Prostate



Prostate






1.1 NONSPECIFIC GRANULOMATOUS PROSTATITIS (NSGP) VS. INFECTIOUS GRANULOMA

Nonspecific Granulomatous Prostatitis (NSGP)

Infectious Granulomas


Age

Teens to elderly, typically older men

Typically adults


Location

Peripheral = transition zone

Transition > peripheral zone


Symptoms

Variable irritative and obstructive symptoms, fever, chills. Most with h/o recent urinary tract infection

Fungal and systemic TB with systemic symptoms. BCG granulomas typically asymptomatic unless rare cases where attenuated bacilli of BCG become active and result in systemic symptoms


Signs

Pyuria frequent. About 50% with indurated rectal exam, hematuria. PSA can be markedly elevated

Can result in indurated nodular rectal exam. PSA typically not elevated


Etiology

Reaction to bacterial toxins, secretions from ruptured acini

Fungal and systemic TB granulomas in immunocompromised hosts. BCG granulomas in men treated for superficial bladder cancer


Histology


  1. Early lesion with dilated ducts and acini filled with neutrophils, debris, foamy histiocytes, and desquamated epithelial cells (Fig. 1.1.1)



  2. Rupture of ducts and acini leads to localized destruction of acini (Fig. 1.1.2).



  3. Lacks central caseation but may have central microabscess formation (Fig. 1.1.3)



  4. Extension of infiltrate into surrounding ductal and acinar units gives rise to lobular dense infiltrate of histiocytes, lymphocytes, plasma cells, and some neutrophils. Older lesions more fibrous (Fig. 1.1.4). Some lesions can have more histiocytes more closely mimicking an infectious granuloma (Fig. 1.1.5)


  1. Early lesions show nonnecrotizing granulomas adjacent to intact glands (Figs.1.1.6, 1.1.7, 1.1.8)



  2. Later lesions show larger granulomas, which can destroy glands (Fig. 1.1.9).



  3. Later lesions develop caseation with granulomatous and mixed inflammatory reaction (Fig. 1.1.10)



  4. Typically not as polymorphous inflammation as NSGP. Mostly lymphocytes/plasma cells with neutrophils also seen in fungal granulomas (Fig. 1.1.6)


Special studies


  • In classic NSGP, no organism stains needed unless if unsure if infectious


  • If no prior BCG, fungal and acid-fast stains should be performed. If h/o of BCG, no need for organism stains


Treatment

Warm sitz baths, fluids, and antibiotics if urinary tract infection is documented

Infectious granulomas in immunocompromised hosts treated with systemic therapy. BCG prostatitis requires no therapy unless a rare case of systemic BCG infection


Prognosis

Most symptoms resolve within a few months

Infectious and systemic granulomas in immunocompromised hosts have a poor prognosis. BCG granulomas unless systemic have no clinical significance








Figure 1.1.1 Early lesion of NSGP.






Figure 1.1.2 NSGP with destruction of acini by polymorphous infiltrate.






Figure 1.1.3 Central area of NSGP with microabscess formation, yet lacking caseation. In addition to neutrophils, there are histiocytes, lymphocytes, and eosinophils.






Figure 1.1.4 Lobular infiltrate of NSGP.






Figure 1.1.5 NSGP with more histiocytes, yet admixed eosinophils and neutrophils more typical of NSGP than of infectious granuloma.






Figure 1.1.6 Infectious granuloma with periglandular granulomas consisting of histiocytes and lymphocytes without admixed plasma cells, neutrophils, or eosinophils.







Figure 1.1.7 Infectious granuloma containing multinucleated giant cells surrounding intact glands.






Figure 1.1.8 Higher magnification of infectious granuloma with intact glands.






Figure 1.1.9 Infectious granuloma with focal intact glands (left) and larger granulomas (center) that have destroyed glands.






Figure 1.1.10 Infectious granuloma with caseous necrosis (bottom).



1.2 INFECTIOUS GRANULOMA VS. POSTBIOPSY GRANULOMA

Infectious Granuloma

Postbiopsy Granuloma


Age

Typically adults

Typically adults after prostate TURP


Location

Transition > peripheral zone

Transition > peripheral zone


Symptoms

Fungal and systemic TB with systemic symptoms. BCG granulomas typically asymptomatic unless rare cases where attenuated bacilli of BCG become active, resulting in systemic symptoms

Asymptomatic


Signs

Can result in indurated nodular rectal exam. PSA typically not elevated

None


Etiology

Fungal granulomas in immunocompromised hosts. BCG granulomas in men treated for superficial bladder cancer

Typically results from cautery injury of prior TURP. Rarely can be seen following needle biopsy. Can be seen from 9 d to 52 mo after TURP


Histology


  1. Early lesions show nonnecrotizing granulomas adjacent to intact glands. Later lesions develop caseation with destruction of acini (Fig. 1.2.1)



  2. Necrosis consists of fine granular debris lacking visible structures (Figs. 1.2.2 and 1.2.3)



  3. Granulomas tend to be round and relatively regular (Fig. 1.2.1)



  4. Lymphocytes/plasma cells predominate with neutrophils also seen in fungal granulomas. Scattered multinucleated giant cells seen (Fig. 1.2.3)


  1. Early and late granulomas show central necrosis and tend to be near urethra and can destroy glands. Nonspecific foreign body giant cell granulomas also seen (Fig. 1.2.4)



  2. Central region of fibrinoid necrosis surrounded by palisading epithelioid histiocytes. Necrosis often contains ghost-like structures of vessels, acini, and stroma (Fig. 1.2.5)



  3. Irregular shapes including wedge-shaped, ovoid, and sinuous (Fig. 1.2.6)



  4. With recent TURP, abundant eosinophils may be identified. Older granulomas are most lymphocytes and plasma cells (Figs. 1.2.7 and 1.2.8)


Special studies

If h/o of BCG, no need for organism stains. If no prior BCG, fungal and acid-fast stains should be performed

None


Treatment

Infectious granulomas in immunocompromised hosts treated with systemic therapy. BCG prostatitis requires no therapy unless a rare case of systemic BCG infection

None


Prognosis

Infectious and systemic granulomas in immunocompromised hosts have a poor prognosis. BCG granulomas unless systemic have no clinical significance

Lesions fibrose over time








Figure 1.2.1 Infectious necrotizing granuloma with relative sparing of glands.






Figure 1.2.2 Caseous necrosis with fine granular debris surrounded by histiocytes.






Figure 1.2.3 Caseous necrosis (left) with adjacent multinucleated histiocytes.






Figure 1.2.4 Oval-shaped postbiopsy granuloma with central necrosis.






Figure 1.2.5 Postbiopsy granuloma with necrobiotic center with ghosts of necrotic vessels.






Figure 1.2.6 Irregular linear necrobiotic granuloma of postbiopsy granuloma.







Figure 1.2.7 Postbiopsy ovoid granuloma mimicking an infectious granuloma with palisading histiocytes and scattered multinucleated histiocytes.






Figure 1.2.8 Higher magnification of Figure 1.2.7 with central necrosis lacking the fine granular amorphous appearance of infectious granulomas.



1.3 POSTBIOPSY GRANULOMA VS. ALLERGIC GRANULOMA

Postbiopsy Granuloma

Allergic Granuloma


Age

Typically adults after prostate TURP

Typically adults


Location

Transition > peripheral zone

Transition > peripheral zone


Symptoms

Asymptomatic

Almost all with either asthma or evidence of systemic allergic reaction at the time of diagnosis of their prostatic lesions. Severity of the asthmatic symptoms may fluctuate synchronously with the severity of urinary obstructive symptoms


Signs

None

Majority have increased blood eosinophil counts


Etiology

Typically results from cautery injury of prior TURP. Rarely can be seen following needle biopsy. Can be seen from 9 d to 52 mo after TURP

Allergic granulomatous prostatitis and Churg- Strauss syndrome


Histology


  1. Variably sized, irregular shapes including wedge-shaped, ovoid, and sinuous (Fig. 1.3.1)



  2. Central region of fibrinoid necrosis surrounded by palisading epithelioid histiocytes (Fig. 1.3.1)



  3. Necrosis often contains ghost-like structures of vessels, acini, and stroma (Fig. 1.3.2)



  4. With recent TURP, abundant eosinophils may be identified immediately around the granulomas (Fig. 1.3.3). Later granulomas with lymphocytes/plasma cells



  5. Nonspecific foreign body giant cell granulomas also seen


  1. Multiple ovoid granulomas of uniform small size (Fig. 1.3.4)



  2. Central eosinophilic necrosis surrounded by histiocytes with less palisading (Fig. 1.3.5)



  3. No visible prostatic structures within necrosis (Fig. 1.3.6)



  4. Granulomas surrounded by numerous eosinophils and extensive eosinophils throughout the stroma (Figs. 1.3.7 and 1.3.8)



  5. Churg-Strauss syndrome may also have necrotizing vasculitis


Special studies

None

Clinically workup for increased peripheral blood eosinophilia and rule out Wegener’s


Treatment

None

Allergic granulomatous prostatitis treated with steroids


Prognosis

Lesions fibrose over time

Systemic granulomas may be seen, possibly contributing to death








Figure 1.3.1 Linear necrobiotic postbiopsy granuloma with palisading histiocytes.






Figure 1.3.2 Postbiopsy granuloma ghost of blood vessels.






Figure 1.3.3 Scattered eosinophils (top) surrounding postbiopsy granuloma.






Figure 1.3.4 Allergic granuloma with multiple relatively uniformly sized and shaped ovoid necrotic granulomas.






Figure 1.3.5 Allergic granuloma central eosinophilic necrosis surrounded by histiocytes and numerous eosinophils.






Figure 1.3.6 Central necrosis of allergic granuloma lacking necrotic prostate structures.







Figure 1.3.7 Allergic granuloma necrosis surrounded by numerous eosinophils.






Figure 1.3.8 Numerous eosinophils of allergic granuloma infiltrating prostatic stroma.



