STUMP vs. Melanoma

presented by DJ Elpern and Jag Bhawan

Abstract:  20 yo woman with two month hx of an aggressive melanocytic neoplasm.

HPI:  This otherwise healthy 20 yo college student noticed a papule on her right upper back two months before her dermatology visit.  It rubbed on her bra and that is how she found it.

O/E:  There was a 5 mm diameter brownish papule on the right upper back.  It had no play of color, no asymmetry, and the border was fairly sharp.  Dermoscopically it was not diagnositic of benign melanocytic neoplasm or melanoma.  It was definitely and "outlier" lesion and was rapidly growing.  She had an excisional biopsy the next week.

Clinical Photo:.

Pathology:  
Excisional biopsy revealed an atypical cellular lesion with a nesting pattern, especially in the upper part of the lesion ( Fig 1,2).  The deeper part showed infiltration of reticular dermis (Fig 3 ) as well as arrector pili ( Fig 4 )by islands of atypical cells. The cells were epithelioid, pleomorphic, large with atypical nuclei and several mitoses including in deep dermis ( Fig 5). Focal pigmentation was seen. There was mild epidermal hyperplasia, but no confluence or pagetoid spread of atypical melanocytes was observed. No radial growth phase was noted. These findings were interpreted as malignant melanoma with a depth of 3.5 mm.  Lack of inflammatory response, confluence and pagetoid spread raised the possibility of melanocytic tumors of uncertain malignant potential ( MEL-TUMP ).
Two of the 5 sentinel lymph nodes were positive with atypical nests of melanocytes confirmed by MART-1 within the parenchyma of the lymph nodes. 

Figures 1 - 5 in sequential order (Courtesy of Jag Bhawan)

                                                                   

                                                                         

                                                        

Surgery.  A wide-local excision and SLN biopsy was done and this showed the tumor was completely excised by the first excision and two of 5 nodes were positive.  She will have a PET scan in a few days.


Questions for Panel:
1. Is this a MELTUMP -- Melanocytic tumor of uncertain malignant potential -- also called STUMP Spitzoid tumor of uncertain malignant potential?
2. Does this impart a better prognosis than if this is a MM?  Is thickness less important for these lesions as a prognostic tool?
3. Do MELTUMPs have a different biological behaviors than MMs?
4. If PET scan is negative, would you recommend ELND?
5.  Should her care be managed at this point by an oncologist with an interest in chemotherapy.  Role for interferon?  Can this be cured by chemotherapy or is pharmacologic therapy just palliative?
6.  Many more questions.  Your thoughts are most welcome.

References:
1.  Balch CM, et al.  Multivariate Analysis of Prognostic Factors Among 2,313 Patients With Stage III Melanoma: Comparison of Nodal Micrometastases Versus Macrometastases.  J Clin Oncol. 2010 Apr 5.
Abstract  PURPOSE: To determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma. PATIENTS AND METHODS: Complete clinicopathologic and follow-up data were available for 2,313 patients with stage III disease in an updated and expanded American Joint Committee on Cancer (AJCC) melanoma staging database. Kaplan-Meier and Cox multivariate survival analyses were performed. RESULTS: Among all 2,313 patients with stage III disease, 81% had micrometastases, and 19% had clinically detectable macrometastases. The 5-year overall survival was 63%; it was 67% for patients with nodal micrometastases, and it was 43% for those with nodal macrometastases (P < .001). Tremendous heterogeneity in survival was observed, particularly in the microscopically detected nodal metastasis subset (from 23% to 87% for 5-year survival). Multivariate analysis demonstrated that in patients with nodal micrometastases, number of tumor-containing lymph nodes, primary tumor thickness, patient age, ulceration, and anatomic site of the primary independently predicted survival (all P < .01). When added to the model, primary tumor mitotic rate was the second-most powerful predictor of survival after the number of tumor-containing nodes. In contrast, for patients with nodal macrometastases, the number of tumor-containing nodes, primary ulceration, and patient age independently predicted survival (P < .01). CONCLUSION: In this multi-institutional analysis, we demonstrated remarkable heterogeneity of prognosis among patients with stage III melanoma, especially among those with nodal micrometastases. These results should be incorporated into the design and interpretation of future clinical trials involving patients with stage III melanoma.

2. Soonh SJ etc.  Predicting Survival Outcome of Localized Melanoma: An Electronic Prediction Tool Based on the AJCC Melanoma Database.  Ann Surg Oncol. 2010 Apr 9. [Epub ahead of print]
Abstract:
BACKGROUND: We sought to develop a reliable and reproducible statistical model to predict the survival outcome of patients with localized melanoma. METHODS: A total of 25,734 patients with localized melanoma from the 2008 American Joint Committee on Cancer (AJCC) Melanoma Database were used for the model development and validation. The predictive model was developed from the model development data set (n = 14,760) contributed by nine major institutions and study groups and was validated on an independent model validation data set (n = 10,974) consisting of patients from a separate melanoma center. Multivariate analyses based on the Cox model were performed for the model development, and the concordance correlation coefficients were calculated to assess the adequacy of the predictive model. RESULTS: Patient characteristics in both data sets were virtually identical, and tumor thickness was the single most important prognostic factor. Other key prognostic factors identified by stratified analyses included ulceration, lesion site, and patient age. Direct comparisons of the predicted 5- and 10-year survival rates calculated from the predictive model and the observed Kaplan-Meier 5- and 10-year survival rates estimated from the validation data set yielded high concordance correlation coefficients of 0.90 and 0.93, respectively. A Web-based electronic prediction tool was also developed ( http://www.melanomaprognosis.org/ ). CONCLUSIONS: This is the first predictive model for localized melanoma that was developed based on a very large data set and was successfully validated on an independent data set. The high concordance correlation coefficients demonstrated the accuracy of the predicted model. This predictive model provides a clinically useful tool for making treatment decisions, for assessing patient risk, and for planning and analyzing clinical trials.