Multiple Squamous Cell Carcinomas Research Articles

Citrullinated Histone H3, a Marker for Neutrophil Extracellular Traps, Is Associated with Poor Prognosis in Cutaneous Squamous Cell Carcinoma Developing in Patients with Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into four groups based on their occurrence (first onset or recurrences) and grading according to clinical, histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analyzed. Five RDEB patients experienced an unfavorable course after the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 patients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment and an increased proportion of neutrophil extracellular traps (NETs). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs.

Advanced Squamous Cell Carcinoma of the Skin Induced by Long-Term Hydroxyurea Treatment in a Patient with Essential Thrombocythemia

Abstract Background and Objective SCCs represents 20-30% of the non-melanocytic skin cancers. It is the second most common skin cancer in the U.S. The main risk factors for SCCs development are: skin phototype l-ll, excessive UV-exposure, chronic inflammatory skin diseases, radiation exposure and drug usage. Hydroxyurea is a drug used for the treatment of chronic myeloid leukemia, polycythemia vera and essential thrombocythemia. The therapy is associated with development of actinic keratoses, Bowen's disease, squamous cell carcinoma and basal cell carcinoma. Patients and methods We present a 70-year-old female patient suffering from essential thrombocythemia, undergoing treatment with hydroxyurea since 2005, who developed advanced squamous cell carcinoma of the skin of the face and wrists. Results The patient was diagnosed with advanced moderately differentiated SCCs (Grade 2), stage III (T4 N0 M0). Immunotherapy with cemiplimab 350 mg i.v. every 21 days was initiated. After 6 therapeutic cycles decrease of erythema and desquamation was registered. In 2022 the patient had an ischemie stroke, decompensated heart failure and acute kidney insufficiency. Unfortunately the patient died. Conclusions Patients undergoing long-term hydroxyurea treatment are prone to develop multiple squamous cell carcinomas of the skin and are subject to regular dermatological examinations.

Multiple squamous cell carcinomas of temporal bone years after radiotherapy for malignancy glottis-report of a rare case with review of literature

Larynx is unique in its anatomy. It is critical to map the lesions accurately so that the patient may benefit from the strategy most likely to preserve a functional larynx with the lowest likelihood of recurrence and the least morbidity. We describe a case of 60-year-old male with malignancy glottis diagnosed at the age of 43, treated with external beam radiotherapy, presented 15 years after with swelling in the right upper part of the face, lateral to the eye. Radiological investigations suggested neoplasm in the skin over the right zygomatic part of the temporal bone. Biopsy confirmed malignancy, basal cell carcinoma type. Wide local excision of the lesion with split skin grafting was done. After 2 years, he presented with right ear pain, discharge, and hard of hearing. Examination and radiological investigations confirmed a mass in the external auditory canal, infiltrating through the temporal bone. Biopsy revealed an acantholytic variant of squamous cell carcinoma (SCC). The patient was advised about treatment options and radiotherapy was chosen. Further, a literature search was conducted to detect similar cases. We describe the incidence and prevalence of radiation-induced temporal bone malignancy, an exceedingly rare and late complication of head and neck irradiation. Radiation induced SCCs are highly malignant secondary neoplasms in the head and neck region. It constitutes a therapeutic challenge because of its anatomy and the known side effects of radiation. Timely intervention with a multidisciplinary approach is necessary.

∆Np63α inhibits Rac1 activation and cancer cell invasion through suppression of PREX1

ΔNp63α, a member of the p53 family of transcription factors, plays a critical role in maintaining the proliferative potential of stem cells in the stratified epithelium. Although ΔNp63α is considered an oncogene and is frequently overexpressed in squamous cell carcinoma, loss of ΔNp63α expression is associated with increased tumor cell invasion and metastasis. We recently identified a ΔNp63α/miR-320a/PKCγ signaling axis that regulates cancer cell invasion by inhibiting phosphorylation of the small GTPase Rac1, a master switch of cell motility that positively regulates cell invasion in multiple human cancers. In this study, we identified a novel mechanism by which ΔNp63α negatively regulates Rac1 activity, by inhibiting the expression of the Rac-specific Guanine Exchange Factor PREX1. ΔNp63α knockdown in multiple squamous cell carcinoma cell lines leads to increased Rac1 activation, which is abrogated by treatment with the Rac1 inhibitor NSC23766. Furthermore, ΔNp63α negatively regulates PREX1 transcript and protein levels. Using a Rac-GEF activation assay, we also showed that ΔNp63α reduces the levels of active PREX1. The inhibition of the PREX1-Rac1 signaling axis by ΔNp63α leads to impaired cell invasion, thus establishing the functional relevance of this link. Our results elucidated a novel molecular mechanism by which ΔNp63α negatively affects cancer cell invasion and identifies the ΔNp63α/Rac1 axis as a potential target for metastasis.

