Multiple Nonmelanoma Skin Cancers Research Articles

Grover's Disease Association with Cutaneous Keratinocyte Cancers: More than a Coincidence?

Better mechanistic understanding of desmosome disruption and acantholysis in Grover's disease (GD) may improve management of this disease. Recent molecular studies highlighted promising pathways to be explored by directly comparing GD and selected features of associated skin diseases. The association between GD and cutaneous keratinocyte carcinomas, the most prevalent non-melanoma skin cancers (NMSC), is not completely characterized. To review the medical literature regarding GD-associated cutaneous keratinocyte cancers, focusing on molecular features, pathophysiological mechanisms, and disease associations, to help guide future research and patient management. GD has been associated with a variety of skin conditions, but its association with skin cancers has been rarely reported. Between 1983 and 2024, only nine scientific papers presented data supporting this association. Interestingly, we found that GD may mimic multiple NMSCs, as few authors reported GD cases misdiagnosed as multiple cutaneous squamous cell carcinomas for more than 4 years or the presence of superficial basal cell carcinoma-like areas associated with focal acantholysis. In conclusion: (a) GD may be an imitator of multiple NMSCs, and (b) the relationship between GD and NMSCs may reveal promising pathways for the mechanistic understanding of desmosome disruption and acantholysis in GD and may even lead to its reclassification as a distinctive syndrome.

Multiple non-melanoma skin cancers during 43-years long therapy with azathioprine in renal transplant recipient

Multiple non-melanoma skin cancers during 43-years long therapy with azathioprine in renal transplant recipient

Patients’ willingness to accept adverse event and cost tradeoffs from oral nicotinamide for reduced risk of non-melanoma skin cancer

BackgroundNon-immunosuppressed patients with a history of multiple non-melanoma skin cancers (NMSCs) taking oral nicotinamide supplementation experienced a 23% decrease in annual NMSC risk in a randomized clinical trial. Patient preferences for risks and costs associated with nicotinamide are unknown.ObjectivesTo understand how patients prioritize NMSC reduction, infection risk, and cost.MethodsA sample of adults with history of ≥2 NMSC within the past five years undergoing Mohs procedure completed a discrete-choice experiment comprising two hypothetical treatments—characterized by varying reductions in NMSC incidence, increased severe infection risk, and cost—and no treatment. The data were analyzed with random-parameters logit models.ResultsA total of 203 subjects (mean age 71.5 years, 65.5% males) participated. For a 23% annual reduction in NMSC incidence, a 26% [95% CI: 8%–45%] annual increase in severe infection risk and $8 [95% CI: $2–14] monthly cost was acceptable. Outcomes across analyzed subgroups (before vs. during COVID pandemic, site of interview, less vs. more prior NMSCs) were similar.ConclusionsPatients were unwilling to accept high severe infection risks to obtain the reduction in NMSC incidence observed in a nicotinamide trial, suggesting that routinely recommending nicotinamide may run counter to some patients’ preferences.

Ultraviolet radiation exposure to the face in patients with xeroderma pigmentosum and healthy controls: applying a novel methodology to define photoprotection behaviour.

SummaryBackgroundIn xeroderma pigmentosum (XP), the main means of preventing skin and eye cancers is extreme protection against ultraviolet radiation (UVR). Protection is most important for the face.ObjectivesWe aimed to assess how well patients with XP adhere to medical advice to protect against UVR by objectively estimating the mean daily dose of UVR to the face.MethodsWe objectively estimated the UVR dose to the face in 36 patients with XP and 25 healthy individuals over 3 weeks in the summer. We used a new methodology which combined UVR dose measurements from a wrist‐worn dosimeter with an activity diary record of face photoprotection behaviour for each 15‐min period spent outside. A protection factor was associated with each behaviour, and the data were analysed using a negative binomial mixed‐effects model.ResultsThe mean daily UVR dose (weighted for DNA damage capacity) to the face in the patients with XP was 0·13 standard erythemal doses (SEDs) (mean in healthy individuals = 0·51 SED). There was wide variation between patients (range < 0·01–0·48 SED/day). Self‐caring adult patients had a very similar UVR dose to the face as cared‐for patients (0·13 vs. 0·12 SED/day), despite photoprotecting much more poorly when outside, because the self‐caring adults were outside in daylight much less.ConclusionsPhotoprotection behaviour varies widely within the XP group indicating that nonadherence to photoprotection advice is a significant issue. The timing and duration of going outside are as important as photoprotective measures taken when outside, to determine the UVR exposure to the face. This new methodology will be of value in identifying the sources of UVR exposure in other conditions in which facial UVR exposure is a key outcome, particularly in patients with multiple nonmelanoma skin cancers.

