Differential diagnosis of Kidney mass

Case

A 55 year old man presents to his primary care physician complaining of gross hematuria and right loin pain. PE reveals a flank mass. The CBC level hemoglobin level of 21g/dl and polycythemia. Ultrasound shows a 6 cm mass at the upper pole of the right kidney.

ImpressionRenal cancer

--classic triad of signs and symptoms includes gross hematuria; dull, aching flank pain; and a smooth, firm, palpable flank mass. Colicky pain may accompany the passage of clots

--Other findings include fever, CVA tenderness, and increased blood pressure. In advanced disease, the patient may develop weight loss, nausea and vomiting, and leg edema with varicoceles.

a.) Transitional cell cancer

b.) Renal calculi

c.) Renal papillary adenoma

d.) IgA Nephropathy

TRANSITIONAL CELL CARCINOMA

Arising from the transitional epithelium lining

The most common type of bladder cancer cancer of the uretercancer of the Urethracancer of the urachus

The second most common type of kidney cancer

(Renal Pelvic)

SIGNS & SYMPTOMS

Hematuria

Pain on urination (without evidence of urinary tract infection)

Need to urinate frequently

Pelvic pain , Back pain, Abdominal pain

Signs of urinary tract obstruction

high mitotic rate

(UROLITHIASIS)

Definition

Urolithiasis is the formation of calculi , or the condition associated with urinary calculi. The term calculi is synonymous with uroliths, stones, or crystals.

Clinical SignsMay observe any of the following:

Difficulty urinating. Cloudy urine. Dampness of fur from urine around perineum. Foul odor. Bladder distention. Hematuria (blood in urine). Absence of urination. Frequent licking or nipping at genitals. Listlessness or hunched posture. Poor appetite. Dehydration. Signs of colicky type pain (intermittent spasms of pain).

Etiology Urolithiasis is the presence of

uroliths/calculi (stones) in the urinary tract. These calculi are formed by deposits of polycrystalline aggregates composed of varied amounts of crystalloid and organic matrix. They can vary in size and may be found anywhere in the urinary tract from the kidney to the bladder.

For stone formation to occur it requires saturated urine dependent upon urine pH, and the concentration of the solute. Different types of stones are: Struvite, which is made up of magnesium

ammonium phosphate. They are found in highly alkaline urine and often a concurrent urinary tract infection is present. They tend to be the most common type of urolith.

Calcium oxalate, and Cystine, found in acidic urine.

Ammonium acid urate, and Silicate uroliths, found in neutral to acidic urine.

Frequency

United StatesRenal calculi occur in 5-12% of the

American population, and they are bilateral in 10-15% of patients. The prevalence of urinary lithiasis is as high as 2-3% in the general population.

InternationalA slightly lower prevalence of urinary stones

is found in less developed countries, possibly because of diets lower in protein.

RaceUrinary stones occur more often in white populations

than in black populations. They are also more prevalent in highly developed countries, possibly as a result of a higher protein diet.

SexMales are at a greater risk than females, with a

male-to-female ratio of 3:1 (except for struvite stones and in black populations).

AgeStones are uncommon but not unknown in children.

The peak age for development is in persons aged 40-60 years.

Presentation

Acute ureteral obstruction by stone causes severe colicky (intermittent) flank pain that can radiate throughout the groin, testicles, back, and periumbilical region. Some patients with renal calculi may have no symptoms at all.

Hematuria usually occurs. It can be intermittent or persistent and microscopic or gross. However, as many as 10% of patients with acute stones may not have hematuria.

Occasionally, recurrent infection may result in pyelonephritis or abscess. Stones can result in renal scarring, damage, and renal failure.

RENAL PAPILLARY ADENOMAaka:

Renal papillary adenomaTubulo-papillary adenoma

--small,discrete proliferations of papillary or tubulo-papillary epithelium in the renal cortex which theoretically have no metastatic potential.

Size

--size criterion in this definition is arbitrary and has become progressively smaller, from 1-3cm in early autopsy series, to more current consensus definitions restricting the lesions to less than 0.5cm

Epidemiology

-- common (7% of nephrectomy specimens and 10-40% of autopsies)

--the lesions are more common in older patients (10% of patients <40 years; 40% in those >70 years).

