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OS 214: Excretory Module Patholog y Dep t.

Lectur er s
Pathology Lab 2 Part 1 Exam 2

OUTLINE Can you delineate the cortex from the


I. Urology LCD module medulla (normal ratio of 1:3 or 1:4)? NO
a. Chronic Pyelonephritis o Light tan color of lesion - the lighter the color
b. Clear Cell Renal Carcinoma of the lesion, the more packed it is with cells
c. Angiomyolipoma o Presence of ulceration? YES (encircled)
d. Wilm’s Tumor
e. Prostate Adenocarcinoma • Light Microscope:
f. Chronic Cystitis
g. Invasive Urothelial Carcinoma
II. Case Discussion
a. Rapidly Progressive GN Type 1
b. IgA Nephropathy
c. Focal Segmental GN
d. Membranous GN
e. Acute Tubular Necrosis
f. Hyperplastic Arteriolitis
III. Gross Specimen
IV. Microscopy

UROLOGY LCD MODULE

Surgical Pathologist
• The one who studies specimens, usually from a
o Glomerulus: bowman’s space is enlarged (A)
surgeon, and makes a diagnosis depending on
what they see from the specimen. They are also the o Tubules: normally found in spaces between
ones who specify if the lesion is benign or the glomeruli. In this picture, you see a
malignant. fibrous area which is almost devoid of
• They rely on what they observe directly from the tubules
o Blood Vessels – wall is thickened (B)
specimen itself and the clinical input coming from
the clinician or surgeon
• Specimen – may be a whole organ or a piece of
tissue
• Tissues are “fixed” by immersing them in formalin.
This prepares the tissue for slide processing.
Changes that may occur because of formalin include:
o Areas of the tissue with increased number of
cells per unit volume tend to become more white
compared to less cellular areas of the tissues
o Color of the tissues usually become lighter

I. Renal Cell Carcinoma

ON High Power
o Inflammatory cells found on the slide (do you
see the lymphocytes below the glomerolus?)
o Thyroidization is present (boxed)
o Casts (Tamm-Horsefall protein) inside
tubules signify a long standing renal problem
with decreased urine flow.
o When the tubules are dilated, they usually
• Kidney: Organ is 5-6 inches in length, and form broad casts and the kidney damage is
covered with fat irreversible.

• When assessing the gross anatomy:


o Calyx and Ureter:
Is there anything blocking it? NO
o Parenchyma
ON Oil Immersion

March 11, 2009 | WEDNESDAY A Page 1 of 8


ADI - LEXI - GILLIAN - BUTCH
OS 214: Excretory Module Patholog y Dep t.
Lectur er s
Pathology Lab 2 Part 1 Exam 2

o Numerous lymphocytes and inflammatory o Grade of the tumor is directly proportional to


cells size of the nucleus and the aggression of the
NtK from Robbins: Renal cell carcinomas represent about tumor.
1% to 3% of all visceral cancers and account for 85% of NtK from Robbins: Renal cell carcinomas represent about 1% to
renal cancers in adults. The tumors occur most often in older 3% of all visceral cancers and account for 85% of renal cancers in
individuals, usually in the sixth and seventh decades of life, adults. The tumors occur most often in older individuals, usually in
showing a male preponderance in the ratio of 2 to 3 : 1. They the sixth and seventh decades of life, showing a male
usually have a gross yellow color and tumor cells resemble preponderance in the ratio of 2 to 3 : 1. They usually have a gross
clear cells of the adrenal cortex but in truth, these tumors yellow color and tumor cells resemble clear cells of the adrenal
arise from the tubular epithelium and are therefore renal cortex but in truth, these tumors arise from the tubular epithelium
adenocarcinomas and are therefore renal adenocarcinomas
Clear cell carcinoma. This is the most common type of renal cell
II. Clear Cell Renal Carcinoma ca, accounting for 70% to 80% of renal cell cancers. On histologic
examination, the tumors are made up of cells with clear or
granular cytoplasm and are nonpapillary. They can be familial,
associated with VHL disease, or in most cases (95%) sporadic.

