Lobular carcinoma of the breast may have a very subtle presentation. There may be a mass or only a vague thickening of the breast. The diagnosis often rests with the pathologist to identify the subtly atypical cells that comprise the tumor.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Invasive lobular carcinoma AGE-RANGE AND MEDIAN Median age 45-56 years
Range 28-86 years
Changing incidence rate of invasive lobular breast carcinoma among older women.
Li CI, Anderson BO, Porter P, Holt SK, Daling JR, Moe RE.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Cancer 2000 Jun 1;88(11):2561-9 Abstract quote
BACKGROUND: In 1998, an unusually large number of invasive lobular breast carcinoma cases were seen at the University of Washington. The purpose of this study was to assess whether the incidence rate of invasive lobular carcinoma has been increasing disproportionately compared with the incidence rate of invasive ductal carcinoma.
METHODS: Age specific and age-adjusted breast carcinoma incidence rates from 1977-1995 were obtained from the nine population-based cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program. Three histologic groupings were used: lobular, ductal, and all invasive breast carcinomas. Overall incidence rates for each grouping, as well as for each stage (local, regional, and distant), were obtained.
RESULTS: The rate of incidence of lobular carcinoma increased steadily from 1977-1995 in women age >/= 50 years whereas it remained stable in women age < 50 years. Alternatively, the rate of incidence of ductal carcinoma increased steadily from 1977-1987, but from 1987-1995 it remained relatively constant across all age groups.
CONCLUSIONS: The incidence rates of invasive lobular breast carcinomas increased steadily since 1977 whereas the incidence rates of invasive ductal carcinoma have plateaued since 1987. This rise occurred specifically among women age >/= 50 years and may be related to postmenopausal status. Further epidemiologic, clinical, and laboratory research is required to assess what factors are contributing to this trend.
Trends in incidence rates of invasive lobular and ductal breast carcinoma.
Li CI, Anderson BO, Daling JR, Moe RE.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, MP 381, PO Box 19024, Seattle, WA 98109-1024.
JAMA 2003 Mar 19;289(11):1421-4 Abstract quote
CONTEXT: Research has suggested that use of combined estrogen and progestin hormone replacement therapy (CHRT) increases breast cancer risk and that CHRT use is more strongly associated with the risk of invasive lobular breast carcinoma than that of invasive ductal carcinoma. Lobular carcinoma is less common than ductal carcinoma but can be more difficult to diagnose because of its subtle elusive infiltrative pattern.
OBJECTIVE: To evaluate trends in invasive lobular and ductal carcinoma incidence rates from 1987 through 1999, during which time use of CHRT increased in the United States.
DESIGN: Descriptive epidemiologic study.
SETTING: Nine cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and that cover Atlanta, Ga; Detroit, Mich; San Francisco-Oakland, Calif; Seattle, Wash; and Connecticut, Hawaii, Iowa, New Mexico, and Utah.
POPULATION: Women 30 years of age and older residing in the areas covered by the 9 SEER registries.
MAIN OUTCOME MEASURES: Proportional changes in incidence rates of invasive lobular and ductal carcinoma among women with no prior history of breast cancer.
RESULTS: A total of 190 458 women were included in this analysis who were identified through the registries as having invasive breast cancer; 7682 of the 198 140 potentially eligible women (ie, those identified as not having in situ breast cancer) were excluded from this analysis because stage of cancer was unknown. Invasive breast cancer incidence rates adjusted for age and for SEER historic stage increased 1.04-fold (95% confidence interval [CI], 1.004-1.07) from 1987-1999 (206.7/100 000 to 214.1/100 000, age-adjusted). However, incidence rates of tumors classified as lobular increased 1.52-fold (95% CI, 1.42-1.63), and those classified as mixed ductal-lobular increased 1.96-fold (95% CI, 1.80-2.14); rates of these types combined increased 1.65-fold (95% CI, 1.55-1.78) (19.8/100 000 to 33.4/100 000, age-adjusted). In contrast, ductal carcinoma rates remained largely constant (153.8/100 000 to 155.3/100 000, age-adjusted; proportional change, 1.03 [95% CI, 0.99-1.06]). The proportion of breast cancers with a lobular component increased from 9.5% in 1987 to 15.6% in 1999.
