Urinary Tract Pathology Lab

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Urinary Tract Pathology Lab
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CASE 1

• History
• This was a 27 week gestational age stillborn.
  Severe oligohydramnios was present. Fetal
  ultrasound was difficult because of the lack of
  amniotic fluid, but enlarged, cystic kidneys were
  thought to be present. At autopsy, the kidneys
  were symmetrically enlarged and on sectioning
  displayed numerous 0.1 to 0.2 cm cysts. Other
  findings included pulmonary hypoplasia,
  flattened nose, and varus deformities of the feet.

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Slide 1.1The gross appearance of the markedly
enlarged kidneys expanding the abdomen are seen
here. Note that the kidneys are symmetrical.
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Slide 1.2At low power, the cysts appear radially
arranged.
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Slide 1.3At high power, the cysts comprise most
of the parenchyma, and there are rare residual
glomeruli.
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Slide 1.4The gross appearance of dominant
polycystic kidney disease is seen here. Note the
large size of the cysts in this 3 kilogram
kidney.
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Slide 1.5The gross appearance of multicystic
renal dysplasia is seen here. Note the asymmetry
of the kidneys
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Slide 1.6The gross appearance of multicystic
renal dysplasia is seen here. Note the variably
sized cysts.
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Slide 1.7The microscopic appearance of
multicystic renal dysplasia is seen here. Note
the variably sized cysts and the cartilage.
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Slide 1.8The normal gross appearance of fetal
kidney is seen here. Note fetal lobulations.
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Slide 1.9The normal gross appearance of the cut
surface of fetal kidney is seen here. Note the
paler cortex.
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Case 1

• Questions
• What is the diagnosis?
• What are the consequences of this disease?
• How would you counsel the family regarding the
  recurrence risk for this disease?
• How does this case differ from the other forms of
  cystic disease of the kidney?

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CASE 1 Recessive Polycystic Kidney Disease
(RPKD)

1. What is the diagnosis? This is recessive
   polycystic kidney disease (RPKD), also known as
   infantile polycystic kidney disease.
2. What are the consequences of this disease? Renal
   failure develops. Those infants who survive for a
   while may develop congenital hepatic fibrosis
   along with cysts in the liver. The disease is
   essentially uniformly fatal.
3. How would you counsel the family regarding the
   recurrence risk for this disease? Since it is
   recessive, there is a 25 recurrence risk.
4. How does this case differ from the other forms of
   cystic disease of the kidney? Dominant polycystic
   kidney disease has an autosomal dominant pattern
   of inheritance, compared to autosomal recessive
   for the infantile form. The disease is usually
   manifested in adults in middle or old age. The
   kidneys are massively enlarged with huge cysts,
   seen in slide 1.4.
5. Multicystic dysplastic kidneys are seen in
   fetuses and infants sporadically with no specific
   pattern of inheritance. The cysts are variably
   sized, and the kidneys are typically asymmetric
   (slides 1.5 and 1.6). The term "dysplasia" here
   means that the development is disordered, with
   few glomeruli and tubules and with an irregular
   primitive stroma, sometimes containing cartilage
   (slide 1.7). This form of cystic renal disease is
   much more common than either RPKD or DPKD.
   (Compare with normal kidney, slides 1.8 and 1.9).

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CASE 2

• History
• This was a 45 year old female who underwent
  autologous bone marrow transplantation for
  metastatic carcinoma of the breast. She was doing
  well in the first two weeks following the
  transplantation, but then she developed decreased
  urine output with fever to 102 F. A urinalysis
  showed increased WBC's with WBC casts.

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Slide 2.1Multiple small yellowish foci are seen
in the renal parenchyma.
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Slide 2.2Leukocytes infiltrate the intersititum
and tubules at low power.
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Slide 2.3Leukocytes infiltrate the intersititum
and tubules at medium power.
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Slide 2.4With PAS stain, budding cells with
pseudohyphae are seen at high power.
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Case 2

• Questions
• What is the diagnosis?
• How does an infectious agent reach the kidney?
• How do you explain the findings present on
  urinalysis?
• What is the organism responsible for this
  infection (look closely)?

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CASE 2 Acute pyelonephritis

1. What is the diagnosis? This is acute
   pyelonephritis.
2. How does an infectious agent reach the kidney?
   Most urinary tract infections are ascending
   infections, but hematogenous spread can also
   occur. Urinary tract stasis from obstruction is a
   common antecedent. Women are more prone to
   infections because of a shorter urethra.
3. How do you explain the findings present on
   urinalysis? With acute inflammation of the lower
   urinary tract, increased numbers of white cells
   would be present. White cell casts would indicate
   acute pyelonephritis of the kidney.
4. What is the organism responsible for this
   infection (look closely)? Budding cells with
   pseudohyphae characteristic of Candida infection
   are present.

