ASCP RISE DESCRIPTORS 2024

SURGICAL PATHOLOGY

Descriptor Explanation
Very early complete hydatidiform mole - may not show gross abnormalities
Microscopic Features:
- No significant villous enlargement or hydrops
- Polypoid, irregular villous shape
- Hypercellular, myxoid villous stroma with apoptosis of primitive stellate cells
- Focal hyperplasia of cytotrophoblasts and syncytiotrophoblasts on both villi and the
undersurface of the chorionic plate
- Atypical trophoblasts lining the villi and at the implantation site
- Rare primitive fetal vessels and fetal red blood cells

Very early complete hydatidiform mole, identification

Grossly encapsulated and well-circumscribed, histologically has characteristic features:

- Zonal areas composed of a cellular area (Antoni A) and a hypocelllular area (Antoni B),
biphasic
- Nuclear palisading (Verocay bodies) often seen in cellular areas
- Cells are narrow, elongated, with tapered ends and interspersed collagen fibers, vessels
may be hyalinized/thickened walls and there also may be pseudoglandular spaces
- Mitotic figures rare

Recognition of schwannoma
 Also called lactational adenoma or nodular lactational hyperplasia, occurs in pregnancy
- Breast tissue with lactational changes forming a mass with circumscribed borders
- Can be tubular adenoma with lactational changes, can have response to hormones focally
which is different from true neoplasms

Diagnosis of lactating adenoma

Found on imaging, usually unrelated to initial reason for diagnostic testing

90% are usually non-functional
Microscopic features:
- Well-circumscribed containing three layers that closely resemble normal adrenal gland
- Difficult to differentiate from normal adrenal in core biopsies

Adrenal nodule, adrenal cortical adenoma

 C4d staining in peritubular capillaries can be indicative of acute humoral rejection, footprint
of antibody-mediated rejection
- Considered an inferior prognostic sign
- C4d is a marker of complement activation

Staining C4d in kidney peritubular capillaries, acute humoral rejection

Intracerebral hemorrhage can be initial presentation of metastatic choriocarcinoma

- Imaging will show irregular hematoma which grew rapidly (within one month)
- Laboratory findings showed increased b-HCG level
- Choriocarcinoma commonly metastasizes to brain, lungs
- Treatment with chemotherapy, some use radiotherapy for brain metastasis in conjunction
with surgery to evacuate hematoma if the metastatic nodule caused a bleed
- Tumor appears as solid sheets of atypical syncytiotrophoblast, cytotrophoblast, and
intermediate trophoblast, no chorionic villi

Choriocarcinoma, intracerebral hemorrhage

 Gross appearance: small, circumscribed yellow-white nodules on the umbilical cord
surface
Microscopic appearance: subamnionic microabscesses where fungal organisms are
present, chorioamnionitis present in all cases

Features of Candida funisitis

Grossly:
Red-gray, very vascular, polypoid mass

Microscopic:
- Low-grade – nests and lobules of monotonous tumor cells with round nuclei, indistinct
nucleoli and scanty cytoplasm, vascular-rich to hyalinized stroma; fibrillary neural matrix
- High-grade – solid growth, marked mitotic activity, nuclear pleomorphism, necrosis and no
neuropil

Identify olfactory neuroblastoma

Differential would include:

- Hemangioma
- Focal nodular hyperplasia
- Adenoma
Vascular lesions in the liver
- Hypervascular metastasis (RCC)
- Hemangioendothelioma
- Hepatic angiosarcoma
- Benign cavernous hemangioma – most common
 Gross description
- Unilateral solid or cystic mass with lobulated/nodular surface
- Fleshy and tan-white to gray cut surface, hemorrhage and necrosis
- Familial cases à bilateral presentation

Microscopic description
- Small, round cells with scant cytoplasm, small nucleoli, brisk mitotic activity
- Diffuse growth of tightly packed cells, nested/corded
- Necrosis seen in most tumors, focal myxoid stroma is common
- Morphology: large cell component, rhabdoid features (greater than 50% of tumor, small
cell carcinoma)

Mutations in ovarian small cell carcinoma of hypercalcemic type

Tufting of cells, lack of fibrovascular cores – characteristics of micropapillary

Recognition of micropapillary histologic subtype of lung adenocarcinoma

 Characteristic features from international consensus criteria
- Dense fibrosis with architectural distortion
- Predominant subpleural and/or paraseptal distribution of fibrosis
- Patchy involvement of lung parenchyma by fibrosis
- Presence of foci of active fibroblastic proliferation
- Absence of features suggesting an alternate diagnosis

