Article Text
PDF
Abstract
A woman in her 60s presented with a 2-week history of non-specific left-sided abdominal pain. She previously underwent a total parotidectomy and adjuvant radiotherapy for left parotid adenoid cystic carcinoma 13 years prior, with a local recurrence 4 years after. Investigations revealed a large left-sided renal mass with appearances of renal carcinoma and no signs of metastatic disease. Pathology following nephrectomy revealed a metastatic adenoid cystic carcinoma.
Metastatic disease recurred 11 months postradical nephrectomy to the contralateral kidney and lung, and she was referred to medical oncology for further management.
This case history demonstrates the highly aggressive nature of an adenoid cystic carcinoma primary of salivary gland origin with rare metastasis to the kidney.
- Urological cancer
- Head and neck surgery
- Urological surgery
- Head and neck cancer
Statistics from Altmetric.com
Background
Adenoid cystic carcinoma (ACC) is an infrequent tumour of the head and neck, representing approximately 1% of all head and neck malignancies.1 However, it is one of the most commonly reported malignant tumour of the salivary glands, that is, the parotid, submandibular, sublingual and minor salivary glands, leading to distant metastasis.2 3 Other malignancies of the salivary glands include salivary duct carcinoma, carcinoma ex pleomorphic adenoma, mucoepidermoid carcinoma and acinic cell carcinoma.3
The majority of patients with ACC present symptomatically, with pain being the most frequent complaint.4 ACCs are described as ‘relentless’ tumours, as they have the tendency to be locally invasive, often presenting with perineural invasion, multiple local recurrences and delayed distant recurrence. While regional lymphatic infiltrates are rare, ACCs are known to metastasise via the haematogenous route, most commonly to the lungs and occasional reports of bone, liver and cerebral metastatic disease.5 6 Given its aggressive nature, ACCs are classified as high-grade neoplasms and the current treatment of choice involves radical resection and potential subsequent adjuvant chemotherapy pending patient suitability.7 In those patients who develop distant metastatic disease, 80% present within 8 years of primary diagnosis.1
Case presentation
A woman in her 60s presented with a 2-week history of intermittent, localised, left-sided abdominal pain. She described the pain as 3 out of 10 and worse on lying down. She was otherwise haemodynamically well and did not report any other associated signs or symptoms. Her abdomen was examined and no significant physical findings were elicited. There was no complaint of visible haematuria, dysuria or any systemic features such as unintentional weight loss, fevers or chills. Nor were there any other significant findings on examination of her head and neck.
Her previous medical history was significant for left parotid ACC which was treated with total parotidectomy and adjuvant radiotherapy 13 years previously. Of note, a localised recurrence within the left platysma muscle was identified 9 years previously at another centre, for which she underwent resection of her left platysma recurrence alongside selective neck dissection, which showed node negative pathology at the time.
Investigations
Baseline laboratory investigations were all within normal limits. Triphasic renal CT demonstrated a 7.5 cm by 9.5 cm hypoattenuating, heterogeneous lobulated mass, involving the superior third of her left kidney (figure 1).
Representative axial images from initial CT demonstrating 7.5 cm×9.5 cm lobulated mass on upper pole of the patient’s left kidney.
The renal hilar vessels were uninvolved and no enlarged retroperitoneal or para-aortic lymph nodes were identified. CT thorax demonstrated a small pulmonary nodule only.
Further imaging with positron emission tomography–CT (PET-CT) was performed and did not demonstrate any additional disease sites.
Treatment
Following the multidisciplinary team discussion, the patient underwent an uncomplicated laparoscopic radical left nephrectomy and left adrenalectomy. The patient was discharged on the fourth postoperative day.
Outcome and follow-up
Histopathology of the left nephrectomy and adrenalectomy specimen demonstrated an ACC within the renal parenchyma, representing metastases from a salivary gland primary (figure 2). Gross macroscopy (figure 3) of the resected specimen revealed solid and cystic components, that is, ‘honeycombing’, shown in white and yellow colours with minimal areas of haemorrhage. While tumour invasion into the renal sinus was demonstrated, there was no evidence of tumour extension into Gerota’s fascia, perinephric fat, vascular invasion or adrenal involvement.
Renal parenchyma showing involvement by a multifocal tumour (circled, left), with prominent basaloid and cribriform architecture, consistent with adenoid cystic carcinoma. Normal kidney architecture demonstrated on the right.
‘Honeycombed’ appearance of nephrectomy specimen (130×100×100 mm, 420 g; comprising left kidney, with attached proximal ureter, perinephric soft tissue and left adrenal). Solid and cystic components of the mutlifocal tumour, shown in yellow and white colours above denote the adenoid cystic carcinoma localised to the upper pole of the left kidney.
These findings were consistent with her previous medical history of left parotid ACC, demonstrating metastatic disease in her kidney. Further imaging with PET-CT was performed and did not demonstrate any additional disease sites.
However, 11 months following the radical nephrectomy, multiple new metastatic deposits were identified on surveillance imaging including two pulmonary nodules (10 mm, 4 mm) and three new lesions in the right kidney. The patient was referred to medical oncology for the consideration of systemic anticancer therapy.
