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Skin Therapy Letter Jun 2006Skin cancer is the most common human cancer, and is currently considered a global epidemic. Recently, there has been a growing interest in immunomodulators, or... (Review)
Review
Skin cancer is the most common human cancer, and is currently considered a global epidemic. Recently, there has been a growing interest in immunomodulators, or up-regulators of the immune response, for the treatment and cure of various forms of skin cancer, including melanoma and nonmelanoma skin cancers, cutaneous T-cell lymphoma, Kaposi's sarcoma, cutaneous extramammary Paget's disease, and vulvar intraepithelial carcinoma neoplasia. Strategies to augment the host's immune response against cancer cells and/or cancer cell antigenicity have been investigated, including recombinant cytokines, immunomodulators, dendritic cell immunization, tumor antigen vaccination, T-cell-based immunotherapy, and gene therapy. Although the current standard of care for most of these cancers includes Mohs micrographic surgery, curettage, and cryo-, laser-, or radiotherapy, immunomodulators are becoming essential in the treatment of patients who are poor surgical candidates and/or require noninvasive therapy.
Topics: Aminoquinolines; Antineoplastic Agents; Humans; Imiquimod; Immunologic Factors; Interferons; Skin Neoplasms
PubMed: 16820869
DOI: No ID Found -
Medicine Sep 2022Vulvar melanoma is a rare and aggressive tumor with a high risk of local recurrence and distant metastasis. The prognosis is poor with a 5-year overall survival rate of... (Review)
Review
RATIONALE
Vulvar melanoma is a rare and aggressive tumor with a high risk of local recurrence and distant metastasis. The prognosis is poor with a 5-year overall survival rate of only 46.6%. Management of vulvar melanoma remains a clinical challenge. Recent evidences have shown that immune checkpoint inhibitors are effective in the treatment of vulvar melanoma.
PATIENT CONCERNS AND DIAGNOSES
A 63-year-old woman with vulvar malignant melanoma suffered inguinal lymph node metastasis after vulvectomy and chemotherapy. She underwent inguinal lymph node dissection and inguinal radiotherapy. The tumor progressed again and she received immunotherapy.
INTERVENTIONS
The tumor progressed again, and she was admitted to our hospital and received toripalimab combined with apatinib and abraxane.
OUTCOMES
After 6 cycles of immunotherapy, the efficacy achieved partial remission. And with toripalimab as maintenance therapy, the patient achieved durable antitumor efficacy and good safety.
LESSONS
In this rare case, the patient with metastatic vulvar malignant melanoma had durable antitumor efficacy and good safety when receiving toripalimab.
Topics: Antibodies, Monoclonal, Humanized; Female; Humans; Melanoma; Middle Aged; Neoplasms, Second Primary; Skin Neoplasms; Vulvar Neoplasms
PubMed: 36086787
DOI: 10.1097/MD.0000000000030239 -
Modern Pathology : An Official Journal... Dec 2022Though uncommon in melanoma, gene fusions may have therapeutic implications. Next generation sequencing-based clinical assays, designed to detect relevant gene fusions,...
