Minimal Prostatic Carcinoma In Needle Biopsies

Prostate adenocarcinoma identified in multiple needle biopsy specimens in an extended biopsy series (10 or 12 biopsies) poses limited diagnostic challenge, provided the appropriate diagnostic criteria are employed, and the numerous mimickers of prostate carcinoma are excluded. The major challenge currently experienced by uropathologists is the increasing frequency of cases with limited carcinoma, which is less than 5% of needle biopsy cores. This is most frequently encountered in cases with only one positive biopsy among the total submitted, thereby compounding the diagnostic challenge and importance of accurately interpreting the single microfocus. In contrast, cases with multiple positive cores typically show tumor volumes in each core that exceeds 10% to 20%.

From the above-mentioned outline two challenges emerge that must be addressed. The small focus of atypical glands must not be overlooked, and, if identified, must be interpreted correctly. The first challenge requires a methodical, complete evaluation of all diagnostic material present in the biopsy, with awareness that needle cores commonly fragment. The second challenge has been addressed in multiple studies of “minimal carcinoma,” threshold definition of malignancy, and diagnostic criteria for diagnosis of limited carcinoma in prostate needle biopsies.

The identification of minimal carcinoma is based on histologic evidence of an invasive pattern of crowded small acini with associated cytologic evidence of nuclear hyperchromasia and enlargement, and prominent nucleoli. The volume of pale or amphophilic cytoplasm is moderate to abundant. Acidic (blue) mucin or crystalloids may be present in the acinar lumen. The lumen configuration of neoplastic acini tends to be round without irregularities and undulations. The adjacent prostatic stroma is typically unchanged. These features constitute the major diagnostic criteria of prostatic adenocarcinoma, whether the focus occupies 50% of the core or less than 1% of the needle core (truly minimal carcinoma). In rare instances, the challenge evaporates if any one of the three pathognomonic features noted earlier are present—mucinous fibroplasia (collagenous micronodules), glomerulations, or perineural invasion.

Application of these diagnostic criteria is done with knowledge that some histologic variants of prostatic carcinoma do not fulfill individual criterion. The atrophic variant of prostate carcinoma has diminished cytoplasm, accounting for its accurately descriptive name. Small acini with rounded lumina are not features of pseudohyperplasitic adenocarcinoma or foamy gland adenocarcinoma. The enlarged nuclei typical of the usual prostate adenocarcinomas are not typical of foamy gland carcinoma.

Additionally, the reliable diagnosis of prostate adenocarcinoma requires the exclusion of any of the multiple “mimickers,” including (in decreasing order of frequency) adenosis (AAH), atrophy, basal cell hyperplasia, HGPIN, and sclerosing adenosis. The mimickers most frequently encountered in cases of misdiagnosis of carcinoma are adenosis and atrophy. The application of appropriate immunostains including AMACR (racemase), 34BE12, p63, and PSA will definitively resolve many of the examples of minimal carcinoma. Finally, the inability to resolve diagnostically challenging minimal carcinoma in a definitive manner, after employing all appropriate criteria, immunostains, and second opinion reviews, the prudent reporting of the case employs the diagnostic category of “ASAP,” with an explanatory note and recommendation to rebiopsy.