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Background
Lobular carcinoma in situ or LCIS was first described in 1941 by Drs. Foote and Stewart, pathologists. It is often an incidental finding and its importance is serving as a marker for the development of invasive carcinoma in either breast. There is no mass lesion or mammographic abnormality associated with this disease. The pathologist is the only physician who makes this diagnosis.
OUTLINE
DISEASE ASSOCIATIONS CHARACTERIZATION Invasive carcinoma About 15% of patients will develop an invasive carcinoma
This risk is greatest within 10-15 years after the diagnosis is established
GROSS OR CLINICAL PRESENTATION CHARACTERIZATION Distribution Most commonly in both breasts in multifocal and multicentric
If LCIS is found in a breast, >50% will have residual LCIS in the ipsilateral breast and >1/3 will have LCIS in the contralateral breast
HISTOLOGICAL TYPES CHARACTERIZATION CLASSIC Involved acini are filled and distended by a uniform population of cells (some state that at least 8 or more cells need to be present across the diameter of an acinus)
At least half of the acini are involved within the lobular unit
Cells may grow along ducts in a pagetoid configuration
INDETERMINATE Carcinomas In Situ of the Breast With Indeterminate Features Am J Surg Pathol 1980;4:241–6.
Rosen's Breast Pathology. Philadelphia, PA: Lippincott-Raven, 1997.
Cancer 1996;78:1403–16.
Diagnostic histopathology of the breast. Edinburgh, Scotland: Churchill Livingstone, 1987.
Pathology of the breast. 2nd ed. Stamford, CT: Appleton and Lange, 1999.
Rosen favors a combined ductal and lobular category
Fisher favors ductolobular carcinoma in situ (DLCIS) for their cases with small monomorphic cells with foci of cribriform or necrosis indicating such lesions should be managed as DCIS
Page and Anderson advise that in most cases an attempt should be made to categorize lesions as DCIS or LCIS but note that on rare occasions this may not be possible, necessitating the diagnosis of carcinoma in situ of both lobular and ductal typeTavassoli advises that LCIS cases with necrosis should be managed similarly to intermediate-grade DCIS, believing that this is a reflection of ``far-advanced lobular neoplasia.''
Am J Surg Pathol 2001;25:229-236
89 cases of breast CIS
(28 LCIS, 33 DCIS, 28 CIS-IF)
CIS-IF cases were divided into three groups based on histology:
Group 1-Cytologic and architectural features typical of LCIS but showed areas of comedo-type necrosis (n = 6)
Group 2-CIS lesions characterized by small, uniform neoplastic cells either growing in a solid pattern with focal microacinar-like structures but with cellular dyshesion, or growing in a cohesive mosaic pattern but with occasional intracytoplasmic vacuoles (n = 17)
Group 3-Marked cellular pleomorphism and nuclear atypia but had the dyshesive growth pattern characteristic of LCIS (n = 5).All 28 cases of LCIS were E-cadherin negative
All 33 DCIS cases were E-cadherin positive by immunohistochemistry
All cases from CIS-IF group 1 and group 3 were negative for E-cadherin
In contrast, CIS-IF group 2 cases were heterogeneous with respect to E-cadherin staining:
Six (35.3%) cases were E-cadherin negative (more akin to LCIS)
5 (29.4%) cases were E-cadherin positive (akin to DCIS)
6 (35.3%) cases had both E-cadherin–positive and E-cadherin–negative tumor cells, suggesting a mixed DCIS/LCIS phenotypeAm J Surg Pathol 2001;25:237-244
12 cases of in situ carcinomas with equivocal features and correlated their histologic attributes with those of the associated invasive carcinomas
E-cadherin–positive in situ lesions were invariably associated with invasive carcinomas of the ductal type
In situ carcinomas that were E-cadherin negative were associated with invasive carcinomas of the lobular type in five of six cases
In all cases, the invasive carcinomas showed the same pattern of E-cadherin reactivity as the in situ lesions
Sharply defined cellular membranes, necrosis, and occasional microacini were seen in both E-cadherin—positive and negative in situ carcinomas
Intracytoplasmic lumina and a noncohesive appearance were seen only in E-cadherin—negative lesions
NECROSIS Ann Diagn Pathol 1999;3:249–59.
Can occur in LCIS and does not necessarily imply that the lesion should be considered DCIS
- Fadare O,
- Dadmanesh F,
- Alvarado-Cabrero I,
- Snyder R,
- Stephen Mitchell J,
- Tot T,
- Wang SA,
- Ghofrani M,
- Eusebi V,
- Martel M,
- Tavassoli FA.
*Department of Pathology, Yale University School of Medicine, New Haven, CT daggerDepartment of Pathology, Wilford Hall Medical Center, Lackland AFB double daggerDepartment of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX section signDepartment of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, CA parallelDepartment of Pathology, Mexican Oncology Hospital, National Medical Center, Mexico City 06700, Mexico paragraph signDepartment of Pathology, Holy Cross Hospital, Silver Spring, MD musical sharpDepartment of Pathology, Central Hospital Falun and Uppsala University, 791 82 Falun, Sweden **Department of Pathology, University of Massachusetts Medical School, Worcester, MA daggerdaggerPathology Section, Oncology Department, Universita di Bologna, Ospedale Bellaria, Bologna, Italy.
The recent finding that lobular, and not ductal intraepithelial neoplasia (DIN) displays loss of E-cadherin expression has greatly facilitated the categorization of a large proportion of morphologically ambiguous intraepithelial neoplasias into ductal or lobular types. One reason for such morphologic ambiguity is the presence of comedo-type necrosis within an intraepithelial lesion that otherwise shows archetypal cytologic and architectural features of lobular intraepithelial neoplasia (LIN).
