Warthin tumor

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Classification according to ICD-10
D11 Benign neoplasm of the parotid gland
ICD-10 online (WHO version 2019)
Classification according to ICD-O-3
8561/0 Warthin tumor
ICD-O-3 first revision online

The Warthin tumor ( Aldred Scott Warthin , American pathologist, Ann Arbor, 1866-1931) is a benign neoplasm or tumor-like lesion that manifests itself almost exclusively in the area of ​​the parotid gland , rarely in neighboring cervical lymph nodes or other locations. After pleomorphic adenoma , Warthin's tumor is the second most common benign salivary gland tumor.

Clinically, the tumor is characterized by slow growth; a malignant degeneration is observed in a few individual cases. A recurrence after surgical removal is rare.

Synonyms

Terms such as adenolymphoma , cystadenolymphoma , papillary cystadenoma lymphomatosum , cystadenoma lymphomatosum papilliferum or cystadenolymphoma papilliferum are sometimes used synonymously . In order to avoid confusion with malignant lymphoma or lymphadenoma , however, it is recommended to use the term Warthin tumor . The terms Albrecht-Arzt-Tumor or Albrecht-Arzt-Warthin-Tumor have only historical significance .

history

The Warthin tumor was first mentioned in 1895 by the German surgeon Otto Hildebrand (1858–1927) under the name adenolymphoma . After Heinrich Albrecht and Leopold Arzt described the entity more precisely around 1910, Warthin used the term in 1929 as papillary cystadenoma lymphomatosum. into American literature.

Epidemiology

The age peak of the Warthin tumor is in the 6th – 7th grade. Decade of life, whereby the mean age of onset is given as 62 years. A manifestation in childhood is possible, but the tumor rarely occurs before the age of 40. The historically clear preference of the tumor for the male sex, which was given as 10: 1 in 1953, has presumably shifted to the disadvantage of the female sex, presumably due to changed lifestyle habits ( tobacco abuse ). More recent figures only show a slightly increased incidence of illness in men or even a balanced gender ratio. The incidence of the disease in African Americans and Black Africans is lower than that of whites, although an increase in incidence has been observed in African Americans over the past few decades.

etiology

The actual causes underlying the tumor development are largely unknown. The lesion is mainly classified as a true neoplasm, but according to one hypothesis it could also belong to a group of acquired multicystic reactive diseases in the head and neck area; The latter approach is supported by the polyclonality of the epithelial tumor component observed in some studies . According to recent findings, the lymphoid stroma of the Warthin tumor is also of polyclonal origin and is therefore probably only reactive and not neoplastic. In turn, other studies were able to demonstrate a translocation between chromosomes 11 and 19 with the formation of a fusion gene (CRTC1-MAML2) at least in some of the Warthin tumors . Interestingly, this change is also found in mucoepidermoid carcinoma . It is believed that the tumor is derived from heterotopic salivary ducts located in lymph nodes. This is supported by the fact that Warthin tumors are most often found superficially at the lower pole of the parotid gland, where most of the intraparotid lymph nodes are usually present. Another hypothesis interprets the Warthin tumor as an adenomatous proliferation , which is secondary to lymphocytic infiltration. A significant risk factor is cigarette smoking, which studies show that the incidence of the disease increases by a factor of 8-15 on average. Apparently there is a dose-effect relationship , with the risk increasing linearly with the duration and non-linearly with the intensity of tobacco abuse. The positive effect of the intensity of the tobacco abuse decreases at high intensities. In one study, 89% of patients with Warthin's tumor were smokers and 66% were heavy smokers. The risk of a Warthin tumor occurring on both sides is also significantly increased in smokers. One possible explanation is the damage to mitochondrial DNA by reactive oxygen species in smokers. Indeed, the epithelial cells of Warthin tumor often show loss of mitochondrial DNA and structurally abnormal mitochondria with decreased metabolic function. A single case report describes a familial occurrence of Warthin tumors in identical twins.

An increased incidence of disease was also observed after exposure to ionizing radiation , for example in atomic bomb survivors.