--associated with prolonged hemodialysis and acquired cystic disease.

Epidemiology

--often occur coincidentally with papillary renal cell carcinoma(PRCC)

○ papillary adenomas in surgical specimens demonstrated that nearly 50% of adenomas were identified in patients with PRCC; less than 10% were present in the setting of other renal diseases including other renal neoplasms and end-stage renal disease

Morphologic basis epithelial lesions with a tubulo-papillary

architecture measuring less than 0.5cm and of low nuclear grade

Grossly, they are pale tan to grey, well-circumscribed, solid nodules in the renal cortex.

Histologically--composed of varying amounts of tubules and papillae lined by cuboidal cells with scant amphophilic to basophilic cytoplasm.

nuclei demonstrate no atypia

Prognosis

Renal papillary adenomas theoretically have no metastatic potential.

IgA NephropathyIgA Nephropathy

• Most common cause of glomerulonephritis in the world

• Common in France, Japan, Italy and Austria

• Affects children and young adults (mostly males)

Clinical ManifestationsClinical Manifestations Recurrent gross hematuria

Onset may follow a respiratory infection

Predominantly nephritic

Associated with Celiac Sprue and Henoch-Schonlein purpura

PathogenesisPathogenesis

• The mechanism is unknown. There is a possible entrapment of circulating immune complexes with activation of the alternate complement pathway. There is also a possible genetic predisposition.


Light microscopyLight microscopy

Variable

Normal

Mesangial proliferation


Immunofluorescence: Immunofluorescence:

mesangial deposits of IgA and C3

Electron microscopy:Electron microscopy:

mesangial immune complex deposits

Prognosis:Prognosis:

many cases slowly progress to renal failure over 25

years

Renal cell carcinoma (RCC) comprises 5% of epithelial cancers with 38,000 new cases diagnosed in the U.S. this year.

The incidence of RCC has been steadily rising over the past 30 years. The majority (75%) of cases are clear-cell RCC.

Clear Cell Carcinoma

Loss of the sequences of the short arm of chromosome 3.

Occurs by deletion or unbalanced chromosomal translocation resulting in the loss of chromosome 3 spanning 3p12 to 3p26

This region harbors the VHL gene 3p25.3

VHL is a tumor-suppressor gene that targets the Hypoxia-Inducible Factor (HIF-1).

When VHL is mutated, HIF-1 levels remain high.

Binding of HIF to VHL is regulated by proline hydroxylation in a reaction involving 2-oxoglutarate, ferrous iron, and prolyl hydroxylase.

In SDH mutations, accumulation of succinate directly inhibits proline hydroxylase and HIF- levels rise

Papillary Carcinoma

Not associated with 3p deletions.

Most common cytogenetic abnormalities are trisomies 7, 16 and 17.

Chromosome 7 encompasses the locus for MET, a protooncogene that serves as the tyrosine kinase receptor for HGF.

Mutations of MET, a HIF target gene, cause type I papillary renal cancer

Another pathway of HIF accumulation and RCC development involves Krebs cycle enzyme mutations: succinate

dehydrogenase (SDH)-B mutations [16] cause clear-cell RCC, while mutations of fumarate hydratase [17] cause type II papillary cancer.

In its early stages, renal cell cancer usually causes no noticeable

symptoms. Symptoms may occur only when the cancer grows and begins to press on surrounding

tissues or spread to other parts of the body. The symptoms vary

considerably from person to person.

Classic triad: Hematuria

Flank Pain

Palpable (abdominal) mass

The classic triad occurs in 10 to 20% of patients

Other Presenting Signs and Symptoms

Weight loss Fever Malaise Weakness Anemia Loin Pain

Varicocele – enlargement of testicle

Night sweats Constipation

PARANEOPLASTIC SYNDROMES(abnormal hormone production)

Polycythemia Hypercalcemia Hypertension Hepatic

dysfunction Feminization or

masculinization

Cushing Syndrome

Eosinophilia Leukemoid

reactions Amyloidosis

A common characteristic of this tumor is its tendency to metastasize widely before giving rise to any local symptoms or signs.

