Tumor Thickness and Mitotic Rate Robustly Predict Melanoma-Specific Survival in Patients with Primary Vulvar Melanoma: A Retrospective Review of 100 Cases

Purpose: Primary vulvar melanoma (PVM) is the second most common vulvar malignancy. Despite their distinct anatomic site and unique molecular–genetic alterations, PVMs are staged according to the American Joint Committee on Cancer (AJCC) guidelines for primary cutaneous melanomas (PCM). However, whether parameters derived for PCM also apply to PVM remain a critical yet largely unexplored clinical question. The objective of this study was to determine the parameters predictive of survival in PVM. Experimental Design: We retrospectively reviewed 100 patients with PVM and determined associations between clinical and histopathologic parameters and disease-specific survival (DSS) and overall survival (OS). Results: Univariate Cox regression analysis demonstrated older age (>56 years), greater tumor thickness, higher dermal mitotic rate, ulceration, lymphovascular invasion, perineural invasion, microscopic satellitosis, and absence of precursor nevus associated with decreased OS. Furthermore, age, midline, and/or multifocal involvement, greater tumor thickness, higher dermal mitotic rate, ulceration, lack of regression, lymphovascular invasion, perineural invasion, and microscopic satellitosis associated with decreased DSS. Multivariate analysis demonstrated tumor thickness, dermal mitotic rate, lymphovascular invasion, microscopic satellitosis, and absence of precursor nevus independently predicted shorter OS. Only tumor thickness and increased dermal mitotic rate (≥2/mm2) independently predicted reduced DSS. In comparison with the AJCC T-category, a novel, bivariate T-category based only on tumor thickness and dermal mitotic rate robustly predicted OS and DSS in our patient cohort. Conclusions: In the largest single institutional study of PVM, we demonstrate a combination of tumor thickness and mitotic rate comprise a simple but robust T-category to direct staging and prognosis. Clin Cancer Res; 23(8); 2093–104. ©2016 AACR.

[1]  G. Bogani,et al.  Surgical Management and Prognostic Factors of Vulvovaginal Melanoma , 2016, Journal of lower genital tract disease.

[2]  P. Fox,et al.  Prognostic Implication of Lymphovascular Invasion Detected by Double Immunostaining for D2-40 and MITF1 in Primary Cutaneous Melanoma , 2016, The American Journal of dermatopathology.

[3]  R. Sullivan,et al.  Primary genitourinary melanoma: Epidemiology and disease-specific survival in a large population-based cohort. , 2016, Urologic oncology.

[4]  Shuyi Wang,et al.  Clinicopathological Features and Prognosis of Sinonasal Mucosal Malignant Melanoma: A Retrospective Study of 83 Cases in a Chinese Population , 2016, ORL.

[5]  David E Elder,et al.  Melanoma progression. , 2016, Pathology.

[6]  A. Sapino,et al.  Association of Histologic Regression in Primary Melanoma With Sentinel Lymph Node Status: A Systematic Review and Meta-analysis. , 2015, JAMA dermatology.

[7]  R. Dummer,et al.  The Genetic Evolution of Melanoma from Precursor Lesions. , 2015, The New England journal of medicine.

[8]  S. Kamel‐Reid,et al.  Malignant Melanoma of Vulva and Vagina: A Histomorphological Review and Mutation Analysis—A Single-Center Study , 2015, Journal of lower genital tract disease.

[9]  N. Pimpinelli,et al.  Vulvar melanoma: a 33 years single Italian center experience. , 2015, Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia.

[10]  J. Gras-Cabrerizo,et al.  Management of Sinonasal Mucosal Melanomas and Comparison of Classification Staging Systems , 2015, American journal of rhinology & allergy.

[11]  R. Botella-Estrada,et al.  Correlation of histologic regression in primary melanoma with sentinel node status. , 2014, JAMA dermatology.

[12]  P. Schirmacher,et al.  Comparison of molecular abnormalities in vulvar and vaginal melanomas , 2014, Modern Pathology.

[13]  J. Grob,et al.  Sinonasal mucosal melanomas: The prognostic value of tumor classifications , 2014, Head & neck.

