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Essential Components of Melanoma Histopathological Reporting: The Surgical Oncologist’s Perspective

Essential Components of Melanoma Histopathological Reporting: The Surgical Oncologist’s Perspective Hindawi Journal of Skin Cancer Volume 2018, Article ID 9838410, 4 pages https://doi.org/10.1155/2018/9838410 Review Article Essential Components of Melanoma Histopathological Reporting: The Surgical Oncologist’s Perspective 1 2 1,3,4 Vinka Nurdjaja, Masato Yozu, and Jon A. Mathy University of Auckland School of Medicine, Auckland, New Zealand Histopathology Department, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand Plastic Surgery Unit, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand New Zealand Melanoma Institute, Auckland, New Zealand Correspondence should be addressed to Jon A. Mathy; Jon.mathy@middlemore.co.nz Received 8 January 2018; Revised 10 March 2018; Accepted 26 March 2018; Published 2 May 2018 Academic Editor: Gun ¨ ther Hofbauer Copyright © 2018 Vinka Nurdjaja et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Histopathological reporting plays a critical role in guiding the surgical oncologist’s management plan in treatment of primary cutaneous melanoma. The International Collaboration on Cancer Reporting (ICCR) espouses various components of structured histopathological reporting as “essential” or “recommended.” From a surgical oncologist’s perspective, we discuss the clinical relevance of each essential component, as well as prognostic and treatment implications with regard to treatment planning. New Zealand and Australia possess the highest incidence of in Table 1 [3]. These components are important in evaluating melanoma in the world [1]. In patients with newly diagnosed prognosis, treatment options, candidacy for clinical trials, early-stage primary cutaneous melanoma, surgery remains and standardized outcomes assessment. The preanalytical the mainstay of initial treatment and is therefore usually elements and components of macroscopic histopathological orchestrated by the surgical oncologist. The surgical oncol- assessment are outside the scope of this article and are not ogist’s management plan depends on patient characteristics discussed. and histopathological features of the primary lesion following Primary lesion Breslow thickness bears the most signif- excisional biopsy. er Th efore, the histopathological report icant prognostic and surgical implications and represents a plays a central role in guiding initial treatment, staging, and cornerstone of American Joint Committee on Cancer (AJCC) prognosisadviceprovidedtomelanomapatients. staging [4]. While substaging is further determined by lesion Here, we summarize for the clinician the relevance of ulceration, Breslow thickness represents the fundamental the essential components of melanoma reporting from the determinant of T-staging [4]. Furthermore, Breslow thick- surgical oncologist’s perspective, emphasizing how these ness acts as the basis of wide local excision (WLE) margins components influence patient prognosis and guide typical [5]. Current guidelines recommend invasive melanomas< surgical management such as resection margins and sentinel 2 mm in thickness to be excised with at least 1 cm margin, node biopsy. while melanomas≥ 2.0mm are excised with at least 2cm The ICCR guidelines were established following evalu- margins [5]. ation of existing histopathological guidelines by the Royal Breslow thickness is also an independent predictor of College of Pathologists (United Kingdom) (RCPath), Royal sentinel lymph node (SLN) status [6]. In a retrospective College of Pathologists of Australasia (RCPA), and College review of 221 patients undergoing sentinel node biopsy, there of American Pathologists (CAP) [2]. Current “essential” isSLNpositiverateof4.8%inT1patients, 11.2% inT2 (mandatory/standard) and “recommended” (nonmanda- patients, 28.1% in T3 patients, and 46.5% in T4 patients tory/guideline) components of structured histopathological [6]. Further data supports performing sentinel node biopsy reporting for primary cutaneous melanoma are summarized (SNB) for microscopic staging of the regional lymph node 2 Journal of Skin Cancer Table 1: Essential and recommended elements of structured micro- dissection should not be conducted in all patients with scopic histopathological reporting for primary cutaneous melanoma positive SN [12]. However, in appropriately selective patients, espoused by the International Collaboration