Recognition of usual interstitial pneumonia pattern of fibrosis

Gross
Well-circumscribed, oval masses
Solid area with multiple cysts and some papillary projections on cut surface

Microscopic
- Papillary cystic structures
- Bilaered oncocytic epithelial cells (inner columnar, outer cuboidal)
- Lymphoid stroma including germinal centers

Warthin tumor
IHC of LCIS

Damage to the cells at the border between the epidermis and dermis
Characteristics:
Vacuolar interface change, lupus erythematosus and erythema multiforme
- Appearance of vacuoles in the basal layer of the epidermis
- Mild inflammatory cell infiltrate may also be present
Myelophthisic anemia – occurs when non-hematopoietic cells take over/crowd the bone
marrow completely

In metastatic carcinoma, this occurs when tumor cells completely overtake the bone
marrow and hematopoietic elements are not present

Metastatic carcinoma, myelophthisic anemia

 Rare tumor that occurs in the thymus of children with HIV
Generally categorized as a response to the presence of the infection

Multilocular thymic cyst, neonatally acquired HIV infection

Also known as nipple adenoma

Characteristics:
- Epithelial proliferation, retained myoepithelial cell layer involving superficial ducts of the
nipple
- May extend and replace the overlying squamous epithelium resulting in erosion,
hemorrhage and inflammation
- Histologic patterns include a mix of sclerosing adenosis, papillary hyperplasia and usual
ductal hyperplasia

Identify florid papillomatosis of the nipple

 Preoperative risk stratification based on serum PSA, clinical stage, biopsy parameters
(tumor extent, grade, cribriform morphology, intraductal carcinoma, perineural invasion)

Primary treatment options based on preoperative risk stratification:

Active surveillance
Focal therapy (cryotherapy, high intensity ultrasound)
Radical prostatectomy
Brachytherapy
Treatment in prostate cancer
External beam radiotherapy
Hormone therapy (e.g., luteinizing hormone releasing hormone [LHRH] analogues,
antiandrogens)
Orchidectomy (rare in contemporary practice)
Chemotherapy (for metastatic disease)
Postprostatectomy options:
Generally, PSA monitoring and early salvage therapy if rising serum PSA
Less commonly adjuvant therapy for high stage disease or margin positivity

Changes that occur in transplanted kidneys can include

Post kidney transplant pathology - Endothelial injury (common) or edema
- Transplant rejection: interstitial edema, tubulitis, presence of eosinophils

Can be found in various organ systems

- Breast
- Colon
- Bladder/urinary tract
- Lung
Rare subtype that is known to be histologically aggressive

Recognition of micropapillary carcinoma

 Quilty lesions, also known as endocardial infiltrates
- associated with the use of cyclosporine and waxing and waning levels of
immunosuppression
- Suggested they may represent a "benign" form of rejection, an analogue of vascular
rejection

identification of cardiac Quilty lesions

Well-circumscribed, encapsulated with fibrous septa separating the tumor into multiple
lobules, hyperchromatic nuclei with occasional PTC nuclear features
- nuclear overlap, grooves, pseudoinclusions, clearing
- Squamoid morules are distinctive, composed of whorls of spindle to ovoid cells with
nuclear clearing and no keratinization, may be rare and difficult to find

Features of cribriform morular variant of papillary thyroid carcinoma

Firm, slow-growing painless mass

Usually appears in the shoulder
Symptoms: swelling, discomfort, and stiffness but most are asymptomatic
Elastofibroma; clinical characteristics Mass can be palpable and can feel as if there is clunking of scapula when shoulder is
moving, often found under the inferior angle of the scapula, bilateral, adhering to the deep
layers, very uncommon benign pseudotumor
Requires MRI/CT for careful diagnosis
 Caused by IgG or IgA autoantibody against epidermal antigens (commonly desmoglein 1
and desmoglein 3)
- Most frequent clinical presentation: flaccid bullae or crusted erosions involving skin or
Pathogenesis of pemphigus mucosa
- Prototypic histopathological feature: intraepidemal acantholysis with intact basal layer
(tombstone sign) and intraepidermal eosinophils
- Direct immunofluorescence shows intercellular IgG / IgA and C3

Amyloid involving lung

identification of parasitic infections and tissue sections

(A) Trypanosoma cruzi (hematoxylin and eosin [H&E] staining)

