COW-2019-32

1. c

1. microacinar / pseudohyperplastic prostate cancer

In 1934, Muir noted that well-differentiated prostate cancer may mimic benign prostatic hyperplasia [BPH]. Tumors exhibiting large gland formations with cystic dilatation, luminal undulation, and/or complex branching are termed ‘pseudohyperplastic’, with a reported incidence of 11% in RP and 2% in NB specimens. As opposed to other deceptively bland carcinomas, e.g. atrophic and foamy gland cancer, which cause diagnostic difficulty due to a lack of malignant cytologic features, it is the deceptively benign-appearing architecture of individual pseudohyperplastic cancer glands which makes distinction from benign glands challenging, as these banal patterns tend to belie malignant cytology, namely, enlarged nuclei and nucleoli. More recently, a subset of these tumors characterized by cystic dilatation/diminished cytoplasm have been described and termed “microcystic” carcinoma. These tumors – such as the ones depicted in this case – may mimic cystic atrophy or BPH yet share the malignant cytologic features of pseudohyperplastic carcinoma. Like usual acinar cancer, microcystic / pseudohyperplastic cancer may demonstrate dense eosinophilic secretions/intraluminal crystalloids which aid in diagnosis.
Distinguishing microcystic / pseudohyperplastic cancer from BPH may be problematic in both RP and NB settings. In RP, the potential for pseudohyperplastic glands to exhibit nodular (transition zone) or clustered growth (peripheral zone) coupled with clear cytoplasm and basally-oriented nuclei may lead to confusion with BPH. Identifying the markedly crowded nature of these glands, absence of characteristic dense BPH stroma, and overtly malignant nuclei should facilitate recognition. As with all forms of prostatic carcinoma, infiltration between obviously benign glands and transitions to more typical acinar prostate cancer will be most helpful. The limited material in NB specimens may hinder accurate diagnosis of microcystic / pseudohyperplastic cancer, which may present as a localized collection of cystically dilated glands (as in our case) or large glands with multiple infoldings that are easily mistaken for hyperplasia. A study has found that only ¼ of pseudohyperplastic cancers on NB demonstrate infiltrative growth and that these tumors are best recognized by their crowded nature and enlarged nuclei. Given the potential for over- and underdiagnosis of pseudohyperplastic carcinoma on NB, it is prudent to utilize adjunctive immunohistochemistry to support one’s diagnosis, specifically the absence of basal cell markers, as well as positive staining for AMACR (the latter present in 75-80% of cases).
Regarding grading of microcystic / pseudohyperplastic foci, we note that included in ‘clear cell carcinoma’, a pattern described by McNeal et al, demonstrating well-differentiated glands of variable size and contour, composed of tall columnar cells with clear to pale pink cytoplasm, basally-oriented nuclei with prominent nucleoli, and occasional eosinophilic luminal secretions, were cancers composed of large caliber glands, arranged in circumscribed nodular masses, resembling benign glands of BPH. Subsequent studies/images of this histology revealed closely packed glands with papillary infoldings and branching and/or straight luminal borders lined by a single layer of basally-oriented enlarged nuclei often with prominent nucleoli. While early reports viewed these carcinomas as low grade (Gleason pattern 1-2) and of transition zone origin, contemporary studies have established that these cancers are nearly always in continuity with usual Gleason pattern 3 acinar adenocarcinoma and evenly distributed between transition and peripheral zones. Furthermore, microcystic / pseudohyperplastic cancers may be associated with foci of Gleason pattern 4, extraprostatic extension and rarely, seminal vesicle invasion. As a result, current grading designates individual microcystic / pseudohyperplastic cancer glands as Gleason pattern 3, rather than as lower grade.

Muir EG. Carcinoma of the prostate.
Lancet 1934;1:667-672.

Humphrey PA, Kaleem Z, Swanson PE, et al. Pseudohyperplastic prostatic adenocarcinoma.
Am J Surg Pathol 1998;22:1239-1246.

Yaskiv O, Cao D, Humphey PA. Microcystic adenocarcinoma of the prostate: a variant of pseudohyperplastic and atrophic patterns.
Am J Surg Pathol 2010;34:556-561.

Levi AW, Epstein JI. Pseudohyperplastic prostatic adenocarcinoma on needle biopsy and simple prostatectomy.
Am J Surg Pathol 2000;24:1039-1046.

Epstein JI, Allsbrook WC Jr., Amin MB, et al. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma.
Am J Surg Pathol 2005;29:1228-1242.

Samson W. Fine, MD
Memorial Sloan Kettering Cancer Center
fines@mskcc.org

Prostate

prostate cancer, adenocarcinoma, pseudohyperplastic, microacinar