CONCLUSIONS: Ductal carcinoma incidence rates remained essentially constant from 1987-1999 while lobular carcinoma rates increased steadily. This increase presents a clinical challenge given that lobular carcinoma is more difficult to detect than ductal carcinoma by both physical examination and mammography.
DISEASE ASSOCIATIONS CHARACTERIZATION HAMARTOMA, MAMMARY
Microinvasive lobular carcinoma associated with intraductal spread arising in a mammary hamartoma.
Kuroda N, Sugimoto T, Numoto S, Enzan H.
First Department of Pathology, Kochi Medical School, Kohasu, Oko-cho, Nankoku City, Kochi 783-8505, Japan.
J Clin Pathol 2002 Jan;55(1):76-7 Abstract quote
A 53 year old woman presented with a lump in the inner lower quadrant of the left breast. Histological examination of the breast tumour confirmed that the lesion was a mammary hamartoma. Carcinoma with foci of microinvasion was observed in the lobules of the hamartoma concomitant with the intraductal spread of lobular carcinoma.
Immunohistochemically, the cancer cells were negative for beta-catenin, which generally stained normal breast ducts and ductal carcinomas. This is only the sixth case of breast carcinoma arising in a mammary hamartoma to be reported and, moreover, the fourth case of lobular carcinoma occurring within a hamartoma.
Despite the apparent rarity of this case, pathologists should be aware of the possibility of carcinomas arising within mammary hamartomas.
PATHOGENESIS CHARACTERIZATION CHROMOSOMAL ABNORMALITIES
Comparative genomic hybridization analysis of lobular carcinoma in situ and atypical lobular hyperplasia and potential roles for gains and losses of genetic material in breast neoplasia.
Lu YJ, Osin P, Lakhani SR, Di Palma S, Gusterson BA, Shipley JM.
Section of Cell Biology and Experimental Pathology, Institute of Cancer Research, Surrey, United Kingdom.
Cancer Res 1998 Oct 15;58(20):4721-7 Abstract quote
Lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) of the breast are cytologically similar breast lesions that reportedly carry different relative risks of subsequent development of invasive carcinoma. They are frequently multifocal and bilateral.
We have identified the chromosomal copy number changes in 31 LCIS and 14 ALH lesions from 28 cases and also the 7 invasive carcinomas that subsequently developed in 6 of these cases. This was achieved by comparative genomic hybridization analysis of microdissected formalin-fixed, paraffin-embedded material. There was no significant difference between the aberrations found in the unilateral versus the bilateral cases of LCIS. Loss of material from 16p, 16q, 17p, and 22q and also gain of material from 6q were found at a similar high frequency in LCIS and ALH.
Loss of these genomic regions may indicate the locations of genes that predispose to the development of the lesions, and the results are consistent with LCIS and ALH representing the same genetic stage of development. Comparison of the comparative genomic hybridization results from LCIS/ALH with those from ductal carcinoma in situ and invasive cancer showed some similarities at the chromosomal level, but it also showed significant differences, including gain of 1q and 8q and evidence for genomic amplification, which were not found in LCIS/ALH.
A genetic model is postulated for the possible relationships between noninvasive lobular lesions and invasive breast carcinoma, delineating potential roles for specific chromosome copy number changes.
Loss of chromosome 16q in lobular carcinoma in situ
Joan E. Etzell, etal
Hum Pathol 2001;32:292-296. (Abstract quote)
Lobular carcinoma in situ (LCIS) and infiltrating lobular carcinoma may represent different forms of the same disease based on their frequent clinical association and similar histologic features. Patients with LCIS are at increased risk of multicentric and bilateral disease. Thus, LCIS may represent both a precursor to infiltrating lobular carcinoma and a marker of risk for breast cancer.