(B) Cerebral malaria (H&E) is a life-threatening disease characterized by parasitized
erythrocytes within small blood vessels (arrow)
(C, D) Leishmaniasis (H&E) is observed as amastigotes within histiocytes.
(E) Strongyloides stercoralis (H&E) appears as early-stage (L1) larvae (arrows), eggs
(arrowhead), and occasionally as adults in tissue sections.
(F) Schistosoma spp. eggs
(G) Cysticercus (H&E) is the larval form of Taenia solium and comprises a thin fluid-filled
sac (asterisk) containing a protoscolex with 4 suckers and a circular row of hooklets
(arrow). Higher magnification
(H) demonstrates the protoscolex with suckers and a circular row of refractile hooklets
(arrow)
prostate carcinoma grading

Hyperplastic thyroid follicles within papillary infoldings

Nuclei are round, basally located, rarely overlap

thyroidectomy; diagnosed diffuse toxic goiter (Graves disease)

recognition of normal colonic mucosa

Epiphysis and metaphysis of long bones

Distal femur and proximal tibia – most common
Giant cell tumor of bone; classic locations Distal radius and proximal humerus can also be affected frequently
Axial skeleton – proximal sacrum is most common, but it can occur in any bone including
the small bones of hands, feet, sesamoid bones (patella)
The most common aggressive variant of papillary thyroid carcinoma
- Characterized by tall cells occupying ≥ 30% tumor and well developed papillary
thyroid carcinoma nuclear features
BRAF mutation; in tall cell carcinoma
BRAF V600E mutation present in most cases
Papillary thyroid carcinomas with tall cell features (≥ 10% tall cells) have worse prognosis
than those without tall cells
Grading is based on amount of immature neuroepithelium

Grading of immature ovarian teratoma

Intestinal adenocarcinoma

Primary tumor (pT)

• T0: No evidence of primary tumor
• T1: Solitary tumor ≤ 2 cm or > 2 cm without vascular invasion
o T1a: Solitary tumor ≤ 2 cm (with or without vascular invasion)
o T1b: Solitary tumor > 2 cm without vascular invasion
• T2: Solitary tumor > 2 cm with vascular invasion or multiple tumors, none > 5 cm
• T3: Multiple tumors, at least one of which is > 5 cm
• T4: Tumor involves a major branch of the portal hepatic vein or directly invades
adjacent organs other than the gallbladder or perforates the visceral peritoneum
Regional lymph nodes (pN)
• N0: No regional lymph node metastasis
• N1: Regional lymph node metastasis
Distant metastasis (pM)
Staging of liver tumors • M0: No distant metastasis
• M1: Distant metastasis
Stage grouping
Stage IA: T1a N0 M0
Stage IB: T1b N0 M0
Stage II: T2 N0 M0
Stage IIIA: T3 N0 M0
Stage IIIB: T4 N0 M0
Stage IVA: any T N1 M0
Stage IVB: any T any N M1
Identification of dividing membrane; twin gestation placenta

(L) Dividing membrane, di-di; (R) diving membrane, mono-di

BRAF is most frequently mutated – variant that is most common is BRAF V600E
RAS mutation occurred with high thyroid differentiation score
Molecular findings and thyroid cancer RET fusion is the most commonly seen
TERT promoter mutation is common in 10% - associated with more aggressive histology and
a poorer prognosis
Abundant cytoplasmic vacuolation
Enlarged nucleus, normal N:C ratio, no nuclear membrane irregularity, smudgy chromatin,
Identification of radiation change in squamous mucosa
fibrosis (chronic) and edema (acute)
Squamous metaplasia can also be seen
Adhesion
Hernia
Inflammatory bowel disease
Causes of bowel obstruction Diverticulitis
Malignancy
Constipation (common)
Medication use (opioids, etc)
Symptoms: fatigue, fever or night sweats, weight loss or recurrent infections
Most patients with follicular lymphoma have no obvious symptoms of the disease
Tissue biopsy (lymph node / extranodal sites)
Diagnosis of follicular lymphoma Needle biopsy (both core needle biopsy and fine needle aspiration biopsy)
Peripheral blood exam / bone marrow biopsy (especially in staging)
Low-grade morphology, staining to differentiate:
- CD3, CD20, BCL-2, BCL-6, Dendritic mesh network stain
Grade 1: Inconspicuous nucleoli at ×400 magnification and basophilic.
Grade 2: Clearly visible nucleoli at ×400 magnification and eosinophilic.
Grading of renal cell carcinoma
Grade 3: Clearly visible nucleoli at ×100 magnification.
Grade 4: Extreme pleomorphism or rhabdoid and/or sarcomatoid morphology
Cough/illness
Vomiting
Impaired consciousness
Known common risk factors for aspiration that are often overlooked Age-associated
Swallowing disorder, neuromuscular disorder
Poor oral care or hygiene
Malposition or presence of feeding/NG tube
Recognition of phyllodes tumor