1.4 ACUTE/CHRONIC PROSTATITIS VS. PROSTATIC ACUTE/CHRONIC INFLAMMATION

Acute/Chronic Prostatitis

Prostatic Acute/Chronic Inflammation


Age

Typically adults

Typically adults seen on needle biopsy, TURP, or radical prostatectomy


Location

Transition = peripheral zone

Transition = peripheral zone


Symptoms

Acute bacterial prostatitis associated with fever, chills, and dysuria. Chronic bacterial prostatitis usually associated with recurrent urinary tract infections (asymptomatic periods). Chronic prostatitis may present with low back pain, dysuria, and perineal and suprapubic discomfort

Asymptomatic


Signs

Acute bacterial prostatitis with an exquisitely tender and boggy prostate on rectal examination. Diagnosis of chronic nonbacterial prostatitis (chronic pelvic pain syndrome) is difficult and requires completion of the NIH Chronic Prostatitis Symptom Index survey by the patient, digital rectal exam, urinalysis, and sequential collection of urine and prostatic fluid specimens, before, during, and after prostatic massage

Conflicting data as to whether either focal acute inflammation or chronic inflammation associated with elevated serum PSA levels


Etiology

Urinary tract infection source of acute and chronic bacterial prostatitis. Unknown for pelvic pain syndrome, which accounts for 90%-95% of prostatitis cases

Nonspecific, unrelated to infections. Almost ubiquitously found in prostates unrelated to clinical prostatitis


Histology


  1. Clinical chronic prostatitis not associated with specific histologic findings



  2. Clinical acute prostatitis consists of numerous neutrophils within acini associated with extensive neutrophils throughout stroma. Microabscess formation can be seen (Figs.1.4.1, 1.4.2, 1.4.3, 1.4.4, 1.4.5, 1.4.6)



  3. Typically, biopsy of acute prostatitis contraindicated due to increased risk of sepsis. Clinically no need to biopsy chronic prostatitis


  1. Focal nonspecific periglandular lymphocytes and plasma cells (Fig. 1.4.7)



  2. Focal nonspecific acute inflammation in acini (Fig. 1.4.8)



  3. Inflammation should not be commented on in pathology reports unless prominent. Can mislead urologists that elevated serum PSA levels result from the inflammation, when in some cases, unsampled carcinoma is the source of the elevated PSA


Special studies

None

None


Treatment

Both acute and chronic bacterial prostatitis treated with antibiotics. No proven therapies for chronic pelvic pain syndrome

None


Prognosis

Favorable for bacterial prostatitis, although acute bacterial prostatitis may be accompanied by sepsis

Inflammation on biopsy is not associated with an increased risk of cancer on subsequent biopsy








Figure 1.4.1 Abscess formation in acute prostatitis.






Figure 1.4.2 Sheets of neutrophils with acute prostatitis.






Figure 1.4.3 Higher magnification of Figure 1.4.2 with abscess formation.






Figure 1.4.4 Diffuse infiltration of stroma by neutrophils in acute prostatitis.






Figure 1.4.5 Low magnification of acute prostatitis with heavily inflamed prostatic stroma.






Figure 1.4.6 Higher magnification of Figure 1.4.5 showing numerous neutrophils infiltrating prostatic stroma.







Figure 1.4.7 Nonspecific periglandular chronic inflammation.






Figure 1.4.8 Nonspecific acute inflammation in prostate glands.



1.5 PROSTATIC CHRONIC INFLAMMATION VS. CHRONIC LYMPHOCYTIC LEUKEMIA

Prostatic Chronic Inflammation

Chronic Lymphocytic Leukemia


Age

Typically adults seen on needle biopsy, TURP, or radical prostatectomy

Most > 60 years old


Location

Transition = peripheral zone

Transition = peripheral zone


Symptoms

Asymptomatic

Prostatic symptoms asymptomatic


Signs

Conflicting data as to whether either focal chronic inflammation associated with elevated serum PSA levels

Most patients are known leukemics or have their diagnosis established at the time of workup for urinary symptoms. May be associated with lymphadenopathy (small lymphocytic lymphoma), eventually anemia and infections. Initial diagnosis may be made on a histologic specimen


Etiology

Nonspecific, unrelated to infections

Unknown


Histology


  1. Inflammation periglandular (Fig. 1.5.1)



  2. Focal inflammation with lymphocytes and plasma cells (Fig. 1.5.2)



  3. Inflammation should not be commented on in pathology reports unless prominent. Can mislead urologists that elevated serum PSA levels result from the inflammation, when in some cases, unsampled carcinoma is the source of the elevated PSA


  1. Infiltrate not restricted to periglandular location. Dense infiltrate of small, mature, round lymphocytes extensively infiltrating the prostatic stroma with preservation of prostatic glands (Figs.1.5.3, 1.5.4, 1.5.5, 1.5.6, 1.5.7)



  2. Infiltrates with monotonous collection of lymphocytes, lacking admixed plasma cells (Fig. 1.5.8)


Special studies

None

None


Treatment

None

Early disease not treated. Late disease is treated with chemotherapy and monoclonal antibodies


Prognosis

Inflammation on biopsy is not associated with an increased risk of cancer on subsequent biopsy

Low-grade lymphoma in the prostate does not impact the therapy or prognosis of prostate cancer, due to its indolent course








Figure 1.5.1 Focal periglandular nonspecific chronic inflammation.






Figure 1.5.2 Higher magnification of Figure 1.5.1 with lymphocytes and plasma cells.






Figure 1.5.3 Extensive periglandular lymphocytic infiltrate of CLL.






Figure 1.5.4 Moderately dense lymphocytic infiltrate of CLL extending into stroma.






Figure 1.5.5 CLL with dense infiltrate extensively involving prostatic stroma.






Figure 1.5.6 Needle biopsy with scattered dense infiltrates of CLL not in a periglandular distribution.







Figure 1.5.7 CLL with effacement of prostate by dense lymphoid infiltrate.






Figure 1.5.8 Monotonous CLL lymphocytic infiltrate.



1.6 EPITHELIOID NONSPECIFIC GRANULOMATOUS PROSTATITIS VS. HIGH-GRADE PROSTATIC ADENOCARCINOMA

Epithelioid Nonspecific Granulomatous Prostatitis

High-Grade Prostatic Adenocarcinoma


Age

Teens to elderly, typically older men

Typically 50 to elderly, although not rare in 40s


Location

Transition = peripheral zone

Peripheral > transition zone


Symptoms

Variable irritative and obstructive symptoms, fever, chills. Most with h/o recent urinary tract infection

Typically asymptomatic. Advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

Pyuria frequent. About 50% with indurated rectal exam, hematuria. PSA can be markedly elevated

Serum PSA levels typically elevated, yet occasionally not increased significantly as poorly differentiated cancers not effectively produce PSA


Etiology

Reaction to bacterial toxins, secretions from ruptured acini

Genetic with differences in the incidence of prostate cancer between countries and ethnicity. Family history with degree of risk related to the age of the relatives at diagnosis and the number of relatives affected. Diet with strongest link with high-fat intake and lower risk with consumption of fruits and vegetables, especially tomatoes. Testosterone and its derivative, dihydrotestosterone, important in prostate cancer growth, yet serum levels of these androgens not consistently associated with prostate cancer risk


Histology


  1. Can be extensive, replacing and effacing the normal architecture of an entire core (Fig. 1.6.1)



  2. Epithelioid histiocytes with prominent nucleoli (Figs. 1.6.2 and 1.6.3)



  3. Admixed lymphocytes, plasma cells, neutrophils, and eosinophils (Figs.1.6.4, 1.6.5, 1.6.6, 1.6.7)



  4. Multinucleated giant cell in only 50% of cases



  5. Earlier lesions localized around ruptured ducts and acini (Fig. 1.6.8)


  1. Can extensively involve a core



  2. Sheets or individual cells with enlarged nuclei and prominent nucleoli. Mitoses vary from scattered to more frequent. Cancers mimicking NSGP tend to be relatively uniform without marked pleomorphism (Fig. 1.6.9)



  3. Typically lacks associated inflammation (Figs. 1.6.9 and 1.6.10)



  4. Lacks multinucleated giant cells



  5. Not localized around ruptured acini


Special studies


  • Epithelioid histiocytes CD68 positive



  • Negative for keratins and prostate markers. Entrapped, disrupted reactive glands are keratin positive (see Section 1.8)


  • CD68 negative



  • Immunohistochemically, high-grade cancers may not express PSA. Best markers to differentiate cancer vs. inflammation/histiocytes are keratins such as CAM5.2 or AE1/AE3, which are not decreased in higher-grade tumors


Treatment

Warm sitz baths, fluids, and antibiotics if urinary tract infection is documented

Stage and age dependent with localized disease treated with either radical prostatectomy or combination hormone therapy/radiation; the latter the best option in men >70 years old. Advanced disease initially treated with hormone therapy


Prognosis

Most symptoms resolve within a few months

Stage dependent








Figure 1.6.1 NSGP at low magnification (bottom core) can extensively involve a core destroying underlying benign glands and stroma, mimicking carcinoma.






Figure 1.6.2 Low magnification of NSGP with sheets of epithelioid cells.






Figure 1.6.3 Higher magnification of Figure 1.6.2 with epithelioid histiocytes having prominent nucleoli (arrows).






Figure 1.6.4 Low magnification of NSGP with sheets of epithelioid cells.







Figure 1.6.5 Higher magnification of histiocytes and admixed neutrophils and lymphocytes.






Figure 1.6.6 Low magnification of NSGP with cords of epithelioid cells.






Figure 1.6.7 Higher magnification of Figure 1.6.6 with epithelioid histiocytes and admixed neutrophils and lymphocytes.






Figure 1.6.8 Partially ruptured dilated prostatic gland with intraluminal and periglandular epithelioid histiocytes.






Figure 1.6.9 Cords of infiltrating relatively bland Gleason score 10 adenocarcinoma without admixed inflammation.






Figure 1.6.10 Gleason score 10 adenocarcinoma with foamy cytoplasm mimicking histiocytes, yet lacking interspersed inflammation.