[14]  D. Elder,et al.  Prognosis of Patients with Melanoma and Microsatellitosis Undergoing Sentinel Lymph Node Biopsy , 2014, Annals of Surgical Oncology.

[15]  N. Hacker,et al.  A clinicopathological review of 33 patients with vulvar melanoma identifies c-KIT as a prognostic marker , 2014, International journal of molecular medicine.

[16]  R. Senetta,et al.  Favourable prognostic role of regression of primary melanoma in AJCC stage I–II patients , 2013, The British journal of dermatology.

[17]  M. Ross,et al.  Immunodetection of phosphohistone H3 as a surrogate of mitotic figure count and clinical outcome in cutaneous melanoma , 2013, Modern Pathology.

[18]  V. Sondak,et al.  Age as a Prognostic Factor in Patients with Localized Melanoma and Regional Metastases , 2013, Annals of Surgical Oncology.

[19]  R. Ali-Fehmi,et al.  Vulvar/Vaginal Melanoma: An Updated Surveillance Epidemiology and End Results Database Review, Comparison With Cutaneous Melanoma and Significance of Racial Disparities , 2013, International Journal of Gynecologic Cancer.

[20]  N. Fernandes The risk of cutaneous melanoma in melanocytic nevi* , 2013, Anais brasileiros de dermatologia.

[21]  A. Abernethy,et al.  Clinicopathologic study of 85 cases of melanoma of the female genitalia. , 2012, Journal of the American Academy of Dermatology.

[22]  A. Mäkitie,et al.  Accuracy of the current TNM classification in predicting survival in patients with sinonasal mucosal melanoma , 2012, The Laryngoscope.

[23]  D. Mutch,et al.  Malignant melanoma of the vulva: an extension of cutaneous melanoma? , 2011, Gynecologic oncology.

[24]  A. Stromberg,et al.  Regression Does Not Predict Nodal Metastasis or Survival in Patients with Cutaneous Melanoma , 2011, The American surgeon.

[25]  V. Sondak,et al.  Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  D. Rosenthal,et al.  Mucosal melanoma of the nose and paranasal sinuses, a contemporary experience from the M. D. Anderson Cancer Center , 2010, Cancer.

[27]  Jeffrey E Gershenwald,et al.  Final version of 2009 AJCC melanoma staging and classification. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  J. Gershenwald,et al.  Immunohistochemical detection of lymphovascular invasion with D2‐40 in melanoma correlates with sentinel lymph node status, metastasis and survival , 2009, Journal of cutaneous pathology.

[29]  P. Buccini,et al.  Vulvar melanoma: a report of 10 cases and review of the literature , 2008, Melanoma research.

[30]  C. Kaur,et al.  The correlation of regression in primary melanoma with sentinel lymph node status , 2007, Journal of Clinical Pathology.

[31]  J. Berek,et al.  Vulvar Melanoma: A Multivariable Analysis of 644 Patients , 2007, Obstetrics and gynecology.

[32]  R. Bilgiç,et al.  Synchronous cervical and vulvar malign melanomas: metastasis or multifocality of the disease? A case report and review of the literature. , 2006, International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.

[33]  M. Nosrati,et al.  The role of microsatellites as a prognostic factor in primary malignant melanoma. , 2005, Archives of dermatology.

[34]  J. Makovitzky,et al.  Primary melanoma of the female genital system: a report of 10 cases and review of the literature. , 2005, Anticancer research.

[35]  R. Bilgiç,et al.  Synchronous cervical and vulvar malign melanomas: metastasis or multifocality of the disease? A case report and review of the literature , 2004, International Journal of Gynecologic Cancer.

[36]  B. Ragnarsson-Olding Primary malignant melanoma of the vulva An aggressive tumor for modeling the genesis of Non-UV light-associated melanomas , 2004, Acta oncologica.

[37]  J. Shah,et al.  Primary mucosal melanoma of the head and neck , 2004, Cancer.

[38]  Jennifer L. Schwartz,et al.  Vulvar melanoma: a report of 20 cases and review of the literature. , 2004, Journal of the American Academy of Dermatology.

