The term precancer was used for the first time by dermatologist Dubreuilh in 1896. He derived the term from a clinical experience on some skin lesions that regularly transform into malignant forms. The term precancers
designates states and lesions that may transform into a carcinoma
. There are also pre-sarcomatoses
giving a rise to sarcomas and pre-melanomatoses
from which a malignant melanoma originates. All these conditions are generally named as pre-blastomas
. At the general medical knowledge, the term precancer is used (not entirely accurately) to describe all pathological lesions that can be a basis for malignant tumorous growth.
Due to the fact that tumors of the oro-facial and stomatological areas are carcinomas in 90% of all cases, it would not be such a mistake to use the common term precancer for pre-neoplastic conditions and lesions at the above described anatomical area. It would be apt to remind here that the term precancer is not definite but relative one, since not all precancers get malignant and not all malignant tumors are derived from precancers. Such relativity by no means decreases the significance of precancerous conditions for etiology and pathogenesis of malignant neoplasias and the oncological prevention (the secondary prevention). For these reasons, clinical oncologists, in concordance with onco-pathologists, recommend to divide the precancerous conditions into those of the narrowest and widest sense of the term.
Precancers in the wide sense
are termed as precancerous conditions
or facultative precancers. Basically
, they are initial affections of the skin of the face and the oral cavity mucosa that are predetermined with a statistically high probability for transformation into a precancer (in the narrowest sense) itself. The list of facultative precancers includes chronic contact dermatoses and mucosidoses (e.g. tar or nicotine induced), electrochemical mucosidoses and glossitises, chronic radiodermatosis, inflammatory and atrophic damages by irradiation with light rays (cheilitis of sailors and agricultural workers) and initial forms of xeroderma pigmentosum. Some forms of simple leukoplakias (transitory, exogenously induced) can be mentioned at this group, as well as the Sjögren’s syndrome which can give rise to a lymphoma with malignant properties, upon chronic non-bacterial sialadenitis (sialosis). We should not overlook odontogenous cysts whose epithelium is also prone to malignant changes and last, benign tumors of the skin and skin adnexa (especially pigmented ones) of the face and the oral mucosa(papillomas).
The above mentioned conditions manifest themselves as clinical units and their facultative transformation into an obvious precancer can be proven upon histo-pathological examination only. It is a matter of experience and predictability, if and when these altered tissues should be verified bioptically. Less experienced physician should consult such cases with a specialist.
Precancers in the narrow sense
are termed as precancerous lesions
or obligatory precancers.
They are often (but not always) derived from corresponding initial forms of facultative precancers. In order to diagnose obligatory precancers, it is necessary to perform cytological
verification of markers, characteristic for precancers. Skin and mucous precancers originate on the etiological basis of both endogenous and external factors. Endogenous (disposition) factors are genetic, race- and constitution-related, and immunological. Exogenous (exposition) factors are both physical effects (mainly radiation) and chemical (carcinogenic compounds). An individually specific constellation of both disposition and exposition factors may result in formation of favorable conditions for initialization of precancerous states (in the widest sense).
Obligatory precancers include the following skin and mucous lesions: keratoses (solar-induced and actinic), xeroderma pigmentosum, morbus Bowen, erythroplasia Queyrat, cheilitis abrasiva praecancerosa, lentigo maligna and leukoplakias.
are probably the most frequent epidermal precancers. They appear at elderly people on the face skin and mucosa of the lips, exposed to light rays or radiation. Keratoses have an appearance of multiple dry and adhering flakes, sometimes forming a cutaneous horn (cornu cutaneum). Histology reveals a dominant hyperkeratosis and nuclear abnormalities at the epidermal cells. Keratinoses of an actinitic origin have a 25% chance to be transformed into a flat-cell carcinoma.
is manifested as an isolated, flaky focus of psoriatic look which appears independently of the exposure to solar or other kinds of irradiation. Some pathologists consider it as a carcinoma in situ (intraepithelial carcinoma that does not overlap the mucosa basal membrane). A histological picture shows cellular polymorphism, nuclear abnormalities, atypical mitoses and other signs of malignant transformation of this lesion. Morbus Bowen may also appear on the mouth mucosa
, namely at the retro-molar area and gingiva. The stage of development of this precancer is determined by an actual degree of proliferation activity (number and quality of mitoses) which can be assessed only histologically.
is characterized by focal hyperpigmentation of the skin of the face, flaking, atrophy and inflammation of the skin stroma. An inflammatory hyperplastic stage is followed by a proliferative process in the skin. Epidermal, as well as mesenchymal malignant tumors may develop from these foci. Again, a diagnosis can be clarified by histological examination only.
is characterized by red colored area located mostly at the border of the skin and lip mucosa, although it may be found on the oral mucosa as well. It is a network of capillaries that can be seen underneath a thin, pigment-lacking layer of horny cells. Based on degenerative and atrophic processes, a precancer with high proliferative tendency may develop. For this reason, the erythroplakia is already considered as a carcinoma in situ. A histological verification only can provide for conclusive results.
