Caveat: These "tests" are
not as exacting as are chemical, analytical tests. All persons involved
ought to be properly trained and competent for interpretation. The
lab should be officially accredited and involved in an official external
competency survey program. The individual test should be quality
controlled with a slide containing tissue elements with known positive
(graded positives...weak/medium/strong...if possible) and negative
control reactions to assure that the test system and reagents all
worked properly. It is further optimal if the pathologist selects
a tissue block for testing which will include some normal patient
tissues which should react positively..."positive internal auto-control" (to assure that the test tissue
was properly handled and processed and is capable of positive reactions).
Prompt fixation (NBF is considered universally OK with at least 6 hours exposure in fixative & not much more than 48 hours) is vital. Not
only should a positive reaction make sense with the control reactions,
but it should make morphological sense, also! Finally, the astute
clinician should always question an odd or clinically discordant
See March 2008 issue of Archives of Pathology & Laboratory Medicine!
|TCC: 100% ck7 +
||breast ca.: 100% ck7+
||78% of Merkel cell
||non-small adeno. of lung & BAT: 100% ck7+
||37% of gastrics
||ovarian ca., serous & endometrioid: 100% ck7+
||endometrial adenoca.: 100% ck7+
|13% of gastrics
||small-cell neuroendocrine lung
||salivary gl. ca.
||adrenal cort. ca.
||chromophobe RCC 82% at least focally ck7 pos.15
||15renal oncocytomas 52% at least focally ck7
- tumor-specific breast-cell marker: BRST-2 (GCDFP-15)...is
it primary or metastatic? [met. LMC-02-5503]
- eccrine tumors can be ER, PR, and GCDFP pos.
- ER is rarely positive in lung cancer & never positive in colon cancer.
- HER-2: at least when 2-3+, works equally well on Hartmann's-fixed
nodes with mets.[LMC-04-2109A3]
- Ki67: use it to help locate the most mitotically
active area of tumor for the Elston score (if need be); and it
reflects entire % of tumor cells in active-proliferation parts
of cell cycle.
- CK7: breast pos. (and so are
the intraepidermal benign, clear, Toker cells located singly
or as small groups around the nipple duct orifices) & especially
in distinguishing intraepidermal Paget's from melanoma (both
can be S100 pos.)
||almost never on nipple
||has nuclear vacuoles
||+- pos (79-100%)
||+- pos (0-40%)
- positive cytoplasmic filaments relatively condensed perinuclear
ring in lobular and diffuse cytoplasmic positivity in ductal
- good for (ck7 and pan-ker also) highlighting a highly cellular
dispersed invasive tumor pattern in proximity to a lumpectomy
surgical margin...possibly more dangerous "close" margin [LMC-01-1915];
remember that it marks both benign and malignant breast epithelium
- a micrometastasis marker in nodes
from breast cancer surgery but can label plasma cells [LMC-01-7388B&C] (as
can EMA) & reticulum cells
[LMC-02-4776] but with a more diffuse
or granular cytoplasmic pos. different from ca. cells (AE1/AE3
cocktail [our pan-keratin
] has least non-epithelial cell
as good/best); pankeratin
highlights intracapsular infiltration and transcapsular invasion
much superior to H&E [LMC-02-5028].
- E-cadherin: lobular carcinoma is negative; ductal carcinoma
is positive; should probably test any relatively small-celled breast
cancer with this in the absence of lots of tubule formation [LMC-02-2144;LMC-02-5160]
- k903(34BE12)(Tavassoli, AJSurg. P 23(9):1048-1058,
- ductal hyperplasia (all cells pos....including non-atypia
parts of "columnar cell hyperplasia" [LMC-04-5858])
vs. ductal-AH (spotty cells pos. plus myoepithelial cells)[LMC-01-1497] vs.
ductal CIS (all cells neg. except myoepithelial cells)...stains "mature
epithelials" & ME cells
- tumor sizing: helps be sure that a benign component is
not counted in the greatest diameter [LMC-01-5927] of
a tumor...falsely causing a greater measurement
- laminin or type 4 collagen: stains basement membranes
- S-100: stains myoepithelial (ME) cells AND
stains the epithelial cells and nuclei of the acini of microglandular
adenosis (MGA) and atypical microglandular adenosis (AMGA)7,
lesions which lack myoepithelial cells but do have anti-laminin
positive intact basement membranes; Paget's can be pos.
