2024 Spring ITE Flashcards
List five subtypes of myeloproliferative neoplasms according to the 5th edition of WHO
- Chronic myeloid leukemia (CML)
- Polycythemia vera (PV)
- Essential thrombocythemia (ET)
- Primary myelofibrosis (PMF)
- Chronic neutrophilic leukemia (CNL)
List the three broad, major categories of myeloid neoplasms.
- Myeloproliferative neoplasms
- Myelodysplastic neoplasms
- Myelodysplastic/myeloproliferative neoplasms
List one genetic abnormality seen in acute myeloid leukemia with defining genetic abnormalities.
AML with RUNX1::RUNX1T1 fusion
AML with BCR::ABL1 fusion
List two most common anatomical sites involved by extramedullary hematopoiesis in primary myelofibrosis
Spleen
Liver
List two clinicopathologic variants of Langerhans cell histiocytosis (LCH).
Single-system LCH
Multisystem LCH
Subtypes of LCH
Eosinophilic granuloma
Letterer-Siwe disease
Hand-Schuller-Christian disease
Most common genetic alteration seen in LCH
BRAF V600E mutation
Other entities with BRAF V600E mutation
Melanoma
Papillary thyroid carcinoma
Anaplastic thyroid carcinoma
Papillary craniopharyngioma
Sessile serrated lesion
Borderline serous ovarian tumor
Hairy cell leukemia
Erdheim-Chester disease
Ameloblastoma
Metanephric adenoma
List three specific immunostains used for diagnosis of LCH
S100
CD1a
Langerin (CD207)
List one specific finding of LCH on electron microscopy
Birbeck granules
What is the characteristic clinical finding in IgA nephropathy?
Recurrent hematuria
What is the specific finding on immunofluorescence in IgA nephropathy?
Mesangial deposition of IgA antibodies within the glomeruli
List three histologic findings that can be seen in IgA nephropathy
Mesangial hypercellularity
Focal segmental endocapillary hypercellularity
Crescents
Tubular atrophy/interstitial fibrosis
Segmental sclerosis
What related (to IgA nephropathy) 1) clinical syndrome can occur in the pediatric population, and what 2) three extrarenal symptoms can be seen in these patients?
Henoch Schonlein Purpura (IgA vasculitis)
Palpable purpura
lower extremity arthralgia
abdominal pain/GI bleeding
List four risk factors for development of urothelial carcinoma
Genetic - Lynch syndrome, Costello syndrome
Aristolochic acid based herbal medicine
Radiation exposure
Schistosoma infection
Smoking
Medications: Cyclophosphamide, phenacetin
3 histologic variants of urothelial carcinomas
Micropapillary, nested, large nested, tubular, microcystic, plasmacytoid, sarcomatoid, lipid-rich, clear cell, giant cell, lymphoepithelioma-like, poorly differentiated
3 types of divergent differentiation of urothelial carcinomas
Squamous differentiation, glandular differentiation, trophoblastic differentiation, Mullerian differentiation
List three urothelial carcinoma variants associated with worse prognosis than conventional urothelial carcinoma
Micropapillary
Sarcomatoid
Clear cell
Poorly-differentiated
List two histologic findings on bladder biopsy/TURB that are associated with higher risk of progression in otherwise T1 urothelial carcinoma
High grade, pT1 stage:
1. tumor size > 30 mm
2. multifocality
3. association with CIS
4. LVI
5. variant histology (those with worse prognosis)
List five clinical manifestations seen in Birt-Hogg-Dube syndrome
Fibrofolliculomas
Trichodiscomas
Acrochordon
Pulmonary cysts
Oncocytic RCC
Chromophobe RCC
What gene is involved in the development of Birt-Hogg-Dube syndrome?
FLCN gene encoding for folliculin
List 1) one immunostain and 1) one histochemical stain most helpful in differentiating oncocytoma from chromophobe renal cell
carcinoma.
CK7 - positive in chromophobe RCC but not oncocytoma
Colloidal iron stain - diffuse/granular staining in chromophobe RCC
List two immunostains most helpful in differentiating oncocytoma from low-grade oncocytic tumor.
