3 types of cytosolic fibers in the cytoskeleton?
The cytoskeleton consists of 3 types of cytosolic fibers: microfilaments (actin filaments), intermediate filaments, and microtubules.
Adjuvant, neoadjuvant, induction, consolidation, maintenance, first line, second line chemotherapy?
Adjuvant chemo is given to destroy leftover (microscopic) cancer that may be present after the known tumor is removed by surgery (primary therapy). Is given to prevent a possible cancer recurrence. If known disease is left behind at surgery, further treatment is technically not adjuvant. Neoadjuvant chemo is given prior to the surgical procedure in an attempt to shrink the tumor so that the surgical procedure may not have to be as extensive. Induction chemo is given to induce a remission. The term is commonly used in the treatment of acute leukemias. Consolidation chemo (also called intensification therapy) is given once remission is achieved. The goal is to sustain the remission. The term is commonly used in the treatment of acute leukemias. Maintenance chemo is chemo given in lower doses to assist in prolonging a remission. Is used only for certain types of cancer, MC ALLs and APLs. First line chemo (also called standard therapy) is chemo that has been determined to have the best probability of treating a given cancer. Second line chemo (also called salvage therapy) is chemo that is given if a disease has not responded or has recurred after first line chemo.
Describe intracytoplasmic inclusions found in sarcoidosis.
ASTEROID BODIES: Small, eosinophilic, star-shaped structures. SCHAUMANN BODIES: Calcium and protein inclusions inside of Langerhans giant cells as part of a granuloma; basophilic, concentrically laminated, calcified, rounded chonchoidal structures. If numerous or large, they may be extruded into extracellular space.
CALCIUM OXALATE CRYSTALS: may serve as a nidus for deposition of calcium leading to formation of Schaumann bodies. HAMAZAKI-WESENBERG BODIES: PAS-positive inclusions which may be giant lysosomes containing lipofuscin or hemolipofuscin. Although H-W bodies may occur as inclusions, they are also found extracellularly in the sinusoids of lymph nodes in sarcoidosis. Are oval or spindle-shaped, range up to several microns in size, and appear yellow-brown with H&E. Stain with acid-fast and silver stains (may be mistaken for fungus). ADDITIONAL POINTS: Schaumann bodies and calcium oxalate crystals are birefringent and must not be mistaken for foreign (exogenous) material.
Although intracytoplasmic inclusions are a frequent finding in sarcoidosis, they may also be found in other granulomatous diseases, including TB, nontuberculous mycobacterial infection, leprosy, hypersensitivity pneumonitis, berylliosis, fungal infection, Crohn’s disease, foreign body granuloma (however, foreign material in sarcoidal granulomata does not exclude the diagnosis of sarcoidosis).
Examples of cell-specific intermediate filaments?
Major types of intermediate filaments are distinguished by their cell-specific expression: CKs in epithelial cells, GFAP in glial cells, desmin in skeletal/visceral/certain vascular smooth muscle cells, vimentin in cells of mesenchymal origin, and neurofilaments in neurons.
GFAP and vimentin in astroglial cells.
GFAP and vimentin form intermediate filaments in astroglial cells and modulate their motility and shape. In particular, vimentin filaments are present at early developmental stages, while GFAP filaments are characteristic of differentiated and mature brain astrocytes.
Oncotype DX (Genomic Health Inc.), MammaPrint (Agendia), Mammostrat (Clarient). How do they work?
Oncotype DX is a real-time RT-PCR assay measuring RNA expression in 16 cancer-related genes and five reference genes, using paraffin-embedded tissue. Results are given as a recurrence score between 0 and 100, which are translated as low risk (a score of 18 or lower), medium risk (19 to 30), or high risk (31 or above). MammaPrint microarray measures expression of 70 genes in fresh or FFPE tissue; it categorizes patients as either high risk, (a so-called poor signature), or low risk (a so-called good signature) for recurrence. Mammostrat is an IHC test measuring five markers: p53, HTF9C, CEACAM5, NDRG1, and SLC7A5. The results are combined into a quantitative risk index: low, moderate, and high. Oncotype DX and MammaPrint are send-out tests, with TATs of 10-14 days, while results from the IHC-based Mammostrat, also a send-out test, are available to local pathologists within 48-72 hours. As of 3/2014, only MammaPrint has FDA clearance.
Solid organ transplant-associated acute graft-versus-host disease.
The occurrence of an immunologically mediated and injurious set of reactions by cells genetically disparate to their host is known as GVHD. Acute GVHD is most commonly associated with hematopoietic stem cell transplantation (35-50%). With solid organs, the highest occurrence is with small intestine transplantation (5.6%), followed by liver transplantation (1-2%). Cases have also been reported after kidney, pancreas, heart, lung, and multivisceral transplants. The clinical presentation of solid organ transplant-associated GVHD includes skin rash (red to violet maculopapular rashes which may coalesce) and diarrhea (green, mucoid, watery, sometimes bloody), and most cases quickly advance to become a multisystem disease affecting bone marrow and other nontransplanted solid organs. The patient often dies of bleeding and infection from bone marrow failure. The mortality rate of solid organ transplant-associated GVHD ranges from 30 to >75%. In the rare reported cases after lung or pancreas transplant, the mortality rate reaches 100%. The diagnosis is based on clinical symptoms, characteristic histopathologic findings on biopsied tissues, and evidence of microchimerism of donor T cells. Solid organ transplant-associated GVHD often occurs between 2-6 weeks after liver transplantation, although this is variable with late-onset cases seen in other transplant settings.
Small intestinal bacterial overgrowth.
SIBO is a common cause of chronic diarrhea and malabsorption. It results from colonization of the proximal small bowel by gram-negative aerobic and anaerobic bacteria that are normally restricted to the colon or, less frequently, from overgrowth of oropharyngeal flora. A predisposition to SIBO exists in diverse conditions where there is altered anatomy from prior surgery (eg, blind loop syndrome) or stricture or where there is impaired gut motility and prolonged orocecal transit time. The gold standard for diagnosis is a small intestinal aspirate culture showing growth of at least 10^5 colony-forming units of bacteria per milliliter (CFU/mL) of duodenal or jejunal fluid. Cultures of small-bowel mucosal biopsies can be substituted when there are inadequate luminal secretions. Histologically, mild or moderate villous blunting is the only change seen, and this is seen in only ~50% of symptomatic pts with the culture diagnosis of SIBO. The high rate of histologically “normal” biopsies does not negate the pathogenic role of bacterial overgrowth in symptomatic pts. It has been hypothesized that excess colonic flora within the small intestine can impede fat digestion by deconjugating bile acids and hindering the formation of micelles, that these bacteria can induce vitamin B12 deficiency, and that they can result in osmotic or secretory diarrhea through the production of organic acids. All of these proposed mechanisms can coexist with microscopically health small bowel mucosa.
AKA asteroid bodies. The in vivo formation of intensely eosinophilic material around microorganisms or biologically intert substances.
What are general categories of disorders that show Mendelian inheritance and non-Mendelian inheritance?
Mendelian inheritance: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive.
Non-Mendelian inheritance: multifactorial disorders, disorders affected by genomic imprinting, trinucleotide repeat disorders, mitochondrial disorders, and chromosomal instability/breakage disorders.
What is desmin?
An intermediate filament protein that is characteristically found in cardiac, smooth, and striated muscle cells. The clones D33, DEB-5, and DER-11, are the 3 most used monoclonal antibodies to desmin.
What is the epithelial-mesenchymal transition (EMT)?
A phenomenon whereby epithelial cells dissemble their junctional structures, start expressing mesenchymal proteins, remodel their extracellular matrix, and become migratory. The EMT is observed in both physiologic (embryogenesis) and pathologic (carcinogenesis) settings.
How has the grading system for GI tract NECs changed from the 2004 to 2010 WHO?
The 2010 grading system emphasizes mitotic count and Ki-67 index (It is recommended that these parameters are assessed over 50 hpf.). Grade 1 NET: < or =2% Ki-67 index. Grade 2 NET: 2-20 mitoses/10 hpf and/or 3-20% Ki-67 index. Grade 3 NET: >20 mitoses/10 hpf and/or >20% Ki-67 index. Most notably, NE lesions of the GI tract are graded and staged separately in the 2010 system. The 2004 system incorporated metastasis, gross invasion, size, vascular invasion, mitotic activity and proliferative rate, which resulted in a change in terminology from “tumor” to “carcinoma” based on the presence of metastasis for tumors of identical grade. Now, NE “tumors” represent G1 and G2 lesions, regardless of the stage.
The granularity of oncocytes is due to __.
The granularity of oncocytes is due to an excessive amount of mitochondria, resulting in an abundant acidophilic, granular cytoplasm.
The diffuse cytoplasmic positivity of chromophobe renal cell carcinoma with Hale’s colloidal iron stain is due to __.
The diffuse cytoplasmic positivity of chromophobe renal cell carcinoma with Hale’s colloidal iron stain is due to staining of acid mucopolysaccharides.
In AJCC (7th edition) staging of lung cancer: What are the tumor sizes for T1a, T1b, T2a, T2b, and T3? Direct tumor invasion into an adjacent ipsilateral lobe (i.e., invasion across a fissure) is classified as __. Multiple tumor nodules in the same lobe are classified as __. Multiple tumor nodules in the same lung but a different lobe are classified as __. Malignant pleural and pericardial effusions are classified as __. Separate tumor nodules in the contralateral lung are classified as __. Distant metastases are classified as __.
T1a is ≤2.0 cm in size, T1b is >2.0 to ≤3.0 cm in size, T2a is >3.0 to ≤5.0 cm in size, T2b is >5.0 to ≤7.0 cm in size, T3 is >7 cm in size. Direct tumor invasion into an adjacent ipsilateral lobe (i.e., invasion across a fissure) is classified as T2a. Multiple tumor nodules in the same lobe are classified as T3. Multiple tumor nodules in the same lung but a different lobe are classified as T4. Malignant pleural and pericardial effusions are classified as M1a. Separate tumor nodules in the contralateral lung are classified as M1a. Distant metastases are classified as M1b.