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CASE 3

• History
• A 52 year old female had a long history of
  hypertension which was poorly controlled despite
  therapy with multiple anti-hypertensive regimens.
  On the day of admission to hospital, she had
  suffered a seizure. Prior to this, she had severe
  headaches for several days. Physical examination
  revealed a blood pressure of 230/140. The skin of
  her fingers appeared taut. A urinalysis revealed
  both proteinuria and hematuria. Laboratory data
  revealed BUN of 81 and creatinine of 4.8.

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Slide 3.1Multiple small petechiae are seen over
the cortex.
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Slide 3.2There are changes in the medium to
small arteries consisting of intimal
proliferation as well as very prominent fibrinoid
necrosis.
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Slide 3.3The renal parenchyma shows many
microinfarcts. The glomeruli are relatively
normal.
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Slide 3.4There is fibrinoid necrosis of the
small artery with surrounding hemorrhage.
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Case 3

• Questions
• What is the diagnosis?
• What additional laboratory findings would you
  suspect?
• What other organs may be affected by this
  disease?
• What is the course of this disease?

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CASE 3 Scleroderma Kidney with Malignant
Hypertension

1. What is the diagnosis? She has scleroderma with
   renal involvement and malignant hypertension.
2. What additional laboratory findings would you
   suspect? Her antinuclear antibody test will
   probably be positive (with an anti-nucleolar
   pattern). The most specific autoantibody for her
   disease is anti-DNA topoisomerase I. The ANA with
   an anti-centromeric pattern would be more typical
   for CREST syndrome in which severe renal disease
   is less likely.
3. What other organs may be affected by this
   disease? The skin shows sclerodactyly. Fibrosis
   in the gastrointestinal tract with dysmotility
   and/or malaborption is common. Pulmonary fibrosis
   may also occur.
4. What is the course of this disease? Patients with
   diffuse scleroderma (diffuse systemic sclerosis)
   and malignant hypertension may die from renal
   failure. Those without severe hypertension may
   die from restrictive lung disease and cor
   pulmonale. The course of CREST syndrome is more
   benign.

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CASE 4

• History
• The mother of a five year old child noted that
  the child's abdomen seemed to be getting larger.
  She took the child to a pediatrician who found a
  large, firm abdominal mass on physical
  examination. Urinalysis was normal. An abdominal
  CT scan revealed a 10 cm solid mass involving the
  right kidney. The right kidney was removed at
  surgery.

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Slide 4.1Most of the kidney is replaced by a
white, lobulated firm tumor mass.
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Slide 4.2At low power microscopically, most of
the neoplasm is composed of small round blue
cells (this is one of the small round blue cell
tumors of childhood).
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Slide 4.3At medium power microscopically in some
areas, the tumor is attempting to form primitive
tubules and glomeruli.
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Slide 4.4The neoplasm tends to resemble the
primitive nephrogenic zone of the fetal kidney
seen at low power here microscopically beneath
the capsule at the right.
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Case 4

• Questions
• What is the diagnosis?
• What is the peak age incidence of this tumor?
• What is the survival of patients with this tumor
  today?

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CASE 4 Wilm's tumor

1. What is the diagnosis? This is a Wilm's tumor of
   the kidney.
2. What is the peak age incidence of this tumor?
   Wilm's tumor is seen most often between ages 2
   and 4.
3. What is the survival of patients with this tumor
   today? With surgery, radiation, and chemotherapy,
   survival is now in excess of 90.

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CASE 5

• History
• A 54 year old psychiatrist noted dull left flank
  pain that was becoming more constant over the
  past few weeks. A urinalysis showed 50-75
  RBC's/hpf. A CT scan of the abdomen revealed a
  large left renal mass that was solid. A left
  radical nephrectomy was performed.