on Cancer Reporting sentinel lymphadenopathy has also been shown to provide (ICCR) [3]. improved treatment outcomes in the node-positive cohort in terms of melanoma-specific survival, regional disease Breslow thickness Essential control, andsurgicalmorbidity [13,14].Apositive sentinel Surgical margin/tissue edge status Essential node biopsy also allows for an earlier opportunity to make Ulceration Essential informed decisions regarding candidacy for further investi- Mitotic count Essential gations, treatments, and/or clinical trials and has implications Satellites Essential for posttreatment surveillance [7]. There are numerous recent Lymphovascular invasion Essential and pending clinical trials studying the effect of immunother- Desmoplastic melanoma component Essential apy for early-stage metastatic melanoma, where studies have Neurotropism Essential shown significant improvement in survival [15]. Margins of excision represent perhaps the most self- Extent of ulceration Recommended explanatory essential parameter of histological reporting. Clark level Recommended Widely clear margins are required to ensure clearance and to Tumour-infiltrating lymphocytes Recommended reduce local recurrence rate. Local recurrence is hypothesized Tumour regression Recommended to arise secondary to unresected microsatellites, intralym- Tumour regression margins Recommended phatic spread, and/or intrinsic regional tumour influence Associated melanocytic lesion Recommended [16]. Wide excisional margins performed per standard of care Intraepidermal melanoma growth pattern Recommended have been shown to reduce that risk [16]. For example, in Melanoma subtype Recommended T2 melanoma, local recurrence has been shown to fall from 3.6% to 0.9% aer ft excision with 1 cm versus 2 cm margins, respectively [17]. Conversely, no signicfi ant difference in basin when tumour thickness meets or exceeds 1 mm, or overall or recurrence-free survival has been shown between greaterthanorequalto 0.75mmwith otherhighriskfeatures 1-2 cm margins and more radical 3–5 cm clinical margins [18]. such as ulceration and/or high mitotic activity [7]. Currently, there is little evidence to guide recommenda- After Breslow thickness, both mitotic rate and ulcera- tions on depth of resection, as long as the deep resection tion reporting are important for the surgical oncologist in margin is clear [18]. The ANZ 2008 guidelines recommend treatment planning. Mitotic rate is no longer considered a resection down to (not including) deep fascia [19], as staging criterion for T1 melanoma in the most recent AJCC supported by its physiologic tendency towards lymphatic guidelines [8]. However, both features correlate with potential blockade. Notably, another study has shown no difference in for metastatic spread and prognosis [2, 8]. Mitotic rate, as survival rates between patients with intact and resected deep a sign of biologic activity, is particularly important in thin fascia [16]. melanomas, where mitotic activity≥ 1/mm is associated with Satellites, defined as disconnected malignant cells greater than 0.05 mm in diameter divided by dermis at least 0.3 mm a decrease in 10-year survival from 95% to 88% [9]. 5-year survival rate in ulcerated melanomas is proportionately worse away from the primary invasive lesion, are postulated to than nonulcerated melanomas of the same T stage, while reflect early metastatic activity along a spectrum with in- transitandregionallymphnodemetastases[9].Bothprogno- being similar to nonulcerated melanomas of the next highest T stage [9]. sis and SLN status are significantly aeff cted, with significant In addition to Breslow thickness, ulceration and mitotic reduction in survival and change in SLN positivity from 11 to rate can also influence the surgical decision to pathologically 43% when comparing microsatellite with nonmicrosatellite stage the regional lymph node basin with SNB. While SNB groups [20]. Presence of ulceration with microsatellitosis positivity has been reported at approximately 5% of all reduces 5-year melanoma-specicfi survival from 83% to 43% primary melanomas< 1 mm overall, the rate increases up to [20]. 