Objectives The aims of this study were to analyze the clinical characteristics of patients with recurrent and metastatic sinonasal undifferentiated carcinoma (SNUC) and evaluate the current treatment strategies to help guide future management. Design This is a retrospective cohort study. Setting The study was conducted at six international tertiary treatment centers. Participants Patients with documented diagnoses of recurrent or metastatic SNUC since 1983 were included in the study. Main Outcome Measures Patient demographics and clinical characteristics were collected. Primary outcome measures included disease-specific survival (DSS), overall survival (OS), and time to recurrence (TTR) following initial treatment. Further univariable and multivariable analyses were performed to assess for prognostic factors. Results A total of 97 patients with a mean (standard deviation [SD]) age of 52.4 (15.6) were identified, 15 of whom presented with metastatic SNUC and 90 of whom developed recurrence. Management in both populations was widely variable. For patients with metastatic disease, the 1-year DSS probability was 33.3% (95% confidence interval [CI], 10.8-100%). For patients with recurrent SNUC, the 1- and 5-year DSS probabilities were 45.7% (95% CI, 31.9-65.6%) and 8.6% (95% CI, 2.9-25.3%), respectively. The median (interquartile range [IQR]) TTR was 8 months (3-18.5 months). Multivariable analyses revealed a significant association between orbital involvement on initial presentation and TTR (hazard ratio [HR] = 3.28; 95% CI, 1.45-7.42; p = 0.004). Conclusions To our knowledge, this is the first study addressing metastatic and recurrent SNUC based on a large patient cohort. Orbital extension of the primary SNUC may predict a higher probability of recurrence following treatment, suggesting the possible utility of a more aggressive treatment in this subgroup of patients. A heterogenous patient population and wide variability in management emphasize the challenges in standardizing care; however, dismal survival rates demonstrate the necessity for further evaluation of current approaches to improve evidence-based recommendations.

INTRODUCTION:The anatomy of the tongue is three-dimensionally complex and is thought to play a central role in the local growth of oral tongue squamous cell carcinoma (OTSCC). Understanding patterns of tumor extension could improve a multimodal therapeutic approach. Thus, the main aim of this study was to provide a histological and microanatomical analysis of surgical specimens after compartmental surgery for OTSCC. MATERIALS AND METHODS:The present prospective observational study included primary cT3 OTSCC (according to the eighth edition of the TNM classification) treated in an academic tertiary referral center with curative compartmental surgery, from July 2016 to July 2019. Analysis of histologic macrosections allowed assessment of standard pathologic parameters as well as a detailed analysis of the position of OTSCC cells from microanatomic and topographic standpoints. RESULTS:Of the 28 patients included, 71.4% were males, with a mean age of 64.9 years. Nine (32.1%) patients presented satellitosis, which was always located within the T-N tract. OTSCCs displaying satellitosis had a significantly higher median pathologic depth of invasion (DOI). A radiologic and pathological DOI > 15 mm significantly predicted the presence of satellites. There was a significant relationship between the presence of satellites and both positive lymph nodes and distant metastases. CONCLUSION:Approximately one-third of cases of intermediate-to-advanced OTSCC are characterized by tumor satellites located in the T-N tract. DOI exceeding 15 mm and the presence of clinically appreciable nodal metastases best predict the presence of satellitosis. Satellite-bearing OTSCC behave more aggressively, with an increased risk of distant metastasis and reduced survival.