Common locations of metastasis:

1. Lungs (more than 50%)

2. Bones (33%)

3. Regional lymph nodes, liver, adrenals, brain

Diagnosis By Signs and symptoms ( Note: early

kidney cancers do not usually cause any signs or symptoms, but larger ones may).

Classic triad (10-15%)

1. Hematuria (blood in the urine), 2. flank pain 3. abdominal mass

- detailed medical review of past health state men ages 50-70 Family history of the disease Smoking Von Hippel-Lindau disease ( Abdominal pain Abnormal urine color (dark, rusty, or brown) Back pain Blood in the urine Emaciated, thin, malnourished appearance

Enlargement of the veins around a testicle (varicocele) Flank pain Swelling or enlargement of the abdomen Unintentional weight loss of more than 5% of body weight Constipation Cold intolerance Excessive hair growth in females Paleness Vision abnormalities

Palpation: abdominal mass

Vital signs: Temp: (high- FEVER)

BP: High blood pressure

Lab tests- CBC

Polycythemia (5%)

Anaemia resulting from depression of erythropoietin (5%)

Lab tests Urinalysis (Urine tests)- check for several

indicators of the cancer such as blood, sugar, proteins, and bacteria.

RESULT: Abnormal urine color (dark, rusty, or brown) Blood in the urine

Blood chemistry tests- (kidney cancer can affect the levels of certain chemicals in the blood.

creatinine

Imaging tests

CT scan

Tumor in the left kidney Tumor in the kidney metastasis from lung CA

Computed tomography(CT) similar with an x-ray test, it creates a detailed cross-

sectional image of the body; one of the most useful tests for finding and looking at a mass inside your kidney, useful in checking whether or not a cancer has spread to organs and tissues beyond the kidney.

precise information about the size, shape, and position of a tumor, and can help find enlarged lymph nodes that might contain cancer

RESULT: enhancement will be noted, and will highlight the tumor relative to normal renal parenchyma

Magnetic resonance imaging(MRI)

provide detailed images of soft tissues in the body.

MRI scans use radio waves and strong magnets instead of x-rays.

provide a better picture of blood vessels Result: enhancement will be noted, and will

highlight the tumor relative to normal renal parenchyma

Abdominal MRI

Ultrasound or ultrasonography

safe, noninvasive and brief test that can detect tumors

a medical technique that uses high-frequency sound waves to create an interior image of the body on a special computer screen

helpful in determining if a kidney mass is solid or filled with fluid

Abdominal ultrasound

Positron emission tomography (PET scan)

provides useful information about the tumor location and how far the cancer has spread

uses radioactive glucose (known as fluorodeoxyglucose or FDG) to locate the cancer, because the cancerous cells absorb a higher amount of this substance than normal tissues.

useful to see if the cancer may have spread to lymph nodes near the kidney

Intravenous pyelogram(IVP) special x-ray examination of the kidneys, bladder,

and ureters (the tubes that carry urine from the kidneys to the bladder).

Evaluate: Blood in the urine Flank pain (possibly due to kidney stones) Tumors

Angiography

uses a contrast dye. This contrast agent is absorbed by the cancerous cells and displayed on an angiogram

help a surgeon plan surgery in some patients who need blood vessels mapped before the operation

also help diagnose renal cancers since the blood vessels usually have a special appearance with this test

Renal angiogram

Others…(help determine if the cancer has spread

(metastasized) to other parts of the body) chest x-rays bone scans 30% of patients with renal carcinoma present with

metastatic disease.

BoNe ScAn

Biopsy if imaging test results are not conclusive

enough to warrant removing a kidney confirm the diagnosis of cancer if a person’s

health is too poor for surgery and other local treatments

Fine needle aspiration -is performed only if the tumor can be easy reached; most used procedure of removing a sample of tissue

Core needle biopsy - removing a small cylinder of tumor tissue.

Fuhrman grade

describe how aggressive the cancer is likely to be

The grade is based on how closely the cancer cells’ nuclei (part of a cell in which DNA is stored) look like those of normal kidney cells.

Gross examination shows a yellowish, multilobulated tumor in the renal cortex, which frequently contains zones of necrosis, hemorrhage and scarring.

