Chapter 10 Oncology

Douglas W. Jones, Thomas A. Brown, MD, Sonali J. Shah

Insider’s Guide to Oncology for the USMLE Step 1

It is no surprise that boards are big on oncology. As with pharmacology, almost every topic area has an oncology-related component. Yet before you can delve into these individual tumor types, you should develop a firm understanding of basic tumor biology. If you have the time to do so, we recommend that you read the “Neoplasia” chapter in Robbins and Cotran Pathologic Basis of Disease. Once you understand these concepts, you will see that every cancer type follows the same basic set of principles, and it will be much easier to focus on mastering specific facts.

Basic concepts—cell biology of cancer

1 What is the difference between an oncogene and a tumor suppressor gene?

An oncogene is a mutated form of a normal gene (proto-oncogene). Proto-oncogenes code for proteins that can lead to cellular proliferation and neoplasia. However, proto-oncogenes are normally silent (unexpressed). Activating mutations convert proto-oncogenes into oncogenes and predispose to neoplasia. Because only a single gene needs to be mutated, oncogenes are seen as dominant mutations. An example of a proto-oncogene is a gene for a growth factor receptor that, when mutated, could lead to inappropriate activation of the receptor, leading to uncontrolled cellular proliferation in the absence of excessive levels of that growth factor.

A tumor suppressor gene is a normally active gene (in contrast with a proto-oncogene). Tumor suppressor genes encode proteins that suppress cellular proliferation; therefore, if its function is lost (disinhibited), cancerous cells are permitted to survive. Mutations in tumor suppressor genes are said to be recessive because mutation must occur in both alleles in order to completely knock out the function of the gene.

2 Which type of mutation is more commonly involved in familial cancer syndromes?

Tumor suppressor genes are more commonly involved in familial cancer syndromes because an embryo with one mutated copy of a tumor suppressor gene is likely to develop normally. However, a second mutation may be acquired at a later date, leading to cancer (loss of heterozygosity). On the other hand, an embryo is less likely to survive if it has inherited an oncogene because the effects of this dominant negative mutation are typically much more disruptive to development.

3 How does Knudson’s “two-hit hypothesis” relate to tumor suppressor genes?

Alfred Knudson studied retinoblastoma, which was later found to be a form of cancer caused by the mutation of the retinoblastoma tumor suppressor gene. At the time, he observed that in familial forms of retinoblastoma, tumors formed in patients at a much younger age than was typical for those arising in patients with no family history of the disease. He theorized that in familial cases, a germ-line mutation was inherited (the first hit) and that a second sporadic mutation occurred early in life (the second hit), thus deactivating both tumor suppressor genes and causing tumor formation. This theory was therefore called the two-hit hypothesis. In nonfamilial cases, however, mutations of both tumor suppressor genes (both hits) had to occur sporadically and thus took much longer to manifest as tumor formation.

4 What are the phases of the cell cycle? Where is the restriction point?

Most cells in the human body are quiescent (i.e., not actively dividing). Exceptions include cells of the hematopoietic system, the integument, and the intestinal mucosa. However, those cells that divide follow a well-defined cyclic pattern. Major challenges in cell replication include high-fidelity DNA duplication (in the S phase) and segregation of chromosomes into daughter cells (during mitosis or the M phase). Different phases and checkpoints help address these issues (Fig. 10-1):

Figure 10-1 Regulation of the cell cycle.

(From Hoffman R, Benz EJ Jr, Shattil SJ, et al: Hematology: Basic Principles and Practice, 4th ed. Philadelphia, Churchill Livingstone, 2005.)

S phase: DNA synthesis

G₂ phase: gap period 2

M phase: mitosis

G₁ phase: gap period 1

R: restriction point

The restriction point occurs just prior to the S phase; it is important because once the restriction point is passed, a cell is committed to complete the cell cycle. Multiple cellular factors interact to allow a cell to pass the restriction point.

