Mucinous cystadenocarcinoma of the oral tongue: malignant transformation from a mucinous cystadenoma?
- 1 Radiology Department, Hospital do Divino Espirito Santo de Ponta Delgada, EPE, Ponta Delgada, Azores, Portugal
- 2 Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
- 3 Head and Neck Surgery Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
- 4 Radiology Department, Instituto Português de Oncologia Lisboa Francisco Gentil, Lisboa, Portugal
- 5 Radiology Department, Champalimaud Foundation for the Unknown, Lisbon, Portugal
- Correspondence to Dr Alexandra Borges; borgalexandra@gmail.com
Abstract
Mucinous cystadenocarcinoma of minor salivary glands is an extremely rare entity that has only recently been described, with a few published cases in the English literature. A 42-year-old woman with a history of a surgically excised mucinous cystadenoma of the oral tongue, presented with a painful swelling in the oral tongue slowly growing for 1 month. On clinical examination, there was a firm, relatively well-circumscribed mass in the left posterior border of the mobile tongue. Subsequent MRI scan revealed a heterogeneous lesion composed of multiple cysts separated by contrast enhancing septa, in the posterior two-thirds of the left tongue. Imaging findings were similar to those of the previously resected mass, suggesting local relapse of the primary lesion. A complete surgical excision was performed and the histopathological examination revealed typical features of a low-grade mucinous cystadenocarcinoma of minor salivary glands.
Background
Cystic lesions of the oral tongue are uncommon, most often benign and managed conservatively. Cystadenocarcinoma of minor salivary glands is an extremely rare entity. To our knowledge, there are only two cases previously reported in the oral cavity (one mucinous cystadenocarcinoma of the upper lip and one papillary cystadenocarcinoma of the ventral tongue). This paper adds yet another case of this rare entity and highlights the importance of its early recognition so that appropriate surgical management is offered and local recurrence is avoided.
Case presentation
A 42-year-old woman with a prior history of a cystic lesion of the oral tongue surgically excised 3 years before, was referred to our institution due to a recurrent painful tongue swelling slowly growing for 1 month. Clinical examination disclosed a firm, relatively well-circumscribed mass in the left posterior border of the mobile tongue.
Her medical history was significant for a cystic lesion in the left border of the oral tongue surgically resected at the age of 8 months. At that time, the patient was diagnosed with a simple retention cyst and recovered uneventfully.
Three years prior to the current presentation, the patient noted a small swelling in the left posterior border of the tongue which caused discomfort during mastication. Clinical observation disclosed a firm, 15 mm submucosal nodule bulging the overlying mucosa, slightly painful on palpation without local inflammatory signs, mucosal discoloration or ulceration. Neck palpation was negative for lymphadenopathies. An ultrasonography and MRI scan of oral cavity and neck was performed showing a cystic lesion with a small internal vegetation adherent to the medial wall, measuring 16×16×15 mm, located in the left posterior border of the tongue (figure 1).
MRI of the oral cavity dated 20 August 2014, (A) Axial contrast enhancement T1W, (B) axial T2W and (C) coronal FS T2W images show a cystic lesion in the left hemitongue with a prominent signal void on T2W images (arrow in B), and a small enhancing nodule (arrow in A) in the inner aspect of the lesion. It shows well-defined borders and bulges the midline raphe to the right side without transgressing it (dotted arrows in C). There is no extension into the tongue base or tongue root. No cervical lymphadenopathy was noted.
An excisional biopsy was performed and the patient recovered uneventfully. Pathological report, at that time, favoured a mucinous cystadenoma of minor salivary gland but included mucocele or a retention cyst with reactive proliferation of the glandular epithelium as potential differential diagnoses. Surgical margins could not be assessed. The patient remained completely asymptomatic for 3 years after which the lesion recurred.
