2014 Pathology Website

Normal Lab Values

Week 4 - Neoplasia & Laboratory Medicine

Suggested readings from
Robbins 8th ed.
pp. 259-330

Pathology Cases for Week 4


Pathology Case Descriptions

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Clinical History: A 72-year-old male with dementia died of bronchopneumonia. This was an incidental finding at autopsy.

Image Gallery:

(Summary of Gross Findings - click here)
In the right lobe of the liver there was a circumscribed, dark red, spongy mass 4 cm in size. In the center of the mass there was a gray, firm, fibrous core.
(Summary of Microscopic Findings - click here)
Inspection reveals a mass with many blood filled spaces. These are formed by anastomosing strands of connective tissue, partially hyalinized, lined by endothelial cells. Notice the subcapsular location of the tumor and its relationship to the liver parenchyma.


155-1. Which feature in a tumor suggests that it is likely to be a benign neoplasm?

  1. Circumscription
  2. Lack of nuclear pleomorphism
  3. Very few mitotic figures
  4. ALL of the above
  5. NONE of the above





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Clinical History: This was a 58-year-old female whose uterus was removed for uterine prolapse and urinary incontinence.

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(Summary of Gross Findings - click here)
The uterus was slightly enlarged, and contained many gray firm circumscribed nodules 0.5 cm - 2 cm in size. These nodules bulged out of the cut surface. Most of them were located intramurally, but there were some are located in the sub mucosal or the subserosal areas.
(Summary of Microscopic Findings - click here)
The tumor nodules are composed of interlacing bundles of cells, which have long spindle nuclei and pink fibrillary cytoplasm. These cells resemble the smooth muscle cells of the myometrium. Portions of the tumor tissue have become pink hyalinized masses in which only a few cells are present. These tumor nodules do not have a definite capsule, though their outlines are rather distinct. A small number of vessels are present within the tumor.


220-1. This tumor in the uterus arises from:

  1. endometrial stromal cells
  2. smooth muscle
  3. endometrial cells
  4. nervous tissue
  5. fibroblasts



220-2. The diagnosis is:

  1. uterine adenomyosis
  2. endometrial adenosarcoma
  3. endometrial stromal sarcoma
  4. uterine leiomyoma
  5. uterine schwannoma



220-3. In the pathologic assessment of uterine leiomyoma:

  1. Nuclear atypia and giant cells are not compatible with a benign tumor.
  2. The distinction between leiomyosarcoma and leiomyoma is based on nuclear atypia, mitotic index and necrosis.
  3. Malignant transformation of a leiomyoma is common.
  4. Subserosal leiomyoma is the most likely cause of menorrhagia.




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Clinical History: This was an incidental autopsy finding in the lung of a 67-year-old white male.

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(Summary of Gross Findings - click here)
A chest CT from another patient illustrating a similar "coin" lesion in the inferior lobe of the right lung is shown. There was a hard, well circumscribed, round nodule with a yellow gray cut surface in the lung.
(Summary of Microscopic Findings - click here)
There is normal cartilage, hyperplastic bronchial epithelium, and fragments of lung tissue with the alveoli filled with mononuclear cells derived from the alveolar epithelial cells. These lesions are common and seldom cause clinical symptoms.


170-1. The MAIN tissue seen in this tumor is:

  1. bone.
  2. collagen.
  3. epithelium.
  4. cartilage.
  5. fat



170-2. This tumor is BEST considered a form of:

  1. sarcoma.
  2. adenoma.
  3. hamartoma.
  4. teratoma.
  5. carcinoma.



170-3. The tumor had been considered a hamartoma, but there is recent evidence to suggest that it should be considered a:

  1. chondrosarcoma because it metastases to distant sites.
  2. chondroma because it is monoclonal.
  3. chondromyxoid fibroma because it occurs in soft tissue as well.
  4. osteosarcoma with chondroid metaplasia because it produces osteoid.
  5. osteochondroma because it contains benign cartilage and bone.