Extramammary Paget's disease

Beta-catenin mutations are implicated in tumor cells with matrical differentiation

Matrical differentiation – features resembling the hair matrix of hair follicles
Examples of tumor types:
Pilomatricoma
Genetics of skin lesions
BCC with matrical differentiation
Melanocytic matricoma
Beta catenin has a role in Wnt signaling
Beta-catenin (nuclear stain) can be useful to show matrical differentiation
 Do not arise from oligodendrocytes, although tumor cells look very similar
- Arise from glial precursor cells
Molecular analysis of IDH1/2 and LOH p1p/19q is required for diagnosis

Oligodendroglioma

Primary focus is checking for following mutations:

identification genetic testing for high-grade serous carcinoma BRCA 1
BRCA 2

Diagnosis of normal menstrual endometrium

 Thickened elongation of overlying epithelium, with jagged rete ridges
Can have keratinization present, lacks atypia

Pseudoepitheliomatous hyperplasia; granular cell tumor in the oral cavity

Age
Hormone-related risk factors like prolonged estrogen exposure, early menarche, late
menopause, nulliparity, first child after age 30, lack of breast feeding
Postmenopausal women – obesity and estrogen producing ovarian tumors
Women using HRT with progestin or estrogen alone
Risk factors for breast cancer Parity – triple negative breast cancers
Familial clustering – first degree relative with breast cancer
BRCA1/2 mutation
Li-Fraumeni syndrome, Cowden disease, Ataxia telangiectasia heterozygous carriers
Female sex, Radiation exposure in women less than age 30 (Hodgkin lymphoma)
“dense breasts” on mammography
EMA+ - helps to differentiate it from schwannoma
Membranous staining

Meningioma; epithelial membrane antigen immunoreactivity

 Second most common pattern, better prognosis
Essential to exclude other lung diseases on histology
Characteristic findings
- Diffuse and uniform inflammation on low power of alveolar wall, bronchovascular
bundles, pleura
- Cellular/fibrotic change – lymphocytic or plasmacytic infiltration, loose fibrosis, lung
architecture is frequently preserved

Nonspecific interstitial pneumonia, characteristics

Tumors associated with t(11;22)(p13;q12)

Chromosomal translocations and desmoplastic small round cell tumor
Chimeric EWS-WT1 RNA and DNA detected by PCR

Ulcerative colitis, Lymphocytic colitis, Focal active colitis

Infectious
Types of colitis Iatrogenic – diversion, radiation
Ischemic colitis
Miscellaneous types – eosinophilic, diverticular-associated
Pathologic hallmark: dense, lymphoplasmacytic infiltrate with IgG4 positive plasma cells,
storiform fibrosis, obliterative phlebitis, eosinophils (variable in amount)
Serum IgG4 is also elevated
This histologic appearance will be the same in all organs with an IgG4 positive subtype

Clinical pathologic features of IgG4 - related pancreatitis

 Absence of high risk HPV bby DNA or RNA in situ hybridization

Characteristic and diagnostic fusion involving MYB, MYBL1 or NFIB gene, the most
common being t(6,9) MYB-NFIB fusion
Translocations and salivary gland carcinomas (adenoid cystic carcinoma)
Additional mutations involving FGF-IGF-PI3K pathway (in 30%) and chromatin state
regulators (e.g. SMARCA2, CREBBP and KDM6A)
Overexpresses c-KIT by immunohistochemistry, it is not associated with c-KIT mutation
POSITIVE
Cytokeratin (CK8, CK18, CK19), EMA, S100, brachyury
If de-differentiated – may lose brachyury, EMA or S100
Immunohistochemical features of chordoma
NEGATIVE
PTEN
CK7, CK20
INI1 (lost in poorly differentiated carcinoma)
Infection with enteric pathogens can show small, basophilic spherical structures attached
to microvillus surface of the epithelium
Intestinal infections
Salmonella – ulcers overlying the Peyer patches with minimal inflammatory cells, often
histiocytes with erythrophagocytosis
Clinical
- Presents in second to fourth decads, improves with age
- Vesicles/bullae in intertriginous areas, exacerbated by perspiration
- Relapsing/remitting clinical course
- Treatment with topical steroids and antimicrobials