Multiple squamous cell carcinomas arising from ulcerative lichen planus of the sole.

Multiple squamous cell carcinomas arising from ulcerative lichen planus of the sole.

Epidemiology and risk factors for multiple squamous cell carcinomas in a cohort of organ transplant recipients from northern Italy: a single center study.

Keratinocyte cancers account for the most frequent oncological complication in organ transplant recipients. To date, many different risk factors have been reported, unless variability among the studies exist. We aimed to determine the incidence and risk factors for keratinocyte neoplasms in a cohort of kidney transplant and liver transplant recipients. A cohort of 338 patients were included in this retrospective study and followed-up from transplantation until the end of December 2021, with a 2-year minimum transplant time. Each skin cancer was collected in a specific database, together with all the demographic data and dermatological history and feature of patients. In our cohort, liver transplant patients presented a higher keratinocyte cancer incidence compared to kidney transplant recipients. Regarding the risk factors for skin cancer in the entire group of patients, we observed a significant association with the detection of actinic keratosis and solar lentigo, and such relation was stronger when considering patients developing multiple skin cancers, in which fair skin types and occupational sun exposure were also associated. Furthermore, while actinic keratosis and a history of previous dialysis were significantly associated with the development of a least one squamous cell carcinoma, the presence of keratotic lesions and azathioprine intake resulted connected with the appearance of multiple squamous neoplasms. We report here that, in our cohort, factors potentially leading to immune dysfunction were found to play a causative role in the development of the more aggressive histotype of keratinocyte tumors, and such association seemed more convincing in case of multiple squamous cell carcinomas.

Hydroxyurea-Associated Multiple Squamous Cell Carcinoma Developed on the Dermatomyositis-Like Eruption

Hydroxyurea-Associated Multiple Squamous Cell Carcinoma Developed on the Dermatomyositis-Like Eruption

Squamous cell carcinoma of the skin after cardiac transplantation: a clinical case

Background. Solid organ transplantation recipients have a high risk of non-melanoma skin tumors. Patients after heart transplantation are prone to a higher incidence of malignant skin tumors due to intensive immunosuppressive therapy. The most common histological type is squamous cell carcinoma, followed by basal cell carcinoma. These tumors have a more aggressive clinical course, including the frequency of recurrence and metastasis, and a tendency to multifocal lesions.
 Materials and methods. We present a clinical case of primary multiple squamous cell carcinoma with metastatic lesions of regional lymph nodes in a patient after heart transplantation.
 Results. A 67-year-old patient underwent an orthotopic heart transplant in September 2018 for ischemic cardiomyopathy. Subsequently, triple immunosuppressive therapy was administered, including tacrolimus combined with mycophenolate mofetil and prednisolone. In May 2022, a solid tumor with ulceration occurred on the skin of the right scapular region. After some time, similar tumors appeared on the skin of the temporal region on the left, the posterior surface of the auricle and the parietal region on the left. The patient later found a solid, painless tumor on the left jaw angle. As a part of the examination in the oncology dispensary, a biopsy of the scapular skin tumor, scrapings from tumors, and aspiration biopsy of the submandibular lymph nodes were performed. Histological and cytological studies of all neoplasms showed squamous cell keratinizing cancer with metastases to the submandibular lymph nodes. Additional examination methods showed no signs of progression. The diagnosis was made: primary multiple synchronous skin cancer: right scapular area, stage III, cT3N0M0; left parietal area, stage II, cT2N0M0; occipital area, stage I, cT1N0M0; left auricle, stage IV, cT1N2M0. Considering the localization of tumors, surgical treatment was performed, including of excision of tumors in the scapular and parietal regions. Radiation therapy was performed on lymph nodes with metastases. After 6 months, a tumor recurrence was detected in the irradiation area.
 Conclusion. After heart transplantation, squamous cell carcinoma of the skin is common. Usually, it affects the scalp and neck with metastases to the regional lymph nodes and is prone to recurrence. The primary treatment method is surgical and radiation therapy.