To identify genomic alterations in LCIS, comparative genomic hybridization was performed on 17 cases without concurrent invasive carcinoma. Loss involving chromosome 16q was present in 88% of cases and was the sole detected alteration in 29%. Gain involving 1q was second in frequency, occurring in 41% of tumors, and in all cases was associated with loss of 16q. Other recurrent changes were loss involving 17p (18%), 8p (12%), and 12q24 (12%). E-cadherin immunohistochemistry was performed on all LCIS cases to evaluate the correlation of loss involving 16q22, the site of the E-cadherin gene, and altered protein expression. Most cases with 16q22 loss showed altered E-cadherin expression (12 of 13).
These results in LCIS are similar to changes reported in infiltrating lobular cancer, confirming a genetic relationship between them.
Invasive lobular carcinoma of the breast: mammographic characteristics and computer-aided detection.
Evans WP, Warren Burhenne LJ, Laurie L, O'Shaughnessy KF, Castellino RA.
Susan G. Komen Breast Center, Baylor University Medical Center, Dallas, TX, USA.
Radiology 2002 Oct;225(1):182-9 Abstract quote
PURPOSE: To characterize the mammographic appearance of invasive lobular carcinoma in a large series of screening-detected consecutive breast cancers and to evaluate the ability of a computer-aided detection system to mark these carcinomas.
MATERIALS AND METHODS: Investigators used the Breast Imaging Reporting and Data System lexicon to characterize lesions as part of a retrospective review of 90 screening mammographic examinations that led to biopsy-proved diagnosis of 94 invasive lobular carcinoma lesions. The 40 available prior mammographic examinations (obtained 9-24 months earlier) were also reviewed to characterize any visible findings. The results of a computer-aided detection analysis were compared with the images, and the sensitivity of the algorithm was calculated for correct detection of the lesions.
RESULTS: Fifty-six (60%) of 94 lesions manifested as masses, of which 40 (71%) were described as irregular and spiculated; 20 (21%) of 94, as architectural distortions; and the remainder, 18 (20%), as either asymmetric densities or calcifications. On the screening mammograms showing biopsy-proved cancers, the sensitivity of the computer-aided detection system was 86 (91%) of 94 lesions. Thirty-one of the 40 prior mammograms showed retrospectively visible findings, and 24 (77%) of 31 were marked by the computer-aided detection system.
CONCLUSION: Spiculated masses and architectural distortions are the predominant appearances of invasive lobular carcinoma, and a computer-aided detection system correctly marked a high percentage of invasive lobular carcinoma lesions.
Role of magnetic resonance imaging in the diagnosis and single-stage surgical resection of invasive lobular carcinoma of the breast.
Munot K, Dall B, Achuthan R, Parkin G, Lane S, Horgan K.
Department of Surgery, The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK.
Br J Surg 2002 Oct;89(10):1296-301 Abstract quote
BACKGROUND: Conventional imaging with mammography and ultrasonography has a low sensitivity for diagnosis and a tendency to underestimate the extent of invasive lobular carcinoma (ILC) of the breast. The aim was to determine whether magnetic resonance imaging (MRI) had any advantages for the characterization of ILC.
METHODS: Twenty patients with histologically proven ILC underwent preoperative imaging with MRI. MRI was performed to aid detection of malignancy in six patients with a clinically suspicious presentation but normal or indeterminate imaging on mammography and ultrasonography. In 14 patients MRI was performed to determine tumour extent.
RESULTS: MRI accurately identified malignancy in five of six patients with normal or indeterminate conventional imaging. In seven of 14 patients in whom MRI was performed to determine tumour extent, it provided significant additional information. These included four patients in whom conventional imaging grossly underestimated tumour size, two patients in whom MRI identified an unsuspected contralateral breast tumour and one patient in whom MRI predicted tumour invasion of the pectoral muscle. The correlation between tumour size on histological examination was better with MRI (r = 0.967) than with mammography (r = 0.663) and ultrasonography (r = 0.673).
