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Dermatology Practical & Conceptual May 2022
PubMed: 35646426
DOI: 10.5826/dpc.1202a50 -
Current Oncology (Toronto, Ont.) Apr 2022In order to identify the molecular pathways governing melanoma and track its progression, the next-generation sequencing (NGS) approach and targeted sequencing of cancer... (Review)
Review
In order to identify the molecular pathways governing melanoma and track its progression, the next-generation sequencing (NGS) approach and targeted sequencing of cancer genes were employed. The primary tumor, as well as metastatic tissue, of an 84-year-old patient diagnosed with vulvar melanoma (VM), were investigated. The primary tumor specimen showed multiple somatic mutations in gene, suggesting its major contribution to melanoma origin. The metastatic sample showed additional alterations, including other melanoma-related genes. Clinical relevancy is postulated to juxtamembrane region instability of gene (c-KIT). We did not identify or alterations, which are typical for the most common melanoma pathway-MAPK cascade. However, it should be noted that this is the first report evidencing in melanoma, although its role in triggering VM needs to be further elucidated.
Topics: Aged, 80 and over; Humans; MAP Kinase Signaling System; Melanoma; Mutation; Proto-Oncogene Proteins B-raf; Skin Neoplasms
PubMed: 35621644
DOI: 10.3390/curroncol29050254 -
International Journal of Surgery Case... Mar 2022Lipoblastoma-like tumors are rare tumors that can be confused with lipoblastomas and liposarcomas but have distinct characteristics. This tumor has previously been...
INTRODUCTION AND IMPORTANCE
Lipoblastoma-like tumors are rare tumors that can be confused with lipoblastomas and liposarcomas but have distinct characteristics. This tumor has previously been identified in the vulva of females, and recently in isolated cases of young males. Given its rarity, we present an instance of this tumor in an older man, demonstrating that this pathology is not limited to a specific age or sex, and surgeons and pathologists must be aware of it in their differential.
CASE PRESENTATION
A 58-year-old male presented for evaluation of an enlarging mass in his right gluteal cleft. Prior to referral for surgical evaluation, the patient underwent an ultrasound-guided biopsy of the mass. Histologically, the tumor was a low-grade cellular spindle cell neoplasm in a fibrous to myxoid stroma. Immunohistochemical and molecular workup ruled out several malignant mesenchymal neoplasms, including myxoid liposarcoma, dedifferentiated liposarcoma, melanoma, low-grade fibromyxoid sarcoma, and sarcomatoid carcinoma. The patient initially declined surgery, but the mass continued to grow, and excision was chosen given the uncertain pathology. The tumor was resected with negative margins and histologically characterized as a "lipoblastoma-like lesion", with features of a myxoid liposarcoma and spindle cell lipoma. Seven months post-resection, there were no signs of recurrence or metastasis.
CLINICAL DISCUSSION
Despite radiologic and pathologic similarities to malignant lipomatous tumors, lipoblastoma-like tumors are benign and have a good prognosis.
CONCLUSIONS
Clinicians should be aware of this entity despite its rarity as resection with negative margins is curative and may be needed to rule out more aggressive tumors.
PubMed: 35245849
DOI: 10.1016/j.ijscr.2022.106889 -
PLoS Biology Feb 2022Cell invasion is an initiating event during tumor cell metastasis and an essential process during development. A screen of C. elegans orthologs of genes overexpressed in...
Cell invasion is an initiating event during tumor cell metastasis and an essential process during development. A screen of C. elegans orthologs of genes overexpressed in invasive human melanoma cells has identified several components of the conserved DNA pre-replication complex (pre-RC) as positive regulators of anchor cell (AC) invasion. The pre-RC genes function cell-autonomously in the G1-arrested AC to promote invasion, independently of their role in licensing DNA replication origins in proliferating cells. While the helicase activity of the pre-RC is necessary for AC invasion, the downstream acting DNA replication initiation factors are not required. The pre-RC promotes the invasive fate by regulating the expression of extracellular matrix genes and components of the PI3K signaling pathway. Increasing PI3K pathway activity partially suppressed the AC invasion defects caused by pre-RC depletion, suggesting that the PI3K pathway is one critical pre-RC target. We propose that the pre-RC, or a part of it, acts in the postmitotic AC as a transcriptional regulator that facilitates the switch to an invasive phenotype.
Topics: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Cycle; Cell Movement; DNA Replication; Female; Gene Expression Profiling; Gene Ontology; Larva; Phosphatidylinositol 3-Kinases; Replication Origin; Signal Transduction; Vulva
PubMed: 35192608
DOI: 10.1371/journal.pbio.3001317 -
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 -
Biomedicines Jan 2022Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in... (Review)
Review
Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM. In this overview, focused on anorectal and genital MM as models of rare melanomas deserving of a multidisciplinary approach, we highlight the need of referring these patients to centers with experts in melanoma, anorectal and uro-genital cancers treatments. Taking into account the rarity, the poor outcomes and the lack of effective treatment options for MM, tailored research needs to be promptly promoted.