III. Angiomyolipoma

• Kidney: presence of hemorrhage (A) and


necrosis (B).
• Normal kidney upper portion (circled) • Kidney: lower part is made of normal renal tissue
• Most of the kidney is occupied with large mass • Tumor is cleaner (less hemorrhage and necrosis
(lower portion) (boxed) compared to clear cell carcinoma) – a probable
sign that the lesion is benign
• Light Microscope:
• Light Microscope:

o Angiomyolipomas are made up of mature


o Clear cell Renal Carcinoma with large nuclei
adipose, smooth muscle and blood vessels.
(Fuhrman grade 4)
o Pathologists are responsible for the T part of NtK from Robbins: Angiomyolipoma. This is a benign tumor
grading consisting of vessels, smooth muscle, and fat.
o Makes use of Fuhrman Grading system Angiomyolipomas are present in 25% to 50% of patients
with tuberous sclerosis, a disease characterized by lesions
The Fuhrman grade is based on nuclear size and shape and of the cerebral cortex that produce epilepsy and mental
the prominence of nucleoli retardation as well as a variety of skin abnormalities
Grade 1: tumors have round, uniform nuclei with
inconspicuous or absent nucleoli. IV. Wilms Tumor / Nephroblastoma
Grade 2: Nuclear contours are more irregular than Grade 1;
nuclei are about 15 microns in diameter. Nucleoli may be
visible at high magnification.
Grade 3: Nuclear contours are even more irregular. Nuclear
diameters can approach 20 microns. Nucleoli are readily
seen
Grade 4: Looks quite different from normal kidney cells and
has the worst prognosis.

** visit
http://webpathology.com/case.asp?case=66
for nice pictures of renal cell cancer 

March 11, 2009 | WEDNESDAY A Page 2 of 8


ADI - LEXI - GILLIAN - BUTCH
OS 214: Excretory Module Patholog y Dep t.
Lectur er s
Pathology Lab 2 Part 1 Exam 2

• Light Microscope:

CUT section
o Multiple cysts on cut section
o May be due to proliferation of stromal
o Highly cellular tissue with no tubules
elements OR both stromal and glandular
o Notice the stroma (A), some gland like elements (when glandular elements
structures made by primitive cuboidal proliferate, they manifest as cystic spaces)
epithelial elements (B), and blastema (C -
dark staining cells) • Light Microscope:
** check
http://webpathology.com/case.asp?case=73 for
more histological pictures of wilm’s tumor

NtK from Robbins: Wilms tumor is the most common primary


renal tumor of childhood and the fourth most common pediatric
malignancy in the United States. Approximately 5% to 10% of
Wilms tumors involve both kidneys, either simultaneously
(synchronous) or one after the other (metachronous). Bilateral
Wilms tumors have a median age of onset approximately 10
months earlier than tumors restricted to one kidney. It is usually
found in 3 syndromes: WAGR syndrome (characterized by
aniridia, genital anomalies, and mental retardation), Denys-
Drash syndrome (which is characterized by gonadal dysgenesis
(male pseudohermaphroditism) and early-onset nephropathy
leading to renal failure. The characteristic glomerular lesion in o Presence of Adenocarcinoma of the Prostate
these patients is a diffuse mesangial sclerosis), and Beckwith- o You see the tumor cells trying to form glands
Wiedemann syndrome (characterized by enlargement of body
organs (organomegaly), macroglossia, hemihypertrophy,
o Gleason Grading system
omphalocele, and abnormal large cells in adrenal cortex (adrenal grades 1-3 = distinct glands
cytomegaly)) grade 4 = fused glands
grade 5 = no glands visible
 Gleason score = predominating grade +
second most predominant grade
V. Nodular Hyperplasia of the Prostate and
Adenocarcinoma of the prostate GLEASON GRADIG SYSTEM
The pathologist assigns a grade to the most common tumor
pattern, and a second grade to the next most common tumor
pattern. The two grades are added together to get a Gleason
score. For example, if the most common tumor pattern was
grade 3, and the next most common tumor pattern was
grade 4, the Gleason score would be 3+4 = 7. A lower
Gleason indicates a well differentiated, or a lower potential to
spread. A higher Gleason grade indicates a poorly
differentiated cancer, or more likely to spread.

• Prostate is normally symmetrical


• Prostate on this picture is not symmetrical. You
can also notice multilobular structures

Gleason scores are associated with the following features:


• Grade 1 - The cancerous prostate closely resembles
normal prostate tissue. The glands are small, well-
formed, and closely packed

March 11, 2009 | WEDNESDAY A Page 3 of 8


ADI - LEXI - GILLIAN - BUTCH
OS 214: Excretory Module Patholog y Dep t.
Lectur er s
Pathology Lab 2 Part 1 Exam 2

• Grade 2 - The tissue still has well-formed glands, but


they are larger and have more tissue between them.
• Grade 3 - The tissue still has recognizable glands, but • Light Microscope
the cells are darker. At high magnification, some of
these cells have left the glands and are beginning to
invade the surrounding tissue.
• Grade 4 - The tissue has few recognizable glands.
Many cells are invading the surrounding tissue
• Grade 5 - The tissue does not have recognizable
glands. There are often just sheets of cells throughout
the surrounding tissue.