Cheilitis abrasiva praecancerosa
, as an obligatory precancer
, is commonly derived from a facultative actinitic cheilitis. It affects large sections or even the whole vermilion of the lower lip. At the stage of confluent erosion it already possesses signs of a carcinoma in situ. The precancer may be obscured by a clinical picture of inflammation and escape from identification for a long time.
(melanosis circumscripta praeblastomatosa) forms dotted pigmentation and indistinctly bordered foci on the face skin exposed to the solar radiation. It may also appear on the oral mucosa of lips, gingiva and palate. Histological picture shows hyperpigmentation of basal melanocytes at early stages, which can later form clusters of melanocytes. This proliferation of the population of melanocytes determines atrophy of the epidermis, under which a strong inflammation of the stroma is apparent.
Early diagnosis of lentigo maligna and its differentiation from benign melanoses (pigmented nevi) is crucial, a timely excision guarantees almost 100% success of therapy. Otherwise almost 50% of lentigo maligna cases get transformed into a malignant melanoma.
is, according to the WHO (World Health Organization), literally a clinical term describing a “white, non-effaceable region of a mucous membrane that cannot be associated with any defined disease”. Different usages and interpretation of the term leukoplakia caused many misunderstandings mainly because the term has been used at clinical and patho-morphological literature most definitely for precancerous lesions. In clinical praxis, one has to consider that differentiation among a benign symptomatic mucous diseased patch (a white patch), a precancer, and a carcinoma in situ can be made only according to the cytological and patho-histological criteria. At present, classification of leukoplakias according to the degree of dysplasia is preferred which means studying mainly polymorphism of cells and cell nuclei
, number and irregularities of mitoses, disappearance or damage of a regular arrangement of mucous layers and continuity (sharpness) of the basal membrane, by means of bioptic sampling. Classification of precancers (and all pre-neoplasias in general) in pathology has a non-disputable importance for a prognosis of the disease. For leukoplakias, a crucial criterion for determination of degree of malignity is the absence or presence of a dysplasia. Leukoplakias without signs of a dysplasia have a benign character and classify in the group of precancers at the widest sense (a facultative precancer). A leukoplakia with an apparent dysplasia of the moderate or high degree is already a precancer in the narrowest sense (an obligatory precancer) or even an early stage of a carcinoma (a carcinoma in situ). This brief and simplified description of pathological classification of leukoplakias can be concluded with a fact that the higher the degree of dysplasia, the higher the frequency of transformation of a leukoplakia into a mucous carcinoma.
Two more notes are worth mentioning from the clinical point of view: The first note provides a closer look on quantitative relationships of individual types of leukoplakia, classified according to the degree of dysplasia. Among all types of leukoplakia, forms with no signs of dysplasia or with very low degree of dysplasia represent 74%, forms with moderate dysplasia 17%, and with high degree of dysplasia 6%. Remaining 3% can already be classified as carcinomas in situ (Seifert and Burghardt). The second note concerns over-growth of Candida albicans at the site of a leukoplakia related infection and its vicinity. Such an infection always presents a risk factor and signals weakening of the cellular immune system. A thrush is observed at as much as 35% cases of leukoplakias with high degree of dysplasia. The oral cavity leukoplakia occurs most frequently during the fifth decennium and its occurrence rate increases with age. Men suffer from it more often than women. Not only age, but also a location are important for prognosis. Leukoplakias on the palate and alveolar mucosa have a minimum tendency to malignant transformation and they almost never recur. On the other hand, leukoplakias of the mouth base possess the least optimistic prognosis due to their tendency to a malignant growth.
