Melanoma of the Skin in the Danish Cancer Registry and the Danish Melanoma Database: A Validation Study.

BACKGROUND: The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance, and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. METHODS: We estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200) during 2004-2014, using the Danish Pathology Registry as "gold standard" reference. We further validated tumor characteristics in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. RESULTS: The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and 93% and 100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database. CONCLUSIONS: The data quality in both the Cancer Registry and the Melanoma Database is high, supporting their use in epidemiologic studies.

Reducing workload in malignant melanoma sentinel node examination: a national study of pathology reports from 507 melanoma patients.

AIMS: Even though extensive melanoma sentinel node (SN) pathology protocols increase metastasis detection, there is a need for balancing high detection rates with reasonable workload. A newly tested Danish protocol recommended examining nodes at six levels 150 µm apart (six-level model) and using SOX10 and Melan-A immunohistochemistry (IHC). We explored if a protocol examining 3 levels 300 µm apart (three-level model) combined with IHC would compromise metastasis detection. The study aim was to optimise the protocol to reduce workload without compromising detection rate. METHODS: 8 months after protocol implementation, we reviewed the pathology reports of SNs from 507 melanoma patients nationwide, including 117 SN-positive patients. Each report was reviewed to determine histopathological features, including detection of metastasis, exact levels with metastasis, exact levels with metastasis >1 mm in diameter and IHC results. RESULTS: The six-level model detected metastases in 23% of patients, whereas the three-level model would have detected metastases in 22% of patients. The three-level model would have missed a few small metastases (n=4), measuring <0.1 mm, 0.1 mm, 0.4 mm and 0.1 mm, respectively. The six-level model detected metastases >1 mm in 7% of patients. One of these metastases (measuring 1.1 mm) would have been detected by the three-level model, but not as >1 mm. SOX10 and Melan-A had equal sensitivity. CONCLUSIONS: Reducing the number of levels examined to three levels 300 µm apart combined with IHC does not have significant impact on metastasis detection rate, and we will therefore recommend that the future melanoma SN guideline takes this into consideration to reduce overall workload.

Thin or early melanoma, risk factors and associated mortality.

INTRODUCTION: The incidence of thin and early-stage melanoma is increasing in many populations, but the clinical significance of these lesions remains partly unknown. METHODS: Firstly, melanoma deaths in Denmark (2009-2018) were followed back to establish melanoma debut in these persons. Secondly, using national registries of cancer incidence and mortality, 27,036 persons with thin or early-stage melanoma were followed-up for melanoma death. RESULTS: It is estimated that in 11% of the persons who died from melanoma, the debut was a thin or early-stage melanoma. On follow-up of persons with thin or early-stage melanoma, the 20-year risk of dying from melanoma was 3%. CONCLUSION: The absolute risk of melanoma death after a diagnosis with thin or early-stage melanoma is low. A subgroup of patients who are at a high risk may possibly be identified by a combination of stage, thickness, ulceration and dermal mitoses. FUNDING: none. TRIAL REGISTRATION: not relevant.

Management Recommendations for Merkel Cell Carcinoma-A Danish Perspective.

Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the skin with a poor prognosis and an apparent increase in incidence. Due to its rarity, evidence-based guidelines are limited, and there is a lack of awareness among clinicians. This review constitutes the consensus management recommendations developed by the Danish MCC expert group and is based on a systematic literature search. Patients with localized disease are recommended surgical excision and adjuvant radiotherapy to the primary site; however, this may be omitted in patients with MCC with low risk features. Patients with regional lymph node involvement are recommended complete lymph node removal and adjuvant radiotherapy in case of extracapsular disease. Metastatic disease was traditionally treated with chemotherapy, however, recent clinical trials with immune therapy have been promising. Immune checkpoint inhibitors targeting the programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1) axis should therefore be strongly considered as first-line treatment for fit patients. A 5-year follow-up period is recommended involving clinical exam every 3 months for 2 years and every 6 months for the following 3 years and PET-CT one to two times a year or if clinically indicated. These national recommendations are intended to offer uniform patient treatment and hopefully improve prognosis.

Rare cause of spontaneous haemothorax: mediastinal and distant lymph node metastases from uveal melanoma.