Background Mucosal Melanomas (MM) are highly aggressive neoplasms arising from mucosal melanocytes. Current treatments offer a limited survival benefit for patients with advanced MM; moreover, the lack of pre-clinical cellular systems has significantly limited the understanding of their immunobiology. Methods Five novel cell lines were obtained from patient-derived biopsies of MM arising in the sino-nasal mucosa and designated as SN-MM1-5. The morphology, ultrastructure and melanocytic identity of SN-MM cell lines were validated by transmission electron microscopy and immunohistochemistry. Moreover, in vivo tumorigenicity of SN-MM1-5 was tested by subcutaneous injection in NOD/SCID mice. Molecular characterization of SN-MM cell lines was performed by a mass-spectrometry proteomic approach, and their sensitivity to PI3K chemical inhibitor LY294002 was validated by Akt activation, measured by pAkt(Ser473) and pAkt(Thr308) in immunoblots, and MTS assay. Results This study reports the validation and functional characterization of five newly generated SN-MM cell lines. Compared to the normal counterpart, the proteomic profile of SN-MM is consistent with transformed melanocytes showing a heterogeneous degree of melanocytic differentiation and activation of cancer-related pathways. All SN-MM cell lines resulted tumorigenic in vivo and display recurrent structural variants according to aCGH analysis. Of relevance, the microscopic analysis of the corresponding xenotransplants allowed the identification of clusters of MITF-/CDH1-/CDH2 + /ZEB1 + /CD271 + cells, supporting the existence of melanoma-initiating cells also in MM, as confirmed in clinical samples. In vitro, SN-MM cell lines were sensitive to cisplatin, but not to temozolomide. Moreover, the proteomic analysis of SN-MM cell lines revealed that RICTOR, a subunit of mTORC2 complex, is the most significantly activated upstream regulator, suggesting a relevant role for the PI3K-Akt-mTOR pathway in these neoplasms. Consistently, phosphorylation of NDRG1 and Akt activation was observed in SN-MM, the latter being constitutive and sustained by PTEN loss in SN-MM2 and SN-MM3. The cell viability impairment induced by LY294002 confirmed a functional role for the PI3K-Akt-mTOR pathway in SN-MM cell lines. Conclusions Overall, these novel and unique cellular systems represent relevant experimental tools for a better understanding of the biology of these neoplasms and, as an extension, to MM from other sites.

The data supporting this study's findings are available from the corresponding author, VM, upon reasonable request.

Background Orf virus (ORFV) is the pathogen responsible for Orf, a zoonotic viral infection that can be spread to humans from sheep and goats. Here, we present a case of human Orf complicated by an immune-related reaction, to raise awareness of this under-recognized disease avoiding unnecessary investigations and overtreatment. Case report A 51-year-old woman with no previous medical history presented with a one-week history of three asymptomatic swelling nodules with a grey necrotic center and red outer halo on her index finger. At physical examination there was also a pruritic papulovesicular eruption on her hands and feet. She reported a recent contact with a goat which had a similar nodular lesion in its mouth. A biopsy of the lesions was performed and a diagnosis of Orf complicated by widespread erythema multiforme was made based on the clinical and histopathological features. The lesions spontaneously resolved within the next 2 weeks. Conclusions Orf is not very prevalent in our region, so we performed a biopsy of the lesion to guide us toward a diagnosis. However, we should remember that the diagnosis of ecthyma relies on clinical evaluation and epidemiological criteria.

BACKGROUND:COronaVIrus Disease 19 (COVID-19) is associated with a wide spectrum of skin manifestations, but SARS-CoV-2 RNA in lesional skin has been demonstrated only in few cases.OBJECTIVE:The objective of this study was to demonstrate SARS-CoV-2 presence in skin samples from patients with different COVID-19-related cutaneous phenotypes.METHODS:Demographic and clinical data from 52 patients with COVID-19-associated cutaneous manifestations were collected. Immunohistochemistry and digital PCR (dPCR) were performed in all skin samples. RNA in situ hybridization (ISH) was used to confirm the presence of SARS-CoV-2 RNA.RESULTS:Twenty out of 52 (38%) patients presented SARS-CoV-2 positivity in the skin. Among these, 10/52 (19%) patients tested positive for spike protein on immunohistochemistry, five of whom had also positive testing on dPCR. Of the latter, one tested positive both for ISH and ACE-2 on immunohistochemistry while another one tested positive for nucleocapsid protein. Twelve patients showed positivity only for nucleocapsid protein on immunohistochemistry.CONCLUSIONS:SARS-CoV-2 was detected only in 38% of patients, without any association with a specific cutaneous phenotype, suggesting that the pathophysiology of cutaneous lesions mostly depends on the activation of the immune system. The combination of spike and nucleocapsid immunohistochemistry has higher diagnostic yield than dPCR. Skin persistence of SARS-CoV-2 may depend on timing of skin lesions, viral load, and immune response.