5 What is the function of checkpoints and cell cycle arrests?

The most important function of cell cycle arrest is to allow for the repair of cellular damage and DNA sequences. If improperly duplicated DNA were not repaired at cell cycle checkpoints, then DNA mutations would quickly propagate, and the integrity of cellular homogeneity could not be maintained. A cell may also arrest in the absence of proper nutrients, growth factors, or hormones.

Cyclins are proteins that regulate progression from one phase of the cell cycle to the next. Cyclins phosphorylate cyclin-dependent kinases (CDKs) to form cyclin-CDK complexes that must be in either an activated or inactivated state for various cell cycle stages to commence or terminate. CDKs are regulated by CDK inhibitors such as p16, p21, and p27. If these CDK inhibitors are mutated, the cell cycle becomes deregulated and cancer can result. Table 10-1 lists the regulators of the cell cycle that you should know for boards.

Table 10-1 Regulators of the Cell Cycle

Stage	Promoter(s)	Inhibitor
G₁ to S	Cyclin D/CDK4 and CDK6 Cyclin E-CDK2	p53 Rb
S to G₂	Cyclin A-CDK2	—
G₂ to M	Cyclin B-CDK1 CDc25	—

6 What is the importance of p53?

The p53 protein (“guardian of the genome”) is a tumor suppressor gene protein responsible for promoting apoptosis in cells that should not propagate because of excessive DNA mutations or cellular damage. p53 has a number of functions. It can activate DNA repair genes during DNA damage, initiate apoptosis in cells that cannot be repaired, activate the CDK inhibitor p21, and prevent the phosphorylation and inactivation of the retinoblastoma (Rb) protein. Loss of p53 can lead to loss of apoptotic regulation and thus to uncontrolled cellular proliferation. The p53 gene, TP53, is the most commonly mutated gene in human cancers.

7 What is the function of the retinoblastoma protein?

Like p53, Rb is a tumor suppressor protein that functions to prevent cell cycle progression from the G₁ to S phase by binding to and inhibiting the transcription factor E2F. It is heavily regulated via p53 and cyclin-CDK complexes. When in a hypophosphorylated state, Rb functions as an active tumor suppressor. As mentioned in the preceding question 6, p53 helps to maintain Rb in a hypophosphorylated state. During G₁ to S transition, increased levels of cyclin D/CDK4 and CDK6 and cyclin E/CDK2 phosphorylate Rb and prevent its binding to E2F. E2F then activates additional proteins which push the cell cycle to the S phase.

8 When can a solid tumor be detected clinically?

A tumor mass may be clinically detectable when it has reached 10⁹ cells or when it weighs approximately 1 g. Assuming the mass began as a single cellular mutation, this equates to approximately 30 to 33 cell doublings. Once a tumor mass has achieved this number of doublings, only a few further doublings will lead to the death of the patient. As a result, the point in time when a tumor can be detected and an intervention offered is very late in the replicative life of the tumor mass. Unsurprisingly, approximately 70% of patients have distant metastases at the time of diagnosis of a solid tumor.

9 What is the importance of angiogenesis in solid tumor growth?

It is thought that a solid tumor must form new blood vessels in order for a mass to grow larger than a few millimeters in diameter. Otherwise a tumor would soon outstrip the physiologic blood supply and the tumor cells would die (this is sometimes seen in larger tumors without effective angiogenesis that develop a necrotic core). Solid tumors, then, must be able to allow for and encourage the formation of new blood vessels as the tumor mass expands.

Note: In some cases growth of solid tumor metastases is promoted by removal of the primary tumor. This phenomenon has led to the idea that in some settings a primary tumor secretes angiogenesis inhibitors that cause distant micrometastases to remain dormant. Removal of the primary tumor also eliminates these inhibitors, allowing the micrometastases to proliferate. Angiogenesis inhibitors are a promising chemotherapeutic field of study.

10 What is dysplasia? What is anaplasia?

Dysplasia refers to abnormal cell growth and is marked by loss of cell shape, orientation, and size compared to normal tissue. Dysplastic changes are commonly precursors to neoplastic conditions, although dysplasia is reversible. By contrast, anaplasia is an irreversible condition that is marked by lack of differentiation. It is difficult to identify the tissue of origin in an anaplastic lesion.