We report a rare case of isolated mediastinal and inferior mediastinal lymph node metastases from choroidal melanoma. The patient was treated for primary choroidal melanoma with local tumour resection and radioactive plaque brachytherapy. Eleven years later, he was diagnosed with metastatic disease. Molecular analysis of the metastatic tumour demonstrated a GNAQ Q209P mutation. There was no evidence of malignant blue naevus or primary melanoma of the central nervous system on physical examination or imaging. The rare modality of clinical presentation highlights the unpredictable nature of metastatic uveal melanoma.

The Danish Melanoma Database.

AIM OF DATABASE: The aim of the database is to monitor and improve the treatment and survival of melanoma patients. STUDY POPULATION: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD). In 2014, 2,525 patients with invasive melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register. MAIN VARIABLES: The main variables include demographic, clinical, and pathological characteristics, including Breslow's tumor thickness, ± ulceration, mitoses, and tumor-node-metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a), results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence, nature, and treatment hereof is registered. In case of death, the cause and date are included. Currently, all data are entered manually; however, data catchment from the existing registries is planned to be included shortly. DESCRIPTIVE DATA: The DMD is an old research database, but new as a clinical quality register. The coverage is high, and the performance in the five Danish regions is quite similar due to strong adherence to guidelines provided by the Danish Melanoma Group. The list of monitored indicators is constantly expanding, and annual quality reports are issued. Several important scientific studies are based on DMD data. CONCLUSION: DMD holds unique detailed information about tumor characteristics, the surgical treatment, and follow-up of Danish melanoma patients. Registration and monitoring is currently expanding to encompass even more clinical parameters to benefit both patient treatment and research.

[Challenging investigation of a metastatic adnexal cutaneous tumour].

Adnexal cutaneous tumours are very rare. A lack of knowledge about their clinical presentations can lead to prolonged diagnostic investigations and disease progression. This case report presents a challenging investigation of a metastatic malignant adnexal tumour due to misleading histology, immunohistochemical analysis and clinical findings.

Treatment influencing down-staging in EORTC Melanoma Group sentinel node histological protocol compared with complete step-sectioning: a national multicentre study.

AIM: Metastasis size in melanoma sentinel lymph nodes (SLNs) is an emerging prognostic factor. Two European melanoma treatment trials include SLN metastasis diameters as inclusion criteria. Whilst diameter estimates are sensitive to the number of sections examined, the level of this bias is largely unknown. We performed a prospective multicentre study to compare the European Organisation for Research and Treatment of Cancer (EORTC) recommended protocol with a protocol of complete step-sectioning. METHODS: One hundred and thirty-three consecutive SLNs from seven SLN centres were analysed by five central sections 50µm apart (EORTC Protocol) followed by complete 250µm step-sectioning. RESULTS: Overall, 29 patients (21.8%) were SLN-positive. The EORTC Protocol missed eight of these metastases (28%), one metastasis measuring less than 0.1mm in diameter, seven measuring between 0.1 and 1mm. Complete step-sectioning at 250µm intervals (Extensive Protocol) missed one metastasis (3%) that measured less than 0.1mm. Thirteen treatment courses (34%) performed if inclusion was based on the Combined Protocol would not be performed if assessed by the EORTC Protocol. Thus, 10 patients would be without completion lymph node dissection (EORTC MINITUB study), whilst three patients would not be eligible for anti-CTLA4 trial (EORTC protocol 18071). The corresponding number with the Extensive Protocol would be three; one patient for the MINITUB registration study and two patients for the anti-CTLA4 study. CONCLUSIONS: Examining SLNs by close central sectioning alone (EORTC Protocol) misses a substantial number of metastases and underestimates the maximum metastasis diameter, leading to important changes in patient eligibility for various treatment protocols.

[Primary mucinous carcinoma of the skin]. / Primaert mucinøst karcinom i huden.

Primary mucinous carcinoma of the skin is a rare malignant tumour originating from the sweat glands. It is often misdiagnosed clinically since it has an uncharacteristic and variable presentation, and microscopically because it resembles a cutaneous metastasis from the more frequent mucinous adenocarcinomas of the colon, mammae, lungs and ovaries. The tumour often recurs, but mortality is low. We present a case with regional lymph node metastases five years after excision of the primary tumour.