From clinical and macroscopical perspectives, these diseases include leukoplakia plana, verrucosa and errosiva. Microscopic pictures correspond to this division, identifying the flat form (plana), papillary-endophytic form, and papillomatous-exophytic form. The flat form of leukoplakia presents about 70% of all cases and appears most often on the mucosa of lips, cheeks and tongue. The papillary-endophytic form of leukoplakia presents about 22% and it is mostly diagnosed on the mouth base and the alveolar ridge. The papillomatous-exophytic form is the least common form (3% of incidence) and appears mostly at the palate and the alveolar ridge. While the simple flat form of leukoplakia rarely turns into a precancer, the verrucous form (grooved patch with wartlike projections) and especially the erosive form (de-epithelized ulcerous patch) possess clearly higher trend towards a malignant transformation into a carcinoma (up to 38% in case of erosive forms, Seifert). These two forms should always rise a clinician’s doubt about a precancer of an obligatory type or even an initial form of a carcinoma. This leads to an important observation that every clinician, including those from the field, get involved in the process of an early diagnostics and therapy just upon a slightest suspicion of a malignant tendency. A clinician has to make sure that these services are delivered. In practice it means that a suspicious lesion is subjected to analysis by a specialist which is in patient’s own interest. A specialist determines the degree of a leukoplakia lesion by the diagnostic excision and organizes further therapy based on its results. The issue of precancers is predominant especially in the stomatologic field since malignant processes at the oro-facial area can be recognized at early stages. This puts a great deal of oncological responsibility onto all stomatologists. Awareness of this responsibility should result at a close and active collaboration of a local clinic with a specialized department capable of dealing with problems of stomatological oncology.
11.6 Survey of the Oro-facial Tumors
Benign tumors of the oro-facial area grow from soft and hard tissues, including odontogenous tissues. They can be by no means underestimated since they may transform into malignant tumors or destroy the original organ and its vicinity by an expansive growth. Vascular tumors posses a danger of excessive bleeding. Based on the tissue of origin, these tumors can be divided into epithelial, mesenchymal and odontogenous.
Benign epithelial tumors grow from the mouth or salivary glands epithelium. Most often, a papilloma occurs as exophytically growing, sometimes pedicled structure on the mucous membranes of the cheeks, tongue and palate. Multiple papillomatosis of the palate or cheeks may occur as well. The verruca (a wart) on the face skin belongs to the same group. Therapy of these tumors is surgical. An adenoma grows from the epithelium of salivary glands. Based on their histological composition, they are mostly mixed tumors - pleomorphic adenomas, or there can be monomorphic adenomas composed of cells of one type (adenolymphoma, oxyphillic adenoma). Also for these tumors, the only appropriate therapy is the surgical removal.
Benign mesenchymal tumors originate from various tissues of the facial area. Based on histological composition, they classify as fibromas, lipomas, myomas, angiomas, lymphangiomas, osteomas, and tumors of neurogenic origin. They manifest commonly as bordered structures of various texture, growing slowly inside the oral cavity. If they grow inside the bony tissue, they result in deformation of the jawbones (osteomas, intra-osseal fibromas). A formation that sits on an alveolar ridge near a tooth appears quite frequently inside the mouth - epulis. It has to be removed surgically, followed sometimes by extraction of a tooth in which vicinity it grows. Hemangiomas (capillary or cavernous forms) grow slowly inside the oral cavity; they may be wounded by a hard food which results in bleeding. Hemangiomas appear also on the skin of face together with the inherited vascular anomaly - naevus flammeus. In case of haemangiomatosis faciei, large angiomas penetrate into the jawbones from soft tissues, making a surgery complicated. For therapy of small hemangiomas of the oral mucosa, a cryo-destruction, sclerotization (injection of Aethoxysklerol) and surgical extirpation are often used with a good success. In cases of extensive facial angiomatoses, a pre-operational selective micro-embolization of supplying vessels by small plastic spirals or globules is used. The subsequent surgery then results in smaller blood losses.
Odontogenous tumors originate from the primitive dental epithelial strip which is the basis of dental tissues during development. Based on contribution of a particular component, tumors are categorized as epithelial, mesenchymal and mixed. One of the most prominent epithelial odontogenous tumors is the ameloblastoma (adamantinoma, multi-locular cystoma). It appears mainly at the lower jawbone around the angle, it has mostly a cystic form and it deforms the mandible and makes it thinner by its expansive growth. An X-ray examination reveals a picture of a multi-ocular cyst with thin partitions. However, solid forms exist, too. Therapeutic surgery has to be radical since when not removed completely, this tumor recurs and tends to become malignant (malignant ameloblastoma). Out of all mesenchymal odontogenous tumors, the cementoma has to be mentioned. It is created by proliferation of cementoblasts of the periodontal membrane. On an X-ray image it appears as homogenous, surrounded shadow around a tooth’s root. The soft odontomas, odontoblastomas and hard odontomas belong among the mixed odontogenous tumors. All these odontogenous tumors should be removed surgically.
