Pathologic Variables
Apart from the size of the tissue sample obtained through different technologies, however, there are other variables that can significantly impact the false negative rate for a stereotactic biopsy. Most importantly, these include how the tissue is processed (Lagios, 2000) and how many levels are obtained (figures). An 11-gauge biopsy core provides a much better chance of sampling a microscopic DCIS since it contains 2.5 X the volume of a 14-gauge gun core. However, this advantage can be entirely lost if the core is sectioned to a depth of only two levels rather than the six or eight that are required to profitably examine the tissue, or if it is processed in such a manner than the core cannot be sampled even with a dozen levels. Such variables are frequently underappreciated by the interventional mammographer.

Definition of DCIS
Inexperience with the interpretation of stereotactic biopsy material can lead to identifying many diagnosable low grade DCIS in particular as ADH, that is biasing the interpretation towards the safer diagnosis and undercalling the lesion. The problem of upgrades of ADH to DCIS/invasion exists only for DCIS defined as low-grade and specifically nuclear grade I lesions without necrosis. Single duct profiles which exhibit nuclear grade II-III morphology with or without necrosis fall outside of this differential, i.e, they are definable as DCIS even with such limited involvement. A significant number of core andmammotome-type diagnoses of ADH are undercalled and on review actually represent DCIS. Although low grade DCIS was originally defined in minimalist terms as totally involving two duct spaces (Page and Anderson, 1987), more recently Tavasolli and Norris (1990) have imposed a quantitative criterion on such foci requiring that the sum of the diameters of the involved duct spaces equal or exceed 2 mm. As a result, smaller-gauge biopsies may not sample sufficient ducts to fulfill the quantitative criteria.

Semi-quantification of ADH
More recently, attempts at mammographic-pathologic correlation for the stereotactic biopsy have allowed a reduction in the need for universal reexcision. In our recent experience an attempt to semi-quantify both the size of the ADH and the degree of sampling stereotactically, have permitted the recognition of patients who can be followed in a manner similar to patients with microscopic ADH incidental to an open excision biopsy of a benign process, e.g., fibroadenoma, etc. In a sample of twelve to fifteen 11-gauge cores, the presence of microscopic ADH involving up to three TDLU and unassociated with the mammographic target microcalcification is generally followed without recourse to open biopsy. On the other hand, ADH associated with target microcalcification, only a part of which has been excised by the stereotactic procedure, will require an open biopsy.

Ely et al (2001) noted that in 51% of 47 14 or 11 gauge core biopsies with ADH that the ADH was limited to 2 or fewer ductolobular units or duct spaces. None of these were upgraded at subsequent open excision. All upgrades occurred amongst the 32% of the core biopsies which demonstrated ADH in 4 or more ductolobular units or duct spaces.

Lim et al (2001) correlate the extent of microcalcifications (mean 16 mm), the degree of sampling and the number of TDLU involved. In 15 cases of ADH documented with 11 and 14 gauge biopsies, there was only 1 upgrade (6.6%) to DCIS, 4 cases exhibited no residual ADH and 10 ADH only on subsequent excision. The one upgraded patient had an estimated 15% sample of a 70 mm extent of microcalcifications. They propose possible followup for patients with 3 or fewer TDLU involved with ADH in whom at least 30% of the microcalcification are sampled.

Gal-Gombos et al (2000) reviewed 43 ADH cases, 33 based on 11 gauge vacuum assisted biopsy, who underwent subsequent open excision. Two pathologist reviewed the diagnostic material and the protocol required documenting the biopsy site in the excision specimen. There were only 2 upgrades (4.6%) one to DCIS, one to invasive carcinoma

Renshaw et al (2001) recently corroborated this thesis in a study of ADH upgrades. Their practice required complete sectioning of the core material with preparation of 8 slides with 2 - 5 levels per slide. The overall upgrade rate of ADH to DCIS was 14% using 14 gauge and 11 gauge ultrasound and stereotactic biopsies. However none of the upgrades were found to have been completely removed based on a blinded review of themammograms. There were no upgrades to invasive carcinoma.

Sneige et al (2003) reviewed 42 patients with vacuum assisted core biopsy diagnoses of ADH who underwent subsequent re-excision. 3/42 were upgraded to DCIS, but no patient whose mammographic target was completely excised or who exhibited 2 or fewer lobules/duct structures with ADH were upgraded.