CK7: Low-grade oncocytic tumors typically show strong and diffuse positivity for CK7. In contrast, oncocytomas usually exhibit weak or focal staining for CK7 or may be negative.
CD117 (C-kit): Low-grade oncocytic tumors often demonstrate positive staining for CD117, whereas oncocytomas are typically negative for CD117.
List the three major parameters used in prognostication of gastrointestinal stromal tumors (GISTs).
Tumor size
Mitotic rate
Tumor location
List three patterns of KIT immunoexpression that can be seen in GISTs.
- Dot-like perinuclear staining
- Membranous pattern
- Cytoplasmic
What are the three most common molecular alterations found in GISTs?
KIT
PDGFRA
Wildtype GIST (SDH-deficient GIST)
BRAF mutation
List three syndromes associated with GISTs
Neurofibromatosis type 1 (NF1)
Familial GIST syndrome
Carney-Stratakis syndrome
Carney triad
List five subtypes of lung adenocarcinoma according to the fifth edition of WHO
Invasive non-mucinous adenocarcinoma of the lung
Invasive mucinous adenocarcinoma of the lung
Colloid adenocarcinoma of the lung
Fetal adenocarcinoma of the lung
Enteric-type adenocarcinoma of the lung
What are the two recognized precursor glandular lesions?
Atypical adenomatous hyperplasia of the lung
Adenocarcinoma in situ of the lung
List the three genes that should be tested in ALL advanced lung adenocarcinomas as per the updated molecular testing guidelines
provided by College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for
Molecular Pathology
EGFR
ALK
ROS1
Provide the diagnostic criteria for diagnosis of minimally invasive lung adenocarcinoma
A small (≤ 30 mm) lepidic-predominant adenocarcinoma with an invasive component ≤ 5 mm, solitary on a resection specimen that is completely sampled
List the five groups constituting the WHO classification of pulmonary hypertension
Group 1: Pulmonary arterial hypertension (PAH)
Group 2: PH due to left heart disease
Group 3: PH due to lung diseases and/or hypoxia
Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH)
Group 5: PH with unclear and/or multifactorial mechanisms
List three clinical signs or symptoms that can be found in patients with advanced idiopathic pulmonary hypertension
Dyspnea
Fatigue
Syncope
Chest pain
Cyanosis
Right ventricular hypertrophy
What is the most common gene mutated in familial pulmonary arterial hypertension?
Bone Morphogenetic Protein Receptor Type 2 (BMPR2 gene)
Name 1) one macroscopic and 2) one microscopic finding that can be seen in pulmonary hypertension
Macroscopic - Atherosclerotic plaques in larger pulmonary arteries, Right ventricular hypertrophy, pulmonary emboli
Microscopic - Pulmonary arteries may have
medial smooth muscle hypertrophy
Intimal (“onion skin”) fibrosis ± adventitial thickening
Plexiform lesions
List five causes of myocarditis.
Viral - coxsackie virus
Bacterial - Strep, Staph, Borrelia
Parasitic infections
Autoimmune - SLE
Toxic substances - cocaine
Allergic reactions
Sarcoidosis
Giant cell myocarditis
Connective tissue disease
List the two histologic criteria required for diagnosis of myocarditis
Inflammatory infiltrate
Myocyte necrosis/degeneration
Which form of myocarditis is associated with particularly bad prognosis?
Giant cell myocarditis
Which form of cardiomyopathy can develop as a consequence of myocarditis?
Dilated cardiomyopathy
Define quality assurance in pathology.
System/program that ensures the final result reported is as correct and accurate as possible and standard is met
Define quality control in pathology.
Tools included in every test to help detect and correct defects in the system and control the quality of the service being output
List three examples of quality control in pathology
Daily assessment of H&E staining
External control tissue in IHC slides
Verifying more than 2 patient identifiers in specimens
Periodic calibration of digital slide scanners
Daily checking of temperature and pH value of staining solution
Define proficiency testing in pathology.