Incidence of Non-Melanoma Skin Cancers in Patients with Chronic Lymphocytic Leukaemia: A Retrospective Study in a Bay of Plenty, New Zealand Population

Background/Aims: Chronic lymphocytic leukaemia (CLL) incurs an increased risk of developing second primary malignancies (SPMs). The pathogenesis underpinning this increased SPM risk is attributable to synergism between genetic aberrations, chronic immune suppression / dysfunction and CLL treatments. Specifically, CLL associated skin cancer is a well-documented phenomenon, with common malignancies such as squamous (SCC) and basal cell (BCC) carcinomas occurring at higher frequencies in CLL patients and are often of a more aggressive phenotype. The incidence of non-melanoma skin cancers (NMSCs) among New Zealand CLL patients is unknown, as NMSCs are not required to be reported to the New Zealand Cancer Registry. Accordingly, this study aimed to analyse the incidence of NMSC in CLL patients from the Bay of Plenty region of New Zealand.Methods: We conducted a retrospective analysis of 213 CLL patients, who were referred to Bay of Plenty District Health Board (BOPDHB) between 2015 and 2020, for the occurrence of SPMs. Clinical notes were reviewed for the demographics of sex, age at time of CLL diagnosis, CLL treatments received and occurrence and type of NMSCs. A control group of 76 patients referred to BOPDHB haematology, for anaemia or thrombocytopenia, of which the cause subsequently remained unknown and was not associated with lymphoproliferative disease, was reviewed for primary malignancy (PM), occurrence and type. NMSC incidence was also compared to a local data, on overall NMSC incidence in the general Bay of Plenty population, in 2015.Results: The predominant SPM types occurring in this CLL patient group were NMSCs. A total of 249 and 170 histological diagnoses of SCC and BCC were made in our group of CLL patients, respectively. Of the 213 CLL patients, 48.8% had a diagnosis of at least one NMSC, with median time between CLL and NMSC diagnosis of 5 years (range, -6 to 19 years). CLL patients that were diagnosed with NMSC developed a mean number of 3.93 ± 2.94 separate lesions, compared to 2.6 ± 1.7 lesions in our control population. Note: comparison of NMSC incidence data between CLL group and Bay of Plenty populationConclusion: Patients with CLL are at increased risk of developing multiple NMSC lesions. Therefore, we believe CLL patients should be assessed by dermatologists or general practitioners for whole-body skin examination, 6 monthly following their CLL diagnosis. This strategy promotes early diagnosis, and patient education on importance of sun protection strategies to reduce NMSC risk. This is essential to the ongoing care of CLL patients in a NZ context, given the increased incidence of NMSC associated with CLL, in combination with the high levels of UV exposure and skin damage among the NZ general population. This study also highlights how NMSC disease burden is likely to be significantly underestimated due to a lack of data collection on these malignancies by the New Zealand Cancer Registry. DisclosuresNo relevant conflicts of interest to declare.

Facial eruptions

A 78-year-old woman presented to her physician with complaints of facial pain 2 weeks into a 3-week prescribed 5-fluorouracil (5-FU) field treatment for facial actinic keratoses (AKs). The patient had a previous medical history of multiple nonmelanoma skin cancers and AKs. Upon examination, the physician noted marked erythema and some crusting over widespread areas of previous AKs.What’s your diagnosis?

Rapid development of multiple nonmelanoma skin cancers secondary to ruxolitinib: a case report

&lt;p class="abstract"&gt;Janus kinase (JAK) inhibitors are immunosuppressive medications that function by deactivating the JAK-STAT pathway causing inhibition of cellular growth. Ruxolitinib is a JAK inhibitor that is commonly used to treat disease processes such as myelofibrosis, polycythemia vera and graft versus host disease, with some evidence of benefit with prostate cancer as well. Side effects of ruxolitinib include increased risk of infection, pancytopenia, cardiovascular disease and malignancy relating to the medication’s immunosuppressive effects. Here we reported a 69-year-old male with prostate cancer being treated with ruxolitinib who developed multiple nonmelanoma skin cancers over a 13-month period.&lt;/p&gt;

