Category Archives: Organ Systems

Organ Systems, Genitourinary, IHC Panels

Bladder vs. Prostate Primary

A relatively uncommon, but occasionally encountered diagnostic dilemma is differentiating between a poorly differentiated primary urothelial carcinoma and a primary prostate carcinoma at the bladder neck.  Commonly used antibodies in the past, such as PSA and PSAP, while very specific, have shown significant loss of sensitivity in less differentiated prostate carcinomas.  Newer markers (GATA-3, S-100P, p63, p501s, NKX3.1, and PSMA) have shown great promise with improved sensitivity and excellent specificity compared to traditional antibodies (CK7, CK20, PSA, and ERG).  The article cited below does an excellent job in highlighting the comparison of these antibodies, including the pros and cons.  In an article by Goldstein, the sensitivity/expression of PSA appeared closer to 50%.
Table 1.  Prostate vs. Urothelial Carcinoma in poorly differentiated lesions at the bladder trigone (Mohanty, et. al.)
 
Antibody
Prostate
Adenocarcinoma (N=20)
Urothelial
Carcinoma (N=16)
0%
100% (16)
0%
88% (14)
0%
75% (12)
0%
56% (9)
15% (3)
75% (12)
20% (4)
63% (10)
25% (5)
0%
100% (20)
0%
100% (20)
0%
100% (20)
0%
AR
100% (20)
13% (2)
ERG
35% (7)
0%
PSA expression and other markers as a function of Gleason score (Goldstein, NS)
 
Gleason Score
PSA
CK7
CK20
PAP
     6 (N=25)
100%
0%
0%
100%
     7 (N=50)
98%
0%
2%
100%
     8 (N=54)
56%
0%
4%
65%
     9 (N=58)
52%
10%
16%
74%
     10 (N=38)
47%
13%
26%
61%
Prostate specific antigen (PSA), Prostatic acid phosphatase (PAP). Reactivity was defined as >25% positive cells.
Practicality Comment
In most immunohistochemistry labs, it is not practical to have “all” of the new and “exciting” antibodies, but there are several above, which are very practical in a general pathology practice laboratory.  GATA-3 is a very good marker for both breast and urothelial carcinomas.  Some issues of specificity have arisen, which should always be considered in the context of the differential diagnosis.  P63 is a commonly used marker in lung squamous cell carcinomas.  Additionally, one may want to consider adding one of the newer prostate antibodies (e.g. p501s, NKX3.1, or PSMA), but again one should consider the specificity of the antibody in the context of the differential diagnosis.
References
Mohanty SK, Smith SC, Chang E, et al. Evaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas. Am J Clin Pathol. 2014;142(2):173–183. doi:10.1309/AJCPK1OV6IMNPFGL.
 
Goldstein NS. Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. Am J Clin Pathol. 2002;117(3):471–477. doi:10.1309/G6PR-Y774-X738-FG2K.
Organ Systems, Gastrointestinal

Liver – Metastatic Disease

The relative incidence of the origin of tumors in the liver depends primarily upon the underlying condition of the liver itself.  The tumor distribution in a cirrhotic liver is significantly different from a non-cirrhotic liver.  The following are the types and frequencies of tumors for cirrhotic and non-cirrhotic livers.
 
 
Tumor Origin
Cirrhotic Liver
Non-Cirrhotic Liver
Liver
77%
2%
Lung
7%
23%
Colon
4%
13%
Pancreas
2%
18%
Stomach
4%
11%
Breast
–
7%
Other
6%
26%
References
Modern Pathology (2007) 20,S49-S60.
Organ Systems, Gastrointestinal

Gastrointestinal Stromal Tumor (GIST)

GIST Immunohistochemistry Expression
IHC Stain
Percentage
~95%
>95%
80% gastric
50% Sm. Int.
95% Esoph.
95% Rectum
Rare
<1%
~5%
SMA
~35%
Liegl-Atzwanger, et. al. Virchows Arch, Feb. 18, 2010.
Mod Path (2008)21,46-53.
GIST Immunohistochemial Diagnostic Panel
IHC Stain
Comment
>95% sensitivity for GIST
Often + in GIST, less specific
Expressed in Schwannomas, which may have similar morphology to spindle cell GISTs
Expressed in leiomyoma/leiomyosarcoma.  Rare GISTs will show expression
 
It is important to interpret these stains as part of a panel to maximize specificity of diagnosis.
Organ Systems, Gastrointestinal

Colon Adenocarcinoma

Colon adenocarcinomas have a usual and distinctive IHC immunophenotype (CK7-/CK20+), which follows the general trend in the GI tract that CK7 expression changes from positive to negative as one moves proximal to distal, and CK20 expression changes from negative to positive as one moves proximal to distal.
 
Colon Adenocarcinoma
Negative (rare + cases)
Positive (>90%)
Positive
Positive
Usually negative, but up to ~10% may be positive!!!  The CK7/CK20 profile should be reassuring to support a colon primary.
Positive
Positive
CA19-9
+/-
 
It is important to remember that IHC performance is variably dependent on tissue fixation, which can vary widely in colon tissue due to the way cases are often grossed.  Therefore, careful selection is critical in identifying characteristic IHC staining profiles (e.g. CK20 may not stain a colon adenocarcinoma in poorly fixed areas).  Different antibodies have different sensitivities to the amount of fixation.
References
Eisen, Richard N, AIMM Annual Meeting, “Selected Topics in Gastrointestinal, Pancreatic and Hepatic Neoplasia”, presentation, 2010.
 
Diagnostic Immunohistochemistry: Theranostic and Genomic Applications. [edited by] DJ Dabbs. 3rd Edition.  Elsevier, 2010.
Gastrointestinal

Small Intestine Adenocarcinoma

Primary adenocarcinomas of the small intestine are rare but do have some discriminating IHC characteristics.  The IHC profile of non-ampullary adenocarcinomas of the small intestine is different from normal small intestine expression of CK7 and CK20, which is CK20 positive (diffusely) and CK7 negative.
Small Intestine (Non-Ampullary) Adenocarcinoma
Positive
Usually Positive (~60-70%)
Positive (~70%)
Positive (~70%)
Reference
Chen, ZM, et. al. “Alteration of CK7 and CK20 Expression Profile is Uniquely Associated with Tumorigenesis of Primary Adenocarcinoma of the Small Intestine.”Am J Surg Pathol. 2004 Oct;28(10):1352-9.