scholarly journals Quantitative multiplex immunohistochemistry reveals inter- and intra-patient lymphovascular and immune heterogeneity in primary cutaneous melanoma

2021 ◽  
Author(s):  
Julia Femel ◽  
Jamie L. Booth ◽  
Tina G Asnaashari ◽  
Sancy A Leachman ◽  
Takahiro Tsujikawa ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Lymphatic Vessels ◽  
Primary Melanoma ◽  
Leukocyte Trafficking ◽  
Spatial Relationships ◽  
Primary Cutaneous Melanoma ◽  
Primary Tumors ◽  
Immune Infiltrate ◽  
Multiplexed Imaging ◽  
Treatment Naïve

Purpose: Quantitative, multiplexed imaging is revealing complex spatial relationships between phenotypically diverse tumor infiltrating leukocyte populations and their prognostic implications. The underlying mechanisms and tissue structures that determine leukocyte distribution within and around tumor nests, however, remain poorly understood. While presumed players in metastatic dissemination, new preclinical data demonstrates that blood and lymphatic vessels (lymphovasculature) also dictate leukocyte trafficking within tumor microenvironments and thereby impact anti-tumor immunity. Here we interrogate these relationships in primary human cutaneous melanoma. Experimental Design: We established a quantitative, multiplexed imaging platform to simultaneously detect immune infiltrates and tumor-associated vessels in formalin-fixed paraffin embedded patient samples. We performed a discovery, retrospective analysis of 28 treatment-naive, primary cutaneous melanomas. Results: Here we find that the lymphvasculature and immune infiltrate is heterogenous across patients in treatment naive, primary melanoma. We categorized five lymphovascular subtypes that differ by functionality and morphology and mapped their localization in and around primary tumors. Interestingly, the localization of specific vessel subtypes, but not overall vessel density, significantly associated with the presence of lymphoid aggregates, regional progression, and intratumoral T cell infiltrates. Conclusions: We describe a quantitative platform to enable simultaneous lymphovascular and immune infiltrate analysis and map their spatial relationships in primary melanoma. Our data indicate that tumor-associated vessels exist in different states and that their localization may determine potential for tumor cell exit (metastasis) or leukocyte trafficking (immune response).

Humoral Immune Response to a Therapeutic Polyvalent Cancer Vaccine After Complete Resection of Thick Primary Melanoma and Sentinel Lymphadenectomy

2003 ◽  
Vol 21 (2) ◽  
pp. 313-319 ◽  
Author(s):  
Mathew H. Chung ◽  
Rishab K. Gupta ◽  
Eddy Hsueh ◽  
Richard Essner ◽  
Wei Ye ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Vaccine ◽  
Cutaneous Melanoma ◽  
Univariate Analysis ◽  
Primary Melanoma ◽  
Vaccine Therapy ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Primary Cutaneous Melanoma ◽  
Sentinel Lymphadenectomy

Purpose: A therapeutic polyvalent cancer vaccine (Canvaxin vaccine; CancerVax Corp, Carlsbad, CA) induces antibodies to a glycoprotein tumor-associated antigen (TA90). However, endogenous immune responses to TA90 have also been reported. This study examined anti-TA90 antibody responses with respect to the survival of patients who received adjuvant vaccine immunotherapy after resection of thick (≥ 4 mm) primary cutaneous melanoma. Patients and Methods: Serum specimens were obtained from 54 patients immediately before and then 1, 2, 4, and 6 months after wide local excision of thick primary cutaneous melanoma and sentinel lymphadenectomy. All patients were offered adjuvant therapies with the vaccine, high-dose interferon, or other agents. An enzyme-linked immunosorbent assay was used to determine serial serum titers of immunoglobulin G (IgG) and IgM antibodies against TA90. These titers were correlated with clinical course. Results: Forty-three patients chose vaccine therapy, and 11 patients chose postoperative observation. Preoperative anti-TA90 IgG and IgM titers were similar for vaccine and observation groups (P = .184). At a median follow-up of 26 months, univariate analysis of Cox regression showed that disease-free survival and overall survival of vaccine patients were significantly correlated with maximal IgM response (P = .0006 and .006, respectively) but not with maximal IgG response (P = .73 and .95, respectively). Neither response predicted survival in the observation group. Conclusion: Postoperative vaccine therapy may enhance IgG and IgM immune responses to TA90 after surgical resection, but only the IgM response is correlated with improved survival. These findings may become useful to guide selection of patients for postoperative adjuvant therapy of high-risk melanoma.