Process of evaluating the results of unknown specimens to a standard test
List 1) the most common primary tumor of the adult heart and 2) one associated syndrome
- Cardiac myxoma
- Carney syndrome, McCune-Albright
List 1) the most common primary tumor of the pediatric heart and 2) one associated syndrome
- Cardiac rhabdomyoma
- Carney complex, Gorlin syndrome, tuberous sclerosis
Two genes associated with tuberous sclerosis
TSC1
TSC2
List three most common causes of metastatic tumors to the heart.
Bronchogenic carcinoma
Hematologic malignancies
Breast cancer
Renal cell carcinoma
Define amyloidosis.
Inherited inflammatory disorder characterized by the deposition of insoluble protein fibrils in various tissues of the body and causing damage.
List two special stains that can highlight amyloid in tissue and specify the expected positive staining for each.
- Congo red - apple green birefringence under polarized light
- Crystal violet - metachromatic staining (purple/blue)
- Sirius red - rose red
Give 1) one example of disease associated with systemic amyloidosis and 2) one example of disease associated with localized amyloidosis.
Systemic: Immunoglobulin light chain (AL) amyloidosis, multiple myeloma, monoclonal plasma cell proliferations, chronic inflammatory disorders, chronic kidney disease
Localized: Primary localized cutaneous amyloidosis - Macular, Nodular, anosacral amyloidosis, Alzheimer’s disease, type 2 diabetes mellitus
What is 1) the major fibril protein in Alzheimer disease and 2) its chemically related precursor protein?
- beta-amyloid
- amyloid precursor protein (APP)
List three indications for intraoperative evaluation of lymph nodes.
Triage for lymphoma protocol
Exclusion of metastatic malignancy
Exclusion of infectious process
List five additional techniques that can be performed on fresh lymph node tissue during intraoperative consultation
B+ fixative (different fixative)
Imprints for cytogenetics
RPMI
Snap freeze for molecular analysis
Microbiology cultures
List four main causes of error during intraoperative consultation
Sampling error
Insufficient/inappropriate clinical history
Technical errors
Interpretative errors
Which among these is the most common cause of error during intraoperative consultation?
Sampling error
Interpretive error
List three extramammary locations that can be involved by myofibroblastoma
inguinal/groin area, including in the vulva/vagina, perineum, and scrotum
trunk/axilla
extremities
abdominal cavity
retroperitoneum
viscera
List the two most useful immunostains for diagnosis of myofibroblastoma.
Desmin
CD34
List the two immunostains that can overlap between myofibroblastoma and invasive lobular carcinoma of the breast.
ER
PR
List four entities to consider in the morphologic differential diagnosis of myofibroblastoma in the breast
Spindle cell lipoma
Pseudoangiomatous stromal hyperplasia
Solitary fibrous tumor
Nodular fasciitis
Invasive lobular carcinoma
Fibromatosis
Define oral leukoplakia
white plaque/patch that cannot be scraped off and cannot clinically be characterized as any other disease
How does erythroplakia differ from leukoplakia?
Erythroplakia is a thin slightly depressed red patch on the oral mucosa
What is the most common predisposing factor to leukoplakia?
Tobacco
List three possible histologic correlates of leukoplakia
Verrucous hyperplasia
Proliferative verrucous leukoplakia
Squanous hyperplasia
Hyperkeratosis
Squamous hyerplasia / dysplasia
List two commonly used scoring systems for assessing PD-L1 immunohistochemical expression and the corresponding formula
Tumor proportion score = (# PDL1 positive tumor cells/total # of viable tumor cells) x 100
Combined positive score = (# of PDL1 positive tumor cells and tumor associated immune cells/total # viable tumor cells) x 100
For each of the two scoring systems for PDL1, list one organ system where the specific scoring system is used
TPS - NSCLC
CPS - ENT (head and neck SCC), GU (urothelial), GI (gastric and esophageal ca), Gyne (cervical ca)
List the two normal tissues that can be used as controls for PD-L1 immunohistochemistry
Tonsil
Placenta
What is the minimum number of cases that would be required for validation of a new PD-L1 antibody within a laboratory?
40 cases
Outline the seven categories in the classification of the epithelial tumors of the ovary according to 5th edition WHO.
