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Purpose: This study examined the clinical outcomes and prognostic factors of patients with metastatic cutaneous SCC metastatic to the axilla and groin when managed with curative‐intent lymphadenectomy and received (neo)adjuvant treatment. Methods and Materials: We conducted a single institution retrospective review. Patients who had nodal disease without distant spread were 18 years or older with no non‐cutaneous primary identified. Results: From January 2000 to July 2015, 78 patients were treated for axilla (64, 82%) or inguinal (14, 18%) involvement with cSCC. The median age was 75.5 years (range: 29–95), and 8 patients (11%) were immunosuppressed. The median size of the largest node was 45 mm (range: 8–135), and extracapsular extension was found in 63 (81%) cases. A majority of patients were treated with surgery alone (21, 26.9%) and surgery with adjuvant radiation therapy (54, 69%). The 2‐year OS and PFS were 50% (95% CI: 40%–63%) and 43% (95% CI: 33%–56%), and 5‐year OS and PFS were 33% (95% CI:23%–47%) and 32% (95% CI:22%–46%) respectively in the entire cohort. On univariable analysis, factors associated with longer OS were as follows: younger age (HR 1.1, 95% CI: 0.9–1.3 P = 0.021), improved performance status (HR 1.5, 95% CI:1.0–2.3 P = 0.026), lack of immunosuppression (HR 3.3, 95% CI: 1.5–7.3 P = 0.001), lower lymph node ratio (HR 1.2, 95% CI:1.0–1.3 P = 0.007), lower number of positive nodes (HR 1.1, 95% CI:1.0–1.2 P = 0.004) and the use of radiation therapy (HR 0.5, 95% CI:0.3–0.9 P = 0.012). Conclusion: Metastasis to the axilla and groin with cSCC has poor outcomes with standard treatment. The addition of immunotherapy warrants investigation. [ABSTRACT FROM AUTHOR]

In‐transit metastases (ITM) of cutaneous melanoma are locoregional recurrences confined to the superficial lymphatics that occur in 3.4–6.2% of patients diagnosed with melanoma. ITM are a heterogeneous disease that poses a therapeutic dilemma. Patients may have a prolonged disease trajectory involving multiple or repeat treatment modalities for frequent recurrences. The management of ITM has evolved without the development of a standardized protocol. Owing to the variability of the disease course there are few dedicated clinical trials, with a number of key trials in stage III melanoma excluding ITM patients. Thus, there is a paucity of quality data on the efficacy of the treatment modalities available for ITM and even fewer studies directly comparing modalities. At present the mainstay of ITM treatment is surgical resection, with intralesional therapies, isolated limb infusion and radiotherapy utilized as second‐line measures. The developing role of targeted therapies and immunotherapy has yet to be explored completely in these patients. This review addresses the evidence base of the efficacy of the various treatment modalities available and those factors that have impacted their clinical uptake. [ABSTRACT FROM AUTHOR]

A sentinel lymph node biopsy is a surgical staging procedure performed for patients with primary cutaneous melanoma who are clinically lymph-node negative to determine whether there is low volume nodal metastasis in the draining lymph node field. A systematic review was recently performed to update the Australian clinical practice guidelines for the diagnosis and management of melanoma, addressing the question, ‘When is a sentinel lymph node biopsy indicated?’ This article discusses the findings of the systematic review and the evidence base for the updated guidelines. [ABSTRACT FROM AUTHOR]