Problem of Lobular Neoplasia (Atypical Lobular Hyperplasia and Lobular Carcinoma in Situ) and Upgrades
It is standard practice not to re-excise open biopsy material which exhibits incidental lobular neoplasia since the yield of more significant disease in the re-excision and the impact on local control of achieve "clear" margins for lobular meoplasia are negligible. Two recent analyses which have appeared in abstract only, challenge this logic when a core biopsy exhibits incidental lobular neoplasia (Shin and Posen, 2001; Elsheikh and Silverman, 2001), and both have advocated re-excision. This conclusion has recently been rebutted by Renshaw et al (2002) who note that lobular neoplasia (ALH and LCIS) was found in only 1.65% of 1958 core biopsies. None of the patients with lobular neoplasia alone exhibit either DCIS or invasion on re-excision, and only 1 of 11 cases with mixed lobular neoplasia AND ADH exhibited DCIS. The authors properly note that the most likely source of the upgrade rates cited in the abstracts was inadequate sampling of the target, and I might add, inadequate leveling of the processed cores in pathology.

Reimbursement
The current level of reimbursement for pathologic evaluation of core biopsy material, particularly the larger vacuum asisted 14 and 11 gauge procedures, is based on CPT code 88305 which covers skin and breast biopsies. The level of compensation for the pathologist and the hospital (technical fee) provided by 88305 provides a profit for examining a shave excision of a seborrhoeic keratosis from the forehead (Table 7), but establishes a loss for both pathologist and hospital if 11 gauge core biopsy material were to be examined with the level of care it deserves. As a result many hospital laboratories simply provide 1 or 2 levels for an 11 gauge core, a number guaranteed to miss some of the pertinent microscopic findings if not miss the diagnosis entirely. Obviously subsequent open excisions which provide a diagnosis in these circumstances will be recorded as upgrades. The"cost savings" which results from this strategem (1 level rather than 6) at $6.00/slide is $30.00 or approximately 0.35% of the cost of a stereotactic core biopsy procedure. Do you know how many levels your laboratory provides for 14 and 11 gauge vacuum assisted biopsies?

Summary
Rather than defining a requirement for an open biopsy, the presence of ADH in a stereotactic core biopsy should first engender a need for quantification and correlation. Although much of the literature on the question of ADH upgrades includes histologic review, mammographic-pathologic correlation to evaluate the extent of sampling is less common.

A word about upgrades of ADH or DCIS to invasive breast cancer. Clearly concluding that a stereotactic procedure is inferior because it cannot exclude invasion is inappropriate. Limitations in defining invasion with a diagnosis of DCIS should be compared to the similar results obtained from an initial needle localization procedure in which more than half are inadequately excised and in which invasion is often found in the re-excision.

Currently, the presence of ADH in a stereotactic biopsy should be evaluated to determine whether or not the pathologic lesion was incidental to the mammographic target, or is part of it but only sampled, that is, with some recognition of the need for pathologic mammographic correlation and the important need to more adequately assess the tissue being involved. The available literature on upgrades of ADH to DCIS and DCIS/invasion does not factor in any of the pathologic factors, i.e., either the technology of tissue processing, the number of levels, or the definition of DCIS or ADH employed.

