(1) Profesor Doctor, Departamento de Anatomía e Histología. Universidad de Zaragoza. Patólogo Investigador,
Instituto Aragonés de Ciencias de la Salud
(2) Especialista en Cirugía Oral y Maxilofacial. Zaragoza
(3) Profesor Doctor, Departamento de Anatomía e Histología. Universidad de Zaragoza
(4) Investigador asociado. Departamento de Anatomía e Histología. Universidad de Zaragoza

Address:
Javier Azúa-Romeo
Servicio de Anatomía Patológica. (Banco de Tumores)
Hospital Universitario Miguel Servet
Pº Isabel la Católica 1 y 3
50009 Zaragoza
Telf: 976 765553
Fax: 976379891
Email: javierazua@hotmail.com

Received: 4-04-2004 Accepted: 21-11-2004

Acinar cell carcinoma is a malignant epithelial neoplasm in which neoplastic cells show acinar differentiation. In 1991 (1) the WHO reviewed the salivary gland tumors classification, redefining this lesion as carcinoma since it was previously named acinar cell tumor.

Classically it has showed a low aggressivity potential, with very few histological signs of malignancy, although since 1950 (2) it is known its capability to metastasize and recurrence. Since the first references investigators tried to find a diagnostic protocol more accurate to the biological behavior of the tumor (3,7), thus nowadays we have immunohistochemical proliferative markers – p53, Ki 67-, electron microscopy and DNA quantification by image and flow cytometry.

CLINIC REPORT

43-years-old male who complained of a painful swelling in the right preauricular region. On physical examination stands out an ill-defined mass measuring 2-cm around the right parotid, lacking other significant findings. Patient refers personal and familial history of no interest.

Image techniques (CT and US) showed a well-defined tumor sized 2,5 x 2 cm located in the parotid that does not affect bone or muscle, suggestive of low-grade neoplasm (figure 1)

Fine needle aspiration (FNA) is performed, using the routinely method of three punctions with 23 gauge needle aided by Cameco device, afterwards 2 smears were fixed in alcohol in order to be stained by Papanicolaou stain and 6 smears were air-dried to use Diff-Quick coloration.

Microscopy showed a seroproteinaceous background with abundant big sized cellularity, round centrally located nuclei with non-prominent nucleolus and finely granular chromatin. Cytoplasm was abundant, pale and foamy with ill-defined borders, vacuolated and containing several bluish granules. Cells were placed in quite compact groups as bidimensional layers, occasionally displaying an acinar pattern. Another cellularity was observed, composed of smaller cells, with scant cytoplasm and centrally located round to oval nucleus.

Cytological image was concordant with pathology of the serous type acinar cells, being probably malignant (figure 2); thus it was proposed to analyze DNA by means of image cytometry over cytological samples. A new FNA was practiced to obtain more cellular material allowing the cytometry; in this sense samples were fixed in methilic alcohol 99º and stained with Gill’s Haematoxiline.

TEXCAN software and a black and white video camera connected to microscope were used to assess the most important factors, such as ploidy, S-phase fraction and 5c exceeding rate (aneuploidy). The histogram obtained revealed a euploidy line without S-phase activity and absence of cells above 5c, thus, classified as low grade of aggressivity (type I histogram) according to Azua classification for image cytometry.

Radical surgery was precluded, resecting parotid gland without cervical lymphadenectomy and conservative of facial nerve.

Macroscopically it is seen a polilobulated white mass, weighting 12 grams and measuring 8x4x3 cm. On sectioning appeared a nodule 1,5 cm of size respecting surgery sides. Surgical specimen was sampled, included in paraffin and finally stained with conventional haematoxilyn-eosin.

Histopathological study revealed a microcystic and solid neoplasm, confined, mainly composed of acinar cells that did not go beyond the capsule. Microcystic spaces were formed by dilated lumen lined by ductal cells and occasionally acinar cells (figure 3). Acinar cells showed serous secretion proved by PAS stain that highlights intra-cytoplasmatic zimogen granules as well as intracystic eosinophilic secretion. Neoplasm did not affect surgery limits neither showed vascular nor nerve invasion.

Definitive diagnosis was: non-invasive Low Grade Acinar Cell Carcinoma.

DISCUSSION

Acinar cell carcinoma is a malignant epithelial neoplasm in which neoplastic cells show acinar differentiation. Although salivary glands have two types of acinar cells, serous and mucinous, it is widely accepted that the term acinar cell carcinoma it is used for serous type. In the 1991 WHO reviewed classification of salivary gland tumors this entity is renamed as carcinoma, since until then it was called acinar cell tumor.

This definition attended to the low potential of malignization and that it is infrequent to find histologic features of malignancy, nevertheless, since 1950 (2) its biological behavior is known, with capability to metastasize and recurrence, even with fatal evolution. This difficulty in achieving an accurate diagnosis lead the development of several diagnostic techniques in the 90´s (3-7), including immunohistochemical proliferation markers –p53, Ki67- electron microscopy and DNA assessment by flow or static cytometry.

Some series (8) defend that that this tumor represents the third malignant epithelial tumor of the salivary glands, behind mucoepidermoid carcinoma and adenocarcinoma NOS, although our experience (9) places it after squamous carcinoma. Its overall media could be around 10% of all salivary gland epithelial tumors.

It is located almost exclusively in the parotid, male gender predilection 3:2, no race differences and median age of 44-years-old. (8)

Clinically it is characterized by a slow growing painful mass, in the parotid region. Facial nerve is affected in up to 5-10% patients.

The diagnostic guideline (10-11) is based on the combination of image methods, ultrasonography, and performance of FNA, which is a not really aggressive technique which yields highly sensitive diagnosis in a very short lapse of time, even less than one hour (12) reducing the surgical delay and the patients anguish.

Our study group has a wide experience (13-14) in the use of image cytometry, that is why we prefer this method in spite of the lack of consensus showed in the current bibliography. While some authors (3,4) did not find relationship to prognosis, others (15-17) including us believe that DNA quantification by image cytometry in salivary gland tumors is a very reliable tool in order to predict a possible neoplastic evolution. Reviewing scientific literature (3-7, 15-17) it is found out that the majority of acinar cell carcinomas were euploid (2c) or near-diploid, with absence or very low S-phase activity, showing high rates of correlation with survival (higher than 15 years after diagnosis). It seems that in cases in which discordance were found between cytometry/survival, this one was more related to extrinsic factors, such as inadequate treatment, poor clinical condition or different intercurrent illness.

The present case showed a normal ploidy, remaining the other molecular parameters within normal limits, which fits perfectly with lack of malignant features in the histological study.

At the present time patient remains alive, asymptomatic and free of residual disease, nevertheless it’s been only one year since the surgical excision and it seems obligatory a close follow-up.

In conclusion, we believe that performing fine needle aspiration cytology and posterior DNA quantification by image cytometry becomes the optimum diagnostic method for salivary gland tumors. Thanks to this protocol one might know in advance the neoplasm behavior, and therefore adapt the treatment to the biological reality of the tumor.

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