Discussion
This case history demonstrates the exceptionally rare incident of a distant metastatic disease of ACC of salivary glands, with renal involvement. On review of current published literature at the time of this writing, there were only six published cases of renal metastasis of ACCs of salivary gland origin, to our knowledge.8–13 These were scattered cases reported globally, with the majority of them presenting in Asia. It is not uncommon for ACCs of salivary glands to be associated with distant metastasis,5 and these predominantly involved the lungs, with a smaller fraction of literature describing bone, hepatic and brain deposits.5 6 14–18
ACCs have been described as having a deceptively indolent course; however, studies have established that they have frequent late-onset distant metastasis, resulting in persistent and recurrent growth patterns.5 Gondivkar et al noted that the peak incidences of late-onset metastasis occur chiefly among women in their fifth to sixth decades of life.19 Metastatic diseases were most commonly identified through surveillance imaging, with a small fraction of patients describing non-specific abdominal discomfort.10–16 20 ACCs are staged with reference to the National Comprehensive Cancer Network Guidelines, where a TNM (tumour, node, metastases) system is used.21 22
Overall survival rate of localised ACCs at 3 years is 73% and 68% at 5 years.1 Patients with metastatic disease have been shown to have an overall survival rate of 41% at 3 years and 16% at 5 years,1 with a mean of 53.8 months from primary diagnosis to detection of metastatic disease.23
A review of studies that examine distant metastasis of ACCs showed that up to 20% of patients present more than 8 years from their primary diagnosis of salivary gland ACC, despite being recurrence free (up to 20 years from primary disease) previously.14 The survival rate for patients with distant metastasis was noted to be significantly lower compared with their counterparts with only localised disease. Patients who have developed recurrence and distant metastasis frequently have multisite metastasis.2 4 5
Treatment options
Treatment of ACCs is dependent on the tumour location, stage and histological grade on histopathological analysis.
The gold standard treatment for resectable, localised ACCs (T1 and T2 disease) is radical excision and adjuvant radiotherapy.5 Neck dissection is not routinely performed, as the natural history of ACCs is to spread via haematogenous route with a low incidence of occult nodal involvement.24 Given its relentless biology, the 5-year to 10-year recurrence rate of ACCs postresection is high, ranging from 30% to 75%.25 A study by Mendenhall et al showed that combined radiotherapy and radical surgical resection yielded more favourable outcomes.25 26 In a report by Simpson et al, the 10-year local control rates postresection and adjuvant radiotherapy were 83%.27 However, given its relentless and aggressive nature, a study has shown that regardless of local control, distant metastasis developed in 50% of patients with the majority involving the lungs (39%), followed by bone (19%), disseminated soft-tissue involvement (10%) and other visceral organ metastasis.5 27 Primary treatment with radiotherapy should be considered when the patient is deemed unsuitable for surgery, that is, for palliation of a brain or bone metastatic disease.28
A watchful waiting approach or metastasectomy could offer a relatively good prognosis in patients who have isolated pulmonary metastases; however, the prognosis appears to be poor in patients with bony and/or liver involvement.18 Prognosis in patients with renal metastasis, unfortunately, remains unclear due to its rare occurrence. To our knowledge, there are only six reported cases of renal metastases from an ACC primary of salivary gland origin globally.8–13 In each of the reported cases, the patients underwent radical nephrectomy with curative intent initially as they were presumed to be primary renal carcinomas. Subsequent histopathological analysis confirmed the diagnosis of metastatic adenoid cystic disease, where patients were then followed up with surveillance imaging and closely monitored for further metastatic disease and disease recurrence. One patient10 developed localised pulmonary metastasis 2 years after radical nephrectomy and underwent a successful surgical resection with no further recurrence reported. Another patient underwent successful radical nephrectomy but unfortunately developed contralateral renal metastatic recurrence 7 years later and progressed to widespread multiorgan metastasis in the subsequent 2 years, with eventual demise 10 years from the time of their first presentation.3 There were no documented follow-up and survival data on the other case reports.
Clinical trials on effective systemic chemotherapy are ongoing at present and the results from several studies over the years have consistently shown ACCs to demonstrate a poor response to cytotoxic chemotherapy for metastatic disease.1 29
Maissa et al have suggested systemic chemotherapy agents such as cyclophosphamide, cisplatin, 5-fluorouracil and doxorubicin may have some efficacy against metastatic ACCs; however, chemotherapeutic management of renal metastases remains not well defined at present.30 Other treatment approaches such as thermoablation and renal embolisation have been proposed by Longo et al, predominantly from a palliative point of view and for the management of painful lesions.31
Of note, a recent study by Sridharan et al has noted Programmed cell Death Ligand-2 (PD-L2) expression on ACC tumour types and suggests a potential role for PD-L2 inhibition and immune modulation as part of an immunotargeted regimen for patients with ACCs.32
In short, further in-depth research into systemic chemotherapy or indeed targeted novel agents is required to identify the most appropriate and effective agent in the management of advanced ACCs.
In conclusion, this case highlights the uncommon and curious presentation of distant metastatic ACC primary of salivary gland origin to the kidneys. Due to its rarity and a lack of current consensus on an effective treatment approach, a fully multidisciplinary approach was indispensable to guide our management of this patient’s aggressive disease.
Learning points
Renal metastatic deposits of parotid adenoid cystic carcinoma (ACC) origins are rare.
ACCs with distant metastatic disease can be aggressive and relentless, despite having achieved good locoregional resectional margins at the original surgery. This occurs predominantly in women in their fifth to sixth decades of life.
The effectiveness of current treatment for distant metastases of ACCs remains unclear, and further development and research are needed to establish clear, evidence-based management options.
Ethics statements
Patient consent for publication
References
Footnotes
Contributors NXH was the lead author of this manuscript, carrying out literature review surrounding the case and contributing to the bulk of the manuscript and initial drafts. SO’M contributed significantly in critical review of subsequent drafts and edits of the manuscript. TM provided critical review of the manuscript in its final stages and provided important edits in the natural history of ACCs. BMCG was the supervising consultant in the management of this case and edited the final version of this case report. BMCG also obtained informed consent from patient for submission. BMCG is the corresponding author for this case.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.