ABSTRACT
BACKGROUND: Although superficial spreading melanomas (SSM) are diagnosed as thinner lesions, nodular melanomas (NM) have a more rapid growth rate and are biologically more aggressive compared with other histologic subtypes. OBJECTIVE: To determine the difference in 5-year relative survival in patients with NM and SSM at the same Breslow depth and TNM stage. METHODS: A population-based cross-sectional analysis compared the 5-year relative survival of patients with NM and SSM using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)∗Stat software (version 8.2.1-8.3.5). Chi-square tests compared the proportions, and Kaplan-Meier method with Z-score compared 5-year relative survival. RESULTS: For patients receiving a diagnosis between 2004 and 2009, 5-year relative survival was lower in NM compared with SSM (53.7% vs 87.3%; Z score, -41.35; P < .001). Similarly, for patients receiving a diagnosis between 2010 and 2015, 5-year relative survival was lower in NM compared with SSM (61.5% vs 89.7%; Z score, -2.7078; P < .01). Subgroup analyses showed inferior survival in NM in T1b, and survival differences remained significant after excluding patients with nodal or distant metastases. CONCLUSIONS: Five-year relative survival is worse in NM compared with SSM especially in T1b, T2a, and T2b melanomas. Melanoma subtype should be taken into consideration when making treatment recommendations.
Subject(s)
Melanoma/mortality , Skin Neoplasms/mortality , Adult , Aged , Cross-Sectional Studies , Female , Humans , Kaplan-Meier Estimate , Male , Melanoma/classification , Melanoma/pathology , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Retrospective Studies , SEER Program , Skin Neoplasms/pathology , Skin Ulcer/epidemiology , Skin Ulcer/etiology , United States/epidemiology , Melanoma, Cutaneous MalignantSubject(s)
COVID-19 , Melanoma , Cohort Studies , Humans , Melanoma/diagnosis , Melanoma/epidemiology , Pandemics/prevention & control , SARS-CoV-2ABSTRACT
Although melanomas with mutant v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) can now be effectively targeted, there is no molecular target for most melanomas expressing wild-type BRAF. Here, we show that the activation of Pleckstrin homology domain-interacting protein (PHIP), promotes melanoma metastasis, can be used to classify a subset of primary melanomas, and is a prognostic biomarker for melanoma. Systemic, plasmid-based shRNA targeting of Phip inhibited the metastatic progression of melanoma, whereas stable suppression of Phip in melanoma cell lines suppressed metastatic potential and prolonged the survival of tumor-bearing mice. The human PHIP gene resides on 6q14.1, and although 6q loss has been observed in melanoma, the PHIP locus was preserved in melanoma cell lines and patient samples, and its overexpression was an independent adverse predictor of survival in melanoma patients. In addition, a high proportion of PHIP-overexpressing melanomas harbored increased PHIP copy number. PHIP-overexpressing melanomas include tumors with wild-type BRAF, neuroblastoma RAS viral (v-ras) oncogene homolog, and phosphatase and tensin homolog, demonstrating PHIP activation in triple-negative melanoma. These results describe previously unreported roles for PHIP in predicting and promoting melanoma metastasis, and in the molecular classification of melanoma.
Subject(s)
Biomarkers, Tumor/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Melanoma, Experimental/metabolism , Melanoma, Experimental/secondary , Melanoma/metabolism , Nerve Tissue Proteins/metabolism , Animals , Base Sequence , Biomarkers, Tumor/genetics , Cell Line, Tumor , Female , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Intracellular Signaling Peptides and Proteins/genetics , Melanoma/genetics , Melanoma/secondary , Melanoma, Experimental/genetics , Mice , Mice, Inbred C57BL , Mice, Nude , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/genetics , RNA, Small Interfering/genetics , Signal TransductionSubject(s)
Eyelid Neoplasms/pathology , Eyelids/pathology , Melanoma/pathology , Aged, 80 and over , Humans , MaleABSTRACT
BACKGROUND: A minority of patients with T1 melanoma will have a positive sentinel lymph node (SLN) biopsy (SLNB) finding. Identifying who will develop metastatic disease is important in determining prognosis and treatment. OBJECTIVE: We sought to identify clinical and histologic features predictive of a positive SLNB result and determine its prognostic significance in patients with T1 melanoma. METHODS: Clinical and histologic parameters were evaluated in 484 patients with T1 melanoma for their ability to predict a positive SLNB result. The impact of various factors on SLN positivity was evaluated. SLN status was examined as a predictor of overall survival. RESULTS: In all, 34 patients had a positive SLNB finding. Four factors predicted a higher risk of SLN positivity: age 43 years or younger, Breslow depth 0.8 mm or greater, tumors on the lower extremity and trunk, and tumor-infiltrating lymphocyte level. By multivariate analysis, low tumor-infiltrating lymphocytes (P = .0015) and decreasing age (P = .0058) independently predicted SLN positivity. If 0 to 2 of these factors were present, the rate of a positive SLNB result was 3%; this increased to 15% with 3 factors present and to 30% if all 4 factors were present (P < .002). SLN-positive patients had significantly decreased survival (P = .003), and SLN status was the most powerful predictor of survival (P = .009). LIMITATIONS: Our data analysis includes patients from 1994 to 2007 and therefore information on mitotic rate, a recently defined T1b criterion, is not recorded for all patients. CONCLUSIONS: Combining clinical and histologic prognostic factors may help identify subgroups of T1 patients at higher risk of SLN positivity. SLN status has significant prognostic impact in patients with thin melanomas.