1.7 SIGNET-RING CELL LYMPHOCYTES VS. PROSTATE ADENOCARCINOMA WITH SIGNET-RING CELL FEATURE

Signet-Ring Cell Lymphocytes

Prostate Adenocarcinoma with Signet-Ring Cell Features


Age

Any age

Typically 50 to elderly, although not rare in 40s


Location

Peripheral > transition zone

Peripheral > transition zone


Symptoms

Asymptomatic

Typically asymptomatic. Advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

Conflicting data as to whether either focal chronic inflammation associated with elevated serum PSA levels

Serum PSA levels typically elevated, yet occasionally not increased significantly as poorly differentiated cancers not effectively produce PSA. If extension from signet-ring cell adenocarcinoma from the colon or bladder (see Section 1.43), also PSA typically not elevated


Etiology

Nonspecific, unrelated to infections. Benign lymphocytes can assume the appearance of signet ring cells, due to thermal injury

Signet-ring cell-like adenocarcinomas can be primary in the prostate and are typically high grade although Gleason pattern 3 cancers can also occasionally have signet ring features. True mucinpositive signet-ring cell adenocarcinomas involving the prostate, with rare exception, represent spread from the intestinal tract or the urinary bladder


Histology


  1. Cluster of lymphocytes with scant cytoplasm with small, dark, bland nuclei (Fig. 1.7.1)



  2. Most cells have a central nucleus surrounded by clear space with occasional cells having an eccentric nucleus and clear vacuole (Fig. 1.7.2)



  3. Often admixed with plasma cells and other nonvacuolated lymphocytes


  1. A greater degree of nuclear atypia, nucleomegaly, and prominent nucleoli compared to signet-ring cell lymphocytes (Figs. 1.7.5 and 1.7.6)



  2. Signet-ring cell-like adenocarcinomas of the prostate contain a clear eccentric vacuole. True signet-ring cell adenocarcinoma, even on H&E-stained sections, often have a suggestion of some substance within the vacuoles; in some cases, blue-tinged mucin is visible



  3. Typically admixed plasma cells and lymphocytes absent


Special studies


  • Keratin stains negative



  • Positive for CD45 (Figs. 1.7.3 and 1.7.4)



  • Negative for mucin stains


  • Immunohistochemically, high-grade cancers may not express PSA. Best markers to label high-grade prostate adenocarcinoma are keratins, such as CAM5.2 and AE1/AE3, which are not decreased in higher-grade tumors



  • CD45 negative



  • Prostatic signet-ring cell-like carcinomas are mucin negative. Secondary spread from other sites with true signet-ring cell carcinomas are mucin positive


Treatment

None

High-grade prostate adenocarcinoma stage and age dependent with localized disease treated with either radical prostatectomy or combination hormone therapy/radiation, the latter the best option in men >70 years old. Advanced disease initially treated with hormone therapy. Secondary involvement by bladder or colon signet-ring cell adenocarcinoma and only treated with chemotherapy


Prognosis

Inflammation on biopsy is not associated with an increased risk of cancer on subsequent biopsy

High-grade prostate adenocarcinoma stage dependent. Secondary involvement by bladder or colon signet-ring cell adenocarcinoma associated with a dismal prognosis








Figure 1.7.1 Bland lymphocytes with some having eccentric vacuoles.






Figure 1.7.2 Lymphocytes with most having a centrally located nucleus surrounded by a clear space.






Figure 1.7.3 Vacuolated lymphocytes.






Figure 1.7.4 CD20 staining of signet-ring cell lymphocytes (same case as Fig. 1.7.3).






Figure 1.7.5 Gleason score 10 adenocarcinoma with vacuoles. Nuclei are more variably shaped, hyperchromatic, and larger than of lymphocytes.






Figure 1.7.6 Extensive signet-ring cell-like change in adenocarcinoma with hyperchromatic nuclei.



1.8 REACTIVE NONCRIBRIFORM PROSTATE GLANDS VS. PROSTATIC ADENOCARCINOMA WITH INFLAMMATION

Reactive Noncribriform Prostate Glands

Prostatic Adenocarcinoma with Inflammation


Age

Any age

Typically 50 to elderly, although not rare in 40s


Location

Peripheral = transition zone

Peripheral > transition zone


Symptoms

Typically asymptomatic

Typically asymptomatic. Advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

Conflicting data as to whether either focal acute or chronic inflammation associated with elevated serum PSA levels

Serum PSA levels variably elevated, no data if different from cancer without inflammation


Etiology

Even a few lymphocytes or neutrophils within epithelium or within acini can result in reactive atypia

Same as usual adenocarcinoma of the prostate (see Section 1.6)


Histology


  1. Reactive glands can be increased in number and crowded, mimicking cancer (Figs. 1.8.1 and 1.8.2)



  2. Nuclear enlargement, prominent nucleoli, and occasional mitotic figures (Fig. 1.8.3). In some small foci, the diagnosis is “atypical inflamed glands” where cannot be distinguished reactive benign glands from carcinoma (Fig. 1.8.4)



  3. Lacks perineural invasion


  1. Cancer with inflammation has numerous crowded small glands infiltrating in between larger benign glands (Fig. 1.8.5) and atypical glands that extend away from inflammation (Fig. 1.8.6)



  2. Degree of cytologic atypia in the small atypical glands is significantly greater than the adjacent benign glands even though both are associated with the same inflammation (Fig. 1.8.7)



  3. May show perineural invasion (Fig. 1.8.8)


Special studies


  • Immunohistochemistry for basal cell markers p63 and high molecular weight cytokeratin (HMWCK) is positive



  • AMACR negative (Fig. 1.8.2)


  • Since benign glands with inflammation can mimic cancer, caution should be exercised in diagnosing cancer in the setting of inflammation. Typically, immunohistochemistry for basal cell markers (p63 and HMWCK) should be performed and entirely negative in the atypical inflamed glands (Figs. 1.8.9 and 1.8.10). If only a few inflamed atypical glands present and negative for basal cell markers, may not be definitive for diagnosis of carcinoma



  • If positive for AMACR also helpful, yet not as critical for the diagnosis as absence of basal cells


Treatment

None

Most are Gleason score 3 + 3 = 6 with no unique treatment compared to usual carcinoma


Prognosis

No affect

Most are Gleason score 3 + 3 = 6 with no unique prognosis compared to usual carcinoma








Figure 1.8.1 Crowded benign glands with intraluminal acute inflammation (right).






Figure 1.8.2 Same case as Figure 1.8.1 with a patchy basal cell layer for high molecular weight cytokeratin ruling out carcinoma.






Figure 1.8.3 Benign atrophic glands with acute inflammation, nucleoli, and mitotic figure (arrow).






Figure 1.8.4 Cluster of crowded glands suspicious for carcinoma, yet a definitive diagnosis cannot be made due to associated inflammation.






Figure 1.8.5 Small atypical glands of carcinoma associated with a lymphocytic infiltrate around benign gland (left).






Figure 1.8.6 Glands with huge nucleoli are associated both with heavily inflamed glands (lower) as well as similarly atypical glands (upper) with less inflammation, the latter diagnostic of carcinoma.







Figure 1.8.7 Inflamed cancer with greater degree of cytologically atypia compared to adjacent benign inflamed gland (upper right).






Figure 1.8.8 Perineural invasion by inflamed carcinoma glands.






Figure 1.8.9 Adenocarcinoma with inflammation.






Figure 1.8.10 Same case as Figure 1.8.9 with numerous inflamed atypical glands negative for p63 and high molecular weight cytokeratin (brown) and positive for AMACR (red), consistent with carcinoma.



1.9 REACTIVE CRIBRIFORM PROSTATE GLANDS VS. CRIBRIFORM HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (PIN)

Reactive Cribriform Prostate Glands

Cribriform High-Grade Prostatic Intraepithelial Neoplasia (PIN)


Age

Any age

Typically adults


Location

Peripheral = transition zone

Peripheral = transition zone


Symptoms

Typically asymptomatic

Typically asymptomatic


Signs

Conflicting data as to whether either focal acute or chronic inflammation associated with elevated serum PSA levels

None. Usually, incidentally detected on prostate needle biopsy performed for elevated serum PSA levels


Etiology

Even a few lymphocytes or neutrophils within epithelium or within acini can result in reactive atypia

As a precursor to some adenocarcinomas of the prostate, etiology assumed to be the same as for adenocarcinoma of the prostate (see Section 1.6)


Histology


  1. Reactive cribriform glands have rounded contours that fit within the normal architecture of benign glands (Fig. 1.9.1)



  2. Nuclear enlargement, prominent nucleoli, and occasional mitotic figures (Fig. 1.9.2)



  3. Epithelium may have a streaming spindled pattern (Fig. 1.9.1)



  4. Variable extent of acute or chronic inflammation present around and within the cribriform glands (Fig. 1.9.3)


  1. Cribriform high-grade PIN glands have rounded contours that fit within the normal architecture of benign glands (Fig. 1.9.4)



  2. Nuclear enlargement, prominent nucleoli, and occasional mitotic figures



  3. Cribriform high-grade PIN has rigid bridges with epithelium unoriented relative to the basement membrane (i.e., no streaming) (Fig. 1.9.4)



  4. Inflammation rarely present (Fig. 1.9.4). Difficult to diagnose high-grade PIN in the setting of inflammation as it is very difficult to distinguish from reactive atypia


Special studies


  • Immunohistochemistry for basal cell markers p63 and HMWCK is positive



  • AMACR typically negative


  • Immunohistochemistry for basal cell markers p63 and HMWCK is positive, yet p63/HMWCK can be patchy or negative in occasional glands



  • AMACR typically positive, yet can be negative


Treatment

None

None


Prognosis

No affect

Rebiopsy depends on extent of PIN (see Section 1.33)








Figure 1.9.1 Partially involved inflamed benign gland with cribriform pattern. Nuclei have a slightly spindled appearance.






Figure 1.9.2 Inflamed benign cribriform gland with intraluminal acute inflammation. Nuclei are enlarged with visible nucleoli yet lack nuclear hyperchromasia.






Figure 1.9.3 Inflamed benign cribriform gland with intraluminal acute inflammation.






Figure 1.9.4 Cribriform high-grade PIN with rigid transluminal bridges, lacking associated inflammation.