Investigations
An MRI scan of the oral cavity revealed a heterogeneous, lobulated, multicystic mass, on the left posterior two-thirds of the mobile tongue, measuring 33×25×15 mm and extending from the dorsal to the ventral surfaces of the tongue (figure 2). The lesion did not cross the midline and was 5 mm away from the lingual septum. There was no tumour extension to the base of the tongue, extrinsic tongue muscles, floor of the mouth or the sublingual space. The lesion was composed of multiple cystic spaces separated by contrast-enhancing septa. No cervical lymphadenopathies were seen.
MRI of the oral cavity dated 22 January 2018, 3 years after surgery (A) axial T2W (B) axial contrast enhancement fat-suppressed and (C) coronal contrast enhancement T1W images show a recurrent multicystic lesion with internal septa, surrounded by a T2 hyperintense rim (arrow in A), suggesting perilesional oedema and showing intense peripheral and central areas of solid contrast-enhancement (arrow in C). The borders are less well defined compared with the original lesion but it is still confined to the left hemitongue. Also, no lymphadenopathy was noted at this stage.
Compared with the prior MRI scan, performed before the surgical intervention, the lesion showed an increase in size and complexity with the appearance of multiple internal septa, a more solidly enhancing peripheral rim and surrounding oedema. The lesion was in the same location as before. Laboratory workup and chest X-ray were unremarkable.
A presumptive diagnosis of recurrent mucinous cystadenoma was proposed. Given that this was a relapsing lesion, with progressive growth and increasing local discomfort, leading to chewing and speaking difficulties, a large marginal tongue resection, followed by a glossoplasty was performed to ensure complete resection with free surgical margins.
The pathology specimen measured 58×45×28 mm and had a lobulated contour. On section, it revealed an encapsulated tumour with a heterogeneous cut surface due to the presence of firm solid components and large cystic areas filled with gelatinous mucinous-like material . Tumour borders were irregular but well defined and the resection margins were free of tumour with a deep closest margin of 3 mm. Microscopic analysis of H&E stains (figure 3) showed multiple variable-sized, mucin-filled cysts separated by fibrous septa lined by a double layer of epithelial cells with focal areas of papillary architecture with infiltrative margins and perineural invasion. No lymphovascular invasion was noted. Immunohistochemistry was positive for CK7, CK20 and CDX2 and negative for TTF1. Analysis with conventional H&E and immunohistochemistry revealed a final diagnosis of cystadenocarcinoma of minor salivary gland. The presence of faint positivity for CK20 and CDX2, featuring a potential intestinal immunophenotype, led to further diagnostic testing with FDG-PET-CT and colonoscopy which ruled out a primary bowel tumour as well as loco-regional and distant metastases. The final stage was pT2 cN0 cM0.
Microscopic slides of the tumour (H&E staining). (A) low magnification and (B) medium power magnification show a general view of the tumour composed of multiple cysts, some lined by single and others by multiple layers of epithelial cells in a disorganised papillary arrangement. (C) high power magnification shows that the cyst lining epithelium is composed by tall cuboidal and columnar atypical cells, with abundant mucinous cytoplasm and basal hyperchromatic nuclei.
Differential diagnosis
Cystic tongue lesions are uncommon, most are benign and include a vast list of differential diagnoses.