[39]  R. Scolyer,et al.  The Prognostic Importance of Tumor Mitotic Rate Confirmed in 1317 Patients With Primary Cutaneous Melanoma and Long Follow-Up , 2004, Annals of Surgical Oncology.

[40]  K. Busam The Prognostic Importance of Tumor Mitotic Rate for Patients with Primary Cutaneous Melanoma , 2004, Annals of Surgical Oncology.

[41]  A. Dobozy,et al.  Tumour regression predicts higher risk of sentinel node involvement in thin cutaneous melanomas , 2003, The British journal of dermatology.

[42]  Yuting Zhang,et al.  Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma , 2003, Cancer.

[43]  U. Ringborg,et al.  Mutations in the TP53 gene in human malignant melanomas derived from sun-exposed skin and unexposed mucosal membranes , 2002, Melanoma research.

[44]  John A Thompson,et al.  The revised American Joint Committee on Cancer staging system for melanoma. , 2002, Seminars in oncology.

[45]  R. Hofmann-Wellenhof,et al.  Melanoma with benign melanocytic naevus components: reappraisal of clinicopathological features and prognosis , 2002, Melanoma research.

[46]  M. Stoler,et al.  Vulvar melanoma: a retrospective analysis and literature review. , 2001, Gynecologic oncology.

[47]  Martin F. Mihm,et al.  Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[48]  M. Ross,et al.  Vulvar melanoma at the M. D. Anderson Cancer Center: 25 years later , 2001, International Journal of Gynecologic Cancer.

[49]  D. Paladini,et al.  Prognostic Indicators in Melanoma of the Vulva , 2000, Annals of Surgical Oncology.

[50]  L. Kanter‐Lewensohn,et al.  Malignant melanoma of the vulva in a nationwide, 25‐year study of 219 Swedish females , 1999, Cancer.

[51]  L. Kanter‐Lewensohn,et al.  Malignant melanoma of the vulva in a nationwide, 25‐year study of 219 Swedish females , 1999, Cancer.

[52]  A Biggeri,et al.  Cutaneous melanoma histologically associated with a nevus and melanoma de novo have a different profile of risk: results from a case-control study. , 1999, Journal of the American Academy of Dermatology.

[53]  D. Tyler,et al.  Mucosal melanoma of the female genitalia: a clinicopathologic study of forty-three cases at Duke University Medical Center. , 1998, Surgery.

[54]  C. Jackisch,et al.  Malignant melanoma of the vulva: Report of 89 patients , 1996, Cancer.

[55]  L. Akslen,et al.  Independent prognostic importance of vascular invasion in nodular melanomas , 1996, Cancer.

[56]  V. Abeler,et al.  Malignant melanoma of the vulva FIGO stage I: Evaluation of prognostic factors in 43 patients with emphasis on DNA ploidy and surgical treatment. , 1996, Gynecologic oncology.

[57]  D. Heller,et al.  Vulvar and vaginal melanoma. A clinicopathologic study. , 1994, The Journal of reproductive medicine.

[58]  M. Weinstock Malignant melanoma of the vulva and vagina in the United States: patterns of incidence and population-based estimates of survival. , 1994, American journal of obstetrics and gynecology.

[59]  P. Grambsch,et al.  Proportional hazards tests and diagnostics based on weighted residuals , 1994 .

[60]  B. Bundy,et al.  Malignant melanoma of the vulva treated by radical hemivulvectomy. A prospective study of the gynecologic oncology group , 1994, Cancer.

[61]  P. Neven,et al.  Malignant melanoma of the vulva and vagina: a report of 23 cases presenting in a 10-year period , 1993, International Journal of Gynecologic Cancer.

[62]  U. Ringborg,et al.  Malignant melanoma of the vulva and vagina. Trends in incidence, age distribution, and long‐term survival among 245 consecutive cases in Sweden 1960–1984 , 1993 .

[63]  A. Lopes,et al.  Malignant melanoma of the vulva: A clinicopathologic study of 18 cases , 1992, Journal of surgical oncology.

