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Soon's + Lawson's notes.

Robbins.


Note that the prostate is composed of lobulated glandular tissue with intervening fibromuscular stroma.

Case one

  • Case one: 67 year old man with progressively worsening symptoms of urinary hesitancy (hard to start and stop), frequency, nocturia, poor urinary stream, terminal dribbling. On PR exam, he had a smooth, enlarged non-tender prostate gland. PSA was within normal limits.
    • Specimen one (nodular prostatic hyperplasia). This section is an H&E specimen with one seen anatomical border (its capsule) with nodular and cystic changes even at low power. There are enlarged glands with mucinous secretions, the cells of which are regular and do not show the cytological features of malignancy. These glands are supported by basal cells underneath. There is also evidence of stromal hyperplastic change which enhances its nodularity. Thus this slide is consistent with NPH with no evidence of malignancy.
    • Note that it is common to have concurrent chronic prostatitis (marked by lymphocytic infilitration) with hyperplastic change.
    • Prostatic secretions can calcify in urinary obstruction (concretions) – also seen in prostate carcinoma.
    • Smooth and enlarged are features of benign disease. Cancer results in a rougher prostate, that is not particularly large
      • Nontender = not prostatitis
      • So alraedy we have a lot of information
    • Serum PSA is normal. PSA is produced by the prostate and is an anticoagulant (keeps semen liquid)
      • PSA is tissue specific, but it's not specific in terms of picking up malignancy. PSA will rise with a range of prostate abnormalities - so it is useful but is problematic diagnostically.
        • Common sense pathology - tells you age ranges for various abnormalities in PSA. Screening with PSA is not useful because 47/48 high PSA doesn't need surgery and people can get unnecessary surgery --> erectile dysfunction and urinary incontinence.
        • Bad diagnostically, good once someone has had cancer for measuring efficacy of treatment. If it's very high --> cancer. If someone has had a prostatectomy then their PSA elevates, then you know they're having metastasis
    • PSA guide: age/10 - 4

Slide

  • Treat BPH with TURP rather than prostatectomy.
  • Prostate = stroma + glandular tissue
    • Prostate glands are normally complex. Stuff in between glands = CT + muscle, for contraction and ejaculation. Normally, cells are simple cuboidal, but with 1-2 layers. 1-2 cuboidal layers= normal = benign
      • The secretory epithelium is mainly pseudostratified, comprising tall columnar cells and basal cells which are supported by a fibroelastic stroma containing randomly orientated smooth muscle bundles. The epithelium is highly variable and areas of low cuboidal or squamous epithelium are also present, with transitional epithelium in the distal regions of the longer ducts.
  • BPH
    • Hyperplasia of epithelium
      • Basal layer and columnar layer [mucin secreting]
    • Stroma hyperplasia
    • Duct/gland dilation (some cystic)
      • Concretion
      • corpora amylacea
    • More cellular; more heaped up; but cells are regular. Cells are bigger. Nuclei not worrying. Therefore hyperplasia.
    • Cystic structures filled with secretions, which causes pressure atrophy of the secretory epithelium
    • Crystalline structures (calculi) can form in the glands - these are concretions (corpora amylacea - looks like a tree trunk: http://www.webpathology.com/slides/slides/Prostate_NormalGlands_CorporaAmylacea2.jpg).
    • Nodular architecture, based on how the CT swirls around. Therefore Nodular Prostate Hyperplasia
      • Can be a lot of muscle or can be a lot of glands
  • NB: enzyme that converts test. to DHT is 5alpha reductase, can block this to prevent growth. 5 alpha reductase inhibitors are used to treat prostate Ca.
  • BPH = big cells, multiple layers. Cancer = small with 1 layer.

Case 2

  • 53 year old man with back pain, and increasing problems with urination over the last three months.
    • Need to elicit other history: quality of back pain (renal calculi can cause back pain that radiates to the groin), urination, neurological symptoms, pain and tenderness (pain on touch).
    • Investigations include x-ray (good for showing bony changes), PSA, MSU and culture, EUC, bone scan and MRI. Send urine for cytology in case it's a bladder cancer, also renal cell carcinoma. Serum calcium (to see problem with bones).

Specimen two (x-ray of lumbosacral vertebrae): This is an x-ray of a 53 year old man. The most prominent abnormality is opacity in L4, consistent with prostatic metastases which have stimulated osteoblasts to produce a sclerotic lesion.

