Malignant Colon Cancer

Adenocarcinoma of the colon

Risk factors 

• Low-fiber diet
• Diet low in fruits and vegetables
•  High red meat and animal fat consumption
• Adenomatous polyps
• Hereditary polyposis syndromes
• Lynch syndrome
• Ulcerative colitis

Genetics

• Multiple mutations are involved
• APC gene
• K-ras oncogene
• p53 gene

Pathology

Microscopically:

It is columnar cell carcinoma originating in the colonic epithelium.

Macroscopically: 4 forms

Annular- may give rise to obstructive symptoms

Tubular- presents with bleeding

Ulcer-presents with bleeding

Cauliflower- least malignant-presents with bleeding

Tumors are more common in the left colon and rectum.

Spread

Direct Spread:

Locally it can invade the bladder, obstruct ureter and may cause hydronephrosis.

Can perforate and cause peritonitis/pericolic abscess/ faecal fistula.

Lymphatic spread:

Growth through lymphatics spreads to pericolic, epicolic, intermediate and principal group of lymph nodes.

Bloodstream spread: To the liver via portal system

Staging colon cancer: Modified Dukes' Staging

Stage

A

B1

B2

C1

C2

D

Extent of Disease

Limited to the mucosa and submucosa

Invasion into but not through the muscularis propria

Invasion through the muscularis propria

Positive lymph nodes; invasion into but not through the muscularis propria

Positive lymph nodes; invasion through the muscularis propria

Distant metastasis

Clinical features

Age: common in patients over 50 yrs of age.

Carcinoma of the left side of the colon:

Most tumors occur in this site and are of stenosing variety.

Main sympton- increasing intestinal obstruction.

Pain

Pain is referred to suprapubic area. Pt. have episodic colicky pain. Constant pain suggests advanced tumors.

Altered bowel habit: 

The episodes of constipation may be followed by attacks of diarrhoea.

Palpable lump

Distension: Lower abdominal distension.

• Carcinoma of sigmoid

Same features as above with there variations:

Pain

Pain 

Tenesmus

Low tumors give rise to a feeling of the need for evacuation, which result in tenesmus accompanied by the passage of mucus (esp. in the early morning)

Bladder symptoms

Carcinoma of transverse colon:

May be mistaken for a carcinoma of the stomach because of the position of the tumor together with anemia and lassitude.

Carcinoma of the caecum and ascending colon:

Anemia

Presence of mass in the right iliac fossa.

Can present with obstruction

Metastatic disease:

Pt. may also present for the first time with liver metastases and an enlarged liver, ascites, 

Rarely pt. may also present metastases to the lung, skin, bone and brain.

Right V/S left sided cancer

Right-Sided Cancer

Gross

Polypoid mass

Barium studies

Polypoid mass

Presentation

Bleeding

Occult blood in stool 

 Iron deficiency anemia 

Left-Sided Cancer

Gross

Circumferential growth producing a "napkinring“ Configuration

Barium studies

"Apple core" lesion

Presentation

Change in bowel habits

Constipation or diarrhea

Reduced caliber stools

Obstruction

Investigations

Sigmoidoscopy

It is a part of the routine investigation of patients passing blood and mucus if it limited to rectum.

Colonoscopy

Used in pts. With presenting symptom of bleeding, those with polyps and in those with radiological doubt.

Radiology

Double-contrast barium enema is used

It shows irregular filling defect and apple core lesion( in lt. sided Ca)

Ix of choice in pt. with a predominant change in bowel habit as a presenting symptom.

USG

For screening of liver metastases

CT

to determine the local invasion in case of large palpable abdominal mass.

Treatment

For right sided growth

Right radical hemicolectomy with ileo transverse anastomosis is done.

Structures removed are-terminal 30cm of ileum, caecum, appendix, ascending colon, 1/3 transverse colon and lymph nodes (epicolic, paracolic, intermediate)

In inoperable right sided growth, ileo-transverse anastomosis is done as a bypass procedure.

For left sided growth

Left radical hemicolectomy is done.

Structures removed are- left ½ of tansverse colon and descending colon is removed along with lymph nodes.

Left sided stenosing type of growth can present with acute intestinal obstruction, in which case initially colostomy is done. Later after 3-6 wks, following proper preparation, required procedure is done, followed by closure of colostomy after 8 wks. 