CONCLUSION: MRI can provide considerable additional information in the detection and characterization of ILC.
GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION Prior and concurrent contralateral carcinomas 6-28% of cases Subsequent contralateral carcinomas 1-2.38 cases/100 women per year
HISTOLOGICAL TYPES CHARACTERIZATION CLASSIC Small to medium sized cells, occasionally with cytoplasmic mucin globules, infiltrating the breast in a linear fashion (Indian file pattern) and in a targetoid arrangement around pre-existing ducts and lobules VARIANTS ALVEOLAR Globular aggregate of 20 or more cells MYOSECRETORY
- Lobular Carcinoma of the Breast With Hybrid Myoepithelial and Secretory ("Myosecretory") Cell Differentiation.
Vecchio MD, Foschini MP, Peterse JL, Eusebi V.
From the *Section of Histopathology and Cytopathology, University of Bologna at Bellaria Hospital, Bologna, Italy; and the daggerDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Am J Surg Pathol. 2005 Nov;29(11):1530-1536. Abstract quote
Three cases of lobular carcinoma of the breast showing a complex morphology that included myoepithelial cell differentiation are reported.
One case was a pure in situ acinar lesion, while the other 2 cases were in situ and invasive carcinomas. Three different cell types were seen in these tumors: one was the phenotype commonly seen in the garden variety of in situ lobular carcinoma (LCIS) constituted by noncohesive round to ovoid cells with round nuclei and positivity for epithelial membrane antigen (EMA), estrogen receptor (ER), and progesteron receptor (PR). E-cadherin was negative in these cells. The second type was represented by cohesive elements with irregular nuclei. These cells were immunoreactive for smooth muscle actin, calponin, keratin 14, p63, and e-cadherin. EMA, ER, and PR were consistently negative. The third type, seen in a minority of cell population of case nos. 2 and 3, consisted of cells showing at the same time EMA and smooth muscle actin in their cytoplasm. This type was defined as "hybrid myosecretory cell" to highlight contractile and secretory properties present at the same time.
Cells with hybrid features probably indicate that myoepithelial and secretory cells are strictly related and the existence of a stem cell, at least for these cases, is not necessary.
Pleomorphic Lobular Carcinoma: Morphology, Immunohistochemistry, and Molecular Analysis
L. P. Middleton, M.D.; D. M. Palacios, M.D.; B. R. Bryant, M.T.; P. Krebs, M.D.; C. N. Otis, M.D.; M. J. Merino, M.D.
From the National Cancer Institute (L.P.M., D.M.P, B.R.B., M.J.M), Bethesda, Maryland; and Baystate Medical Center (P.K., C.N.O.), Tufts University School of Medicine, Springfield, Massachusetts, U.S.A.
Am J Surg Pathol 2000;24:1650-1656 Abstract quote
Infiltrating pleomorphic lobular carcinoma (PLC) is an aggressive variant of infiltrating lobular carcinoma. Recently, in situ changes identical to PLC (PLCIS) have been described. The role of prognostic markers and their correlation with therapeutics, clinical outcome, and genetic changes is not well established in PLC.
The authors examined 38 cases of this entity to understand better this tumor's biology.