      • Differentials include Paget’s disease, which looks bigger.
    • Examination: include neurological examination to see if spinal nerve or spinal cord is compressed. Check bilateral signs (spinal cord vs spinal nerve). Also hyperreflexia vs hyporeflexia. PR exam, urinalysis (micro hematuria, protein, WBCs, signs of infection, kidney injury, abdo exam).
      • PR: 1) prostate cancer - irregular, median raphe missing 2) BPH - nodular, smooth, can feel median raphe
    • Prostate cancer starts in the peripheral zone (posteriorly + peripherally), so you're less likely to have urinary symptoms until very late
    • Renal calculi: colicky loin-groin pain.

Case slide

    • Specimen three (prostatic adenocarcinoma): This is a haematoxylin and eosin (HE) slide of prostatic adenocarcinoma, in which there is complete destruction of normal prostate architecture, replaced with grossly abnormal glands. These glands are small, are adherent to each other, are supported by little stroma and are infilitrating through the prostate due to the absence of basal cells. These cells show the cytological features of malignancy and demonstrate perineural invasion.
  • For people with BPH, you do a TURP which treats the disease and also is diagnostic as the pathologist can study the chips
  • Top left = ink, note capsule is intact: he got it all out, and it's not invading through
  • Section shows a prostate gland with effaced (destroyed) architecture. This is prostatic carcinoma. There are atrophic glands focally. This is infiltrating prostatic adenocarcinoma.
  • Malignant glands have only 1 layer of cells around then, they don't have an obvious basal layer, unlike normal glands.
  • We use the architecture to grade it.
  • Prominent nucleoli (unlike normal prostatic tissue), strong indicator of prostate cancer
  • Gland is atrophic away from the cancer
  • Lymphocytic infiltration as a reaction to infiltrating carcinoma
    • Interaction of glands and stroma: glandular cells are infiltrating into the stroma

High grade PC slide

  • Poorly differentiated, not even forming glands. Just forming strands of malignant cells.
  • Gleason score 10.
  • Perineural invasion
  • Can stain for PSA to make sure it's a prostate primary, if it is so undifferentiated that you don't recognise it as prostate

X-ray

X-ray features:

  • Radio-opaque L4–osteosclerotic
    • Patchy processes in L5 also
  • Osteoblastic lesions: prostate, and breast, Paget's disease, lymphoma (NB: DDx is narrow because it's lytic; note prostate can also cause lytic mets)
    • Often a mixed picture
    • Ivory vertebral body

Diagnosis

  • Obstructive symptoms - treat with TURP. If you examine the chips and find cancer you don't need to do the transrectal biopsy.
  • Transrectal biopsy is not for obstructive symptoms, which are uncommon in prostate cancer.
  • Know the Gleason grade and score. Sum the two most common grades (from 1-5), then you get a score (from 2-10)
  • 3: little glands infiltrating between layers. 4: malignant glands start fusing. 5: poorly differentiated sheets.
    • 1: draw circle around, 2: less differentiated, 3: malignant glands infiltrate as individual glands through normal glands, 4: small glands aggregate together again, 5: poorly differentiated

Treatment

  • In a lot of situations, it's very slow growing, so it's not worth the morbidity to cut it out
    • Normally old men die with prostate cancer, not because of it

Bladder cancer

  • Bladder cancer distinguished by papillary urothelium vs flat urothelium
  • Papillary carcinomas are divided into low grade and high grade
  • Flat lesions - if confined to urothelial layer then it's Ca in situ
  • Bladder cancer: even if the atypical cells are confined to the mucosa, then we still call it carcinoma (papillary urothelial carcinoma if it has papillary architecture and atypical cells)
    • But invasion into underlying bladder wall is important for prognosis
  • Urothelium: renal pelves, ureter, urethra, bladder. Look at thickness of the wall to distinguish organ
  • Haematuria - see Harrisons, have a classification
    • UTI
    • Stones
    • Trauma
    • Anticoagulation (warfarin, heparin)
    • Glomerulonephritis
    • Malignancy
  • Investigations of haematuria: cytology, ultrasound, IVP, cystoscopy

Slide: papillary urothelial neoplasm

  • Papillary, not flat
  • Urothelial lined organ, thick wall - ureter
  • has long fingers that protrude into the bladder lumen (papilloma, which has a fibrovascular core), the cells of which may be identified on MSU cytology. The layers of transitional epithelium has been vastly increased (from 5-6 normally, too many layers). Shedding and blood vessel rupture causes haematuria.
    • Risk factors include smoking, working in the tanning/dye industries (aniline dyes), APC powder use (Bex powder), schisomoniasis infection (parasite which proliferates in the urothelium, causing chronic inflammation), cyclophosphamide
  • Invasion diagnosis: Look for desmoplasia and lymphocytic response. Not present here
  • Thick transitional epithelium, lots of mitoses
  • Diagnosis: low grade papillary urothelial carcinoma; no invasion