1.10 POST-ATROPHIC HYPERPLASIA OF THE PROSTATE (PAH) VS. ATROPHIC PROSTATIC ADENOCARCINOMA

Post-atrophic Hyperplasia of the Prostate (PAH)

Atrophic Prostatic Adenocarcinoma


Age

Typically 50 to elderly, yet can even occur in children

Typically 50 to elderly, although not rare in 40s


Location

Peripheral > transition zone

Peripheral > transition zone


Symptoms

Asymptomatic

Same as usual adenocarcinoma of the prostate


Signs

Usually none

Same as usual adenocarcinoma of the prostate


Etiology

None

In minority of cases, associated with antiandrogen therapy


Histology


  1. Very basophilic at low power due to glands’ scant cytoplasm and crowded nuclei (Fig. 1.10.1); at low magnification one is merely seeing a nuclear outline of the gland



  2. Multiple crowded small round atrophic acini



  3. Typically lobular. May see small acini surrounding a dilated atrophic gland (Figs. 1.10.2 and 1.10.3). Appears invasive as a patch not as individual glands infiltrating in between larger benign glands (Fig. 1.10.4)



  4. Often associated sclerotic stroma, mimicking an infiltrative process (Fig. 1.10.4)



  5. May show enlarged nuclei and nucleoli with mitotic figures (Fig. 1.10.5). Although larger nucleoli with inflammation, latter may be absent or scant



  6. Tangential section of PAH shows multilayered cords of cells with scant cytoplasm and small bland nuclei (Fig. 1.10.6)



  7. PAH not associated with carcinoma. In some cases, diagnosis is atypical glands, cannot rule out atrophic adenocarcinoma


  1. Very basophilic at low power due to glands’ scant cytoplasm and crowded nuclei



  2. Multiple crowded small round atrophic acini



  3. Truly infiltrative process with individual small atrophic glands situated between larger benign glands (Figs.1.10.7, 1.10.8, 1.10.9, 1.10.10)



  4. Typically not associated with sclerotic stroma



  5. May show enlarged nuclei and prominent nucleoli, sometimes accompanied by mitotic figures. May see more prominent nucleoli than PAH (Fig. 1.10.11)



  6. Cords of adenocarcinoma composed of short single row of cells typically with enlarged nuclei, abundant cytoplasm, and visible nucleoli



  7. May be intimately associated with less atrophic carcinoma (Fig. 1.10.12)


Special studies


  • Immunohistochemistry for basal cell markers (p63 and HMWCK) typically strongly and diffusely positive



  • AMACR usually negative


  • Basal cell markers entirely negative in the atypical atrophic glands (Fig. 1.10.10). If only a few atypical glands present and negative for basal cell markers, may not be definitive for diagnosis of carcinoma



  • AMACR variably positive


Treatment

None

Same as usual adenocarcinoma


Prognosis

Not a risk factor for cancer on repeat biopsy

Same as usual adenocarcinoma








Figure 1.10.1 Benign atrophic glands (lower right) with very basophilic appearance compared to adenocarcinoma with amphophilic cytoplasm (upper left).






Figure 1.10.2 Lobular collections of rounded basophilic glands.






Figure 1.10.3 Post-atrophic hyperplasia with central dilated glands and surrounding smaller atrophic glands.






Figure 1.10.4 Post-atrophic hyperplasia with sclerosis imparting an infiltrative pattern on needle biopsy where the entire lesion is not visualized.






Figure 1.10.5 Post-atrophic hyperplasia showing occasional nucleoli and mitotic figure (arrow).






Figure 1.10.6 Tangential section of PAH with columns composed of cells with bland, small nuclei and scant cytoplasm.







Figure 1.10.7 Small glands of atrophic adenocarcinoma infiltrating between larger benign glands with luminal undulations (asterisk).






Figure 1.10.8 Higher magnification of Figure 1.10.7 showing some of the small atrophic glands of adenocarcinoma with prominent nucleoli (arrow).






Figure 1.10.9 Atrophic adenocarcinoma infiltrating between two benign glands (asterisk).






Figure 1.10.10 Triple stain of Figure 1.10.9 with atrophic adenocarcinoma lacking basal cells (brown) and positive for AMACR (red).






Figure 1.10.11 Atrophic adenocarcinoma with diffuse very prominent nucleoli.






Figure 1.10.12 Atrophic adenocarcinoma showing a spectrum of nuclear atypia from none (left) to focal moderate (center) to marked (right) where the glands begin having slightly more cytoplasm.



1.11 PARTIAL ATROPHY VS. PROSTATIC ADENOCARCINOMA

Partial Atrophy

Prostatic Adenocarcinoma


Age

Typically 50 to elderly, although not rare in 40s

Typically 50 to elderly, although not rare in 40s


Location

Peripheral > transition zone

Peripheral > transition zone


Symptoms

None

Typically, asymptomatic. Advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

None

Serum PSA levels variably elevated, no data if different from cancer without inflammation


Etiology

None known

Same as usual adenocarcinoma of the prostate (see Section 1.6)


Histology

Most common mimicker of prostate cancer. Typically more disorganized pattern and lacks the low-magnification basophilic appearance than PAH, although can merge with glands of PAH





  1. Crowded small/medium glands (Figs. 1.11.1 and 1.11.2)



  2. Noninfiltrative but often multifocal (Figs. 1.11.1 and 1.11.2)



  3. Slight undulations of luminal surface (Figs.1.11.3, 1.11.4, 1.11.5)



  4. Pale, lightly eosinophilic cytoplasm



  5. Apical cytoplasm partially strophic with nuclei extending almost to top of the cell. Abundant lateral cytoplasm (Figs.1.11.3, 1.11.4, 1.11.5, 1.11.6, 1.11.7, 1.11.8)



  6. Nuclei at most slightly enlarged (Fig. 1.11.5)



  7. At most small nucleoli



  8. Mitoses and apoptosis absent



  9. Lumen typically lacks crystalloids, blue mucin, pink secretions


  1. Crowded small/medium glands



  2. May show small atypical glands on both sides of benign glands



  3. Often straight luminal border (Fig. 1.11.10)



  4. Cytoplasm may be pale or amphophilic



  5. Typically more abundant apical cytoplasm



  6. Nuclei may be significantly enlarged



  7. May have prominent nucleoli (Fig. 1.11.10)



  8. Occasional mitoses and apoptosis



  9. Lumen may have crystalloids, blue mucin, pink secretions


Special Studies


  • Immunohistochemical studies for basal cell markers (p63 and HMWCK) shows patchy positive cells in some glands and no staining in other glands (Figs. 1.11.4 and 1.11.7). In some clusters of PTAT, the entire focus is negative for basal cell markers (Fig. 1.11.9)



  • AMACR can be positive in a significant minority of cases (Fig. 1.11.4)


  • Negative for basal cell markers (p63 and HMWCK)



  • On biopsy, about 80% positive for AMACR


Treatment

None

Stage and age dependent


Prognosis

Not a risk factor for cancer on repeat biopsy

Cancers in the differential diagnosis with PTAT are Gleason score 3 + 3 = 6 and typically have an excellent prognosis








Figure 1.11.1 Multiple foci of partial atrophy on needle biopsy.






Figure 1.11.2 Higher magnification of Figure 1.11.1.






Figure 1.11.3 Partial atrophy with several glands having luminal undulation.






Figure 1.11.4 Triple stain of Figure 1.11.3 with several glands of partial atrophy having a patchy basal cell layer (bottom) with others negative for basal cells and positive for AMACR (top).






Figure 1.11.5 Partial atrophy with slightly enlarged nuclei.






Figure 1.11.6 Partial atrophic glands admixed with some benign glands having more abundant cytoplasm.







Figure 1.11.7 Some of the partially atrophic glands have patchy basal cells with others lacking high molecular weight cytokeratin staining.






Figure 1.11.8 Classic example of partial atrophy.






Figure 1.11.9 Partial atrophy negative for high molecular weight cytokeratin.






Figure 1.11.10 Adenocarcioma where malignant glands have straight luminal borders, slightly more apical cytoplasm, and numerous prominent nucleoli.



1.12 SEMINAL VESICLES VS. PROSTATIC ADENOCARCINOMA

Seminal Vesicles

Prostatic Adenocarcinoma


Age

On biopsy or TURP, typically 50 to elderly, although not rare in 40s

Typically 50 to elderly, although not rare in 40s


Location

More commonly on biopsy but can be seen on TURP

Peripheral > transition zone


Symptoms

SVs sampled on needle biopsy or TURP typically not cause symptoms

Typically asymptomatic. Advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

Occasionally, seminal vesicle targeted for biopsy in patients with advanced cancer toward the base on imaging or rectal exam

Serum PSA levels variably elevated, no data if different from cancer without inflammation


Histology

Intact SVs have central large dilated lumina with numerous small glands budding off and clustered around the periphery (Fig. 1.12.1)





  1. On needle biopsy, the dilated lumen is seen as a flat epithelial lining on the tip or side of the core, where the core has fragmented as it enters the seminal vesicle lumen. Surrounding these strips of epithelium are clusters of smaller glands (Figs.1.12.2, 1.12.3, 1.12.4). In cases when the needle biopsy does not transect the central lumen, only crowded glands are seen, which more closely mimics prostatic carcinoma (Figs.1.12.5, 1.12.6, 1.12.7, 1.12.8)



  2. Epithelium in strips and small glands characteristically has scattered atypical cells with markedly enlarged, hyperchromatic, and pleomorphic nuclei. Atypia is degenerative in nature with smudgy chromatin, lacking mitotic activity (Figs. 1.12.8 and 1.12.9)



  3. Prominent, globular, golden brown lipofuscin granules within the epithelium (Figs. 1.12.6 and 1.12.8)


  1. Adenocarcinoma glands do not cluster around a strip of epithelium at the tip or edge of the core



  2. Gleason score 6 carcinomas, which the small glands of seminal vesicles mimic have only slight to moderate nuclear atypia that is uniform throughout the gland



  3. Benign prostate tissue, high-grade PIN, and rarely carcinoma may contain lipofuscin pigment, but it differs in that the granules are smaller and more red-orange or blue (Fig. 1.12.10)


Special studies


  • Basal cell markers (p63 and HMWCK) are positive around SVs



  • AMACR negative



  • MUC6 positive



  • Prostatic markers (PSA, PSAP, PSMA, P501s, NKX3.1) negative


  • Basal cell markers (p63 and HMWCK) are negative in carcinoma



  • Usually positive for AMACR



  • MUC6 negative



  • Prostatic markers (PSA, PSAP, PSMA, P501s, NKX3.1) uniformly positive in Gleason score 6 carcinomas


Treatment

None

Grade and stage dependent


Prognosis

Does not cause morbidity if biopsied

Grade and stage dependent








Figure 1.12.1 Seminal vesicle on a TURP showing central lumen surrounded by small glands.






