Malignant melanoma presenting as a thyroid mass with synchronous retroperitoneal metastases in a 55-year-old male: a case report

Introduction

Malignant melanoma (MM) is an aggressive neoplasm characterized by high metastatic potential and a poor clinical prognosis (1). Approximately 2% to 3% of MM patients have only metastatic lesions, but no primary lesion can be found. This situation is referred to as melanoma of unknown primary (MUP) (2).

Secondary involvement of the thyroid due to melanoma is relatively rare, accounting for less than 5% of melanoma cases (1). Most frequently, thyroid metastases are discovered as late-stage events or during post-mortem autopsies (1,3). MUP presenting primarily as a rapidly growing, clinically dominant thyroid mass accompanied by synchronous retroperitoneal metastases is an extraordinary clinical rarity. In the absence of a definitive skin lesion history, the lesion is easily confused with primary anaplastic or medullary thyroid carcinoma, potentially causing delayed diagnosis and improper local therapy.

This case report presents a 55-year-old male with MUP who presented with a rapidly enlarging thyroid mass, regional lymphadenopathy, and a synchronous occult splenorenal recess mass. This report aims to illustrate the real-world diagnostic challenge of managing metastatic lesions that mimic primary thyroid cancer, and to detail how whole-body ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and patient-specific three-dimensional (3D)-printed physical models can be utilized by a multidisciplinary team to plan safe, effective multi-site cytoreductive surgeries. We present this article in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0270/rc).

Case presentation

A 55-year-old man presented with a painless, progressively enlarging mass in the neck and right shoulder over the past three months. The patient has no obvious difficulty swallowing, nor any respiratory distress caused by tracheal compression. The patient reported no personal or family history of malignancy. Physical examination revealed a large, firm mass in the left thyroid lobe and a palpable mass in the right supraclavicular region (Figure 1). No suspicious pigmented lesions were identified on the skin, oral mucosa, genital mucosa, or uvea, and the patient reported no prior excision of skin lesions. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Figure 1 Clinical and intraoperative images of the patient. (A) A distinct mass can be palpated in the right supraclavicular region, and the thyroid area on the left side of the neck is slightly elevated. (B) Intraoperative laparoscopic view of the hypermetabolic lesion located in the splenorenal recess. The lesion demonstrates focal black pigmentation.

A fine-needle aspiration cytology (FNAC) was then performed on the left thyroid nodule, revealing highly atypical cells suggestive of an undifferentiated malignant tumor. The patient subsequently underwent ¹⁸F-FDG PET/CT, which revealed multi-system involvement. A hypodense mass measuring 5.1 cm ×4.1 cm was identified in the left thyroid lobe, exhibiting a maximum standardized uptake value (SUV_max) of 13.2. Additionally, an enlarged lymph node measuring 4.9 cm × 3.9 cm with an SUV_max of 10.6 was detected in the right supraclavicular fossa (Figure 2). Furthermore, a hypermetabolic nodule measuring 2.0 cm × 1.9 cm with an SUV_max of 8.6 was found within the splenorenal recess.

Figure 2 Preoperative ¹⁸F-FDG PET/CT imaging findings. (A) Coronal and sagittal maximum intensity projection images demonstrating hypermetabolic lesions in the left thyroid lobe, right supraclavicular region, and splenorenal recess. (B-D) Axial fused PET/CT images demonstrating hypermetabolic lesions in the splenorenal recess (B), left thyroid lobe (C), and right supraclavicular fossa (D). ¹⁸F-FDG PET/CT, ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography.

Preoperatively, 3D printing technology was utilized to delineate the anatomical relationship between the cervical masses and adjacent critical neurovascular structures (Figure 3). Given the limited number of metastatic sites and the resectability of the detected tumors, the patient underwent total thyroidectomy, right cervical lymph node dissection, and synchronous resection of the retroperitoneal lesion for cytoreduction and diagnostic confirmation, thereby improving the therapeutic response to later systemic treatment.

Figure 3 Preoperative 3D reconstruction of cervical anatomy. 3D, three-dimensional.

Postoperative histopathological examination confirmed metastatic melanoma in the left thyroid gland, right supraclavicular lymph nodes, right cervical lymph nodes (levels III and V), and splenorenal recess (Figure 4). Immunohistochemical analysis of the resected tumor specimen showed that the neoplastic cells were positive for melanocytic markers (HMB-45, MART-1, S-100, and vimentin) and negative for epithelial, lymphoid, vascular, and myogenic markers. The Ki-67 proliferation index is approximately 35%. Molecular analysis identified the BRAF V600E mutation.

Figure 4 Histopathological features of the metastatic melanoma (H&E staining). (A) Low-power view (×100 magnification) showing scattered pigmented deposits. (B) High-power view (×400 magnification) demonstrating scattered melanin pigmentation, consistent with the diagnosis of melanoma. H&E, hematoxylin and eosin.