Background: Programmed death-ligand 1 (PD-L1) checkpoint inhibitors represent a mainstay of therapy in head and neck squamous cell cancer (HNSCC). However, little is known about the influence of combined therapy on PD-L1 expression. The study aims to gather evidence on this topic. Methods: A systematic search was carried out in electronic databases Pubmed-MEDLINE and Embase to retrieve studies on the comparison of PD-L1 expression before and after conventional therapy. Data were extracted and a quantitative analysis with pooled odds ratios (ORs) was performed when applicable. Results: Of 5688 items, 15 were finally included. Only a minority of studies assessed PD-L1 with the recommended combined positive score (CPS). The results are highly heterogeneous, with some studies reporting an increase in PD-L1 expression and others reporting a decrease. Three studies allowed for quantitative analysis and showed a pooled OR of 0.49 (CI 0.27–0.90). Conclusions: From the present evidence, a clear conclusion towards an increase or decrease in PD-L1 expression after combined therapy cannot be drawn, but even with few studies available, a trend towards an increase in expression in tumor cells at a cutoff of 1% can be noted in patients undergoing platinum-based therapy. Future studies will provide more robust data on the effect of combined therapy on PD-L1 expression.

2595 Background: Oral Potentially Malignant Disorders (OPMD) represent the most common oral precancerous condition, with a variable risk of malignant transformation. The most effective biomarker in predicting malignant transformation risk is loss of heterozygosity (LOH). Patients (pts) carrying OPMD with LOH at 3p14 and/or 9p21 plus LOH at another locus have an expected 3-year risk of developing oral cancer of 35%. This chromosomal profile is found in about 30% of OPMD. IMPEDE is a phase II, open-label, single-arm trial designed to evaluate the efficacy of PD-L1 inhibitor avelumab in reverting cancer transformation risk in OPMD with LOH. In this analysis, we report the first safety results, while data about treatment activity need longer follow up. Methods: During the screening period, pts undergo OPMD biopsy. If pathological diagnosis of dysplasia is confirmed, LOH valuation is performed and in case of positivity of this biomarker, subjects receive a short course of immunotherapy with avelumab 800 mg every 2 weeks for 4 total administrations. Follow-up after last avelumab dose is performed monthly and adverse event data are collected at every visit. Six months after treatment start, surgery and LOH re-assessment are performed. Results: Between November 2020 and December 2022, 49 pts were screened in 8 Italian centers. Of these, 16 pts (33%) had a LOH and 12 received the treatment (3 males, median age 65.5 years, range 49-81). Nine out of 12 treated patients had a previous oral cancer. After a median follow up of 14 months, 39 adverse events (AE) of any grade were reported, of these 18 were considered as immune related AEs (irAE). The most frequent AEs was grade 1 (G1) oral pain (4/12 pts), managed with local painkillers. Only three G2 irAEs were reported, namely amylase/lipase increase, psoriasis and fever. No grade 3-4 AEs were described, and no patient had to stop immunotherapy because of toxicities. Local excision after immunotherapy was not delayed by any treatment toxicities. Conclusions: This is the first trial with immunotherapy in an enriched population of OPMD selected according to LOH. First results support the feasibility of this approach, showing that immunotherapy with avelumab is safe and does not compromise subsequent local surgery. Clinical trial information: NCT04504552 .

• Enzalutamide has a promising activity in preselected androgen receptor positive salivary gland carcinomas . • In castration sensitive patients, high testosterone levels may hindered enzalutamide activity. • Molecular and different phenotypic selection of androgen receptor positive salivary gland carcinomas may lead to tailor treatment for such patients.

Objectives. Head and neck adenosquamous cell carcinoma (HN-ASCC) is a rare, aggressive neoplasm, with limited data reported in the literature. The aim of this study was to assess tumour behaviour and prognostic factors impacting overall survival (OS) in a retrospective, single institution series. Methods. A retrospective study on patients affected by HN-ASCC who were treated surgically between 2002 and 2019 at the Department of Otorhinolaryngology -Head and Neck Surgery of the University of Brescia was conducted. Demographics, clinical data, OS, and relative prognostic factors were analysed. Results. The study included 32 patients, with a median age of 66 years, mostly males (84.4%) and untreated (68.8%). Adjuvant treatments followed surgery in 28.1% of patients. Compared to conventional SCC, ASCC showed a higher proportion of cases arising in the larynx (40.6%); no difference was found in other features. Advanced (pT3-4) local stage at presentation (p = 0.023), perineural invasion (PNI, p = 0.01), and positive margins (p = 0.007) were independent negative prognostic factors for OS. Conclusions. HN-ASCC is a rare, aggressive cancer, most frequently arising in the larynx of elderly males, usually diagnosed in an advanced local stage. OS is generally poor, affected by local advanced stage, PNI, and positive resection margins.