• ON High Power

o There is some inflammation in the mucosa


• When evaluating the urothelium look for: number
of cell layers (normal is 7 layers but if it is a
tangential section there may be more than 7
layers), polarity, crowding of nuclei

o Close up of merging glands


o The picture shows a grade 4 gleason grade
due to the presence of fused glands

o Normally, there are 7 layers of urethelium


o Notice polarity of the nucleus and look for
crowding of nuclei
o There is peculiar alignment – long axis of
nuclei is perpendicular to the basement
membrane

o The picture shows a grade 5 lesion since no NtK from Robbins: Chronic Cystitis. The common etiologic
agents of cystitis are the coliforms: Escherichia coli, followed
glands are present in the field by Proteus, Klebsiella, and Enterobacter. Women are more
o This picture shows pleomorphic likely to develop cystitis as a result of their shorter urethras.
hyperchromatic nuclei Most cases of cystitis take the form of nonspecific acute or
chronic inflammation of the bladder. In gross appearance,
VI. Chronic Cystitis there is hyperemia of the mucosa, sometimes associated
with exudate.
Persistence of the infection leads to chronic cystitis, which
differs from the acute form only in the character of the
inflammatory infiltrate. There is more extreme heaping up of
the epithelium with the formation of a red, friable, granular,
sometimes ulcerated surface. Chronicity of the infection
gives rise to fibrous thickening in the muscularis propria and
consequent thickening and inelasticity of the bladder wall.
Histologic variants include follicular cystitis, characterized
by the aggregation of lymphocytes into lymphoid follicles
within the bladder mucosa and underlying wall, and
eosinophilic cystitis, manifested by infiltration with
submucosal eosinophils together with fibrosis and
occasionally giant cells. Most cases of eosinophilic cystitis
represent nonspecific subacute inflammation, although,
rarely, these lesions are manifestations of a systemic allergic
disorder. All forms of clinical cystitis are characterized by a
triad of symptoms: (1) frequency, which in acute cases may
necessitate urination every 15 to 20 minutes; (2) lower
Notice the ureter on the Right is dilated (probably abdominal pain localized over the bladder region or in the
suprapubic region; and (3) dysuria-pain or burning on
because of the presence of a stone impacted on
urination. Associated with these localized changes, there
the outlet) may be systemic signs of inflammation such as elevation of
temperature, chills, and general malaise. In the usual case,
Bladder also shows the bladder infection does not give rise to such a
areas of hemorrhage constitutional reaction.

March 11, 2009 | WEDNESDAY A Page 4 of 8


ADI - LEXI - GILLIAN - BUTCH
OS 214: Excretory Module Patholog y Dep t.
Lectur er s
Pathology Lab 2 Part 1 Exam 2

VII. Invasive Urothelial Carcinoma Grading of Urothelial (Transitional Cell) Tumors

WHO/ISUP Grades*

Urothelial papilloma

Urothelial neoplasm of low malignant potential

Papillary urothelial carcinoma, low grade

Papillary urothelial carcinoma, high grade

WHO Grades†

Urothelial papilloma
• Urinary bladder cut in half. Notice that the lesion
has occupied the whole bladder space Urothelial neoplasm of low malignant potential
• This lesion is malignant
Papillary urothelial carcinoma, Grade 1
• Upper area is normal Urinary Bladder mucosa –
has a smooth surface Papillary urothelial carcinoma, Grade 2
• Lower portion is stiff and nodular with thick walls -
lesion Papillary urothelial carcinoma, Grade 3

• Light Microscope: 

o Presence of fibrovascular core. CASE DISCUSSION by DR. TUAZON


o Since it is invasive, grading is not required
because regardless of a low or high grade Case 1 – Rapidly Progressive Glomerulonephritis
tumor, prognosis and management are still (RPGN) Type I / Crescentic Glomerulonephritis
the same
o Treatment is via radial cystectomy
o When do you grade a tumor? When the
tumor is not invading.

NtK from Robbins: Urothelial carcinoma. gross patterns of


urothelial cell tumors vary from purely papillary to nodular or flat.
The tumors may also be invasive or noninvasive. Papillary lesions
appear as red, elevated excrescences varying in size from less
than 1 cm in diameter to large masses up to 5 cm in diameter.
Multicentric origins may produce separate tumors. As was noted,
the histologic changes encompass a spectrum from benign
papilloma to highly aggressive anaplastic cancers. Overall, the
majority of papillary tumors are low grade. Most arise from the
lateral or posterior walls at the bladder base.