Figure 1.12.2 Needle biopsy with strip of seminal vesicle at edge (left) surrounded by small crowded glands.






Figure 1.12.3 Needle biopsy with seminal vesicle epithelium on each side of break in tissue representing seminal vesicle lumen (bottom core).






Figure 1.12.4 Needle biopsy with strip of seminal vesicle at edge (left) surrounded by small crowded glands.






Figure 1.12.5 Crowded glands of seminal vesicle mimicking prostatic adenocarcinoma.






Figure 1.12.6 Higher magnification of Figure 1.12.5 where glands have degenerative atypia and golden brown lipofuscin pigment.







Figure 1.12.7 Crowded glands of seminal vesicle.






Figure 1.12.8 Same case as Figure 1.12.7 with glands showing degenerative atypia and golden brown lipofuscin pigment.






Figure 1.12.9 Degenerative atypia in seminal vesicle epithelium.






Figure 1.12.10 Benign prostate epithelium with small cytoplasmic blue (left, arrows) or red-orange (right) lipofuscin granules.



1.13 BENIGN PROSTATE TISSUE WITH RADIATION AFFECT VS. PROSTATIC ADENOCARCINOMA WITH RADIATION AFFECT

Benign Prostate Tissue with Radiation Affect

Prostatic Adenocarcinoma with Radiation Affect


Age

Typically 50 to elderly, although not rare in 40s

Typically 50 to elderly, although not rare in 40s


Location

Peripheral = transition zone

Peripheral > transition zone


Symptoms

Typically asymptomatic unless bleeding from sloughed benign tissue with radiation necrosis

Typically asymptomatic unless bleeding from sloughed cancer with radiation necrosis. Advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

Typically, following radiotherapy, serum PSA level decreases to a nadir level in men without cancer. Occasional bleeding or obstruction due to sloughed tissue with radiation necrosis within the urethra

In some men, PSA rises following radiation (nadir PSA + 2 defines radiation failure). Recommended that biopsies be performed 30-36 mo after radiotherapy


Etiology

Degree of cytologic atypia in nonneoplastic glands and degree of stromal fibrosis higher after brachytherapy compared to external beam radiation. Marked epithelial atypia tends to persist for a longer time (up to 6 y) following brachytherapy

Quiescent cancer with radiation affect or cancer without radiation affect resistant to radiation therapy


Histology


  1. Glands maintain their normal architectural configuration. Nonneoplastic glands are separated by a modest amount of prostatic stroma (Fig. 1.13.1)



  2. Typically atrophic (Fig. 1.13.2)



  3. Multilayered with epithelium streaming parallel to the basement membrane (Fig. 1.13.3)



  4. Scattered markedly atypical nuclei within well-formed acini (Fig. 1.13.3). Scattered atypical nuclei often lack apparent nucleoli and are either large with bizarre shapes or pyknotic with smudged chromatin. Occasionally nucleoli can be seen (Fig. 1.13.2)



  5. Diagnosis is benign prostate tissue with radiation affect


  1. Architecturally, inconsistent with benign glands. Cancers with radiation affect show numerous infiltrating individual epithelial cells or poorly formed glands. Usual morphology of adenocarcinoma without radiation affect (Figs.1.13.4, 1.13.5, 1.13.6, 1.13.7, 1.13.8, 1.13.9, 1.13.10)



  2. With radiation affect, individual cells have abundant vacuolated cytoplasm or single cells with indistinct cytoplasm (Figs.1.13.4, 1.13.5, 1.13.6, 1.13.7, 1.13.8, and 1.13.10). Abundant cytoplasm typically in cancers without radiation affect (Fig. 1.13.9)



  3. Cancer with radiation affect typically lacks well-formed glands vs. gland-forming cancer without radiation affect shows a single cell layer without streaming



  4. Nuclei in cancer with radiation affect often benign appearing, lacking nucleoli (Figs. 1.13.5 and 1.13.8). Occasionally can appear pleomorphic with degenerative atypia (Fig. 1.13.10). In cancer without radiation affect, nuclei often have prominent nucleoli



  5. Cancers with significant radiation affect are not graded. Cancers without significant radiation affect are graded the same as cancers that have not been radiated


Special Studies


  • HMWCK and p63 show multilayered positive staining



  • AMACR negative


  • HMWCK and p63 are negative



  • Often positive AMACR in both cancers with and without radiation affect


Treatment

None

Cancer with radiation affect not further treated. Cancer without radiation affect may be treated depending on age and comorbidity with salvage therapies (cryosurgery, HIFU, radical prostatectomy) and/or hormonal therapy


Prognosis

If postradiation serum PSA levels keep rising, a negative biopsy probably reflects sampling error

Cancers with radiation affect have a favorable prognosis. Cancer without radiation affect ultimately will progress








Figure 1.13.1 Benign prostate tissue with radiation atypia. At low magnification, glands are separated by a modest amount of stroma and are the size of normal benign prostate glands. Glands appear very blue due to atrophic cytoplasm.






Figure 1.13.2 Atrophic benign-radiated glands. Scattered nuclei are enlarged and hyperchromatic.






Figure 1.13.3 Multilayered benign-radiated gland with cells streaming parallel to the basement membrane.






Figure 1.13.4 Scattered crowded smaller glands with vacuolated cytoplasm diagnostic of adenocarcinoma with treatment affect (arrows) adjacent to a larger multilayered benign gland with radiation atypia (upper right).







Figure 1.13.5 Higher magnification of Figure 1.13.4 with vacuolated crowded glands lined by bland nuclei.






Figure 1.13.6 Radiated carcinoma with clusters of vacuolated cells invading between larger benign atrophic glands with radiation atypia.






Figure 1.13.7 Crowded smaller glands with vacuolated cytoplasm diagnostic of adenocarcinoma with treatment affect in between darker, larger, more evenly spaced benign glands.






Figure 1.13.8 Higher magnification of Figure 1.13.7 with small vacuolated cancer glands (center) lacking prominent atypia invading between benign glands (lower left and upper right).






Figure 1.13.9 Atrophic glands of adenocarcinoma with abundant mucin showing treatment affect (top) adjacent to adenocarcinoma without treatment affect (lower left).






Figure 1.13.10 Adenocarcinoma with treatment affect with single cells with vacuolated cytoplasm. There is more prominent nuclear atypia, yet still with a degenerative appearance, than is typically seen in cancer with radiation affect.



1.14 XANTHOMA VS. PROSTATIC ADENOCARCINOMA WITH HORMONE THERAPY AFFECT AND HIGH-GRADE FOAMY GLAND CARCINOMA

Xanthoma

Prostatic Adenocarcinoma with Hormone Therapy Affect and High-Grade Foamy Gland Carcinoma


Age

Typically, adults seen on needle biopsy, TURP, or radical prostatectomy

Typically, adults seen on needle biopsy, TURP, or radical prostatectomy


Location

Transition = peripheral zone

Transition < peripheral zone


Symptoms

Asymptomatic

May be asymptomatic or advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

None

Serum PSA levels variably elevated


Etiology

Xanthomas unrelated to serum lipid levels

High-grade cancer mimicking xanthoma can be seen following hormonal therapy. High-grade foamy gland cancer of unknown etiology can also mimic xanthoma


Histology


  1. Background may reveal stroma that is unremarkable or elastotic, yet typically not fibrotic (Fig. 1.14.1)



  2. Collections of histiocytes in clusters (Figs. 1.14.1 and 1.14.2)



  3. Nuclei are bland (Figs. 1.14.1 and 1.14.3)



  4. In some cases can form cords (Fig. 1.14.4)



  5. Foci are typically small, yet occasionally can occupy larger areas (Fig. 1.14.5)


  1. Hormone-treated patients with typically fibrotic stroma (Fig. 1.14.8). High-grade foamy gland cancer has variably fibrotic stroma



  2. Neoplastic glands can develop pyknotic nuclei and abundant xanthomatous cytoplasm resembling histiocytes (Figs. 1.14.8 and 1.14.9). Histiocytic-appearing cancer cells can be seen as desquamated cells in cancer lumina or as scattered cells in the stroma. Xanthomatous cytoplasm also seen in high-grade foamy gland cancer (Fig. 1.14.10)



  3. Small bland nuclei can be seen in cancers following hormonal therapy and in foamy gland cancer (Figs.1.14.9, 1.14.10, 1.14.11, 1.14.12)



  4. Can form cords and single cells



  5. Typically Gleason score 10 adenocarcinoma is extensive on TURP and needle biopsy, although uncommon cases exist with small foci of high-grade cancer


Special studies


  • Negative for keratins such as CAM5.2 and AE1/AE3



  • Positive for CD68 (Figs. 1.14.6 and 1.14.7)


  • Positive for keratins, such as CAM5.2 or AE1/Ae3. Prostate markers may be negative in Gleason score 10 adenocarcinoma



  • CD68 negative


Treatment

None

High-grade foamy gland cancer same treatment as usual high-grade cancer


Prognosis

Inflammation on biopsy is not associated with an increased risk of cancer on subsequent biopsy

Following a response to combination endocrine therapy, the grade of the tumor appears artifactually higher and should not be assigned a Gleason score. High-grade foamy gland cancer same poor prognosis as usual high-grade cancer








Figure 1.14.1 Xanthoma with bland cells.






Figure 1.14.2 Cluster of xanthoma cells.






Figure 1.14.3 Bland cytology of xanthoma cells.






Figure 1.14.4 Cords of xanthoma cells.






Figure 1.14.5 Unusual case of relatively extensive xanthoma on needle biopsy.






Figure 1.14.6 Individual cells and nests of xanthoma.







Figure 1.14.7 Same case as Figure 1.14.6 with positive staining for CD68.






Figure 1.14.8 Adenocarcinoma with hormone treatment affect consisting of nests of cells with foamy cytoplasm in a slightly fibrotic stroma.






Figure 1.14.9 Higher magnification of Figure 1.14.8 showing cords of cells resembling xanthoma. Focal glandular differentiation is noted (top).






Figure 1.14.10 High-grade foamy gland adenocarcinoma.






Figure 1.14.11 Hormone-treated prostate cancer with pyknotic hyperchromatic nuclei and abundant xanthomatous cytoplasm.






Figure 1.14.12 Adenocarcinoma of the prostate with hormone therapy affect with small nuclei, xanthomatous cytoplasm, and clear cleft-like spaces lined by pyknotic tumor nuclei resembling lymphocytes.



