Adrenocortical carcinoma Presented by: Dr. M. K. M. Foisal Quader Chowdhury Chittagong Medical College Hospital

Adrenocortical carcinoma

Presented by:

Dr. M. K. M. Foisal Quader Chowdhury

Chittagong Medical College Hospital

Case presentation

Name of the patient: Md. Yunus.

Age: 30 years.

Address: Puichori, Banskhali.

Occupation: Shopkeeper.

Date of admission: 20th August, 2013.

Bed: 09, Ward: 24, Reg: 7324/ 89.

CMCH.

Chief Complaints: • Generalized weakness, weight loss, effort

intolerance, occasional vertigo, burning sensation in the scalp for 8 months;

• Anorexia for 6 months,• Diffuse pain in the right flank and right upper

abdomen, grasping in nature associated with frequent rise of temperature for 4 months;

• Urgency with Frequency of Micturition and occasional sleep disturbances for 2 months.

Case presentation

For these complaints he consulted local doctor and was advised for ultrasonograph of whole abdomen that revealed (24 – 06 – 13) big solid retroperitoneal mass above right kidney, later, from which, ultrasonograph guided FNAC was taken that revealed (29 – 06 – 13) Adrenocortical carcinoma. Then he was referred to CMCH for further management.

Patient is non diabetic, non hypertensive, non icteric, with no history of any other major medical or surgical illness.

Case presentation

General examination: On admission, findings were almost within normal range with

Pulse 72 / min;

Blood pressure 90 / 60 mm of Hg;

Not anaemic, cyanosed, edematous or dehydrated;

No abnormality was detected on examination of chest with normal heart sound & clear, vesicular breath sound.

No enlarged lymph node was found on palpation.

Case presentation

Local Examination:

His abdomen was soft, not distended,

No palpable organomegally or intra-abdominal mass,

No scar mark,

Hernial orifice was intact,

Mild tenderness in right hypochondriac region and right renal angle.

His bowel and bladder habit has also been normal.

Case presentation

His investigation profile shows :

Case presentation

Date Investigation Findings

23/06/13 CBC

Hb 12.1 gm/dl; ESR 110; RBC 4.04 mill/cmm; WBC 6500/cmm; Platelet 170000/cmm; Neutrophil 73%; Lymphocyte 21%, Monocyte 5%, Eosinophil 1%, Basophil 0%

24/06/13 USG of W/A Fairly big solid soft tissue mass of 12 X 9.7 cm size in right retroperitoneal space above right kidney.

25/06/13 Tuberculin test Negative

29/06/13 USG guided FNACPositive for malignant cell, suggestive of Adrenocortical carcinoma.


Case presentation


19/08/13 CT scan of abdomen

Fairly large mildly hypo dense soft tissue mass lesion involving right adrenal gland located Anteromedial and superior to the right kidney, measuring 15.5 X 12 X 8 cm. Outline of the lesion is regular. No calcification. IVC and pancreas pushed to the left by the mass. No evidence of invasion to surrounding structure is noted. Few sub centimeter lymph node is noted (09 mm and less) in epigastric region.

21/08/13 ECG Normal study

21/08/13 HBsAg Positive

21/08/13 CBC Hb 11gm/dl; ESR 102; WBC 8800/cmm; Platelet 200000/cmm; Neutrophil 68%; Lympocyte 27%; Monocyte 2%; Eosinophil 3%;


Case presentation


21/08/13 Urine R/M/E Normal study (Epithelial cell 3-4/HPF, Pus cell nil/HPF)

21/08/13 S. Creatinine 0.6 mg/dl

22/08/13 Chest X ray Normal study

22/08/13 FBS & 2HPP BS 90 mg/dl and 110 mg/dl

22/08/13 Serum electrolyte Na+ 133 mmol/L; K+ 4.5 mmol/L; Cl- 100 mmol/L; HCO3

- 25.2 mmol/L

22/08/13 S. Fasting Cortisol 13.3 micro gm/dl.

22/08/13 DHEAS 58.2 micro gm/dl [Normal = 80 – 560 micro gm/dl]

On the basis of the clinical presentation and investigation profile, the patient was diagnosed as a case of Adrenocortical Carcinoma of non functioning variety. He has been on conservative management so far.

Next plan for management was Surgical resection of the tumor after senior consultation.

In order to prepare for the perioperative medical, hormonal & other possible complications, a medical board was arranged on 31st August, 2013.

Case presentation

Medical Board: Date: 31 – 08 – 13 ; Time: 10:00 AM ; Ward: 24.

Respected members of Medical Board: • Professor Dr. Omar Faruque Yusuf, Head, Dept. of Surgery. • Professor Dr. A. K. M. Shamsul Alam, Head, Dept. of

Anesthesiology. • Professor Dr. Md. Mahtab Uddin Hasan, Head, Dept. of

Medicine. • Professor Dr. Khandker A. K. Azad, Hesd, Surgery unit – II • Associate Professor Dr. G. M. Jakir Hossain, Dept. of Surgery. • Associate Professor Dr. Iftekhar Hossain Khan, Dept. of

Endocrinology.

