Dermatology Projects 2022

Non melanoma skin cancer in SOC

Faculty Mentor’s Name: Dr. Beverly Johnson
Email: johnsonb2@ufl.edu
Phone Number: (352) 594-1500
Project Category: Case Review
International Component or Travel: No

Research Project Description:

Skin cancer is often caused by sun exposure and sunburn. When patients with darker skin get non melanoma skin cancer, the reasons are not clear. When patients who don’t have light skin, and dont burn easily, there may be other factors at play that have yet to be studied. This project will be a case review of skin cancers diagnosed in non whites at the U F dermatology clinic from 2015 to the present. Our goal will be to identify and risk factors that might inform a better outcome if we know how to avoid them. The history and skin examination should also be more focused on non sun exposed skin since this is where these cancers are often located.
The medical study will help us collate the data from our dermatology surgery database.

Pediatric Epithelioid Melanocytoma

Faculty Mentor’s Name: Dr. Jennifer Schoch
Email: johnsonb2@ufl.edu
Phone Number: (352) 594-1500
Project Category: Case Review
International Component or Travel: No

Research Project Description:

Skin

This is a multicenter retrospective study exploring the rare diagnosis of pediatric epithelioid melanocytoma. The MSRP student will be responsible for reviewing all possible cases of PEM and entering data into REDCap database. A self-study of medical writing will also be included. The student will also be asked to assist with other clinical trials/research projects as available.

Cutaneous Squamous Cell Carcinoma (cSCC) Database Development: Focusing on High Risk cSCCs, with a Focus on the Presence of Perineural Invasion (PNInv).

Faculty Mentor’s Name: Dr. Scott Fosko
Email: sfosko@dermatology.med.ufl.edu
Phone Number: (314) 757-0996
Project Category: Literature Review
International Component or Travel: No

Research Project Description:

Background
Cutaneous squamous cell carcinoma (cSCC) is a growing public health concern with an estimated 1,000,000 cases to occur annually in the United States. (Rogers et al., 2015) Fortunately, the majority of cSCC present early, have indolent behavior and are effectively managed most commonly with surgery, radiation or other destructive therapies. Most (80-90%) occur on the head and neck area. Long-term survival for all cSCC patients is high with 5 year survival rates greater than 90%. There are a minority (3-5%) of cSCC that display aggressive clinical behavior as either locally advanced cSCC (lacSCC) or metastatic cSCC (mcSCC). (Stratigos et al.,2020; Dessinioti et al., 2022; Schmults et al., 2013) These high risk cSCC have increased risk of local recurrence, regional lymph node disease and distant metastases. Most mcSCC occur on the head and neck with the involvement of the parotid gland and/or cervical lymph nodes. (Venables et al., 2019). Metastatic cSCC have a much worse prognosis with long term survival rates significantly decreased with 10 year survival less than 30% reported in one cohort of head and neck cSCCs. (Goepfert et al., 1984) There is some evidence that deaths from cSCC may outpace those from melanoma, due to the much greater growing incidence of cSCC. (Karia et al., 2013).

Advanced cSCC disease is a much more challenging cohort and is reported to have higher rates of local recurrence and metastases. (Dessinioti 2022) Identifying high risk cSCC tumors early in their initial presentation can be challenging. Risk factors predicting adverse prognosis have been well identified. (Veness, 2007; Schmults et al., 2013, Thompson et al., 2015)These include tumor clinical features, primarily tumor size and depth of tissue invasion, tumor histopathologic features, primarily degree of differentiation and the presence of perineural invasion, and host factors, primarily immune status. While high risk features are known, they are not always identified, especially at the patient’s initial presentation.

One particular risk factor is the presence of perineural invasion (PNInv). PNInv contributes to a tumor having a higher rate of local recurrence, regional disease and metastatic potential. (Goepfert et al., 1984; Lobl et al., 2022; Feinstein et al., 2019). When detected PNInv prompts a more aggressive management approach. This most commonly involves Mohs surgery, where surgical margins are more thoroughly evaluated versus conventional wide local excision (WLE). Further surgical resection maybe required for example with tumors of the head and neck, where a superficial parotidectomy and neck lymph node dissection may be recommended. Additionally, the role of adjuvant radiation therapy is often discussed. (Mendenhall et al., 2012; Holtzman et al., 2020; Han et al., 2007).