1.15 BASAL CELL HYPERPLASIA WITH NUCLEOLI VS. HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA

Basal Cell Hyperplasia with Nucleoli

High-Grade Prostatic Intraepithelial Neoplasia


Age

Typically, adults seen on needle biopsy, TURP, or radical prostatectomy

Typically adults


Location

Transition > peripheral zone

Peripheral = transition zone


Symptoms

Asymptomatic

Typically asymptomatic


Signs

None

Usually incidentally detected on biopsy performed for elevated serum PSA levels


Etiology

Usually nonspecific and focal. If diffuse, usually associated with antiandrogen therapy. Basal cells with nucleoli can be seen as a component of normal glands as either single or multiple rows of cells underlying secretory cells or as a hyperplastic process

See Section 1.6


Histology


  1. Basal cells with blue nuclei having prominent nucleoli undermining secretory cells with red/violet nuclei lacking prominent nucleoli (Fig. 1.15.1). Basal cells in normal glands or in basal cell hyperplasia may have prominent nucleoli (Figs. 1.15.1 and 1.15.2)



  2. May consist of proliferation of small crowded glands (Fig. 1.15.2)



  3. Basal cell nuclei tend to be round (Figs. 1.15.2 and 1.15.3)



  4. Occasional solid nests (Figs. 1.15.2 and 1.15.3)



  5. May have coarse calcifications (Fig. 1.15.4)



  6. Glandular lumina have atrophic cytoplasm (Fig. 1.15.3)



  7. Pseudocribriform glands with back to back to individual glands maintaining their own identity (Figs. 1.15.5 and 1.15.6)


  1. Basal cells are often indistinct and lack prominent nucleoli with overlying high-grade PIN nuclei having prominent nucleoli (Figs.1.15.8, 1.15.9, 1.15.10). May show maturation of high-grade PIN nuclei with more benign-appearing nuclei toward the center of the gland (Fig. 1.15.10)



  2. Large architecturally benign glands without much crowding



  3. High-grade PIN nuclei are columnar (Figs. 1.15.8 and 1.15.9)



  4. Lacks solid nests; has well-formed lumina (Figs. 1.15.8 and 1.15.9)



  5. Lacks calcifications



  6. Glandular lumina have nonatrophic cytoplasm (Figs. 1.15.9 and 1.15.10)



  7. True cribriform glands with rounded sheet of cells having punched out lumina and more benign-appearing nuclei in the center (Fig. 1.15.11)


Special Studies


  • Atypical nuclei positive for HMWCK/p63 although staining not present in all cells; within a nest or gland, centrally located cells may not be immunoreactive (Fig. 1.15.7)



  • AMACR negative


  • Atypical nuclei negative for HMWCK/p63 with often a patchy basal cell layer positive for HMWCK/p63 (Fig. 1.15.12)



  • AMACR frequently positive


Treatment

None

None


Prognosis

Basal cells with prominent nucleoli were in the past called “atypical basal cell hyperplasia.” As no worse prognosis than basal cell hyperplasia without nucleoli should merely be called basal cells or basal cell hyperplasia with prominent nucleoli

Rebiopsy depends on the extent of PIN (see Section 1.33)








Figure 1.15.1 Basal cells with blue-gray nuclei containing prominent nucleoli undermine secretory cells with red-violet nuclei.






Figure 1.15.2 Proliferation of small glands of basal cell hyperplasia with prominent nucleoli. While one gland is larger resembling high-grade PIN (upper left), others are small with either a small central lumen with atrophic cytoplasm or composed of solid nests.






Figure 1.15.3 Basal cell hyperplasia with prominent nucleoli composed of solid nests surrounding the central lumen with atrophic cytoplasm.






Figure 1.15.4 Basal cell hyperplasia with coarse calcifications.






Figure 1.15.5 Pseudocribriform hyperplasia back-to-back glands of basal cell hyperplasia.






Figure 1.15.6 Pseudocribriform hyperplasia back-to-back glands of basal cell hyperplasia. Each gland maintains its integrity, where one can still identify each gland surrounding a lumen.







Figure 1.15.7 High molecular weight cytokeratin stain of basal cell hyperplasia labeling multilayered peripheral cells with prominent nucleoli.






Figure 1.15.8 Tufted high-grade PIN with small basal cells (arrows) and overlying columnar PIN nuclei with prominent nucleoli.






Figure 1.15.9 Flat high-grade PIN with small bland basal cells undermines columnar cells with nuclei containing prominent nucleoli.






Figure 1.15.10 Tufted high-grade PIN with maturation of nuclei toward the center of the gland. However, note the presence of a distinct bland basal cell layer (arrows) with an abrupt transition to overlying atypical high-grade PIN nuclei.






Figure 1.15.11 Cribriform high grade PIN.






Figure 1.15.12 Patchy basal cell staining with p63 and high molecular weight cytokeratin. Overlying atypical PIN nuclei are negative.



1.16 BASAL CELL HYPERPLASIA WITH NUCLEOLI VS. PROSTATIC ADENOCARCINOMA

Basal Cell Hyperplasia with Nucleoli

Prostatic Adenocarcinoma


Age

Typically adults seen on needle biopsy, TURP, or radical prostatectomy

Typically 50 to elderly, although not rare in 40s


Location

Transition > peripheral zone

Peripheral > transition zone


Symptoms

Asymptomatic

Typically asymptomatic. Advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

None

Serum PSA levels variably elevated


Etiology

If focal, none known. If diffuse, usually associated with antiandrogen therapy

Cases mimicking basal cell hyperplasia consist of either individual glands of Gleason pattern 3 or cribriform glands of Gleason pattern 4


Histology


  1. May have solid nests of cells (Fig. 1.16.1)



  2. Cases that most closely mimic carcinoma have retention of lumina with only a couple of basal cell layers (Figs.1.16.2, 1.16.3, 1.16.4, 1.16.5)



  3. Cytoplasm tends to be atrophic, yet can be more abundant (Fig. 1.16.3)



  4. Glands can be crowded and in between acini appearing infiltrative (Fig. 1.16.3)



  5. Very prominent nucleoli with occasional mitotic figures can be seen (Fig. 1.16.5)



  6. Often with calcifications (Fig. 1.16.6)



  7. Minority of cases with cytoplasmic eosinophilic globules (Fig. 1.16.7)


  1. Solid cell nests not a pattern of adenocarcinoma



  2. Typically, there is only a single cell layer, yet occasionally cancers can appear multilayered (Fig. 1.16.9)



  3. Cytoplasm tends to be abundant (Fig. 1.16.9)



  4. Glands can be crowded and situated between benign with an infiltrative appearance



  5. Very prominent nucleoli with occasional mitotic figures can be seen



  6. Rare carcinomas can have calcifications (Fig. 1.16.10)



  7. Cancers lack cytoplasmic eosinophilic globules


Special Studies


  • Atypical nuclei positive for HMWCK/p63 although staining not present in all cells; within a nest or gland, centrally located cells may not be immunoreactive



  • AMACR negative (Fig. 1.16.8)


  • Cancer glands negative for HMWCK/p63



  • AMACR variably positive


Treatment

None

Depends on grade as well as stage


Prognosis

Benign. Should not use the term “atypical basal cell hyperplasia”

Depends on grade as well as stage








Figure 1.16.1 Basal cell hyperplasia on needle biopsy consisting of multilayered glands and solid nests.






Figure 1.16.2 Basal cell hyperplasia.






Figure 1.16.3 Same case as Figure 1.16.2 with two rows of basal cells and scant cytoplasm.






Figure 1.16.4 Basal cell hyperplasia glands interspersed between usual prostate glands.






Figure 1.16.5 Basal cell hyperplasia with prominent nucleoli.






Figure 1.16.6 Basal cell hyperplasia with calcification.







Figure 1.16.7 Same case as Figure 1.16.6 with numerous intracytoplasmic globules.






Figure 1.16.8 HMWCK and p63 staining of basal cell hyperplasia.






Figure 1.16.9 Adenocarcinoma with multilayered nuclei.






Figure 1.16.10 Adenocarcinoma with calcifications.



1.17 BASAL CELL HYPERPLASIA VS. BASAL CELL CARCINOMA

Basal Cell Hyperplasia

Basal Cell Carcinoma


Age

Typically adults, more commonly on TURP or radical prostatectomy compared to needle biopsy

Typically adults seen on needle biopsy, TURP, or radical prostatectomy


Location

Transition > peripheral zone

Transition > peripheral zone


Symptoms

Asymptomatic

Typically urinary obstructive symptoms


Signs

None

None. Serum PSA levels not elevated as a result of basal cell carcinoma


Etiology

Usually nonspecific and focal. If diffuse, usually associated with antiandrogen therapy. In cases mimicking carcinoma, seen as a hyperplastic process

No risk factors known. Basal cell hyperplasia does not progress to basal cell carcinoma


Histology


  1. Uniformly sized small glands or nests with multilayered basal cells (Fig. 1.17.1). May be extensive and appear diffusely as opposed to nodular (Fig. 1.17.2)



  2. Pseudocribriform or cribriform glands (Fig. 1.17.3)



  3. Lack of large nests and absence of necrosis



  4. Lack of central eosinophilic cells



  5. May have prominent nucleoli yet not pleomorphic (Fig. 1.17.4)



  6. Confined to the prostate. Lacks perineural invasion



  7. Lack of prominent stromal reaction, although occasionally slightly myxoid (Fig. 1.17.1)


  1. Variably small/medium-sized nests with irregular shapes with multilayered basal cells (Figs. 1.17.5 and 1.17.6)



  2. Adenoid cystic pattern (Fig. 1.17.7)



  3. Large basaloid nests with necrosis (Fig. 1.17.8)



  4. Anastomosing basaloid nests and tubules centrally lined by eosinophilic cells (Fig. 1.17.9)



  5. Indistinguishable from basal cell hyperplasia (Fig. 1.17.10)



  6. Extension into periprostatic adipose tissue, seminal vesicles, or bladder neck muscle (Fig. 1.17.10). May show perineural invasion



  7. Occasional dense or myxoid stromal reaction (Fig. 1.17.11)


Special Studies


  • Lack of diffuse strong BCL2 staining



  • Ki-67 typically <5% and should not be >20%



  • Basal cell markers (p63 and HMWCK) may highlight multiple cell layers, just the outermost layers or only a few scattered cells with some negative for HMWCK


  • Strong diffuse strong BCL2 staining



  • May show Ki-67 >20% (Fig. 1.17.12)



  • Basal cell markers (p63 and HMWCK) may highlight multiple cell layers, just the outermost layers or only a few scattered cells with some negative for HMWCK


Treatment

None

Radical prostatectomy depending on stage, age, and comorbidity


Prognosis

Basal cells with prominent nucleoli were in the past called “atypical basal cell hyperplasia.” As no worse prognosis than basal cell hyperplasia without nucleoli should merely be called basal cells or basal cell hyperplasia with prominent nucleoli

Can locally recur. Distant metastases most commonly seen with large solid nests with central necrosis, high Ki-67 rate, and less staining with basal cell markers








Figure 1.17.1 Basal cell hyperplasia on needle biopsy consisting of crowded, uniformly sized, and distributed small glands in prostatic stroma without a desmoplastic reaction.