170-4. With regard to the presentation of lung tumors:

  1. Carcinoid tumor is a type of neuroendocrine tumor with low grade malignant behavior.
  2. Inflammatory myofibroblastic tumor is more common in adults.
  3. Hypercalcemia is a paraneoplastic syndrome most commonly seen in small cell carcinoma.
  4. Bronchioloalveolar carcinoma is a form of squamous cell carcinoma commonly seen in male smokers.
  5. Horner syndrome is a common complication of a peripheral lung tumor.




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Clinical History: A 43-year-old white female had a four-month history of intermittent bloody stools. Sigmoidoscopy revealed pedunculated polyps 15 cm above the sphincter. She had a family history of colon cancer and the colon was removed prophylactically.

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(Summary of Gross Findings - click here)
The resected tissue contained several polps. The largest polyp was 1.5 cm in diameter. The stalk was 2 cm in length. The base of the stalk and the adjacent mucosa showed no induration.
(Summary of Microscopic Findings - click here)
The exophytic structure of the polyp can be seen with the naked eye. There is a short stalk lined by normal colon mucosa with blood vessels in the submucosa. The finger-like villi of the polyp are lined by adenomatous mucosa, the hallmark of a neoplastic polyp. Compared to the nearby normal mucosa, the nuclei are elongated, hyperchromatic and stratified. There is increased nuclear to cytoplasmic ratio and decreased cytoplasmic mucin.


166-1. This is an example of a:

  1. hyperplastic polyp.
  2. Adenomatous polyp.
  3. juvenile polyp.
  4. hamartomatous polyp.
  5. inflammatory polyp.


166-2. The polyp is lined by epithelium that features stratified hyperchromatic nuclei, increased nuclear-cytoplasmic ratio and reduced cytoplasmic mucin. This appearance of the lining epithelium is BEST described as:

  1. normal.
  2. metaplasia.
  3. dysplasia.
  4. hyperplastic.
  5. hamartomatous.


166-3. This lesion is best characterized as:

  1. tubular adenoma.
  2. tubulovillous adenoma.
  3. villous adenoma.
  4. hyperplastic polyp.


166-4. The highest risk for colon carcinoma is seen in:

  1. tubular adenoma.
  2. tubulovillous adenoma.
  3. villous adenoma.
  4. hyperplastic polyp.




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Clinical History: This 84-year-old female developed weakness and weight loss six months prior to death. She saw a physician twelve days prior to death with signs and symptoms of intestinal obstruction. A tumor mass was palpated in the rectum. The colon was resected.

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(Summary of Gross Findings - click here)
A tumor was present 4 cm from the anus. It was hard and had completely surrounded the bowel, reducing the lumen to less than 0.5 cm in diameter. Small tumor implants were present over the peritoneum and mesentery nearby. No distant metastases were noted.
(Summary of Microscopic Findings - click here)
The the lumen of the bowel can be recognized. Note the thickened bowel wall and masses of tumor surrounding fat. Under low power note the tendency in some areas toward a gland-like structure. There is considerable variation in nuclear staining, size and shape. In some areas clumps of tumor cells are in the midst of mucus which the tumor cells are producing. Note the relatively large amount of dense collagen which accompanies the tumor cells in the fat.


84-1. In what section of the colon do MOST adenocarcinomas arise?

  1. Ascending colon
  2. Transverse colon
  3. Descending colon
  4. Rectosigmoid colon


84-2. What type of colonic polyp has the GREATEST malignant potential?

  1. Hyperplastic polyp
  2. Villous adenoma
  3. Tubular adenoma
  4. Peutz-Jeghers polyp


84-3. Which of the following has resulted in reduced incidence of colon cancer?

  1. Vitamin E
  2. Vitamin C
  3. N-Acetylcysteine
  4. Aspirin


84-4. If this patient’s neoplasm were found to have penetrated into the subserosa and to have spread to one regional lymph node but not to distant sites, its stage is:

  1. T2 N1 M0
  2. T3 N0 M1
  3. T3 N1 M0
  4. T4 N1 M1





CASE NUMBER 199 (slide 003_ZZ)
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Clinical History: A 34-year-old woman discovered a mass in her breast. Mammogram revealed microcalcifications. A mastectomy was perfomed.