- smooth muscle actin (SMA): stains myofibroblasts
and ME cells
- CD10: stains ME cells
- CD34 marks myofibroblasts (The Breast J. 7:263-265,
- smooth muscle heavy-chain myosin (smm-hc)
: labels myoepithelial (ME) cells so as to be excellent
help to distinguish invasion (ME neg.) from
CIS (ME pos.)[LMC-01-1384; LMC-02-4316]; in
an ordinary adenosis area mixed with invasion (sort out the
extent of the invasion); some complex benign stellate adenosis
or epitheliosis vs. invasion [S-01-1380; LMC-01-4299];
and invasion vs. a complex papilloma [S-01-3967] or
sclerosing papilloma [S-01-9404]
- ER, PR, and HER-2: we have had cases that are HER-2 2+ by IHC & FISH
neg. [LMC-01-7037 & 7323]
|ductal NOS S-B-R grade 1
||99% neg gene amp.13
|ductal NOS S-B-R grade 2
||83% neg g.a.13
|ductal NOS S-B-R grade 3
||87% neg g.a.13
||<10% are pos.
||<10% are pos.
|(true) apocrine ca.
||about 75% pos.20
||about 45% pos.20
||about 36% positive20
||98.5% neg g.a.13
||usually not high
|pleomorphic lobular (nuc. grade 3)
|| pos. g.a.13
|Central & Peripheral nervous system:
- gliomas & GFAP: negative GFAP doesn't exclude
glioma, especially if vimentin pos.14
- to predict behavior category:
- increased Ki67 rate: increases likelihood to recur
(Dr. Peter Burger @ Johns Hopkins
[LMC-02-825]; (< about 4% Ki67 positive nuclei
in meningioma indicates negative likelihood to recur;
about 4-16% positive indicates atypical meningioma and >16%
suggests "anaplastic meningioma"...Human Path,
- PR: 87% of malignant, 57% of atypical, and 36% of
benign meningiomas have 0-9% of nuclei PR pos. & only
13% of malignants have 10% or greater positive nuclei19.
- Mitotic index/rate: benign, low (ave. < than 1)
per 10 40x hpfs; atypical, ave. 5.15 (+- 0.93); malignant,
ave. 17.53 (+- 3.73)19.
- risky histology: 2 or more of: high cellularity,
sheeting (absence of lobulation or whorls), prominent
nucleoli, and obvious mitotic figures19. So,
worse meningioma outcome when combined PR = 0,
mitotic >6, and malignant histology19.
- grading glioma/astrocytoma: in a 3-grade system, Ki67 helps
chose between I and II....if <3% positive, I; if >7%,
- ubiquitin: labels Alzheimer's disease tangles;
EGBs in pilocytic astrocytoma
- peripheral nerve evaluation: S-100 finds them; CD10 stains
axonal myelin sheath [LMC-03-2740].
- GI medical issues:
- Helicobacter pylori: the IHC stain is
great for identifying the organism, especially when sparsely
present (easier than histochem. stains
); and a negative stain is a "must" to be sure
no H. p. in any case where EGD is done and results
in a biopsy
- LCA or CD3: helps one appreciate lumenal epithelial
lymphocytic exocytosis of celiac
disease in proximal small bowel (duodenal)...can
look H&E normal...[LMC-01-2410; S-01-6591]; and collagenous
or microscopic lymphocytic colitis (diff.
dx.) in the colonic biopsies. [S-01-289;
- CD10: identifies brush
border of absorptive cells:
- so as to note either non-goblet-cell intestinal
metaplasia in esophageal biopsies
- or a reduction in celiac disease of normal
high ratio of absorptive cells to crypt lining cells [LMC-01-2410]
- or reduction or loss of border in disaccharidase
- CDX2: a nuclear marker for GI origin & is helpful when pos. (lung cancer is rarely positive and breast cancer never positive).