Malignant tumors of the oro-facial area are marked by an invasive and destructive growth, formation of metastases and cachectization of patients.
Malignant epithelial tumors originate from the covering epithelium of the skin, oral mucosa or salivary glands mucosa. Among the most frequently occurring carcinomas of the oro-facial area is the lip carcinoma, which appears on the lower lip of men in 95% of cases. It is a spinous cellular carcinoma which appears in two forms. The surface form grows exophytically. It begins in most cases as a small focus of peeling hyperkeratosis on the lip vermilion, grows gradually, it develops the form of verruca and finally gets ulcerous. Resulting ulcer possesses a stiff base, infiltrated edges and is painless. On the mucous side, the ulcer is covered often with a leukoplakia-like altered mucosa. The deep, endophytic form begins by a primary lip infiltration. A crater-like ulcer with reddish edges appears soon. Metastases into regional lymph nodes appear rarely at late stages. Surgical therapy - the quadratic excision - has a very good prognosis at early stages. On the other hand, the tongue carcinoma has much worse prognosis. It appears mainly in young men. It begins on the tongue’s edge, around the base, and sometimes on the underside of the tongue. An initial rough infiltrate quickly assumes an ulcerous form and tumor grows into the oral cavity. It often forms metastases at the deep lymph nodes of the neck. Therapy of carcinomas of the tongue is very tedious and requires utilization of all components of the complex, integrated treatment. The carcinoma of the maxillary sinus that originates from the mucosa of epithelial lining of the antrum, causes diagnostic difficulties. Due to its location, it can remain hidden for a long time (crypto-carcinoma) with vague signs that resemble rather a chronic sinusitis. The first signs are feeling of stuffy nose, loosening of the teeth, eventually a prolapse of neoplastic tissue from the extracted tooth alveolus at the upper jaw. At late stages, the tumor spreads through the bone walls of antrum into adjacent areas and outgrows into cheeks and orbits. A prognosis depends on the stage at which the tumor is identified. The carcinoma of the buccal mucosa originates mostly from a proliferating leukoplakia around the occlusal line and the mouth corners. It is characterized by cauliflower-like projections of tumor tissue, formation of ulcers and infiltration into adjacent tissues. The carcinoma of the lower jaw manifests as an ulcerous structure of the alveolar mucosa which grows into the bone, the oral base and soft tissues. A central form of carcinoma occurs rarely, originating from remaining epithelial Malassez’s cells. If osteolysis of jawbones is found on X-ray images, it is necessary to consider metastasizing tumors of remote organs into jawbones, e.g. carcinomas of the thyroid gland, mammary glands, lungs or seminomas.
Malignant mesenchymal tumors.
According to the place of origin
, these tumors can be identified as sarcomas of soft tissues and jawbones.
Soft tissue sarcomas
arise from submucosal ligaments, fascial connective tissues and lympho-reticular tissue. On the basis of prevalent types of cells they can be divided further as sarcomas with round cells, spindle cells and polymorphic cells.
Compared to malignant epithelial tumors, sarcomas affect younger population and children with a bad prognosis. Metastases are spread by the bloodstream. Tumors grow rapidly and infiltrate adjacent structures. Somewhat better prognosis have partially differentiated sarcomas - fibrosarcomas and myxosarcomas.
Sarcomas of the bones
(osteogenous) metastase into the lungs shortly. The osteolytic form
causes rapid destruction of the jawbones and outgrowths into surrounding tissues. The osteoplastic form
(sclerotic) grows at slower pace and often reaches a considerable size. Areas of diffusive clear patches and condensed bony tissue can be seen on X-ray images, with radially arranged spikes on the bone edges (spikula). Sarcomas that arise from the lympho-reticular tissue
, namely hemo-blastomas
form a separate group. Diagnostics and therapy of these tumors belong to the scope of specialists. A skilled stomatologist can identify some of these tumors based on a clinical picture of changes inside the oral cavity (hyperplastic ulcerous gingivitis associated with leukemia etc.).