Basic concepts—cancer epidemiology

11 What are three leading causes of death in the United States?

1. Heart disease

2. Cancer

3. Stroke

12 Aside from skin cancer, which cancers have the highest incidence in men and in women? Which cancers are the leading cause of death in men and in women?

Cancers with the highest incidence in men:

Prostate cancer

Lung cancer

Colorectal cancer

Cancers with the highest incidence in women:

Breast cancer

Lung cancer

Colorectal cancer

Leading causes of cancer deaths in men:

Lung cancer

Prostate cancer

Colorectal cancer

Leading causes of cancer deaths in women:

Lung cancer

Breast cancer

Colorectal cancer

Note: The incidence of lung cancer and colorectal cancer both exceed incidence of prostate and breast cancer when data for men and women are combined.

Basic concepts—cancer classification

13 What is the difference between “grade” and “stage” of a neoplasm?

Grade: The grade of a neoplasm is determined pathologically. This designation usually refers to cellular characteristics of the neoplasm, especially the degree of differentiation of the cells involved. Grading of a neoplasm requires tissue, usually from a biopsy. Grades are reported by roman numerals I to III or I to IV, with the higher numbers representing more poorly differentiating cellular patterns.

Stage: The stage of a cancer is determined clinically but often takes into account information provided by the pathologist (the grade). Stage is most frequently reported using the tumor-node-metastasis (TNM) system:

T: Tumor size. T refers to local growth measured by the size of the primary tumor.

N: Nodes. N refers to the involvement of regional lymph nodes and is an indication of the extent of tumor spread.

M: Metastases. M refers to the presence or absence of distant metastases. Presence of metastases typically confers a high stage.

Staging is most helpful in determining prognosis. Higher stages indicate a poorer prognosis.

Step 1 Secret

You will not be asked to determine the grade or stage of a cancer on Step 1, but you should understand the general concepts.

14 What is the difference between a benign tumor and a malignant tumor?

The distinction between benign and malignant tumors is primarily based on invasiveness, although other characteristics are also evident.

Benign tumors remain localized and may be surrounded by a capsule (the exception to this rule is leiomyoma, which is a benign tumor that is not surrounded by a capsule). They grow slowly and do not metastasize. With reference to tumor grade, these tumors tend to be well differentiated but may undergo malignant transformation.

Malignant tumors are characterized by their invasive properties. They are not surrounded by a capsule, and tumor cells locally invade the tissues that surround them. They tend to grow rapidly and may metastasize. Histologically, these tumors can be poorly differentiated, indicating uncontrolled cellular proliferation.

Even though malignant tumors generally have a worse prognosis than benign tumors, you should not be fooled into thinking that benign tumors are harmless. Depending on location, benign tumors can cause major obstruction that can severely compromise the function of that organ. Brain tumors are great examples of this principle.

15 How are cancers named according to the cell type they originate from?

Epithelial cells are the most common cells that lead to the formation of cancers (likely due to their high levels of replication). Cancers may arise from glandular cells, squamous cells, or transitional cells. Benign epithelial tumors frequently end in the suffix -oma. Malignant tumors of epithelial origin are referred to as carcinomas. So a benign tumor of squamous cell origin may simply be called a papilloma, but when it becomes malignant it is called a squamous cell carcinoma.

Mesenchymal cells can lead to benign tumors (also typically ending in -oma), but their malignant counterparts are called sarcomas. So a benign tumor originating from skeletal muscle may be called a rhabdomyoma, whereas its malignant counterpart is called a rhabdomyosarcoma.

Other cancers may originate from cell types that are not completely differentiated and may be able to give rise to other cell types (i.e., totipotential cells/germ cells). Leukemias and lymphomas are classified in this way and have a unique naming system. Many variations exist in the naming of cancers, but the rules mentioned here are helpful to remember.

Case 10-1

A 50-year-old man is evaluated for a 6-month history of mild upper abdominal pain. The pain is associated with mild nausea and bloating but is unrelated to meals. He denies a retrosternal burning sensation. His appetite has been poor, and he has unexplainably lost 10 lb in the last 3 months. He is otherwise feeling well and has been taking no medications.