In AJCC (7th edition) staging of lung cancer, what are definitions of PL0, PL1, PL2, and PL3?
PL0 is defined as tumor located within the lung parenchyma or only superficially invading in the pleural connective tissue, but not beyond the elastic layer of the visceral pleura (i.e., falls short of completely traversing the elastic layer). PL1 is defined as tumor invading into the visceral pleura beyond the elastic layer, and PL2 is defined as tumor invading to the visceral pleural surface. Either PL1 or PL2 status allows classification of the primary tumor as T2. PL3 is defined as tumor invading into the parietal pleura or the chest wall, and PL3 status categorizes the tumor as T3.
Clear cell meningiomas are classified as WHO grade __.
Clear cell meningioma is a variant of meningiomas classified as WHO grade II for its propensity to recur. Similar to atypical meningiomas, recurrence can be local or distant and may have a mortality rate of up to 23%.
What are sentinel events?
A sentinel event is an unexpected occurrence involving patient death or serious physical or psychological injury. Serious injury specifically includes loss of limb or function. The phrase “or the risk thereof” includes any process variation for which a recurrence would carry a significant chance of a serious adverse outcome. In addition to patient events which fall within this definition, The Joint Commission has specifically defined the following events as Sentinel: Unanticipated death or major permanent loss of function unrelated to the natural course of the patient’s illness or underlying condition. Suicide of any inpatient or within 72 hours of discharge. Unanticipated death of a full-term infant. Abduction of an individual receiving care, treatment, or services. Discharge of an infant to the wrong family. Sexual abuse/assault including rape of any patient receiving care, treatment, or services. Hemolytic transfusion reaction involving administration of blood or blood products having major blood group incompatibilities. Invasive procedure, including surgery, on the wrong patient, wrong site, or wrong procedure. Unintended retention of a foreign object in an individual after surgery or invasive procedure. Severe neonatal hyperbilirubinemia (bilirubin >30 mg/dL). Prolonged fluoroscopy with cumulative dose >1500 rads to a single field or any delivery of radiotherapy to the wrong body region or >25% above the planned radiotherapy dose. Rape, assault (leading to death or permanent loss of function), or homicide of a staff member, licensed independent practitioner, visitor, or vendor while on site at the healthcare organization.
Define: Advance care plan.
Advance care plan: An instructional document voluntarily executed by a competent patient authorizing the provision, withholding, or withdrawal of health care if the patient’s condition is irreversible and he/she lacks capacity. It may also be used to appoint a health care agent and/or to add special instructions or limitations including organ/tissue donation.
Define: Advance directive.
Advance directive: An individual instruction (oral or written) or a written statement voluntarily executed by a competent patient relating to the subsequent provision of health care for the individual.
Define: Agent, in the context of Advance Directives.
Agent: An individual designated in an Advance Directive to make a health care decision for the individual granting the power. The Agent may make any health care decision the patient could have made for him/herself while competent.
Define: Appointment of a health care agent.
Appointment of a health care agent: A written document voluntarily executed by a competent patient appointing another person (“Agent”) to make health care decisions in the event the patient lacks capacity.
Define: Capacity, in the context of Advance Directives.
Capacity: An individual’s ability to understand the significant benefits, risks, and alternatives to proposed health care and to make and communicate a health care decision.
Define: Designated physician, in the context of Advance Directives.
Designated physician: A physician designated by an individual or the individual’s agent, guardian, or surrogate, to have primary responsibility for the individual’s health care or, in the absence of a designation or if the designated physician is not reasonably available, a physician who undertakes such responsibility.
Define: Durable power of attorney for health care.
Durable power of attorney for health care: A written document voluntarily executed by a competent patient appointing another person (“Agent”) to make health care decisions in the event the patient lacks capacity. While still a valid Advance Directive, TN law encourages use of the Appointment of a Health Care Agent.
Define: Living will.
Living will: A limited instructional document voluntarily executed by a competent patient authorizing the provision, withholding, or withdrawal of health care if the patient is in a terminal condition or permanently unconscious. While still a valid Advance Directive, TN law encourages use of an Advance Care Plan.
Define: Physician orders for scope of treatment (“POST”), in the context of Advance Directives.
Physician orders for scope of treatment (“POST”): A standardized form containing orders written by a physician who has personally examined a patient regarding his/her preferences for end of life care. The POST complements but does not replace an Advance Directive.
Define: Surrogate, in the context of Advance Directives.
Surrogate: An individual, other than a patient’s Agent or guardian, authorized to make a health care dicision for the patient. TN law recognizes a Patient-Designated Surrogate and a Physician-Designated Surrogate. Patient-Designated Surrogate: Patient’s oral or written designation, given directly to the Designated Physician, of an individual to make a health care decision for the patient. Physician-Designated Surrogate: An individual recognized by law to make health care decisions for a person who lacks capacity and who has not appointed an Agent or designated a Surrogate and does not have a guardian, or whose Agent, Surrogate, or guardian is not reasonably available.
If a test has high sensitivity, a negative result means ___.
If a test has high specificity, a positive result means ___.
If a test has high sensitivity, a negative result is used to rule out the disease/there is a low probability of disease.
If a test has high specificity, a positive result is used to rule in the disease/there is a high probability of disease.
SPIN and SNOUT are commonly used mnemonics which says: A highly SPecific test, when Positive, rules IN disease (SP-P-IN), and a highly ‘SeNsitive’ test, when Negative rules OUT disease (SN-N-OUT).
A small positive predictive value indicates that many of the positive results from this testing procedure are ___. Thus it will be necessary to follow up any positive result with a more reliable test to obtain a more accurate assessment. Nevertheless, such a test may be useful if it is inexpensive and convenient.
A small positive predictive value indicates that many of the positive results from this testing procedure are false positives. Thus it will be necessary to follow up any positive result with a more reliable test to obtain a more accurate assessment. Nevertheless, such a test may be useful if it is inexpensive and convenient.
What is lipofuscin?
Lipofuscin is the name given to finely granular yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered one of the aging or “wear-and-tear”pigments, found in the liver, kidney, heart muscle, adrenals, nerve cells, and ganglion cells. It is specifically arranged around the nucleus, and is a type of lipochrome. Lipochrome is a form of pigment associated with amber and gold tones in the eyes of mammals. The term carotenoid is sometimes considered a synonym of lipochrome, but that term usually refers to specific molecules, while lipochrome refers to accumulations of varied molecules. Lipofuscin appears to be the product of the oxidation of unsaturated fatty acids, and may be symptomatic of membrane damage, or damage to mitochondria and lysosomes. Aside from a large lipid content, lipofuscin is known to contain sugars and metals, including mercury, aluminum, iron, copper, and zinc.
What is ceroid?
A golden, waxy (from cera, Latin for wax; eidos, Greek for form), alcohol-insoluble pigment. It is acid-fast and sudanophilic. It is a complex of oxidized polyunsaturated lipid pigment(s) (?polymer of oxidized lipid and protein?) resulting from the peroxidation of unsaturated lipids that are similar or identical to lipofuscin. Ceroid accumulates in macrophages of the heart, (cirrhotic) liver, GI tract, nervous system, muscles, and brain in the elderly and is thus termed “wear and tear” pigment.
IHC antibodies are classified as Class __ medical devices.
In 1998, the US FDA classified IHC antibodies as analyte-specific reagents. Within this defined group, most antibodies are deemed Class I medical devices, exempting them from premarket FDA notification, which entails providing evidence of safety and efficacy. A few IHC markers, including ER and PR, are Class II medical devices, meaning they have associated guidance documents. The rationale behind Class I categorization is that IHC results are just one part of the final diagnostic interpretation by the pathologist. The flexibility provided by such a designation can be credited with rapid development of new antibodies, but lends itself to divergent practices and inconsistent results among labs. CLSI guidelines require that individual labs validate each new antibody; however, the details are left to the laboratory director. Predictive markers, such as HER2/neu, whose results bear prognostic and treatment implications, have been the first target of standardization. In 12/2006, ASCO and CAP introduced guidelines for HER2/neu testing, which were published in 1/2007. Additional measures toward enhanced quality include guidelines for validation of hormone receptor assays (2010), and in 6/2009, the CAP LAP added new checklist items that probe documentation of new antibody validation and verification of new lots of antibody.
What does a screening mammogram consist of?
Screening mammograms consist of 2 views (mediolateral oblique view and craniocaudal view) of each breast for 4 images. In radiology, the standard convention is to label the view with the x-ray source first and the film location second. In an MLO view, the x-ray beam enters medially and the film is located laterally. In a CC view, the x-ray enters cranially and the film is located caudally. The MLO view is not orthogonal to the CC view but oriented 30 to 60 degrees to it. The oblique view is used to increase the quality of the image in the UOQ, which is where most breast cancers arise. In general, the film should be placed as close as possible to the lesion being examined to make the image as clear as possible. Screening is performed annually on asymptomatic women starting at 40 to 50 years.
In mammography, what is the difference between a mass and a density?
A mass is a lesion that is seen on more than one view. A density is seen only on one view. To determine whether an area of concern is a mass or a density, the radiologist will estimate or measure the distance of the lesion seen on one view from the nipple and look for a possible lesion the same distance from the nipple on the other view. The density may be a mass that is visible only on one view because of overlying shadows that obscure it on the other view. It could also be a summation shadow from normal structures that appear denser along one axis. If there is an apparent density, the radiology may order additional views to confirm or refute the presence of a mass or obtain short-term, followup imaging, depending on the level of suspicion.
What does a diagnostic mammogram consist of?
Diagnostic mammograms are used to confirm or refute the presence of a mass, parenchymal distortion, asymmetry, or microcalcification seen on a screening mammogram; to further characterize an abnormality seen on screening mammogram; to diagnose a patient with breast symptoms, such as a palpable mass, abnormal nipple discharge, or noncyclical localized pain; and to localize a nonpalpable mass. A diagnostic mammogram is more detailed than a screening mammogram but examines only the area of interest identified on the screening mammogram or by the physician. There are many different views that are considered for a diagnostic mammogram. One of the most common views ordered as part of a diagnostic mammogram is a spot compression view, with or without magnification.