Cystadenomas are benign tumours of glandular origin, which may affect multiple different organs, including the salivary glands.1 They are quite infrequent in the minor salivary glands of the oral cavity with around 30 cases described in the English literature and only three in the oral tongue.2–4 The few published series describe a predilection for the female gender and for the sixth decade of life.5 There are no distinctive clinical or imaging features from other tongue cysts and therefore the diagnosis requires pathological examination.1 6
Cystadenocarcinomas are most often found in major salivary glands, particularly in the parotid and are exceedingly rare in the minor salivary glands of the oral cavity.7 The highest prevalence occurs in adults, with a mean age of 58.8 years old, with no gender predilection.8 On imaging, they present as multicystic masses with contrast-enhancing septa and variable solid components. Ill defined, infiltrating borders may be present as well as locoregional lymphadenopathy.7 These are, however, low-grade malignancies with a favourable prognosis contrasting with that of mucinous adenocarcinomas.9 On pathology, the differential diagnosis between these two entities can be challenging and requires immunohistochemical analysis, often supported by molecular studies (table 1).9 On microscopic analysis, cystadenocarcinomas are featured by variably sized cysts separated by fibrous septa.8 10 Cysts are lined by single or multiple layers of epithelial cells (small cuboidal, large cuboidal and/or tall columnar), which can focally form a papillary, mesh-like or a cribriform architecture and infiltrate the surrounding stroma.8–11 Depending on the dominant feature (mucin-filled cysts or papillary projections) the Armed Forces Institute of Pathology further categorise these tumours as mucinous or papillary cystadenocarcinomas. Differential diagnosis with its benign counterpart, cystadenoma, requires the identification of invasion of adjacent structures, solid extraluminal growth and cellular atypia (box 1).10–12
Differential diagnostic criteria between mucinous salivary gland malignancies on histopathology (adapted from Schneller et al)9
| Mucinous salivary gland malignancies | Cysts size and content | Nuclei | Squamous differentiation |
| Mucinous cystadenocarcinoma | Large mucin containing | Bland | Absent |
| Mucinous adenocarcinoma | Small mucin containing | Atypical | Absent |
| Low-grade mucoepidermoid carcinoma | Variable in size | Bland | Present (intermediate and basaloid cells) |
Differential diagnostic criteria between cystadenoma and cystadenocarcinoma of salivary glands on histopathology (adapted from Foss et al)11
Diagnostic criteria for cystadenocarcinomas:
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Cystic or multicystic with or without papillary components.
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Invasive growth pattern (extraluminal growth) and invasion of adjacent stroma.
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Absent acinar and mucoepidermoid differentiation.
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No evidence of origin in a pleomorphic adenoma.
Mucinous adenocarcinomas are featured by a more solid and aggressive infiltrating pattern and are further subdivided into three different subgroups, according to their microscopic architecture and immunophenotype, into adenocarcinoma not otherwise specified, intestinal-type and papillary-oncocytic adenocarcinomas.13 14 Cellular atypia is more striking compared with that of cystadenocarcinomas and a higher number of mitoses is also seen.9
Mucoepidermoid carcinoma, the most common primary malignancy of salivary origin, is featured by the presence of a heterogeneous cell population (mucous, squamous, intermediate and clear cells).15 However, low-grade tumours, containing prominent mucinous cystic components and intermediate cells with bland nuclei forming glandular spaces, can easily mimic other mucous producing adenocarcinomas.15
Treatment
The patient underwent a complete surgical resection with a left marginal glossectomy and glossoplasty. Given the low histological grade of this mucinous cystadenocarcinoma, the early stage of the disease (pT2 cN0 cMo), absence of unfavourable prognostic criteria on the surgical specimen except for perineural invasion, and the delay on the final pathologic report, adjuvant therapy was waived after a thorough explanation of the situation to the patient, who agreed with this decision. Active close follow-up was strongly encouraged.
Outcome and follow-up
No postoperative complications were noted. The patient has altered speech and phonation and noticed a changed tonality of her voice related to the wide tongue excision. These symptoms have been slowly improving under speech therapy. The patient is under active follow-up with quarterly ear nose and throat consultations. Up to an 18-month follow-up, there has been no clinical or imaging evidence of locoregional recurrence .
Discussion
Cystadenoma of salivary glands are rare benign neoplasms, comprising 0.7%–8.1% of all benign salivary gland tumours and 7% of minor salivary gland tumours.5 Tongue location is exceedingly rare with only three cases reported in the literature: a papillary cystadenoma of the tongue in a 66-year-old man, a papillary cystadenoma of the anterior mobile tongue and a congenital cystadenoma in the right border of the tongue in a full-term neonate.2–4
The diagnosis of cystadenoma is strictly histopathologic.1 The recommended treatment for this benign tumour is simple surgical excision with clear surgical margins.5 In a series of 30 cases of papillary cystadenomas of minor salivary glands, authors found three recurrences after a mean follow-up time of 2.8 years, available in 19 patients.2 Therefore, a follow-up of these patients is necessary to detect a relapse or a potential malignant transformation.