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(Summary of Gross Findings - click here)
There is inflammation and dimpling of the areola. The cut surface of the resected breast tissue reveals a 3 x 3 x 2 cm firm mass with stellate borders. The center of the mass is firm, scirrhous and white because of the desmoplasia. There are areas of yellowish necrosis in the portions of neoplasm infiltrating into the surrounding breast. Such tumors appear very firm and non-mobile on physical exam.
(Summary of Microscopic Findings - click here)
The virtual image was derived from a breast biopsy on another patient and shows both intraductal carcinoma with a comedo pattern of necrosis and invasive infiltrating ductal carcinoma. Ductal carcinomas range from well-differentiated tumors characterized by good duct formation to poorly-differentiated tumors. This one is composed of infiltrating glands and sheets of pleomorphic cells which infiltrate into the adjacent breast tissue. This infiltrating ductal carcinoma of breast at low magnification appears to radiate from a central area of desmoplasia. This collagenous component gives the neoplasm a hard "scirrhous" consistency that is palpable on physical examination or breast self-examination. Such an invasive carcinoma may be fixed to underlying chest wall, making it non-mobile. Also note the nerve which is invaded by tumor. It would also be important for treatment and prognosis to determine if the tumor cells were estrogen and progesterone receptor positive.


199-1. What is the likely diagnosis?

  1. Medullary carcinoma
  2. Lobular carcinoma
  3. Infiltrating ductal carcinoma
  4. Lymphoma
  5. Adenoid cystic carcinoma


199-2. The following are elements used in the staging of this tumor:

  1. Degree of tubule formation
  2. Amount of nuclear pleomorphism
  3. Mitotic rate
  4. ALL of the above
  5. NONE of the above


199-3. The following are elements used in the grading of this tumor:

  1. The size of the tumor
  2. How many axillary lymph nodes contain metastatic tumor
  3. Distant metastases to lung and/or brain
  4. ALL of the above
  5. NONE of the above


199-4. The following features are poor prognostic markers in breast cancer EXCEPT?

  1. Tumor stage
  2. Tubular carcinoma histological type
  3. Invasion of chest wall
  4. Negative estrogen and progesterone receptors by immunohistochemistry
  5. Lymphovascular invasion


199-5. Concerning BRCA1 and BRCA2 genes, which of the following is FALSE?

  1. Mutations in either account for about 25% of familial breast cancers.
  2. Mutated BRCA1 is also associated with 20-40% higher risk of ovarian cancer.
  3. BRCA1 mutation is common in sporadic breast cancer.
  4. Hypermethylation of BRCA1 is common in breast cancers of medullary and mucinous types.





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Clinical History: Clinical History: This 77-year-old male had an enlarged hard prostate gland on digital rectal exam. Blood test for prostate specific antigen was elevated. The prostate gland was surgically removed.

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(Summary of Gross Findings - click here)
The prostate was quite large and firm with multiple rubbery nodules measuring 2 mm to 6 mm in diameter. Some of the nodules contain yellowish flecks. The seminal vesicles were firm bilaterally.
(Summary of Microscopic Findings - click here)
There are a number of glands shown in varied patterns. In some cases the epithelial cells are found in non-glandular masses. The epithelial cells are cuboidal or polygonal with central, round, deeply pigmented nuclei. Few, if any, mitotic figures can be seen. The presence of perineural and perivascular invasion is clearly in evidence. This is a useful diagnostic characteristic of adenocarcinoma of the prostate.


5-1. The BEST histological diagnosis is:

  1. prostatic hypertrophy.
  2. prostatic intraepithelial neoplasia (PIN).
  3. prostatic adenocarcinoma.
  4. leiomyoma.
  5. small cell neuroendocrine carcinoma.


5-2. Which of the following features are seen in this tumor?

  1. Islands of squamous cells
  2. Perineural spread of the tumor
  3. Highly pleomorphic nuclei
  4. Production of mucus
  5. Signet ring cells


5-3. Which group has the HIGHEST incidence of this disease?

  1. Caucasians living in USA
  2. Chinese living in Singapore
  3. African-Americans living in USA
  4. Japanese living in USA


5-4. Which of the following bones is MOST LIKELY to receive metastases from this neoplasm?

