Atypical Small Acinar Proliferation (ASAP)
Estimation of prostate needle biopsy specimen
ANDREAS C. LAZARIS
1. Under low magnification we notice prostate glands of medium and small size (yellow and green arrows, respectively) , some basophilic areas (black arrows) and the fibromuscular prostate stroma (pink asterisks).
The epithelium of non cancerous prostate glands consists of basal cells (which are immunoreactive to high molecular weight cytokeratins and p63) and luminal secretory cells. With regard to their luminal border, non cancerous prostate glands frequently demonstrate micropapillary folds, unless they are atrophic.
2. Under medium magnification , we notice that the focally basophilic appearance of the fibromuscular stroma is due to lymphocytic aggregates (blue asterisks).
The conventional , acinar type of adenocarcinoma consists of small sized glands. There are three types of small sized prostate glands in the present field:
the more basophilic ones (blue arrows) may show either reactive atypia, complete atrophy or basal cell hyperplasia ( the latter condition, however, is mainly observed in the central zone of the prostate gland and thus it is not likely to be noticed in needle biopsy specimens which are taken from the peripheral zone of the gland),
the small glands with microcystic dilation (orange circles) are probably atrophic and
the central ones (red arrows) which are vertically orientated alongside the biopsy, are suspicious for cancer. The cells in the latter glands contain a sufficient amount of cytoplasm in contrast to the atrophic ones. Furthermore, the suspicious glands interrupt the muscular bundles of the prostate stroma (red double arrow).
3. Nearby, we notice prostate glands of a larger size with luminal micropapillary folds (black arrows) and of a slightly basophilic appearance due to focal stratification of nuclei (blue arrows).The size of the glands and their folded luminal border are against the diagnosis of invasive malignancy. Furthermore, basal cells are probably present in these glands (green arrow). Focally, a nucleus located close to the basement membrane (red arrow) is of bigger size by comparison to other nuclei towards the centre of the lumen (yellow arrow), in other glands, though. This maturation phenomenon could be indicative of prostatic intraepithelial neoplasia (PIN), a term used to describe cellular dysplasia of the prostatic epithelium; nevertheless, it is not so consistently detected in the above glands ,so the diagnosis of high grade PIN cannot be made with certainty in this field stained by haematoxylin-eosin. This morphology might be consistent with low grade PIN, a lesion which should not be reported in the pathologic examination since it is of ambiguous clinical significance. To sum up, these large glands should finally be considered as normal, not dysplastic.
4. Let’s have a closer look at the suspicious glands in the centre of this image. Note their vertical orientation, the interruption of muscular bundles (pink asterisks), the sufficient amount of cytoplasm and their sharp luminal border (brown circles). In addition to the suspicious glands, we notice the basophilic small sized glands (blue arrows) surrounded by inflammation (blue asterisks).
5. In some epithelial cells’ nuclei, nucleoli are visible (black arrows) and occasionally conspicuous (red arrow). Prominent nucleoli favor the diagnosis of prostate adenocarcinoma. Some of the nuclei are hyperchromatic (purple arrows). Since elements of the basal cell layer are not always easy to observe in haematoxylin-eosin sections, immunohistochemistry with specific markers against basal cells [ ie, high molecular weight cytokeratins ( e.g. 34βE12, CK5/6 ) ] is performed.
6. An intact high molecular weight cytokeratin –immunoreactive , basal cell layer is noticed in normal prostate glands on the left . Relatively increased immunoreactivity is noticed in the small sized glands on the right by comparison to the other benign prostate glands on the left. The glands on the right correspond to the basophilic small sized glands we noticed in the previous haematoxylin-eosin sections (blue arrows, figs2 &4); glands with complete atrophy are basophilic and since their luminal cells are atrophic, the immunoreactive intact basal cells predominate.
7. With regard to the suspicious glands, no specific immunostaining against basal cells is observed; so, these glands appear to lack basal cells . A minimal immunostaining , possibly aberrant, is detectable in one or two glands (black arrows); we cannot be sure whether it represents remnants of the basal cell layer or not. In order to make a safe diagnosis of prostate cancer with certainty, we shouldn’t be able to observe any basal cells at all.
8. Additional immunohistochemistry is performed , this time against AMACR, an enzyme detected in neoplastic prostatic epithelium. We can see that this marker is strongly expressed in the small sized suspicious glands (red arrows) as well as in the larger prostate glands with normal morphology (green arrows). When AMACR is expressed in normal glands, it loses its specificity as a prostate cancer marker. The small sized, benign basophilic glands with complete atrophy and prominent basal cells (blue arrows) are AMACR-immunonegative, since basal cells do not express AMACR.
In conclusion, as far as the present biopsy specimen is concerned, there is some evidence that a limited prostate acinar adenocarcinoma has developed. However, since the pathologist is not fully convinced, the diagnosis of atypical small acinar proliferation (ASAP) favoring malignancy, can be made.
Practical tips from the present case
Basophilic appearance of prostate epithelium may correspond to prostate intraepithelial neoplasia (PIN) when medium to large glands are involved. When small sized glands are concerned, basal cell hyperplasia and complete atrophy must be considered.
In needle biopsy specimens, a vertical orientation of small sized glands interrupting the muscular bundles of prostate stroma , a sufficient amount of cytoplasm , a sharp luminal border and conspicuous nucleoli are in favour of the diagnosis of acinar adenocarcinoma of the prostate.
Immunohistochemistry is a valuable complementary tool for the diagnosis of prostate cancer; however, immunostaining results should be interpreted with caution and always in relation to morphology.