Case presentation

Medical Board:Conclusion: The respected members of Medical Board have examined the

patient and gone through all the papers and diagnosed the patient as a case of Adrenocortical Carcinoma. Detailed discussion regarding hormonal evaluation, possible perioperative complications and necessary precaution & preparation for their management took place. Finally, following decisions were made:

• Surgical resection of the Tumor; • Special Precaution for the HBsAg; • Essential support for the hormonal fluctuation and other

medical emergencies during and after operation.

Case presentation

On Adrenocortical

Carcinoma

DISCUSSION

Anatomy & Histology

Anatomy & Histology

Physiology AdrenalCortex Zona GlomerusaAldosteron

Zona FasciculataCortisol

AdrenalAndrogenOestrogen

Zona Reticularis

DHEAOestrogen

Glucocorticoides

Physiology

Adrenal Medulla secrets Epinephrine and nor-epinephrin.

• Aldosteron = Helps to maintain water & electrolyte balance, by absorption of Na+ & excretion of K+.

• Cortisol = Helps to maintain blood gloucose level by affecting glucose metabolism in the body.

• Androgen = Promotes Hair growth, masculinization. • Oestrogen = Promotes feminization. • Epinephrine and nor-epinephrine = Stimulates

body’s sympathetic activity.

Non-functional and Benign: • Adenoma• Myelolipoma• Hematoma• Cyst• Macronodular Hyperplasia

Tumors of Adrenal Gland

Functional tumors:

– Adrenal Medullary Tumors:• Pheochromocytoma• Childhood tumors: ganglioneuromas,

neuroblastomas– Adrenal Cortical Tumors:

• Cortisol-secreting adenoma• Aldosteronoma• Adrenocortical Carcinoma

Tumors of Adrenal Gland

• Oncocytic adrenal cortical carcinoma, • Myxoid adrenal cortical carcinoma,• Carcinosarcoma, • Adenosquamous adrenocortical carcinoma, • Clear cell adrenal cortical carcinoma.• Secondary metastatic tumor of adrenal gland.

Types of Adrenocortical Ca

Etiology & genetics of Adrenocortical Carcinoma

Risk factors for adrenocortical carcinoma include having the following hereditary diseases:

• Li-Fraumeni syndrome.• Beckwith-Wiedemann syndrome.• Carney complex.

Following genes have been found to be involved:• IGF-II gene• Suppression of p53 gene • c-myc gene

Staging of Adrenocortical Carcinoma

The following stages are used for adrenocortical carcinoma:

Pea, peanut, walnut, and lime show tumor sizes.


• In stage I, the tumor is 5 centimeters or smaller and is found in the adrenal gland only.Stage I

• In stage II, the tumor is larger than 5 centimeters and is found in the adrenal gland only.

Stage II

• tumor can be of any size and has spread:• to fat or lymph nodes near the adrenal gland; or• to nearby tissues, but not to the organs near the

adrenal gland.Stage III

• In stage IV, the tumor can be any size and has spread:• to nearby tissues and to fat and lymph nodes

near the adrenal gland; or• to organs near the adrenal gland and may have

spread to nearby lymph nodes; or• to other parts of the body, such as the liver or

lung.

Stage IV


According to the International Union Against Cancer:

Tumor criteria

T1 - Tumor diameter £ 5 cm with no local invasion

T2 - Tumor diameter > 5 cm with no local invasion

T3 - Tumor of any size with local extension but not involving adjacent organs

T4 - Tumor of any size with local invasion of adjacent organs

Lymph node criteria

N0 - No regional lymph node involvement

N1 - Positive regional nodes

Metastasis criteria

M0 - No distant metastasis

M1 - Distant metastasis


Stages

Stage 1 - T1, N0, M0


Stage 3 - T1 or T2, N1, M0

T3, N0, M0


T4, any N, M0

Any T, any N, M1

Clinical presentation of Adrenocortical Carcinoma

A functioning adrenocortical tumor makes too much of one of the following hormones:

• Cortisol.• Aldosterone.• Testosterone.• Estrogen.


Too much cortisol may cause:• Weight gain in the face, neck, and trunk of the body and

thin arms and legs.• Growth of fine hair on the face, upper back, or arms.• A round, red, full face (Moon face).• A lump of fat on the back of the neck ("buffalo hump”).• A deepening of the voice and swelling of the sex organs or

breasts in both males and females.• Muscle weakness.• High blood sugar.• High blood pressure.


Too much aldosterone may cause:• High blood pressure.• Muscle weakness or cramps.• Frequent urination.• Feeling thirsty.