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Slide 5.1A large mass involves the lower pole of
the kidney and is variegated, with yellow, tan,
and hemorrhagic necrotic areas. The tumor in this
case did not involve the renal vein.
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Slide 5.2The tumor cells are fairly uniform and
aggregate in small nests surrounded by
capillaries. The cells have abundant clear
cytoplasm dut to large amounts of glycogen. The
nuclei are small and bland. Mitoses are rare.
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Slide 5.3At low power, the adjacent kidney shows
chronic inflammation microscopically.
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Slide 5.4At high power, the adjacent kidney
shows chronic inflammation with lymphocytes and
plasma cells.
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Case 5

• Questions
• What the diagnosis of the neoplasm? What
  additional diagnosis can you make in the kidney
  adjacent to the neoplasm?
• Name some paraneoplastic syndromes associated
  with this lesion.
• What is the natural history of this lesion? What
  does the size of the tumor tell you?
• What is the lesion in the adjacent kidney and
  what caused it?

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CASE 5 Renal cell carcinoma Chronic
pyelonephritis

1. What is the diagnosis of the neoplasm? What
   additional diagnosis can you make in the kidney
   adjacent to the neoplasm? This is a renal cell
   carcinoma. Adjacent renal parenchyma shows
   infiltrates of lymphocytes and plasma cells
   consistent with chronic pyelonephritis, probably
   consequent to obstruction by the tumor.
2. Name some paraneoplastic syndromes associated
   with this lesion. Paraneoplastic syndromes
   associated with renal cell carcinomas include
   polycythemia, hypercalcemia, hypertension,
   femininization, masculinization, Cushing's
   syndrome, amyloidosis, leukemoid reactions (very
   high white cell count).
3. What is the natural history of this lesion? What
   does the size of the tumor tell you? Renal cell
   carcinomas may metastasize just about anywhere.
   Sometimes they can have solitary metastases
   which, if resected, result in a cure. Metastases
   may be so slow growing that they appear 1 to 2
   decades after the primary is discovered.
4. What is the lesion in the adjacent kidney and
   what caused it? The adjacent kidney shows chronic
   pyelonephritis, probably as a result of
   obstruction by the tumor.

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CASE 6

• History
• A 64 year old male with a 50 pack/year history of
  smoking and who worked for many years in a
  printing shop noted that for the past week there
  was blood in his urine when he first urinated in
  the morning. He went to a urologist who did
  cystoscopy but did not see a lesion in the
  bladder. Biopsies and urine cytology specimens
  were sent to the laboratory. The biopsies showed
  benign transitional epithelium, but the cytology
  specimens showed atypical cells present. The
  urologist then did another cystoscopy and took
  separate urine cytology samples from each ureter.
  The atypical cells were present on the left. An
  intravenous pyelogram showed a filling defect of
  the left renal pelvis. A left nephrectomy was
  performed.

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Slide 6.1The kidney has been bivalved to show
the collecting system. A soft pink papillary mass
is attached to the urothelium and fills part of
the collecting system.
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Slide 6.2At low power microscopically, the
neoplasm has a papillary configuration with the
epithelium covering frond-like papillae.
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Slide 6.3The urothelium looks very similar to
normal, except it is more than seven layers thick
and has occasional mitoses. The tumor is limited
to the urothelium and has not invaded through the
renal pelvis.
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Case 6

• Questions
• What is the diagnosis?
• Where do these tumors occur?
• Are there any risk factors or environmental
  causes of this tumor?
• What must be remembered about the origin of these
  tumors?

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CASE 6 Transitional cell carcinoma of renal
pelvis

1. What is the diagnosis? This is a transitional
   cell carcinoma of the renal pelvis.
2. Where do these tumors occur? Transitional cell
   carcinomas occur anywhere in the urinary tract,
   but they are most common in the bladder.
3. Are there any risk factors or environmental
   causes of this tumor? Smoking, exposure to
   analine or azo dyes, and napthylamine exposure
   are the best known associations with urothelial
   cancers.
4. What must be remembered about the origin of these
   tumors? Urothelial tumors often have a
   multicentric origin. These patients need careful
   followup.

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CASE 7

• History
• A 71 year old male had increasing hesitancy and
  frequency of urination over several years' time.
  He noted difficulty in starting the stream of
  urine. His physician found that the prostate
  appeared enlarged to twice normal size and was
  firm with palpable nodules on physical
  examination. A urinalysis showed no RBC's but did
  show 10-15 WBC's/hpf, and the urine was nitrite
  positive. He was referred to a urologist who
  performed a biopsy. This was followed by
  prostatectomy (usually this is a transurethral
  resection).

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Slide 7.1The prostate weighed 75 grams (three
times normal size) and is nodular.
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Slide 7.2At low power, the prostate has several
ill-defined nodules.
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Slide 7.3At medium power, the nodules contain
glands with complex branching and two layers of
cells.
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Slide 7.4At high power, the nodules contain
glands with benign appearing epithelial cells.
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Case 7

• Questions
• What is the diagnosis?
• What are the consequences of his disease if left
  untreated?
• Who gets this disease and why?
• Is prostatic hyperplasia a "pre-malignant"
  condition?