The clinicopathologic features of 18 such cases are described in this report. These 18 cases of classic LIN were accumulated from the recent databases of 6 institutions. All cases, by definition, showed no expression of E-cadherin. The 18 patients, all women, were 41 to 85 years of age (mean 61.3). The lesions were initially identified in an excisional biopsy or mastectomy in 12 cases and in an incisional/core biopsy in the remaining 6 cases. An associated invasive carcinoma was present in 12 (67%) of 18 cases (7 classic lobular, 1 pleomorphic lobular, 1 ductal, 1 mixed lobular and ductal, 1 tubular, and 1 case with ductal and lobular carcinomas as separate foci).
The average age of the 6 patients with pure LIN (ie, LIN without an invasive component (62.5 y) was not significantly different from the 12 patients in which there was an invasive component (60.7 y) (P=0.78). The lesions had associated calcifications, typically within the necrotic foci, in 10 (55%) of 18 cases. Immunoreactivity for estrogen receptor, progesterone receptor (in >10% of lesional cells), and high-molecular weight keratin was present in 17/18 (94%), 15/18 (83%) and 17/18 (94%) of cases, respectively.
Overexpression of HER2/neu, as assessed immunohistochemically, was absent in all 15 cases available for such evaluation. Foci of DIN, separate from the lobular lesions, were present in 6 (33%) of 18 cases. LIN with necrosis seems to occur at an older age than classic LIN, is commonly associated with invasive carcinoma and is significantly more frequently associated with lobular than ductal invasive carcinoma. When present without an invasive component, it may be mistaken for DIN 2 (grade 2 ductal carcinoma in situ). Although the necrosis suggests a ductal phenotype for these intraepithelial proliferations, architectural and cytologic features, high-molecular weight keratin[+], estrogen receptor[+], progesterone receptor[+], and human epidermal growth factor receptor 2 /neu[-] immunoprofile, frequent association with invasive lobular carcinoma, and lack of immunoreactivity for E-cadherin, strongly suggests that these lesions are within the morphologic spectrum of lobular neoplasia. Long-term follow-up studies are required to define the true natural history of these lesions.
However, because classic LIN with necrosis is apparently rare in its pure form, reexcision is recommended when this lesion is detected in isolation in a core biopsy.VARIANTS PLEOMORPHIC LOBULAR (DUCTAL-LOBULAR) CARCINOMA IN SITU
Clinical, histopathologic, and biologic features of pleomorphic lobular (ductal-lobular) carcinoma in situ of the breast: a report of 24 cases.Sneige N, Wang J, Baker BA, Krishnamurthy S, Middleton LP.
Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Mod Pathol 2002 Oct;15(10):1044-50 Abstract quote We reviewed 10 cases of pleomorphic lobular (ductal lobular) carcinoma in situ (PL/DLCIS) of the breast and compared them with 14 cases of pleomorphic lobular carcinoma in situ (PLCIS) found in association with invasive pleomorphic lobular carcinoma.
The histologic features; immunohistochemical staining for estrogen receptors (ERs), p53, Ki67, E-cadherin, and gross cystic disease fluid protein-15 (GCDFP-15); and results of fluorescence in situ hybridization for HER-2/neu gene amplification were evaluated in all 24 cases. Histologically, PL/DLCIS cells were similar to those of PLCIS with invasion in that they were discohesive and medium to large in size with moderate to marked nuclear pleomorphism, small to prominent nucleoli, and moderate to abundant eosinophilic or vacuolated cytoplasm.
In both groups, central necrosis was present in a small number of cases, and classic LCIS coexisted with the in situ lesion in less than half of the cases; in situ carcinomas were positive for ERs in 23 (100%) of 23 cases, p53 in 6 (25%) of 24 cases, and GCDFP-15 in 14 (74%) of 19 cases. The percentage of Ki67-positive tumor nuclei indicated moderate to high (more than 20%) proliferative activity in 8 (47%) of 17 cases. Immunostaining for E-cadherin was negative in all 24 cases. HER-2/neu gene amplification was observed in 1 (4%) of 23 cases. In cases with associated invasion, PLCIS had cytologic features and immunostaining patterns similar to those of the invasive pleomorphic component. Seven of the 10 patients who had PL/DLCIS without invasion underwent lumpectomy or simple mastectomy. Six of these patients had no evidence of disease in follow-up periods ranging from 4 to 32 months; the seventh patient developed recurrent disease 12 months after undergoing lumpectomy.
We conclude that the cytologic features and biomarker expression profile of PL/DLCIS are similar to those of PLCIS with invasion but somewhat different from those of classic LCIS and ductal carcinoma in situ. Long-term follow-up studies are needed to further define the natural history of PL/DLCIS and its optimal management.
Mammographically detected in situ lobular carcinomas of the breast.
Sapino A, Frigerio A, Peterse JL, Arisio R, Coluccia C, Bussolati G.
Department of Biomedical Sciences and Oncology, University of Turin, Italy.
Virchows Arch 2000 May;436(5):421-30 Abstract quote
We present ten cases of mammographically detected lobular carcinoma in situ (LCIS), involving a single area of variable size (up to a quadrant) in seven cases and the entire gland in three cases.
Histologically, calcifications were associated with necrotic central areas within the in situ carcinomatous foci. Multiple foci of LCIS were observed in all five cases in which mastectomy had been performed. Cytologically, the lesions were characterized by a solid proliferation of round noncohesive cells with nuclei of intermediate size. Immunocytochemically, all cases were E-cadherin and p53 negative, and c-ErbB-2, GCDFP-15 and estrogen receptor positive. The proliferation index, evaluated with Ki67, was in the low range. Four cases were associated with foci of infiltrating lobular carcinoma (ILC). These findings contradict the commonly held opinion that LCIS is not mammographically detectable because of its lack of necrosis and calcification.
This study documents the existence of a variant of LCIS exhibiting the mammographic features and central necrosis classically associated with ductal carcinoma in situ (DCIS), while retaining the spatial distribution, cytological composition and immunocytochemical features of lobular carcinoma.