- premalignant assessments:
- Ki67: prove a colon polyp (especially
if family history of cancer; or is larger size and right
colonic location) is not a serrate adenoma by showing
that all positive epithelial nuclei are in the deep 66%
of crypts [AJSP 23(9):1158-1160, 1999] [S-01-2292;
S-01-2127; LMC-01-8025; S-01-14482].
malignancy issues & tumor classification:
- ck7/ck20: stains to determine if G-E junction
focal or short-segment intestinal metaplasia is
of the Barrett's type (connoting premalignancy potential)
or the gastric type (no or much less neoplastic connotation).
Normal pattern=ck20 pos. in surface foveolar cells & ck7
pos. in mucosal glands=gastric-type intestinal metaplasia.
A staining reversal occurs in Barrett's-type intestinal
metaplasia (Barrett's CK7/20 pattern): ck20 marks
only superficial surface & ck7 marks deep & surface3,
24 [LMC-01-1860; S-01-5944;
S-01-1771]. Have had cases where only partial
reversal (& signif. is uncertain) [S-01-11069]
- p53 is being touted as a Barrett's high-grade dysplasia
marker16 (coupled with c/w histology/cytology),
p53 detectibility...nuclear over-expression...is
indicative of p53 gene mutation (the normal gene
inhibits...brakes...a cell's entry into S-phase).
- CD10: if you are unsure whether there
is a bit of intestinal metaplasia or not in the biopsies,
CD10 can tag the brush border of non-goblet absorptive
- pan keratin: to check MALT-like lymphomatous
processes and highlight any intra-tumoral epithelials in
search of occult/obscure/residual lymphoepithelial
- GIST: (CD117 positive by definition...the product
of the c-kit proto-oncogene, but a few said to be negative; 70 % [the myoid GISTs] CD34+; most are desmin
[LMC-01-8061], see tumors, below.
- unknown primary: COL-1 variant of CEA marks
colorectal/intestinal adenocarcinoma [LMC-02-5503],
to include small bowel [LMC-04-10307] and
- 33% gastric adenoca. can be CD68+ [LMC-03-35].
- medical issues:
- tumor identification:
- biopsies and CIN & HPV and
- Ki67: helps discern early koilocytotic atypia
(HPV viropathic change) because more than a few positive
nuclei much higher than just basal/parabasal zone (Advances
in A. P., 8(2):83-92, 3/01)(Crum, et. al., AJSP 25:884-891,
2001) [S-01-2899; LMC-01-7221; S-01-8116;
S-01-8237]; positivity correlates with HPV-type
viropathic effect [LMC-01-6187]
- therefore, if questionable koilocytotic cell change
(perinuclear haloes and raisinoid nuclei) and Ki67
positivity not in those nuclei or high in epithelial
layer, it may be best to just call minor atypia, if
anything [S-01-8117, S-01-8542] ;
but, note that,
- in HPV lesions, Ki67 only stains some of the obviously
abnormal and koilocytotic cells positive
- reactive epithelium, or squamous metaplasia with
atypia, might have "a few" positive
nuclei at higher zone...but mostly basal/parabasal [S-01-13041;
- reactive/early atrophy has reduced Ki67 positivity,
even in basal/parabasal zone [S-01-12475;
- Reed-Sternberg cells: fascin (very R-S cell sensitive; dendritic cells pos.); CD15, CD30
- discern obscure follicular pattern in hyperplasia & PTGC: IgD18
- Ki67 proliferation marker: useful in follicular hyperplasia vs. follicular lymphoma...high rate and pattern of follicle polarity favors hyperplasia12
- hairy-cell leukemia marker: touch prep or marrow smear, air-dried & then acetone fix prior to IHC with CD11c (LMC-01-8103); monocytes stain pos. (at least with flow cytometry)
- Bcl-2: pos. in many types B lymphomas [see write up] and value is in follicular hyperplasia vs. nodular B lymphoma12
- CD3 pan-T cell: most specific pan-T marker because no CD3 antigen in B cells...but some really immature T neoplasms can be void of CD3 & some can lose their CD3 antigen
- CD4 T helper/inducer: these hold the HIV receptor
- CD5: pan-T and a B subset (spleen & node mantel zone cells and pleural B lymphs; MCL & CLL/SLL pos. lymphoma) (cutaneous sweat gland sometimes pos.)
