Structural differences between alcoholic and diabetic parotid sialosis
Diferencias estructurales entre las sialosis parotidea de etiología diabética y alcohólica

 

Carmen Carda ⁽¹⁾, Miriam Carranza ⁽²⁾, Adriana Arriaga ⁽²⁾, Anselmo Díaz ⁽³⁾, Amando Peydró⁽⁴⁾,
Maria Elsa Gomez de Ferraris ⁽⁵⁾

(1) Profesora Titular de Histología, Departamento de Patología, Facultad de Medicina y Odontología, 
Universidad de Valencia, España
(2) Docente de Histología y Embriología, Facultad de Odontología, Universidad Nacional de Córdoba, Argentina
(3) Servicio de Otorrinolaringología del Hospital General Universitario de Valencia, España
(4) Catedrático de Histología, Director del Departamento de Patología, Facultad de Medicina y Odontología, 
Universidad de Valencia, España
(5) Catedrática de Histología y Embriología, Directora del Departamento de Biología Bucal, Facultad de Odontología, 
Universidad Nacional de Córdoba, Argentina

Address:
Dra. Carmen Carda
Departamento de Patología,
Facultad de Medicina y Odontología; Universidad de Valencia.
Avda. Blasco Ibañez, 17, 46010 Valencia, España.
Teléfono 963864145. Fax 963864173.
Email: carmen.carda@uv.es

Received: 28-05-2004  Accepted: 10-10-2004

Carda C, Carranza M, Arriaga A, Díaz A, Peydró A, Gomez de Ferraris ME. Structural differences between alcoholic and diabetic parotid sialosis. Med Oral Patol Oral Cir Bucal 2005;10:309-14. © Medicina Oral S. L. C.I.F. B 96689336 - ISSN 1698-4447

SUMMARY Between the sialosis’ etiologic agents, we can find the chronic alcoholism and diabetes. Both nosologic entities are descirbed using a similar histopathologic pattern. Objectives: The purpose of this work has been analyzing and comparing the histopathological differences between the diabetic and alcoholic sialosis.Study design: We studied 7 parotid glands samples of diabetic patients and 4 samples of normal glands obtained from surgical material were used as a control. For the comparative study, we used 12 parotid glands from chronic alcoholic patients with clinical diagnosis of cirrhosis and 6 autopsies on individuals who had died from alcoholic hepatic cirrhosis. This material was fixed in formaline, processed for embedding in paraffin, standart coloration techniques and immunotechnique for cytokeratin EA/1 y EA/3. Results: In the cases of diabetics, the parotid gland was characterised by the presence of small acini, a bigger number of lipid intracytoplasmic droplets in the acinar and ductal cells, as well as an abundant adipose infiltration in the stroma when compared to the alcoholics. We observed that the cytoqueratins’ expression was heterogeneous at the acinar level, and very positive in the hyperplasic ducts, compared to the alcoholic and control groups. Conclusions: These qualitative valorations indicate the differences between the histopathologic pattern of sialosis with different origins. Key words: Structural modifications, sialosis, alcoholism, diabetes, parotid gland

RESUMEN Entre los agentes etiológicos de la sialosis se citan el alcoholismo crónico y la diabetes. Ambas entidades nosológicas se describen con un cuadro histopatológico similar. Objetivos: El objetivo de este trabajo fue analizar y comparar las modificaciones estructurales de la sialosis diabética con las de etiología alcohólica. Diseño del estudio: Se analizaron 7 biopsias de glándula parótida de individuos diabéticos y 4 de pacientes no diabéticos (controles), con patología oncológica en regiones vecinas. El estudio comparativo se efectuó con muestras de archivo que comprendieron 12 biopsias parotídeas de pacientes con diagnóstico clínico de cirrosis hepática alcohólica y 6 autopsias de individuos que fallecieron por cirrosis hepática alcohólica. El material fijado en formol e incluído en parafina, se coloreó con técnicas de rutina y se marcó con anticuerpos para citoqueratinas EA/1 y EA/3. Resultados: En los diabéticos, la parótida se caracterizó por presentar acinos de tamaño más reducido, mayor cantidad de inclusiones lipídicas intracitoplasmáticas en las células acinares y ductales e infiltración grasa abundante en el estroma, comparado con los alcohólicos. Se observó que la expresión de citoqueratinas fue heterogénea a nivel de los acinos e intensamente positiva en los ductos hiperplásicos, comparada con los grupos alcohólico y control. Conclusion: Estas valoraciones cualitativas indican diferencias en el cuadro histopatológico entre estas sialosis de distinto origen. Palabras clave: Modificaciones estructurales, sialosis, alcoholismo, diabetes, glándula parótida.