SPECIAL STAINS/
IMMUNOPEROXIDASECHARACTERIZATION E-Cadherin J Pathol 1997;183:404–11
Am J Pathol 1993;143:1731–42.E-cadherin protein expression is lost in invasive lobular carcinoma and in LCIS but not in invasive ductal carcinoma or DCIS
E-cadherin reactivity of 95 noninvasive ductal and lobular lesions of the breast. Implications for the interpretation of problematic lesions.
Goldstein NS, Bassi D, Watts JC, Layfield LJ, Yaziji H, Gown AM.
Dept of Anatomic Pathology, William Beaumont Hospital, 3601 W Thirteen Mile Rd, Royal Oak, MI 48073, USA.
Am J Clin Pathol 2001 Apr;115(4):534-42 Abstract quote
Studies suggest that E-cadherin is useful to classify epithelial breast lesions as ductal or lobular, but extensive experience with this antibody is lacking.
We studied reactivity of lesions with classic and indeterminate morphologic features. We reviewed 95 lesions and divided them into unanimous and nonunanimous diagnosis groups; the unanimous group served as benchmark lesions to which E-cadherin reactivity could be standardized and compared.
All 37 ductal lesions in the unanimous group had strong, diffuse E-cadherin reactivity. Two of 22 classic lobular carcinoma in situ (LCIS) lesions had sparse E-cadherin-reactive lobular cells within a few terminal duct lobular units. Neither displayed transition from nonreactive to reactive cells. Of 36 lesions in the nonunanimous group, 19 had insufficient morphologic features for definitive classification. Only 6 of 19 were E-cadherin reactive, including several minimally proliferative lesions. The other 17 lesions in the nonunanimous group had LCIS and ductal carcinoma in situ (DCIS) features. All had no E-cadherin, or strong membrane reactivity of constituent cells in varying proportions, without a transition between reactive and nonreactive cells.
Results suggest that the majority of morphologically nondiagnostic atypical lesions are lobular, including those associated with DCIS. E-cadherin seems to be absent in most lobular lesions.
Solid low-grade in situ carcinoma of the breast: role of associated lesions and E-cadherin in differential diagnosis.
Maluf HM, Swanson PE, Koerner FC.
Department of Pathology and Immunology, Washington University Medical School, St Louis, Missouri 63110-1093, USA.
Am J Surg Pathol 2001 Feb;25(2):237-44 Abstract quote
Low-grade solid in situ carcinomas of the breast are difficult to classify. The authors investigated 12 cases of in situ carcinomas with equivocal features and correlated their histologic attributes with those of the associated invasive carcinomas as well as with E-cadherin expression in both in situ and invasive disease.
E-cadherin-positive in situ lesions were invariably associated with invasive carcinomas of the ductal type. In situ carcinomas that were E-cadherin negative were associated with invasive carcinomas of the lobular type in five of six cases.
In all cases, the invasive carcinomas showed the same pattern of E-cadherin reactivity as the in situ lesions. Sharply defined cellular membranes, necrosis, and occasional microacini were seen in both E-cadherin-positive and negative in situ carcinomas, whereas intracytoplasmic lumina and a noncohesive appearance were seen only in E-cadherin-negative lesions.
Combined E-cadherin and high molecular weight cytokeratin immunoprofile differentiates lobular, ductal, and hybrid mammary intraepithelial neoplasias.Bratthauer GL, Moinfar F, Stamatakos MD, Mezzetti TP, Shekitka KM, Man YG, Tavassoli FA.
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC.
Hum Pathol 2002 Jun;33(6):620-7 Abstract quote The terminal duct-lobular unit is the origin of 2 distinct variants of intraepithelial neoplasia traditionally separated into ductal and lobular types based on a combination of cytologic and architectural features.
In general, distinction of the fully developed or classic lobular intraepithelial neoplasia (LIN) from various grades of ductal intraepithelial neoplasia (DIN) is not a problem. An increasing number of lesions that appear to have intermediate, overlapping ductal and lobular features are being sent to us for consultation because of the distinctly different clinical implication of the 2 diagnoses.
We have separated and designated these as MIN (mammary intraepithelial neoplasia, not otherwise specified), whereas others have categorized them into either a definitive ductal or lobular subtype. The recent findings that LIN lacks immunoreaction for E-cadherin coupled with significantly diminished to absent expression of the high molecular weight (HMW) cytokeratins in more than 90% of grade 1b or higher DIN prompted us to evaluate intraepithelial neoplasias for a possibly more precise immunohistochemical categorization. One hundred and ten examples of intraepithelial neoplasias, consisting of 40 classic LIN, 20 unequivocal DIN 1c to DIN 3 (ductal carcinoma in situ), and 50 MIN, were acquired from the files of the Armed Forces Institute of Pathology.
These specimens were tested with an antibody to E-cadherin and with antibody 34ssE12 reactive against HMW cytokeratins 1, 5, 10 and 14. All samples of LIN showed complete absence of reactivity with anti-E-cadherin, whereas all cases of DIN displayed a positive immunoreaction. In contrast, the DIN lesions displayed little or no reactivity with 34ssE12, whereas the lobular lesions showed cytoplasmic reactivity, often in a distinct perinuclear pattern. Twenty-three of the morphologically indeterminate cases could be classified as either ductal or lobular based on the immunoprofile, and 27 demonstrated an immunoprofile that differed from either typical DIN or classic LIN. Among the 27 MIN, 11 were negative for both markers (negative hybrids), whereas 16 were positive for both markers (positive hybrids). These 2 antibodies in combination are extremely useful in distinguishing lobular and ductal lesions and clarifying the nature of some of the morphologically intermediate cases. Also, they have confirmed the presence of a group of intraepithelial lesions (MIN) with not only overlapping morphologic features, but also immunoprofiles distinctly different from either DIN or LIN.