Too much testosterone (in women) may cause:• Growth of fine hair on the face, upper back, or arms.• Acne.• Balding.• A deepening of the voice.• No menstrual periods.


Too much estrogen (in women) may cause:• Irregular menstrual periods in women who have not

gone through menopause.• Vaginal bleeding in women who have gone through

menopause.• Weight gain.

Too much estrogen (in men) may cause:• Growth of breast tissue.• Lower sex drive.• Impotence.


• Adrenocortical carcinoma may present differently in children and adults. Most tumors in children are functional, and virilization is by far the most common (~80%) presenting symptom, followed by Cushing's syndrome (~6%) and precocious puberty.

• Among adults presenting with hormonal syndromes, Cushing's syndrome (~40%) alone is most common, followed by mixed Cushing's and virilization (glucocorticoid and androgen overproduction).


• Feminization and Conn syndrome (mineralocorticoid excess) occur in less than 10% of cases.

• Non-functional tumors (about 40%) usually present with abdominal or flank pain, or they may be asymptomatic and detected incidentally.


Endocrine syndromes associated with adrenocortical carcinoma – Cushing syndrome (30%)– Virilization and precocious puberty (22%)– Feminization (10%)– Primary hyperaldosteronism (2.5%)– Combined hormone excess (35%)– Polycythemia ( < 1%)– Hypercalcemia ( < 1%)– Hypoglycemia ( < 1%)– Adrenal insufficiency (particularly from primary adrenal

lymphomas)– Non–glucocorticoid-mediated insulin resistance– Catecholamine excess due to rare instances of coexisting

pheochromocytoma– Cachexia (usually preterminal)

Differential Diagnosis

Differential diagnosis includes:

I. Adrenocortical adenoma,

II. Renal cell carcinoma,

III. Adrenal medullary tumors,

IV. Hepatocellular carcinoma.

V. Neuroblastoma.

VI. Pancreatic Cancer.

Investigations

Routine Investigations

For Diagnosis

For staging

Investigations

Routine Investigation:

1) Complete Blood Count

2) Urine R/M/E

3) Chest X ray

4) ECG

5) Serum Creatinine

6) HBsAg

7) RBS/ FBS with 2 hrs post prandial blood sugar

Investigations

For Diagnosis

Imaging: CT scan detects 98% of

adrenal carcinomasMRI scanning can also

provide vascular invasion/ tumor thrombosis

information.PET scan

MIBG scan

Hormonal Assay: Twenty-four-hour urine for cortisol or 17-ketosteroid.

Serum TestosteroneSerum DHEA and DHEA-SPlasma estradiol, estrone,

aldosterone/ reninUrinary catecholamines/

metanephrines

In this case, CT scan shows ...

Investigation

Other tests for diagnosis: USG of whole abdomen & USG guided FNAC.

[In this case, this procedure first detected the pathology]

Biopsy – for confirmation of diagnosis and histological typing of cancer – done after surgical resection.

Investigation

For staging: CT scan MRI

CT scans of the chest and bone scans are routinely performed to look for metastases to the lungs and bones respectively. These studies are critical in determining whether or not the tumor can be surgically removed.

They are useful for identifying the site of the tumor, differentiating it from other diseases, such as adrenocortical adenoma, and determining the

extent of invasion of the tumor into surrounding organs and tissues.

Treatment

The only curative treatment is complete surgical excision of the tumor, which can be performed even in the case of invasion into large blood vessels, such as the renal vein or inferior vena cava.

Surgical Care• Preoperative screening

– Include a full evaluation to determine the extent of disease and staging, which has implications for the ultimate prognosis.

– Look for the most common sites for metastases. They are the lungs, liver, bone, and lymph nodes. Contiguous spread to the kidney and liver (if the primary is on the right side) and tumor extension into the venous drainage system of the adrenals and the inferior vena cava are common.

Treatment

Surgical resection

When feasible, total resection remains the management modality of choice for the definitive management of AC. It also remains the only potentially curative therapeutic modality.

Recurrent local and metastatic disease is common, even among patients who undergo a successful complete resection. In such settings, the only effective treatment is attempted reoperation.

Treatment

Preoperative diagnostic accuracy should improve in the following years with improved MRI technology, percutaneous core needle biopsy technology, and advances in molecular, genetic, and immunotyping interpretation.

Aggressive resection of locally recurrent disease may prolong survival in some patients, while percutaneous radiofrequency ablation (RAF) may have a place in providing local symptom control related to local compression by an invasive tumor.

Treatment

Open AdrenalectomySuitable for large tumor, esp when there is evidence/

suspicion for local spread.

Treatment

Laparoscopic AdrenalectomySuitable for smaller tumor, esp when there is no

evidence/ suspicion for local spread.