What is the BIRADS score?
All mammograms are classified into 1 of 7 major categories to facilitate follow-up and treatment. This is called a Breast Imaging and Reporting Database System (BIRADS) score. It was created by the American College of Radiology to force radiologists to categorize mammograms into understandable categories, avoid unclear reports, reduce variability in reports, and standardize workup. (BIRADS score, interpretation, risk of cancer, and follow-up.) 0, needs more imaging, unknown, additional imaging. 1, normal, 0%, routine. 2, benign finding, 0%, routine. 3, probably benign, < or = 2%, 6-mo repeat or biopsy. 4a, suspicious, >2 to or = 10 to or = 90%, biopsy. 5, highly suspicious, > or = 90%, biopsy. 6, biopsy-proven cancer, 100%, treatment.
How is microvesicular steatosis defined?
In cellular pathology, steatosis (also called fatty change, fatty degeneration or adipose degeneration) is the process describing the abnormal retention of lipids within a cell. It reflects an impairment of the normal processes of synthesis and elimination of triglyceride fat. Excess lipid accumulates in vesicles that displace the cytoplasm. Microvesicular steatosis is defined by multiple small lipid droplets (liposomes) in the hepatocyte without nuclear dislocation, as compared with macrovesicular steatosis, which is usually composed of a large cytoplasmic lipid vacuole that displaces the nucleus peripherally.
What is peliosis?
The Greek word “pelios” means “discoloured by extravasated blood,” or “livid”. Peliosis is a pathological entity characterized by the gross appearance of multiple cyst-like, blood-filled cavities within parenchymatous organs. The classical pathoanatomical concept is based upon the opinion that peliosis exclusively develops in organs belonging to the mononuclear phagocytic system (liver, spleen, bone marrow, and lymph nodes). However, a paucity of studies indicates that other organs such as lungs, parathyroid glands, and kidneys may be affected too. Since the disease may culminate in spontaneous rupture of the affected organ and thus may mimic a violent death at autopsy, peliosis is far more than just another morphological curiosity.
Ki-67 protein and antibodies against it.
Antigen KI-67, also known as Ki-67 or MKI67 is a protein that in humans is encoded by the MKI67 gene. It is a nuclear protein that is associated with and may be necessary for cellular proliferation. Furthermore it is associated with ribosomal RNA transcription. Inactivation of antigen KI-67 leads to inhibition of ribosomal RNA synthesis. The Ki-67 protein (also known as MKI67) is a cellular marker for proliferation. It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0). Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. Ki67 and MIB-1 monoclonal antibodies are directed against different epitopes of the same proliferation-related antigen. The Ki-67 protein was originally defined by the prototype monoclonal antibody Ki-67; The name is derived from the city of origin (Kiel, Germany) and the number of the original clone in the 96-well plate.Whereas Ki67 works only on frozen sections, MIB1 may be used also on fixed sections. MIB-1 is used in clinical applications to determine the Ki-67 labeling index. One of its primary advantages over the original Ki-67 antibody (and the reason why it has essentially supplanted the original antibody for clinical use) is that it can be used on formalin-fixed paraffin-embedded sections, after heat-mediated antigen retrieval.
What is ecchordosis physaliphora?
A notochordal remnant usually found incidentally at autopsy. It is a small gelatinous hamartomatous lesion located in the intradural space and attached by a pedicle to the clivus. It has similar histological features of chordoma but does not destroy bone or invade tissues.
What are the four main autopsy techniques/methods for evisceration? What are some advantages and disadvantages for each?
Rokitansky technique (in situ dissection): Advantageous because it allows one to open and examine organs without removing them from the body, a condition somestimes mandated by a restrictive autopsy consent or severe time limitations. Virchow technique (removing organs one by one): Excellent for demonstrating pathologic changes in organs but sacrifices interorgan relationships and makes interpretation of regional disease more difficult. Ghon technique (en bloc-removing organs in regional and functional groups): Excellent preservation of the interrelationships of the various organs, their regional lymphatic drainage, and their vasculature. Is easier to perform without and assistant compared with the Letulle technique; however, the Ghon technique transects the esophagus and aorta at the diaphragm, a disadvantage in cases of aortic dissection, aneurysm, esophageal varices, or neoplasm. Letulle technique (en masse-removing all organ blocks as a single group): Excellent preservation of the interrelationships of the various organs, their regional lymphatic drainage, and their vasculature. Allows the most rapid preparation of the body for removal to the mortuary and, because there is less dissection within the confines of the body cavity, probably offers greater safety to the prosector. However, may be difficult to perform without an assistant and takes longer compared with the Virchow method.
Analysis of postmortem glucose, enzymes, and drugs shows significant differences between specimens taken from the right side of the heart, the left side of the heart, and the peripheral blood vessels. ___ or ___ specimens best approximate the antemortem values.
Analysis of postmortem glucose, enzymes, and drugs shows significant differences between specimens taken from the right side of the heart, the left side of the heart, and the peripheral blood vessels. Peripheral venous or peripheral arterial specimens best approximate the antemortem values.
What are the primary and secondary sites for obtaining blood for autopsy toxicologic studies?
The best samples for toxicologic analysis are obtained from the femoral artery or vein. The subclavian vessels serve as secondary collection sites.
What are filter blots obtained from autopsy cases used for?
300 uL of blood may be spotted on specialized filter papers. Several samples can be collected, dried overnight, wrapped in plastic wrap, and stored at -20 C. Such samples are useful for genotype and protein analyses available through commercial and academic laboratories. An example would be using tandem mass spectrometry on postmortem blood spotted on filter paper to detect specific enzyme defects. Filter blots of liver tissue, bile, and vitreous humor may also be used.
What is the best fluid for postmortem chemical analysis?
Vitreous humor provides one of the best samples for postmortem chemical analysis because it comes from a closed space and postmortem values often approximate the antemortem levels. Vitrous humor may not become contaminated after embalming, so it may still provide material for analysis in these cases. However, a sample of the embalming fluid should also be submitted to the laboratory as a control.
Postmortem determination of premortem glucose levels. Discuss.
Postmortem serum glucose decreases rapidly because of glycolysis, preventing detection of antemortem hypoglycemia. Even elevated levels of postmortem blood glucose require careful interpretation. Death from asphyxia, cerebral hemorrhage, CHF, electrocution, or terminal CPR may increase postmortem peripheral vascular glucose and falsely indicate hyperglycemia. Glycosuria, ketonuria, or elevated serum acetone can help confirm diabetic ketoacidosis. Blood samples taken from the right atrium or IVC may have a high glucose content because of glycogenolysis in the liver and subsequent diffusion of glucose into adjacent vessels. Thus, a low glucose level in blood from the right atrium and a positive test for ketones may support starvation. Vitreous humor provides more reliable data for determination of antemortem hyperglycemia. Glycolysis reduces the postmortem concentration of vitreous humor glucose; however, values greater than 200 mg/dL usually indicate that the decedent had uncontrolled diabetes.
List the four general patterns of postmortem vitreous humor concentrations of sodium, chloride, potassium, urea nitrogen, and creatinine, which allow some assessment of the terminal metabolic condition of the decedent.
- Dehydration pattern: Increased sodium and chloride concentrations. Moderate elevation of urea nitrogen levels. 2. Uremic pattern: No substantial increase in sodium and chloride values. Urea nitrogen and creatinine levels increased. 3. Low-salt pattern: Low sodium and chloride concentrations. Relatively low potassium level (20 mEq/L or 20 mmol/L).
What is the most stable postmortem chemistry blood constituent?
Urea nitrogen is perhaps the most stable blood constituent after death as it approximates premortem levels even after moderate decomposition. Urea nitrogen also remains stable in CSF, vitreous humor (even after embalming), and synovial fluid. In addition to their use in assessing renal function, urea nitrogen concentrations aid in the interpretation of hypernatremia. Similarly, creatinine levels in the blood remain stable after death, as they do in CSF and vitreous humor, making creatinine a valid postmortem marker of nitrogen retention and renal function.
What is the FNCLCC grading system for soft tissue sarcomas?
The 2 most widely used grading systems are the FNCLCC (Federation Nationale des Centre de Lutte Contre la Cancer) and NIH systems. The CAP recommends the French system over the NIH system for reasons of ease of use/reproducibility and perhaps slightly superior performance. The FNCLCC grade is determined by 3 parameters: differentiation (histology specific), mitotic activity, and extent of necrosis. Each parameter is scored: differentiation 1-3, mitotic activity 1-3, and necrosis 0-2. The scores are summed to designate grade: score of 2 or 3 = grade 1, score of 4 or 5 = grade 2, and score of 6-8 = grade 3. The tumor differentiation score is histology specific and is generally scored as follows: Score 1 is for sarcomas closely resembling normal, mature mesenchymal tissue. Score 2 is for sarcomas of definite histologic type. Score 3 is for synovial sarcomas, embryonal sarcomas, undifferentiated sarcomas, and sarcomas of unknown/doubtful tumor type.
WHO 2010 classification of neuroendocrine tumors in GI tract and pancreas.
Low grade (G1): 20 mitoses/10 HPF, OR >20% Ki-67 index.
How are neuroendocrine tumors graded in GI tract and pancreas, and for lung and thymus?
For GI tract and pancreas, WHO 2010 classification: Low grade (G1): 20 mitoses/10 HPF, OR >20% Ki-67 index. For lung and thymus, WHO 2004 classification: Low grade (G1): 10 mitoses/10 HPF.
What are the equations for calculating sensitivity and specificity?
Sensitivity is the probability that a person having a disease will be correctly identified (positive in disease). Sensitivity = TP/(TP+FN). Specificity is the probability that a person who does not have a disease will be correctly identified. Specificity = TN/(TN+FP).