Figure 1.17.2 Extensive basal cell hyperplasia on TURP.






Figure 1.17.3 Pseudocribriform structure with individual well-defined glands surrounded by solid cells.






Figure 1.17.4 Basal cell hyperplasia with prominent nucleoli.






Figure 1.17.5 Basal cell carcinoma with irregular variably sized glands and nests in a desmoplastic stroma. Within inner aspect of some nests are tubules lined by eosinophilic cytoplasm.






Figure 1.17.6 Small and medium nests of basal cell carcinoma in a desmoplastic stroma.







Figure 1.17.7 Adenoid cystic pattern of basal cell carcinoma with perineural invasion.






Figure 1.17.8 Basal cell carcinoma with solid nests with necrosis.






Figure 1.17.9 Small nests of basal cell carcinoma with tubules lined by eosinophilic cytoplasm.






Figure 1.17.10 Basal cell carcinoma resembling basal cell hyperplasia. Nests and tubules infiltrated thick bladder neck muscle diagnostic of carcinoma.






Figure 1.17.11 Basal cell carcinoma with prominent myxoid stromal reaction.






Figure 1.17.12 Elevated Ki-67 in basal cell carcinoma.



1.18 COWPER GLANDS VS. FOAMY GLAND PROSTATIC ADENOCARCINOMA

Cowper Glands

Foamy Gland Prostatic Adenocarcinoma


Age

Typically adults seen on needle biopsy, uncommonly on TURP

Same as usual prostate adenocarcinoma


Location

Located just distal to the prostate in skeletal muscle of the urogenital diaphragm

Same as usual prostate adenocarcinoma


Symptoms

Normal anatomical structure. No symptoms

Typically asymptomatic


Signs

Normal anatomical structure. No signs

Detected as a result of abnormal digital rectal examination or elevated serum PSA level


Etiology

Typically not biopsied since external to the prostate but occasionally sampled on apical biopsy

Same as usual prostate adenocarcinoma


Histology


  1. Crowded Cowper glands in skeletal muscle (Fig. 1.18.1). No prostate tissue in core with Cowper glands



  2. Lobular pattern (Fig. 1.18.2)



  3. Dimorphic population of nonmucinous ducts and mucinous acini (Figs. 1.18.2 and 1.18.3). Lacks dense pink intraluminal secretions



  4. Distended rounded cells with distinct cell borders (Fig. 1.18.3)



  5. Small, round, bland, basally situated nuclei (Fig. 1.18.3)



  6. Glandular lumina are often totally or subtotally occluded (Fig. 1.18.2)


  1. Crowded well-formed glands in prostate tissue (Fig. 1.18.6)



  2. Diffuse growth pattern (Fig. 1.18.7)



  3. Uniform population of mucinous acini (Fig. 1.18.8)



  4. Columnar cells lacking the distended ovoid cytoplasm (Figs. 1.18.9 and 1.18.10)



  5. Small, round, bland, basally situated nuclei, uncommon to see prominent nucleoli (Figs.1.18.9, 1.18.10, 1.18.11)



  6. Glandular lumina well developed with dense pink amorphous secretions (Fig. 1.18.8)


Special Studies


  • Acini positive for neutral mucin (Fig. 1.18.4)



  • PSA negative



  • HMWCK and p63 outline the peripheral of acini (Fig. 1.18.5)


  • Negative for neutral mucin



  • PSA positive



  • Lacks HMWCK and p63 (Fig. 1.18.12)


Treatment

None

Same as usual prostate adenocarcinoma


Prognosis

Normal structures that only very rarely develop neoplasia

Patients with differential diagnosis of Cowper glands are Gleason score 3 + 3 = 6. Less frequently, foamy gland cancer can be higher grade with cribriform or poorly formed glands (Gleason pattern 4) or lack of gland formation (Gleason pattern 5)








Figure 1.18.1 Cowper glands in skeletal muscle.






Figure 1.18.2 Lobular Cowper glands with mucinous glands and atrophic ducts lined by cuboidal nonmucinous epithelium. Distended cytoplasm results in small central lumina.






Figure 1.18.3 Higher magnification of Figure 1.18.2 with central duct and surrounding mucinous glands. Some cells have rounded distended appearance (arrow).






Figure 1.18.4 Mucicarmine-positive Cowper glands.






Figure 1.18.5 Cowper glands lined by HMWCK-positive basal cells (arrows).






Figure 1.18.6 Foamy gland carcinoma infiltrating in prostate stroma around the benign gland (arrow).







Figure 1.18.7 Foamy gland carcinoma with crowded glands with well-formed open lumina.






Figure 1.18.8 Dense pink secretions in a foamy gland carcinoma.






Figure 1.18.9 Foamy gland carcinoma with cuboidal to columnar bland nuclei. More atypical nuclei are seen in adjacent nonfoamy gland carcinoma (upper right).






Figure 1.18.10 Foamy gland carcinoma with bland nuclei and columnar cells with abundant xanthomatous-appearing cytoplasm.






Figure 1.18.11 Foamy gland carcinoma (right) with bland nuclei compared to usual prostate cancer with greater cytologic atypia (left).






Figure 1.18.12 Foamy gland carcinoma lacking basal cells (brown) and positive for AMACR (red). An entrapped benign gland surrounded by basal cells is present (same case as Fig. 1.18.6).



1.19 ADENOSIS VS. PROSTATIC ADENOCARCINOMA

Adenosis

Prostatic Adenocarcinoma


Age

Adults, more commonly on TURP or radical prostatectomy compared to needle biopsy. Diffuse adenosis of the peripheral zone (DAPZ) predilection for men in their 40s-50s

Typically 50 to elderly, although not rare in 40s


Location

Transition > peripheral zone. DAPZ: Predominantly the peripheral zone

Peripheral > transition zone


Symptoms

Asymptomatic

Typically asymptomatic. Advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

None

Serum PSA levels variably elevated


Etiology

No known risk factors

Cases mimicking adenosis consist of individual glands of Gleason pattern 3


Histology


  1. Lobular collection of glands, easier to appreciate on TURP or radical prostatectomy compared to needle biopsy (Figs.1.19.1, 1.19.2, 1.19.3). Can be minimal infiltration at periphery



  2. Typically small but can extensively involve the entire core or large percentage of a TURP specimen. DAPZ involves multiple cores



  3. Glands can be as crowded as cancer with back-to-back glands (Figs.1.19.2, 1.19.3, 1.19.4)



  4. Small glands share features with admixed larger more benign-appearing glands (Fig. 1.19.4)



  5. Scattered poorly formed glands and single cells can be seen due to tangential sectioning (Fig. 1.19.5)



  6. Pale-clear cytoplasm



  7. Indistinct or small- or medium-sized nucleoli



  8. Blue mucinous secretions rare



  9. Corpora amylacea common (Fig. 1.19.6)



  10. Intraluminal crystalloids common (Fig. 1.19.7)



  11. Can be admixed with basal cell hyperplasia or clear cell cribriform hyperplasia


  1. Haphazard growth pattern, easier to appreciate on TURP or radical prostatectomy compared to needle biopsy (Fig. 1.19.9). Some cases may appear lobular, mimicking adenosis (Figs.1.19.10, 1.19.11, 1.19.12)



  2. Range in size from focal to extensive



  3. Glands often crowded, yet not a differentiating feature from adenosis



  4. Small glands differ from adjacent benign glands in terms of nuclear, cytoplasmic, or luminal features (Fig. 1.19.11)



  5. Scattered poorly formed glands and single cells can be seen due to tangential sectioning of Gleason pattern 3



  6. Occasionally amphophilic cytoplasm



  7. Range of size of nucleoli with occasionally large nucleoli



  8. Blue mucinous secretions common



  9. Corpora amylacea rare



  10. Intraluminal crystalloids common



  11. Typically not admixed with benign mimickers of carcinoma


Special Studies


  • HMWCK and p63 positive, yet typically only a few glands per nodule having immunoreactive basal cells. Positive glands typically show patchy basal cell staining of one to two basal cells per glands (Fig. 1.19.8)



  • AMACR positive in 10%-25% of cases


  • Carcinomas are negative for HMWCK and p63 with uncommon exceptions (see Sections 1.46 and 1.47) (Fig. 1.19.12)



  • AMACR positive in 80% of carcinomas on biopsy


Treatment

None

Grade and stage dependent


Prognosis

Also known as atypical adenomatous hyperplasia (AAH), which is not a preferred term since not associated with an increased risk of subsequent adenocarcinoma. DAPZ has an increased risk of prostate adenocarcinoma on subsequent rebiopsy

Cases mimicking adenosis typically Gleason scores 6








Figure 1.19.1 Lobular focus of adenosis. Glands lack interspersed large bundles of smooth muscle.






Figure 1.19.2 Adenosis on needle where a lobular pattern can still be appreciated.






Figure 1.19.3 Adenosis on needle biopsy.






Figure 1.19.4 Same case as Figure 1.19.1 with small crowded glands sharing cytoplasmic and nuclear features with more benign-appearing glands (left).






Figure 1.19.5 Same case as Figure 1.19.1 with some glands with a visible basal cell layer (arrows). Some of the glands are tangentially sectioned (left).






Figure 1.19.6 Adenosis with corpora amylacea.







