Kidney neoplasms and histological exam

Question 1

82. A 67-year-old male was referred to the urology department in view of painless macroscopic haematuria. Cystoscopy was carried out and an exophytic lesion was identified. A transurethral resection (TUR) of the lesion was carried out and the fragmented material was sent to the laboratory in formaldehyde. The pathologist issued the report as follows: “There is an invasive tumour which consists of fused papillae which are lined by highly pleomorphic, hyperchromatic and enlarged nuclei with brisk mitotic activity. The detrusor muscle is not represented.”
    a. What is macroscopic haematuria and how does it differ from microscopic haematuria? (4 marks)
    b. What is cystoscopy? (3 marks)
    c. From the data give in the histopathology report above, what type of tumour is present in this case? (2 marks)
    d. What features support your answer for question (1c)? (3 marks)
    e. Where else can this tumour arise from? (2 marks)
    f. The biopsies are said to be ‘inadequate for staging’. Why? (4 marks)

Answer 1

a) Macroscopic haematuria is when blood can be seen in the urine with the naked-eye, that is the urine has a red-tinge. Microscopic haematuria on the other and is when there is blood in the urine but the concentration is very low and red blood cells are only detected by urinalysis and/or microscopy but no evidence of haemorrhage can be seen on gross investigation of the urine or when urinating.
b) Cystoscopy is when a fibre-optic tube is inserted through the urethra to visualise directly the urinary bladder and obtain a specimen if required. This is indicated for aiding with the diagnosis and guiding investigations for several benign and malignant conditions.

c. High-grade papillary urothelial carcinoma

d. The report says that an exophytic lesion was seen with a cystoscope which is a lesion protruding outwards and is more common in malignant lesion, so this was the first clue.
The TUR showed invasive tumour with fused papillae suggesting that the lesion was of the papillary type and it is not a pre-neoplastic lesion as it infiltrated beyond the basement membrane.
It also showed neoplastic changes - highly pleomorphic, hyperchromatic and enlarged nuclei and mitotic activity all consistent with a high-grade carcinoma.

e. This tumour can arise in the renal pelvis or the ureters
f. This is because the detrusor muscle is not present and this is required for staging. Infiltration of tumour cells into the detrusor muscle upstages the cancer from T1 to possibly T2a, T2b etc depending on how far into the muscle it invaded. Therefore, if this is not present invasion cannot be determined and staging cannot be done.

Question 2

c) How would you treat the Transurehtral biopsy that was sent in fragments to the laboratory? (4 marks)
d. Would you use inking in this case? (1 mark) Why? (2 marks)

Answer 2

c) 1. Confirm the patient identification on the container matches that on the request form.
2. Note down that it was submitted in formalin and the number of specimen present.
3. Weigh the specimen fragments together and measure the smallest fragment and largest fragment and document them indicating that the fragment range from the two dimensions.
4. All embedded in one if possible or 10 cassettes for the first 20g and one cassette for every additional 5g. important to submit section of detrusor muscle if present, if its absent more sections are submitted.
5. On the report give a brief description and note any signs of hemorrhage or calcification.

d) No, because the margin status is not required, the sections were taken for diagnosis and not for therapeutic purposes.

Question 3

83. How would you process a nephrectomy specimen?

Answer 3

1. Confirm that the patient identification on the container matches that on the request form and look at the patients history, to see what is to be looked for. In addition, confirm that the resected tumour matches the description on radical imaging.
2. Document the type of resection and determine why this method was chosen e.g. partial nephrectomy used for stage 1 carcinoma while radical nephrectomy is used for more advanced stages.
3. Describe the specimen, the site from where it was taken, and any additional structures identified e.g. adrenal glands and ureter. Weight the specimen and leave to fix if necessary.
4. Measure the specimen – kidney, adrenal glands, and ureter separately if present.
5. Orient the specimen using the adrenal glands which sit superiorly and the ureter which is interiorly. If these are not present the Gerota’s fascia is used which sits anteriorly and the renal hilium – going from anterior to posterior there is the renal vein, artery and ureter. It is important to orient properly and confirm that the left or right kidney is present.
6. Shave the ureter, renal vein and renal artery margins and place them in cassettes.
7. Ink the perinephric fat and bivalve the kidney, then cut the kidneys in parallel sections from lateral to medial.
8. Identify the tumour and measure the length and width as well as thickness. Give a description of the tumour including the colour, location and texture e.g. well-circumcised yellow to orange lesion.
9. Document any other abnormal findings and the tumour relationship with the surgical margin, if invasion is suspected this should be inked.
10. Submit sections of the tumour and normal renal parenchyma for diagnosis.
11. For staging submit sections of the tumour relationship with the renal capsule, renal pelvis, major blood vessels, perinephric fat and adrenal glands if present.
12. Submit sections of normal adrenal glands or adrenal metastasis to be distinguished from direct spread.
13. Palpate the specimen and look for lymph nodes, each one should be submitted to determine the lymph node status and possible lymphovascular invasion

Question 4

How is oncocytoma different than Renal cell carcinoma?