SECONDARY RADIATION CARIES RELATED TO XEROSTOMIA: A CASE REPORT ABOUT THE IMPACT OF FOLLOW-UP LOSS

This case report is about a 48-year-old man with advanced radiation caries caused by the loss of follow-up, treated surgically, in 2018, for multiple Squamous and Basal Cell Carcinomas of the skin, using radiotherapy (IMRT) for squamous cell carcinoma on left parotid skin. Although he was submitted to preventive oral treatments to avoid acute and chronic consequences of radiation, he abandoned the accompaniment in the same year, returning in March 2022 with dental pain related to advanced radiation caries. Upon physical and radiographic examinations, a severe destruction of the maxillary teeth and a lower-level destruction of the mandibular teeth was noticed. The doses higher than 40Gy did not reach the maxilla, showing that the radiation caries were secondary to xerostomia. The patient is currently undergoing surgical and restoration treatments. This case reveals a reflection on the importance of follow-up in post radiation patients. This case report is about a 48-year-old man with advanced radiation caries caused by the loss of follow-up, treated surgically, in 2018, for multiple Squamous and Basal Cell Carcinomas of the skin, using radiotherapy (IMRT) for squamous cell carcinoma on left parotid skin. Although he was submitted to preventive oral treatments to avoid acute and chronic consequences of radiation, he abandoned the accompaniment in the same year, returning in March 2022 with dental pain related to advanced radiation caries. Upon physical and radiographic examinations, a severe destruction of the maxillary teeth and a lower-level destruction of the mandibular teeth was noticed. The doses higher than 40Gy did not reach the maxilla, showing that the radiation caries were secondary to xerostomia. The patient is currently undergoing surgical and restoration treatments. This case reveals a reflection on the importance of follow-up in post radiation patients.

Abstract 400: TIP60-mediated regulation of DNp63a is associated with cisplatin resistance

Abstract About 5.4 million basal and squamous cell skin cancers are diagnosed each year in the US. The chemotherapeutic drug, Cisplatin is often used to treat squamous cell carcinoma (SCC) patients, but low response rates and disease recurrence is common. ΔNp63α, a member of the p53 family of transcription factors, is overexpressed and considered oncogenic in non-melanoma skin cancer where it regulates cell survival, promotes proliferation and inhibits cell apoptosis. ΔNp63α has also been shown to promote resistance to cisplatin by transcriptionally regulating several DNA damage response (DDR) genes. A previous study from our lab showed that the histone acetyltransferase (HAT) TIP60 promotes SCC proliferation by positively regulating ΔNp63α protein levels in manner dependent on the catalytic activity of TIP60. This finding suggested that TIP60 may contribute to the failure of platinum-based drugs in SCC and led us to hypothesize that TIP60-mediated acetylation of ΔNp63α regulates its stability and transcriptional activity to promote chemoresistance. Silencing endogenous TIP60 led to a decrease in ΔNp63α transcript and protein levels in multiple SCC cell lines, indicating the positive regulation of ΔNp63α by TIP60 is not cell-line specific. Further, TIP60 levels positively correlated with ΔNp63α stability, protein levels and cisplatin resistance. Stable expression of TIP60 or ΔNp63α individually promoted resistance to cisplatin and reduced cell death, whereas loss of ΔNp63α and TIP60 induced G2/M arrest, increased cell-death and sensitized cells to cisplatin. Moreover, pharmacological inhibition of TIP60 reduced acetylation of ΔNp63α and sensitized resistant cells to cisplatin. Finally, we demonstrated that ΔNp63α and TIP60 levels positively correlated with DNA repair capacity and negatively correlated with cisplatin-DNA adduct formation. Silencing of either TIP60 or ΔNp63α enhanced cisplatin-DNA adduct formation and significantly reduced expression of genes involved in DDR. Taken together, our data indicate that TIP60-mediated stabilization of ΔNp63α increases cisplatin resistance and provides critical insights into the mechanisms by which ΔNp63α confers cisplatin resistance through regulation of genes involved in DNA damage repair. Our findings suggest that inhibition of TIP60 may be therapeutically advantageous in overcoming cisplatin resistance in SCC other epithelial cancers. Citation Format: Akshay Hira, Andrew J. Stacy, Jin Zhang, Mike Kemp, Madhavi P. Kadakia. TIP60-mediated regulation of DNp63a is associated with cisplatin resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 400.