The possibility of viruses being involved in the development of the disease is also being discussed . For example, the human herpes virus type 8 (HHV-8) is often found in Warthin tumors. An etiological role of the Epstein-Barr virus (EBV) or the cytomegalovirus (CMV) is now considered unlikely. The incidence of Warthin tumors is said to be higher in HIV- infected patients.

Finally, an association of Warthin's tumor with various autoimmune diseases is also reported.

pathology

A rounded-oval, sharply demarcated Warthin tumor of gray-brownish color (center right). Left: normal salivary gland tissue.
Warthin tumor histology.

The tumor almost always manifests itself within the parotid gland (> 90%), preferably in its lower organ pole. 3-8% of patients show tumors in extra-land, usually in high cervical lymph nodes . This must not be confused with a lymph node metastasis , which is not observed in the pure Warthin tumor. Individual reports describe Warthin tumors in the area of ​​the mandibular salivary gland, the lacrimal gland, the larynx, the buccal mucosa, the hard palate or the lip. In 7-12% of cases bilateral tumors are present, in 2-6% multifocal tumors. Warthin tumors account for 14-30% of all salivary gland tumors in total and 70% of all bilateral salivary gland neoplasms. Macroscopically , Warthin tumors usually appear as well-circumscribed, round to ovoid tissue masses with a light brown to gray-brown color, which is due to the high cytochrome content of the tissue. In addition to solid parts, the tumor often shows slit-shaped cystic structures up to several centimeters in size , which are filled with clear, slimy or whitish to brownish fluid.

Histologically , there is a tumor that is sharply demarcated by a thin connective tissue capsule and consists of an epithelial, solid area and cyst-forming component, which is embedded in a lymphoid stroma . The epithelium lining the cyst structures shows a two-layer structure of oncocytic, highly cylindrical cells and basal, flat to cubic cells. Papillae with fibrovascular stroma are also formed. Cell debris and eosinophilic secretion products are often found in the cyst lumens . There are no noteworthy cell or nuclear atypia or significant mitotic activity . Infarcts , necroses , squamous cell metaplasia or bleeding can distort the typical histological picture. These changes can occur spontaneously or as a result of a previous fine needle biopsy . The stroma often contains lymph follicles with germinal centers and is rich in B lymphocytes .

According to Seifert, a distinction is made between four histological subtypes of Warthin's tumor, mainly depending on the quantitative ratio of the epithelial and stromal components. This classification has no clinical significance, but it does indicate to the pathologist the morphological range of the tumor.

Histological subtype definition Relative frequency
Type 1 (classic type) 50% epithelium, 50% stroma 77%
Type 2 (low-current type) 70-80% epithelium, 20-30% stroma 13.5%
Type 3 (high current type) 20-30% epithelium, 70-80% stroma 2%
Type 4 (metaplastic type) extensive squamous cell metaplasia 7.5%

Immunohistochemistry

Immunohistochemically , the oncocytic cells of the Warthin tumor show an expression of the cytokeratins 7, 8, 18 and 19, which is typical for highly cylindrical epithelia.Like the normal salivary gland parenchyma and most benign salivary gland tumors, Warthin tumors express the glycoprotein CD 9 for ribonuclease , lactoferrin , carcinoembryonic antigen (CEA) and lysozyme , while the detection of the markers amylase , vimentin and desmin is negative. In the majority of cases, bcl-2 expression can be localized in the luminal and basal epithelia . In contrast to some other benign and malignant salivary gland tumors, the epithelial tumor cells of the Warthin tumor form somatostatin in some cases . In addition, the epithelial tumor component shows an expression of progesterone but not of estrogen receptors.

cytology

The cell material obtained from a Warthin tumor by means of fine needle aspiration shows a characteristic appearance cytomorphologically - provided that a sufficient and representative amount of tissue has been obtained. Flat cell plates of oncocytic (i.e., intensely red stained in the HE staining) cell elements appear against a background consisting of lymphocytes and / or amorphous cell debris.

