Hans Blaauwgeers

140 Chapter 11 lymph vessels have their anchoring fibers attached to the during inhalation stretched elastic fibers, the negative pressure in the lymph vessels sucks the intercellular oedema into the lymph vessel lumen120. During a limited resection the surgeon clamps part of the lobe. The normal size of the clamp is up to 6 cm long and 1.2 cm width (Ethicon parenchyma stapler, Johnson & Johnson, USA; ENDO GIATM Ultra, Medtronic, Eindhoven, NL)) The clamping (e.g., during segmentectomy, wedge resection), by pressing the tissue in between the clamps, will be likely to cause a lymph flow to both sides of the clamp (see Figure 3B). This clamping of pulmonary parenchyma will cause an artifact upon histology: beside iatrogenic collapse of the alveoli, the lymph between the clamps is pressed into the adjacent parenchyma, causing so called “clamping edema” (see Figure 3C)120 223. If a lymph vessel has tumour cells in the lumen, they may be displaced by the surgical clamping force quite a distance (also in adjacent alveolar spaces). In the study of Gross and colleagues a cartoon shows the location of the tissue sampling for microscopy: close to the staple margin. This location perfectly matches the area with the forcefully clamped dispersed lymph. In the study of Gross and colleagues 5 out of the 10 patients had clear lymphovascular invasion and an additional patient had pleural invasion. Other conventional morphological signs of invasion were not mentioned (such as bronchial, arterial and stromal invasion). IHC analysis (e.g., D2-40) supporting possible lymph vessel invasion in the remaining cases was not performed. In addition, the detailed cytonuclear image of STAS in the completion lobectomy shows condensed chromatin and eosinophilic cytoplasm, more looking like a proapoptotic state than a vital tumour. In this respect, a direct comparison of the STASassigned tumour cells in the completion lobectomy with the tumour cells of the initial resection would be useful. In addition, extravasated erythrocytes are abundantly present in the shown examples (see paragraph below). Compared to previous publications of this institute200 117 the 10 cases in the study of Gross and colleagues199 is biased towards lymph vessel invasion. Considering all arguments, clamping displacement is a more likely explanation for tumour cells seen in the completion lobectomy specimen. In addition, if vascular cooption was essential for tumour cell to survive and grow (as previously stated by the same research group), such a phenomenon should be somehow recognizable on the provided microscopic pictures documenting STAS, but this is not persuasive by showing small inserts inside them. Another observation is that elapsed time between primary and additional (subsequent) resection for all investigated patients was immediate to one month later, with STAS occurring in completion specimens upon wedge resection of primaries. This is again in line with STAS as an artifact via the underrecognized role of lymphatic vessel drainage alterations upon surgical clamping, as above stated.

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