1 What is dyspepsia?

Dyspepsia refers to acute, chronic, or recurrent discomfort in the upper abdomen. It can be associated with abdominal fullness, early satiety, bloating, and nausea and vomiting. Dyspepsia is different from heartburn, which is a retrosternal burning sensation more commonly associated with esophageal reflux. However, dyspepsia and heartburn often coexist.

2 What is the differential diagnosis for dyspepsia?

It is broad and includes gastric causes such as peptic ulcer disease, gastroesophageal reflux disease, and gastric cancer; pancreatic causes such as pancreatitis and pancreatic carcinoma; biliary tract diseases such as cholelithiasis and choledocholithiasis; and “functional dyspepsia” when no obvious organic cause is found. Functional dyspepsia is the most common cause of chronic dyspepsia. Finally, cardiac ischemia can also present with dyspepsia.

Case 10-1 continued:

The patient is given a trial of omeprazole without relief of symptoms. He now notes early satiety and worsening fatigue. Physical examination reveals conjunctival pallor, and rectal examination reveals stool positive for blood. Laboratory workup reveals hemoglobin of 10.2 g/dL with a mean corpuscular volume (MCV) of 65 fL.

3 How does this information change your differential diagnosis?

The patient is bleeding into his gastrointestinal tract, most likely from peptic ulcer disease or from a gastric adenocarcinoma. He needs to have upper endoscopy performed as soon as possible.

Step 1 Secret

Whenever a patient has unintentional weight loss, particularly if appetite is suppressed, you should consider cancer as part of your differential diagnosis.

4 What is the significance of his anemia?

He has a microcytic anemia that is most likely an iron deficiency anemia related to ongoing blood loss. An anemia of chronic disease is also possible but less likely in the setting of ongoing blood loss.

Case 10-1 continued:

The patient undergoes upper endoscopy, during which an ulcer is located in the distal antrum of the stomach. It is not actively bleeding at the time of endoscopy. Biopsies are taken of the ulcer margin and of the antrum.

5 Why were biopsies taken at these sites?

Gastric ulcers are always biopsied on endoscopy due to the fact that approximately 3% to 5% of ulcers, often benign-appearing, are malignant. The antral biopsy is taken to test for Helicobacter pylori infection.

Case 10-1 continued:

Biopsy of the ulcer margin shows gastric adenocarcinoma, and biopsy of the antrum is positive for H. pylori.

6 What is the significance of the Helicobacter pylori–positive biopsy?

H. pylori is one of the two major etiologic agents for peptic ulcer disease (nonsteroidal anti-inflammatory drug [NSAID] use being the other), but it is also highly correlated with gastric adenocarcinoma. Chronic H. pylori gastritis of the distal stomach increases the relative risk for developing gastric adenocarcinoma 4- to 20-fold.

7 What are the different pathologic types of gastric cancer?

Adenocarcinoma accounts for 90% to 95% of the cases.

Lymphoma, gastrointestinal stromal tumor, carcinoid, adenocanthoma, and squamous cell carcinoma make up the rest.

8 In gastric adenocarcinoma, what are the two histologic patterns in which neoplastic cells can distribute?

Diffuse type: In this pattern, there is no cellular cohesion. Neoplastic cells invade the wall of the stomach diffusely without producing a distinct lesion. This type tends to occur in younger patients and has a poor prognosis. Note: Diffuse gastric adenocarcinomas present with signet ring cells (Fig. 10-2).

Intestinal type: In this pattern, cells do cohere and form glandular structures that often have an ulcerative appearance. Lesions are most often found in the antrum and lesser curvature of the stomach. This type tends to occur in older patients and has a better prognosis than the diffuse type.

Figure 10-2 Diffuse type of gastric carcinoma with signet ring tumor cells.

(From Kumar V, Cotran RS, Robbins SL: Robbins Basic Pathology, 8th ed. Philadelphia, WB Saunders, 2007.)