A case of squamous cell carcinoma arising in porokeratosis of Mibelli

Background: Porokeratosis is an uncommon disorder of epidermal keratinisation. Characteristic features include hyperkeratotic lesions with an atrophic centre and raised wall-like border, and the pathognomonic histological finding of a coronoid lamella.1 Malignant transformation into squamous, bowenoid or basal cell carcinoma rarely has been reported in all major variants.2 Aims: To describe a case of squamous cell carcinoma arising in porokeratosis of Mibelli. Methods: A 73-year-old man presented for routine skin malignancy surveillance with a new, asymptomatic lesion within a porokeratosis of Mibelli on his right calf, clinically suspicious for squamous cell carcinoma. His history included multiple non-melanoma skin cancers and one previous melanoma in situ. No other lesions typical for porokeratosis were found on examination. Histopathological examination of the lesion confirmed moderately differentiated squamous cell carcinoma arising in background changes of porokeratosis. The lesion was completely excised within a week of biopsy. Results and conclusions: Porokeratosis is a premalignant condition, however malignant transformation is rare.1 It is hypothesised that chromosomal instability and reduced immune surveillance with overexpression of p53 can contribute to the development of cutaneous malignancy within porokeratoses.2 Risk factors for malignancy include ionising radiation, sun exposure, immunosuppression, long history of the lesion and large size of the porokeratosis.3 This case adds to the existing literature surrounding malignant transformation of porokeratoses and highlights the importance of regular skin surveillance in affected patients.

Neoplasia-related spiny keratoderma: Dermoscopic findings of two cases and a literature review.

Neoplasia-related spiny keratoderma: Dermoscopic findings of two cases and a literature review.

Scalp and Skull Reconstruction in Patients Irradiated for Tinea Capitis in Childhood: The Scalp Exchange Procedure

AbstractBackground Approximately 70,000 Israelis underwent scalp irradiation for tinea capitis infection during their childhood, as did many other children worldwide. Long-term follow-up data showed that these children had an increased risk of aggressive and multiple nonmelanoma skin cancers, meningiomas, and other malignancies. Resection of these lesions creates a defect of soft tissue, bone, and dura, and requires scalp and skull reconstruction with local or free flaps in the irradiated field.Methods Sixteen patients with a history of childhood scalp irradiation underwent scalp and skull reconstruction in our department (2000–2018). Data on demographics, oncological status, operative details, and postoperative outcome were retrospectively collected and analyzed.Results The study group included 11 males and 5 females (average age at surgery, 70 years). The most common lesions were meningiomas (n = 9) and basal cell carcinomas (n = 8), and the most common indication for reconstruction was chronic exposure of deep structures (skull, dura, brain tissue, and titanium mesh; n = 9). Thirteen patients underwent primary free flap reconstruction and three underwent primary local flap reconstruction. Flap failure requiring reoperation occurred in one patient of the free flap reconstruction group (7%) and in all three patients of the local flap reconstruction group.Conclusion Long-term consequences of childhood depilatory treatments of the scalp by irradiation are now surfacing. Our experience showed that in such cases, surgeons should aim for a more aggressive approach with wide resection and primary free flap reconstruction, and that favorable long-term functional and aesthetic results can safely be achieved using this reconstruction approach.

Families with BAP1-Tumor Predisposition Syndrome in The Netherlands: Path to Identification and a Proposal for Genetic Screening Guidelines.

Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1-tumor predisposition syndrome (BAP1-TPDS, OMIM 614327). BAP1-TPDS is associated with an increased risk of developing uveal melanoma (UM), cutaneous melanoma (CM), malignant mesothelioma (MMe), renal cell carcinoma (RCC), meningioma, cholangiocarcinoma, multiple non-melanoma skin cancers, and BAP1-inactivated nevi. Because of this increased risk, it is important to identify patients with BAP1-TPDS. The associated tumors are treated by different medical disciplines, emphasizing the need for generally applicable guidelines for initiating genetic analysis. In this study, we describe the path to identification of BAP1-TPDS in 21 probands found in the Netherlands and the family history at the time of presentation. We report two cases of de novo BAP1 germline mutations (2/21, 9.5%). Findings of this study combined with previously published literature, led to a proposal of guidelines for genetic referral. We recommend genetic analysis in patients with ≥2 BAP1-TPDS-associated tumors in their medical history and/or family history. We also propose to test germline BAP1 in patients diagnosed with UM <40 years, CM <18 years, MMe <50 years, or RCC <46 years. Furthermore, other candidate susceptibility genes for tumor types associated with BAP1-TPDS are discussed, which can be included in gene panels when testing patients.