20% for patients with thickness between 0.75 and 0.99 mm Lymphovascular invasion (LVI) has also been shown to significantly correlate with prognosis and metastatic in the presence of mitotic rate ≥1/mm and/or ulceration [7]. This is important as melanomas ≤ 1 mm are reported to potential. Analysis of 2,243 patients with thin melanomas comprise over 70% of diagnoses made and also comprise 25% showed that LVI is an independent prognostic factor and is associated with increased SLN positivity [21]. Among patients of all melanoma-specicfi deaths [10, 11]. eTh decision to perform SNB is important for the surgical with supercfi ial spreading melanoma > 1.0 mm in thickness oncologist, as the presence of regional lymph node metastasis undergoing SLN biopsy, LVI was an independent risk factor represents the most significant prognostic factor in early- reducing disease-free survival in the form of both local and stage melanoma [7]. For T1 primary lesions, the 5-year Can- in-transit recurrence [22]. A recent large analysis of all pri- mary melanomas undergoing SLN biopsy has substantiated cer Specific Survival (CSS) has been shown to fall from 94% to 69% when comparing SN-negative and SN-positive patients, LVI as a predictor of SLN positivity independent of Breslow respectively [11]. While results from the MSLT-II trial cannot thickness [23], further reflecting the surgical oncologist’s consideration of multiple tumour parameters in evaluating be freelyextrapolatedtopatientswithheavytumour or nodal burden, findings suggest that completion lymph node and managing nodal metastatic risk. Journal of Skin Cancer 3 Desmoplastic melanoma (DM) represents a relatively reporting (ICCR),” eTh American Journal of Surgical Pathology , vol. 37, no. 12, pp. 1797–1814, 2013. rare variant of cutaneous melanoma with a clinical course more similartoso-ft tissuesarcoma [24].Itisassociatedwith [3] The Royal College of Pathologists of Australasia. Primary Cuta- neous Melanoma Structured Reporting Protocol,RCPA, New increased local recurrence, possibly due to perineural skip South Wales, 2nd edition, 2014. lesions or missed areas of positive margin [24, 25]. u Th s, surgical oncologists may steer towards wider local excision [4] M. B. Amin, S. B. Edge, F. L. Greene et al., AJCC Cancer Staging Manual, Springer International Publishing, New York, margins, as several studies show that this improves OS and NY, USA, 2017. reduces local recurrence [25]. Furthermore, there may be [5] M. G. Niebling, L. E. Haydu, R. Z. Karim, J. F. Thompson, and R. a role for adjuvant local radiation therapy in patients with A. Scolyer, “Pathology review significantly aeff cts diagnosis and DM to reduce risk of local recurrence [25]. Notably, further treatment of melanoma patients: An analysis of 5011 patients classifying DM into “pure” versus “mixed” subtypes may add treated at a melanoma treatment center,” Annals of Surgical clinical value, as mixed DM has been associated with poorer Oncology,vol.21, no.7,pp. 2245–2251, 2014. prognosis, including a worse 5-year melanoma-specific mor- [6] V. Teixeira, R. Vieira, I. Coutinho et al., “Prediction of Sentinel tality of 31% compared to 11% in pure DM [25]. Conversely, Node Status and Clinical Outcome in a Melanoma Centre,” pure DM may be associated with relatively improved prog- JournalofSkinCancer,vol.2013, pp.1–7,2013. nosis compared to other melanoma subtypes, with similar [7] S. L. Wong, C. M. Balch, P. Hurley et al., “Sentinel lymph node mortality rates and lower rates of SLN positivity despite being biopsy for melanoma: American society of clinical oncology 3 times thicker on average at time of diagnosis [25]. and society of surgical oncology joint clinical practice guide- Perineural, intraneural invasion and “neural transforma- line,” Journal of Clinical Oncology, vol. 30, no. 23, pp. 2912–2918, tion,” in which the tumour forms neural structures, constitute neurotropism [2]. It is commonly found in DM but may [8] J. E. Gershenwald, R. A. Scolyer, K. R. Hess et al., “Melanoma also occur in other melanoma subtypes [2]. Neurotropic staging: Evidence-based changes in the American Joint Com- melanoma is associated with increased local recurrence and mittee on Cancer eighth edition cancer staging manual,” CA: A may compel the surgical oncologist to consider adjuvant Cancer Journal for Clinicians,vol.67, no.6,pp. 472–492, 2017. radiotherapy and/or wider excisional margins [2]. [9] C.M.Balch,J.E.Gershenwald,S.