Figure 1.19.7 Same case as Figure 1.19.1 with crystalloids.






Figure 1.19.8 Same case as Figure 1.19.1 with adenosis showing some glands with HMWCK patchy, positive basal cells and other glands negative. Negative glands have the same morphology as positive glands.






Figure 1.19.9 Irregular growth pattern of cancer with glands interspersed between large bundles of smooth muscle.






Figure 1.19.10 Adenocarcinoma mimicking adenosis on needle biopsy.






Figure 1.19.11 Same case as Figure 1.19.10 with adenocarcinoma showing prominent nucleoli (arrows) compared to benign gland (lower left).






Figure 1.19.12 Negative stains for HMWCK (same case as Figs. 1.19.10 and 1.19.11). Note entrapped benign glands (bottom) with circumferential staining.



1.20 SCLEROSING ADENOSIS VS. HIGH-GRADE PROSTATIC ADENOCARCINOMA

Sclerosing Adenosis

High-Grade Prostatic Adenocarcinoma


Age

Typically adults, more commonly on TURP or radical prostatectomy. Rare on needle biopsy

Typically 50 to elderly, although not rare in 40s


Location

Transition zone

Peripheral > transition zone


Symptoms

Asymptomatic

Typically asymptomatic. Advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

None

Serum PSA levels variably elevated


Etiology

No known risk factors

See Section 1.6


Histology


  1. Mixture of well-formed glands, single epithelial cells, and cellular spindle cells (Figs.1.20.1, 1.20.2, 1.20.3)



  2. Usually focal, although uncommonly can be extensive



  3. Relatively circumscribed with minimal infiltration at its perimeter



  4. Glandular component composed of cells with pale to clear cytoplasm and relatively benign-appearing nuclei (Figs. 1.20.4 and 1.20.5)



  5. Hyaline sheath of collagen surrounds some of the glands (Figs. 1.20.4, 1.20.5, and 1.20.7)



  6. Individual cells may have very prominent nucleoli



  7. Associated dense, spindle cell component (Figs. 1.20.1, 1.20.4, and 1.20.6)


  1. Lesions mimicking sclerosing adenosis would typically be graded as Gleason score 3 + 5 = 8 (Fig. 1.20.10)



  2. Range in size from focal to extensive



  3. Irregularly infiltrative



  4. Gleason pattern 3 may have cells with amphophilic cytoplasm and prominent nucleoli



  5. Absence of periglandular collagenous sheath



  6. Individual cancer cells can be identical to single cells in sclerosing adenosis



  7. Usually, no apparent stromal response or at most a hypocellular fibrotic reaction


Special Studies


  • HMWCK and p63 positive around some of the glands (Fig. 1.20.8)



  • Positive for muscle-specific actin and S100 protein consistent with myoepithelial cell differentiation in some of the spindle cells and basal cell (Fig. 1.20.9)



  • Spindle cell component keratin positive, consistent with myoepithelial cell differentiation


  • Absence of HMWCK and p63



  • Muscle-specific actin negative



  • Stroma surrounding cancer glands that are keratin negative


Treatment

None

Stage dependent


Prognosis

Benign with no risk of subsequent carcinoma

Variably aggressive depending on stage. Gleason score 8 treated by radical prostatectomy approximately 60% cure rate








Figure 1.20.1 Sclerosing adenosis with scattered glands and single epithelial cells (arrows) with cellular stroma background.






Figure 1.20.2 Limited focus of sclerosing adenosis on TURP.






Figure 1.20.3 Sclerosing adenosis consisting of well-formed glands (right) and poorly formed glands (left) with cellular spindle cells in background.






Figure 1.20.4 Higher magnification of Figure 1.20.2 showing a gland surrounded by hyaline rim of connective tissue. Background of cellular spindle cells.






Figure 1.20.5 Higher magnification of Figure 1.20.3 with atrophic glands having hyaline rim (arrow).






Figure 1.20.6 Sclerosing adenosis.







Figure 1.20.7 Higher magnification of Figure 1.20.6 with a gland having hyaline rim of connective tissue (arrow). Glands have nuclei with prominent nucleoli.






Figure 1.20.8 Same case of Figures 1.20.6 and 1.20.7 with HMWCK positivity of basal cells.






Figure 1.20.9 Same case as Figures 1.20.6, 1.20.7, 1.20.8 with S100 protein showing myoepithelial cell differentiation in basal and some spindle cells.






Figure 1.20.10 Adenocarcinoma, Gleason score 5 + 3 = 8 lacking cellular background stroma and hyaline rim of connective tissue around glands.



1.21 PSEUDOHYPERPLASTIC PROSTATE ADENOCARCINOMA VS. CROWDED BENIGN PROSTATE GLANDS

Pseudohyperplastic Prostate Adenocarcinoma

Crowded Benign Prostate Glands


Age

Typically 50 to elderly, although not rare in 40s

Typically adults


Location

Peripheral > transition zone

Peripheral = transition zone


Symptoms

Typically asymptomatic

Asymptomatic


Signs

Serum PSA levels variably elevated

None


Etiology

See Section 1.6

No known risk factors. Commonly seen


Histology


  1. Crowded focus of larger glands with branching and papillary infolding (Figs.1.21.1, 1.21.2, 1.21.3, 1.21.4, 1.21.5)



  2. Crowded large glands with abundant cytoplasm and a sharp, straight, luminal border (Figs.1.21.6, 1.21.7, 1.21.8, 1.21.9)



  3. Typically requires prominent nucleoli for diagnosis (Figs. 1.21.5 and 1.21.6)


  1. Crowded variably sized glands often with branching and papillary infolding (Fig. 1.21.10)



  2. Large benign glands with abundant cytoplasm typically have papillary infolding or luminar undulations (Fig. 1.21.10)



  3. Lack of prominent nucleoli (Fig. 1.21.11)


Special Studies


  • Diagnosis verified with absent HMWCK/p63 in many cytologically atypical glands (Figs. 1.21.3, 1.21.7, and 1.21.9). A few glands absent for HMWCK or p63 are not diagnostic of carcinoma, as HGPIN can have same histology and immunohistochemistry


  • Although a few benign glands may be entirely absent for HMWCK or p63, a patchy basal cell layer is present in the setting of more glands (Fig. 1.21.12)


Treatment

Same as usual prostate adenocarcinoma

None


Prognosis

Equivalent to usual adenocarcinoma Gleason score 3 + 3 = 6

Benign








Figure 1.21.1 Pseudohyperplastic carcinoma with large crowded glands with papillary infolding.






Figure 1.21.2 Same case as Figure 1.21.1 with numerous prominent nucleoli.






Figure 1.21.3 Same case as Figures 1.21.1 and 1.21.2 with absence of a basal cell layer. Note benign gland with basal cells (right).






Figure 1.21.4 Pseudohyperplastic carcinoma with crowded glands with papillary infolding.






Figure 1.21.5 Same case as Figure 1.21.4 with numerous prominent nucleoli in cancer glands (right) compared to benign gland (lower left). Stains showed an absence of basal cells.






Figure 1.21.6 Pseudohyperplastic carcinoma with large glands with straight luminal borders and abundant cytoplasm and prominent nucleoli (arrows).







Figure 1.21.7 Same case as Figure 1.21.6 with absence of a basal cell layer in large glands with straight luminal border (right). Less crowded benign glands without atypia have a basal cell layer (left).






Figure 1.21.8 Pseudohyperplastic carcinoma with large glands with straight luminal borders and abundant cytoplasm.






Figure 1.21.9 Same case as Figure 1.21.8 with absence of a basal cell layer in large glands with straight luminal border.






Figure 1.21.10 Benign crowded cluster of larger glands with papillary infolding.






Figure 1.21.11 Same case as Figure 1.21.10 with totally benign cytology.






Figure 1.21.12 Same case as Figures 1.21.10 and 1.21.11 with absence of a basal cell layer. As the focus on H&E is totally benign, negative staining for basal cells in a small focus of glands is still consistent with a benign diagnosis.



1.22 BENIGN PROSTATE GLANDS WITH PERINEURAL INDENTATION VS. PROSTATE ADENOCARCINOMA WITH PERINEURAL INVASION

Benign Prostate Glands with Perineural Indentation

Prostate Adenocarcinoma with Perineural Invasion


Age

Typically adults, equally common on TURP, radical prostatectomy, and needle biopsy

Typically 50 to elderly, although not rare in 40s


Location

Peripheral > transition zone

Peripheral > transition zone


Symptoms

Asymptomatic

Typically asymptomatic. Advanced disease with urinary obstructive symptoms and/or hematuria or from distant metastases


Signs

None

Serum PSA levels variably elevated


Etiology

Unknown

Initially thought to be pathway of least resistance. Currently, related to complex interactions between nerves and carcinoma. Present in 20% of needle biopsies of the prostate showing adenocarcinoma


Histology


  1. Glands typically have benign cytology without prominent nucleoli (Fig. 1.22.1)



  2. Architecturally larger glands typically with papillary infolding (Fig. 1.22.2)



  3. Glands only partially encircle (Figs. 1.22.1 and 1.22.2)



  4. May show intraneural growth (Fig. 1.22.3)



  5. Perineural indentation may be present (Fig. 1.22.4)


  1. Vast majority of cases have malignant features such as visible nucleoli, nuclear enlargement, nuclear hyperchromasia, amphophilic cytoplasm, or blue luminal mucin (Figs.1.22.6, 1.22.7, 1.22.8)



  2. Small glands with straight luminal border



  3. Glands in some cases circumferentially surround the nerve. Even if benign cytology, if totally surrounding a nerve, then diagnostic of carcinoma (Fig. 1.22.9)



  4. Intraneural growth rare (Fig. 1.22.7)



  5. Perineural indentation may be present


Special Studies


  • Basal cell stains typically positive (Fig. 1.22.5)



  • AMACR negative



  • S100 not needed to highlight nerve


  • Basal cell stains typically negative



  • AMACR positive



  • In rare equivocal cases, S100 protein immunohistochemistry can be performed to verify the presence of a nerve (Fig. 1.22.10)


Treatment

None

Can affect the type of radiotherapy regimen used. Less affect on treatment by radical prostatectomy. Should not exclude a patient from active surveillance


Prognosis

No prognostic significance

Perineural invasion associated with an increased risk of extraprostatic extension

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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Prostate

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