These MIN lesions may reflect either a transient stage in the development of DIN and LIN (the immediate post-stem cell stage) or a plastic group in transition from one type to the other. This group needs further evaluation for better understanding of its significance, pattern of progression, and behavior.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Aytpical lobular hyperplasia Fewer than half of the acini are expanded or distorted by a uniform population of lobular cells
Other cell types may be interspersedDCIS Should have at least small gland like spaces
Cell wall is sharply defined
In higher grade lesions, cell morphology will be too pleomorphicDCIS with cancerization of the lobules
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS
Invasive Mammary Carcinoma After Immediate and Short-Term Follow-up for Lobular Neoplasia on Core Biopsy.Crisi GM, Mandavilli S, Cronin E, Ricci Jr A.
Am J Surg Pathol 2003 Mar;27(3):325-33 Abstract quote Lobular neoplasia (LN), including atypical lobular hyperplasia (ALH) and lobular carcinoma in situ, may be encountered in breast core biopsies performed for mammographic abnormalities even though LN is often not, in itself, responsible for the abnormal mammogram. The need for surgical excision following a diagnosis of LN on core biopsy is not well defined.
We examined pathologic and mammographic findings in a consecutive series of cases diagnosed as LN to address this issue. Radiology/pathology records were reviewed for cases with a pathology diagnosis of pure LN during the period 1998-2001. Specifically excluded were cases with associated atypical ductal hyperplasia, ductal carcinoma in situ, invasive mammary carcinoma, or any history of breast malignancy.
Thirty-five women 39-76 years of age (mean 52 years) were identified. Specimens were obtained as stereotactic core (31) or limited wire-guided biopsy (four). The diagnoses were lobular carcinoma in situ (12), lobular carcinoma in situ/ALH (10), and ALH (13). Fourteen patients did not undergo excisional biopsy and had no subsequent clinical follow-up to warrant additional biopsy (follow-up 6 months to 3 years). Five patients had no immediate excision, but eventually during clinical follow-up for LN (1 month to 3 years), two developed mammographic lesions in the ipsilateral (one patient) or contralateral breast (one patient) that led to diagnoses of invasive mammary carcinoma (lobular and composite ductal-lobular types, 10 and 8 mm, respectively); three patients had subsequent mammographic findings in the ipsilateral or contralateral breast leading to biopsies showing only LN (two patients) or no neoplastic pathology (one patient). The remaining 16 patients (all core biopsied) underwent immediate wire-guided excisions. Thirteen (81%) showed additional foci of LN, one (6.3%) with atypical ductal hyperplasia, and two (12.5%) with invasive lobular carcinoma (3 mm and <1 mm). Three (19%) had no residual disease; however, additional clinical follow-up in one of these patients revealed an invasive mammary carcinoma in the contralateral breast (false-negative mammography). Radiographic findings were calcifications and density/mass lesions in 27 and 8 cases, respectively. Of 27 cases presenting with Ca, 10 showed colocalization of LN and Ca.
In the eight cases presenting with density/mass, incidental microscopic microcalcifications colocalized to LN were found in two cases. When present, histologic Ca was associated with LN in 12 of 29 cases studied (41%). Of the 21 patients with immediate or subsequent excision, five (24%) were found to have an associated invasive mammary carcinoma (two on immediate excision and three after short-term follow-up of up to 3 years). The bilaterality of cancer risk was expected; however, the number of invasive carcinomas was not. That the invasive carcinomas detected at follow-up were small implies that they might have been present (but occult) at initial presentation.
We conclude that lobular carcinoma in situ detected on core biopsy is potentially a significant marker for concurrent and near-term breast pathology requiring complete intensive multidisciplinary clinical follow-up with specific individualization of patient care.
Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease.
Page DL, Kidd TE Jr, Dupont WD, Simpson JF, Rogers LW.
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Hum Pathol 1991 Dec;22(12):1232-9 Abstract quote
We have stratified the cancer risk implications of lobular pattern in situ neoplasias of the breast by separating marked examples of this histologic spectrum (lobular carcinoma in situ [LCIS]) from lesser examples (atypical lobular hyperplasia). The lesser-developed examples have been shown previously to have a lower relative risk (RR) of later invasive carcinoma of the breast (IBC).
Forty-eight examples of LCIS were found in 10,542 otherwise benign breast biopsies, representing an incidence of 0.5%. Nine patients were excluded from follow-up because of bilateral mastectomy within 6 months of entry biopsy, IBC within 6 months of entry biopsy, or prior IBC.
Follow-up of the remaining 39 patients was complete, averaged 18 years, and revealed an RR of subsequent IBC of 6.9 (P less than .00001). Average overall follow-up for LCIS patients was 19 years; it was 25 years for those alive and free of IBC at the time of their follow-up interview. Neither family history of IBC nor postmenopausal estrogen therapy further affected risk. The absolute risk of IBC after LCIS was 17% at 15 years (adjusted for withdrawals), and the RR was 8.0 in the first 15 years of follow-up compared with the general population. An analysis based on a time-dependent hazards model found that during the first 15 years following biopsy women with LCIS had 10.8 times the risk of breast cancer compared with biopsied women of comparable age who lacked proliferative disease. Some previously published articles reporting lobular neoplasia (LN) suggest that those series with the greatest incidences of LN (whether termed LN or LCIS) have the lowest RR of subsequent breast cancer. Those series with higher incidences of LN include less well-developed histologic patterns of LN (atypical lobular hyperplasia).
We conclude that our study of LN and studies performed by others support the higher risk of IBC after histologically flagrant examples (LCIS, about nine times higher) and a relatively lower but definable risk after more histologically subtle examples (atypical lobular hyperplasia, four to five times lower). This relative cancer risk is probably not constant over more than 15 years; thus, cancer risk 15 to 25 years after initial diagnosis of LCIS is uncertain.