-J.Soongetal.,“Final version Of note, Clark’s level is no longer an essential component of 2009 AJCC melanoma staging and classification,” Journal of of structured reporting according to ICCR guidelines [2]. Clinical Oncology,vol.27,no.36,pp.6199–6206,2009. Clark’s level has been largely superseded by mitotic rate as [10] S. V. Ward, G. Cadby, A. Lee et al., “eTh Western Australian the more important parameter in characterizing melanomas Melanoma Health Study: Study design and participant charac- aer ft ulceration, and is no longer considered an independent teristics,” Cancer Epidemiology,vol.35,no.5,pp.423–431,2011. prognosticator [9]. However, it still adds management value [11] T. J. Hieken, T. E. Grotz, N. I. Comfere, J. W. Inselman, and E. to Breslow thickness in extremely thin skin (e.g., eyelid skin B. Habermann, “eTh eeff ct of the AJCC 7th edition change in or atrophic skin) and when mitotic rate cannot be accurately T1 melanoma substaging on national utilization and outcomes of sentinel lymph node biopsy for thin melanoma,” Melanoma determined [9]. Research,vol.25, no.2,pp.157–163, 2015. In summary, the essential elements of structured histo- pathological reporting contain invaluable information for the [12] A. Falk Delgado and A. Falk Delgado, “Melanoma sentinel- node metastasis,” eTh New England Journal of Medicine ,vol.377, surgical oncologist. Although reporting has been shown to be no.9,pp. 891-892,2017. most consistent for Breslow’s thickness and Clark’s level [1], each parameter has independent implications on prognosis [13] M. B. Faries, J. F. Thompson, A. J. Cochran, R. H. Andtbacka, N. Mozzillo, J. S. Zager et al., “Completion Dissection or andpatient management.Wehopethatthe clinical context Observation for Sentinel-Node Metastasis in Melanoma,” The provides a meaningful context to the role of the clinician New England journal of medicine, vol. 376, no. 23, pp. 2211–2222, in either reporting or interpreting of these elements in rendering individualised prognosis and treatment decisions [14] U. Leiter, R. Stadler, C. Mauch et al., “Complete lymph node for the patient. dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, Conflicts of Interest randomised, phase 3 trial,” The Lancet Oncology ,vol.17, no.6, pp. 757–767, 2016. eTh authors state that there are no conflicts of interest to [15] G. C. Sim, J. Chacon, C. Haymaker et al., “Tumor-infiltrating disclose. lymphocyte therapy for melanoma: Rationale and issues for further clinical development,” BioDrugs,vol.28,no.5,pp.421– 437, 2014. References [16] T. E. Grotz, S. N. Markovic, L. A. Erickson et al., “Mayo [1] L. E. Haydu, P. E. Holt, R. Z. Karim et al., “Quality of Clinic consensus recommendations for the depth of excision in primary cutaneous melanoma,” Mayo Clinic Proceedings,vol. histopathological reporting on melanoma and influence of use of a synoptic template,” Histopathology,vol.56, no.6,pp. 768– 86,no.6, pp.522–528,2011. 774, 2010. [17] L.E. Hudson,S.K.Maithel,G.W.Carlson etal.,“1or2 [2] R.A.Scolyer,M.J.Judge, A. Evansetal.,“Datasetfor cm margins of excision for T2 melanomas: Do they impact recurrence or survival?” Annals of Surgical Oncology,vol.20, pathology reporting of cutaneous invasive melanoma: Rec- ommendations from the international collaboration on cancer no. 1, pp. 346–351, 2013. 4 Journal of Skin Cancer [18] M. J. Sladden, C. Balch, D. A. Barzilai et al., “Surgical excision margins for primary cutaneous melanoma.,” Cochrane Database of Systematic Reviews (Online), no. 4, p. CD004835, 2009. [19] New Zealand Guidelines Group, eTh Cancer Council Australia, Australian Cancer Network, Clinical Practice Guidelines for the Management of Melanoma in Australia and New Zealand,The Ministry of Health, Wellington, 2008. [20] E.K.Bartlett,M.Gupta,J.Datta etal.,“Prognosis ofpatients with melanoma and microsatellitosis undergoing sentinel lymph node biopsy,” Annals of Surgical Oncology,vol.21,no.3, pp. 1016–1023, 2014. [21] M. E. Egger, J. E. Gilbert, A. L. Burton, K. M. McMasters, G. G. Callender, A. R. Quillo et al., “Lymphovascular invasion as a prognostic factor in melanoma,” The American Journal of Surgery,vol.77,no.8,pp.992–997, 2011. [22] M. E. Egger, L. O. Stepp, G. G. Callender et al., “Outcomes and prognostic factors in superficial spreading melanoma,” The American Journal of Surgery,vol.206,no.6, pp.861–868,2013. [23] A. Kibrite, H. Milot, P. Douville et al., “Predictive factors for sentinel lymph nodes and non-sentinel lymph nodes metastatic involvement: A database study of 1,041 melanoma patients,” The American Journal of Surgery,vol.211,no.1,pp. 89–94, 2016. [24] C. S.Pace,J.P.Kapil,L.G.Wolfe,B.J.Kaplan, andJ.P.Neifeld, “Desmoplastic Melanoma: Clinical Behavior and Management Implications,” Eplasty,vol.16,2016. [25] L. L. Chen, N. Jaimes, C. A. Barker, K. J. Busam, and A. A. Marghoob, “Desmoplastic melanoma: A review,” Journal of the American Academy of Dermatology,vol.68,no.5,pp.825–833, 2013. 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Essential Components of Melanoma Histopathological Reporting: The Surgical Oncologist’s Perspective