9 What is linitis plastica?

Linitis plastica (“leather bottle”) is a term used to describe involvement of the submucosa throughout the stomach, producing a rigid, atonic stomach. The histologic features are those of diffuse type adenocarcinoma.

10 If the patient were to be examined again at a much later stage of disease, what specific signs might be found on physical examination that might indicate metastasis?

Virchow’s node: left supraclavicular lymphadenopathy

Sister Mary Joseph nodule: umbilical nodule

Krukenberg tumor (in women): ovarian tumors (often bilateral) that may be palpable on pelvic examination

11 In retrospect, what aspects of this patient’s presentation are most suspicious for gastric cancer?

Onset of dyspepsia after age 40

Unintentional weight loss of 10 lb in 3 months

No response to proton pump inhibitor therapy

Development of early satiety

Iron deficiency anemia from occult intestinal bleeding

Summary Box: Gastric Adenocarcinoma

The presentation of gastric adenocarcinoma is very similar to that of peptic ulcer disease and gastroesophageal reflux disease.

From 60% to 90% of cases of distal gastric adenocarcinoma are attributed to chronic Helicobacter pylori infection.

An ulcerated gastric lesion should always be biopsied because as many as 5% may harbor gastric cancer cells.

Adenocarcinoma comprises almost all gastric cancers and can be classified by gross or microscopic pathologic appearance.

Adenocarcinoma may produce distinct lesions or may infiltrate the stomach diffusely.

Case 10-2

A 28-year-old woman presents with a lump in her left breast. She does monthly breast self-examinations and found this new lump 2 days ago. She has had no pain around the site of the lump and has noticed no nipple discharge. She is tearful and anxious. On examination, a 2-cm poorly localized, nontender mass is palpated in the upper left quadrant of the left breast. There are no skin changes in the area overlying the mass and no structural distortion of the breast. She has no lymphadenopathy.

1 When examining a new breast lump, what findings may suggest breast cancer?

Nontender, firm or hard masses with poorly delineated margins can suggest breast cancer. There may be skin or nipple retraction and slight asymmetry.

2 What is the most common presentation of breast cancer and where are most cancers found?

Approximately 70% of new cases of breast cancer present with a new lump in the breast. About 90% of all lumps are found by the patient. Up to 60% of breast carcinomas are found in the upper outer quadrant of the involved breast.

3 What do the following physical examination findings indicate?

A. Bloody discharge from the nipple

This can be a sign of breast cancer but is more commonly found in intraductal papilloma (a small benign tumor of the milk duct) when the discharge is found to be coming from a single duct.

B. Small erosions (1-2 mm) of the nipple epithelium

Dermatitis or Paget carcinoma is possible. Although nipple erosions most frequently represent a dermatitis or bacterial infection, this sign may also indicate an underlying ductal carcinoma in situ (DCIS). As pictured in Figure 10-3, the neoplastic cells propagate toward the surface of the breast without violating the basement membrane. The presence of neoplastic cells does violate the epithelial barrier, allowing extrusion of extracellular fluid onto the nipple surface.

Figure 10-3 Paget disease of the nipple. DCIS, ductal carcinoma in situ.

(From Kumar V, Abbas AK, Fausto N: Robbins and Cotran Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2005.)

C. Rapidly growing breast with erythematous, edematous, and warm overlying skin

Inflammatory carcinoma is possible. Invasion of the subdermal lymphatics by carcinoma can cause spreading erythema that can often be mistaken for infection. Resultant edema produces typical peau d’orange appearance (Fig. 10-4).

Figure 10-4 Peau d’orange (“skin of the orange”) or edema of the skin of the breast.

(From Townsend CM, Beauchamp RD, Evers BM, et al: Sabiston Textbook of Surgery, 17th ed. Philadelphia, WB Saunders, 2004.)

4 What is the most common cause of a dominant breast mass for a woman in her 20s?

Fibroadenomas are typically described as round, rubbery, discrete, relatively mobile, and measuring 1 to 5 cm. No treatment is usually necessary. Diagnosis must be based on tissue biopsy or cytologic examination so as to avoid misdiagnosis of a malignancy.

