Prognostic impact of regression in patients with primary cutaneous melanoma &gt;1 mm in thickness

Ribero, Simone; Galli, Francesca; Osella‐Abate, Simona; Bertero, Luca; Cattaneo, Laura; Merelli, Barbara; Tondini, Carlo; Ghilardi, Laura; Giorgi, Vincenzo De; Occelli, Marcella; Quaglino, Pietro; Cassoni, Paola; Palmieri, Giuseppe; Massi, Daniela; Mandalà, Mario; Queirolo, Paola; Stanganelli, Ignazio; Botti, Gerardo; Caracò, Corrado; Chiarion-Sileni, Vanna; Giacomo, Anna Maria Di

doi:10.1016/j.jaad.2018.06.054

Cited by 18 publications

(29 citation statements)

References 16 publications

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“…Melanoma is considered an 'immunogenic' cancer because it is often associated with lymphocytic infiltration and has the ability of spontaneous regression. [14][15][16][17] Those phenomena are strictly related, share some similarities, but probably represent different time-points and different mechanisms during the biological history of this tumour. Although the lymphocytic infiltrate has been described as a favourable prognostic feature, 18 complete agreement on the role of histological regression has not been reached to date; indeed, either a negative or protective role on prognosis has been attributed to regression.…”

Section: Discussionmentioning

confidence: 94%

“…Moreover, we considered only lesions with regression up to 75%, because melanomas with regression higher than 75% are extremely rare and harbour uncertain clinical behaviour. 15,35 The limited number of samples could help in explaining why statistical significance was not achieved in survival analysis, even though a trend was observed; this finding is probably also due to the increased use of immunomodulatory therapies in recent years. Another potential limitation could be the intrinsic operator-dependency in immunophenotype assessment, but we tried to overcome it by employing multiple independent observers.…”

Section: Discussionmentioning

confidence: 99%

“…Extensively regressed melanoma (>75%) was not considered eligible for the study. Regression >75% in horizontal extension according to the College of American Pathologists (CAP) definitions was not considered eligible for the study because in our experience it is present in only 4% of cases; 15 for this reason, we focused our analysis on the prognostic role of tumour regression <75%.…”

Section: Histological Regression: Ratio/percentagementioning

confidence: 99%

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Phenotypic characterisation of immune cells associated with histological regression in cutaneous melanoma

et al. 2019

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Histological regression and tumour infiltrating lymphocytes represent an early sign of activation of the immune system against primary melanoma. The first phenomenon has been especially discussed in the literature because of its prognostic role, but no clear agreement on its evaluation has been reached. Immunotherapy of advanced stage melanoma has recently shown promising results; an improved understanding of the initial interplay between melanoma cells and the immune system would potentially help tailor treatment for patients. Seventy consecutive melanomas with regression were analysed to identify a prognostic cutoff value of regression extension. Then, we compared the immune infiltrate between regressed and not regressed areas of these regressed melanomas, assessing CD3, CD4, CD8, CD20, CD123, PD1 and FOXP3/CD25 expression. The immune infiltrate of these cases was further compared with 28 control melanomas without regression. A regression extension of 10% represented a reliable cutoff to distinguish two different risk categories in regressed melanomas. Regressed areas were less infiltrated by CD4/ CD25, FOXP3/CD4 or PD1/CD4 compared to not regressed areas of each sample. These lymphocyte subsets are associated with anergy and hamper the immune CD8+ response towards the cancer cells. Moreover, the relevance of these findings was further supported by the observation that not regressed controls were significantly more infiltrated by these anergic immune cell subsets compared to the regressed cases. These results help understand the real meaning of regression in melanoma. Moreover, the association here identified between specific immunomodulatory immune cell subsets and regression could help in developing new therapeutic strategies.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Histological Regression: Ratio/percentagementioning

confidence: 99%

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Phenotypic characterisation of immune cells associated with histological regression in cutaneous melanoma

et al. 2019

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“…The microscopic features of melanoma are used to determine portions of stage and prognosis of disease. While Breslow depth and ulceration are established prognostic indicators, the utility of other microscopic features such as mitotic rate and regression is less clear 2‐9 . The current study investigated the microscopic features of head and neck melanoma in 191 patients.…”

Section: Discussionmentioning

confidence: 96%

“…The significance of other commonly reported microscopic features of melanoma such as regression remains more controversial 5‐9 . Histopathologically, regression is used to describe spontaneous tumor fading and is thought to represent a partial host immune mediated response directed against tumor antigens 10,11 .…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of regression and mitotic rate in head and neck cutaneous melanoma