Answer 4

Renal oncocytoma is a benign neoplasm that arises from intercalated cells of the collecting duct. Gross-ly, oncocytomas are well-circumscribed, firm, and mahogany or tan lesions due to the abundance of mitochondria present. Renal cell carcinoma is a malignant neoplasm that arises from renal tubules and the most common type is clear cell carcinoma, but there are also papillary type and chromophobe. The gross appearance of renal cell carcinoma, classically yellow or orange with areas of necrosis, may over-lap with that of oncocytoma when the lesion is large, firm, tan, and well-circumscribed.
Microscopically, oncocytomas resent with eosinophilic cells – oncocytes with dense granular cytoplasm and even round nucleus but may have moderate variation in size. Mitotic figures are not commonly pre-sent, necrosis is not observed and haemorrhage is only focal. On the contrary, renal cell carcinoma morphology is dependent on the type of cancer present. Clear cell carcinoma shows cells with clear cytoplasm due to abundance of glycogen, while papillary cell carcinoma has a papillary like growth.

Question 5

What is the grading system used for kidney cancer?

Answer 5

The Fuhrman grading system is based on microscopic features of the tumour cells including the size and shape of the nucleus as well as the prominence of the nucleoli.

Question 6

What is the difference between an exophytic, flat and endophytic urothelial neoplasm

Answer 6

Exophytic papillary neoplasms are lesions that protrude into the lumen. histological classification of these papillary urothelial neoplasms as follows: benign papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP), noninvasive papillary urothelial carcinoma (low grade or high grade), and invasive urothelial carcinoma. Inverted neoplasms are benign and rarely become neoplastic. Carcinoma in situ is defined by the presence of overtly malignant appearing cells within a flat urothelium.

Question 7

Advantages and disadvantages of ureteroscopy?

Answer 7

Ureteroscopy is when a fibreoptic tube is inserted into the urethra and guided through the bladder and ureters into the kidney. It might be used for therapy to remove kidney stones, calyceal drainage, treat-ment of malignant urothelial tumour as well as benign and evaluation of ureteral injury.
Advantages:
- Out patient surgery – no hospitalisation required
- No incision required
- Direct visualisation of the lesions, kidney stones etc
- Capable of differentiating between benign and malignant lesions
- A biopsy can be obtained if necessary for further investigation
- The direct site of bleeding can be identified
Disadvantages:
- Stent may be needed which causes irritation of the bladder and ureter
- Patient needs to fast
- Complications: Sedation effects
- Pain
- False passage – the endoscope can injure and enter the mucosa causing damage
- Haematuria
- Pyelonephritis – introduction of certain organisms
- Damage to the mucosa
- Strictures – narrowing from damaged urothelium
- Urosepsis

Question 8

How would you process a Nephroureterectomy?

Answer 8

1. The specimen arrives at the laboratory placed in formalin
2. Confirm that the patient identification on the container matches that on the request form and look at the patients history, to see what is to be looked for. In addition, confirm that the resected tumour matches the description on radiological imaging.
3. Document the type of resection, site of specimen and any additional structures identified.
4. Measure the length of the ureter and the dimensions of the kidney and orient the specimen using the the ureter
5. Bivalve the kidney and then transverse slice through each half to assess depth of invasion.
6. Give a description of the specimen, and investigate, perinephric, pelvic, vascular and capsular invasion. If the specimen appears close to any of these margins, it should be inked and the documented accordingly.
7. Measure the size of the tumour and give a description of the location and the depth of invasion.
8. Submit sections of the normal renal parenchyma and pelvis and tumour for confirmed diagnosis. For staging it is important to submit sections of the deepest point of invasion, ureteric, vascular and capsular margins and the relationship of the tumour with perinephric fat and adrenal gland if present. Submit also cross-sections of ureter at 10mm intervals and uretric tumour invading periureteric tissue.
9. Palpate the specimen and look for lymph nodes, each one should be submitted to determine the lymph node status, especially hilar and para-aortocaval lymph nodes.

Summary the blocks should include:

i. Ureteric margin
ii. Vascular margins
iii. Selected cross-sections of ureter at 10mm intervals
iv. Adrenal gland
v. Normal renal parenchyma
vi. Normal renal pelvis
vii. Tumour invading fat or renal parenchyma
viii. Ureteric tumour invading periureteric tissues
ix. Hilar lymph nodes or tumour deposits in fat
x. Para-aortocaval lymph nodes

Question 9

What sections are submitted for cystectomy?

Answer 9

i. Submit the following sections:
a. Ureteric and urethral margins
b. Tumour including the deepest point of invasion
c. Other mucosal abnormalities
d. Suspicious areas as determined by radiology
e. Males: Prostate and seminal vesicles to exclude involvement by urothelial carcinoma, for fe-males submit sections of anterior wall of uterus, cervix and vagina to assess direct spread of tumour and vaginal margin if tumour appears to be in close proximity
f. Other representative blocks from included organs
g. All lymph nodes found by palpation of the specimen – important to document the number of lymph nodes submitted
j. Place the cassettes in formalin and leave to fix.

Question 10

90. What is the difference between papillary and non-papillary transitional cell carcino-ma

Answer 10

Papillary: must have true papillae, are very common and tend to be benign/indolent
Non-papillary: lack papillae and tend to be more aggressive