• Light microscopy: crescents from proliferation of


parietal epithelial cells, infiltrating monocyte and
macrophages, and fibrin (fibrin came from clotting
mechanisms in the blood)
• Urinalysis: presence of macrophages

March 11, 2009 | WEDNESDAY A Page 5 of 8


ADI - LEXI - GILLIAN - BUTCH
OS 214: Excretory Module Patholog y Dep t.
Lectur er s
Pathology Lab 2 Part 1 Exam 2

Case 3 – Focal Segmental Glomerulosclerosis


Six year old girl with idiopathic nephritic syndrome.
Unresponsive to steroid and immunosuppressive
therapy
• Clue from the case in the diagnosis:
unresponsive to steroid

• Immunofluorescence: linear deposit of IgG


Case 2 – IgA Nephropathy
Sixteen year old boy with isolated hematuria and
renal insufficiency
• Presents with hematuria (nephritic syndrome)
• Source of hematuria may be upper or lower
urinary tract
• NOTE: hematuria from the upper urinary tract
shows dysmorphic RBC and red cell cast

• Light microscope:
o 3 glomeruli present in the field (encircled)
o Inflammatory cells in the interstitium
(lymphocytes) (A)
o Segmental sclerosis – collapsed lumen with
increased matrix (B)
o Thickened basement membrane signaling
Tubular atrophy ©
o Presence of hyaline cast inside some
tubules. The basement membrane of these
tubules are thinner because the cells have
sloughed off due to cell death/necrosis (D)
• Light microscopy: mesangial hypercellularity / ** the term hyalinization is used for blood
vessels and arterioles, while hyaline deposit
proliferation
is used for the glomerulus

• Immunofluorescence: mesangial granular IgA • HPO


o Segmental sclerosis showing increased
matrix which signifies that this area are not
functioning – in other words, DEAD.

Case 4 – Membranous Glomerulonephropathy /


Glomerulonephritis / Glomerulopathy
50 year old man with idiopathic nephritic
syndrome
• Idiopathic / primary

• EM: mesangial electron dense deposits (A),


nucleus of mesangial cell (B)

March 11, 2009 | WEDNESDAY A Page 6 of 8


ADI - LEXI - GILLIAN - BUTCH
OS 214: Excretory Module Patholog y Dep t.
Lectur er s
Pathology Lab 2 Part 1 Exam 2

• Light microscope: tubules have thin walls with


• Light microscope: loss of epithelial cells
o Diffuse thickening of BM Case 6 – Acute Tubular Necrosis
Sixty year old man who was poisoned by his wife.
• Caused by a nephrotoxic substance

o Silver staining BM spikes

• Light microscope: destroyed tubules with no cells


(arrows)

Case 7 – Hyperplastic Arteriolitis


Thirty year old woman with severe skin problems,
severe hypertension, and acute renal failure
• Skin lesion of the patient is scleroderma
• Malignant hypertension - leads to ischemia by
decreasing GFR and renal blood flow
** Most sensitive to ischemia: tubules since it
is where active processes take place
** Most resistant to ischemia: glomerulus

• Immunofluorescence: finely granular diffuse


capillary wall, presence of IgG

• Light microscope:
o Thickening of the arterial wall (formation of
onion skin walls) sometimes leading to
• EM: numerous subepithelial deposits (arrows) obliteration of arterial lumen
o Hyperplasia of the wall leads to onion
Case 5 – Acute Tubular Necrosis skinning (feature of malignant HTN)
Twenty five year old man who had been stabbed with o Fibrinoid necrosis of arteries causing fibrin
a knife and shot with a gun clots
• ATN may progress to acute renal failure  There is decrease of GFR

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ADI - LEXI - GILLIAN - BUTCH
OS 214: Excretory Module Patholog y Dep t.
Lectur er s
Pathology Lab 2 Part 1 Exam 2

 Leads to Ischemia (tubules are first bleed! Congrats sa lahat ng pumasa!  now I
affected while the glomerulus is resistant believe when they say renal is the hardest! Damn
to ischemia) can’t wait for summer vacaction!!! 

--------------------------- END OF PART


1--------------------------

Greetings:
ADI: good luck sa exams next week! Lapit na
bakasyon yehey!!! 

LEXI: groupmates! We shined kay dr. tuazon!


Yay! Grabe ang renal magpaexam ano? Nose

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ADI - LEXI - GILLIAN - BUTCH