Immunohistochemical (IHC) analysis was performed in 21 specimens for estrogen and progesterone steroid receptors, p53, Her 2 (p185), and GCDFP-15. Genomic deoxyribonucleic acid was obtained from microdissected tumor as well as normal control cells, and loss of heterozygosity was investigated at the ESR (16q24), p53 (TP53 17p), Her 2 (17q 11-12), and BRCA 1 (17q12-25) loci. In this series, the average patient age was 57.5 years (age range, 24–92 years). Twenty-seven women were postmenopausal. Tumor size ranged from 1.2 to 25 cm. Six patients were a pathologic stage I; 19, stage II; 12, stage III; and one, stage IV. Histologically, multifocal nodular aggregates of discohesive pleomorphic tumor cells were seen interspersed in dense and fibrotic breast parenchyma. Twenty-nine percent of the specimens demonstrated associated signet ring cells. The remainder had dishesive, globoid, plasmacytoid cells with high-grade nuclear features. PLCIS was identified in 17 of 38 patients (45%), and lobular carcinoma in situ (LCIS) was noted in 8 patients (21%). IHC analysis showed estrogen immunoreactivity in 81%, progesterone in 67%, GCDFP-15 in 71%, and Her 2 in 81% (2+ to 3+ membranous staining) of specimens. Antibodies to p53 stained the tumor cell nuclei in 48% of the tumors. Loss of heterozygosity was identified in 52% of the specimens at the p53 locus, 18% at the ESR locus, 19% to 24% at the Her 2 loci, and 27% to 32% at the BRCA 1 locus. Follow-up was available in 19 patients and ranged from 12 months to 15 years (mean, 73 months). Seven patients had no evidence of disease at last examination (range, 1–15 years), three patients were alive with disease (range, 2–14 years), and nine patients were dead of disease (range, 2 months–9 years). Six patients had subsequent diagnoses of tumor in the contralateral breast.
Analysis shows that PLC tends to appear in older postmenopausal women who present with locally advanced disease. PLCIS was found to be associated with PLC 45% of the time. The aggressive clinical course of patients with PLC is supported by tumor immunoreactivity with unfavorable markers Her 2 and p53. Overexpression of Her 2 in PLC may be therapeutically relevant, enabling the use of novel chemotherapeutic drugs like Herceptin. Interestingly, tumors that were Her 2 immunoreactive also maintained estrogen hormone immunoreactivity.
SOLID Solid nests with classic pattern TUBULOLOBULAR CARCINOMA Small tubules and cords of tumor cells in classic pattern
- Tubulolobular Carcinoma of the Breast: An Analysis of 27 Cases of a Tumor With a Hybrid Morphology and Immunoprofile.
Wheeler DT, Tai LH, Bratthauer GL, Waldner DL, Tavassoli FA.
From the *Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC; daggerDepartment of Pathology, Potomac Hospital, Woodbridge, VA; double daggerDepartment of Pathology, Madigan Army Medical Center, Tacoma, WA; and section signDepartment of Pathology, Yale University School of Medicine, New Haven, CT.
Am J Surg Pathol. 2004 Dec;28(12):1587-1593. Abstract quote
Tubulolobular carcinoma (TLC) is a rare subtype of mammary carcinoma that has eluded precise classification, exhibiting features of both ductal and lobular differentiation.
The clinicopathologic features of 27 cases of TLC were analyzed by both hematoxylin and eosin and immunohistochemical stains for E-cadherin and 34betaE12 (high molecular weight cytokeratin). Five cases of both pure tubular and classic lobular carcinoma were included as controls. Patients with TLC ranged in age from 43 to 79 years (median, 60 years). Tumor characteristics were as follows: size, 0.5 cm to 2.5 cm (median, 1.4 cm); bilaterality, 1 of 27 (4%); and multifocality, 5 of 27 (19%). Twenty-two of the 27 cases (81%) contained an in situ component: 8 (36%) lobular (LIN); 4 (18%) ductal (DIN); and 10 (46%) mixed. All 27 cases were intensely positive (3+) for E-cadherin, a feature of ductal differentiation, while 25 of 27 (93%) cases showed variable positivity for 34betaE12 (1 to 3+), a feature far more common in tumors with lobular differentiation.
Clinical follow-up was available on 25 of 27 (93%) patients. Three of 24 (13%) patients developed axillary lymph node metastases and 1 of 25 (4%) patients developed a local recurrence over a follow-up period of 2 to 91 months (median, 39 months). In conclusion, TLCs are a distinct subtype of mammary carcinoma with overlapping morphologic features that are mirrored by a hybrid immunohistochemical profile. The uniform 3+ expression of E-cadherin in TLC supports the ductal differentiation of these tumors, despite a dominant lobular growth pattern.