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Copyright © 2018 Vinka Nurdjaja et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Journal of Skin Cancer Volume 2018, Article ID 9838410, 4 pages https://doi.org/10.1155/2018/9838410 Review Article Essential Components of Melanoma Histopathological Reporting: The Surgical Oncologist’s Perspective 1 2 1,3,4 Vinka Nurdjaja, Masato Yozu, and Jon A. Mathy University of Auckland School of Medicine, Auckland, New Zealand Histopathology Department, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand Plastic Surgery Unit, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand New Zealand Melanoma Institute, Auckland, New Zealand Correspondence should be addressed to Jon A. Mathy; Jon.mathy@middlemore.co.nz Received 8 January 2018; Revised 10 March 2018; Accepted 26 March 2018; Published 2 May 2018 Academic Editor: Gun ¨ ther Hofbauer Copyright © 2018 Vinka Nurdjaja et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Histopathological reporting plays a critical role in guiding the surgical oncologist’s management plan in treatment of primary cutaneous melanoma. The International Collaboration on Cancer Reporting (ICCR) espouses various components of structured histopathological reporting as “essential” or “recommended.” From a surgical oncologist’s perspective, we discuss the clinical relevance of each essential component, as well as prognostic and treatment implications with regard to treatment planning. New Zealand and Australia possess the highest incidence of in Table 1 [3]. These components are important in evaluating melanoma in the world [1]. In patients with newly diagnosed prognosis, treatment options, candidacy for clinical trials, early-stage primary cutaneous melanoma, surgery remains and standardized outcomes assessment. The preanalytical the mainstay of initial treatment and is therefore usually elements and components of macroscopic histopathological orchestrated by the surgical oncologist. The surgical oncol- assessment are outside the scope of this article and are not ogist’s management plan depends on patient characteristics discussed. and histopathological features of the primary lesion following Primary lesion Breslow thickness bears the most signif- excisional biopsy. er Th efore, the histopathological report icant prognostic and surgical implications and represents a plays a central role in guiding initial treatment, staging, and cornerstone of American Joint Committee on Cancer (AJCC) prognosisadviceprovidedtomelanomapatients. staging [4]. While substaging is further determined by lesion Here, we summarize for the clinician the relevance of ulceration, Breslow thickness represents the fundamental the essential components of melanoma reporting from the determinant of T-staging [4]. Furthermore, Breslow thick- surgical oncologist’s perspective, emphasizing how these ness acts as the basis of wide local excision (WLE) margins components influence patient prognosis and guide typical [5]. Current guidelines recommend invasive melanomas< surgical management such as resection margins and sentinel 2 mm in thickness to be excised with at least 1 cm margin, node biopsy. while melanomas≥ 2.0mm are excised with at least 2cm The ICCR guidelines were established following evalu- margins [5]. ation of existing histopathological guidelines by the Royal Breslow thickness is also an independent predictor of College of Pathologists (United Kingdom) (RCPath), Royal sentinel lymph node (SLN) status [6]. In a retrospective College of Pathologists of Australasia (RCPA), and College review of 221 patients undergoing sentinel node biopsy, there of American Pathologists (CAP) [2]. Current “essential” isSLNpositiverateof4.8%inT1patients, 11.2% inT2 (mandatory/standard) and “recommended” (nonmanda- patients, 28.1% in T3 patients, and 46.5% in T4 patients tory/guideline) components of structured histopathological [6]. Further data supports performing sentinel node biopsy reporting for primary cutaneous melanoma are summarized (SNB) for microscopic staging of the regional lymph node 2 Journal of Skin Cancer Table 1: Essential and recommended elements of structured micro- dissection should not be conducted in all patients with scopic histopathological reporting for primary cutaneous melanoma positive SN [12]. However, in appropriately selective patients, espoused