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Spontaneous regression of Markel cell carcinoma in anterior mediastinum without cutaneous involvement

Published online by Cambridge University Press:  09 November 2020

My-Lien Nguyen ,
M. Kole Melton ,
Salahuddin Ahmad Open the ORCID record for Salahuddin Ahmad [Opens in a new window]  and
Christina Henson
My-Lien Nguyen
Affiliation:
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, and Stephenson Cancer Center, Oklahoma City, Oklahoma, USA
M. Kole Melton
Affiliation:
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, and Stephenson Cancer Center, Oklahoma City, Oklahoma, USA
Salahuddin Ahmad*
Affiliation:
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, and Stephenson Cancer Center, Oklahoma City, Oklahoma, USA
Christina Henson
Affiliation:
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, and Stephenson Cancer Center, Oklahoma City, Oklahoma, USA
*
Author for correspondence: Salahuddin Ahmad, Department of Radiation Oncology, University of Oklahoma Health Sciences Center, and Stephenson Cancer Center, Oklahoma City, Oklahoma, USA. E-mail: salahuddin-ahmad@ouhsc.edu
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Abstract

Background:

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy typically involving the skin. The majority of MCC involves the head/neck region and the extremities. Despite the aggressive nature of the disease, there have been several case studies that report spontaneous regression. We report a unique case of spontaneous regression of an MCC in a peculiar region in the anterior mediastinum with no cutaneous involvement.

Methods:

A 50-year-old man who presented with a mobile low anterior neck mass, proven by biopsy, to be MCC. Subsequent PET/CT confirmed an FDG (Flurodeoxyglucose)-avid upper mediastinal mass. The mass gradually regressed over the course of 1 month subsequent to biopsy and was no longer palpable on exam or visible on subsequent CT scans. The patient was treated with intensity modulated radiation therapy with a total dose of 6,160 cGy in 28 fractions to the site of previously visible primary disease. At-risk nodal basins were also treated. On subsequent follow-up, the patient continued to have no clinical or radiographic signs of disease.

Discussion:

Spontaneous regression of an MCC is rare but has been reported mostly in the head/neck region following biopsy. It is unknown why spontaneous regression occurs. There is a possibility that biopsy may stimulate T-lymphocytes resulting in spontaneous regression.

Conclusion:

This is the first case to our knowledge of spontaneous regression of an MCC in the anterior mediastinum with no cutaneous involvement. Most MCC are seen clinically due to skin changes with a majority of cases occurring in the head/neck region.

Keywords

cutaneous involvementintensity modulated radiation therapyMerkel cell carcinomaspontaneous regression
Type
Case Study
Information
Journal of Radiotherapy in Practice , Volume 21 , Issue 2 , June 2022 , pp. 287 - 288
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Copyright
© The Author(s), 2020. Published by Cambridge University Press

Introduction

Merkel cell carcinoma (MCC) was first described by Toker Reference Toker1 in 1972 as a trabecular carcinoma of the skin. It is a rare, highly aggressive neuroendocrine malignancy that most commonly affects the skin. MCC most commonly occurs on the head and neck (50%) and extremities (40%), with the remainder occurring on the trunk. Reference Vesely, Murray and Neligan2 It predominantly affects older adults with fair skin and has a propensity for local recurrence and regional lymph node metastases, resulting in a 5-year survival rate of around 60%. Reference Tothill, Estall and Rischin3,Reference Schrama, Ugurel and Becker4 The annual incidence of MCC has risen from 0·5 cases per 100,000 cases in 2000 (95% CI: 0·4–0·5) to 0·7 cases per 100,000 cases in 2013 (95% CI: 0·7–0·8). Reference Paulson, Park and Vandeven5 Despite the aggressive nature of this malignancy, there have been reports of spontaneous regression. We report the first case of primary complete spontaneous regression (CSR) of MCC involving the anterior mediastinum and lacking cutaneous involvement.