Case 10-2 continued:

During examination of the patient’s right breast, a 1.5-cm discrete, nontender, mobile lump is found in the lower outer quadrant. The patient is very upset with the discovery of a lump in her right breast and reveals that her mother died of breast cancer at the age of 40 and that her older sister was diagnosed with breast cancer at the age of 27.

5 What do bilateral breast lumps indicate with regard to a malignant or benign cause?

Fibroadenomas can occur at multiple sites in up to 10% to 15% of patients. Simultaneous bilateral breast cancers can also occur, so a bilateral malignant process is also a possibility.

6 What disease is she at risk for with the finding of bilateral breast masses and a family history of two first-degree relatives?

She is at risk for hereditary breast cancer. Up to 45% of familial cases of breast cancer are associated with a germ-line mutation, and in these syndromes, presentation with simultaneous bilateral breast lumps is common. A family history of breast cancer in more than one first-degree relative is highly suggestive of an inherited germ-line mutation.

7 What specific genetic mutations confer a lifetime risk of 50% to 85% for developing breast cancer?

BRCA1 and BRCA2 both are tumor suppressor genes whose gene products inhibit tumor growth. A single mutation is inherited and the second gene acquires a mutation (the “second hit”) at some point in the patient’s life. Multiple different inherited mutations to these genes have been identified. Though these genes have been well documented, they account for only approximately 25% of familial cases.

8 If her tumor is found to be positive for BRCA1, for what other malignancy would this patient be at risk?

She would be at risk for ovarian cancer.

Case 10-2 continued:

The lump in her left breast is biopsied and is found to harbor ductal carcinoma. Surgical excision is planned.

9 What are the common histologic types of breast cancer?

Carcinomas are divided into two broad categories: in situ and invasive carcinomas.

Breast cancers are also classified as ductal or lobular based on where they arise: Ductal origin refers to cancers arising from the epithelial lining of the large or intermediate-sized ducts, and lobular origin refers to cancers arising from the epithelium of the terminal ducts of the lobules (Fig. 10-5).

Figure 10-5 Anatomy of the breast.

(From Hayes D: Breast cancer. In Skarin AT [ed]: Atlas of Diagnostic Oncology. Philadelphia, Lippincott, 1991.)

In situ carcinoma describes a neoplastic population of cells that has not penetrated the basement membrane of the affected duct or lobule.

DCIS makes up 80% of in situ carcinomas. Approximately half of mammographically detected cancers are DCIS because they tend to present with calcifications. DCIS is thought to progress to invasive ductal carcinoma in most women.

Lobular carcinoma in situ (LCIS) never forms a density or calcifications and is therefore always an incidental finding on breast biopsy. It is found to be bilateral in 20% to 40% of women and turns into invasive cancer at a rate of approximately 1% per year; therefore, LCIS can be thought of as a risk factor for the development of invasive carcinoma.

Invasive carcinoma is characterized by neoplastic cells that have penetrated the basement membrane and may affect significant architectural distortion.

Ductal carcinoma accounts for up to 80% of invasive carcinomas. Most histologic types of invasive cancer (colloid, medullary, etc.) are subtypes of invasive ductal carcinoma.

Lobular carcinoma shows the classic histologic description of linear arrangements of cells (sometimes only one cell wide) invading surrounding tissue.

Medullary carcinoma is found in women with the BRCA1 gene; up to 13% of cancers are of this type.

10 What are two important biomarkers of a breast cancer that help guide treatment?

Estrogen receptor (ER)/progesterone receptor (PR): If these receptors are present in the cytoplasm of cancer cells, then there is a better prognosis. After resection, patients are typically treated with tamoxifen (a selective estrogen receptor modulator [SERM]), which inhibits endogenous hormone stimulation of tumor cells. As a result, breast cancer is less likely to recur and mortality rate may be decreased by as much as 25% among women with receptor-positive tumors. Anastrazole (an aromatase inhibitor) is used when the patient has contraindications to tamoxifen use.