Risk of contralateral breast cancer among women with carcinoma in situ of the breast.
Habel LA, Moe RE, Daling JR, Holte S, Rossing MA, Weiss NS.
Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, Washington, USA.
Ann Surg 1997 Jan;225(1):69-75 Abstract quote
BACKGROUND: Information is limited on the risk of contralateral breast cancer after a diagnosis of breast carcinoma in situ (BCIS). METHODS: In western Washington, between 1974 and 1993, 1929 women with a first primary ductal carcinoma in situ (DCIS) and 282 women with a first primary lobular carcinoma in situ (LCIS) were followed for contralateral breast cancer. Rates of contralateral invasive breast cancer and BCIS were compared with population rates of first primary breast cancer using Poisson regression to adjust for age and calendar year.
RESULTS: The rate of contralateral invasive disease after BCIS was approximately twice the population rate for women with DCIS and three times the population rate for women with LCIS; relative rates decreased somewhat with increasing time since diagnosis of LCIS, but were fairly stable after DCIS. The relative rate of contralateral DCIS after BCIS was substantially higher than for contralateral invasive disease, but dropped dramatically after the first year after the initial BCIS, especially among women with LCIS. Contralateral BCIS usually was of the same histologic type as the initial BCIS; histologic concordance of BCIS was 71% for women with an initial LCIS and 78% for women with DCIS.
CONCLUSIONS: Data suggest that the rate of contralateral invasive breast cancer is elevated for at least 5 years after a diagnosis of BCIS compared with the rate of first primary breast cancer in the population, and that the rate is only slightly higher for women with LCIS than for women with DCIS. The markedly elevated rate of contralateral DCIS may result in large part from increased medical surveillance of women diagnosed with BCIS, especially during the first year after the initial diagnosis.
Clinicopathologic implications of E-cadherin reactivity in patients with lobular carcinoma in situ of the breast.
Goldstein NS, Kestin LL, Vicini FA.
Department of Anatomic Pathology, William Beaumont Hospital, 3601 West Thirteen Mile Road, Royal Oak, MI 48073, USA.
Cancer 2001 Aug 15;92(4):738-47Abstract quote
BACKGROUND: The current study addressed two questions pertaining to lobular carcinoma in situ (LCIS) of the breast. First, does the risk of a subsequent carcinoma decrease over time after an LCIS biopsy and second, what is the clinical significance of E-cadherin-reactive LCIS?
METHODS: Eighty-two consecutive patients with a biopsy containing LCIS only, no prior history of breast carcinoma, and follow-up information available for the period 1955-1976 were reviewed. No patients underwent a mastectomy for LCIS. Four hundred eighty-six sections were stained with E-cadherin. E-cadherin reactivity was correlated with clinicopathologic features of the LCIS and subsequent tumors. The mean number of blocks stained per case was 5.9. The mean follow-up period was 21.6 years.
RESULTS: Sixteen patients (19.5%) developed 21 subsequent invasive carcinomas (9 ipsilateral, 2 contralateral, and 5 bilateral carcinomas). The 10-year and 20-year actuarial rates of developing subsequent carcinoma were 7.8% and 15.4%, respectively. Six of the 21 carcinomas (29%) developed after 20 years. Nine LCIS cases (10.9%) had focal E-cadherin reactivity. When compared with patients with nonreactive LCIS, patients with E-cadherin-reactive LCIS more frequently developed a subsequent ipsilateral carcinoma that had a ductal component (55.5% vs. 12.3%; P < 0.01). The subsequent carcinomas also developed after significantly shorter time periods (mean of 7.6 years vs. 19.6 years; P < 0.01).
CONCLUSIONS: LCIS appears to confer a persistent, increased risk of subsequent breast carcinoma that does not appear to decrease over time. E-cadherin reactivity appears to identify a subset of LCIS patients with risk factors for subsequent carcinoma similar to those of patients with low-grade intraductal carcinoma.
TREATMENT
- Follow-up Surgical Excision Is Indicated When Breast Core Needle Biopsies Show Atypical Lobular Hyperplasia or Lobular Carcinoma In Situ: A Correlative Study of 33 Patients With Review of the Literature.
Elsheikh TM, Silverman JF.
From *Pathologists Associated/Ball Memorial Hospital Muncie, IN; and daggerDepartment of Pathology, Allegheny General Hospital, Pittsburgh, PA.
Am J Surg Pathol. 2005 Apr;29(4):534-543. Abstract quote
Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) diagnosed in core needle biopsy (CNB) are generally regarded as risk indicators for developing invasive ductal or lobular carcinoma in either breast. Currently, there are no well-established guidelines for management of these patients. The most common management options are careful observation and endocrine chemoprophylaxis for high-risk patients. Previous studies had contradicting recommendations regarding follow-up surgical excision (FSE) of CNB yielding ALH or LCIS. These studies, unfortunately, have been limited by their retrospective nature, small number of patients examined, and association with other high-risk lesions. Only CNB diagnosed as pure LCIS or ALH (not associated with other high-risk lesions such as ADH, radial scar, or papilloma) were included in the study.
We reviewed 33 CNB (20 ALH and 13 LCIS) with subsequent FSE from 33 patients (age range, 30-83 years; mean, 58 years). Eighteen of these patients were prospectively analyzed, where FSE was performed in an unselected fashion. All CNBs were obtained by mammotome (11-gauge, 30 cases; and 14-gauge, 3 cases). Mammography identified calcifications in 29 cases (88%) and a mass in 4 cases (12%). FSE revealed infiltrating ductal and/or lobular carcinoma in 4 of 13 LCIS (31%). FSE of 20 ALH revealed cancer in 5 cases (25%), including 4 ductal carcinoma in situ (DCIS) and 1 invasive lobular carcinoma. Seven of these nine cancers were associated with calcifications, and two presented as masses. Sampling error and underestimation of cancer (DCIS or invasive carcinoma) was associated with CNB diagnosis of LCIS or ALH in 27% of all cases. Underestimation of cancer was seen in 28% of prospectively examined patients, including 20% of ALH and 38% of LCIS. CNB associated with mass lesions or that showed histologic features of pleomorphic LCIS or extensive classic LCIS had a higher rate of cancer underestimation. Despite removal of all abnormal mammographic calcifications by CNB in 6 patients, one cancer was detected on FSE.