What are the definitions of sensitivity and specificity in statistics?
Sensitivity is the probability that a person having a disease will be correctly identified (positive in disease). Sensitivity = TP/(TP+FN). Specificity is the probability that a person who does not have a disease will be correctly identified. Specificity = TN/(TN+FP).
How are positive predictive value and negative predictive value calculated?
Positive predictive value is the probability that an individual who tests positive has the disease. PPV = TP/(TP+FP). Negative predictive value is the probability that an individual who tests negative does not have the disease. NPV = TN/(TN+FN).
What are the definitions of positive predictive value and negative predictive value?
Positive predictive value is the probability that an individual who tests positive has the disease. PPV = TP/(TP+FP). Negative predictive value is the probability that an individual who tests negative does not have the disease. NPV = TN/(TN+FN).
How are incidence and prevalence calculated?
Incidence is the number of new cases of disease in the population over a given time. Incidence is generally calculated by: number of new cases/susceptible population. Prevalence is the total number of cases in a population at a given time. Prevalence is calculated by: TP+FN/(TP+FP+TN+FN) but generally calculated by: incidence x duration of disease.
What is the relationship among the statistical variables: sensitivity, false-negative ratio, and negative predictive value?
Sn and FNR are inversely related: Sn=1-FNR. Therefore, increasing the sensitivity of a test decreases the FNR (the number of false negatives) and increases the NPV.
What is the relationship among the statistical variables: specificity, false-positive ratio, and positive predictive value?
Sp and FPR are inversely related: Sp=1-FPR. Therefore, increasing the specificity of a test decreases the FPR (the number of false positives) and increases the PPV.
Why is a screening test more useful in a population where the disease is highly prevalent?
As prevalence increases, PPV increases, and clinical usefulness if reflected in PPV.
High-sensitivity tests are better suited for ___, while high-specificity tests are better suited for ___.
High-sensitivity tests are better suited for screening purposes, while high-specificity tests are better suited for confirmatory testing.
In the WHO classification and grading of CNS tumors, what are the entities under “astrocytic tumors” and what are the grades?
Pilocytic astrocytoma (PA) - WHO grade I. Pilomyxoid astrocytoma (PMA) - WHO grade II. Subependymal giant cell astrocytoma (SEGA) - WHO grade I. Pleomorphic xanthoastrocytoma (PXA) - WHO grade II. Diffuse (infiltrating) astrocytomas (DA) - WHO grade II: Fibrillary astrocytoma; Gemistocytic astrocytoma; Protoplasmic astrocytoma. Anaplastic astrocytoma (AA) - WHO grade III. Glioblastoma multiforme (GBM) - WHO grade IV: Giant cell GBM; Gliosarcoma. Gliomatosis cerebri - WHO grade III.
In the WHO classification and grading of CNS tumors, what are the entities under “oligodendroglial tumors” and what are the grades?
Oligodendroglioma - WHO grade II. Anaplastic oligodendroglioma - WHO grade III.
In the WHO classification and grading of CNS tumors, what are the entities under “oligoastrocytic tumors” and what are the grades?
Oligoastrocytoma - WHO grade II. Anaplastic oligoastrocytoma - WHO grade III.
In the WHO classification and grading of CNS tumors, what are the entities under “ependymal tumors” and what are the grades?
Subependymoma - WHO grade I. Myxopapillary ependymoma - WHO grade I. Ependymoma - WHO grade II: Cellular; Papillary; Clear cell; Tanycytic. Anaplastic ependymoma - WHO grade III.
In the WHO classification and grading of CNS tumors, what are the entities under “choroid plexus tumors” and what are the grades?
Choroid plexus papilloma - WHO grade I. Atypical choroid plexus papilloma - WHO grade II. Choroid plexus carcinoma - WHO grade III.
In the WHO classification and grading of CNS tumors, what are the entities under “other neuroepithelial tumors” and what are the grades?
Astroblastoma (AB) - not yet graded. Angiocentric glioma (AG) - WHO grade I. Chordoid glioma of the third ventricle (CG) - WHO grade II.
In the WHO classification and grading of CNS tumors, what are the entities under “neuronal and mixed neuronal-glial tumors” and what are the grades?
Dysplastic cerebellar gangliocytoma (DCG) (Lhermitte-Duclos disease) - WHO grade I. Desmoplastic infantile astrocytoma/desmoplastic infantile ganglioglioma (DIA/DIG) - WHO grade I. Dysembryoplastic neuroepithelial tumor (DNT) - WHO grade I. Gangliocytoma - WHO grade I. Ganglioglioma (GG) - WHO grade I. Anaplastic GG - WHO grade III. Central neurocytoma - WHO grade II. Extraventricular neurocytoma - WHO grade II. Cerebellar liponeurocytoma - WHO grade II. Papillary glioneuronal tumor (PGNT) - WHO grade I. Rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) - WHO grade I. Paraganglioma - WHO grade I.
In the WHO classification and grading of CNS tumors, what are the entities under “tumors of the pineal region” and what are the grades?
Pineocytoma - WHO grade I. Pineal parenchymal tumor of intermediate differentiation (PPTID) - WHO grade II and III. Papillary tumor of the pineal region (PTPR) - WHO grade II and III. Pineoblastoma - WHO grade IV.
In the WHO classification and grading of CNS tumors, what are the entities under “embryonal tumors” and what are the grades?
Medulloblastoma - WHO grade IV: Desmoplastic/nodular medulloblastoma; Medulloblastoma with extensive nodularity; Anaplastic medulloblastoma; Large cell medulloblastoma. CNS PNET - WHO grade IV: CNS neuroblastoma; CNS ganglioneuroblastoma; Medulloepithelioma; Ependymoblastoma. Atypical teratoid/rhabdoid tumor (AT/RT) - WHO grade IV.
In the WHO classification and grading of CNS tumors, what are the entities under “tumors of cranial and paraspinal nerves” and what are the grades?
Schwannoma (neurilemoma, neurinomas) - WHO grade I: Cellular; Plexiform; Melanotic. Neurofibroma - WHO grade I: Plexiform. Perineurioma, NOS - WHO grade I, II, or III: Perineurioma (intraneural) - WHO grade I; Malignant perineurioma - WHO grade III. MPNST - WHO grade II or III: Epithelioid MPNST; MPNST with mesenchymal differentiation; Melanotic MPNST; MPNST with glandular differentiation.
In the WHO classification and grading of CNS tumors, what are the subtypes of meningioma and what are the grades?
Benign meningiomas (WHO grade I): Meningothelial; Fibrous (fibroblastic); Transitional (mixed); Psammomatous; Angiomatous; Microcystic; Secretory; Lymphoplasmacyte-rich; Metaplastic. Atypical meningiomas (WHO grade II): Chordoid; Clear cell; Atypical. Anaplastic (malignant) meningiomas (WHO grade III): Papillary; Rhabdoid; Anaplastic (malignant).
In the WHO classification and grading of CNS tumors, what are the entities that are WHO grade IV?
GBM: Giant cell GBM; Gliosarcoma. Pineoblastoma. All of the “embryonal tumors” category: (Medulloblastoma: Desmoplastic/nodular medulloblastoma; Medulloblastoma with extensive nodularity; Anaplastic medulloblastoma; Large cell medulloblastoma. CNS PNET: CNS neuroblastoma; CNS ganglioneuroblastoma; Medulloepithelioma; Ependymoblastoma. Atypical teratoid/rhabdoid tumor (AT/RT)).
What are the top 3 most common metastatic tumors to the oral cavity in males and females?
Males: lung > kidney > prostate. Females: breast > genital organs > kidney.
Screening tests require high (sensitivity/specificity) so that no case is missed. Confirmatory tests require high (sensitivity/specificity) to be certain of the diagnosis. Receiver operator characteristic (ROC) curves plot the ___ rate versus the ___ rate and graphically present the range of sensitivities and specificities at all test cutoffs. If two tests are compared, the more accurate test is closer to the upper left-hand corner of the ROC curve.
Screening tests require high sensitivity so that no case is missed. Confirmatory tests require high specificity to be certain of the diagnosis.
Receiver operator characteristic (ROC) curves plot the true-positive rate versus the false-positive rate and graphically present the range of sensitivities and specificities at all test cutoffs. If two tests are compared, the more accurate test is closer to the upper left-hand corner of the ROC curve.
What is Bayes’ theorem?
Bayes’ theorem uses information about test characteristics (sensitivity and specificity) and disease prevalence (pretest probability) to obtain the posttest probability of disease, given a positive test. Similarly, it can be used to determine the posttest probability of no disease, given a negative test.
Evidence-based medicine is a process by which ___.
Evidence-based medicine is a process by which medical decisions can be made by using as many objective tools as possible; it integrates the most current and the best medical evidence with clinical expertise and patient preferences.
What is a critical value?
A critical value (also known as a panic or alert value) is a laboratory result that may represent a life-threatening situation that may not otherwise be readily detectable and therefore requires rapid communication with a health care provider who can provide necessary medical interventions. The speedy communication of such results is required by federal law and regulatory agencies, and The Joint Commission has made it one of its National Patient Safety Goals.
Describe sensitivity and specificity.
Sensitivity is the ability of a test to detect disease and is expressed as the proportion of persons with disease in whom the test is positive. It may also be thought of as the probability of a positive test given a true disease state as defined by the gold standard. A test that is 90% sensitive will give positive results in 90% of diseased patients (TP) and negative results in 10% of diseased patients (FN). Specificity is the ability to detect the absence of disease and is expressed as the proportion of persons without disease in whom the test is negative. It may be thought of as the probability of a negative test, given no disease as defined by the gold standard. Thus a test that is 90% specific will give negative results in 90% of patients without disease (TN) and positive results in 10% of patients without disease (FP). A test with a higher sensitivity identifies a greater proportion of persons with disease, and a test with a higher specificity excludes a greater proportion of persons without disease.
How are sensitivity and specificity related to lab test value cutoffs?
