Cytological characteristics of acinic cell carcinoma (ACC) diagnosed by fine-needle aspiration biopsy (FNAB).
A study of four cases
Características citopatológicas del carcinoma de células acinares (CCA) de glándula salival.
A propósito de cuatro observaciones

 

Mireya Prieto Rodríguez ⁽¹⁾, María Josefa Artés Martínez ⁽¹⁾, María Navarro Hervás ⁽²⁾, Alicia Camañas Sanz ⁽³⁾,
Francisco José Vera-Sempere ⁽⁴⁾

(1) Médico Adjunto de Anatomía Patológica. Hospital Universitario La Fe. Valencia
(2) Médico Especialista de Anatomía Patológica. Hospital La Ribera. Alzira (Valencia)
(3) Jefa de Sección de Citopatología-PAAF. Hospital Universitario La Fe. Valencia
(4) Profesor Titular de Anatomía Patológica y Jefe de Servicio de Anatomía Patológica del Hospital Universitario La Fe.
Universidad de Valencia. España

Address:
Prof. Dr. F. J. Vera-Sempere
C/ Daoíz y Velarde nº 8,14
46021 - Valencia
Tlfno: 96 3862799, Fax: 96 1973089
E-mail: vera_fra@gva.es

Received : 22-10-2003. Accepted: 23-05-2004

 

 

 

INTRODUCTION

Tumoral pathology of the salivary gland represents 3% of all neoplasms of the head and neck. Within the wide variety of tumors of the salivary gland, there exist very infrequent forms, of which ACC makes up between 1% and 6% of these entities, being considered a neoplasm of low-grade malignancy, having a survival at five years of 83.3% (1, 2). It is more frequent in females, with a certain familial association having been described (3), as well as a possible bilateral presentation (4). Its histogenesis is established through the reserve cells of the terminal duct on the basis of their ultrastructural characteristics (5).

Numerous publications exist on the efficacy of FNAB in the diagnosis of lesions of the salivary glands (2,6,7,8). However, there is little information on the cytopathological characteristics of the more infrequent salivary gland tumors.

The first cytologic descriptions of ACC were made in the seventies by Swedish authors (9,10), and since then publications on ACC diagnosed by puncture are scarce, the majority of which correspond to isolated cases. Various publications (9,11) indicate that FNAB is able to correctly diagnose the existence of a tumor of the salivary gland in 93% of cases, define that it corresponds to a malignant neoplasm in 83%, and arrive at a specific diagnosis of ACC in only 68%. This lack of precision necessitates the detailed study of the cytologic images.

In this context, we present the cytological characteristics of four cases of acinic cell carcinoma diagnosed by FNAB, commenting on its cyto-histological correlation, and the differential diagnostic problems that may arise.

CLINICAL CASES

In the period between January 1992 and July 2003, a total of 325 punctures of the salivary gland were carried out at the Servicio de Anatomía Patológica del Hospital Universitario La Fe, four of which (2.70%), were diagnosed as ACC of the salivary gland, three corresponding to primitive tumors of the parotid and the other to a metastasis of ACC.

Case 1. A 52 year-old male with a painful tumor of the right parotid of three months evolution. On palpation, the tumor was soft, well delimited and not adhered to deep structures. The ultrasonography and CAT revealed a solid tumor of 4cm in diameter, affecting both parotid lobes, with no evidence of adenopathies. Following direct FNAB with a diagnosis of ACC, a total parotidectomy was carried out. In the postoperative period, the patient developed transient facial paresis, recovering in a few months. The histological study confirmed the diagnosis, detecting involvement of the surgical limits, which required coadjuvant radiotherapy. The patient is free of disease following three years of follow up.

Case 2. A 53 year-old male with a 2cm diameter, slow, steadily growing tumor of the right parotid, of one year's evolution. The ultrasonography and CAT revealed a partially cystic mass on the right superficial parotid lobe, with no evidence of regional adenopathies. The FNAB established a diagnosis of ACC, which was confirmed following the subsequent superficial parotidectomy. Transient facial paresis remained as a sequela. At one year following the intervention, the patient is recovered with no signs of relapse.

Case 3. A woman, 81 years of age, with a previous history of right parotid ACC, and two extirpated relapses, who presented various palpable right laterocervical nodules. The FNAB diagnosed metastatic ACC. This diagnosis was confirmed histologically following the extirpation of various nodules. Owing to the age of the patient, no other therapy was carried out.

Case 4. A 12 year-old girl who presented a slow growing tumor of the right parotid, of 6 months evolution. On palpation, an elastic, painless, well-defined nodule was detected. Radiology revealed a solid homogenous mass, with no evidence of regional adenopathies. An FNAB was carried out, and, following a diagnosis of ACC, a parotidectomy with right cervical emptying was performed, observing a carcinoma of acinar cells located on the superficial parotid lobe, no lymph node metastases were identified.

In all the cases studied, the punctures were realised using a Cameco^® pistol, with 20cc syringes and 25G calibre needles. In all cases, a rapid staining was made using the Romanowsky method (Diff-Quick^®) in order to evaluate the reliability of the sample. The remaining smears were stained following alcohol fixation with Papanicolaou and Hematoxylin-Eosin.

CYTOLOGIC RESULTS

In all the cases studied, the cytologic smears revealed a clean background, with foamy protein-like material, upon which an abundant monomorphic tumoral cellularity existed, similar to the acinar cells of a normal salivary gland. The cells were distributed in isolation or in small monolayered sheets forming acinar structures (Fig. 1) which made up rosette or follicular formations (Fig. 2).

