A rare breast carcinoma with a syncitial growth pattern and high grade cytology reported to have a good prognosis
Diagnostic Criteria
Syncitial growth pattern in at least 75% of tumor
Cell margins not distinct
Heavy mononuclear inflammatory infiltrate
Microscopically circumscribed
No infiltration
Absence of neoplastic ducts or glands
High grade pleomorphic nuclei with prominent nucleoli
We require all five features to make the diagnosis
Carcinomas lacking one of these features have been termed "atypical medullary carcinoma" by some
We do not use that term, diagnosing them instead as infiltrating ductal carcinoma
Richard L Kempson MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting:: May 1, 2006
Supplemental studies
Immunohistology
Demonstration of myoepithelial cells can confirm the in situ or benign nature of a process while their absence supports invasion
We prefer to use both p63 and calponin on problematic cases
A variety of markers have been used for myoepithelial cells:
Marker
Sensitivity
Specificity
Calponin
Excellent
Very good
p63
Excellent
Excellent
Smooth muscle myosin heavy chain
Good
Excellent
CD10 (CALLA)
Good
Good
High molecular weight cytokeratin
Very good
Poor
Maspin
Good
Poor
S100
Good
Very poor
Actin
Good
Very poor
Estrogen receptor (ER) and progesterone receptor (PR) are important markers for directing therapy and determining prognosis
Current consensus is that any level of positivity should be reported as positive
Medullary carcinomas are reported to be negative in 90% of cases
Her2neu status can be determined by either immunohistology or by FISH
The other technique can be used for borderline cases
Medullary carcinomas are reported to be negative in 94% of cases
Genetics
Medullary carcinoma is associated with BRCA1 germ line mutations in a minority of cases, but increased compared to the general population (2 of 18 cases tested)
Differential Diagnosis
Infiltrating ductal carcinoma
We designate simply as infiltrating ductal carcinoma those carcinomas that lack any of the five required diagnostic criteria
Many of these will be high grade, so the distinction is critical
We do not make the diagnosis of atypical medullary carcinoma
Large cell lymphoma
Lacks syncitial growth pattern and circumscription
Can simulate medullary carcinoma because of cytology, lymphoid infiltrate and absence of ducts or glands
Immunohistochemistry for lymphoid antigens and keratin can easily resolve this if it is a problem
Clinical
Rare type of carcinoma utilizing strict criteria
Early reports indicated a significantly better prognosis than high grade infiltrating ductal carcinoma as long as nodes are negative
Some recent studies do not confirm this improved prognosis
Problems with interobserver reproducibility and with adherence to strict criteria may explain these variable reports
A minority of cases may be associated witih germ line BRCA1 mutations
Recurrences are very rare more than 5 years post detection
Grading / Staging / Report
Grading
Bloom-Scarff-Richardson grading does not apply to medullary carcinoma
It is histologically high grade by definition
It is clinically low grade as long as the nodes are negative
Staging
TNM staging is the most widely used scheme for breast carcinomas but is not universally employed
Critical staging criteria for regional lymph nodes
Isolated tumor cell clusters
Usually identified by immunohistochemistry
Term also applies if cells identified by close examination of H&E stain
No cluster may be greater than 0.2 mm
Multiple such clusters may be present in the same or other nodes
Micrometastasis
Greater than 0.2 mm, none greater than 2.0 mm
Metastasis
At least one carcinoma focus over 2.0 mm
If one node qualifies as >2.0 mm, count all other nodes even with smaller foci as involved
Critical numbers of involved nodes: 1-3, 4-9 and 10 and over
Note extranodal extension
Report
Excisions: the following are important elements that must be addressed in the report for infiltrative breast carcinomas
Grade
Total score and individual components
Size of neoplasm
Give 3 dimensions or greatest dimension
Critical cutoffs occur at 0.5 cm and at 2 cm
Margins of resection
Measure and report the actual distance of both invasive and in situ carcinoma
Angiolymphatic invasion
Indicate if confined to tumor mass, outside tumor mass or in dermis
(Extensive DCIS is not currently felt to be a significant predictor of behavior)
Results of special studies performed for diagnosis
Results of prognostic special studies performed
ER, PR, Proliferation marker, Her2neu
If studies were performed on a prior specimen, refer to that report and give results
Needle or core biopsies
Provisional grade may be given but may defer to excision for definitive grade
Presence of absence of angiolymphatic invasion
Results of special studies performed for diagnosis
Results of prognostic special studies if performed
ER, PR, Proliferation marker, Her2neu
State if studies are deferred for a later excision specimen
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