Sensitivity and specificity are measures of the diagnostic accuracy of a test; they are indicators of a test’s ability to distinguish between disease and absence of disease at a chosen cutoff. Sensitivity and specificity therefore are not fixed characteristics of a test and must be calculated from a different 2 × 2 table for each cutoff chosen. When a test cutoff is altered, an inverse relationship between sensitivity and specificity is noted, and a trade-off between the numbers of FP and FN results can be seen. Altering a cutoff changes a test’s sensitivity and specificity because it relates to overlapping normal and abnormal patient distributions along the test value continuum. For tests where high values indicate disease, lowering the cutoff (i.e., moving the cutoff line to the left) will lead to more diseased patients being classified as abnormal. Thus, changing the cutoff increases sensitivity. If the cutoff is moved to the point where the diseased curve croses the x axis, then all diseased persons will have a positive test, and the sensitivity will be 100%. However, increased sensitivity is associated with decreased specificity, and the number of nondiseased persons with a positive test (FPs) increases as the cutoff is moved downwards. If the cutoff is raised (i.e., the cutoff line is moved to the right), more nondiseased patients are classified correctly, and specificity increases. If the cutoff is moved to the point where the non-diseased curve crosses the x axis, then all nondiseased persons will have a negative test, and the specificity will be 100%. However, this will be accompanied by concomitant decreased sensitivity and additional FN results.
How does prevalence affect PPV and NPV?
The higher the prevalence, or pre-test probability, the higher the posttest probability, or predictive value of a positive test. For a disease with low prevalence, even a test with high sensitivity and specificity will yield a low predictive value because most positive test results will be FPs. On the other hand, the predictive value of a negative test decreases as the prevalence of disease increases. However, the effect is small, especially when sensitivity and specificity are high. Prevalence influences the predictive value of a negative test to a noticeable extent only when the starting prevalence is high.
Sensitivity and specificity influence the predictive value. Further, the predictive value of a positive test increases with increasing ___ and improved ___. (Sensitivity/Specificity) has the biggest impact on the predictive value of a positive test, whereas (sensitivity/specificity) determines the predictive value of a negative test.
Sensitivity and specificity influence the predictive value. Further, the predictive value of a positive test increases with increasing prevalence and improved accuracy (i.e., sensitivity and specificity). Specificity has the biggest impact on the predictive value of a positive test, whereas sensitivity determines the predictive value of a negative test.
What is Bayes’ theorem? Why is it used?
Clinical assessment and diagnostic tests are inherently flawed, and these uncertainties must be considered when medical decisions are made. Sensitivity and specificity represent a summary of the diagnostic accuracy of a test, but they do not indicate the probability that an individual patient has a disease after the test result is obtained. It would be useful to know how the test result changes the probability of disease (i.e., posttest probability), given certain assay characteristics and disease prevalence (i.e., pretest probability). Alternatively, it is useful to know that a condition can be ruled out given a negative test if the probability of disease after a negative test is very low. To determine this information, one must consider predictive value theory, also known as Bayes’ theorem. Bayes’ theorem describes the relationship between posttest and pretest probability of disease or no disease based on the sensitivity and specificity of the test. The theorem applies population data and test characteristics directly to an individual subject, and calculates the probability of the presence of a disease for a particular patient after a positive test result is obtained and, alternatively, the probability of the absence of disease given a negative test. Although sensitivity and specificity describe a test at a particular cutoff value (e.g., what percent of diseased patients have abnormal results?), the predictive value describes the state of the patient (e.g., how likely is it that a given patient’s positive result indicates disease?).
What are likelihood ratios?
The LR is a convenient measure that combines sensitivity and specificity into a single number. Similar to these other measures of test accuracy (sensitivity and specificity), the LR is an assessment of test performance, and not of disease status, in the patient being tested. Two likelihood ratios are known: the likelihood ratio of a positive test (LR+) and the likelihood ratio of a negative test (LR−). LR+ is the ratio of two probabilities: the probability of a positive test result when disease is present (TP) divided by the probability of the same test result when disease is absent (FP). In other words, the calculation gives the likelihood that a test result will occur in a diseased patient as opposed to a healthy one. Alternatively, the LR− is the probability that an individual with the disease will have a negative test divided by the probability that an individual without the disease will have a negative test. Additional advantages of the LR are that it is not influenced by disease prevalence, and the LR can be calculated for multiple test cutoffs. Thus, a result’s degree of abnormality can be taken into account and medical decisions can be made at a point where fewer FN and FP results are seen.
What are the formulas for likelihood ratios?
LR = (probability of test result in persons with no disease) / (probability of same result in persons with no disease). LR+ = (sensitivity) / (1-specificity). LR- = (1-sensitivity) / (specificity).
What is a Fagan nomogram?
Calculating out posttest probability can be cumbersome. The Fagan nomogram is a convenient graphic tool that uses a logarithmic scale to determine posttest probability, given the LR at a specified cutoff and the pretest probability. The pretest probability (e.g., clinical suspicion, prevalence) is plotted on the y-axis on the left-hand side, the posttest probability on the right-hand side, and the LR between them. When the Fagan nomogram is used, the pretest probability is located on the left axis, and a line is drawn from that point to the LR+ value. Then this line is further extended until it intersects the right axis at the posttest probability.
What is evidence-based medicine?
In contrast to traditional approaches, EBM is a process by which medical decisions can be made by using as many objective tools as possible. This, in turn, can help reduce the uncertainty of medical decision making. EBM is a systematic practice that integrates the most current and best evidence with clinical expertise and patient preferences when making medical decisions. It places emphasis on critically analyzing information from the literature and developing knowledge for medical practice. Also, it encourages the cultivation of continuous learning and sharing of medical knowledge at all levels of training from medical student to attending physician.
The things that we measure, count, or otherwise delineate are termed variables because the values they can assume vary. Variables are usually considered to fall into what 3 scales?
Nominal scale is where a variable can take on only a limited number of values, usually called categories (or characters). Examples of nominal variables are gender (male or female) and risk factors (e.g., smoker or nonsmoker). Ordinal scale is where the variable takes on specific values that have some inherent order such as magnitude but without equivalent distances between categories (e.g., trace amount, 1+, 2+, etc. of protein in urine). Interval scale is where a variable takes on values in a quantitative range with defined differences between points. It is conventional to treat most numeric laboratory measurements as continuous variables, even though they may be reported as discrete values (e.g., glucose values of 123 or 124 mg/dL, but not 123.857… mg/dL).
What are: standard deviation, coefficient of variation, and confidence interval?
Standard deviation (SD) is the square root of the sum of the squared differences of each data point from the mean divided by n−1 for samples (divided by n for populations). The SD is a predictable measure of dispersion from the mean in a Gaussian normal distribution. Coefficient of variation (CV) is the standard deviation of a set of data points divided by the mean result expressed as a percentage or as a decimal fraction. Confidence interval (CI) is the interval that is computed to include a parameter such as the mean with a stated probability (e.g., commonly 90%, 95%, 99%) that the true value falls into that interval.
What is Gaussian (normal) distribution?
Gaussian (normal) distribution is a spread of data in which elements are distributed symmetrically around the mean with most values close to the center. It is explicitly described by a mathematical equation and so is a parametric distribution. Random scatter or random selection of a population often results in a Gaussian normal distribution. This type of distribution is often a criterion for completely valid application of many parametric tests.
What are parametric and nonparametric statistics?
Parametric statistics are statistical measures that are calculated based on the assumption that the data points follow a Gaussian distribution and include parameters such as mean, variance, and standard deviation. Nonparametric statistics are based on rank or order of data and include parameters such as median.
What are significance level and statistical power?
Significance level (p or α) is the probability that a difference between groups occurred by chance alone, by convention set at less than .05. Statistical power (1−β) is the probability that a difference between groups will be detected by the study, generally set at least to 80%.
In statistics, what are independent and dependent variables?
Statistical questions are often posed in terms of input versus output, cause and effect, or correlation between two or more variables. The input or cause is considered an independent variable because it is already determined and so is not influenced by other factors. Examples of independent variables are age, gender, temperature, and time. In contrast, dependent variables are those things that might change in response to the independent variable. Examples of dependent variables are blood glucose concentration, enzyme activities, and the presence or absence of malignancy. Of course we can change our thinking and switch which is the independent and which is the dependent variable if the experimental question changes.
In a Gaussian (normal) distribution, __% of data points will fall within +/- 1 SD, __% will fall within 2 +/- SD, and __% will fall within 3 +/- SD.
In a Gaussian (normal) distribution, 68.2% of data points will fall within +/- 1 SD, 95.5% will fall within 2 +/- SD, and 99.7% will fall within 3 +/- SD.
What is proficiency testing?
Proficiency testing (or external quality assessment) consists of evaluation of method performance by comparison of results versus those of other laboratories for the same set of samples. PT providers circulate a set of samples among a group of laboratories. Each laboratory includes the PT samples along with patient samples in the usual assay process. Results for the PT samples are reported to the PT provider for evaluation. PT allows a laboratory to verify that its results are consistent with those of other laboratories using the same or similar methods for an analyte, and to verify that it is using a method in conformance with the manufacturer’s specifications.
What is quality management?
Quality management (QM) refers to the overall process used to ensure that laboratory results meet the requirements for health care services to patients. Laboratories are required to develop procedures to monitor and ensure quality in all aspects of laboratory services. A QM program defines data-based metrics or indicators that are monitored at regular recurring intervals to provide information on the adequacy of all influences on laboratory quality. A QM program is an accreditation requirement, and good documentation of the metrics, the review process, and the improvements made is necessary.
Define the following terms applicable to pathology informatics: computer, hardware, software, file, folder, bit, operating system.