Identifying PNInv preoperatively can prompt imaging studies such as computed tomography (CT) scans or magnetic resonance imaging (MRI). These imaging modalities may detect subclinical disease and support a more aggressive treatment plan. The identification of PNInv with cSCC can be difficult to detect histopathologically. There is limited literature providing guidance on when to suspect the presence of PNInv when reviewing cSCC histopathologic tissue samples, such as the presence of perineural inflammation (PNInf) or poorly or moderately differentiated cSCC. (Green et al., 2012; Beal et al., 2018).

Objectives and Hypotheses
The main objective of this research project is to focus on high risk features for cSCC with the focus on PNInv. The question to be addressed is, “when during a patient’s clinical course is PNInv identified and detected?” Is it found at 1. initial presentation on skin biopsy? 2. At the time of initial management with surgical resection with Mohs surgery or WLE? or 3. At the time of clinical recurrence and its management? The hypothesis is that cSCC with PNInv is more commonly identified at the time of clinical recurrence. It is also hypothesized that Mohs surgery provides the opportunity to detect cSCC with PNInv compared to conventional WLE and associated histopathologic evaluation.

Methods
The research project will be a chart review with data collection of cases of cSCC managed at the University of Florida College of Medicine clinical practices, both in Gainesville and Jacksonville. Potential data sources will include 1. Mohs surgical logs, Jacksonville and Gainesville, including Veterans Administration Hospital 2. Department of Oral and Maxillofacial Surgery, Jacksonville case logs 3. Department of Otolaryngology, Gainesville, , 4. Radiation Oncology case logs, 5. Dermatopathology lab information system, 6. Surgical pathology lab information system, 7. Cancer Center Tumor Registry. Each of these data sources provide unique opportunities with regard to patient presentations, with primary tumors commonly managed in the Department of Dermatology/Mohs Surgery and recurrent tumors more commonly seen in the Departments of Radiation Oncology and Head and Neck Surgery.

Role of Medical Student
The medical student’s role will be to work with respective Departments’ data sources and extract key data variables and enter them in the database. Once a sufficient number of cases are entered, data analysis will begin. This will be coordinated with our biostatisticians. Students will have the opportunity to participate in various outputs of the research, which include: 1. Oral and Poster presentations at Department Research Symposiums, 2. Abstract submissions, 3. Manuscript development and publication, and 4. Possible presentation of research work at regional and national meetings as funding is available and 5. Grant applications.

The scope of the research project touches many Departments in the College of Medicine. This research project will provide medical students with a broad exposure across many areas of medicine, surgery and pathology. It will support their interest development with regard to future residency programs. They include Dermatology, Head and Neck Surgery, Radiation Oncology, Medical Oncology, Family Medicine, Internal Medicine, Dermatopathology and Surgical Pathology.

Potential Patient Benefit to the Research
If it is found that PNInv is more commonly detected at tumor recurrence, a time where it is known the patient is now at a significant disadvantage to having a good outcome, this identifies a clinical practice gap. The gap will focus on identifying why perineural invasion is more often identified in a delayed fashion, rather than at the time of the patient’s initial presentation. With this information, data could contribute to practice guidelines that can improve the detection of PNInv at an earlier time in the patient’s presentation. In doing so, this could provide the patient a better initial evaluation and treatment approach and drive better patient outcomes. It is possible that early detection of perineural invasion can prompt a more thorough evaluation and treatment approach that will provide patients with survival rates closer to the reported overall high survival rates of all patients with cSCC. This work can potentially minimize the risk of a patient with cSCC progressing to a more locally advanced cSCC with possible metastases.

An overarching goal from this research, through presentations and publications, will be to document the many benefits of coordinated multidisciplinary care for our patients with high risk cSCC at the University of Florida. This can contribute to the University of Florida continue to develop and grow its expertise in the field of cutaneous oncology and strengthen its leadership in patient care, locally, regionally and nationally.