Based on immunohistochemical and molecular analyses, the disease was ultimately diagnosed as metastatic MUP, classified as stage IV disease (TxN3M1c) according to the American Joint Committee on Cancer (AJCC) staging system. The distribution of lesions and absence of a confirmed primary tumor suggested a diagnosis of metastatic MUP origin. The patient began receiving combination targeted therapy with dabrafenib and trametinib three weeks after surgery, tolerated the treatment well, and showed encouraging early oncological response. At the three-month follow-up, the patient’s wound healing was favorable, with no infection or other complications such as abnormalities in liver or kidney function.

Discussion

Melanoma-related thyroid metastasis typically presents as a solitary or multinodular mass, indistinguishable from primary thyroid carcinoma on imaging or cytology (3). Although an abundant blood supply may facilitate the circulation of melanoma cells to the thyroid, the microenvironment characterized by high oxygen levels, high iodine concentration, and rapid blood flow may be unfavorable for long-term tumor cell engraftment and proliferation, thereby leading to rare thyroid metastases (4). Autopsy series suggest that secondary malignancies of the thyroid account for only 1.4% to 3.9% of all thyroid neoplasms (5). In this case, the patient’s main manifestation was a large left thyroid and right supraclavicular mass, closely mimicking primary thyroid cancer with regional metastasis. The occult nature of the retroperitoneal metastasis further complicated treatment.

The complex and compact anatomy of the head and neck often renders routine imaging insufficient for delineating tumor boundaries and surgical margins (6). In this case, 3D printing technology was employed to clarify the spatial relationship between the thyroid and supraclavicular masses and adjacent nerves and vessels. The integration of 3D printing facilitates the formulation of individualized surgical strategies, enhancing resection precision while safeguarding vital anatomical structures (7).

Given the high glycolytic activity characteristic of melanoma cells, ¹⁸F-FDG PET/CT is an effective tool for assessing the extent of distant metastasis (8). Here, ¹⁸F-FDG PET/CT successfully identified an occult metastatic lesion in the splenorenal recess (SUVmax 8.6). By integrating data from multiple sites, the modality provided a comprehensive assessment of the systemic tumor burden, offering a strategic roadmap for multi-site surgery and establishing a rationale for postoperative systemic therapy. While histopathology is mandatory to establish a definitive diagnosis of MUP, whole-body ¹⁸F-FDG PET/CT provides critical imaging evidence to differentiate metastatic melanoma from primary thyroid neoplasms, either by uncovering undetected primary cutaneous lesions or validating multifocal systemic metastatic involvement (9,10).

Distinguishing MUP from primary thyroid tumors before definitive histopathologic diagnosis remains a diagnostic challenge in this case (1). Due to its pleomorphic cellular morphology, MM can be easily confused with other malignancies, such as medullary or anaplastic thyroid carcinoma. In addition, soft tissue clear cell sarcoma (CCS) has similar immunohistochemical features, which also pose a challenge for differential diagnosis (2). Melanocyte lineage markers are essential for distinguishing metastatic melanoma from other malignancies, such as anaplastic or medullary thyroid carcinoma (11). Immunohistochemistry showed strong positivity for melanocytic markers (HMB-45, MART-1, S-100, vimentin) and a Ki-67 index of ~35%, strongly supporting the diagnosis of MUP.

The BRAF V600E mutation is associated with constitutive activation of the MAPK signaling pathway, promoting tumor proliferation and survival. BRAF-mutant melanomas often exhibit a propensity for early and widespread dissemination, which may explain the concurrent involvement of the thyroid and retroperitoneum in this patient (12). Targeted immunotherapy with dabrafenib combined with trametinib was initiated three weeks after surgery based on the mutation (13). Though initially worried about widespread metastatic disease, the patient fully accepted surgical resection and targeted therapy, showing excellent medication adherence and tolerability during three months of follow-up.

The management of metastatic melanoma has shifted from empirical treatment to precision, individualized care guided by molecular profiling and metabolic imaging (14). Complete surgical resection for the treatment of metastatic melanoma enables both definitive diagnosis and effective cytoreduction (15). In this case report, Preoperative ¹⁸F-FDG PET/CT and patient-specific 3D printing technology were used to guide the surgical approach and planning. The combination of systemic drug therapy and surgical resection can significantly improve the long-term survival rate of patients. In BRAF V600E-positive patients, adjuvant BRAF/MEK inhibitors or immune checkpoint inhibitors reduce recurrence and extend progression-free survival (13).

Conclusions

This case demonstrates that MM should be considered in the differential diagnosis of rapidly enlarging thyroid masses, even when no primary tumor is evident. ¹⁸F-FDG PET/CT identifies clinically silent metastatic foci throughout the body, while patient-specific 3D printing refines surgical strategy for combined cervical and retroperitoneal resection. In combination with the patient’s histopathology, immunohistochemistry, or molecular testing should be performed to confirm the diagnosis. A multidisciplinary approach is vital for managing the complexity of MUP and ensuring that patients receive precise, evidence-based care.

Acknowledgments

The authors thank the patient and his families for their assistance, as well as all clinical departments.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0270/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0270/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0270/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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