Serous tumors
Mucinous tumors
Seromucinous tumors
Endometroid tumors
Clear cell tumors
Brenner tumor
Other carcinomas
List three precursor lesions of mucinous carcinoma of the ovary.
Mucinous borderline tumors
Mature cystic teratoma
Brenner tumor
List four pathologic features that favor ovarian involvement by metastatic carcinoma rather than a primary mucinous carcinoma of the ovary.
Bilaterality (metastatic are usually bilateral while primary are unilateral)
Smaller size
Surface involvement / hilar involvement
Infiltrative growth pattern
High grade cytology
Dissecting mucin
List five immunostains that can be used to distinguish ovarian involvement by metastatic carcinoma versus a primary mucinous carcinoma of the ovary.
Things in the differential of mucinous neoplasm: breast, GI, ovary
PAX8
CK7
CK20
CDX2
SATB2
WT1
ER
PR
SMAD4
GATA3
List the four most important points to include in a pathology report on salivary gland carcinoma.
Tumor histologic type and pattern
Anatomic site of origin / location, side
Tumor size
Tumor histologic grade (for mucoepidermoid carcinoma, adenocarcinoma, NOS, malignant mixed tumor, adenoid cystic carcinoma)
Tumor extension (intra or extraglandular), to adjacent structures
Status of resection margins
Vascular invasion
Perineural invasion
Lymph node involvement
Name two specific salivary gland carcinomas for which histologic grading is pathologically relevant.
Mucoepidermoid carcinoma
Adenoid cystic carcinoma
Carcinoma exPA
Adenocarcinoma NOS
List two risk factors for the development of salivary gland carcinoma.
Age
Sex - more common in males
Radiation
Tobacco chewing NOT smoking
EBV
Genetic predisposition
Nickel exposure
Chromium exposure
In general, what is the single most important pathologic prognostic factor for carcinoma of the head and neck?
Lymph node status
List three criteria of malignancy in conventional adrenocortical neoplasms in adult patients.
Weiss criteria: ≥ 3 for adrenal cortical carcinoma
1. Nuclear grade III or IV (Fuhrman)
2. > 5 mitotic figures/50 high power fields*
3. Atypical mitotic figures*
4. Clear or vacuolated cells ≤ 25% tumor
5. Diffuse architecture (> 33% of tumor)
6. Necrosis
7. Venous invasion* (of smooth muscle walled vessels)
8. Sinusoidal invasion
9. Capsular invasion
*= major criteria; 1 is required to diagnose adrenal cortical carcinoma
List two immunostains useful in distinguishing adrenocortical adenocarcinoma from pheochromocytoma
SF1, α-inhibin - negative in pheochromocytoma
Melan A - negative in pheochromocytoma
Chromogranin - positive in pheochromocytoma
GATA3 - positive in pheochromocytoma
List one adverse prognosis factor in adrenocortical adenocarcinomas
Angioinvasion
Advanced tumor stage
Lack of completeness of the tumor excision
Tumor functionality
High-mitotic tumor grade
High Ki67 proliferation index
List five causes of adrenal insufficiency.
Primary Adrenal Insufficiency: caused by
1. Autoimmune diseases
2. Amyloidosis
3. Congenital Adrenal Hyperplasia
4. Adrenal bleeding due to trauma
5. Fungal infections
Secondary adrenal insufficiency:
1. Pituitary dysfunction
2. Long-term use of high-dose corticosteroids
What is the definition of sudden unexpected death in epilepsy (SUDEP)?
Sudden unexpected death in epilepsy (SUDEP) is sudden, unexpected, witnessed or unwitnessed, non-traumatic and non-drowning death, occurring in benign circumstances, in individual with epilepsy, ± evidence for seizure and excluding documented status epilepticus, in which postmortem examination does not reveal cause of death
List five causes of death that can be seen in patients with epilepsy
SUDEP
Status epilepticus
Seizure-related injuries (head injury)
Suicide
Arrhythmia
Trauma
Drowning
Postictal asphyxia
List two macroscopic findings in epileptic death.
foam cone
tongue biting
muscle rigidity
urinary incontinence
gastric aspiration
What is the most common histologic finding in brain in epileptic death?
normal brain