Subject(s)
Melanoma/pathology , Sentinel Lymph Node Biopsy , Skin Neoplasms/pathology , Adult , Female , Humans , Male , PrognosisSubject(s)
Academic Medical Centers , Biopsy/methods , Disease Management , Hospital Administrators , Nevus, Pigmented/surgery , Skin Neoplasms/surgery , Dysplastic Nevus Syndrome/diagnosis , Dysplastic Nevus Syndrome/pathology , Dysplastic Nevus Syndrome/surgery , Humans , Margins of Excision , Melanoma/diagnosis , Melanoma/pathology , Melanoma/surgery , Nevus, Epithelioid and Spindle Cell/pathology , Nevus, Epithelioid and Spindle Cell/surgery , Nevus, Pigmented/diagnosis , Nevus, Pigmented/pathology , Severity of Illness Index , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , United StatesABSTRACT
Verruciform xanthoma is a rare, benign lesion classically presenting on the oral mucosa or genital area. The etiology is not yet completely understood; however, verruciform xanthoma is often associated with (a) conditions of chronic inflammation or trauma, such as lichen sclerosis, recessive dystrophic epidermolysis bullosa, and pemphigus vulgaris, as well as in a setting of (b) chronic lymphedema, (c) chronic graft versus host disease, or (d) congenital epidermal nevi, such as those associated with the Congenital Hemidysplasia with Ichthyosiform nevus and Limb Defects (CHILD) syndrome. We report a case of a solitary verruciform xanthoma on the forearm of an 82-year-old man without history of chronic dystrophic skin disease or syndrome. In addition, a thorough literature review of extra-oral and extra-genital verruciform xanthomas is presented. On the basis of this review, we believe this case is an extremely rare presentation of a solitary verruciform xanthoma on the upper-extremity of an otherwise healthy individual.
Subject(s)
Rare Diseases/pathology , Skin Diseases/pathology , Xanthomatosis/pathology , Aged, 80 and over , Chronic Disease , Humans , MaleABSTRACT
Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined. Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM. Evidence Review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45). Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status. Conclusions and Relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.
Subject(s)
Melanoma , Skin Neoplasms , Humans , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Melanoma/diagnosis , Melanoma/genetics , Melanoma/pathology , Prognosis , Transcriptome , Public Health , Risk Assessment , Melanoma, Cutaneous MalignantABSTRACT
Determining the underlying etiology of recurrent erythema multiforme (EM) can be a difficult endeavor. Although infection with herpes simplex virus (HSV) has been implicated in some cases, the precise trigger of a given patient's recurrent EM often remains elusive. We discuss the case of a woman with a recurrent blistering eruption that was clinically and histopathologically consistent with EM. An investigation into the etiology of the patient's EM suggested that HSV was not the causative factor but instead pointed toward a hormonal influence that we interpret as autoimmune progesterone dermatitis (APD). This case is presented to highlight the importance of considering hormonal triggers in women with recurrent EM that consistently flares during the luteal phase of the menstrual cycle, the point at which serum progesterone levels peak. A brief review of the literature regarding the diagnosis, histopathology, etiology and treatment of APD is further provided.
Subject(s)
Erythema Multiforme/pathology , Autoimmune Diseases/complications , Autoimmune Diseases/pathology , Dermatitis , Erythema Multiforme/etiology , Female , Humans , Progesterone/adverse effects , Young AdultABSTRACT
Rituximab is a B-cell depleting monoclonal antibody targeting CD20. Data concerning the behavior of psoriatic disease following rituximab therapy are extremely limited. In this report, the clinical course of a patient with established psoriasis who received rituximab therapy for vasculitis associated with mixed cryoglobulinemia (MC) type II is described. In addition to marked improvement in MC manifestations, modest improvement in psoriatic lesions also was observed following therapy. The literature concerning B-cell depletion in the setting of psoriatic disease is briefly reviewed.
Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Cryoglobulinemia/drug therapy , Psoriasis/drug therapy , Antibodies, Monoclonal, Murine-Derived/pharmacology , B-Lymphocytes/immunology , Cryoglobulinemia/complications , Humans , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Male , Middle Aged , Psoriasis/complications , Rituximab , Treatment Outcome , Vasculitis/drug therapy , Vasculitis/etiologyABSTRACT
Importance: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care. Objective: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies. Evidence Review: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed. Findings: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility. Conclusions and Relevance: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.
Subject(s)
Clinical Decision-Making/methods , Gene Expression Profiling/standards , Melanoma/diagnosis , Practice Guidelines as Topic , Skin Neoplasms/diagnosis , Consensus , Consensus Development Conferences as Topic , Humans , Melanoma/genetics , Melanoma/pathology , Melanoma/therapy , Neoplasm Staging , Prognosis , Sentinel Lymph Node Biopsy/standards , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Skin Neoplasms/therapyABSTRACT
BACKGROUND: With no U.S. Food and Drug Administration-approved standard therapy other than high-dose interleukin-2 and dacarbazine for metastatic melanoma, biochemotherapy has shown promise, with long-term survival in selected patients. We felt that the study of prognostic factors would determine which patients might benefit from this intensive therapy. METHODS: One hundred thirty-five consecutive patients with metastatic melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy over 5 years were retrospectively studied to determine the most important prognostic factors for both overall survival and progression-free survival. RESULTS: The median overall survival (OS) time was 16.6 months, with 1-year and 5-year survival rates of 70% and 28%, respectively. The median progression-free survival (PFS) time was 7.6 months, with 15% of patients progression free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS, a performance status score of zero, normal lactate dehydrogenase (LDH) level, stage M1a, and nonvisceral sites of metastasis were favorable factors. The group with normal LDH levels and skin or nodes as one of their metastatic sites had a relatively good prognosis, with median survival time of 44 months and an estimated 5-year survival rate of 38%. Conversely, patients with an elevated LDH level without any skin or nodal metastases had a poor prognosis, with no long-term survivors. CONCLUSIONS: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy who have either a normal LDH level or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Immunotherapy , L-Lactate Dehydrogenase/blood , Melanoma/therapy , Skin Neoplasms/therapy , Adolescent , Adult , Aged , Analysis of Variance , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/blood , Disease Progression , Disease-Free Survival , Female , Humans , Interleukin-2/therapeutic use , Male , Melanoma/blood , Melanoma/mortality , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Prognosis , Proportional Hazards Models , Retrospective Studies , Skin Neoplasms/blood , Skin Neoplasms/mortality , Survival Rate , Young AdultABSTRACT
Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a clinically heterogeneous entity, encompassing a variety of debilitating conditions that have in common inflammation of the skeletal system and skin. To date, there is a paucity of documented efficacious treatment options. We report a 48-year-old man with skeletal and cutaneous signs and symptoms who improved dramatically after treatment with a combination of isotretinoin and pamidronate. This report provides an alternative treatment regimen for SAPHO that addresses the possible underlying pathophysiology of this likely underdiagnosed syndrome.
Subject(s)
Acneiform Eruptions/drug therapy , Diphosphonates/therapeutic use , Hyperostosis/drug therapy , Isotretinoin/therapeutic use , Osteitis/drug therapy , Psoriasis/drug therapy , Skin Diseases/drug therapy , Synovitis/drug therapy , Drug Therapy, Combination , Humans , Male , Middle Aged , Pamidronate , SyndromeABSTRACT
Angiokeratomas are benign proliferations of dilated thin-walled blood vessels in the upper dermis with overlying epidermal hyperkeratosis. There are several clinical variants of angiokeratomas: 1. Fordyce: smooth reddish-purple papules on scrotum or vulva; 2. Mibelli: hyperkeratotic papules on fingers or toes, solitary, multiple, or circumscriptum (grouped papules usually on an extremity); 4. angiokeratoma corporis diffusum, widespread papules that are a manifestation of one of several inherited lysozomal storage diseases. Herein, we report a rare case of multiple angiokeratomas of Fordyce on the corona of the glans penis.
Subject(s)
Angiokeratoma/pathology , Penile Neoplasms/pathology , Skin Neoplasms/pathology , Humans , Male , Middle AgedABSTRACT
Pyoderma gangrenosum (PG) is a rare chronic ulcerative skin condition often associated with systemic disease. PG associated with pregnancy is an extremely rare presentation; only 9 other cases have been reported in the literature. We present PG in a pregnant patient (third trimester) with pathergy. No associated systemic disease was identified. Histology was consistent with PG and the lesions responded to intralesional triamcinolone therapy.