Adenoid cystic carcinoma (ACC) of salivary gland is a slowly growing tumor showing a propensity for delayed recurrence, with decreased survival rates. The identification of poor prognosis patients may help in defining molecular-based targeted strategies in this rare disease orphan of new treatments. Through a gene expression microarray-based approach followed by GSE functional analysis the expression profile of 46 primary untreated ACC samples and of ACC (h-TERT) tumor cells was analyzed. Patients who experienced early relapse showed enrichment in proliferation-related gene sets, including the G2-M checkpoint, E2F and myc targets, and in gene sets related to IFN signaling and aberrant proteostasis (FDR < 0.1), indicating increased mitotic and transcriptional activity in aggressive ACC. Similar functions were enriched in ACC samples classified by immunohistochemical staining as p63-negative, which exhibited increased protein burden and activation of pro-survival stress response pathways compared to p63-positive tumors. Compared to ACC tissues, ACC (h-TERT) cells share transcriptional features of aggressive p63-negative tumors. These data suggest association of specific pathway alterations with histopathological features of ACC, as recapitulated by p63 testing in patient prognostic stratification, anticipating new avenues for therapeutic intervention.

e21574 Background: From 25 to 50% of radically resected Merkel Cell Carcinomas (MCCs) develop local or distant recurrence with a 5 year Overall Survival (OS) of 35% and 13%, respectively. Due to the rarity of the disease, there are limited data about clinical/histological risk factors related to patients (pts) prognosis. Methods: We retrospectively evaluated a series of 57 MCCs pts treated with surgical curative intent at two Italian Centres from 2000 to 2020. For 43 of them, archival histological material was retrieved for further analysis. The following clinical and histological data were analyzed and related to time to relapse (TTR), OS and cancer specific survival (CSS): gender, age, Charlson Comorbidity Index value, immunodepression, surgical margins, re-excision and/or radiotherapy (RT) in case of positive margins, stage, perineural/lymphovascular infiltration, presence of inflammatory infiltrate (tumoral infiltrating lymphocyte (TILs) (> 1 positive cell per high-power field) and its composition CD3+, CD4+ T and CD8+ T cells), positivity for MCC-polyomavirus (MCCpV), Ki67 index and PDL1 expression CPS. Results: Pts were mainly female (52%), median age was 75 years (49-99), 70% were immunocompetent and 51% presented T1 stage. All pts received surgery as main treatment approach; in case of positive margins, pts received re-excision or RT, when feasible. During a median follow-up of 37 months (1- 188), 40% had a locoregional or distant recurrence. Median TTR of relapsed pts was 3 months (1-88); median OS and CSS in the whole population was 117 months (1-188) and not reached, respectively. At univariate analysis, only male gender was associated with a higher risk of relapse (HR 1.6; 1.07-2.55; p 0.02). Older age (HR 1.09; 1.04-1.14, p < 0.001), T stage ≥2 (HR 4.79, 1.99-11.53, p < 0.001) and positive margins after re-excision (HR 17.49, 1.09-279.74, p 0.043) were associated with shorter OS and negatively related to CSS. Re-excision and/or RT in cases of positive margins at diagnosis improved OS (HR 0.154, 95% CI 0.028-0.851, p = 0.032) and CSS (HR 0.15; 0.02-0.85, p 0.03). MCCpV positivity (HR 0.23, 0.08-0.62, p 0.004), TILs (HR 0.30, 0.11-0.80, p 0.017), a moderate or high content of CD3+ T cells (HR 0.33, 0.119-0.968, p 0.04), CD8+ T cells (HR 0.35, 0.12-0.99, p 0.04), and PDL1 CPS > 1 (HR 0.26, 0.08-0.82, p 0.02) resulted in longer OS. The impact of MCCpV positivity (HR 0.27; 0.08-0.88 p 0.03) and high TILs (HR 0.31, 0.09-0.99, p 0.04) was also confirmed for CSS. Conclusions: In primarily surgically treated MCCs, female gender, younger age, low T stage, positivity for MCCpV and tumoral immune cells infiltration were associated with better prognosis, as well as an aggressive management comprising re-excision and/or RT in case of positive margins.