Purpose: Circulating tumor DNA (ctDNA) allows noninvasive disease monitoring across a range of malignancies. In metastatic melanoma, the extent to which ctDNA reflects changes in metabolic disease burden assessed by 18F-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) is unknown. We assessed the role of ctDNA analysis in combination with FDG-PET to monitor tumor burden and genomic heterogeneity throughout treatment. Patients and Methods: We performed a comprehensive analysis of serial ctDNA and FDG-PET in 52 patients who received systemic therapy for metastatic melanoma. Next-generation sequencing and digital polymerase chain reaction were used to analyze plasma samples from the cohort. Results: ctDNA levels were monitored across patients with mutant BRAF , NRAS , and BRAF/NRAS wild type disease. Mutant BRAF and NRAS ctDNA levels correlated closely with changes in metabolic disease burden throughout treatment. TERT promoter mutant ctDNA levels also paralleled changes in tumor burden, which provide an alternative marker for disease monitoring. Of note, subcutaneous and cerebral disease sites were not well represented in plasma. Early changes in ctDNA and metabolic disease burden were important indicators of treatment response. Patients with an early decrease in ctDNA post-treatment had improved progression-free survival compared with patients in whom ctDNA levels remained unchanged or increased over time (hazard ratio, 2.6; P =.05). ctDNA analysis contributed key molecular information through the identification of putative resistance mechanisms to targeted therapy. A detailed comparison of the genomic architecture of plasma and multiregional tumor biopsy specimens at autopsy revealed the ability of ctDNA to comprehensively capture genomic heterogeneity across multiple disease sites. Conclusion: The findings highlight the powerful role of ctDNA in metastatic melanoma as a complementary modality to functional imaging that allows real-time monitoring of both tumor burden and genomic changes throughout therapy. [ABSTRACT FROM AUTHOR]

The prognosis for patients with stage IV melanoma has historically been extremely poor and there have until recently been no effective treatment options. The last 3 years have seen a seismic shift in the management of these patients with the entry to the clinic of a number of novel agents with proven efficacy. These agents fall into two main classes: molecular-targeted therapy and immunotherapy. Molecular therapies have primarily targeted the mitogen-activated protein kinase pathway, most notably with oral inhibitors targetting oncogenic BRAF. Immunotherapy agents such as ipilimumab, and more recently antibodies against PD-1 boost the host immune response against the melanoma. It is important for surgeons to be aware of these advances for a number of reasons. Firstly, to be able to inform their patients of the general options available in the event of disease progression. Secondly, these agents are currently being assessed in the adjuvant setting and are likely to demonstrate efficacy for earlier stages of disease. Finally, it is important for surgeons to be able to advocate on their patients' behalf to minimize the lag time between publication of these promising results and the availability of these agents in the clinic. Furthermore, patients with advanced melanoma should be offered participation in clinical trials in order to refine the indications for these agents to maximize their chance of benefit. [ABSTRACT FROM AUTHOR]

Macrophages, derived from circulating monocytes, are located within virtually all adult tissues. There, these specialized cells adopt tissue-specific functions that are important for normal tissue homeostasis and response to physiological challenges. Increasing evidence suggests that macrophages play a role in the normal development of certain organs, such as the breast. Intriguingly, macrophages are often found in the stroma of breast tumours, where they may promote tumour growth and metastasis. In this review we discuss this emerging area of developmental and tumour biology. [ABSTRACT FROM AUTHOR]

The article presents a case study of 47-year-old women with soft tissue mass in the inguinal region diagnosed as ectopic breast cancer. Topics include the recurrence of the tissue mass after patient underwent surgical resection, the histopathology and immunohistochemical examination of the lesion, and the need for embryology in identifying rare tumors.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy with a propensity for recurrence and a poor prognosis. Incidence of MCC is on the rise and is known to increase with advanced age, immunosuppression, and UV exposure. Merkel cell polyomavirus is implicated in the pathogenesis of virus-positive MCC and accounts for 80% of MCCs in the northern hemisphere and 25% in southern latitudes. In contrast, tumorigenesis of virus-negative MCC is linked to UV-induced DNA damage. Interplay between ubiquitous Merkel cell polyomavirus skin infections that commonly occur in healthy skin and other established risk factors, such as immunosuppression and UV exposure, remains poorly understood. Surgery and radiotherapy achieves excellent locoregional control; however, invariably, a significant proportion of patients develop disseminated disease that is incurable. Chemotherapy offers a high response rate for metastatic disease, but responses are short-lived and the impact on survival is not established. Recent advances in our understanding of the genetic landscape and immunobiology of MCC has led to investigation of novel treatments, including immune checkpoint inhibitors, which are likely to rapidly transform the way we manage these patients. We review epidemiologic, clinical, and histopathologic features of MCC; describe recent insights in MCC biology; and discuss novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4–12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies. • The efficacy of immunotherapy for melanoma in-transit metastases is unknown. • An international multicenter retrospective cohort study. • Systemic immunotherapy is an effective treatment for melanoma in-transit metastases. [ABSTRACT FROM AUTHOR]