  1. Femur
  2. Skull
  3. Pelvis
  4. Spine


5-5. What histological feature MOST RELIABLY identifies this neoplasm on biopsy?

  1. Large glands
  2. Small glands
  3. Perineural invasion
  4. Nuclear anaplasia


5-6. What combined Gleason score would you assign to this case?

  1. 2
  2. 5
  3. 7
  4. 9


5-7. Which combined Gleason score is associated with the WORST prognosis?

  1. 2
  2. 5
  3. 7
  4. 10


5-8. Which prostate cancer patient will MOST BENEFIT from radical prostatectomy?

  1. >65 years, neoplasm confined to prostate
  2. <65 years, neoplasm confined to prostate
  3. >65 years, distant metastases present
  4. >65 years, distant metastases present




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Clinical History: A 64-year-old man who had smoked two packs a day for 40 years, complained of hoarseness and throat pain. A laryngectomy was performed.

Image Gallery:

(Summary of Gross Findings - click here)
An ulcerated tumor involved the left true and false vocal cords and extended across the midline.
(Summary of Microscopic Findings - click here)
The mucosa is partially columnar, representing the ventricular mucosa. There is a transition to squamous mucosa with marked nuclear pleomorphism. The abnormal squamous cells extend into the underlying stroma where the cells keratinize. Focal necrosis and an inflammatory infiltrate are present.


154-1. The histological type of this tumor is BEST described as:

  1. adenocarcinoma.
  2. adenosquamous carcinoma.
  3. squamous cell carcinoma.
  4. small cell neuroendocrine carcinoma.
  5. large cell undifferentiated carcinoma.


154-2. Which of the following risk factors is MOST associated with this disease?

  1. Smoking
  2. Copper deficiency
  3. Hepatitis B virus
  4. Aniline dye
  5. NONE of the above




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Clinical History: A 68-year-old man was found to have guaiac positive stools. Colonoscopy revealed a sigmoid colon mass. Elevated liver function tests raised the suspicion of metastases and CT scan showed a liver mass. The colon primary was resected. However, he expired six months later.

Image Gallery:

(Summary of Gross Findings - click here)
Large areas of the liver were replaced by a tumor masses. The tumors were firm and white in comparison to the surrounding soft, golden brown liver. Note the serrated edges of the metastases and the prominent central necrosis seen in the larger nodules. Of all neoplasms involving the liver, metastases are the most common and are usually multiple throughout the liver.
(Summary of Microscopic Findings - click here)
A small portion of residual liver can be seen in most sections. The tumor mass is made up of irregular glandular spaces lined by malignant, cuboidal to columnar epithelium. The neoplastic glands are dispersed in desmoplastic (fibrotic) stroma.


139-1. This type of neoplasm is more common than:

  1. hepatocellular carcinoma.
  2. cholangiocarcinoma.
  3. liver cell adenoma.
  4. ALL of the above.



NEOPLASIA Review Items

Key Vocabulary Terms

adenoma exophytic  oncology
anaplasia grade papilloma
angiogenesis hamartoma paraneoplastic syndrome 
aplasia  heterotopia parenchyma
atrophy hyperplasia Philadelphia chromosome
benign hypertrophy pleomorphism
borderline malignancy hypoplasia point mutation 
cachexia in situ polyp
cancer initiation premaligant
carcinogen intraepithelial prognosis
carcinoid invasion progression
carcinoid syndrome leukoplakia promotion
carcinoma low malignant potential proto-oncogene
carcinosarcoma malignant sarcoma
cystadenocarcinoma  medullary scirrhous
cystadenoma metastasis serous  
dermoid microinvasion stage 
desmoid mixed tumor tumor  
desmoplasia mucinous tumor associated antigen
differentiation neoplasia tumor marker
DNA repair gene occult malignancy tumor specific antigen
dysplasia oncogene tumor suppressor gene

Regarding "oncogenes" and "tumor suppressor genes:"

Oncogenes are a general class of genes that, when mutated, permit or induce uncontrolled cellular proliferation and malignant change.