They usually have a gross yellow color and tumor cells resemble clear cells of the adrenal cortex but in truth, these tumors arise from the tubular epithelium and are therefore renal adenocarcinomas

Kidney: Organ is 5-6 inches in length, and covered with fat

When assessing the gross anatomy:

Calyx and Ureter:

Is there anything blocking it? NOParenchyma

Can you delineate the cortex from the medulla (normal ratio of 1:3 or 1:4)? NOLight tan color of lesion - the lighter the color

of the lesion, the more packed it is with cellsPresence of ulceration? YES (encircled)

Renal cell carcinoma

Clear cell carcinoma

composed of large cells with clear or granular cytoplasm, and prominent vasculature

Clear cell


The cells have a clear cytoplasm and you can see their borders easily. Some of the clear staining is due to lipid, which make the tumors look yellow grossly. Like most renal cell carcinomas, this tumor is rich in blood vessels.


Acinar tubule formation is noted Aggregates of mononuclear infiltrates

are also seen

Clear cell

Where does renal cell carcinomas arises? Renal cell carcinomas arises in the

proximal tubule cells or the renal epithelium.

Some said that it arises in the adrenal glands.


This is the most common type, accounting for 70% to 80% of renal cell cancers.

On histologic examinations, the tumors are made up of cells with clear or granular cytoplasm and are nonpapillary.

The neoplastic cells are characterized by a clear cytoplasm surrounded by a distinct cell membrane, but eosinophilic cells could be predominant.

Usually tumors has an alveolar or acinar pattern.

There is a network of delicate interconnecting capillaries or sinusoidal stroma supported by a network of thin reticulin fibers.

Papillary carcinoma

Accounts for 10% to 15% or renal cancers.

Papillary RCC consists predominantly of papillary or tubulopapillary architecture.

The neoplastic cells are cuboidal or columnar with eosinophilic granular cytoplasm, but foci of clear cells could be observed.

Fine fibrovascular stalks are present.

The stroma contains plasma cells, lymphocytes, neutrophils, and macrophages with focal or diffuse accumulation of foamy

macrophages in the stromal spaces.

Psammoma bodies are identifiable.

Papillary carcinoma

Chromophobe renal carcinoma

Represents 5% of renal cell cancers.

Composed of cells with prominent cell membranes and pale eosinophilic cytoplasm, usually with a halo around the nucleus

Nuclei are central, and some are binucleated.

The cytoplasm is slighty positive for Periodic Acid Schiff and strongly positive for Hale's acid iron colloid stain.

In all of these tumors, areas of necrosis,

hemorrhage, and fibrosis could be identified

Chromophobe renal carcinoma

Collecting duct (Bellini duct) carcinoma

Represents approximately 1% or less of renal epithelial neoplasms.

Arise from collecting duct cells in the medulla.

These tumors are characterized by nests of malignant cells enmeshed within a prominent fibrotic stroma, typically in a medullary location.

Staging guidelines for kidney cancer are as follows (2.5 cm equals approximately 1 in):

Stage I: Primary tumor is 5 cm or less in greatest dimension and is limited to the kidney, with no lymph node involvement.

Stage II: Primary tumor is larger than 5 cm in greatest dimension and is limited to the kidney, with no lymph node involvement.

Stage III: Primary tumor may extend into major veins or invade adrenal glands or perinephric tissues, but not beyond Gerota's fascia. There may be metastasis in a single lymph node.

Stage IV: Primary tumor invades beyond Gerota's fascia. Metastasis in more than one lymph node. Possible metastasis to distant structures in the body.

The five year survival rate is around 90-95% for tumors less than 4 cm.

For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80-85%.

For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%.

If it has metastasized to the lymph nodes, the 5-year survival is around 5 % to 15 %.

If it has spread metastatically to other organs, the 5-year survival rate is less than 5 %.

For those that have tumor recurrence after surgery, the prognosis is generally poor.

Renal cell carcinoma does not generally respond to chemotherapy or radiation.

Immunotherapy, which attempts to induce the body to attack the remaining cancer cells, has shown promise.

Recent trials are testing newer agents, though the current complete remission rate with these approaches are still low, around 12-20% in most series.

