| |
|
[Back to Breast Cancer
Index]
It is now a conventional concept that non-invasive carcinoma (CIS)
of the breast originates in the TDLU (terminal duct lobular unit).
The TDLUs hang like groups of 0.5-1.0 mm. grapes from the serpentine
ducts which tend be very imperfectly radiated from the nipple
in a somewhat radial-segmental fashion. All TDLUs, during lactation,
produce milk which moves to the nipple. The key components of the
TDLUs are ductal cells, lobular cells, and myoepithelial cells.
Conservative breast surgery (CBS) has lead to studies producing
some interesting clues for decision making in individual cases.
It may be that IHC will be necessary to discern the difference
between invasive and non-invasive carcinoma, particularly when
CIS involves various types of adenosis [LMC-01-4299]. See breast
DIN criteria |
Hyperplasia2: Minor degrees
of duct-cell proliferation are commonly seen as part of fibrocystic
mastopathy, as forms of adenosis (excessive ductular profiles) or
intraductal hyperplasia (excessive ductal epithelium...epitheliosis).
Any degree of non-lactational proliferation of lobular cells
falls into a category of "noninvasive lobular neoplasia". Duct adenosis
and/or hyperplasia can be very florid. The diagnosis of ductal CIS
requires the right combination of (1) architectural change plus (2)
cytological change. As to ductal CIS, any cases with only partial
fulfillment of the two criteria are "atypical duct hyperplasia" (d-AH
or ADH). That is, d-AH approximates...but does not unequivocally
satisfy...the criteria for d-CIS (Fisher). "Severe d-AH" is
used when the process seems more widespread in a biopsy. Ductal cytological "atypicalities" include:
nuclear enlargement that reduces the N/C ratio, nuclear hyperchromasia,
irregular chromatin pattern or nucleoli, distinct cell borders of
these types of cells, easily identified mitotic figures, and mucin-containing
intracytoplasmic lumens. Ductal architectural change
includes: loss of cell polarity, loss of cell-heterogenic streaming
(as birds in flight or fish in a school), and loss of uneven lumen
spacing...becoming a more even cribriform lumen spacing.
Columnar
cell hyperplasia2 (CCH) is a separate situation of
hyperplastic TDUs on a spectrum from columnar cell change (CCC),
to CCH, to flat epithelial atypia (FEA). CCH can be multifocal
and bilateral and microcalcifies: it is a cystic increase in enlarged
crowded columnar epithelium which has apocrine change
with snouts. Because the entity has been previously thought to be
associated with tubular carcinoma [LMC-05-8748] or
lobular neoplasia, excisional biopsy is warranted when there is a
core biopsy diagnosis...as with d-AH. |
- types of CIS:
- lobular (l-CIS)
- ductal (d-CIS)
-
mixed (E-cadherin may
give important information as to type or mixed or uniform small cells...next item below).
-
ductal of small uniform cells and solid pattern (d-CIS
that looks like l-CIS)
-
indeterminate
- l-CIS: the criterion to go from LAH to LCIS is highly subjective & having to do with whether the lobules are barely/mildly lobular-hypercellular (LH) vs. filled & slightly/mildly distended with lobular cells (LAH) or definitely distended & overfilled..."blown up"...with lobular cells (LCIS). If LCIS has what looks like comedo-CIS but is lobular, it is referred to as "florid lobular CIS2", a lesion which can have microcalcification & be highly associated with microinvasive or invasive lobular carcinoma elsewhere in the lesion.
- d-CIS:
-
as to ADH: the minimal criteria
to make a diagnosis of at least low grade DCIS are13:
- cytology: monotonous uniform round cells; round nuclei which are
equidistant; maybe a subtle increase in N/C & maybe nuclear hyperchromia.
- architecture: solid; or, arcade/cribriform rigidity; or, micropapillary...see
next.
- architectural types:
- solid: ductules filled with
CIS cells
- comedo: tubules lined by CIS cells and
lumens containing necrotic neoplastic debris (often calcified)
- cribriform: (can be predominantly tubules)
- papillary: lumenal paillations more bulky than "micropapillary" and even to the point of being "encysted" nodules/masses.