Actinic keratosis as a predictor of primary multiple synchronous squamous cell skin cancer: a clinical case

We present a clinical case of a primary multiple synchronous highly differentiated keratinizing squamous cell skin cancer in an 84-year old patient with multiple actinic keratosis and actinic cheilitis. The clinical case is unique for the simultaneous development of primary multiple squamous cell carcinoma of the tip of the nose and the vermilion zone of the lower lip in a patient with a past occupational and solar burden, a light phenotype, and signs of chronic photo injury the skin. Clinical, dermatoscopic and sonographic signs of keratotic actinic keratosis were identified in the patient and confirmed by pathomorphological examination. The risk factors for malignant transformation of actinic keratosis were found, such as multiple efflorescences and a long disease history. The malignant transformation of the actinic areas manifested as rapidly progressive ulceration zones more than 1 cm in diameter, pronounced hyperkeratosis, inflammation and infiltration of the underlying tissues, increased bleeding and pain. It is to be underlined that definitive and differential diagnosis requires pathomorphological assessment of the skin biopsy sample. This clinical case indicates that patients with multiple foci of actinic keratosis should be under a lifelong follow-up by dermatovenereologists, with mandatory treatment and prevention measure.

A 73‐year‐old woman with multiple crusted lesions

A 73-year-old woman was attended for multiple crusted lesions on her head and hands for more than 1 year. These lesions had appeared 1 year ago as red patches with adherent scales without accompanying itch or pain. The patches gradually enlarged and proliferated with thick scales and an ulcer on the left side of her face. The patient suffered from polycythemia vera and had been treated with hydroxyurea (HU), 500 mg daily for 6 years. There was no personal history of local radiotherapy or heavy sun exposure and no family history of malignancy. On examination, several large infiltrated plaques with irregular borders were seen on the eyebrows, cheeks, jaw, nose and hands. The largest one was located on the left cheek (6 × 3 cm2) (Figure 1a,b). A thick scale covered all lesions. In addition, there were smaller red plaques with fine scaling in sun-exposed areas (Figure 1a,b). Lab analyses including blood cell counts and serum chemistry were normal. A skin biopsy from the lesion on her left cheek was done (Figure 1b). Histologic findings of the skin biopsy showed an invasive, moderately differentiated, keratinizing squamous cell carcinoma (SCC). A positron emission tomography scan and ultrasound revealed enlarged lymph nodes on the left side of the neck, but a lymph node biopsy was negative. The lesion on the left cheek was widely excised with complete grafting, and the other lesions were treated with 5% imiquimod cream since the patient declined surgical excision. HU was discontinued and imatinib was started. After 12 months of follow-up, her polycythemia vera was well controlled, no new SCC lesions had developed, and the previous lesions had not progressed. HU is very frequently used as a first-line treatment of polycythemia vera.1-3 HU also has a role in selected skin conditions.4 HU may also play a role in reducing the mortality of coronavirus disease 2019.5 HU selectively acts on the most actively dividing cells such as basal layer keratinocytes. Hence, cutaneous adverse effects have been described, including xerosis, hyperpigmentation and skin atrophy and, less frequently, nonmelanoma skin cancers.3, 6 SCCs associated with HU therapy are seen in patients who used HU for long periods of time. Most patients present multiple SCC lesions.7, 8 The SCCs are usually located in photodistributed areas, which suggests that ultraviolet plays an important adjuvant role in HU-associated SCCs.7-9 Strict photoprotection is thus mandatory in patients on long-term HU therapy. In patients with HU-associated SCCs, HU treatment must be discontinued. Patients should be evaluated basally and then on a regular basis, especially for older patients and those with a propensity to skin cancer.3 As an aggressive and metastatic tumour, the SCCs must be widely excised, and metastases promptly identified and adequately treated.7 So far, no study has compared outcomes in HU-associated SCCs with regular SCCs. Patients on long-term HU therapy must undergo dermatological examination at baseline and regularly thereafter. If a cutaneous malignancy is suspected, a biopsy is mandatory. If malignancy is confirmed, discontinuation of HU must be considered. Ronghui Zhu collected the clinical data and tissue specimens. Shangshang Wang was responsible for the study design and drafted the manuscript. All authors read and approved the final manuscript. This work was supported by grants from the National Natural Science Foundation of China (82003357). The authors declare no conflict of interest. The study was approved by the Institutional Review Board of Huashan Hospital, Shanghai, China, and the patient provided written informed consent. The authors confirm that the data supporting the findings of this case report are available within the article. Raw data that support the findings are available from the corresponding author upon request.