Case 3: testicular tumour

  • 90% in younger men <40 years. 90% of them are germ cell tumours (seminoma; from seminiferous tubules --> can form teratoma). 90% go to paraaortic lymph nodes.
    • There are other ones that arise from the background stroma e.g. Leydig cells (make testosterone). Sertoli cells support sperm and make inhibin.
  • Seminomas remain localised for a much longer time and are radiotherapy reponsive. Non-seminomas are relatively radio-resistant.
    • Seminomas don't secrete hormones, but there are other things we can measure: Beta-HCG and alpha-fetoprotein
  • Intratubular germ cell neoplasia is a precursor to seminoma
  • Cells are totipotent; you can get an embryoma that looks like a
  • Teratoma: has endoderm, mesoderm and ectoderm
  • Can also get differentiation into placental elements (choriocarcinoma or yolk sac tumour)
  • Commonest: mixed germ cell tumour - bits of everything
  • Germ cell tumours can also occur in children - teratomas or yolk sac tumours. These tumours in children don't arise from intratubular germ cell neoplasia


  • 30 year old man with a lump in his scrotum, detected on self- examination. Biopsy revealed seminoma, a common germ cell neoplasm of the testis. Tests for serum markers of testicular tumours, β-HCG and αFP (fetoprotein) were negative.
  • Testicular cancers are either germ cell or non-germ cell related.
  • Germ cell tumours are either seminomatous (50%), or non-seminomatous (they can show embryonal, trophoblastic [placental] or somatic [teratoma] differentiation because they are derived from primitive pluripotent cells which can differentiate into anthing).
  • Specimen six (seminoma of testes): This is a specimen of a testicular

seminoma, a tumour derived from germinal epithelium within the seminiferous tubules. The tumour is composed of sheets of cells divided into poorly demarcated lobules by delicate septa of fibrous tissue containing some lymphocytes. The classical seminoma cell is large, round, has a large central nucleus with one or two prominent nucleoli, and an abundant cytoplasm.

    • Note that most testicular germ cell tumours originate from lesions from intratubular germ cell neoplasia (ITGCN), which is believed to occur in utero and stay dormant until puberty, when it can progress to seminomas or non-seminatmous tumours.
  • Choriocarcinoma macro: tiny fibrotic lesion in children, hard to see, but it has lesions in all sorts of organs (metastasises really quickly; choriocarcinoma)
  • Seminoma macro: grows very large before it metastasises (e.g. lance armstrong); not very aggressive. Looks like a potato
  • Seminoma: testis totally replaced and effaced. Tumours consists of sheets of atypical cells (malignant features). Lobules of tumour separated by fibrovascular stroma


Slide

  • Lobules of cells demarcated by vascular stroma
  • Atypical cells demonstrating cytological features of malignancy

Spread of seminoma

  • Spreads to capsule, then paraaortic nodes
  • May go to mediastinal nodes, then systemically via subclavian v


Types: o Germcellstumours 􏰁 More common • Mostly malignant 􏰁 Types: • Seminoma o Remainlocalisedforalongtime 􏰁 Commonly present: painless testicular mass (potato tumour) 􏰁 Invades into spermatic cord o Eventuallycanmetastasistopara-aortic,iliaclymphnodes􏰀mediastinal􏰀 supraclavicular o Mostpeoplepresentinearlystage(1) o Goodprognosis,extremelyradiosensitive • Non-seminomatous o Subtypes:embryomalcarcinoma,teratoma,choriocarcinoma,yolksactumours o Disseminateearly(particularchoriocarcinoma)withasmallprimary 􏰁 Haematogenous spread early 􏰀 lung, liver, brain 􏰁 Nodal spread o Prognosisgood,chemosensitive • Most are mixed-type o Sex-cordstroma(sertoli,leydig)tumours 􏰁 Mostly benign 􏰁 Leydig cell tumour 􏰁 Sertoli cell tumour • Risk factors o Youngmen,15-35 o TDS:testiculardyskineticsyndromes 􏰁 Cryptoorchidism, etc o Family,pasthistory • Markers o Alpha-feto-protein􏰀yolksactumour o BetahCG􏰀choriocarcinoma 􏰁 15% of seminomas have syncytiocytotrophic cells scattered through them • Small amount of beta-hCG produced 􏰁 Response to treatment, volume of tumour, monitoring


Slide

  • Mixed embryonal carcinoma and choriocarcinoma [mixed germ cell tumour]
  • Some areas look like syncitiotrophoblast (placenta)
  • Cells show obvious malignant features
  • Label the areas with immune staining and imaging, can support diagnosis with biopsy and stained markers
  • Even a high stage disease may respond to chemotherapy
  • Wouldn't be beta HCG positive (no chorion components) and wouldn't be alpha-FP positive (because no yolk sac components)