To the best of our knowledge, this is the largest study reported to date, and the only one to include prospectively examined patients with no pre-selection bias. Our data strongly suggests that subsequent FSE is warranted in all patients with CNB diagnoses of LCIS or ALH, to exclude the presence of cancer.
Lobular carcinoma in situ diagnosed by core needle biopsy: when should it be excised?Middleton LP, Grant S, Stephens T, Stelling CB, Sneige N, Sahin AA.
Departments of Pathology (LPMSG, NS, AAS) and Radiology (TS, CBS), The University of Texas MD Anderson Cancer Center, Houston, Texas.
Mod Pathol 2003 Feb;16(2):120-9 Abstract quote Core needle biopsy is the preferred technique for evaluating breast masses and abnormal mammographic findings. The frequency of detection of noninvasive lobular lesions by core needle biopsy is increasing. Historically, the diagnosis of lobular carcinoma in situ has been considered a risk factor for the development of invasive carcinoma, and treatment has consisted of careful clinical follow-up with or without chemopreventive therapeutic agents such as tamoxifen citrate.
We retrospectively reviewed core needle biopsy material with the primary diagnoses of lobular carcinoma in situ, atypical lobular hyperplasia, and lobular neoplasia in conjunction with clinical and radiographic findings to make recommendations as to when excision may be merited. We searched our database for core needle biopsy cases with lobular carcinoma in situ, atypical lobular hyperplasia, and lobular neoplasia as the primary diagnosis. Microcalcifications had been sampled with a stereotactically guided, 11 G Mammotome biopsy device, and masses had been sampled with an ultrasound guided, 18 G core needle. Glass slides were reviewed and histological parameters assessed. Mammographic findings were reviewed, and clinical information was obtained from the medical record. When available, excisional biopsy material was reviewed. The 2337 breast core needle biopsies performed from January 1995 to December 2001 included 35 (1.5%) with classic lobular carcinoma in situ (14), lobular neoplasia (4), and atypical lobular hyperplasia (17) as the primary diagnosis. Twelve of these 35 cases (34%) had histological evidence of microcalcifications directly associated with the lobular carcinoma in situ, lobular neoplasia, atypical lobular hyperplasia. Radiologic review revealed 21 calcifications, 6 ultrasonographic masses, and 8 mammographic masses and/or architectural distortions. Excisional biopsy had been performed in 17 cases (49%). In six cases diagnosed as in situ on core needle biopsy, excisional biopsy revealed invasive carcinoma. All of these patients had radiographically detectable masses. Eleven cases had excisional biopsies that showed histology similar to that of the core needle biopsies.
The most important predictor of invasive carcinoma on excision was a synchronous mass lesion. Lobular carcinoma in situ involving adenosis and lobular carcinoma in situ with pagetoid spread on core needle biopsies did not show a histologically more aggressive lesion on excision and, therefore, may not require additional surgery. Histologically identified calcifications were associated with lobular lesions 34% of the time; however, their presence inside an in situ lobular lesion did not portend worse pathology on re-excision and should not be a criterion for excision.
Based on these findings, we recommend excisional biopsy of lobular carcinoma in situ, atypical lobular hyperplasia or lobular neoplasia only when it is associated with a synchronous mass lesion.
Excisional Biopsy Should Be Performed if Lobular Carcinoma In Situ Is Seen on Needle Core Biopsy.Shin SJ, Peter Rosen P.
Department of Pathology, New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, NY.
Arch Pathol Lab Med 2002 Jun;126(6):697-701 Abstract quote Context.-Percutaneous image-guided core biopsy is increasingly becoming the method of choice to evaluate impalpable breast lesions presenting with mammographically detected calcifications or as a mammographically detected mass. Infrequently, a diagnosis of a primary lobular lesion is rendered by needle core biopsy. Although lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) are not themselves detectable by mammography, they can be associated with calcifications. The management of patients with a primary diagnosis of LCIS or ALH on needle core biopsy is uncertain. Recommendations include excisional biopsy, tamoxifen citrate therapy, mammographic surveillance, or a combination of these approaches.
Objective.-The purpose of this study was to report the histologic findings of excisional biopsies performed after ALH or LCIS was found in a needle core biopsy. Design.-Hematoxylin-eosin-stained slides of 20 needle core biopsy specimens from patients with a primary diagnosis of LCIS or ALH were retrieved from the consultation and surgical pathology files of New York Presbyterian Hospital-Weill Medical College of Cornell University. Histologic diagnoses were confirmed in all cases.
Results.-Fourteen cases of primary LCIS and 6 cases of ALH found on needle core biopsy were identified. Subsequent excisional biopsy of the 14 LCIS cases revealed the following: LCIS, ductal carcinoma in situ, invasive carcinoma (1 patient; 7%); LCIS, infiltrating lobular carcinoma (1 patient; 7%); LCIS, ductal carcinoma in situ (1 patient; 7%); LCIS (8 patients; 57%); and ALH with or without atypical ductal hyperplasia (3 patients; 21%). Among the 6 patients with ALH on needle core biopsy, 1 had infiltrating lobular carcinoma and LCIS and 2 had LCIS in subsequent excision; other excisions for ALH were benign. Overall, 3 (21%) of 14 patients with a primary diagnosis of LCIS on needle core biopsy had a more significant lesion (ductal carcinoma in situ or invasive carcinoma) in a subsequent excisional biopsy.
