Secondary Primary Tumors

Recent innovations in the fields of surgical techniques, radiotherapy and chemotherapy have significantly increased the rate of local control of head and neck malignancies, both in the primary focus and in their lymphatic spread. However, the positive developments in local control of the disease have unfortunately not been reflected equally in the life expectancy of patients. The two main reasons for this situation are distant metastasis and disease, which increase in parallel with the success of local control. secondary primary tumors It is one of the problems.

secondary primary tumorsWhat are Secondary Primary Tumors?

While local recurrence and metastases mostly affect the short-term survival of patients with head and neck malignancy, secondary primary tumors are now shown to be the most important factor affecting the long-term survival of these patients. The first publication drawing attention to the importance of secondary primary tumors was made by Billroth in 1889, followed by Warren and Gates's publication based on 1259 cases in 1932.' The definition of secondary primary carcinoma proposed by Warren and Gates is still accepted worldwide today. Accordingly, the criteria necessary to define a tumor as secondary primary are as follows:
1. Malignancy of the tumor must be proven histologically.
2. First and secondary primary tumors should be clearly separate topographically, and there should be no submucosal or intra-epithelial spread.

3. It should be determined that the second tumor is not metastatic. Secondary primary tumors, are described as simultaneous (synchronous) or at different times (metachronous) in terms of their emergence times. Synchronous are those diagnosed with the first tumor or within the first 6 months after the diagnosis of the first tumor. Differentiated tumors are tumors diagnosed at least 6 months after the diagnosis of the first tumor. There are also authors who group tumors diagnosed at the same time as the first tumor into a third group as simultaneous tumors.


Various theories have been proposed to explain the multifocal development of carcinomas. The field cancerization view put forward by Slauhter et al. in 1953 is the most accepted today. According to this view, the epithelium of the upper digestive tract, along with all respiratory tract, forms a common carcinogenic area where anatomical and pathological changes occur due to external influences, especially smoking and alcohol. Precancerous tissue changes may begin in more than one focus in this area, and different foci of cancer may appear at different times depending on the degree of precancerous changes.

There are studies showing that genetic predisposition, as well as external factors, is a very important factor in the development of multiple cancers. According to Faber, one of the pioneers of this view, cancer occurs as a result of step-like tissue changes that develop over a long period of time. Accordingly, there are three main periods in cancer development, defined as initiation, promotion and progression. In the initial period, a permanent change in the phenotype of a few target cells occurs due to carcinogenic external factors. During the growth period, these target cells proliferate and form proliferation foci similar to benignneoplasia.

These foci then either turn into normal tissue again or progress towards cancer. In some other studies, people with genetic deficiencies in DNA repair mechanisms secondary primary tumors It has been shown to develop more easily. This genetic deficiency can be revealed by investigating sensitivity to mutagens such as bleomycin. In conclusion; It is accepted that exposure to environmental carcinogenic factors and genetic predisposition play a role in the development of secondary primaries.

secondary primary tumorsFREQUENCY

Literatürde baş boyun malignansilerindeki sekonder primer sıklığı olgu sayısı, izleme süresi ve coğrafik özelliklere bağlı olarak %2.4 ile %35 arasında değişmekle beraber, genel olarak %10-15 civarındadır. Sekonder tümörler histolojik olarak çoğunlukla skuamöz hücreli kanserlerdir. Metakron sekonder kanserler, senkronlara göre genellikle 3/2 oranında daha sıktır. Senkron tümörler daha çok oral kavite, larenks, farenks ve özofagusta, metakron olanlar ise daha çok akciğerde görülmektedir. İlk tümörün tanısı 60 yaşından önce konan olgularda sekonder tümör şansı daha çoktur. Sekonder tümörler en sık 60-70 yaş grubunda ortaya çıkmaktadır ve erkeklerde daha fazladır.

Annually after diagnosis of first tumor secondary primary tümörler gelişme riski çeşitli serilerde %1.5 ile %6 arasında değişmektedir ve bu risk oranı seneler boyunca sabit kalmaktadır. 1920 Sekonder tümörler büyük sıklıkla üst solunum ve sindirim yolları epiteli ile akciğerlerde görülmektedir. Daha nadir olarak gastrointestinal sistem, ürogenital sistem, deri, tiroid bezi, iskelet sistemi ve diğer bölgelerde de ortaya çıkabilir. Sekonder primerlerin genel olarak %40-50 kadarı üst solunum ve sindirim yollarında yerleşim gösterir. Oral kavite, orofarenks ve hipofarenkste görülme sıklığı, larenkse göre daha fazladır. Değişik çalışmalarda akciğerlerdeki sekonder tümör oranı %10 ile 50 arasında değişmektedir.

Initial tumor size, stage, histology and nodal metastasis factors and lung secondary tumor No relationship was found between the frequency of Lung secondary tumors are most often squamous cell cancers, more rarely adenocarcinoma and small cell cancers. Difficulties in differentiating a lung lesion from metastasis or secondary tumor still persist. Histological criteria are important in differentiation. Findings supporting a secondary tumor include the lesion being hilar or endobronchial, appearing a long time after the initial tumor, and the absence of metastasis in the neck. In addition, it is reported that isolated lung nodal opacities detected radiologically are mostly secondary primary rather than metastases. In recent years, molecular level research on cancer cells has been able to distinguish metastatic and secondary tumors more clearly.


