Home Surgery, adjuvant immunotherapy plus chemotherapy and radiotherapy for primary malignant melanoma of the parotid gland (PGMM): A case report
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Surgery, adjuvant immunotherapy plus chemotherapy and radiotherapy for primary malignant melanoma of the parotid gland (PGMM): A case report

  • Qiang Zhao , Zhi-Ke Li EMAIL logo , Yan Gui , Dai-Yuan Ma , Guo-Bo Du and Xian-Fu Li EMAIL logo
Published/Copyright: February 9, 2023
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Open Life Sciences
From the journal Open Life Sciences Volume 18 Issue 1

Abstract

Primary malignant melanoma of the parotid gland (PGMM) is extremely rare, with a poor prognosis. Surgery is the main treatment option followed by adjuvant treatments such as radiotherapy, but which adjuvant treatment to be optimal is still controversial. In this case, a 63-year-old male PGMM patient was first misdiagnosed as a “myoepithelial tumor” and then treated with surgery, postoperative immunotherapy (sintilimab), chemotherapy, and radiotherapy successfully. The progression free survival was more than 19 months without signs of metastasis or recurrence to date. To our best knowledge, this is the first report of postoperative immunotherapy combined with chemotherapy and radiotherapy for PGMM. Our case indicated that combination therapy including surgery, adjuvant immunotherapy (sintilimab) combined with chemotherapy and radiotherapy may be a potential treatment option for PGMM, which needs further research.

Keywords: primary malignant melanoma; parotid gland; adjuvant immunotherapy; combination therapy; radiotherapy

1 Introduction

Malignant melanoma is a highly invasive form of cancer with a poor prognosis [1]. Most malignant melanomas arise from melanocytes in the skin, but they can also arise from melanocytes in some internal organs and even the central nervous system. In developed countries, the incidence and mortality rates of cutaneous melanoma are approximately (9.3–10.2)/1,000 and (1.2–2.0)/1,000, respectively [2].

Primary malignant melanomas of the head and neck account for 25–30% of all malignant melanomas [3]. Primary malignant melanoma of the parotid gland (PGMM) is extremely rare, accounting for less than 0.7% of parotid malignancies [4], and its prognosis is poor and staging is difficult [5]. Surgery is the first treatment option for PGMM, followed by adjuvant therapies such as radiation, immunotherapy, targeted therapy, and chemotherapy, according to the previous reports [6].

Here, we reported a case of PGMM, which was misdiagnosed as a “myoepithelial tumor” first, and then treated with surgery, postoperative immunotherapy plus chemotherapy combined with radiotherapy successfully.

2 Case report

In January 2021, a 63-year-old male found a painless mass behind his left ear for more than 10 months, with no specific past medical, family, nor personal history. Enhanced computer tomography (CT) of the parotid gland on April 11, 2021 suggested a tumor in the left parotid gland, with a size of approximately 3.0 cm × 2.2 cm (Figure 1a). According to the preoperative images, the clinical diagnosis of a benign tumor was considered. Therefore, the mass was resected as a benign parotid tumor on April 13, 2021. During the operation, the facial nerve was separated, and a 3.0 cm × 2.0 cm × 2.0 cm black mass was found on the deep side of the facial nerve, with clear borderline and tough texture. Intraoperative rapid histopathologic analysis showed a “myoepithelial tumor.” Interestingly, the postoperative histopathologic analysis of two different hospitals (West China Hospital, Sichuan University and Affiliated Hospital of North Sichuan Medical College) was inconsistent with intraoperative analysis. And both immunohistochemistry showed S-100 (+), SOX10 (+), HMB-45 (+), Melan A (+), CK (−), EMA (−). In addition, no EWSR1 gene translocation was found, all supported a malignant melanoma of the left inferior parotid gland (Figure 2), but as the patient refused to accept the gene detection, we could not obtain the gene state of BRAF or MEK. Careful physical examination was performed, and no sign of primary lesions was found. We did not find residual tumor in postoperative MRI (Figure 1b), what else, F-18 FDG PET/CT showed no abnormal tumor metabolic uptake. Therefore, according to immunohistochemical staining and radiographic report, the diagnosis of PGMM was confirmed.