[64]  E. P. van der Esch,et al.  A clinicopathological study of 30 melanomas of the vulva , 1992, Gynecologic oncology.

[65]  E. Trimble,et al.  Management of vulvar melanoma. , 1992, Gynecologic oncology.

[66]  K. Mclaren,et al.  Histological regression in primary cutaneous melanoma: recognition, prevalence and significance , 1992, Histopathology.

[67]  G. Sutton,et al.  Vulvar melanoma reconsidered , 1991, Cancer.

[68]  C. McConkey,et al.  Malignant melanoma of the vulva: a clinicopathological study of 50 women , 1990, British journal of obstetrics and gynaecology.

[69]  C. D. White,et al.  Prognostic features of vulvar melanoma: a clinicopathologic analysis. , 1986, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[70]  J. Benda,et al.  Malignant Melanoma of the Vulva: A Clinical‐Pathologic Review of 16 Cases , 1986, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[71]  U. Beller,et al.  Vulvovaginal melanoma. A clinicopathologic study. , 1986, The Journal of reproductive medicine.

[72]  H. Wanebo,et al.  Regression in thin malignant melanoma. Microscopic diagnosis and prognostic importance. , 1985, Archives of dermatology.

[73]  M. Mihm,et al.  “Microscopic satellites” are more highly associated with regional lymph node metastases than is primary melanoma thickness , 1984, Cancer.

[74]  K. Podratz,et al.  Melanoma of the vulva: an update. , 1983, Gynecologic oncology.

[75]  V. McGovern,et al.  Ulceration and prognosis in cutaneous malignant melanoma , 1982, Histopathology.

[76]  J. Bouma,et al.  Malignant melanoma of the vulva: report of 18 cases. , 1982, European journal of obstetrics, gynecology, and reproductive biology.

[77]  M. Mihm,et al.  Malignant Melanoma: Prognostic Significance of “Microscopic Satellites” in the Reticular Dermis and Subcutaneous Fat , 1981, Annals of surgery.

[78]  D. Silvers,et al.  Cutaneous and vulvar melanoma: an update. , 1978, Clinical obstetrics and gynecology.

[79]  Rutledge Fn,et al.  Melanoma of the vulva. , 1972 .

[80]  A. E. Kanter,et al.  Melanoma of the Vulva , 1958, Obstetrics and gynecology.

[81]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[82]  G. Boland,et al.  Principles of Melanoma Staging. , 2016, Cancer treatment and research.

[83]  Fracs Michael J. Quinn MBBS,et al.  Melanoma of the Vulva and Vagina: Principles of Staging and Their Relevance to Management Based on a Clinicopathologic Analysis of 85 Cases , 2014, Annals of Surgical Oncology.

[84]  R. Neves,et al.  Vulvar melanoma: report on eleven cases and review of the literature. , 2010, Sao Paulo medical journal = Revista paulista de medicina.

[85]  G. C. Guimarães,et al.  Melanoma de vulva: Relato de onze casos e revisão da literatura , 2010 .

[86]  J. Grant-Kels,et al.  Melanoma prognostic factors found in the dermatopathology report. , 2009, Clinics in dermatology.

[87]  T. Peretz,et al.  Mucosal melanoma of the female genital tract is a multifocal disorder. , 2003, Gynecologic oncology.

[88]  G. Fabrizi,et al.  Melanocytic dysplasia and multiple melanoma of the vulva. , 2002, European Journal of Gynaecological Oncology.

[89]  V. Abeler,et al.  Malignant melanoma of the vulva. Evaluation of prognostic factors with emphasis on DNA ploidy in 75 patients , 1995, Cancer.

[90]  C. Slingluff,et al.  "Thin" malignant melanoma: risk factors and clinical management. , 1992, Annals of plastic surgery.

[91]  Plate Wp [Malignant melanoma of the vulva]. , 1949, Nederlandsch tijdschrift voor verloskunde en gynaecologie.

[92]  R. Carswell,et al.  On Melanosis , 1824, Transactions. Medico-Chirurgical Society of Edinburgh.

[93]  D.,et al.  Regression Models and Life-Tables , 2022 .