Introduction

Previous studies have shown the lateralization of different paired organ cancers. While breast cancer was noted more frequently on the left side in females [1, 3, 12, 13, 23, 25, 27, 29], the right-sided lateralization of the head-neck [24], lung [5], kidney [30] and testis [2] cancers were also reported. In the same manner, a large study of a UK cohort involving over a quarter of a million cancer patients has been shown that the right-sided lateralization was reported for the lung, testis, ovarian and kidney cancers, except breast cancer in which there was a left-side lateralization [29]. In that study, the incidence ratio (left/right) were 0.88 for male lung cancer, 0.86 female lung cancers, 0.87 for testis cancer, 0.99 for ovarian cancer, 0.86 for ovarian germ cell cancer, 0.96 for male kidney cancer and 0.94 for female kidney cancer. However, this ratio was unlikely higher than one (1.07) for breast cancer.

Data from human and animal studies have suggested that lymphoid organs have an anatomical asymmetry along the left–right axis in which right-sided lymph nodes was more in number than left-sided ones [6, 11, 17]. The left-sided axillary lymph nodes were fewer in number but larger in size than the right-sided ones in women with breast cancer [17].

Furthermore, it has been shown that there was a left–right asymmetry in pelvic lymph nodes distribution in patients with gynecologic malignancies and there was right-side prevalence for the number of lymph nodes [14, 20, 26]. In addition, in a recent study, a left–right asymmetry in pelvic lymph node involvement by metastatic invasion of endometrial, cervical and ovarian cancers was studied and right-side prevalence was found [14, 20].

Neck dissection is a well-established and widely used procedure for staging and therapeutic decision-making of laryngeal malignancies. It is important that the locations of nerves and vessels in neck surgery especially in thyroid surgery. In this respect, it was shown that the mean lengths of the left recurrent laryngeal nerves (RLN) are longer than the right RLNs. According to this study, it is claimed that RLN has a morphological and functional asymmetry [21]. In addition, superior and inferior thyroid arteries have some different positions and configurations in neck region [16, 18, 28].

To our knowledge, no study in the literature has specifically addressed the existence of a left–right asymmetry in neck lymph node involvement by metastatic invasion of laryngeal malignancies. In this study, we aimed to examine (1) left–right asymmetry in neck lymph nodes distribution in patients with laryngeal malignancies and (2) to investigate if there is left–right asymmetry in neck lymph node involvement by metastatic invasion of laryngeal malignancies.

Materials and methods

The oncologic database of Otorhinolaryngology Department of Medical Faculty, Ataturk University, Erzurum, Turkey were used to identify all patients who underwent functional or radical neck dissection between January 2007 and December 2012. Forty-six patients with only bilateral laryngeal cancer from total 112 patients with laryngeal cancer who underwent neck dissection during the study period were included in the study. Others with unilateral laryngeal cancer or unilateral neck dissection were excluded. The databases include details on demographics, stage, surgical procedures, pathologic examinations, such as lymph node count and involved lymph node count by metastatic cancer cells, intra- and postoperative complications, and hospital stay. In all cases, neck lymph dissection was part of the treatment of laryngeal cancers. All procedures were performed by one surgeon with a comparable background of expertise in head-neck surgical oncology.

During neck dissection procedures, nodal packets of right and left neck regions were removed and sent for pathologic examination as individual specimens. Neck dissection was made in four levels: Level I: submandibular region, Level II: upper neck, Level III: middle neck, Level IV: bottom neck.

All specimens were analyzed by one pathologist from Pathology Department of Medical Faculty, Ataturk University, Erzurum, Turkey. Pathological examination was performed on formalin fixed specimen; lymph nodes were palpatorily identified and isolated from fat tissue, counted and macroscopically examined. Lymph nodes were embedded in paraffin and from each block, 5 μ thick sections were obtained and they were subsequently stained with hematoxylin and eosin.

The study was conducted in accordance with the requirements of the Ethical Committee of the Faculty of Medicine of the University of Fatih. Institutional review board approved the study.

For statistical evaluation, nonparametric Wilcoxon’s test for paired sample in the SPSS 11.0 for Windows program was applied.

Results

In the present study, the numbers of neck lymph nodes were significantly higher on right side than on left side for all neck levels and all neck in bilateral laryngeal malignancies (Table 1). Moreover, the numbers of neck lymph nodes involved by metastatic cancer cells were significantly higher on right side than on left side for level I and II and all neck in bilateral laryngeal malignancies (Table 1).

Table 1 Number of total and involved lymph nodes (mean ± SD) on right and left sides in patients with laryngeal cancer (N = 46)
Full size table

Discussion

In the present study, the numbers of neck lymph nodes were significantly higher on right side than on left side for all neck levels and all neck in bilateral laryngeal malignancies. These results are consistent with those of two recent studies performed in gynecologic malignancies [14, 20, 26]. A right-sided prevalence of the external and common iliac lymph nodes in 54 % of cases in 152 autopsy examinations of individuals died from causes other than lymphatic organ disorders was found [11]. In addition, it has been performed a modified pelvic lymphadenectomy on 30 cadavers showing that both external iliac and obturator nodes were prevalent on the right side than on the left [10]. Moreover, a left–right asymmetry in nodal distribution with a lateral right prevalence has been reported in a variety of nodal groups [6]. The left-sided axillary lymph nodes were fewer in number but larger in size than the right-sided ones in women with breast cancer [17].

The numbers of neck lymph nodes involved by metastatic cancer cells were significantly higher on right side than on left side for levels I and II and all neck in laryngeal malignancies. These right sided asymmetries in the numbers of both total (involved + noninvolved) and involved lymph nodes may result from functional immune asymmetry. Besides, the cell-mediated immune hypersensitivity is stronger in the left side both in human [22] and mice [4]. The stronger cell-mediated immune activity in the left sides of humans may be associated with the blocking of the metastatic invasion of cancer cells from laryngeal malignancies in the left body side.

Morphological, biochemical, physiological, and pathological asymmetries at different levels of the neuroendocrine system have been reviewed [8]. It has been claimed that there is asymmetrical function of a bilateral immune organ, the thymus [15]. Furthermore, a more frequent appearance of herpes zoster infection in the left body side of women was reported [7, 19]. It has also been reported that there was left-sided lateralization of all immune reactions and diseases in a single left-handed female subject [9].

Conclusion

As a consequence, the results of the present study suggest the existence of a left–right asymmetry in neck lymph node distribution and in the neck lymph node distribution involved by laryngeal cancer cells. This situation may be due to the asymmetry in the number of the neck lymph nodes. However, it can be associated with asymmetric configuration of vascular and neural structures in neck region. In addition, the stronger cell-mediated immune activity in the left side of humans may be associated with the blocking of the metastatic invasion of cancer cells from laryngeal malignancies in the left body side.