The prognosis of these tumors appears to be excellent, especially in those cases that are unilateral and less than 2 cm in size.
CHARACTERIZATION Special stains Immunoperoxidase E-Cadherin
Am J Clin Pathol 2001;115:85-98
Moderate to strong membrane expression found in all invasive (100/100) and in situ ductal carcinomas (131/131)
41/42 invasive and 50/53 in situ lobular carcinomas showed complete loss of expression
Invasive carcinomas with both features (41) showed three staining patterns:
Complete or almost complete lack of membrane staining similar to lobular CA
Uniform membrane expression througout the tumor similar to ductal CA
Focal loss of staining
- Aberrant Expression of E-cadherin in Lobular Carcinomas of the Breast.
*Molecular and Cellular Pathology, Mayne Medical School, University of Queensland †The Queensland Institute of Medical Research ‡The Royal Brisbane and Womenʼs Hospital, Brisbane, Australia.
- Am J Surg Pathol. 2008 May;32(5):773-783. Abstract quote
Invasive lobular carcinoma (ILC) and lobular carcinoma in situ characteristically show loss of E-cadherin expression and so immunohistochemistry for E-cadherin is being increasingly used as a tool to differentiate between lobular and ductal lesions in challenging situations. However, misinterpretation of "aberrant" positive staining may lead some to exclude a diagnosis of lobular carcinoma.
E-cadherin and beta-catenin immunohistochemistry was analyzed in 25 ILCs. E-cadherin "positive" ILCs were subjected to molecular analysis including comparative genomic hybridization. Different morphologic components of case 25, showing heterogenous E-cadherin expression, were analyzed by E-cadherin gene sequencing, methylation, and DASL gene expression profiling. Four ILCs were positive for E-cadherin, but each also had neoplastic cells with aberrant staining. Two of these ILCs were positive for beta-catenin, again with some aberrantly stained neoplastic cells, and 2 were negative. The solid component of case 25 was positive for E-cadherin whereas the classic and alveolar areas were negative. All components harbored an in-frame deletion in exon 7 (867del24) of the E-cadherin gene and loss of the wild type allele. Comparative genomic hybridization demonstrated evidence of clonal evolution from E-cadherin-positive to E-cadherin-negative components. E-cadherin down-regulation seems to be through transcriptional repression via activation of transforming growth factor-beta/SMAD2 rather than methylation.
Positive staining for E-cadherin should not preclude a diagnosis of lobular in favor of ductal carcinoma. Molecular evidence suggests that even when E-cadherin is expressed, the cadherin-catenin complex maybe nonfunctional. Misclassification of tumors may lead to mismanagement of patients in clinical practice, particularly in the context of in situ disease at margins.
E-Cadherin Reactivity of 95 Noninvasive Ductal and Lobular Lesions of the Breast Implications for the Interpretation of Problematic Lesions
Neal S. Goldstein, etal.
Am J Clin Pathol 2001;115:534-542 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.
E-cadherin expression in pleomorphic lobular carcinoma: An aid to differentiation from ductal carcinoma.
Wahed A, Connelly J, Reese T.
Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston; the Department of Pathology, St Luke's Episcopal Hospital, Houston, TX.
Ann Diagn Pathol 2002 Dec;6(6):349-51 Abstract quote
Pleomorphic lobular carcinoma is a recently described entity separated from classical lobular carcinoma by cytologic pleomorphism. It can have an aggressive clinical course with a higher frequency of recurrence. Histologic differentiation with ductal carcinoma may be difficult, but it is important for this differentiation to be made. E-cadherin is a transmembrane glycoprotein, and complete loss of E-cadherin expression has been observed in invasive lobular carcinoma and lobular carcinoma in situ. Ductal carcinoma retains at least some expression of E-cadherin.
We examined the pattern of E-cadherin expression in a series of 14 cases of pleomorphic lobular carcinoma by immunohistochemistry. Twelve of the 14 cases showed no staining (86%); the remaining two cases exhibited 10% to 25% positive cells.
