Via Research Recognition Day Program VCOM-Carolinas 2025

Case Reports

Melanoma in an Unthinkable Location: A Case Report of Primary Cervical Melanoma with Metastasis Michael S. Benavidez Arias, MA, OMS-III, 1 Danielle Pierson, MA,OMS-III, 1 Grant Warren M.D. 2 , Carlton Schwab M.D. 2

1 Edward Via College of Osteopathic Medicine, Spartanburg, SC 2 Spartanburg Regional Healthcare System, Spartanburg, SC

Introduction

Discussion

Case Presentation, continued

Background: Cervical cancer is one of the most prevalent gynecological cancers globally. While squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the predominant histological subtypes, primary malignant melanoma of the cervix (PMMC) is extremely rare (Table 1). 1

Findings & Novel Therapeutic Approach Overview • The patient presented with persistent vaginal bleeding, leading to the discovery of a cervical mass. • Histopathological analysis confirmed PMMC, and imaging studies revealed metastatic spread to the liver. • The innovative aspect of this case lies in the combination of chemotherapy and immunotherapy, a treatment strategy not commonly reported in PMMC management, especially at such an advanced stage. • This approach introduces a potentially transformative method for tackling this aggressive malignancy. • Showcases an adaptation of therapeutic strategies in response to the specific challenges posed by stage IVB PMMC. Uniqueness and Literature Comparative Analysis • While PMMC cases are rare, stage IVB presentations are even rarer, with no comprehensive reports available at all • The existing literature primarily focuses on early-stage diagnoses, with treatments predominantly involving surgical interventions, making the advanced stage of this case particularly noteworthy. 2 • It provides a crucial comparison point by detailing a multimodal treatment strategy in a late-stage context, thus offering a new perspective on potential efficacy and outcomes. • Sets an important example for future documentation and research, emphasizing the necessity for innovative approaches in similarly advanced stages of PMMC. Limitations and Clinical Insights • The rarity of PMMC, especially at stage IVB, poses significant challenges in establishing standardized treatment protocols. 3 • The absence of extensive clinical trials or large case series limits the ability to generalize findings. • Long-term follow-up data would be crucial to understand the durability of the response to the treatment regimen. • Unlike SCC and AC, PMMC lacks premalignant precursors detectable on a Pap smear. Biopsies should be performed for cervical abnormalities even with normal Pap results to ensure timely diagnosis. 4 Early biopsy and histopathological examination are essential for prompt diagnosis. Future Research and Clinical Impact • Optimal management of PMMC has not achieved consensus due to scarcity, with clinicians often adapting protocols used for SCC and AC. • Larger collaborative studies are needed to establish evidence-based treatment strategies and improve outcomes for this aggressive malignancy.

Biopsy pathology report • Immunohistochemical stains p16: Negative HPV E6/E7 mRNA ISH: Negative (no signal) CK AE1/AE3: Negative

PET-CT Imaging of Tumor Sites

SOX10: Positive Mart-1: Positive

SOX-10 RED: Positive Mart-1 RED: Positive CD45: Negative PAX-8: Weakly positive CK OSCAR: Negative CK8-18: Negative ER: Negative S100 RED: Positive HMB45: Positive

Case Presentation Chief Complaint: Vaginal bleeding History of Present Illness: 58 y.o. G4P4000 post-menopausal presents to clinic for a cervical biopsy. She was referred from the emergency department due to persistent vaginal bleeding for approximately 6-7 weeks. At the emergency department, an initial pelvic examination and transvaginal ultrasound revealed a heterogeneous mass on her cervix. Her last Pap smear, conducted about two years ago, was reported as normal. Physical Exam: VITALS: BP 112/74, HR 80, T 98 ° F (36.7 ° C). GENERAL: well-developed, alert and in no acute distress BREASTS: symmetrical without masses, dimpling, or nipple discharge Past Medical Hx: Anxiety, Asthma, Bipolar 1 disorder, Depression Past Surgical Hx: Breast biopsy excision (benign), hernia repair, mandible fracture surgery, shoulder surgery, tonsillectomy Family Hx: Mother-cervical cancer (onset 19-20y), maternal Table 1 . This table compares the relative prevalences in cervical cancer, HPV association, cell origin, tumor markers, and clinical courses of SCC, AC, and PMCC. SC and AC are the most common types of cervical cancer with a strong link to HPV, while PMCC is rare, not associated with HPV, and exhibits an aggressive clinical course. Goal: This case study aims to emphasizes the importance of recognizing PMMC in the differential diagnosis of atypical cervical lesions and highlights the need for tailored treatments. We seek to contribute valuable insights into the complexities of diagnosing and treating this rare cancer form, advocating for better patient outcomes.