- micropapillary: (1) usual situation: microcalcifications don't
match the lesion which tends to be multifocal and
to extensively involves most of the duct segment at
time of diagnosis, expressing as ductules lined by low papillaltions
of d-CIS cells. Lumpectomies of this variant have positive
margins 90% of the time & it is "quick" to
become invasive 7 once invasive, quick to go to nodes
5. (2) "clinging" variant3:
minimally manifest papillations or Roman arches lining lumens
lined by d-CIS cells.
-
alternate designation: some prefer to
speak in terms of comedo-CIS vs. noncomedo-CIS .
-
cell variants:
-
biology not special: apocrine (but ER & PR
neg., below)2;
-
biology, special considerations:
-
nuclear types:
-
small, regular, grade 1
-
intermediate, mildly variable, grade 2
-
large, variable, nucleoli, grade 3
-
extent of disease notes:
-
grade 3 d-CIS clinical extent tends
to nicely match the imaging extent of microcalcification (Holland,
Cancer 56:979-990, 1985)
-
micropapillary d-CIS tends to be widely
segmental and multifocal (Patchefsky, Cancer 63:731-741,
1989)
-
non-high grade: if non-high-grade and
even small amounts involve more than 1 quadrant (non-high
more likely to poorly match mammographic microcalcifications)[LMC-01-7409]
-
grading notes:
-
architectural type as a grade surrogate is poor
-
Bloom-Richardson nuclear grade is the
way to go
-
by whatever system of designating grade, high
grade tends to recur short term and in high percentage
(even with XRT4)
-
high grade nicely matches extent of
mammographic microcalcification and less apt to have skip
areas
-
low/intermediate grades mismatch beyond
mammographic extent of microcalcification
-
radiation therapy (XRT) definitely helps reduce high
grade recurrence rate
-
conservative breast surgery (CBS) surgical margin notes:
-
NSABP B17 def. of clear margin as one
that does not transect tumor yields a recurrence rate of
22% @ 43 months (Fisher, NEJM 328:1581-1586, 1993)
-
1 mm. margin as a clear margin yields 16% recurrence
rate (Lagios, Breast J. 1:67-78, 1995)
-
notes as to markers:
-
apocrine d-CIS is typically ER & PR
neg.
(androgen pos.)2 [S-01-7806]
-
prognostic factor notes:
-
recurrence notes:
-
of all grading schemes, only those based
on nuclear grade stratify as to recurrence differences
and Van Nuys was best (Badve, Human Path. 29:915-923,
1998)
-
schemes based on nuclear grading can identify
most of the cases likely for short-term local recurrence
and invasive transformation (Sneige, Human Path. 30:257-262,
1998)
-
d-CIS recurs as d-CIS or transformed to invasive
ductal ca. in same breast in same segment, often at old scar
(Holland, 1985; Faverly, Sem. Diag. Path.11:193-198, 1994)
-
low 5-10 year recurrence in non-comedo, grade
I & II but about 37% at 30 years and without risk diminishing
after menopause (Page, Cancer 75:1219-1221, 1995)
-
VNPI developed to predict risk of local recurrence
after CBS
-
with margins of 10mm. or greater, high
grade recurs in 10 years in up to 8% (taken to mean that
92% of recurrences are due to unresected residual d-CIS)
-
non-high grade is nearly 100% recurrence
free
-
radiation therapy notes:
-
radiation therapy (XRT) definitely helps reduce high
grade recurrence rate
-
Van Nuys grouping scheme has greatest degree
of inter-observer agreement (Bethwaite, J. Clin. Path. 51:450-454,
1998) while Lagios system study showed complete agreement
between 6 pathologists in only 35% of cases. Therefore,
-
if grade goal is to exclude XRT in non-high-grade,
there should be 100% agreement of grade among, say, a
cohort of no less than 3 pathology group members
-
chemoprevention notes:
-
Consensus Conference Recommendations as to Pathology:
|
References:
-
6th Annual Breast Symposium, Columbia, SC,
18 May 2001 (Dr. Lagios was key pathologist speaker)
-
Rosen's Breast Pathology, text book, 2nd Ed.,
2001
-
Weidner N, The Difficult Diagnosis in S. P.,
1996.
-
Page DL, Special Article (2002 A. P. Stout
Society Symposium), Ductal Carcinoma In Situ of the Breast:
Impact of Pathology on Therapeutic Decisions, A. J. S. P.
27(6):828-831, 2003.
-
Conferee statements, LMC weekly multidisciplinary
Breast Conference.
(posted June 2001;
latest addition/update, 24 May 2006) |
|
|