Cellular disassociation often predominated, with an abundance of bare nuclei in the background of the smear, indicative of a high cytoplasmic lability, cytoplasmic remains being observed in the background of the preparations.

The acinar differentiation cells, which usually predominate, were of eccentric, round or oval monomorphic nuclei, with scant nucleoli and abundant granular cytoplasm, but showing azurophile granules with May-Grünwald-Giemsa staining. The cellular boundaries were poorly defined with frayed edges, although some of the monolayered sheets showed well-delimited cells giving a 'honeycombe' appearance. We found, in a lesser proportion, acinar elements of finely vacuolate or foamy cytoplasm, with a clear cell appearance (fig 3), together with cells of a more oncocytic appearance, with more dense and homogenous cytoplasm and better-defined limits. On occasions, the smear showed three-dimensional, cohesive groups, of non-specific glandular cells, with scant, finely granulated cytoplasm.

All the cell types described, always presented eccentrically situated round or oval nuclei, with no increase in the nuclear-cytoplasmic relation, but with discreet nuclear polymorphism and one or various evident nucleoli. No divisional figures, multi-nucleate phenomena, inflammatory cellularity, necrosis, epithelial ductal fragments, nor adipose cells were observed. Two of the four cases showed, intermingled with tumoral cellularity, true lymph node cells (cases 3 and 4); case 3 being a lymph node metastasis of a parotid carcinoma extirpated years before, and in case nº 4, probably in relation to the fact that the tumor was located in the sinus of an intraparotid ganglion.

DISCUSSION

ACC of the salivary glands is found fundamentally in the parotid, being a low-grade malignancy neoplasm, with a recurrence of between 12% and 35%, and survival at five years of 83.3%. It manifests as a slow growing, glandular tumor, with no clinical peculiarity which differentiates it from other lesions of the salivary glands.

The cytologic key for the diagnosis of ACC resides in the recognition of the neoplastic acinar cells (9, 10). They are round, oval or polygonal cells, with a granular cytoplasm that may contain azurophile granules, although it is possible to recognise other neoplastic acinar cellular variants, such as vacuolate cells, and cells of oncocytic appearance.

The smear usually shows abundant disperse and grouped cellularity, observing acinar structures, represented by rosette or follicular forms. Numerous bare nuclei frequently exist in the background of the smear, owing to the high cytoplasmic lability of the acinar cells, which in turn provides the protein-like foamy background to the areas.

In a study of 40 primary tumors and 18 metastatic ACC by Nagel et al., the presence of numerous bare nuclei was observed in more than 90% of the cases. Likewise, in the cases that we have had the opportunity to study, the existence of frequent bare nuclei was a constant finding. However, ACC frequently presents serious diagnostic difficulties. In all cases, the cytologic differential diagnosis should be considered with the cytology of a hyperplastic or normal salivary gland, due to the fact that the monotone acinar cellularity of a well-differentiated ACC is very similar to normal acinar cellularity. The difference resides in the fact that normal salivary gland cells are arranged intermingled with adipose tissue and ductal epithelial cells.

In sialoadenosis, there is the greater additional difficulty caused by the extreme cytoplasmic fragility of the acinar cells in both lesions, making the background of the smears reveal numerous bare nuclei in the background of the foamy protein.

Those ACC with a predominance of cells of oncocytic appearance create differential diagnostic problems with oncocytomas. On these occasions, greater attention must be paid to the cellular details, in the knowledge that cells of oncocytomas possess broader cytoplasms, are better delimited, more dense and granular; the nuclei are usually more atypical, with nucleoli more evident than in ACC. Furthermore, in oncocytomas the bare nuclei are not so frequent.

Warthin's tumor with scarce or no lymphoid component can, likewise, create diagnostic difficulties with ACC, knowing that this tumor also possesses sheets of oncocytic cells, and that the bare nuclei of ACC can simulate mature lymphocytes. On the contrary, a subtype of ACC exists, denominated 'with lymphoid stroma' that can, in the same way, create differential diagnostic problems, since it simulates the metastasis of an intraparotid ganglion (9,12).

Another possible source of error, in our experience, is the interpretation of the clear cells of ACC as mucosecretory cells, which can lead to an erroneous diagnosis of a low-grade mucoepidermoid carcinoma. This could, in the same way, create problems of differentiation of an ACC against metastatic tumors (as would be in the case of a clear cell renal carcinoma, or clear cell thyroid follicular carcinoma). In these cases, it is very important to have adequate clinical information.

Our four observations confirm the validity of FNAB in the first diagnosis of those lesions accessible to direct puncture, as well as in the diagnosis of a metastatic illness and tumoral stage, it being important to familiarise ourselves with the cytological characteristics of ACC, and with its differential diagnostic problems, with the aim of being able to identify this neoplasm as malignant, separating it from other entities which require a different therapeutic approach.

In conclusion, FNAB in the parotid area is able to discriminate neoplastic conditions from the non-neoplastic in the pre-surgical phase, and, in a high percentage of cases, it is also an effective method for the identification of an ACC. It is convenient to be familiar with the recognition of this entity, distinguishing it in the differential diagnosis from those entities commented on above, taking into account the fact that the experience and qualifications of the cytologist in the preparation and study of the smears influences the diagnosis.

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