Signet ring-like cells: No longer a “signature” of glandular differentiation

Pleural metastasis from pulmonary primary signet‐ring squamous cell carcinoma. Case report and literature review

“…The first of them is due to the accumulation of substances such as sialomucin, immunoglobulins, glycogen, keratin, or intermediate filaments. The second is linked to the formation of vacuoles, either by hydropic degeneration, invagination of the cytoplasmic membrane, dilation of the endoplasmic reticulum, or processing artifact 1,15 . As we have already mentioned, in adenocarcinomas with signet‐ring cells, the associated mechanism would be the accumulation of mucin, detectable by classical histochemical techniques such as PAS or Alcian blue.…”

“…The second is linked to the formation of vacuoles, either by hydropic degeneration, invagination of the cytoplasmic membrane, dilation of the endoplasmic reticulum, or processing artifact. 1,15 As we have already mentioned, in adenocarcinomas with signet-ring cells, the associated mechanism would be the accumulation of mucin, detectable by classical histochemical techniques such as PAS or Alcian blue. A different pathway has been postulated for signet-ring cell squamous cell carcinomas.…”

“…Various studies propose dilation of the endoplasmic reticulum as the first option. 1,2,8 Another less plausible hypothesis points to hydropic degeneration or accumulation of intercellular fluid. 1,15 Although it is necessary to elucidate the pathophysiological mechanism by which signetring cells are produced in squamous cell carcinoma, we consider it just as important or even more important to make a correct microscopic diagnosis, as some authors have pointed out, 11 taking into account their therapeutic implication.…”

“…The characteristic morphology of signet-ring cells implies the presence of a large intracytoplasmic vacuole, and/or accumulation of intracytoplasmic material, which causes compression of the nucleus and its displacement to the periphery. 1,2 The nucleus-cytoplasm ratio is usually low, with little nuclear atypia. 3 The presence of signet-ring cells is traditionally linked to mucin-producing epithelial neoplasms, of the adenocarcinoma type, whose most frequently described locations have been the stomach, breast, pancreas, ovary, and colon.…”

“…The characteristic morphology of signet‐ring cells implies the presence of a large intracytoplasmic vacuole, and/or accumulation of intracytoplasmic material, which causes compression of the nucleus and its displacement to the periphery 1,2 . The nucleus‐cytoplasm ratio is usually low, with little nuclear atypia 3 .…”