Location of the first tumor in the head and neck, secondary primary tumors sıklığını etkileyen önemli bir faktör olarak görünmektedir. Sekiz yüz elli bir olguda yapılan bir çalışmada, sekonder primerler beş yıllık bir izleme süresi içinde en sık dil kökü kanserlerinde (%41), daha sonra sıklık sırasına göre piriform sinüs (%34), oral kavite (%27), larenks (%23) ve tonsil kanserlerinde (%15) ortaya çıkmıştır. İlk tümörün histolojisi ve diferensiyasyon derecesi, sekonder tümör sıklığını etkilememektedir.12 Ayrıca baş boyundaki ilk tümöre uygulanan tedavi şeklinin de (cerrahi ya da radyoterapi), sekonder tümör sıklığına etkisi yoktur.

"Larynx and oral cavity cancers are the most common head and neck malignancies in our country, as is the case around the world." Secondary primaries in laryngeal cancers frequently occur in the lung and esophagus. Although the possibility of secondary tumors in early stage (T1-T2) tumors with high local and regional control of the larynx is higher than in advanced stage tumors (T3-T4), the degree of differentiation of the tumor does not affect the frequency of secondary tumors.

The possibility of secondary tumors is slightly higher in supraglottic tumors than in glottic tumors. On the other hand, secondary primary tumors are twice as common in patients who underwent conservative surgery for laryngeal cancer compared to those who underwent total laryngectomy. In oral cavity cancers, secondary tumors are usually seen in the oral cavity and oropharynx. In oral cavity cancer, it is reported that the probability of secondary primary in the oral cavity is 75 times higher in men and 190 times more in women than in the normal population, and the chance of secondary primary in the esophagus is 25 times higher in men and 45 times higher in women. In cancers of the lower region of the oral cavity (floor of the mouth, lower alveolar ridge and retromolar trigone) that are more exposed to external factors such as smoking and alcohol, the possibility of secondary primary is higher than in other regions of the oral cavity.

In oropharynx and hypopharynx cancers secondary primers It most commonly develops in the oral cavity and hypopharynx, and in esophageal cancers, it often develops in the upper digestive tract, especially in the hypopharynx, oropharynx and buccal mucosa. On the other hand, secondary cancers located in the head and neck, especially the larynx, are common in lung cancers.


Since the risk of secondary tumors in head and neck malignancies continues at a constant rate over the years, patients need to be monitored periodically throughout their lives after the diagnosis and treatment of the first tumor. The recommendation of the American Cancer Society (ACS) on this subject is that patients should be checked monthly for the first year, every 2 months for the second year, every 3 months for the third year, and every 6 months for the remainder of their lives. In the follow-up of patients, it is important to examine the head and neck region, where secondary primary tumors are most common.

For this purpose, in addition to routine mouth and throat examination, indirect and direct laryngoscopy, rigid and flexible endoscopic examinations of the nasal cavities, nasopharynx, oropharynx and larynx should be performed. There are also authors who recommend esophageal abrasive cytological examinations in addition to routine panendoscopic examination, including esophagoscopy and bronchoscopy, at periodic check-ups. However, in our department and many other centers, esophagography and selective endoscopy are preferred instead of panendoscopy, considering the symptoms of the patients. Secondary primary tumors To evaluate the lungs where it is most common, radiological examination is recommended every 6 months.

This monitoring is especially important in laryngeal cancers, where lung secondary tumors are more common. Depending on the available resources, radiological examination can be performed as conventional radiography or computed tomography, but it is reported that computed tomography is much more sensitive in the early detection of lung secondary tumors. Nearly half of the secondary primaries other than the head, neck and lungs occur in the urogenital system.
Therefore, patients' complaints in this regard should be carefully evaluated during follow-up. There are many studies investigating the value of biological tumor markers (tumor markers) in monitoring patients with head and neck malignancy in terms of secondary primary, but today, a marker that has proven its value has not yet been found.


Secondary in patients with head and neck malignancy primary tumor In order to reduce the possibility, emphasis is placed on the elimination of carcinogenic external factors such as smoking, alcohol, occupational and environmental irritants, as well as the benefit of chemoprevention with retinoid derivatives. It has been shown that high doses and long-term use of retinoid derivatives cause regression of precancerous lesions. However, it has side effects such as dry mouth, dysphagia, weight loss, and cachexia, and the lesions often recur after discontinuation of treatment.

secondary primary tumorsPROGNOSIS

Baş boyun malignansilerinde sekonder primer varlığı, prognozu dramatik bir şekilde kötüleştirmektedir. Metakron tümörlerde prognoz senkronlara göre biraz daha iyidir.” Baş boyun yerleşimli sekonder tümörlerde 5 yıllık sağkalım şansının %20 civarında, özofagus ve akciğer yerleşiminde ise %5’in altında olduğu bildirilmektedir.10122 İlk tümörün tanı ve tedavisinden sonra periyodik olarak izlenen hastaların ortalama sağkalım şansı, ortaya çıkan semptomlarla kendiliğinden başvuranlara göre yaklaşık 2 kez daha fazladır.


Secondary primary tumors günümüzde baş boyun malignansili hastalarda prognozu olumsuz yönde etkileyen önemli bir sorundur. Baş boyun malignansilerinde senkron ya da metakron olarak olguların %10-15’inde görülen sekonder primerler, en sık olarak yine baş boyun bölgesinde ve ikinci sıklıkla akcigerlerde ortaya çıkmaktadır. İlk tümörün tanısından sonra sekonder tümör olasılığının yıllarca sabit bir oranda sürmesi, baş boyun malignansili olguların ömür boyu periyodik izlenmelerini gerektirmektedir.

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