Oncogenes are further classified as either protooncogenes OR tumor suppressor genes (anti-oncogenes). Protooncogenes encode proteins that stimulate DNA synthesis and cell division, including peptide growth factors and their cellular membrane receptors; second-messenger cascade proteins, which transmit information from cell membrane to nucleus; and nuclear transcription factors, which control gene expression by binding to DNA. Conversion of a protooncogene to an oncogene by amplification, translocation, or point mutation can lead to unrestrained cellular proliferation and malignant change. Only 1 copy (allele) of a protooncogene need undergo mutation to induce tumor formation. Protooncogenes are not involved in inherited cancer syndromes, with the exception of the RET protooncogene in multiple endocrine neoplasia.

Tumor suppressor genes (antioncogenes), which encode proteins that normally serve to restrain cell proliferation, can be inactivated by point mutation, deletion, or loss of expression. An inherited mutation in 1 copy of a tumor suppressor gene is the basis of most familial predispositions to cancer. Malignant cellular proliferation does not occur until the remaining, functional copy of the gene is inactivated by mutation or by deletion of part or all of its chromosome. In a person born with two normal copies of a tumor suppressor gene, both must be inactivated by mutation before tumor formation occurs. BRCA1 and BRCA2, which predispose to familial early-onset breast cancer and ovarian cancer, are tumor suppressor genes.


Absolutely critical information you must know to practice medicine is in bold font.
Important information that will be needed for routine patient care is in regular font.
Information about less common diseases that you may encounter in clinical practice and that will probably appear on examinations is in italics

  1. Compare and contrast gross, microscopic features and mode of spread:
  2. List the general cytologic, biochemical, antigenic, metabolic, karyotypic, and molecular genetic changes found in neoplastic cells.

  3. List the most common sites of origin of the following neoplasms
  4. Compare and contrast grading vs. staging of neoplastic disease, in terms of general principles and clinical significance

  5. Cite local and general mechanisms which are believed to affect the rate of tumor growth.

  6. Discuss how tumor growth rates are evaluated with mitotic rate and proliferation markers.

  7. List four major pathways by which neoplasms spread.

  8. Discuss metastasis of malignant neoplasms, in terms of:
    • molecular genetics
    • cellular adhesion
    • mechanisms of invasion of extracellular matrix
    • mechanisms of vascular dissemination and homing of tumor cells
    • tissues and organs in which metastases are common or uncommon.

  9. Describe carcinogenesis, initiation, neoplastic progression and sequence of gene mutations.

  10. Evaluate critically the role of each of the following in the development of human cancer, general significance and at least one neoplasm associated with each:
    • physical agents
    • genetic diseases
    • chemical agents
    • genetic predispositions
    • infectious agents
    • hormones
    • chronic inflammatory conditions
    • immune response
    • benign tumors

  11. Match the following agents or conditions the neoplasms with which it is related:
    • cyclophosphamide
    • hepatitis B and C viruses
    • circumcision
    • Epstein-Barr virus
    • tobacco 
    • human papillomavirus (HPV)
    • smoked fish
    • human immunodeficiency virus (HIV)
    • aniline dyes
    • human T cell leukemia virus type 1
    • aflatoxin
    • ultraviolet radiation
    • asbestos
    • ionizing radiation 
    • benzene
    • radon
    • 2-naphthylamine
    • heredity 
    • vinyl chloride
    • hormonal imbalance
    • Helicobacter pylori

  12. Discuss precancerous lesions in terms of definition, etiology, pathogenesis and growth kinetics and give common examples.

  13. Describe and understand the metaplasia --> dysplasia --> carcinoma-in-situ --> invasive carcinoma sequence.

  14. Discuss, compare, and contrast the following theories of origin of neoplasia:
    • multifactorial theory
    • immune-surveillance dysfunction
    • genetic mutations
    • monoclonal origin
    • viral oncogene
    • field origin
    • epigenetic theory

  15. List the DNA viruses which have been linked to tumor formation in man and animals.

  16. List the connections between viruses and tumors in terms of:
    • epidemiology
    • interactions of virus proteins with cell regulatory proteins
    • modulation of the host immune system

  17. Contrast the mechanisms of neoplasm formation by DNA viruses and RNA viruses.

  18. Discuss the relationship between protooncogenes and oncogenes, as well as the relationship between cellular oncogenes and viral oncogenes.