P8.042: Non-melanoma Skin Cancer With an Aggressive Course in Kidney Transplant Patients Treated With Rapamycin

Introduction: Non-melanoma skin cancer (NMSC) represents the most frequent malignancy in patients with solid organ transplantation, with a high risk of metastasis (MTS) and death related to factors such as chronic immunosuppression, exposure to ultraviolet (UV) radiation, and HPV infections. Objectives: • To describe the features of non-melanoma skin cancer (NMSC). • To report the development of multiple NSCLC and metastasis in patients treated with rapamycin. • To highlight the need for dermatological control in order to assess risk factors, precancerous lesions and make an early diagnosis. Materials and methods: We present three renal transplant patients assisted by Dermatology at the Renal Transplant Unit of CRAI Sur, Hospital Interzonal General de Agudos “Gral. San Martín”, La Plata, Argentina. Patients with multiple lesions under treatment with rapamycin and aggressive evolution were chosen. Risk factors related to the multiplicity and dismal evolution of NCC (signs of photodamage, preneoplastic lesions, history of NCC) were evaluated prior to evaluation at the unit; we also analysed age of presentation, sex, transplantation timing, initial immunosuppressive regimen and subsequent modifications, type of NMSC, treatment and evolution. Patients:Case 1: 68 year-old male, with prior history of basal cell carcinomas (back and face) and actinic keratoses. He developed multiple squamous cell carcinoma 5 years post transplantation. Induction: thymoglobulin. Immunosuppression: rapamycin, MMF and steroids. Therapy: surgery. Death due to multiple lung MTS. Case 2: 69 year-old male, with prior history of actinic keratoses and basal cell carcinoma (face). He developed multiple metatypic basal cell carcinoma 9 years post-transplantation. Induction: Basiliximab. Immunosuppression: tacrolimus, MMF and steroids. Switch to rapamycin after diagnosis. Therapy: surgery and Imiquimod. Death due to acute myocardial infarction. Case 3: 43 year-old male, with prior history of actinic keratoses and squamous cell carcinoma (face). He developed squamous cell carcinoma (face) and multiple skin MTS 7 years post-transplantation. Induction: thymoglobulin. Immunosuppression: tacrolimus, MMF and steroids. Switch to rapamycin after diagnosis. Therapy: chemotherapy. Death due to multiple lung MTS. Conclusions: 1- The NMSC in these patients presented with multiple lesions and clinical and histological characteristics related to an aggressive course (MTS and death in two cases). 2- Immunosuppressive therapy with rapamycin did not modify the outcome and development of multiple lesions despite its known antiproliferative and angiogenesis effects. 3- All our patients were men and presented risk factors for NMSC (photodamage, actinic keratoses, more than five years post-transplantation, history of prior NMSC, induction and immunosuppressive therapy). 4- Dermatological control is crucial in order to identify risk factors, promote photoeducation and make a prompt diagnosis.