SUBSIDIADO: Secretaria de Ciencia y Tecnología, Universidad Nacional de Córdoba N° 123/04

INTRODUCTION

Sialosis is a multifactorial pathology of the salivary glands, characterised by a bilateral, non-painful increase in size of the the salivary glands, preferably the parotid gland (1-3). This glandular enlargement, also called sialomegaly, is generally accompanied by a salivary hypofunction or xerostomia (4, 5).

This pathology is not considered neither inflamatory nor tumoral, but a degenerative one. It is also linked to an alteration in the autonomous glandular neuroregulation (3, 6, 7), produced by a demielination (or sympatic denervation) and an atrophy of the mioepithelial cells. This would interfere with the secretion mechanism that is produced by the stimulation of the alpha and beta adrenergic receptors of the acinar cells, that fisiologically induce exocytosis (1, 3, 8).

Sialosis has been described as a consequence of chronic alcoholism and diabetes. In the alcoholic-origined sialosis, 50% of the adult patients with hepatic damage presented parotidomegaly (5, 9).

Boht nosologic entities are described with a very similar histopathologic pattern, although clinically it is said that the swelling of alcoholic origin is located at an retromandibular level, different from the diabetic origined, which frequently has a prearicular ubication (1, 6, 7). In addition, the diabetic sialosis shows a more pronounced swelling due to the abundant adipose infiltration in the parenchyma (6, 9).

In previous studies of parotid glands from individuals who had died from alcoholic hepatic cirrhosis we osberved: acinar hypertrophy and hyperplasy with heterogeneous accumulations of secretory granules and lipid droplets, ductal interlobulillar hiperplasy and enlarged ductal lumen with stasis secretory material and ephitelial atrophy (10-12). In the parotid samples, we could state the presence of isolated acinar cells of mucosal appearance, and the stroma presented a moderate adipose infiltration together with the presence of isolated periductal lymphocytic foci (13). These glandular modifications were relationed to the changes in the number and size of the area of the nucleolar organization areas in acinar and ductal cells (AgNOR technique), which indicates the changes in the transcriptional activity (14).

The type 2 mellitus diabetes (non insulin-dependent) or adult diabetes affects people aged over 40 and frequently obese or with overweight. This metabolic variety is characterised by the parcial shoratge of insulin that is proved by alterations in the metabolism of glucose and therefore the normal assimilation process is affected (6, 15). The most common alterations, at a stomachologic level, include periodontal diseases, caries, candidiasis, commisural quelitis and sialomegaly. All of the already mentioned are linked to the xerostomy and glandular hypofunction (1, 4, 6, 8, 16). Some authors (1, 7, 15) state that the decrease of the salivary stream in the diabetics is caused by the increase of diuresis or poliuria, that make the extracellular liquid decrease notoriously, and as a consequence, the production of saliva.

Actually, the percentage of type 2 diabetic patients represent the 80 - 90% of the total number of diabetics in Spain and Argentina (6, 17). At the same time, the excessive consumption of alcohol is getting more frequent every day, and starting each time form a younger age in both societies (18). The importance of characterizing these diseases with a more accurate precision is reduced to establishing more apropriate strategies for prevention and treatment.

In this study, we analised comparatively the morphologic characteristics of the parotid glands in patients with either alcoholic or diabetic sialosis, with the aim of supplying facts for the differential histopathologic diagnosis between both pathologies.

MATERIALS AND METHODS

7 biopsies of parotid glands fom diabetic patients were used (with diagnosis confirmed by a laboratory) and 4 biopsies from non-diabetic patients (controls), all being surgical patients from the Otorrinolaringology Department from the General Universitary Hospital (Valencia, Spain). The comparative study was carried out with alcoholic sialosis: 12 parotid biopsies from patients with clinical and anatomicopathological diagnosis of hepatic cirrhosis from the Department of Pathology from the Clinical Universitary Hospital (Valencia, Spain) and 6 samples obtained from autopsies from the Medical Forensic Institute (Córdoba, Argentina).

The material was fixed in formol 10% pH 7 and embedded in paraffin for the optical microscope study. Five micra sections were stained with hematoxilin-eosin, PAS, Toluidin blue pH 3.8 and immunomarked with cytokeratin antibodies EA/1 -EA/3 (DAB avidin-biotin method).

RESULTS

The parotid glands from diabetic patients showed small acini (Fig 1) whose cells contained many lipid in appearance inclusions (Fig 2). In these structures, the labelling of the cytoqueratins was intensively expressed at a cell limit level, even though some acinar cells had a higher reactivity than others when compared between them and with the alcoholic and control glands, having a negative reaction in both the alcoholic and control ones (Fig. 3).