Though uncommon in melanoma, gene fusions may have therapeutic implications. Next generation sequencing-based clinical assays, designed to detect relevant gene fusions, mutations, and copy number changes, were performed on 750 melanomas (375 primary and 375 metastases) at our institution from 2014-2021. These included 599 (80%) cutaneous, 38 (5%) acral, 11 (1.5%) anorectal, 23 (3%) sinonasal, 27 (3.6%) eye (uveal/ conjunctiva), 11 (1.5%) genital (vulva/penile), and 41 (5.5%) melanomas of unknown primary. Sixteen fusions (2%) were detected in samples from 16 patients: 12/599 (2%) cutaneous, 2/38 (5%) acral, 1/9 (11%) vulva, 1/23(4.3%) sinonasal; and 12/16 (75%) fusions were potentially targetable. We identified two novel rearrangements: NAGS::MAST2 and NOTCH1::GNB1; and two fusions that have been reported in other malignancies but not in melanoma: CANT1::ETV4 (prostate cancer) and CCDC6::RET (thyroid cancer). Additional fusions, previously reported in melanoma, included: EML4::ALK, MLPH::ALK, AGAP3::BRAF, AGK::BRAF, CDH3::BRAF, CCT8::BRAF, DIP2B::BRAF, EFNB1::RAF1, LRCH3::RAF1, MAP4::RAF1, RUFY1::RAF1, and ADCY2::TERT. Fusion positive melanomas harbored recurrent alterations in TERT and CDKN2A, among others. Gene fusions were exceedingly rare (0.2%) in BRAF/RAS/NF1-mutant tumors and were detected in 5.6% of triple wild-type melanomas. Interestingly, gene rearrangements were significantly enriched within the subset of triple wild-type melanomas that harbor TERT promoter mutations (18% versus 2%, p < 0.0001). Thirteen (81%) patients were treated with immunotherapy for metastatic disease or in the adjuvant setting. Six of 12 (50%) patients with potentially actionable fusions progressed on immunotherapy, and 3/6 (50%) were treated with targeted agents (ALK and MEK inhibitors), 2 off-label and 1 as part of a clinical trial. One patient with an AGAP3::BRAF fusion positive melanoma experienced a 30-month long response to trametinib. We show that, detecting fusions, especially in triple wild-type melanomas with TERT promoter mutations, may have a clinically significant impact in patients with advanced disease who have failed front-line immunotherapy.
Topics: Male; Female; Humans; Proto-Oncogene Proteins B-raf; Melanoma; Gene Fusion; Mutation; Receptor Protein-Tyrosine Kinases; Nerve Tissue Proteins
PubMed: 35871080
DOI: 10.1038/s41379-022-01138-z -
Journal of Clinical Pathology Oct 2000Mammary and extramammary Paget's disease are uncommon intraepithelial adenocarcinomas. Both conditions have similar clinical features, which mimic inflammatory and... (Review)
Review
Mammary and extramammary Paget's disease are uncommon intraepithelial adenocarcinomas. Both conditions have similar clinical features, which mimic inflammatory and infective diseases. Histological diagnostic confusion can arise between Paget's disease and other neoplastic conditions affecting the skin, with the most common differential diagnoses being malignant melanoma and atypical squamous disease. The glandular differentiation of both mammary Paget's disease and extramammary Paget's disease is indicated by morphological appearances, the presence of intracellular mucin in many cases, and positive immunohistochemical staining for glandular cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen. This article provides an overview of mammary and extramammary Paget's disease and discusses recent evidence regarding the cell of origin. The concepts of primary and secondary Paget's disease are presented and the differential diagnosis is discussed with reference to immunohistochemical markers that might be of diagnostic value.
Topics: Breast Neoplasms; Diagnosis, Differential; Female; Humans; Paget Disease, Extramammary; Paget's Disease, Mammary; Vulvar Neoplasms
PubMed: 11064666
DOI: 10.1136/jcp.53.10.742 -
Oncology (Williston Park, N.Y.) Jan 2004The sentinel node evaluation has revolutionized the modern surgical management of cutaneous melanoma and breast cancer. In gynecologic oncology, sentinel node mapping... (Review)
Review
The sentinel node evaluation has revolutionized the modern surgical management of cutaneous melanoma and breast cancer. In gynecologic oncology, sentinel node mapping has been mainly studied in vulvar and cervical cancer. In vulvar cancer, data from 12 studies including 353 cases indicate that the sentinel node detection rate is 92% and the negative-predictive value is 99%. Three groin recurrences have been documented so far (< 1%). The technique has more recently been studied in cervical cancer. Data from 12 studies including 323 cases indicate a lower sentinel node detection rate of 80% to 86% and a negative-predictive value of 99%. Three false-negative cases have been reported so far (< 1%). Review of the literature suggests that the combined approach with blue dye and lymphoscintigraphy is superior to the blue dye alone for sentinel node detection. It also suggests that the sentinel node mapping technique is feasible in vulvar and cervical cancer and that it may become a valuable alternative to the traditional groin and pelvic lymphadenectomy. However, results have not been duplicated in large multi-institutional trials, and the technique should still be performed in the context of clinical trials. Complications of the sentinel node mapping technique are rare and usually benign but physicians should be aware of the serious risk of anaphylactic reaction to the blue dye (1% to 2%). Before this technique becomes a standard approach in the management of gynecologic malignancies, more data will be needed to clarify some of the related controversies.