Objective. To evaluate the diagnostic performance of magnetic resonance (MR) with surface coils in assessing cartilage invasion in recurrent laryngeal carcinoma after carbon dioxide transoral laser microsurgery (CO2 TOLMS). Methods. Two expert head and neck radiologists assessed cartilage invasion (infiltrated or non-infiltrated) in submucosal recurrences of laryngeal carcinoma after CO2 TOLMS: results were compared with histopathological report after salvage laryngectomy. Results. Thirty patients met the inclusion criteria and 90 cartilages were assessed. Overall sensitivity, specificity, and positive and negative predictive values for cartilage infiltration were 76, 93, 72 and 94%, respectively; for thyroid cartilage, the values were 82, 79, 69 and 88% respectively; for cricoid cartilage, all values were 100%; and for arytenoids, the values were 33, 96, 56 and 93% respectively. Conclusions. MR with surface coils was able to detect most thyroid and cricoid infiltration in the complex setting of post-CO2 TOLMS laryngeal carcinoma recurrence. In particular, the optimal performance in assessing cricoid invasion can be valuable in choosing the most appropriate treatment among total laryngectomy, open partial horizontal laryngectomies and non-surgical strategies.

Dear Editor, Cutaneous reactions to messenger RNA (mRNA)-1273 SARS-CoV-2 vaccine had an important impact on dermatology practice, posing diagnostic and therapeutic challenges. Most reactions consist in injection site adverse events, although reports about generalized exanthemas, urticaria, chilblain-like lesions, autoimmune diseases and severe acute adverse reactions are growing.1, 2 We report a case of interstitial granulomatous dermatitis developed after the (m-RNA)-1273 vaccine and recurring after booster. A previously healthy 57-year-old Caucasian woman was referred to our outpatient dermatologic clinic due to multiple itchy dome-shaped skin-coloured or erythematous papules coalescing into plaques, located on the back, lateral part of the thighs and forehead (Figure 1a,b). In anamnesis, the patient reported the onset of an erythematous lesion at the site of injection 3 days after the first dose of (mRNA)-1273 vaccination. The lesion rapidly progressed to an erythematous plaque associated with homolateral axillary adenopathy. The lesion lasted for 10 days, followed by fever, wrists and knees arthralgias, and the development of dome-shaped papules. She was treated with oral prednisolone 25 mg/day for 20 days, leading to remission of all signs and symptoms. Upon administration of the second dose of vaccine as scheduled, the same clinical picture recurred and skin biopsy was performed. Antineutrophil cytoplasmic antibodies (ANCA), extractable nuclear antigens (ENAs), anticyclic citrullinated peptide (Anti-CCP) antibodies and rheumatoid factor were absent. Erythrocytes sedimentation rate (ESR) and C-reactive protein (CRP) levels were within normal range. Screenings for Borrelia Burgdorferi and Giardia Lambia resulted negative, as was drug intake history. On histology, the skin biopsy showed mild perivascular lympho-histiocytic infiltrate in the upper dermis and areas of interstitial infiltration of small CD68-positive histiocytes with rare giant cells; the histiocytes were in intimate apposition to collagen; no mucin deposition was observed. At the dermoepidemral junction, focal basal vacuolopathy and rare lymphocytes were found (Figure 2a–d). Vascular damage or necrosis were not observed. All together the findings supported a diagnosis of interstitial granulomatous drug-induced dermatitis (IGDR). Interstitial granulomatous drug-induced dermatitis, first described by Magro et al,3 represents a drug-associated skin disease reported in association with various medications.4 Histopathologically, it resembles interstitial granulomatous dermatitis but lacking of deep dermis extension and rimming of collagen bundles, while it shows a vacuolar interface reaction. Time of onset, correlation with vaccine administration with relapse after the second dose, the absence of previous medications intake able to induce IGDR and negative history for any correlated autoimmune or infectious disease, also support the hypothesis of a cutaneous reaction to (m-RNA)-1273 SARS-CoV-2 vaccine. The clinical differential diagnoses that should be considered are cutaneous T-cell lymphoma (CTCL), erythema annulare centrifugum (EAC), granuloma annulare (GA), subacute cutaneous lupus erythematosus (SCLE) and sarcoidosis. Various dermatoses have been reported to be induced by vaccines including granulomatous reactions, either localized or as a generalized eruption. Rare cases of granuloma annularis following anti-tetanus, Bacillus Calmette-Guérin (BCG) and hepatitis B vaccinations have been reported,5 there are no data in literature about IGDR. To the best of our knowledge, this is the first reported case of IGDR following (mRNA)-1273 SARS-CoV-2 vaccination. We hypothesize that IGDR may be related to the host immune response against one or more transcriptional products of the m-RNA-1273 sequence, capable to cause an immune dysregulated environment promoting a reaction against dermal collagen antigens.6 Development of IGDR after (mRNA)-1273 SARS-CoV-2 vaccination appears to be a rare event, therefore further reports are needed to determine the exact incidence of this entity. Professor Fabio Facchetti (Department of Pathology, University of Brescia, Brescia, Italy) for his valuable advice. The patients in this manuscript have given written informed consent to publication of their case details. The authors report no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Objectives  Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods  We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results  One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p  < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p  = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p  = 0.036). Conclusions  We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

