All posts by peferguson

Organ Systems, Breast

Breast – Fat Necrosis

Fat necrosis may sometimes present as a palpable mass, which may raise clinical concern or distress in the patient.  Approximately 1/2 of cases have a history of trauma.  Fat necrosis is also a common finding in excision specimen after a preceding biopsy.

The characteristic findings of fat necrosis include mixed inflammation (neutrophils, histiocytes, etc.), fibroblastic proliferation, and liquefactive fat necrosis.  Each of the component may vary in prominence.  The most important thing is not to mistake fat necrosis for malignancy, and not miss an area of malignancy masked by fat necrosis (AE1/AE3 or CAM5.2 may be helpful in such situations).

Photomicrographs
Fat Necrosis
Fat Necrosis
Fat Necrosis
Fat Necrosis
Fat Necrosis
Fat Necrosis with giant cell reaction
References
Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015.
Organ Systems, Breast

Breast – Epithelial Proliferations

There are many features of breast disease that encompass a wide spectrum of morphologic and radiologic findings, which have a varying risk of subsequent carcinoma.  Some of these entities are thought to be direct precursors to invasive carcinoma, and others just signify a component of future risk of invasive carcinoma.

Non-Atypical Lesions
Miscellaneous Findings
Atypical Lesions
Breast Lesions and Risk of Developing an Invasive Carcinoma
Breast Immunohistochemsitry
Organ Systems, Breast

Breast Lesions and Risk of Developing an Invasive Carcinoma

The following table and figure illustrate the risk of developing an invasive breast carcinoma based on the type of lesions previously identified.  This information does not take into consideration other factors such as race and family history (complicated topic).

Relative and Absolute Risk of Invasive Breast Carcinoma
Relative
Risk
Absolute
Risk
(lifetime)
Breast
Lesion
1
3%
1.5 – 2
5-7%
4 – 5
13-17%
8 – 10
25-30%
Breast Cancer Risk Chart
Breast Cancer Risk Chart
References

Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Philadelphia, PA: Elsevier/Saunders, 2015. 

Organ Systems, Gynecological, Cervix, Uterus, IHC Panels

Endometrial vs. Endocervical Adenocarcinoma

Endocervical vs. Endometrial Adenocarcinoma
Endocervical and endometrial adenocarcinomas may be morphologically indistinguishable morphologically.  The question often comes up as to whether a case represents an endometrial adenocarcinoma involving the cervix, or and endocervical adenocarcinoma involving the endometrium.  The following antibodies may be helpful in such circumstances:
 
 
Endocervical
Adenocarcinoma
Endometrial
Adenocarcinoma
Negative (7-8%+)
Positive (70-93%)
Positive (65-95%)
Usually Negative
Negative (4-20%+, 38% weak)
Strong Positive (67-90%)
Strong & Diffuse Positive (90-100%)
Patchy Positive cells (~35%)
HPV
Positive (67%)
Negative
References
AJSP 2002;26:998
 
“Endocervical vs. Endometrial Adenocarcinoma:  Update on Useful Immunohistochemical Markers.”  RT Miller,The Focus ProPath Immunohistochemistry.”   April 2003.
Organ Systems, Pulmonary, IHC Panels

Mesothelioma vs. Adenocarcinoma

Immunohistochemistry
It is generally recommended to perform two mesothelioma markers and two carcinoma markers, since there is no single sensitive and specific marker for either entity.  The data below is a snapshot of several studies.
 
IHC Marker
Adenocarcinoma
Mesothelioma
8%
100%
CK5/6 (CK5)
2%
100%
0%
93%
Thrombomodulin
14%
61-77%
N-Cadherin
30%
73%
93-100%
8%
80-100%
18%
BG8
96%
7%
81-88%
0%
84%
0%
72-74%
0%
72-85%
0%
 
Obviously the main source of adenocarcinoma in this differential setting is with a primary lung adenocarcinoma and mesothelioma.  If a metastasis is likely, then the stain performance expectations for adenocarinoma may vary significantly (e.g. metastatic ovarian serous carcinoma would likely express WT-1).
References
Marchevsky AM. Application of immunohistochemistry to the diagnosis of malignant mesothelioma. Arch Pathol Lab Med. 2008;132: 397–401. 
 
Sandeck HP, Røe OD, Kjærheim K, Willén H, Larsson E. Re-evaluation of histological diagnoses of malignant mesothelioma by immunohistochemistry. Diagnostic pathology. 2010;5: 47. doi:10.1186/1746-1596-5-47
 
Ordóñez NG. Immunohistochemical diagnosis of epithelioid mesothelioma: an update. Arch Pathol Lab Med. 2005;129: 1407–1414.
Organ Systems, Genitourinary

Urothelial Carcinoma

Urothelial carcinoma is the primary tumor in the bladder.  It may have morphologies or adenocarcinoma, urothelial carcinoma (transitional), or squamous cell carcinoma.
IHC Expression Characteristics
CK7 is expressed in a majority of urothelial carcinomas. (CK7+/CK20+)  Bladder adenocarcinomas with intestinal differentiation may lose CK7 expression.
(++/-) Wide variation in reported expression (15-97%), but appears a majority are positive (CK7+/CK20+).  There is some evidence that CK20 may be helpful in CIS dx.  Reactive urothelium shows CK20 expression in the umbrella cells.  Most dysplasia/CIS cases show at least focal transmural CK20 expression.  Sensitivity and specificity for CK20 have been shown to be >70% and >90%, respectively.  (Ki-67. p53, & p16 may also be useful)
p63 staining is found in >90% of urothelial layer nuclei.  PSA combined with p63 may be a helpful combination to differentiate a primary prostate tumor from urothelial carcinoma.
34betaE12
CK5/6
HMWK which is expressed in the basal layer of prostate glands, and urothelium (highly sensitive).  Practically any tumor with squamous differentiation will usually express HMWKs.
p53
Expression found in 40-60% of bladder carcinomas (worse prognosis).  Expression of p53 in >50% of cells is seen in CIS, whereas reactive urothelium show weak patchy nuclear staining.
Increased expression in flat CIS and low grade tumors.
CD44
May be useful in that it is normally expressed in the basal layer, and is absent in full thickness CIS.
Often positive in urothelial dysplasia.
References
Diagnostic Immunohistochemistry: Theranostic and Genomic Applications. [edited by] DJ Dabbs. 3rd Edition.  Elsevier, 2010.
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.