TIP60 mediated regulation of ΔNp63α is associated with Cisplatin resistance

About 5.4 million basal and squamous cell skin cancers are diagnosed each year in the US. Cisplatin, a chemotherapeutic drug is often used to treat squamous cell carcinoma (SCC) patients. However, 55% of cancers fail to respond leading to lower response rates and higher rates of disease re‐occurrence. ΔNp63α a member of the p53 transcription factor family is overexpressed and considered oncogenic in non‐melanoma skin cancer where it regulates cell survival and proliferation. TIP60 (Tat‐interacting protein 60kDa), a histone acetyltransferase has been shown to mediate cellular processes such as transcription regulation and the DNA damage response (DDR). We recently reported that TIP60 positively regulates ΔNp63α protein levels in a catalytic‐dependent manner to promote SCC proliferation. Since ΔNp63α is known to transcriptionally regulate several DDR genes and promote resistance to cisplatin, its stabilization by TIP60 may contribute to the failure of platinum‐based drugs in SCC. We hypothesis that TIP60 mediated acetylation of ΔNp63α regulates its transcriptional activity thereby modulates chemoresistance. In this study, we showed that silencing of endogenous TIP60 in multiple SCC cell lines led to decrease in ΔNp63α transcript and protein levels confirming that TIP60 positively regulates ΔNp63α. Increased levels of TIP60 positively correlated with increased ΔNp63α expression and contributes to cisplatin resistance. Further, stable expression of TIP60 or ΔNp63α individually promoted resistance to cisplatin and reduced cell death, whereas loss of ΔNp63α and TIP60 sensitized cells to cisplatin. Higher acetylation of ΔNp63α and TIP60 were seen in cisplatin resistant cell line. Taken together, our data suggest that TIP60‐mediated stabilization of ΔNp63α increases cisplatin resistance and has potential implication for SCC cancer treatment and drug design. Additionally, since ΔNp63α confers cisplatin resistance through regulation of genes involved in DNA damage repair, our findings provide critical insights into the mechanism by which genes involved in chemoresistance are regulated and may lead to strategic treatment for resistant SCC tumors and other epithelial cancers with increased efficacy.

Comparative Genomic Analysis Reveals Genetic Variations in Multiple Primary Esophageal Squamous Cell Carcinoma of Chinese Population.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and lethal malignant tumors. The incidence of malignant transformation of esophageal mucosa increases greatly due to long-term exposure to factors such as smoking, drinking, and poor eating habits. Furthermore, multiple primary tumors could occur synchronously or asynchronously in the upper aerodigestive tract, especially in the esophagus, adding difficulty to the treatment of ESCC. Genetic mutations are important during the malignant transformation from normal mucosa to esophageal cancer, but the underlying mechanism has not been fully elucidated. In this study, we used whole-exome sequencing (WES) to profile genetic variations in physiologically normal mucosa (PNM) and ESCC tumors, as well as PNM of non-ESCC subjects. We found significant differences in mutation frequencies of NOTCH1 and NOTCH2, copy number variations (CNVs) at both gene and chromosomal arm levels, and cancer-related HIPPO, WNT, and NRF2 signaling pathways between ESCC tumors and normal mucosa. Our analysis of both primary tumors and paired PNM in bifocal ESCC revealed three different primary tumor evolution modes, and the most common mode exhibited a complete genomic divergence in all the samples from the same patient. Furthermore, the mutation frequency of TP53 was significantly higher in ESCC cases than that in non-ESCC cases. Overall, our results provide important evidence for further elucidating the mechanisms of genetic mutations underlying the cause of ESCC.

Clinical Treatment Study of Secondary Multiple Squamous Cell Carcinoma with Psoriasis Vulgaris.

Dermatologic diseases are the fourth most frequent nonfatal common illness, yet they have a psychological, economical, and professional burden that is comparable to or larger than other chronic conditions. From a survey in China of 6 provinces, the overall prevalence of psoriasis with squamous cell carcinoma was 0.47%. According to the current investigation, the outburst of skin disease was not associated with gender, but mainly with the climate of the environment; that is, dry cold weather will more likely to induce psoriasis. Approximately 3% of people around the world have psoriasis, which is near the most common autoimmune skin disease in adults. By simple estimation, there are at least two hundred million psoriasis patients in the world. Therefore, it is not just a simple health problem in a country or a region but a serious global challenge. Of note, about half of the adult patients had been reported to be sick in their childhood and they mostly fell ill around 10 years old. Actinic keratosis is perhaps the most common, followed by squamous cell carcinoma and, to a lesser extent, acne vulgaris, psoriasis, and hidradenitis suppurativa, as well as dermatitis herpetiformis. 5-Fluorouracil (5-FU) 0.5 percent is used topically to treat actinic keratosis and squamous cell carcinoma with good outcomes, while it might cause significant toxicity in certain patients. Dapsone, a Valosin-containing protein, is a medication that is often used to treat inflammatory skin disorders like psoriatic arthritis, but it can occasionally cause hemolytic anemia. Furthermore, biologic medications for the treatment of moderate-to-severe psoriasis and multiple squamous cell carcinoma have proven to be successful and safe; nevertheless, a small percentage of patients do not react to biologic treatment in the long term or do not respond at all. Based on the data from the China Food and Drug Administration, the majority of chemical drugs are utilized as the topical formulations, while Chinese medicines are mainly delivered by an oral route, suggesting that the market for topical preparations of Chinese medicine to treat skin diseases like psoriasis is worth exploration. This large interindividual diversity in response could be caused by changes in genes that encode proteins implicated in the disease's pathologic environment or the medication's mechanism of action. Pharmacogenetics is the study of the association between genetic differences and medication response, which is valuable for identifying nonresponsive patients and those who are more likely to suffer toxicity as a result of treatment. This study highlights the pharmacogenetic recommendations for dermatology therapies that have the strongest evidence at this time, highlighting those that have been incorporated in clinical practice guides. Pharmacogenetic clinical guidelines for multiple squamous cell carcinoma and psoriasis vulgaris were found in this investigation. Here, for multiple squamous cell carcinoma trichohyalin-like 1 (TCHHL1), 5-fluorouracil (5-FU) 0.5% is recommended. Along with that dapsone, Valosin-containing protein can be recommended for treating the psoriasis vulgaris. We made some clinical trials over the two diseases, and from the result obtained, we hypothesize that the suggested drug may be a novel therapeutic target in treating the multiple squamous cell carcinoma with psoriasis vulgaris.

