasis > 70%): No survival benefit May improve outcome if regional micrometastasis are isolated sufficiently to prevent further dissemination to distant sites
25 Regional LN Dissection - 2 Sentinel node assessment: Presumed regional lymphadenectomy prolongs survival The Multicenter Selective Lymphadenectomy Trial (MSLT) for CMM: Wide local excision alone VS wide local excision plus sentinel node assessment with SCLND (Selective Complete LN Dissection) for tumour >1mm without clinically regional LN metastasis
26 Adjuvant Treatment Adjuvant therapy for deep lesions and positive LNs/metastatic disease: Radiotherapy: radio-resistant (may respond to higher dosage) Chemotherapy (Dacabazine VS combination): palliative Chemotherapy with tamoxifen Immunotherapy: High dose interferon alfa-2b in patients with +ve LNs Limited by high toxicity, at least 67% grade 3 toxicity, 1/3 require dose delay or reduction, life threatening hepatotoxicity Vaccines Clinical Trials
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