HER2/neu (also known as ERBB2): If a patient has a metastatic breast carcinoma that overexpresses this gene, trastuzumab (Herceptin) may be used. Trastuzumab is a monoclonal antibody directed against the HER-2 protein. When used with first-line chemotherapy following surgery, trastuzumab increases the time to disease progression.

Summary Box: Breast Cancer

Nontender, firm breast masses with poorly delineated margins are concerning for invasive breast cancer.

Other findings concerning for breast cancer include nipple discharge, nipple scaling, breast asymmetry, nipple inversion, peau d’orange, erythema, and warmth.

The most common cause of breast masses in young women is fibroadenoma.

BRCA1 and BRCA2 mutations predispose to the development of breast cancer and account for approximately 25% of familial breast cancer syndromes.

BRCA1 mutations additionally confer increased risk for development of ovarian cancer.

Most breast cancers arise from the intermediate ducts and are invasive (invasive ductal carcinoma).

Ductal carcinoma in situ (DCIS) is thought to progress to invasive ductal carcinoma in most women.

Lobular carcinoma in situ (LCIS) progresses to invasive lobular carcinoma in some women but not at the same rate of DCIS progression.

Estrogen receptor/progesterone receptor (ER/PR) and HER2/neu (ERBB2) are important biomarkers and may guide adjuvant therapy for breast cancer following resection.

Case 10-3

A 78-year-old man presents with a 2-month history of epigastric pain. He describes the pain as a vague pressure that occasionally radiates to his back. It does not reliably occur before or after meals. He has lost 20 lb in the last 2 months, though he attributes this to his recent lack of appetite. He has taken NSAIDs with no relief. The pain occasionally subsides when he leans forward while sitting up. He smoked two packs of cigarettes per day for 35 years but quit 2 years ago. Examination is significant for scleral icterus and a nontender palpable gallbladder.

1 What diagnosis is suggested by this presentation and what are the key pieces of evidence?

Pancreatic carcinoma is likely. Pain is present in over 70% of cases of pancreatic carcinoma and often radiates to the back. Weight loss is suggestive of underlying neoplasm but may also be related to depressive symptoms often seen in pancreatic cancer. Scleral icterus indicates obstruction of the biliary ductal system. Courvoisier’s sign describes the finding of a nontender palpable gallbladder on abdominal examination and also indicates obstruction of the biliary ductal system. Courvoisier’s sign is more commonly seen in obstruction by a neoplasm, whereas scleral icterus results from obstruction by any mechanism.

2 Where would a pancreatic mass most likely be located in order to cause biliary obstruction?

Pancreatic head. Two thirds of pancreatic cancers are located in the head of the pancreas, where they can easily obstruct the biliary ductal system. One third of pancreatic cancers occur in the body or tail.

3 What are important acquired and hereditary risk factors for the development of pancreatic cancer?

Acquired risk factors include cigarette smoking (note that this patient was a smoker), industrial chemical exposure, type 2 diabetes mellitus, and obesity.

Hereditary risk factors include a family history of pancreatic cancer (7-8% of pancreatic cancer patients have a first-degree relative with pancreatic cancer, versus 0.6% of control subjects) and a familial form of chronic pancreatitis. The following familial cancer syndromes also confer an increased risk of developing pancreatic cancer:

Peutz-Jeghers syndrome

Ataxia-telangiectasia

Hereditary nonpolyposis colorectal cancer (HNPCC)

Familial breast cancer (BRCA2-positive)

4 What is the prognosis with pancreatic adenocarcinoma?

Prognosis is poor. Tumors located in the body or tail have an even poorer prognosis than those located in the head because they often do not produce signs and symptoms until they have invaded adjacent structures. Surgical resection offers a median survival time of 18 months and a 5-year survival rate of approximately 20%. When tumors are not resectable, median survival time is 4 to 8 months. Only 10% to 15% of all tumors are resectable at presentation.

Tags: USMLE Step 1 Secrets

Apr 7, 2017 | Posted by admin in NURSING | Comments Off

Fastest Nurse Insight Engine

Oncology

Share this:

Related

Related posts:

Stay updated, free articles. Join our Telegram channel

Full access? Get Clinical Tree