- CD8 T suppressor/cytotoxic (tumor infiltrating): marker is specific for this cell; labels cells of "large granular lymphocytic leukemia"
- CD10 (CALLA): granulocytes, normal follicular-center B cells, and acute leukemia and follicular lymphoma with pos. cells spilling into the interfollicular zone12 ; also some early B & T cells22; and some in MCL and CML in blast crisis and Burkitt's (polys are positive; some spindly stromal cells are pos.); also stains gut mucosal & renal tubular brush border & peri-axonal sheath.
- CD11c: HCL, above
- CD20: pan-B cell (the intracellular epitope is L26...clone L26 reagent antibody) but epitope may not have developed yet in less mature, precursor-B neoplasms (see CD79alpha); as many as 20% of myeloma cases are pos.
- CD23: SLL/CLL pos.; B follicular dendritic cells pos.12; mature B cells22
- CD 30: Golgi "dot" positive in large cells of ALCL & syncytial variant of HD [L10-6325].
- CD56 T natural-killer (NK): best on formalin
- CD68: histiocytic cells; 33% gastric adenoca.
- CD79 alpha: is a pan-B but appears earlier and positive in precursor-B tumors; is sort of an immunoglobulin marker & marks plasma cells and 50% myeloma cases positive
- CD117: mast cells have strong membrane positivity.
- CD138: plasma-cell marker (also + with many carcinomas)
- cyclin D1: mantel cell lymphoma has pos. cells; (we've noted supranuclear "dot" cytoplasmic pos. in ileal epithelium [LMC-03-5237]).
- ALK-1 protein positive cells in ALCL
- epithelial markers positive: p63 can be positive in diffuse large B cell lymphoma34; EMA & cytokeratin can be positive in ALCL.
- S100 positive cells Langerhans cell sarcoma (LCS) [with big pale eosinophilic cells] and Langerhans cell histiocytosis (LCH) cells are positive.
- ubiquitin: labels Mallory's hyalin
- hunting cholangiocytes (biliary damage...ductopenia): may need to use ck7 and ck19 to hunt residual cholangiocytes; biliary adenoca. CEA, EMA, and keratin pos.8
- tumors, HCC vs. met. adenoca. vs. cholangioca.:
- polyclonal CEA: canalicular pattern in 80% hepatomas
- Hep Par 1: 95% sensitive for HCC & HCC can be negative & some at least few pos. cells in some gastric, adrenal cortical, & lung cancers.
- unknown primary met. vs. lung primary: non-small cell non-squamous ca.
lung or thyroid TTF-1 positive; neuroend. neg [LMC-02-6548
intermediate neuroend.] for TTF-1.
- lymphangioleiomyomatosis: HMB-45 + (leiomyosarcoma is HMB-45
- angiomyolipoma HMB-45 +
- histo. type of carcinoma (radiation
oncology does adjuvant CNS XRT if an adenoca. because much
more likely than SCC to have occult CNS mets... remember
that bronchogenic ca. may be mixed squamous and adeno):
- small & non-small SCC: ck5 marks SCC (and mesothelioma) & K903 marks SCC; and SCC usually
ck7 & LMW-keratin (ck 8, 18, and 19) neg. (non-small,
nonsquamous pos. [LMC-02-6548 neuroend.]) and
HMK-keratin (ck1, 5, 10, and 14) positive4.