The ductal system, often hyperplasic at intercalar and striated ducts (Fig 1) presented an epithelium with small lipidic inclusions, with round nuclei and an intense positivity to the cytoqueratins, compared to the controls. The stroma showed an abundant adipose infiltration (Fig 1) with few lymphocytic sources with a periductal ubication.

The comparative analysis made between the parotid glands from both chronic alcoholic and diabetic patients showed differences in the acinar size, being bigger the acinar from the chronic alcoholic patients. As well as the already mentioned, these were characterised by the presence of atypical accumulation of very basophilic secretory granules, with different sizes and slightly positive PAS. The lipidic drops of the acinar and ductal cells were much more blatant, both in number and in size, in the diabetic glands (Fig 2). In these samples we did not detect alterations in the morphology and distribution of the nuclei of the striate ducts, differently from what was observed in the alcoholic sialosis.

There was also a notorious increase in the stroma’s adipose infiltration in the diabetic’s glands (Fig 1), whereas in the alcoholics there were sources of lymphocitary cell nuclei of periductal ubication found more frequently. Further differential characteristics between these two groups of patients was the heterogeneous and weak expression of the cytoqueratins at an acinar level and the presence of mucose-type acinus in biopsies as well as in autopsies form the chronic alcoholics. (Fig. 3).

DISCUSSION AND CONCLUSIONS

The studies of sialosis with different origins describe similarly the histopathologic pattern. Bermejo Fenoll (1), when referring to the general structure of sialosis, states that the acinar hypertrophy is produced when three causes coincide: the "cytoplasmic insuflation", the parenchyma’s fibrosis and the adipose degeneration. Different authors point out that the most typical structural modification is the increase in size of the acinar cells due to the atypical accumulation of cytoplasmic secretory granules (1, 2, 3, 7). In previous morphometric studies, it was determined that this morphologic characteristic in the parenchyma of the submaxilar gland and lingual glands affected by the chronic consumption of alcohol (19, 20).

Garcia Pola (6), mentions that in the diabetic sialosis, the parotid gland shows a decrease in the number of acini and hypertrophy. Our findings do not coincide, as the acinus were of a reduced size compared to the control and alcoholic samples. However, we already demonstrated that the glands of patients who had died form alcoholic hepatic cirrhosis developed a significant acinar hypertrophy and hyperplasy, specially in the submaxilar and in the von Ebner and Blandin-Nühn linguals, although the same behaviour was not identified in the labial glands (19, 20).

Our obseravtions do not coincide in the stratified appearance of the striated ducts described by Garcia Pola (6). This structural sign was not present in the diabetics, but we could, as well as others, observe it (12) and prove it at an ultrastructural level (10,13) in biopsies and autopsies of chronic alcoholics where atypical nuclei could be distinguished. On the other hand, the acinar cells from the diabetics showed differences in the localisation and intensity of the labelling of the cytoqueratins compared to the control and alcoholic groups. These immunohistochemical variations suggest a change in the cytoskeleton and thus in the differentiation state of the acinar cells, who in normal conditions do not express the cytokeratins (21).

Gorlin and Goldman (22) describe the parotid swelling as caused by the hydropic degeneration of its ductal and acinar cells. In the diabetics analyzed for this study, the increase in glandular size would be due to the labelled adipose infiltration in the stroma as well as to the ductal dilatation, as the acinus have a reduced size. In this, Garcia Pola (6) and Rodrigo (23) coincide in stating that an important adipose infiltration exists in the parotid gland of patients who are carriers of the diabetes mellitus. Our comparative study showed a notorious adipose infiltration in the diabetics that differentiated them from the adipose degeneration in the glandular stroma of the alcoholics. The presence of the lymphocitic of periductal ubication was scarcer in the glands of the diabetics’ glands compared to the alcoholics’ (9).

This comparative analyisis indicates that the main structural differences betweem the parotid glands of the affected patients by type 2 diabetes with respect to the alcoholic patients, are relationed to:

• Notorious decrease in volume of the acinar structures

• Bigger quantity of intracytoplasmic lipidic vacuoles and few secretory granules.

• Absence of the metaplasic mucose acinus.

• Strong immunolablelling of the cytoqueratins in the ducts and a heterogeneous expression in the acinus.

• Abundant adipose infiltration in the stroma.

These qualitative valorations demonstrate structural findings that differentiate both sialosis, being of interest for establishing a more precise diagnosis and creating a more complete differential histopathologic pattern in order to carry out new studies with complementary techniques. Therefore, in our study, the immunohistochemical differences between both types of sialosis have been specific.

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