Microscopic
- Suprabasilar and intraepidermal clefting with acantholysis of keratinocytes
“Dilapidated brick wall”
- No pronounced dyskeratosis, but dyskeratotic keratinocytes have well-defined nucleus,
preserved cytoplasm
- Sparing of adnexal structures
Recognize the histologic appearance and know clinical and immunofluorescence characteristics IF is negative
of Hailey -Hailey disease
 Detects chromosomal translocation on the Xp11.2 locus which leads to fusion gene
involving TFE3
- FISH identifies the genetic abnormality which searches for a “break apart” pattern
in the TFE3 gene on the X chromosome

Xp11.2 translocation associated renal cell carcinoma (RCC), TFE 3 by FISH

CLINICAL
Most common in children and young women, present in pure form or component of
malignant mixed germ cell tumor
Symptoms on presentation: abdominal pain or distention

PATHOLOGIC
Identical morphology to testicular seminoma with nests of large, uniform polygonal cells
with clear or eosinophilic cytoplasm and distinct cell membrane, stroma is loose and
delicate
- Numerous mitotic figures
- Separated with fibrous septae
- Lymphoid follicles may be present

Clinical pathologic features of dysgerminoma

 Characteristic pathologic features:
- Negri bodies (intracytoplasmic eosinophilic inclusions in neurons of hippocampus and
cerebellum) + Lyssa bodies – viral replication within a circumscribed region
- Principle reservoirs are urban/canine or sylvatic (wildlife)

Inhalation rabies infection from bat infested caves

POSITIVE
- OCT 3/4
- CD117
- D2-40
- PLAP
Diagnosis and immunohistochemical profile of seminoma
- SALL4
- SOX17
- PAS

NEG: CD30, AFP, glypican 3, hCG, EMA, AE1/AE3, CK7, Inhibin, p63, PAX8, GATA3

Immunohistochemistry; differentiate germ cell tumors

More frequent than prepubertal teratoma

Associated with germ cell neoplasia in situ and chromosome 12p amplification
Diagnosis of post pubertal teratoma Clinically: associated with swelling of the testicle and pain, hemorrhage or hematoma
Microscopic features: varying degrees of atypia, any type of tissue is present, will have
GCNIS present as well, associated with atrophic testis with sclerosis and microliths
 Rare, multisystem disease attributed to Tropheryma whipplei – can affect any part of the
gastrointestinal tract
Microscopy – infiltration of lamina propria by foamy macrophages containing PAS positive,
AFB negative bacteria

Characteristics of Whipple disease

Pathologic change in the glomerular basement membrane – accumulated immune complex

deposition
Pathogenesis of membranous glomerulopathy - Appears as granular deposits of IgG on immunofluorescence
- Most common targeted antigen is phospholipase A2 receptor (PLA2R) expressed on
podocytes with antibodies against receptor detected in majority of cases

Immunohistochemical staining pattern of testicular sex cord stromal tumors

MOLECULAR
Pedigrees and inheritance patterns

Interpreted as:
Interpretation of NGS
pathogenic, likely pathogenic, variant of uncertain significance, likely benign, benign

Gain of signal
Presence of signal
Loss of signal
Interpreting FISH test
Positioning of signal
- Break apart probe (two separate color signals seen)
- Fusion probe (overlap/juxtaposition of two diuerent color signals)

Growth of DNA sequencing methods aided growth of bioinformatic technology and research,
Bioinformatics process outline in NGS needed more euicient process with higher throughput and greater accuracy, refinement of the
bioinformatic algorithms

Can be prone to error in a variety of areas

- Assay complexity – error in process of creating and printing sequences will create
misidentification and false data
Chromosomal microarray optimization - Signal variation and analysis – the hybridization, washing, and quantification steps are
very influenced by external environment
- Incomplete oligonucleotide and cDNA synthesis – altered probes can drastically alter
hybridization and invalidate assay results
 - Data analysis and evaluation – any error at any step in the creation of the microarray will
result in an error, background intensity analysis can be complex in high density
microarrays

