Methods

A 24 year old white woman was seen in July 1994 at a Public Hospital in São Paulo, with a complaint of a swelling involving the soft and hard palate. Intraoral examination revealed a 3 cm painless, firm, nodular mass with well defined borders and normal overlying mucosa. No neck masses or palpable lymph nodes were noticed. The patient was otherwise in good health. The clinical impression was that this was a salivary gland tumour. Computed tomography revealed minimal alteration in osseous thickness in the right palate, and no relation to the dental roots. The lesion was excised and the specimen was sent to the oral pathology department of the University of São Paulo. After a diagnosis of basal cell adenocarcinoma was made the patient underwent further surgery, and the excision was extended until surgical margins were free of tumour. The postoperative period was uneventful and a follow up of almost five years has shown no evidence of recurrence.

Biopsy material obtained at the surgery was fixed in 10% neutral formalin for 24 hours, embedded in paraffin, and 5 μm sections cut for haematoxylin and eosin (H&E) stain. For immunohistochemical reactions, 3 μm sections were obtained and processed by the streptavidin-biotin method. The antibodies used, with their concentrations, time of incubation and suppliers, are listed in table 1. Before reaction with cytokeratins, the sections were treated in a microwave oven for antigen retrieval using three 5 minute baths at 700 W, with the slides immersed in citric acid (10 mM, pH 6.0). Diaminobenzidine was used as the chromogen, and the slides were counterstained with Mayer's haematoxylin. Appropriate positive and negative controls were included.

Results

Histologically the tumour consisted of an uncapsulated mass composed of uniform basaloid cells showing oval or round nuclei and usually one prominent central or peripheral nucleolus. These cells were arranged in small solid islands or cords, sometimes showing a duct lumen, and when the cords anastomosed, a cribriform pattern was seen. Squamous metaplasia was a conspicuous finding, present in all the arrangements, sometimes forming extensive areas. Individual keratinising cells were also seen. The tumour invaded the adjacent epithelium and salivary gland tissue. Neural invasion was a frequent finding. Mitosis was rarely seen. Neutrophils and lymphocytes were present, scattered in the tumour (fig 1, A–D).

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Figure 1

Haematoxylin and eosin stained sections of basal cell adenocarcinoma. (A) Basaloid cells arranged in a trabecular aspect. Within the trabecules small lumens or pseudocystic lumens are evident, as well as squamous metaplasia (×92). (B) Two foci of squamous metaplasia are seen within the blocks of basaloid cells (×92). (C) Cribriform aspect of the tumour. Observe a mitosis (arrowhead) at right bottom (×294). (D) Tumour cells are seen surrounding a nerve structure (asterisk) (×92).

Immunohistochemical reactions indicated that vimentin was expressed by most of the tumour cells, except for luminal cells in the ductal structures and in areas of squamous metaplasia. Actin was positive in the outer cells of the ductal structures and in cells of the cords and cribriform arrangements. Cytokeratin (CK) 14 was present in all of the tumour cells. CK 7 and CK 19 were present in luminal cells of duct-like structures and also in a few cells present in the vicinity of squamous metaplasia areas; CK 8 and CK 18 were expressed only in luminal cells of duct-like structures. In areas of squamous metaplasia the cells were positive to CK 13, CK14, and also CK19 in the peripheral region (fig 2, A–F). Laminin was positive as a thin line around the arrangements and sometimes inside pseudocystic spaces and in the walls of vessels present in the stroma.

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Figure 2

Immunophenotype of basal cell adenocarcinoma (streptavidin-biotin method). (A) Vimentin is expressed by most of the tumour cells, except for squamous areas (×184). (B) Actin strongly stains cells at the periphery of squamous cells (×184). (C) Cytokeratin (CK) 13 is expressed in squamous metaplasia areas (×92). (D) CK19 in peripheral cells of squamous metaplasia (×184). (E) Immunostaining of CK 14 in tumour cells involving a peripheral nerve (×92). (F) Expression of CK 7 in luminal cells of ductal structures (×92).

Discussion

The tumour in this case was composed of relatively uniform monotonous basaloid cells distributed mainly in a cribriform pattern, with infiltrative growth and perineural invasion. In addition, the tumour showed squamous metaplasia as a conspicuous characteristic.

Immunohistochemical staining revealed a profile similar to that seen in intercalated duct derived tumours, with the presence of myoepithelial tumour cells characterised by vimentin, muscle specific actin, and CK14. Luminal cells of intercalated duct origin, characterised by the positivity for cytokeratins 7, 8, 18, and 19, were not often seen. It seems that these elements were the ones that underwent squamous metaplasia, as the myoepithelial cells were apposed to areas of squamous metaplasia.

The differential diagnosis includes other tumours in which basal cells are the main cellular component: basaloid squamous cell carcinoma, adenoid cystic carcinoma, and basal cell adenoma. Fusion of the tumour with the overlying epithelium was present, so a diagnosis of basaloid squamous cell carcinoma was considered. However, this was excluded on the basis that there was no associated squamous cell carcinoma or carcinoma in situ.¹⁵ The cribriform pattern and the positivity of most cells for actin reinforced this decision.

Among tumours that are composed mainly of basaloid cells and share the immunohistochemical intercalated duct profile are adenoid cystic carcinoma and basal cell adenoma. As these tumours mimic the intercalated duct, it is to be expected that they would have features in common.¹⁶ Adenoid cystic carcinoma was considered as a possible diagnosis in this case. However, the cytological features of the tumour, especially the large pale cells with oval and clear nuclei, are different from the hyperchromatic and angular nuclei usually seen in adenoid cystic carcinoma cells.⁴ In addition, the positivity of most cells for cytokeratin 14 is not found in adenoid cystic carcinoma, where only duct luminal cells are positive. Myoepithelial cells positive to cytokeratin 14 are only occasionally present in the tubular type of adenoid cystic carcinoma.¹⁷

Squamous metaplasia has occasionally been observed in pleomorphic adenoma and basal cell adenoma and adenocarcinoma. Moreover, it has been reported in an isolated case of myoepithelioma composed of clear cells¹⁸ and also in a case of adenoid cystic carcinoma.¹⁹ However in this latter case, even the authors were not convinced of the diagnosis.

Basal cell adenocarcinoma and adenoid cystic carcinoma may produce a hyalinised, eosinophilic basal lamina, but in basal cell adenocarcinoma it is more striking in the membranous type.²⁰ In the present case, reaction with laminin showed a discrete positivity around duct-like structures and in the lumen of pseudocysts. In adenoid cystic carcinoma, laminin is seen as a thick line in the lumen and around pseudocysts.²¹

As stated in published reports, basal cell adenoma is differentiated from basal cell adenocarcinomas mainly by the invasive growth of the latter. Ellis and Wiscovitch¹ define basal cell adenocarcinomas as tumours having the cytomorphological features of basal cell adenomas, but with growth characteristics of a malignant neoplasm. In the present case, neural invasion and glandular invasion were readily observed.

On the basis of the considerations outlined above, and the fact that squamous metaplasia is a feature of basal cell adenomas, we considered this tumour to be a basal cell adenocarcinoma. Owing to the rarity of the lesion, a prognosis cannot be given. In the present case, the patient is being followed up, and five years after surgery she is very well, without any signs of tumour recurrence.