References

1. Burbank F. 1997. Stereotactic breast biopsy of atypical duct hyperplasia and ductal carcinoma in situ lesions: Improved accuracy with directional vacuum assisted biopsy. Radiology 202: 843-847.
2. Elsheikh TM and Silverman JF. 2002. Is follow-up surgical excision indicated when breast core needle biopsies show atypical lobular hyperplasia or lobular carcinoma in situ. Mod Pathol, 14: abstract 25A.
3. Ely KA, Carter BA, Jensen RA et al. 200l. Core biopsy of the breast with atypical ductal hyperplasia: A probabilistic approach to reporting. Am J Surg Pathol, 25: 1017-1021.
4. Gal-Gombos EC, Esserman LE, Saiz E et al. 2000. Accuracy of image-directed large core needle biopsy in atypical intraductal hyperplasia of the breast. The Breast Journal, 6: 342. Abs.
5. Jackman RJ, Nowels KW, Shepart MJ et al. 1994. Stereotactic large-core needle biopsy of 450 nonpalpable breast lesions with surgical correlation in lesions with cancer or atypical hyperplasia. Radiology, 193: 91-95.
6. Jackman RJ, Nowels KW, Radriguez-Soto J, et al. 1999. Stereotactic, automated large-core needle biopsy of nonpalpable breast lesions: False-negative and histologic underestimation rates after long-term followup. Radiology 210: 799-805.
7. Lagios MD. 2000. Pathology procedures for evaluation of the specimen with potential or documented ductal carcinoma in situ. Sem Breast Dis, 3:42-49,
8. Liberman L, Cohen MA, Dershawa DD, et al. 1995. Atypical ductal hyperplasia diagnosed at stereotactic core biopsy of breast lesion: an indication for surgical biopsy. AJR 164: 1111-1113.
9. Lim SC, Whitman GJ, Krishnamurthy S et al. 2001. Directional vacuum assisted stereotactic biopsy (DVAB) of breast microcalcifications with atypical ductal hyperplasia (ADH): Surgical excision is not always necessary. Mod Pathol, 14: 30A. Abs. 159.
10. Renshaw AA, Cartagena N, Schenkman RH et al. 2001. Atypical ductal hyperplasia in core needle biopsies. Correlation of size of the lesion, complete removal of the lesion and the incidence of carcinoma in follow-up biopsies. Am J Clin Pathol. 116: 92-96.
11. Renshaw AA, Cartagena N, Derhagopian RP and Gould EW. 2002. Lobular neoplasia in breast core needle biopsy specimens is not associated with an increased risk of ductal carcinoma in situ or invasive carcinoma. Am J Clin Pathol, 117: 797-799.
12. Sneige N, Lim SC, Whitman GJ, Krisnamurthy S, et al. 2003. Atypical ductal hyperplasia diagnosis by directional vacuum-assisted stereotactic biopsy of breast microcalcifications. Am J Clin Pathol, 119: 248-253.
13. Tavassoli FA and Norris HJ. 1990. A comparison of the results of long-term follow-up for atypical intraductal hyperplasia of the breast. Cancer 65: 39-52.

Table 1: ADH in Stereotactic Biopsy Alternative Management

I. Requires Mammographic Correlations ADH with microcalcification Target Acquisition Complete: Followup Incomplete: Re-excision ADH without microcalcification Incidental to Target < 3 TDLU: Followup > 3 TDLU: Consider re-excision II. Based on Pathology Alone ADH in single TDLU Size: < 3 mm: Followup Followup - Ely et al (2000 & in press (upgrades 0/41))

Table 2: Variables in ADH/DCIS Upgrades

Sample size • Core weight • Number of cores Pathology prepartion • Orientation in cassette • N - levels and depth Diagnostic Criteria • Qualitative vs. Quantitative • Inclusion of NG II - II •Interobserver variability

Table 3: Sample Size vs. Core Technology

Technique	Mean Mg/Core	N	Total Mg
14 G gun	17	4-6	68-102
14 G vacuum	35	10-15	350-525
11 G vacuum	100	10-15	1000-1500

Table 4: ADH Upgrades

1. All ADH upgrades had been incompletely excised. 2. ADH upgrades only to DCIS. 3. Complete excision rates: 14 gauge - 10% 11 gauge - 50% Renshaw et al, 2001. Am J Clin Pathol., 116: 92-96

Table 5: ADH Upgrades - Core Dx: ADH (N95)*

Excision	N	%
BPD	45	(48)
ADH	31	(33)
LCIS	6	(6)
DCIS	13	(14)
Inv. CA	0	(0)

*based on complete sectioning, 8 slides, 2-5 levels/slide
Renshaw et al, 2001. Am J Clin Pathol, 116: 92-96.

Table 6: Cost Analysis and Compensation for CPT 88305
skin, breast and other diagnositc biopsies exclusive of cysts

	Professional Component	Technical Component	Total
Amount billed	$135.00	$102.00	$237.00
Reimbursement @ mean 35%	$ 47.25	$ 35.70	$ 82.95

Table 7: Professional Profit Margin - CPT 88305
Biopsy: Skin, shave excision
Diagnosis: Seborrhoeic keratosis and solar damage

	Professional	Technical
gross	$47.25	$35.70
costs	$ 3.00	$16.00
profit	$44.25	$19.70

Interpretation: 30 seconds Edited report: 1 minute @ $120/hr

slides: 1@ $6/slide report: $10.00

Table 8: Professional Profit Margin - CPT 88305
Biopsy: 11 gauge mammotome x2 with 6 levels
Diagnosis: DCIS, intermediate grade (NG I-II with zonal necrosis), cribriform and solid with microcalcification

	Professional	Technical
Gross	$47.25	$35.70
Costs	$62.00	$136.00
Loss	-$14.75	-$100.30

21 slides @ 1.5 min/slide @ $120/hr

21 slides @ $6/slide report: $10.00