PubMed: 35052829
DOI: 10.3390/biomedicines10010150 -
Medicina (Kaunas, Lithuania) Nov 2021A 80-year-old woman underwent vulvar melanoma resection and segmental lung resection for pulmonary metastasis. Immunotherapy with Nivolumab was performed. One year...
A 80-year-old woman underwent vulvar melanoma resection and segmental lung resection for pulmonary metastasis. Immunotherapy with Nivolumab was performed. One year later, the patient was admitted for gastrointestinal (GI) recurrent bleeding and severe anemia. Esophagoastroduodenoscopy and colonoscopy did not show any abnormality, while videocapsule endoscopy (VCE) revealed an irregular and exophytic whitish area with a "coal-black" central depression. Small bowel resection was performed and histological examination revealed S100 protein strongly positive melanoma metastasis. The patient died six months later from disease progression. A "coal-black" appearance of intestinal metastatic melanoma has been described only twice before this report. In one case the patient had been treated by immunotherapy with interferon A and dendritic cell-based vaccination. In our patient, it is presumable that the picture we observed was a consequence of Nivolumab treatment inducing the disappearance of melanocytes in the area surrounding the metastasis with the onset of the central coal-black lesion encircled by whitish tissue. This picture should be emblematic of intestinal metastatic melanoma in subjects treated with immunotherapy showing occult/obscure bleeding.
Topics: Aged, 80 and over; Capsule Endoscopy; Coal; Female; Humans; Intestine, Small; Melanoma; Neoplasm Recurrence, Local
PubMed: 34946258
DOI: 10.3390/medicina57121313 -
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 -
Gynecologic Oncology Reports Nov 2021The primary treatment of both in situ and invasive vulvar melanoma is wide local excision of the primary neoplasm. However, this can be a surgical challenge for size,...
The primary treatment of both in situ and invasive vulvar melanoma is wide local excision of the primary neoplasm. However, this can be a surgical challenge for size, multifocal presentation with proximity to urethra or anus and tendency for local recurrence. The data on adjuvant therapy for vulvar MIS is very limited. A 69-year-old patient with melanoma of the vulva underwent a simple vulvectomy with positive margins in peri-clitoral area, followed by modified radical vulvectomy and bilateral inguinofemoral sentinel lymph node dissection with negative margins. She was later diagnosed with MIS of the vulva on different locations and had multiple wide local excisions over several years. One lesion was close to the urethra and a complete excision was difficult. Topical imiquimod × 16 weeks (5% cream) was given. The regimen was augmented from 3 to 5 times weekly. Complete resolution was found at 16 weeks and patient was disease free for 4 years. Recently however, a vaginal melanoma was detected. Imiquimod appeared to be beneficial in the treatment of melanoma in situ of the vulva/ vagina when surgical options were not feasible producing local control of disease with the remaining risk for local and distant metastasis. Metastasis can appear years later, therefore long-term follow-up of patients treated with topical imiquimod is needed.
PubMed: 34926757
DOI: 10.1016/j.gore.2021.100875 -
Current Oncology (Toronto, Ont.) Oct 2021Primary mucosal melanomas of the female genital tract account for one percent or less of all cases of melanoma with even fewer originating in the clitoris. Given the... (Review)
Review
Primary mucosal melanomas of the female genital tract account for one percent or less of all cases of melanoma with even fewer originating in the clitoris. Given the rarity of diagnosis of clitoral melanoma, there is a paucity of data guiding management. There is no supporting evidence that radical vulvectomy (with or without inguinal lymphadenopathy) is associated with improved disease-free or overall survival compared to partial vulvectomy or wide local excision. Additionally, there is no data to evaluate the role of sentinel lymph node biopsy or extensive lymphadenectomy in clitoral melanoma, however previous evidence demonstrates the utility of regional lymph node sampling in predicting survival in women with female genital tract mucosal melanoma. Adjuvant therapy considerations are often extrapolated from their use in treating cutaneous melanomas, including immune checkpoint inhibitors and other immunotherapy agents. Adjuvant radiation therapy has limited utility except in cases of bulky, unresectable disease, or when inguinal lymph nodes are positive for metastasis. The 52 year-old patient presented in this review was diagnosed with locally invasive advanced stage clitoral melanoma presenting as an exophytic clitoral mass. She underwent diagnostic primary tumor resection, which demonstrated ulcerative melanoma with spindle cell features extending to a Breslow depth of at least 28 mm. She subsequently underwent secondary wide local excision with groin sentinel lymph node biopsy, and adjuvant treatment with pembrolizumab. This article also emphasizes the importance of a multidisciplinary team involving gynecologic oncology, medical oncology, radiology, and pathology for management of this rare type of primary mucosal melanoma of the female genital tract.
Topics: Clitoris; Female; Humans; Lymphatic Metastasis; Melanoma; Middle Aged; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 34898540
DOI: 10.3390/curroncol28060362