Funding

Funding will be based on:

  1. Medical Student Summer Research Program Scholarships
  2. Department of Dermatology Medical Student Trust Fund
  3. Cancer Center Funding

Publications

Beal BT, Dhanda MM, Chu, MB, Varra V, Armbrecht ES, Slutsky JB, Fosko, SW. Tumor Characteristics Predicting Perineural Invasion in Cutaneous Squamous Cell Carcinoma Identified by Stepwise Logistic Regression Analysis.. SKIN The Journal of Cutaneous Medicine, [S.l.], nov. 2018. ISSN 2574-1624. Available at: https://jofskin.org/index.php/skin/article/view/356.

Dessinioti C, Pitoulias M, Stratigos AJ. Epidemiology of advanced cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol. 2022;36(1):39-50. doi:10.1111/jdv.17709

Feinstein S, Higgins S, Ahadiat O, Wysong A. A Retrospective Cohort Study of Cutaneous Squamous Cell Carcinoma With Lymph Node Metastasis: Risk Factors and Clinical Course. Dermatol Surg. 2019;45(6):772-781. doi:10.1097/DSS.0000000000001828

Goepfert H, Dichtel WJ, Medina JE, Lindberg RD, Luna MD. Perineural invasion in squamous cell skin carcinoma of the head and neck. Am J Surg. 1984;148(4):542-547. doi:10.1016/0002-9610(84)90385-4
Green JS, Tournas JA, Allen EJ, Youker SR, Fosko SW. Mohs frozen tissue sections in comparison to similar paraffin-embedded tissue sections in identifying perineural tumor invasion in cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2012;67(1):113-121. doi:10.1016/j.jaad.2011.03.015

Han A, Ratner D. What is the role of adjuvant radiotherapy in the treatment of cutaneous squamous cell carcinoma with perineural invasion?. Cancer. 2007;109(6):1053-1059. doi:10.1002/cncr.22509

Holtzman AL, Mendenhall WM. High-dose conformal proton therapy for clinical perineural invasion in cutaneous head and neck cancer. Oral Oncol. 2020;100:104486. doi:10.1016/j.oraloncology.2019.104486

Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013;68(6):957-966. doi:10.1016/j.jaad.2012.11.037

Lobl M, Feinstein S, Lauer S, Sutton A, Wysong A. Recurrence Status, Perineural Invasion, and Hypothyroidism Are Associated With Lymph Node Metastasis in Cutaneous Squamous Cell Carcinoma: A Case-Control Study [published online ahead of print, 2022 Feb 1]. Dermatol Surg. 2022;10.1097/DSS.0000000000003396. doi:10.1097/DSS.0000000000003396

Mendenhall WM, Ferlito A, Takes RP, et al. Cutaneous head and neck basal and squamous cell carcinomas with perineural invasion. Oral Oncol. 2012;48(10):918-922. doi:10.1016/j.oraloncology.2012.02.015

Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence Estimate of Nonmelanoma Skin Cancer (Keratinocyte Carcinomas) in the U.S. Population, 2012. JAMA Dermatol. 2015;151(10):1081-1086. doi:10.1001/jamadermatol.2015.1187

Stratigos AJ, Garbe C, Dessinioti C, et al. European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention. Eur J Cancer. 2020;128:60-82. doi:10.1016/j.ejca.2020.01.007

Schmults CD, Karia PS, Carter JB, Han J, Qureshi AA. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol. 2013;149(5):541-547. doi:10.1001/jamadermatol.2013.2139

Thompson AK, Kelley BF, Prokop LJ, Murad MH, Baum CL. Risk Factors for Cutaneous Squamous Cell Carcinoma Recurrence, Metastasis, and Disease-Specific Death: A Systematic Review and Meta-analysis. JAMA Dermatol. 2016;152(4):419-428. doi:10.1001/jamadermatol.2015.4994

Venables ZC, Autier P, Nijsten T, et al. Nationwide Incidence of Metastatic Cutaneous Squamous Cell Carcinoma in England. JAMA Dermatol. 2019;155(3):298-306. doi:10.1001/jamadermatol.2018.4219

Veness MJ. High-risk cutaneous squamous cell carcinoma of the head and neck. J Biomed Biotechnol. 2007;2007(3):80572. doi:10.1155/2007/80572