by the International Collaboration on Cancer Reporting sentinel lymphadenopathy has also been shown to provide (ICCR) [3]. improved treatment outcomes in the node-positive cohort in terms of melanoma-specific survival, regional disease Breslow thickness Essential control, andsurgicalmorbidity [13,14].Apositive sentinel Surgical margin/tissue edge status Essential node biopsy also allows for an earlier opportunity to make Ulceration Essential informed decisions regarding candidacy for further investi- Mitotic count Essential gations, treatments, and/or clinical trials and has implications Satellites Essential for posttreatment surveillance [7]. There are numerous recent Lymphovascular invasion Essential and pending clinical trials studying the effect of immunother- Desmoplastic melanoma component Essential apy for early-stage metastatic melanoma, where studies have Neurotropism Essential shown significant improvement in survival [15]. Margins of excision represent perhaps the most self- Extent of ulceration Recommended explanatory essential parameter of histological reporting. Clark level Recommended Widely clear margins are required to ensure clearance and to Tumour-infiltrating lymphocytes Recommended reduce local recurrence rate. Local recurrence is hypothesized Tumour regression Recommended to arise secondary to unresected microsatellites, intralym- Tumour regression margins Recommended phatic spread, and/or intrinsic regional tumour influence Associated melanocytic lesion Recommended [16]. Wide excisional margins performed per standard of care Intraepidermal melanoma growth pattern Recommended have been shown to reduce that risk [16]. For example, in Melanoma subtype Recommended T2 melanoma, local recurrence has been shown to fall from 3.6% to 0.9% aer ft excision with 1 cm versus 2 cm margins, respectively [17]. Conversely, no signicfi ant difference in basin when tumour thickness meets or exceeds 1 mm, or overall or recurrence-free survival has been shown between greaterthanorequalto 0.75mmwith otherhighriskfeatures 1-2 cm margins and more radical 3–5 cm clinical margins [18]. such as ulceration and/or high mitotic activity [7]. Currently, there is little evidence to guide recommenda- After Breslow thickness, both mitotic rate and ulcera- tions on depth of resection, as long as the deep resection tion reporting are important for the surgical oncologist in margin is clear [18]. The ANZ 2008 guidelines recommend treatment planning. Mitotic rate is no longer considered a resection down to (not including) deep fascia [19], as staging criterion for T1 melanoma in the most recent AJCC supported by its physiologic tendency towards lymphatic guidelines [8]. However, both features correlate with potential blockade. Notably, another study has shown no difference in for metastatic spread and prognosis [2, 8]. Mitotic rate, as survival rates between patients with intact and resected deep a sign of biologic activity, is particularly important in thin fascia [16]. melanomas, where mitotic activity≥ 1/mm is associated with Satellites, defined as disconnected malignant cells greater than 0.05 mm in diameter divided by dermis at least 0.3 mm a decrease in 10-year survival from 95% to 88% [9]. 5-year survival rate in ulcerated melanomas is proportionately worse away from the primary invasive lesion, are postulated to than nonulcerated melanomas of the same T stage, while reflect early metastatic activity along a spectrum with in- transitandregionallymphnodemetastases[9].Bothprogno- being similar to nonulcerated melanomas of the next highest T stage [9]. sis and SLN status are significantly aeff cted, with significant In addition to Breslow thickness, ulceration and mitotic reduction in survival and change in SLN positivity from 11 to rate can also influence the surgical decision to pathologically 43% when comparing microsatellite with nonmicrosatellite stage the regional lymph node basin with SNB. While SNB groups [20]. Presence of ulceration with microsatellitosis positivity has been reported at approximately 5% of all reduces 5-year melanoma-specicfi survival from 83% to 43% primary melanomas< 1 mm overall, the rate increases up to [20]. 