Objectives: Adenoid cystic carcinoma (AdCC) is a rare disease, with indolent behavior and poor long-term survival. Many studies have evaluated the role of clinical and pathological factors at presentation on the risk of recurrence. In this study we investigated whether baseline demographic, clinical, and pathological characteristics at the time of primary curative treatment could influence the prognosis of patients once local and/or distant recurrence occurred. Methods: All patients affected by primary salivary gland AdCC and treated with curative surgery from January 1997 to June 2016 were reviewed, evaluating those who later developed loco-regional recurrence and/or distant metastasis. Time from the first relapse to death (recurrent/metastatic overall survival, RMOS) was considered the outcome of interest. Results: Out of 87 surgically treated AdCC patients, 36 relapsing lesions were included. Median ages at first presentation and recurrence were 55 and 60-year-old, respectively; 58% were females. Median disease-free interval (DFI) was 22.0 months. Five-year RMOS was 47%. At univariate analysis, age >= 60-year-old (HR:2.67, p = 0.030), primary tumor lympho-vascular invasion (LVI) (HR:5.38, p = 0.003), adjuvant radiotherapy (RT) in the primary setting (HR:0.37, p = 0.043), and DFI < 30 months (HR:3.94, p = 0.008) significantly affected RMOS. Multivariable analysis confirmed the presence of LVI and shorter DFI as independent risk factors. Conclusions: Knowledge of baseline clinicopathological features is helpful in the prognostic stratification of patients with recurrent AdCC, with LVI as the most relevant baseline factor. Adjuvant RT demonstrated its protective role on survival even once recurrence occurred, further supporting its adoption in the primary setting.

and analyzed for the presence of heavy metals. All the metals tested for were below the EPA range for “maximum contaminant level (MCL)” for drinking water except copper, which was elevated by 8% of normal (MCL = 1, result = 1.08). Metals below the MCL included barium, cadmium, chromium, lead, silver, and zinc. Arsenic, selenium, and mercury were not detected in the water sample. Three years after the initial skin eruption, he remains asymptomatic. This patient represents a unique and rapid resolution of LP upon purification of his well water supply. The manifestations of LP are thought to entail any of the following causes: immune dysregulation, infectious, and environmental and genetic factors. Our patient’s condition, with a follicular pattern of LP, would have been expected to persist longer and been recalcitrant to standard therapy approaches given remission rates within 1–2 years. We initially postulated that there may have been contaminant trace elements or metals that contributed to this patient’s condition given the spontaneous resolution of symptoms after addition of a water softening system. It has previously been documented that copper-containing dental prosthetics can induce oral LP and that symptoms resolved with removal of the appliance. Our hypothesis is that the copper contaminant found in this patient’s water could have induced a generalized lichenoid dermatitis like those that have been described in the oral cavity secondary to metallic components from metal tooth restorations. The metals previously described in the oral cavity as inducers of allergic oral lichenoid contact lesions have been Ag, In, Au, Pd, Zn, Cu, Ni, and Cr. However, there is no literature to our knowledge describing cutaneous LP due to contact or ingestion of high levels of copper due to a contaminated water supply. At this point, it is not known whether the patient developed this reaction secondary to cutaneous contact or systemic ingestion of the contaminant, but we postulate that it may have been the increased levels of copper that induced his condition.

Objective: Sinonasal mucosal melanoma (SNMM) is a rare malignancy, comprising 4% of sinonasal cancers. Treatment involves complete surgical resection while the role of adjuvant therapy remains controversial. Recurrent disease is common and survival is extremely poor, having been reported as low as 28% at 5 years. Due to the rarity of SNMM, our understanding of its clinical presentation, course and optimal treatment remains limited. Therefore, few advancements in improving its management have been made in the recent past.