Unique Patterns Behind the Most Common Prostate Cancer: Acinar Adenocarcinoma

Acinar adenocarcinoma is the most commonly diagnosed form of prostate cancer, which starts in the gland cells of the prostate. However, if your doctor has mentioned a name that sounds complicated or unfamiliar in addition to this diagnosis, you may have a rarer variant of acinar adenocarcinoma — usually showcasing a different pattern in cancer cell organization or structure. You may feel uneasy, and wonder if this classification actually means a worse prognosis for you.

While some of these variants may simply be difficult to diagnose, others do signal a riskier outlook. We aim to alleviate and clarify your concerns here, by introducing some of the rarer types of prostate acinar adenocarcinoma, according to the World Health Organization (WHO)’s 2022 classification of prostate tumors.

Atrophic

This pattern may be seen occasionally after radiation therapy or androgen deprivation therapy (also known as hormone therapy). It is identified by a loss in volume of the cancer cell cytoplasm, but may be challenging to pick out due to a low expression of its key diagnostic marker, α-Methylacyl-CoA racemase (AMACR). However, this pattern should not raise concern about your prognosis, as no associations have been found with changes in Gleason grade or prostate cancer stage.

Pseudohyperplastic

With a highly varied morphology, this variant is easily mistaken for other benign lesions, or other kinds of carcinoma. It can look similar to typical hyperplasia in the prostate lining, featuring papillary infoldings, irregular and wavy patterns within inner cavities, and enlarged cyst formations within tissues. The prognosis for this variant is not as worrying, as it is likely to mirror that of early grade acinar adenocarcinoma.

Microcystic

The microcystic variant is identified by enlarged glands about 10 times the size of those seen in normal acinar adenocarcinoma. It is usually found together with normal acinar adenocarcinoma, and considered a low-grade form of prostate cancer.

Foamy

Commonly found together with normal acinar adenocarcinoma as well, this variant is identified by a foamy, or frothy bubble-like appearance. It tends to showcase yellowish cytoplasm, due to an accumulation of cholesterol, or other fatty molecules.

While the nuclei of cells may shrink, they still maintain their regular shape, unlike most cancers, making them look deceptively normal. This makes spotting this particular variant a challenge. Generally, foamy variants of prostate adenocarcinoma are found at an intermediate Gleason grade (6 or 7), although higher grades may still be seen. However, after radical prostatectomy, their post-surgery prognosis remains similar to non-foamy variants.

Prostatic intraepithelial neoplasia (PIN)-like carcinoma

While exhibiting similar features to the subtype high-grade PIN, this subtype of acinar adenocarcinoma can only be differentiated by crowding of the glands and a lack of basal cells. It is usually mainly composed of glands of a moderate to large size with either a flat or tufted lining. It also has a generally favorable prognosis, and is not usually associated with high-grade carcinomas.

Sarcomatoid carcinoma

This subtype includes a mixture of malignant gland cells, and spindle cell elements. Cases most frequently develop only after irradiation to treat a high-grade acinar carcinoma. Unfortunately, the prognosis for patients is unfavorable, with metastasis present in half the cases, and a 20% chance of death a year post-diagnosis. Aggressive chemotherapy may need to be considered to treat this variant.

Pleomorphic giant cell adenocarcinoma

A rare and aggressive subtype of adenocarcinoma, pleomorphic giant cell adenocarcinoma most frequently arises following prior treatment with androgen deprivation or radiation. It's identified through histological analysis by giant bizarre cells with pleomorphic nuclei. Notably, a risk of death of 37% was reported within a year after diagnosis.

Mucinous (colloid) carcinoma

This variant is exceedingly rare (approximately 2%) and would only be used to describe a tumor if more than 25% of the tumor volume is made up of extravasated mucin. This appearance can be described as colloid-like as well, similar to a suspension of droplets or globules, or pooling. It can be associated with a worse prognosis than typical acinar adenocarcinomas, but still metastasizes similarly, and responds to hormonal therapy.

Signet ring cell carcinoma

Another rare variant, this is usually classified by tumors comprising at least 25% signet ring cell-like morphology. More often, this formation is seen as a small fraction in high grade adenocarcinomas (e.g. Grade 5). A large amount of mucin in the vacuole pushes the nucleus to the edge of the cell, reflecting the appearance of a ring face. While rare, cases reported have also suggested a worse prognosis than the usual adenocarcinoma.

While known to be the most common type of prostate cancer, acinar adenocarcinoma still has many rare and varied subtypes and patterns that may pose some difficulties in diagnosis. Beyond acinar adenocarcinoma, other notable types of prostate cancer include:

• Ductal adenocarcinomas (second-most common prostate cancer, associated with poorer prognosis)
• Intraductal carcinoma of the prostate (strongly associated with higher tumor grades and metastasis)
• Neuroendocrine prostate cancer (aggressive type of prostate cancer that typically develops in the later stages of the disease)

Clinicians are focused on recognizing and classifying these types of prostate cancer, as it reduces the chances of a false negative result — failing to detect the cancer. Hopefully, gaining insight into this diagnostic challenge, as well as understanding the outlook behind your rare subtype, will provide you with a realistic perspective on your cancer journey.