Clinical History

We report on the treatment of a 50-year-old male patient who presented with a 3-month history of a mobile mass in his low anterior neck, near the sternal notch. Diagnostic CT confirmed a hypo-enhancing soft tissue mass in the upper anterior mediastinum at the level of the sternoclavicular joint, measuring 2·6 cm, without overlying skin changes. Ultrasound-guided FNA (Fine Needle Aspiration) biopsy was positive for MCC, CK20 (Cytokeratin 20) with dot-like perinuclear positive, synaptophysin positive, TTF (thyroid transcription factor)-1 negative and chromogranin negative. A few weeks later, PET/CT confirmed a hypermetabolic paratracheal mass measuring approximately 3·1 cm with no other signs of FDG-avid disease. When the patient was seen in our ENT department approximately 1 month later, he reported that over a couple of months since the biopsy, the mass had gradually disappeared. On physical exam, there were no visible abnormalities or palpable masses within the neck or mediastinum. A CT scan of the chest for metastatic workup, which included the entire mediastinum and the low neck, was negative for the disease. Figure 1 displays a CT scan prior to and after the biopsy.

Figure 1. CT scan of mediastinal mass before biopsy (left) and after biopsy (right).

The case was discussed at the Head and Neck tumour board, with a decision to recommend radiation to the area where the tumour had been for microscopic tumour control. CT done at the time of radiation simulation was negative for the disease. He was then treated with intensity modulated radiation therapy to a dose of 6,160 cGy in 28 fractions to the site where the tumour was visible on previous imaging. At-risk nodes (levels III–VI) were also treated to 5,000 cGy in 28 fractions. Treatment duration was for a total of 43 calendar days. Treatment was well tolerated. The patient experienced odynophagia not requiring medication and dry desquamation at the treatment field requiring Silvadene.

He was seen for follow-up at 3 and 6 months following completion of radiation therapy with resolution of acute toxicities at the 3-month mark. The exam was performed at both follow-up appointments with no evidence of the disease. PET/CT 3 months after the completion of radiation therapy showed no new/residual sites of FDG avidity. This study is approved by a broad-based Institutional Review Board dosimetric study.

Discussion

Several case reports have been published regarding spontaneous regression of MCC following incisional biopsy. This is the first case at our institution to have spontaneous regression both seen on physical exam and imaging for an anterior mediastinal lesion, with no evidence of skin involvement.

CSR of an MCC is rare and predicted to be 1·5–3% but may be greater than reported. Reference Ciudad, Aviles, Alfageme, Lecona, Suarez and Lazaro6,Reference Sais, Admella and Soler7 While most cases of primary CSR were originally located on the cheek, no report has shown CSR of a biopsy-proven anterior mediastinal MCC. The mechanism of spontaneous regression is not clearly understood. Evidence suggests increased immune activity around the tumour regression site in the form of tumour-infiltrating lymphocytes may play a role. Reference Walsh8 Several studies reported heavy infiltration of CD4+, CD8+, CD3+ T-lymphocytes and foamy macrophages around the tumour nest. As in most previously reported cases, CSR in our case occurred following a biopsy, which suggests a potential stimulation of the immune system. Reference Takenaka, Kishimoto and Shibagaki9

Baker utilised TCR (T-cell receptor) sequencing to demonstrate that spontaneous regression of an MCC is driven by the expansion of novel and pre-existing adaptive cellular immune responses. Similar results were seen with immunohistochemical staining and TCR sequencing performed in an MCC tumour regressing during the treatment with the PD-L1 (programmed death-ligand 1) inhibitor, avelumab. Reference Baker, Roman and Reuben10

Conclusion

In summary, this is an isolated case report of spontaneous regression of an MCC in the anterior mediastinum with no cutaneous involvement. Most cases of MCC with reported spontaneous regression are in the head/neck region with evidence of cutaneous involvement.

Acknowledgements

None.

References

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Figure 0

Figure 1. CT scan of mediastinal mass before biopsy (left) and after biopsy (right).