Small-cell SCCs neuroendocrine neg., TTF-1 neg., & HMW-ker
pos.; spindled variant may be scant on keratin and pos.
vimentin.11 Cytology: tend to
heavier chromatin, less likely large nucleoli, and more
likely pyknotic nuclei as cells die; focal, dense squamous
- small & non-small-cell adeno & BAT: most are ck7 pos.;
ck20 neg.; 60-75% TTF-1 pos.; villin pos.; LMW-keratin (ck
8, 18, and 19) pos.; also, if CEA+, or CD15+, or LMW-ker+,
it favors adeno over squamous. I'd advise using no less than
two adeno markers so that a poorly differentiated non-small
is SCC only if two or more "adeno" markers are
- small-cell neuroendocrine: ck7 neg.; they are typically
neuroendocrine pos. (synaptophysin most sens.), HMW-ker neg.
and LMW-ker punctate pos., and high % are TTF-1 pos.& may
have rare ck7 pos cell.11[a
small-bowel met LMC-03-1869]
- large-cell neuroendocrine: usually co-express keratin
- basaloid: nests of relatively undiff. small cells
with lots of necrosis and some peripheral palisading (HMW-ker & LMW-ker
- atypical carcinoid:
- lymphoepithelioma-like carcinoma: large anaplastic
cells & most express LMW & HMW ker
- giant-cell carcinoma: at least 40% of cells are
greater than 40 microns & usually co-express keratin
- clear-cell carcinoma HMB-45 +
- ck7 highlights alveolar walls/pneumocytes
- CD68 shows histiocytic/macrophage component [LMC-02-559]
- CD34 shows alveolar capillary pattern or absence thereof [LMC-02-559].
- Lymph node micrometastases:
- pankeratin (AE1/AE3): best for beast cases, see "breast" above.
- benign vs. malignant: it will take skillful comparison of the cytohistology of the primary vs. the node deposit to decide the DDX.
- nodal nevus vs. malignant met.27: capsule & parenchymal septal nevi will have no or very low Ki67 proliferation positivity & melanoma 2-80% of cells positive; & likely HMB45 negative & not have nucleoli28 & can be present in cases which also have mets [L07-5254].
- S100: global...most sensitive & least specific...will also stain all the numerous intranodal dendritic cells/macrophages (4 types: follicular dendritic, extrafollicular fibroblastic [S100 neg, desmin/sm-actin pos, vimentin pos] histiocytic, and interdigitating
- vimentin: nearly all are pos.11
- panmelanoma (HMB45, MART1, and tyrosinase cocktail): most likely to be positive for melanoma-specific marking
- HMB45: 50% of pulmonary primary are pos11; some type of single mononuclear cells [LMC-01-6340] may stain pos. & may not be optimally sensitive1
- MART1: highly melanoma specific and no obscuring of nuclear detail
||n & c +5;
||68% strong memb. +5
||4-25% wk.? memb.+5
- Oral cavity:
- S-100: lichen planus lesions sometimes have intraepithelial
positive dendritic cells
some definite cases [S-01-2388] do
- Ki67: increased basal and parabasal positivity
in an odontogenic keratocyst [S-01-12766]
- Parathyroid gland:
- we have found that a cellular adenoma [LMC-02-608] has
a Ki67 of about <10% and a carcinoma that subsequently
metastasized [LMC-99-2428] was 50-75%.