A computer is a device that follows instructions to work with electronic data based on user input. Hardware refers to the physical components of an information system. Software refers to programs (which are essentially sets of instructions) that allow computers or other devices to perform tasks. hardware, software, file, folder, bit, operating system. A file is a collection of data identified by a specific name and grouped in relation to a specific purpose. The two main types are applications (also referred to as “executable” files) and data files (e.g., image, text/document, sound). A folder (or directory) simply refers to a collection of files. A bit (derived from “binary digit”) is the basic unit of digital information, and a byte, the most common unit of measurement used, almost always refers to 8 bits. ASCII (American Standard Code for Information Interchange) is the standard dictionary for combinations of bits that represent the common letters, numbers, and symbols by which characters are represented on a computer screen or paper printout. The operating system of a device, whether a computer or an analyzer, refers to a set of programs responsible for the management and coordination of activities and the sharing of resources. In the case of a computer, the operating system acts as a host for application programs.
Define the following terms applicable to pathology informatics: network, client, server, internet, World Wide Web, HTML.
A network is an interconnected group of computers that share information and resources, and as it pertains to the laboratory, the term refers to the ability to obtain orders from and send results to other information systems. Most computers need a card or adapter to connect to the network, and Ethernet is the most common type of networking standard. Networking often involves a client and a server environment. The client is the workstation with which the end user interacts and the server runs applications and maintains databases. The different client types are “thin” and “thick” or “fat”; the difference between the two is that in the former, all application logic executes on the client server, whereas in the latter, the client performs the bulk of any data processing operations itself. The Internet refers to a worldwide, publicly accessible series of interconnected computer networks. Data are transmitted by packet switching using the standard Internet protocol (IP). The World Wide Web (WWW) refers to a hypertext-based data system that uses the Internet as its transportation (hypertext = text on a computer that will lead the user to other related information on demand). The language used is most commonly hypertext markup language (HTML), which specifies the appearance of a web page when interpreted by a web browser.
What are the 5 components of a computer network?
A network is an interconnected group of computers that share information and resources, and as it pertains to the laboratory, the term refers to the ability to obtain orders from and send results to other information systems. The 5 components are: modem, router, server, client, and firewall. A modem (“modulator-demodulator”) modulates an analog carrier signal to encode digital information. A router routes and forwards information. A server accepts connections to service requests by sending back responses. A client is an application or system that accesses the server. A firewall is a device and/or software that inspects network traffic passing through it, and denies or permits passage based on a set of rules.
How can costs be described?
Costs can be described in different ways, depending on how they relate to laboratory operations (direct/indirect), change with test volume (variable/fixed), pertain to staffing (salary/nonsalary), or are associated with the useful life of supplies or equipment (operating/capital). Cost per reportable result is a key indicator.
Why is inpatient laboratory testing considered to be a “cost center,” while outpatient laboratory testing is considered to be a “revenue center?”
Inpatient laboratory testing charges are usually not reimbursed directly; they are considered part of a per diem rate (i.e., general hospital daily room reimbursement rate) or a case rate, such as diagnosis-related group rate (i.e., set rate for the entire hospital stay, regardless of actual length of stay). Thus, inpatient laboratory testing is usually considered a “cost center.” In contrast, outpatient laboratory charges are reimbursed directly; therefore, outpatient testing is usually considered a “revenue center.”
What does it mean for an entity/hospital to be “not-for-profit?”
Most U.S. hospitals are tax exempt, not-for-profit entities. Though “not-for-profit” suggests that no profit is made, it actually means that profits are not distributed to owners or shareholders; instead, profits are reinvested in the organization. Historically, not-for-profit status led hospital administrators to be less profit conscious than counterparts in other businesses. However, today’s hospitals are having a difficult time just covering operating costs, given dwindling reimbursement and increasing supply and labor costs. With scarce money left for capital reinvestment in equipment, buildings, facilities, and technology, hospitals are aggressively seeking new ways to produce a profit to invest for the future.
What are direct costs and indirect costs?
Direct costs are expenses that can easily be traced directly to an end product. In the laboratory setting, the end product is a billable test. Examples are reagents, consumables, and testing staff/hands-on technologist time. In contrast, indirect costs are not directly related to a billable test, but are necessary for its production. Indirect costs are often referred to as overhead. Examples are proficiency testing, analyzers, analyzer service, management staff, rent, and utility expenses.
What are variable costs and fixed costs?
Variable costs change proportionately with the volume of tests. As test volume grows, so do reagent costs. If the reagent cost per test is $1.00, when 1000 tests are performed, the reagent cost is $1000; when 20,000 tests are performed, the reagent cost is $20,000. Fixed costs do not change with the volume of tests performed. Fixed costs include PT, analyzers, analyzer services, testing staff, management staff, and rent. If a laboratory pays $5000 per month to rent its space, this expense remains the same if the laboratory produces 1000 or 20,000 tests per month. Because fixed costs do not vary with activity, the goal is to produce as much as possible from fixed costs to achieve economies of scale.
What is the fixed cost per activity?
Fixed costs do not change with the volume of tests performed (rent is an example). Because fixed costs do not vary with activity, the goal is to produce as much as possible from fixed costs to achieve economies of scale. The more that is produced, the lower is the fixed cost per activity. If a laboratory produced 1000 tests, the fixed cost per test is $5.00; with 20,000 tests, the fixed cost per test falls to $0.25. Note that even some fixed costs have a variable component. For example, if an instrument’s capacity is 20,000 tests per month and the volume increases beyond that, another instrument will have to be purchased, increasing the fixed costs per test. Fixed costs that change with increments of volume are called step costs.
What are salary costs?
Salary costs need to be looked at differently from nonsalary costs because salary costs have fringe benefits associated with them (Social Security, health insurance, tuition reimbursement, pension plans, and life insurance). Salary expenses account for approximately 60%–80% of the laboratory budget. Because salary expenses are generally fixed, it is important to strive for economies of scale. The hourly pay or salaried wage of an employee is not the entire cost of employment. Fringe benefits can represent an additional 16%–28% expense above the base salary. Costs are also associated with the recruitment, interview, and selection process. Once an employee is hired, orientation, training, and ongoing growth and development costs are incurred.
What are operating costs and how do they relate to capital items?
Operating costs are the expenses incurred to produce a product or service. Many items have only a one-time use, and once used the item has no further value. Examples of one-time operating costs include reagents, electricity, disposable pipets, and the salary expense in the production of a test. Other items, such as analytic equipment, computers, and the physical plant, have a useful life greater than one production cycle. These items are capital items. To qualify as a capital item, the item must meet three criteria: Time, price, and purpose. To meet the time criterion, the item must have a useful life of longer than 1 year. The institution must designate a minimum dollar amount, usually $1000–$5000, that qualifies an item as capital. The purpose of acquiring capital items is usually to replace older equipment with safer and more efficient models, or to add new equipment to support new products or services. With time, capital equipment loses its value. The annual loss of a capital item’s value is called depreciation and is an annual expense that is deducted from the revenue of a business.
What are some ways that the cost of producing a test can be derived?
Microcosting determines the total direct labor and supply costs of producing a test. When microcosting a test, it is important to consider how a test is performed because labor and supply costs vary according to workflow and laboratory policy for quality control and repeats. The cost per reportable result (CPRR) distributes the total direct costs of a run over the patient “reportable” results for that run. Testing efficiency is defined as the total reportable patient results/total test results. Thus, the more repeats and controls are performed, the lower is the efficiency, and the higher is the CPRR. The incremental cost is the cost of producing one additional test that, typically, does not require additional salary or capital. Incremental costing is especially useful when one is trying to determine whether additional outreach work is profitable or not. The fully loaded cost for a test is the sum of direct and indirect costs. Make versus buy decisions should be based on the fully loaded cost to produce the test compared with the price offered by a commercial or reference laboratory (but TAT, methods, and reliability of the potential alternative supplier also need to be considered). The contribution margin is the balance remaining after the fully loaded costs are deducted from the price charged for a test.
What is the total cost of ownership for a laboratory?
TCO is the life cycle cost of its capital assets. It focuses attention on the sum of all costs of owning and maintaining all assets for a specific service or product, as opposed to the initial capital or operating costs. In the laboratory, TCO includes acquisition, setup (construction, training), support (ordering supplies, dealing with back orders), ongoing maintenance (scheduled and unscheduled downtime), service, and operating expenses (reagents, controls, repeat testing, inventory control, proficiency testing, testing personnel, supervisory personnel) of a specific workbench and its associated testing instrumentation. TCO is useful in considering make versus buy decisions, but determining an accurate TCO can be very difficult.
What are: gross patient revenue, net patient revenue, deductions from revenue, and contractural adjustments?
Gross patient revenue consists of the total charges at a facility’s full-established rates (list price) for provision of inpatient and outpatient care before deductions from revenue are applied. Net patient revenue is the gross inpatient and outpatient revenue minus all related deductions. Deductions from revenue include contractual adjustments, provision for bad debts, charity care, and other adjustments and allowances that reduce gross patient revenue. Contractual adjustments account for the difference between billings at full-established rates and amounts received or receivable from third-party payers under formal contract agreements. For example, if the list price of a test is $10 but the contracted payment from the insurance company is $6, the adjustment is $4. If all deductions and contractual allowances are correct, net patient revenue should equal cash collected, or $6 in the above example.
What are the 2 main categories that private health insurance falls into?
Indemnity and managed care. Indemnity plans, also known as fee-for-service, are traditional insurance plans that give patients absolute freedom to choose their physicians and medical facilities. Insurance companies usually require the beneficiaries to fulfill a yearly deductible, usually between $300 and $500 per person per year. After the deductible is fulfilled, the insurance company pays a certain coinsurance rate of the usual and customary charge (UCC). The UCC (or fee schedule) is set by the payer and is usually less than the actual billed charge, in which case the patient may be responsible for the balance. managed care was introduced in 1973 with the passage of the Health Maintenance Organization Act. This Act encouraged and funded the development of health maintenance organizations (HMOs) as a strategy to contain the rising cost of health care. HMOs utilized managed care features that coupled health care reimbursement with delivery of service and allowed payers significant economic control over how, where, and what services were delivered.
What are capitation agreements?