Treatment Management • Involved a multi disciplinary approach including the initiation of a chemotherapy and immunotherapy regimen comprising carboplatin, paclitaxel, pembrolizumab, and bevacizumab. metastatic disease to the liver (Fig. 1) , corroborated by MRI findings. Imagining Results • PET/CT scan indicated

Figure 1: PET-CT Imaging in the Staging of Endocervical Melanoma A whole-body PET-CT scan using 10.9 millicurie of Fluorodeoxyglucose F-18 was conducted for detailed imaging and anatomical localization. Axial PET-CT slices of the liver depict multiple hypermetabolic lesions, the most significant in the right lobe with SUV(Standardized Uptake Value) max of 5.0 (A) and another with SUV max of 4.8 (B) , suggestive of metastatic involvement. (C) Axial PET-CT through the pelvis shows an intensely hypermetabolic tumor mass in the endocervical region extending into the lower uterine segment, with SUV max of 20.4, measuring 4.9 x 3.3 cm. (D) Whole-body PET scan highlighting areas of increased metabolic activity throughout the body, with specific focus on the endocervical region and liver.

Follow up • Throughout her treatment, she has consistently maintained a good level of function and managed side effects effectively. • She has shown great resilience and adherence to her treatment plan. • We will continue to perform periodic scans to monitor her response to the treatment and schedule her for regular evaluations every three weeks to repeat her CBC, CMP, TSH, T4, and magnesium levels before her next infusion. Outcome • The patient’s treatment course has involved managing chemotherapy induced alopecia and fatigue, with ongoing supportive counseling and smoking cessation efforts.

ABDOMEN: soft, +BS, no hernia UTERUS: anteverted, nontender, normal size and contour ADNEXA: not palpable CERVIX: normal without lesions VAGINA: well rugated, well supported, physiologic discharge. 3-4 cm mass protruding through the cervical os into the vagina

grandmother- lung caner Social Hx: 45 pack-year

smoking, Marijuana drug user, no alcohol, defer sexual history question Review of Systems: Negative for all except vaginal bleeding

References 1) Rimal, Surya & Shrestha, Ramesh & Adhikari, Purbesh & Basnet, Pritha & Rijal, Pappu & Regmi, Mohan. (2020). Primary Malignant Melanoma of Uterine Cervix. Nepal Journal of Obstetrics and Gynaecology. 15. 86-88. 10.3126/njog.v15i1.29352. 2) Jiang, G., Li, R. H., Sun, C., Liu, Y. Q., & Zheng, J. N. (2014). Dacarbazine combined targeted therapy versus dacarbazine alone in patients with malignant melanoma: a meta-analysis. PloS one , 9 (12), e111920. https://doi.org/10.1371/journal.pone.0111920 3) Zhang, M., Yin, R., Song, L., Zhong, L., & Wang, R. (2024). Primary cervical malignant melanoma that was successfully treated with pembrolizumab: a case report and literature review. Frontiers in oncology , 14 , 1400257. https://doi.org/10.3389/fonc.2024.1400257 4) National Comprehensive Cancer Network. (2024). Cervical Cancer (version 4.2024) . Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf

Special thanks to Dr. Warren and Dr. Schwab for their guidance and helpful feedback. We deeply appreciate the patient for giving us permission to share this case report. Acknowledgements

2025 Research Recognition Day

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