Elsevier

Medical Hypotheses

Volume 75, Issue 2, August 2010, Pages 185-186
Medical Hypotheses

Lymphangiogenesis may explain adrenal selectivity in lung cancer metastases

https://doi.org/10.1016/j.mehy.2010.02.016Get rights and content

Summary

The ‘seed and soil’ hypothesis of organ selectivity in cancer metastasis dated back to the 1870s. A century later, a review of significant selectivity data revealed that the adrenals featured in 11 of 12 classes of it, thus promoting these two organs for research. Fortunately, two discoveries have also occurred, namely, (a) that cancer stimulates lymph vessel formation, i.e., lymphangiogenesis, and (b) that lymph and blood vessels are differentially stainable. Accordingly, these interesting ideas should be exploited with a hypothesis. Therefore, it is proposed that, at autopsy in lung cancer cases, the tissues between the primary lung tumor and the adrenal secondary should be meticulously serially sectioned and disjunctively stained because they must reveal what naturally occurs in this zone during life. It is predicted that this maneuver will identify lymphangiogenesis as the phenomenon responsible for the age-old puzzle of adrenal selectivity. Indeed, it may explain other puzzles such as intracranial lymphatic connectivity.

Introduction

An article written in 2009 attributed to Paget’s 1889 publication the ‘seed and soil’ hypothesis of organ preferences of different tumors with respect to metastatic spread [1]. However, it is worth recalling that, in 1871, no less an authority than Billroth [2] generalised with regard to metastasis that, being “like the seed of some lower plants, they find almost everywhere soil suited for their development, and can grow in most tissues of the body”.

Body wide susceptibility to cancer colonization was a relatively simple concept. That which was unique was selective subjugation of target tissues. This was what Coats [3], the first Professor of Pathology at Glasgow University, was perspicacious about in 1878, when he reviewed a Continental work on metastasis. As he specified narrowly, “The selection of the tissues is perfectly consistent with the circumstance that the seed requires a suitable soil”.

Section snippets

Soil/organ selectivity

In a review [4] published almost a century later, twelve classes of organ or soil selectivity were delineated as follows: oddity, singularity, peculiarity, partiality, propensity, proclivity, susceptibility, suitability, cryptogenicity, capacity, facility, and disparity. Next, it was argued that “Nature herself has indicated the organ on which to concentrate research (because) the adrenal gland featured in all but one of the selectivity patterns classified above.” After noting that five

Adrenal metastases

A statistical study of 1000 cases of lung cancer led to the conclusion that, with reference to adrenal metastasis, the lymphatic route probably supervenes [6]. On increasing the tally to 6000 cases and including practical illustrations, a London University doctoral thesis [7] was equally conclusive. What did others find? Firstly, Spencer’s [8] own thesis from the same University highlighted Fig. 65 which showed:

a lymphatic channel leaving the adrenal capsule which is continuous with those deep

Lymphangiogenesis hypothesis

As its name implies, lymphangiogenesis simply means the bodily formation of new lymph vessels. In 1959, Zeidman [11] demonstrated that this phenomenon occurred in 70 experimental animals. Following his footsteps, it was shown in 1963, using a lung cancer series [12], that this occurs also in human beings. Although Bell [13] accepted this finding soon afterward in 1965, most authors have not done so, including the year 2007 reviewers [14] whose 93 references included 10 that dealt with

Future prospects

Other puzzling patterns should be pursued on the basis of lymphangiogenesis. For instance, there is the vexed question of intracranial lymphatic connection [16]. Now, as Kyzas and colleagues [17] reiterated, “These results indicate that lymphangiogenesis indeed occurs in head and neck squamous cell carcinoma.” Therefore, serial sections should be investigated with large enough tissues that encompass intracranial metastases and upper neck metastases when squamous cell carcinomas occur.

Conflict of interest statement

None declared.

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