Capitation agreements pay the service provider (e.g., physician) a fixed dollar amount per member per month (PMPM). From this amount, the provider agrees to cover all care for plan members. For example, if a laboratory signs a capitation agreement to accept $1.50 PMPM for the outpatient testing needs of 2000 HMO members, the laboratory receives $3000 per month, and $36,000 per year. If it costs the laboratory more than $36,000/year to provide the services, it realizes a financial loss; if it costs less than $36,000, it realizes a profit. In a capitation testing agreement, a laboratory assumes the risk of spending more than it is paid. One key to managing this risk is gaining access to test utilization of plan members and accurately assessing laboratory costs.
What is Medicare?
Medicare is federal health insurance for individuals age 65 and older, individuals who are permanently disabled, and those with end-stage renal disease who have met the specified waiting period. Medicare was established in 1965 by Title XVIII of the Social Security Act. It is administered by CMS, a division of HHS. Coverage is provided under Parts A, B, C, and D. For a clinical laboratory to qualify for Medicare/Medicaid reimbursement, the laboratory must maintain Clinical Laboratory Improvement Act of 1988 certification.
What is Medicare Part A, Part B, Part C, and Part D?
Medicare Part A covers inpatient hospitalization, hospice care, skilled nursing care, and home health care. Coverage is automatic for those who are eligible. Medicare Part B covers outpatient laboratory tests, physician professional services, and other medical services and devices. Coverage is not automatic. Eligible beneficiaries must enroll for Part B coverage and pay premiums. Beneficiaries must pay an annual deductible and a 20% copayment for all Part B services, except for clinical laboratory testing, which is covered in full, provided certain conditions are met. The Part B fee schedule plays an important role in reimbursement because it is a baseline that nongovernment payers use to establish their own rates. For example, a private insurance company may set its fee schedule at 110% of the Part B fee schedule. Medicare Part C (also known as Medicare Advantage) is an alternative to the traditional Part B fee-for-service program. It is designed to reduce patient “out of pocket” costs by providing services through health maintenance organizations and other managed care service models. Medicare Part D provides prescription drug coverage.
What is Medicaid?
Medicaid is a Federal program that offers health care coverage for select low-income families. It was authorized in 1965 as a Federal/State-sponsored program designed to pay medical costs for certain families with low income or inadequate resources. Eligibility extends to people who are aged, blind, or disabled, and those in families with dependent children. Although Medicaid is a Federal program, it is under the jurisdiction of each individual state. This means that each state determines who is eligible, the range of health services offered, and how they are reimbursed. It is a common misconception that Medicaid covers health care costs for all low-income persons. Medicaid does not provide paid medical assistance to every single poor person. To receive medical assistance, a person must meet eligibility requirements.
What are the Healthcare Common Procedure Coding System and International Classification of Diseases 9th Revision with Clinical Modification used for?
To be paid, a medical claim must document the patient’s medical condition (or diagnosis) and must list the services (or tests) provided. This information is conveyed via a standardized coding system, recognized by all government and private payers: HCPCS codes describe the test or service and ICD-9-CM codes describe the patient’s condition or diagnosis. These coding standards allow data to be accurately communicated among physicians, patients, and third-party payers.
What are the 2 levels of Healthcare Common Procedure Coding System codes?
HCPCS was developed in 1983 and consists of two levels of codes. Level I is the Current Procedural Terminology coding system and is used to identify nearly all clinical laboratory tests and most medical services. CPT codes are assigned by the American Medical Association and are reviewed and updated annually to keep current with changes in technology and medical practice. Each CPT code consists of five digits and a description of the test or service. Level II HCPCS codes are assigned by CMS. CPT does not contain all the codes needed to report services or to describe special circumstances that may apply to Medicare. CMS developed this second level of codes to fill the gap. HCPCS Level II codes begin with a single letter (A through V) followed by four digits. These codes are updated annually by CMS. These codes allow CMS to assign different criteria for reimbursement, based on why a test is ordered.
The ICD-9 was originally developed by ___ as a classification system for ___.
The ICD-9 was originally developed by the World Health Organization (WHO) as a classification system for reporting of mortality and morbidity statistics by physicians throughout the world. The ICD-9-CM is a U.S. clinically modified revision of the WHO’s ICD-9. This modification is maintained and updated by the National Center for Health Statistics. These modifications assist health care providers to index patient records, retrieve case data for clinical studies, and submit claims for health care services.
What are diagnosis-related-groups?
DRGs make up a patient classification system that is used to reimburse inpatient (Part A) hospital costs for Medicare patients. Although the costs associated with inpatient clinical laboratory tests are included in the DRG, it does not cover physician services (Part B). After a Medicare patient has been discharged from the hospital, the patient’s medical record is reviewed by health information management coders and is assigned appropriate ICD-9-CM and HCPCS codes for one or more diagnoses and procedures for the inpatient stay. These codes along with the patient’s demographic information are grouped by decision trees (this process is computerized) into a specific DRG. Currently, more than 500 DRGs are used. CMS assigns a weight to each DRG based on the severity of the diagnoses, the types of procedures performed, the number of laboratory tests, the volume and type of drugs administered, and the presence of complications or comorbidity conditions. CMS assigns each hospital a specific rate that is calculated on the basis of the type of facility (community hospital vs. teaching hospital), the setting (urban vs. rural), and the location (West Coast vs. Midwest). The CMS-assigned rate for the DRG is multiplied by the hospital’s assigned rate to determine reimbursement for the hospital stay. This amount is payment-in-full for the inpatient hospitalization. If it costs the hospital more than the reimbursed amount to treat the patient, the hospital must absorb the cost. The patient cannot be billed for any nonreimbursed Part A services.
What is an advanced beneficiary notice?
Under certain conditions, Medicare does not pay for laboratory tests. If a laboratory expects Medicare to deny payment because a test does not meet medical necessity requirements, it must inform the patient before the service is provided. An advanced beneficiary notice (ABN) is used to document that the beneficiary was told the test might not be covered by Medicare, the reason(s) for the possible denial, and the decision by the patient to pay for the test if Medicare does not reimburse or to refuse the test entirely.
What is the CMS 72-hour rule?
An important consideration for hospitals that have laboratories that perform outpatient testing on Medicare patients is the 72-hour rule. This rule states that a hospital cannot bill an outpatient (Part B) claim for laboratory tests performed within 72 hours of an inpatient admission. Outpatient testing that is performed 72 hours before the admission must be included with the inpatient claim and is reimbursed according to the assigned DRG for that stay. Hospital laboratories must identify outpatient Medicare services that are affected by this rule and must make sure they are not billed separately. A nonhospital independent laboratory is not subject to the 72-hour rule. Thus preadmission tests performed 3 days before hospitalization are not reimbursed if performed in the admitting hospital’s laboratory but are reimbursed if done in an independent laboratory.
Financial accounting is a system used to report business information to external entities such as the Internal Revenue Service or its stockholders. Generally accepted accounting principles are used to standardize this information. Balance sheet, income statement, and statement of cash flows are the financial statements most commonly used to assess an organization’s financial position. What are the balance sheet, income statement, and statement of cash flows?
The balance sheet is the statement of an organization’s financial position at a specific point in time, usually generated at the end of an organization’s fiscal year or at the end of the calendar year. It records the organization’s assets (what it owns), its liabilities (what it owes), and its equity or net worth (what is left after subtracting what it owes from what it owns). The income statement, also known as the statement of profit and loss, summarizes the organization’s revenues and expenses over an accounting period, usually quarterly or annually. The income statement records all of a laboratory’s gross patient revenue, less allowances for a given period, and deducts the expenses for that same period to arrive at net income before taxes. The statement of cash flows shows the amount of cash generated by an organization over a period of time. Cash outflows (cash paid out) are subtracted from cash inflows (cash received) to calculate the net change in cash for the period.
In evaluating a capital project, payback period, breakeven point, and return on investment are often considered. Define.
The payback period is the length of time required for an investment’s net revenue to cover the cost of the initial investment. Many institutions want to see a payback in 3 years or less. Once the initial investment is recovered, net revenue (Revenue − Expense) from this investment represents a profit to the organization. The breakeven point of a capital project is reached when the volume of sales is such that total revenue equals total costs (fixed and variable), and therefore profit is zero. Before the breakeven point is reached, the project is operating at a loss; after it is reached, the project is realizing a profit. The rate of return on an investment (ROI) for a capital project is the ratio of net income it generates to the total investment of the project. ROI is a standard for evaluating how wisely management uses its capital dollars.
The payback period and return on investment calculations do not consider the time value of money (they assume that the value of future cash flows remains constant). To address this shortcoming, the net present value and internal rate of return are used. Define.
The NPV calculation is used to determine whether a project’s cash flows (i.e., cash it generates in the future) are sufficient to repay the original investment, taking into account that money loses value over time. Thus, cash received in the future has to be discounted (i.e., the value has to be reduced) to determine how much it is worth in today’s dollars. The discount rate is usually the inflation rate (if no money was borrowed to finance the project) or the interest rate on a loan used to fund the project. When the NPV is a positive number, the project will generate enough cash to pay for the original investment. When the NPV is a negative number, the project cost is not recouped and/or the future cash flows are not sufficient to cover the interest costs for borrowing the money. The internal rate of return (IRR) also discounts cash flow into today’s value. It determines the actual rate of return that the investment earns. The IRR is the discount rate at which the present value of a capital project’s expected cash inflows equals the present value of its costs, or in other words, when the NPV equals zero. Identifying a project’s IRR is necessary to ensure that its rate is higher than the cost of the capital borrowed for the project. The higher the IRR, the faster the project pays for itself.
The terms “optimization,” “validation,” and “verification” relate to the processes that the laboratory must undertake before new diagnostic, prognostic, or predictive immunohistochemistry markers are used for clinical and/or pathologic decisionmaking. Describe “validation” and “verification.”