Narrow Resection of Cutaneous Melanoma

1998 ◽  
Vol 2 (3) ◽  
pp. 133-137 ◽  
Author(s):  
K. Beasley ◽  
R.C. Cartotto
Keyword(s):  
Local Recurrence ◽  
Cutaneous Melanoma ◽  
Primary Melanoma ◽  
Extent Of Resection ◽  
Resection Margins ◽  
Progressive Reduction ◽  
Recurrence Rates ◽  
Primary Cutaneous Melanoma ◽  
Intermediate Group ◽  
The Relationship

Background: There has been a progressive reduction in the extent of resection of primary cutaneous melanoma. Although overall survival appears to have been unaffected by this trend, the effect of narrow resection on local recurrence is not entirely clear. Objective: To examine the relationship between narrow resection margins and local recurrence of primary cutaneous melanoma. Methods: Primary melanoma, 104 cases, treated by surgical resection were reviewed retrospectively. Results: “Thin” (< 1 mm) melanomas (31 cases) were resected with a mean margin of 0.87 cm; “intermediate” (1–4 mm) melanomas (37 cases) were resected with a mean margin of 1.26 cm; and 14 “thick” (> 4 mm) melanomas were resected with a mean margin of 1.25 cm. Local recurrence rates were 6.5%, 16.2%, and 42.9%, respectively. In the “intermediate” group, two local recurrences occurred in melanomas < 2 mm thick despite use of margins of 1.7 cm and 2.4 cm. Conclusions: The results do not support the use of excessively narrow resection margins around primary cutaneous melanoma. Additionally, we question the true safety of currently accepted 1 to 2 cm margins for 1 to 2 mm thick melanomas.

Excision Margin and Survival in Patients with High-Risk, Primary Cutaneous Melanoma: A Retrospective Study Based on Surveillance Epidemiology and End Result (SEER) Database

Dermatology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Meng-Nan Xu ◽  
Qiu Rao
Keyword(s):  
High Risk ◽  
Cutaneous Melanoma ◽  
Primary Melanoma ◽  
Surgical Excision ◽  
Primary Cutaneous Melanoma ◽  
Term Survival ◽  
Wide Margin ◽  
Excision Margin ◽  
Therapeutic Benefits ◽  
Excision Margins

<b><i>Objectives:</i></b> The optimal excision margin of primary cutaneous melanoma greater than 2 mm in thickness is still a controversial topic. The aim of the present study was to compare the long-term survival between narrow and wide excision margins in the surgical excision of patients with high-risk primary melanoma. <b><i>Methods:</i></b> We chose the patients with primary melanoma of the skin thicker than 2 mm in The Surveillance, Epidemiology, and End Results database. Patients were divided into a narrow margin group (1–2 cm) and a wide margin group (&#x3e;2 cm) according to the resection margin information. The primary outcome was overall survival and disease-specific survival. <b><i>Results:</i></b> From 2004 to 2015, a total of 2,772 patients diagnosed as having melanoma of the skin were recruited into this study and were assigned to the narrow margin group (<i>n</i> = 1996) and the wide margin group (<i>n</i> = 776). A total of 1,098 patients died during the follow-up, and 681 of these were due to melanoma. There were 779 deaths in the narrow margin group and 319 deaths in the wide margin group (HR: 0.96, 95% CI: 0.84–1.10, <i>p</i> = 0.26). A total of 490 melanoma-specific deaths were reported in the narrow margin group and 191 were reported in the wide margin group (HR: 1.01, 95% CI: 0.85–1.19, <i>p</i> = 0.91). <b><i>Conclusions:</i></b> Wider excision margin greater than 2 cm did not provide any additional therapeutic benefits compared to narrow excision margin between 1 and 2 cm. A 2-cm margin is adequate and safe for high-risk primary melanoma of the skin thicker than 2 mm.

scholarly journals Multiple Primary Melanoma Incidence Trends Over Five Decades: A Nationwide Population-Based Study