In solitary liver secondary

Segmental hepatic resection is done.

In case of multiple secondaries confined to one lobe of the liver, hemihepatectomy can be done.

Adjuvant therapy

Chemotherapy using 5-FU and cyclophosphamide.

Regimes-Levamisole and 5-FU or Leucoverin and 5-FU

Indications-Positive nodes, T4 lesion, Venous spread, Signet cell type, Poorly differentiated, Changes in CEA level.

Hepatic metastases

Hepatic resection after recovery from colonicresection.

Irresectable symptomatic hepatic metastases may be treated with cytotoxic drugs or ablaative treatments.

Thyroid Neoplasms

“CLASSIFICATION”

Benign: follicular adenoma

Malignant:

       
1. Primary-

        a. Follicular epithelium ( differentiated)

            Follicular

            Papillary

        b. Follicular epithelium (undifferentiated)

            Anaplastic

        c. Parafollicular cells

            Medullary

        d. Lymphoid cells

            Lymphoma

        
2. Secondary

            Metastatic        

Papillary Carcinoma

a. Epidemiology

    Accounts for 80% of malignant thyroid tumors.

    F>M ; Age 20-50

    Risk factor: radiaton exposure

b. Micro

    exhibits a papillary pattern.

    psammoma bodies present.

    characteristic nuclear features:

       clear “Orphan Annie eye” nuclei.

       nuclear grooves.

       intranuclear cytoplasmic inclusions.

c. Lymphatic spread to cervical nodes is commom.

d. Treatment: Resection is curative in most cases.

                      Radiotherapy with iodine 131 is effective for metastases.

e. Prognosis: excellent

Follicular carcinoma

     

a. Accounts for 15% of malignant thyroid tumors

     

b. Females> males; age 40-60

     

c. Hematogenous metastasis to the bones or lungs is common

Medullary carcinoma

     

a. Accounts for 5% of malignant thyroid tumors

     

b. Arises from C cells (parafollicular cells) and secretes    calcitonin

     

c. Micro: nests of polygonal cells in an amyloid stroma

    

d. Minority (25%) are associated with MEN II and MEN III syndromes

Anaplastic carcinoma

a. Presentation

i. Females> males; age >60

ii. Firm, enlarging, bulky mass

iii. Dyspnea and dysphagia

iv. Tendency for early widespread metastasis and invasion of the trachea and esophagus

          

b. Micro: undifferentiated, anaplastic, and pleomorphic cells

         

c. Prognosis: very aggressiveand rapidly fatal

Surgical terms:

Lobectomy: complete removal of one lobe including isthmus.

Near total thyroidectomy: Total lobectomy with isthmusectomy with subtotal lobectomy.

Subtotal thyroidectomy: isthmusectomy with subtotal lobectomy b/l

Total thyroidectomyb/l lobectomy with isthmusectomy.

Management of thyroid cancers

Papillary Ca. thyroid surgery:

• Node negative, <1cm---lobectomy
• >1cm----Total thyroidectomy
• Evidence of spread present----Total thyroidectomy
• Familial disease---Total thyroidectomy
• Neck irradiation in childhood---Total thyroidectomy

Follicular Ca. surgery

Minimal capsular invasion, <1cm---lobectomy
Vascular invasion---Total thyroidectomy

Anaplastic Ca.

Surgery rarely indicated.

L/N surgery

Neck surgery

RENAL TUMORS

Classification

Benign

• Cortical adenoma
• Angiomyolipoma

Malignant

• RCC
• Upper tract TCC
• Nephroblastoma
• Squamous CA of renal pelvis

Cortical adenoma

• Discovered incidentally, mostly found on autopsy
• Less than 1 cm without malignant features (pea like)
• Symptoms are unusual

Microscopically uniform basophilic or acidophilic with monotonous nuclear and cellular composition

Renal angiomyolipoma

• May occur alone or a part of tuberous sclerosis
• Hamartomas composed of fat, smooth muscle, and blood vessels
• AML may be found in the eyes, heart, lung and bone

• Malignant Tumors

Wilms tumor (nephroblastoma)

 Peak age:2-5 years

Risk factors

. WAGR syndrome-Wilms tumor, aniridia, genital anomalies, and mental retardation

. Beckwith-Wiedemann syndrome

.Tumor suppressor genes

 . WT-l (llp13)

 . WT-2 (llp15)

Gross: large solitary tan mass

Micro

1. Metanephric blastema

ii. Epithelial elements (immature glomeruli and tubules)

iii. Stroma

C/F:

Abdominal mass

Pyrexia

Hematuria

Metastasis occurs early, mainly to lungs.

