I had previously written about a spectrum from pure bronchioloalveolar carcinoma (BAC) to invasive adenocarcinoma in one of my first posts here, but the real credit for this concept goes back to Dr. Masayuki Noguchi from the National Cancer Center Hospital in Tokyo, Japan, who characterized a classification system for peripheral lung adenocarcinomas back in 1995 (abstract here). This paper led to the "Noguchi" system of grading the more typical adenocarcinomas from A to D, with some important implications. While other proposed classification systems have been developed, and none is uniformly accepted and used, the Noguchi classification system comes up more than others in describing the continuum I alluded to previously that progresses from pure BAC to invasive adenocarcinoma.

Obviously, this was a Japanese study, which has important implications, because the Japanese world of lung cancer i(LC) s different from that in the US or Europe. In Europe, LC is still very disproportionately male, related to tobacco, and about 50% squamous cancers, while Japan is the other extreme, with some studies showing a closer balance of women and men, 30-50% of patients as never-smokers, and remarkably few cases of squamous cancer, with LC being comprised of generally adenocarcinoma and its well-differentiated subset. A North American population generally shows results between these two extremes.

The Noguchi study involved a detailed analysis of 236 patients with peripheral adenocarcinoma lung tumors (near the outer edges of the lung), all 2 cm or less in diameter. The specifics of the grading system and the definitions of the classes are complex and worth knowing only if you're a pathologist carefully reviewing tissue and describing lung tumors. The important the highlights are that groups A to D are far more common than rare adenocarcinoma subtypes known as tubular and papillary adenocarcinoma, and also that there is a gradation from A to D of most differentiated to least differentiated. Men comprise the vast majority of group D, while the sexes are much more evenly split in the groups that are well differentiated and would be considered BAC or a variant. The likelihood of finding nodal involvement was also related to the Noguchi group; no patients in groups A or B had any lymph node spread of their cancer, compared with 28% in group C and 48% in group D. In addition, pleural involvement and vascular invasion were significantly more common in groups C & D than in groups A & B. Growth and cell division were also factors, with the rate of cell division far higher for the less differentiated cancers. The number of mitoses (my-TOW-sees), or cells in the process of dividing on a detailed look at the slide, was more than 5 per "high-powered field" in only 6% of groups A & B, compared with 26% for group C, and 53% for group D. But the most important factor, correlating with the rates of cancer cell division, was survival, which was 100% after 5 years for groups A & B, but lower as you move stepwise from type C to type D:

(Click on image to enlarge)

This type of trend has also been seen outside of just BAC and adenocarcinoma; I've written that tumor grade is well correlated with survival (see prior post), and specifically that people with well-differentiated LC do better overall than those people with poorly differentiated tumors.

One other important point is that this study demonstrated that patients with small, peripheral, and very well differentiated lung adenocarcinomas had a survival of 100%, while none demonstrated evidence of nodal spread. This raised the question of whether it's necessary to do as extensive a surgery in the setting of a well-differentiated lung adenocarcinoma as you would routinely do for other cancers. If the prognosis is outstanding, perhaps we can do smaller surgeries and still achieve such excellent results. I'll cover the question of optimal surgery for small and well-differentiated lung adenoarcinomas later. This raises the unusual but welcome question in the field of LC, "what is the least we can do to still nearly assure ourselves of excellent results?" Could less be more?