- Pituitary adenoma/tumors:
- neuropath lab at Univ.
of Va. says that it is one of the few labs in North
America focusing IHC & EM in this area 804-924-9175
- our neurosurgeons don't need marker specification9
- S100: though non-specific, nearly all mark
with this and it can help prevent a misdiagnosis when
working up an atypical fibroxanthoma (AFX)/malignant
fibrous histiocytoma (MFH), always be sure that you've
checked the melanoma angle with at least this marker [S-02-4382]
- "all" (5-10% false neg.4) melanoma
cells pos. (CIS or invasive) vs. spotty pos.
with dysplastic nevi vs. neg. with ordinary nevi [S-01-3737]
- watch out for false pos. monocytes [LMC-01-6340] in
- helpful for an exacting Breslow thickness measure
when lots of inflammatory cells and when mixed
with residual pre-existing melanocytic nevus [S-01-3737]
- MART-1(Melan-A): marks benign and malignant (there
are false negs.4) melanocytes and
can help discern upward intra-epidermal scatter [S-01-9340] and
it gives a clean view to help discern an accurate Breslow
thickness AND to precisely document the early papillary
dermal invasion of level II [S-01-9340] or
reticular dermal invasion of a Clark level IV [LMC-01-5805;
- it may take a cocktail (our panmelanoma)
of 3 or more melanoma markers to prove melanoma4
- vascular...CD34: marks vascular endothelium
(much better than factor VIII), solitary fibrous tumor, DFSP
[LMC-03-6618], and Kaposi's
- eccrine: calretinin pos.23
- mycosis/CTCL (cutaneous T-cell lymphoma): epidermotrophic
cells said to be "CD4 helper" pos.
||Pleomorphic small T cell
||CD30 pos. large cell
||Reactive dermatitis (eczema; allergic
|CD4 (T helper/ inducer)
|CD8 (T suppressor /cytotoxic)
|CD20 (mature B)
- Skin, continued
- mast cells: CD117+ (as is an occassional melanoma & small cell lung cancer).
- Merkel cell tumor: IHC for neurofilament protein (NFP) pos. in 50% with a "dot" character discernable29; most are CD56 pos.; NE lung met to skin is TTF-1 pos & Merkel neg.; 90% are ck20 pos. with a "dot" character discernable29; & 80% are NSE pos.29; commonly neuropeptide (chromogranin & synaptophysin) pos.
- carcinoma...possible adnexal
- Soft tissue & vascular:
- vascular/endothelial: CD34 marks vascular endothelium
(much better than factor VIII), solitary fibrous tumor, DFSP [S-01-14379CD34
NEG.], and Kaposi's.
- AFX/MFH mark with vimentin & alpha-1 ACT [LMC-02-128;
S-03-12071] and negative for spindled/sarcomatoid SCC by K903 [LMC-06-8409].
- peripheral nerve sheath tumors S100 & CD34+.
- CD-1a marks Langerhans histiocytes (usual histiocytes are
- CD68: histiocytes4.
- epithelioid angiomyolipoma is HMB-45 + & neg. for S100 & cytokeratin.
- GIST CD34 + and CD-117 + (see below).
- IMFT is ALK-1 pos.
- neurofilament (NFP): neurons, neuroma, neuronal tumors:
ganglioneuroma, ganglioneuroblastoma, neuroblastoma, paraganglioma,
pheochromocytoma, carcinoid, skin neuroendocrine ca. (Merkel
cell), neuroendocrine ca. elsewhere. Presence of S100+ sustentacular cells in an orderly, ordinary pattern tends to favoe a benign paraganglioma or pheochromocytoma (along with smaller size, excellent circumscription, negativity for necrosis, and low mitotic rate).
- desmin (smooth & skeletal) and myogenin are skeletal
- smooth muscle actin (SMA) marks smooth muscle4.
- unknown primary: non-small cell & non-squamous ca.
lung and thyroid are TTF-1 positive (but any definite
thyroid cancer primary which is truly TTF-1 negative is a
cancer that cannot produce thyroglobulin); medullary ca.
TTF-1 pos. & atypical carcinoid of larynx is negative
- ck19: marks papillary carcinoma positive (valuable
in proving papillary variant of follicular carcinoma) (Human
Pathology, Jan. 2001); BUT positive...diffuse reactivity...in
only 66% of papillary2.