Cystadenocarcinomas are clinically and morphologically similar to cystadenoma and can be considered its malignant counterpart.
According to the National Comprehensive Cancer Network, the first-line treatment for carcinomas of major and minor salivary glands is surgical excision with adjuvant treatment reserved for tumours with unfavourable prognostic criteria. In cases of low-grade cystadenocarcinoma, because of its indolent behaviour and low malignant potential, local but complete excision appears to be sufficient.8
To the best of our knowledge, this is the second case of a mucinous cystadenocarcinoma of the mobile tongue ever reported in the English literature and the first case of a recurrence in which both imaging studies and pathology specimens were available for review.
Although, unfortunately, the pathology of the cystic tongue lesion resected at 8 months of age was not available for review, its relationship with the following clinical history seems likely. This cyst, probably congenital, was described as ‘benign’ and the patient remained asymptomatic, with no noticeable tongue lesions during the following 38 years. We can speculate that this lesion was indeed a congenital cystadenoma of the mobile tongue, similar to another case described in the literature reporting a cystadenoma in a full-term neonate.4 The lesion appearing at the exact same location, 38 years later, could potentially be a relapsed mucinous cystadenoma. The pathology review of this second lesion treated by an excisional biopsy showed an irregularly shaped cystic lesion filled with mucus and lined by mucus-producing columnar epithelium. No cellular atypia was present, nor signs of invasive, extraluminal growth, invasion of adjacent stroma, lymphovascular or perineural invasion to suggest malignancy.
The relapse, 3 years later, showed more aggressive MRI findings and the pathology specimen of the wide marginal tongue excision, demonstrated clear malignant features and the presence of perineural invasion.
In spite of the absence of morphological features suggesting an intestinal type adenocarcinoma, the positive immunostaining for CK20 and CDX2 engaged a search for an intestinal or a sinonasal primary tumour with 18FDG-PET, sinonasal endoscopy and colonoscopy which were all negative.
Although it has never been reported, we have reasons to believe that this case represents a local relapse of a mucinous cystadenoma with malignant transformation into a mucinous cystadenocarcinoma of the tongue. This believe is supported by the absence of malignant features on the previous resection specimen, even on retrospective pathological analysis, reducing the chances of a misdiagnosed or incompletely resected primary cystadenocarcinoma on the first surgery.
Learning points
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Cystic tongue lesions are uncommon but include several differential diagnosis.
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Clinical and imaging diagnosis is challenging as there are no distinctive features from other cystic lesions in the tongue.
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Mucinous cystadenomas are rare benign cystic tumours that may recur when incompletely excised.
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Malignant transformation has only been described in cystadenomas of major salivary glands and this is the first case showing malignant transformation of a mucinous cystadenoma into a cystadenocarcinoma in minor salivary glands.
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Knowledge of this entity and a high degree of suspicion are mandatory to offer adequate surgical excision and to prevent local recurrence.
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Complete surgical excision is the treatment of choice for a cystadenocarcinoma and may be sufficient in these low-grade tumours with an indolent behaviour.
Footnotes
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Contributors SD: Reviewed the subject, wrote, prepared and reviewed the manuscript. MR: Made the pathological diagnosis and reviewed the pathology specimens available, reviewed the pathology part of the manuscript. MV: Consulting surgeon responsible for the surgery, clinical management and follow-up of the patient and reviewed the manuscript. AB: Conceptualised and organised the manuscript, performed the imaging examinations a nd reviewed those performed in an outside institution, collected the images, responsible for the imaging follow-up, helped with the writing and reviewed the manuscript.
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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.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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