Dominant gene is expressed in BOTH heterozygous and homozygous states

Dominant gene expressed in hetero and homozygous states - PHENOTYPE will be observed regardless of whether or not the individual is homozygous
or heterozygous

Store information about genes and their pertinent information that leads to knowledge regarding
Genomic databases euect on diagnosis and treatment
Examples are ClinVar, OncoKB

Ability of RNA molecules to maintain structure and function over time

à helps to preserve genetic date, determines how RNA degrades and functions in cells
Factors that influence stability
- Temperature
RNA stability - Acidity
- Oxidative stress
- Nucleotide mRNA sequence
- The 5’ cap and 3’ polyA tail – mitigate mRNA decay
- 3’ UTR length – can auect stability of the RNA
System for describing human chromosomes and their abnormaltities
Describes genomic changes through karyotype, FISH, microarray and other techniques
- Numbering system starts at centromere
- Chromosome assigned a long arm/short arm

ISCN nomenclature
 Hydrogen bonds

DNA double helix bonds

 Involved in guidelines for thiopurines like mercaptopurine and azathioprine
TPMT pharmacogenetics
Responsible for creating the TPMT enzyme, which breaks down thiopurine drugs

Defined as genetic testing for children for a genetic condition that they do not yet have
Presymptomatic genetic testing in minors Acceptable only if preventive action like preventive surgery or early detection aimed at therapeutic
invention can be initiated before adulthood, otherwise not recommended

Amplification techniques that proceed through RNA

Isothermal amplification for transcription-mediated amplification and nucleic acid

sequence based amplification

Blood sample is taken from the pr egnant mother

Blood is analyzed for amount of DNA from chromosomes 13, 18, and 21
Cell-free prenatal screening Results are indicative of whether or not the fetus has a higher or lower RISK of having the condition
Can be done as early as 10 weeks, negative result does not ensure pregnancy is unauected, does
not test for all genetic conditions

Coverage—the proportion of the genome (or targeted region) that has been sequenced at least
Define sequencing coverage
once.

Assessed by monitoring patient blood counts (neutrophil count) to see if it reaches sustained level
above a certain threshold
Bone marrow engraftment interpretation
Molecular – usually uses a short tandem repeat genotype analysis of bone marrow that requires
identification of informative STR loci that distinguish the recipient DNA from the donor DNA
 Requires very little material – at least twenty identifiable tumor cells (ideally more)
Evaluates areas that are identified by sequence-specific probes
Unique capabilities of FISH
Can be performed on FFPE, smears, various other samples and can evaluate multiple cells
Also relatively fast – 1-2 days

Defined as when a genetic disorder becomes more severe or appears at an earlier age in
Genetic anticipation
successive generations

Sibling match HLA-A, B and C loci

DNA sequencing method that determines sequence of DNA by repeatedly adding fluorescently
labeled nucleotides to a growing DNA strand – allows identification of the incorporated base at
each cycle

Features of sequencing by synthesis

 Process that controls which genes are expressed in an individual by silencing one copy of each
Genomic imprinting Occurs during egg and sperm formation – only one copy of a gene in an individual either maternal
or paternal is expressed, other copy is suppressed

Around 10-15 amino acids long formed by joining the V-D-J segments
Majority of length coming from D segment and junctional diversity added by enzyme TdT between
the segments
- Variability is crucial for antibody specificity against diuerent antigens

Heavy chain CDR3 length, V, D and J segments

Chromosome structure

CYTOLOGY
Benign mesothelial cells, recognize in pleural effusion

Cervical lesion, diagnose high grade squamous intraepithelial lesion

QUALITY CONTROL
Laboratories must review at least 10% of negative gynecologic cases
Develop QA plan
Monitor performance

PROFICIENCY
CMS-approved proficiency testing program
Participate in one PT event per year
Knowledge of lab management and CLIA 88 regulations
Must pass the PT with a score of at least 90%
PT must be ouered at least once per year

WORKLOAD LIMIT
Examine no more than 100 slides in a 24-hour period
Must have at least 8 hours to examine 100 slides
Intended to reduce the false negative rate of the Pap test and improve the quality of
laboratory testing
 Numerous anucleated squamous cells, dirty background