- ret: nonreactive in benign lesions; pos. in 69% of papillary2.
- calcitonin: marks medullary carcinoma [LMC-01-5521] and
thyroid C cells and moderately differentiated neuroendocrine
(atypical carcinoid) carcinoma of larynx
- HBME-1: positivity may be an indicator of malignancy2.
- 9/138 papillary carcinomas (7 follicular variant & 2
classic) negative for all 3 of ck19, ret, and HBME-12.
- Tumor classification:
- GIST: the specific marker for this tumor is CD117 (stains
the c-kit growth factor receptor as cytoplasmic, membranous, or perinecluar "dot" positivity) [4/2000] & positivity
identifies tumor as from interstitial cell of Cajal and NOT
an ordinary sarcoma; GIST is CD34+ [LMC-01-8061] & responds
to the tyrosine kinase inhibitor STI571 (Gleevec) [6/6/01]; CD117
also stains mast cells and melanocytes [S-02-10146]. Epithelioid GIST may mark poorly for both.
- neuroendocrine tumors (NET, NEC): need compatible light microscopy nuclei; are NSE pos. but NSE almost too sensitive & poorly specific; NFP & CD56 are sort of
pan-neuroendocrine ca. markers & chromogranin & synaptophysin follow. Over 80% of hypercalcemic NET (or NEC) of ovary are WT-1 & infrequent in others,
while high % NEC of lung are TTF-1 positive, and most NEC of cervix are HPV positive31.
- medical issues:
- tumor types:
- EMA: RCC positive.
- c-kit (CD117) cytoplasmic pos. with papillary
and membrane pos. with chromophobe.
- EGFR neg. in oncocytoma & pos. in chromophobe25.
- CD10 pos. clear cell & papillary & neg.
- IHC & other all types.
- urothelial is vimentin neg. (?).
- medical issues:
- cancer diagnosis:
- keratin903: stains basal acinar cells positive;
(1) absence of staining in radiated prostate or relative
to ASAP (atypical small acinar profiles) lesions PLUS (2) suspicious
pattern (3) & cytological features is strong evidence
in favor of adenocarcinoma.
- ERG: on the scene in 2011, nuclear staining over-expression contributes to development of androgen-independent prostate cancer through disruption of androgen receptor signaling. Studies have shown that the TMPRSS2-ERG fusion is associated with a more aggressive phenotype & may be another tool to use on prsotate biopsies (1) if any doubt that a cancer is Gleason score 3 + 3 = 6 or less and (2) in trying to decide as to "watch & wait" or not.
- P504S18: stains acinar cancer
cells in 92% of cases and also stains hi-grade
- Ki67: a labeling index of 7.1% or higher is
related to biochemical failure of therapy, distant
metastasis, and cancer specific death
; behaves more like a Gleason 8 [S-04-202].
- poorly diff. prostate acinar vs. urothelial:
IHC for PSA pos. >95% cases; HMWK & p63
pos. in urothelial & negative in prostate.
- neuroendocrine prostate can be TTF-1 positive30.
- calretinin: Leydig (and Sertoli ?) cells
pos23 and adenomatoid tumor positive [L10-14863].
- PLAP: seminoma marker (but can see +- in embryonal & neg. in chorio.)
- vimentin: embryonal & chorio are neg.
- HCG: trophoblastic positive & not other testicular GCTs.
- CD30: embryonal carcinoma positive26 & not other testicular GCTs; all seminomas were negative33.
- CD117: seminoma positive26 & not other testicular GCTs; all embryonals were negative33.
- AFP: yolk sac pos. (rare +- embryonal)
- Urinary bladder & urethra:
- Ki67 is basal in reactive/hyperplasia & variably
upward in dysplasia21.
- reactive vs. CIS: ck20 normally + only for surface "umbrella
cells" & all + for CIS; p53, normals neg. & CIS
- And, using H&E morphology and possibly molecular markers (such as ck7 & ck20 & possibly K903: SCC is ck7/20 negative while TCC is ck7/20 positive; SCC should also be K903 positive), is it SCC or TCC with some SCC features [L06-9298]?