Kim

Obermeyer

Rubin

et al. 2020

Laryngoscope Investig Oto

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Importance While regression is a commonly reported microscopic feature of melanoma, its prognostic significance is unclear. Objective To examine the impact of regression on sentinel node status and the likelihood of recurrence in primary cutaneous melanoma of the head and neck. Design Retrospective analysis of 191 adults who underwent surgical management for primary cutaneous melanoma of the head and neck between May 2002 and March 2019. Setting Tertiary academic center. Participants Patients appropriate for the study were identified by the Academic Health Center Information Exchange using a list of current procedural terminology codes. One hundred and ninety‐one cases of invasive melanoma of the head and neck were included from 830 patients identified. Clinical features assessed for each patient included age, sex, location of primary lesion, date of diagnosis, and current disease status (alive with or without disease). Histologic features assessed were histological melanoma subtype (nodular vs non‐nodular), Breslow thickness, Clark level, presence/absence of ulceration, mitotic rate per square millimeter, and regression. If applicable, sentinel lymph node biopsy (SLNB) status, date of recurrence, interval treatments, and date of death related to melanoma were recorded. Exclusion criteria included melanoma outside the anatomic parameters of head and neck, ocular or choroidal melanoma, mucosal melanoma, metastatic melanoma to the head or neck with no known primary tumor, melanoma of the head or neck with no surgical intervention, and non‐melanoma skin cancers of the head and neck. Intervention/Exposure Surgery for cutaneous melanoma of the head and neck. Main Outcome(s) and Measure(s) The association between presence of regression and Breslow thickness, sentinel node status, and recurrence. Results Of the 191 patients identified, 30.9% were female and 69.1% were male with a mean age at diagnosis of 62.6 (range 20‐97) years. Mean Breslow thickness was 1.2 mm in those with regression and 2.0 mm in those without regression. In patients with regression, 17.6% had a positive sentinel node, and 13.0% experienced a recurrence. In patients without regression, 26.5% had a positive sentinel node, and 31.4% experienced a recurrence. When adjusted for other factors above, regression was not associated with positive sentinel node (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.13‐2.00) or recurrence (OR = 0.33, CI = 0.07‐1.01). Mitotic rate >2 was associated with recurrence (OR = 2.71, CI = 1.11‐6.75, P = .03). Conclusions and Relevance Patients with presence of regression had thinner melanomas and trended toward decreased rates of sentinel node positivity and recurrence, suggesting regression may not be a negative prognostic indicator in patients with cutaneous melanoma of the head and neck.

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The Changing Kinetics of Advanced Melanoma

Coit

2019

JAMA Dermatol

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The current issue of JAMA Dermatology contains 3 articles that attempt to describe some aspect of disease kinetics of selected subsets of patients with melanoma.The first of these studies, from von Schuckmann and colleagues 1 in Australia, attempts to describe factors predictive of early recurrence (within 2 years) among patients who presented for treatment of clinically localized T1b to T4b melanoma in Queensland.Patients were recruited prospectively from a number of hospital and private clinic sources. Of 1245 patients identified and invited to participate, 700 (56%) were included in the analysis. Most of the follow-up was obtained as a patient-reported binary recurrence status (yes/no) every 6 months. In the event of patients lost to follow-up, local hospital records and Queensland Cancer Registry data were reviewed. All recurrences were verified insofar as possible by medical record review. Factors identified predicting recurrence within 2 years were not surprising and included the presence of ulceration, an increased mitotic index, increasing T stage, and head and neck location. Descriptive statistics were provided comparing outcomes by the seventh and eighth editions of the AJCC Staging Manual, and describing the initial sites of recurrence.The biggest challenge in interpreting the significance of this study is the heterogeneity of the patient data set, a data set that included 442 patients with clinical T1b to T4b who did not undergo sentinel lymph node biopsy (SLNB), 213 patients with pathologic T1b to T4b who had a negative SLNB result, and 38 patients with at least stage IIIa after a positive SLNB result (the SLNB numbers do not quite add up to 700 in Table 1). This heterogeneity recalls that of the AJCC7 data set, where pathologic staging of clinically localized melanomas was not required. The A JCC8 has addressed this shortcoming by including only patients who underwent SLNB, 2 thus describing more homogeneous T-stage subsets. Excluding the patients with T1a disease, the AJCC8 data set depicted describes the dynamic kinetics of outcome in 10 466 patients with pathologic T1b to T4b melanomas. As expected, more advanced tumors generally recur more frequently and earlier. Importantly, the AJCC8 data set demonstrated that most events in this cohort of patients are expected to occur after the 2-year threshold described in the study by von Schuckmann et al, 1 with continued attrition out to at least 10 years. Thus, the second concern: the 2-year interval, although entirely practical for a prospective study such as this, may not be entirely reflective of the true biology of this heterogeneous cohort.

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Prognostic impact of regression in patients with primary cutaneous melanoma >1 mm in thickness

Cited by 18 publications

References 16 publications

Phenotypic characterisation of immune cells associated with histological regression in cutaneous melanoma

Phenotypic characterisation of immune cells associated with histological regression in cutaneous melanoma

Prognostic significance of regression and mitotic rate in head and neck cutaneous melanoma

The Changing Kinetics of Advanced Melanoma

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