  19. Compare and contrast protooncogenes and tumor suppressor genes, in terms of genotypic vs. phenotypic expression.

  20. Explain the concept of recessive cancer genes.

  21. Describe the clinical features of following cancer-susceptibility syndromes:

  22. Discuss the following chromosomal translocations describing the mechanism of oncogenesis and associated neoplasms:
    • t(8;14)
    • t(9;22)

  23. Discuss chemical carcinogenesis in terms of dose dependency.

  24. Explain the carcinogenic effect of irradiation.

  25. Cite evidence for estrogens as carcinogens.

  26. Describe the body's immune system and its role in the development of neoplasms including anti-tumor immunity and immunologic surveillance

  27. Discuss the different types of escape mechanisms utilized by neoplasms to evade the immunosurveillance system of an immunocompetent host.

  28. Discuss tumor specific antigens and tumor related antigens, in terms of:
    • presence on normal cells
    • importance in anti-tumor immunity

  29. Compare and contrast tumors transmitted by dominant inheritance and recessive inheritance. Give examples of each.

  30. Compare and contrast acquired cancer-causing genetic mutations and germline cancer-causing genetic mutations. Give examples of each.

  31. Describe the indications, advantages, and disadvantages of diagnostic procedures and laboratory tests used to diagnose, and monitor the progression of neoplasms:
    • conventional radiography
    • frozen section
    • computed tomography (CT)
    • immunohistochemistry
    • magnetic resonance imaging (MRI) 
    • electron microscopy
    • ultrasound
    • exfoliative cytology
    • nuclear medicine
    • fine needle aspiration (FNA) cytology
    • positron emission tomography (PET)
    • tumor markers
    • needle biopsy
    • flow cytometry
    • open biopsy
    • genetic analysis

  32. List the secretions or other fluids examined by cytology for diagnosis of malignancy.

  33. List the organs in which cytology plays an important role in cancer case findings.

  34. For both males and females, list in descending order:
    • five most common cancers
    • five most common causes of cancer death

  35. List the relative incidence and mortality of cancer for each sex and decade of age.

  36. Discuss the mechanism by which neoplasms produce each of the following, listing neoplasms that are commonly associated with each effect:
    • anemia
    • ischemia
    • endocrine effects
    • jaundice
    • episodic flushing  
    • leukocytosis
    • fever
    • leukopenia
    • fracture
    • masculinization
    • hypercalcemia
    • obesity
    • infection
    • obstruction
    • itching
    • pain
    • thrombophlebitis

  37. Match each of the following public health measures with neoplasms in which it may be used.
    • cytological examination
    • routine x-rays
    • avoidance of ionizing radiation
    • self-examination
    • avoidance of excessive sunlight
    • routine laboratory studies
    • avoidance of tobacco
    • routine physical examination
    • cancer genetic studies

  38. Match each of these tumor markers with the neoplasm(s) with which it is associated:
    • human chorionic gonadotrophin (HCG)
    • calcitonin
    • catecholamines
    • α-fetoprotein (AFP)

  39. Contrast the effects of benign and malignant tumors on the host.

  40. List the common signs and symptoms of malignancy.

  41. List the common causes of death from cancer.



Key Vocabulary Terms

accuracy monitoring test screening test
analytic variables postanalytic variables sensitivity
clinical pathology preanalytic variables specificity
coefficient of variation  precision standard deviation
false negative predictive value true negative
false positive prevalence true positive
incidence reference range turnaround time


  1. Describe the activities of clinical pathologists, (laboratory medicine).

  2. Describe the appropriate uses of clinical laboratories.

  3. Calculate sensitivity and specificity from a 2 X 2 table.

  4. Compare and contrast precision and accuracy.

  5. Discuss development of "normal range", including reference group method, prognosis/treatment derived, threshold value, and therapeutic drug reference range.

  6. Compare and contrast preanalytical, analytical, and postanalytical variables in laboratory testing, and give examples of each.

  7. Discuss the effects of sample handling on laboratory results, including turnaround time, type of tube used for blood collection, timing of collection, transport, and storage.



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