In cases with histologic equivocal features, immunohistochemical detection of E-cadherin expression can be a useful diagnostic aid for the differentiation of pleomorphic lobular and ductal carcinoma.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES MEDULLARY THYROID CARCINOMA
Medullary thyroid carcinoma metastatic to breast masquerading as infiltrating lobular carcinoma.
Ali SZ, Teichberg S, Attie JN, Susin M.
Department of Laboratories, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030.
Ann Clin Lab Sci 1994 Sep-Oct;24(5):441-7 Abstract quote
Metastatic tumors to the breast from an extramammary site are rare entities and may present diagnostic difficulties for the surgical pathologist because of frequent histological similarities to primary neoplasms in this location.
A case is reported of medullary thyroid carcinoma metastatic to the breast in a 28-year-old woman with a family history of MEN IIA (Sipple's) syndrome.
Histological features resembled infiltrating lobular carcinoma and included the so-called "targetoid" and "Indian file" patterns. Immunostaining revealed the true nature of the lesion and was diffusely positive for calcitonin, chromogranin, and carcinoembryonic antigen. Electron microscopy disclosed typical neurosecretory granules confirming the diagnosis. A brief review of the literature and differential diagnosis is also presented.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS Stage is most important GRADE
- Invasive lobular carcinoma: to grade or not to grade.
Bane AL, Tjan S, Parkes RK, Andrulis I, O'malley FP.
Mod Pathol. 2005:18;621-628 Abstract quote
Grading of invasive ductal carcinoma of no special type using the Nottingham combined histologic grading system provides independent prognostic information. The prognostic utility of grading invasive lobular carcinomas, however, has not been fully elucidated. In addition, the relationship between grade in invasive lobular carcinomas and expression of predictive biomarkers is less certain.
The purpose of this study was to correlate histologic grade in invasive lobular carcinoma with known prognostic and predictive markers. All primary resections for invasive mammary carcinomas diagnosed in Mount Sinai Hospital, Toronto, between the years 1996 and 2002 were reviewed (n=1053). Of these cases, 50 were pure invasive lobular carcinoma (incidence 4.7%). The median age at diagnosis was 64 years. These tumors were graded using the Nottingham combined histologic grading system and analyzed for estrogen receptor, progesterone receptor, HER2/neu and E-cadherin expression. Tumor grade was correlated with tumor size (P=0.03), and the American Joint Committee on Cancer nodal status (P=0.05). Assessment of the individual components of grade showed that the mitotic score was highly correlated with tumor size (P=0.02), lymph node positivity (P=0.02) and overall American Joint Committee on Cancer stage (P=0.01). Estrogen receptor and progesterone receptor were highly expressed irrespective of the grade of tumor. HER2/neu protein overexpression and E-cadherin protein expression was absent in all invasive lobular carcinomas studied.
We conclude that pure invasive lobular carcinoma is uncommon and occurs predominantly in postmenopausal women. Increasing tumor grade is correlated with median tumor size and the American Joint Committee on Cancer nodal stage, but not correlated with the expression of estrogen receptor, progesterone receptor, E-cadherin or HER2/neu protein overexpression.
Pleomorphic lobular carcinoma
Hum Pathol 1992;23:1167-1171
Trend to decrease in overall survival as compared to classic carcinoma
6/10 patients died within 42 months of diagnosis
5 Year Survival 72% overall
Probably overall better prognosis than infiltrating ductal carcinoma
Metastasis Local recurrence 12% after 5 years Cytokeratin immunohistochemistry detects clinically significant bone marrow biopsy metastaes
Am J Surg Pathol 2000;24:1593-1599
A total of 65 biopsies from 54 patients
13/65 identified as containing metastatic tumor on H and E stain alone
Keratin staining revealed additional 7 cases
Two year disease free survival was 33% for H and E negative/Keratin positive cases versus 90% for H and E negative/keratin negative cases
Bilaterality and recurrence rates for lobular breast cancer: considerations for treatment.