Identification of Risk Factors for Multiple Non-Melanoma Skin Cancers in Italian Kidney Transplant Recipients.

Background and objectives: Non-melanoma skin cancers (NMSCs) represent the most frequently encountered malignancy in organ transplant recipients and their incidence increases proportionally to the duration of immunosuppression. Furthermore, patients of this group often develop multiple and more aggressive cancers and, to date, risk factors for the development of multiple NMSCs have not been yet established. The present study aimed to identify risk factors for multiple NMSCs in a cohort of Italian kidney transplant recipients (KTRs). Materials and Methods: We consecutively included all KTRs referring to two post-transplant outpatient clinics of North-Western Italy between 2001 and 2017. In this cohort, we evaluated different clinical (endogenous and exogenous) risk factors in order to establish their correlation with NMSCs. Results: 518 KTRs were included, of which 148 (28.6%) developed keratinocyte cancers, with a single tumor in 77 subjects, two skin cancers in 31 patients, 3 in 21 patients, whereas at least 4 NMSCs developed in 19 KTRs. We observed an increased risk of the development of cutaneous neoplasms for the male gender, old age at transplantation (>50 years), light phototype, solar lentigo, history of sunburns, or chronic actinic damage. Considering patients affected by multiple keratinocyte neoplasms, we observed a significant association of actinic damage and solar lentigo with an increased risk of NMSCs; their significance was confirmed even at the multivariable model. Conclusions: Our results confirm the role played by chronic cutaneous actinic damage in carcinogenesis on KTRs and highlight the significance of individualized periodic dermatological screening.

Pembrolizumab treatment of a patient with xeroderma pigmentosum with disseminated melanoma and multiple nonmelanoma skin cancers

Pembrolizumab treatment of a patient with xeroderma pigmentosum with disseminated melanoma and multiple nonmelanoma skin cancers

Basal Cell Carcinoma with Adnexal Differentiation, a Rare Entity and Challenging Histopathology Presentation. Case Report

We report an 88 year-old male with a history of multiple non-melanoma skin cancers who presented for Mohs micrographic surgery with a biopsy proven infiltrative and nodular basal cell carcinoma located on the right posterior ear. During Mohs surgery, frozen sections revealed a typical nodular BCC on stage 1. However, on stage 2, frozen section showed nodular aggregates of regular cuboidal cells with pale cytoplasm with areas mimicking multi-nucleated giant cells. Deeper permanent sections were consistent with BCC with adnexal differentiation. This histopathological presentation of basal cell carcinoma is uncommon and we sought to report the clinical and pathological features of this case.

Viruses in case series of tumors: Consistent presence in different cancers in the same subject.

Studies investigating presence of viruses in cancer often analyze case series of cancers, resulting in detection of many viruses that are not etiologically linked to the tumors where they are found. The incidence of virus-associated cancers is greatly increased in immunocompromised individuals. Non-melanoma skin cancer (NMSC) is also greatly increased and a variety of viruses have been detected in NMSC. As immunosuppressed patients often develop multiple independent NMSCs, we reasoned that viruses consistently present in independent tumors might be more likely to be involved in tumorigenesis. We sequenced 8 different NMSCs from 1 patient in comparison to 8 different NMSCs from 8 different patients. Among the latter, 12 different virus sequences were detected, but none in more than 1 tumor each. In contrast, the patient with multiple NMSCs had human papillomavirus type 15 and type 38 present in 6 out of 8 NMSCs.

Filaggrin genotype does not determine the skin's threshold to UV-induced erythema

Filaggrin genotype does not determine the skin's threshold to UV-induced erythema

Epidemiology and clinical evolution of non-melanoma skin cancer in renal transplant recipients: a single-center experience in São Paulo, Brazil.

