Primary cutaneous and anal malignant melanoma: A complete histomorphological study and BRAF mutation analysis

Nufina, T A (2018) Primary cutaneous and anal malignant melanoma: A complete histomorphological study and BRAF mutation analysis. Masters thesis, Christian Medical College, Vellore.

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Abstract

OBJECTIVES: To carry out a retrospective complete histomorphological study with survival analyses and BRAF mutation status of primary cutaneous and anal melanoma. METHODS: A cohort study was conducted on primary cutaneous and anal melanomas (January 2013 to December 2015) wherein a complete histomorphological study, in accordance with AJCC (2010) pathological staging criteria along with clinicopathological correlation and BRAF V600E mutation analysis by polymerase chain reaction was carried out.AJCC (2010) classification for cutaneous melanomas were applied to anal melanomas as they did not have any standard pathological staging criteria. RESULTS: There were 39 cutaneous and 11 anal melanomas, both displaying earlier age at presentation (median: 51.5 years) and male preponderance. The most common invasive subtypes were acrallentiginous (cutaneous) and nodular (anal). Anal melanomas presented as thicker tumours (median: 7.8 mm). Presence of ulceration (88%), lymphovascular invasion (70%), perineural invasion (42%), satellite/in transit metastases (28%) and regression (16%) were noted. Six (42.9%) of 11 patients with nodal metastases displayed extracapsular extension. Metastases developed in 23 (46%) patients, the most common site being liver; five patients developed clinical recurrence. Majority of tumours were of stage T3&T4 (94%), N2&N3 (42%) and M1c (38%). Anal melanomas showed higher rates of recurrence and metastases with the propensity to develop metastases in multiple sites, especially on presentation. Increased frequency of metastases on diagnosis is associated with nodular melanomas (both anal and cutaneous) and melanomas exhibiting regression. Anal melanomas presented with thicker and ulcerated tumours and showed 2.4 times higher risk (95% CI: 1.4-4.1) for development of metastases as compared to cutaneous melanomas. Acrallentiginous melanomas were associated with elevated levels of serum LDH as compared to nodular melanomas which showed no difference in the serum LDH levels. Extranodal extension of tumour was associated with the presence of distant metastases. The 1-year, 2-year and 3-year overall survival (OS) rates of all melanomas were77.8%, 22.2% and 5.6% respectively with a median OS of 16 months (95% CI: 14-35 months). Lesser OS was significantly associated with medium cell size and involved peripheral margin of invasive component. The 1-year, 2-year and 3-year distant metastases free survival (DMFS) rates were 64.3%, 28.6% and 14.3% respectively (median: 25 months, 95% CI: 8-36 months). Presence of satellitosis and in transit metastases had a significant negative impact on the distant metastases free survival. At the end of one year, 40% patients were found to be free of recurrence (mean: 29.8 months, 95% CI: 22.5-37.1 months). Factors associated with poor prognosis included gender (females), ulceration, increased Clark level, vertical growth phase, absence of tumour infiltrating lymphocytes, increased mitotic rate (> 12/mm2), amelanotictumours, involved margins, larger metastatic nodal size (> 6cm), elevated levels of serum LDH and advanced stage. These findings were not statistically significant. There was complete absence of BRAFV600E mutation in all the amplifiable cases (n=45), with an estimated probable prevalence of 2.7% in our population. Increased nest formation and upward scatter, larger pigmented cells with epithelioid morphology and continuous lateral circumscription were associated with absent BRAFV600E mutation in our population. CONCLUSIONS: Primary melanomas, both cutaneous and anal, show earlier age at presentation as compared to Caucasian population. Acrallentiginous melanoma is the most common subtype, unlike Caucasians who have predominance of superficial spreading melanoma. Anal melanomas display higher recurrence and metastases rate, especially on presentation involving multiple sites, similar to global studies. Significant adverse prognostic factors for overall survival include medium cell size and involved peripheral margins. Presence of satellite/in transit metastases is significantly associated with increased metastases and reduced survival. Female gender and amelanotic tumours tend to have poor overall prognosis. Complete absence of BRAFV600E mutation in all the amplifiable cases, with an estimated probable prevalence of 2.7% in our population shows that the actual prevalence of BRAFV600E mutation in the Indian population is much lower than that described in Asian literature. Increased nest formation and upward scatter, larger pigmented cells with epithelioid morphology and continuous lateral circumscription are associated with absent BRAFV600E mutation in our population.

Item Type: Thesis (Masters)
Additional Information: Reg. No. 201513354
Uncontrolled Keywords: Melanoma ; Histomorphology ; BRAF.
Subjects: MEDICAL > Pathology
Depositing User: Subramani R
Date Deposited: 19 Aug 2018 07:19
Last Modified: 19 Aug 2018 07:19
URI: http://repository-tnmgrmu.ac.in/id/eprint/9321

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