Figure 1 Imaging of the parotid gland. (a) CT scan before surgery, the red arrow shows a left parotid occupancy (on April 11, 2021). (b) Nuclear magnetic resonance (MRI) scan after surgery and before chemotherapy and radiotherapy (RT) (on May 15, 2021). (c) MRI scan after chemotherapy and RT (on November 11, 2021). (d) MRI scan recently (on December 5, 2022).
Figure 1

Imaging of the parotid gland. (a) CT scan before surgery, the red arrow shows a left parotid occupancy (on April 11, 2021). (b) Nuclear magnetic resonance (MRI) scan after surgery and before chemotherapy and radiotherapy (RT) (on May 15, 2021). (c) MRI scan after chemotherapy and RT (on November 11, 2021). (d) MRI scan recently (on December 5, 2022).

Figure 2 Histopathology of the parotid tumor. (a) The spindle-cell neoplastic cells present variable amounts of melanin (hematoxylin–eosin stain, original magnification, ×40). (b–d) Immunohistochemical staining of the tumor shows strong immunoreactivity in HMB-45, S-100, and SOX10, respectively (immunohistochemical stain, original magnification, ×100).
Figure 2

Histopathology of the parotid tumor. (a) The spindle-cell neoplastic cells present variable amounts of melanin (hematoxylin–eosin stain, original magnification, ×40). (b–d) Immunohistochemical staining of the tumor shows strong immunoreactivity in HMB-45, S-100, and SOX10, respectively (immunohistochemical stain, original magnification, ×100).

Two months after surgery, the patient returned to our hospital, and received two cycles of immunotherapy combined with chemotherapy (sintilimab 200 mg plus albumin paclitaxel 400 mg, q3w) from June 22, 2021 to July 12, 2021. Then he received radiotherapy for the tumor bed area and the cervical lymph node drainage area with a dose of 48 Gy/12 Fx from August 1, 2021 to August 16, 2021. The MRI right after radiotherapy did not find a tumor (Figure 1c). But after that, he refused further treatment for personal reasons and underwent regular follow-up since then. Up to now, no tumor recurrence or metastasis was found (Figure 1d).

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the Medical Ethics Committee of Affiliated Hospital of North Sichuan Medical College.

3 Discussion

Most parotid malignant melanomas are secondary [5], and primary malignant melanoma is extremely rare. The clinical, pathological, and cytological features of malignant melanoma are variable [7]; therefore, PGMM is extremely easy to be misdiagnosed. Immunohistochemical staining is the gold standard for diagnosis. Based on previous reports, the following rules must be met for the diagnosis of PGMM: (1) the mass must be contained within the parotid gland, (2) parotid masses do not contain metastatic lymph nodes, (3) after careful physical examination, there is no suspected primary lesion of malignant melanoma, and (4) no history or evidence of excision of malignant melanoma or progressive pigmented lesions [8]. The patient in this case met all these conditions. Besides, in our case, immunohistochemistry showed S-100 (+), SOX10 (+), HMB-45 (+), Melan A (+), CK (−), EMA (−). In addition, no EWSR1 gene translocation was found. And no evidence of other primary lesions was found by F-18 FDG PET/CT or physical examination. These results were confirmed in two different large hospitals, thus the diagnosis of PGMM was reliable.

The first treatment options for PGMM are parotidectomy and cervical lymph node dissection [9]. But, the parotidectomy approach is still controversial. Some researchers have shown that total parotidectomy does not improve life expectancy but leads to poorer quality of life, so radical parotidectomy should be avoided if possible [4]. However, Wertz et al. supported complete parotidectomy, they concluded that total parotidectomy may have a lower recurrence rate than superficial lobectomy [10]. Because of the high incidence of occult metastatic lymph nodes, at least selective lymph node dissection should be performed even when no lymph node metastasis to be found in the neck, which can reduce the probability of recurrence while reducing the incidence of adverse events and improving the quality of life [9].

Local recurrence occurs in about 30–50% of patients who do not receive adjuvant therapy after surgery, and the 10-year overall survival (OS) is about 25–40% [11]. If patients have high risk factors, such as tumor invasion of facial nerve, the prognosis is even worse. Postoperative adjuvant therapy can reduce the risk of postoperative recurrence, and the reported main postoperative therapies are radiotherapy, immunotherapy, targeted therapy, interferon, and chemotherapy [6]. The efficacy of chemotherapy, radiotherapy, and interferon for PGMM is controversial [4], and it is still unknown which adjuvant therapy is the best [6].