Non-melanoma skin cancer (NMSC) is very common among renal transplant recipients (RTRs) as a result of the immunosuppressed status of these patients and other factors. Few studies have examined the clinical characteristics and evolution of NMSC in RTRs in tropical countries. The aim of this study was to characterize the epidemiology and clinical evolution of NMSC in RTRs. We conducted a retrospective study including 68 RTRs with NMSC diagnosed from July 2004 to December 2009 with a minimum follow-up of three years. We analyzed demographic and transplant- and NMSC-related data. The mean age of patients at the first diagnosis of NMSC was 51 years (range: 29-71 years). Most first diagnoses occurred within nine years post-transplant. The majority of patients (n = 48) had Fitzpatrick skin phototype II, although NMSC was also observed in those with skin phototypes III and IV. Forty-six (67.6%) RTRs had received a kidney from a living donor. Fifty-five (80.9%) RTRs had received cytotoxic immunosuppressives, 51 (75.0%) had received calcineurin inhibitors, and two (2.9%) had received mTOR inhibitors. Most of the RTRs developed about eight NMSC lesions, but up to 25 NMSC lesions were diagnosed in one patient. Most lesions (67.6%) were located on sun-exposed areas. Squamous cell carcinoma (SCC) represented the predominant tumor type, accounting for 70.6% of all tumors, whereas basal cell carcinoma accounted for 29.4% of all tumors. Invasive SCC predominated over in situ SCC. Finally, 48.5% of patients had a previous history of viral warts. Long-term use of immunosuppressive therapy increases the risk for tumor occurrence. Multiple NMSC tumors can develop in patients in tropical countries, even in patients with a high skin phototype. Therefore, RTRs should understand the high risk for the development of malignant tumors and should be properly informed about the prevention and treatment of NMSC.

Non-melanoma skin cancer is reduced after switch of immunosuppression to mTOR-inhibitors in organ transplant recipients.

Organ transplant recipients are prone to the development of non-melanoma skin cancer. Organ transplant recipients often develop multiple non-melanoma skin cancers and the tumors show an aggressive growth pattern, therefore surgical therapy can be difficult. Switch of the immunosuppressive regimen to mTOR-inhibitors such as everolimus or sirolimus can have an antitumor effect. In a monocentric retrospective study we evaluated organ transplant recipients who presented with non-melanoma skin cancer in the years 2008-2010. Experience with patients who were switched to an mTOR-inhibitor due to non-melanoma skin cancer are reported in detail, and recent clinical studies are reviewed. 60 organ transplant recipients with non-melanoma skin cancer were evaluated. Due to the development of multiple non-melanoma skin cancer within a few years, the immunosuppressive regimen was switched to everolimus in 7 patients and to sirolimus in 5 patients. Eight patients were evaluable for the effect of mTOR-inhibitors on the development of non-melanoma skin cancer; 4 patients had to discontinue the medication with mTOR-inhibitors early due to various side effects. In the year before the switch to mTOR-inhibitors, 8 patients developed 16 squamous cell carcinomas, 3 Basal cell carcinomas and 22 cases of Bowen's disease. All tumors were histologically confirmed. In the year after switch of immunosuppression, the rate of squamous cell carcinomas (n = 2) and Bowen's disease (n = 3), but not of basal cell carcinomas (n = 2) was significantly reduced. Moreover, 5 prospective randomized trials recently have demonstrated a reduced number of non-melanoma skin cancers in organ transplant recipients after switch of the immunosuppressive regimen to mTOR-inhibitors. Switch of the immunosuppressive regimen to mTOR-inhibitors should be considered for organ transplant recipients suffering from multiple non-melanoma skin cancers.

Multiple unilateral nonmelanoma skin cancers arising within chronic lymphedema

Multiple unilateral nonmelanoma skin cancers arising within chronic lymphedema

Primary Cutaneous Angiosarcoma on the Nose in a Patient with Multiple Nonmelanoma Skin Cancers

Cutaneous angiosarcoma is an uncommon, potentially metastatic and highly aggressive vascular tumor that may arise as de novo or be associated with previous radiotherapy. A 70-year-old female with a solitary lesion on the nose was initially diagnosed as actinic keratosis. However, when the recurring lesion at the same region within 6 months was reexcised, the histological diagnosis was definitively established as well-differentiated angiosarcoma. This case was presented in order to increase awareness of this rare malignancy in an uncommon localisation, especially in the light of pathological findings. Moreover, occurrence of cutaneous angiosarcoma within a short period following a previous excision in a patient with a history of multiple nonmelanoma skin cancers was interestingly pointed out.