- Komorowski R, Eval. of Micromet. in SLN of Cutaneous Melanoma,
- Modern Pathology 14:338-342, 2001.
- Ormsby AH, et. al., @ Cleveland Clinic, Gastroenterology 119:683-690,
- PhenoPath Clin. Ref. Manual & e-mails
- Roberts F, et. al., Scotland, AJCP 116:253-262, 8/2001
- we perform @ LML
- F. A. Tavassoli, MD, or Daniel Sullivan, MD, Medical
College of Ga., Seminar, 21 April 2001
- Ackerman's Surgical Pathology [text], 8th Ed., 1996, Juan Rosai
- members of specialties on our medical staff
- Applied Immunohistochem. 3(2):101, 1995
- Dabbs text
- Chan JKC, syllabus, 111th Semi-annual Seminar (CTTR), 2 Dec.
2001 [we all have a copy]
- Hoff ER, et. al. HER2/nue Amplification in Breast Cancer, AJCP
117:916-921, June 2002.
- Burger PC text, SP of the Nervous system and Its Coverings,
4th Ed., 2002 (Dr. Carter's office)
- Wu SL, Modern Pathology 15(7):712-717, July 2002.
- e-mails, letters, communications: GI path. experts
- AFIP Fascicle, "Tumors of Neuroglia and Choroid Plexus
- PhenoPath Lab letter, Dr. Allen Gown, 5(3):2, Nov. 2002
- Hsu DW, et. al., J. Neurosurg., 86:113-120, Jan. 1997.
- Rosen PP, Rosen's Breast Pathology 2nd Ed., 2001.
- Sun W, Applied Immunohistochemistry & Molecular Morphology
10(4):327-331, Dec. 2002 (Dr. Armstrong's journal)
- Caldwell CW & Lacombe F, Evaluation of Peripheral Blood
Lymphocytosis, 125 pages (a flow cytometry book), 2000. [Dr.
- Zymed catalogue, 2002-2003.
- Goldblum, John R, chair of AP @ Cleveland Clinic, ASCP Teleconference
10/10/03, AV & handout.
- Shah, Sejal, "Expression of EGFR...", Poster #29, ASCP annual meeting in Las Vegas, 10/2006.
- Leroy X, et. al., "CD30 and CD117 (c-kit) Used in Combination Are Useful for Distinguishing Emryonal Carcinoma from Seminoma", from France, J. of Histochem. & Cytochem. 50(2):283-5, 2002.
- Lohmann CM, et. al., @ Memorial SKCC in New York, "Expression of Melanocytic Differentiation Antigens and Ki-67 in Nodal Nevi and Comparison of Ki-67 Expression With Metastatic Melanoma", AJSP 26(10):1351-1357, 2002.
- Biddle DA, et. al., "Intraparenchymal Nevus Cell Aggregates in Lymph Nodes..." Am. J. Surg. Path. 27(5):673-681, 2003.
(posted Feb. 2001; latest
addition 30 May 2007).
- McKee, Calonje, & Granter, Pathology of The Skin... Two volumes, 3rd Ed. 2005.
- True LD, CME course 1 May 2005, 12th Annual SP Seminar, Pittsburgh .
- Carlson JW, et. al., "Biomarker-assisted...", Histopathology 51:305-312, 2007 [EBS subscribes].
- Archives of Pathology & Lab. Med., "Special Issue: Diagnostic Immunohistochemistry" 132(3):319-509, March 2008.
- Lau SK, Weiss LM, & Chu PG, "D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30", Modern Path. 20:320-325, March 2007.
- Hedvat, CV, et. al., "Expression of p63 in Diffuse Large B-Cell Lymphoma", [HERE]
- some ERG info HERE.
(posted about 2000; latest addn. 5 June 2014)