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CASE 7 Nodular prostatic hyperplasia

1. What is the diagnosis? This is nodular prostatic
   hyperplasia.
2. What are the consequences of his disease if left
   untreated? Untreated prostatic hyperplasia can
   result in urinary tract infections, including
   pyelonephritis. Pyelonephritis may destroy enough
   kidney to cause renal failure. Such obstruction
   may explain the urinalysis findings in this
   patient (suggestive of urinary tract infection).
   Obstructive uropathy from prostatic hyperplasia
   may lead to hydronephrosis and renal failure.
3. Who gets this disease and why? Older men get
   prostatic hyperplasia, which may have something
   to do with increased estradiol levels (relative
   to testosterone).
4. Is prostatic hyperplasia a "pre-malignant"
   condition? No. The hyperplasia of the prostate is
   not like endometrial hyperplasia in that there is
   not a progression to carcinoma.

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CASE 8

• History
• A 76 year old male noted increased hesitancy with
  urination. His physician palpated a firm nodule
  in the region of the prostate on physical
  examination. A urologist biopsied the prostate.
  This was followed by a radical prostatectomy

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Slide 8.1The prostate is seen on transverse
sectioning. It is enlarged and shows multiple
yellow to tan firm areas
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Slide 8.2At low power, the glands at the left
are crowded and irregular, while normal appearing
prostate is at the right.
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Slide 8.3At medium power, the glands are
irregular and crowded with virtually no
intervening stroma.
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Slide 8.4At high power, the epithelial cells
have nuclei that are pleomorphic and contain
prominent nucleoli.
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Case 8

• Questions
• What is the diagnosis?
• Who gets this disease?
• How important is histopathologic study of this
  disease?
• Are there any tests on serum from blood that can
  be helpful?

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CASE 8 Prostatic adenocarcinoma

1. What is the diagnosis? What is the diagnosis?
   This is adenocarcinoma of the prostate. Note how
   the normal prostatic glands are lined by a tall
   columnar epithelium and have stroma between the
   large glands. The neoplastic glands are smaller,
   more irregular, with cells having a higher N/C
   ratio and prominent nucleoli.
2. Who gets this disease? Carcinoma of the prostate
   is the most common cancer in men and is the third
   leading cause of cancer death in men (after lung
   and colon). It occurs primarily over the age of
   50.
3. How important is histopathologic study of this
   disease? Grading of prostate cancers is extremely
   important because there is a good correlation
   between the grade and the prognosis.
4. Are there any tests on serum from blood that can
   be helpful? Testing for serum prostate specific
   antigen (PSA) often reveals an elevated level
   with prostate cancers. The PSA can be slightly
   elevated with prostatic hyperplasia and with
   prostatitis. However, PSA levels tend to remain
   the same over time with benign conditions, while
   PSA levels increase when an adenocarcinoma is
   present. The PSA is not generally useful for
   general screening of the population.

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CASE 9

• History
• This 46 year old homeless male was found in a
  stuporous condition one morning by the owner of
  an auto parts store. Apparently the man had
  broken into the store. A half empty container of
  antifreeze was found next to him (go to any store
  that sells automobile antifreeze to view the
  container warning label). The owner called
  paramedics, who transported him to a local
  hospital. He was admitted. It was noted that he
  had no urine output. His BUN and creatinine were
  rising. He died a week later.

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Slide 9.1The glomeruli and vessels are normal.
However, the tubules are dilated with thinned
epithelium. The tubular epithelium also shows
vacuolization. Many tubules contain irregular
blue calcifications (calcium oxalate crystals).
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Case 9

• Questions
• What is the diagnosis?
• What histopathologic findings are present in the
  kidney?

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CASE 9 Acute tubular necrosis with ethylene
glycol poisoning

• What is the diagnosis? This is acute tubular
  necrosis due to ethylene glycol poisoning.
  Alcoholics will sometimes drink anything that
  smells like alcohol. Ethylene glycol is a
  nephrotoxin.
• What histopathologic findings are present in the
  kidney? The tubules are dilated and the tubular
  epithelium shows vacuolization. In addtion, there
  are many scattered calcium oxalate crystals.
• Note most cases of acute tubular necrosis are
  due to ischemia from hypotension (usually from
  heart failure).