Residency - Prostate Flashcards
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The “default” prostate cancer
Acinar adenocarcinoma
Major features of prostatic acinar adenocarcinoma
- Usually fairly indolent
- Hormonally responsive
- Often multifocal - multiple tumors in the same prostate, usualy in the posterior of the gland
- The single most common male cancer
Prostatic acinar adenocarcinoma - atrophic variant
This is a tricky one! The cytology is very similar to normal glandular atrophy. Luckily, these glands are often adjacent to more obviously malignant ones, and of course will have no myoepithelial cells.
May occur as the primary variant, or occur sporadically after therapy.
Prostatic acinar adenocarcinoma - Pseudohyperplastic variant
Simulates normal prostatic hyperplasia with papillary infoldings and luminal undulations and branching.
Round nuclei, not pseudostratified, with prominent nucleoli.
Prostatic acinar adenocarcinoma - Foamy gland variant
Abundant, foamy, xanthomatous cytoplasm with small, simple, pyknotic nuclei.
Often among more typical prostatic acinar adenocarcinoma variants.
Can look kind of like Cowper’s glands, so make sure to rule these out!
Prostatic acinar adenocarcinoma - microcystic variant
Large, dilated round glands with flattened luminal
cells. Like atrophic variant, this can simulate atrophy.
Prostatic acinar adenocarcinoma - Mucinous or Colloid variant
The requisite for diagnosis is ≥25% of tumor has extracellular mucin pools. As such, this can only be Dx’d on prostatectomy. So, on the biopsy, you would say “Pancreatic acinar adenocarcinoma with mucinous features”
When assigning a grade, try to mentally subtract the mucin.
Prostatic acinar adenocarcinoma - Signet ring-like variant
All in the name. Looks like signet ring morphology, but not as perfect as the gastric variant.
Like all other signet ring cell malignancies, you have to consider that it may be a metastasis – especially from the stomache or elsewhere in the GI tract.
Gleason 5 by definition. This variant has a poorer prognosis.
Prostatic acinar adenocarcinoma - sarcomatoid variant
This is a really tough diagnosis to make on morphology alone – you are going to need stains. Just be aware that a sarcomatoid spindle cell variant exists for this entity.
Gleason 5 by definition. This variant has a poorer prognosis.
Prostatic acinar adenocarcinoma - hypernephroid variant (sometimes called vanishing variant)
Looks like clear cell RCC, eh? Wrong! It’s prostate.
. . . probably. You have to rule out a metastatic clear cell process. But yeah, prostate cancer can look like this too. Gleason 4 by definition.
Prostatic acinar adenocarcinoma - pleomorphic giant cell variant
Bad news. But that’s kind of obvious, everything pleomorphic is bad news.
Of note, a spindle cell component disqualifies this diagnosis – that would make it sarcomatoid variant, which can have pleomorphic components.
Gleason 5 by definition. Poorer prognosis.
ERG in prostate biopsies
Used for staining cancer specifically before we had AMACR.
Only ~50% sensitive compared to the ~90% sensitivity of AMACR.
How many atypical glands do you need to call it prostate cancer?
There is no universal definition, but most urologic pathologists will want to see at least three
“Atypical Small Acinar Proliferation”
A descriptive term, not really a diagnosis.
Designed to be used when you have a collection of small glands suspicious for cancer but lack definitive diagnostic features or are too small to be certain that they do not represent the edge of a benign lesion.
Basal cells may be missing in benign small glands, so, immunohistochemistry is primarily useful to disprove cancer, not to prove cancer. Detection of even rare basal cells in any of the glands of the suspicious population essentially excludes carcinoma for the entire population.
Clinical followup for a biopsy like this is. . . repeat biopsy.
General cytologic/architectural features of benign vs malignant prostate glands
How to report discontinuous prostate cancer
For right now, there is still debate as to whether to call this “10%” or “95%”. There is evidence to suggest that the linear total correlates better, but there is no consensus.
Report both (linear and additive) in these situations unless told otherwise.
What features count as extraprostatic extension?
- Invasion of fat
- Perineural invasion within a neurovascular bundle
- Invasion of the urinary bladder neck (smooth muscle layers without benign prostate)
- Invasion of the seminal vesicle (muscular wall of the vesicle)
- Invasion of extraprostatic loose connective tissue (may be difficult to eval on a core biopsy)
- “Beyond the confines of the normal prostate”, which cannot be evaluated on biopsy at all – this is for resections
Genetic features of prostatic acinar adenocarcinoma
- Recurrent mutations of the ETS transcription factor family (most commonly TMPRSS2-ERG fusion)
- TP53
- PTEN
- BRCA2
Treatment effect in the prostate - anti-hormonal therapy
Benign glands: diffuse atrophy with prominent basal cells
Adenocarcinoma: atrophic with vacuolated cytoplasm and small inconspicuous nuclei/nucleoli (shown)
Relevant history for prostate cancer biopsies
- Age
- Hormonally active medications
- BRAC2 status
- If previous diagnosis, reason for biopsy?
- Previous therapies (rads, anti-hormonal)?