Evaluation of the risk of metachronous multiple squamous cell carcinoma of the head and neck after transoral surgery based on the genetic polymorphisms of alcohol dehydrogenase 1B and aldehyde dehydrogenase 2.

Patients with superficial head and neck squamous cell carcinoma (HNSCC) can be completely treated by techniques of transoral surgery (TOS). The aim of this study was to evaluate the risk of metachronous multiple HNSCC arising after TOS based on alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2). We registered patients who underwent TOS for superficial HNSCC. Buccal cell samples were obtained by using a cotton swab to examine two single nucleotide polymorphisms in ADH1B and ALDH2 genotyping. We used Cox proportional hazards models to examine the risk of metachronous HNSCC. A total of 198 patients who underwent TOS for HNSCC were evaluated. In multivariate analysis, risks for second HNSCC were ADH1B*1/*1 [hazard ratio (HR), 1.88; 95% confidence interval (CI), 1.11-3.19; P = 0.02], ALDH2*1/*2 (HR, 2.11; 95% CI, 1.00-5.16; P = 0.048) and alcohol consumption before TOS (HR, 1.17; 95% CI, 1.06-1.27; P = 0.01). The 5-year incidence rates of second primary HNSCC in the temperance group and the non-temperance group were 20.8 and 46.5%, respectively (HR, 0.54; 95% CI, 0.31-0.92; P = 0.02). Cumulative development rates of third HNSCC in the temperance group and non-temperance group at 10 years were 11.3 and 36.1%, respectively (HR, 0.19; 95% CI, 0.03-0.65; P = 0.006). ADH1B*1/*1, ALDH2*1/*2 and moderate or heavy alcohol consumption before treatment are independent risk factors of metachronous HNSCC. Since it was shown that temperance decreased the incidences of second and third metachronous HNSCC, advice to discontinue alcohol drinking is necessary.

Evaluation of Pharyngeal Background Mucosa in Patients with Superficial Hypopharyngeal Carcinoma

Transoral surgery (TOS) has become increasingly popular for patients with superficial hypopharyngeal squamous cell carcinoma (SCC). However, the number of patients in whom metachronous multiple SCC of the head and neck (HNSCC) occurs has also increased. In this study, we investigated whether multiple lugol-voiding lesions (LVLs) in the pharyngeal background mucosa observed during TOS would be a biomarker of metachronous HNSCC. Retrospective study. We examined 362 patients who underwent TOS for superficial hypopharyngeal carcinoma. Endoscopic images were reviewed in a blinded fashion by two endoscopists. LVLs in the pharyngeal mucosa were graded as follows: A, no lesions; B, 1 to 4 lesions; and C, ≥5 lesions per endoscopic view. Cumulative incidence curves of secondary HNSCC in the groups of grades A, B, and C revealed 3-year incidence rates of 14.4%, 18.8%, and 29.3%, respectively (P=.001 for A vs. C and P=.002 for B vs. C). Cumulative incidence curves of third HNSCC in the groups of grades A, B. and C revealed 5-year incidence rates of 3.9%, 9.8%, and 19.6%, respectively (P=.001 for A vs. C and P=.006 for B vs. C). Cumulative incidence curves of fourth HNSCC in the groups of grades A, B, and C revealed 7-year incidence rates of 0%, 2.3%, and 13.2%, respectively (P=.025 for A vs. C and P=.009 for B vs. C). Multiple LVLs in the pharyngeal mucosa increase the risk of development of metachronous multiple HNSCC. 3 (nonrandomized, controlled cohort/follow-up study) Laryngoscope, 131:2036-2040, 2021.