Inv:

USG

Urography or

CT

Treatment: 

Nephrectomy followed by radiation with or without chemotherapy

If B/L tumor: Partial Nephrectomy

Prognosis: excellent; long-term survival rate of 90%

Renal Cell carcinoma

Epidemiology

- Male: Female  2:1

- 40-60 years of age

Risk factors

i. Cigarette smoking

ii. Chronic analgesic use

iii. Asbestos exposure

iv. Chronic renal failure and acquired cystic disease

v. Von Hippel- Lindau disease

Gross

. Large solitary yellow mass found in the poles (most commonly in the upper pole: most common site- PCT)

. Areas of necrosis and hemorrhage are commonly present

. The tumor often invades the renal vein and may extend into the vena cava and heart

Pathology

Clear cell types

• more than 80%
• polygonal or round cells with clear cytoplasm

Papillary variant

• 14% of RCC
• macroscopic feature-small, confined to cortex and nearly completely encapsulated
• Micro: papillae covered by small cells with scanty cytoplasm, arranged in a single layer on the papillary basement membrane with low nuclear grade

Sarcomatoid

• aggressive behavior and poor prognosis
• microscopic features- spindle cell pattern

Chromophobe variant

• 4% of RCC
• microscopic features light and transparent cytoplasm
• better prognosis

Signs and symptoms

Classic triad (pain, lump and hematuria) is found only in 10% cases

Weight loss, fever, hematuria, night sweats and sudden development of varicocele

Paraneoplastic syndromes from ectopic hormone production

   . Polycythemia(erythropoietin production)

   . Hypertension (renin production)

   . Cushing syndrome (corticosteroid synthesis)

   . Hypercalcemia (PTH-like hormone)

   . Feminization or masculinization (gonadotropin release)

High incidence of metastasis on initial presentation

May cause amyloidosis, a leukemoid reaction, or eosinophilia

Investigations

IVU

CT scan

• Renal Angiogram
• CX-Ray
• Bone scan

Treatment

• RCC is highly resistant to radio and chemotherapy
• Nephrectomy with removal of the perinephric fat

LUNG TUMORS

Bronchogenic carcinoma

•  Epidemiology
•  Leading cause of cancer death among both men and women
•  Increasing in women (increased smoking) in the past few decades
•  Occurs most commonly from 50-80 years of age

Major risk factors

i. Cigarette smoking

ii. Occupational exposure (asbestosis, uranium mining, radiation, etc.)

iii. Air pollution

Common genetic mutations

i. Oncogenes 

 L-myc: small cell carcinomas

 K-ras: adenocarcinomas

ii. Tumor suppressor genes p53 and the retinoblastoma gene

Clinical features

•  Cough
•  sputum production
•  weight loss
•  anorexia
•  fatigue
•  dyspnea
•  hemoptysis and
•  chest pain
•  hoarseness of voice
•  Obstruction may produce focal emphysema, atelectasis, bronchiectasis or pneumonia

Adenocarcinoma (35%)

.Males=females

.less closely associated with smoking than squamous cell

.Gross: peripheral gray-white mass with pleural puckering

.May develop in areas of parenchymal scarring (scar carcinoma)

.Micro: tumor forms glands and may produce mucin.

Bronchioloalveolar carcinoma (5%)

. Subset of adenocarcinoma

. Arises from terminal bronchioles or alveolar walls

. Gross: peripheral mucinous gray-white nodules

Micro:

     columnar tumor cells grow along the walls of pre-existing alveoli

Squamous cell carcinoma (30%)

. Males> females

. strongly related to smoking

Gross: usually centrally located, gray-white bronchial mass

            Arises from bronchial epithelium after a progression:

metaplasia ~dysplasia ~ carcinoma in situ ~ invasive carcinoma

Micro:

. Invasive nests of squamous cells

. Intercellular bridges (desmosomes)

. Keratin production ("squamous pearls")

Small cell (oat cell) carcinoma (20%)

. Males> females

. strong association with smoking

 Very aggressive: rapid growth and disseminate  early

Gross: central, gray-white masses

Micro:

small round or polygonal cells in clusters

EM: cytoplasmic dense-core neurosecretory 

granules

Commonly associated with paraneoplastic syndromes.