In recent years, more and more studies have demonstrated the therapeutic benefit of immunotherapy in malignant melanoma, which is gradually becoming the most promising treatment modality for malignant melanoma [12]. In the NCT00636168 trial, ipilimumab, an anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA 4) monoclonal antibody, has been reported to be effective in malignant melanoma. The Food and Drug Administration had approved ipilimumab in 2015 as an adjuvant therapy for stage III melanoma patients with high-risk recurrence, but its use was limited by autoimmune toxicity [13]. As adjuvant immunotherapy, the anti-programmed death 1 (PD-1) inhibitor nivolumab has a higher recurrence-free survival (RFS) and better tolerance compared to ipilimumab [14]. Adjuvant pembrolizumab (a PD-1 inhibitor) for resectable stage III malignant melanoma is effective, with 1-year RFS rate of 75% [15].

Sintilimab is a human immunoglobulin G4 monoclonal antibody which can bind to PD-1, block PD-1 interaction with its ligand, and help restore the endogenous antitumor response of T-cells. Compared with nivolumab and pembrolizumab, sintilimab has a similar antitumor effect, better safety profile, and significant economic advantage [16]. Sintilimab is mainly used to treat lymphoma, lung cancer, liver cancer, stomach cancer, and esophageal carcinoma [17]. Sintilimab combined with anti-CTLA-4 is also effective in advanced melanoma [18].

In our case, considering that the patient did not receive radical resection of the parotid gland or lymph node dissection of the neck, and without genetic testing, the gene state of BRAF and MEK was unknown, thus there is no evidence for targeted therapy. He started radiotherapy with a dose of 48 Gy/12 Fx after two cycles of postoperative adjuvant immunotherapy in combination with chemotherapy (sintilimab 200 mg plus albumin paclitaxel 400 mg, q3w). The biological equivalent dose of radiotherapy was higher than previous reports [19].

Most studies about PGMM are case reports. One study showed that approximately 89.7% of PGMM patients underwent parotidectomy, 52.5% of PGMM patients underwent cervical lymph node dissection, and 25% of PGMM patients underwent postoperative radiotherapy [20]. Distant metastases occurred in two-thirds of PGMM patients during follow-up, with a mean follow-up time of 7.1 months [20]. An article reported a PGMM patient who underwent total parotidectomy with facial nerve preservation and cervical lymph node dissection, followed by interferon α-2a treatment, with a progression-free survival (PFS) of more than 6 years [21], indicating that long-term survival may be possible for patients who received immunotherapy.

This is the first report of postoperative sintilimab combined with chemotherapy and radiotherapy for PGMM. The prognosis of primary and metastatic parotid malignant melanoma is both poor, with an average OS of less than 2 years [5]. In our case, the patient’s PFS was more than 19 months with no signs of recurrence or metastasis. The therapeutic value of sintilimab in PGMM needs to be evaluated in further clinical trials. However, based on the outcome of this patient, adjuvant immunotherapy of sintilimab combined with chemotherapy and radiotherapy may be a potential adjuvant treatment option for PGMM.

4 Conclusion

In conclusion, this case may suggest that surgery, adjuvant immunotherapy of sintilimab combined with chemotherapy and radiotherapy may be a potential treatment for PGMM, which needs further research.

# Qiang Zhao and Zhi-Ke Li contributed equally to this work and share first authorship.

tel: +86-0817-2598242

  1. Funding information: Authors state no funding involved.

  2. Conflict of interest: Authors state no conflict of interest.

  3. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2022-10-16
Revised: 2022-12-20
Accepted: 2023-01-02
Published Online: 2023-02-09

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
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  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
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  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
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  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
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  245. Animal Sciences
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  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
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  252. Plant Sciences
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  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
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  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
https://doi.org/10.1515/biol-2022-0555
Keywords for this article
primary malignant melanoma; parotid gland; adjuvant immunotherapy; combination therapy; radiotherapy
Creative Commons
BY 4.0

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  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
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