Ultrastructural

Under the electron microscope , the cytoplasm of the luminal cell elements of the Warthin tumor is almost completely occupied by enlarged and abnormally shaped mitochondria. The abundance of mitochondria explains the affinity of these cells for acidic dyes and thus their light microscopic oncocytic morphology. On the surface, the cells show microvilli and apocrine protrusions. Individual luminal cells are apparently also equipped with cilia. Besides mitochondria, the basal cell elements show abundant tonofilaments . Within the lumen of the cystic structures formed by the epithelial cell elements, there are cell debris to varying degrees, some of which may have been derived from degenerated lymphocytes. The stroma is formed by tightly packed lymphocytes that are stored within a mesh of reticular cells.

clinic

The affected patients are usually noticeable by a painless swelling in the area of ​​the parotid gland. At the time of diagnosis, the average tumor size is 2-4 cm, in the extreme up to 12 cm. Less than 10% of patients have symptoms of variable magnitude.

Possible complications are infection of the tumor tissue or compression of the facial nerve running between the superficial and deep parts of the parotid gland . A facial palsy but is rarely observed.

diagnosis

Sonography , computed tomography or magnetic resonance tomography are suitable for preoperative diagnosis . Scintigraphy , which uses the property of Warthin tumors to accumulate technetium 99m pertechnetate more than the surrounding normal salivary gland tissue, has more historical significance . Under certain circumstances, a definitive diagnosis can already be made on the basis of a preoperative fine needle biopsy, although the diagnostic accuracy of this procedure for Warthin's tumor is high with over 95 percent correct diagnosis. At the latest on the surgical specimen, the diagnosis can be confirmed after a histological examination by the pathologist.

Differential diagnosis

The histological picture of the Warthin tumor is usually characteristic, so the diagnosis is usually unproblematic. Differential diagnoses to be excluded by the pathologist are lymphoepithelioma-like carcinoma or mucoepidermoid carcinoma . Warthin tumors with extensive squamous epithelial metaplasia can occasionally cause diagnostic difficulties, especially if there are simultaneous infarctions. In particular, there is a risk of being mistaken for squamous cell carcinoma , especially since the metaplastic variant of the Warthin tumor can also have cell atypia .

therapy

The standard therapy is the complete surgical tumor removal, usually in the form of a superficial (lateral) parotidectomy , in which the mostly tumor-bearing outer lobe of the parotid gland is removed, or an enucleation (peeling). The advantages of enucleation are shorter operating times, a lower frequency of complications (injury to the facial nerve with postoperative facial nerve palsy , Frey's syndrome ) and better maintenance of the function of the parotid gland. The cosmetic result is also usually cheaper. Since the Warthin tumor is a less aggressive, benign neoplasm, once the diagnosis has been confirmed, surgery can be dispensed with in multimorbid patients with a high risk of anesthesia. However, it must be carefully considered that if a diagnosis is made solely by fine needle biopsy, there is a fundamental risk that malignant tumors will also be overlooked.

forecast

Warthin tumors are characterized by slow growth. Malignant transformation has only been described in a few individual cases so far; The derived malignancies include non-Hodgkin and Hodgkin lymphomas , epidermoid carcinomas , mucoepidermoid carcinomas , squamous cell carcinomas , oncocytic adenocarcinomas and Merkel cell carcinomas . Due to the small number of cases, however, it is by no means clear whether Warthin tumors are actually associated with a statistically increased risk of degeneration, or whether it is simply a coincidental temporal and spatial coincidence of a malignant tumor with the Warthin tumor.

As a complication of the diagnostic fine needle puncture, inflammatory changes (swelling, pain, abscess formation ) occur in some cases , although there is not necessarily a bacterial infection present. This can result in a spontaneous infarction of the tumor tissue, which according to a study is observed in around 9 percent of cases after a puncture.

After surgical treatment of the Warthin tumor, low recurrence rates of 2.5-5% are observed. A recurrence of the tumor is favored by a multicentricity of the tumor tissue and an incomplete surgical removal. In contrast, an intraoperative tumor rupture does not seem to have any negative effects in this regard.

Individual evidence

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Web links

Commons : Warthin's tumor  - collection of images, videos and audio files