Also most common cause of venacaval obstruction syndromes.

Large cell carcinoma (10%)

In early stages, is associated with cavitation

Gross: peripherally located lesion

Micro: 

          large anaplastic cells without evidence of differentiation

Intrathoracic spread

i. Lymph nodes (50%):

         hilar, bronchial, tracheal, and mediastinal

ii. Pleural involvement (adenocarcinoma)

iii. Pancoast tumor (apical tumor) causing Horner syndrome

iv. Superior vena cava syndrome

     Obstruction of SVC by tumor 

     .Distended head and neck veins

     .Plethora

     .Facial and upper arm edema

v. Esophageal obstruction: dysphagia

vi. Recurrent laryngeal nerve involvement: hoarseness

vii. Phrenic nerve damage: diaphragmatic paralysis

Extrathoracic sites of metastasis:

   adrenal (>50%)

    liver

    brain and

    bone

Paraneoplastic syndromes

i. Endocrine/metabolic syndromes

    . ACTH ~ Cushing syndrome 

    . ADH~ SIADH

    . PTH ~ hypercalcemia (squamous cell carcinomas)

ii. Eaton-Lambert syndrome

iii. Acanthosis  nigricans

iv. Hypertrophic pulmonary osteoarthropathy 

. Periosteal new bone formation

. Clubbing 

. Arthritis

Investigations

Sputum cytology

Bronchoscopy:

                         Best for centrally located lesions

Fine Needle Aspiration Bx

                         for peripheral lesions

Pleural Bx in all patients presenting with pleural effusion.

CX-Ray: common features-

     a. U/L hilar lymphadenopathy

c. Lung, lobe or segmental collapse

d. Pleural effusion

b. Peripheral pulmonary opacity

c. Lung, lobe or segmental collapse

d. Pleural effusion

e. Broadening of mediastinum, enlarged cardiac shadow, elevation of hemidiaphragm.

f. Rib destruction


CT Chest

Others:
CT head
Liver ultrasound
Bone marrow biopsy

Treatment

1.Surgical resection
   Symptoms that suggest unresectable lesion: Wt. loss >10%
                                                                               

• Bone pain

other extrathoracic metastases
CNS symptoms
Tumor involving trachea, esophagus, pericardium and chest wall.

Small cell CA

2. Radiotherapy:
    palliation of distressing complications like SVC obstruction, rec. hemoptysis, pain caused by chest wall invasion.
Used in adjunct to Chemothrapy for small cell ca.
 

3. Chemotherapy

   
esp. used in small cell CA along with RT.
 
I.v Cyclophophamide, doxorubicin and vincristine
                              OR
 
I.v  Etoposide and Cisplatin are used.

4. Neoadjuvant and adjuvant CT
   CT given  surgery for down staging the disease in non small cell CA.
 Post-op CT used if lymph node is involved

5. Effusion sclerosed with tetracycline.

Prognosis:
Poorest for small cell carcinoma
Best after surgical resection of squamous cell CA.

Secondary lung tumors

Blood borne metastatic deposits from many primary tumors: part. Breast
                                                                                                         kidney
                                                                                                         uterus
                                                                                                         ovary
                                                                                                         testes
                                                                                                         thyroid
Deposits are usually multiple and bilateral.
Often there are no respiratory symptoms and diagnosis is made by radiological examination.

Malignant mesotheliomas

. Rare highly malignant neoplasm affecting the pleura.
. Occupation exposure to asbestos in 90% of cases
. Presents with recurrent pleural effusions, dyspnea, chest pain

. Gross: encases and compresses the lung

. Micro: carcinomatous and sarcomatous elements (biphasic pattern)

. EM: long, thin microvilli
.No curative treatment and chain pain is often difficult to control.
. Poor prognosis.