Simultaneous endoscopic submucosal dissection for synchronous multiple early esophageal squamous cell carcinoma: a propensity score-matched analysis.

The clinical effect of endoscopic submucosal dissection (ESD) in the treatment of early esophageal squamous cell carcinoma (EESCC) is widely recognized. However, the long-term treatment outcome of simultaneous ESD for multiple EESCC currently remained unknown. Hence, this study was aimed at further evaluating the long-term outcome of simultaneous ESD for synchronous multiple EESCC by comparing with ESD for single EESCC. Consecutive patients who underwent ESD for EESCC from June 2008 to June 2018 were included. Propensity score-matched analysis was used to compensate for the differences in age, sex, tumor location, tumor size, and tumor invasion depth between simultaneous and single ESD groups. Treatment outcomes including en bloc resection rate, curative resection rate, complication rate, and long-term outcomes including overall survival (OS), recurrence-free survival (RFS), metachronous recurrence were compared between the 2 groups after matching. The propensity score-matched analysis included 332 lesions (166 patients) and 332 lesions (332 patients) in simultaneous and single ESD groups, respectively. Among all the outcomes, en bloc resection, curative resection, 5-year OS, and 5-year RFS rates were comparable. Complications were more common in the simultaneous ESD group (15.06% vs. 9.64%, P = 0.073). The 5-year metachronous recurrence rates were significantly high in the simultaneous ESD groups (24.28% vs. 6.99%). Simultaneous ESD is an effective and safe methodology for synchronous multiple EESCC; it also reduces hospital stay and medical expenses. The risk of metachronous recurrence is higher for patients with synchronous multiple EESCC; thus, more intensive strategies are required.

Leukemia Cutis in a Patient with Rare Indolent T-Prolymphocytic Leukemia - A Case Report and Review of the Literature

Abstract Introduction/Objective T-cell prolymphocytic leukemia (T-PLL) is rare, comprising 2% of mature lymphocytic leukemias in adults. Clinical course is usually aggressive, however, 20-30% patients can have an indolent early phase. Most patients present with extensive disease with peripheral blood lymphocytosis, hepatosplenomegaly, and lymphadenopathy. T-PLL has a higher incidence in patients with ataxia-telangiectasia. Methods We present a case of a 67-year old man with history of somatic mutation of ataxia-telangiectasia gene (ATM) and multiple malignancies, including melanoma, skin and laryngeal squamous cell carcinomas, adrenal adenoma and spindle cell lung tumor (diagnosed on biopsy), who developed leukemia cutis during an indolent phase of T-PLL. Results Initial diagnosis of T-PLL was on routine complete blood count when patient had mild atypical lymphocytosis (5.5 x 109/L). Flow-cytometry immunophenotyping detected CD4 + 8 positive mature T-cells with no aberrant loss of T- cell antigens, and molecular studies confirmed clonal T-cell receptor beta and gamma gene rearrangements. T-PLL associated leukemia cutis was diagnosed on a leg skin nodule biopsy 10 months later. Subsequent bone marrow biopsy demonstrated low level involvement by T-PLL. The patient’s T-PLL followed an indolent trajectory for three years and treatment was withheld until symptomatic presentation. Rapid disease progression was heralded with emergence of widespread T-PLL leukemia cutis, rapidly increasing lymphocytosis, extensive lymphadenopathy, splenomegaly and increasing LDH levels. Conclusion Skin involvement is reportedly identified in 20% to 50% of T-PLL cases in some series. Skin manifestations can be heterogenous with a broad clinical differential. T-PLL associated leukemia cutis may not be recognized owing to the overall low incidence and in skin lesions appearing during an undiagnosed indolent early phase of T-PLL.We highlight the importance of accurate evaluation of non-specific skin lesions in early detection of T- PLL. Being aware of this diagnosis and early engagement in an interdisciplinary approach may allow for better outcomes of this aggressive malignancy.