Chemotherapy is not commonly used to manage metastasized renal cell carcinoma (mRCC) due to it relatively low response rate

New knowledge about molecular mechanisms involved in the development and metastasis of RCC is expanding available therapeutic options

Cytokine therapy (IL-2) has been the standard for managing mRCC

Several promising new anti-angiogenic and multitarget agents are demonstrating activity in mRCC. They work by binding to different growth factor receptors

Treatment The application of newly acquired

molecular knowledge is helping us shift the management paradigm from palliation to disease control

For non-metastasized cases, roughly 90% can be cured with surgery

After the CA spreads to local lymph nodes, adjunctive therapy would be required

RCC responses well to immunotherapy with interleukin 2 or interferon alpha

Surgery Small renal tumors (<4cm) are treated

with partial nephrectomy Laparoscopic cryotherapy can also be

done on smaller lesions Kidneys can be embolized prior to

surgery to minimized blood loss Tumors >5cm has greater chances of

distance metastases and surgical removal of all or part of the kidney is recommended

Medications RCC elitcits an immune response which

results in sponstaneous remissions Reproduce this response in treatment by using

immunomodulating therapies such as cancer vaccines and IL-2

Restore the function of VHL gene to destroy the proteins that promote inappropriate vascularization. Bevacizumab, an antibody to VEFG has significantly prolonged time to progression

Sunitinib and Sorafenib are drugs that interfere with tumor growth by inhibiting angiogenesis and cell proliferation

Chemotherapy

Most currently available cytostatics are ineffective for the treatment of RCC

The response rate s are very low (5-15%)

Cancer Vaccine

No RCC tumor vaccine in the market yet TroVax has shown promising results in

phase 2 trials

Care for Patients Undergoing Treatment Chemotherapy related side effects are mild

and manageable. They are related to the cytotoxic effects on normal cells that have rapid turnover rate

Cytokine induced symptoms are dose limiting

Side effects associated with targeted and multi-targeted agents are usually mild and can be treated symptomatically. They are reversible on discontinuation of therapy

Common Problems with RCC Treatment and Their ManagementGeneral Problem Management Patient Teaching

Points

Fatigue Encourage patient to rest and to pace activities in accordance with energy level

Ask patient to use log diary to monitor trends and keep note of aggravating and alleviating factors

Mucositis Assess incidence and severity using standard grading scale; observe for infectious complicationsUse anti-infective agents

Discontinue use of tobacco and alcoholApply topical anesthetics

Nausea and vomitting Assess seerity with rating scaleAdminister antiemetic agents

Dietary interventionsAvoid fatty and high salt foods

General Problems with RCC Treatment and Their ManagementGeneral Problem Management Patient Teaching

Points

Diarrhea Give antidiarrhea, antimotility and anticholinergic agentsModified diet and increase fluid intake

Instruct patient to recognize sign and symptoms that require immediate medical attention: fever, palpitation, thirst, cramping

Anorexia Monitor weightReferral to a nutritionistPrescribe enteral supplements

Encourage patient to eat small meals but more frequently

Hematologic Problems with RCC Treatment and Their ManagementHematologic Problem Management Patient Teaching

Points

Anemia Monitor hemoglobin and hematocrit levelsAdminister RBC growth factors as needed

Ask patient to report dizziness, SOB fatigue

Neutropenia Monitor WBCAdminister WBC growth factors as needed

Ask patient to report temp elevation above 100FStress handwashing and avoid crowded places

Thrombocytopenia Monitor platelet countObserve signs of bleeding

Avoid activities that could impare skin and mucous membrane integrity

Integumentary Problems with RCC Treatment and Their ManagementIntegumentary Problem Management Patient Teaching

Points

Hair changes Discuss impact of hair loss and self image

Skin rashes Assess severity with grading scalePrescribe anti infective creams

Ask patient to report potential skin changesAvoid sun exposure

Hand-foot syndrome Assess severity with grading scaleDiscontinue or modify therapy if problem is severe

Apply skin moisturizer creamAvoid activities that put pressure on feet and handsAvoid heat and hot water

Differential diagnosis of Kidney mass

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