2020 ◽  
Author(s):  
Hildur Helgadottir ◽  
Karolin Isaksson ◽  
Ildiko Fritz ◽  
Christian Ingvar ◽  
Jan Lapins ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Statistical Significance ◽  
Primary Melanoma ◽  
Population Based ◽  
Steady Increase ◽  
Second Primary ◽  
Primary Cutaneous Melanoma ◽  
Population Based Study ◽  
Incidence Trends ◽  
The 1960S

Abstract Background Over the past decades, many regions have experienced a steady increase in the incidence of cutaneous melanoma. Here, we report on incidence trends for subsequent primary melanoma. Methods In this nationwide population-based study, patients diagnosed with a first primary cutaneous melanoma reported to the Swedish Cancer Registry were followed for up to 10 years for a diagnosis of subsequent primary melanoma. Patients were grouped with patients diagnosed with first melanoma in the same decade (1960s, 1970s, 1980s, 1990s, and 2000s, respectively). Frequencies, incidence rates (IRs), standardized incidence ratios (SIRs), and 95% confidence intervals (CIs) for second melanomas were calculated. All tests of statistical significance were 2-sided. Results Of patients with melanoma, 54 884 were included and 2469 were diagnosed, within 10 years, with subsequent melanomas. Over the 5 decades, there was a statistically significant steady increase in the frequency, IR, and SIR for second primary melanoma. For example, in the 1960s cohort, less than 1% (IR = 1.0, 95% CI = 0.5 to 1.7, and IR = 1.1, 95% CI = 0.5 to 1.9 per 1000 person-years in women and men, respectively) had second primary melanoma, and this rose to 6.4% (IR = 7.5, 95% CI = 6.8 to 8.3, per 1000 person-years) in the women and 7.9% (IR = 10.3, 95% CI = 9.3 to 11.2, per 1000 person-years) in the men in the 2000s cohort. This rise was seen independent of age, sex, invasiveness, or site of the melanoma. Further, in patients diagnosed with a second melanoma, the frequency of those having more than 2 melanomas increased statistically significantly and was 0.0% in the 1960s and rose to 18.0% in the 2000s (P &lt; .001). Conclusions This is the first study to evaluate and report on a rising trend for subsequent primary melanoma. Additional primary melanomas worsen the patients’ survival, and precautions are needed to turn this steep upgoing trend.

scholarly journals 1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study

2018 ◽  
Vol 25 (9) ◽  
pp. 2541-2549 ◽  
Author(s):  
Marc D. Moncrieff ◽  
David Gyorki ◽  
Robyn Saw ◽  
Andrew J. Spillane ◽  
Howard Peach ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Surgical Margin ◽  
Primary Melanoma ◽  
Lymph Node Biopsy ◽  
Phase Iii ◽  
Primary Cutaneous Melanoma ◽  
Definitive Answer ◽  
Surgical Closure ◽  
Excision Margin ◽  
Excision Margins

Abstract Background There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma > 1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma > 1 mm in BT. Methods This phase III, multicentre trial [NCT02385214] administered by the Australia & New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma > 1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients’ QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation. Results Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p < 0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p = 0.036). After 12 months’ follow-up, no differences were noted in QoL between groups. Discussion This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma.

PRIMARY MELANOMA OF THE GALLBLADDER MANIFESTED BY ACUTE CHOLECYSTITIS. DESCRIPTION OF A SINGLE CASE

2018 ◽  
Vol 64 (2) ◽  
pp. 253-255
Author(s):  
Oleg Kit ◽  
Yevgeniy Kolesnikov ◽  
Roman Myagkov ◽  
Leonid Kharin ◽  
Yevgeniya Nepomnyashchaya
Keyword(s):  
Acute Cholecystitis ◽  
Mucous Membrane ◽  
Cutaneous Melanoma ◽  
Multidisciplinary Approach ◽  
Single Case ◽  
Primary Melanoma ◽  
Metastatic Lesions ◽  
Long Term Follow Up

Most of melanomas of the gallbladder are metastatic lesions of cutaneous melanoma. Primary melanomas of the gallbladder are described as single, polypoid, intraluminal masses emanating from the mucous membrane. The most important characteristic is the absence of melanoma damage to the skin. If it is not possible to localize primary melanoma a multidisciplinary approach to diagnostic search comes to the fore. Predicting for primary melanoma of the gallbladder is a difficult task due to the small number of cases and the absence of long-term follow-up for this category of patients.

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