Ports for Laparoscopic Adrenalectomy

Treatment

Treatment

Role of radiotherapy:

For a long time, radiotherapy seemed to be less effective for curative purpose. However, There are emerging case reports demonstrating improved outcomes when palliative XRT used for localized lesions.

Treatment

Role of Chemotherapy:Mitotane• This drug remains the major chemotherapeutic option

for the management of AC because it is a relatively specific adrenocortical cytotoxin. It is used as primary therapy, as adjuvant therapy, and as therapy in recurrent or relapsing disease.

• Chemical relative to DDT• Found to have adrenolytic activity in dogs in vivo

(selectively destroyed the zonae reticularis and fasciculata)

Treatment

Role of Chemotherapy:Mitotane• Side effects are major and frequent, including:

– CNS disturbance (vertigo, somnolence, ataxia)– Liver Toxicity– Renal Toxicity– Nausea, Vomiting– Diarrhea– Rash

Treatment

Role of Chemotherapy:

Other symptom- palliative Options:• Metyrapone (11B hydroxylase inhibitor)• Ketoconazole• Aminoglutehamide

CytotoxicsMost studied have been Etoposide, cisplatin, and

adriamycin.

Treatment

Newer options:Biologic therapy is a treatment that uses the patient's

immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

Precaution & management for Perioperative risks, complications Most aspects of preparation are the same as in other major operations. In addition, hormone imbalances are often a major challenge. Whenever possible, physicians will try to correct hormone imbalances through medication in the days or weeks before surgery. Adrenal tumors may cause other problems such as hypertension or inadequate potassium in the blood, and these problems also should be resolved if possible before surgery is performed. Therefore, a patient may take specific medicines for days or weeks before surgery.

Precaution & management for Perioperative risks, complicationsPatients stay in the hospital for various lengths of time after adrenalectomy. The longest hospital stays are required for open surgery using an anterior approach

Hospital stays of about three days are indicated for open surgery using the posterior approach or for laparoscopic adrenalectomy.

The special concern after adrenalectomy is the patient's hormone balance. There may be several sets of required lab tests to define hormone problems and monitor the results of drug treatment. In addition, blood pressure problems and infections are more common after removal of certain types of adrenal tumors.

Precaution & management for Perioperative risks, complications

Risks • The risks of adrenalectomy include major hormone imbalances, caused

by the underlying disease, the surgery, or both. These can include problems with healing, blood pressure fluctuations, and other metabolic problems.

Other risks are typical of many operations. These include: • bleeding • damage to adjacent organs (spleen, pancreas) • loss of bowel function • blood clots in the lungs • lung problems • surgical infections • pain • scarring

Prognosis

Adrenocortical Carcinoma generally, carries a poor prognosis.

Five-year disease-free survival for a complete resection of a stage I–III ACC is approximately 30%.

Almost 90% cases recur after primary syrgery.

Prognostic factors are

Age of the patient.

Nutritional Status & overall condition of the patient.

Stage of the tumor.

Prognosis

Poor prognostic factors:

Mitotic activity,

Venous invasion,

Weight of tumor 50g+;

Diameter of 6.5 cm+

Outcome of ACC surgery worldwide.

Complete surgical resection is the primary treatment modality.

Summary

• Adrenocortical carcinoma is a rare disease that often presents late

• Primary curative therapy is surgical• No role for adjuvant chemotherapy has

been definitively demonstrated to date• Palliative therapy with mitotane may be

useful; its palliative effect may be entirely due to adrenolytic effect

Summary

• Re-operation appears to be the only long term curative option in recurrent cases

• A well coordinated approach by Surgeon, Anesthesiologist, Internist, Endocrinologist & Oncologist is essential for a successful outcome.

• Cytotoxic chemotherapy in the advanced/ metastatic setting has not been definitively demonstrated to be useful in controlled trials

Referance

• Bailey & Love Short practice of Surgery (25th edition) • Essential Surgical Practice – Sir Alfred Cuschiery (4th edition) • Current Surgical Diagnosis & Treatment – Gerard M. Doherty (12th edition)• General Surgical Operations – R. M. Kirk (5th edition) • Essentials of Human Anatomy – A. K. Dutta • Bradley, Edward L., III. The Patient's Guide to Surgery. Philadelphia:

University of Pennsylvania Press.• Fauci, Anthony S., et al., ed. Harrison's Principles of Internal Medicine. New

York: McGraw-Hill. • Little, M., and D. C. Garrell. The Endocrine System: The Healthy Body. New

York: Chelsea House. • Miller BS, Gauger PG, Hammer GD, et al. Proposal for modification of the

ENSAT staging system for adrenocortical carcinoma using tumor grade. Langenbecks Arch Surg 2010; 395:955.

Documents

Adrenocortical carcinoma Presented by: Dr. M. K. M. Foisal Quader Chowdhury Chittagong Medical College Hospital