Conclusions.-Data obtained in this study and in previously published reports lead us to conclude that excisional biopsy may be indicated and should be considered when LCIS is found on needle core biopsy in order to more fully examine the biopsy site for coexistent, clinically inapparent intraductal or invasive carcinoma that may be present in about 25% of these patients. The small number of ALH cases studied produced inconclusive results. We recommend that excisional biopsy be considered if atypical ductal hyperplasia is present with ALH in a needle core biopsy or if the diagnosis of the biopsy specimen is discordant with the mammographic findings.
The relation between the presence and extent of lobular carcinoma in situ and the risk of local recurrence for patients with infiltrating carcinoma of the breast treated with conservative surgery and radiation therapy.
Abner AL, Connolly JL, Recht A, Bornstein B, Nixon A, Hetelekidis S, Silver B, Harris JR, Schnitt SJ.
Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA 02215, USA.
Cancer 2000 Mar 1;88(5):1072-7 Abstract quote
BACKGROUND: When found in an otherwise benign biopsy, lobular carcinoma in situ (LCIS) has been associated with an increased risk of development of a subsequent invasive breast carcinoma. However, the association between LCIS and the risk of subsequent local recurrence in patients with infiltrating carcinoma treated with conservative surgery and radiation therapy has received relatively little attention.
METHODS: Between 1968 and 1986, 1625 patients with clinical Stage I-II invasive breast carcinoma were treated at the Joint Center for Radiation Therapy at Harvard Medical School with breast-conserving surgery (CS) and radiation therapy (RT) to a total dose to the primary site of > or =60 grays. Analysis was limited to 1181 patients with infiltrating ductal carcinoma, infiltrating lobular carcinoma, or infiltrating carcinoma with mixed ductal and lobular features who, on review of their histologic slides, had sufficient normal tissue adjacent to the tumor to evaluate for the presence of LCIS and also had a minimum potential follow-up time of 8 years. The median follow-up time was 161 months.
RESULTS: One hundred thirty-seven patients (12%) had LCIS either within the tumor or in the macroscopically normal adjacent tissue. The 8-year crude risk of recurrence was not significantly increased for patients with LCIS associated with invasive ductal, invasive lobular, or mixed ductal and lobular carcinoma. Among the 119 patients with associated LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%, compared with 12% for the 1062 patients without associated LCIS. For the 70 patients with moderate or marked LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%. The extent of LCIS did not affect the risk of recurrence. The risks of contralateral disease and of distant failure were similarly not affected by the presence or extent of LCIS.
CONCLUSIONS: Breast-conserving therapy involving limited surgery and radiation therapy is an appropriate method of treating patients with invasive breast carcinoma with or without associated LCIS. Neither the presence nor the extent of LCIS should influence management decisions regarding patients with invasive breast carcinoma.
Lobular carcinoma in situ on core biopsy-what is the clinical significance?
O'Driscoll D, Britton P, Bobrow L, Wishart GC, Sinnatamby R, Warren R.
Department of Radiology, Addenbrooke's Hospital, Cambridge, UK.
Clin Radiol 2001 Mar;56(3):216-20 Abstract quote
AIM: To retrospectively review the surgical histological findings in all cases where lobular carcinoma in situ(LCIS) was identified on percutaneous core biopsy (CB) performed as part of the Cambridge and Huntingdon breast screening programme.
MATERIALS AND METHODS: We retrospectively reviewed all the core biopsies performed in our department for screen detected abnormalities over a 5-year period between 1 April 1994 and 31 March 1999. All patients where LCIS was identified on CB were reviewed. As the significance of LCIS on CB was unclear all went on to surgical excision. We reviewed the clinical and imaging findings, biopsy technique and subsequent surgical histology of each patient.
RESULTS: During the study period 60 769 women were invited for screening, of whom 47 975 attended (attendance rate = 79%). Of these, 2330 (4.9%) were recalled for assessment and 749 (1.6%) underwent CB. A malignant diagnosis was obtained in 311 (42%), 211 invasive and 100 in situ lesions. LCIS was identified on CB in 13 (2%). LCIS was the only lesion identified in seven cases. All seven cases subsequently underwent surgical excision. Surgical histology revealed a single case of LCIS and invasive lobular carcinoma. There were two cases of LCIS and DCIS one with a probable focus of invasive ductal carcinoma. In one case LCIS was identified in association with a radial scar. In three of the seven cases LCIS was the only abnormality on both CB and surgical biopsy.
CONCLUSION: Our series shows that isolated LCIS on CB following mammographic screening is an infrequent finding, and it may be associated with either an invasive cancer or DCIS. It is therefore advisable that when LCIS is identified on CB, surgical excision of the mammographic abnormality should be performed. Decisions on management should be undertaken in a multidisciplinary setting taking into account clinical and imaging findings.
Lobular Neoplasia in Breast Core Needle Biopsy Specimens Is Not Associated With an Increased Risk of Ductal Carcinoma In Situ or Invasive Carcinoma
Andrew A. Renshaw, MD, Norberto Cartagena, MD, Robert P. Derhagopian, MD, and Edwin W. Gould, MDAm J Clin Pathol 2002;117:797-799 Abstract quote
Recent reports suggest that the finding of lobular neoplasia (atypical lobular hyperplasia [ALH] or lobular carcinoma in situ [LCIS]) in breast core needle biopsy specimens may be associated with an increased risk of both ductal carcinoma in situ (DCIS) or invasive carcinoma at excision.We reviewed our breast core biopsy material to see if we could confirm this finding. From 4,297 biopsies, 71 cases of lobular neoplasia alone and 35 cases of lobular neoplasia associated with atypical ductal hyperplasia were identified. Biopsy follow-up revealed DCIS or invasive carcinoma in none of 6 cases of ALH, none of 9 cases of LCIS, and DCIS in 1 of 11 cases with both atypical ductal hyperplasia and LCIS.