Neck nodule, diagnose epidermal inclusion cyst from Pap stain

Diagnose high grade urothelial cell carcinoma, urine

Foamy alveolar casts with alveolar macrophages in BAL

Morphologic features of Pneumocystic jiroveci in cytology specimens

 Basal cell adenoma – tightly cohesive basaloid cells in a scant matrix
Pleomorphic adenoma - mixture of myoepithelial cells, ductal cells, and extracellular
stroma
Oncocytoma - cellular oncocytic aspirate, clean background

Recognition of benign salivary gland neoplasms and their specific molecular abnormalities

False positives occur in brushings due to inflammation and other changes in bile duct cells
Primary sclerosing cholangitis; false positive diagnoses in biliary brushings
that can appear to be atypical

Diagnosis of small cell carcinoma, heavy smoking history

 Screening – identify potential for disease development in an asymptomatic individual
- Pap test
Screening vs diagnostic test
Diagnosis – Confirm suspected disease in someone exhibiting symptoms
- Concerning cells leading to biopsy/FNAs for staging
Nests/cheets of cells with clear cytoplasm and distinct membrane
Sometimes can see arborizing vessels, thin-walled

Morphologic features of clear cell renal cell carcinoma

TP53
PIK3CA
Most common chromosome aberrations associated with high grade urothelial cell carcinoma
RB1
FGFR3

Bronchial wash, reactive bronchial cells

Non-smoking females who develop lung cancer have a higher risk of carrying EGFR
Lung adenocarcinomas, non-smoking females, EGFR mutation
mutation which auects their potential for targeted therapy with tyrosine kinase inhibitors
 BRAF V600E
RET/PTC rearrangements
Papillary thyroid carcinoma, common genetic lesions
- Alterations of the MAPK signaling pathway, considered key drivers of PTC
development

Large B-cell lymphoma and lymphoglandular body detection

Recognition of adenocarcinoma in a cerebrospinal fluid specimen

Highly cellular smears with cytologic features based on level of diuerentiation of HCC
- Well: polygonal, monotonous with granular cytoplasm and enlarged nuclei,
increased N:C and membrane irregularity with coarse chromatin
- Poorly: marked nuclear pleomorphism, multinucleated tumor cells, spindle
cells, atypical mitosis and necrosis

Liver, fine-needle aspiration, identify hepatocellular carcinoma

 Loosely cohesive groups and isolated cells sometimes around branching capillaries
Rosette structure may be seem
Uniform population of small tumor cells, round/plasmacytoid shape
Smooth nuclear outlines, salt and pepper chromatin, small nucleoli, rare mitoses
Scant, granular cytoplasm – no molding, nuclear crush, and necrosis

Cytology of carcinoid tumor

Autoantibodies
TPO – thyroid peroxidase
Thyroglobulin

Recognition of chronic lymphocytic thyroiditis and the most common autoantibodies that cause it
Cerebrospinal fluid plasma cells, multiple sclerosis

Papillary lesions of the breast

Identification of LSIL
Recognize radiation change

Recognition of mesothelioma in a pleural fluid; BAP-1 immunohistochemical staining in malignant

mesothelial cells
 Immunohistochemistry: Calcitonin, CEA, TTF1, PAX8
Negative for thyroglobulin, ER, HMB45

Medullary thyroid carcinoma, relevant confirmatory immunohistochemical stains

Cervicovaginal specimen, identify endometrial cells

Diuerentials:
Renal cell carcinoma
Differential diagnosis of renal mass fine-needle aspiration, recognize adrenal cortical cells Simple renal cyst
Oncocytoma
Adenoma or adrenal cortical adenoma
Esophageal brushing, diagnose adenocarcinoma
Metastatic breast carcinoma to the neck

At least ten well-preserved endocervical or squamous metaplastic cells, singly or in

Adequacy for transformation zone sampling in cervical cytology
clusters

“Decoy” cell

Urine, diagnose polyomavirus

Recognition of the cytomorphology of colorectal adenocarcinoma

Recognition of squamous metaplasia in cervical cytology

Recognition of follicular cervicitis, Chlamydia infection

Secondary type of angiosarcoma, rare and aggressive that develops in any tissue
Knowledge of post-radiation angiosarcoma previously exposed to radiation therapy, considered a secondary malignancy
Risk factors – history of breast cancer, long latency period

Identification of fungal organism in specimen where presence signifies life-threatening

infection, requires immediate medical attention and treatment
Critical values in cytology; fungal identification in cytologic material - Aspergillus
- Blastomycosis
- Mucor
Lung fine-needle aspiration, squamous cell carcinoma

Recognition of cytomorphology of common salivary gland tumors