20% for patients with thickness between 0.75 and 0.99 mm Lymphovascular invasion (LVI) has also been shown to significantly correlate with prognosis and metastatic in the presence of mitotic rate ≥1/mm and/or ulceration [7]. This is important as melanomas ≤ 1 mm are reported to potential. Analysis of 2,243 patients with thin melanomas comprise over 70% of diagnoses made and also comprise 25% showed that LVI is an independent prognostic factor and is associated with increased SLN positivity [21]. Among patients of all melanoma-specicfi deaths [10, 11]. eTh decision to perform SNB is important for the surgical with supercfi ial spreading melanoma > 1.0 mm in thickness oncologist, as the presence of regional lymph node metastasis undergoing SLN biopsy, LVI was an independent risk factor represents the most significant prognostic factor in early- reducing disease-free survival in the form of both local and stage melanoma [7]. For T1 primary lesions, the 5-year Can- in-transit recurrence [22]. A recent large analysis of all pri- mary melanomas undergoing SLN biopsy has substantiated cer Specific Survival (CSS) has been shown to fall from 94% to 69% when comparing SN-negative and SN-positive patients, LVI as a predictor of SLN positivity independent of Breslow respectively [11]. While results from the MSLT-II trial cannot thickness [23], further reflecting the surgical oncologist’s consideration of multiple tumour parameters in evaluating be freelyextrapolatedtopatientswithheavytumour or nodal burden, findings suggest that completion lymph node and managing nodal metastatic risk. Journal of Skin Cancer 3 Desmoplastic melanoma (DM) represents a relatively reporting (ICCR),” eTh American Journal of Surgical Pathology , vol. 37, no. 12, pp. 1797–1814, 2013. rare variant of cutaneous melanoma with a clinical course more similartoso-ft tissuesarcoma [24].Itisassociatedwith [3] The Royal College of Pathologists of Australasia. Primary Cuta- neous Melanoma Structured Reporting Protocol,RCPA, New increased local recurrence, possibly due to perineural skip South Wales, 2nd edition, 2014. lesions or missed areas of positive margin [24, 25]. u Th s, surgical oncologists may steer towards wider local excision [4] M. B. Amin, S. B. Edge, F. L. Greene et al., AJCC Cancer Staging Manual, Springer International Publishing, New York, margins, as several studies show that this improves OS and NY, USA, 2017. reduces local recurrence [25]. Furthermore, there may be [5] M. G. Niebling, L. E. Haydu, R. Z. Karim, J. F. Thompson, and R. a role for adjuvant local radiation therapy in patients with A. Scolyer, “Pathology review significantly aeff cts diagnosis and DM to reduce risk of local recurrence [25]. Notably, further treatment of melanoma patients: An analysis of 5011 patients classifying DM into “pure” versus “mixed” subtypes may add treated at a melanoma treatment center,” Annals of Surgical clinical value, as mixed DM has been associated with poorer Oncology,vol.21, no.7,pp. 2245–2251, 2014. prognosis, including a worse 5-year melanoma-specific mor- [6] V. Teixeira, R. Vieira, I. Coutinho et al., “Prediction of Sentinel tality of 31% compared to 11% in pure DM [25]. Conversely, Node Status and Clinical Outcome in a Melanoma Centre,” pure DM may be associated with relatively improved prog- JournalofSkinCancer,vol.2013, pp.1–7,2013. nosis compared to other melanoma subtypes, with similar [7] S. L. Wong, C. M. Balch, P. Hurley et al., “Sentinel lymph node mortality rates and lower rates of SLN positivity despite being biopsy for melanoma: American society of clinical oncology 3 times thicker on average at time of diagnosis [25]. and society of surgical oncology joint clinical practice guide- Perineural, intraneural invasion and “neural transforma- line,” Journal of Clinical Oncology, vol. 30, no. 23, pp. 2912–2918, tion,” in which the tumour forms neural structures, constitute neurotropism [2]. It is commonly found in DM but may [8] J. E. Gershenwald, R. A. Scolyer, K. R. Hess et al., “Melanoma also occur in other melanoma subtypes [2]. Neurotropic staging: Evidence-based changes in the American Joint Com- melanoma is associated with increased local recurrence and mittee on Cancer eighth edition cancer staging manual,” CA: A may compel the surgical oncologist to consider adjuvant Cancer Journal for Clinicians,vol.67, no.6,pp. 472–492, 2017. radiotherapy and/or wider excisional margins [2]. [9] C.M.Balch,J.E.Gershenwald,S.-J.Soongetal.,“Final version Of note, Clark’s level is no longer an essential component of 2009 AJCC melanoma staging and classification,” Journal of of structured reporting according to ICCR guidelines [2]. Clinical Oncology,vol.27,no.36,pp.6199–6206,2009. Clark’s level has been largely superseded by mitotic rate as [10] S. V. Ward, G. Cadby, A. 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