Topics: Female; Humans; Laparoscopy; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Radiography; Radionuclide Imaging; Rosaniline Dyes; Sentinel Lymph Node Biopsy; Uterine Cervical Neoplasms; Vulvar Neoplasms
PubMed: 14768408
DOI: No ID Found -
Sentinel Node Methods in Penile Cancer - a Historical Perspective on Development of Modern Concepts.Seminars in Nuclear Medicine Jul 2022Malignant penile tumors are of squamous cell origin in more than 95% of cases and the occurrence of a distant metastasis without prior inguinal lymph node metastatic... (Review)
Review
Malignant penile tumors are of squamous cell origin in more than 95% of cases and the occurrence of a distant metastasis without prior inguinal lymph node metastatic deposits is very rare. This makes inguinal lymph node staging very reliable and of great prognostic significance since undiscovered and untreated inguinal metastases may lead to a fatal clinical course. In lack of a sufficiently accurate noninvasive lymph node staging modality, penile cancer relies on surgical lymph node removal for regional staging. In this respect sentinel node biopsy offers a favourable minimally invasive alternative to prophylactic inguinal lymph node dissection which is associated with significant surgery-related morbidity. Today sentinel node biopsy is widely used in surgical oncology within high volume cancers such as breast cancer and melanoma. In rare cancers sentinel node biopsy is also emerging as a minimal invasive staging tool in patients with no obvious lymph node involvement. At several specialized units across Europe sentinel node biopsy has been practiced by dedicated specialist within vulva and penile cancer for more than two decades. In fact, the rare disease penile cancer was a model entity for development of the original sentinel node concept as early as the 1970'es due to work by the Paraguayan penile cancer pioneer, Cabañas, the sentinel node concept was subsequently successfully adapted in breast cancer and melanoma. This turned out mutually beneficial since the sequential development of sentinel node biopsy in penile cancer in the 1990s eventually adopted new insights and added conceptual details from the experiences harvested in the broader clinical application possible in these high-volume diseases. The prerequisite to conceptualising the sentinel node approach was the gradual anatomical and functional understanding of the lymphatic system which in western medicine rooted in ancient Greece and gradually increased in details and comprehension with significant contributions from many great notabilities during the last centuries including Hippocrates, Galen, Fallopio, Malpighi, Virchow, Starling, Cabañas, Hodgkin and Horenblas. Sentinel node biopsy in penile cancer is a complex multimodality procedure involving inguinal ultrasonography by radiologists, precise tracer-injection and interpretation of nuclear images by nuclear medicine physicians, radio-tracer- and dye guided open surgical biopsies by urologists and thorough step-sectioning, immunostaining and accurate lymph node specimen analysis by pathologists. This team effort requires well-tested protocols, experience and good collaboration and in rare diseases this calls for centralization of service.
