atypical small acinar proliferation （ASAP）

  非典型小腺泡增殖

记得有一次看前列腺电切标本，看到一小灶非典型小腺泡，把剩余的组织取光，都是良性增生的组织，做了p504s，34BE12和p63，胞浆内似有p504s浅染，小腺泡大部分34BE12和p63（-），不能定癌量太少了，但报告怎么写？就去找文献-看文献，，，

  后来得知，对小灶腺泡非典型增生来说，免疫组化对区别ASAP还是腺癌作用不大！

The term atypical small acinar proliferation ASAP was introduced in 1993 by a panel addressing the differential diagnosis of AAH (adenosis) and well-differentiated prostate adenocarcinoma. Concern was expressed that occasionally lesions observed in needle biopsies were more atypical than that expected in adenosis, but were insufficiently atypical to be confidently interpreted as adenocarcinoma. Multiple studies published subsequently during the 1990s confirmed the existence of such a “lesion” and the term atypical small acinar proliferation took root. These studies addressed the appropriateness of its application and the clinical significance and predictive value of ASAP. In 1999, the subject was the focus of an editorial condemning its use in interpreting prostate biopsies. Multiple letters to the editor of the journal, Human Pathology, were written in response to the editorial.  The distillate of this historical flap about ASAP is that although it is not regarded as a nosologic entity, and there have been no diagnostic criteria formulated, it is a valuable functional diagnosis and appropriately applied in the diagnostic interpretation of prostate needle biopsies. Currently, the matter is apparently settled, judging by the lack of renewed criticism of the term. Alternative terms for this diagnostic conundrum have been offered—focal atypical glands, borderline lesion, atypical focus suspicious for malignancy. However, none has gained any substantial acceptance. The reported frequency of ASAP in needle biopsies is 3% reflecting a mean of multiple studies. The lesion is typically a single focus of a few small acini. The interobserver concurrence of interpretation of such foci has been reported to be 62% to 78% in two studies.

Lacking evidence that ASAP is a nosologic entity and has definable diagnostic criteria, ASAP is nonetheless a most valuable functional diagnostic entity. The term is applied when sufficient atypical features of malignancy are not present. The minimal diagnostic criteria for prostatic adenocarcinoma are lacking, but those features present are sufficient to make the focus suspicious (Fig. 7.17A to C). Therefore, although suspicious, the focus is not diagnostic of malignancy. ASAP is the appropriate diagnosis when the confidence level of a diagnosis of malignancy, with resultant definitive therapy, is not achieved. The clinical aspects, most importantly, the PSA level, contribute nothing to the final diagnostic interpretation. The final diagnosis must rest only on the morphologic features present on the hematoxylin and eosin (H&E) slides, occasionally assisted by appropriate immunostains.

Reported circumstances most frequently underwriting the diagnosis of ASAP include the following:

•     Small size of focus and small number of atypical acini

•     Small number of nuclei with enlarged nucleoli

•     A clustered growth pattern lacking infiltrative features

•     Adjacent HGPIN

•     Associated inflammation with possible reactive changes in epithelium

•     Loss of the focus in deeper sections precluding immunohistochemical staining

•     Technical deficiencies of the slide such as overstaining or thick sectioning

名称：图1
描述：The atypical small acini were suspicious for but not diagnostic of adenocarcinoma.

名称：图2
描述：These atypical acini were regarded as most probably benign.

名称：图3
描述：These small acini, regarded as atypical, were of indeterminate risk of malignancy.

名称：图4
描述：A focus of clustered small acini below larger duct/acini with benign features

名称：图5
描述：The corresponding field of small acini show positive staining with p63 in the basal cells present.

Although the diagnosis of ASAP on needle biopsy does not support a definitive diagnosis of malignancy, the patient is at significantly elevated risk of malignancy being identified in follow-up biopsies. Multiple studies have demonstrated that the risk of identifying unequivocal carcinoma on rebiopsy, following a sextant biopsy protocol, ranges from 37% to 60% with a mean risk of 43%. Most studies provide their data on rebiopsies performed within 6 months of the original ASAP diagnosis. Noteworthy is that only 23% to 48% of the malignancies are found at the site of the original ASAP focus. Rabani and associates have reported a 23% rate of false-negative rebiopsies. More recent studies evaluated an elevated detection of invasive malignancy following extended 10- to 12-biopsy protocol.