Prostatic ductal adenocarcinoma
Distinct malignancy from acinar adenocarcinoma. Previously called “endometrioid” because it can look very blue and architecturally similar to endometrial malignancy.
Characterized by tall, columnar, pseudostratified epithelium with elongated nuclei and a higher degree of nuclear atypia than conventional prostate cancer. Frequent necrosis. Dilated glands may show papillary and cribriform architecture.
Like acinar adenocarcinoma, no basal cells and AMACR+.
Defined as Gleason 4. Poorer prognosis.
Prostatic neuroendocrine cells
They sit amongst the glands, usually unnoticed. However, they can have “Paneth cell-like change” where they acquire eosinophilic granules.
Prostatic small cell carcinoma
High-grade neuroendocrine malignancy of the prostate, arising from prostatic neuroendocrine cells. Identical to that of the lung by morphology, and may also be TTF-1+. Ki67 is near 100%.
Very aggressive, very poor prognosis (like lung small cell)
Stromal tumor of uncertain malignant potential (STUMP)
Tumor of the specialized prostatic stroma.
Typically looks like a hypercellular stroma with scattered, degenerative-appearing cells admixed with leaf-like branching glands. There is also a Phylloides-like variant with even more prominent leaf branching. Sometimes myxoid or epithelioid.
IHC: CD34+, PR+
Usually has a good prognosis, but may recur or progress.
Prostatic stromal sarcoma
Sarcoma arising from STUMP.
Phyllodes-like growth pattern with malignant, pleomorphic stroma or fascicular growth similar to a leiomyosarcoma.
Of course, it is always possible to have a more conventional soft tissue tumor involved (leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, etc etc).
Like STUMP, **CD34+ and PR+. **
Basal cell hyperplasia
Mimic of malignancy. Note how the lobular architecture and smooth borders of the glands are maintained. Cells are also bland with very small nucleoli.
Of course, basal cell markers will be strongly positive.
Sure looks like a Gleason 3 acinar adenocarcinoma, huh?
Actually, this is adenosis – but it is damn convincing for cancer. This is a case where you would really need that p63/AMACR stain to tell you whether or not these are benign glands.
Carcinoma must lack basal cells completely
Simple prostate atrophy
Normal caliber glands with normal spacing. Scant cytoplasm both apically and laterally.
Postatrophic prostate hyperplasia
Tightly packed very small cytologically bland glands. Very blue at low-power. Usually clustered around a larger dilated “feeder” duct (the prostate equivalent of the breast TDLU).
Bland nuclei, basal cells present, often a sclerotic stroma.
The architecture here may look convincing for a Gleason 3 – so have this on your radar.
Clear cell hyperplasia of the prostate
Usually seen in the setting of BPH.
Sclerosing adenosis
Note how the stroma here is spindled and partially hyalinized. There is also no cytologic atypia.
Basal cells will be present.
Squamous cell metaplasia of the prostate
Usually an incidental finding associated with inflammation or infarction in the setting of BPH.
Keratin pearls may be seen, but are rare. Atypia and mitoses may be present near infarcts.
Can be seen more diffusely after radiation or hormonal therapy, usually without keratinization.
Urothelial metaplasia
Should be distinguished from urothelial cells that normally line the prostatic urethra, and from urothelial carcinoma extending into the prostatic ducts.
Mucinous metaplasia
Focal, incidental finding of benign secretory cells with blue mucin. Goblet cells and intraliminal secretion of mucin are uncommon.
Eosinophilic metaplasia (Paneth-like metaplasia, neuroendocrine metaplasia)
Benign epithelium with large, supra-nuclear, eosinophilic granules. Represent exocrine differentiation with lysosome-like granules.
Associated with variable degrees of chronic inflammation and atrophy.
Of note, Paneth-like change can also be seen in PIN or carcinoma with neuroendocrine differentiation.
Stromal hyperplastic nodule, a variant of usual BPH
A pure stromal nodule! May appear myxoid, hyalinized, or leiomyomatous. Usually prominent, thick-walled vessels and lymphocytes are present.
Mixed epithelial and stromal hyperplasia
The most common variant of BPH.
Variable admixtures of spindled stromal cells and complex, benign glands with papillary, branching architecture.
Cystic changes, inflammation, and basal cell hyperplasia are common. Fibroadenomatoid changes may also be seen.
Epithelial-predominant hyperplasia
Variant of BPH nodule.
Cribriform prostatic hyperplasia
The prostate is one of the places in which cribriform pattern can be completely benign, and this is a good example. Note the prominent basal cell layer.
Verumomantum gland hyperplasia
The verumomantum (or seminal colliculus) is the region of the urethra where the prostatic ducts and ejaculatory duct merge with the urethral canal. It typically has urothelium, but may display papillary prostatic epithelium as well.
Benign, small gland proliferation of the verumomantum, adjacent to the posterior urethra.
They are closely packed, but there is no atypia, and basal cells are present.
Adenosquamous carcinoma of the prostate
Very rare! Note the squamous cytology in combination with the secretory phenotype and classical glomeruloid proliferation.