Topics: Breast Neoplasms; Female; Humans; Lymphatic Metastasis; Male; Melanoma; Neoplasm Staging; Penile Neoplasms; Sentinel Lymph Node Biopsy
PubMed: 34933740
DOI: 10.1053/j.semnuclmed.2021.11.010 -
Human Pathology Oct 2020Vulvar malignant melanoma (VMM), although uncommon, comprises 5-10% of all vulvar malignancies. Local control is notoriously poor in VMM with recurrence rates of 30-50%... (Comparative Study)
Comparative Study
Vulvar malignant melanoma (VMM), although uncommon, comprises 5-10% of all vulvar malignancies. Local control is notoriously poor in VMM with recurrence rates of 30-50% compared with approximately 3% in cutaneous melanomas. We studied clinicopathologic features of 37 women with VMM, after reviewing three decades of clinical follow-up data in our institutional databases. Most patients were Caucasian (n = 35) with an average age at diagnosis of 60.6 years (range 23-83). The most common subtype was mucosal lentiginous melanoma (n = 25). We compared Kaplan-Meier survival curves of 31 patients defined by clinical and microscopic attributes using exact log-rank tests. Younger patients at diagnosis (23-64 years), those with thin melanomas (≤1 mm), and those with Clark's level II or III tumors had better 5-year survival rates than older patients (65-83 years) and those with thick melanomas (>1 mm) and those with Clark's level IV or V (P ≤ 0.05), respectively, by exact log-rank test. Local recurrence of melanoma occurred in 15 patients. Nine patients (24%) had eventual urethral involvement by malignant melanoma, and this feature was associated with significantly shorter survival (P = 0.036). Patients with urethral involvement had shorter median time to death and worse 5-year survival rates. Given that spread to the urethra is common in VMM and urethral recurrence is also associated with mortality, pathology excision specimens should be carefully reviewed with attention to urethral involvement as a potentially important prognostic factor.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Databases, Factual; Female; Humans; Melanoma; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Philadelphia; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Urethra; Urethral Neoplasms; Vulvar Neoplasms; Young Adult
PubMed: 32702401
DOI: 10.1016/j.humpath.2020.07.017 -
Epidemiology and Molecular Profile of Mucosal Melanoma: A Population-Based Study in Southern Europe.Cancers Feb 2022Mucosal melanoma is a rare neoplasm on which few epidemiological population-based studies have been published. A good surgical approach is the standard treatment, but...
BACKGROUND
Mucosal melanoma is a rare neoplasm on which few epidemiological population-based studies have been published. A good surgical approach is the standard treatment, but the prognosis is worse than that of skin melanoma. The analysis of mucosal melanoma's mutational profile can help to develop target therapies in advanced disease or adjuvant settings.
METHODS
We analyzed the database of the Cancer Registry of Girona, a region located in the north-east of Spain, in the period of 1994-2018. We selected cases of primary invasive melanoma, excluding those located in the skin, eye, central nervous system and an unknown primary site. Epidemiological analysis included incidence and survival. Mutational profile analysis was performed with a custom gene panel.
RESULTS
Forty-two patients were identified: 14 (33%) had vulvar-vaginal melanoma, 15 (35.7%) had rectal melanoma, 12 (28.6%) had melanoma located in the head and neck sphere and 1 male patient had a urethral melanoma. European age-standardized incidence rates for vulvar-vaginal, rectal and head and neck melanoma were 0.09, 0.1 and 0.09 cases/100,000 inhabitant-years, respectively. Five-year observed survival rates were 37.5%, 20% and 25% for these types of cancers. NRAS Q61 was the most frequent mutation found.
CONCLUSION
Our study confirms the steady incidence and low survival of mucosal melanomas in a region of southern Europe. NRAS and NF1 play a role in the molecular landscape of mucosal melanoma. MEK and PI3K/mTOR inhibitors could be reasonable treatment options and are being studied in clinical trials.
PubMed: 35159047
DOI: 10.3390/cancers14030780 -
PloS One 2023Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that...
Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that MOGS would display unique miR and mRNA expression profiles. The miR and mRNA expression profile in RNA from formalin fixed, paraffin embedded vaginal melanomas (relative to vaginal mucosa) and vulvar melanomas (relative to cutaneous melanoma) were measured with the Nanostring Human miRNA assay and Tumor Signaling mRNA assay. Differential patterns of expression were identified for 21 miRs in vaginal and 47 miRs in vulvar melanoma (fold change >2, p<0.01). In vaginal melanoma, miR-145-5p (tumor suppressor targeting TLR4, NRAS) was downregulated and miR-106a-5p, miR-17-5p, miR-20b-5p (members of miR-17-92 cluster) were upregulated. In vulvar melanoma, known tumor suppressors miR-200b-3p and miR-200a-3p were downregulated, and miR-20a-5p and miR-19b-3p, from the miR-17-92 cluster, were upregulated. Pathway analysis showed an enrichment of "proteoglycans in cancer". Among differentially expressed mRNAs, topoisomerase IIα (TOP2A) was upregulated in both MOGS. Gene targets of dysregulated miRs were identified using publicly available databases and Pearson correlations. In vaginal melanoma, suppressor of cytokine signaling 3 (SOCS3) was downregulated, was a validated target of miR-19b-3p and miR-20a-5p and trended toward a significant inverse Pearson correlation with miR-19b-3p (p = 0.093). In vulvar melanoma, cyclin dependent kinase inhibitor 1A (CDKN1A) was downregulated, was the validated target of 22 upregulated miRs, and had a significant inverse Pearson correlation with miR-503-5p, miR-130a-3p, and miR-20a-5p (0.005 < p < 0.026). These findings support microRNAs as mediators of gene expression in MOGS.
Topics: Humans; Female; Melanoma; Skin Neoplasms; MicroRNAs; Genes, cdc; Vulvar Neoplasms; Suppressor of Cytokine Signaling Proteins
PubMed: 37384650
DOI: 10.1371/journal.pone.0285804 -
JAMA Dermatology Nov 2020Vulvar melanosis is a common pigmentary change that accounts for most pigmented vulvar lesions. It presents as single or multiple asymptomatic macules or patches of...
IMPORTANCE
Vulvar melanosis is a common pigmentary change that accounts for most pigmented vulvar lesions. It presents as single or multiple asymptomatic macules or patches of varying size and color that may be asymmetric with poorly defined borders. The differential diagnosis of melanocytic lesions includes melanoma, which creates anxiety for patients and the physicians who diagnose the condition and treat the patients.
OBJECTIVE
To evaluate the clinical and dermoscopic features of vulvar melanosis and their changes over time.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study, patients with vulvar melanosis were recruited and followed up in the Department of Dermatology, University of Florence, Florence, Italy, between January 1, 1998, and June 30, 2019. Data on patient characteristics and on both the clinical and dermoscopic features of the vulvar lesions were collected. Each lesion was photographed clinically and dermoscopically at initial evaluation and at annual follow-up visits.
MAIN OUTCOMES AND MEASURES
The clinical, dermoscopic, and histopathologic features of vulvar melanosis and their changes over time.
RESULTS
This cohort study included 129 women (mean age at diagnosis, 46 years [range, 19-83 years]) with vulvar melanosis. A total of 87 patients (67%) with vulvar melanotic lesions were premenopausal, and 84 patients (65%) had received some type of hormone therapy. The most frequent location for vulvar melanosis was the labia minora (55 [43%]), followed by the labia majora (33 [26%]). In 39 of 129 cases (30%), the lesions increased in size and changed color after initial evaluation but ultimately stabilized. No malignant evolution was documented in any patient during a median follow-up of 13 years (range, 5-20 years).
CONCLUSIONS AND RELEVANCE
This study suggests that vulvar melanosis was a benign entity, and changes in lesions over time did not signify malignant transformation. An association between hormonal status and vulvar melanosis may be hypothesized.
Topics: Adult; Aged; Aged, 80 and over; Biopsy; Color; Dermoscopy; Diagnosis, Differential; Disease Progression; Female; Follow-Up Studies; Hormone Replacement Therapy; Humans; Italy; Melanoma; Melanosis; Middle Aged; Mucous Membrane; Photography; Retrospective Studies; Vulva; Vulvar Diseases; Vulvar Neoplasms; Young Adult
PubMed: 32785609
DOI: 10.1001/jamadermatol.2020.2528