Our results suggest that patients with lobular neoplasia in breast core biopsy specimens are not at increased risk of either DCIS or invasive carcinoma at excision, and patients with this finding and no other clinical or pathologic indications for biopsy can be followed up rather than routinely undergo excision.
Lobular carcinoma in situ as a component of breast cancer: the long-term outcome in patients treated with breast-conservation therapy.
Moran M, Haffty BG.
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Int J Radiat Oncol Biol Phys 1998 Jan 15;40(2):353-8 Abstract quote
PURPOSE: The purpose of this study is to assess the long-term outcome of breast cancer patients with a component of lobular carcinoma in situ (LCIS) treated with conservative surgery and radiation therapy.
METHODS AND MATERIALS: The pathology reports of all patients treated with conservative surgery and radiation therapy at our institution prior to 1992 were reviewed to identify patients who had LCIS as a histologic component. A total of 51 patients were identified. Primary histology of the 51 patients was as follows: 53% infiltrating lobular, 20% invasive and intraductal, 18% invasive ductal, 10% intraductal. There were no patients treated who had LCIS only. One thousand forty-five patients treated conservatively during the same time interval without LCIS served as a control group. All patient characteristics, staging, treatment and outcome variables were entered into a computer database.
RESULTS: As of 3/96, the median follow-up for the LCIS-containing group and control group was 10.6 and 11.4 years, respectively. There were no significant differences in age of presentation, clinical stage, nodal status, estrogen receptor status, or adjuvant therapy received between the two groups. Twenty-two patients (43%) in the LCIS group underwent reexcision. Of those, 69% had residual LCIS in the reexcision specimen. LCIS was characterized as focal in 29%, diffuse in 25%, and not specified in all other cases. The primary histology of the two populations differed significantly with a larger percentage of infiltrating lobular primaries in the LCIS group (53 vs. 5%, p < 0.001). The LCIS group also differed from the control group with respect to the percentage of patients with bilateral disease (17 vs. 8%, p = 0.05), and the percentage of patients with "false negative" mammograms (20 vs. 10%, p = 0.02). There was no statistically significant difference between the LCIS group and control group in the 10-year overall survival (67 vs. 72%), distant disease-free survival (62 vs. 79%), or ipsilateral breast tumor recurrence-free survival (77% LCIS vs. 84% control).
CONCLUSION: Patients with LCIS as a histologic component of breast cancer do not carry a worse prognosis than breast cancer patients without an LCIS component. Furthermore, the comparable local control rates between conservatively treated patients with or without LCIS suggests that patients with a histologic component of LCIS are suitable candidates for conservative surgery and radiation therapy.
Lobular carcinoma in situ: observation without surgery as an appropriate therapy.
Carson W, Sanchez-Forgach E, Stomper P, Penetrante R, Tsangaris TN, Edge SB.
Department of Surgical Oncology, Roswell Park Cancer Institute, State University of New York, Buffalo 14263.
Ann Surg Oncol 1994 Mar;1(2):141-6 Abstract quote
BACKGROUND: The finding of lobular carcinoma in situ (LCIS) in the breast has generally prompted treatment with unilateral or bilateral mastectomy. Most experts now feel that LCIS simply identifies a woman who is at high risk to develop future breast cancer and requires only close clinical and mammographic follow-up. This approach has been recommended at our institution for > 15 years. This study defines the natural history of a population of women with LCIS who were treated by observation alone.
METHODS: Women with a pathologic diagnosis of LCIS were identified by tumor registry search. Records and pathology were reviewed. Radiographic-pathologic correlation was performed on women who had undergone mammographic-localized breast biopsies. One hundred forty-nine women with LCIS were identified. Eighty four were excluded from analysis because of synchronous invasive cancer or ductal carcinoma in situ (DCIS). The remaining 65 women formed the basis of this report.
RESULTS: Sixty-five women with LCIS were treated from 1963 through 1990. Median follow-up was 83 months. No women were lost to follow-up. Median age at diagnosis was 48 years (range 37-81), and 32% had a family history of breast cancer. Clinical findings leading to biopsy were breast mass in 43, nipple discharge in three, and mammographic abnormality in 19. Mammographic-pathologic correlation showed that the focus of LCIS in these 19 women was not associated with the mammographic abnormality. Fourteen of 65 women underwent mastectomy after diagnosis of LCIS (nine ipsilateral, five bilateral). Fifty-one of 65 women elected observation alone. In the observation group, 13 of 51 women (25%) underwent a second breast biopsy for a clinical or mammographic abnormality during the follow-up period. The median interval to biopsy was 50 months. Pathology was benign in two, LCIS in seven, DCIS in one, and invasive cancer in three. All seven women with LCIS on subsequent biopsy continued with observation and none developed breast cancer. All four cancers were detected by mammography without an associated palpable mass. Three of four cancer masses were < 1 cm in diameter. The woman with DCIS was 47 years of age and developed DCIS 106 months after LCIS diagnosis. She was treated by total mastectomy and is disease free 108 months later. The three women with invasive cancer developed this at 41, 53, and 69 months after diagnosis of LCIS. All were < 50 years of age. All three cancers were in the same breast as the previous LCIS. Two women were treated by modified radical mastectomy, and the third had wide excision/axillary dissection followed by radiation therapy. They are alive and disease-free at 16, 82, and 116 months.
CONCLUSIONS: Four of 51 women treated with observation alone after diagnosis of LCIS developed breast cancer. All were detected by screening at an early stage. LCIS appeared to be an incidental finding on biopsy of mammographic abnormalities. The policy of observation alone for the finding of LCIS spares women mastectomy. Furthermore, cancers that develop in follow-up are likely to be detected at an early stage and be amenable to curative therapy. Observation alone is appropriate treatment for women with LCIS.
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