The terms validation and verification are often used interchangeably. Strictly speaking, however, they apply to different types of IHC assays. Verification is the process by which a laboratory determines that an assay performs according to the recommendations set forth by the manufacturer as documented in the product insert at the assay conditions determined during the optimization step. This process typically involves staining a number of cases that span the range of expected protein expression of the chosen protein, including a number of anticipated negative cases. The laboratory director should determine the number of cases that should be stained. Generally speaking, the number of cases to be tested during verification is larger if the results are to be used solely as a prognostic or predictive marker (for example, HER2). Also, if the number of result categories is higher than simply positive or negative, the number of verification cases should be high enough to test each of the result categories. Validation is a more rigorous process than verification and applies only to laboratory-developed tests (LDTs). Since the test performance characteristics of an LDT have not, by definition, been determined by a manufacturer, a greater number of cases must be stained to confirm that the LDT performs according to the specifications determined by the laboratory director. Both verification and validation require that the results of the assay be compared to a known standard. These standards include cases stained in the same laboratory using a previously validated/verified assay, cases stained in another laboratory with a validated/verified assay, comparison with another technique, or comparison of results with findings reported in the peer-reviewed literature.
The terms “optimization,” “validation,” and “verification” relate to the processes that the laboratory must undertake before new diagnostic, prognostic, or predictive immunohistochemistry markers are used for clinical and/or pathologic decisionmaking. Describe “optimization.”
Optimization is the process by which the laboratory director determines provisional assay conditions, which most often involves staining a single case or small number of cases at varying assay conditions. The conditions that may be altered include primary antibody dilution, duration of primary antibody incubation, type of antigen retrieval buffer, antigen retrieval time, and detection chemistry, with the goal of having the strongest positive reaction with appropriate subcellular localization and minimizing, or eliminating, any reaction in cells that do not contain the protein in question. Once the laboratory director is satisfied that the quality of staining is optimal, as assessed in this small number of cases, one can proceed to the validation or verification step.
List in vitro assays that have been developed for identification of cancer stem cells.
Animal studies are relatively expensive and require considerable time and effort. Therefore, numerous in vitro assays have been developed for CSC identification, which include: The colony forming cell assay/colony assay (assesses the ability of progenitor cells, in a semisolid media or methylcellulose-based culture media, to proliferate and differentiate into colonies in response to cytokine stimulation). The microsphere assay/sphere assay (assesses the ability of neural stem cells from mammalian adult brain subventricular neural cells to grow in serum-free medium in nonadherent conditions, forming sphere-shaped cell aggregates). The “side population” (SP) assay by Hoechst labeling (measures upregulation of P-glycoprotein by CSCs, which leads to active transport of some dyes, such as Hoechst or rhodamine, out of the cells). Staining for CSC surface antigens (such as ABCG2 and other markers). The aldehyde dehydrogenase (ALDH) activity assay (high levels of ALDH activity have recently been identified as a characteristic of CSCs, and the Aldefluor flow cytometric assay has been widely used for isolation and study of CSCs). Label-retaining cell assay using PKH (Paul Karl Horan) dyes (identifies CSCs by demonstrating their asymmetric division).
What is a CUSA?
Cavitron Ultrasonic Surgical Aspirator. CUSA Excel is an ultrasonic surgical aspirator enabling fragmentation, suction, and irrigation to occur simultaneously, allowing the surgeon to remove tissue with accurate control. Tissues with weak intracellular bonds (low-strength) are the easiest to fragment, and include tissues with moderate or high fl uid content, such as some tumors, parenchyma, and fat. Tissues with strong intracellular bonds (high-strength) are the most diffi cult to fragment, and include vessel walls, ducts, nerves, tendons, ligaments, and organ capsules. These structures contain less fl uid and more collagen and/or elastin, which provide resistance to fragmentation. The CUSA is used in multiple surgical subspecialties, including neurosurgery, gastrointestinal, hepatobiliary surgery, gyne cology, and urology.
For bone tumors, metastases are far more common than primary bone tumors in a ratio of __:1. The 5 most common primary sites are ___.
For bone tumors, metastases are far more common than primary bone tumors in a ratio of 25:1. The 5 most common primary sites are lung, breast, prostate, kidney, and thyroid. After lungs and liver, skeleton is 3rd most frequent site of metastatic disease.
Metastatic tumors to the breast comprise ~1% of all tumors encountered in the breast. In adult women, what are the top 3 most common metastases to the breast?
Malignant melanoma, followed by lung and gynecologic cancers.
Although there are no universally accepted “critical values” in surgical pathology, as there are in the clinical laboratory, the Association of Directors of Anatomic Pathology approved the concept in 2006, and suggested what situations that might merit a phone call to a clinician?
Crescents in renal bxs. Primary vasculitis. Bacteria within circulating leukocytes or bone marrow. Evidence of any opportunistic infection. Uterine contents thought to be products of coneption, but without villi or trophoblasts (possibly indicating an ectopic pregnancy). Evidence of transplant rejection. Malignancy in a pt with superior vena cava syndrome. Large vessels in a core bx. Any tissue that suggest perforation, such as bowel tissue, fat, mesothelial cells, etc.
Under CLIA, a laboratory director can direct a maximum of __ laboratories.
Under CLIA, a laboratory director can direct a maximum of 5 laboratories.
Under CLIA, a laboratory director can direct a maximum of 5 laboratories. Do laboratories performing only waived tests apply towards this total?
No. The maximum limit of directing 5 labs (labs in this case means the number of certificates) is only applicable for labs performing nonwaived tests. However, the CLIA requirements have 3 exceptions for each certificate type that will allow one individual to direct multiple locations under one certificate (labs not at a fixed location, not-for-profit or federal/state/local government labs engaging in limited public health testing, and labs within a hospital located at contiguous buildings on the same campus).
In the 2013 ASCO/CAP guideline recommendations for HER2 IHC, what are cutoff values for considering a tumor HER2 positive/equivocal/negative?
Positive: IHC 3+ (circumferential membrane staining that is complete and intense in >10% of invasive tumor cells). Equivocal: IHC 2+ (circumferential membrane staining that is incomplete and/or weak/moderate and within >10% of the invasive tumor cells, or complete and circumferential membrane staining that is intense and within 10% or less of the invasive tumor cells). Negative: IHC 1+ (incomplete membrane staining that is faint/barely perceptible and within >10% of the invasive tumor cells. Also negative: IHC 0 (no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within 10% or less of the invasive tumor cells).
What is the appearance of amyloid on EM?
Random arrays of nonbranching fibrils measuring 9-12 nm in diameter.
The CAP makes recommendations for the minimum requirements for the retention of laboratory records and materials. They meet or exceed the regulatory requirements specified in the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). For the general laboratory, how long must the following be kept: accession logs, maintenance/instrument maintenance records, quality control records?
Accession logs - 2 yrs. Maintenance/instrument maintenance records - 2 yrs. Quality control records - 2 yrs.
The CAP makes recommendations for the minimum requirements for the retention of laboratory records and materials. They meet or exceed the regulatory requirements specified in the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). For surgical pathology (including bone marrows), how long must the following be kept: wet tissue, paraffin blocks, slides, reports?
Wet tissue - 2 wks after final report. Paraffin blocks - 10 yrs. Slides - 10 yrs. Reports - 10 yrs.
The CAP makes recommendations for the minimum requirements for the retention of laboratory records and materials. They meet or exceed the regulatory requirements specified in the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). For cytology, how long must the following be kept: slides, FNA slides, reports?
Slides (includes unsatisfactory, negative, suspicious, and positive) - 5 yrs. FNA slides - 10 yrs. Reports - 10 yrs.
The CAP makes recommendations for the minimum requirements for the retention of laboratory records and materials. They meet or exceed the regulatory requirements specified in the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). For non-forensic autopsy, how long must the following be kept: wet tissue, paraffin blocks, slides, reports?
Wet tissue - 3 months after final report. Paraffin blocks - 10 yrs. Slides - 10 yrs. Reports - 10 yrs.
The CAP makes recommendations for the minimum requirements for the retention of laboratory records and materials. They meet or exceed the regulatory requirements specified in the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). For forensic autopsy, how long must the following be kept: wet stock tissue, paraffin blocks, slides, gross photographs/negatives, accession log, body fluids and tissues for toxicology, representative tissue suitable for DNA analysis?
Wet stock tissue - 1 yr. Paraffin blocks - indefinitely. Slides - indefinitely. Gross photographs/negatives - indefinitely. Accession log - indefinitely. Body fluids and tissues for toxicology - 1 yr. Representative tissue suitable for DNA analysis - indefinitely.
The CAP makes recommendations for the minimum requirements for the retention of laboratory records and materials. They meet or exceed the regulatory requirements specified in the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). For cytogenetics, how long must the following be kept: permanently stained slides, fluorochrome stained slides, wet specimen/tissue, fixed cell pellet, final reports, diagnostic images (digitized, prints or negatives)?
Permanently stained slides - 3 yrs. Fluorochrome stained slides - at the discretion of the lab director. Wet specimen/tissue - until adequate metaphase cells are obtained. Fixed cell pellet - 2 wks after final report. Final reports - 20 yrs. Diagnostic images (digitized, prints or negatives) - 20 yrs.
The CAP makes recommendations for the minimum requirements for the retention of laboratory records and materials. They meet or exceed the regulatory requirements specified in the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). For flow cytometry, how long must gated dot plots and histograms be kept?
What are the 3 most common metastatic tumors associated with granuloma formation in lymph nodes?
Squamous cell carcinoma, seminoma, and thymoma.
What are the 5 mechanisms for increased vascular permeability?
- Gaps due to endothelial contraction (venules; vasoactive mediators such as histamine and leukotrienes; fast and short-lived (minutes)). 2. Direct injury (arterioles, capillaries, and venules; toxins, burns, chemicals; fast and may be long-lived (hours to days)). 3. Leukocyte-dependent injury (mostly venules; pulmonary capillaries; late response; long-lived (hours)). 4. Increased transcytosis (venules; vascular endothelium-derived growth factor). 5. New blood vessel formation (sites of angiogenesis; persists until intercellular junctions form).