Yeatman TJ, Lyman GH, Smith SK, Reintgen DS, Cantor AB, Cox CE.
Department of Surgery, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa 33612, USA.
Ann Surg Oncol 1997 Apr-May;4(3):198-202 Abstract quote
BACKGROUND: The purpose of this study was to evaluate the tumor biology with respect to bilaterality and recurrence rates for bilateral infiltrating lobular (IL) breast carcinoma in comparison with other histological types.
METHODS: A prospectively accrued data base containing 1,548 breast cancer cases as well as H. Lee Moffitt Cancer Center's cancer registry compiled during the same period were queried for specific features relating to bilaterality and recurrence. The 116 patients in this study had been treated at the Comprehensive Breast Cancer Clinic and had documented bilateral breast cancer (invasive on situ).
RESULTS: Eighty-two of the patients (70.7%) had metachronous breast cancer, and 34 (29.3%) had synchronous cancer. Although median follow-up times were short, the risk of developing breast cancer in the contralateral breast after the diagnosis of cancer in the ipsilateral breast was estimated to be 0.7% per patient-year of follow-up. Recurrence rates for IL cancers were compared with those for invasive ductal (ID) and for ID + IL cancers. IL cancers recurred 8.1% of the time, whereas ID cancers recurred at a rate of 7.8%. Recurrences were equally divided between local and distant sites.
CONCLUSIONS: Although IL cancers have demonstrated insidious behavior, their incidence of bilaterality is only slightly higher than other histologies and their rates of recurrence are low when properly evaluated and treated. The risk to the opposite breast also appears to be low. These data do not support the routine use of blind contralateral biopsy or prophylactic mastectomy.
Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation.
Sasson AR, Fowble B, Hanlon AL, Torosian MH, Freedman G, Boraas M, Sigurdson ER, Hoffman JP, Eisenberg BL, Patchefsky A.
Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19104, USA
Cancer 2001 May 15;91(10):1862-9 Abstract quote
BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy.
METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years.
RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women.
CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.
Infiltrating lobular carcinoma of the breast. Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns.
Sastre-Garau X, Jouve M, Asselain B, Vincent-Salomon A, Beuzeboc P, Dorval T, Durand JC, Fourquet A, Pouillart P.
Department of Pathology, Institute Curie, Paris, France.
Cancer 1996 Jan 1;77(1):113-20 Abstract quote
BACKGROUND. The clinicopathologic features of infiltrating lobular carcinoma (ILC), which represents 5% to 15% of all breast cancers, are still controversial. In particular, the high frequency of multicentric lesions has led to questioning of the effectiveness of conservative treatment for this type of cancer. By studying a large number of cases, we aimed to compare the clinicopathological features of ILC with those of nonlobular infiltrating carcinoma (NLIC) and to assess the advisability of conservative therapy in the management of ILC.
METHODS. The population analyzed included 726 cases of ILC, 249 cases of mixed ILC/invasive ductal carcinoma (ILC/IDC), and 10,061 cases of NLIC. The age of patients, TNM status, estrogen- and progesterone-receptor status (ER, PR), and histologic grades of the 3 groups were compared. The follow-up was carried out on a subgroup of 5846 cases.
RESULTS. At diagnosis, ILC tumors were found to be larger on average and were detected in patients older than those with NLIC, but the degree of lymph node involvement was lower in patients with ILC than in NLIC. In ILC, tumors are more frequently grade I and ER-positive than in NLIC. Multicentric lesions were not significantly more frequent in ILC than in NLIC. The overall survival, locoregional control, disease free interval, and metastatic spread rates were not different among the three groups neither by univariate nor multivariate analysis, but the pattern of metastatic dissemination was different. In 480 cases of ILC considered for conservation therapy, the local recurrence and overall survival rates were similar to those observed for IDC.
CONCLUSIONS. Our analysis specifies the clinicopathological features of ILC and confirms that conservation therapy may be an appropriate treatment for this type of cancer.
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